salicylates and Body-Weight

Topics: Absorption; Animals; Blood Glucose; Blood Volume; Body Weight; Indicators and Reagents; Infusions, Parenteral; Iodine Radioisotopes; Iothalamic Acid; Lung; Male; Methods; Prostatectomy; Radioisotopes; Salicylates; Serum Albumin, Radio-Iodinated; Sodium; Technetium; Therapeutic Irrigation; Urethra; Xenon

Recent trials show salicylates improve glycemic control in type 2 diabetes, but the mechanism is poorly understood. Expression of the glucocorticoid-generating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in adipose tissue is increased in vitro by proinflammatory cytokines and upregulated in obesity. 11β-HSD1 inhibition enhances insulin sensitivity. We hypothesized that salicylates downregulate 11β-HSD1 expression, contributing to their metabolic efficacy. We treated diet-induced obese (DIO) 11β-HSD1-deficient mice and C57Bl/6 mice with sodium salicylate for 4 weeks. Glucose tolerance was assessed in vivo. Tissue transcript levels were assessed by quantitative PCR and enzyme activity by incubation with (3)H-steroid. Two weeks' administration of salsalate was also investigated in a randomized double-blind placebo-controlled crossover study in 16 men, with measurement of liver 11β-HSD1 activity in vivo and adipose tissue 11β-HSD1 transcript levels ex vivo. In C57Bl/6 DIO mice, salicylate improved glucose tolerance and downregulated 11β-HSD1 mRNA and activity selectively in visceral adipose. DIO 11β-HSD1-deficient mice were resistant to these metabolic effects of salicylate. In men, salsalate reduced 11β-HSD1 expression in subcutaneous adipose, and in vitro salicylate treatment reduced adipocyte 11β-HSD1 expression and induced adiponectin expression only in the presence of 11β-HSD1 substrate. Reduced intra-adipose glucocorticoid regeneration by 11β-HSD1 is a novel mechanism that contributes to the metabolic efficacy of salicylates.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Adipocytes; Adipose Tissue; Adult; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Cell Differentiation; Cell Line; Cross-Over Studies; Gene Expression Regulation; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Mice; Mice, Knockout; Middle Aged; Obesity; Salicylates; Sodium Salicylate

There has been significant interest recently in the technique of mesotherapy as a method of 'melting fat' for body contouring.. The aim of this study was to evaluate the safety, efficacy and lipolytic potential of several compounds commonly used in cosmetic mesotherapy.. A total of 75 women (mean age: 33 years) were separated randomly into three mesotherapy groups. Injections were performed for 15 treatments once a week. The main component of each cocktail was phosphatidylcholine/deoxycholic acid for group 1, caffeine for group 2, and Conjonctyl® for group 3. Outcome was evaluated by weight, body fat percentage (BFP), circumference measurements, and patient questionnaires.. Seventy-two of all the patients (96%) showed a circumference loss. An average circumference reduction of 4.41 cm per site for group 1, 2.99 cm for group 2, and 2.10 cm for group 3 was achieved. Mean body circumference loss was statistically significant, with p < 0.00. Weight loss was 5.33 ± 1.09 kg for group 1, 3.74 ± 1.51 kg for group 2, and 2.82 ± 1.43 kg for group 3. Seventy-four subjects (98.7%) showed a BFP decrease. A questionnaire indicated high patient satisfaction (63%). No patient showed irregularities, dimples or any serious side effects after treatment.. Mesotherapy is a well-tolerated and effective alternative treatment modality for reducing the diameter of body circumference.

Topics: Adipose Tissue; Adult; Body Weight; Caffeine; Dermatologic Agents; Drug Combinations; Female; Humans; Hyaluronic Acid; Lower Extremity; Mesotherapy; Middle Aged; Organ Size; Organosilicon Compounds; Patient Satisfaction; Phosphatidylcholines; Salicylates; Waist Circumference; Young Adult

Hybrid male turkeys were fed to 18 wk of age in a completely randomized design with 10 replicate pens (18 birds each) per treatment to compare growth promoters. Four dietary treatments were used: negative control (CON), bacitracin methylene disalicyate (BMD) at 55 mg/kg to 6 wk and 27.5 mg/kg thereafter, mannan oligosaccharide (MOS) at 0.1% to 6 wk and 0.05% thereafter, and BMD and MOS at concentrations listed above. There were 3 toms/m2 (3.59 ft2/tom) on fresh pine shavings inoculated with used litter. A 6-phase feeding program was used, with crumbles the first 3 wk and pellets thereafter. At wk 6 and 18, one bird per pen was killed, and the large intestinal microbial populations, after being frozen, were enumerated (i.e., bifidobacteria, Clostridium perfringens, coliforms, enterococci, Escherichia coli, lactobacilli, and total anerobes). Body weights at wk 18 were as follows: CON, 11.87 kg; BMD, 12.46 kg; MOS: 12.56 kg; and BMD + MOS, 12.79 kg. The BMD and MOS turkeys were (P < 0.05) heavier than CON birds, and those fed the combination were significantly heavier than all other treatments. At wk 18, BMD + MOS feed conversion ratio of 2.66 was significantly lower than CON at 3.00 with BMD and MOS being intermediate (2.83 and 2.79, respectively). Mortality was not affected by treatment. The BMD and MOS each reduced large intestinal concentrations of Clostridium perfringens (log transformed data analysis) at wk 6 but not at wk 18. The BMD or MOS each improved turkey performance, and when used together, exhibited further beneficial effects.

Topics: Animal Nutritional Physiological Phenomena; Animals; Bacitracin; Body Weight; Clostridium perfringens; Hybridization, Genetic; Intestines; Mannans; Mortality; Oligosaccharides; Salicylates; Turkeys

Bismuth subsalicylate is a common constituent of over-the-counter medications for diarrhea. However, it is uncertain whether bismuth offers any more benefit than standard oral rehydration therapy with early feeding.. We conducted a placebo-controlled, randomized trial to evaluate the effect of bismuth subsalicylate (100 or 150 mg per kilogram of body weight per day for up to 5 days) on the duration and volume of acute watery diarrhea in 275 male infants and young boys (mean age, 13.5 months). Serum salicylate and bismuth levels were monitored throughout the study and were also measured two weeks after discharge. All the patients received fluid replacement by the oral route and early feeding of easily digestible foods with high caloric density.. Diarrhea stopped within 120 hours of admission in 74 percent of the patients given placebo, 89 percent of those given 100 mg of bismuth per kilogram (P = 0.009 vs. the placebo group), and 88 percent of those given 150 mg of bismuth per kilogram (P = 0.019 vs. the placebo group). As compared with the patients given placebo, those given bismuth had significant reductions in their total stool output (P = 0.015), total intake of oral rehydration solution (P = 0.013), and duration of hospitalization (P = 0.005); there was no significant difference between the two groups given bismuth in these clinical outcomes. All measurements of bismuth and salicylate concentrations in blood were well below concentrations considered toxic. No adverse reactions were seen.. Treatment with bismuth subsalicylate decreases the duration of diarrhea and is a safe and effective adjunct to oral rehydration therapy for infants and young children with acute watery diarrhea.

Topics: Acute Disease; Bismuth; Body Weight; Chemotherapy, Adjuvant; Child, Preschool; Diarrhea, Infantile; Double-Blind Method; Fluid Therapy; Humans; Infant; Male; Multivariate Analysis; Organometallic Compounds; Salicylates

Twenty-nine infants and children, age 2-70 months with chronic diarrhea, were admitted to a double-blind, parallel clinical trial. The subjects were randomly assigned to receive either a bismuth subsalicylate liquid or a placebo liquid formulation. Treatment was given for 7 days with dosage varied according to age. Analysis of the results showed that the subjects in the bismuth subsalicylate-treated group gained significantly more weight (p less than 0.05), had significantly fewer (p less than 0.01) and firmer (p less than 0.01) stools with less water content (p less than 0.01) during the course of the study than did the placebo-treated group. Response to treatment, as graded by nursing staff, family, and physicians was moderate to excellent in 86% of the treated group while none of the placebo group received such a rating (p less than 0.01). No differences were noted between stool weights or bile acid excretion.

Topics: Bismuth; Body Weight; Child, Preschool; Chronic Disease; Clinical Trials as Topic; Defecation; Diarrhea, Infantile; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infant; Male; Organometallic Compounds; Prospective Studies; Random Allocation; Salicylates

A review is presented of both published work and unpublished observations concerned with: a) the 'efficacy' of copper bracelets for arthritis; b) the bio-reactivity of metallic copper (especially with human sweat); c) permeation of the skin by Cu(II) when complexed with certain ligands (such as salicylates); d) the pharmacological and clinical activity of AlcusalR and DermcusalR, two formulations of copper salicylate with ethanol and dimethyl sulphoxide respectively that can be applied to the skin. Topical application promises to be a superior alternative to orally ingested drugs.

Topics: Administration, Topical; Arthritis; Body Weight; Clinical Trials as Topic; Copper; Humans; Salicylates; Skin Absorption

To test in mice with a double mutation of the ApoE gene (ApoE-/-) whether spinal cord injury (SCI) hastens the native trajectory of, and established component risks for, atherosclerotic disease (AD), and whether Salsalate anti-inflammatory pharmacotherapy attenuates the impact of SCI.. ApoE-/- mice were anesthetized and underwent a T9 laminectomy. Exposed spinal cords were given a contusion injury (70 k-dynes). Sham animals underwent all surgical procedures, excluding injury. Injured animals were randomized to 2 groups: SCI or SCI+Salsalate [120 mg/Kg/day i.p.]. Mice were serially sacrificed at 20-, 24-, and 28-weeks post-SCI, and body mass was recorded. At sacrifice, heart and aorta were harvested intact, fixed in 10% buffered formalin, cleaned and cut longitudinally for en face preparation. The aortic tree was stained with oil-red-O (ORO). AD lesion histomorphometry was calculated from the proportional area of ORO. Plasma total cholesterol, triglycerides and proatherogenic inflammatory cytokines (PAIC's) were analyzed.. AD lesion in the aortic arch progressively increased in ApoE-/-, significant at 24- and 28-weeks. AD in SCI is significantly greater at 24- and 28-weeks compared to time-controlled ApoE-/-. Salsalate treatment attenuates the SCI-induced increase at these time points. Body mass in all SCI groups are significantly reduced compared to time-controlled ApoE-/-. Cholesterol and triglycerides are significantly higher with SCI by 24- and 28-weeks, compared to ApoE-/-, and Salsalate reduces the SCI-induced effect on cholesterol. PAIC's interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-C motif) ligand 5 (CCL-5) are significantly greater with SCI compared to ApoE-/- at varying timepoints. Salsalate confers a marginal reducing effect on PAIC's by 28-weeks compared to SCI. Regression models determine that each PAIC is a significant and positive predictor of lesion. (p's <0.05).. SCI accelerates aortic AD and associated risk factors, and anti-inflammatory treatment may attenuate the impact of SCI on AD outcomes. PAIC's IL-1β, IL-6, TNFα, MCP-1, and CCL-5 may be effective predictors of AD.

Topics: Animals; Anti-Inflammatory Agents; Aorta, Thoracic; Atherosclerosis; Body Weight; Cardiometabolic Risk Factors; Cytokines; Inflammation; Lipids; Mice, Knockout, ApoE; Regression Analysis; Risk Factors; Salicylates; Spinal Cord Injuries

The search constantly continues to identify potential alternatives to the use of antimicrobial growth promoters (AGP) in broiler production. This trial was conducted with broiler chicks to investigate the effect of different levels of Pulicaria gnaphalodes powder (PGP) in comparison with AGP, and probiotic (PRO) on growth performance, gut microflora, intestinal morphology, antioxidant enzyme activity, and fatty acid profile of meat. Ross 308 male broiler chicks (n = 576) were randomly assigned into 6 dietary treatments with 8 replicate pens per treatment and 12 birds per pen. The dietary treatments consisted of a basal diet as control (CON, with no additive), CON + 0.1% PGP, CON + 0.2% PGP, CON + 0.3% PGP, CON + 0.1% probiotic mixture (PRO), and CON + 0.05% bacitracin methylene disalicylate (AGP). Higher body weight gain and lower feed conversion ratio were obtained in birds fed AGP and 0.3% PGP compared with those fed CON and 0.1% PGP during grower, finisher, and the entire study (P < 0.05). On day 42, birds on PRO, 0.2 and 0.3% PGP treatments had lower counts of Escherichia coli and higher lactobacillus spp. in ileum and cecal contents compared to the CON and 0.1% PGP (P < 0.05). Villus height and villus height to crypt depth ratio of the duodenum were increased (P < 0.05) in response to dietary AGP, PRO, and 0.3% PGP. The diets containing PRO and different levels of PGP increased superoxide dismutase and glutathione peroxidase activities and decreased malondialdehyde level in serum, liver, and thigh muscle (P < 0.05). Total polyunsaturated fatty acid and n-3 fatty acid of birds fed PRO and PGP diets were higher than birds in CON and AGP groups (P < 0.05). In summary, supplementation of PGP could be a potential alternative to AGP in broiler diets due to its combined positive impacts on performance, serum cholesterol, intestinal health, antioxidant activity, and fatty acid profile in meat. Such effects, however, need to be further verified under compromised health or a disease challenge condition.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Anti-Bacterial Agents; Antioxidants; Bacitracin; Body Weight; Chickens; Cholesterol; Diet; Fatty Acids; Gastrointestinal Microbiome; Glutathione Peroxidase; Male; Malondialdehyde; Meat; Probiotics; Pulicaria; Salicylates; Superoxide Dismutase

Alzheimer's disease (AD) is characterized by progressive decline of cognition and associated neuropsychiatric signs including weight loss, anxiety, depression, agitation, and aggression, which is particularly pronounced in the female gender. Previously, we have shown that a novel ionic co-crystal of lithium salicylate proline (LISPRO) is an improved lithium formulation compared to the carbonate or salicylate form of lithium in terms of safety and efficacy in reducing AD pathology in Alzheimer's mice. The current study is designed to compare the prophylactic effects of LISPRO, lithium carbonate (LC), and lithium salicylate (LS) on cognitive and noncognitive impairments in female transgenic APPswe/PS1dE9 AD mice. Female APPswe/PS1dE9 mice at 4 months of age were orally treated with low-dose LISPRO, LS, or LC for 9 months at 2.25 mmol lithium/kg/day followed by determination of body weight, growth of internal organs, and cognitive and noncognitive behavior. No significant differences in body or internal organ weight, anxiety or locomotor activity were found between lithium treated and untreated APPswe/PS1dE9 cohorts. LISPRO, LC, and LS prevented spatial cognitive decline, as determined by Morris water maze and depression as determined by tail suspension test. In addition, LISPRO treatment was superior in preventing associative memory decline determined by contextual fear conditioning and reducing irritability determined by touch escape test in comparison with LC and LS. In conclusion, low-dose LISPRO, LC, and LS treatment prevent spatial cognitive decline and depression-like behavior, while LISPRO prevented hippocampal-dependent associative memory decline and irritability in APPswe/PS1dE9 mice.

Topics: Alzheimer Disease; Animals; Behavior; Body Weight; Conditioning, Psychological; Fear; Female; Hindlimb Suspension; Lithium Carbonate; Lithium Compounds; Locomotion; Maze Learning; Memory; Mice; Mice, Transgenic; Motor Activity; Proline; Salicylates; Spatial Memory

The intestinal gut health is one of the primary determinants of broiler growth and performance. Among the various enteric diseases, necrotic enteritis (NE) is an enterotoxemic disease caused by Clostridium perfringens, which can result in severe economic losses in poultry farming. Antibiotics like bacitracin methylene disalicylate (BMD) and avilamycin (AVL) are commonly used antibiotic growth promoters (AGP) in poultry feed to control necrotic enteritis in birds. Bacillus subtilis PB6 was reported to prevent necrotic enteritis and improve performance in birds. This paper investigated the influence of Bacillus subtilis PB6 in improving the performance of broiler birds in comparison with BMD and avilamycin. A 35 day trial was conducted with 240 day-old commercial broiler chicks (VenCobb 400), which were divided into four treatment groups, where each treatment group was composed of 6 replicates each containing 10 birds, for a total of 60 birds per treatment. The treatment groups included a negative control (no AGP), Bacillus subtilis PB6, BMD, and avilamycin. The parameters analyzed included body weight, feed conversion ratio (FCR), mortality, villus histomorphometry, and European efficiency factor (EEF). Bacillus subtilis PB6 significantly (P < 0.05) improved body weight and FCR (8 points) compared to the control. The group supplemented with B. subtilis PB6 or BMD had higher (P < 0.05) body weight compared to all other treatment groups. The supplementation of B. subtilis PB6 significantly improved the villus height (P < 0.05) compared to control and other AGP groups. The EEF was found to be the highest in the B. subtilis PB6 supplemented group at 35th day as compared to other treatment groups. The combined data from this study indicate that supplementation of B. subtilis PB6 improves overall performance of broilers compared to BMD and avilamycin, and can be used as potential AGP replacement in poultry farming.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Anti-Bacterial Agents; Bacillus subtilis; Bacitracin; Body Weight; Chickens; Diet; Energy Metabolism; Female; Intestines; Longevity; Male; Oligosaccharides; Probiotics; Random Allocation; Salicylates

Topics: Adipose Tissue, White; Animals; Body Weight; Cell Line; Diabetes Mellitus, Type 2; Diet, High-Fat; Energy Metabolism; Fatty Liver; Gene Expression; Gluconeogenesis; Glucose; Humans; Insulin; Lipid Metabolism; Liver; Male; Mice; Muscle, Skeletal; Obesity; Pyruvic Acid; Salicylates; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Signal Transduction; Thermogenesis

Salsalate (salicylsalicylic acid) is an anti-inflammatory drug that was recently found to exert beneficial metabolic effects on glucose and lipid metabolism. Although its utility in the prevention and management of a wide range of vascular disorders, including type 2 diabetes and metabolic syndrome has been suggested before, the potential of salsalate to protect against non-alcoholic steatohepatitis (NASH) remains unclear. The aim of the present study was therefore to ascertain the effects of salsalate on the development of NASH.. Transgenic APOE*3Leiden.CETP mice were fed a high-fat and high-cholesterol diet with or without salsalate for 12 and 20 weeks. The effects on body weight, plasma biochemical variables, liver histology and hepatic gene expression were assessed.. Salsalate prevented weight gain, improved dyslipidemia and insulin resistance and ameliorated diet-induced NASH, as shown by decreased hepatic microvesicular and macrovesicular steatosis, reduced hepatic inflammation and reduced development of fibrosis. Salsalate affected lipid metabolism by increasing β-oxidation and decreasing lipogenesis, as shown by the activation of PPAR-α, PPAR-γ co-activator 1β, RXR-α and inhibition of genes controlled by the transcription factor MLXIPL/ChREBP. Inflammation was reduced by down-regulation of the NF-κB pathway, and fibrosis development was prevented by down-regulation of TGF-β signalling.. Salsalate exerted a preventive effect on the development of NASH and progression to fibrosis. These data suggest a clinical application of salsalate in preventing NASH.

Topics: Alanine Transaminase; Animals; Apolipoproteins E; Aspartate Aminotransferases; Blood Glucose; Body Weight; Cholesterol Ester Transfer Proteins; Cholesterol, Dietary; Diet, High-Fat; Gene Expression Regulation; Insulin; Lipid Metabolism; Lipogenesis; Liver; Male; Mice, Transgenic; Non-alcoholic Fatty Liver Disease; Salicylates

Type 2 diabetes mellitus (T2DM) arises owing to insulin resistance and β-cell dysfunction. Chronic inflammation is widely identified as a cause of T2DM. The Goto-Kakizaki (GK) rat is a spontaneous rodent model for T2DM with chronic inflammation. The purpose of this study was to characterize diabetes progression in GK rats and evaluate the potential role of the anti-inflammatory agent salsalate. The GK rats were divided into control groups (n = 6) and salsalate treatment groups (n = 6), which were fed a salsalate-containing diet from 5 to 21 weeks of age. Blood glucose and salicylate concentrations were measured once a week. Glucose concentrations showed a biphasic increase in which the first phase started at approximately 5 weeks, resulting in an increase by 15 to 25 mg/dl and a second phase at 14 to 15 weeks with an upsurge of more than 100 mg/dl. A mechanism-based model was proposed to describe the natural diabetes progression and salsalate pharmacodynamics by using a population method in S-ADAPT. Two transduction cascades were applied to mimic the two T2DM components: insulin resistance and β-cell dysfunction. Salsalate suppressed both disease factors by a fraction of 0.622 on insulin resistance and 0.134 on β-cell dysfunction. The substantial alleviation of diabetes by salsalate supports the hypothesis that chronic inflammation is a pathogenic factor of diabetes in GK rats. In addition, body weight and food intake were measured and further modeled by a mechanism-based growth model. Modeling results suggest that salsalate reduces weight gain by enhancing metabolic rate and energy expenditure in both GK and Wister-Kyoto rats.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Disease Models, Animal; Disease Progression; Male; Models, Biological; Random Allocation; Rats; Rats, Inbred WKY; Salicylates; Sodium Salicylate; Software

Advanced glycation end products (AGE) have been implicated in the pathogenesis of diabetic complications. The purpose of this study was to examine the novel coumarin-aspirin compound XLF-III-43 in the inhibition of AGE formation in diabetic nephropathy. In vitro analysis showed XLF-III-43 in a dose-dependent manner decreased glucose induced formation of glycation adducts on albumin and inhibited AGE-lysozyme crosslinking. The streptozotocin-induced diabetic rats were used to investigate the beneficial effects of XLF-III-43 treatment on diabetic nephropathy. Administration of XLF-III-43 significantly decreased (P<0.05) blood urea nitrogen and urinary albumin excretion. Moreover, XLF-III-43 ameliorated kidney hypertrophy, mesangial expansion and glomerulosclerosis in diabetic rats relative to untreated model group. These data correlated with decreased both AGE and downstream markers of AGE stress (TGF-beta1, CTGF, fibronectin and collagen IV fibrolysis) in kidneys of diabetic rats. These data support further development of XLF-III-43 for prevention of nephropathy via inhibition of AGE formation consequent to chronic hyperglycemia.

Topics: Animals; Body Weight; Coumarins; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Female; Gene Expression Regulation; Glycation End Products, Advanced; Hyperglycemia; Hypertension; Kidney; Rats; Rats, Sprague-Dawley; Salicylates

Diabetic neuropathy is manifested either by loss of nociception (painless syndrome) or by mechanical hyperalgesia and tactile allodynia (pain in response to nonpainful stimuli). While therapies with vasodilators or neurotrophins reverse some functional and metabolic abnormalities in diabetic nerves, they only partially ameliorate neuropathic pain. The reported link between nociception and targets of the anti-inflammatory drug sulfasalazine prompted us to investigate its effect on neuropathic pain in diabetes.. We examined the effects of sulfasalazine, salicylates, and the poly(ADP-ribose) polymerase-1 inhibitor PJ34 on altered nociception in streptozotocin-induced diabetic rats. We also evaluated the levels of sulfasalazine targets in sciatic nerves and dorsal root ganglia (DRG) of treated animals. Finally, we analyzed the development of tactile allodynia in diabetic mice lacking expression of the sulfasalazine target nuclear factor-kappaB (NF-kappaB) p50.. Sulfasalazine completely blocked the development of tactile allodynia in diabetic rats, whereas relatively minor effects were observed with other salicylates and PJ34. Along with the behavioral findings, sciatic nerves and DRG from sulfasalazine-treated diabetic rats displayed a decrease in NF-kappaB p50 expression compared with untreated diabetic animals. Importantly, the absence of tactile allodynia in diabetic NF-kappaB p50(-/-) mice supported a role for NF-kappaB in diabetic neuropathy. Sulfasalazine treatment also increased inosine levels in sciatic nerves of diabetic rats.. The complete inhibition of tactile allodynia in experimental diabetes by sulfasalazine may stem from its ability to regulate both NF-kappaB and inosine. Sulfasalazine might be useful in the treatment of nociceptive alterations in diabetic patients.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Glucose; Body Weight; Chromatography, High Pressure Liquid; Diabetes Mellitus, Experimental; Ganglia, Spinal; Immunoblotting; Inosine; NF-kappa B p50 Subunit; Pain; Pain Measurement; Phenanthrenes; Rats; Salicylates; Sciatic Nerve; Sulfasalazine; Tandem Mass Spectrometry

A series of compounds containing one or two salicylic acid moieties were synthesized, and their efficacy to inhibit the phosphohydrolase activity of PTP1B examined. Some of the methylenedisalicylic acid derivatives were potent inhibitors of PTP1B. Of those derivatives, 3c exhibited about a 14-fold selectivity against TC-PTP, and this compound was tested in a mouse model for its efficacy to prevent diet-induced obesity. It effectively suppressed the increases in body weight and adipose mass, without any noticeable toxic effect. The compound also prevented increases in the plasma triglyceride, cholesterol, and nonesterified fatty acid concentrations; thus, expanding its therapeutic potential to other related metabolic diseases, such as hyperlipidemia and hypercholesterolemia.

Topics: Animals; Anti-Obesity Agents; Body Weight; Enzyme Inhibitors; Male; Mice; Mice, Inbred C57BL; Molecular Structure; Obesity; Organ Size; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Salicylates; Structure-Activity Relationship

EAN induced in Lewis rats by immunization with peripheral bovine myelin was treated by the Ras inhibitor farnesylthiosalicylate (FTS). Treatment from day 0 with FTS (5 mg/kg intraperitoneally twice daily) attenuated peak clinical scores (mean+/-S.E., 2.5+/-0.5 compared to 4.1+/-0.5 in saline treated controls, p=0.018, t-test) but not recovery. Treatment from day 10 with FTS attenuated peak disability (2.5+/-0.6, p=0.032 compared to saline treated controls) and improved recovery (0.84+/-0.42, untreated controls 2.4+/-0.6, p=0.028 by repeated measures ANOVA). Effects were confirmed by rotarod and nerve conduction studies. An inactive analogue, geranylthiosalicylate, had no clinical effect. Inhibition of Ras is of potential use in the treatment of inflammatory neuropathies.

Topics: Analysis of Variance; Animals; Behavior, Animal; Body Weight; Cell Proliferation; Cells, Cultured; Concanavalin A; Disease Models, Animal; Dose-Response Relationship, Immunologic; Drug Interactions; Electromyography; Enzyme Inhibitors; Farnesol; Female; Lymphocytes; Motor Activity; Mycobacterium tuberculosis; Myelin Proteins; Neural Conduction; Neuritis, Autoimmune, Experimental; ras Proteins; Rats; Rats, Inbred Lew; Rotarod Performance Test; Salicylates; Severity of Illness Index

Previous studies found that repeated application of smoke condensate from tobacco-burning reference cigarettes to chemically initiated SENCAR mouse skin promoted the development of tumors in a statistically significant and dose-dependent manner, while condensate from prototype cigarettes that primarily heat tobacco promoted statistically fewer tumors. Based on the recognized correlation between sustained, potentiated epidermal hyperplasia and tumor promotion, we conducted tests to examine the utility of selected short-term analyses for discriminating between condensates exhibiting significantly different promotion activities. In vitro analyses assessing the potential for inducing cytotoxicity (ATP bioluminescence) or free radical production (cytochrome c reduction, salicylate trapping) demonstrated significant reductions when comparing condensate collected from prototype cigarettes to reference condensate. Short-term in vivo analyses conducted within the context of a mouse skin, tumor-promotion protocol (i.e., comparative measures of epidermal thickness, proliferative index, myeloperoxidase activity, leukocyte invasion, mutation of Ha-ras, and formation of modified DNA bases) provided similar results. Reference condensate induced statistically significant and dose-dependent increases (relative to vehicle control) for nearly all indices examined, while prototype condensate possessed a significantly reduced potential for inducing changes that we regarded as consistent with sustained epidermal hyperplasia and/or inflammation. Collectively, these data support the contention that selected short-term analyses associated with sustained hyperplasia and/or inflammation are capable of discriminating between smoke condensates with dissimilar tumor-promotion potentials. Moreover, our results suggest that comparative measures of proliferative index and myeloperoxidase activity, both possessing favorable correlation coefficients relative to tumor formation (i.e., > or = 0.95 after 8 or 12 weeks of promotion), may constitute reasonable end points for further investigation.

Topics: Adenosine Triphosphate; Animals; Body Weight; Carcinogenicity Tests; Carcinogens; Cell Proliferation; Cytochromes c; DNA Adducts; Genes, ras; Hydroxyl Radical; Hyperplasia; Inflammation; Leukocytes; Luminescent Measurements; Mice; Mice, Inbred SENCAR; Oxidation-Reduction; Oxidative Stress; Peroxidase; Salicylates; Skin; Skin Neoplasms; Smoke; Superoxides

Muscle wasting accompanies aging and pathological conditions ranging from cancer, cachexia, and diabetes to denervation and immobilization. We show that activation of NF-kappaB, through muscle-specific transgenic expression of activated IkappaB kinase beta (MIKK), causes profound muscle wasting that resembles clinical cachexia. In contrast, no overt phenotype was seen upon muscle-specific inhibition of NF-kappaB through expression of IkappaBalpha superrepressor (MISR). Muscle loss was due to accelerated protein breakdown through ubiquitin-dependent proteolysis. Expression of the E3 ligase MuRF1, a mediator of muscle atrophy, was increased in MIKK mice. Pharmacological or genetic inhibition of the IKKbeta/NF-kappaB/MuRF1 pathway reversed muscle atrophy. Denervation- and tumor-induced muscle loss were substantially reduced and survival rates improved by NF-kappaB inhibition in MISR mice, consistent with a critical role for NF-kappaB in the pathology of muscle wasting and establishing it as an important clinical target for the treatment of muscle atrophy.

Topics: Animals; Body Weight; Cachexia; Cell Line; Cytokines; Enzyme Activation; Enzyme Inhibitors; Female; Hindlimb; Humans; I-kappa B Kinase; Male; Mice; Mice, Transgenic; Muscle, Skeletal; Muscular Atrophy; Neoplasm Transplantation; NF-kappa B; Organ Size; Phenotype; Protein Serine-Threonine Kinases; Salicylates; Signal Transduction; Survival Rate; Ubiquitin

The ability of Cu(II)(2)(3,5-diisopropylsalicylate)(4), CuDIPS, which exhibits superoxide dismutase (SOD)-like activity, to prevent cisplatin-induced nephrotoxicity was examined in rats. Rats were divided into four groups and treated as follows: (i) vehicle control; (ii) cisplatin (16 mg/kg, intraperitoneally); (iii) CuDIPS (10 mg/kg, intraperitoneally); and (iv) cisplatin plus CuDIPS. Rats were sacrificed 3 days post-treatment. Cisplatin alone resulted in significantly increased plasma creatinine and urea. Administration of 10 mg/kg CuDIPS prevented the cisplatin-induced elevation of plasma creatinine and urea and protected against kidney damage. Relative to controls, rats that received cisplatin treatment displayed a decrease of reduced glutathione (GSH) and elevated platinum and thiobarbituric acid reactive substances (TBARS) levels in the kidney. In comparison with controls, activities of antioxidant enzymes (SOD, CAT, GSH-Px and GSH-Rd) were also reduced in the kidney of rats treated with cisplatin. Administration of 10 mg/kg CuDIPS prevented cisplatin-induced alterations in renal platinum, GSH, TBARS, and antioxidant enzyme activities. This study suggests that the protection offered by CuDIPS against cisplatin-induced nephrotoxicity is partly related to maintenance of renal antioxidant systems.

Topics: Animals; Antineoplastic Agents; Antioxidants; Body Weight; Catalase; Cisplatin; Creatinine; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Kidney; Male; Platinum; Rats; Salicylates; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Urea

We have studied the effect of lysine acetylsalicylate (LAS; Aspegic), a soluble salt of aspirin, on motor deficits in transgenic mice expressing a human superoxide dismutase SOD1 mutation (Gly-93 --> Ala), an animal model of familial amyotrophic lateral sclerosis (FALS). In nontreated FALS mice, motor impairments appear at 12-14 weeks of age, whereas paralysis is not observed before 20 weeks of age. Life expectancy is 140-170 days. Early treatment with LAS from 5 weeks of age delayed the appearance of motor deficits in FALS mice as measured by extension reflex, loaded grid, and rotarod tests. This beneficial effect of treatment was maintained up to 18 weeks of age, until just before onset of end-stage disease. When treatment was started at 13 weeks, no significant beneficial effect was observed. These results demonstrate that chronic LAS treatment is able to delay the appearance of reflex, coordination, and muscle strength deficits in this animal model of ALS if the treatment is started early enough. However, neither the onset of paralysis nor end-stage disease were improved by the LAS treatment. In the absence of an effect on survival, the functional improvement demonstrated here is probably the maximum that this demanding model could allow. Although other properties of LAS may have contributed to its beneficial effect, we suggest that the antioxidant properties of aspirin are responsible for the positive effects in this model and support the use of antioxidants as effective therapy for ALS.

Topics: Amyotrophic Lateral Sclerosis; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Body Weight; Brain; Humans; Lysine; Male; Mice; Mice, Transgenic; Motor Activity; Muscle, Skeletal; Mutation; Postural Balance; Reflex; Salicylates; Solubility; Superoxide Dismutase

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

Local lymph node activation and increased total serum IgE levels are suggested to be predictive parameters of airway hypersensitivity caused by low molecular weight (LMW) chemicals. Whether increases of total serum IgE are indicative of actual induction of specific airway reactions (morphological and functional) after inhalation challenge was examined in the present study. In Brown Norway (BN) and Wistar rats, serum IgE concentrations were examined following topical exposure of chemicals with known diverse sensitization potential in humans: trimellitic anhydride (TMA), a dermal and respiratory sensitizer; dinitrochlorobenzene (DNCB), a dermal sensitizer with no known potential to cause respiratory allergy; and methyl salicylate, a skin irritant devoid of sensitizing properties. Functional and histopathological changes in the respiratory tract were examined after subsequent inhalatory challenge with these chemicals. Of the three tested chemicals, only topical exposure to TMA resulted in a significant increase in total serum IgE concentrations in the high-IgE-responding BN rat. Upon subsequent inhalatory challenge of these rats, TMA induced specific airway reactions which included a sharp decrease in respiratory rate during challenge, followed by an increase in breathing rate with a concomitant decrease in tidal volume 24 and 48 h after inhalatory challenge, and histopathological changes in the larynx and lungs of animals necropsied 48 h after challenge. Interestingly, despite low IgE levels, TMA induced histopathological changes in the larynx and lungs of Wistar rats too. Laryngeal changes were also observed in Wistar rats upon sensitization and challenge with DNCB. These data suggest that increased total serum IgE after topical sensitization is associated with immediate-type specific airway reactivity after inhalation challenge in BN rats and thus may be a valuable parameter in testing for respiratory sensitization potential of LMW compounds. Histopathological examination upon subsequent inhalation challenge of sensitized low-IgE-responders may provide information on other allergic inflammatory airway reactions.

Topics: Allergens; Animals; Body Weight; Bronchi; Dermatitis, Allergic Contact; Dinitrochlorobenzene; Female; Immunoglobulin E; Organ Size; Phthalic Anhydrides; Rats; Rats, Inbred BN; Rats, Wistar; Respiratory Function Tests; Respiratory Hypersensitivity; Salicylates

Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Female; Flavoring Agents; Male; Mice; Perfume; Pregnancy; Reproduction; Salicylates

Topics: Animals; Birth Weight; Body Weight; Dose-Response Relationship, Drug; Female; Fertility; Flavoring Agents; Litter Size; Male; Mice; Perfume; Pregnancy; Reproduction; Salicylates

Limited information exists on the disposition of aspirin in rabbits. Such information is of value not only for treatment but also for development of experimental protocols with human applications. We evaluated the pharmacokinetics of aspirin at different doses by monitoring serum concentrations of the major metabolite, salicylic acid (SA). Four groups of six female New Zealand white rabbits received 2.5, 10, 20, or 50 mg of aspirin/kg of body weight. Aspirin was given once daily via the oral-gastric route, and blood samples were obtained after the third dose. Samples were collected before the last dose, then at 0.25, 0.50, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 h after dosing. Analysis of SA was completed by a validated assay on a high-performance liquid chromatography system. Mean maximal serum SA concentration was 7.54, 22.65, 43.2, and 70 micrograms/ml for the 2.5, 10, 20, and 50 mg/kg doses respectively. The total systemic clearance of SA was not altered by increasing doses of aspirin, but statistically significant differences were noted in the volume of distribution. The SA elimination half-life also increased proportionally with the aspirin dose. Bleeding tendency was associated with the highest dose of aspirin. Results of this study suggest that the 20 and 50 mg/kg dosages produced serum SA concentrations that simulate those observed in humans after 600-mg and 1.2-g aspirin doses respectively.

Topics: Animals; Aspirin; Body Weight; Chromatography, High Pressure Liquid; Female; Kinetics; Rabbits; Salicylates; Salicylic Acid

Day-old Cobb broiler breeder pullets were randomly allotted into 20 floor pens where they were brooded and reared to 23 wk of age. Eight pens received a control diet containing no growth promotant. The other 12 were fed 55 mg of bacitracin methylene disalicylate/kg of diet. Males were reared separately on the control diet. Pullets were full-fed for the first 8 wk of life, then placed on a skip-a-day program with breeder-recommended feed allocations. At 23 wk of age bird numbers were reduced to 26 females per pen, three males added, and diets changed to the layer regimen. Levels of 0, 27.5, 55, or 110 mg/kg of zinc bacitracin were each assigned to five pens with factorial attention to growing treatment. Layer treatments were continued for 280 days. No significant differences were associated with the feeding of bacitracin methylene disalicylate among body weight or mortality data summarized at 8 and 23 wk. Eight-week feed efficiency was also not affected. In the laying phase, 110 mg/kg of zinc bacitracin significantly improved egg production and fertility over the unsupplemented controls. Hatch of fertile eggs, overall hatchability, and the number of chicks per pen were all significantly improved by 27.5 mg/kg of zinc bacitracin. Higher drug levels supported no additional improvement. Feed efficiency, mortality rate, and final body weight were not significantly influenced by any level of supplementation. No effect of grower treatment upon subsequent layer performance was noted.

Topics: Animal Feed; Animals; Bacitracin; Body Weight; Chickens; Coccidiostats; Diet; Eating; Eggs; Female; Fertility; Male; Oviposition; Random Allocation; Salicylates

A buffered propionic acid (BPA) was added to broiler diets fed in floor pens with litter. The BPA was fed continuously at 0, .2, .4, and .8% in Trial 1 and at 0 and .4% in Trial 2. The BPA was also fed at .4% for the last 7 days in Trial 2. Natural salmonellae exposure versus periodic dosage with Salmonella typhimurium was compared in Trial 2. In Trial 1, the BPA supplement had no adverse effects on growth, feed utilization, or abdominal fat with a significant (P less than or equal to .05) increase in the female dressing value at .8% of buffered propionic acid. The total number of coliforms and of Escherichia coli in the duodenum were significantly reduced by .4% BPA; in the jejunum, by all levels used in the trials; and in the ileum, by .4% and .8% of buffered propionic acid. The intestinal pH was not influenced by the BPA addition. In Trial 2, the BPA at .4% fed continuously had no adverse effect on growth, feed utilization, the abdominal fat of females, or the dressing percentage of males while significantly reducing the abdominal fat for males and increasing the dressing percentage for females. Feeding .4% BPA for the last 7 days had no effect on any of these parameters. Periodic dosage with S. typhimurium had no effect on body weight, feed utilization, or abdominal fat and significantly increased the dressing percentage. There was a significant interaction between the Salmonella dosage and the time of feeding BPA on dressing percentage.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bacitracin; Body Weight; Buffers; Chickens; Coccidiostats; Diet; Enterobacteriaceae; Female; Food Microbiology; Intestines; Male; Meat; Propionates; Random Allocation; Roxarsone; Salicylates

The effects of immunization in modulating the pathogenesis of Bacteroides (Porphyromonas) gingivalis infection in a murine model system were examined. BALB/c mice were immunized by intraperitoneal injection with B. gingivalis ATCC 53977 (one injection per week for 3 weeks), or with a lithium diiodosalicylate (LIS) extract (one injection per week for 3 weeks), or with lipopolysaccharide (LPS; one intravenous or intraperitoneal injection) from this same strain. Two weeks after the final immunization, the mice were challenged by subcutaneous injection of B. gingivalis ATCC 53977. Mice immunized with bacteria had no secondary lesions and no septicemia, whereas mice immunized with LIS extract had few secondary lesions and no septicemia. Mice immunized with LPS and nonimmunized mice demonstrated secondary abdominal lesions and septicemia after challenge. Bacterial cells and LIS extract, but not LPS, induced serum antibody and antigen reactive lymphocytes, as measured by enzyme-linked immunosorbent assay, immunoblot, Western immunoblot transfer, and in vitro lymphoproliferative responses. The present study suggests that immunization with a LIS extract or whole cells may induce a protective response against experimental B. gingivalis infection.

Topics: Animals; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Outer Membrane Proteins; Bacteroides; Bacteroides Infections; Blotting, Western; Body Weight; Electrophoresis, Polyacrylamide Gel; Female; Immunization; Iodobenzoates; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Polysaccharides, Bacterial; Salicylates

Survival as a function of salicylate dose and the intensity of environmental noise was investigated in 150 adult female pigmented rats. Rats were assigned to groups (n = 6/group) defined by combinations of salicylate levels from 0-(saline) to 300 mg/kg, injected subcutaneously, and noise levels from ambient noise to 98 dB SPL, presented daily for 10-h periods for up to 17 days. Mortality occurred in groups exposed to the higher combinations of salicylate and noise.

Topics: Animals; Body Weight; Female; Mortality; Noise; Rats; Salicylates

Six trials were conducted at different locations to examine the response of broiler chickens to roxarsone and bacitracin in the form of bacitracin methylene disalicylate (BMD) in the presence of the anticoccidal narasin. All diets contained narasin (80 mg/kg) and were fortified with a factorial arrangement of roxarsone (0 to 50 mg/kg) and BMD (0 or 55 mg/kg). Broilers were grown to market weights with narasin and roxarsone removed from the diets for the final 5 days. Addition of both roxarsone and BMD resulted in significant (P less than .05) improvements in body weight and feed utilization. Response to roxarsone for feed utilization was influenced to some extent by the presence or absence of BMD. Although the response to roxarsone was always positive, the degree of response was lessened by the presence of BMD. This resulted in a significant (P less than .10) interaction between roxarsone and BMD for feed utilization but not for body weight.

Topics: Animal Feed; Animals; Arsenicals; Bacitracin; Body Weight; Chickens; Coccidiostats; Female; Food Additives; Male; Pyrans; Roxarsone; Salicylates

Two experiments were conducted to evaluate the response of broiler chickens to addition of bacitracin methylene disalicylate (BMD) to diets containing salinomycin. In each experiment, five tests were conducted at different locations. In Experiment 1, all diets contained 66 mg salinomycin/kg of diet for the first 42 days and either 0 or 33 mg BMD/kg of diet for the entire 49-day feeding period. In Experiment 2, all diets contained 66 mg salinomycin and 50 mg roxarsone/kg of diet for the first 42 days and either 0, 11, 33, or 55 mg BMD/kg of diet for the entire 49-day feeding period. In Experiment 1, addition of 33 mg BMD/kg of diet significantly (P less than .05) improved body weights and feed utilization. Results were similar in all five tests. In Experiment 2, addition of 11, 33, or 55 mg BMD/kg of diet significantly (P less than .05) increased body weights. In one location the addition of 55 mg BMD/kg of diet resulted in no significant difference in body weight compared with those fed the unsupplemented diet, but in all other locations the response was similar. Addition of 33 or 55 mg BMD/kg of diet resulted in improved (P less than .05) feed utilization when all tests were combined. Feed utilization was not improved in all locations by the addition of BMD.

Topics: Animal Feed; Animals; Anti-Bacterial Agents; Arsenicals; Bacitracin; Body Weight; Chickens; Diet; Drug Therapy, Combination; Pyrans; Roxarsone; Salicylates

Salicylate kinetics following single, 650-mg intravenous and oral doses of aspirin were evaluated in humans in 2 studies. Complete conversion of aspirin to salicylate was assumed. The first study involved 25 young (25-40 years) and 21 elderly (66-89 years) healthy male and female volunteers. Mean salicylate clearance was lower in elderly females compared with that in young females; however, the difference between young men and elderly men was not significant. Salicylate free fraction in plasma increased significantly with age in men and women. After correction for free fraction, unbound mean clearance was reduced in elderly men compared with young men, and in elderly women compared with young women. Peak plasma salicylate concentrations after taking oral aspirin were not significantly influenced by age, and systemic availability of salicylate in all groups was complete. The second study compared 20 obese subjects (mean weight 113 kg) with 20 normal weight controls (mean weight 67 kg) matched for age, sex, height, and smoking habits. Small differences between obese and control groups were observed in total salicylate volume of distribution (Vd), unbound Vd, and mean clearance of total or unbound salicylate. Following normalization for total weight, however, values of total Vd and mean clearance were significantly smaller in obese subjects than in normal weight subjects. Rate and completeness of salicylate absorption were not influenced by obesity when aspirin was ingested, although peak levels were lower in obese subjects. If applied to multiple doses, the reduced unbound clearance of salicylate in the elderly would imply increased accumulation unless doses are appropriately adjusted downward. During long-term therapy, salicylate dosage for obese individuals should not be adjusted upward in proportion to total weight.

Topics: Administration, Oral; Adult; Age Factors; Aged; Aspirin; Body Weight; Female; Humans; Infusions, Parenteral; Kinetics; Male; Obesity; Salicylates; Salicylic Acid; Sex Factors

Three experiments were conducted to determine the effect of receiving diets containing alfalfa meal and certain feed additives on performance of comingled feeder pigs transported 900 to 1,100 km. In Exp. 1, the inclusion of 9.4% dehydrated alfalfa meal in receiving diets for 2 wk resulted in no difference (P greater than .1) in gain or feed conversion from purchase to market compared with pigs fed a basal corn-soybean meal (CS) diet or a diet containing 20% ground whole oats (O). In Exp. 2, pigs fed receiving diets containing 10% dehydrated alfalfa meal had no improvement (P greater than .1) in gain (.60 vs .61 kg/d) or conversion (3.25 vs 3.17) compared with CS-fed pigs. In Exp. 3, pigs fed a receiving diet for 2 wk containing 10% mid-bloom alfalfa ate more (P less than .002) feed daily for 2 wk (.82 vs .76 kg) and overall (P less than .04; 1.92 vs 1.85 kg) and had an improved (P less than .03) daily gain from purchase to market (.61 vs .59 kg) compared with CS-fed pigs. In Exp. 2, pigs fed diets containing 44 mg/kg tylosin (T) gained similar to pigs fed no additive (O) and slower (P less than .01) than pigs fed 110 mg/kg chlortetracycline (CTC; .59, .60 and .63 kg/d), with no significant differences in feed to gain conversion (3.12, 3.23 and 3.18).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animal Feed; Animals; Bacitracin; Body Weight; Chlortetracycline; Diarrhea; Female; Food Additives; Leucomycins; Male; Medicago sativa; Salicylates; Swine; Swine Diseases; Transportation; Tylosin

A 32-week experiment was carried out in floor pens with Cobb X Cobb breeder pullets that were 28 weeks old at initiation. Ten replicate pens, each containing 13 pullets and 2 males, received one of four dietary treatments. These treatments were either an unmedicated feed or 27.5, 55, or 110 mg/kg of bacitracin methylene disalicylate (BMD). All feeds contained 13.2 mg/kg of hygromycin B. Feed was allocated at a rate of 159 g per day and water was provided continuously. Hen-day egg production was significantly improved by the feeding of 27.5 mg/kg or more of BMD. Egg weights were significantly lower for all groups receiving the drug. Eggs of birds receiving 110 mg/kg were significantly heavier than those produced with 27.5 mg/kg, but neither differed statistically from those of the 55 mg/kg group. Neither final body weight nor overall mortality was significantly related to treatment. Egg fertility was significantly improved by 27.5 mg/kg or more of BMD. Hatchability of fertile eggs was not affected by the drug, but total hatchability was significantly increased through BMD feeding, largely on the strength of improved fertility.

Topics: Animals; Bacitracin; Body Weight; Chickens; Female; Fertility; Food Additives; Male; Mortality; Oviposition; Reproduction; Salicylates

The effect of glutathione and a glutathione reductase inhibitor on the antitumor effect of Cu(II)(3,5-diisopropylsalicylate)2 (CuDIPS) was studied. CuDIPS is a low-molecular-weight copper coordination compound that exhibits superoxide dismutase-like activity. CuDIPS had antitumor activity against intraperitoneal Ehrlich ascites carcinoma in Swiss mice. A single ip injection of glutathione partially eliminated the antitumor effect of CuDIPS, whereas a single ip injection of 1,3-bis(2-chloroethyl)-1-nitrosourea enhanced the antitumor effect of CuDIPS. These results are consistent with the hypothesis that CuDIPS exerts part of its antitumor effect by producing H2O2.

Topics: Animals; Antineoplastic Agents; Body Weight; Carcinoma, Ehrlich Tumor; Chemical Phenomena; Chemistry; Glutathione; Glutathione Reductase; Male; Mice; Neoplasm Transplantation; Salicylates; Superoxide Dismutase; Time Factors

Recent research indicates that endogenous copper is involved in anti-inflammatory and tissue repair processes. Of interest also is the analgesic efficacy of Cu complexes, since rheumatoid arthritis and similar inflammatory conditions are extremely painful. In pilot experiments, arthritic rats failed to increase voluntarily their rate of drinking a 5 mg/ml solution of copper salicylate (Cu Sal). The data from the experiment reported here showed that a forced oral dose of Cu Sal calculated at 200 mg/kg body weight significantly reduced sensitivity to mechanical pressure in less than 30 minutes but more than 15 minutes. The analgesic effect of the Cu Sal was greater for arthritic than for non-arthritic rats, suggesting that two types of analgesia are involved. First, it produces a direct analgesic effect which works irrespective of the presence of inflammation. Second, it appears to have an indirect analgesic effect due to reduction of inflammatory hyperalgesia. It was also found that Cu Sal administered orally reduces inflammation in rats with adjuvant arthritis. In summary, the results from this experiment demonstrate that Cu Sal has specific and general analgesic properties and anti-inflammatory potential.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Arthritis, Experimental; Body Weight; Copper; Male; Organometallic Compounds; Rats; Salicylates

The effect of the inducers of drug-metabolizing enzymes on the urinary excretion of aspirin metabolites in rats was studied. As to the inducer, rats were administered polychlorinated biphenyls (KC-500: 10, 50, and 100 mg/kg b.w.), phenobarbital (80 mg/kg b.w.), or 3-methylcholanthrene (25 mg/kg) intraperitoneally once a day for three days. The rats were orally administered aspirin (50 mg/kg) on the second-10th day after the pre-treatment with each inducer, and the urine were collected respectively. Aspirin metabolites (salicylic acid, salicyluric acid, and gentisic acid) in the urine were simultaneously determined with high-performance liquid chromatography and the liver microsomal cytochrome P-450 was determined. The results obtained were as follows. Excretion rate of total gentisic acid and salicylate glucuronide in the urine collected for first 6 hours were increased significantly by the pre-treatment with KC-500 or phenobarbital. In the pre-treated rats with various dose of KC-500, positive correlation was observed between the amount of liver microsomal cytochrome P-450 and the urinary excretion rate of gentisic acid (p less than 0.001). Salicylic acid hydroxylating activity of liver microsome was increased in the rats pretreated with KC-500, phenobarbital, or 3-methylcholanthrene. These results show that the increased urinary excretion of total gentisic acid and salicylate glucuronide may be due to the induction of drug-metabolizing enzymes in the liver. Therefore, it may be expected that these two aspirin metabolites are good indicators for the estimation of the activities of drug-metabolizing enzymes in vivo.

Topics: Animals; Aspirin; Biotransformation; Body Weight; Cytochrome P-450 Enzyme System; Gentisates; Male; Methylcholanthrene; Mice; Mice, Inbred Strains; Microsomes, Liver; Organ Size; Phenobarbital; Rats; Salicylates

The mechanism for the enhancing effect of pyrogen (lipopolysaccharide, LPS) on the fetal toxicity of acetylsalicylic acid (ASA) was studied in pregnant rats. The lethality of ASA was significantly enhanced by LPS in male rats. The fetal toxicity of ASA including fetal death, resorption, growth retardation, and skeletal anomalies (wavy rib and asymmetry of sternebra) was slightly observed in the dams that received a single dose of ASA (125 to 500 mg/kg, p.o.) on the 15th day of gestation, but it was markedly increased by LPS (20 micrograms/kg, i.v.). The enhancement of the toxicity of ASA by LPS was also observed in the maternal body weight gain until term. The plasma concentrations of ASA and salicylic acid (SA), the major metabolite of ASA, were increased by LPS. The tissue concentrations of SA were also increased in the following order: placenta, brain, fetus, uterus, liver and kidney. The ATP levels of placenta and fetus were not influenced by ASA alone, but markedly decreased by both LPS and ASA.

Topics: Abnormalities, Drug-Induced; Adenosine Triphosphate; Animals; Aspirin; Body Weight; Drug Synergism; Female; Fetus; Humans; Infant, Newborn; Lipopolysaccharides; Male; Maternal-Fetal Exchange; Pregnancy; Pyrogens; Rats; Salicylates; Salicylic Acid; Tissue Distribution

Topics: Aspirin; Blood Pressure; Body Weight; Humans; Renin; Salicylates; Time Factors

Topics: Adult; Body Weight; Humans; Ichthyosis; Male; Risk; Salicylates; Skin Absorption

Juvenile rheumatoid arthritis (JRA) in the Union of Soviet Socialist Republics (USSR) and the United States (USA) shows a remarkable similarity in age of disease onset, subtype onset, frequency, and most laboratory measurements. There is variation in the therapeutic approach with heavier reliance on aspirin in the USA. The evolution of JRA from onset subtype to final subtype over 5 years was the same in both groups and was independent of the type of therapy.

Topics: Adrenal Cortex Hormones; Arthritis, Juvenile; Blood Sedimentation; Body Height; Body Weight; Child; Child, Preschool; Hemoglobins; Humans; Indomethacin; Male; Phenylbutazone; Salicylates; United States; USSR

A total of 879 broiler strain chickens ranging from 2 1/2- to 7 1/2 weeks of age was utilized in four battery experiments to determine whether Roxarsone and/or bacitracin MD added to halofuginone were compatible and beneficial in reducing the effects of coccidial infections. The additives were generally beneficial as measured by weight gain and feed efficiency but not as measured by other parameters such as dropping score, lesion score, or oocyst production. The addition of 200 g of bacitracin/ton of feed did not give an additional response above that from 50 g/ton. Roxarsone in the ration was more effective in younger chickens (2 1/2 week old) than older ones (6 weeks, 2 days and 7 weeks, 3 days).

Topics: Animals; Arsenicals; Bacitracin; Body Weight; Chickens; Coccidiosis; Coccidiostats; Drug Combinations; Eimeria; Feeding Behavior; Piperidines; Poultry Diseases; Quinazolines; Quinazolinones; Roxarsone; Salicylates

Topics: Acetanilides; Animals; Aspirin; Blood Coagulation; Body Weight; Liver; Male; Mice; Rats; Salicylates; Stomach

Topics: Adult; Aspirin; Body Weight; Drug Administration Schedule; Female; Humans; Kinetics; Male; Models, Biological; Salicylates

Aspirin was given by continuous intravenous infusion to 35 intact cats for 7 days in doses ranging from 25 to 200 mg kg-1 day-1. Gastric mucosal lesions occurred in 50 to 70% of the animals in the various dosage groups, including deep ulcers in 20%. All of the ulcers were in antral mucosa near its border with oxyntic mucosa. The incidence of lesions, including ulcers, showed no apparent relation to the dose of aspirin. With all but the highest dose, plasma salicylate levels were within or below what is regarded as the therapeutic range for man. Asprin, 100 mg kg-1 day-1, was given for 7 days to 4 cats with pouches containing all of the antral mucosa plus some oxyntic mucosa. One or more deep ulcers occurred in the antral mucosa of the pouches in each of these 4 cats. The electrical potential difference across the mucosa did not decrease, and net fluxes of hydrogen ions out of the pouch and of sodium ions into the pouch did not increase during the 7 days of aspirin administration despite the occurrence of ulcers in the pouches. It is concluded that intravenous aspirin, in doses giving plasma levels within or below the therapeutic range for man, causes gastric mucosal lesions including deep ulcers within 7 days in cats. These lesions occur without the changes in electrical potential difference and hydrogen and sodium fluxes that are regarded as characteristic of the "broken barrier."

Topics: Animals; Aspirin; Body Weight; Cats; Dose-Response Relationship, Drug; Female; Gastric Mucosa; Hydrogen-Ion Concentration; Infusions, Parenteral; Ions; Male; Membrane Potentials; Salicylates; Stomach Ulcer

Topics: Age Factors; Animals; Body Weight; Diet; Male; Rats; Rats, Inbred Strains; Salicylates

1. The growth of rats treated with 3,5-dimethyoxy salicylic acid was retarded in comparison to that of normal rats. 2. The free cholesterol level of plasma of rats treated with 3,5-dimethoxy salicylic acid diminished while the pyruvate level of erythrocyte under the same condition increased in comparison with their normal levels; but on administration of thiamine both the cholesterol and pyruvate levels became normal. 3. The growth of a thiamine dependent strain of S. aureus was retarded when the organism was incubated in the medium containing 3,5-dimethoxy salicylic acid and this growth can be restored with the supplementation of thiamine in the medium.

Topics: Animals; Body Weight; Cholesterol; Erythrocytes; Growth; Male; Pyruvates; Rats; Salicylates; Staphylococcus aureus; Thiamine

Topics: Aspirin; Body Weight; Humans; Kinetics; Salicylates

Topics: Animals; Body Weight; Depression, Chemical; Drinking Behavior; Feeding Behavior; Female; Hematocrit; Hemoglobinometry; Kidney; Lung; Male; Organ Size; Rats; Salicylates; Time Factors

Two and three Dow Cordis Hollow Fiber and Gambro Lundia artificial kidneys were used for high efficiency dialysis in large patients, intoxications, and for rapid ultrafiltration. BUN clearances of up to 240 ml/min were achieved. One episode of severe neuropathy occurred during high efficiency dialysis, and hypotensive episodes were more common. High efficiency dialysis has certain indications particularly in intoxication cases. However, because of possible side effects more experience is needed before its ultimate place in the treatment of uremia can be ascertained.

Topics: Barbiturates; Blood Urea Nitrogen; Body Weight; Calcium; Creatinine; Edema; Headache; Humans; Hypotension; Kidneys, Artificial; Nausea; Phenobarbital; Phenytoin; Poisoning; Primidone; Renal Dialysis; Salicylates; Substance-Related Disorders; Ultrafiltration; Uremia; Uric Acid

The absorption rates of two model drugs, salicylate and antipyrine, from the small intestines of rats deprived of food for various periods of time were compared with rats fed ad libitum. Fasting reduced the absorption rate constants for both drugs with the salicylate rates being depressed more severely than the rates for antipyrine. Intestinal mass studies showed that the weight/length ratio of the rat intestine is progressively decreased as fasting is prolonged up to 96 hr. The intestinal weight loss was much more pronounced than the total body weight loss. The loss in intestinal weight and the observed decrease in drug absorption rate are believed to be related to the inhibition of intestinal cell proliferation due to fasting, resulting in a decreased absorptive surface and reduced mucosal cell viability.

Topics: Animals; Antipyrine; Body Weight; Fasting; Intestinal Absorption; Male; Organ Size; Rats; Salicylates; Time Factors

Toxicity of imbrimycin administered orally and its local irritating effect was studied experimentally. Imbrimycin was diluted with flagosol for decreasing its local irritating effect on the mucosa of the eye conjunctiva and vagina of rabbits. Administration of imbrimycin suspension to albino rats in doses of 10 and 50 mg/kg for 14 days had no effect on the body weight, liver antitoxic function and pathomorphological indices. Oral administration of the drug to dogs in a dose of 10 mg/kg caused a decrease in the body weight, vomiting and diarrhea, had no effect on the dog blood picture and induced no pathomorphological changes in the inner organs. The local irritating effect of imbrimycin was found to be equal to that of azalomycin F. Flagosol significantly decreased the irritating effect of imbrimycin on the eye conjunctiva and the vagina mucosa.

Topics: Animals; Antifungal Agents; Blood; Body Weight; Conjunctiva; Dogs; Drug Combinations; Drug Interactions; Female; Growth; Japan; Kinetics; Lethal Dose 50; Liver; Macrolides; Mice; Rabbits; Rats; Salicylates; Samarium; Time Factors; Urine; USSR; Vagina

The influence of salicylic acid on pathological epithelial proliferation has been evaluated by means of the peidermal hyperplasia inhibition test in the guinea pig. 3% w/w salicylic acid dissolved in ethanol reduced surface epithelial hyperplasia by 15%, i.e. exhibited activity comparable to that of hydrocortisone 0.1% w/w. 1% w/w salicylic acid dissolved in a dimethylacetamide-acetone-ethanol mixture exerted an even greater degree of antihyperplastic activity on the surface epithelium (-18%) and also a marked inhibitory effect on deep epithelial proliferation (-10%).

Topics: Acetamides; Acetone; Administration, Topical; Animals; Body Weight; Cell Division; Drug Evaluation, Preclinical; Drug Synergism; Epithelial Cells; Epithelium; Ethanol; Guinea Pigs; Hydrocarbons; Hyperplasia; Male; Salicylates; Skin; Skin Diseases; Solvents

Topics: Adult; Body Weight; Calcium; Carbimazole; Erythema Nodosum; Female; Hematocrit; Hemoglobins; Humans; Hyperthyroidism; Salicylates; Sarcoidosis; Thyroid Function Tests

Topics: Acetates; Animals; Anti-Inflammatory Agents; Body Weight; Cortisone; Gastric Mucosa; Hexosamines; Hydroxyproline; Male; Phenylbutazone; Prednisone; Rats; Rats, Inbred Strains; Salicylates; Staining and Labeling; Stomach; Stomach Ulcer; Time Factors

Topics: Adult; Aged; Anesthesia, Local; Body Weight; Boric Acids; Ear Diseases; Eustachian Tube; Female; Hearing Disorders; Humans; Middle Aged; Palate; Posture; Pressure; Salicylates; Sphenoid Bone; Tendons; Therapeutic Irrigation; Tinnitus

Topics: Anilides; Animals; Behavior, Animal; Body Weight; Brain; Bromine; Chromatography, Gas; Hexachlorophene; Male; Neurologic Manifestations; Organ Size; Paralysis; Pituitary Gland; Prostate; Rats; Reproduction; Salicylamides; Salicylates; Seminal Vesicles; Testis; Time Factors

Topics: Albumins; Aminohippuric Acids; Animals; Body Weight; Carbon Isotopes; Cats; Central Nervous System; Cerebral Ventricles; Cisterna Magna; Heart Rate; Iodides; Iodine Isotopes; Kinetics; Penicillin G; Perfusion; Respiration; Salicylates; Serum Albumin; Sucrose; Time Factors; Tritium

Topics: Acetaminophen; Animals; Anti-Inflammatory Agents; Arthritis; Aspirin; Body Weight; Chlorpromazine; Cyclophosphamide; Dexamethasone; Dose-Response Relationship, Drug; Drug Interactions; Hydrocortisone; Indomethacin; Male; Mycobacterium; Phenytoin; Prednisolone; Rats; Salicylates; Spironolactone; Time Factors

Topics: Administration, Oral; Animals; Aspirin; Autopsy; Autoradiography; Biopsy; Body Weight; Dogs; Epithelial Cells; Gastric Mucosa; Gastrointestinal Hemorrhage; Histocytochemistry; Mucins; Salicylates; Stomach; Stomach Ulcer; Time Factors

Topics: Animals; Body Weight; Diet; Dose-Response Relationship, Drug; Feeding Behavior; Humans; Hydrocortisone; Immobilization; Male; Peptic Ulcer; Rats; Salicylates; Stress, Psychological

Topics: Animals; Antipyrine; Biological Transport; Blood Proteins; Body Weight; Cell Membrane Permeability; Female; Goats; Half-Life; Hydrogen-Ion Concentration; Injections, Intravenous; Kinetics; Male; Metabolism; Pentobarbital; Phenylbutazone; Protein Binding; Quinine; Salicylates; Sex Factors; Sulfanilamides; Time Factors; Tolazoline

Topics: Abnormalities, Drug-Induced; Animals; Body Weight; Female; Fetal Diseases; Fetus; Gestational Age; Hydronephrosis; Injections, Intraperitoneal; Kidney; Maternal-Fetal Exchange; Organ Size; Pregnancy; Rats; Salicylates

Topics: Animals; Body Weight; Cholera; Cholera Vaccines; Formaldehyde; Hot Temperature; Lactones; Mercury; Mice; Phenols; Salicylates; Suspensions; Vaccination; Vibrio

Topics: Administration, Oral; Age Factors; Blood Glucose; Blood Specimen Collection; Body Height; Body Weight; Contraceptives, Oral; Diabetes Mellitus; Diagnostic Errors; Diuretics; Drug-Related Side Effects and Adverse Reactions; Follow-Up Studies; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Salicylates; Sex Factors; Steroids

Topics: Animals; Anti-Inflammatory Agents; Betamethasone; Body Weight; Carrageenan; Collagen; Diet; Granuloma; Indomethacin; Injections, Subcutaneous; Male; Phenylbutazone; Rats; Salicylates

Topics: Age Factors; Analgesics; Animals; Anticonvulsants; Aspirin; Body Weight; Electric Stimulation; Electrodes; Hindlimb; Male; Methods; Mice; Pain; Pentazocine; Phenobarbital; Salicylates; Tail; Time Factors; Urea

Topics: Adult; Aged; Body Height; Body Surface Area; Body Weight; Humans; Iodine Radioisotopes; Liver; Middle Aged; Salicylates; Sodium Salicylate; Stimulation, Chemical; Thyroxine; Thyroxine-Binding Proteins

Topics: Aminobenzoates; Animals; Body Weight; Histidine; Immunity; Pantothenic Acid; Rats; Salicylates; Taurine; Trypanosoma; Trypanosomiasis

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Body Weight; Circadian Rhythm; Female; Humans; Intestinal Absorption; Male; Middle Aged; Salicylates; Solubility; Tablets, Enteric-Coated

Topics: Anilides; Animals; Aspirin; Benzoates; Body Weight; Carcinoma, Hepatocellular; Kidney; Liver; Liver Neoplasms; Male; Mice; Microscopy, Electron; Organ Size; Organoids; Rats; Salicylates

Topics: Animals; Animals, Newborn; Aspirin; Body Weight; Growth; Humans; Infant, Newborn; Rats; Salicylates; Tibia

Topics: Blood Sedimentation; Body Weight; Child; Cortisone; Erythrocytes; Infant; Rheumatic Fever; Salicylates