Hypercalcemic effect of insulin in thyroparathyroidectomized alloxan-treated rats

The acute effect of a hypoglycaemic dose of 0.5 U/100 g BW insulin administered intramuscularly on calcium metabolism was investigated in fasted alloxan-treated rats. It was found that the hypercalcaemic effect of insulin was evident only in thyroparathyroidectomized (TPTX) and not in parathyroidectomized (PTX) rats. A subcutaneous administration of 180 MRC mU/100 g BW calcitonin abolished the calcium raising effect of insulin in TPTX rats suggesting a protective role of calcitonin against insulin action in intact rats. In an attempt to elucidate the mechanism of the calcium raising effect of insulin 45Ca administered intravenously was used to indicate the movement of calcium from the plasma pool. Insulin administration delayed the plasma 45Ca disappearance rate but had no effect on bone 45Ca uptake within 120 min. In contrast, insulin administration resulted in a 31% reduction of urinary 45Ca excretion while the urine volume remained unchanged. However, the insulin-induced reduction of urinary calcium excretion could not totally account for the calcium raising effect of insulin in TPTX animals.     

Role of nifedipine in treatment of hypertension.

The efficacy of nifedipine in the treatment of hypertension was assessed in 15 patients whose hypertension continued while being treated with atenolol 100 mg and bendrofluazide 5 mg daily. Nifedipine was added in doses of 10, 20, and 30 mg three times daily in a placebo controlled, double blind trial. One patient was withdrawn from the trial because of severe postural hypotension with the highest dose. Erect and supine blood pressure in the remaining 14 patients were significantly reduced by all doses of nifedipine. The drug was well tolerated but plasma potassium fell by 0.3 mmol(mEq)/1 during treatment (p less than 0.05). Nifedipine is thus effective in the treatment of hypertension but should probably be used in combination with a potassium sparing diuretic.     

The effect of nifedipine on skin-flap survival

Nifedipine, a calcium-channel blocker, is a peripheral vasodilator and has been shown to increase blood flow to skin. The hypothesis that nifedipine would thereby improve skin-flap viability was tested by comparing the extent of necrosis of long pedicle flaps in control and nifedipine-treated rats. Thirty male Sprague-Dawley rats were randomized to receive either 2.5 mg/kg nifedipine in chocolate PO t.i.d. or plain chocolate according to protocols. Serum nifedipine levels were determined by gas chromatography. Dorsal cephalad-based random vascular pedicle flaps (2 X 6 cm) were elevated, sutured to their beds, and photographed for computer-aided surface area determinations. The extent of distal flap necrosis was expressed as a percentage of the total flap area, and differences were studied by one-way analysis of variance. The differences between the mean percentages of necrosis at 1 and 2 weeks for the groups were not statistically significant. We conclude that nifedipine has no effect on the extent of necrosis of the random skin flap in the rat.     

Rebound of vasospastic angina after cessation of long-term treatment with nifedipine.

The beneficial effect of calcium antagonists in the treatment of vasospastic angina is now well recognized. Although withdrawal symptoms have been reported following abrupt cessation of therapy with some cardiovascular drugs, there is no detailed report on similar complications of the cessation of therapy with calcium antagonists. In a 4-month period eight patients with well documented and well controlled vasospastic angina experienced a marked increase in the frequency and duration of anginal episodes at rest following the involuntary cessation of treatment with nifedipine, 10 to 20 mg four times a day. The increase began within 2 to 5 days after the cessation of treatment. Substitute therapy with isosorbide dinitrate, 30 mg, and verapamil, 80 to 120 mg, each four times a day, was effective in all cases. Although the mechanism responsible for this rebound phenomenon is not known, awareness of its existence is essential considering the widespread use of calcium antagonists.     

Indomethacin increases abortifacient effect of PGE2 in man.

Results of this study indicate that pretreatment with indomethacin significantly increases the abortifacient effect of an intravenous infusion of PGE2 in patients admitted for abortion as a result of fetal death in utero. Indomethacin pretreatment shortened the duration of PGE2-induced abortion in primigravid and multigravid groups of patients by about 4 and 2 hours respectively. When primigravid and multigravid groups were combined, the dose of PGE2 needed for complete delivery decreases in the indomethacin-treated group by 39.9%.     

The Pathophysiology and Clinical Aspects of Hypercalcemic Disorders

For the purposes of this review, the vast and increasingly complex subject of hypercalcemic disorders can be broken down into the following categories: (1) Physiochemical state of calcium in circulation. (2) Pathophysiological basis of hypercalcemia. (3) Causes of hypercalcemia encountered in clinical practice: causes indicated by experience at the University of California, Los Angeles; neoplasia; hyperparathyroidism; nonparathyroid endocrinopathies; pharmacological agents; possible increased sensitivity to vitamin D; miscellaneous causes. (4) Clinical manifestations and diagnostic considerations of hypercalcemic disorders. (5) The management of hypercalcemic disorders: general measures; measures for lowering serum calcium concentration; measures for correcting primary causes—the management of asymptomatic hyperparathyroidism.     

Suppressive effect of cyproheptadine on L-DOPA-induced growth hormone release in man.

In order to elucidate the relationship between dopaminergic and serotoninergic mechanisms in regulating secretion of human growth hormone (hGH), the effect of cyproheptadine, an antiserotoninergic agent, on l-DOPA-induced hGH secretion was studied in normal subjects. Oral administration of 500 mg of l-DOPA caused a rise in plasma hGH in 6 of 7 subjects studied. This rise in plasma hGH was significantly blunted by the intravenous infusion of 5 mg of cyproheptadine. These results suggest the close relationship between dopamine and serotonin in the control of hGH secretion.     

The effect of fluoxetine on warfarin metabolism in the rat and man.

Fluoxetine, a selective blocker of serotonin uptake, inhibits the metabolism of warfarin in rats. In contrast, after a single dose or seven daily doses of fluoxetine to human subjects, no inhibition of warfarin metabolism was observed.     

The effect of exogenous TSH and Achilles tendon reflex time in man.

The effect of exogenous thyrotropin (TSH) -- 3 X 10 IU daily -- on Achilles tendon reflex time (ART) was investigated in the group of 38 in-patients, treated for thyroid cancer. A significant shortening of ART was recorded in a subgroup of hypothyroid persons after the 2nd and 3rd dose of TSH. Moreover, a significant correlation was proved between initial values of ART and their changes after the 2nd and 3rd TSH injection in this group. No significant interrelationship was observed between changes of thyroid function and ART after TSH administration. In interpretation of this finding the possibility of direct effect of TSH on muscle metabolism in hypothyroid man should be considered.