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S Alex

Publications and source records attributed to S Alex.

52 records · Page 3Linked to original sources
PubMed1988

Effect of L-thyroxine administration on the incidence of iodine induced and spontaneous lymphocytic thyroiditis in the BB/Wor rat.

Chronic L-thyroxine administration (6 micrograms/100g BW, ip, daily) for 2 or 3 months suppressed serum TSH concentrations and decreased both the incidence of spontaneous lymphocytic thyroiditis (LT) and the serum levels of anti-thyroglobulin (anti-Tg) antibodies in the diabetes prone BB/Wor rat. This suggests that TSH may play a role in the occurrence of LT in this rat model. In contrast to these observations, L-thyroxine administration did not affect the markedly increased incidence of LT or the elevated serum anti-Tg antibodies in iodine supplemented BB/Wor rats, suggesting that TSH stimulation is not necessary for the development of iodine induced LT in this rat model. Other factors, such as the increased antigenicity of highly iodinated Tg, may be more important.

Animals↗
PubMed1988

The effect of thyroid dysfunction and fasting on placenta inner ring deiodinase activity in the rat.

The placenta contains iodothyronine 5-deiodinase activity (P5-Dase) that probably acts on iodothyronines in the fetal circulation to convert T4 to rT3 and T3 to 3,3'-T2. Since thyroid status and fasting have profound effects on iodothyronine deiodinases in other tissues, the present studies were performed to determine if these perturbations affected P5-Dase. Control and treated rats were mated and killed near term on the 20th day of gestation. P5-Dase was determined in placenta homogenates enriched with dithiothreitol by measuring the conversion of T4 to rT3. In four of five studies, P5-Dase was similar in dams that underwent thyroidectomy (Tx) on day 7 of gestation and sham Tx dams. P5-Dase was not altered in dams that were treated with methimazole (MMI) to induce maternal and fetal hypothyroidism. Treatment of dams with supraphysiological doses of T4, beginning on the seventh day of gestation, did not significantly affect P5-Dase. In three of four studies, P5-Dase was similar in fed dams to values in dams fasted for the last 5 days of pregnancy. Placenta iodothyronine 5'-deiodinase activity (P5'-Dase) was also measured in some studies. P5'-Dase was not decreased in Tx rats and was modestly decreased in MMI-treated rats. However, the effect of MMI was not reversed by the administration of supraphysiological doses of T4, Tx, MMI treatment, and fasting all decreased hepatic T4 5'-deiodinase activity in pregnant rats. These results strongly suggest that thyroid status and fasting do not alter P5-Dase activity.

Animals↗
PubMed1988

Thyroxine binding to serum thyronine-binding globulin in thyroidectomized adult and normal neonatal rats.

The amount of tracer [125I]T4 bound to serum thyronine-binding globulin (TBG) was measured by polyacrylamide gel electrophoresis in adult thyroidectomized (TX) rats and normal 1-day to 4-week-old rat puts. Thyroidectomy was associated with the appearance of significant amounts of [125I]T4 binding to serum TBG in lean rats, but not in obese Zucker rats. Treatment of the TX rats in vivo with replacement doses of T4 prevented this increase in TBG binding, but enrichment of serum from TX rats with T4 did not. Significant amounts of tracer [125I]T4 binding to TBG was present in serum from 1- to 3-week-old normal rat pups, but not in 1-day- or 4-week-old pups. There were significantly higher levels of TBG binding of [125I]T4 in serum from 2-week-old rat pups raised in litters of 16 pups compared to those raised in litters of 4 pups. All manipulations that result in the appearance of TBG in rat serum also result in either weight loss or a slowing in the rate of growth, suggesting that the appearance of TBG in rat serum has a nutritional component. This possibility is further supported by the observations that increases in TBG binding of [125I]T4 are not found in obese Zucker rats fed a low protein-high carbohydrate diet for 14 days or fasted for 7 days, or after thyroidectomy, perhaps owing to the large stores of fuel in the obese rat.

Aging↗
PubMed1986

Total and free serum thyroid hormone concentrations in fetal and adult pregnant and nonpregnant guinea pigs.

Information on total and free serum thyroid hormone concentrations in the adult and fetal guinea pig (Cavia porcellus) is limited. These variables were studied in adult male and female guinea pigs and in pregnant guinea pigs and their fetuses at various times during gestation. Total serum T4 levels in adult males, nonpregnant females, and pregnant females did not differ significantly [range, 2.5 +/- 0.3 to 3.2 +/- 0.8 micrograms/dl (mean +/- SD)]. Similarly, there were no significant differences in the percent free T4 (0.046-0.068%), free T4 (1.26-2.03 ng/dl), total T3 (39-44 ng/dl), the percent free T3 (0.521-0.638%), and free T3 (0.221-0.260 ng/dl) among adult males, nonpregnant females, and pregnant females. rT3 was undetectable in adult male, nonpregnant female, and pregnant female guinea pig serum. T4 values were similar and those for T3 were lower in fetal compared to maternal serum at 45 days of gestation, whereas serum rT3 was detectable in fetal serum. Between 45 and 62 days of gestation, fetal serum T4 increased from 2.5 to 0.3 to 4.3 +/- 1.3 micrograms/dl (mean +/- SD, P less than 0.01), fetal serum T3 remained unchanged, and fetal serum rT3 increased from 5.2 +/- 3.3 to 25.0 +/- 11.4 ng/dl (P less than 0.01). Near term, fetal serum total and free T4 and total rT3 concentrations were significantly higher and total and free T3 concentrations were significantly lower than the corresponding values in maternal serum. Total serum T4 is higher in the guinea pig than in the rabbit, is similar to values in the rat, and is lower than values in man. The free T4 concentration in guinea pig serum is similar to those in humans and rats. The ontogenesis of thyroid hormones differs strikingly in the guinea pig fetus compared to that in the rat fetus and shares many similarities with sheep and human fetal thyroid development.

Animals↗
PubMed1985

Laser Raman spectra of calf thymus chromatin and its constituents.

Extensive Raman measurements have been made on calf thymus chromatin, core chromatin, the (H3,H4)/DNA complex, and isolated DNA. The results indicate that the alpha-helical content of the nucleosomal histones gradually increases as they form the heterocomplexes that lead to the formation of the octameric nucleosome core. The secondary structure of the latter is not modified as it binds to DNA. The spectra indicate that the DNA essentially retains its B conformation in nucleosomes, although slight changes probably occur in the ribose-phosphate backbone. No specific interactions between the nucleosomal histones and DNA can be established from the spectra, but histone H1 possibly interacts selectively with the thymine bases.

Animals↗
PubMed1985

Inner-ring deiodination of 3,5,3'-triiodothyronine in the in situ perfused guinea pig placenta.

Broken cell preparations of rat and human placentas contain an inner (tyrosyl)-ring iodothyronine deiodinase enzyme with greatest activity when the substrate is 3,5,3'-triiodothyronine (T3). This report describes the deiodination of T3 in the intact placenta and the effect of sodium iopanoate (IA) and propylthiouracil (PTU) on T3 deiodination. Under nembutal anesthesia, the placenta of 60-65-d-old pregnant guinea pigs was surgically exposed, a single umbilical artery and the umbilical vein were cannulated, and the fetus was removed. In a temperature-controlled chamber (37 degrees C), the fetal side of the placenta was perfused through the umbilical artery at a rate of 1 ml/min with 3% bovine serum albumin Krebs-Henseleit buffer containing 0.14 nM outer ring labeled [125I]T3. Placenta effluent fractions were collected at timed intervals from the umbilical vein cannula throughout a 120-min perfusion period. The contents of the perfusion buffer and the various effluent fractions were analyzed for their iodothyronine content by high pressure liquid chromatography. In five experiments, the percent composition of 125I-labeled iodothyronines in the perfusion buffer and placenta effluent was 95.3 +/- 1.0 (mean +/- SE) and 70.2 +/- 2.1 for T3 (P less than 0.01), 2.5 +/- 0.7 and 20.1 +/- 1.8 for 3,3'-T2 (P less than 0.01), and 0 and 8.2 +/- 0.9 for 3'-T1. There was no difference between the percent [125I]iodide in the perfusion buffer and in the placenta effluents. When placentas were perfused with IA and [125I]T3, after perfusion with [125I]T3 alone, there was a significant increase (P less than 0.01) in the percent [125I]T3 in the placenta effluents, and a significant decrease in [125I]3,3'-T2 (P less than 0.01) and [125I]3'-T1 (P less than 0.01). In contrast, PTU did not affect the composition of labeled iodothyronines in the placenta effluents, despite the fact that the addition of PTU significantly (P less than 0.001) inhibits the inner-ring deiodination of [125I]T3 in human or guinea pig placenta microsomes in the presence of low (0.25 mM) concentrations of dithiothreitol. The present studies demonstrate that T3 is actively deiodinated in the inner ring to 3,3'-T2 by the intact guinea pig placenta. A portion of 3,3'-T2 is further deiodinated in the inner ring to generate 3'-T1. No outer ring deiodination of T3 was seen under the conditions employed. IA, but not PTU, inhibits T3 deiodination in the placenta perfused in situ. We conclude that the placenta is probably a site for fetal T3 metabolism.

Animals↗
PubMed1985

Thyrotropin-releasing hormone metabolism and extraction by the perfused guinea pig placenta.

This report describes the extraction of synthetic TRH and its metabolic conversion in the perfused guinea pig placenta. These studies were performed to obtain an estimate of fractional fetal TRH losses through the placenta and to determine if some of these losses are due to TRH metabolism. The in situ guinea pig placenta was perfused through an umbilical artery for 90 min, and placental effluent fractions were collected at timed intervals from the umbilical vein. Experiments were performed in which the perfusion buffer contained 0.01, 1, and 10 micrograms/ml or no synthetic TRH. Synthetic TRH was always perfused in the presence of 3H2O. In experiments in which TRH was perfused, the perfusion reservoir contents and placental effluent fractions were counted for 3H, and TRH and deamido-TRH were determined by RIA. Similarly, cyclo(His-Pro) was measured when 10 micrograms/ml TRH were perfused. When no TRH was perfused, the perfusion reservoir and placental effluent contents were processed to determine their content of TRH immunoreactivity. When synthetic TRH was perfused, steady state TRH concentrations were achieved in placental effluent fractions by 20-30 min. The single pass extraction of TRH by the placenta was 11.4 +/- 2.6% (mean +/- SE) compared to 56.9 +/- 7.0% for 3H2O (P less than 0.001). No significant difference was detected regardless of whether 10, 1, or 0.01 micrograms/ml TRH were perfused. A portion of the TRH that perfused the placenta was converted to deamido-TRH at all concentrations of perfused TRH. No conversion of TRH to cyclo(His-Pro) was noted when the highest concentration (10 micrograms/ml) of TRH was perfused. The conversion of TRH to TRH-OH was 4.2 +/- 0.7% in a single pass. When the perfusion buffer was devoid of synthetic TRH, a small but significant increase in the content of TRH immunoreactivity was noted in the placental effluent compared to that in the perfusion reservoir. This was not large enough to affect calculations of the placental extraction of TRH. These studies, in addition to demonstrating that the placenta contains TRH deamidase activity, suggest that losses of fetal TRH through the placenta are not large. They do not support the current impression, based on the fetal TSH response to maternal TSH administration, that the placenta is freely permeable to TRH.

Animals↗
PubMed1984

The effect of adrenergic blockade on glucose-induced thermogenesis.

The effect of alpha, beta, or combined sympathetic blockade on the increase in energy expenditure and concentrations of norepinephrine, glucose, and insulin following oral intake of 100 g of glucose was studied in lean subjects. Alpha blockade with intravenous (IV) phentolamine (n = 5) infusion increased oxygen consumption after glucose ingestion but no more than it increased the oxygen consumption when no glucose was given. Beta blockade with IV propranolol (n = 13) and combined alpha and beta blockade (n = 6) did not affect basal metabolic rate or the increase in metabolic rate after glucose ingestion. Phentolamine or combined propranolol plus phentolamine administration markedly increased plasma norepinephrine concentrations. Basal glucose and insulin concentrations were not affected by any of the infused drugs. Glucose-stimulated insulin concentrations were unchanged by propranolol and combined blockade, whereas there was a trend (P = 0.07) toward an increased response to glucose during phentolamine administration. These data do not support a role for the sympathetic nervous system in the increase in metabolic rate following glucose ingestion. The increase in metabolic rate during phentolamine administration can be attributed to beta adrenergic stimulation.

Adolescent↗
PubMed1984

The pharmacokinetics of thyrotropin-releasing hormone (TRH) and deamido-TRH in the rat.

The pharmacokinetics of TRH and its metabolite deamido-TRH (TRH-OH) were evaluated and compared. After a 60- to 90-min infusion of the appropriate peptide into rats, the MCR, half-life of disappearance (t 1/2), and volume of distribution were calculated. The MCR of TRH averaged 4 ml/min, whereas that of TRH-OH was 6.5 ml/min. The serum concentrations of both TRH and TRH-OH decreased in a biexponential manner after stopping the corresponding peptide infusions. The t 1/2 values were 2.4 and 3.9 min for the initial phase of disappearance and 14.1 and 20.6 min for the later phase of disappearance for TRH and TRH-OH, respectively. The volume of distribution of TRH-OH was twice that of TRH. The fractional conversion rate of TRH to TRH-OH, based on serum TRH-OH concentrations measured during TRH infusions, was 0.7-1.4%. Less than 1 ng TRH-OH was excreted in the urine during the last 30 min of TRH infusion. The rapid clearance of TRH-OH and low fractional conversion of TRH to TRH-OH, as measured in serum, suggest that little TRH secretion will be reflected in serum TRH-OH concentrations.

Animals↗
PubMed1982

Ontogenesis of placental inner ring thyroxine deiodinase and amniotic fluid 3,3',5'-triiodothyronine concentration in the rat.

Human and rat placentae contain enzymatic activity which converts T4 to rT3 and T3 to 3,3'-diiodothyronine and 3'-monoiodothyronine. This study presents data on the ontogeny of this inner ring iodothyronine deiodinase activity (P-T4ase) in rat placenta. P-T4ase was measured by quantitating the conversion of T4 to rT3 in 700 x g supernatants of placental homogenates. Groups of rats were mated to permit the dams to be killed on the same day, on days 12, 14, 16, 18, and 20 of gestation. Sufficient placental tissue was obtained to measure P-T4ase on all but the 12th day of gestation. The highest level of P-T4ase was observed on day 16. P-T4ase on days 14, 18, and 20 was 52%, 77%, and 41%, respectively, of that observed on day 16 (P less than 0.01, day 16 vs. all other days). Amniotic fluid rT3 concentrations were highest on day 18 and were 61% and 64%, respectively, of that observed on day 18 (P less than 0.01, days 16 and 20 vs, day 18). At 20 days, maternal serum T4 concentrations were significantly lower (P less than 0.01) than on days 14, 16, or 18. A brief period of maternal hypothyroidism (4 or 9 days before the time that the animals were killed on day 20 of gestation) did not significantly alter P-T4ase. These studies indicate that there are age-dependent changes in placental inner ring deiodinase activity in the rat. Amniotic fluid rT3 concentrations may reflect these changes. Brief reductions in maternal serum T4 concentrations do not account for changes in placental inner ring deiodinase activity. These studies emphasize the importance of gestational age in studies of placental inner ring iodothyronine deiodinase.

Amniotic Fluid↗
PubMed1981

A study of the effect of the thyrotropin-releasing hormone metabolite, histidyl-proline diketopiperazine, on prolactin secretion in vivo.

TRH, a PRL secretogogue, is metabolized to histidyl-proline diketopiperazine (HPD) in brain and plasma. HPD has been reported to inhibit PRL secretion in vitro. In the present study, intravascular pulse injections or infusions of HPD were carried out in the rat to determine whether HPD affected 1) TRH-induced PRL secretion, 2) the PRL proestrous surge, 3) the PRL surge in the ovariectomized, estrogen-primed rat and 4) pimozide-induced hyperprolactinemia. HPD had no effect on TRH-induced PRL secretion in estrogen-primed male rats when administered in molar ratios of 1:1.5 to 1:150 (TRH:HPD). The infusion of 1 microgram/min HPD for 360 min to rats before and during the proestrous PRL surge did not inhibit or augment PRL secretion, nor was there any influence of pulse injections of HPD on PRL secretion during the proestrous surge. HPD did not influence spontaneous PRL surges in the ovariectomized estrogen-primed rat. Finally, HPD, given with pimozide and again 2 days later, did not influence the PRL surge after pimozide administration or the elevated serum PRL concentrations noted 2 days after pimozide treatment. Despite the promising in vitro data demonstrating that the TRH metabolite, HPD, has PRL inhibitory factor activity, this study does not support the concept that HPD is a physiological PRL inhibitory factor.

Animals↗
PubMed1980

Dual nucleotide specificity of bovine glutamate dehydrogenase. The role of negative co-operativity.

The thionicotinamide analogues of NAD+ and NADP+ were shown to be good alternative coenzymes for bovine glutamate dehydrogenase, with similar affinity and approx. 40% of the maximum velocity obtained with the natural coenzymes. Both thionicotinamide analogues show non-linear Lineweaver-Burk plots, which with the natural coenzymes have been attributed to negative co-operativity. Since the reduced thionicotinamide analogues have an isosbestic point at 340nm and have an absorption maximum at 400nm, it is possible to monitor reduction of natural coenzyme and thionicotinamide analogue simultaneously by dual-wavelength spectroscopy. When glutamate dehydrogenase is presented with NADP+ and thio-NADP+ simultaneously, the enzyme oligomer senses saturation of its coenzyme-binding sites irrespective of the exact nature of the coenzyme and locks the oligomer into its highly saturated form even when low saturation of the monitored coenzyme is present. These experiments substantiate the suggestion that glutamate dehydrogenase shows negative co-operativity in its catalytically active form.

Animals↗
PubMedDate not supplied

The effect of ciamexone on lymphocytic thyroiditis and insulin-dependent diabetes mellitus in the BB/Wor rat.

Previous studies have suggested that ciamexone, a 2-cyan-aziridine derivative, is a selective immunomodulatory agent with potential therapeutic application in a variety of autoimmune diseases. In the present study, the effects of ciamexone on autoimmune lymphocytic thyroiditis and diabetes mellitus were studied in the BB rat. The data suggest that, in this animal model, ciamexone does not affect the frequency of autoimmune diabetes or lymphocytic thyroiditis nor does it affect the serum TSH or T4 concentrations.

Adjuvants, Immunologic↗