The effect of age and thyroid hormones upon the ability of the chick heart to deaminate monoamines.

The effect of age and thyroid hormones upon the ability of chick heart homogenates to metabolize monoamines has been investigated. 5-Hydroxytryptamine is entirely metabolized by a monoamine oxidase (MAO) with the characteristics of MAO-A, whereas some of the tyramine and all of the benzylamine are oxidatively deaminated by a clorgyline-resistant, but semicarbazide-sensitive enzyme, with a similar subcellular distribution to that of MAO. The remainder of the tyramine deamination is brought about by MAO-A and MAO-B. The specific activities of both clorgyline-sensitive and resistant enzymes are increased by the same proportion by increase in age or by treatment with (--)-thyroxine, and decreased by 2-thiouracil. The significance of these results is discussed.     

Selective influences of age and thyroid hormones on Type A monoamine oxidase of the rat heart

The specific activity of rat heart MAO, towards both tyramine and benzylamine as substrates, was found to increase with the age of the animal, and also after administration of (?)-thyroxine to young male rats. Conversely, enzyme activity was decreased in animals made hypothyroid by including 2-thiouracil in their diet. However, with both age and altered thyroid status, relatively greater changes in the deamination of tyramine rather than in that of benzylamine, were obtained. Clorgyline and deprenyl, used as inhibitors of rat heart MAO, indicated that tyramine is metabolized solely by MAO-A, whereas benzylamine is a substrate for both MAO-A and -B, and also a clorgyline- and deprenyl-resistant enzymic activity. The proportional contribution of MAO-A, -B and the clorgyline-resistant enzyme towards the total benzylamine deamination in the rat heart was found to vary with the age and with altered thyroid status of the animal in such a way that selective changes in the activity of MAO-A appear to be largely responsible for the overall changes in the specific activity of rat heart MAO which occur in response to these developmental factors.     

Selective influences of age and thyroid hormones on type A monoamine oxidase of the rat heart.

The specific actiivty of rat heart MAO, towards both tyramine and benzylamine as substrates, was found to increase with the age of the animal, and also after administration of (-)-thyroxine to young male rats. Conversely, enzyme activity was decreased in animals made hypothyroid by including 2-thiouracil in their diet. However, with both age and altered thyroid status, relatively greater changes in the deamination of tyramine rather than in that of benzylamine, were obtained. Clorgyline and deprenyl, used as inhibitors of rat heart MAO, indicated that tyramine is metabolized solely by MAO-A, whereas benzylamine is a substrate for both MAO-A and -B, and also a clorgyline- and deprenyl-resistant enzymic activity. The proportional contribution of MAO-A, -B and the clorgyline-resistant enzyme towards the total benzylamine deamination in the rat heart was found to vary with the age and with altered thyroid status of the animal in such a way that selective changes in the activity of MAO-A appear to be largely responsible for the overall changes in the specific activity of rat heart MAO which occur in response to these developmental factors.     

The effects of thyroid hormones on monoamine oxidase in the rat heart

The administration of thyroxine to young male rats produced an increase in the specific activity of their cardiac monoamine oxidase (MAO). A reduction in the circulating concentrations of thyroid hormones, brought about by 2-thiouracil, led to a decrease. The relative change in activity produced was greater with tyramine than with benzylamine as substrate. By following the time-course of the return of enzyme activity, with tyramine as substrate, after a single injection of pargyline in vivo, it was concluded that both excess and lack of thyroid hormones cause their effects on MAO activity by changing the rate of synthesis of the enzyme and not its degradation rate constant. The degradation rate constant did change with the age of the animal. The MAO activity, which increased towards tyramine as substrate in hyperthyroid rat hearts, behaved in the same way as that of controls to heat treatment, irreversible inhibition by pargyline or by clorgyline and also in K_m determinations. The pattern for benzylamine oxidation was similar, except for the effect of the inhibitor clorgyline which shifted the plateau region of the double sigmoid inhibition curve significantly using enzyme from hyperthyroid rat hearts. The plateau region was also shown to be affected by the age of the animal. The possibility is discussed that the increased cardiac MAO activity produced by thyroid hormones and by the growth of the animal is mediated by that form of the enzyme primarily responsible for the oxidation of tyramine. Mixed substrate experiments suggested that tyramine oxidation could be inhibited competitively by benzylamine.     

The teratogenic effect of phenobarbital on the embryonic chick heart

Phenobarbital was observed to produce cardiovascular malformations in embryonic chicks. Malformations included simple ventricular septal defect, ventricular septal defect associated with dextroposition of the aorta, double outlet right ventricle, and several types of aortic arch anomalies. Embryos were exposed to phenobarbital at doses of 1-25 mumol on day 4 of incubation (Hamburger-Hamilton developmental stage 24). Doses equal to and greater than 5 mumol phenobarbital (26 mg/kg egg) significantly increased the frequency of embryos with cardiovascular malformations compared with lesser doses and with saline. A significant reduction in heart rate and abnormal rhythm of the heart were observed in embryos treated with teratogenic doses of phenobarbital. No arrhythmia nor significant changes in heart rate were observed in embryos exposed to subteratogenic doses of phenobarbital or to saline.     

The effect of thyroid hormones on the action of some centrally acting drugs

1. The effect of administration of thyroxine or thyroidectomy on the pharmacological action of (+)-amphetamine, caffeine, hexobarbitone and morphine was determined in rats or mice.2. Locomotor activity induced by (+)-amphetamine or caffeine was increased by hyperthyroidism and decreased by hypothyroidism.3. The LD50s of (+)-amphetamine and caffeine in hyperthyroid rats were 1/30 and 2/5 that of control rats. With each drug, the LD50 regression lines in hyperthyroid and control rats were not parallel, suggesting that hyperthyroidism modifies the mechanism of the toxic effects. Hypothyroidism reduced toxicity to (+)-amphetamine.4. Hexobarbitone sleeping time was prolonged in hyperthyroid male rats, but was shortened in hyperthyroid female rats. In control rats, sleeping time was approximately four times as long in females as it was in males. Ethinyloestradiol treatment and castration also prolonged sleeping time in male rats. No further prolongation was produced by combined administration of thyroxine and ethinyloestradiol, but thyroxine further prolonged the sleeping time of castrated rats indicating that its mode of action in producing these changes is not mediated via sex hormones.5. In contrast to rats, a sex difference in the duration of action of hexobarbitone was not found in mice. Thyroxine prolonged sleeping time equally in each sex.6. Analgesia induced by morphine in mice was unaffected by hyperthyroidism. No increase in sedative or ;Straub tail' activity could be detected, but toxicity was increased when higher doses of morphine were used.7. The mechanism by which thyroid hormones produce these changes in sensitivity to centrally acting drugs is discussed. It is suggested that the effects of thyroxine vary according to whether the mode of action of the drug or its metabolism is modified.     

The effect of age and frailty upon blood esterase activities and their response to dietary supplementation

1. The aims of this study were two-fold. First, to define ranges of blood esterase activities in three groups, namely young subjects, fit community dwelling elderly and frail, chronically hospitalised elderly subjects, and second, to determine whether low blood esterase activities in the frail patients could be altered by increasing their nutritional intake. 2. Plasma cholinesterase, aspirin esterase, paraoxonase and phenylacetate esterase activities were all significantly lower in the frail elderly compared with the young and fit elderly volunteers. The activity of red blood cell esterase was not different in the frail elderly. 3. Fourteen frail elderly patients were randomly assigned to receive either hospital meal provision plus supplemental feeding with Build-up (Nestle) and Maxijul (SHS Ltd) or hospital provision alone for 8 weeks. Dietary intake was measured for all patients at the start of the study and at week 8. Measurements of blood esterase (cholinesterase, phenylacetate esterase, paraoxonase, aspirin esterase and red blood cell esterase), albumin and anthropometric indices (weight, triceps skinfold thickness and mid arm circumference) were made before the study and repeated at week 4 and 8. 4. There was a significant increase in plasma cholinesterase at week 4 (P < 0.05) but this was not statistically significant at week 8. There were no significant changes in any of the other esterase activities or anthropometric measurements. 5. We conclude that the lower esterase activities of the frail chronically hospitalised elderly do not respond to dietary supplementation for a period of 8 weeks with routinely available products. The hypothesis that lower esterase activities are the direct result of undernutrition which would be corrected by dietary supplementation has not been supported by this study.     

冠心病患者甲状腺激素检测的临床价值

目的评价冠心病患者甲状腺激素检测的临床价值。方法测定74例冠心病患者及36例正常对照健康成人血清中TT4、TT3、FT3、FT4、TSH水平,采用SPSS 11．0软件比较各指标水平有无统计学差异。结果冠心病组与健康对照组在TT4、TT3、FT3、FT4、TSH水平上差异无显著性（P〉0．05）;冠心病心衰组的血清FT3水平显著低于冠心病非心衰组（P〈0．05）与非冠心病组（P〈0．01）;而冠心病非心衰组血清FT3,水平与非冠心病组相比差异无显著性（P〉0．05）。结论冠心病合并心衰患者FT3明显降低,与心衰的严重程度成正相关,临床上可以作为反映冠心病预后的一个指标。     

The effect of thyroid hormones and other kinetic modifiers on bisphosphoglyceromutase from human erythrocytes

Bisphosphoglyceromutase (E.C. 2.7.5.4) is inhibited by thyroxine, tri-iodothyronine and diiodothyronine and activated by glucagon. Several other hormones have no effect. The enzyme is activated by various thiols, but not by NADH, NADPH or ascorbic acid. The inhibition by α- and β-glycerophosphate and the activation by phosphoglycollic acid [1] have been confirmed. 2-Hydroxy-4-phosphobutyric acid, an isostere of β-glycerophosphate, has no effect on the kinetics. Nicotine is slightly inhibitory at concentrations much higher than the plasma level in smokers.     

2型糖尿病病人甲状腺相关激素水平与冠心病的关联分析

目的探讨 2型糖尿病病人甲状腺相关激素水平与冠心病之间的关联。方法选取 2016年 3月至 2018年 6月滁州市中西医结合医院糖尿病病人 360例,分为冠心病组 80例,非冠心病组 280例,测量两组病人血清甲状腺激素水平及其他生化指标含量,使用 logistic回归分析两组病人血清甲状腺相关激素水平与冠心病发生的关系,并使用多元线性回归分析 2型糖尿病病人冠脉病变程度的可能影响因素。结果在年龄、性别均衡可比的情况下,冠心病组病人血清促甲状腺激素( TSH)水平为(3.80±1.63)ng/L,高于非冠心病组的( 1.91±0.67)ng/L,而血清游离三碘甲状腺原氨酸( FT3)水平小于非冠心病组( 3.79±0.49)pg/L比 4.19±0.43)pg/L。logistic回归分析结果显示:血清 TSH水平较高的病人发生冠心病的 OR值为 2.02(1.38~2.97),而 FT3水平较低的病人发生冠心病的 OR值为 1.32(1.15~1.71)。多元线性回归结果显示高血压、 TSH、低密度脂蛋白胆固醇(LDL?C)水平为冠心病病人冠脉狭窄程度的独立影响因素( P＜0.05)。结论 2型糖尿病病人血清 TSH、FT3水平与冠心病发病风险之间存在关联,同时 TSH也与冠心病病人冠脉病变程度有关。     

The effect of acute nicotine administration on plasma levels of the thyroid hormones and corticosterone in the rat

The effects of a single intraperitoneal injection of nicotine hydrogen tartrate (200 μg/kg) on the plasma levels of thyroxine, triiodothyronine and corticosterone were monitored over a 24 hour period. Nicotine did not alter the plasma levels of either of the thyroid hormones but did produce a significant increase in plasma corticosterone, an effect which peaked at 20 min post-injection and lasted for 45 min.     

Interactions of beta-adrenoceptor antagonists and thyroid hormones in the control of heart rate in the dog.

Propranolol, sotalol and nadolol have been infused into conscious dogs, and doses at which the three drugs are equipotent as beta-adrenoceptor antagonists determined. In euthyroid dogs, sotalol was more effective at lowering heart-rate than an equivalent dose of propranolol, while an equivalent dose of nadolol was without effect. Hyperthyroidism potentiated the lowering of heart-rate by sotalol, but inhibited that by propranolol. The effect of sotalol on heart-rate was correlated with its prolongation of the Q-T interval of the ECG. That of propranolol was correlated with its prolongation of the P-R interval. Nadolol did not affect P-R interval or Q-T interval except at relatively high dosage. We conclude that the tachycardia of hyperthyroidism is not affected by blockade of beta-adrenoceptors and therefore that it is not mediated by adrenergic mechanisms. The effectiveness of propranolol and sotalol in lowering heart-rate must be due to actions peculiar to those drugs, and not to beta-adrenoceptor antagonism.