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PubMed1978

The influence of thyroid and testicular hormones on globule leucocytes in the rat duodenal crypt epithelium.

The globule leucocyte is a cell with a wide distribution in the digestive, respiratory, biliary, urinary and genital tract epithelia of homeotherms. It occurs in the crypts of the rat small intestine and within the epithelium on the villous bases but not on the remainder of the villi. A characteristic feature of this cell is the presence of acidophilic cytoplasmic granules, 0.5 to a few micrometers in diameter. The nucleus resembles that of intraepithelial intestinal lymphocytes. In this investigation, a quantitative study was made of the effect of thyroidectomy and/or castration on the number of globule leucocytes in the duodenal crypts of immature and adult rats. In sham-operated rats, globule leucocytes were rare, occurring with a frequency of 1 or 2 per 1,000 epithelial cells. After thyroidectomy, they increased to 14--20 per 1,000 epithelial cells. Castration did not influence the number of globule leucocytes but resulted in an increase in the number, size and acidophilia of their cytoplasmic granules. In immature rats, but not in adults, castration combined with thyroidectomy enhanced the effect of thyroidectomy, increasing globule leucocyte number to 32 per 1,000 epithelial cells. Treatment of thyroidectomized-castrates with thyroxine, initiated 38 days after operation, reduced the crypt globule leucocyte population to normal, whereas treatment with testosterone did not. Growth hormone failed to influence the elevated number of globule leucocytes in thyroidectomized rats, suggesting that this action of thyroxine was not mediated via an influence on growth hormone release. Because of their similar nuclear morphology, intraepithelial crypt lymphocytes were also counted and there was no obvious relationship in the fluctuations of these two cell populations. It is suggested that the greater number of crypt globule leucocytes in thyroid deficiency may reflect changes in the intestinal secretory immunoglobulin system and this is being investigated, beginning with a study of the distribution of IgE.

Animals↗
PubMed1991

Effect of L-thyroxine (LT4) and D-thyroxine (DT4) on cardiac function and high-energy phosphate metabolism: a 31P NMR study.

31P NMR spectroscopy was used to monitor the cardiac energy metabolism in hypothyroid rat hearts. Differential alterations in phosphocreatine and inorganic phosphate levels were observed upon treatment of hypothyroid animals with DT4 and LT4, while both agents were equipotent in reducing cholesterol. These results show potential for NMR spectroscopy as a technique to determine therapeutic selectivity.

Adenosine Triphosphate↗
PubMed1982

Effect of neomycin sulphate alone and in combination with D-thyroxine on serum lipoproteins in hypercholesterolaemic subjects.

Treatment with neomycin sulphate 1.5 g/d for 8 weeks significantly lowered total serum cholesterol by an average of 19% in 15 out of 19 patients with primary hypercholesterolaemia and LDL-cholesterol by 21%, without significantly changing the corresponding triglyceride and HDL-cholesterol concentrations. Combined treatment with neomycin sulphate 1.5 g/d and d-thyroxine 6 mg/d for 8 weeks lowered total serum cholesterol in the same patients by an average of 30%, LDL-cholesterol by 27% and serum triglycerides by 18%, without significantly changing the HDL-cholesterol concentration. Continued treatment for 10 patients with neomycin sulphate 1.5 g/d for up to 13 months did not further change the reduced serum cholesterol level. 10 of 19 patients complained of side effects after 4-8 weeks of treatment with neomycin: 8 of recurrent diarrhoea, abdominal pain or poor appetite, and 4 of acute attacks of vertigo with nystagmus. All side effects were reversed a few days after stopping the neomycin treatment. No additional serious side effects due to d-thyroxine were observed. These serious side effects of neomycin sulphate limit its use to selected high risk patients with hypercholesterolaemia, who have failed to respond successfully to other LDL-cholesterol-lowering drugs. They stress the necessity for frequent monitoring for the side effects described.

Adult↗
PubMed1978

[Drug treatment of primary hyperlipoproteinemia (author's transl)].

Cardiovascular disease has become the major cause of death in the Western countries. There is strong evidence that elevations of serum lipids contribute to the pathogenesis of premature atherosclerosis. The classification of the hyperlipoproteinemias has been most beneficial as a guide to development of dietary and pharmacological regimens for lowering serum lipid concentrations. The results of dietary and drug prevention trials are discussed. Insight into the mechanisms involved in lipoprotein metabolism as well as the mode of action and of side-effects of hypolipidemic drugs is reviewed. Using present knowledge of heart disease research, it is reasonable to suggest dietary and drug treatments for the high risk patient.

Anion Exchange Resins↗
PubMed1981

Stereospecific determination of D-thyroxin and L-thyroxin in serum.

A new method for separate determination of D-thyroxin and L-thyroxin in the serum was applied to study the response of serum levels of these isomers and of radioimmunologically determined total T3, total T4, free T4 and TSH upon administration of 2, 4 and 6 mg of a highly purified D-thyroxin preparation in six male patients with diffuse nontoxic goiter. D- and L-thyroxin are determined separately following extraction of the hormone from the serum and formation of diastereomeric dipeptides. The separation and final determination are accomplished by means of ion-pair chromatography on reversed-phase columns using an iodine-selective catalytic detector. A significant decrease in TSH takes place during the 3-days observation period. The values of D-T4, total T3 and free T4 are highest 4 hours after administration of the tablets and get to be to initial values after 24 hours. L-T4 shows no significant change. A direct suppressive effect of D-T4 on the pituitary gland may therefore be assumed as the cause of the suppression of TSH secretion.

Adult↗
PubMed1987

Acute and chronic effects of dextro-thyroxine on pituitary thyroid axis and on reverse triiodothyronine production in euthyroid subjects.

Serum levels of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and TSH were measured in euthyroid subjects after a single dose of 4 mg D-thyroxine (DT4) or of 0.25 mg L-thyroxine (LT4). The same parameters and TSH response to TRH were also evaluated in 7 dyslipidemic patients before and after one month of treatment with 6 mg DT4. T4 levels increased about 165% at h 4 after DT4 and only 47% after LT4; T3 levels remained unchanged until h 10 both after DT4 and after LT4; rT3 levels increased almost 179% after DT4 and only 32% after LT4. TSH levels decreased about 30% after both DT4 and LT4. In the long term study similar variations of the same parameters were observed: basal TSH levels decreased and TSH response to TRH was inhibited in all patients but one; T4 levels increased 62%, T3 levels increased 35%, while rT3 levels increased 545%. Our results show that: both acute and long-term treatment with DT4 suppress TSH secretion; DT4 both in acute and in long-term administration, is preferentially dealogenated in the alaninic ring with production of rDT3, instead of in the phenolic ring with production of DT3. This may contribute to explain its lower metabolic activity.

Adult↗
PubMed1977

Primary prevention of coronary heart disease: a critique.

The question is whether alteration of risk factors will aid primary and secondary prevention of coronary heart disease. Critical review of available evidence indicates that inferences have been made about the beneficial effects of risk factor modification without an adequate test of the hypothesis. Trial interventions to assess the efficacy of serum cholesterol-lowering measures have had negative or equivocal results. It remains to be seen whether the findings of clinical trials on hypertension can be applied toward primary prevention of coronary heart disease in the community. The cigarette smoking habit seems to be unique among coronary heart disease risk factors. The evidence appears sufficient to justify serious consideration of a strategy of preventing the smoking habit now, persuading patients to stop and encouraging teenagers not to start.

Adult↗
PubMed1984

Comparison of effectiveness of thyrotropin-suppressive doses of D- and L-thyroxine in treatment of hypercholesterolemia.

In an attempt to compare the cholesterol-lowering effects of equivalent doses of D- and L-thyroxine, 10 euthyroid, hypercholesterolemic subjects were treated with graded doses of each medication in a cross-over design using thyrotropin suppression following thyrotropin-releasing hormone administration as the end-point. The mean thyrotropin-suppressive dose of D-thyroxine was 2.4 +/- 0.66 mg per day, which resulted in mean reductions of 10 percent in total plasma cholesterol, 10 percent in plasma low-density lipoprotein cholesterol, and 11 percent in plasma high-density lipoprotein cholesterol. The mean thyrotropin-suppressive dose of L-thyroxine was 135 +/- 46 micrograms per day, which resulted in mean reductions of 7 percent in total plasma cholesterol, 6 percent in plasma low-density lipoprotein cholesterol, and 14 percent in plasma high-density lipoprotein cholesterol. The reductions in total, low-density, and high-density cholesterol achieved with D-thyroxine were not significantly different from those achieved with L-thyroxine. Neither medication produced a significant increase in heart rate or ventricular ectopy as determined by Holter monitoring. These data do not support the belief that D-thyroxine has a preferential cholesterol-lowering effect in humans when compared with equivalent doses of L-thyroxine. In addition, both D- and L-thyroxine reduced plasma high-density lipoprotein cholesterol.

Adult↗
PubMed1988

Steinernema feltiae (= Neoaplectana carpocapsae): effect of sterols and hypolipidemic agents on development.

The structure and concentration of sterol in a lipid-defined artificial medium affected the development of the entomogenous nematode, Steinernema feltiae (= Neoaplectana carpocapsae). The nematode grew normally in vitro when the medium was supplemented with delta 5-desalkylsterol (cholesterol) or delta 5-desalkylsteryl ester (cholesterol oleate). The minimum amount of cholesterol in the medium that was necessary to support the development of S. feltiae to the climax population (i.e., dauer stage) was 0.0025%. The nematode also completed its life cycle normally when delta 0- or delta 7-desalkylsterols (cholestanol and lathosterol) were substituted for cholesterol. In contrast, development was inhibited when the medium contained delta 5,7-desalkylsterol (7-dehydrocholesterol); however, the nematode population reached the climax stage, in medium containing this sterol, when cholesterol was also present. S. feltiae was able to utilize delta 5- and delta 0-24 alpha-ethylsterols (sitosterol and sitostanol) as dietary sterols; however, when a delta 22-bond was introduced into the side chain (stigmasterol) the rate of development of the nematode slowed significantly. The growth of the nematode was also retarded when the medium contained delta 5,7,22-24 beta-methylsterol (ergosterol). The nematode population reached the climax stage in medium containing delta 8,24-4,14 alpha-trimethylsterol (lanosterol) only when cholesterol was also present. When S. feltiae was exposed to certain hypolipidemic agents, which are known to lower the level of lipids in human plasma (clofibrate, cholestyramine resin, niacin, and D-thyroxine), all but D-thyroxine affected the growth and development of the nematode in vivo (in Heliothis zea) and/or in vitro. Therefore further studies are warranted to determine how these drugs affect the lipid biochemistry of this nematode.

Animals↗
PubMed1984

Nuclear receptors for L-triiodothyronine in quail liver.

Binding studies were conducted using in vitro-labeled quail liver nuclei to identify and characterize receptors for L-triiodothyronine (T3). Saturation binding experiments were analyzed by Scatchard analysis and indicated a single class of high-affinity, limited-capacity T3 binding sites. These receptors exhibited binding specificity as demonstrated by competition experiments between labeled T3 and unlabeled thyroid hormones or hormone analogs. Binding specificity was virtually identical in quail and rat liver nuclei. Thus, apparent differences between mammals and birds, in regard to the biological potency of T4 versus T3, are not apparent at the level of the nuclear T3 receptor.

Aging↗
PubMed1980

Lipid changes in atherosclerotic aortas of Macaca fascicularis after various regression regimens.

plasma and aortic tissue lipid changes in atherosclerotic Macaca fascicularis monkeys were studied following various regression regimens for 18 months. Atherosclerosis was induced in groups of 18 Macaca fascicularis monkeys by feeding a semipurified diet containing 43% of the calories as fat and 1.2 mg/kcal cholesterol for 6 months. Five groups of animals were continued on the same diet containing 0.34 mg/kcal cholesterol during the regression period, and were given the following hypocholesterolemic regimens: none (positive controls); D-thyroxine; pyrimidine derivative; cholestyramine; and alfalfa. Another group of animals was maintained on regular monkey chow alone during the regression period (negative control). Among the hypocholesterolemic agents, cholestyramine very effectively reduced the plasma cholesterol, and aorta free- and esterified cholesterol and phospholipids. D-Thyroxine significantly lowered the plasma cholesterol levels but, surprisingly, tissue lipid levels were the highest among the groups studied. Alfalfa, although not as effective as cholestyramine, tended to reduce the plasma and tissue lipids more than other drugs. Pyrimidine derivative actually increased the mean levels of plasma and tissue cholesterol. Plasma cholesterol correlated positively with aortic tissue cholesterol, free and esterified cholesterol. Both the plasma percentage distribution of alpha-lipoprotein and the phospholipid/cholesterol ratio were inversely related to all tissues lipids. Plasma cholesterol accounted for 43% and 30% respectively of the variability in tissue total and esterified cholesterol. Thus the effectiveness of any hypocholesterolemic regimen is probably dependent on achieving a favorable lipoprotein distribution in plasma without any adverse effect on the arterial wall metabolism.

Animals↗