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Biomedical subjects

P Komanicky

Publications and source records attributed to P Komanicky.

16 recordsLinked to original sources
PubMed1990

An evaluation of the therapeutic effects and dosage equivalence of glyburide and glipizide.

Nineteen noninsulin-dependent diabetic patients [ten women, nine men, aged 36-80 years (mean +/- SE 56.8 +/- 2.7 years)] were randomized to receive either glyburide or glipizide for 16 weeks, in a double-blind crossover fashion. A 2-week washout period preceded each treatment period. The patients measured blood glucose concentrations 16 times weekly using Chemstrip-bG. The medication dosages were titrated to achieve fasting blood glucose concentrations of less than or equal to 6.2 mM and preprandial and postprandial concentrations of less than or equal to 9.0 mM, or to a total daily dose of 20 mg for glyburide and 40 mg for glipizide. Glyburide therapy resulted in a significant decline in fasting, preprandial, postprandial and bedtime blood glucose levels, while glipizide treatment led to a significant lowering of postprandial and bedtime blood glucose. Furthermore, fasting, preprandial and postprandial blood glucose concentrations were significantly lower during glyburide as compared to glipizide treatment phase. Glycosylated hemoglobin levels were decreased only with glyburide. Serum C-peptide and insulin concentrations were not altered over the entire study. The mean final daily dose of glyburide (15.4 +/- 1.6 mg) was markedly lower than that of glipizide (29.7 +/- 3.1 mg). Thus, in this patient population, glyburide was twice as potent on a weight basis than glipizide.

Adult↗
PubMed1989

Loss of pubic and axillary hair following treatment with glucocorticoids.

A woman with prior bilateral oophorectomy developed loss of pubic and axillary hair following treatment with glucocorticoids. Serum androgens were low while cortisol and aldosterone levels were normal. This unusual presentation, which continued for at least 3 years, was most likely attributable to the prolonged selective suppression of adrenal androgens by glucocorticoids.

Aldosterone↗
PubMed1987

Metabolic degradation and synthesis of calcitriol in spontaneously hypertensive rat.

Plasma calcitriol concentration is unexpectedly low in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY) in view of previous findings of low plasma ionized calcium, hypophosphatemia, and hyperparathyroidism in SHR. Also, parathyroid hormone (PTH) and other exogenous stimuli cause a smaller increment in plasma calcitriol in SHR than in WKY. We investigated whether these differences in plasma calcitriol levels were due to decreased production rate (PR) or increased metabolic clearance rate (MCR) in SHR using the continuous infusion-isotope equilibration technique. In the basal state, MCR was 0.306 +/- 0.048 ml X min-1 X kg-1 in SHR and 0.284 +/- 0.026 ml X min-1 X kg-1 in WKY (P = NS). Estimated PR was lower in SHR (22.7 vs. 33.7 ng X day-1 X kg-1). With PTH infusion (3 U X h-1 X 100 g-1 for 20 h), MCR was 0.220 +/- 0.011 ml X min-1 X kg-1 in SHR and 0.256 +/- 0.017 ml X min-1 X kg-1 in WKY (P = NS). Measured PR was markedly lower in SHR (154 +/- 24 vs. 262 +/- 27 ng X day-1 X kg-1; P less than 0.02). Basal plasma PTH, total plasma calcium, and plasma inorganic phosphate were not different between SHR and WKY. Thus, SHR show diminished calcitriol production under basal condition and with PTH stimulation. MCR is not increased in SHR and does not appear to be influenced by PTH or the accompanying elevation in plasma calcium and calcitriol.

Animals↗
PubMed1984

Subacute and chronic action of acrylonitrile on adrenals and gastrointestinal tract: biochemical, functional and ultrastructural studies in the rat.

A single dose of acrylonitrile can produce fatal adrenal apoplexy within approximately 2 h. Our previous studies also indicate that multiple injections of the chemical cause acute hemorrhagic and occasional nonperforating duodenal ulcers. Other authors have reported increase in gut and lung neoplasia after chronic exposure. The present study was designed to elucidate the subacute and chronic actions of acrylonitrile on the adrenals, stomach and duodenum by correlating biochemical, functional and morphologic investigations, as well as to gain insight into the mechanisms of action of acrylonitrile. Rats were exposed to 0, 0.0001% (1 ppm), 0.002%, 0.01%, 0.05% or 0.2% acrylonitrile in drinking water, or to the same amount of the chemical given through daily gavage, for 7, 21 or 60 days. Acrylonitrile caused a time- and dose-dependent decrease in plasma corticosterone levels; aldosterone was affected only by the 'high' dose and prolonged time of exposure. Young rats were more susceptible than adults to this action of acrylonitrile. The adrenal cortex, especially the zona fasciculata, was atrophic in rats that had ingested the nitrile through drinking water. At 0.05% and 0.2%, it also caused decreased food intake and body weight gain. The adrenals were enlarged with a hyperplastic zona fasciculata after daily doses of a bolus of acrylonitrile. Ingestion of the chemical did not interfere with compensatory enlargement of the adrenal gland following unilateral adrenalectomy. On the other hand, the ACTH-induced elevation of corticosterone plasma concentration was significantly attenuated by acrylonitrile in drinking water. Electron microscopy of the adrenal glands revealed no consistent changes in the steroid-producing cells. We thus postulate that accelerated turnover of circulating corticoids and/or interference with the secretion or action of ACTH may primarily be responsible for the decreased plasma levels of corticosterone and aldosterone in rats that ingest acrylonitrile. The mucosa in the stomach at the junction of the forestomach and glandular region of animals that had ingested acrylonitrile was hyperplastic. The corpus also showed regional mucosal hyperplasia with the appearance of 'cobble-stoning'. These changes were preceded and associated with an elevated concentration of non-protein sulfhydryls mostly in the mucosa of the glandular stomach. A similar, less prominent elevation also occurred in the proximal duodenum. These alterations may resemble the preneoplastic combination of elevated glutathione and focal hyperplasia described in the liver with hepatocarcinogens.(ABSTRACT TRUNCATED AT 400 WORDS)

Acrylonitrile↗
PubMed1982

Role of endocrine function tests in the evaluation of transsphenoidal hypophysectomy for advanced breast cancer.

Forty-three women underwent transsphenoidal hypophysectomy for metastatic breast cancer. Endocrine tests (luteinizing hormone, follicle-stimulating hormone, thyrotropin, prolactin and growth hormone) were done in 28 patients to evaluate the completeness of the procedure. Response of the metastatic breast cancer and duration of survival after hypophysectomy were determined and statistically compared with the posthypophysectomy hormone levels. Only one patient had an endocrinologically complete hypophysectomy, but the objective remission rate (32 percent) is comparable to the 30 to 40 percent objective remission rate reported in other studies that claim to have achieved complete hypophysectomy. No statistically significant associations were found between the levels of the hormones measured and the type of response (objective, subjective or none) to hypophysectomy. However, objective responders survived longer than nonresponders (p = 0.01). When analyzing the associations of the various hormone levels with the duration of survival after hypophysectomy, a positive correlation (p less than 0.05) of peak thyrotropin levels with duration of survival was found. Our data indicate that the clinical benefit advanced breast cancer patients received from an endocrinologically incomplete hypophysectomy is probably as great as that received from an endocrinologically complete hypophysectomy. It appears that a nonspecific disturbance of the hormonal milieu may adversely affect the growth of breast cancer. More studies are needed to elucidate the nature of the endocrine disturbance produced by hypophysectomy and its effects on hormone-sensitive tumors.

Adult↗
PubMed1982

Amiloride in Bartter's syndrome.

Hypokalemia in Bartter's syndrome (BS) is often difficult to correct despite all measures. Amiloride is a new potassium-sparing diuretic that blocks sodium channels in distal renal tubular cells, independent of aldosterone. Four patients with BS were studied, in an outpatient clinic, while on amiloride therapy (10 to 40 mg/day). Before receiving amiloride the patients were treated with combinations of prostaglandin synthetase inhibitors, potassium-sparing diuretics, and potassium supplements. After a baseline observation period, the potassium-sparing diuretics were discontinued and amiloride therapy was instituted. Cumulative mean plasma potassium level rose after amiloride (0.5 mEq/l; P less than 0.05). The mean plasma potassium levels in three of the patients rose and one of these patients eventually became normokalemic. There were very few adverse reactions and none could be attributed to amiloride alone. Amiloride may be a useful and safe drug for the treatment of the hypokalemia of BS.

Adult↗
PubMed1982

Amiloride in primary hyperaldosteronism.

Amiloride is a potassium-sparing diuretic used in spontaneous and diuretic-induced hypokalemia. The effect of amiloride was studied prospectively in 12 patients with primary hyperaldosteronism. Four patients had unilateral adrenal adenomas and eight had bilateral adrenal hyperplasia. All patients were hypertensive and their mean plasma potassium levels were low. Amiloride, 10 to 40 mg daily, was given for 6 mo. Mean plasma potassium levels rose (0.96 mEq/l, P less than 0.001) and remained normal throughout the study without potassium supplementation. Mean blood pressure was lowered by amiloride (22/10 mm Hg, P less than 0.001) but normotension required concomitant antihypertensive therapy in most patients. No significant adverse clinical or laboratory experiences could be directly attributed to amiloride therapy. There was no correlation between the response to therapy and the plasma aldosterone levels, aldosterone secretion rate, or presence of a unilateral adrenal adenoma. Our study demonstrates the efficacy of amiloride in the correction of hypokalemia and amelioration of hypertension in primary hyperaldosteronism.

Adult↗
PubMed1982

Role of adrenal steroidogenesis in etiology of hypertension in the spontaneously hypertensive rat.

We measured peripheral adrenal steroid levels in spontaneously hypertensive rats (SHR), killed by nitrogen suffocation, at different ages during the development of hypertension. SHR became hypertensive by 8 weeks of age. Circulating plasma aldosterone (Aldo) levels of SHR gradually declined with age compared to their male Wistar-Kyoto (WKY) normotensive controls. On the other hand, corticosterone (B) concentrations rose relatively as the rats grew older, however, they were significantly lower in SHR at 16 weeks of age. Deoxycorticosterone (DOC) levels were significantly lower at 8 weeks and 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) were lower at 16 weeks of age. Steroid ratios at age 4 weeks showed significantly higher B to 18-OH-DOC and lower B to DOC, 18-OH-DOC to Aldo, and 18-OH-DOC to DOC values in SHR. Furthermore, the B to 18-OH-DOC ratio remained significantly higher at 12 weeks and the B to DOC ratio remained lower at 16 weeks. These data imply the possibility of the secretion of an unknown steroid(s) and the existence of another, fourth pathway of Aldo biosynthesis in young SHR. Thus, major alterations of adrenal steroidogenesis exist in young SHR which may be causative in the development of hypertension. After the onset of hypertension, steroidogenesis tends to return to normal, by which time, however, SHR may have developed metacorticoid hypertension.

18-Hydroxydesoxycorticosterone↗
PubMed1981

5 alpha-Dihydro-11-deoxycorticosterone: effect on blood pressure in the rat.

The bioactivity of 5 alpha-reduced sex steroids such as 5 alpha-dihydrotestosterone has increased interest in an analogous role for 5 alpha-reduced mineralocorticoids in hypertensive syndromes. In view of its relatively high mineralocorticoid receptor affinity despite relatively low electrolyte-altering effects, 5-alpha-dihydro-11-deoxycorticosterone, or 5 alpha DHDOC (2) was compared to 11-deoxycorticosterone acetate (DOCA) for blood pressure-altering ability by continuous subcutaneous infusion into uninephrectomized saline-drinking Sprague-Dawley male rats, at doses selected on the basis of relative mineralocorticoid receptor affinity. After three weeks of treatment, DOCA significantly raised blood pressure, body weight, heart and kidney weight, and produced a discernible increase in fluid intake; 5 alpha DHDOC failed to affect any of these parameters commonly influenced by mineralocorticoids. We conclude that 1) the ability of 5 alpha DHDOC to affect blood pressure was not predicted by its relatively high affinity for the mineralocorticoid receptor, and 2) these data do not support a role for 5 alpha DHDOC in mineralocorticoid hypertension, although differences in protein binding and clearance could affect its blood pressure-altering activity.

Animals↗
PubMed1981

Experimental hypertension induced by 19-nor-progesterone treatment in the rat.

Fifty-day-old unilaterally nephrectomized and 1% saline-drinking Sprague-Dawley CD male rats were divided into three comparable groups on the basis of blood pressure, body weight, and fluid intake. The control group received vehicle only, the second group received 19-nor-progesterone [19-nor-pregn-4-ene-3,20-dione (19-Nor-Prog)] in a dose of 250 micrograms/24 h, and the third group received aldosterone-acetate (Aldo-Ac) in a dose of 125 micrograms/24 h, by means of Alzet osmotic minipumps implanted sc for 21 days. Both the 19-Nor-Prog- and the Aldo-Ac-treated rats became hypertensive to a similar degree in the course of the study. Rats given Aldo-Ac also developed polydipsia, decreased body weight, cardionephromegaly, and hypokalemia. The 19-Nor-Prog-treated rats showed no significant changes in heart and kidney weights. The hypertensinogenicity of 19-Nor-Prog is unrelated to significant changes in heart and kidney weight, as is the case with potent mineralocorticoids.

Animals↗
PubMed1978

Treatment of Cushing's syndrome with trilostane (WIN 24,540), an inhibitor of adrenal steroid biosynthesis.

Seven patients with Cushing's syndrome were treated with trilostane (WIN 24,540) 4 alpha,5-epoxy-17 beta-hydroxy-3-oxo-5 alpha-androstane-2 alpha-carbonitrile), an inhibitor of adrenal steroid biosynthesis. Trilostane treatment reduced steroid biosynthesis and it also improved biochemical manifestations of the disease in all of the patients treated. The average cortisol secretory rate decreased significantly with treatment, from 47.1 to 23.4 mg/24 h (P less than 0.005), and urinary 17-hydroxycorticosteroids decreased from 15.7 to 8.7 mg/24 h (P less than 0.01). Urinary free cortisol excretion decreased from 277 to 88 microgram/24 h (P less than 0.01), and 0800 h plasma cortisol levels declined from 25.0 to 12.0 microgram/dl (P less than 0.05). Conversely, dehydroepiandrosterone sulfate excretion in urine increased from 1.3 to 5.8 mg/24 h (P less than 0.0025) and in plasma increased from 162 mg/24 h (P less than 0.025). Plasma and urinary free dehydroepiandrosterone increased 2-fold. Urinary 17-ketosteroid excretion increased from 18 to 43 mg/24 h (P less than 0.001). A significant reduction in urinary excretion of tetrahydroaldosterone, tetrahydrodeoxycorticosterone, and 18-hydroxytetrahydrodeoxycorticosterone was observed with treatment. Inhibition of steroid biosynthesis was accompanied by a 2-fold increase in PRA and no change in serum cholesterol levels. Mean arterial blood pressure decreased with treatment from 109 to 97 mm Hg (P less than 0.005), and fasting blood sugar decreased from 117 to 98 mg/dl (P less than 0.005), accompanied by rise in plasma potassium levels from 3.8 to 4.3 milliequivalents/liter (P less than 0.025). Two patients on long term therapy also showed an improvement in clinical features of their disease. There were no significant treatment-related carcinoma, simultaneously producing both an excessive amount of cortisol and ACTH, is described. It is concluded that trilostane is an effective inhibitor of 3 beta-hydroxysteroid dehydrogenase enzyme system in human adrenal gland; it inhibits biosynthesis of cortisol and it is useful in the treatment of Cushing's syndrome.

17-Ketosteroids↗
PubMed1976

Steroidogenic responses to varying parenteral routes of administered (alpha 1-18) ACTH.

In healthy human subjects, the steroidogenic responses to a single injection of alpha 1-18 ACTH by the subcutaneous, intramuscular, and intravenous (IV) routes were assessed by measurement of plasma cortisol levels, 17-hydroxycorticosteroid excretion, and cortisol secretion rates. Results showed that regardless of the parenteral route used, alpha 1-18 ACTH at doses of 1.0 and 0.5 mg was an effective adrenocorticotropic agent; however, with the IV route, the effect was considerably prolonged. The patterns of disappearance within the plasma of alpha 1-18 ACTH and alpha 1-24 ACTH were compared following a single IV injection of these compounds labeled with 125I. ALPHa 1-18 acth produced only a slight initial rise and a slower decline in plasma radioactivity compared to alpha 1-24 ACTH, suggesting slower degradation of alpha 1-18 ACTH. Administered as a single IV injection, alpha 1-18 ACTH has a prolonged effect on steroidogenesis and has potential for being a useful diagnostic and therapeutic ACTH preparation.

17-Hydroxycorticosteroids↗
PubMed1976

Radioimmunoassay of 18-hydroxy-11-deoxycorticosterone in plasma.

A method is described for the radioimmunoassay of 18-OH-DOC using antibodies generated in rabbits against the carboxymethoxime derivative coupled to bovine serum albumin. The procedure uses 4 ml of plasma with intra and interassay variations of 8 and 9% respectively. Standard 18-OH-DOC added to plasma from an adrenalectomized patient gave a regression equation, Y=0.974X+/-2.210 and a correlation coefficient of 0.999. The only cross reacting steroid, 18-OH-B which may lead to falsely high levels is removed by a single thin layer chromatographic step. Blood levels in normal subjects agree closely with those calculated indirectly by metabolic clearance and secretion rate measurements. ACTH stimulation produced an 18-fold increase in plasma concentration while dexamethasone suppression decreased levels 3-fold. Four hours in the upright position resulted in a decreased plasma concentration while aldosterone increased. No significant response to dietary sodium restriction could be demonstrated.

18-Hydroxydesoxycorticosterone↗
PubMedDate not supplied

Hypertensinogenic potencies of aldosterone and deoxycorticosterone in the rat.

Hypertensinogenic potency and other effects of acetate salts of aldosterone (ALA) and deoxycorticosterone (DOCA) were evaluated in 50-day-old mononephrectomized and saline-drinking Sprague-Dawley CD male rats. The steroids were administered by continuous subcutaneous infusion in a dose of 100 microgram/24 hrs by means of Alzet osmotic minipumps implanted subcutaneously. Within 3 weeks of steroid treatment, systolic blood pressure, measured in the tail of conscious animals by a photoelectric cell method at 27 degrees C environmental temperature, increased significantly in ALA rats as compared to that in DOCA rats, which was not different from controls. ALA rats exhibited marked polydipsia, decreased body weight, hypernatremia, hypokalemia, cardiomegaly, and kidney enlargement, whereas DOCA rats exhibited only cardiomegaly when compared with controls. The degree of cardiomegaly in ALA and DOCA rats was statistically much greater than the differences in their respective blood pressure levels when compared to controls. Under the conditions of this study, it is concluded that: 1) the hypertensinogenic potency of ALA is greater than that of DOCA; 2) ALA and DOCA may induce cardiomegaly, independent of their effect on blood pressure; 3) Alzet osmotic minipumps are effective tools for the administration of steroids by continuous infusion.

Aldosterone↗