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Biomedical subjects

J Kolanowski

Publications and source records attributed to J Kolanowski.

At least 19 recordsLinked to original sources
PubMed1992

Effect of dexfenfluramine treatment on body weight, blood pressure and noradrenergic activity in obese hypertensive patients.

The effect of dexfenfluramine (dF) on body weight, blood pressure and noradrenergic activity were studied in 30 obese hypertensive patients randomly divided into two groups and treated for 3 months either with dF (30 mg daily; 16 subjects) or placebo (Pl; 14 subjects). 11 patients from the dF group and 9 patients given Pl completed the entire experimental protocol, including monthly visits for metabolic and hormonal measurements, as well as a bicycle exercise test with arterial catheterisation for haemodynamic and catecholamine measurements performed before and after 3 months of treatment. A progressive significant decrease in body weight, averaging 6.0 kg after 3 months was observed in the dF-treated group, whereas loss of weight in the placebo group (1.4 kg) was not significant. While blood pressure and noradrenergic activity, assessed as changes in the plasma levels and urinary excretion of norepinephrine, remained unaffected in the Pl group, a significant drop in the supine systolic and diastolic blood pressures, as well as in the resting venous norepinephrine level and in urinary norepinephrine excretion was found after the first month of dF administration. In addition, the exercise-induced rise in systolic and diastolic blood pressure, as well as in arterial plasma norepinephrine and epinephrine concentrations, was significantly reduced after 3 months of dF administration; there were no such changes in the Pl-treated group. The results of the present study indicate that, in addition to the weight-reducing effect of dexfenfluramine, its hypotensive effect may be mediated by a decrease in noradrenergic activity.

Adult↗
PubMed1992

An unusual cause of factitious mineralocorticoid excess.

The presence of hypokalaemia in hypertensive patient must prompt a search for increased mineralocorticoid activity. We describe and discuss the observation of a patient with biological markers of hypermineralocorticoidism, despite low plasma and urinary aldosterone levels, and suppressed plasma renin activity. This typical syndrome of apparent mineralocorticoid excess was secondary, in our patient, to prolonged administration of a mineralocorticoid-containing nasal spray.

Alkalosis↗
PubMed1992

Pathophysiology and treatment of the obesity-related arterial hypertension.

While obesity is frequently associated with arterial hypertension, the underlying mechanism is still poorly understood. A marked drop in blood pressure in response to hypocaloric carbohydrate-poor diet, occurring usually in obese hypertensive patients even before any significant reduction of body weight is achieved, strongly suggests that the obesity related metabolic abnormalities rather than the degree of fatness as such, are involved in the association between obesity and overweight. Among several possible mechanisms, the state of insulin resistance with hyperinsulinaemia, as well as increased activity of the sympathetic nervous system, are probably responsible for the development of arterial hypertension in obese subjects. The arterial hypertension may be promoted by these two mechanisms, which are probably causally related, closing the pathophysiologic loop leading to hypertension. Both mechanisms may promote the development of haemodynamic abnormalities which characterize the hypertension associated with obesity, i.e. the renal sodium and fluid retention with ensuing expansion of the extracellular volume and the increased peripheral vascular resistance.

Antihypertensive Agents↗
PubMed1992

Reappraisal of the role of insulin on sodium handling by the kidney: f1fect of intrarenal insulin infusion in the dog.

Since several studies suggest that increased insulin levels may induce antinatriuresis, the present work was undertaken to determine whether a physiological increase in insulin levels in blood perfusing the kidney may exert direct effect on kidney function, and more specifically on sodium reabsorption. To this end, insulin was infused directly into one renal artery of 10 anaesthetized dogs at the rate of 4 mU min-1 for a period of 90 min. The contralateral kidney was infused with saline alone, to provide reference values. Insulin level in the renal vein of the insulin-infused kidney went up from 1.4 +/- 0.9 before to 30.6 +/- 7.1 microU ml-1 after 90 min of insulin perfusion. There was no significant effect on renal plasma flow, glomerular filtration rate and renal uptake of substrates or oxygen between ipsi- and contralateral kidney. The fractional excretion of sodium was likewise unaffected, since it averaged at the end of insulin infusion 0.41 +/- 0.11% vs. 0.50 +/- 0.14% for the contralateral saline infused kidney. Even if one may assume that the baseline low insulin concentrations promote tubular sodium reabsorption, the results of the present study suggest that a moderate hyperinsulinaemia is without any additional effect on renal sodium handling.

3-Hydroxybutyric Acid↗
PubMed1992

Fluoxetine therapy in obese diabetic and glucose intolerant patients.

A double-blind placebo-controlled trial was conducted, involving 97 obese diabetic and glucose intolerant patients receiving either 60 mg fluoxetine daily (47 patients) or a placebo (50 patients); a similar calorie-restricted diet was prescribed to all patients. Weight loss was significantly higher in the fluoxetine-treated patients, whose diabetic status improved. Drop-out rate was not significantly different for both groups of patients.

Blood Glucose↗
PubMed1991

The effects of glucose ingestion and fasting on plasma immunoreactive beta-endorphin, adrenocorticotropic hormone and cortisol in obese subjects.

It has been demonstrated that opioid peptides are involved in the stimulation of food intake in rats and that the circulating beta-endorphin levels are increased in genetically obese rodents. Therefore, to assess whether the changes in food intake may influence circulating beta-endorphin levels in obese subjects, plasma beta-endorphin, ACTH and cortisol concentrations were determined in obese patients after an oral glucose load and during a 7-day total starvation. Baseline plasma beta-endorphin concentrations were significantly higher in obese patients than in control normal-weight subjects, while ACTH and cortisol levels were similar in both groups. Plasma beta-endorphin, ACTH and cortisol concentrations were not affected by the ingestion of 75 g glucose, neither were plasma beta-endorphin concentrations modified during prolonged starvation. Moreover, the lack of nycthemeral variations in beta-endorphin levels, documented before and during starvation while plasma ACTH and cortisol were significantly reduced in the evening, suggests that some extra anterior pituitary sources or some obesity-related changes in beta-endorphin metabolism may contribute to the pool of circulating beta-endorphin in obese subjects. On the other hand, even the extreme changes in nutritional conditions, such as total food deprivation or glucose ingestion, are devoid of any detectable influence on circulating beta-endorphin levels.

Adrenocorticotropic Hormone↗
PubMed1991

The influence of vanadate on insulin counter-regulatory hormones in obese fa/fa rats.

Vanadate has been shown to improve glucose homoeostasis in mildly glucose-intolerant and severely insulin-resistant fa/fa rats. The present study examined whether changes in insulin counter-regulatory hormones contribute to this beneficial effect of vanadate. Since oral administration of Na3VO4 caused a decrease in food intake and stopped the increase in body weight, vanadate-treated fa/fa rats were compared with both controls with food available ad libitum and pair-fed rats. Slightly lower plasma glucose levels were maintained in conjunction with markedly lower plasma insulin levels in vanadate-treated rats, and this effect was not simply due to the smaller body weight of the animals. Compared with control rats, treatment with vanadate affected neither basal plasma glucagon levels nor the increase in glucagon levels observed after insulin-induced hypoglycaemia or after i.v. injection of arginine. Compared with pair-fed rats, treatment with vanadate prevented the fall in basal plasma glucagon and its exaggerated rise in response to insulin that mere food restriction produced. Plasma corticosterone levels were high in fa/fa rats. Vanadate and pair-feeding similarly decreased basal plasma levels of corticosterone as well as nocturnal corticosteronuria. Thus the attenuation of the hypercorticism of fa/fa rats results from the reduction in body weight gain rather than from a specific action of vanadate. Vanadate did not influence urinary excretion of noradrenaline, an index of neural sympathetic activity, but prevented the increase in adrenaline excretion, an index of adrenal medulla activity, that was produced by food restriction in pair-fed rats. In conclusion, vanadate administration has no or little specific effects on three major insulin counter-regulatory hormones. This reinforces the suggestion that the beneficial effects of vanadate on glucose homoeostasis in fa/fa rats are mainly due to a correction of insulin resistance in peripheral tissues.

Animals↗
PubMed1990

Hormonal regulation of the rat small intestine: responsiveness of villus and crypt cells to insulin during the suckling period and unresponsiveness after weaning.

To further document the effect of insulin on intestinal maturation, suckling rats were treated either with exogenous insulin (12.5 mU.g body wt, intraperitoneally, twice daily) or with saline from d 8 to 12 postpartum. Sucrase activity in brush border membrane extracts was precociously induced by insulin, whereas the activities of other brush border membrane enzymes (maltase, aminopeptidase, and neutral lactase) were enhanced (+ 30 to + 131%, p less than 0.01 versus controls). The lysosomal enzyme, N-acetyl-beta-glucosaminidase, which normally declines at weaning was significantly (p less than 0.025) decreased in both villus (-51%) and crypt cells (-57%) isolated from the jejunum of insulin-treated rats. The microsomal enzyme, sulfatase C, and the cytosolic enzyme, lactate dehydrogenase, were also sensitive to insulin with decreases in activity ranging from -37 to -63% (p less than 0.05) compared to saline-treated control rats. Insulin at doses of 0.5 or 12.5 mU did not influence plasma total corticosterone levels, which were about 9-fold lower in suckling than in 25-d-old weaned rats. In weaned rats (from d 25 to 32) insulin treatment (12.5 mU) failed to influence the activity of brush border membrane hydrolases or of lysosomal, microsomal, and cytosolic enzymes. The synthesis rate of mature sucrase-isomaltase, measured in weaned rats (32 d) by the incorporation of 14C-leucine into the enzyme precursor protein, was equivalent in both groups. These data demonstrate that the immature enterocyte of the suckling rat is responsive to insulin, whereas the mature enterocyte of the weaned rat is unresponsive.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Corticotropin-induced changes in enzymatic activities of the post-pregnenolone steroidogenic pathway in rabbit adrenocortical cells.

In an attempt to delineate the effect of corticotropin (ACTH) on post-pregnenolone steroidogenesis, the activity of enzymatic systems operative in conversion of pregnenolone into glucocorticoids and androgens was studied in adrenocortical cells from control rabbits and from animals treated with ACTH for 12 days (ACTH 1-24, 200 micrograms s.c. daily). The cells from ACTH-treated rabbits exhibited an increased overall steroidogenic capacity and produced much more cortisol (P less than 0.0005) as well as other 17-hydroxylated steroids as a result of increased activity of 17 alpha-hydroxylase; corticosterone generation was concomitantly reduced. The increased conversion of pregnenolone or progesterone into androgens, as a result of previous treatment with ACTH, provides additional evidence for an effect of ACTH on 17 alpha-hydroxylase activity. A stimulatory effect of ACTH on 11 beta-hydroxylase was also evidenced by these cells, since conversion of 11-deoxycortisol into cortisol was enhanced (P less than 0.005). The increased production of androgens from 17-hydroxylated precursors by cells from ACTH-treated rabbits suggests that ACTH also exerts a prolonged stimulatory effect on 17,20-lyase. The activity of 3 beta-hydroxysteroid dehydrogenase-isomerase was apparently not influenced by chronic treatment with ACTH, judged from unchanged conversion of dehydroepiandrosterone into androstenedione. The activity of 11 beta-dehydrogenase was likewise unchanged in these conditions.

Adrenal Cortex↗
PubMed1988

Stabilization of left ventricular function with D-(-)-3-hydroxybutyrate after coronary occlusion in the intact dog.

The D-(-) isomer or natural form of 3-hydroxybutyrate (D-(-)-3OHB) is a readily used energy substrate. Studies on anesthetized intact dogs in our laboratory have demonstrated that raising the arterial level of D-(-)-3OHB to 1 mM enhances the ketone uptake not only by the normal, but also by the acutely ischemic myocardium, though at a lower rate. Whether this moderate rise in arterial D-(-)-3OHB does modify the time course of left ventricular (LV) function during acute regional ischemia remains unsettled. In the present study, 13 anesthetized intact dogs with occluded left anterior descending (LAD) coronary artery (balloon catheter) were infused with D-(-)-3OHB as the L-(+)-arginine salt at a rate of 20 mumol/kg/min i.v. for 90 min, starting 40 min after the LAD occlusion. Arterial D-(-)-3OHB rose to 1.1 mM. Arterial pH was not modified. By comparison with the decline observed in 13 saline-treated ischemic dogs, the ketone treatment significantly stabilized the time course of LV peak positive dP/dt and output per minute. This effect was not attributable to the simultaneous infusion of arginine since it was not observed with equimolar infusions of this amino acid alone in eight additional ischemic dogs.

3-Hydroxybutyric Acid↗
PubMed1987

Chronic treatment with corticotropin increases the capacity of rabbit adrenocortical cells to convert pregnenolone into androgens.

The present study was conducted to evaluate whether the previously demonstrated enhancement in adrenocortical androgen secretion in rabbits chronically treated with ACTH results, in addition to an increased pregnenolone production, from a more efficient conversion of this precursor of steroidogenesis into androgens. To this end, the adrenocortical cells from 14 control and 14 ACTH-treated rabbits (ACTH 1-24,200 micrograms s.c. daily for 12 days) were incubated either in the presence of different concentration of ACTH or with pregnenolone added in amounts from 0.5 to 250 micrograms. The total steroidogenic potency (maximal response to ACTH) was significantly enhanced for cells from ACTH-treated animals, as was the ACTH-induced production of dehydroepiandrosterone (DHEA), DHEA-sulfate, androstenedione and testosterone. In addition the production of these androgens from given amounts of exogenous pregnenolone was also significantly increased. The maximal capacity of adrenocortical cells to convert pregnenolone into androgens averaged (for ACTH-treated vs control group) 130 +/- 34 vs 43 +/- 10 pmol for DHEA, 138 +/- 43 vs 46 +/- 14 pmol for DHEA-sulfate, 99 +/- 31 vs 10 +/- 2 pmol for androstenedione and 8.0 +/- 2.6 vs 2.4 +/- 0.3 pmol for testosterone (P less than 0.001 for all androgens). The addition of ACTH to adrenocortical cells incubated with pregnenolone did not modify the maximal capacity of conversion of pregnenolone into androgens, which was in both experimental groups similar to that documented in the absence of ACTH. Thus, while an acute stimulatory effect of ACTH on adrenocortical steroidogenesis is devoid of any influence on the activity of the post-pregnenolone pathway of androgen synthesis, the chronic exposure of adrenocortical cells to ACTH lead to increased activity of steroidogenic pathway involved in the conversion of pregnenolone into androgens.

Adrenal Cortex↗
PubMed1986

Urinary catecholamine excretion in patients with secondary adrenocortical insufficiency.

To evaluate the relationship between the secretion of cortisol and the activity of adrenal medulla in the secondary adrenocortical insufficiency, the excretion of epinephrine and norepinephrine was documented in 8 patients suffering from panhypopituitarism. Plasma levels and urinary excretion of cortisol were very low in baseline conditions, and the increase in these parameters of cortisol secretion occurring upon ACTH infusion was significantly reduced with respect to the response to ACTH documented in normal subjects. The mean value of urinary epinephrine excretion was at the lower limit of normal values, and a highly significant positive correlation was found between cortisolemia or cortisoluria and urinary epinephrine excretion in these patients. Despite a significant increase in cortisolemia and cortisoluria upon ACTH administration, this acute increase in adrenocortical activity was without any stimulatory effect on epinephrine or norepinephrine excretion. But, as in baseline conditions, a significant correlation was documented for the degree of adrenocortical activity and epinephrine excretion on the day of ACTH administration. It appears, therefore, that in severe secondary adrenocortical insufficiency the excretion of epinephrine is reduced proportionally to the decrease in adrenocortical activity.

Adrenal Insufficiency↗
PubMed1986

Enhanced 17 alpha-hydroxylation of pregnenolone and increased androgen production by rabbit adrenocortical cells stimulated chronically with corticotropin.

The postulated chronic stimulatory effect of corticotropin (ACTH) on pregnenolone production and on 17 alpha-hydroxylase activity was evaluated on adrenocortical cells obtained from control and chronically ACTH-treated rabbits. The cells were incubated with various concentrations of ACTH added alone or together with trilostane, so as to inhibit further conversion of pregnenolone and dehydroepiandrosterone. The maximal steroidogenic effect of ACTH (determined in the absence of trilostane) was increased 2-fold in adrenocortical cells from ACTH-treated animals; furthermore, cortisol production was increased whereas that of corticosterone decreased. While the generation of pregnenolone was of comparable magnitude for cells from both experimental groups, chronic in vivo treatment with ACTH was followed by a 40-fold enhancement in 17-hydroxypregnenolone production. Concomitantly, maximal DHEA production documented in the presence of ACTH and trilostane was enhanced more than 200-fold, from 0.45 +/- 0.20 pmol in control rabbits to 147 +/- 67 pmol in cells from ACTH-treated animals. The corresponding values of DHEA-sulphate production were 0.86 +/- 0.12 and 432 +/- 334 pmol, respectively. Thus, a prolonged stimulatory effect of ACTH on rabbit adrenocortical cells consists in an enhancement of the capacity to generate pregnenolone, and to convert this compound into 17-hydroxylated steroids.

17-alpha-Hydroxypregnenolone↗
PubMed1986

In vivo effect of the D-(-) isomer or natural form of 3-hydroxybutyrate on initial release of lactate dehydrogenase from the acutely ischaemic myocardium.

D-(-)-3-hydroxybutyrate, the isomer found in the circulation and in the urine of diabetic patients, generally is believed to be the physiologically important form of 3-hydroxybutyrate [10]. Little is known concerning the effects of an elevated plasma level of the D-(-) isomer of 3-hydroxybutyrate upon the acutely ischaemic heart. Using anaesthetized intact dogs with a balloon catheter inserted into the proximal part of the left anterior descending coronary artery (LAD), we have recently demonstrated that a 1 mM ketonaemia induced with the arginine salt of D-(-)-3-hydroxybutyric acid reduces the uptake of non-esterified fatty acids (NEFA) in the myocardial area distal to the inflated balloon [4]. The question arises as to whether the concomitant increase in ketone uptake in this area could be detrimental to the acutely ischaemic myocardium. Indeed, a previous study on isolated coronary ligated hearts from normal rats has shown that the rate of release of lactate dehydrogenase (LDH) during the first 90 min of ischaemia can be enhanced by replacing glucose (11 mM) in the perfusion fluid with either albumin-bound palmitate (0.9 mM) or sodium DL-3-hydroxybutyrate (10 mM) as the sole energy substrate [11]. This would suggest that the ketone might be as deleterious as its metabolic precursors for membrane integrity in the acutely ischaemic myocardium. In the present report, we examine the effect of arginine D-(-)-3-hydroxybutyrate on LDH release from ischaemic myocardium in our in vivo preparation. The dogs were treated with lidocaine in order to minimize the frequency and, hence, the adverse metabolic effects of ectopic beats.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1986

The mechanism of the prolonged stimulatory effect of corticotrophin on pregnenolone production by guinea-pig adrenocortical mitochondria.

The postulated prolonged stimulatory influence of ACTH on the adrenocortical mitochondrial synthesis of pregnenolone in response to ACTH was studied in adrenal mitochondria isolated from control guinea-pigs and from animals treated s.c. with 100 micrograms ACTH(1-24) twice daily on the day before the animals were killed. The animals from both groups were injected with 100 micrograms ACTH s.c. 30 min before killing. The mitochondrial production of pregnenolone (expressed in nmol per mg mitochondrial protein after 10-min incubation) increased from 1.52 +/- 0.46 (S.E.M.) in the control group to 4.50 +/- 0.59 for mitochondria from ACTH-treated animals, despite a similar free cholesterol content in the mitochondria, even when determined after a previous in-vivo treatment with aminoglutethimide to block further metabolism of cholesterol into pregnenolone. In addition, in the presence of an excess of exogenous cholesterol (100 mumol/l), the production of pregnenolone remained higher for mitochondria from ACTH-treated animals. In contrast, when the calcium concentration in the incubation medium was raised to 1 mmol/l, with subsequent enhancement in pregnenolone synthesis, the mitochondrial pregnenolone production became similar for both groups (8.28 +/- 1.11 nmol in the ACTH-treated group and 9.55 +/- 1.90 nmol in the control group), even in the presence of 100 mumol cholesterol/l (13.5 +/- 1.80 nmol in ACTH-treated animals and 14.8 +/- 1.93 nmol in controls). Cycloheximide treatment administered on the day before the animals were killed was without any effect on pregnenolone production in control animals (3.51 +/- 0.43 nmol before and 3.65 +/- 0.63 nmol after cycloheximide treatment).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1985

Enhanced androgen production by rabbit adrenocortical cells stimulated chronically with corticotropin: evidence for increased 17 alpha-hydroxylase activity.

The effects of prolonged treatment with corticotropin (ACTH1-24, 200 micrograms s.c. daily during 12 days) on the production of androgens and glucocorticoids were studied on rabbit dispersed adrenocortical cells. The steroidogenic capacity of adrenocortical cells, expressed in terms of the maximal response to ACTH of glucocorticoid (i.e. corticosterone and cortisol) production, was significantly increased after treatment with ACTH. This was associated with a loss of sensitivity to this peptide: indeed, the concentration of ACTH required to induce a half maximal secretory response was one order of magnitude higher with cells from ACTH-treated animals. Among the C21 steroids measured the changes observed involved the 17 alpha-hydroxylated compounds (cortisol, cortisone, 11-deoxycortisol) while corticosterone production was significantly depressed. This effect of prolonged ACTH treatment on steroidogenic pathways involving 17 alpha-hydroxylation, was further evidenced by a clear-cut enhancement in androgen secretion (dehydroepiandrosterone, androstenedione and testosterone) by adrenocortical cells from ACTH-treated animals. The changes observed after treatment of the animal with ACTH were equally obvious, whether the adrenocortical cells were incubated with ACTH or with dibutyryl-c-AMP.

Adrenal Cortex↗
PubMed1985

Inhibitory effects of the D(-)isomer of 3-hydroxybutyrate on cardiac non-esterified fatty acid uptake and oxygen demand induced by norepinephrine in the intact dog.

The effects of ketosis on the norepinephrine-induced high rates of cardiac uptake of non-esterified fatty acids (NEFA = free fatty acids = FFA) and oxygen consumption were studied in anesthetized intact dogs. After a control infusion of norepinephrine (500 ng/kg.min into the left ventricle), the D(-) isomer or natural form of 3-hydroxybutyrate was infused intravenously as the arginine salt at rates of 20 mumol/kg.min in group A (10 dogs) and 80 mumol/kg.min in group B (10 dogs) and a second norepinephrine infusion was superimposed on the ketone treatment. At the time the effects of the second catecholamine infusion were measured, the arterial 3-hydroxybutyrate concentration averaged 1.2 +/- 0.1 mM in group A and 8.3 +/- 0.4 mM in group B, and the cardiac uptake of the ketone amounted to 17.4 +/- 0.6 and 35.8 +/- 5.3 mumol/min.100 g, respectively. Relative to the control norepinephrine infusion, the arterial NEFA concentration was reduced to 88 +/- 4% in group A and to 62 +/- 8% in group B, but the cardiac uptake of NEFA was significantly more depressed, to 65 +/- 7% in group A and to 35 +/- 8% in group B. These changes were not observed in ten non-ketotic animals under repeated norepinephrine infusion. Thus, ketosis inhibited the norepinephrine-stimulated uptake of NEFA, presumably through (1) a lowered availability of NEFA from arterial blood, attributable to a reduction of extracardiac lipolysis, and (2) competition of 3-hydroxybutyrate with NEFA for metabolism by the myocardium in the face of still high arterial NEFA concentrations, 1.7 +/- 0.1 mM in group A and 1.1 +/- 0.2 mM in group B. In both groups, the lowering of the contribution of NEFA to cardiac metabolism was associated with a reduction of the estimated oxygen demand per beat (ratio of cardiac oxygen consumption/min to the pressure-rate product), while the pressure response to norepinephrine was not modified. There was no evidence for abnormal cardiac function.

3-Hydroxybutyric Acid↗