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At least 865 records · Page 48Linked to original sources
PubMed2001

Antiatherogenic effects of 17 beta-estradiol and 17 alpha-estradiol and its derivative J811 in cholesterol-fed rabbits with thyroid inhibition.

OBJECTIVE: The aim of this study was to investigate the antiatherogenic effects of 17 beta-estradiol and 17 alpha-estradiol and its derivative J811 (estra-1,3,5(10),8-tetraene-3, 17 alpha-diol), having a non-feminizing effect and high antioxidant potential, in male rabbits. EXPERIMENTAL DESIGN: Male White-Russian rabbits weighing 2.1-2.6 kg were fed either a standard or a high-cholesterol (200 mg/kg) diet, with thyroid function-inhibiting thiouracil (20 mg/kg) combined with cholic acid (40 mg/kg) administered daily in sunflower oil for 3 months. During the last month of the study, estrogens were administered by gavage at a dose of 0.02 or 0.1 mg/kg. RESULTS AND CONCLUSIONS: All three estrogens exerted remarkable antiatherosclerotic effects. Decreases in serum and aortic-wall lipid parameters and the index of atherogenicity were dependent on estrogen dose. Morphological evaluation of the aortic wall (height of plaques, size of plaque relative to aortic half-circumference) showed only weak therapeutic effects with all three estrogens. It is an open question whether the treatment period was too short to reverse the above changes. On the other hand, the data clearly suggest that 17 alpha-estradiol and J811 offer new perspectives for the prevention of atherosclerosis in men, which is similar to that found with 17 beta-estradiol in women.

Animals↗
PubMed2001

Structural basis of pyrimidine specificity in the MS2 RNA hairpin-coat-protein complex.

We have determined the X-ray structures of six MS2 RNA hairpin-coat-protein complexes having five different substitutions at the hairpin loop base -5. This is a uracil in the wild-type hairpin and contacts the coat protein both by stacking on to a tyrosine side chain and by hydrogen bonding to an asparagine side chain. The RNA consensus sequence derived from coat protein binding studies with natural sequence variants suggested that the -5 base needs to be a pyrimidine for strong binding. The five -5 substituents used in this study were 5-bromouracil, pyrimidin-2-one, 2-thiouracil, adenine, and guanine. The structure of the 5-bromouracil complex was determined to 2.2 A resolution, which is the highest to date for any MS2 RNA-protein complex. All the complexes presented here show very similar conformations, despite variation in affinity in solution. The results suggest that the stacking of the -5 base on to the tyrosine side chain is the most important driving force for complex formation. A number of hydrogen bonds that are present in the wild-type complex are not crucial for binding, as they are missing in one or more of the complexes. The results also reveal the flexibility of this RNA-protein interface, with respect to functional group variation, and may be generally applicable to other RNA-protein complexes.

Adenine↗
PubMed1975

Relationship between iodination and the polypeptide chain composition of thyroglobulin.

Thyroglobulin was isolated from thyroid glands of normal guinea pigs and from animals treated with thiouracil. These preparations were fractionated by isopyknic centrifugation in RbCl into proteins of varying iodine content. When the disulfide bonds of these protein fractions were reduced and analyzed by polyacrylamide gel electrophoresis in Na dodecyl-SO4, t hree species were observed with molecular weights of 295,000 (A), 210,000 (B), and 110,000 (C). Species A comprised 80% of the protein in thyroglobulin of 0.04% iodine and 13% in thyroglobulin of 0.68% iodine content. Species C showed the opposite relationship, comprising 10% of the low and 70% of the high iodine thyroglobulin. Species B was relatively independent of the iodine content and represented approximately 20% of the protein. Iodine analysis of these proteins showed species A to be lowest and species C highest. It appears that the subunit composition of thyroglobulin depends on the degree of iodination and that species A should be the only one present in the absence of iodination.

Animals↗
PubMed2002

1,3-Dibromo-5,5-dimethylhydantoin (DBH) as oxidant and precipitant for drug identification according to PH. EUR Analytical methods of pharmacopoeias with DBH in respect of environmental and economical concern, Part 15(1).

Elemental bromine serves as oxidant for the identification of propylthiouracil, 2-thiouracil and sulphur according to PH. EUR. 2002. Phenol is identified according to PH. EUR. 2002 with bromine water as the sparingly water-soluble 2,4,4,6-tetrabromo-2,5-cyclohexadiene-1-one. These tests can be performed better using 1,3-dibromo-5,5-dimethylhydantoin (DBH).

Bromine↗
PubMedDate not supplied

An analytical method to screen for six thyreostatic drug residues in the thyroid gland and muscle tissues of food producing animals by liquid chromatography with ultraviolet absorption detection and liquid chromatography/mass spectrometry.

A method was developed and validated to screen for residues of the thyreostatic drugs, tapazole (TAP), mercaptobenzimidazole (MBI), thiouracil (TU), methylthiouracil (MTU), propylthiouracil (PrTU), and phenylthiouracil (PhTU) in bovine, equine, ovine, and porcine thyroid and muscle tissues at concentrations > or = 5 ng/g using 2-methoxy-mercaptobenzimidazole (MeMBI) and dimethylthiouracil (DMTU) as internal standards. In this method, the drugs were solvent extracted from thyroid and muscle tissue and cleaned up on an amino-propyl solid-phase extraction (SPE) cartridge. The unretained fraction containing TAP and MBI and the internal standard, MeMBI, was collected as Fraction 1. The retained fraction containing TU, MTU, PrTU, PhTU, and the internal standard, DMTU, was eluted with 3% acetic acid-isopropanol as Fraction 2. Fraction 1 was further cleaned up on an alumina B SPE cartridge and analyzed by gradient elution on a C18 high-performance liquid chromatography (HPLC) column with ultraviolet detection at wavelengths of 255 and 300 nm. Fraction 2 was taken to dryness, derivatized with 4-chloro-7-nitrobenzo-2-furazan at pH 8, and analyzed by gradient elution on a C18 LC column with mass spectrometry (MS) detection. Any "presumptive positive" test results were submitted for further analysis by LC/MS/MS. The validated method was applied to the analysis of over 300 thyroid tissue samples.

Animals↗
PubMed2006

Evaluation of 2 thione primers and 3 resin adhesives for silver-palladium-copper-gold alloy bonding.

OBJECTIVE: The purpose of this study was to evaluate 2 thione primers and 3 resin adhesives for enhancement of bonding strength to a silver-palladium-copper-gold alloy. METHOD AND MATERIALS: Two different sized disk specimens (10- and 8-mm diameter by 2.5-mm thick) were prepared from a silver-palladium-copper-gold alloy (Castwell M.C. 12, GC). The specimens were airborne-particle abraded with 50-microm-grain alumina, conditioned either with a thiouracil primer (Metaltite, Tokuyama Dental) or with a triazine dithione primer (V-Primer, Sun Medical), and then bonded with 1 of 3 acrylic resins: a benzoyl peroxide-amine redox-initiated resin adhesive (Multi-Bond, Tokuyama Dental) or a tri-nbutylborane-initiated resin adhesive (Super-Bond C&B and Super-Bond Quick, Sun Medical). For each adhesive, unprimed specimens were prepared as experimental controls. Shear bond strength was determined after thermocycling (100,000 cycles). RESULTS: Use of primers significantly (P < .05) enhanced the bond strength of specimens in all adhesives. Irrespective of the type of primer, the strength of Multi-Bond adhesive was significantly (P < .05) lower than that of Super-Bond C&B and Super-Bond Quick adhesives. The strength of the 2 tri-n-butylborane-initiated adhesives did not differ significantly (P > .05). The mean strength of the Super-Bond C&B adhesive was 40.4 MPa with Metaltite and 37.8 MPa with V-Primer; that of Super-Bond Quick adhesive was 40.9 MPa with Metaltite and 36.5 MPa with V-Primer. CONCLUSION: Use of thione primers effectively enhanced the strength of the bond to the silver-palladium-copper-gold alloy. Furthermore, the combinations of primers and tri-n-butylborane-initiated adhesives were found to be more efficient for bonding.

Air Abrasion, Dental↗
PubMedDate not supplied

Elimination of the antiviral drug 5-ethyl-2'-deoxyuridine by the isolated perfused rat liver.

The elimination of the antiviral drug 5-ethyl-2'-deoxyuridine (EdUrd) by the isolated perfused rat liver was investigated. EdUrd (3.9-39 mumol) was injected into the perfusion reservoir and serial samples were collected for HPLC determination of EdUrd and its metabolites 5-ethyluracil (EUra) and 5-(1-hydroxyethyl)uracil (HEUra). At each dosage level, semilogarithmic plots of concentration vs. time showed apparent first order disappearance of EdUrd. However, with increasing dose, there was a progressive increase in EdUrd half-life from 18.9 to 36.4 min and decrease in total clearance from 5.5 to 2.5 ml/min, indicating dose-dependent elimination. Dose dependence was confirmed by the lack of superposition of logarithm concentration/dose vs. time plots obtained with different doses. After EdUrd administration, the concentration of EUra reached a peak value in about 1 hr, and then gradually decreased. The concentration of HEUra, which was initially much lower than that of EUra, increased throughout the experiment and appeared to approach a plateau at 2-3 hr. Biliary excretion of each ethylpyrimidine was negligible. 6-Benzyl-2-thiouracil, a thymidine phosphorylase inhibitor, slowed the disappearance of EdUrd and decreased the peak concentrations of EUra and HEUra. Cimetidine, a cytochrome P-450 inhibitor, had little effect on the rate of EdUrd disappearance, but caused a large increase in the peak EUra concentration and decrease in HeUra concentration. 3-Methylcholanthrene, a cytochrome P-450 inducer, increased the formation of HEUra but had little effect on the rate of EdUrd disappearance. The results indicate that the hepatic elimination of EdUrd is dose-dependent and involves an initial cleavage to EUra, which is then oxidized to HEUra.

Animals↗
PubMed1989

An attempt to prevent or delay denervation changes in rat muscles.

A number of drugs which are known to affect lysosomes and their enzyme activities were used in an attempt to inhibit or delay the onset of denervation changes in rat muscles. The following parameters were used: the occurrence of fibrillations in electromyographs; diameters of muscle fibers; acid phosphatase activity; acetylcholinesterase activity and distribution in end plates. Differences between denervated and non-denervated limbs were evaluated and compared in the different treatment groups. The various parameters were differently affected by the different drugs. Chloroquin, thiouracil and streptomycin appeared to be more effective than other treatments in the inhibition of denervation changes.

Animals↗
PubMedDate not supplied

Role of inhibin in polycystic ovarian syndrome.

The possible role of inhibin in the etiology of polycystic ovarian syndrome (PCO) was studied. In rats PCO was induced by thiouracil and human chorionic gonadotropin (hCG). These animals were grouped under different treatment schedules: inhibin; antibodies to inhibin; ovine follicle stimulating hormone (FSH). In rats treated with antibodies to inhibin, there was a decrease in ovarian weight concomitant with specific increase in serum FSH levels. No changes in serum luteinizing hormone (LH) and prolactin levels were observed. However, testosterone levels were significantly decreased. Histological examination of the ovaries showed a marked arrest in the cyst formation with new growing follicles. In animals treated with inhibin, testosterone levels increased without any accompanying changes in ovarian weight. The circulating levels of prolactin and LH were unaffected. A decrease in serum FSH levels was accompanied by an increase in the number of cysts. The study corroborates the hypothesis that inhibin is involved in the development of PCO syndrome. Hence, an antagonist to inhibin may prove useful for the treatment of women with this condition.

Animals↗
PubMed1977

An aspartate transcarbamylase lacking catalytic subunit interactions. Study of conformational changes by ultraviolet absorbance and circular dichroism spectroscopy.

A modified form of aspartate transcarbamylase is synthesized by Escherichia coli in the presence of 2-thiouracil which does not exhibit homotropic cooperative interactions between active sites yet retains heterotropic cooperative interactions due to nucleotide binding. The conformational changes induced in the modified enzyme by the binding of different ligands (substrates, substrate analogs, a transition state analog, and nucleotide effectors) were studied using ultraviolet absorbance and circular dichroism difference spectroscopy. Comparison of the results for the modified enzyme and its isolated subunits to those for the native enzyme and its isolated subunits showed that the conformational changes detected by these methods are qualitatively similar in the two enzymes. Comparison of the absorbance difference spectra due to the binding of a transition substrate analog to the intact native or modified enzymes to the corresponding results for the isolated subunits suggested that ligand binding causes an increased exposure to solvent of certain tyrosyl and phenylalanyl residues in the intact enzymes but not in the isolated subunits. This result is consistent with a diminution of subunit contacts due to substrate binding in the course of homotropic interactions in the native enzyme. Such conformational changes, though perhaps necessary for homotropic cooperativity, are not sufficient to cause homotropic cooperativity since the modified enzyme gave identical perturbations. Interactions of the transition state analog, N-(phosphonacetyl)-L-aspartate, with the modified enzyme were studied. Enzyme kinetic data obtained at low aspartate concentrations showed that this transition state analog does not stimulate activity, but rather exhibits the inhibition predicted for the total absence of homotropic cooperative interactions in the modified enzyme. Spectrophotometric titrations of the number of catalytic sites with the transition state analog showed that the modified enzyme and its isolated subunits possess, respectively, four and two high affinity sites for the inhibitor instead of six and three observed in the case of the normal enzyme and its isolated catalytic subunits. These results are correlated with the lower specific enzymatic activities of the modified enzyme and its catalytic subunits compared to the normal corresponding enzymatic species.

Aspartate Carbamoyltransferase↗
PubMed1987

Effects of zinc deficiency on thyroid function.

Interactive combinations of altered zinc and thyroid states were studied in rats to assess pathophysiologic effects. Clinical signs of zinc deficiency or thyroid alteration were limited to effects on growth rate. Changes in organ and glandular weights and serum thyrotropin levels reflected changes in serum thyroid hormone concentrations. Significantly (probability less than .001), zinc-deficient rats had enhanced hepatic thyroxine-5'-monodeiodinase activity. In addition, the zinc-deficient state was found to be protective against thiouracil-induced suppression of the microsomal-monooxygenase and thyroxine-5'-monodeiodinase enzyme complex. This protective effect was evident by greater thyroxine-5'-monodeiodinase and reduced nicotinamide-adenine dinucleotide phosphate cytochrome c reductase activities, as well as cytochrome P-450 content, in zinc-deficient/thiouracil-treated animals. Thus, the enzyme complex had increased triiodothyronine-generating capacity in conditions of zinc deficiency, which may be important because of the greater biological reactivity of triiodothyronine. Primary zinc deficiency conditions of the magnitude seen in this study and in this-age rat did not appear to alter serum thyroid hormone levels or organ/glandular function. However, concurrent zinc deficiency and altered thyroid status did change thyroid hormone response and disposition, which may be important to populations at risk because of thyroid dysfunctional states.

Animals↗
PubMed1980

Inhibition of mosaic virus of Vigna sinensis Endl. with four chemicals.

Four chemicals--gibberellic acid, indoleacetic acid, 2,4-6 and thiouracil were tested for their inhibitory effect against a virus disease of Vigna sinensis (cowpea). All the four chemicals inhibited the virus to a considerable extent in in vitro studies. Pre and post-inoculation treatments were equally effective in inhibiting the virus, viz. local lesion formation on Chenopodium amaranticolor leaves. The level of inhibition subsequently decreased with lower concentration of the chemicals. Seed soaking in the chemicals controlled the virus infection.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1978

Effect of thyroid state on magnesium concentration of rat tissues.

The effect of alteration of thyroid status by thiouracil (0.1% concentration in drinking water for 60 days) or exogenous thyroxine (25 mg/dg of body weight administered SC from days 30 to 60) on magnesium content of rat tissues following exogenous magnesium was evaluated. Treatment of rats with magnesium solution (25 mg of magnesium sulfate/dg of body weight) resulted in increased magnesium concentration in most tissues of hypothyroid and hyperthyroid rats, with the mesenchymal-derived tissues (aorta, trachea, and ear cartilage) exhibiting the greatest increases (respectively, 154, 130, and 133% of control group values for hypothyroid rats, and 115, 108, and 107% of control group values for the hyperthyroid group). Magnesium concentration in skeletal and cardiac muscle was similar for hyperthyroid and control rats, but magnesium concentration in these same tissues of hypothyroid rats was decreased. Magnesium distribution and retention in rat tissues is altered considerably, depending on the functional status of thyroid gland.

Animals↗
PubMed1982

Shedding of dense cell fragments into the follicular lumen early in involution of the hyperplastic thyroid gland.

Membrane-bounded fragments of thyroid epithelial cells are found in the lumen of the thyroid follicle at early stages of involution of the hyperplastic gland. To demonstrate this, thyroid glands were made hyperplastic by feeding rats a low iodine diet containing thiouracil for 3 weeks. Involution was induced by the feeding of a high iodine diet. Three types of dense cell fragments were observed in the lumen at its periphery within 5 hours after the change of diet: (1) single, relatively large fragments that contained vesicles occasionally, (2) a cluster of rounded fragments of relatively small size. Some of these had a narrow tail, and (3) elongated narrow fragments in a row parallel to the apical surface of one or more epithelial cells. The fragments are probably derived from the thyroid epithelial cells since no other cell types were generally present. By 14 hours the fragments were distributed randomly throughout the lumen. Fragments were no longer present by 12 days of involution in most follicles. Fragment formation may be a mechanism for disposal of excess plasma membrane deposited by exocytic vesicles during rapid secretion of thyroglobulin into the follicular lumen early in involution.

Animals↗
PubMed1995

Mechanism of the hyperthermic effect of the novel thyrotropin-releasing hormone analogue Na-((1S,2R)-2-methyl-4-oxocyclopentylcarbonyl)-L-histidyl-L- prolinamide monohydrate in mice with reserpine-induced hypothermia.

To investigate the mechanism of the antagonistic effect of Na-((1S,2R)-2-methyl-4-oxocyclopentylcarbonyl)-L-histidyl-L-prolin amide monohydrate (CAS 131404-34-7, JTP-2942) on reserpine-induced hypothermia, the role of the autonomic nervous system, adrenal gland, and thyroid gland regarding the effects of JTP-2942 has been studied in mice. Both phenoxybenzamine and propranolol significantly attenuated the hyperthermic effect of JTP-2942 on reserpine-induced hypothermia, although neither drug caused complete inhibition. A high dose of hexamethonium also significantly antagonized the hyperthermic effect of JTP-2942. The hyperthermic effect of JTP-2942 was almost abolished by adrenal demedullation. In mice with thiouracil-induced hypothyroidism, both thyrotropin-releasing hormone (TRH) and JTP-2942 significantly increased the rectal temperature. However, the increase induced by TRH was smaller in hypothyroid mice than in control mice, while the temperature increase induced by JTP-2942 was similar in both hypothyroid and control mice. These results suggest that the hyperthermic effect of JTP-2942 is mainly mediated by the adrenal gland and the autonomic nervous system. In addition, the hypothalamic-pituitary-thyroid axis does not regulate the hyperthermic effect of JTP-2942, unlike that of TRH.

Adrenal Medulla↗
PubMed1976

Microhemorrhage in the hyperplastic thyroid gland of the rat.

A microhemorrhagic process was consistently observed in association with the induction of thyroid hyperplasia by dietary thiouracil in the rat. This process appeared to involve the extravasation of erythrocytes (RBCs) through hyperplastic capillary walls. Those sites of extravasation which were directly visualized involved endothelial openings of less than 1 mu. These openings were surrounded by endothelial cytoplasm containing a dense fibrous material and were associated with RBC constriction during passage. Extravasated RBCs were most often noted singly or in small groups, either in columns between follicular epithelial cells or embedded amongst the basal epithelial infoldings. Occasionally, extravasated RBCs were also observed within follicular lumens. Extravasated RBCs were usually intact ultrastructurally, but occasionally an apparent hemolytic process was observed, both for RBCs embedded amongst epithelial cells and for those within follicular lumens. The nature and etiology of this microhemorrhagic process are considered in relation to the hypervascularity of the gland, the possibility of capillary wall alterations, the presence of endothelial cell mitoses, and the localization of the process.

Animals↗
PubMed1998

Drug-associated agranulocytosis: 20 years of reporting in The Netherlands (1974-1994).

In this descriptive study, all 425 reports were included concerning drug-associated agranulocytosis as registered between 1974 and 1994 in the files of the Drug Safety Unit of the Dutch Inspectorate for Health Care. All reports were analysed as to the probability of agranulocytosis or neutropenia according to previously defined criteria. Subsequently, the causal relationship between exposure and outcome was assessed. It concerned 149 men and 271 women. One hundred and twelve reports were unclassifiable because age, gender, or total number of leukocytes at the time of reaction were unknown. In 100 reports agranulocytosis was probable, in 78 possible, in 8 reports neutropenia was probable, in 20 reports neutropenia was possible, and in 107 reports agranulocytosis or neutropenia were unlikely. In the 13 reports of probable agranulocytosis or neutropenia with a certain causal relationship, causative drugs were cimetidine, dipyrone, sulphasalazine, methyldopa, spironolactone, propylthiouracil (2), thiamazole, sulphamethoxazole with trimethoprim, gentamicin, a combination preparation containing aminophenazone, benzylpenicillin and indomethacin. The individual drugs most often reported to cause agranulocytosis or neutropenia were: dipyrone (19), mianserin (15), sulphasalazine (13), sulphamethoxazole with trimethoprim (11), the group of penicillins (9), cimetidine (8), the thiouracil derivatives (8), phenylbutazone (8), and penicillamine (8). Agranulocytosis is a serious and fairly frequently reported adverse reaction. The reporting system of the Drug Safety Unit can be used very well for signal generation concerning adverse reactions to drugs.

Adult↗
PubMed2000

(E)-1-alkyl-4-

(E)-1-Alkyl-4-[2-(alkylsulfonyl)-1-ethenyl]pyridinium salts were synthesized in two steps. These sulfones were stable at pH 7.3 and underwent a nucleophilic vinylic substitution (S(N)V) with mercaptans, including thiouracile, to give the corresponding 4-(thiovinyl)-pyridinium salts. The X-ray diffraction structure of (E)-1-methyl-4-[2-(ethylsulfanyl)-1-ethenyl]pyridinium iodide indicated conjugation of the sulfur with the pyridinium ring. (Z)-1-Methyl-4-[2-(methylsulfanyl)-1-ethenyl]pyridinium iodide, prepared from the corresponding thioether by reaction with methyl iodide in diethyl ether, underwent isomerization to the E isomer in a first-order reaction in deuterated [D6]DMSO with an activation energy of 14 kcalmol(-1). At pH 7, the (E)-1-methyl-4-[2-(methylsulfonyl)-1-ethenyl]pyridinium iodide (19) reacted specifically with thiols. The reaction of this sulfone with glutathione in a TES buffer at pH 7 was a second-order reaction (k = 4,100 M(-1)s(-1) at 30 degrees C) and gave the corresponding substitution product with an intense long wavelength absorption band (lambdamax=360 nm, epsilon = 27,500 M(-1)cm(-1)). The modification of different enzymes of known structure with 19 showed the high selectivity of this reagent towards thiol groups and its usefulness in the quantitative determination of free thiol groups in proteins.

Journal Article↗