Reduced somatostatin-like immunoreactivity in the brain of LEC rats with hepatic encephalopathy.

Somatostatin-14-like immunoreactivity (S14LI) and somatostatin-28(1-12)-like immunoreactivity (S28(1-12)LI) in the brain of LEC (Long Evans Cinnamon) rats with hepatic encephalopathy were measured. Significant reduction of both S14LI and S28(1-12)LI was observed in the hypothalamus, medulla oblongata, striatum and spinal cord. Both of the immunoreactivities in the hypothalamus of these rats were approx. 50% of those in LEC rats without hepatic encephalopathy. The amounts of reduction of S14LI significantly correlated with those of reduction of S28(1-12)LI. No significant difference in gel chromatographic profiles of S14LI and S28(1-12)LI was observed between LEC rats with and without hepatic encephalopathy. These results suggest that the reduction of somatostatin-like immunoreactivity in LEC rats with hepatic encephalopathy may be caused by a decrease in production of prosomatostatin rather than altered degradation.

Effects of sex difference, gonadectomy, and estrogen on N-methyl-N-nitrosourea induced rat thyroid tumors.

The occurrence of thyroid tumors induced by N-methyl-N-nitrosourea (MNU) and low iodine diet in Long-Evans (LE) rats was studied with special reference to sex difference, effect of gonadectomy, and estradiol administration. Rats of experimental groups 1-6 were given i.v. injections of 40 mg of MNU/kg of body weight at 50 days of age and fed on low iodine diet from 28 days of age to the end of the experiment (30 weeks after MNU administration). They consisted of male, female, castrated male, ovariectomized female, and gonadectomized male and female rats given 2.5 mg estradiol pellets s.c. Rats of groups 7-10 served as the respective controls without MNU or low iodine diet. Levels of serum thyroid stimulating hormone and estrogen receptor of the thyroid lesions were also examined. It was noted that the incidence of thyroid carcinoma was higher in females than in males (P less than 0.01) and did not change by castration in males but decreased in ovariectomized rats (P less than 0.01). Administration of estradiol after gonadectomy significantly increased the incidence of thyroid carcinomas in castrated and ovariectomized rats. Increase of mean serum thyroid stimulating hormone levels and thyroid and pituitary weights was also predominant in females. Mean thyroid stimulating hormone levels of both sexes were decreased by gonadectomy. Mean thyroid and pituitary weights were inhibited from increasing not by castration but by ovariectomy. Estradiol supplemented after gonadectomy significantly increased all of these factors. Estrogen receptors were detected in transplanted thyroid tumors but not in euthyroid tissues. The results suggest that estradiol promoted the thyroid tumorigenesis through activation of thyrotrophs in pituitary or direct interaction of estradiol and estrogen receptors in the thyroid.

Zinc, copper, manganese, and selenium metabolism in thyroid disease.

This study was designed to evaluate trace metal metabolism in adults with thyroid diseases. Erythrocyte zinc values were significantly lower than normal in hyperthyroidism and higher in hypothyroidism. A significantly higher than normal urinary excretion of zinc was observed in hyperthyroidism. The mean concentrations of plasma and erythrocyte copper were significantly above normal in hyperthyroidism. Plasma selenium levels were significantly lower than normal in hyperthyroidism. No statistically significant difference was found in plasma zinc, erythrocyte manganese, or urine copper values between patients with thyroid diseases and healthy controls. The erythrocyte manganese content correlated well with thyroxine and triiodothyronine levels. Plasma prealbumin and retinol-binding protein correlated well with the erythrocyte zinc content but not with plasma zinc levels. There was no correlation between erythrocyte superoxide dismutase activity and erythrocyte copper or zinc concentrations. The results of this study suggest that the metabolism of zinc, copper, manganese, and selenium is abnormal in thyroid diseases.

Screening of various immunopotentiators in spontaneously hypertensive rats with T-cell depression.

A strain of SHR which develops hypertension spontaneously is marked by a selective depression of T-cell functions associated with an early appearance of natural thymocytotoxic autoantibody and a deficiency of thymic hormone. Present results demonstrate that various immunopotentiators (IPs) such as thymostimulin (TS), PS-K, SPG, neurotropin (NSP), and K-247 partially or almost completely reversed the T-cell depression in these SHR as detected by a rosette forming test, plaque-forming assay and blastogenesic response to PHA and Con A. In contrast, these IPs had no effect on the immune responsiveness of WKA rats with normal T-cell functions. Among the IPs, NSP, which had an almost complete restorative effect on the T-cell functions of SHR, induced significant transplantation resistance to the syngeneic tumor challenge. A new synthetic product K-247 also induced a significant suppression of lethal tumor growth in SHR, though its restorative effect on T-cell functions was weak. The fact that K-247 had a suppressive effect on tumor cell growth in vitro indicates that biochemical modifications rather than immunological ones may be involved. However, none of the IPs induced antitumor resistance in normal WKA rats. These results suggest that this strain of SHR provides a useful animal model for evaluation of various IPs.