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Biomedical subjects

W Zidek

Publications and source records attributed to W Zidek.

At least 127 records · Page 7Linked to original sources
PubMed1997

Differential effects of diadenosine phosphates on purinoceptors in the rat isolated perfused kidney.

1. The activation of various purinoceptors in rat renal vasculature by P1,P2-diadenosine pyrophosphate (Ap2A), P1,P3-diadenosine triphosphate (Ap3A), P1,P4-diadenosine tetraphosphate (Ap4A), P1,P5-diadenosine pentaphosphate (Ap5A), P1,P6-diadenosine hexaphosphate (Ap6A) was studied by measuring their effects of perfusion pressure of a rat isolated perfused kidney. 2. The vasoconstrictive response to Ap5A was completely due to P2x purinoceptor activation, that to Ap4A and Ap6 was P2x purinoceptor mediated to a large extent, as evidenced by the inhibitory effects of suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium (PPADS). 3. The vasoconstrictive effects of Ap2A and Ap3A were mostly due to stimulation of A1-receptors, as shown by the inhibitory effect of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). 4. The vasoconstrictive response to Ap6A was partially insensitive to A1 and P2x purinoceptor blockers. 5. In raised tone preparations Ap2A and Ap3A evoked vasodilatation, which was blocked by the A2 receptor blocker, 3,7-dimethyl-1-propargylxanthine (DMPX). 6. In raised tone preparations Ap4A evoked vasodilatation when the P2-purinoceptors were blocked by suramin. 7. The activation of different purinoceptor subtypes by diadenosine phosphates critically depends on the number of phosphate groups.

Adenosine↗
PubMed1997

Decreased cellular Mg2+ concentrations in a subgroup of hypertensives--cell models for the pathogenesis of primary hypertension.

A new method to determine total Mg2+ content in lymphocytes was developed, offering advantages for routine measurements as compared to fluorescence methods. Intracellular Mg2+ measurements were performed in lymphocytes of 18 untreated normotensive and 19 untreated essential hypertensive patients. Mg2+ content was referred to lymphocytic protein, which was determined according to Bradford's method. Mg2+ measurements were performed by atomic absorption spectroscopy using a Video 12 apparatus from Thermo Electron Instrumentation Laboratory, Andover, MA, USA. The results show that in patients with essential hypertension, total intralymphocytic Mg2+ content is significantly lower (0.07 +/- 0.05 mmol/g lymphocytic protein, mean +/- s.d.) as compared to controls (0.11 +/- 0.04 mmol/g lymphocytic protein, mean +/- s.d., P < 0.05). Free intracellular Mg2+ content was measured in lymphocytes by the fluorescent indicator mag-fura-II, showing no significant difference in normotensives and hypertensives (0.30 +/- 0.16 vs 0.38 +/- 0.17 mmol/l). In platelets free intracellular Mg2+ concentrations were not found of significant difference in normotensive and hypertensive patients (0.52 +/- 0.23 vs 0.47 +/- 0.27 mmol/l) using mag-fura-II. In plasma Mg2+ concentrations there was no significant difference in the normotensive and hypertensive group (0.92 +/- 0.07 vs 0.88 to 0.07 mmol/l). There was no correlation between plasma, free or total cellular magnesium concentrations in each group. Furthermore this method also seems suitable for routine measurements of total intracellular Mg2+ concentrations in even larger groups of patients in comparison with fluorescent indicator measurements like mag-fura-II. Lowered total intracellular Mg2+ concentrations in a subgroup of primary hypertension may contribute to the development of this disorder, perhaps due to different buffering systems.

Adult↗
PubMed1997

Cellular protective action of angiotensin converting enzyme inhibitors.

In several studies organ protective effects of ACE inhibitors independent from their antihypertensive action have been demonstrated. The mechanisms of the protective effects of angiotensin converting enzyme (ACE) inhibitors on vasculature and kidney are largely unknown. In the present study the modulatory action of captopril on the angiotensin II (AngII), arginine vasopressin (AVP), and platelet derived growth factor (PDGF)-induced increase of cytosolic free calcium concentration ([Ca2+]i) was investigated in cultured vascular smooth muscle cells (VSMC) and cultured glomerular mesangial cells (MC) from rats using the fluorescent dye technique. Resting [Ca2+]i in VSMC or MC was not significantly affected by captopril. The preincubation of VSMC with 1 mumol/l captopril significantly reduced the AngII-induced [Ca2+]i increase in VSMC from 90 +/- 10 nmol/l (n = 78; mean +/- SEM) to 51 +/- 16 nmol/l (n = 53; p < 0.05) and in MC from 102 +/- 42 nmol/l (n = 14) to 43 +/- 12 nmol/l (n = 7; p < 0.05). In the absence of extracellular calcium captopril produced no effect on AngII induced changes of [Ca2+]i. Captopril significantly attenuated the AVP-induced [Ca2+]i increase in VSMC and MC. The preincubation of MC with 1 mumol/l captopril for 40 min significantly reduced the PDGF-induced [Ca2+]i increase in MC from 127 +/- 31 nmol/l (n = 11) to 61 +/- 32 nmol/l (n = 5, p < 0.05). The present results may indicate that part of the protective effects of ACE inhibitors on vasculature and kidney may be promoted by inhibition of growth-factor induced changes of calcium homeostasis.

Angiotensin II↗
PubMed1997

Elemental mercurial poisoning.

A 39-year-old man injected 40 mL of elemental mercury in an attempted suicide 3 years before coming to our facility. No specific treatment regimen had been done since then. Chest x-ray films showed mercury deposits in the lungs, as well as around the injection site. The mercury concentration in his blood was at 96.3 micrograms (0.480 nmol/L), thus significantly elevated (given a reference range of up to 2 micrograms Hg/L), as was the renal mercury elimination. Despite mercurial deposits within the pulmonary circulation, the pulmonary function showed normal values, with no reduction of the diffusion capacity. There were signs of polyneuropathy. The patient was given sodium dimercaptopropanesulfate (Dimaval) for mercury complexation. This case report outlines the diagnosis and therapy for mercurial poisoning through metallic mercury.

Adult↗
PubMed1997

Influence of proteinuria on long-term transplant survival in kidney transplant recipients.

Long-term prognosis in kidney transplant recipients depends on multiple factors. To investigate whether mild proteinuria within the first 6 months following transplantation is a determinant of the long-term function and survival of kidney transplants, 357 patients transplanted between 1980 and 1990 were retrospectively examined over a period of 5 years. 25.5% of the patients developed an early proteinuria between 0.25 and 1.0 g/day over 6 or more months. This group was well matched concerning gender, age of recipient, underlying disease, time on hemodialysis, donor age, cold ischemia time and HLA mismatches with the group without proteinuria (n = 266). Five-year transplant survival in the group with proteinuria was 58.9% in contrast to 85.6% in recipients without proteinuria. Intermittent proteinuria did not worsen long-term prognosis. Proteinuria of 12 months or longer further reduced 5-year transplant survival to 42.6%. Over the whole observation period, serum creatinine in recipients with proteinuria was about 0.5 mg/dl higher as compared with patients without proteinuria. No correlation between proteinuria and gender, age of recipient, duration of hemodialysis, age of donor, cold ischemia time and mismatches could be detected. In conclusion, early proteinuria apparently is not due to established donor or recipient factors. However, there is a strong correlation of proteinuria with worse transplant function and survival.

Adult↗
PubMed1997

Right ventricular dysfunction in patients with obstructive sleep apnoea syndrome.

There is conclusive evidence that obstructive sleep apnoea syndrome (OSAS) influences right heart haemodynamics and can also induce pulmonary hypertension. It is not known, however, whether right ventricular dysfunction can occur in patients with OSAS in the absence of lung disease. We studied 107 patients (94 males, 13 females, mean age 55 +/- 11 yrs) with polysomnographically verified OSAS in whom clinically significant lung disease was excluded. Right ventricular ejection fraction (RVEF) was determined by radionuclide ventriculography. In addition, pulmonary function tests, arterial blood gas analysis and right heart catheterization were performed. RVEF was impaired in 19 patients (18%). Eighteen (95%) had signs or symptoms consistent with mild right ventricular failure. Patients with or without impaired RVEF did not differ with respect to body mass index, age or lung function. Stepwise multiple logistic regression analysis revealed that RVEF was significantly associated with the apnoea/hypopnoea index (r = -0.68; p = 0.0009) and the extent of nocturnal oxyhaemoglobin saturation (r = 0.42; p = 0.035), but not with age, body mass index, blood gas analysis, gender, lung function, pulmonary artery pressure and left ventricular ejection fraction. We conclude that in patients with otherwise unexplained right ventricular failure, obstructive sleep apnoea syndrome may underlie the right ventricular dysfunction.

Adult↗
PubMed1997

Na+/H+ exchange during an oral glucose challenge in patients with essential hypertension.

To determine the effects of an oral glucose challenge on cellular Na+/H+ exchange in vivo we measured plasma glucose concentrations, plasma insulin concentrations, plasma C-peptide concentrations, arterial blood pressure, cytosolic pH (pHi) and cellular Na+/H+ exchange in 24 patients with essential hypertension (HT) and 41 age-matched healthy normotensive control subjects (NT) during a standardized oral glucose tolerance test. Under resting conditions, the plasma glucose concentrations, plasma insulin concentrations, plasma C-peptide concentrations and Na+/H+ exchange activity were significantly higher in HT compared with NT (P < 0.05 in each case). A significant increase in lymphocytic Na+/H+ exchange activity was only seen in NT (resting 0 h: (4.23 +/- 0.2) x 10(-3) pHi/s; mean +/- S.E.M.; 1 h after glucose administration: (6.00 +/- 0.56) x 10(-3) pHi/s; 2 h after glucose administration: (6.65 +/- 0.64) x 10(-3) pHi/s; P = 0.0003 by Friedman's two-way ANOVA), but not in HT (resting 0 h: (6.07 +/- 0.36) x 10(-3) pHi/s; 1 h after glucose administration: (6.72 +/- 1.02) x 10(-3) pHi/s; 2 h after glucose administration: (6.71 +/- 0.62) x 10(-3) pHi/s; P = 0.7470). During an oral glucose challenge the systolic (P < 0.0001) and diastolic (P < 0.0001) blood pressure significantly decreased in HT but not in NT. Essential hypertension shows abnormal in vivo regulation of Na+/H+ exchange and blood pressure following oral glucose intake.

Analysis of Variance↗
PubMed1997

Ciguatera fish poisoning following travel to the tropics.

A 40-year-old man-as well as 15 more participants of the same meal-suddenly experienced vomiting and watery diarrhea four hours after having eaten a meal of grouper in the Dominican Republic. Symptoms persisted for four hours and were followed by a generalized pruritus and paresthesias of the lips, tongue, palms, and soles of the feet. Physical examination was normal with the exception of a pulse of 45 beats per minute, a blood pressure of 80/50 mmHg, and paradoxical temperature perception. Laboratory values were regular except for the erythrocyte sedimentation rate of 40 mm per hour. 24-hour Holter electrocardiogram showed a normal sinus rhythm with impaired heart rate variability (37-100 beats per minute). Due to the typical history and the clinical findings, ciguatera toxin ingestion was diagnosed. Pruritus decreased slightly with symptomatic therapy, but it took 16 weeks for all symptoms to resolve. Ciguatera fish poisoning is rare in temperate countries. Symptoms of this neurotoxic disease are gastrointestinal, neurologic, and cardiovascular manifestations with paresthesias, paradoxical sensor disturbances, and muscular weakness as well as bradycardia and hypotension. With travel to and from the tropics and increasing imports of tropical fish ciguatera will be of growing importance even in nontropical areas.

Adult↗
PubMed1997

Effects of cyclosporin A and FK 506 on lipid metabolism and fibrinogen in kidney transplant recipients.

After allogenic transplantations a dramatic increase in the development of arteriosclerotic plaques can be observed, which might be due to metabolic alterations, influenced by changes of the transplant organ or immunosuppression. In this study the effects of FK 506 in kidney transplant patients on cardiovascular risk factors were compared to cyclosporin A (CsA) immunosuppression. Both groups showed no statistical differences in number, kidney function, age, body weight, sex distribution, steroid dosage and follow-up time after transplantation. Total cholesterol was similar in FK 506-treated patients (231 +/- 22 vs. 278 +/- 52 mg/dl) as compared with patients with CsA immunosuppression. Furthermore, there were no differences in triglycerides (220 +/- 72 vs. 210 +/- 67 mg/dl), HDL-cholesterol (67 +/- 14 vs. 52 +/- 18 mg/dl) and fasting glucose (112 +/- 36 vs. 116 +/- 17 mg/dl). However, the concentration of LDL-cholesterol (114 +/- 21 vs. 167 +/- 37 mg/dl), the independent risk factor Lp(a) (11 +/- 9 vs. 27 +/- 8 mg/dl) and fibrinogen (216 +/- 71 vs. 297 +/- 47) was lower in FK 506-treated patients. Our results indicate that FK 506 immunosuppression offers some advantages in cardiovascular risk factors.

Adult↗
PubMed1996

Diadenosine polyphosphates regulate cytosolic calcium in human fibroblast cells by interaction with P2x purinoceptors coupled to phospholipase C.

The effects of diadenosine pentaphosphate (AP5A), and diadenosine hexaphosphate (AP6A) on the cytosolic-free Ca2+ concentration ([Ca2+]i) were evaluated in cultured human fibroblast cells (HF cells) using the fluorescent dye technique. AP5A, and AP6A concentration-dependently increased [Ca2+]i in HF cells. The addition of 10 mumol/1 AP5A and AP6A significantly increased [Ca2+]i in HF cells from 71 +/- 3 nmol/1 (n = 184) to 241 +/- 39 nmol/1 (n = 11; P < 0.001 compared to resting value) and to 227 +/- 26 nmol/1 (n = 23; P < 0.001), respectively. The purinoceptor P2 blockers, suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), inhibited the diadenosine polyphophate-induced [Ca2+]i increase, whereas the P2y purinoceptor blocker, reactive blue, had no effect. Adenosinetriphosphate (ATP) and the P2x agonist, alpha 1 beta-methylene-ATP also significantly increased [Ca2+]i in HF cells, whereas the P2y agonist methylthio-ATP showed only a small [Ca2+]i response. Diadenosine polyphosphates mainly induced transplasmamembrane Ca2+ influx as was confirmed by experiments in the absence of extracellular Ca2+ or by manganese quenching studies. Organic (verapamil) and inorganic Ca2+ channel blockers (NiCI2) significantly reduced the AP6A induced transplasmamembrane Ca2+ influx. The inhibitor of phosphatidylcholine-specific phospholipase C, D609, significantly reduced the effect of diadenosine polyphosphates on [Ca2+]i in HF cells. It is concluded that diadenosine polyphosphates regulate transplasmamembrane Ca2+ influx after occupation of P2x receptors via activation of phosphatidylcholine-specific phospholipase C and hence of voltage-operated Ca2+ channels.

Bridged-Ring Compounds↗
PubMed1996

Increased lymphocytic Na+/H+ exchange activity after hemodialysis: evidence for an endogenous inhibitor of Na+/H+ exchange in patients with end-stage renal failure.

The Na+/H+ exchange antiport activity was measured in lymphocytes from 16 patients with end-stage renal failure pre- and postdialysis. In addition the effect of the patients' plasma on lymphocytes from healthy subjects was tested. Resting pH (pHi) was not significantly different in lymphocytes pre- and postdialysis. On the other hand, the Na+/H+ exchange activity was significantly lower in lymphocytes before hemodialysis (6.22 +/- 0.73 x 10(-3) pHi/s) than after hemodialysis (9.32 +/- 1.58 x 10(-3) pHi/s; n = 16; p < 0.05). The buffer capacity was not significantly different before and after hemodialysis. The incubation of lymphocytes from healthy control subjects with plasma from patients with end-stage chronic renal failure significantly reduced the lymphocytic Na+/H+ exchange activity. The addition of ultrafiltrate also significantly reduced the Na+/H+ exchange activity in lymphocytes from healthy control subjects. The study indicates the existence of an endogenous inhibitor of the Na+/H+ exchange that is accumulated in plasma from patients with end-stage chronic renal failure.

Adult↗
PubMed1996

Low concentrations of ouabain increase cytosolic free calcium concentration in rat vascular smooth muscle cells.

1. Low ouabain concentrations in the nanomolar range significantly increased cytosolic free calcium concentration. 2. The ouabain-induced cytosolic free calcium concentration increase was due to transplasmamembrane calcium influx, which could be prevented in the absence of extracellular calcium or by addition of the calcium channel blocker nifedipine. 3. The amount of stored cellular Ca2+, as determined by the thapsigargin-induced cytosolic free calcium concentration increase, was also enhanced by 1 nmol/l ouabain. 4. It is concluded that low ouabain concentrations affect intracellular cytosolic free calcium concentration homoeostasis.

Animals↗
PubMed1996

Diadenosine polyphosphates induce transplasma membrane calcium influx in cultured glomerular mesangial cells.

The effects of diadenosine tetraphosphate (AP4A) diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A) on the cytosolic-free calcium concentration ([Ca2+]i) were evaluated in cultured rat glomerular mesangial cells (MCs) using the fluorescent dye technique. The addition of 10 mumol L-1 AP4A, AP5A or AP6A significantly increased [Ca2+]i in MCs by 57 +/- 9 nmol L-1 n = 17; P < 0.01), 76 +/- 27 nmol L-1 (n = 9; P < 0.01) or 65 +/- 12 nmol L-1 (n = 18; P < 0.01) respectively. In the absence of extracellular calcium, there was no significant change in [Ca2+]i in MCs after administration of diadenosine polyphosphates, indicating that these agents induce transplasma membrane Ca2+ influx. AP6A significantly enhanced the angiotensin II-induced changes in [Ca2+]i in MCs. The AP5A-induced transplasma membrane Ca2+ influx was inhibited by the P2 purinoceptor blockers suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), but was not affected by the adenosine A1 receptor blocker 8-cyclopentyl-1.3-dipro-pylzanthine (CPDPX). Adenosine triphosphate (ATP) and adenosine 5'-O-(3-thio)triphosphate (ATP-gamma S) increased [Ca2+]i in MCs, whereas alpha, beta-methylene ATP had no effect on [Ca2+]i in MCs. Measurements of diacylglycerol and phosphatidic acid showed that AP5A and AP6A also stimulated phospholipase C, but had no effect on phospholipase D. The inhibition of phosphatidylcholine-specific phospholipase C significantly reduced the AP5A-induced [Ca2+]i increase. In summary, diadenosine polyphosphates induce Ca2+ influx through P2 purinoceptors and may be involved in the local regulation of vascular resistance evoked by the Ca(2+)-dependent contractile response of mesangial cells.

Adenosine Triphosphate↗
PubMed1996

Vascular actions of diadenosine phosphates.

1. Diadenosine phosphates were isolated from platelets, adrenal gland and autonomic nerves. The presence of diadenosine phosphates in storage pools releasable into the circulation suggests an important role in the control of blood pressure, and potentially to a modulation of the actions of catecholamines. 2. Besides a role of the diadenosine phosphates in platelet aggregation, these agents have potent vasoactive properties. Vasoactive actions of the diadenosine phosphates were demonstrated in numerous vascular models including most of the physiologically important elements of blood pressure regulation. Mostly, the vasoactive action depends on the number of phosphates in the diadenosine phosphates. Vasodilation can be observed in intact vessels after administration of Ap2A, Ap3A and Ap4A whereas contraction is affected by Ap5A and Ap5A and Ap6A. Vasocontraction induced by the diadenosine phosphates in vascular smooth muscle cells is mediated by an increase in intracellular free Ca2+. 3. In vivo, intravenous injection of Ap4A lowers blood pressure whereas injections of Ap5A and Ap6A caused a prolonged increase in blood pressure. In blood, in contrast to ATP, diadenosine phosphates are relatively long-lived molecules, suggesting that the action of the latter is of intermediate time span. In a similar manner to the vasoconstrictor angiotensin II, diadenosine phosphates also act as mitogens. It can be assumed that diadenosine phosphates may be involved in pathophysiological events of circulation including hypertension and atherosclerosis.

Animals↗
PubMed1996

Negative chronotropic and inotropic effects exerted by diadenosine hexaphosphate (AP6A) via A1-adenosine receptors.

1. Diadenosine hexaphosphate (AP6A) exerts vasoconstrictive effects. The purpose of this study was to investigate whether AP6A has any effect on cardiac function. 2. The effects of AP6A (0.1-100 microM) on cardiac contractility and frequency were studied in guinea-pig and human isolated cardiac preparations. Furthermore, the effects of AP6A on the amplitude of the L-type calcium current, on the adenosine 3':5'-cyclic monophosphate (cyclic AMP) content and on the phosphorylation of regulatory phosphoproteins, i.e. phospholamban and troponin inhibitor, were investigated in guinea-pig isolated ventricular myocytes. 3. In isolated spontaneously beating right atria of the guinea-pig AP6A exerted a negative chronotropic effect and reduced the rate of contraction maximally by 35% (IC20 = 35 microM). 4. In isolated electrically driven left atria of the guinea-pig AP6A exerted a negative inotropic effect and reduced force of contraction maximally by 23% (IC20 = 70 microM). 5. In isolated electrically driven papillary muscles of the guinea-pig AP6A alone was ineffective, but attenuated isoprenaline-stimulated force of contraction maximally by 23% (IC20 = 60 microM). Furthermore, AP6A attenuated the relaxant effect of isoprenaline. 6. In human isolated electrically driven ventricular preparations AP6A alone was ineffective, but attenuated isoprenaline-stimulated force of contraction by maximally 42% (IC20 = 18 microM). Moreover, AP6A attenuated the relaxant effect of isoprenaline. 7. All these effects of AP6A were abolished by the selective A1-adenosine receptor antagonist 1,3-dipropyl-cyclopentyl-xanthine (DPCPX, 0.3 microM), whereas the M-cholinoceptor antagonist atropine (10 microM) and the P2-purinoceptor antagonist suramin (300 microM) failed to abolish the effects of AP6A. 8. AP6A 100 microM had no effect on the amplitude of the L-type calcium current, but attenuated isoprenaline-stimulated L-type calcium current. The maximum of the current-voltage relationship (I-V curve) was shifted to the left by isoprenaline and additional application of AP6A shifted the I-V curve back to the right to the control value. The phosphorylation state of phospholamban and the troponin inhibitor was unchanged by AP6A alone, but was markedly attenuated by AP6A in the presence of isoprenaline. Cyclic AMP levels remained unchanged by AP6A, even after stimulation with isoprenaline. 9. In summary, AP6A exerts negative chronotropic and inotropic effects in guinea-pig and human cardiac preparations. These effects are mediated via A1-adenosine receptors as all effects were sensitive to the selective A1-adenosine receptor antagonist DPCPX. Furthermore, the effects of AP6A on cyclic AMP levels, protein phosphorylation and the L-type calcium current are in accordance with stimulation of A1-adenosine receptors.

Animals↗
PubMed1996

Na+/H+ exchange in patients with mild chronic renal failure.

Cytosolic pH (pHi) and Na+/H+ exchange activity were measured in lymphocytes from 22 patients with mild chronic renal failure, and 21 age- and sex-matched normotensive healthy control subjects using the fluorescent dye technique. The basal pHi in resting lymphocytes was not significantly different in both groups tested (control, pHi 7.18 +/- 0.04; patients with mild chronic renal failure, 7.17 +/- 0.05). The initial rate of pHi recovery immediately after intracellular acidification with 100 mmol/l propionic acid, representing the maximum Na+/H+ exchange activity, was significantly higher in lymphocytes from patients with mild chronic renal failure (7.10 +/- 0.52 dpHi/s, mean +/- SEM) when compared with control subjects (5.42 +/- 0.47 dpHi/s; p < 0.05). No significant correlation between Na+/H+ exchange activity and blood pressure could be obtained in patients with mild chronic renal failure. Furthermore, there was no relationship of Na+/H+ exchange activity to cytosolic pH or extracellular pH. It is concluded that an enhanced Na+/H+ exchange activity can be detected in patients with mild chronic renal failure and may not be related to the significant abnormalities of electrolyte and acid-base metabolism commonly observed in patients with end-stage renal failure or on hemodialysis.

Acid-Base Equilibrium↗