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Biomedical subjects

P Kotanko

Publications and source records attributed to P Kotanko.

17 recordsLinked to original sources
PubMed1992

Beta 2-adrenoceptor density in fibroblast culture correlates with human NaCl sensitivity.

To study salt sensitivity in humans and its relation to expression of adrenoceptors, 20 male normotensive Caucasians were investigated on a diet of 180 mmol NaCl/day followed by 60 mmol NaCl/day over 2 wk and again by 180 mmol NaCl/day over 2 wk, and blood pressure changes were assessed by long-term oscillatory blood pressure monitoring under basal conditions. Individual cell cultures of skin fibroblasts from skin biopsies were also established, and alpha 2- and beta 2-adrenoceptors were measured. Seven subjects were salt sensitive, and the remainder were salt resistant. Cultured skin fibroblasts in salt-sensitive subjects express less than half the number of beta 2-adrenoceptors compared with salt-resistant subjects (65 +/- 12.7 vs. 173 +/- 14.8 fmol/mg, P less than 0.001), and there is a correlation between the absolute rise of blood pressure on a high-salt diet and the density of beta 2-adrenoceptors (r = -0.67, P less than 0.01). It remains to be established whether a reduced in vitro density of beta 2-adrenoceptors in cultured cells is causally related to salt sensitivity in normotensive humans.

Binding Sites↗
PubMed1991

[Further advances in the salt sensitivity hypothesis in man].

The hypothesis, proposed by us since 1981, that genetically determined salt sensitivity exists in the normotensive population has been confirmed by other groups. We propose that in salt sensitive subjects an augmented upregulation of alpha-2 combined with simultaneous downregulation of beta-2 adrenoceptors by a high salt diet (resulting in an increase in the "operative" adrenoceptor ratio) is responsible for the rise of blood pressure. In salt resistant subjects the "operative alpha-2/beta-2 adrenoceptor ratio" does not increase on a high salt intake. The adrenoceptor changes in salt sensitive subjects probably lead to an increased central sympathetic outflow (through receptor changes in certain brain areas) and to simultaneous enhanced end-organ response in resistance vessels and in the kidney, causing enhanced vasoconstriction and enhanced sodium reabsorption. Long term follow up of salt sensitive normotensives will show, whether they develop "essential hypertension" in the future.

Absorption↗
PubMed1990

Urinary excretion of N-acetyl-beta-D-glucosaminidase in patients after cyclosporin-treated corneal grafting.

Allograft rejection occurs in up to 70% of high-risk keratoplasty patients. For this reason short-term Cyclosporin treatment was administered for three months to prevent graft loss. Of 23 renal healthy patients, 19 enjoyed long-term graft acceptance. We evaluated in these patients N-acetyl-beta-D-glucosaminidase (NAG) excretion as a marker of renal tubular damage. All patients, except one, showed urinary NAG excretion to be within the normal range. From this we conclude that no renal tubular damage occurs after short-term Cyclosporin treatment.

Acetylglucosaminidase↗
PubMed1989

Inverse regulation of alpha-2 and beta-2 adrenoceptors in salt-sensitive hypertension: an hypothesis.

A high salt diet leads to up-regulation of alpha-2 adrenoceptors and down-regulation of beta-2 adrenoceptors in normotensive subjects. Although the increase in blood pressure with a high salt diet is not related to the magnitude of the alpha-2 or beta-2 adrenoceptor changes alone, it is related to the increase in the ratio of the receptor changes (operative alpha/beta adrenoceptor ratio). An increase in the operative alpha/beta adrenoceptor ratio with a high salt intake results in vasoconstriction and reduced vasodilatation at resistance vessels, as well as increased renal proximal tubular sodium reabsorption. An influence of heredity on this relationship is supported by four lines of evidence: 1) salt-sensitivity of blood pressure occurs predominantly in subjects with a family history of hypertension; 2) studies in twin children document the influence of genetic variance on salt-sensitivity of blood pressure; 3) subjects with a family history of hypertension have a significantly lower salivary sodium concentration and an altered urinary sodium excretion after salt loading compared to subjects with no such history; 4) salt-sensitivity of blood pressure may be associated with specific genetic markers. On the basis of these observations, we propose the hypothesis that enhanced inverse alpha-beta-adrenoceptor regulation in response to a high salt intake may be responsible for salt sensitivity in the normal population, and may contribute to the development of essential hypertension in susceptible individuals. This alteration is likely to be genetically mediated.

Down-Regulation↗
PubMed1988

Noninvasive diagnosis of renal allograft rejections--application of an information-theoretical model.

This paper describes an information-theoretical model developed for detection of renal allograft rejection on the basis of various laboratory data. In this report the mathematical background of the model is described in detail and the rationale of its use is discussed. An example is given for the practical application of the model in kidney grafted patients. In the 30 patients of the test collective, seven rejection episodes were diagnosed by the clinicians and verified histologically. All seven rejection episodes were detected by the model, in the mean 2.4 days (median; 3 days) before the clinical diagnosis.

Biopsy, Needle↗
PubMed1986

Urinary enzyme analysis in renal allograft transplantation.

The urinary excretion of four enzymes (fructose-1,6-bisphosphatase, glutathione S-transferase, N-acetyl-beta-D-glucosaminidase and pyruvate kinase) was assayed daily in 59 patients following renal cadaveric allografting. 51 patients were given cyclosporin A (CyA group) as an immunosuppressive, 8 patients were treated conventionally with azathioprine and prednisolone (CON-group). Urinary enzyme output was evaluated by two different mathematical models. Model A follows single enzyme excretion, whereas model B also analyzes enzyme patterns. The best results were obtained by a combined analysis of all four enzymes with model B. In the CON-group the sensitivity was 1.00, the specificity 0.85, the predictive values of positive test 0.45 and all 12 graft rejections were diagnosed correctly. In the CyA group the sensitivity was 0.40, the specificity 0.99, the predictive value of positive test 0.33, and 6 out of 9 rejections were recognized. The evaluation of the single enzymes did not produce similarly good results with either model.

Acetylglucosaminidase↗
PubMed1986

Morphological and biochemical observations in rat nephron epithelia following cyclosporine A (CsA) treatment.

Morphology, urinary enzyme excretion and mitochondrial function was studied in rats fed over a period of 30 days with 20 and 40 mg CsA/kg body weight. Already on day 8 vacuolisation and augmentation of autophagic vacuoles, lipid droplets and a loss in microvilli can be observed in the S-3 segment of the proximal nephron using the lower CsA dose. These effects are enhanced during the treatment period. The overall effect, however, is a subtle one. The dose of 40 mg/kg produces more pronounced cellular alterations, a more severe vacuolisation, but also focal prenecrotic damage of proximal tubular S-2 and S-3 cells. The cells altered in that manner amount to roughly 5% of the total proximal tubular epithelium. Enhanced urinary excretion of the proximal cytosolic enzymes, fructose-1,6-bisphosphatase, glutathione S-transferase, pyruvate kinase and the lysosomal N-acetyl-beta-D-glucosaminidase appear to parallel the morphologic changes, whereby only the excretion of pyruvate kinase is significantly elevated on day 30 using 40 mg/kg. Decrease in oxidative phosphorilation capacity (ADP:O ratio) was found with both CsA doses, however, this result seems to be dissociated from changes in morphology and enzyme excretion. Studies on isolated tubular fragments in vitro, exposed to CsA exhibited an inhibition of the cytosolic malate dehydrogenase isoenzyme, which could be interpreted as a possible source of the CsA induced tubular alteration.

Acetylglucosaminidase↗
PubMed1986

Up-regulation of alpha 2 adrenoceptors and down-regulation of beta 2 adrenoceptors by high-salt diet in normotensive men: enhanced up-regulation of operative (alpha 2:beta 2) adrenoceptor ratio predicts salt sensitivity.

In 24 normotensive male volunteers (age 20-25 years) reduction of sodium intake from 200 to 50 mmol/day over 2 weeks resulted in a 14% fall of alpha 2-adrenoceptors of platelets from 209.5 to 179.4 fmol/mg (P less than 0.01) and in a 16% rise of beta 2-adrenoceptors of lymphocytes from 13.3 to 16.2 fmol/mg (P less than 0.05) which was reversible by 2 weeks of high sodium intake. In contrast to the comparatively minor changes of alpha 2- and beta 2-adrenoceptor density, the functionally probably more relevant 'operative (alpha 2:beta 2) adrenoceptor ratio' decreased by 53% from 22.9 to 14.9 (P less than 0.01) during the low-salt diet. Although neither the individual changes of alpha 2- and of beta 2-adrenoceptor densities correlated with individual blood pressure changes induced by variations in sodium intake, there was a highly significant positive correlation (r = 0.55, n = 33; P less than 0.01) between the rises of the 'operative adrenoceptor ratio' and the rises of blood pressure induced by high salt intake. We conclude that the 'operative adrenoceptor ratio', although only determined on alpha 2- and beta 2- and not on alpha 1- and beta 1-adrenoceptors, and only on circulating blood cells, may be representative for sympathetic resistance vessel tone, at least as a function of variations of salt intake. Enhanced up-regulation of the 'operative adrenoceptor ratio' in the salt-sensitive part of the population may be one important early step in the development of essential hypertension.

Adult↗
PubMed1985

Interrelation between oxygen consumption and Na-K-ATPase activity in rat renal proximal tubule suspension.

The portion of Na-K-ATPase activity on oxygen consumption was determined in suspensions of rat proximal tubules by monitoring oxygen consumption (QO2) under different metabolic states: in the presence or absence of succinate or lactate (10 mmol/l) and increasing concentrations of ouabain (0.4; 0.8; 1.2 and 1.6 mmol/l). In the metabolic states tested, the ouabain induced decrease of QO2 was identical, which implies a fixed rate between Na-K-ATPase activity and QO2. On the basis of these results, Ki and maximal inhibition rate were determined by Lineweaver-Burk and Eadie-Hofstee plots Ki was 0.67 mmol/l ouabain and the maximal inhibition of QO2 was 77%. This corresponds to an absolute decrease of QO2 of 1,630 mumol O2 . h-1 . g-1 protein. Since this value represents the real portion of Na-K-ATPase on QO2, the activity of Na-K-ATPase can be calculated, yielding an activity of 163 mumol ATP . min-1 . g-1 tubule protein.

Animals↗
PubMedDate not supplied

Quantitative morphologic changes in nephron structures and urinary enzyme activity pattern in sodium-maleate-induced renal injury.

The morphologic changes in sodium-maleate-induced acute renal injury in the rat were quantified by a stereologic analysis. The major changes were confined to an increase in endocytic vacuoles and a decrease in mitochondrial inner membrane surface area. These results were found to be linked to significantly increased urinary activities of the cytosolic of the cytosolic enzymes fructose-1,6-bisphosphatase (FBP) and lactate dehydrogenase, the lysosomal enzyme N-acetyl-beta-glucosaminidase (NAG) and the NAD-dependent mitochondrial isocitrate dehydrogenase (ICDH). The highest increase was found for NAG, followed by FBP and ICDH.

Animals↗