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Biomedical subjects

J M Gray

Publications and source records attributed to J M Gray.

At least 73 records · Page 4Linked to original sources

Effect of estrogen on lipoprotein lipase activity and cytoplasmic progestin binding sites in lean and obese Zucker rats.

Injections of 5 micrograms estradiol benzoate (EB) for 5 days resulted in decreases in the rate of body weight gain in both lean (Fafa) and obese (fafa) Zucker rats. EB administration also resulted in significant induction of cytoplasmic progestin binding sites in both hypothalamic-preoptic area (H-POA) and adipose tissues from rats of both genotypes. However, EB treatment significantly decreased lipoprotein lipase (LPL) activity in adipose tissue from lean, but not obese, Zucker rats and the same treatment increased LPL activity in the uteri from lean, but not obese, Zucker rats. The data are discussed in terms of the metabolic and reproductive dysfunctions observed in the genetically obese rat.

Adipose Tissue↗

United States experience with oxprenolol in hypertension.

Double-blind, randomized, parallel-group studies have confirmed that oxprenolol, either alone or in combination with a thiazide, is effective in reducing elevated blood pressure. In 2 of 3 comparisons with placebo, the blood pressure reduction was significantly more effective with oxprenolol; in 1 study, even though the placebo response was pronounced, oxprenolol was still more effective than placebo. In 2 studies propranolol reduced blood pressure by about 2 mm Hg more than oxprenolol. In the larger, longer-term study this difference was significant at the end of the dose-titration period, but there were no significant differences between the 2 treatment groups at study end. Moreover, oxprenolol reduced heart rate less and was associated with fewer side effects. Oxprenolol effectively lowered blood pressure when given once daily and was well tolerated, even in large doses. Blood pressure was reduced less with oxprenolol than with hydrochlorothiazide, -14/-11 versus -20/-13 mm Hg. The mean reduction with oxprenolol was less for black patients than for white. In a 1-year safety study, 86% of the patients continued to have a diastolic pressure of less than 90 mm Hg at study end.

Blood Pressure↗

Hyperkalaemia in patients in hospital.

Significant hyperkalaemia occurred in 406 out of 29 063 patients admitted to a major Scottish teaching hospital in one year (1.4%). Mortality was higher in these patients than in control patients and was strongly correlated with the severity of the hyperkalaemia. Overall seven deaths were directly due to hyperkalaemia (out of 58 deaths among patients with hyperkalaemia). Factors contributing to a poor prognosis were severity and speed of onset of hyperkalaemia and the presence of appreciable renal impairment. Patients with hyperkalaemia were older and more likely to be male; this trend was present in all diagnostic subcategories. Genitourinary disease, gastrointestinal disease, and cancer were significantly more common among the patients with hyperkalaemia than the controls. Hyperkalaemia due to drug treatment was invariably mild and non-fatal, whereas genitourinary disease was often associated with moderate to severe hyperkalaemia, which in two cases proved fatal. Use of electrocardiographic monitoring was rare, and although the treatment of hyperkalaemia was effective, it was often used when not required. Hyperkalaemia is a potential hazard in diabetic ketoacidosis, and use of potassium supplements should be carefully monitored during correction of the acidosis.

Diabetic Ketoacidosis↗

Uterine and adipose lipoprotein lipase activity in hormone-treated and pregnant rats.

We report for the first time the presence of lipoprotein lipase (LPL) activity in the uteri of adult rats. This uterine LPL activity was significantly elevated by administration of the estrogen, estradiol benzoate (EB), but not by treatment with the antiestrogen, nafoxidine. Both EB and nafoxidine, however, greatly reduce both parametrial and retroperitoneal adipose tissue LPL activities. Uterine LPL activity also changed as a function of the duration of pregnancy, increasing severalfold between days 14 and 18 and then decreasing by about 20% on day 21. These data suggest the existence of a hormone-dependent system of providing lipids for storage and/or utilization by metabolic and reproductive tissues as needed.

Adipose Tissue↗

Total body potassium in patients receiving chlorthalidone and metoprolol for hypertension.

Measurements of potassium status were reviewed in 23 hypertensive patients receiving metoprolol either alone or in combination with chlorthalidone or chlorthalidone plus potassium over an average period of nine months. There was no statistically significant change in plasma potassium, total blood cell or total body potassium in patients on long-term metoprolol. Four subjects (17%) in the diuretic groups developed hypokalaemia (serum potassium less than 3.0 mmol/l) in the absence of significant falls in total blood cell or total body potassium. Thus the use of chlorthalidone plus potassium did not provide adequate prophylaxis against hypokalaemia even in metoprolol recipients. The study confirms that monitoring parameters of potassium handling is still necessary in beta-blocker recipients who also receive diuretics alone or in a fixed-dose combination with potassium.

Adult↗

Slow-release oxprenolol compared with oxprenolol in hypertensive patients: a multicenter clinical trial.

Oxprenolol (OX) is a nonselective, beta-adrenergic blocking agent with intrinsic sympathomimetic activity. We studied 178 patients in five centers to determine whether a polymer-matrix-based, slow-release preparation of oxprenolol (SR-OX) given once daily was as effective as the standard preparation given twice daily for the treatment of patients with mild to moderate hypertension. After a placebo washout phase, patients were treated with OX until blood pressure was controlled. They were then randomized in a double-blind fashion to continue the same dose, given as either OX bid or SR-OX qd with a placebo as the second dose. All patients took hydrochlorothiazide 50-100 mg/d throughout the study. Blood pressure was reduced 23/15 mm Hg (p less than 0.001) and pulse 8 beats/min in the SR-OX group (n = 67) and 24/17 mm Hg (p less than 0.001) and 8 beats/min in the OX group (n = 72) by titrating standard OX. After randomization to SR-OX or OX, there were no further changes over six weeks. Home-determined blood pressures showed no loss of control in the evening. There were no unexpected adverse effects. We conclude that SR-OX given once daily is as effective as OX given twice daily for the treatment of hypertension.

Adult↗

Recognition of emotion from facial expression in mental handicap.

When mildly and severely mentally retarded people saw photographs showing expressions of basic emotions their overall performance was found to be correlated with intelligence. Certain specific patterns of confusion were determined, clinically the most significant being an inability to cope with high intensity emotions.

Adult↗

Time course of effects of ovarian hormones on food intake and metabolism.

The effects of administration of estradiol benzoate (EB) or EB plus progesterone (EB + Prog) on feeding behavior and lipid metabolism were examined in ovariectomized rats killed 1, 2, 3, 7, or 14 days after the onset of hormone treatment. EB caused a transient decrease in food intake and body weight gain and a sustained decrease in adipose tissue lipoprotein lipase activity, and progesterone attenuated this EB effect. Hepatic acetyl CoA carboxylase (ACC) and fatty acid synthetase (FAS) activities decreased in the first days of hormone treatment (both EB and EB + Prog treatments) and returned to normal at 1 wk in both treatment groups. At 2 wk, hepatic ACC and FAS activities were greatly elevated in the EB, but not the EB + Prog group. These data demonstrate the complexity of the patterns of behavioral and metabolic responses after ovarian hormone manipulation in adult female rats.

Adipose Tissue↗

Do anticonvulsant drugs commonly induce osteomalacia?

Twenty adult epileptic out-patients who had received anticonvulsant therapy for a mean duration of 15 years were assessed for clinical, biochemical, radioisotopic and bone biopsy evidence of osteomalacia. Occasional biochemical abnormalities were demonstrated but no individual subject was found to have osteomalacia. There is increasing evidence to cast doubt on the existence of a strong relationship between anticonvulsant drugs and osteomalacia. This evidence is reviewed and it is concluded that in the presence of adequate sunlight exposure anticonvulsant therapy alone is most unlikely to lead to osteomalacia in adults.

Adult↗

Acute respiratory failure and CNS-depressing drugs.

Data from a drug surveillance programme were analysed to estimate the frequency with which patients with a diagnosis of respiratory failure had been exposed to CNS-depressing drugs. Eleven out of 37 patients with respiratory failure had received such medication. A detailed comparison of these patients and controls admitted to hospital because of respiratory disease who did not develop respiratory failure failed to reveal significant differences in drug usage. This unexpected finding suggests that patients with respiratory disease of equal severity may vary greatly in their tendency to develop carbon dioxide retention following administration of drugs with respiratory depressant properties.

Acute Disease↗

In vivo cell nuclear binding of 17 beta-[3H]estradiol in rat adipose tissues.

Rat adipose tissues contain high-affinity, hormone-specific cytoplasmic estrogen receptors. If adipose tissues are actually estrogen target tissues, then it should be possible to demonstrate in vivo binding and retention of 17 beta-[2H]estradiol in adipose tissue cell nuclei, the putative subcellular site of steroid action. Gonadectomized rats were given an intravenous injection of 40 microCi (0.11 microgram) 17 beta-[2,4,6,7-3H]estradiol. Animals were then killed, and cell nuclei were isolated from hypothalamus and various fat pads. Cell nuclear levels of radioactivity peaked at 1 h in both hypothalamus and parametrial adipose tissue, but the peak cell nuclear concentration in the fat pad was more than twice that in hypothalamus. At 1 h, 89% of the adipose tissue nuclear radioactivity migrated with 17 beta-estradiol on thin-layer plates. Radioactivity was retained in cell nuclei for more than 6 h in both tissues. This cell nuclear binding was estrogen specific. Pretreatment with radioinert estrogens (17 beta-estradiol or R 2858) abolished cell nuclear 17 beta-[3H]estradiol uptake, but other steroids (progesterone, corticosterone, and 5 alpha-dihydrotestosterone) were without effect. Cell nuclear binding was found in all fat pads studied in both males and females. Levels were highest in parametrial (females) and epididymal (males) fat pads, the depots with the highest concentration of cytoplasmic estrogen receptor. There were no sex differences in cell nuclear binding. Taken together these findings provide strong support for the contention that 17 beta-estradiol could affect lipid metabolism and body fat content in part by direct action on adipose tissues.

Adipose Tissue↗

Food intake, body weight, and adiposity in female rats: actions and interactions of progestins and antiestrogens.

A series of experiments examined the effects of two progestins, progesterone and R 5020, and two nonsteroidal antiestrogens, nafoxidine and MER-25, on body weight and composition in female rats. Both progesterone and R 5020 increased food intake, body weight, and carcass adiposity in ovariectomized (OVX) rats treated with estradiol benzoate (EB), but neither progestin had any effect on these measures in OVX rats not treated with EB. R 5020 was substantially more effective than progesterone on all end points. Nafoxidine and MER-25 mimicked the actions of estradiol and decreased adipose tissue lipoprotein lipase (LPL) activity by 75-80%. For adipose tissue LPL activity, both nafoxidine and MER-25 were full estrogen agonists and without antiestrogenic activity. Nafoxidine also mimicked the effects of EB by reducing food intake, body weight, and carcass adiposity in OVX rats. In contrast, nafoxidine antagonized the induction of cytoplasmic progestin ([3H]R 5020) binding sites by EB in parametrial adipose tissue of OVX rats. In nafoxidine-treated OVX rats, concurrent progesterone administration had no effect on adipose tissue LPL activity, but progesterone did increase food intake, body weight, and carcass fat content. Some physiological mechanisms by which gonadal steroids may act to influence eating and adiposity are discussed.

Adipose Tissue↗

Cytoplasmic estrogen, but not progestin, binding sites in male rat adipose tissues.

Male rat adipose tissues contain cytoplasmic estrogen binding sites comparable to those found in females. This bindng is of high affinity (Kd = 1.7 x 10(-10) M) and is estrogen specific. Binding of 17 beta-estradiol was inhibited by radioinert estrogens (17 beta-estradiol and R 2858) but not by other steroids (progesterone, 5 alpha-dihydrotestosterone, and corticosterone). Estrogen binding sites were found in all fat pads studied, but levels were highest in the epididymal pads. Treatment of female rats with 17 beta-estradiol benzoate (E2B) induced cytoplasmic progestin receptors in adipose tissues, but in three separate experiments, E2B treatment (20 microgram/day for 3 days) failed to induce measurable progestin ([3H]R 5020) binding sites in males. E2B treatment reduced lipoprotein lipase (LPL) activity by approximately 75% in epididymal (male) and parametrial (female) fat pads. Concurrent progesterone treatment increased parametrial LPL activity in E2B-treated females, but progesterone had no effect on epididymal fat pad LPL activity in males. These findings are consistent with the hypothesis that in male rats aromatized (estrogenic) metabolites of testosterone may reduce body fat content and alter lipid metabolism by direct actions on adipose tissues.

Adipose Tissue↗