Long-term efficacy and tolerability of pravastatin in hypercholesterolemia in patients with non-insulin-dependent diabetes mellitus. Hyogo Pravastatin Study Group.

This study reports the result of a 12-month, open-label multicenter study of the efficacy and tolerability of pravastatin in the management of hypercholesterolemia associated with non-insulin-dependent diabetes mellitus. Pravastatin produced a decrease, in 138 diabetic and 51 non-diabetic patients, in total serum cholesterol by 19 and 20%, in low-density lipoprotein (LDL) cholesterol by 25 and 29%, in apolipoprotein B by 15 and 19% and in triglycerides by 8 and 5%, respectively. High-density lipoprotein cholesterol levels were increased by 9% in both groups. All of these changes were significant (P < 0.001) except for triglycerides changes in non-diabetic patients, where the change was not significant and no significant differences were observed between the two groups. These favorable effects on LDL cholesterol and apolipoprotein B were not influenced by gender, the type of diabetic therapy, baseline hemoglobin A1c levels and by the presence of hypertension or gross proteinuria, although a decrease in the two variables were less in those with body mass index > or = 26.4 kg/m2 or in those with age < 60 years. Adverse experiences were similar between treatment groups and the drug was well tolerated. Only one diabetic patient was withdrawn from the study because of pruritus. Pravastatin produced no change in fasting plasma glucose concentrations and hemoglobin A1c levels in diabetic patients throughout the study. Pravastatin was generally effective in improving the serum lipids of hypercholesterolemic diabetic patients.

Effects of thyroxine and cold exposure on hypothalamic TRH levels in rats with various pituitary-thyroid states.

The hypothalamic content and concentration of thyrotropin-releasing hormone (TRH) were determined by radioimmunoassay in normal, thyroidectomized, hypophysectomized and cold-exposed rats with or without thyroxine. In normal animals, the single administration of thyroxine (1,5 and 20 microgram/100 g B.W.) altered neither the content nor the concentration of TRH in the hypothalamus. However, seven days' administration of this hormone resulted in the dose-dependent increase in the hypothalamic TRH levels. In thyroidectomized rats the hypothalamic TRH levels were slightly reduced in spite of the marked increase of plasma TSH levels and decrease of pituitary TSH levels. In the animals given thyroxine (10 microgram/100 g B.W.) for 7 days in addition to thyroidectomy, however, the TRH levels exceeded that in the animals which underwent throidectomy alone. The hypothalamic TRH levels were markedly reduced in hypophysectomized rats. Conversely, in hypophysectomized rats given 7 days' thyroxine (1 and 5 microgram/100 g B.W.), the levels were increased dose-dependently. In cold-exposed rats, the plasma TSH levels roughly doubled, but the TRH levels remained unchanged. These findings strongly suggest that the feedback site of thyroxine extends not only to the pituitary gland but also to the hypothalamus, and that thyroxine has an increasing effect of the hypothalamic TRH level, though the mechanism(s) remain to be clarified.

Diurnal variation of the human urinary TRH excretion measured by radioimmunoassay.

Urine TRH was estimated by the radioimmunoassay which was accomplished according to the method of Bassiri and Utiger. Minimum detectable dose of TRH was 25 pg and recovery of TRH ranged from 72% to 112% in our laboratory. Intraassay coefficients of variation were 5.4% to 14.0% and interassay variations were 10.6% to 15.0%. Of the TRH analogues tested, only two (Ser-His-Pro-NH2, Thr-His-Pro-NH2) had potent reactivity to anti-TRH serum in large dose of 100 ng/tube. Urine samples were kept at -20 degrees C after adjusted to pH 3.0 because the inactivation of TRH in urine was markedly dependent on temperature and pH value. Using this radioimmunoassay, diurnal variation of the urinary TRH excretion at regular intervals in normal subjects was observed. Peak TRH excretion occurred around early morning, while minimum of the excretion was observed around noon. Total urinary TRH excretion of 24 hours was 817-1579 ng (M+/-SE: 1241+/-89 ng) in normal subjects. In patients with chronic renal failure, urinary excretions of TRH was obviously lower than those of normal subjects.