dinoprost and Body-Weight

It has been previously reported that pasta containing wholegrain sorghum flour exhibits high content of polyphenols and antioxidant capacity and hence might enhance antioxidant status and reduce markers of oxidative stress in vivo; however no clinical studies have yet been reported. Therefore, the present study assessed the effect of pasta containing red or white wholegrain sorghum flour on plasma total polyphenols, antioxidant capacity and oxidative stress markers in humans. The study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN: 12612000324819).. In a randomised crossover design, healthy subjects (n = 20) consumed three test meals of control pasta (CP), 30% red sorghum pasta (RSP) or 30% white sorghum pasta (WSP), 1-2 wk apart. The test meals were consumed as breakfast after an overnight fast. Blood samples were obtained at fasting and 2 h after consumption and analysed for total polyphenols, antioxidant capacity, superoxide dismutase (SOD) activity, protein carbonyl and 8-isoprostanes.. Compared to baseline, the 2 h post-prandial levels following the RSP meal of plasma polyphenols, antioxidant capacity and SOD activity were significantly (P < 0.001) higher while the protein carbonyl level was significantly lower (P = 0.035). Furthermore, net changes in polyphenols, antioxidant capacity and SOD activity were significantly (P < 0.001) higher while protein carbonyl were significantly (P = 0.035) lower following consumption of the RSP meal than the CP meal.. The results demonstrated that pasta containing red wholegrain sorghum flour enhanced antioxidant status and improved markers of oxidative stress in healthy subjects.

Topics: Adult; Antioxidants; Biomarkers; Body Mass Index; Body Weight; Cross-Over Studies; Dinoprost; Female; Flour; Healthy Volunteers; Humans; Male; Oxidative Stress; Polyphenols; Protein Carbonylation; Sorghum; Superoxide Dismutase; Surveys and Questionnaires; Waist Circumference; Young Adult

Two experiments were designed to test the hypothesis that pregnancy rates after fixed-time artificial insemination (FTAI) in beef heifers and cows may be improved by delaying insemination of females that have not expressed estrus before FTAI. In Exp. 1, estrus was synchronized for 931 heifers across 3 locations using the 14-d CIDR-PG protocol (controlled internal drug-release [CIDR] insert [1.38 gm progesterone] on d 0 with removal of CIDR insert on d 14; 25 mg PGF2α 16 d after CIDR insert removal on d 30; and 100 μg GnRH on d 33, 66 h after PGF2α). Estrous detection aids (Estrotect) were applied at PGF2α on d 30, and estrous expression was recorded at GnRH on d 33. Heifers within each location were randomly assigned to 1 of 2 treatments based on weight and reproductive tract score (RTS): 1) FTAI (concurrent with GnRH, 66 h after PGF2α) regardless of estrous expression or 2) FTAI for heifers expressing estrus and delayed AI (20 h after GnRH) for heifers failing to express estrus. Heifers assigned to treatment 2 achieved a higher AI pregnancy rate than heifers assigned to treatment 1 (54 versus 46%; P = 0.01). The observed increase in AI pregnancy rate is attributed to the delayed AI of non-estrous heifers in treatment 2, as AI pregnancy rates for non-estrous heifers were significantly higher for treatment 2 (49 versus 34%; P = 0.02), while AI pregnancy rates of estrous heifers did not differ by treatment (P = 0.24). In Exp. 2, estrus was synchronized for 951 mature, suckled cows across 9 locations using the 7-d CO-Synch + CIDR protocol (100 μg GnRH + CIDR insert [1.38 gm progesterone] on d 0; 25 mg PGF2α at CIDR insert removal on d 7; and 100 μg GnRH on d 10, 66 h after CIDR insert removal). Estrus detection aids (Estrotect) were applied at PGF2α and CIDR insert removal on d 7, and estrous expression was recorded at GnRH on d 10. Cows within each location were assigned to 1 of 2 treatments based on age, days postpartum, and BCS: 1) FTAI (concurrent with GnRH, 66 h after PGF2α) regardless of estrous expression or 2) FTAI for cows expressing estrus and delayed AI (20 h after GnRH) for cows failing to express estrus. No significant effect of treatment was found on AI pregnancy rate (P = 0.76). In summary, FTAI pregnancy rates in heifers can be improved through a strategy of "split-time" AI. However, a statistically significant increase was not observed in the pregnancy rates of mature suckled cows when using a similar strategy.

Topics: Animals; Body Weight; Cattle; Delayed-Action Preparations; Dinoprost; Estrus; Estrus Detection; Estrus Synchronization; Female; Gonadotropin-Releasing Hormone; Insemination, Artificial; Postpartum Period; Pregnancy; Pregnancy Rate; Progesterone; Semen; Time Factors

Feed scarcity during hot summer months is one of the major predisposing factors for low reproductive efficiency of livestock reared in hot semiarid environment. A study was conducted to assess the effect of concentrate supplementation during summer months on growth, reproductive performance, and blood metabolites in Malpura ewes. Twenty adult Malpura ewes were used in the present study. The ewes were divided into two groups viz, group 1 (n = 10; control) and group 2 (n = 10; concentrate supplementation). The study was conducted for a period of 35 days covering two estrus cycles. In the first cycle, only PGF(2α) was given to all ewes, while in second cycle, all ewes were synchronized for estrus using progesterone-impregnated intravaginal sponges and pregnant mare serum gonadotropin. The animals were allowed for grazing for 8-10 h per day. Apart from grazing, group 2 ewes were supplemented with concentrate mixture at 1.5 % of body weight. Concentrate supplementation had significant influence on body weight, ADG, estrus percentage, estrus duration, onset of estrus, ovulation response, plasma glucose, total protein, and urea. The present study reveals that ewes supplemented with concentrate mixture at 1.5 % of body weights during summer season significantly influenced the growth and reproductive performance of Malpura ewes. Further, the study signifies the importance of providing additional feed supplementation to ewes kept grazing under the conditions of a hot, semiarid environment to improve their reproductive efficiency.

Topics: Animal Feed; Animals; Blood Chemical Analysis; Body Weight; Breeding; Climate; Dietary Supplements; Dinoprost; Estrus; Female; Gonadotropins, Equine; India; Pregnancy; Reproduction; Seasons; Sheep, Domestic; Tropical Climate

The objective of this experiment was to determine if dietary inclusion of fish meal would increase plasma and luteal tissue concentrations of eicosapentaenoic and docosahexaenoic acids. Seventeen nonlactating Angus cows (2 to 8 yr of age) were housed in individual pens and fed a corn silage-based diet for approximately 60 d. Diets were supplemented with fish meal at 5% DMI (a rich source of eicosapentaenoic acid and docosahexaenoic acid; n = 9 cows) or corn gluten meal at 6% DMI (n = 8 cows). Body weights and jugular blood samples were collected immediately before the initiation of supplementation and every 7 d thereafter for 56 d to monitor plasma n-3 fatty acid composition and BW. Estrous cycles were synchronized using 2 injections of PGF(2α) administered at 14-d intervals. The ovary bearing the corpus luteum was surgically removed at midcycle (between d 10 and 12) after estrus synchronization, which corresponded to approximately d 60 of supplementation. The ovary was transported to the laboratory, and approximately 1.5 g of luteal tissue was stored at -80°C until analyzed for n-3 fatty acid content. Initial and ending BW did not differ (P > 0.10) between cows supplemented with fish meal and those with corn gluten meal. Plasma eicosapentaenoic acid was greater (P < 0.05) beginning at d 7 of supplementation and docosahexaenoic was greater (P < 0.05) beginning at d 14 of supplementation for cows receiving fish meal. Luteal tissue collected from fish meal-supplemented cows had greater (P < 0.05) luteal n-3 fatty acids and reduced (P < 0.05) arachidonic acid and n-6 to n-3 ratio as compared with tissue obtained from cows supplemented with corn gluten meal. Our data show that fish meal supplementation increases luteal n-3 fatty acid content and reduces available arachidonic acid content, the precursor for PGF(2α). The increase in luteal n-3 fatty acids may reduce PGF(2α) intraluteal synthesis after breeding resulting in increased fertility in cattle.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Body Weight; Cattle; Corpus Luteum; Diet; Dinoprost; Estrus Synchronization; Fatty Acids, Omega-3; Female; Fish Products

This study was designed to determine the effect of exenatide on inflammatory and oxidative stress markers in type 2 diabetes mellitus (T2DM) patients who were suboptimally controlled with metformin and/or sulfonylurea.. Twenty-three patients with T2DM with inadequate glucose control were randomly divided into two groups: exenatide group (E group) (12 patients, 5 μg b.d. × 4 weeks followed by 10 μg b.d. × 12 weeks) and placebo group (P group) (11 patients). Glycosylated hemoglobin (HbA1c), the seven-point glucose profile, daily mean glucose, and glycemic excursion were determined. The effects of exenatide on 8-iso-prostaglandin F2α (PGF2α), monocyte chemoattractant protein-1 (MCP-1), and high-sensitivity C-reactive protein (hs-CRP) were investigated.. Exenatide treatment reduced body weight and body mass index (BMI) and improved HbA1c, the seven-point glucose profile, and daily mean glucose compared with placebo (P < 0.05). Limited glycemic excursion was found in the E group compared with the P group (P < 0.05), including a smaller SD and postprandial glucose excursion. In addition, the oxidative stress maker PGF2α was significantly reduced by exenatide treatment (P < 0.05). The inflammatory markers hs-CRP and MCP-1 were also significantly reduced in the E group compared with the P group (P < 0.05). PGF2α was significantly correlated with glycemic excursion (P < 0.05), whereas MCP-1 was significantly correlated with body weight, BMI, glycemic excursion, and HbA1c (P < 0.05 for all).. Exenatide treatment reduced patient body weight and BMI, improved HbA1c and the seven-point glucose profile, reduced daily mean glucose, limited glycemic excursion, and reduced oxidative stress and inflammatory markers in patients of T2DM having inadequate glucose control.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; C-Reactive Protein; Chemokine CCL2; Diabetes Mellitus, Type 2; Dinoprost; Double-Blind Method; Exenatide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; In Vitro Techniques; Insulin Resistance; Male; Middle Aged; Oxidative Stress; Peptides; Pilot Projects; Venoms

Glycemic excursion is significantly associated with oxidative stress, which plays a role in the development of chronic complications in type 2 diabetes mellitus (T2DM). Acarbose has been reported to reduce cardiovascular risk in patients with impaired glucose tolerance and T2DM. We hypothesize that treatment with acarbose could attenuate glycemic excursions and reduce oxidative stress in patients with T2DM.. This study aimed to evaluate the effects of acarbose versus glibenclamide on mean amplitude of glycemic excursions (MAGE) and oxidative stress in patients with T2DM who are insufficiently controlled by metformin.. T2DM outpatients aged 30 to 70 years who were taking single or dual oral antidiabetic drugs for ≥3 months and had a glycosylated hemoglobin (HbA(1c)) value between 7.0% and 11.0% were eligible. Patients were treated with metformin monotherapy (1500 mg daily) for 8 weeks, followed by randomization to either acarbose or glibenclamide add-on for 16 weeks. The dosage of acarbose and glibenclamide was 50 mg TID and 2.5 mg TID, respectively, for the first 4 weeks. In the following 12 weeks, the dosage was doubled in both groups. Continuous glucose monitoring (CGM) for 72 hours and a meal tolerance test (MTT) after a 10-hour overnight fast were conducted before randomization and at the end of study. MAGE was calculated from CGM data. β-cell response to postprandial glucose increments was assessed by the ratio between incremental AUC of insulin and glucose during MTT. Oxidative stress was estimated by plasma oxidized LDL (ox-LDL) and urinary excretion rates of 8-iso prostaglandin F(2α) (8-iso PGF(2α)). The primary outcomes included changes in MAGE, plasma ox-LDL, and urinary excretion of 8-iso PGF(2α). Adverse events, including hypoglycemia, were recorded.. A total of 55 patients were randomized (mean age, 54 years; males, 47%; mean body mass index, 25.9 kg/m(2); mean duration of diabetes, 6.9 years; mean HbA(1c), 8.3%) and 51 patients completed this study (acarbose, n = 28; glibenclamide, n = 23). HbA(1c) decreased significantly in both treatment groups (acarbose: 8.2 [0.8]% to 7.5 [0.8]% [P < 0.001]; glibenclamide: 8.6 [1.6]% to 7.4 [1.2]% [P < 0.001]). MAGE did not change significantly in glibenclamide-treated patients (6.2 [2.8] mmol/L to 6.3 [2.3] mmol/L; P = 0.82), whereas ox-LDL (242.4 [180.9] ng/mL to 470.7 [247.3] ng/mL; P = 0.004) and urinary excretion of 8-iso PGF(2α) (121.6 [39.6] pmol/mmol creatinine to 152.5 [41.8] pmol/mmol creatinine; P = 0.03) increased significantly. Acarbose decreased MAGE (5.6 [1.5] mmol/L to 4.0 [1.4] mmol/L; P < 0.001) without significant change in ox-LDL levels (254.4 [269.1] ng/mL to 298.5 [249.8) ng/mL; P = 0.62) or 8-iso PGF(2α) excretion rates (117.9 [58.1] pmol/mmol creatinine to 137.8 [64.4] pmol/mmol creatinine; P = 0.12). Body weight and serum triglycerides (fasting and 2-hour postprandial) decreased (all, P < 0.01) and serum adiponectin increased (P < 0.05) after treatment with acarbose, whereas HDL-C decreased (P < 0.01) after treatment with glibenclamide. β-cell response to postprandial glucose increments was negatively correlated with MAGE (r = 0.570, P < 0.001) and improved significantly with acarbose (35.6 [32.2] pmol/mmol to 56.4 [43.7] pmol/mmol; P = 0.001) but not with glibenclamide (27.9 [17.6] pmol/mmol to 36.5 [24.2] pmol/mmol; P = 0.12).. In this select population of adult Taiwanese patients with T2DM who were inadequately controlled by metformin, add-on acarbose or glibenclamide significantly reduced HbA(1c). However, treatment with acarbose decreased MAGE, body weight, and serum triglyceride and increased serum adiponectin without significant effect on oxidative stress. Treatment with glibenclamide had no statistically significant effect on MAGE but increased oxidative stress and decreased HDL-C. ClinicalTrials.gov identifier: NCT00417729.

Topics: Acarbose; Adult; Aged; Biomarkers; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dinoprost; Drug Therapy, Combination; Female; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Lipids; Lipoproteins, LDL; Male; Medication Adherence; Metformin; Middle Aged; Outpatients; Oxidative Stress; Regression Analysis; Taiwan; Time Factors; Treatment Outcome

We estimated the effect of estrus synchronization on reproduction, production and economic outcomes in 272 beef heifers randomly allocated to a synchronized Test group or an unsynchronized Control group. The Test group received AI upon estrus detection for 6 days followed by PGF2 treatment of heifers that had not shown estrus by day 6 (PGF/6). In both groups AI was continued for 50 days, followed by a 42-day bull breeding period. Heifers were followed through their second breeding season and until they had weaned their first calves. Synchronization resulted in a reduction in median days to first insemination (8 vs. 11 in the Test and Control groups, respectively, P<0.01) and median days to calving of calves born to AI (14 vs. 20, P=0.04). There was no significant difference in pregnancy rate to the AI period (60.0% vs. 51.8%, P=0.18), final pregnancy rate (82.2% vs. 83.2%, P=0.87) or pregnancy rate to the subsequent breeding season (96.0% vs. 95.0%, P=1.00). Although mean calf weaning mass was not significantly different (207.0 kg vs. 201.4 kg, P=0.32), the total mass of calves weaned in this study was 14,843 kg vs. 13,060 kg and the benefit: cost ratio for synchronization was 2.8. It was therefore concluded that a PGF/6 protocol may affect the total mass of calves weaned by changing days to calving, weaning rate, the ratio of male: female calves born and/or the birth mass of calves.

Topics: Animals; Body Weight; Breeding; Cattle; Dinoprost; Estrus Synchronization; Female; Fertility; Insemination, Artificial; Male; Pregnancy; Sex Ratio; Weaning

The objectives were to evaluate factors affecting reproductive performance of dairy heifers. Holstein heifers (6389) were housed in a feed lot located in Parma, ID. Each week heifers weighing > or =290 kg were initiated in the reproductive program, which consisted of one injection of PGF(2alpha) and AI on detection of estrus. Heifers not inseminated by 11 days after the initiation of the breeding program received a second injection of PGF(2alpha). Pregnancy was diagnosed at 40+/-3 and 90+/-3 days after AI. Average daily minimum temperature (ADMnT), average daily maximum temperature (ADMxT), and average daily rainfall (ARF) were recorded between 15 days prior to and 15 days after the day of AI or the day of initiation of the breeding program. Exposure to air temperature was classified as: cold stress (CS=ADMnT< or =4 degrees C), no stress (NS=ADMnT>4 degrees C and ADMxT<29 degrees C), and heat stress (HS=ADMxT> or =29 degrees C). Exposure to rainfall was classified as above (HRF) or below (LRF) the mean for the period in question. Heifers were classified according to body weight at initiation of the breeding program as thin (TH<340 kg); moderate (MD=340-365 kg); and heavy (HY>365 kg). Service sire was associated with conception rate at 40 and 90 days after first AI. Although exposure to air temperature was not correlated with conception rate at 40 days after first AI, heifers exposed to cold stress had smaller conception rates at 90 days after first AI because they were more likely to lose pregnancy between 40 and 90 days of gestation. The proportion of heifers inseminated after initiation of the breeding program was correlated with body weight and exposure to cold stress. Exposure to cold stress was also correlated with the proportion of heifers conceiving within 11 and 22 days after initiation of the breeding program. From this study a correlation was established between body weight and rate of insemination and between the exposure to cold stress and reproductive efficiency of Holstein heifers.

Topics: Abortion, Veterinary; Aging; Animal Husbandry; Animals; Body Weight; Cattle; Dinoprost; Environment; Estrous Cycle; Female; Insemination, Artificial; Light; Odds Ratio; Oxytocics; Pregnancy; Reproduction

Dietary patterns that involve both a decrease in fat and an increase in fruit and vegetable (FV) intake may decrease cancer risks. In this study, a total of 122 premenopausal women with a family history of breast cancer were randomized into one of four diets for 12 mo: nonintervention, low-fat (15% of energy from fat), high-FV(9 servings/d), and combination low-fat/high-FV Fasting blood samples were obtained at baseline and after 3, 6, and 12 mo. Levels of 8-isoprostane-F2a in plasma were deter-mined by immunoassay kits. Statistical analyses indicated that levels of 8-isoprostane-F2a decreased significantly with time in the low-fat arm, which is the only intervention that resulted in weight loss; there were no significant changes in the other three diet arms. It is unlikely that this is due to changes in levels of blood lipids because there was little change overtime in plasma total cholesterol, high-density lipoprotein,low-density lipoprotein (LDL), or triglyceride levels in any diet arm, although mean LDL did decrease slightly in women who reduced fat intake after adjustment for change in body mass index (BMI). Levels of baseline 8-isoprostane-F2a were significantly higher in obese women than in overweight or normal weight women, and change in BMI was significantly correlated with change in 8-isoprostane-F2a levels. These results indicate that low-fat diets or high-FV diets are unlikely to affect plasma levels of 8-isoprostane-F2a in healthy,premenopausal women who do not lose weight during dietary change.

Topics: Adult; Body Mass Index; Body Weight; Breast Neoplasms; Dietary Fats; Dinoprost; Energy Intake; Female; Fruit; Humans; Lipids; Middle Aged; Oxidative Stress; Vegetables

The objective of the present study was to determine the effect of level of feed intake of pasture on P4 clearance rates in dairy cows. Twelve non-lactating Holstein-Friesian cows aged 4-9 years were randomly allocated to a restricted or ad libitum group. The ad libitum group had unrestricted access to irrigated pasture, whereas the restricted group had access for only 2h per day. Each animal was drenched orally twice daily with a chromic oxide capsule to allow daily feed intake to be estimated from faecal output (FO). Endogenous progesterone (P4) production was eliminated by subcutanously implanting a capsule containing 6 mg of a potent GnRH-agonist (deslorelin) into the ear of each animal 3 weeks before inserting a CIDR device containing 1.9 g P4 into the vagina. Two luteolytic PGF2alpha were given 10 days later. Each device was removed after 11 days and residual P4 measured. Daily plasma samples were assayed for P4. Faecal samples were also taken daily and assayed for pregnanes (FP4M) containing a 20-oxo-, a 20alpha- or a 20beta-OH group with EIAs. The average daily dry matter (DM) intake of pasture was higher for cows in the ad libitum group (15.9 versus 6.3 kg DM, P=0.001). Their plasma P4 concentrations were lower (1.08 versus 1.71 ng/ml, P=0.05), even though the average residual P4 content of the used CIDR devices was not affected by feed intake (1.20 versus 1.25 g, P>0.05). The concentrations of FP4M were not affected by level of feed intake (20-oxo-: 3.3 versus 1.7, 20alpha-: 3.5 versus 3.7, 20beta-: 2.1 versus 3.2 microg/g DM). Daily excretion rates of 20-oxo- and 20alpha- were higher in ad libitum cows (20-oxo-: 17.8 versus 4.3mg per day, P=0.05; 20alpha-: 18.2 versus 8.9 mg per day, P=0.001), but daily yield of faecal 20beta- was not affected by feed intake (11.9 versus 8.6 mg per day, P=0.5). These results show that there was a negative relationship between feed intake and plasma P4 concentrations in these CIDR-treated GnRH-downregulated Holstein cows. Concentrations of FP4M were not affected by level of feed intake or FO, but daily excretion rate of FP4M was associated with the volume of faeces.

Topics: Animals; Body Weight; Cattle; Diet; Dinoprost; Eating; Feces; Female; Food Deprivation; Gonadotropin-Releasing Hormone; Metabolic Clearance Rate; Pregnanes; Progesterone; Triptorelin Pamoate

In a prospective, open-label, assessor-blind, randomised parallel group study the efficacy and safety of Hemabate (Pharmacia-Upjohn Pharmaceuticals, Milton Keynes, Buckinghamshire) an analogue of 15-methyl-prostaglandin (PGF2alpha) analogue was compared with Syntometrine (Alliance Pharmaceuticals, Chippenham, Wilts) the standard combination of ergometrine and syntocinon used for the active management of the third stage of labour and the prevention of primary postpartum haemorrhage (PPH). The study was set in a district general hospital with approximately 4,000 deliveries annually. The study was discontinued at the time of the interim analysis because of unacceptable gastrointestinal side effects. At the time of the interim analysis, a total of 529 women had completed the study with 263 randomised to receive PGF2alpha and 266 to receive ergometrine and syntocinon. In a pre-specified subgroup analysis, women delivered vaginally were further subdivided into those considered to be at high or low risk of primary PPH. The measured blood loss and incidence of PPH was similar in both treatment groups whether delivered by caesarean section or vaginally independent of whether women were considered to be at high or low risk. Adverse gastrointestinal events were recorded more often in the Hemabate group. The most common symptom was diarrhoea which occurred in 21% of women who received Hemabate compared to only 0.8% of Syntometrine users. PGF2alpha is as effective as Syntometrine in the prophylaxis of primary PPH in all groups studied but there was a statistically significantly increased risk of diarrhoea among users of PGF2alpha.

Topics: Adult; Blood Pressure; Body Height; Body Weight; Carboprost; Cesarean Section; Dinoprost; Disease Susceptibility; Drug Combinations; Ergonovine; Female; Gastrointestinal Diseases; Humans; Nausea; Oxytocin; Parity; Postpartum Hemorrhage; Pregnancy; Random Allocation; Single-Blind Method; Tromethamine

The effects on estrus and fertility of 3 estrus synchronization protocols were studied in Brahman beef heifers. In Treatment 1 (PGF protocol; n=234), heifers received 7.5 mg, i.m. prostianol on Day 0 and were inseminated after observed estrus until Day 5. Treatment 2 (10-d NOR protocol; n = 220) consisted of norgestomet (NOR; 3 mg, s.c. implant and 3 mg, i.m.) and estradiol valerate (5 mg, i.m.) treatment on Day -10, NOR implant removal and 400 IU, i.m. PMSG on Day 0, and AI after observed estrus through to Day 5. Treatment 3 (14-d NOR+PGF protocol; n = 168) constituted a NOR implant (3 mg, sc) on Day -14, NOR implant removal on Day 0, PGF on Day 16, and AI after observed estrus through to Day 21. All heifers were examined for return to estrus at the next cycle and inseminated after observed estrus. The heifers were then exposed to bulls for at least 21 d. During the period of estrus observation (5 d) after treatment, those heifers treated with the PGF protocol had a lower (P<0.01) rate of estrual response (58%) than heifers treated with the 10-d NOR (87%) or 14-d NOR+PGF (88%) protocol. Heifers treated with the 10-d NOR protocol displayed estrus earlier and had a closer synchrony of estrus than heifers treated with either the PGF or the 14-d NOR+PGF protocol. Heifers treated with the 14-d NOR+PGF protocol had higher (P<0.05) conception and calving rates (51 and 46%) to AI at the induced estrus than heifers treated with the PGF (45 and 27%) or the 10-d NOR (38 and 33%) protocol. Calving rate to 2 rounds of AI was greater (P<0.05) for heifers treated with the 14-d NOR-PGF (50%) protocol than heifers treated with the 10-d NOR (38%) but not the PGF (43%) protocol. Breeding season calving rates were similar among the 3 protocols. The results show that the 14-d NOR+PGF estrus synchronization protocol induced a high incidence of estrus with comparatively high fertility in Brahman heifers.

Topics: Animal Husbandry; Animals; Body Weight; Cattle; Dinoprost; Drug Interactions; Estrus Synchronization; Female; Fertility; Male; Ovary; Pregnenediones; Progesterone Congeners; Seasons; Ultrasonography

The effect of an intraumbilical prostaglandin (PG) F2 alpha injection on the third stage of normal labor was studied in 54 normal, laboring women at term. Either 1 mg of PGF2 alpha diluted to 20 mL in normal saline (27 women) or 20 mL of normal saline alone (27 women) was injected into the umbilical vein immediately after delivery using a randomized, double-blind protocol. The mean (+/- SD) duration of the third stage was 7.31 +/- 6.37 minutes in the PGF2 alpha patients and 8.94 +/- 7.10 in the normal saline patients. Intraumbilical PGF2 alpha did not influence the third stage of normal labor.

Topics: Adult; Birth Weight; Body Height; Body Weight; Dinoprost; Double-Blind Method; Female; Humans; Injections, Intravenous; Labor Stage, Third; Mothers; Parity; Pregnancy; Sex Ratio; Time Factors; Umbilical Veins

This 2-yr study evaluated the growth and puberty attainment of Bos indicus-influenced beef heifers offered 2 different postweaning concentrate supplementation amounts and delivery frequencies. On day 0 of each year, 64 Brangus crossbred heifers were stratified by initial body weight (BW) and age (mean = 244 ± 22 kg; 314 ± 17 d) and assigned into 1 of 16 bahiagrass pastures (4 heifers/pasture/yr). Treatments were randomly assigned to pastures in a 2 × 2 factorial design (4 pastures/treatment/yr) and consisted of concentrate dry matter (DM) supplementation at 1.25% or 1.75% of BW which were offered either daily (7×) or 3 times weekly (3×) for 168 d. On day 56 of each year, heifers were assigned to an estrus synchronization protocol consisting of intravaginal controlled internal drug release (CIDR) insertion on day 56, CIDR removal on day 70, i.m. injection of 25 mg of prostaglandin F2α (PGF2α) on day 86, and i.m. injection of 100 µg of gonadotropin-releasing hormone and timed-AI at 66 h after PGF2α injection (day 89). Heifers were exposed to Angus bulls from day 89 to 168 (1 bull/pasture). Pregnancy diagnosis was assessed on day 213 of each year. Supplementation amount × frequency effects were not detected (P ≥ 0.12) for any variable, except for plasma concentrations of glucose (P = 0.10) and urea nitrogen (PUN; P = 0.01). Herbage mass, herbage allowance, and nutritive value did not differ (P ≥ 0.12) among treatments. Increasing supplementation DM amount from 1.25% to 1.75% of BW increased (P ≤ 0.05) plasma concentrations of insulin-like growth factor 1 (IGF-1), overall average daily gain (ADG), final BW, percentage of pubertal heifers on day 89, pregnancy and calving percentages, and percentage of heifers calving within the first 21 d of the calving season. However, reducing the supplementation frequency from daily to 3× weekly, regardless of supplementation amount, did not impact overall pregnancy and calving percentages (P ≥ 0.42), but caused (P ≤ 0.05) fluctuations in plasma concentrations of insulin and IGF-1 and decreased (P ≤ 0.03) overall ADG, final BW, puberty attainment on days 56, 89, and 168, and percentage of heifers calving during the first 21 d of the calving season. Hence, increasing the supplement DM amount did not prevent the negative effects of reducing the frequency of supplementation (3× vs. 7× weekly) on growth and reproduction of replacement Bos indicus-influenced beef heifers.

Topics: Animals; Body Weight; Cattle; Dietary Supplements; Dinoprost; Eating; Estrus Synchronization; Female; Gonadotropin-Releasing Hormone; Insulin-Like Growth Factor I; Male; Nutritive Value; Paspalum; Pregnancy; Reproduction; Seasons; Sexual Maturation

The objective of the present study was to determine the influence of dietary supplementation with pomegranate seed oil (PSO) and/or an aqueous extract of dried bitter melon fruits (BME) on breast cancer risk and fatty acid profile in serum of female rats with chemical carcinogen-inflicted mammary tumours. Sprague-Dawley rats (n = 96) were fed control diet or experimental diets supplemented with 0.15 ml PSO/day, BME or jointly PSO and BME. After 21 weeks mammary tumours were subjected to histopathological examination and in serum fatty acids, 8-isoprostaglandin F

Topics: Animals; Body Weight; Carcinogenesis; Dietary Supplements; Dinoprost; Dose-Response Relationship, Drug; Fatty Acids; Female; Mammary Neoplasms, Experimental; Momordica charantia; Organ Size; Plant Oils; Pomegranate; Rats; Rats, Sprague-Dawley; Risk; Seeds

Active glucocorticoid levels are elevated in the adipose tissue of obesity due to the enzyme 11 beta-hydroxysteroid dehydrogenase type 1. Glucocorticoids can bind and activate both glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), and pharmacological blockades of MR prevent high-fat diet-induced obesity and glucose intolerance. To determine the significance of MR in adipocytes, we generated adipocyte-specific MR-knockout mice (AdipoMR-KO) and fed them high-fat/high-sucrose diet. We found that adipocyte-specific deletion of MR did not affect the body weight, fat weight, glucose tolerance or insulin sensitivity. While liver weight was slightly reduced in AdipoMR-KO, there were no significant differences in the mRNA expression levels of genes associated with lipogenesis, lipolysis, adipocytokines and oxidative stress in adipose tissues between the control and AdipoMR-KO mice. The results indicated that MR in mature adipocytes plays a minor role in the regulation of insulin resistance and inflammation in high-fat/high-sucrose diet-induced obese mice.

Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Body Weight; Diet, High-Fat; Dinoprost; Lipid Metabolism; Liver; Male; Metabolic Syndrome; Mice, Knockout; Obesity; Primary Cell Culture; Receptors, Mineralocorticoid; RNA, Messenger; Sucrose; Triglycerides

The objective of this study was to evaluate if short-term dietary concentrate supplementation increased IGF-I serum concentration and resulted in a reproductive response during estrus synchronization treatment in non-lactating beef cows. Thirty non-lactating beef cows (Bos indicus × Bos taurus) were allocated to the same pastureland and fed native tropical grasses as a basal diet. Cows were synchronized using a 7-day CO-Synch plus controlled internal drug release (CIDR) protocol and received fixed time artificial insemination (FTAI). Cows were divided into two groups; the control group (n = 16) received 0.5 kg of concentrate/cow/day, whereas the supplemented group (n = 14) received 4.0 kg of concentrate/cow/day. The period of supplementation was 10 days from the day of CIDR insert to FTAI. The concentration of IGF-I increased (P < 0.05) in the supplemented group, while no significant changes were observed in the control group. Moreover, at the time of insemination, IGF-I serum concentrations were higher in supplemented cows compared with control cows (P < 0.05). Notably, metabolite and insulin concentrations did not differ (P > 0.05) between treatment groups or sampling day. The response to estrus induction, measured as estrus presentation, ovulation rate, and pregnancy rate, was similar between experimental groups (P > 0.05). In conclusion, our results indicated that supplementation with dietary concentrate for 10 days in non-lactating beef cows changed the endocrine milieu, specifically increasing IGF-I serum concentration. However, these endocrine changes did not affect response to estrous induction treatment.

Topics: Animal Husbandry; Animals; Behavior, Animal; Body Composition; Body Weight; Cattle; Delayed-Action Preparations; Dietary Supplements; Dinoprost; Estrus; Estrus Synchronization; Female; Gonadotropin-Releasing Hormone; Insemination, Artificial; Insulin-Like Growth Factor I; Ovarian Follicle; Ovulation; Pregnancy; Pregnancy Rate; Progesterone; Red Meat; Time Factors

Caffeine or ketorolac decrease the risk of retinopathy of prematurity and may act synergistically to improve beneficial effect. Combination of caffeine (Caff) and ketorolac (Keto) to prevent oxygen-induced retinopathy was studied.. Newborn rats exposed to room air (RA) or intermittent hypoxia (IH) consisting of 12% O2 during hyperoxia (50% O2) from birth (P0) had single daily IP injections of Caff from P0-P13 or saline; and/or ocular Keto (Acuvail, 0.45% ophthalmic solution) administered subcutaneously over the eyes from P5-P7. Pups were studied at P14 or placed in RA for recovery from IH (IHR) until P21. Eyes were examined for neovascularization, histopathology, growth factors, and VEGF-signaling genes.. Severe retinal damage noted during IHR in the untreated groups evidenced by hemorrhage, neovascularization, and oxygen-induced retinopathy (OIR) pathologies were prevented with Keto/Caff treatment. Keto and/or Caff treatment in IH also promoted retinal neural development evidenced by eye opening (92%, P < 0.001 vs. 31% in the placebo-treated IH group). No corneal pathologies were noted with Keto.. Caff or Keto given individually reduced retinal neovascularization, but the two drugs given together prevented severe OIR.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Apyrase; Arteries; Body Weight; Caffeine; Central Nervous System Stimulants; Choroid; Citrates; Dinoprost; Drug Synergism; Female; Hemorrhage; Hypoxia-Inducible Factor 1, alpha Subunit; Insulin-Like Growth Factor I; Intercellular Signaling Peptides and Proteins; Ketorolac; Neovascularization, Pathologic; Oxygen; Rats; Rats, Sprague-Dawley; Retina; Retinopathy of Prematurity; Signal Transduction; Time Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1

The concentration of adenosine in the normal kidney increases markedly during renal hypoxia, ischemia, and inflammation. A recent study reported that an A3 adenosine receptor (A3AR) antagonist attenuated the progression of renal fibrosis. The adriamycin (ADX)-induced nephropathy model induces podocyte injury, which results in severe proteinuria and progressive glomerulosclerosis. In this study, we investigated the preventive effect of a highly selective A3AR antagonist (LJ1888) in ADX-induced nephropathy. Three groups of six-week-old Balb/c mice were treated with ADX (11 mg/kg) for four weeks and LJ1888 (10 mg/kg) for two weeks as following: 1) control; 2) ADX; and 3) ADX + LJ1888. ADX treatment decreased body weight without a change in water and food intake, but this was ameliorated by LJ1888 treatment. Interestingly, LJ1888 lowered plasma creatinine level, proteinuria, and albuminuria, which had increased during ADX treatment. Furthermore, LJ1888 inhibited urinary nephrin excretion as a podocyte injury marker, and urine 8-isoprostane and kidney lipid peroxide concentration, which are markers of oxidative stress, increased after injection of ADX. ADX also induced the activation of proinflammatory and profibrotic molecules such as TGF-β1, MCP-1, PAI-1, type IV collagen, NF-κB, NOX4, TLR4, TNFα, IL-1β, and IFN-γ, but they were remarkably suppressed after LJ1888 treatment. In conclusion, our results suggest that LJ1888 has a renoprotective effect in ADX-induced nephropathy, which might be associated with podocyte injury through oxidative stress. Therefore, LJ1888, a selective A3AR antagonist, could be considered as a potential therapeutic agent in renal glomerular diseases which include podocyte injury and proteinuria.

Topics: Actins; Adenosine; Adenosine A3 Receptor Antagonists; Albuminuria; Animals; Body Weight; Creatinine; Dinoprost; Disease Models, Animal; Doxorubicin; Immunohistochemistry; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Membrane Proteins; Mice; Mice, Inbred BALB C; NF-kappa B; Oxidative Stress; Plasminogen Activator Inhibitor 1; Proteinuria; Transforming Growth Factor beta1

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Dinoprost; Dinoprostone; Disease Models, Animal; Female; Glutathione; Liver; Placenta; Pregnancy; Pregnancy in Diabetics; Pregnancy, Animal; Prostaglandin-Endoperoxide Synthases; Rats; Thioctic Acid

Preeclampsia is responsible for more than one-third of all maternal deaths in Brazil. The objectives of the present study were to evaluate magnesium status and its association with oxidative stress and inflammation in preeclamptic women, and to identify the predictor variables of the disorder.. The study population consisted of 36 women divided into preeclamptic (n = 18) and control groups (n = 18). The preeclamptic group included women (≥20 weeks of pregnancy) with arterial pressure ≥ 140/90 mmHg and proteinuria >0.3 g/24 h, while the control group comprised pregnant women with no clinical/obstetric complications. Magnesium intake was assessed via a food frequency questionnaire validated for pregnant women in Brazil. Plasma, erythrocyte and urinary magnesium levels were determined by flame atomic absorption spectroscopy, while oxidative stress and inflammatory markers were assessed using standard protocols. Logistic regression analysis was used to identify the predictors of preeclampsia.. Preeclamptic and control groups were similar with respect to magnesium intake and urinary excretion, while plasma and erythrocyte magnesium concentrations were higher in the former group. Plasma magnesium was positively correlated with catalase and glutathione peroxidase activities and with concentrations of interleukin-6 and tumor necrosis factor alpha. Regression analysis showed that plasma magnesium and urinary 8-isoprostane were associated with preeclampsia.. Magnesium status appears to result from homeostatic imbalance and physiological alterations typical of preeclampsia. Increased plasma magnesium and decreased urinary 8-isoprostane were considered predictors of preeclampsia.

Topics: Adolescent; Adult; Biomarkers; Body Mass Index; Body Weight; Brazil; Case-Control Studies; Catalase; Dinoprost; Female; Glutathione Peroxidase; Humans; Inflammation; Interleukin-6; Logistic Models; Magnesium; Oxidative Stress; Pre-Eclampsia; Pregnancy; Tumor Necrosis Factor-alpha; Young Adult

Oxidative stress has been implicated in the pathogenesis of many conditions, including insulin resistance and obesity. However, in vivo data concerning these relationships are scarce and conflicting. Therefore, the aim of this study was to investigate the association of oxidative stress with abdominal adiposity and insulin resistance in individuals at high cardiometabolic risk.. A total of 116 overweight/obese individuals participating in the HealthGrain and Etherpaths European Projects, having waist circumference (WC) and any other component of the metabolic syndrome, were included in this cross-sectional evaluation. 8-Isoprostane concentrations in 24-hr urine were measured as marker of oxidative stress in vivo. Baseline anthropometric and metabolic parameters were analyzed according to quartiles of 8-isoprostanes. Linear regression (LR) analysis was used to assess clinical correlates of oxidative stress.. Urinary 8-isoprostane levels were 52% higher in men than in women (P<0.001). Across the isoprostanes quartiles, there was a significant increase in WC and body weight [P for trend<0.001; analysis of variance (ANOVA) P<0.001] and fasting triglycerides (P for trend<0.05; ANOVA P<0.05), and a significant decrease in high-density lipoprotein cholesterol (P for trend<0.001; ANOVA P=0.001). No significant association between urinary isoprostane concentrations and insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] was found. WC circumference and body weight remained significant after adjustment for age and gender (P=0.023 and P=0.014, respectively) and independently associated with isoprostanes at LR (P<0.005 for both).. Central obesity was independently associated with oxidative stress even in a population homogeneous for adiposity and cardiometabolic risk, whereas no relationship was observed between oxidative stress and insulin resistance.

Topics: Abdominal Fat; Adiposity; Adult; Age Factors; Aged; Body Weight; Cholesterol, HDL; Cross-Sectional Studies; Dinoprost; Female; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Oxidative Stress; Risk Assessment; Sex Characteristics; Triglycerides; Waist Circumference

Lifetime productivity and longevity are greater in beef cows that give birth early in their first calving season. The ability of heifers to conceive early in the breeding season is traditionally thought to be a function of pubertal status; however, recent evidence suggests that antral follicle count is positively associated with calving day in pubertal beef heifers. Additionally, there is evidence to suggest that the total number of ovarian follicles may alter response to hormonal synchronization protocols. The objectives of this study were to confirm the beneficial influence of antral follicle count on calving day in beef heifers and to determine whether response to PGF2α is associated with differences in antral follicle counts. A 2 × 2 factorial experiment was designed to investigate the interaction between calving period (early vs. late) and PGF2α (control vs. PGF) on calving day and antral follicle count in yearling beef heifers (n = 95). As intended, calving day was less in the early calving period compared to the late calving period (P < 0.01). There were no differences in calving day in response to treatment with PGF2α (P > 0.05). There was a significant interaction between calving period and PGF2α on age at first calving (P < 0.01), such that heifers treated with PGF2α that gave birth early were younger than heifers treated with saline that gave birth early. Calf weaning weights were greater in the early calving group than in the late calving group (P < 0.01). Heifers that gave birth in the early calving group possessed more antral follicles at prebreeding ultrasonographic examination than heifers that gave birth in the late calving group (P = 0.05). These findings confirm that antral follicle counts are associated with calving day in pubertal beef heifers. The use of antral follicle counts as a prebreeding phenotype provides additional utility to reproductive tract scoring for commercial production because of its association with calving day. As a prebreeding ovarian phenotype, antral follicle counts may hold additional applicability for organic beef producers looking to reduce the length of their calving season without increasing the total number of replacement heifers retained.

Topics: Animals; Birth Weight; Body Weight; Breeding; Cattle; Dinoprost; Female; Male; Ovarian Follicle; Parturition; Pregnancy; Sexual Maturation; Ultrasonography; Weaning

To investigate the relationship between oxidative stress and biochemical parameters and the expression of TXNIP, IL-6, IL-1β and TNF-α in peripheral mononuclear cells (PMCs) from type-2 diabetic patients.. We studied 60 males: 20 normal-weight type- 2 diabetic patients (NW), 20 obese diabetic patients (OB) and 20 controls (C). Biochemical and oxidative stress parameters were evaluated. PMCs were isolated and total RNA was extracted in order to determine the expression of TXNIP, IL-6, IL-1β and TNF-α by qRT-PCR.. OB had higher weight, BMI and abdominal circumference (One way ANOVA, p<0.0001). NW had higher fasting glycemia (One way ANOVA, p=0.0034) however OB had higher HbA1c (One way ANOVA, p<0.0001). OB also had higher hsCRP (One way ANOVA, p=0.0158). TBARS and AGES were elevated in both NW and OB (One way ANOVA, p<0.0001 and p=0.0008, respectively). Compared to OB and C participants, the expression of TXNIP was significantly higher in NW (Kruskal Wallis, p=0.0074); IL-1β, IL-6 and TNF-α transcripts were higher in NW and OB (Kruskal Wallis, p<0.0001, for all). In NW patients, the expression of TXNIP was positively correlated with fasting glycemia and AGES and negatively correlated with HOMA-β (r=0.72; r=0.59; r=-0.44, respectively, for all p<0.05), in OB there was correlation only with 8-Isoprostanes (r=0.42, p=0.046).. Our results suggest that fasting glycemic control, independent of adiposity and nutritional status, represents a risk factor for β-cell dysfunction, increases oxidative stress markers and it is related with an elevation of TXNIP expression.. Objetivo: Investigar la relación existente entre parámetros bioquímicos y de estrés oxidativo y la expresión de TXNIP, IL-6, IL-1y TNF-en células mononucleares periféricas (CMPs) de sujetos diabéticos. Material y métodos: Se estudió 60 sujetos hombres: 20 con peso normal y diabetes tipo 2 (NW), 20 sujetos obesos con diabetes (OB) y 20 sujetos controles (C). Se evaluaron parámetros bioquímicos y de estrés oxidativo. Además se aislaron CMPs para la extracción de RNA total y se determinó la expresión de los genes TXNIP, IL-6, IL- 1y TNF-mediante PCR de tiempo real cuantitativo. Resultados: Los OB presentaron mayor IMC y circunferencia abdominal que los NW y los C (ANOVA de una vía, p.

Topics: Adult; Anthropometry; Blood Glucose; Body Mass Index; Body Weight; Carrier Proteins; Diabetes Mellitus, Type 2; Dinoprost; Female; Glycated Hemoglobin; Glycation End Products, Advanced; Humans; Hypoglycemic Agents; Inflammation; Insulin; Interleukin-1beta; Interleukin-6; Lipids; Male; Middle Aged; Overweight; Oxidative Stress; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha

Increasing levels of obesity within women of reproductive age is a major concern in the UK. Approximately, 13% of women aged <30 and 22% of 31- to 40-year-old women are obese. Obesity increases complications during pregnancy and the risk of caesarean section due to prolonged labour and poor uterine activity. The aim was to investigate whether a high-fat, high-cholesterol (HFHC) diet decreases markers of uterine contractility during parturition in the rat. Female Wistar rats were fed control (CON, n=10) or HFHC (n=10) diets for 6 weeks. Animals were mated and, once pregnant, maintained on their diet throughout gestation. On gestational day 19, rats were monitored continuously and killed at the onset of parturition. Body and fat depot weights were recorded. Myometrial tissue was analysed for cholesterol (CHOL), triglycerides (TAG), and expression of the contractile associated proteins gap junction protein alpha 1 (GJA1; also known as connexin-43, CX-43), prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclo-oxygenase-2, COX-2) and caveolin-1 (CAV1) and maternal plasma for prostaglandin F(2)(α) (PGF(2)(α)) and progesterone. HFHC fed rats gained greater weight than CON (P<0.003) with significant increases in peri-renal fat (P<0.01). The HFHC diet increased plasma CHOL, TAG and progesterone, but decreased PGF(2)(α) versus CON (P<0.01, P<0.01, P=0.05 and P<0.02 respectively). Total CHOL and TAG levels of uterine tissue were similar. However, HFHC fed rats showed significant increases in PTGS2 (P<0.037), but decreases in GJA1 and CAV1 (P=0.059). In conclusion, a HFHC diet significantly increases body weight and alters lipid profiles that correlate with decreases in key markers of uterine contractility. Further work is required to ascertain whether these changes have adverse effects on uterine activity.

Topics: Animals; Blotting, Western; Body Weight; Caveolin 1; Cholesterol; Connexin 43; Cyclooxygenase 2; Dietary Fats; Dinoprost; Female; Parturition; Pregnancy; Progesterone; Radioimmunoassay; Rats; Rats, Wistar; Triglycerides; Uterine Contraction

Salt-induced hypertension in the Dahl rat is associated with increases in angiotensin II, aldosterone, free radical generation and endothelial dysfunction. However, little is known about the specific mechanism(s) associated with the end-organ damage effects of aldosterone. We hypothesised that eplerenone reduces kidney damage by blocking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.. Dahl salt-sensitive rats fed either a low-salt (LS) or high-salt (HS) diet were treated with aldosterone in the presence of eplerenone or apocynin. Indirect blood pressure was measured prior to start of diet and weekly thereafter. Levels of plasma nitric oxide (NO) and urinary 8-isoprostane were measured following treatment. Protein levels of selected subunits of NADPH were assessed by western blot.. Eplerenone and apocynin inhibited the rise in blood pressure induced by HS and/or aldosterone. This observation was accompanied with a parallel change in kidney protein levels of NADPH oxidase 4 (NOX-4) and p22phox. Aldosterone and high salt were associated with lower NO levels and greater renal oxidative stress.. NADPH oxidase is associated with the vascular and renal remodelling observed in high dietary salt intake. Aldosterone-induced expression of NOX-4 plays a pivotal role in the end-organ damage effect of aldosterone, as eplerenone tended to reduce kidney damage and inhibit NOX expression.

Topics: Acetophenones; Aldosterone; Animals; Blood Pressure; Blotting, Western; Body Weight; Dinoprost; Eplerenone; Male; NADPH Oxidase 4; NADPH Oxidases; Nitric Oxide; Protein Subunits; Proteinuria; Rats; Rats, Inbred Dahl; Sodium; Sodium Chloride, Dietary; Spironolactone; Systole; Urinalysis

The key roles that obesity, hyperglycemia, hyperlipidemia, inflammation, and oxidative stress play in the progression of diabetes vascular complications are well recognized; however, the relative contribution and importance of these individual factors remain uncertain. At 6, 10, or 14 weeks old, blood samples and thoracic aortae were collected from db/db mice and their non-diabetic controls. Plasma samples were analyzed for glucose, 8-isoprostane, CRP, triglycerides, LDL, and HDL as markers of glycemic status, oxidative stress, inflammation, and dyslipidemia, respectively. The responses of the aortic rings to high KCl, phenylephrine (PE), acetylcholine (ACh), and sodium nitroprusside were examined. Statistical methods were used to estimate the strength of the association between plasma variables and vascular functions. Systemic inflammation occurred in db/db mice at an earlier age than did hyperglycemia or oxidative stress. Aortae of db/db showed augmented contractions to PE which were positively correlated with weight, plasma glucose, 8-isoprostane, and CRP. Also, db/db mice showed impaired endothelium-dependent ACh vasorelaxation which was negatively correlated with weight, plasma glucose, and 8-isoprostane. Multivariate analysis and stepwise modeling show that CRP is the major determinant of the contractile responses, while weight and HDL are the major determinants of ACh-induced relaxation. Among the traditional risk factors of obesity, hyperglycemia, oxidative stress, inflammation, and dyslipidemia, our study reveals that weight and inflammation are the major determinants of vascular dysfunction in the aortae of db/db mice. Our findings partially resolve the complexity of diabetes vasculopathies and suggest targeting weight loss and inflammation for effective therapeutic approaches.

Topics: Animals; Aorta; Biomarkers; Blood Glucose; Body Weight; C-Reactive Protein; Diabetes Mellitus, Experimental; Dinoprost; Dyslipidemias; Inflammation; Lipids; Male; Mice; Mice, Inbred Strains; Multivariate Analysis; Oxidative Stress; Vasodilation

The foal requires an active hypothalamo-pituitary-adrenal (HPA) axis for organ maturation and post natal survival. Prenatal administration of synthetic glucocorticoids may provide an effective method for inducing fetal maturation safely in the mare.. To determine whether dexamethasone administered to late pregnant mares: 1) will induce fetal maturation and precocious delivery; 2) is safe to use and 3) to identify endocrine responses in the mare and foal.. Pregnant Thoroughbred mares received either 100 mg dexamethasone i.m. (treated n = 5) or 50 ml saline i.m. (control n = 5) at 315, 316 and 317 days of gestation. Plasma progestagens, cortisol and prostaglandin F(2α) metabolite (PGFM) concentrations were measured before and after treatment. The foals were weighed, the crown-rump length (CRL) measured and an adrenal stimulation test performed on Day 1.. Dexamethasone significantly (P<0.01) reduced gestation length in treated mares without apparent adverse effects. Plasma progestagens increased (P<0.05), and cortisol and PGFM (P<0.05) decreased, following dexamethasone treatment compared with control mares. Foals were clinically mature but those from dexamethasone treated mares had reduced (P<0.05) CRL, but not bodyweights, compared with controls. Their cortisol concentrations increased following exogenous adrenocorticotrophic hormone stimulation but 2 foals from dexamethasone treated mares showed evidence of adrenal suppression.. Dexamethasone stimulates precocious fetal maturation and delivery in healthy late pregnant mares. However, fetal HPA activity may be suppressed.. Dexamethasone treatment could be used to improve foal viability in mares at risk of preterm delivery. The endocrine effects of such a therapy must be evaluated before clinical intervention with glucocorticoids can be recommended.

Topics: Animals; Animals, Newborn; Body Weight; Crown-Rump Length; Dexamethasone; Dinoprost; Female; Glucocorticoids; Horses; Hydrocortisone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Pregnancy; Progestins

This study investigated the cardioprotective effect of N-acetylcysteine (NAC) on isoproterenol (ISO)-induced cardiotoxicity in rats. Male Sprague-Dawley rats were divided into control, NAC alone (100 mg/kg BW orally for 14 days), ISO-control (85 mg/kg BW), and ISO with NAC (for 14 days). Serum creatine kinase-MB and Lactate dehydrogenase were measured. From the heart homogenate lipid hydroperoxides (LPO), superoxide dismutase (SOD), total glutathione (GSH), and 8-isoprostane (IP) were measured. Histopathological examination of the heart was also carried out. There was a significant increase (P < 0.05) in LPO and IP levels in ISO-control group and NAC treatment reduced these changes. Antioxidant enzyme, SOD and GSH, level decreased significantly (P < 0.05) in ISO-control group, and treatment with NAC was able to reverse these changes significantly (P < 0.05). Histopathologically, ISO-control group showed morphological changes suggestive of cardiotoxicity with large areas of coagulative necrosis, with diffused interstitial edema. NAC treatment successfully reduced these histopathological changes. In conclusion, the study proves that NAC has a strong cardioprotective effect against isoproterenol-induced cardiac changes. NAC decreases isoproterenol-induced LPO and IP levels in the heart tissue and prevented free radicals-induced damage to the myocardium.

Topics: Acetylcysteine; Animals; Body Weight; Cardiotonic Agents; Creatine Kinase, MB Form; Dinoprost; Drug Therapy, Combination; Edema; Free Radical Scavengers; Glutathione; Heart; Isoproterenol; L-Lactate Dehydrogenase; Lipid Peroxidation; Male; Myocardium; Necrosis; Organ Size; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

The aim of the present study was to look into the possible protective effects of glycyrrhizic acid (GA) against isoproterenol-induced acute myocardial infarction in Sprague-Dawley rats. The effect of three doses of glycyrrhizic acid in response to isoproterenol (ISO)-induced changes in 8-isoprostane, lipid hydroperoxides, super oxide dismutase and total glutathione were evaluated. Male Sprague-Dawley rats were divided into control, ISO-control, glycyrrhizic acid alone (in three doses-5, 10 and 20 mg/kg BW) and ISO with glycyrrhizic acid (in three doses) groups. ISO was administered at 85 mg/kg BW at two consecutive days and glycyrrhizic acid was administered intraperitoneally for 14 days. There was a significant increase in 8-isoprostane (IP) and lipid hydroperoxide (LPO) level in ISO-control group. A significant decrease in total superoxide dismutase (SOD) and total glutathione (GSH) was seen with ISO-induced acute myocardial infarction. Treatment with GA significantly increased SOD and GSH levels and decreased myocardial LPO and IP levels. Histopathologically, severe myocardial necrosis and nuclear pyknosis and hypertrophy were seen in ISO-control group, which was significantly reduced with GA treatment. Gycyrrhizic acid treatment proved to be effective against isoproterenol-induced acute myocardial infarction in rats and GA acts as a powerful antioxidant and reduces the myocardial lipid hydroperoxide and 8-isoprostane level.

Topics: Animals; Body Weight; Cardiotonic Agents; Dinoprost; Glutathione; Glycyrrhizic Acid; Isoproterenol; Lipid Peroxidation; Male; Myocardial Ischemia; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

Certain polymorphisms reduce serotonin (5-HT) reuptake transporter (5-HTT) function and increase susceptibility to psychiatric disorders. Heterozygous (5-HTT(+/-))-deficient mice, models for humans with these polymorphisms, have elevated brain 5-HT concentrations and behavioral abnormalities. As postsynaptic 5-HT(2A/2C) receptors are coupled to cytosolic phospholipase A(2) (cPLA(2)), which releases arachidonic acid (AA) from membrane phospholipid, 5-HTT-deficient mice may have altered brain AA signaling and metabolism. To test this hypothesis, signaling was imaged as an AA incorporation coefficient k(*) in unanesthetized homozygous knockout (5-HTT(-/-)), 5-HTT(+/-) and wild-type (5-HTT(+/+)), mice following saline (baseline) or 1.5 mg/kg s.c. DOI, a partial 5-HT(2A/2C) receptor agonist. Enzyme activities, metabolite concentrations, and head-twitch responses to DOI were also measured. Baseline k(*) was widely elevated by 20-70% in brains of 5-HTT(+/-) and 5-HTT(-/-) compared to 5-HTT(+/+) mice. DOI increased k(*) in 5-HTT(+/+) mice, but decreased k(*) in 5-HTT-deficient mice. Brain cPLA(2) activity was elevated in 5-HTT-deficient mice; cyclooxygenase activity and prostaglandin E(2) and F(2alpha) and thromboxane B(2) concentrations were reduced. Head-twitch responses to DOI, although robust in 5-HTT(+/+) and 5-HTT(+/-) mice, were markedly fewer in 5-HTT(-/-) mice. Pretreatment with para-chlorophenylalanine, a 5-HT synthesis inhibitor, restored head twitches in 5-HTT(-/-) mice to levels in 5-HTT(+/+) mice. We propose that increased baseline values of k(*) in 5-HTT-deficient mice reflect tonic cPLA(2) stimulation through 5-HT(2A/2C) receptors occupied by excess 5-HT, and that reduced k(*) and head-twitch responses to DOI reflected displacement of receptor-bound 5-HT by DOI with a lower affinity. Increased baseline AA signaling in humans having polymorphisms with reduced 5-HTT function might be identified using positron emission tomography.

Topics: Amphetamines; Analysis of Variance; Animals; Arachidonic Acid; Autoradiography; Body Weight; Brain; Brain Mapping; Carbon Isotopes; Chromatography, Gas; Dinoprost; Dinoprostone; Fatty Acids; Fenclonine; Head Movements; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Phospholipases A2, Cytosolic; Prostaglandin-Endoperoxide Synthases; Serotonin Antagonists; Serotonin Plasma Membrane Transport Proteins; Serotonin Receptor Agonists; Signal Transduction; Thromboxane B2; Wakefulness

The aim was to examine the role of cyclooxygenase (COX)-2-mediated inflammation in the development of obese linked insulin resistance and fatty liver. The rats were fed separately regular diet (CONT), high-fat diet (HFD) ad libitum, or energy restrictedly for 12 weeks. Rats fed HFD ad libitum were further divided into three subgroups co-treated with vehicle (HFa), or a selective COX-2 inhibitor celecoxib (HFa-Cel) or mesulid (HFa-Mes). Euglycemic hyperinsulinemic clamp (EHC) experiment was performed at the end of study. Another set of rats with similar grouping was further divided into those with a 4, 8, or 12-week intervention period for hepatic sampling. Body weight was increased significantly and similarly in HFa, HFa-Cel, and HFa-Mes. Time-dependent increases in plasma insulin, glucose, 8-isoprostanes, leptin levels, homeostasis model assessment of insulin resistance (HOMA-IR) and hepatic triglyceride contents shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. During EHC period, the reduction in stimulation of whole body glucose uptake, suppression of hepatic glucose production and metabolic clearance rate of insulin shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. The enhanced COX-2 and tumor necrosis factor-alpha (TNF-alpha) but attenuated PPAR-gamma and C/EBP-alpha mRNA expressions in epididymal fat shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. The increases in average cell size of adipocytes and CD68 positive cells shown in HFa were also significantly reversed in HFa-Cel and HFa-Mes. Our findings suggest that COX-2 activation in fat inflammation is important in the development of insulin resistance and fatty liver in high fat induced obese rats.

Topics: Adipocytes; Adipogenesis; Adipose Tissue; Animals; Blood Glucose; Body Weight; Celecoxib; Cell Size; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprost; Disease Models, Animal; Fatty Liver; Insulin; Insulin Resistance; Leptin; Liver; Macrophages; Male; Membrane Proteins; Obesity; Panniculitis; Pyrazoles; Rats; Rats, Sprague-Dawley; Sulfonamides; Time Factors; Triglycerides; Tumor Necrosis Factor-alpha

In Exp. 1, we evaluated the effects of 2 lengths of progesterone exposure [CIDR (controlled intravaginal drug release); 7 vs. 14 d] before a modified CO-Synch protocol [50.0-microg injection of GnRH 6.5 d before a 25.0-mg injection of PGF(2alpha) followed by another injection of GnRH and fixed-time AI (TAI) 2 d after PGF(2alpha)], with or without temporary weaning (TW) before GnRH treatments, on fertility of suckled multiparous Bos indicus cows (n = 283) and on calf performance. Timed AI pregnancy rates for cows receiving 7 d CIDR + TW, 7 d CIDR, 14 d CIDR + TW, and 14 d CIDR were 53, 47, 46, and 41%, respectively (P > 0.10). Calves submitted to two 48-h TW 6 d apart had decreased mean BW at 240 d (187.9 +/- 2.7 vs. 195.5 +/- 2.7 kg; P < 0.05), but BW at 420 d was not affected by TW (240.1 +/- 5.1 kg). In Exp. 2, we evaluated the effect of no treatment and treatment with or without a CIDR insert between GnRH and PGF(2alpha) treatments of a modified CO-Synch protocol on pregnancy rate to TAI, and throughout a 90-d breeding season in suckled multiparous Bos indicus cows (n = 453). The inclusion of a CIDR between first GnRH and PGF(2alpha) treatments of a modified CO-Synch protocol did not improve pregnancy rate (29 and 33% for cows receiving CO-Synch + CIDR and CO-Synch protocol, respectively), and cycling cows had poorer TAI pregnancy rates than anestrous cows treated with either synchronization protocol (21.7 vs. 40.7%; P < 0.05). However, regardless of treatment with CIDR, cows submitted to TAI protocol had greater (P < 0.05) pregnancy rates at 30 (54.8 vs. 11.2%), 60 (72.1 vs. 38.8%), and 90 d (82.0 vs. 57.9%) of breeding season than untreated cows.

Topics: Animals; Body Weight; Cattle; Dinoprost; Female; Fertility; Gonadotropin-Releasing Hormone; Hormones; Insemination, Artificial; Ovarian Follicle; Ovulation; Oxytocics; Pregnancy; Pregnancy Rate

In order to characterize whether different degrees of adipose tissue storage may be associated with markers of early atherosclerosis, we evaluated oxidant-antioxidant status and inflammatory markers and determined carotid intima-media thickness (cIMT) in healthy constitutional lean and obese pre-pubertal children.. Eighty healthy pre-pubertal lean and obese children were recruited and compared with 40 age, gender, and pubertal stage-matched normal controls. Anthropometric measurements, oxidant (urinary isoprostanes (PGF-2alpha), lag phase, and malondialdehyde (MDA)) and antioxidant status (vitamin E), inflammatory markers (high sensitive C-reactive protein (hs-CRP)), and insulin sensitivity (fasting glucose-insulin ratio, homeostasis model assessment of insulin resistance (HOMA-IR)) were investigated. Furthermore, cIMT was measured by high-resolution ultrasound.. hs-CRP was not different between lean and control subjects (P=0.45), while higher values were found in obese compared with lean and control children (P<0.001 and P<0.001 respectively). PGF-2alpha and MDA were higher while lag phase shorter in lean and obese subjects compared with controls (lean P<0.001; P<0.001; P<0.001 and obese P<0.001; P<0.001; P<0.001 respectively), while no differences were documented between lean and obese subjects (P=0.78, P=0.019, and P=0.53 respectively). Compared with controls, cIMT was increased in lean and in obese subjects (P=0.001; P=0.004), while no differences were documented between obese and lean subjects (P=0.1). In a multiple stepwise linear regression analysis, cIMT was related with PGF-2alpha (beta=0.641, P<0.001) and HOMA-IR (beta=0.307; P<0.001).. Pre-pubertal lean and obese children present increased oxidative stress and impaired inflammation and insulin sensitivity, which in turn seem to result in similar impaired endothelial dysfunction and early signs of atherosclerosis, already in childhood.

Topics: Antioxidants; Biomarkers; Body Weight; C-Reactive Protein; Carotid Arteries; Carotid Artery Diseases; Child; Chronic Disease; Dinoprost; Female; Humans; Inflammation; Insulin Resistance; Male; Malondialdehyde; Obesity; Oxidants; Regression Analysis; Severity of Illness Index; Tunica Intima; Ultrasonography; Vitamin E

In the present study, we described ultrastructural changes occurring in the neurons of the hypothalamic arcuate nucleus after food deprivation. Young male Wistar rats (5 months old, n = 12) were divided into three groups. The animals in Group I were used as control (normally fed), and the rats in Groups II and III were fasted for 48 hours and 96 hours, respectively. In both treated groups, fasting caused rearrangement of the rough endoplasmic reticulum forming lamellar bodies and membranous whorls. The lamellar bodies were rather short in the controls, whereas in the fasting animals they became longer and were sometimes participating in the formation of membranous whorls composed of the concentric layers of the smooth endoplasmic reticulum. The whorls were often placed in the vicinity of a very well developed Golgi complex. Some Golgi complexes displayed an early stage of whorl formation. Moreover, an increased serum level of 8-isoprostanes, being a reliable marker of total oxidative stress in the body, was observed in both fasting groups of rats as compared to the control.

Topics: Age Factors; Aging; Animals; Appetite Regulation; Arcuate Nucleus of Hypothalamus; Biomarkers; Body Weight; Dinoprost; Endoplasmic Reticulum, Rough; Endoplasmic Reticulum, Smooth; Energy Metabolism; Fasting; Food Deprivation; Golgi Apparatus; Intracellular Membranes; Male; Neurons; Oxidative Stress; Rats; Rats, Wistar

This study was designed to examine the role of cyclooxygenase (COX) 2-mediated low-grade inflammation in the development of fructose-induced whole body and muscular insulin resistance in rats. The rats were on regular or fructose-enriched diets for 8 weeks. Fructose-fed rats were further divided into 3 groups (n = 8 per group). There were fructose-fed rats, fructose-fed rats with nimesulide (a selective COX2 inhibitor, 30 mg/kg/day, gavage) and fructose-fed rats with celecoxib (a selective COX2 inhibitor, 30 mg/kg/day, gavage). The present result showed that fructose-induced time-dependent increases in systolic blood pressure and fasting plasma insulin and triglyceride levels were significantly suppressed in rats treated with nimesulide or cerecoxib. The ratio of area under glucose curve divided by area under insulin curve obtained during the oral glucose tolerance test was significantly decreased in fructose-fed rats, which were markedly reversed in those co-treated with nimesulide or celecoxib. Accordingly, fructose-induced decrease in insulin-stimulated glucose uptake in soleus muscle was significantly reversed in those combined with nimesulide or celecoxib. Fructose-induced time-dependent increases in plasma 8-isoprostane and PGE metabolites were concomitantly suppressed by nimesulide or celecoxib co-treatment. The present study demonstrates that the COX2-mediated low-grade inflammation, especially mediated by increase in oxidative stress was important in the development of insulin resistance in fructose-fed rats.

Topics: Animals; Blood Pressure; Body Weight; Cyclooxygenase 2; Dinoprost; Disease Models, Animal; Fructose; Glucose; Glucose Tolerance Test; Hypoglycemic Agents; Inflammation; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Muscle, Skeletal; Prostaglandins E; Rats; Rats, Sprague-Dawley; Sweetening Agents

Regulation of coronary function in diabetic hearts is an important component in preventing ischemic cardiac events but remains poorly studied. Exercise is recommended in the management of diabetes, but its effects on diabetic coronary function are relatively unknown. We investigated coronary artery myogenic tone and endothelial function, essential elements in maintaining vascular fluid dynamics in the myocardium. We hypothesized that exercise reduces pressure-induced myogenic constriction of coronary arteries while improving endothelial function in db/db mice, a model of type 2 diabetes. We used pressurized mouse coronary arteries isolated from hearts of control and db/db mice that were sedentary or exercised for 1 h/day on a motorized exercise-wheel system (set at 5.2 m/day, 5 days/wk). Exercise caused a approximately 10% weight loss in db/db mice and decreased whole body oxidative stress, as measured by plasma 8-isoprostane levels, but failed to improve hyperglycemia or plasma insulin levels. Exercise did not alter myogenic regulation of arterial diameter stimulated by increased transmural pressure, nor did it alter smooth muscle responses to U-46619 (a thromboxane agonist) or sodium nitroprusside (an endothelium-independent dilator). Moderate levels of exercise restored ACh-simulated, endothelium-dependent coronary artery vasodilation in db/db mice and increased expression of Mn SOD and decreased nitrotyrosine levels in hearts of db/db mice. We conclude that the vascular benefits of moderate levels of exercise were independent of changes in myogenic tone or hyperglycemic status and primarily involved increased nitric oxide bioavailability in the coronary microcirculation.

Topics: Animals; Blood Glucose; Body Weight; Coronary Circulation; Coronary Vessels; Diabetes Mellitus, Type 2; Dinoprost; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular; Exercise Therapy; Hyperglycemia; Insulin; Mice; Microcirculation; Nitric Oxide; Oxidative Stress; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

Angiotensin II type 1 receptor may contribute to atherogenesis by facilitating the proliferative and inflammatory response to hypercholesterolemia. In the present study, we investigated the long-term effect of angiotensin II type 1a receptor (AT1a) deficiency on hypercholesterolemia-induced atherosclerosis by the use of AT1a-knockout (AT1a-KO) mice and apolipoprotein E-knockout (apoE-KO) mice. AT1a-KO were crossed with apoE-KO, generating double-knockout (D-KO) mice. Mice were fed a standard diet and analyzed at 25- or 60-weeks-old. The quantification of atherosclerotic volume in the aortic root revealed that the atherosclerotic lesions of D-KO mice were significantly smaller than those of apoE-KO mice at 25-week-old (0.81+/-0.16 mm2 vs. 1.05+/-0.21 mm2, p<0.001) and at 60-week-old (0.89+/-0.11 mm2 vs. 2.44+/-0.28 mm2, p<0.001). Surprisingly, there was no significant difference in atherosclerotic lesion size of D-KO mice at 25- and 60-week-old, suggesting that AT1a deficiency completely protected against the age-related progression of atherosclerosis. The amounts of collagen and elastin, the expression of p22phox, serum amyloid P (SAP), matrix metalloproteinase (MMP)-2, and MMP-9, and the number of apoptotic cells of D-KO mice were lower than those of apoE-KO mice. Furthermore, we confirmed that the expression of procollagen alpha1(I), procollagen alpha1(III), tropoelastin, p22phox, SAP, MMP-2, and MMP-9 decreased in cultured vascular smooth muscle cells from D-KO mice compared with those of apoE-KO mice. In conclusion, AT1a deficiency reduces atherosclerotic lesion size of apoE-KO mice and protects against the age-related progression of atherosclerosis. Reduction of oxidative stress, apoptosis, and MMP expression in atherosclerotic lesions by AT1a deficiency may contribute to plaque size.

Topics: Animals; Aorta; Apolipoproteins E; Apoptosis; Atherosclerosis; Blood Pressure; Body Weight; Cells, Cultured; Cholesterol; Dinoprost; Extracellular Matrix; Heart Rate; Hypercholesterolemia; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Smooth, Vascular; Oxidative Stress; Receptor, Angiotensin, Type 1

Squalene is an intermediate of cholesterol biosynthesis which can be obtained from the diet where it is abundant, for example, in olive oil. The effect of this isoprenoid on the development of atherosclerosis was investigated on apoE-knockout mice.. Two groups of animals, separated according to sex, were fed on standard chow diet: the control group receiving only vehicle and the second group an aqueous solution of squalene to provide a dose of 1g/kg/day in male and female mice. This treatment was maintained for 10 weeks. At the end of this period, plasma lipid parameters, oxidative stress markers and hepatic fat were measured as well as cross-sectional lesion area of aortic root in both groups. Data showed that in males squalene feeding reduced atherosclerotic lesion area independently of plasma lipids and activation of circulating monocytes. In contrast, squalene intake did not decrease lesion area in females, despite reducing plasma cholesterol and triglycerides, isoprostane and percentage of Mac-1 expressing white cells. In males, atherosclerotic lesion area was positively and significantly associated with hepatic fat content and the plasma triglycerides were also strongly associated with liver weight.. These results indicate that administration of squalene modulates lesion development in a gender specific manner, and that accumulation of hepatic fat by liver is highly correlated with lesion progression in males. Hence, squalene administration could be used as a safe alternative to correct hepatic steatosis and atherosclerosis particularly in males.

Topics: Animals; Apolipoprotein A-I; Apolipoprotein A-V; Apolipoproteins; Apolipoproteins E; Aryldialkylphosphatase; Atherosclerosis; Body Weight; CD11b Antigen; Cholesterol; Dinoprost; DNA-Binding Proteins; Fatty Liver; Female; Liver; Liver X Receptors; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Orphan Nuclear Receptors; Receptors, Cytoplasmic and Nuclear; Receptors, LDL; RNA, Messenger; Scavenger Receptors, Class B; Sex Characteristics; Squalene; Triglycerides

Whole raw soybeans (SB), wet corn gluten feed (WCGF), and corn dried distillers grains (DDG) are sources of protein in heifer development rations. The objectives of this study were to compare puberty status before synchronization of estrus, response to synchronization, and AI and final pregnancy rates in heifers developed on diets containing SB, WCGF, or DDG that were formulated to be similar in energy and CP. These ingredients vary substantially in fat content, which may affect reproductive performance. Rate of gain during the feeding period and post-AI performance were also compared. In a preliminary experiment, 104 crossbred heifers were fed diets containing either 1.25 kg of SB/d or 2.0 kg of WCGF/d for 110 d (DM basis), beginning at 10 mo of age. In Exp. 1, 100 crossbred heifers received either 1.25 kg of SB/d or 2.5 kg of WCGF/d from approximately 7 to 10 mo of age (91 d; 4 pens/diet), and then were fed 1.25 kg of SB/d for an additional 114 d (4 pens/diet). In Exp. 2, 1.25 kg of SB/d or 1.25 kg of DDG/d was fed to 100 crossbred heifers for 226 d, beginning at 6 mo of age (4 pens/diet). At approximately 13 mo of age, heifers were fed melengestrol acetate (0.5 mg/d) for 14 d, followed by an i.m. injection of PGF(2 alpha) (25 mg) 19 d later to synchronize estrus. Heifers (14 mo of age) received AI for 5 d after PGF(2 alpha), at which time the dietary treatments were ended. Heifers were commingled while grazing on native pasture and were exposed to bulls for approximately 60 d beginning 10 d after the last day of AI. Pregnancy to AI was determined by ultrasound 45 d after the last day of AI. Heifers fed SB in the preliminary experiment had a lower (P < 0.05) synchronization rate (81 vs. 96%) and longer interval (P = 0.05) from PGF(2 alpha) to estrus (76.6 vs. 69.2 h) compared with heifers fed WCGF. In Exp. 1, the age at which the heifers were begun on SB diets did not alter (P > 0.10) the synchronization rate (79%) or timing of estrus after PGF(2 alpha) (77.8 h). In Exp. 2, the synchronization rate (86%) and timing of estrus after PGF(2 alpha) (69.3 h) did not differ (P > 0.10) because of diet. No differences (P > 0.10) were due to diet for AI conception rates (overall mean for each experiment: 76.5, 60, and 68.5%), percentage of all heifers becoming pregnant to AI (67, 46, and 59%), or final pregnancy rates (92, 90, and 90%) in the preliminary experiment, Exp. 1, or Exp. 2, respectively. In summary, SB, DDG, and WCGF can be used as sources of protein i

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Body Weight; Cattle; Dietary Proteins; Dinoprost; Estrus; Estrus Synchronization; Female; Glycine max; Insemination, Artificial; Melengestrol Acetate; Pregnancy; Pregnancy Rate; Random Allocation; Sexual Maturation; Weight Gain; Zea mays

ANG II promotes inflammation through nuclear factor-kappaB (NF-kappaB)-mediated induction of cytokines and reactive oxygen species (ROS). The aim of the present study was to examine the effect of tetradecylthioacetic acid (TTA), a modified fatty acid, on NF-kappaB, proinflammatory markers, ROS, and nitric oxide (NO) production in two-kidney, one-clip (2K1C) hypertension. The 2K1C TTA-treated group had lower blood pressure (128 +/- 3 mmHg) compared with 2K1C nontreated (178 +/- 5 mmHg, P < 0.001). The p50 and p65 subunits of NF-kappaB were higher in the clipped kidney (0.44 +/- 0.01 and 0.22 +/- 0.01, respectively) compared with controls (0.25 +/- 0.03 and 0.12 +/- 0.02, respectively, P < 0.001). In the 2K1C TTA-treated group, these values were similar to control levels. The same pattern of response was seen in the nonclipped kidney. In 2K1C hypertension, cytokines plasma were higher than in control: TNF-alpha was 13.5 +/- 2 pg/ml (P < 0.03), IL-1beta was 58.8 +/- 10 pg/ml (P = 0.003), IL-6 was 210 +/- 33 pg/ml (P < 0.001), and monocyte chemoattractant protein-1 was 429 +/- 21 pg/ml (P = 0.04). In the 2K1C TTA-treated group, these values were similar to controls, and the same pattern was seen in the clipped kidney. Clipping increased 8-iso-PGF-2alpha (P < 0.01) and decreased NO production (P < 0.01 vs. control) in the urine. TTA treatment normalized these values. NO production was also lower in clipped and nonclipped kidney (P < 0.001). After TTA treatment, these values were similar to controls. The results indicate that TTA has a potent anti-inflammatory effect in 2K1C by inhibition of p50/p65 NF-kappaB subunit activation, reduction of cytokines production and ROS, and enhanced NO production.

Topics: Animals; Body Weight; Chemokine CCL2; Dinoprost; Disease Models, Animal; Eating; Free Radical Scavengers; Hypertension, Renal; Interleukin-1beta; Interleukin-6; Kidney Cortex; Male; Nephritis; NF-kappa B p50 Subunit; Nitrates; Nitric Oxide; Nitrites; Rats; Rats, Wistar; Reactive Oxygen Species; Sodium, Dietary; Sulfides; Surgical Instruments; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Polysomnography is the standard method for evaluating results of treatments for obstructive sleep apnea syndrome (OSAS), but it is time-consuming and often unavailable.. This study aimed to analyze the correlations between sleepiness, anthropometric parameters, exhaled breath condensate (EBC) and serum cytokine levels with changes in the apnea-hypopnea index (AHI), in order to identify potential measurements that could be an alternative to polysomnography.. Based on AHI results, 22 non-OSAS and 68 OSAS cases were followed up. Among the 68 patients, 5 underwent surgery, 2 were treated with oral appliances, 33 were treated using continuous positive airway pressure and 28 were untreated. AHI, anthropometric parameters, serum and EBC levels of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha) and 8-isoprostane were measured at baseline and after a 2-month follow-up. Correlations between the AHI and the other parameters were examined. Akaike's information criterion (AIC) was used to evaluate the fit of logistic regression models, predicting improvements in the severity of the condition from the parameters.. IL-6 and TNF-alpha in EBC and serum gave the highest correlation coefficients (r = 0.62 and r = 0.71 in EBC; r = 0.58 and r = 0.66 in serum, respectively) as well as the lowest AIC values (63.87, 68.97; 62.65, 70.64, respectively). Reductions in waist circumference and weight also correlated with changes in AHI (r = 0.69, AIC = 80.26 and 88.76, respectively).. IL-6 and TNF-alpha measurements may be used in OSAS treatment follow-ups, when polysomnography is not available. Waist circumference and weight could also be used when cytokine laboratory facilities are unavailable.

Topics: Adult; Biomarkers; Body Weight; Case-Control Studies; Cytokines; Dinoprost; Female; Humans; Male; Predictive Value of Tests; Prospective Studies; Severity of Illness Index; Sleep Apnea, Obstructive; Waist Circumference

There is evidence that plasma homocysteine augments angiopathy in patients with diabetes mellitus. Although lowering homocysteine with folic acid improves endothelial function, the precise mechanisms underlying this effect are unknown. To study this area further, the effect of administration of folic acid to diabetic rabbits on intraaortic oxidative stress was studied by assessing the formation of superoxide (O(2)(-)), 8-isoprostane F(2alpha) (8-IPF(2alpha)), and prostacyclin (as 6-keto-PGF(1alpha)) as well as acetylcholine-stimulated relaxation and gp47(phox) content. Nonketotic diabetes mellitus was induced in New Zealand rabbits with alloxan, and low- and high-dose folic acid was administered daily for 1 month. Rabbits were killed, aortae were excised, and rings were prepared. Rings were mounted in an organ bath, and relaxation was elicited with acetylcholine. The O(2)(-) release was measured spectrophotometrically; the gp47(phox) expression, by Western blotting; and the 8-IPF(2alpha) and 6-keto-PGF(1alpha) formation, by enzyme-linked immunosorbent assay. Blood was collected for measurement of homocysteine, red blood cell folate, and glucose. In aortae from the diabetic rabbits, acetylcholine-induced relaxation was significantly impaired compared with that in untreated controls. The O(2)(-) release, p47(phox) expression, and 8-IPF(2alpha) formation were all enhanced and 6-keto-PGF(1alpha) formation was reduced compared with controls. All these effects were reversed by both low- and high-dose folic acid. Plasma total homocysteine was reduced by high-dose, but not low-dose, folic acid. Red blood cell folate was elevated in both groups. The improvement of endothelial function in patients receiving folic acid may be due to inhibition of nicotinamide adenine nucleotide phosphate oxidase (NADPH) oxidase expression and therefore conservation of nitric oxide and prostacyclin bioavailability, 2 vasculoprotective factors.

Topics: Alloxan; Animals; Aorta; Body Weight; Diabetes Mellitus, Experimental; Dinoprost; Epoprostenol; Folic Acid; Homocysteine; Male; NADPH Oxidases; Oxidative Stress; Rabbits; Superoxides

Aging is accompanied by increased oxidative stress (OS) and accumulation of advanced glycation end products (AGEs). AGE formation in food is temperature-regulated, and ingestion of nutrients prepared with excess heat promotes AGE formation, OS, and cardiovascular disease in mice. We hypothesized that sustained exposure to the high levels of pro-oxidant AGEs in normal diets (Reg(AGE)) contributes to aging via an increased AGE load, which causes AGER1 dysregulation and depletion of anti-oxidant capacity, and that an isocaloric, but AGE-restricted (by 50%) diet (Low(AGE)), would decrease these abnormalities. C57BL6 male mice with a life-long exposure to a Low(AGE) diet had higher than baseline levels of tissue AGER1 and glutathione/oxidized glutathione and reduced plasma 8-isoprostanes and tissue RAGE and p66(shc) levels compared with mice pair-fed the regular (Reg(AGE)) diet. This was associated with a reduction in systemic AGE accumulation and amelioration of insulin resistance, albuminuria, and glomerulosclerosis. Moreover, lifespan was extended in Low(AGE) mice, compared with Reg(AGE) mice. Thus, OS-dependent metabolic and end organ dysfunction of aging may result from life-long exposure to high levels of glycoxidants that exceed AGER1 and anti-oxidant reserve capacity. A reduced AGE diet preserved these innate defenses, resulting in decreased tissue damage and a longer lifespan in mice.

Topics: Adaptor Proteins, Signal Transducing; Aging; Animals; Body Weight; Collagen Type IV; Diet; Dinoprost; Eating; Glucose; Glutathione; Glycation End Products, Advanced; Insulin; Kidney; Life Expectancy; Male; Mice; Mice, Inbred C57BL; Oxidants; Oxidative Stress; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Shc Signaling Adaptor Proteins; Src Homology 2 Domain-Containing, Transforming Protein 1; Transforming Growth Factor beta1

Recent studies have uncovered various pleiotrophic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase-inhibiting drugs (statins). Several studies have identified a beneficial effect of statins on diabetic nephropathy; however, the molecular mechanisms are unclear. In this study, we show that statin ameliorates nephropathy in db/db mice, a rodent model of type 2 diabetes, via downregulation of NAD(P)H oxidase NOX4, which is a major source of oxidative stress in the kidney. Pitavastatin treatment for 2 weeks starting at 12 weeks of age significantly reduced albuminuria in the db/db mice concomitant with a reduction of urinary 8-hydroxy-2'-deoxyguanosine and 8-epi-prostaglandin F(2alpha). Immunohistochemical analysis found increased amounts of 8-hydroxy-2'-deoxyguanosine and NOX4 protein in the kidney of db/db mice. Quantitative reverse transcription-polymerase chain reaction also showed increased levels of NOX4 mRNA. Pitavastatin normalized all of these changes in the kidneys of diabetic animals. Additionally, 12-week treatment with the statin completely normalized the levels of transforming growth factor-beta1 and fibronectin mRNA as well as the mesangial expansion characteristic of diabetic nephropathy. Our study demonstrates that pitavastatin ameliorates diabetic nephropathy in db/db mice by minimizing oxidative stress by downregulating NOX4 expression. These findings may provide insight into the mechanisms of statin therapy in early stages of diabetic nephropathy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Albuminuria; Animals; Blood Glucose; Body Weight; Cell Proliferation; Deoxyguanosine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dinoprost; Disease Models, Animal; Down-Regulation; Fibronectins; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Mesangial Cells; Mice; NADPH Oxidase 4; NADPH Oxidases; Oxidative Stress; Quinolines; RNA, Messenger; Time Factors; Transforming Growth Factor beta1

After parturition, immune functions such as lymphocyte response to mitogens and production of antibodies are depressed in dairy cows. Dietary regimens that improve the immune function of dairy cows after calving may improve uterine health and lead to earlier breeding after parturition. The objective of this study was to examine the effect of feeding a calcium salt of trans isomers of fatty acids (tFA) to periparturient Holstein cows on plasma biomarkers of inflammation. Dietary treatments were initiated approximately 28 d before expected calving date and continued through d 21 postpartum. Prepartum and postpartum diets were formulated to be isolipidic, containing 1.5% saturated fats (n = 15) or 1.8% tFA (n = 15). Multiparous cows were heavier at calving (+32%) and produced more milk (+17%) than primiparous cows. Periparturient tFA supplementation increased plasma PGF(2alpha) metabolite concentration in multiparous cows, but not in primiparous cows. Concentrations of prostaglandin E(2), tumor necrosis factor-alpha, and interleukin-4 in plasma did not differ between diets and parities. Results raise the possibility that peripartum tFA supplementation may affect uterine health and reproductive efficiency of early lactation dairy cows through alteration of peripheral PGF(2alpha) concentration.

Topics: Animal Nutritional Physiological Phenomena; Animals; Biomarkers; Body Weight; Calcium Compounds; Cattle; Dinoprost; Fatty Acids; Female; Health Status; Interleukin-4; Lactation; Milk; Parity; Parturition; Pregnancy; Trans Fatty Acids; Tumor Necrosis Factor-alpha

Cysteinyl leukotrienes (cysLT) are pro-inflammatory and vasoactive products suspected to be involved in the regulation of vascular tone and blood pressure in hypertension.. We investigated, in spontaneously hypertensive rats (SHR), the involvement of cysLT in the in-vivo regulation of blood pressure and the in-vitro endothelium-dependent contraction to acetylcholine in isolated aorta.. SHR and Wistar-Kyoto rats (WKY) were orally treated for 3 weeks with either the cysLT biosynthesis inhibitor MK-886 (0.1 mg/ml) or vehicle. After mean arterial blood pressure (MABP) measurement, aortic ring preparations were removed from all groups of animals, and contractions and relaxations were monitored subsequent to stimulation with acetylcholine.. MABP was higher in SHR. Chronic treatment with MK-886 did not alter MABP in either SHR or WKY. In the presence of the N-nitro-L-arginine (L-NA, 100 micromol/l), and on prostaglandin F2alpha (PGF2alpha)-induced tone, acetylcholine evoked concentration-dependent contractions in intact aortic rings from SHR only. Pretreatment with either MK-886 (10 micromol/l), the 5-lipoxygenase (5-LO) inhibitor AA861 (10 micromol/l), or the cysLT1 receptor antagonist MK571 (1 micromol/l) reduced (P < 0.05) acetylcholine-induced contractions in intact aortic rings from SHR only. Acetylcholine-induced contractions were weaker (P < 0.01) in SHR chronically treated with MK-886 than in SHR. In the presence of L-NA, leukotriene (LT) D4 induced greater (P < 0.05) concentration-dependent contractions in aortic rings from SHR than from WKY. MK571 abolished LTD4-evoked contractions.. These data suggested that 5-LO-derived products, through the activation of cysLT1 receptors, could be involved in the endothelium-dependent contraction to acetylcholine in aorta from SHR but not in the regulation of MABP in SHR.

Topics: Acetylcholine; Animals; Aorta, Thoracic; Arachidonate 5-Lipoxygenase; Benzoquinones; Biopterins; Blood Pressure; Body Weight; Dinoprost; Endothelium, Vascular; Hypertension; Indoles; Leukotriene D4; Lipoxygenase Inhibitors; Male; Membrane Proteins; Nitroarginine; Propionates; Quinolines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Leukotriene; Vasoconstriction

Intrauterine infection may be causally related to inflammation and injury of the fetal brain, however the mechanisms by which this occurs are unclear. We have investigated whether nuclear factor (NF)-kappaB, a transcription factor for proinflammatory cytokines, is activated in the fetal brain after acute LPS-exposure. At 95 days of gestation (term = approximately 147 days), 5 fetuses received a single intravenous bolus dose of LPS (1 microg/kg); 6 fetuses served as controls. Fetal blood samples were taken hourly for 6 hr post LPS-exposure to assess physiological status. Ewes and fetuses were then euthanased, placental and brain tissue examined histologically, and NF-kappaB activation assessed in several regions of the fetal brain using an electromobility shift assay (EMSA). Oxidative stress was measured using lipid peroxidation and 8-isoprostane biochemical assays and brain cytokine concentrations analysed by enzyme linked immunosorbent assay (ELISA). LPS-exposed fetuses (relative to controls) were hypoxemic and the haematocrit and lactate levels had increased. In the brains of LPS-exposed fetuses compared to controls, NF-kappaB binding activity was elevated in the hippocampus and the thalamus/basal ganglia; 8-isoprostane levels were elevated overall (P < 0.05) in the parietal/occipital/temporal lobes and thalamus/basal ganglia. TNF-alpha and IL-6 concentrations were not elevated, however, there was a tendency for an elevation of IFN-gamma concentrations in the thalamus/basal ganglia. IFN-gamma concentration was elevated (P < 0.05) in the plasma 4 hr after LPS-exposure. In the placenta, NF-kappaB binding activity was increased (P < 0.05). We conclude that acute systemic administration of LPS leads to increased binding activity of NF-kappaB subunits in specific regions of the fetal brain and in the placenta, but that there is no clear-cut relationship between this elevation and vulnerability to endotoxic damage.

Topics: Animals; Body Weight; Brain; Brain Chemistry; Cytokines; Dinoprost; Electrophoretic Mobility Shift Assay; Female; Interferon-gamma; Interleukin-6; Lipid Peroxidation; Lipopolysaccharides; NF-kappa B; Organ Size; Oxidative Stress; Placenta; Pregnancy; Sheep; Tumor Necrosis Factor-alpha

To investigate the relationship between oxidative stress and circulating levels of adiponectin in Japanese metabolically obese, normal-weight [MONW; BMI<25 and visceral fat area; VFA > or =100 cm2 by abdominal computed tomography (CT) scanning] men with normal glucose tolerance (NGT), we measured the plasma levels of free 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) and adiponectin in 28 MONW and 23 normal men. The plasma levels of free 8-epi-PGF2alpha were measured using a commercially available enzyme immunoassay (EIA) kit (Cayman Chemical, Ann Arbor, MI). The plasma levels of adiponectin were measured using a radioimmunoassay kit (LINCO Research, St. Charles, MO). Plasma levels of 8-epi-PGF2alpha in MONW subjects (30.4+/-4.0 pg/ml; P<0.01) were significantly increased compared to controls (8.1+/-1.3 pg/ml). The plasma levels of adiponectin were significantly decreased in MONW subjects (8.6+/-0.9 microg/ml; P<0.01) as compared to normal subjects (11.6+/-0.6 microg/ml). The plasma levels of 8-epi-PGF2alpha and adiponectin were significantly correlated in MONW (r=-0.617, P<0.01) and in all (MONW+normal) (r=-0.620, P<0.01) subjects. The plasma levels of 8-epi-PGF2alpha and adiponectin were significantly correlated after adjustment for VFA in MONW subjects (F=11.042, P<0.01). The present study showed that systemic increase in oxidative stress correlates with decreased circulating levels of adiponectin in Japanese MONW men with NGT. Although correlation does not prove causation, this observation suggests that increased oxidative stress may decrease the production of adiponectin in Japanese MONW men with NGT.

Topics: Adiponectin; Adult; Blood Glucose; Body Weight; Dinoprost; Glucose Tolerance Test; Humans; Intra-Abdominal Fat; Japan; Lipids; Male; Obesity; Oxidative Stress; Radioimmunoassay

Oxidative stress has been proposed as important in the pathogenesis of hypertension. Measurement of 8-iso prostaglandin F2alpha (8-ISO) is introduced for evaluating oxidative stress in vivo. 8-ISO is the major urinary metabolite of F2-isoprostanes and is formed nonenzymatically from the attack of superoxide radicals on arachidonic acid. We examined the oxidative stress level in the Dahl salt-sensitive (Dahl-S) rats and the Dahl salt-resistant (Dahl-R) rats. Dahl-S and Dahl-R rats were fed either a high salt diet (8% NaCl; HS) or low salt diet (0.3% NaCl; LS) for 3 weeks, and systolic blood pressure (SBP) and 24-hr urinary excretion of 8-ISO (U-8-ISO) were measured. In Dahl-S rats, the high salt diet induced hypertension (139 +/- 3 mmHg in LS versus 186 +/- 2 mmHg in HS, p < .05) and significantly increased the U-8-ISO (24.9 +/- 3.6 ng/24 hr in LS versus 63.2 +/- 14.6 ng/24 hr in HS, p < .05). No significant difference in blood pressure or U-8-ISO was observed between high-salt and low-salt treated Dahl-R rats. U-8-ISO concentration was correlated with SBP in all four experimental groups (r = 0.866). Moreover, urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), which is one of the most commonly used markers for evaluation of oxidative stress, was higher in Dahl-S-8% rats than in Dahl-S-0.3% rats (136.1 +/- 48.4 ng/24 hr in LS versus 322.8 +/- 46.7 ng/24 hr in HS, p < .05), and U-8-OHdG was correlated with SBP (r = 0.681) in Dahl-S rats. These results suggest oxygen radicals are involved in the pathogenesis of hypertension.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biomarkers; Blood Pressure; Body Weight; Deoxyguanosine; Dinoprost; Heart Rate; Hypertension; Male; Oxidative Stress; Rats; Rats, Inbred Dahl

Aging is characterized by renal functional and structural abnormalities resembling those observed in diabetes. These changes have been related to the progressive accumulation of advanced glycation end-products (AGEs) and cumulative oxidative stress occurring in both conditions. We previously reported that galectin-3 ablation is associated with increased susceptibility to diabetes- and AGE-induced glomerulopathy, thus indicating a protective role of galectin-3 as an AGE receptor. To investigate the role of the AGE/AGE receptor pathway in the pathogenesis of age-related renal disease, we evaluated the development of glomerular lesions in aging galectin-3 knockout (KO) vs. wild-type (WT) mice and their relation to the increased AGE levels and oxidative stress characterizing the aging process. KO mice showed significantly more pronounced age-dependent increases in proteinuria, albuminuria, glomerular sclerosis, and glomerular and mesangial areas, starting at 18 mo, as well as renal extracellular matrix mRNA and protein expression, starting at 12 mo vs. age-matched WT mice. Circulating and renal AGEs, plasma isoprostane 8-epi-PGF2alpha levels, glomerular content of the glycoxidation and lipoxidation products N(epsilon)-carboxymethyllysine and 4-hydroxy-2-nonenal, and renal nuclear factor-kappaB activity also increased more markedly with age in KO than WT mice. AGE levels correlated significantly with renal functional and structural parameters. These data indicate that aging galectin-3 KO mice develop more pronounced changes in renal function and structure than coeval WT mice, in parallel with a more marked degree of AGE accumulation, oxidative stress, and associated low-grade inflammation, thus supporting the concept that the AGE/AGE receptor pathway is implicated in age-related renal disease.

Topics: Age Factors; Aging; Aldehydes; Animals; Body Weight; Dinoprost; Extracellular Matrix; Galectin 3; Glomerulonephritis; Glycation End Products, Advanced; Kidney Glomerulus; Lysine; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Receptor for Advanced Glycation End Products; Receptors, Immunologic; RNA, Messenger; Transforming Growth Factor beta; Transforming Growth Factor beta1

Dietary advanced glycosylation end products (AGEs) have been linked to insulin resistance in db/db(++) mice. To test whether dietary AGEs play a role in the progression of insulin resistance in normal mice fed high-fat diets, normal C57/BL6 mice were randomly assigned to high-fat diets (35% g fat), either high (HAGE-HF group; 995.4 units/mg AGE) or low (by 2.4-fold LAGE-HF group; 329.6 units/mg AGE) in AGE content for 6 months. Age-matched C57/BL6 and db/db(++) mice fed regular diet (5% g fat, 117.4 units/mg AGE) served as controls. After 6 months, 75% of HAGE-HF mice were diabetic and exhibited higher body weight (P < 0.001), fasting glucose (P < 0.001), insulin (P < 0.001), and serum AGEs (P < 0.01) than control mice, while none of the LAGE-HF mice were diabetic despite a similar rise in body weight and plasma lipids. The HAGE-HF group displayed markedly impaired glucose and insulin responses during glucose tolerance tests and euglycemic and hyperglycemic clamps and altered pancreatic islet structure and function compared with those of LAGE-HF mice, in which findings resembled those of control mice. The HAGE-HF group had more visceral fat (by two- and fourfold) and more AGE-modified fat (by two- and fivefold) than LAGE-HF and control mice, respectively. In the HAGE-HF group, plasma 8-isoprostane was higher (P < 0.01) and adiponectin lower (P < 0.001) than control mice, while in the LAGE-HF group, these were more modestly affected (P < 0.05). These results demonstrate that the development of insulin resistance and type 2 diabetes during prolonged high-fat feeding are linked to the excess AGEs/advanced lipoxidation end products inherent in fatty diets.

Topics: Adiponectin; Adipose Tissue; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dietary Fats; Dinoprost; Fasting; Female; Glucose Clamp Technique; Glucose Tolerance Test; Glycation End Products, Advanced; Hyperplasia; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Islets of Langerhans; Lipids; Mice; Mice, Inbred C57BL

Topics: Blood Glucose; Body Mass Index; Body Weight; Dinoprost; Glucose Clamp Technique; Humans; Hyperinsulinism; Insulin Resistance; Japan; Male; Obesity; Oxidative Stress; Reference Values; Triglycerides

To probe into therapeutic effect and its mechanism of "Huo Xue Bu Qi Fang" (HXBQF) on fetal rats with intrauterine growth retardation (IUGR).. The model of pregnant rat with IUGR was established by passive smoking method. Forty pregnant rats with IUGR were randomly divided into intervention group (with high-, middle- and low-dose Chinese traditional medicine) and non-intervention group. In addition, 10 normal pregnant rats were taken into control group. Intervention group was adminstered with 16.2, 5.4 and 1.62 g/kg HXBQF respectively. Non-intervention group and control group were administered with 10 ml/kg saline. Fetal rats were taken out, and blood and urine samples were collected from pregnant rats on day 21 of the pregnancy. The weight, nose-hip-length and poundera index of these fetal rats were measured. Serum NO, plasma ET-1 and urine 8-epi-PGF2 alpha level from pregnant rats were determined by nitro-reductase method, radioimmunoassay (RIA) and enzyme immunoassay (EIA) respectively.. Compared with fetal rats from non-intervention group, fetal weight, distance between nose-hip, poundera index serum NO level and NO/ET-1 were increased, plasma ET-1 level and urine 8-epi-PGF2 alpha level were decreased in those from intervention group (P < 0.01).. There is an enhancement of lipid peroxidation and NO/ET-1 ratio imbalance in pregnant rats with IUGR. HXBQF has good therapeutic effect on IUGR since it can inhibit lipid oxidation and regulate NO/ET-1 balance.

Topics: Animals; Antioxidants; Body Weight; Dinoprost; Drugs, Chinese Herbal; Endothelin-1; Female; Fetal Growth Retardation; Nitric Oxide; Pregnancy; Random Allocation; Rats; Rats, Sprague-Dawley

We investigated the hypothesis that thromboxane A2 (TxA2)-prostaglandin H2 receptors (TP-Rs) mediate the hemodynamic responses and increase in reactive oxygen species (ROS) to ANG II (400 ng x kg(-1) x min(-1) sc for 14 days) using TP-R knockout (TP -/-) and wild-type (+/+) mice. TP -/- had normal basal mean arterial blood pressure (MAP) and glomerular filtration rate but reduced renal blood flow and increased filtration fraction (FF) and renal vascular resistance (RVR) and markers of ROS (thiobarbituric acid-reactive substances and 8-isoprostane PGF2alpha) and nitric oxide (NOx). Infusion of ANG II into TP +/+ increased ROS and thromboxane B2 (TxB2) and increased RVR and FF. ANG II infusion into TP -/- mice reduced ANG I and increased aldosterone but caused a blunted increase in MAP (TP -/- : +6 +/- 2 vs. TP +/+: +15 +/- 3 mmHg) and failed to increase FF, ROS, or TxB2 but increased NOx and paradoxically decreased RVR (-2.1 +/- 1.7 vs. +2.6 +/- 0.8 mmHg x ml(-1) x min(-1) x g(-1)). Blockade of AT1 receptor of TP -/- mice infused with ANG II reduced MAP (-8 mmHg) and aldosterone but did not change the RVR or ROS. In conclusion, during an ANG II slow pressor response, AT1 receptors activate TP-Rs that generate ROS and prostaglandins but inhibit NO. TP-Rs mediate all of the increase in RVR and FF, part of the increase in MAP, but are not implicated in the suppression of ANG I or increase in aldosterone. TP -/- mice have a basal increase in RVR and FF associated with ROS.

Topics: 6-Ketoprostaglandin F1 alpha; Aldosterone; Angiotensin I; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Body Weight; Dinoprost; Electrolytes; Epoprostenol; Female; Heart Rate; Hematocrit; Hypertension, Renal; Kidney; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitrates; Nitrites; Organ Size; Receptor, Angiotensin, Type 1; Receptors, Thromboxane A2, Prostaglandin H2; Renal Circulation; Specific Pathogen-Free Organisms; Thiobarbituric Acid Reactive Substances; Thromboxane B2; Urine; Vascular Resistance; Vasoconstrictor Agents

Adrenomedullin (AM) is expressed in cardiac tissue, and plasma AM levels increase in patients with acute myocardial infarction (MI). This study was performed to determine whether AM administration immediately after acute MI inhibits progression of heart failure in rats.. Rats were infused with 1.0 microg/h IP AM or saline over 7 days immediately after MI inducted by left coronary ligation and were examined 9 weeks after MI. Compared with the saline infusion, AM infusion significantly improved survival (59% versus 81%; P<0.05) and body weight gain (32%; P<0.01) and reduced heart weight (-28%; P<0.01), lung weight (-26%; P<0.01), left ventricular (LV) end-diastolic pressure (11.4+/-2.0 versus 4.0+/-0.6 mm Hg, mean+/- SEM; P<0.01), collagen volume fraction of noninfarcted LV (-39%; P<0.05), and plasma levels of endogenous rat AM (-38%; P<0.05) without affecting infarct size. To investigate the mechanism of AM actions, another series of MI rats infused with AM were killed on day 7. AM infusion had no effect on organ weights and hemodynamic parameters on day 7 of MI but significantly reduced urinary excretion of isoprostane (-61%; P<0.01) and noninfarcted LV mRNA levels of ACE (-31%; P<0.05) and p22-phox (-30%; P<0.05).. AM administration during the early period of MI improved the survival and ameliorated progression of LV remodeling and heart failure. This beneficial effect was accompanied by reductions in oxidative stress and ACE mRNA expression in noninfarcted LV in the AM infusion period.

Topics: Adrenomedullin; Aldosterone; Animals; Body Weight; Dinoprost; Disease Progression; Drug Evaluation, Preclinical; Heart Failure; Hemodynamics; Ligation; Lung; Male; Membrane Transport Proteins; Models, Animal; Myocardial Infarction; Myocardium; NADPH Dehydrogenase; NADPH Oxidases; Organ Size; Peptides; Peptidyl-Dipeptidase A; Phosphoproteins; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; RNA, Messenger; Ventricular Remodeling

The aim of this study was to evaluate the effects of ram introduction after the second prostaglandin F2alpha (PG F2alpha) injection on day 11 on the secretion characteristics of pre-ovulatory LH surge of fat-tailed ewes. Multiparous Morkaraman ewes (n=12) were divided into three groups by balancing the groups for liveweight (BW) and body condition score (BCS). On the day of second PGF2 alpha injection (0 h), performance tested rams (n=2) were either introduced to the ewes at 0 h (ram 0 group, n=4) or at 18 h (ram 18 group, n=4) or were not introduced (control group, n=4). Blood samples were collected at 6, 18, 42, 48, 56, 62, 66, 70, 74, 78 and 90 h for the determination of pre-ovulatory LH surge. BCS and BW during the experimental period were 2.2 +/- 0.2 units and 50.9 +/- 2.3 kg, 2.4 +/- 0.4 units and 49.2 +/- 6.2 kg, 2.1 +/- 0.3 units and 45.9 +/- 4.4 kg, respectively for the ram 0, ram 18 and control groups (p > 0.05). No significant difference was observed in LH surge characteristics for the experimental groups. Peak LH concentrations were also not different between groups (p > 0.05) and they were 12.2 +/- 8.3, 29.1 +/- 9.9 and 15.8 +/- 9.5 microg/l for the ram 0, ram 18 and control groups, respectively. There was, however, a significant correlation between peak LH concentrations and BCS (p < 0.05, R2=0.373). In conclusion, it appears that, compared with ram introduction, variability in body condition of the ewe has much pronounced effect on the amount of LH secreted after the usage of two PGF2 alpha injections (11 days apart) as a tool for oestrus synchronization.

Topics: Animals; Body Weight; Dinoprost; Estrus Synchronization; Female; Luteinizing Hormone; Male; Nutritional Status; Random Allocation; Sexual Behavior, Animal; Sheep; Time Factors

Estrus synchronization contributes to optimizing the use of time, labor, and financial resources by shortening the calving season, in addition to increasing the uniformity of the calf crop. We determined whether acceptable pregnancy rates could be achieved after synchronization of ovulation and fixed-time artificial insemination (AI) in peripuberal replacement beef heifers using gonadotropin-releasing hormone (GnRH) and PGF2alpha. Crossbred heifers from two herds (MH, n=239; SS, n=330) were wintered at a single location. After a prebreeding examination revealed that 55 heifers had a reproductive tract score (RTS) of 1 (infantile reproductive tracts), they were culled and the remaining heifers were assigned randomly to one of three treatment groups: administration of 25mg PGF2alpha i.m. on Days -12 and 0 followed by estrus detection and insemination between 10 and 14 h after an observed estrus (Control; n=173); administration of 100 microg GnRH i.m. on Day -6, followed by 25 mg PGF2alpha i.m. on Day 0, then fixed-time AI and administration of 100 microg GnRH i.m. on Day +2 (GPG; n=172); and, treatment as for group GPG in addition to administration of 100 microg GnRH i.m. on Day -12 (GGPG; n=169). Bulls were introduced 10 days after AI for 60 days to breed heifers which did not conceive after AI (clean-up bulls). On Days -12, -6, and 0 transrectal ultrasonography was used to monitor ovarian structures in a subset of heifers (30 per treatment). At 30-35 days after AI, ultrasound was used to determine the presence of a viable fetus. Presence of a fetus and stage of pregnancy were determined via palpation per rectum 61-63 days after the conclusion of the breeding season. Heifers in the MH herd (309+/-1.9 kg) were heavier (P<0.001) than those in the SS herd (283+/-1.7 kg) at initiation of the breeding season. Synchronized pregnancy rates were greater (P<0.05) in GGPG (25.4%) and GPG (22.1%) than Control (12.7%) heifers. Pregnancy rates were 9, 21, 32, or 31% for heifers with RTS of 2, 3, 4, or 5, respectively. The average diameter of 22 follicles induced to ovulate in heifers treated with GnRH (GPG and GGPG treatments) was 14.2+/-0.8 mm (range=10.0-23.6 mm). In conclusion, a fixed-time ovulation synchronization program using GnRH and PGF2alpha improved pregnancy rates in peripuberal, lightweight replacement beef heifers.

Topics: Animals; Body Weight; Dinoprost; Estrus Detection; Estrus Synchronization; Female; Gonadotropin-Releasing Hormone; Insemination, Artificial; Male; Ovulation; Pregnancy; Sexual Maturation; Time Factors

Effect of prostaglandin F2alpha (PGF2alpha) on carbohydrate accumulation in gonads of the multivoltine silkworm (hybrid: Xinhang x Keming) has been studied by means of topical application to larvae of the silkworm. Increased weights of larvae and reproduction organs, as well as carbohydrate metabolism in gonads of the silkworm, Bombyx mori L. was found after treatment with prostaglandin F2alpha. The increase in weight (larvae 21.9%, testis 28.9%, and ovary 33.3%) was associated with increases in the biomolecules (20-30%) and LDH and aldolase activity (18-25%). The results suggest that the accumulation of carbohydrates denotes a higher extent of utility of the energy sources in function of the testes and ovaries, and the routine application of prostaglandin F2alpha would be helpful in improving the reproductivity and egg quality of the silkworm.

Topics: Animals; Body Weight; Bombyx; Carbohydrate Metabolism; Dinoprost; Female; Fructose-Bisphosphate Aldolase; L-Lactate Dehydrogenase; Male; Ovary; Testis

Two experiments were carried out to study the effect of nutrition on embryo development in two periods in superovulated ewes (Expt 1) and on oocyte developmental capacity during the late follicular phase (Expt 2). In Expt 1, a lower superovulation response in terms of animals ovulating (P < 0.05), ovulation rate per ewe ovulating (P = 0.1) and number of good quality embryos per animal treated (P < 0.07) was noted in ewes fed an ad libitum diet compared with ewes offered control (1.5 times the daily maintenance energy requirements, 1.5 x M) or low energy (0.5 x M) diets. Nutrition also modified the morphological and functional quality of the oocytes and embryos recovered. Thus, 92% of day 4 embryos recovered from ewes offered the control diet were classified as good embryos, compared with 70 and 82% of those recovered from ewes offered the ad libitum and low diets, respectively (P < 0.05). Ewes offered the ad libitum diet had a greater percentage of poorly developed embryos compared with ewes offered the control or low diets (P < 0.05). Ewes fed the low diet tended to have more non-fertilized oocytes than ewes offered the control diet (P = 0.09). Diet of recipient ewes to which good quality embryos were transferred on day 4 did not affect embryo quality, when assessed 12 days later (day 16 of pregnancy). However, recipient diet affected prostaglandin F(2alpha) (PGF(2alpha)) production in vitro, and uterine tissue that originated from recipient ewes on the low diet secreted more PGF(2alpha) relative to uterine tissue that originated from recipients on the control diet (P < 0.05). In Expt 2, fewer total (P < 0.05) and good quality (P < 0.01) oocytes and a lower percentage of good quality oocytes (P < 0.01) were obtained from superovulated ewes offered the ad libitum diet compared with ewes offered the low diet. In addition, cleavage rate tended to be higher (51 versus 35%, P = 0.09) in ewes offered the low diet compared with ewes offered the ad libitum diet. In conclusion, changes in diet can affect the quality of the oocyte and embryo in superovulated sheep. A lower superovulation response and a decrease in the quality of oocytes and embryos indicate that ad libitum diets are highly detrimental for superovulatory programmes when compared with low and control diets. In addition, the results from the present study indicate that a low energy diet during early embryo development increased the uterine production in vitro of PGF(2alpha) which could lead to a poor

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Cells, Cultured; Dinoprost; Dinoprostone; Embryo Transfer; Embryonic and Fetal Development; Endometrium; Female; Insulin; Insulin-Like Growth Factor I; Liver; Oocytes; Organ Size; Pregnancy; Pregnancy, Animal; Progesterone; Sheep; Superovulation

We hypothesised that maternal uterine artery vascular dysfunction could contribute to cardiovascular dysfunction in offspring of rats fed a diet rich in fat. Sprague-Dawley rats were fed for 10 days prior to pregnancy and throughout gestation either: (a) a control breeding diet, or (b) the same diet supplemented with 20 % w/w lard, vitamins, essential micronutrients and protein to control values. At 20 days gestation vascular function was assessed in uterine arteries and third-order mesenteric arteries. Vascular reactivity in response to application of potassium, noradrenaline, the thromboxane analogue U46619, acetylcholine and nitric oxide was assessed. Maternal plasma concentrations of factors likely to contribute to endothelial dysfunction were measured. Maximum acetylcholine-induced relaxation was impaired in the mesenteric arteries of the lard-fed dams (max % relaxation: lard-fed, 69.7 +/- 6.48; control, 85.37 +/- 2.69, P = 0.03). Uterine artery vascular function was similar in the two groups (max % acetylcholine-induced relaxation: lard-fed, 73.7 +/- 4.01; control, 77.5 +/- 4.72, P = 0.98). Concentrations of plasma lipids, 8-epi-PGF(2alpha) and leptin were normal, whereas insulin and corticosterone concentrations were raised in the lard-fed group (insulin (ng ml(-1)): lard-fed, 8.04 +/- 0.47; control, 1.35 +/- 0.37, P < 0.0001; corticosterone (ng ml(-1)): lard-fed, 1164.0 +/- 170.9; control, 541.9 +/- 96.3, P = 0.005). Fetal and placental weights were reduced in lard-fed dams (fetus (g): lard-fed, 4.27 +/- 0.38; control, 2.96 +/- 0.40, P = 0.025; placenta (g): lard-fed, 0.72 +/- 0.06; control, 0.57 +/- 0.04, P = 0.05). Cardiovascular dysfunction in offspring is not associated with reduced uterine artery endothelial function but is associated with activation of the hypothalamic-pituitary-adrenal axis, hyperinsulinaemia and fetoplacental growth retardation.

Topics: Animal Feed; Animals; Arteries; Body Weight; Cholesterol; Corticosterone; Diet; Dietary Fats; Dinoprost; Eating; Endothelium, Vascular; Energy Metabolism; F2-Isoprostanes; Female; Insulin; Leptin; Lipid Peroxidation; Litter Size; Mesenteric Arteries; Pregnancy; Rats; Rats, Sprague-Dawley; Reproduction; Uterus; Vasoconstriction; Vasodilation

Calcineurin-inhibitor nephrotoxicity plays a role in the pathogenesis of chronic allograft nephropathy by causing renal ischemia mediated by vasoconstrictive metabolites of the prostanoid pathway. The purpose of our study was to evaluate whether altering the prostanoid profile using juniper oil (JO) would afford renoprotection in rats treated with tacrolimus.. Diets supplemented with biologic oils (no supplementation, JO, fish oil [FO], safflower oil [SO], and arachidonic acid [AA]) were fed to five groups of rats for 5 weeks; during the last 2 weeks, tacrolimus was administered to all groups except for a control group of animals. At week 5, urinary prostaglandin (PG)F(2-alpha) and inulin clearances were measured. The rat kidneys were harvested to determine the renal cell membrane composition for arachidonic, eicosatrienoic, and eicosapentaenoic acids.. Both JO and FO completely reversed the decrease in inulin clearance seen with tacrolimus, the greatest effect being with JO (inulin clearance 15.1+/-3 vs. 6.0+/-1.1 ml/min in the nonsupplemented group; P<0.001); urinary PGF(2-alpha) excretion was also highest in the JO group (328+/-23 pg/mL, P<0.001 vs. the nonsupplemented group). Fatty acid membrane analysis showed greatest incorporation of eicosapentaenoic and eicosatrienoic acids in the JO- (5.7+/-0.6% and 3.1+/-0.4%, respectively) and FO- (8.1+/-0.7% and 2.8+/-0.6%, respectively) treated animals.. JO supplementation in tacrolimus-treated rats was associated with incorporation of vasodilatory prostanoids in the renal-cell membrane and elevated urinary PGF(2-alpha) excretion, and the precipitous fall in inulin clearance induced by tacrolimus was completely prevented. Whether this benefit will translate into a reduction in chronic allograft nephropathy remains to be determined. However, our preliminary data point towards the need for human trials.

Topics: Animals; Arachidonic Acid; Body Weight; Cell Membrane; Dinoprost; Drug Interactions; Fatty Acids; Fish Oils; Immunosuppressive Agents; Inulin; Kidney Diseases; Male; Plant Oils; Rats; Rats, Inbred Lew; Safflower Oil; Tacrolimus

Diet and exercise can affect blood pressure and atherosclerotic risk.. The present study was designed to examine the effects of a short-term, rigorous diet and exercise intervention on blood pressure, hyperinsulinemia, and nitric oxide (NO) availability. Men (n=11) were placed on a low-fat, high-fiber diet combined with daily exercise for 45 to 60 minutes for 3 weeks. Pre- and post fasting blood was drawn for serum lipid, insulin, 8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)), and glucose measurements. Anthropometric parameters, blood pressure (BP), and 24-hour urinary NO metabolite excretion (NO(X)), a marker of NO bioavailability, were measured. Systolic (P<0.01) and diastolic BP (P<0.01) and 8-iso-PGF(2alpha) decreased (P<0.05), whereas urinary NO(X) increased (P<0.05). There was a significant reduction in fasting insulin (P<0.01) and a significant correlation between the decrease in serum insulin and the increase in urinary NO(X) (r2=0.68, P<0.05). All fasting lipids decreased significantly, and the total cholesterol to high-density lipoprotein cholesterol ratio improved. Although body weight and body mass index (P<0.01) decreased, obesity was still present and there were no correlations between the change in body mass index and the change in insulin, BP, or urinary NO(X).. This intervention resulted in dramatic improvements in BP, oxidative stress, NO availability, and the metabolic profile within 3 weeks, mitigating the risk for atherosclerosis progression and its clinical sequelae.

Topics: Adult; Aged; Arteriosclerosis; Blood Pressure; Body Mass Index; Body Weight; Combined Modality Therapy; Dinoprost; Exercise; F2-Isoprostanes; Humans; Hypertension; Insulin; Male; Middle Aged; Nitric Oxide; Oxidative Stress

Evidence exists to support the beneficial effects of superoxide dismutase on endothelial dysfunction induced by hyperglycemia in vitro. In vivo, however, studies of the effects of native superoxide dismutase preparations on the vascular complications accompanying diabetes are limited, and their therapeutic application potential has so far been disappointing. The objective of this study was to evaluate, for the first time in vivo, the effects of long-term administration of tempol, a stable superoxide dismutase-mimic compound, on diabetes-induced endothelial dysfunction in rats. Diabetes was induced by streptozotocin and rats were monitored for 8 weeks with or without treatment with tempol (100 mg/kg, s.c., b.i.d). Diabetic rats showed increased vascular levels of superoxide, which was accompanied by increased levels of the oxidative stress markers malondialdehyde and 8-epi-prostaglandin F(2alpha). In addition, the vasorelaxant as well as the cGMP-producing effects of acetylcholine and glyceryl trinitrate were reduced in diabetic rats. Treatment with tempol abolished not only the differences in the vascular content of superoxide, malondialdehyde and 8-epi-prostaglandin F(2alpha), but also the differences in the relaxation and cGMP responses of aortic rings to both acetylcholine and glyceryl trinitrate between control and diabetic rats. These results support the involvement of reactive oxygen species in mediation of hyperglycemia-induced endothelial dysfunction in vivo, and provide the rationale for potential utilization of stable superoxide dismutase-mimic nitroxides for the prevention of the vascular complications accompanying diabetes.

Topics: Acetylcholine; Animals; Antioxidants; Aorta; Blood Glucose; Body Weight; Cyclic GMP; Cyclic N-Oxides; Diabetes Mellitus, Experimental; Dinoprost; Dose-Response Relationship, Drug; Endothelium, Vascular; In Vitro Techniques; Male; Malondialdehyde; Rats; Rats, Sprague-Dawley; Spin Labels; Superoxides; Vasodilation; Vasodilator Agents

Although it is well known that dietary lipids affect the course of glomerulonephritis in rats and humans, the precise mechanisms involved have not been fully elucidated. The aim of this study was to investigate the effects of different types of dietary lipids (fish oil and vegetable oil) on daunomycin (DM)-induced nephropathy in mice fed on soybean oil (SO) or cod liver oil (CLO). Urinary protein excretion, serum albumin, creatinine, total cholesterol, and TG were measured, and glomerular histological changes were evaluated. Antioxidant enzymes were also measured, along with the levels of lipid peroxide, GSH, thromboxane (Tx) B2, and 6-keto prostaglandin F1alpha in renal cortical tissue. Dietary CLO significantly reduced urinary albumin excretion and ameliorated the histological changes induced by DM. The increase of tissue lipid peroxide levels seen in SO-fed mice was suppressed in CLO-fed mice, whereas CLO-fed mice showed higher GSH levels than SO-fed mice throughout the experiment. In addition, renal tissue GSH peroxidase activity was significantly higher at 72 h after DM injection in CLO-DM mice than in SO-DM mice. Both renal cortical TxB2 and 6-keto PGF1alpha levels were significantly lower in CLO-DM mice than in SO-DM mice. These results suggest that inhibition of oxidative damage by dietary CLO played an important role in the prevention of DM nephropathy in this mouse model. The effect of CLO was closely associated with the inhibition of Tx synthesis.

Topics: Albuminuria; Animals; Body Weight; Cod Liver Oil; Daunorubicin; Dietary Fats; Dinoprost; Glutathione; Kidney; Kidney Diseases; Lipid Peroxides; Male; Mice; Mice, Inbred Strains; Soybean Oil; Thromboxane B2

We have previously shown that the number of ovarian follicles <4 mm in diameter can be increased by enhanced dietary intake in heifers. This study investigated the effect of the same dietary treatment on superovulatory response. The estrous cycles of 24 mature Hereford x Friesian heifers were synchronized by a standard progesterone plus prostaglandin protocol. The animals were fed with either 100% (group M, n = 12) or 200% (group 2M, n = 12) maintenance requirements for a 3-week period. Starting from day 4 of the synchronized estrous cycle, all the animals were superovulated using a standard 4-day FSH regime followed by an injection of GnRH analogue (GnRHa) to induce ovulation. Rectal ultrasound scanning was carried out to assess ovarian follicular populations at the start of FSH treatment and on the day of GnRHa injection, and to determine the number of corpora lutea 5 days after GnRHa injection. The body weight (BW) and body condition score (BCS) were recorded weekly and plasma samples were collected throughout the experimental period. There were no differences in either BW or BCS between two groups at the start of the experiment. The BW and BCS were maintained during the experiment in the group M, whilst animals in the group 2M showed a non-significant (P > 0.05) increase in BW and BCS. Circulating concentrations of insulin were significantly (P < 0.01) higher in heifers from the group 2M throughout the controlled feeding period. The group 2M had significantly (P < 0.05) more follicles 2-4 mm in diameter at the start of FSH treatment and more (P < 0.01) follicles >9 mm in diameter on the day of GnRHa injection, when compared with the group M. Similarly, 5 days after GnRHa injection there were significantly (P < 0.01) more corpora lutea in the group 2M (18.1+/-2.2) than in the group M (10.6+/-3.0). In addition, plasma progesterone concentrations following GnRHa injection were significantly (P < 0.01) higher in heifers from the group 2M. In conclusion, these results confirm that increased dietary intake can enhance the recruitment of ovarian follicles in heifers. This treatment may provide a valuable approach to improving superovulatory response in cattle.

Topics: Animals; Body Composition; Body Weight; Buserelin; Cattle; Cloprostenol; Corpus Luteum; Diet; Dinoprost; Estrus Synchronization; Female; Follicle Stimulating Hormone; Insulin; Ovarian Follicle; Ovulation; Progesterone; Superovulation

The mechanisms underlying the development of hypertension in obesity are not yet fully understood. We recently reported the development of hypertension in a rat model of diet-induced obesity. When Sprague-Dawley rats (n=60) are fed a moderately high fat diet (32 kcal% fat) for 10 to 16 weeks, approximately half of them develop obesity (obesity-prone [OP] group) and mild hypertension (158+/-3.4 mm Hg systolic pressure), whereas the other half (obesity-resistant [OR] group) maintains a body weight equivalent to that of a low fat control group and is normotensive (135.8+/-3.8 mm Hg). We examined the potential role of oxidative stress in the development of hypertension in this model. Lipid peroxides measured as thiobarbituric acid-reactive substances showed a significant increase in the LDL fraction of OP rats (2.8+/-0.32 nmol malondialdehyde/mg protein) compared with OR and control rats (0.9+/-0.3 nmol malondialdehyde/mg protein). Also, aortic and kidney thiobarbituric acid-reactive substances showed a significant (3- and 5- fold) increase in OP rats after 16 weeks of diet. In addition, superoxide generation by aortic rings, measured by lucigenin luminescence, showed a 2-fold increase in the OP group compared with both the OR and control groups. In addition, free isoprostane excretion and nitrotyrosine in the kidney showed an increase in OP rats only. The urine and plasma nitrate/nitrite measured by the LDH method showed a 1.8-fold decrease in OP rats compared with OR rats. However, endothelial NO synthase expression in the kidney cortex and medulla assessed by reverse transcriptase-polymerase chain reaction showed a strong increase in the OP rats versus OR and control rats (endothelial NO synthase/beta-actin ratio 1.3+/-0.04 in OP rats versus 0.44+/-0.02 in OR rats), suggesting a possible shift toward superoxide production by the enzyme. Collectively, the data show a decreased NO bioavailability in OP animals that is due in part to the increased oxidative stress.

Topics: Animals; Aorta, Thoracic; Blood Pressure; Body Weight; Dietary Fats; Dinoprost; Disease Models, Animal; F2-Isoprostanes; Hyperlipidemias; Hypertension; Kidney Cortex; Kidney Medulla; Lipid Peroxides; Male; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Obesity; Oxidative Stress; Rats; Rats, Sprague-Dawley; Renin; Thiobarbituric Acid Reactive Substances

1. The effects of an oral daily dose (10 mg kg(-1)) of the flavonoid quercetin for 5 weeks in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) were analysed. 2. Quercetin induced a significant reduction in systolic (-18%), diastolic (-23%) and mean (-21%) arterial blood pressure and heart rate (-12%) in SHR but not in WKY rats. 3. The left ventricular weight index and the kidney weight index in vehicle-treated SHR were significantly greater than in control WKY and these parameters were significantly reduced in quercetin-treated SHR in parallel with the reduction in systolic blood pressure. 4. Quercetin had no effect on the vasodilator responses to sodium nitroprusside or to the vasoconstrictor responses to noradrenaline or KCl but enhanced the endothelium-dependent relaxation to acetylcholine (E(max)=58+/-5% vs 78+/-5%, P<0.01) in isolated aortae. 5. The 24 h urinary isoprostane F(2 alpha) excretion and the plasma malonyldialdehyde (MDA) levels in SHR rats were increased as compared to WKY rats. However, in quercetin-treated SHR rats both parameters were similar to those of vehicle-treated WKY. 6. These data demonstrate that quercetin reduces the elevated blood pressure, the cardiac and renal hypertrophy and the functional vascular changes in SHR rats without effect on WKY. These effects were associated with a reduced oxidant status due to the antioxidant properties of the drug.

Topics: Acetylcholine; Animals; Antioxidants; Aorta; Blood Pressure; Body Weight; Dinoprost; Endothelium, Vascular; Heart Rate; Heart Ventricles; Hypertension; In Vitro Techniques; Kidney; Male; Malondialdehyde; Nitroprusside; Norepinephrine; Organ Size; Oxidants; Potassium Chloride; Quercetin; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

Selenium and vitamin E deficiencies were studied as part of an evaluation of oxidant defenses in guinea pigs. Male guinea pigs (100-120 g) were fed a control diet (C) or the diet without selenium (0 Se), without vitamin E (0 E), or without either selenium or vitamin E (0 Se-0 E). Between d 30 and 35, 7 of 13 guinea pigs fed the 0 Se-0 E diet were euthanized because of severe weakness of their extremities. No guinea pigs in the other diet groups developed weakness. Guinea pigs from each group were killed on d 37. Selenium deficiency and vitamin E deficiency were verified by measurement of glutathione peroxidase and alpha-tocopherol. Creatine phophokinase (CPK) activity was greater than controls in both groups fed vitamin E-deficient diets, but the increase was greater in the 0 Se-0 E group than in the 0 E group. Muscle F(2)-isoprostanes were greater than controls in both groups fed vitamin E-deficient diets with the level in the 0 Se-0 E group greater than that in the 0 E group. Histologic muscle necrosis was severe in the 0 Se-0 E group, minimal in the 0 E group and absent from other groups. The diets used in this study induced selenium and vitamin E deficiencies in guinea pigs. The study demonstrates that combined selenium and vitamin E deficiency results in a fatal myopathy in guinea pigs that is associated with lipid peroxidation in the affected muscle. This nutritional myopathy is much more severe than the myopathy that occurs with vitamin E deficiency alone.

Topics: Animals; Body Weight; Creatine Kinase; Diet; Dinoprost; F2-Isoprostanes; Guinea Pigs; Liver; Male; Muscle, Skeletal; Muscular Diseases; Necrosis; Selenium; Survival Analysis; Vitamin E; Vitamin E Deficiency

This article describes a procedure for the quantitation of the isoprostane 15-F2t-IsoP (9a,11a,15S-trihydroxy-(8b)-prosta-5Z,13E-dien-1-oic acid [CAS#27415-26-5] formerly known as 8-epi-PGF2a or 8-iso-PGF2a, and also as iPF2a-III). We have combined features from several earlier methods for 15-F2t-IsoP and prostaglandins, and identified and modified those steps that may lead to poor recoveries. The resulting protocol is precise and reliable, and was validated by a blind time-course study of plasma levels in rats treated with 120 and 1200 mg CCl4/kg body weight. Plasma levels of 15-F2t-IsoP, as measured according to the procedure described above, are good indicators of acute oxidative stress as induced by CCl4. The precision of the measurements allows detection of elevated plasma 15-F2t-IsoP levels as long as 16 h after an acute exposure of 120 mg CCl4/kg body weight, and 2 h after an exposure of 1 mg CCl4/kg body weight. The results of this low-dose, pilot study suggest that this method has sufficient analytical precision to allow the detection of the small changes in plasma isoprostane levels, which result from chronic and/or lower-level exposures to agents causing oxidative stress.

Topics: Animals; Body Weight; Carbon Tetrachloride; Dinoprost; Dose-Response Relationship, Drug; Fatty Acids, Monounsaturated; Gas Chromatography-Mass Spectrometry; Hydrolysis; Male; Oxidative Stress; Pilot Projects; Rapeseed Oil; Rats; Rats, Inbred F344; Reproducibility of Results; Sensitivity and Specificity; Time Factors

Biochemical assessment of liver damage during ethanol-induced stress was done by measuring the activities of serum enzymes, viz., aspartate transaminase (AST) and alkaline phosphatase (ALP), which were significantly elevated in rats fed ethanol. Ethanol administration for a period of 60 days modifies the fatty acid composition, and the analysis of fatty acids showed that there was a significant increase in the concentrations of palmitic acid (16:0), stearic acid (18:0), and oleic acid (18:1) in liver, kidney, and brain, whereas the concentrations of palmitoleic (16:1) and arachidonic acid (20:4) were significantly decreased. The breakdown products of arachidonic acids (20:4), prostaglandins, were elevated. The antioxidants curcumin and N-acetylcysteine (NAC) decreased the activities of serum AST and ALP. Curcumin and NAC decreased the concentrations of fatty acids, viz., palmitic, stearic, and oleic acid, whereas arachidonic acid and palmitoleic acid were elevated. The prostaglandin concentrations were also decreased after curcumin and N-acetylcysteine treatment. Thus the present investigation shows that curcumin and N-acetylcysteine prevent the fatty acid changes produced by ethanol and also reduce the inflammatory response of ethanol by reducing the level of prostaglandins.

Topics: Acetylcysteine; Alprostadil; Animals; Antioxidants; Arachidonic Acid; Body Weight; Brain; Central Nervous System Depressants; Curcumin; Dinoprost; Dinoprostone; Enzyme Inhibitors; Ethanol; Fatty Acids; Kidney; Liver; Male; Phospholipids; Prostaglandin D2; Rats; Rats, Wistar

Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has recently been reported to have the antioxidative activity in vitro. However, it is still unclear whether chronic treatment with this drug actually leads to amelioration of the redox status in the body. In this study, we investigated the antioxidative effect of fluvastatin in vivo, using a vitamin E-deficient hamster model, an in vivo model of enhanced oxidative stress. After pre-treatment with a vitamin E-deficient diet for 2 months, fluvastatin, pravastatin or probucol was added to the diet for 1 month. Vitamin E deficiency caused a significant increase in the levels of plasma oxidative stress markers such as 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) and hydroperoxides. Furthermore, there was a significant increase in the oxidizability of plasma lipids in the vitamin E-deficient animals, indicating that the oxidative stress was increased in the circulation. Fluvastatin markedly depressed the above oxidative stress markers in plasma, and significantly decreased the oxidizability of plasma lipids without affecting their levels. Probucol, a reference antioxidant, also showed a similar effect while pravastatin, another HMG-CoA reductase inhibitor, showed only a weak improvement. We suggest that the treatment with fluvastatin leads to a reduction of oxidative stress in vivo, which is mainly derived from its antioxidative property rather than its lipid-lowering activity.

Topics: Animals; Body Weight; Chromatography, High Pressure Liquid; Cricetinae; Dinoprost; Eating; F2-Isoprostanes; Fatty Acids, Monounsaturated; Fluvastatin; Indoles; Lipid Peroxidation; Lipid Peroxides; Liver; Myocardium; Oxidation-Reduction; Oxidative Stress; Time Factors; Vitamin E; Vitamin E Deficiency

Lipid peroxidation is thought to be an important factor in the pathophysiology of a number of diseases and in the process of aging. We investigated the effects of supplementation with vitamin E on lipid peroxidation in rats. Both free radical-induced nonenzymatic- and cyclooxygenase-catalyzed enzymatic lipid peroxidation were investigated by measuring the levels of F(2)-isoprostanes (8-iso-PGF(2alpha)) and PGF(2alpha)-metabolite (15-K-DH-PGF(2alpha)), respectively, in blood, urine and liver. Samples were collected from control rats (n = 6) and from rats supplemented with vitamin E in the diet for 3 wk (n = 8, 20 g/kg diet of DL-alpha-tocopherol hydrogen succinate). Plasma alpha-tocopherol concentration and antioxidative capacity were greater in the vitamin E-supplemented rats than in the control rats (17.9 +/- 1.7 vs. 50.4 +/- 10.4 micromol/L, P < 0.001 and 181 +/- 6 vs. 275 +/- 27 micromol/L trolox equivalents, P < 0.001). Urine 8-iso-PGF(2alpha) tended to be lower in the vitamin E-supplemented rats (0.72 +/- 0.40 vs. 0.34 +/- 0.19 nmol/mmol creatinine, P = 0.056). Urine 15-K-DH-PGF(2alpha) was lower due to vitamin E supplementation (0.97 +/- 0.38 vs. 0.56 +/- 0. 21 nmol/mmol creatinine, P < 0.05), as was liver-free 8-iso-PGF(2alpha) concentration (0.47 +/- 0.11 vs. 0.18 +/- 0.04 nmol/g, P < 0.001). Supplementation with vitamin E did not affect plasma 8-iso-PGF(2alpha) or 15-K-DH-PGF(2alpha) concentrations, liver total 8-iso-PGF(2alpha) or plasma malondialdehyde levels. Thus, vitamin E supplementation reduced urine basal levels of biomarkers of both nonenzymatic and enzymatic lipid peroxidation. In liver, vitamin E reduced the basal level of free 8-iso-PGF(2alpha) but not total 8-iso-PGF(2alpha).

Topics: Animals; Body Weight; Chromatography, High Pressure Liquid; Diet; Dinoprost; F2-Isoprostanes; Lipid Peroxidation; Liver; Male; Malondialdehyde; Oxytocics; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Vasoconstrictor Agents; Vitamin E

An experiment was conducted to determine whether feeding rumen-protected fatty acids (FA) to postpartum heifers would increase plasma concentrations of linoleic acid and PGF2, metabolite (PGFM), shorten the interval from calving to first increase in plasma concentrations of progesterone (P4), and increase pregnancy rate relative to controls. Hereford x Angus heifers (346 kg) were assigned randomly to treatments containing either lipid or barley supplemented diets for the first 30 d postpartum. Lipid was .23 kg.heifer(-1).d(-1) of calcium salts of FA (CSFA; n = 20), and an isocaloric amount of barley served as the control (n = 19). Supplements, with .23 kg of barley as a vehicle, and a basal diet of meadow and alfalfa hays were pen fed to heifers (5/pen). Heifers were bled on alternate days (d1 to 30) and twice weekly (d 30 to 2 wk after first estrus) for RIA of plasma PGFM and P4, respectively. Weight percentage of major FA in plasma on d1 and 7 was determined with gas chromatography. First behavioral estrus was detected by use of intact bulls and confirmed by an increase in plasma P4. On d 7, but not d 1, plasma from heifers fed CSFA had altered proportions of major FA (P < .01), including an increase in linoleic acid compared with those of controls (29.1 vs 25.6% of total FA; SE = .75; P < .01). Analysis of variance of contrast variables revealed an effect of treatment on direction of change in PGFM from d 3 to 5 (P < .01). By d 7 and on d 9, plasma concentrations of PGFM were greater in heifers fed CSFA than in controls (P = .02 and P = .06, respectively). There was no difference in plasma concentration of PGFM between treatments on d 1, 3, 5, 11, 13, and 15 postpartum (P = .80, .17, .52, .82, .46, and .77, respectively). Days to first estrus with ovulation, pregnancy rate, and calving interval were not affected by treatments (P = .58, .52, and .24, respectively). Although supplemental lipid fed to primiparous beef heifers increased plasma levels of linoleic acid and production of PGFM in the early postpartum period, it did not improve the fertility of these heifers in the subsequent breeding season.

Topics: Animals; Body Weight; Cattle; Dietary Fats; Dinoprost; Fatty Acids; Female; Male; Postpartum Period; Pregnancy; Pregnancy Rate; Radioimmunoassay; Reproduction; Rumen

We examined the effects of undernutrition on lipid metabolism in reindeer (<1 year) during mid-winter and spring, with particular focus on the proportions of polyunsaturated fatty acids (PUFAs) in major serum lipids. The reindeer (n=8) were fed their winter feed, lichen, ad libitum for 5 weeks, followed by 40% restriction of energy for 8 weeks and refeeding to normal for 6 weeks. The concentrations of major serum lipids, cholesterol and phospholipids decreased significantly during the ad libitum period (by 50 and 44%, respectively). The proportion of major PUFA, linoleic acid in serum cholesteryl esters, decreased from 48.2 to 38.4% during the ad libitum period (P < 0.01), and to 29.2% during the restriction period (P < 0.001). The proportion of linoleic acid in phospholipids decreased from 27.9 to 15.6% during the ad libitum period (P < 0. 001), and to 13.0% during the restriction (P < 0.01). Also alpha-linolenic acid in the major lipids decreased significantly during the ad libitum and restriction periods. The decreases in the major lipids and linoleic acid were reversed during the refeeding. The control group (n=8) which was fed high-quality concentrates ad libitum gained weight most of the spring but showed similar although slower decreases in the major serum lipids and PUFAs than the lichen group. Our results indicate that feeding reindeer on lichen during winter leads to the retardation of growth and reductions in major serum lipids and their principal C18-PUFA proportions. The decreased proportions of the principal PUFAs most probably reflect their low dietary intake but may have been modified also by seasonal factors.

Topics: Animals; Blood Glucose; Body Weight; Cholesterol Esters; Diet; Dinoprost; Eating; Fatty Acids, Unsaturated; Lipids; Male; Nutrition Disorders; Reindeer; Seasons

Prepubertal F1 heifers (n = 246; from crossbred dams bred to either Hereford [H], Limousin [L], or Piedmontese [P] sires) were fed 1.9% (LF) or 4.4% (HF) dietary fat from 254+/-4 d of age until they reached puberty or the breeding season started. Safflower seeds (37% oil with 79% linoleic acid) were the added fat source. Blood samples and backfat thickness measurements were obtained from 60 randomly selected heifers representing the sire breeds and diets studied. In addition, five H-sired heifers from both diets were serially bled at 28-d intervals. Total gain, ADG, body condition score, and backfat thickness were affected by sire breed (P < 0.001) but not diet. Backfat thickness was affected (P < 0.01) by the diet x time on feed interaction. Diet did not affect pubertal age (P > 0.10) but tended (P = 0.08) to affect the percentage of heifers pubertal by the beginning of breeding (June 4). Sire breed effects on puberty age at beginning of breeding, percentage pubertal at the beginning of breeding, and puberty age during the entire study were all highly significant. The effect of the diet x sire breed interaction on percentage of heifers pubertal at beginning of breeding (P < 0.05) was 74.4 vs 76.3% in H-sired, 69.8 vs 60.5% in L-sired, and 76.2 vs 97.6% in P-sired heifers (LF vs HF, respectively). Number of AI services per pregnancy and final pregnancy percentage were not affected by diet or the diet x sire breed interaction. Diet affected progesterone (P < 0.05) and cholesterol (P < 0.001) concentrations, and sire breed tended to affect (P = 0.06) cholesterol concentrations. The effect of the diet x time on feed interaction on cholesterol concentrations was highly significant. There were no effects of diet or sample period on insulin or growth hormone concentrations in serially collected blood samples. We conclude that effects of supplemental dietary fat may be breed-dependent and hypothesize that a feeding period of approximately 60 d duration may be more appropriate than the 162 d used in this study.

Topics: Animal Feed; Animals; Body Weight; Cattle; Dietary Fats; Dietary Supplements; Dinoprost; Female; Genomic Imprinting; Growth Hormone; Insulin; Male; Pregnancy; Progesterone; Reproduction; Sexual Maturation

The objective of this study was to determine the effect of feeding strategies in cows that allowed BW loss followed by BW gain on the efficiency of feed utilization for calf production. The first treatment (H-H-H) was designed to maintain body condition score of mature cows at 5.5 from the second trimester until the subsequent breeding season. The second treatment (L-H-H) was designed such that cows lost body condition during the second trimester and regained it during the third trimester and were equal in weight and body condition scores at parturition to cows assigned to the H-H-H treatment. The third treatment (L-L-H) was designed such that cows lost body condition during the second trimester and gained body condition after 28 d of lactation so that they would be equal to the other two treatments at breeding. Forty-eight cows were assigned to each treatment. Total DMI over the entire study did not differ between the H-H-H and L-H-H treatments (P = 0.23), but intake on both were higher than the L-L-H treatment (P < 0.001). Calf birth weight of the H-H-H treatment did not differ (P = 0.43) from those of L-H-H, but both groups were greater than those of the L-L-H (P < or = 0.002) treatment. At 28 d of age, H-H-H (P = 0.008) and L-H-H (P = 0.007) calves weighed more than the L-L-H calves, but at 58 d of age there was no difference in calf BW among the treatments (P = 0.81). The percentage of cows that were diagnosed pregnant at weaning with their next calf did not differ (P = 0.71) among treatments. We interpret the results of this study to suggest that weight cycling in mature beef cows may be a viable management tool for decreasing food costs.

Topics: Animals; Birth Weight; Body Weight; Cattle; Dinoprost; Energy Intake; Female; Food Deprivation; Pregnancy; Pregnancy, Animal; Random Allocation; Time Factors

Recent work indicates that free radical-mediated lipid peroxidation takes place within the diaphragm on strenuous contraction. This phenomenon has only been demonstrated using fairly artificial experimental models and has not been studied during the type of sustained respiratory loading typically seen in patients with lung disease. The purpose of the present study was to measure the levels of several biochemical markers of protein oxidation (protein carbonyl levels) and lipid peroxidation (8-isoprostane, reduced glutathione, and oxidized glutathione levels) in diaphragms of rats subjected to chronic respiratory loading. Respiratory loading was accomplished by tracheal banding; groups of animals were loaded for 4, 8, or 12 days, and a group of sham-operated unloaded animals was used as controls. After loading, animals were killed, diaphragm contractility was assessed in vitro by using a portion of the excised diaphragm, and the remaining diaphragm and the soleus muscles were used for biochemical analysis. We found diminished force generation in diaphragms from all groups of banded animals compared with muscles from controls. For example, twitch force averaged 7.8 +/- 0.8 (SE) N/cm2 in unloaded animals and 4.0 +/- 0.4, 3.0 +/- 0.4, and 3.4 +/- 0.4 N/cm2 in animals loaded for 4, 8, and 12 days, respectively (P < 0.0001). Loading also elicited increases in diaphragmatic protein carbonyl concentrations (P < 0.001), and the time course of alterations in carbonyl levels paralleled loading-induced alterations in the diaphragm force-frequency relationship. Although loading was also associated with increases in diaphragmatic 8-isoprostane levels (P < 0.003) and reductions in diaphragm reduced glutathione levels (P < 0.003), the time course of changes in these latter parameters did not correspond to alterations in force. Soleus glutathione and carbonyl levels were not altered by banding. We speculate that respiratory loading-induced alterations in diaphragmatic force generation may be related to free radical-mediated protein oxidation, but not to free radical-induced lipid peroxidation.

Topics: Animals; Body Weight; Diaphragm; Dinoprost; F2-Isoprostanes; Glutathione; Glutathione Disulfide; Lipid Metabolism; Lipid Peroxidation; Muscle Contraction; Muscle Proteins; Muscle, Skeletal; Organ Size; Oxidative Stress; Rats; Time Factors

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Corpus Luteum; Dinoprost; Endometrium; Energy Metabolism; Female; Melatonin; Ovulation; Progesterone; Random Allocation; Sheep

We have concurrently investigated oxidant stress, glucose tolerance and glucose-stimulated insulin responses in the obese Zucker rat, a widely used model of insulin resistance. The plasma level of the lipid peroxidation product 8-epi-prostaglandin F2alpha, a sensitive in vivo marker of oxidant stress, was elevated approximately 5-fold in 13-week old obese relative to age-matched, insulin-sensitive lean Zucker rats. Supplementation of the diet with vitamin E (as (+)-alpha-tocopherol acetate, 0.5% w/w) for 4 weeks, reduced plasma 8-epi-prostaglandin F2alpha and concomitantly reversed glucose-stimulated hyperinsulinaemia in the obese Zucker rat without worsening glucose tolerance. We therefore provide evidence of oxidant stress, measured as elevated plasma 8-epi-prostaglandin F2alpha, for the first time in the obese Zucker rat which now provides a rationale for the beneficial effects of antioxidants on insulin action previously reported in this model of insulin resistance.

Topics: Animals; Blood Glucose; Body Weight; Dietary Supplements; Dinoprost; Hyperglycemia; Hyperinsulinism; Insulin; Insulin Resistance; Male; Obesity; Oxidative Stress; Rats; Rats, Zucker; Vitamin E

Effects of lipid infusion into postpartum (PP) beef heifers on plasma concentrations of linoleic acid and prostaglandin (PG) F(2alpha) metabolite (PGFM), days to first estrus, and subsequent pregnancy rate were examined. Treatments (n = 5 per group) of 1 L intralipid (20% soybean oil; IL), 1 L 50% dextrose (DEXT; isocaloric to IL), 0.5 L intralipid (0.5 IL), and 1 L physiological saline (SAL) were infused i.v. over 4 h on each of Days 7 through 11 PP. Capacity of the uterus to produce PG was evaluated after i.v. injection of 150 IU of oxytocin (OT) to IL- and DEXT-treated heifers Day 12 PP. Change in plasma concentrations of PGFM from 0 to 4 h was greater for IL-treated heifers than for heifers given other treatments on Day 7 (P = 0.04) and on Day 11 (P = 0.01), but not on Day 9 (P>0.10). Plasma linoleic acid on Day 11 and OT-induced release of PGFM on Day 12 were greater in IL-treated heifers compared with DEXT-treated heifers (P<0.06 and P = 0.01, respectively). There were no significant differences among treatments for mean days to first estrus or pregnancy rate. Infusion of lipid increased systemic concentrations of linoleic acid and increased the capacity of PP heifers to produce uterine PGF(2alpha) as indicated by plasma PGFM concentration after OT injection.

Topics: Animals; Behavior, Animal; Birth Weight; Body Weight; Cattle; Dinoprost; Eating; Estrus; Fat Emulsions, Intravenous; Fatty Acids, Nonesterified; Female; Fertility; Linoleic Acid; Ovary; Postpartum Period; Pregnancy; Prostaglandins

Forty pluriparous (M) and 20 primiparous (P) suckled Brahman cows were used to evaluate the effect of aspirin and parity on plasma 13,14-dihydro-15-keto-prostaglandin F2alpha (PGFM) and progesterone (P4) concentrations and some reproductive parameters. On Day 7 after calving (PP), the cows were allocated within parity into 2 groups: the aspirin group received concentrate containing aspirin at a rate of 100 mg/kg of body weight every 12 h until Day 13 PP; and the control received concentrate every 12 h for the same interval. Blood samples were collected after first and last aspirin feeding and daily from Day 1 PP to Day 6 PP and from Day 14 PP to Day 21 PP, twice daily from Day 7 PP to Day 13 PP, and weekly until first non-return to estrus. Plasma salicylate concentrations in the aspirin group cows were affected by parity (P < 0.01) and time after feeding (P < 0.0001). P cows showed higher plasma salicylate concentrations with a later peak and slower decrease than M cows. Aspirin-treated P cows had longer PP intervals than either control P, control M, or aspirin-treated M cows. Cows receiving aspirin had a lower pregnancy rate, an increased incidence of abnormal estrous cycles, and a decline in the presence of corpora lutea after estrus. Cows that formed a corpora lutea and had received aspirin had higher P4 release between Day 6 and 14 after estrus. Aspirin-treated cows that did not form corpora lutea had lower P4 release between Days 9 and 14 after estrus. A treatment by parity interaction affected mean PGFM proportions (P < 0.01) during the treatment period. Aspirin-fed P cows increased PGFM release as measured by mean proportion of Day 6 PP values. Aspirin-fed M cows showed a decrease in mean PGFM proportions. Aspirin feeding during the early PP showed different effects on some reproductive parameters in P and M Brahman cows, indicating differences in PP physiology between parities.

Topics: Animals; Aspirin; Body Weight; Cattle; Dinoprost; Estrus; Female; Parity; Postpartum Period; Pregnancy; Pregnancy, Animal; Progesterone; Salicylates; Sex Factors

Oxidative DNA damage is emerging as an biomarker of effect in studies assessing the health risks of occupational chemicals. Trichloroethylene (TCE) and perchloroethylene (PERC) are used in the dry cleaning industry and their metabolism can produce reactive oxygen compounds. The present study examined the potential for TCE and PERC to induce oxidative DNA damage in rats that was detectable as increased urinary excretion of 8-hydroxydeoxyguanosine (8OHdG). Thiobarbaturic acid reactive substances (TBARS) and 8-epiprostaglandin F2alpha (8epiPGF) were also measured as biomarkers of increased oxidative stress. Male Fischer rats were administered a single i.p. injection of 0, 100, 500, or 1000 mg/kg of PERC or TCE. Control rats received only vehicle (1:4 v/v of Alkamuls/water). A positive control group received 100 mg/kg 2-nitropropane (2NP). Rats were sacrificed 24 h after dosing. In rats receiving 2NP or TCE but not PERC, TBARS and the 8OHdG/dG ratios were significantly elevated in liver. Lymphocyte 8OHdG/dG was not affected significantly by 2NP, TCE or PERC. In rats receiving 2NP, urinary excretion of 8OHdG and 8epiPGF2 were significantly increased. In rats receiving TCE or PERC, significant increases in 8epiPGF2 or 8OHdG were not evident. Results indicate that a single high dose of TCE, but not PERC, can induce an increase in oxidative DNA damage in rat liver. However, the usefulness of 8OHdG as a biomarker of TCE-induced oxidative DNA damage is questionable.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Body Weight; Chromatography, High Pressure Liquid; Creatinine; Deoxyguanosine; Dinoprost; DNA Damage; Electrochemistry; Enzyme-Linked Immunosorbent Assay; Injections, Intraperitoneal; Kidney; Liver; Lymphocytes; Male; Organ Size; Oxidative Stress; Rats; Rats, Inbred F344; Tetrachloroethylene; Trichloroethylene; Urine

Oxidative stress and dyslipidaemia are key features of diabetes mellitus and may be involved in mediating the vascular endothelial dysfunction associated with this disease. The aim of this study was to examine the effect of dietary lipid-lowering and antioxidant agents on vascular endothelial function and oxidative stress. Diabetic male Sprague-Dawley rats (i.v. streptozotocin, 45 mg/kg) were fed for 4 weeks on a standard diet or on a diet supplemented with either the lipid-lowering antioxidant probucol (1% w/w in diet) or the 3-hydroxy 3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitor simvastatin (0.01% w/w in diet). Responses to noradrenaline, acetylcholine, and sodium nitroprusside were assessed in small mesenteric arteries (mean internal diameter 300+/-5 microm, n = 80) mounted on a small vessel myograph. Plasma concentrations of total cholesterol and triglycerides were significantly raised in standard-fed diabetic rats and significantly reduced in probucol and simvastatin-fed diabetic rats 8-epi-prostaglandin (PG)F2alpha, an indicator of oxidative stress, was raised in liver and aorta from diabetic rats compared to controls. Probucol supplementation reduced 8-epi-PGF2alpha in aorta and liver of diabetic rats but increased 8-epi-PGF2alpha content in plasma and aorta from control animals. The abnormal relaxation to acetylcholine in arteries from the diabetic rats (pEC550 diabetic 6.763+/-0.172 vs control 7.541+/-0.175; p < 0.05) was not improved by probucol or simvastatin. These data, therefore, do not support a role for oxidative stress or dyslipidaemia in mediating the impaired ACh-induced endothelium-dependent relaxation of small mesenteric arteries from the streptozotocin-diabetic rat.

Topics: Animals; Antioxidants; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diet; Dinoprost; Eating; Endothelium, Vascular; F2-Isoprostanes; Hypolipidemic Agents; Lipid Peroxidation; Lipids; Male; Mesenteric Arteries; Muscle Relaxation; Oxidative Stress; Probucol; Rats; Rats, Sprague-Dawley; Simvastatin; Tissue Distribution

Chronic hypoxia is associated with altered pulmonary vasoreactivity, and it has been suggested that an increased response to voltage-dependent vasodilators may relate to enhanced Ca++ entry via voltage-dependent channels, secondary to depolarization. Few studies have been performed on small pulmonary arteries, and it is unknown whether they are depolarized after chronic hypoxia. We examined the resting membrane potential, and the actions of voltage-dependent (verapamil, levcromakalim) and -independent (isoproterenol, forskolin, papaverine) vasodilators in small ( approximately 300 microm internal diameter) pulmonary arteries from chronically hypoxic rats. The resting membrane potential was more positive in arteries after chronic hypoxia (control: -60 +/- 0.5 mV; hypoxic: -54.4 +/- 1.1 mV; P < .01), and this was reflected by a shift to the left of the response curves for K+ and 4-aminopyridine. In arteries constricted with prostaglandin F2alpha the response to verapamil and levcromakalim was increased after chronic hypoxia, although maximum prostaglandin F2alpha-induced tension was unchanged, which implies a reduction in voltage-independent constrictor mechanisms. Although vasorelaxation to isoproterenol was depressed in arteries from hypoxic rats, forskolin-induced relaxation was enhanced substantially, and because the response to the phosphodiesterase inhibitor papaverine was unchanged, we suggest that this reflects an up-regulation of adenylate cyclase. In conclusion, chronic hypoxia resulted in a significant depolarization in small pulmonary arteries, but this may explain only partly the increased efficacy of voltage-dependent vasodilators. Whether the reduction in voltage-independent constrictor mechanisms is related to the apparent up-regulation of adenylate cyclase remains to be elucidated.

Topics: Animals; Body Weight; Cromakalim; Dinoprost; Dose-Response Relationship, Drug; Heart Ventricles; Hematocrit; Hypoxia; Isoproterenol; Male; Membrane Potentials; Papaverine; Potassium Channel Blockers; Pulmonary Artery; Rats; Rats, Wistar; Vasodilation; Vasodilator Agents; Verapamil

Plasma concentrations of progesterone, oestradiol-17beta, oestrone, oestrone sulphate and PGFM have been measured daily during the first peri-partum period of 45 Hereford x Friesian heifers bred at 11 months of age. Anatomical measurements of dam and calf were also recorded. Twelve of the calvings were scored easy, 33 difficult. Each of five models (fitted by linear logistic regression) relating difficulty of calving to the hormonal and anatomical measurements, predicts with at least 94% accuracy the calving score (easy or difficult) among the calvings. The models predict that increases of progesterone concentration on the day before calving, of oestrone sulphate concentration on the day after calving and of heifer heart girth decrease the odds of difficult calving, whereas increases of heifer body length and of calf head circumference increase the odds of difficult calving.

Topics: Animal Feed; Animals; Animals, Newborn; Body Weight; Cattle; Cattle Diseases; Dinoprost; Dystocia; Estradiol; Estrogens; Estrogens, Conjugated (USP); Estrone; Female; Insemination, Artificial; Labor, Obstetric; Logistic Models; Male; Multivariate Analysis; Numerical Analysis, Computer-Assisted; Pregnancy; Progesterone; Radioimmunoassay

The response to Claviceps purpurea sclerotia administration in pregnant goats was examined in terms of changes in the levels of plasma hormones, the development of pregnancy and kid production. Six treated goats were each given 15 mg milled sclerotia (i.e. 0.105 mg ergotamine) per kilogram live weight twice daily via a stomach tube from days 98 +/- 2 to 107 +/- 2 of gestation. Seven control goats were given water twice daily via a stomach tube during the same period of gestation. The goats were observed for clinical signs of disease, rectal temperatures and live weights were recorded and the condition of the foetuses was monitored by real-time ultrasonography. All control goats delivered live kids. In the treated group two goats aborted 33 and 47 days, respectively, after the start of the administration period, two goats each delivered one normal and one weak kid, and the two remaining goats delivered apparently normal kids. All six treated goats became depressed and had poor appetite during the period of sclerotia administration. Rectal temperatures were significantly increased and live weight changes significantly decreased in the animals in the treated group compared to the control group during the period of C. purpurea administration. Ultrasound examination revealed that foetal deaths occurred between 1 and 42 days before abortion or birth. The appearance of the aborted foetuses varied from fresh to mummified, depending on the number of days between foetal death and expulsion. Microbiological and serological investigations revealed no infectious causes of reproductive failure. The level of 15-ketodihydro-PGF2 alpha was high in goats that aborted following administration of C. purpurea compared with the level in control goats. The oestrone sulphate level did not increase before abortion in the treated goats as in the controls before parturition. There were also changes in these hormones in the four treated goats that delivered live kids, but the changes were considerably smaller. These findings indicate that the endocrine foetal-placental function was disturbed, probably due to injury caused by the C. purpurea toxin ergotamine in the placenta and foetus.

Topics: Abortion, Veterinary; Adrenergic alpha-Agonists; Animals; Body Weight; Claviceps; Dinoprost; Endocrine Glands; Enzyme-Linked Immunosorbent Assay; Ergotamine; Estrone; Female; Fetal Death; Goats; Heart Rate, Fetal; Placenta; Pregnancy; Pregnancy Outcome; Progesterone; Toxoplasma; Toxoplasmosis, Animal

The effects of fasting for 4 days on the isometric developed tension (IDT) and on the metabolism of labelled glucose and arachidonic acid in uteri from intact and spayed (25 days) rats, were explored. Starvation produces a fall in the contractile activity of intact rats, while in ovariectomized ones, no differences can be seen with respect to their controls. Fasting produces a fall in the glucose metabolism of both intact and ovariectomized rats, being more noticeable in the former group. Indomethacin (5 x 10(-6) M) increases the metabolism of labelled glucose in all experimental groups, significantly. The metabolism of exogenous arachidonic acid into different eicosanoids, PGE2, PGF2 alpha, 6-keto-F1 alpha and TXB2, shows that total food deprivation diminishes significantly the production of PGE2 in intact rats. In contrast, in ovariectomized starved rats, PGE2 increases markedly. The rest of the metabolites studied are not influenced by fasting. These results show that the effects of fasting on the contractile activity and on the release of some metabolites from arachidonic acid by the uteri isolated from intact rats are not seen in ovariectomized animals.

Topics: 6-Ketoprostaglandin F1 alpha; Alprostadil; Animals; Arachidonic Acid; Body Weight; Carbon Dioxide; Dinoprost; Fasting; Female; Glucose; Indomethacin; Isometric Contraction; Ovariectomy; Rats; Thromboxane B2; Uterine Contraction; Uterus

The objective of this study was to evaluate the timing of follicular waves in cows treated with bovine somatotropin (bST) by measuring ovarian responses to a luteolytic dose of PGF 2 alpha on d 12 of the estrous cycle. Thirty lactating cows (26 Holstein and 4 Guernsey) were assigned to receive bST (500 mg; n = 18) or saline (control; 1.5 ml; n = 12) every 14 d for three injection cycles. On d 12 of a synchronized estrous cycle, cows were injected with PGF 2 alpha to induce luteolysis. Following PGF 2 alpha, 9 cows ovulated from the dominant follicle during the first follicular wave (4 cows treated with bST and 5 control cows), and 14 cows ovulated from the dominant follicle during the second follicular wave (8 cows treated with bST and 6 control cows). Of the cows that ovulated during the second follicular wave, cows treated with bST had more class 3 follicles (> or = 10 mm) than did control cows. Concentrations of estradiol rose earlier after PGF 2 alpha injection in cows treated with bST than in control cows. This rise in estradiol was parallel to the development of dominant follicles. Serum concentrations of FSH were decreased in cows treated with bST. During the first and second estruses, equivalent numbers of cows treated with bST and control cows ovulated, but fewer cows treated with bST expressed estrus. These results are consistent with the hypothesis that cows treated with bST have reduced FSH, a faster turnover of dominant follicles, and differences in the timing of follicular waves. Treatment of cows with bST also increased the incidence of undetected estrus.

Topics: Animals; Body Composition; Body Weight; Cattle; Corpus Luteum; Dinoprost; Estradiol; Estrus; Female; Follicle Stimulating Hormone; Growth Hormone; Lactation; Ovarian Follicle; Ovulation; Pregnancy; Progesterone

1. The pulmonary vasculature is normally in a low resting state of tone. It has been hypothesized that this basal tone is actively maintained by the continuous release of a vasodilator in the resting state. However, evidence for basal release of nitric oxide (NO) is inconclusive. 2. We studied the release of NO in arteries from the pulmonary circulation of male Wistar-Kyoto rats by examining the effects of the L-arginine analogue NG-nitro-L-arginine methyl ester (L-NAME) on resting pulmonary arteries and on vessels pre-contracted with prostaglandin F2(alpha) (PGF2 alpha). 3. Rats (n = 21) were killed by an overdose with pentobarbitone. Pulmonary arteries were dissected (mean internal diameter 459 +/- 11 microns) and mounted in a small vessel wire myograph. Resting tensions were to set to stimulate transmural pressures of 17.5 mmHg. 4. L-NAME (100 microM) was found to produce a contraction of 0.64 +/- 0.09 mN mm-1 in resting pulmonary arteries when added alone to the myograph bath. This contraction was not produced following removal of the endothelium. Vessel contraction to PGF(2 alpha) (100 microM) was found to be significantly greater when carried out in the presence of L-NAME (100 microM) -1.37 +/- 0.15 mN mm-1 compared with 1.96 +/- 0.17 mN mm-1. Dilation following acetylcholine (ACh) (1 microM) was abolished in the presence of L-NAME (100 microM). 5. Rat pulmonary artery contraction in response to the addition of L-NAME and the absence of contraction upon removal of the endothelium provides supportive evidence of the active release of nitric oxide for the maintenance of resting tone.

Topics: Animals; Body Weight; Dinoprost; Endothelium, Vascular; Enzyme Inhibitors; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth, Vascular; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Pulmonary Artery; Rats; Rats, Inbred WKY; Vasoconstriction

To investigate the involvement of (n-6) essential fatty acids, such as linoleic acid [18:2(n-6)] or gamma-linolenic acid [18:3(n-6)], and of prostaglandins on liver lipid accumulation in Japanese quail.. Effects of graded amounts of aspirin, which inhibits prostaglandin synthesis, on liver weight were determined in experiment 1. Experiment 2 was designed to clarify the effect of dietary essential fatty acid sources and inhibition of prostaglandin synthesis on the liver fat and fatty acid profile.. Female Japanese quail.. In experiment 1, from 1 to 3 weeks of age, birds were fed ad libitum the essential fatty acids-free or linoleic acid-adequate (2%) diets with graded amounts of aspirin (0, 0.1, 0.2, and 0.4%). In experiment 2, from 1 to 4 weeks of age, birds were fed the same amount of essential fatty acids-free, linoleic acid-adequate, or gamma-linolenic acid (0.4%) diets with (0.2%) or without aspirin.. In experiment 1, in groups given the essential fatty acids-free diet, liver weight increased with an increase in dietary aspirin concentration. In experiment 2, gamma-linolenic acid completely prevented liver triacylglycerol and cholesterol accumulation induced by the essential fatty acids-free diet. Aspirin treatment significantly lowered plasma prostaglandin F2 alpha concentration, but did not affect liver lipid concentrations. In groups fed the essential fatty acids-free diets, however, aspirin treatment increased liver weight and liver triacylglycerol concentration by 20 and 40%, respectively.. gamma-Linolenic acid or its metabolites, but not linoleic acid itself, are important factors in reducing fatty liver in Japanese quail with the essential fatty acids-deficient condition.

Topics: Animals; Aspirin; Body Weight; Coturnix; Dietary Fats; Dinoprost; Fatty Acids, Essential; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Linoleic Acid; Linoleic Acids; Lipid Metabolism; Liver; Organ Size; Prostaglandins

We have investigated the modulatory effect of dietary perilla oil which is rich in the n-3 polyunsaturated fatty acid, alpha-linolenic acid, on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats. Animals were given three weekly subcutaneous injections of AOM (15 mg/kg body weight) to induce ACE. The rats were fed a basal diet containing either 12% olive oil, 12% safflower oil, 12% perilla oil, 6% perilla oil plus 6% olive oil, or 3% perilla oil plus 9% olive oil for 5 weeks, starting 1 week before the first dosing of AOM. All rats were sacrificed 2 weeks after the last AOM injection. The amount of food consumed and body weight gain were identical among every dietary group. The frequency of ACF was significantly lower in the rats fed 12% perilla oil than in those fed 12% olive oil or 12% safflower oil (P < 0.01 and P < 0.05, respectively). The suppressive effect of perilla oil was dose-dependent, as the number of ACF was 20.7, 40.7 and 47.4% of those of the 12% olive oil-fed controls in rats fed 12% perilla oil, 6% perilla oil plus 6% olive oil and 3% perilla oil plus 9% olive oil, respectively. Perilla oil significantly reduced ras expression as well as the AgNORs count (cell proliferation biomarkers) in the colonic mucosa, as compared with olive oil or safflower oil (P < 0.01, respectively). Marked increases in n-3 polyunsaturated fatty acids in membrane phospholipid fractions and decreased PGE2 levels were observed in colonic mucosa of perilla oil-fed rats. These results suggest that perilla oil, even in small amounts, suppresses the development of aberrant crypt foci, and is therefore a possible preventive agent in the early stage of colon carcinogenesis.

Topics: alpha-Linolenic Acid; Animals; Anticarcinogenic Agents; Azoxymethane; Body Weight; Carcinogens; Cell Division; Colon; Colonic Neoplasms; Dinoprost; Dose-Response Relationship, Drug; Eating; Fatty Acids, Omega-3; Intestinal Mucosa; Male; Nucleolus Organizer Region; Phospholipids; Plant Oils; Precancerous Conditions; Rats; Rats, Inbred F344; Silver Staining

We investigated differences in maternal plasma and trophoblast prostaglandin metabolism associated with preterm births. Tissue prostaglandins (PGs) E2 and F2 alpha and the stable plasma PGF2 alpha metabolite, 13,14-dihydro-15-keto-PGF2 alpha, were measured in preterm (< 37 weeks) and term (< or = 37 weeks) births. Amnion PGE2 in preterm (106.1 +/- 15.7 ng/g wet weight tissue; x +/- SEM; n = 37) was lower than in term (176.6 +/- 22.7 ng/g wet weight; x +/- SEM; n = 34, P < 0.02). Placenta PGE2 was lower in preterm (34.7 +/- 19.7 ng/g wet weight; x +/- SEM) than in term (103.3 +/- 28.0 ng/g wet weight; x +/- SEM, P < 0.04). Preterm PGF2 alpha was consistently lower in the amnion (106.8 +/- 17.5 ng/g wet weight) and placenta (102.5 +/- 8.7 ng/g wet weight) than in term amnion (188.2 +/- 24.8 ng/g wet weight; P < 0.01) and placenta (128.9 +/- 7.8 ng/g wet weight; P < 0.03). Chorionic PGE2 and plasma PGF2 alpha metabolite followed this trend but did not reach significance. These findings suggest qualitative and quantitative differences in maternal and trophoblast eicosanoid metabolism between term and preterm parturition.

Topics: Adult; Age Factors; Amnion; Birth Weight; Body Weight; Chorion; Dinoprost; Dinoprostone; Embryo, Mammalian; Female; Gestational Age; Humans; Infant, Newborn; Labor, Obstetric; Obstetric Labor, Premature; Placenta; Pregnancy; Prostaglandins

The effect of excess dietary urea on ovulation and early embryo development of sheep was studied. Thirty Border Leicester x Scottish Black face ewes randomly assigned to three treatments were given a basal control diet (C) which met energy requirements for body weight maintenance. Other treatments were basal diet plus 24 g of urea/day (low urea, L) or plus 48 g (high urea, H)/day. The reproductive cycles of the ewes were synchronized using a single injection of prostaglandin (PGF2 alpha) and progesterone by an intravaginal controlled internal drug release (CIDR) device for 12 days. Ovulation was induced by the use of pregnant mare serum gonadotrophin (PMSG). Ewes were inseminated approximately 52 hours after CIDR device removal using a laparoscopic technique. Embryos were recovered at Day 4 or Day 11 after insemination from half of the ewes from each treatment group. There were no significant differences in ovulation rates among the three groups. The embryo recovery rates were not affected by day of recovery. At embryo recovery on Day 4, 7/13 in C, 3/6 in L and 0/7 in H embryos were morulae. After 72 hours of in vitro culture 6/10 in C, 2/3 in L and 0/4 in H embryos developed to the blastocyst stage. Pregnancies sustained were C 6/8, L 5/7 and H 1/3 of the autotransfers. Throughout the experiment plasma urea levels were significantly affected by diet (p < 0.01). Plasma ammonia levels in the H group were significantly higher than those in the C and L groups (p < 0.05) for 4 hours after each feed. There was no treatment effect on plasma progesterone concentration. The luteinizing hormone (LH) surge onset time and amplitude were not correlated to ovulation rate and were not affected by treatment. It is concluded that high circulating concentrations of plasma urea and ammonia have an adverse effect on early embryo development. This effect was independent of any alterations in progesterone and LH concentrations.

Topics: Ammonia; Animals; Body Weight; Diet; Dinoprost; Dose-Response Relationship, Drug; Embryonic and Fetal Development; Estrus Synchronization; Female; Gonadotropins, Equine; In Vitro Techniques; Laparoscopy; Luteinizing Hormone; Ovulation; Pregnancy; Progesterone; Random Allocation; Sheep; Time Factors; Urea

To determine the effects of active immunization against prostaglandin F2 alpha (PGF) on estrous activity and performance traits of beef heifers, 50 14-mo-old cyclic heifers (358 +/- 3.3 kg) were assigned to two treatments (n = 25 per treatment): 1) heifers (controls) given 3.3 mg of human serum albumin (HSA) on d 0 (primary) and 27 (booster), and 2) heifers (PGF-immunized) given 3.3 mg of PGF-HSA on d 0 and 27. The adjuvant was DEAE-dextran, and the duration of the experiment was 167 d. Plasma progesterone concentrations (every 3 to 4 d) were used to monitor corpus luteum (CL) presence; PGF antibody titers were determined every 2 wk. Heifers were checked twice daily for estrous behavior and were weighed every 2 wk. Data were analyzed using ANOVA. Antibody titers for PGF-immunized heifers increased to a peak (43 +/- 2.9% binding at a plasma dilution of 1:1,250) on d 55 +/- 4.6. Antibody titers were greater (P = .02) in PGF-immunized than in control heifers by d 15 and remained elevated (P < or = .001) throughout the experiment. Twenty-four of 25 PGF-immunized heifers formed persistent CL with a mean duration of 129 +/- 6.4 d. The mean number of estrous period per heifer were less for PGF-immunized (1.5 +/- .27) than for control heifers (7.0 +/- .32). Mean daily live weight gain of the PGF-immunized heifers was decreased (P < .05; .75 +/- .024 kg) compared with that of controls (.83 +/- .014 kg), largely due to a 31.5% decrease during the 28-d period after booster.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Antibody Formation; Behavior, Animal; Body Weight; Cattle; Dinoprost; Estrus; Extremities; Female; Immunization, Secondary; Ovary; Progesterone; Random Allocation; Serum Albumin; Vaccination; Weight Gain

Brahman cows were used to evaluate the effects of postpartum nutrition and suckling on reproductive and calf performance. Cows received high or low TDN and once-daily or unrestricted suckling. High TDN (H; 111% of NRC recommendation) cows received a 75% corn: 25% soybean meal diet. Low TDN (L; 93% of NRC recommendation) cows received no concentrates. Once-daily suckled (restricted, R) cows nursed calves for 30 min/d starting at d 21 after calving. In the unrestricted (U) suckling groups, calves had continuous access to cows. By 2 wk of suckling restriction, more (P < .01) R than U cows had progesterone concentrations of > or = .7 ng/mL (55 vs 0%) and more (P < .05) HR than LR cows had progesterone concentrations > or = .7 ng/mL (70 vs 40%). All groups had increases in progesterone and 13,14-dihydro-15-keto-prostaglandin F2 alpha before estrus. The interval to first estrus was shorter (P < .01) for R than for U cows (42 vs 65 d). By d 42 postpartum, more (P < .01) R than U cows exhibited estrus (67 vs 0%), and more (P < .05) HR than LR cows exhibited estrus (89 vs 44%). Calving interval was shorter (P < .01) for R than for U cows (361 vs 395 d). Initial ADG were lower (P < .01) for R than for U calves (.02 vs .69 kg), but weaning weights were similar. Once-daily suckling permitted ovarian activity, hastened return to estrus, and reduced calving interval without reducing weaning weights. Increased postpartum energy intake enhanced the response to restricted suckling.

Topics: Anestrus; Animal Nutritional Physiological Phenomena; Animals; Body Weight; Cattle; Dinoprost; Female; Fertility; Lactation; Male; Parity; Pregnancy; Progesterone; Random Allocation

To study the changes of endothelium-dependent and -independent relaxation in structurally remodeled pulmonary arteries with hypoxic pulmonary hypertension and their reversibility during recovery in room air, rats were exposed to hypobaric hypoxia (air at 380 mmHg) for 10 days and then allowed to recover in room air for 3, 14, 28, or 56 days. Relaxation by acetylcholine, sodium nitroprusside (SNP), and isoproterenol was depressed in large- and small-conduit pulmonary arterial rings from rats exposed to 10 days of hypoxia. The relaxant response to isoproterenol and SNP was normalized completely after 3 and 28 days of recovery, respectively. The relaxation by acetylcholine was still impaired at high concentrations after 56 days. A cyclooxygenase inhibitor, indomethacin, enhanced relaxation by acetylcholine of rings from experimental rats but not from control rats. Endothelium-denuded rings showed no difference in the response to acetylcholine between control and experimental rats. In conclusion, the impaired response to acetylcholine may be related to acetylcholine-induced, cyclooxygenase-dependent production of a vasoconstrictor by endothelial cells and to depressed smooth muscle response to nitric oxide (NO). During recovery, the NO-induced guanosine 3',5'-cyclic monophosphate-dependent dilation returned to normal. However, the release of cyclooxygenase-dependent production of a vasoconstrictor may persist even after 56 days of recovery.

Topics: Animals; Body Weight; Dinoprost; Endothelium, Vascular; Hypertension; Hypertrophy, Right Ventricular; Hypoxia; Male; Nitric Oxide; Potassium Chloride; Pulmonary Artery; Rats; Rats, Wistar; Vasodilator Agents

Data on the effect of vitamin E and selenium deficiency on lipid peroxidation in vivo have been limited. F2-isoprostanes are novel prostanoids that, free in plasma and esterified to phospholipids in tissues, are markers of lipid peroxidation in vivo. To address the importance of vitamin E and selenium in defense against lipid peroxidation in vivo, we determined F2-isoprostane concentrations in the plasma and organs of rats fed diets deficient in one or both nutrients. Weanling rats were fed a vitamin E- and selenium-deficient diet for 12 wk and then divided into four groups. One group continued to receive the doubly deficient diet, and the other three groups were fed the diet supplemented with vitamin E, selenium or both nutrients (control diet) for 4 wk. Plasma F2-isoprostanes in rats fed the doubly deficient diet were 5.2-fold higher than in animals changed to a control diet. In addition, there were significant differences in liver, lung, kidney, heart and skeletal muscle phospholipid-esterified F2-isoprostanes between these two groups. Lesser increases were noted in the group fed the vitamin E-deficient diet. Selenium deficiency alone was not associated with greater lipid peroxidation. Lipid peroxidation occurs in tissues of rats fed a vitamin E-deficient diet and is increased by concomitant selenium deficiency.

Topics: Animals; Body Weight; Chromatography, Gas; Diet; Dinoprost; Lipid Peroxidation; Liver; Nutritional Status; Pilot Projects; Rats; Rats, Sprague-Dawley; Selenium; Vitamin E; Vitamin E Deficiency

Post-ischemic metabolism of arachidonic acid by cyclooxygenase results in the elaboration of numerous eicosanoids and in the generation of free radicals. Accordingly, the effect of cyclooxygenase inhibition by ibuprofen on post-ischemic eicosanoid production and delayed neuronal death was evaluated in Wistar-Kyoto rats subjected to incomplete forebrain ischemia. In control (C) and ibuprofen-treated groups (n = 5 each), pre- and post-ischemic eicosanoid production in the caudate nucleus (CN) and dorsal hippocampus (HPC) were evaluated by microdialysis. The ibuprofen-treated animals were given ibuprofen, 15 mg/kg i.v., prior to insertion of microdialysis probes. Forebrain ischemia was induced by bilateral carotid artery occlusion (BCAO) for 10 min with simultaneous hypotension to 35 Torr. The concentrations of thromboxane B2 (TxB2), 6-keto-PGF1 alpha and PGF2 alpha in the microdialysate were measured by radioimmunoassay. In two additional concurrent groups of rats (n = 10 each), neuronal injury in the HPC, CN and cortex (parietal, temporal and entorhinal regions) was evaluated histologically three days after 10 min of forebrain ischemia with and without pre-ischemic ibuprofen administration. In the control microdialysis group, levels of TxB2, 6-keto-PGF1 alpha and PGF2 alpha increased in both CN and HPC after probe insertion. These probe related increases were substantially reduced in the ibuprofen group. After ischemia and reperfusion in the control group, the levels of TxB2 and PGF2 alpha increased in both CN and HPC. Levels of 6-keto-PGF1 alpha increased in the CN but not in the HPC. The administration of ibuprofen substantially reduced post-ischemic TxB2 and PGF2 alpha levels in both CN and HPC and decreased 6-keto-PGF1 alpha levels in the CN. The results of these initial microdialysis studies left the possibility that, in the ibuprofen group, the reduction in eicosanoid levels after probe penetration might have influenced the subsequent post-ischemic eicosanoid production. Therefore, in an additional group of animals (n = 5), ibuprofen was administered after probe insertion. Only PGF2 alpha levels were measured in this group. Increased levels of PGF2 alpha comparable to the original control group were detected after probe penetration. Nonetheless, after ibuprofen administration, the pre- and post-ischemic levels of PGF2 alpha were again significantly reduced. In the histologic evaluation groups, overall neuronal injury was significantly less in the ibu

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Brain Ischemia; Caudate Nucleus; Cell Death; Dialysis; Dinoprost; Eicosanoids; Hippocampus; Ibuprofen; Neurons; Prosencephalon; Rats; Rats, Inbred WKY; Stereotaxic Techniques

For the effects of voltages on health and reproduction, 40 cows in second to fifth lactation were divided into four groups of 10. These included a control group that was not subjected to voltages and three treatment groups that were given either 1, 2, or 4 V at the water bowl. Cows in the treatment groups were exposed during the entire lactation to voltage whenever they drank. Voltages did not sufficiently affect milk yield. General health parameters studied were mastitis, hoof problems, and changes in body weight. Reproductive and calving parameters examined were days to first breeding, days open, services per conception, response to PGF2 alpha, calving intervals, visible abortion, and calves born dead. Voltages did not significantly influence cow health or reproductive performance.

Topics: Abortion, Veterinary; Animals; Body Weight; Cattle; Cattle Diseases; Dinoprost; Electricity; Female; Fetal Death; Foot Diseases; Hoof and Claw; Lactation; Mastitis, Bovine; Pregnancy; Reproduction

The study was designed to determine whether sex and fat calories altered hepatic prostaglandin (PG) F2 alpha status; a factor which may reflect susceptibility to cancer development. For 4 weeks, groups of 8 male and 8 female F344/N rats were fed diets with 9% of energy (en%) from linoleate and 15.5, 20, 30 or 40 en% fat. Females had greater hepatic stearate, arachidonate and PGF2 alpha whereas males had greater hepatic myristate, palmitate and oleate. Females also had greater plasma stearate levels. Greater hepatic arachidonate may have stimulated PG production in females. Hepatic oleate increased and hepatic palmitate decreased with increasing en% fat (p < 0.05). Hepatic stearate was greater and hepatic linoleate less when 40 en% fat was fed compared with other levels of dietary fat (p < 0.05). Plasma oleate was greater at 30 or 40 en% fat than at lower levels of fat, whereas plasma linoleate was less at 40 en% than at 15.5% en% fat. The ability of a 30 en% fat diet, containing equal proportions of linoleate and oleate, to suppress hepatic PG production may be related to the effects of dietary fat content and composition on plasma fatty acid profiles. Because suppressed PG production has been linked with suppression of cancer development, dietary recommendations to consume 30 en% fat with a P:M ratio of 1:1 may be cancer-protective.

Topics: Animals; Body Weight; Dietary Fats; Dinoprost; Disease Susceptibility; Energy Intake; Fatty Acids; Female; Liver; Liver Neoplasms, Experimental; Male; Rats; Rats, Inbred F344; Sex Characteristics

The contractile effect of methacholine, prostaglandin F2 alpha (PGF2 alpha) and electrical stimulation of cholinergic neurones, and the relaxant effect of nitric oxide (NO), vasoactive intestinal polypeptide (VIP) and electrical stimulation of inhibitory non-adrenergic non-cholinergic (NANC) neurones were studied in longitudinal smooth muscle strips of the gastric fundus of young (3 months), adult (12 months) and old (24 months) male Wistar rats. The contractile responses to methacholine and to electrical stimulation of cholinergic neurones were not significantly different between the three age groups. The responses to PGF2 alpha were significantly more pronounced in young than in adult and old rats. The relaxant response to electrical stimulation of NANC neurones with a cumulative increase in frequency showed a decreased response in old rats at the higher stimulation frequencies. This was mimicked by a decreased response to VIP, suggesting that there is a decrease in muscular sensitivity to VIP rather than an impaired capacity to VIP release with increasing age. The relaxant response to electrical stimulation of NANC neurones with short trains was similar in the three age groups, while the sensitivity to exogenous NO increased with age. The latter might be a compensatory mechanism for a decrease in stimulation-induced NO release with age.

Topics: Aging; Animals; Autonomic Nervous System; Body Weight; Dinoprost; Electric Stimulation; Gastric Fundus; Male; Methacholine Compounds; Muscle Contraction; Muscle, Smooth; Neurons; Nitric Oxide; Organ Size; Parasympathetic Nervous System; Rats; Rats, Wistar; Vasoactive Intestinal Peptide

The present study was designed to determine if dietary-fat-induced alterations in the fatty acid composition of skeletal-muscle lipid alters insulin-dependent and basal muscle metabolism, including glucose and amino acid transport, prostaglandin (PG) synthesis and protein turnover. Rats were fed on high-fat semi-purified diets providing 19% or 1% omega 3 fatty acids in the form of fish oil, for 6 weeks. After 3 weeks, half of the rats were made diabetic by a single injection of streptozotocin (50 mg/kg body wt.). After a further 3 weeks, contralateral epitrochlearis and extensor digitorum longus (EDL) muscles from each rat were incubated in vitro. High levels of dietary omega 3 fatty acids decreased PGE2 and PGF2 alpha synthesis in EDL and epitrochlearis muscle (P less than 0.0001). Diabetes and insulin had no effect on PG synthesis. Diet did not alter basal glucose or amino acid transport in EDL muscle from healthy or diabetic rats. Insulin increased glucose and amino acid transport (P less than 0.0001); the increase in glucose transport by insulin was significantly greater in muscles of rats fed on high levels of omega 3 fatty acids (P less than 0.05). Epitrochlearis from rats fed on high levels of omega 3 fatty acids showed decreased net protein degradation in the presence and absence of insulin, owing to decreased rates of protein degradation and synthesis. The data suggest that high levels of dietary omega 3 fatty acids that alter muscle membrane composition also result in alterations in glucose transport and the metabolism of muscle protein.

Topics: Amino Acids; Animals; Biological Transport; Body Weight; Diabetes Mellitus, Experimental; Dietary Fats; Dinoprost; Dinoprostone; Fatty Acids, Omega-3; Feeding Behavior; Glucose; Male; Muscle Proteins; Muscles; Prostaglandins; Rats; Rats, Inbred Strains

Measurements were made of PGE2, PGF2 and TXB2 in the urine of male and female Munich-Wistar rats. Initial urine were collected in the awake state in metabolic cages and were followed by collections of ureteral urine during surgery and anesthesia both before and during cyclooxygenase inhibition with indomethacin. The excretion rate of all eicosinoids in the awake state was similar between the sexes. PGE2 excretion remained unaffected after anesthesia/surgery in both sexes indicating that providing plasma volume is maintained, the PGE2 system is not activated by the stress of anesthesia/surgery. Near complete inhibition of PGE2 was observed during indomethacin administration in both sexes. TXB2 excretion rates rose in both males and females with anesthesia/surgery and were slightly suppressed during indomethacin in males only. PGF2 excretion rose following surgery/anesthesia and was statistically significant in female rats. During indomethacin, TXB2 excretion was moderately reduced in male rats and unaffected in the female. Near complete inhibition of PGF2 was observed during indomethacin in both sexes. The urinary eicosinoid responses to indomethacin seen in these studies failed to provide an explanation for our earlier observations of a fall in renal vascular resistance in the female rat, studied under anesthesia and during indomethacin administration.

Topics: Anesthesia; Animals; Body Weight; Dinoprost; Dinoprostone; Eicosanoic Acids; Female; Male; Rats; Rats, Inbred Strains; Sex Factors; Surgical Procedures, Operative; Thromboxane B2

Contractile responses to prostaglandin F2 alpha, serotonin, noradrenaline, and potassium were examined in isolated intramyocardial arteries of Wistar rats 8 weeks after the induction of diabetes mellitus by administration of streptozotocin (STZ). The concentration-response curves obtained were compared with those noted in vessels both from age- and from weight-matched control rats. Light and electron microscopy did not reveal any major change in coronary artery wall thickness or morphology. There was no difference in the pattern of vasomotor responses between the two control groups. Contractile responses to prostaglandin F2 alpha, and potassium were significantly reduced, while contractile responses to serotonin and noradrenaline were unaltered in coronary arteries from diabetic rats. The vasomotor responses to noradrenaline and potassium showed a biphasic pattern in control vessels, i.e. contraction noted at high agonist concentrations was preceded by slight, but reproducible relaxation at lower concentrations. In diabetic vessels these relaxant responses were absent. The contraction produced by noradrenaline was markedly enhanced by the presence of propranolol in both diabetic and control vessels. Dilator responses to verapamil, diltiazem, nifedipine, papaverine and magnesium were studied in serotonin-precontracted coronary arteries; the concentration-response curves obtained by verapamil and diltiazem were shifted to the right in diabetic vessels. It appears justified to use vessels from age-matched rats as controls when vasomotor reactivity in coronary arteries from STZ-diabetic rats is investigated. The reduction in contractile responses to prostaglandin F2 alpha and potassium, and the reduction or lack of relaxant responses to noradrenaline, potassium, verapamil and diltiazem, in diabetic coronary arteries, indicate a selective modification of the coronary circulation by the diabetic disease.

Topics: Animals; Arteries; Body Weight; Coronary Vessels; Diabetic Angiopathies; Dinoprost; Male; Muscle Contraction; Muscle, Smooth, Vascular; Norepinephrine; Potassium; Rats; Rats, Inbred Strains; Serotonin; Vasodilator Agents

Administration (3 mg/kg body weight/day, for 21 days) of prostaglandin F2 alpha (PGF2 alpha) caused marked suppression of spermatogenesis and significant reduction in the weights of the testis, epididymis and accessory sex glands. The seminiferous tubules were devoid of spermatozoa and contained only Sertoli cells, spermatogonia, spermatocytes and occasionally spermatids; several multinucleated giant cells were observed in the lumen of the tubules. The Leydig cells were atrophied. The levels of RNA, DNA and protein in the testis were, however, unaffected by drug therapy. In drug-treated mice the epididymal epithelium presented a degenerate appearance; the lumen was generally devoid of spermatozoa and contained mainly exfoliated immature germ cells and sperm debris; cauda epididymidal spermatozoa, when present, were immotile and fragmented. PGF2 alpha treatment also caused significant decrease in the levels of sialic acid in the caput and cauda epididymides and of fructose in the seminal vesicle. The results suggest that the regressive changes induced by PGF2 alpha in the reproductive organs of the mouse are due to the interference with the secretion of androgen. The alterations induced in the reproductive organs by administration of PGF2 alpha were reversible and 56 days after drug withdrawal the organs returned to their normal state.

Topics: Animals; Body Weight; Bulbourethral Glands; Dinoprost; Epididymis; Male; Mice; Organ Size; Prostaglandins F; Seminal Vesicles; Sperm Motility; Spermatogenesis; Spermatozoa; Testis

We studied the effects of hypercholesterolemia on vascular responsiveness in different arteries isolated from rabbits: control groups of rabbits and groups receiving the atherogenic diet consisted of eight animals each. In the arteries, 16 weeks of cholesterol-rich (0.3%) diet evoked intimal lesions which were more pronounced than those noted after 8 weeks of hypercholesterolemia; the aortic arch was affected significantly more by the lesions than the abdominal aorta and the pulmonary artery. Segments of the arteries were mounted in organ chambers for isometric tension recording or for measurement of the endothelium-derived relaxant factor. Contractions caused by acetylcholine and prostaglandin F2 alpha were not altered by the hypercholesterolemia; those evoked by serotonin were moderately augmented only in the aortic arch of hypercholesterolemic rabbits. As the degree of intimal lesion formation increased, the contractions to norepinephrine and clonidine were progressively inhibited. The endothelium-independent relaxations to nitroglycerin were inhibited in only the most severely affected arteries; the endothelium-dependent relaxations to acetylcholine and adenosine triphosphate were progressively inhibited as the degree of fatty streak formation augmented. Thus, in the aortic arch, the relaxations to 3 X 10(-6) M acetylcholine, expressed as percent of the initial contraction, decreased from 86.7 +/- 3.3% in control tissues to 16.3 +/- 8.6% in the 16-week hypercholesterolemic vessels; in the abdominal aortas these relaxations averaged 93.5 +/- 2.2% in control vessels and 72.0 +/- 6.9% in the hypercholesterolemic tissues. The acetylcholine-induced release of endothelium-derived relaxant factor from the abdominal aorta was not significantly affected by the hypercholesterolemia. We conclude from these studies that in arteries obtained from hypercholesterolemic rabbits: the contractions caused by serotonergic mechanisms tend to be augmented, while those to alpha-adrenergic activation are decreased, the endothelium-independent relaxations are modified only in the more severely affected arteries, and the endothelium-dependent relaxations are progressively inhibited as the degree of fatty streak formation augments, probably because a step subsequent to the release of endothelium-derived relaxant factor is altered.

Topics: Acetylcholine; Animals; Aorta; Body Weight; Cholesterol; Cholesterol, Dietary; Dinoprost; Endothelium; Hypercholesterolemia; In Vitro Techniques; Isometric Contraction; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth, Vascular; Nitric Oxide; Prostaglandins F; Rabbits; Time Factors; Triglycerides; Vasodilator Agents

The contribution of sex steroids to sex-related differences in renal prostaglandin dehydrogenase activity and urinary prostaglandin excretion was examined in 7-8-week-old male and female rats subjected to sham-operation or gonadectomy at 3 weeks of age. Rats were injected subcutaneously twice over a 6-day interval with vehicle (peanut oil, 0.5 mg/kg) or with depot forms of testosterone (10 mg/kg), estradiol (0.1 mg/kg), progesterone (5 mg/kg), or with estradiol and progesterone combined (0.1 and 5 mg/kg). After the second injection, 24-h urine samples were collected for prostaglandin measurement by radioimmunoassay; the rats were killed, and renal and pulmonary prostaglandin dehydrogenase activities were determined by radiochemical assay. Renal prostaglandin dehydrogenase activity was 10-times higher in intact male rats than in intact females. Gonadectomy increased renal prostaglandin dehydrogenase activity 4-fold in females, but had no effect in males; estradiol, alone or combined with progesterone, markedly suppressed renal prostaglandin dehydrogenase activity in both sexes, while testosterone or progesterone alone had no effect. Pulmonary prostaglandin dehydrogenase did not differ between the sexes and was unaffected by gonadectomy or sex-steroid treatment. Intact female sham-operated rats excreted 70-100% more prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha in urine than did males; gonadectomy abolished the difference in urinary prostaglandin E2 excretion. Estradiol decreased urinary prostaglandin E2 in females but not in males; treatment with other sex steroids did not alter urinary prostaglandin excretion.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Dinoprost; Dinoprostone; Estradiol; Female; Hydroxyprostaglandin Dehydrogenases; Kidney; Lung; Progesterone; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Sex Factors; Testosterone

This study was designed to investigate relationships between dietary potassium and the renal prostaglandin system in rats. The potassium content of the diet was 0.162 mmol/g during the control period and 0.004, 0.162, 1.351, or 2.702 mmol/g during the experimental period. Relative to control data in rats fed a 0.162 mmol/g potassium diet, the urinary excretion of 6-keto-PGF1 alpha was not affected by high potassium intake but increased (P less than 0.05) by 25% in rats fed a low potassium diet for 13 days and was associated with reduction of plasma potassium and with elevation of both plasma renin and net release of 6-keto-PGF1 alpha from renal inner medulla slices incubated in Krebs solution. The excretion of PGF2 alpha was not affected by low potassium intake but increased (P less than 0.05) by about twofold in rats fed a potassium-rich diet (1.351 and 2.702 mmol/g) for 13 days and was associated with elevation of plasma potassium concentration, renal prostaglandin 9-keto-reductase activity, and urinary excretion of kallikrein and vasopressin. The urinary excretion of PGE2 was not altered in rats fed either low or high potassium diets. Altogether, these results indicate selective influence of dietary potassium on the urinary excretion of prostaglandins in the rat.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Diet; Dinoprost; Dinoprostone; Hydroxyprostaglandin Dehydrogenases; Kallikreins; Kidney; Male; Potassium; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Renin; Vasopressins; Water-Electrolyte Balance

The effects of prostaglandin synthetase inhibitors PGF2 alpha and PGI2 on the tone of isolated basilar and coeliac arteries were studied in healthy and alloxan-diabetic dogs. PGF2 alpha (1 mumol 1-1) produced a significantly higher tone in diabetic basilar arteries (1.15 +/- 0.16 mN) than in normal cerebral vessels (0.7 +/- 0.10 mN). By contrast, the contractile responses of normal and diabetic coeliac arteries to PGF2 alpha did not differ. The cyclooxygenase inhibitors indomethacin (3 mumol 1-1) and suprofen (0.58 mumol 1-1) potentiated the PGF2 alpha-evoked contractions in all of the vessels studied. The percent potentiation was greater (50-60%) in the basilar arteries from alloxan-treated dogs than in normal basilar vessels (22-30%). There was not such a difference between diabetic and normal coeliac arteries. Prostacyclin produced a concentration-related relaxation in the presence of indomethacin or indomethacin + PGF2 alpha. The relaxant potencies of PGI2 were similar in the vessels from metabolically healthy and diabetic dogs. The IC50 values for PGI2 were 11.6 +/- 1.3 and 11.8 +/- 1.8 nmol 1-1 in normal and diabetic basilar arteries, respectively; they were 25.4 +/- 3.2 and 26.2 +/- 3.9 nmol 1-1 in control and alloxan-treated coeliac vessels. These results indicate that normal and diabetic vessels may have differential reactivity to cyclooxygenase inhibitors, this difference being dependent on the vascular region.

Topics: Animals; Basilar Artery; Body Weight; Celiac Artery; Cyclooxygenase Inhibitors; Diabetes Mellitus, Experimental; Dinoprost; Dogs; Epoprostenol; Female; In Vitro Techniques; Indomethacin; Male; Muscle Contraction; Muscle, Smooth, Vascular; Prostaglandins F; Suprofen

In an attempt to study the interrelationship between aldosterone, Na balance, prostaglandin (PG) and kallikrein excretion, we investigated the influence of adrenalectomy and aldosterone administration on kallikrein and PG excretion during dietary manipulation of extracellular volume in Sprague-Dawley rats. Adrenalectomy decreased while aldosterone administration increased urinary kallikrein and PG excretion during both low and high Na intake. Aldosterone induced a prompt change in Na/K ratio; however, kallikrein and PG excretion increased gradually during the 7 days of treatment. When the animals were forced into a negative Na balance during the administration of aldosterone by reducing their Na intake, kallikrein and PG excretion still increased but to a lesser extent than on a constant diet. In adrenalectomized rats given only vehicle, shifting the diet to a low Na intake caused a decrease in kallikrein and PG excretion. Corticosterone failed to correct the changes evoked by adrenalectomy, and it did not reproduce the effects of aldosterone. It is concluded that the effect of aldosterone on kallikrein and PG excretion is not mediated by changes in extracellular volume; however, in the absence of aldosterone a change in Na balance itself may influence kallikrein and PG excretion.

Topics: Adrenalectomy; Aldosterone; Animals; Body Weight; Diet, Sodium-Restricted; Dinoprost; Dinoprostone; Female; Kallikreins; Potassium; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Sodium; Time Factors

The effect of fatty acids (prostaglandins, arachidonic and linoleic acids) and prostaglandin synthetase inhibitors on food intake (measured as change in weight) were studied in newborn and young rats. PGE2 (0.1, 0.5 mg/kg) and PGF2 alpha (0.5 mg/kg) inhibited feeding in the 6 hr deprived 1 day old rat. Under the same deprivation PGF2 alpha (0.5, 1 mg/kg) also caused anorexia in 5, 10 and 15 day old rats. S.C. injection of arachidonic acid (2.5-20 mg/kg) and linoleic acid (150 mg/kg) depressed while aspirin (200-400 mg/kg) and indomethacin 8-32 mg/kg) increased feeding in the non-deprived 1 day old rat. The anorectic activity of arachidonic acid is antagonized by prior (1 hr) administration of aspirin (100 mg/kg) and indomethacin (4 mg/kg) indicating the involvement of prostaglandins in arachidonic acid-induced anorexia. S.C. injection of aspirin (400 mg/kg), indomethacin (4,8 mg/kg) and flurbiprofen (3.12-25 mg/kg) to 1.5 hr deprived 5 day old rats also increased food intake. It is hypothesized that the prostaglandin-generating system and endogenous aspirin (endospirin)-like substances, which inhibit such a generation, play an important physiological role in the regulation of hunger-satiety in the newborn rat.

Topics: Animals; Animals, Newborn; Animals, Suckling; Aspirin; Body Weight; Dinoprost; Dinoprostone; Eating; Female; Food Deprivation; Indomethacin; Injections, Intraperitoneal; Injections, Subcutaneous; Pregnancy; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Time Factors

A field trial was conducted to evaluate the use of prostaglandin F2 alpha (PGF2 alpha) (lutalyse)a in lactating dairy cattle with unobserved estrus in the presence of a functional corpus luteum (CL) and clinically normal reproductive tract. Seventy-three Holstein and 9 Jersey cows, weighing between 340.0 and 772.7 kg, were allotted to treatment and control groups. All treated cows were inseminated within 80 hours after treatment as assigned by this trial. Control cows were inseminated at the first observed estrus. Of the treated cows, 50% showed estrus within 80 hours after treatment. In this trial, 96% of the treated cows and 92% of the control cows were determined to have at least 1 functional CL on the day of treatment. For the treatment group and the control group, mean serum progesterone concentrations were 4.1 ng and 3.5 ng (P less than 0.2, by Student's t test), respectively, on day of treatment and were 0.4 ng and 5.0 ng (P less than 0.005, by Student' t test) on day 5 after treatment. Pregnancy rates were 57% for treated and 47% for control cows (P = 0.5, by X2). Days from treatment to first-observed estrus, treatment to first service, and treatment to conception were significantly reduced in the treatment group compared with these criteria for the control group (P less than 0.05, 0.005, and 0.01 respectively). It was concluded that induction of luteolysis with PGF2 alpha in lactating dairy cattle with unobserved estrus and a palpable functional CL will be an effective addition to reproductive health programs.

Topics: Animals; Body Weight; Breeding; Cattle; Dinoprost; Estrus Detection; Female; Fertility; Insemination, Artificial; Lactation; Pregnancy; Progesterone; Prostaglandins F

DIPA [5,6-bis(dibenzyloxy)-1-oxo-2-propyl-2-indanpropionic acid] was evaluated for its antiabortifacient action in mice. PGF2 alpha administered intramuscularly twice daily at 525 micrograms/kg per dose starting on day-17 of gestation resulted in premature delivery (prior to day-19 of gestation) in 55% of the animals. This constituted an ED50 abortifacient dosage schedule of PGF2 alpha. Intramuscular administration of DIPA at a dose of 50 mg/kg twice daily, starting on day-15 of gestation, protected the mice against the premature delivery induced by the ED50 dosage schedule of PGF2 alpha in that only 20% of the animals delivered prematurely. In saline-treated controls, none of the animals delivered prior to day-19 of gestation. Thus, DIPA appears to be an effective antiabortifacient agent.

Topics: Abortion, Spontaneous; Animals; Animals, Newborn; Biometry; Body Weight; Dinoprost; Embryo Implantation; Embryo, Mammalian; Female; Fetal Death; Indans; Indenes; Male; Mice; Pregnancy; Pregnancy, Animal; Prostaglandins F; Sex Ratio

Topics: Animals; Body Weight; Diarrhea; Dinoprost; Dinoprostone; Inflammation; Intestinal Diseases; Male; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Time Factors

The influence of PGF2 alpha on pregnancy and fetal outcome was investigated in the hamster. Following subcutaneous treatment with 50, 100, 200, 400, and 800 micrograms PGF2 alpha prenatal loss was significantly increased only at the highest dose level. The offspring of the treated animals were all alive and normal. Fetal weight was not affected. However, following intravenous injection of 100 and 200 micrograms PGF2 alpha there was a significant reduction in fetal weight, and at the 400 micrograms dose level an increase in fetal indicate that PGF2 alpha is not teratogenic in hamsters despite the apparent greater sensitivity of the hamster embryo to prostaglandin.

Topics: Animals; Body Weight; Cricetinae; Dinoprost; Dose-Response Relationship, Drug; Female; Fetal Resorption; Fetus; Injections, Intravenous; Injections, Subcutaneous; Pregnancy; Pregnancy, Animal; Prostaglandins F

Contractile responses to PGF2 alpha of isolated coronary arteries from 7 healthy and 12 alloxan-diabetic dogs without ketosis were considerably increased by indomethacin and decreased by PGI2. The increasing effect of indomethacin was more prominent on diabetic vessels than on those of normal animals while PGI2 had the same relaxant potency in both groups. The contractions induced by PGF2 alpha were inhibited more effectively by PGI2 than those evoked by PGE2 both in healthy and alloxan-diabetic groups.

Topics: Animals; Blood Glucose; Blood Urea Nitrogen; Body Weight; Coronary Vessels; Diabetes Mellitus, Experimental; Dinoprost; Dinoprostone; Dogs; Epoprostenol; Female; In Vitro Techniques; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth, Vascular; Prostaglandins; Prostaglandins E; Prostaglandins F