thiouracil and Body-Weight

The effects of thyroid suppression induced during the rearing period by providing various dietary thiouracil (TU) regimens on plasma thyroxine (T4) concentrations, growth, and subsequent egg production (EP) and eggshell quality were determined in Single Comb White Leghorn chickens. Thiouracil was provided in the feed at levels of 0, .1, and .2% from 0 to 6 wk of age in Experiment 1, and at levels of 0, .05, and .1% from 6 to 16 wk of age in Experiment 2. In both experiments, T4 concentrations were reduced during TU treatment. However, T4 later became elevated at 12 and 20 wk in both dosage level groups in Experiment 1. Additionally, BW and egg weights were suppressed by both TU treatments, and EP was reduced up to Week 23 in the .1% TU-treated birds and through Week 25 in the .2% TU-treated birds. No effects on EP were noted in Experiment 2, but feed consumption (FC) was reduced during Week 6 in birds fed .05% TU and during Weeks 6, 10, and 19 in birds fed .1% TU. Both liver and thyroid weights were increased in .1% TU-treated birds relative to controls at Week 16. Eggshell quality was affected only in Experiment 2, in which birds given .05% TU had a higher relative conductance, or maximum rate of water loss, at Week 38 than 0 and .1% TU dosage levels, and .1% TU-treated birds had a higher breaking strength than 0 and .05% TU-treated birds at Week 22.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animal Feed; Animals; Body Weight; Chickens; Eating; Egg Shell; Eggs; Female; Statistics as Topic; Thiouracil; Thyroxine

The effect of the thyroid activity on the formation of lipid peroxidation and on liver and heart antioxidant enzyme activities was investigated in Wistar rats. Hypothyroidism and hyperthyroidism conditions were induced for five weeks by the administration of 0.05% benzythiouracile (BTU) and L-thyroxine sodium salt (0.0012%), in drinking water, respectively. No significant effect was observed on the rates of both lipid peroxidation and the vitamin E in hepatic and cardiac tissues of hypothyroidism rats compared to the controls, contrary to the hyperthyroidism rats, which expressed a pronounced increase. The increased glutathione peroxidase activity in rats suffering from hyperthyroidism was associated with a fall of the reduced glutathione in the homogenate and a marked increase in the glutathione reductase activity. An increase in superoxide dismutase and catalase activities was also recorded in hyperthyroidism. Our results explain the thyroid activity variation in relation to the lipid peroxidation and the tissular contents of the enzymatic and the non-enzymatic antioxidants. To conclude, our results show the occurrence of a state of oxidizing stress in relation to hyperthyroidism.

Topics: Animals; Body Weight; Catalase; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Hyperthyroidism; Hypothyroidism; Lipid Peroxidation; Liver; Male; Myocardium; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase; Thiouracil; Thyroid Gland; Thyroxine

The purpose of this investigation was to evaluate the effectiveness of oral 5-(phenylthio)acyclouridine (PTAU) in reducing 5-fluorouracil (FUra) host-toxicity and enhancing its chemotherapeutic efficacy against human colon tumors. PTAU is a potent and specific inhibitor of uridine phosphorylase (UrdPase, EC 2.4.2.3), the enzyme responsible for uridine catabolism.. SCID mice bearing human colon DLD-1 or HCT-15 tumors were injected intraperitoneally with FUra (50, 200 or 300 mg/kg) on days 17, 24 and 31 after tumor cell inoculation. PTAU (120 mg/kg), uridine (1,320 mg/kg) or their combination was administered orally 2 or 4 h after FUra injection. Another four administrations of PTAU+uridine were given every 8 h after the first treatment with PTAU plus uridine. Survival and body weight were used to evaluate host toxicity. Tumor weight was used to evaluate the efficacy of the drugs on tumor growth. The mice were monitored for 38 days.. Administration of the maximum tolerated dose (50 mg/kg) of FUra reduced DLD-1 and HCT-15 tumor weights by 48 and 59%, respectively, at day 38 post implantation. Administration of 200 mg/kg FUra resulted in 100% mortality. Oral administration of uridine (1,320 mg/kg) alone, 2 h following the administration of 200 mg/kg FUra, did not alleviate FUra host-toxicity as all the mice died. Administration of 120 mg/kg PTAUresulted in partial rescue from this lethal dose of FUra as 63% of mice survived and tumor weights were reduced by approximately 60%. Coadministration of PTAU plus uridine resulted in complete rescue from the toxicity of FUra as 100% of the mice survived and tumor weights were reduced by 81-82%. Delaying the administration of the combination of PTAU plus uridine to 4 h post FUra treatment was less effective in rescuing from FUra toxicity as only 88% of the mice survived and tumor weights were reduced by only 62%. Administration of PTAU alone, under the same conditions, resulted in a 38% survival rate while the tumor weights were reduced by 47%. Treatment with uridine alone did not protect from FUra toxicity at the dose of 200 mg/kg as all mice died. At the higher dose of 300 mg/kg FUra, neither uridine nor PTAU alone, administered 2 h following the treatment with FUra, had any rescuing effect. On the other hand, the use of the PTAU plus uridine combination reduced the tumor weight by 79%, although this reduction in the tumor weight was accompanied by 37% mortality. There was no significant difference between DLD-1 and HCT-15 in their response to the different regimens employed in this study despite the fact that the tumors have different levels of UrdPase.. The present results demonstrate that the combination of PTAU plus uridine represents an exceptionally efficient method in increasing FUra chemotherapeutic efficacy while minimizing its host-toxicity. The efficiency of the PTAU plus uridine combination can be attributed to the extraordinary effectiveness of this combinationin raising and maintaining higher levels of uridine in vivo (Al Safarjalani et al., Cancer Chemo Pharmacol 55:541-551, 2005). Therefore, the combination of PTAU plus uridine can provide a better substitute for the large doses of uridine necessary to rescue or protect from FUra host-toxicities, without the toxic side-effects associated with such doses of uridine. This combination may also allow for the escalation of FUra doses for better chemotherapeutic efficacy against human colon carcinoma while avoiding FUra host-toxicities. Alternatively, the combination of PTAU and uridine may be useful as an antidote in the few cases when cancer patients receive a lethal overdose of FUra.

Topics: Administration, Oral; Animals; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Cell Line, Tumor; Colonic Neoplasms; Dose-Response Relationship, Drug; Enzyme Inhibitors; Fluorouracil; Humans; Male; Mice; Mice, SCID; Survival Analysis; Thiouracil; Uridine; Uridine Phosphorylase; Xenograft Model Antitumor Assays

The purpose of this investigation was to evaluate the effectiveness of oral 5-(phenylthio)acyclouridine (PTAU) in improving the pharmacokinetics and bioavailability of oral uridine. PTAU is a potent and specific inhibitor of uridine phosphorylase (UrdPase, EC 2.4.2.3), the enzyme responsible for uridine catabolism. This compound was designed as a lipophilic inhibitor in order to facilitate its access to the liver and intestine, the main organs involved in uridine catabolism. PTAU is fully absorbed after oral administration with 100% oral bioavailability.. Uridine (330, 660 or 1320 mg/kg) and/or PTAU (30, 45, 60, 120, 240 or 480 mg/kg) were orally administered to mice. The plasma levels of uridine, its catabolite uracil, and PTAU were measured using HPLC, and pharmacokinetic analysis was performed.. Oral PTAU up to 480 mg/kg per day is not toxic to mice. Oral PTAU at 30, 45, 60, 120 and 240 mg/kg has a prolonged plasma half-life of 2-3 h, and peak plasma PTAU concentrations (C(max)) of 41, 51, 74, 126 and 161 microM with AUCs of 70, 99, 122, 173 and 225 micromol h/l, respectively. Coadministration of uridine with PTAU did not have a significant effect on the pharmacokinetic parameters of plasma PTAU at any of the doses tested. Coadministration of PTAU (30, 45, 60 and 120 or 240 mg/kg) with uridine (330, 660 or 1320 mg/kg) elevated the concentration of plasma uridine over that following the same dose of uridine alone, a result of reduced metabolic clearance of uridine as evidenced by decreased plasma exposure (C(max) and AUC) to uracil. Plasma uridine was elevated with the increase of uridine dose at each PTAU dose tested and no plateau was reached. Coadministration of PTAU at 30, 45, 60, 120 and 240 mg/kg improved the low oral bioavailability (7.7%) of uridine administered at 1320 mg/kg by 4.3-, 5.9-, 9.9-, 11.7- and 12.5-fold, respectively, and reduced the AUC of plasma uracil (1227.8 micromol h/l) by 5.7-, 6.8-, 8.2-, 6.3-, and 6.9-fold, respectively. Similar results were observed when PTAU was coadministered with lower doses of uridine. Oral PTAU at 30, 45, 60, 120 and 240 mg/kg improved the oral bioavailability of 330 mg/kg uridine by 1.7-, 2.4-, 2.6-, 5.2- and 4.3- fold, and that of 660 mg/kg uridine by 2.3-, 2.7-, 3.3-, 4.6- and 6.7-fold, respectively.. The excellent pharmacokinetic properties of PTAU, and its extraordinary effectiveness in improving the oral bioavailability of uridine, could be useful to rescue or protect from host toxicities of 5-fluorouracil and various chemotherapeutic pyrimidine analogues used in the treatment of cancer and AIDS, as well as in the management of medical disorders that are remedied by the administration of uridine including CNS disorders (e.g. Huntington's disease, bipolar disorder), liver diseases, diabetic neuropathy, cardiac damage, various autoimmune diseases, and transplant rejection.

Topics: Administration, Oral; Animals; Antimetabolites, Antineoplastic; Biological Availability; Body Weight; Female; Fluorouracil; Mice; Mice, Inbred Strains; Thiouracil; Uracil; Uridine; Uridine Phosphorylase

Hypothyroidism in the developing rat brain is associated with enhanced oxidative stress, one of the earliest manifestations of which is a decline in the level of glutathione (GSH). To investigate the role of thyroid hormone (TH) on GSH homeostasis, the effect of TH on gamma-glutamyl transpeptidase (gammaGT), the key enzyme involved in the catalysis of GSH, was studied. Hypothyroidism declined the specific activity of cerebral gammaGT at all postnatal ages examined (postnatal day 1-20) with a maximum inhibition of 42% at postnatal day 10. Intraperitoneal injection of TH to 15-day-old rat pups increased the specific activity of gammaGT by 25-30% within 4-6 hr. Treatment of primary cultures of astrocytes by TH also enhanced the specific activity of gammaGT by 30-40% within 4-6 hr. The induction of gammaGT by TH was blocked by actinomycin D or cycloheximide. gammaGT is an ectoenzyme that is normally involved in the catabolism of GSH released by astrocytes. In the presence of the gammaGT-inhibitor, acivicin, GSH released in the culture medium of astrocytes increased linearly for at least 6 hr and TH had no effect on this accumulation pattern. In the absence of acivicin, GSH content of the medium from TH-treated cells was significantly lower than that of untreated controls due to activation of gammaGT by TH and a faster processing of GSH. Because the products of gammaGT reaction are putative precursors for neuronal GSH, the activation of gammaGT by TH may be conducive to GSH synthesis in neurons and their protection from oxidative stress.

Topics: Age Factors; Animals; Animals, Newborn; Antithyroid Agents; Astrocytes; Body Weight; Cell Survival; Cerebral Cortex; Drug Interactions; Enzyme Activation; Enzyme Inhibitors; Female; gamma-Glutamyltransferase; Glutathione; Hypothyroidism; Immunohistochemistry; Isoxazoles; Male; Pregnancy; Radioimmunoassay; Rats; Thiouracil; Thyroid Hormones; Time Factors

The Donryu rat is resistant to a high cholesterol diet in that typical atheromatous lesions do not develop. Using electron microscopic immunocytochemical techniques, the effects of a CCT diet (4% cholesterol with 1% cholic acid and 0.5% thiouracil) on the distributions of neuronal, macrophage, and endothelial specific nitric oxide synthase (NOS I, NOS II, and NOS III) and endothelin-1 (ET-1) immunoreactivity were examined in the thoracic aortic intima. Atheromatous lesions were absent, but immunocytochemistry showed 1. 4+/-0.52% and 4.0+/-0.9% endothelial cells (EC) with positive staining for NOS I and NOS III, respectively, compared with 16.3+/-2. 5% and 88.6+/-2.48% in control Donryu rats. The CCT-supplemented diet induced expression of NOS II immunoreactivity in thoracic aortic intimal cells. EC, subendothelial macrophages, and smooth muscle cells (SMC) also showed high NOS II-positive staining. The percentage of NOS II-immunoreactive EC was 43+/-1.8%. In control groups, no NOS II immunoreactive cells were observed. The percentage of ET-1 immunopositive cells was also significantly increased by 9. 2+/-0.66% and 64.2+/-1.4% in control and CCT-fed groups, respectively. It is concluded that the administration of a high cholesterol diet in Donryu rats produces endothelial dysfunction associated with changes in the balance of the different isoforms of NOS and ET-1. Therefore, the increase in inducible NOS and ET-1 immunoreactivity seen during the cholesterol-enriched diet appears to be a compensatory reaction of aortic wall cells to the high cholesterol supplementation.

Topics: Animals; Aorta; Body Weight; Cholesterol, Dietary; Cholic Acid; Diet; Endothelin-1; Endothelium, Vascular; Immunohistochemistry; Lipids; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Rats; Rats, Inbred Strains; Thiouracil

The effects of consecutive exposures to dietary thiouracil (TU) in juvenile and adult Single Comb White Leghorn chickens on plasma thyroxine (T4) concentrations, egg production (EP), egg weight (EW), concentrations eggshell quality were determined. Thiouracil was provided in the feed at levels of 0, 0.1, or 0.2% (PTRT) from 0 to 6 wk of age and at levels of 0 or 0.1% (TRT) from 32 to 38 wk of age. Body weight gain was simulated but T4, EW, EP, and eggshell quality were generally reduced by 0.1% TU TRT. However, TU PTRT alleviated a latent depressing effect of TU TRT on BW after 38 wk of age. Thiouracil PTRT, particularly at the 0.2% level, induced significant decreases in EW but increased EP between 32 and 50 wk. The effects of early thyroid suppression in juveniles with TU PTRT on the subsequent reproduction of adults were primarily in response to a delay in the onset of sexual maturity, and not directly to prolonged responses in T4 or BW that extended into lay.

Topics: Aging; Animals; Antithyroid Agents; Body Weight; Chickens; Diet; Drug Administration Schedule; Egg Shell; Eggs; Female; Fertility; Oviposition; Thiouracil; Thyroxine; Weight Gain

The objective of the current study was to determine whether thyroid physiology may affect molting time in turkeys. Two trials using approximately 144 hens were conducted to elucidate thyroidal factors that limit the molting process. Thyroid hormones or a thyroid blocker (thiouracil) were given to the hens during a molt by supplementing the diet with thyroxine (T4), triiodothyronine (T3), or thiouracil. Supplementing with T4 reduced the number of days to return to egg production, whereas supplementing with thiouracil or T3 prolonged days to first egg. The observations support previous suggestions of separate functions for T3 and T4 during molting. As had been observed many times previously, the feeding of thiouracil delayed the molt but did not completely stop the molting process. The hens fed thiouracil returned to 50% egg production nearly 10 d after the control group, whereas T3 prolonged the return to 50% egg production nearly 1 wk later. The data indicate the endogenous low levels of T4, but not T3 in modern strains of turkeys may contribute to a relatively longer molting period of turkey breeder hens induced to molt out of season.

Topics: Analysis of Variance; Animals; Body Temperature; Body Weight; Breeding; Eating; Female; Food, Fortified; Lighting; Molting; Oviposition; Radioimmunoassay; Random Allocation; Thiouracil; Thyroid Hormones; Thyroxine; Time Factors; Triiodothyronine; Turkeys

Enteric bacteria have been postulated to have a role in thyroid economy by promoting the hydrolysis of thyroid hormone conjugates of biliary origin, thus permitting the absorption and recycling of thyroxine (T4) and triiodothyronine (T3). An enterohepatic circulation of T3 might be more pronounced under conditions in which type I iodothyronine deiodinase activity (5'D-I) is inhibited, because this augments the accumulation of T3 sulfate conjugates in bile. This potential of increased gut reabsorption of T3 might explain, at least in part, the failure of serum T3 values to decrease appreciably when marked reductions in peripheral 5'D-I activity are induced by selenium deficiency or 6-anilino-2-thiouracil (ATU) administration. Thus, studies were performed to determine the effect of intestinal decontamination, in the absence and in the presence of 5'D-I inhibition, on plasma T4 and T3 concentrations. Groups of adult male rats received either enteric antibiotics or no antibiotics for 12 days and then, in half of the rats in each group, treatment for 10 days with ATU, a 5'D-I inhibitor that does not affect thyroid hormone synthesis. The activity of intestinal arylsulfatase and arylsulfotransferase, enzymes that catalyze hydrolysis of thyroid hormone conjugates, was reduced markedly by approximately 87% in rats that received antibiotics, regardless of whether or not they also received ATU. The ATU treatment markedly inhibited liver 5'D-I activity in antibiotic-treated as well as in non-antibiotic-treated rats (control = 399 +/- 32 U/mg protein (mean +/- SEM); ATU = 152 +/- 17: antibiotics = 351 +/- 29; antibiotics + ATU = 130 +/- 10; p < 0.01) and significantly increased plasma T4 and T3 sulfate (T4S, T3S) concentrations (control: T4S = 2.8 +/- 0.4 and T3S = 6.7 +/- 1.3 ng/dl; ATU: T4S = 6.2 +/- 1.4 and T3S = 10.6 +/- 2.1 ng/dl; antibiotics: T4S = 1.8 +/- 0.2 and T3S = 3.6 +/- 1.0 ng/dl; antibiotics + ATU: T4S = 6.8 +/- 0.7 and T3S = 9.7 +/- 1.8 ng/dl; p < 0.05). The ATU treatment was associated with a significant increase in plasma T4 and rT3 concentrations but did not affect plasma T3 concentrations, and intestinal decontamination did not alter these ATU-associated effects on circulating thyroid hormones. These results suggest that anaerobic enteric bacteria in the rat do not have an important role in recycling of thyroid hormones, either under normal conditions or in circumstances where 5'D-I activity is markedly reduced, and that increased gut absorption of

Topics: Aniline Compounds; Animals; Anti-Bacterial Agents; Body Weight; Enzyme Inhibitors; Intestines; Iodide Peroxidase; Male; Organ Size; Rats; Rats, Sprague-Dawley; Thiouracil; Thyroid Gland; Thyroxine; Triiodothyronine

The analysis of covariance is often used in the context of premeasure/postmeasure designs to compare treatment and control groups in both randomized [1] and nonrandomized [2] studies. The intent is to adjust the difference between the changes in the 2 groups for any difference which might exist at baseline, i.e., for any difference between the premeasures in the 2 groups. An important assumption underlying the use of the analysis of covariance is that the slopes of the lines for the regression of the postmeasure on the premeasure in the 2 groups are equal. In this paper we describe a program which can be used to test the hypothesis of equal slopes; and performs an alternative analysis which does not depend on this assumption. This is done in the context of comparing treatment and control groups with respect to a measurement subject to natural maturation as in [3]. Equal slopes in this context means equal growth rates; unequal slopes implies that the 2 groups are growing at different rates. The method, known as the Johnson-Neyman procedure [4] is, however, more general than this, and can be used in any two-sample comparison where an alternative to the usual analysis of covariance is deemed appropriate. The procedure identifies a 'region of significance' which is especially useful in practice. This region consists of a set of values of the premeasure for which the treatment and the control groups are significantly different with respect to the postmeasure.

Topics: Analysis of Variance; Animals; Body Weight; Computer Simulation; Growth; Mathematical Computing; Microcomputers; Models, Biological; Models, Statistical; Rats; Regression Analysis; Research Design; Software; Thiouracil

We studied the effects of clentiazem, a calcium channel blocker (1) on the accumulation of lipid in the aorta, (2) on the level of plasma lipids, and (3) on the number of adherent intimal monocytes and foam cells. Seventy Wistar rats were assigned to one of the following groups: (1) regular diet, (2) an atherogenic diet consisting of regular chow with 2% cholesterol, 1% cholic acid, and 0.5% thiouracil (CCT), (3) CCT supplemented with 5 mg/kg/day clentiazem, and (4) CCT with 25 mg/kg/day clentiazem. Animals were sacrificed after 6 or 12 weeks of diet. Aortas were studied by light microscopy after staining with oil red O (ORO) and/or hematoxylin. ORO staining was quantified in both abdominal and thoracic regions of the aorta. The aortas of the clentiazem groups demonstrated significantly less ORO staining than CCT diet controls in thoracic aorta after 6 weeks and abdominal aorta after 12 weeks. There was no significant difference in the plasma lipid concentrations. The clentiazem-treated groups had fewer numbers of adherent monocytes and foam cells. We conclude that clentiazem inhibits lipid deposition in cholesterol-fed rats without lowering plasma lipid concentrations and that the number of intimal monocytes and foam cells is decreased in the presence of this calcium antagonist.

Topics: Animals; Aorta; Blood Pressure; Body Weight; Calcium Channel Blockers; Cell Adhesion; Cell Count; Cholesterol; Cholic Acids; Diet, Atherogenic; Diltiazem; Heart Rate; Hypercholesterolemia; Lipid Metabolism; Lipids; Male; Models, Biological; Monocytes; Rats; Rats, Wistar; Thiouracil

Because ascorbic acid (AA) and the thyroid hormones are known to influence eggshell formation, the effects of AA on body weight, total plasma thyroxine (T4), egg production, and eggshell quality of Single Comb White Leghorn (SCWL) hens concurrently and previously treated with thiouracil (TU) were determined. Hens were provided feed containing either 0 or 100 ppm AA from 47 to 67 wk of age and either 0 or .1% TU from 47 to 57 wk of age. A three-way split-plot analysis was employed to test for the effects of AA, TU, and time, and their interactions. Dietary TU increased body weight between 53 and 59 wk, and increased thyroid weight at 67 wk; however, TU only depressed plasma T4 level at 51 wk. Dietary TU depressed egg production from 50 to 56 wk and egg weight at 49, 51, and 57 wk. Dietary TU depressed eggshell weight per unit surface area at 49 wk. There was no significant effect due to AA and no AA by TU interaction for any of the parameters examined. It was concluded that .1% dietary TU from 47 to 57 wk of age did not alter eggshell quality and that dietary AA at the 100 ppm level did not influence the effects of .1% TU on body weight, egg production, or egg weight of SCWL hens.

Topics: Animals; Ascorbic Acid; Body Weight; Chickens; Egg Shell; Eggs; Female; Organ Size; Oviposition; Thiouracil; Thyroid Gland; Thyroxine

Large White turkey breeder hens from a strain exhibiting poor hatchability were fed thyroid-altering diets. The following dietary treatments were fed to randomized groups of hens for 15 wk of egg laying: 1) 16.5% protein turkey breeder diet (control), 2) the control diet containing 2.1 ppm supplemental iodine, 3) the control diet containing .1% thiouracil, and 4) the control diet containing .5 ppm triiodothyronine (T3). Blood samples were taken from hatching embryos from hens fed each diet. Embryonic hearts and livers were weighted prior to and during pipping as well as after hatching. Blood plasma was analyzed for thyroxine (T4), T3, and glucose. Livers were assayed for glucose-6-phosphatase activity. Supplemental maternal dietary iodine elevated embryonic T4 concentrations prior to pipping. Dietary T3 and iodine increased hepatic glucose-6-phosphatase activity and blood plasma glucose concentration prior to pipping. Feeding thiouracil increased embryonic liver weights but decreased heart and body weights. Blood plasma T4 was elevated in embryos from hens fed thiouracil but blood glucose levels were depressed because of a lack of increased glucose-6-phosphatase activity. Feeding iodine decreased the enzyme activity at internal pipping. It is suggested from the data that maternal thyroid metabolism may influence hatchability via embryonic thyroid and carbohydrate metabolism during hatching.

Topics: Animals; Body Weight; Female; Fertility; Glucose-6-Phosphatase; Heart; Iodine; Liver; Organ Size; Oviposition; Thiouracil; Thyroid Hormones; Thyroxine; Triiodothyronine; Turkeys

Three experiments were conducted to measure changes in plasma thyroxine (T4) concentrations occurring in male and female Japanese quail in response to treatment with dietary thiouracil (TU) and different CP levels prior to sexual maturity and to determine the influence of selection for growth under TU and protein stress on this response. Selected and unselected lines of quail were fed diets containing .2% TU or two levels of CP (20 or 28%) or both from 0 to 4 wk of age. Body weight and plasma T4 were measured at 5, 7, and 9 wk of age in Experiments 1 and 2. In Experiment 3, body weight was measured at 2, 4, 5, 7, and 9 wk and T4 at 4, 7, and 9 wk. Thiouracil inhibited growth to a greater degree than did decreased dietary CP. However, offspring from selected quail were more resistant to dietary TU when selection diets contained TU. When fed as part of a selection regimen rather than to unselected birds, low CP, TU diets inhibited body weight increase to a greater degree and longer after birds were returned to control diets. Thyroxine concentrations between 4 and 9 wk were affected by TU but not by CP level. Thiouracil significantly reduced T4 during treatment; however, T4 was elevated by 3 wk after cessation of TU treatment. Increases in T4 were greater and more immediate in selected than in unselected birds. These findings reveal the ability of quail to compensate for thyroid suppression after TU is removed from the diet and the influence of selection on this compensatory response.

Topics: Animals; Body Weight; Breeding; Coturnix; Dietary Proteins; Female; Male; Sex Characteristics; Thiouracil; Thyroid Gland; Thyroxine

Ten hyperthyroid patients were assessed for muscle strength before and after a period of medical treatment that averaged 12 months. The subjects did not change their habitual level of physical activity between the two test occasions. Maximal voluntary isokinetic knee extensor muscle strength was determined during various concentric, eccentric and isometric conditions. Average increases in strength from before to termination of treatment ranged from 25 to 41% for the concentric and isometric tests (P less than 0.01, n = 10), and from 19 to 35% for the eccentric tests (P less than 0.01, n = 6). The present study demonstrates that medical treatment of hyperthyroid patients results in a marked increase in muscle strength.

Topics: Adult; Analysis of Variance; Body Weight; Female; Humans; Hyperthyroidism; Male; Methimazole; Muscles; Propranolol; Thiouracil

Experiments were conducted to evaluate the ability of thymic and bursal lymphocytes from hypothyroidic chicks to take up 3H-thymidine. To produce hypothyroidism, chicks were fed a diet containing thiouracil (0.1%) from day of hatch to 3 weeks of age. At 1, 2 and 3 weeks of age, body weights were significantly lower for hypothyroid chicks, and at 2 and 3 weeks of age, the relative weights of the thymus and bursa were significantly less than those of controls. Furthermore, chicks treated with thiouracil had significantly lower serum concentrations of 3,5,3'-triiodothyronine (T3) and thyroxine (T4). Thymic cells from hypothyroid chicks incorporated less 3H-thymidine at 1 and 3 weeks of age as assessed by liquid scintillation counting and autoradiography. Liquid scintillation counts for labeled bursal cells from hypothyroid chicks were not lower at 1 week of age, but the counts were lower at 3 weeks of age. Autoradiographic studies with bursal cells revealed that 3H-thymidine incorporation was less, but not significantly less, in medium-size lymphocytes from thiouracil-treated chicks at both 1 and 3 weeks of age. Thymidine incorporation into large bursal cells was affected more by thiouracil treatment at 1 than 3 weeks of age.

Topics: Animals; Animals, Newborn; B-Lymphocytes; Body Weight; Bursa of Fabricius; Cells, Cultured; Chickens; Diet; Hypothyroidism; T-Lymphocytes; Thiouracil; Thymidine; Thymus Gland

The effects of thyroxine (T4) and thiouracil (TU) on growth and protein metabolism were examined in male mice given diets containing different levels of protein (casein) at two different growth stages (25 and 60 days old). Changes in protein metabolism were assessed from the expiratory 14CO2 from [U-14C]leucine injected, the liver nucleic acid contents and the rates of synthesis and degradation of liver protein estimated by single injection method using [6-14C]arginine. Each mouse, excluding the control group, received daily intraperitoneal injection of 10 micrograms of L-thyroxine sodium salt per 100 g b.w. (T4 group) or were given a diet containing 0.05% 2-thiouracil (TU group). In the 25-day-old mice, growth of the T4 group was accelerated at protein levels above 15% and that of the TU group was severely retarded at protein levels below 10%. On the other hand, in the 60-day-old mice, growth of the TU group tended to be accelerated at protein levels from 10% to 25%, while it was significantly retarded at the 5%-protein level. The expiratory 14CO2 increased when the growth was retarded, and decreased when growth was accelerated by T4 or TU in both age groups, but was not significant in either case. The nucleic acid content of the liver was increased by both T4 and TU when the dietary protein level was above 15%. The rate of protein synthesis was increased, but not significantly, by T4, while it was not affected by TU. The rate of protein degradation was increased, but not significantly, by TU, while it was not affected by T4 in the 25-day-old mice. In the 60-day-old mice, the rates of both liver-protein synthesis and degradation were significantly increased by TU, while they were not affected by T4. These results definitely indicate that the growth stage and the dietary protein level change the effects of thyroid function on growth protein metabolism of mice.

Topics: Animals; Body Weight; Dietary Proteins; DNA; Growth; Liver; Male; Mice; Mice, Inbred Strains; Organ Size; Proteins; RNA; Thiouracil; Thyroid Hormones; Thyroxine

Long-term (35 days) effects of thyroid hormone on the number of myocardial beta-adrenergic receptors and the c-AMP concentration were studied in the rat. The ventricles from triiodothyronine-administered rats (T3 rats) showed an increase in the number of beta-receptors compared to controls (54.3 +/- 3.1 vs 39.3 +/- 1.8 fmole of [125I]-iodohydroxybenzylpindolol (IHYP) binding sites/mg protein p less than 0.001) on the 35th day. Conversely, the ventricles from thiouracil-administered rats (TU rats) showed a decrease in the number of beta-receptors compared to controls (31.4 +/- 1.6 vs. 38.4 +/- 2.6 fmole/mg protein, p less than 0.05). The equilibrium dissociation constants (Kd) for the interaction of receptors with IHYP did not differ significantly (0.10 to 0.15 nM). The myocardial concentration of cyclic AMP was not significantly different (T3 rats, 1.09 +/- 0.09 nM/g wet weight tissue; T3 controls, 1.12 +/- 0.07; TU rats, 1.13 +/- 0.07; TU controls, 1.16 +/- 0.12) on the 35th day. On serial effects of triiodothyronine from the first to the 35th day, the number of beta-receptors of T3 rats increased significantly on the 24th and the 35th day, but the c-AMP concentration was not significantly different from that in control rats. These results demonstrated that thyroid hormone affects the number of myocardial beta-receptors in rats, and suggested a different mechanism of action of thyroid hormone on the myocardium from that of catecholamines.

Topics: Animals; Body Weight; Cyclic AMP; Hyperthyroidism; Hypothyroidism; Male; Myocardium; Organ Size; Rats; Rats, Inbred Strains; Receptors, Adrenergic, beta; Thiouracil; Triiodothyronine

The involvement of the thyroid gland in the response of young chickens to heat stress was studied. Mean survival times when exposed to 50 C were significantly shorter for 3-week-old broiler male chickens injected with 40 micrograms L-thyroxine (T4)/100 g body weight compared to chickens injected with 30, 20, or 0 microgram of T4/100 g body weight. A significant reduction in heat stress survival time was obtained when T4 was injected 12, 18, or 24 hr before heat stress but not 6 hr before. Triiodothyronine (T3) reduced heat stress survival time when administered 12 to 24 hr before the stress but not when given 6 hr before. Chickens made hypothyroid by radiothyroidectomy had significantly longer heat stress survival times than controls. Likewise, chickens fed a diet containing .2% thiouracil 10 days before heat stress at 28 days had significantly longer survival times than control birds.

Topics: Animals; Body Weight; Chickens; Hot Temperature; Male; Poultry Diseases; Stress, Physiological; Thiouracil; Thyroid Gland; Thyroxine; Triiodothyronine

A number of parallels can be drawn between the reported endocrine status of thiouracil-fed young rodents and that of aged animals, particularly with regard to the hypothalamus-pituitary-adrenal axis. Since the activity of the adrenal steroidogenic enzyme 3beta-hydroxy-delta5-steroid dehydrogenase (3beta-HSD) has been shown to be depressed in aged rats and mice, the present study was done to determine whether exposure of young mice to thiouracil had a similar effect on adrenal 3beta-HSD activity. Feeding the goitrogen thiouracil at 0.25% (w/w) of the maternal diet from conception, and keeping it 0.25% of the offsprings' diet after weaning, significantly elevated activity of 3beta-HSD per gram of adrenal gland above control levels in 4-month-old mice, perhaps to compensate for depressed adrenal mass. Daily subcutaneous injections of physiological saline (0.9%) for 4 days was sufficient to increase 3beta-HSD activity per gram of adrenal tissue in euthyroid (P less than 0.05) but not in thiouracil-fed mice. Subcutaneous administration of ACTH (2 IU daily for 4 days) significantly increased adrenal 3beta-HSD activity to comparable levels in thiouracil-fed and euthyroid animals. Thus, thiouracil enhances the activity of 3beta-HSD per gram of adrenal tissue and does not prevent response of enzyme activity to exogenous ACTH.

Topics: 3-Hydroxysteroid Dehydrogenases; Adrenal Glands; Adrenocorticotropic Hormone; Aging; Animals; Body Weight; Diet; Male; Mice; Organ Size; Thiouracil

Thyroidal activity was studied in chicks given dietary thiouracil in conjunction with daily doses of thyroxine and with diets adequate and deficient in iodine. DL-thyroxine administered at doses up to 1.0 microgram per day for 10 to 12 days had no effect or slightly increased thyroid weight. Both the epithelial and colloid components of the thyroid gland were increased in response to thiouracil and to thiouracil in combination with low dosages of exogenous thyroxine. Radioiodine uptake was increased above the control with thiouracil and with thiouracil in conjunction with .5 and 1.0 microgram DL-thyroxine given daily. Birds receiving thiouracil, with and without exogenous thyroxine, showed a different pattern of radioiodine uptake and release than the control birds. Thiouracil-treated birds showed a rapid uptake of iodine following its administration, which was followed by a rapid decline immediately after peak accumulation, whereas in control birds thyroidal radioiodine concentration reached a plateau at the maximum concentration attained. The goitrogenic response to thiouracil was much greater when the diet was supplemented with iodine than when the diet was iodine-deficient. Thyroids under iodine deficiency contained greater percentages of epithelial tissue than with iodine-supplemented diets. Thyroid glands of chicks given thiouracil in an iodine-supplemented diet contained much more colloid than glands from iodine-deficient chicks with or without thiouracil. DL-thyroxine at a dosage of .5 microgram per day to chicks given thiouracil in an iodine-adequate diet increased, whereas higher dosages decreased thyroidal colloid. It is concluded that some minimal concentration of thyroid hormone is required for maximum goitrogenic response. It is not clear whether the response is entirely due to an effect on thyrotropin production or whether there is an effect of thyroid hormone on the thyroid gland itself.

Topics: Animal Feed; Animals; Body Weight; Chickens; Iodine; Iodine Radioisotopes; Male; Organ Size; Thiouracil; Thyroid Gland; Thyrotropin; Thyroxine

Broiler chickens were reared in batteries and fed diets designed to determine the effects of either ascorbic acid, aspirin (acetylsalicylic acid), lysine, or thiouracil on thyroid weight and serum thyroid hormone concentrations. Thyroxine (T4) and 3,5,5'-triiodothyronine (T3) concentrations in serum were determined by radioimmunoassay. Neither ascorbic acid nor lysine affected T3 or T4 concentration, but thiouracil significantly reduced T3 concentration after 1 day and reduced T4 concentration after 3 days. After 3 days or more of thiouracil feeding, relative reduction was greater for T4 than T3. Dietary aspirin significantly reduced T3 concentration at 7 of 16 sampling times but significantly reduced T4 concentration at only 1 of 16 sampling times. After 11 days of the dietary treatment, chickens fed thiouracil had significantly heavier thyroids than the controls but ascorbic acid, aspirin, and lysine had no effect on thyroid weight.

Topics: Animals; Ascorbic Acid; Aspirin; Body Weight; Chickens; Diet; Lysine; Organ Size; Thiouracil; Thyroid Gland; Thyroid Hormones; Thyroxine; Triiodothyronine

Topics: Animals; Body Temperature Regulation; Body Weight; Catecholamines; Columbidae; Epinephrine; Female; Male; Norepinephrine; Serotonin; Species Specificity; Temperature; Thiouracil; Thyroxine

Topics: Animals; Body Weight; Chickens; Male; Muscle Development; Muscles; Organ Size; Thiouracil; Thyroid Gland; Thyroid Hormones; Thyroxine; Time Factors

Topics: Animals; Behavior, Animal; Birth Weight; Body Weight; Congenital Hypothyroidism; Dose-Response Relationship, Drug; Female; Humans; Hypothyroidism; Learning Disabilities; Litter Size; Male; Maternal-Fetal Exchange; Pregnancy; Rats; Thiouracil; Thyroid Gland; Time Factors

Topics: Animals; Body Weight; Brain; Exploratory Behavior; Female; Habituation, Psychophysiologic; Handling, Psychological; Hypothyroidism; Male; Motor Activity; Organ Size; Rats; Social Isolation; Thiouracil

Possible interrelationships of manganese-deficient and hypothyroid (thiouracil treatment) states in rats were examined. Clinical signs, necropsy changes, and plasma thyroxine concentrations were determined in control rats (group A), thiouracil-treated (hypothyroid) rats (group B), rats given manganese-deficient feed (group C), and rats given thiouracil and manganese-deficient feed (group D). Clinical signs observed included a hyperemic condition of the ears in group C and D rats that was considerably more severe in the latter group. One rat from group D also had middle ear changes, as reflected by a tilting of the head. Fluid intake was severely reduced in group D rats near the end of the 60-day experimental period and resulted in marked dehydration. Pathologic change (fatty liver) was observed at necropsy in only 1 rat from group D. Thiouracil treatment of rats reduced plasma thyroxine concentration to 48 to 68% of base line from experimental days 20 to 60. The same thiouracil treatment combined with feeding a manganese-deficient ration significantly reduced plasma thyroxine concentrations to 37% of base line at day 20 and 5% of base line at day 40; the concentration at day 60 was 76% of base line, apparently approaching normal because of concentration of the plasma (and thyroxine) in the dehydrated rats. Mean adrenal gland weight was significantly less than normal in group D rats, whereas mean thyroid gland weight in this group was increased, although less than that of group B rats treated with thiouracil only. Thus, clinical signs of deficiency were enhanced when athyreotic and manganese-deficient states were combined, and plasma thyroxine concentrations were markedly decreased, giving added meaning to the need for awareness of hormonal and trace mineral status of animals.

Topics: Animals; Body Weight; Dehydration; Ear Diseases; Hyperemia; Hypothyroidism; Male; Manganese; Rats; Rodent Diseases; Thiouracil; Thyroxine

Topics: Analysis of Variance; Animals; Antithyroid Agents; Body Weight; Organ Size; Potassium; Quail; Selection, Genetic; Sulfadiazine; Sulfaguanidine; Thiocyanates; Thiouracil; Thiourea; Thyroid Gland

Topics: Animals; Body Weight; Collagen; Decalcification Technique; Glycosaminoglycans; Histocytochemistry; Hypothyroidism; Periodontium; Rats; Thiouracil; Thyroid Gland

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Bone and Bones; Calcification, Physiologic; Calcium; Chickens; Deficiency Diseases; Erythropoiesis; Goiter; Hypothyroidism; Iodine; Iodine Radioisotopes; Male; Mitochondria, Muscle; Oxygen Consumption; Thiouracil; Thyroid Gland; Vitamin D Deficiency; Vitamin E

Topics: Adipose Tissue; Animals; Body Composition; Body Water; Body Weight; Diet; Dietary Carbohydrates; Dietary Proteins; Eating; Hypothyroidism; Locomotion; Male; Rats; Thiouracil; Thyroid Gland

Topics: Age Factors; Animal Feed; Animals; Body Weight; Chickens; Female; Food Additives; Growth; Male; Thiouracil

Topics: Animal Feed; Animals; Body Weight; Coturnix; Guanidines; Iodine; Iodine Isotopes; Organ Size; Sulfaguanidine; Sulfones; Thiocyanates; Thiouracil; Thyroid Gland

Topics: Administration, Oral; Age Factors; Animal Feed; Animals; Body Weight; Organ Size; Quail; Thiouracil; Thyroid Gland; Water

Topics: Animal Feed; Animals; Body Weight; Dietary Proteins; Drug Resistance; Hot Temperature; Poultry Diseases; Quail; Selection, Genetic; Stress, Physiological; Thiouracil

Topics: Administration, Oral; Animal Feed; Animals; Body Weight; Chickens; Escherichia coli Infections; Male; Organ Size; Oxygen Consumption; Poultry Diseases; Thiouracil; Thyroid Gland; Thyroxine

Topics: Animals; Body Weight; Coturnix; Male; Organ Size; Proteins; Selection, Genetic; Testis; Thiouracil; Thyroid Gland; Time Factors

Topics: Age Factors; Animals; Animals, Newborn; Avoidance Learning; Body Weight; Conditioning, Operant; Critical Period, Psychological; Discrimination Learning; Dose-Response Relationship, Drug; Extinction, Psychological; Female; Fetus; Gestational Age; Humans; Hypothyroidism; Learning Disabilities; Male; Maternal-Fetal Exchange; Pregnancy; Rats; Reflex; Reversal Learning; Space Perception; Thiouracil

Topics: Age Factors; Analysis of Variance; Animals; Birds; Body Composition; Body Weight; Dietary Proteins; Fats; Food Additives; Genetics, Population; Phenotype; Proteins; Species Specificity; Thiouracil; Water

Topics: Animals; Birds; Body Weight; Feathers; Gonadotropins, Pituitary; Male; Metamorphosis, Biological; Organ Size; Seasons; Testis; Thiouracil; Thymus Gland

Topics: Adrenal Glands; Animals; Body Weight; Epinephrine; Hypothyroidism; Norepinephrine; Organ Size; Rats; Thiouracil; Thyroid Gland; Thyroidectomy; Time Factors

Topics: Amino Acids; Animals; Body Weight; Depression, Chemical; Diet; Feeding Behavior; Growth; Liver; Male; Mixed Function Oxygenases; Mortality; Phenylpyruvic Acids; Rats; Thiouracil; Thyroxine; Tyrosine; Tyrosine Transaminase

Topics: Amino Acids; Animals; Body Weight; Cortisone; Hypophysectomy; In Vitro Techniques; Inulin; Leucine; Male; Organ Size; Protein Biosynthesis; Rats; Thiouracil; Thyroid Gland; Tritium

Topics: Animals; Anthropometry; Body Weight; Male; Oxygen Consumption; Physical Exertion; Pulmonary Alveoli; Rats; Thiouracil; Thyroid Gland; Thyroxine

Topics: Amidines; Amino Acids; Animals; Biological Assay; Body Weight; Depression, Chemical; Drug Synergism; Growth Hormone; Guanidines; Hypophysectomy; Kidney; Male; Methods; Organ Size; Rats; Thiouracil; Thyroidectomy; Thyroxine; Transferases

Topics: Animals; Animals, Newborn; Body Weight; Female; Growth; Iodine Radioisotopes; Male; Methimazole; Rats; Reproduction; Sexual Behavior, Animal; Thiouracil; Thyroid Function Tests; Thyroid Gland; Thyroxine

Topics: Animals; Body Weight; Cardiac Output; Heart Rate; Hyperthyroidism; Hypothyroidism; Male; Organ Size; Rats; Temperature; Thiouracil; Thyroxine

Topics: Animals; Anura; Biometry; Body Weight; Depression, Chemical; Growth Hormone; Metamorphosis, Biological; Prolactin; Stimulation, Chemical; Thiouracil; Thyroid Gland

Topics: Animals; Antithyroid Agents; Body Weight; Bursa of Fabricius; Caseins; Chickens; Comb and Wattles; Fasting; Hepatomegaly; Hypertrophy; Hypothyroidism; Liver; Liver Glycogen; Male; Organ Size; Propylthiouracil; Testis; Thiouracil; Thyroid Gland

Topics: Animals; Blood Proteins; Body Weight; Diet; Fatty Acids, Essential; Female; Glycine max; Iodine; Iodine Isotopes; Oils; Organ Size; Protein Binding; Rats; Thiouracil; Thyroid Gland

Topics: Animals; Aortic Rupture; Blood Pressure; Body Weight; Diethylstilbestrol; Drug Synergism; Lipids; Male; Poultry; Thiouracil; Thyroid Gland

Topics: Adaptation, Physiological; Animals; Body Weight; Cold Temperature; Liver; Male; Rats; Thiouracil; Vitamin A; Vitamin A Deficiency

Topics: Anemia, Hemolytic; Animals; Animals, Laboratory; Body Weight; Dogs; Female; Haplorhini; Hyperplasia; Male; Mice; Microscopy, Electron; Pigmentation; Rats; Tetracycline; Thiouracil; Thyroid Gland

Topics: Animals; Body Weight; Brain; Ear, Middle; Goiter; Hypertrophy; Hypothalamus; Male; Methods; Organ Size; Rats; Thiouracil; Thyroid Gland; Thyrotropin

Topics: Animals; Body Weight; DNA; Goiter; Hypophysectomy; Iodides; Iodine; Iodine Isotopes; Male; Mice; Organ Size; Pituitary Gland; Proteins; RNA; Thiouracil; Thyroid Gland; Thyroid Hormones; Thyrotropin; Trichloroacetic Acid

Topics: Animals; Blood Protein Electrophoresis; Body Weight; Dental Caries Susceptibility; Female; Food; Hyperthyroidism; Hypothyroidism; Male; Organ Size; Protein Biosynthesis; Rats; Saliva; Submandibular Gland; Thiouracil; Thyroid Gland

Topics: Androsterone; Animals; Body Weight; Cholesterol; Diet; Estradiol; Hypercholesterolemia; Organ Size; Rats; Testosterone; Thiouracil

Topics: Androgens; Animals; Body Weight; Castration; Liver; Poultry; Sex Characteristics; Thiouracil; Thyroidectomy

Topics: Body Weight; Castration; Humans; Kidney; Male; Orchiectomy; Organ Size; Pharmacology; Prostate; Rats; Research; Seminal Vesicles; Testosterone; Thiouracil; Thyroid Gland; Thyroxine

Topics: Bile Acids and Salts; Blood Coagulation; Blood Coagulation Tests; Body Weight; Cholesterol; Diet, Atherogenic; Dietary Fats; Mortality; Nicotine; Rats; Research; Salts; Thiouracil; Whole Blood Coagulation Time

Topics: Animals; Bile Acids and Salts; Body Weight; Cholecystolithiasis; Cholelithiasis; Cholesterol; Cholic Acid; Diet; Dietary Fats; Dietary Proteins; Gallstones; Lipid Metabolism; Liver; Mice; Pathology; Pharmacology; Research; Salts; Thiouracil

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Blood; Body Weight; Estradiol; Growth Hormone; Hydrocortisone; Neoplasms; Neoplasms, Experimental; Pharmacology; Pituitary Neoplasms; Prolactin; Rats; Research; Thiouracil; Thymus Gland; Thyroxine

Topics: Body Weight; Body Weights and Measures; Hoarseness; Hypothyroidism; Iodine Isotopes; Larynx; Myxedema; Pathology; Rats; Research; Thiouracil; Thyroid Function Tests; Vocal Cords

Topics: Antithyroid Agents; Body Weight; Caseins; Dietary Proteins; Pharmacology; Rats; Research; Thiouracil; Thyroid Gland; Triiodothyronine

Topics: Animals; Body Weight; Castration; Female; Humans; Hysterectomy; Light; Male; Orchiectomy; Pineal Gland; Rats; Thiouracil

Topics: Adrenal Glands; Androgens; Animals; Body Weight; Body Weights and Measures; Cholesterol; Cortisone; Methandriol; Rats; Thiouracil

Topics: Adrenal Cortex; Adrenal Glands; Ascorbic Acid; Body Weight; Body Weights and Measures; Cholesterol; Propylthiouracil; Thiouracil

Topics: Antithyroid Agents; Body Weight; Humans; Kidney; Thiouracil

Topics: Adrenal Glands; Ascorbic Acid; Body Weight; Thiouracil; Thyroidectomy; Vitamins