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Biomedical subjects

W Zidek

Publications and source records attributed to W Zidek.

At least 199 records · Page 11Linked to original sources
PubMed1993

Therapeutic efficiency of phlebotomy in posttransplant hypertension associated with erythrocytosis.

Hypertension is a major complication in kidney transplantation and contributes to the high cardiovascular mortality of renal transplanted recipients. The aim of the present study was to evaluate the therapeutic effect of phlebotomy on blood pressure in posttransplant hypertension associated with erythrocytosis. In 12 renal transplanted patients (7 male, 5 female, aged 29-52 years) with erythrocytosis (defined by hematocrit > 52% or hemoglobin > 170 g/l), a 24-hour-monitoring of blood-pressure and heart rate (SpaceLabs SL90207) was performed before, 2 and 6 weeks after phlebotomy. Patients with iron-deficiency and/or transplant rejection were excluded from the study. Ten of 12 patients were on antihypertensive treatment before phlebotomy. Phlebotomy (500 ml) was repeated three times on average within the first two weeks, until hematocrit decreased below 45%. The phlebotomy therapy lowered the hematocrit after two weeks from 54.8 +/- 2.8% to 44.3 +/- 4.2% and 43.0 +/- 5.6% after six weeks. Before phlebotomy, the blood pressure was systolic 153.2 +/- 15.1 mmHg and diastolic 95.2 +/- 9.5 mmHg. After repeated phlebotomy, there was a significant decrease of blood pressure to systolic 139.0 +/- 14.1 and diastolic 85.3 +/- 8.2 mmHg (p < 0.01). Without change of hematocrit and hemoglobin, there was no further change of blood pressure after six weeks (systolic 140.1 +/- 9.9 mmHg, diastolic 86.3 +/- 9.5 mmHg). The heart rate did not change significantly during the therapy. The antihypertensive treatment could be reduced in most of the patients. The present study demonstrates the therapeutic effect of phlebotomy in posttransplant hypertension associated with erythrocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Application of cross-flow filtration to the purification of biologically active peptides in human plasma after incubation with a protease-rich extract.

The aim of this study was to find an experimental procedure to purify biologically active peptides from a complex biological matrix (plasma), which was incubated with a protease-rich extract (submandibular gland extract). Special interest was focused on the practicability of cross-flow filtration for this purpose. Therefore, peptides in the incubation mixture were purified with a combination of high-performance liquid chromatographic steps. Purification of biologically active peptides was monitored by a sensitive bioassay and by laser desorption/ionization mass spectrometry. This permitted not only purity control at each purification step but also identification of one of the peptides with vasoconstrictor properties as angiotensin II. This result demonstrates the practicability of cross-flow filtration for extracting enzymatic reaction products from complex substrate-enzyme mixtures during the incubation.

Animals↗
PubMed1992

A vasopressor factor partially purified from human parathyroid glands.

Recently, a parathyroid hypertensive factor was postulated to play a role in the pathogenesis of hypertension in genetically hypertensive rats. Therefore it was examined, whether in human parathyroid glands a vasopressor substance can be detected. For this purpose, homogenates of hyperplastic parathyroid glands from 20 patients with tertiary hyperparathyroidism were deproteinized and fractionated by gel chromatography. The fractions obtained were tested for vasopressor activity in isolated perfused rat kidneys. A vasopressor fraction containing substances of 0.6-2.5 kDa was identified in the parathyroid glands. The responsible product was heat sensitive, peptidase-, trypsin- and carboxypeptidase y- sensitive and hydrophilic, as it did not bind to hydrophobic reversed-phase gel. These results suggest that parathyroid glands contain a hydrophilic peptide-like vasopressor substance different from the parathyroid hormone.

Angiotensin II↗
PubMed1992

[Pseudoxanthoma elasticum. Clinically typical but frequently overlooked].

A 52-year-old man had small yellowish, striated or reticular papules since the age of 5 years. These appeared first on the large flexures, and later on the neck, abdomen, penis and the mucosa of the lips. He developed angina at the age of 47 years. A bypass operation, however, did not lead to complete regression of cardiac symptoms. Four years later, the vision in his right eye deteriorated because of arterial occlusion, and the patient was treated with laser coagulation; he was started on long-term treatment with acetylsalicylic acid (250 mg/d) and calcium dobesilate (1,500 mg/d). Despite this, the vision in his left eye also deteriorated progressively. Fundoscopy revealed bilateral pigmentary changes in the macular region, variations in the retinal arterial diameters and "angioid streaks". Pulses were absent in the right radial artery, the left posterior tibial artery and both dorsalis pedis arteries, but there were no trophic changes or symptoms. The serum total cholesterol (246 mg/dl), triglycerides (177 mg/dl) and LDL-cholesterol (193 mg/dl) were only slightly elevated. The diagnosis of pseudoxanthoma elasticum with typical changes in the elastic fibres was confirmed by elastin staining in a biopsy from one of the lesions.

Biopsy↗
PubMed1992

Erythropoietin in thrombotic thrombocytopenic purpura and acute renal failure.

In this study, erythropoietin serum levels were serially determined in eight patients with acute renal failure to get a lead on the etiology of anemia in acute renal failure and to address the relationship between erythropoietin synthesis and renal excretory performance. Erythropoietin serum levels rapidly decreased after onset of acute renal failure to values of 12.8 +/- 10.3 mU/ml compared to 16.8 +/- 9.4 mU/ml in healthy controls. After restoration of renal function, erythropoietin levels climbed slowly in six patients (15.2 +/- 5.3 mU/ml), and in relation to prolonged anemia in these patients, a relative deficiency of erythropoietin could be observed. In one patient with thrombotic thrombocytopenic purpura causing acute renal failure, the decline of erythropoietin secretion was not observed, and in a phase of the disease when plasma exchange therapy was interrupted, markedly increased erythropoietin levels, up to 182 mU/ml, were detected despite the renal failure. Focusing on erythropoietin secretion in thrombotic thrombocytopenic purpura, we followed hormone synthesis in two other patients with the same disease, one of whom had mild renal insufficiency and one had normal renal function. High erythropoietin levels of up to 205 mU/ml were found in these patients, similar to the peak levels found in the patient with complete renal failure. Plasmapheresis treatment reduced erythropoietin production in all three patients with thrombotic thrombocytopenic purpura. In summary, our study indicates that in most cases of acute renal failure, erythropoietin synthesis is compromised and may contribute to the development of anemia in renal failure and aggravate the persistence of anemia after restoration of renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1992

Erythropoietin induced transmembrane calcium influx in essential hypertension.

The effects of erythropoietin (EPO) on cytosolic free calcium concentration ([Ca2+]i) in platelets of 20 essential hypertensive patients (HT) and of 25 normotensive subjects (NT) were investigated using the fura2 technique. In resting platelets [Ca2+]i were not significantly higher in HT compared to NT (74.3 +/- 7.8 nM vs 59.8 +/- 7.0 nM, mean +/- SEM). Addition of EPO significantly increased [Ca2+]i in HT compared to NT (13.8 +/- 5.3 nM vs 0.9 +/- 1.9 nM, p less than 0.01). EPO increased the amount of calcium in intracellular stores. This was confirmed independently using thrombin-induced changes of [Ca2+]i in a calcium-free medium and using chlorotetracycline as a marker of stored calcium. After preincubation with EPO thrombin-induced changes of [Ca2+]i were significantly lower in HT compared to NT (306.1 +/- 30.0 nM vs 407.7 +/- 35.7 nM, p less than 0.05). In a calcium-free medium after preincubation with EPO thrombin-induced changes of [Ca2+]i were significantly lower in HT compared to NT (54.7 +/- 11.8 nM vs 100.9 +/- 10.5 nM, p less than 0.05) indicating lower storage capacity in HT. It is concluded that elevated response to EPO may provide a powerful tool to evaluate diagnosis and underlying pathophysiological mechanisms in essential hypertension.

Adult↗
PubMed1992

Isolation of an ultrafilterable Ca(2+)-ATPase inhibitor from the plasma of uraemic patients.

1. Calcium concentration and Ca(2+)-ATPase activity under basal conditions and after maximal stimulation with calmodulin were measured in erythrocytes from 32 patients with end-stage renal failure on haemodialysis and from 27 healthy subjects. 2. In patients with renal failure the Ca2+ concentration in erythrocytes was elevated compared with healthy subjects (4.27 +/- 1.02 versus 2.86 +/- 0.57 mumol/l, P less than 0.05). 3. Basal Ca(2+)-ATPase activity was lower in the patients with renal failure than in healthy subjects (4.62 +/- 1.34 versus 5.43 +/- 1.23 pmol of phosphate min-1 10(-6) erythrocytes). After maximal stimulation, Ca(2+)-ATPase activity reached 6.93 +/- 2.81 pmol of phosphate min-1 10(-6) erythrocytes in the patients with renal failure, whereas in healthy subjects stimulation yielded a Ca(2+)-ATPase activity of 32.54 +/- 8.48 pmol of phosphate min-1 10(-6) erythrocytes. 4. Incubation of erythrocytes from healthy subjects with plasma from uraemic patients caused inhibition of Ca(2+)-ATPase. Likewise, the ultrafiltrate from plasma obtained by haemofiltration treatment inhibited Ca(2+)-ATPase. 5. Gel chromatography of the ultrafiltrate and laser desorption/ionization mass spectroscopy revealed that a fraction containing substances with a molecular mass of about 300 Da inhibited Ca(2+)-ATPase. 6. It is concluded that, in uraemia, a Ca(2+)-ATPase inhibitor accumulates in the plasma, and this could contribute to the toxicity of uraemia by inhibiting cellular Ca2+ transport in erythrocytes and possibly other tissues.

Adult↗
PubMed1992

Generation of angiotensin II from human plasma by tissue kallikrein.

1. Human plasma was incubated with tissue kallikrein from porcine pancreas, dialysed to obtain a fraction with a molecular mass < 10 kDa and further purified by reverse-phase chromatography. 2. Vasopressor activity in the fractions obtained was tested in the isolated perfused rat kidney. 3. In one fraction a strong vasopressor action was found, which was blocked by saralasin and by an angiotensin II antibody. 4. Aprotinin inhibited the formation of vasopressor substances by tissue kallikrein. 5. U.v.-laser desorption/ionization mass spectrometry revealed a molecular mass of 1046 Da in the purified active fraction. 6. It is concluded that tissue kallikrein forms not only kinins, but also angiotensin II, from human plasma under physiological conditions.

Angiotensin II↗
PubMed1992

Effect of inhibition of Na, K-ATPase on cytosolic free sodium and calcium in platelets of spontaneously hypertensive rats.

Cytosolic free sodium concentrations ([Na+]i) in intact platelets of 18 spontaneously hypertensive rats (SHR) and of 18 age-matched normotensive Wistar-Kyoto rats (WKY) were measured using the sodium-sensitive fluorescent dye sodium-binding-benzofuran-isophthalate. In resting platelets [Na+]i tended to be higher in SHR compared to WKY (20.5 +/- 3.5 mmol/L v 15.1 +/- 1.9 mmol/L, mean +/- SEM), but the differences were not statistically significant. Stimulation of the Na-H-exchange by 1.0 U/mL thrombin increased [Na+]i in SHR by 22.9 +/- 4.3 mmol/L and in WKY by 35.0 +/- 5.6 mmol/L in a similar way. After inhibition of Na, K-ATPase by 1 mmol/L ouabain there was a significant rise of [Na+]i both in platelets of SHR to 38.0 +/- 5.1 mmol/L (P < .01 compared to resting platelets) and in platelets of WKY to 26.5 +/- 4.3 mmol/L (P < .01). However, no significant difference could be observed between these two groups. Using the calcium-sensitive dye fura-2, resting cytosolic free calcium concentrations ([Ca2+]i) were found to be significantly higher in platelets of SHR compared to WKY (171.9 +/- 21.5 nmol/L v 93.14 +/- 19.7 nmol/L, P < .05). After the addition of ouabain [Ca2+]i was significantly higher in SHR compared to WKY (245.5 +/- 32.6 nmol/L v 159.6 +/- 22.5 nmol/L, P < .05). The results do not support the hypothesis that altered sodium-calcium exchange causes elevated cytosolic free calcium in SHR.

Animals↗
PubMed1992

Differential regulation of protein synthesis in smooth muscle cells from normotensive and spontaneously hypertensive rats by a three-dimensional matrix of type I collagen.

OBJECTIVE: The objective of this study was to gain insight into the metabolic and morphological properties of smooth muscle cells (SMC) from spontaneously hypertensive rats (SHR) when cultured in vivo under similar conditions. DESIGN: Three-dimensional cell-collagen systems represent living tissue equivalents in vitro and simulate natural conditions more closely than conventional monolayer cultures. METHODS: The effect of a three-dimensional matrix of type I collagen on ultrastructure, total protein and collagen synthesis and cell cycle distribution of SMC from SHR and normotensive Wistar-Kyoto (WKY) rats was studied. RESULTS: Collagen lattice-cultured SMC from SHR and WKY rats showed the synthetic phenotype, i.e. the cytoplasm was filled with organelles characteristic of secretory protein synthesis. There was a decrease in the percentage of cells in the 5 phase compared with monolayer cultures. Total protein synthesized by SMC from SHR and WKY rats in lattices was lowered compared with monolayer cultures. However, reduction of protein synthesis in SMC from SHR was less than in SMC from WKY rats. Differences in the proportion of collagen in SMC from SHR and WKY rats were not demonstrable in collagen lattice cultures. CONCLUSION: The present study suggests that a three-dimensional matrix of type I collagen may modulate total protein synthesis in SMC from SHR and WKY rats. However, cells from SHR react less to this matrix than those from WKY rats.

Animals↗
PubMed1992

Mechanisms of ciclosporin A-induced vasoconstriction in the isolated perfused rat kidney.

Hypertension is a well-known side effect of ciclosporin A (CsA). In the present study the mechanisms of vasoconstriction in renal vessels were examined in the isolated perfused rat kidney. Kidneys were perfused with constant flow at a temperature of 37 degrees C with Tyrode's solution equilibrated with 95% O2/5% CO2. CsA was dissolved in ethanol. 500 and 2000 ng/ml increased resistance of renal vessels by 0.97 +/- 0.55 x 10(5) and 2.29 +/- 1.33 x 10(5) dyn s cm-5, respectively (mean values +/- SD, n = 12). The vasoconstriction developed gradually over 4 min. The vasopressor effect of CsA was not changed by saralasin (10(-6) M), nifedipine (10(-6) M) and ketanserin (10(-6) M), but was completely blocked by phentolamine and prazosin (each 10(-6) M). CsA-induced vasoconstriction was not prevented by perfusion with Ca(2+)-free solution containing 2 mmol EGTA. Similarly, pretreatment with reserpine to deplete sympathetic nerve endings from catecholamines did not affect CsA-induced vasoconstriction. The findings suggest that CsA-induced vasoconstriction is mediated by stimulation of alpha 1-receptors. Ca2+ influx does not play a role for CsA-induced vasoconstriction. Prolonged perfusion of rat kidneys with the vehicle cremophor EL elicits an irreversible increase in perfusion pressure.

Animals↗
PubMed1992

Reduced cytosolic free Na+ concentration in intact platelets of essential hypertensives.

OBJECTIVE: The role of intracellular Na+ concentration in the pathogenesis of essential hypertension is a point of considerable discussion. DESIGN: Since the novel fluorescent dye technique offers the possibility of measuring cytosolic free Na+ concentration in intact living cells, the role of Na+ was reinvestigated in resting and stimulated human platelets. METHODS: Cytosolic free Na+ concentration was measured in intact blood platelets of 20 essential hypertensive patients and 21 age- and sex-matched normotensive control subjects using the fluorescent dye Na(+)-binding benzofuran isophthalate. RESULTS: Cytosolic free Na+ concentration was significantly reduced in hypertensives compared with normotensives. Inhibition of Na+,K(+)-adenosine triphosphatase by ouabain elevated cytosolic free Na+ concentration in hypertensives and normotensives in a similar way. Addition of thrombin increased cytosolic free Na+ concentration both in hypertensives and normotensives. CONCLUSIONS: Previous concepts concerning the role of Na+ in the pathogenesis of essential hypertension based upon measurements in destructed cells need to be reinvestigarted using new techniques in living cells.

Adult↗
PubMed1992

[Pentamidine inhalation in prevention of pneumocystis carinii pneumonia in treatment of rejection with monoclonal antibody Orthoclone (OKT-3)].

The use of the monoclonal antibody OKT-3 (Orthoclone) is associated with an increased risk of pneumocystis carinii pneumonia. In a retrospective study, the efficiency of a prophylactic inhalation of pentamidine during acute renal allograft rejection therapy with OKT-3 was investigated. From July 1988 until October 1989 32 renal transplanted patients with acute rejection refractory to steroids had been treated with OKT-3. Twelve of the patients developed a pneumonia (four pneumococcus, one klebsiella, one cytomegalovirus), in six cases, a pneumocystis carinii infection was diagnosed in the bronchial lavage. Four of these patients with pneumocystis carinii pneumonia died despite high dose treatment with cotrimoxazole. From November 1989, a prophylactic inhalation of pentamidine was performed during acute renal allograft rejection therapy with OKT-3. From 33 patients, in eleven cases, a pneumonia was diagnosed (three pneumococcus, one klebsiella, two legionella, three cytomegalovirus, one candida), one patient developed a pneumocystis carinii pneumonia, which was successfully treated with cotrimoxazole. No patient in this group died because of pulmonary infection. The results suggest, that a prophylactic inhalation of pentamidine in severely immunosuppressed solid organ transplant recipients can prevent pneumocystis carinii pneumonia.

Administration, Inhalation↗