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W Zidek

Publications and source records attributed to W Zidek.

At least 37 records · Page 2Linked to original sources
PubMed2004

Influence of treatment on leptin levels in patients with obstructive sleep apnoea.

Obstructive sleep apnoea syndrome (OSAS) is a common disorder in obesity. Leptin, an adipocyte-derived signalling factor, plays an important role in metabolic control. There is growing evidence that leptin regulation is altered in OSAS. Therefore, the aim of this study was to test the hypothesis that effective treatment will influence leptin levels in OSAS patients. Serum leptin levels were determined in 86 consecutive patients (aged 57.5 +/- 11.0 yrs) with polysomnographically verified OSAS. In addition, leptin levels were reassessed and treatment efficacy was evaluated by polysomnography after 6 months of therapy. Patients were treated with continuous or bilevel positive airway pressure, a mandibular advancement device or conservatively, depending on the clinical symptoms. Mean serum leptin levels did not change with treatment in the whole study group (7.3 +/- 5.0 versus 7.5 +/- 4.8 ng.mL-1), however, leptin levels decreased in effectively treated patients (8.5 +/- 5.0 versus 7.4 +/- 5.1 ng.mL-1) while they increased in ineffectively treated patients (5.0 +/- 4.0 versus 7.7 +/- 4.1 ng.mL-1). Furthermore, not only was there a significant and independent correlation between the change in leptin levels with treatment and the change in body mass index, but also with the change in apnoea/hypopnoea index. Effective treatment of sleep-disordered breathing may have significant effects on leptin levels in obstructive sleep apnoea syndrome patients. Changes in leptin levels are related to changes in apnoea/hypopnoea index in obstructive sleep apnoea syndrome patients.

Adult↗
PubMed2003

Identification of dinucleoside polyphosphates in adrenal glands.

Dinucleoside polyphosphates have been characterised as extracellular mediators controlling numerous physiological functions like vascular tone or cell proliferation. Here we describe the isolation and identification of dinucleoside polyphosphates Ap(n)A (with n=2-3), Ap(n)G (with n=2-6) as well as Gp(n)G (with n=2-6) from adrenal glands. These dinucleoside polyphosphates are localised in granules of the adrenal glands. The dinucleoside polyphosphates diadenosine diphosphate (Ap(2)A), diadenosine triphosphate (Ap(3)A), adenosine guanosine polyphosphates (Ap(n)G) and diguanosine polyphosphates (Gp(n)G), both with phosphate group (p) numbers (n) ranging from 2 to 6, were identified by fractionating them to homogeneity by preparative size-exclusion- and affinity-chromatography as well as analytical anion-exchange and reversed-phase-chromatography from deproteinised adrenal glands and by analysis of the homogeneous dinucleoside polyphosphates containing fractions with post-source-decay (PSD) matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS). The identity of the dinucleoside polyphosphates was confirmed by retention time comparison with authentic dinucleoside polyphosphates. Enzymatic analysis demonstrated an interconnection of the phosphate groups with the adenosines in the 5(')-positions of the riboses in all dinucleoside polyphosphates purified from adrenal glands. In conclusion, the identification of these dinucleoside polyphosphates in adrenal gland granules emphasises that these dinucleoside polyphosphates can be released from the adrenal glands upon stimulation into the circulation.

Adrenal Glands↗
PubMed2003

Identification of dinucleoside polyphosphates by matrix-assisted laser desorption/ionisation post-source decay mass spectrometry.

Dinucleoside polyphosphates are a group of intra- and extracellular mediators controlling numerous physiological functions. In this study dinucleoside polyphosphates were examined by positive ion matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MADLI-TOFMS). 3-Hydroxypicolinic acid was used as UV-absorbing matrix. For the individual dinucleoside polyphosphates Ap(n)A (n = 2-7), Ap(n)G (n = 2-6) and Gp(n)G (n = 2-6), MALDI post-source decay (PSD) mass spectra were measured. Each mass peak in the MALDI-PSD mass spectra could be assigned to individual fragments of dinucleoside polyphosphates. The comparison of the fragmentation patterns of the dinucleoside polyphosphates presented here demonstrates that dinucleoside polyphosphates preferably cleave to fragment ions consisting of the corresponding mononucleoside polyphosphates as well as the corresponding nucleosides and bases during flight in the field-free drift path of the MALDI mass spectrometer. Therefore, the MALDI-PSD approach described here is suitable for identification of other dinucleoside polyphosphates. The present MALDI-PSD mass spectra may be used as MALDI-PSD mass reference spectra for future identification of dinucleoside polyphosphates and other nucleotides.

Dinucleoside Phosphates↗
PubMed2003

Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression.

NO prevents atherogenesis and inflammation in vessel walls by inhibition of cell proliferation and cytokine-induced endothelial expression of adhesion molecules and proinflammatory cytokines. Reduced NO production due to inhibition of either eNOS or iNOS may therefore reinforce atherosclerosis. Patients with end-stage renal failure show markedly increased mortality due to atherosclerosis. In the present study we tested the hypothesis that uremic toxins are responsible for reduced iNOS expression. LPS-induced iNOS expression in mononuclear leukocytes was studied using real-time PCR. The iNOS expression was blocked by addition of plasma from patients with end-stage renal failure, whereas plasma from healthy controls had no effect. Hemofiltrate obtained from patients with end-stage renal failure was fractionated by chromatographic methods. The chromatographic procedures revealed a homogenous fraction that inhibits iNOS expression. Using gas chromatography/mass spectrometry, this inhibitor was identified as phenylacetic acid. Authentic phenylacetic acid inhibited iNOS expression in a dose-dependent manner. In healthy control subjects, plasma concentrations were below the detection level, whereas patients with end-stage renal failure had a phenylacetic acid concentration of 3.49 +/- 0.33 mmol/l (n = 41). It is concluded that accumulation of phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. That mechanism may contribute to increased atherosclerosis and cardiovascular morbidity in patients with end-stage renal failure.

Adult↗
PubMed2002

Captopril and quinapril reduce reactive oxygen species.

BACKGROUND: Angiotensin-converting enzyme inhibitors may affect reactive oxygen species in humans in vitro and in vivo. In the present study we evaluated whether angiotensin-converting enzyme inhibitors may affect NAD(P)H oxidase activity. MATERIALS AND METHODS: The production of reactive oxygen species was measured spectrophotometrically in mononuclear leukocytes using the fluorescent dye, dichlorofluorescein diacetate. The effects of quinaprilat, captopril, enalaprilat and lisinopril on phorbol myristate acetate-induced reactive oxygen species generation were investigated in vitro. The effects of quinaprilat, captopril, enalaprilat and lisinopril on the NAD(P)H oxidase activity of the mononuclear leukocytes were measured photometrically. In addition, reactive oxygen species were measured before and 4 h after oral administration of quinapril. RESULTS: In vitro, the addition of quinaprilat (72 +/- 6% of control; mean +/- SEM; n= 19; P < 0.001) and captopril (48 +/- 2% of control; n= 19; P < 0.001) significantly reduced the phorbol-12-myristate-13-acetate-induced reactive oxygen species generation by the mononuclear leukocytes, whereas enalaprilat and lisinopril showed no effect. The effect of captopril on phorbol-12-myristate-13-acetate-induced reactive oxygen species generation in vitro was concentration-dependent. Quinaprilat and captopril significantly inhibited the NAD(P)H oxidase activity. After the oral administration of 10 mg of quinapril the phorbol-12-myristate-13-acetate-induced reactive oxygen species generation by the mononuclear leukocytes was significantly decreased from 1981 +/- 292% to 988 +/- 141% (n = 14; P < 0.01). CONCLUSION: Quinapril and captopril decrease the production of reactive oxygen species.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

MRI of the pharynx and treatment efficacy of a mandibular advancement device in obstructive sleep apnoea syndrome.

In obstructive sleep apnoea syndrome (OSAS), prosthetic mandibular advancement devices (MAD) seem to be a promising treatment alternative to conventional continuous positive airway pressure therapy. Unfortunately, while they are effective in some patients, they are ineffective in others or may even worsen OSAS. At present, it is not known whether predictors can be defined which allow for estimation of the potential effect of oral appliances on the severity of OSAS. Clinical and polysomnographical efficacy of a MAD was evaluated in 15 patients with OSAS. In addition, ultrafast magnetic resonance imaging (MRI) of the pharynx was performed in 13 of these patients at rest during transnasal shallow respiration and during performance of the Muller manoeuvre, both with and without the MAD, and the site of closure was determined. The MAD reduced the mean apnoea/hypopnoea index (AHI) from 19.8+/-14.5 to 7.2+/-7.4 x h(-1). Seven subjects (53.8%) had at least a 50% reduction in AHI to a value <10 x h(-1) with the MAD, whereas the MAD was ineffective in six patients. Five of the seven treatment responders had no significant pharyngeal obstruction during the manoeuvre with the device, while all of them had pharyngeal obstruction when not equipped with the device. Four of the six patients with treatment failure had a single velopharyngeal obstruction and two a combined obstruction of the velo- and glossopharynx during the Muller manoeuvre while wearing the device. The results of this study suggest that airway patency during the Muller manoeuvre while wearing a mandibular advancement device may be predictive of the success of obstructive sleep apnoea syndrome treatment with a mandibular advancement device.

Adult↗
PubMed2001

[New guidelines in hypertension. What is relevant for general practice?].

The latest guidelines aim to help improve the diagnosis and treatment of hypertension. This purpose is served by the following recommendations: Blood pressure values of 140/90 must already be considered to signal hypertension. Normotension in turn, is subdivided into optimal, normal and high-normal blood pressure. This is relevant in particular to certain high risk groups, for whom an appreciable lowering of blood pressure is associated with a further decrease in mortality. Particular attention is warranted in isolated systolic hypertension, which represents a cardiovascular risk that should not be underestimated. Every hypertensive should undergo a basic examination during which pointers to secondary hypertension must be investigated. Evidence-based, non-medication measures include weight reduction, salt restriction, reduction of alcohol use, and regular "endurance" exercise. The selection of antihypertensive drugs should be determined by concomitant diseases. All in all, the therapeutic strategy will be increasingly be oriented to such additional risk factors as diabetes mellitus, dyslipidemia or already present organic damage.

Adult↗
PubMed2001

Sleep-Disordered breathing in patients referred for angina evaluation--association with left ventricular dysfunction.

BACKGROUND: Clinical observations have linked sleep-disordered breathing to cardiovascular morbidity and mortality, and especially to coronary artery disease. HYPOTHESIS: The study was undertaken to determine the prevalence of sleep-disordered breathing in consecutive patients referred for angina evaluation, and analyzed the parameters influencing the severity of sleep-disordered breathing. METHODS: In all, 68 consecutive patients (53 men, 15 women, aged 63.4 +/- 10.0 years) referred for angina evaluation were studied. Coronary angiography, selective left ventriculography, and a polygraphic study with a validated six-channel monitoring device were performed. Full-night polysomnography was used to reevaluate patients with an apnea/hypopnea index > or = 10/h. RESULTS: Sleep-disordered breathing as defined by an apnea/hypopnea index > or = 10/h was found in 30.9% of patients; its prevalence was not increased in patients with and without coronary artery disease (26.5 vs. 42.1%). Multiple stepwise linear regression analysis revealed that the severity of sleep-disordered breathing was significantly and independently associated with left ventricular ejection fraction (r = -0.38; p = 0.002), but not with age, body mass index, gender, diabetes mellitus, hypertension, hyperuricemia, hypercholesterolemia, smoking habits, or coronary artery disease. In this group of patients, multiple logistic regression analysis could not demonstrate sleep-disordered breathing to be an independent predictor of coronary artery disease. CONCLUSIONS: Sleep-disordered breathing is common in patients referred for angina evaluation. The degree of sleep-disordered breathing is mainly determined by the extent of left ventricular dysfunction.

Angina Pectoris↗
PubMed2001

Mass-spectrometry-linked screening of protein fractions for enzymatic activities--a tool for functional genomics.

A simple and rapid strategy is described to screen protein fractions for defined enzymatic activity. A protein fraction from a porcine kidney extract was immobilized by covalent coupling to activated affinity beads. The immobilized proteins were incubated with probes specific for different enzyme activities. The reaction products were analyzed by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. The MALDI spectra indicate the presence of 5'-nucleotidase, phosphatase, kinase, glutathione reductase, and renin activities in the kidney protein extract. Furthermore, the method can be used to screen for inhibitors of enzymatic reactions. The method is adaptable to high-throughput sample handling and automated mass spectrometric analysis and therefore suited for functional genomics.

Animals↗
PubMed2001

CoenzymeA glutathione disulfide is a potent modulator of angiotensin II-induced vasoconstriction.

CoenzymeA glutathione disulfide (CoASSG) has recently been isolated from bovine adrenal glands and is assumed to play an important role in blood pressure (BP) control. We used the isolated perfused rat kidney to investigate the modulating effects of CoASSG on angiotensin II (AngII)-induced vasoconstriction. Permanent perfusion with CoASSG (1 micromol/L) for 60 min induced a significant (P < .05) shift to the left in the dose-response curve for AngII (about 3.1-fold), whereas the dose-response curve for norepinephrine (NE) was unaffected. During continuous perfusion with 1 micromol/L CoASSG, the repetitive application of 10 pmol AngII significantly increased its vasoconstriction by 170% +/- 14% (P < .05) and 235% +/- 50% (P < .05) for 60 and 120 min, respectively. The potentiation of AngII by permanent perfusion with CoASSG is dose- and time-dependent and shows a plateau at 120 min. Glutathione, oxidized coenzymeA, and coenzymeA (each 1 micromol/L) are not able to enhance the vasoconstriction induced by AngII. We conclude that CoASSG is able to potentiate the vasoactive properties of AngII, and that CoASSG might play an important role in BP regulation via modulating effects of AngII.

Angiotensin II↗
PubMed2001

The critical role of adenosine and guanosine in the affinity of dinucleoside polyphosphates to P(2X)-receptors in the isolated perfused rat kidney.

1. The activation of P(2x)-receptors in the rat renal vasculature by dinucleoside polyphosphates with variable phosphate group chain length (Xp(n)X; X=Adenin (A) /Guanin (G), n=4 - 6) was studied by measuring their effects on perfusion pressure of the isolated perfused rat kidney at constant flow in an open circuit. 2. Like Ap(4)A, Ap(5)A and Ap(6)A the dinucleoside polyphosphates Ap(4)G, Ap(5)G and Ap(6)G exerted a vasoconstriction which could be blocked by suramin and pyridoxal-phosphate-6-azophenyl-2; 4-disulphonic acid (PPADS). 3. Gp(4)G, Gp(5)G and Gp(6)G showed only very weak vasoconstriction at high doses. 4. Ap(6)A and alpha, beta-meATP could not be blocked by the selective P(2x1)-receptor antagonisten NF023 (30 microM), whereas Ap(4)A, Ap(4)G, Ap(5)A, Ap(5)G and Ap(6)G were partially blocked by NF023. 5. Inhibition of endothelial NO-synthase by N(omega)-nitro-L-arginine methyl ester (L-NAME) did not affect vasoconstrictions induced by dinucleosidepolyphosphates. 6. P(2x)-receptor can only be activated if at least one adenosine moiety is present in the molecule. 7. Ap(n)G show a weaker vasoconstrictive action than corresponding Ap(n)A, concluding that two adenosine moieties enhance the P(2x)-receptor binding and activation. 8. Xp(n)X containing five phosphate groups show the most pronounced vasoconstrictive effect whereas four phosphate groups show the less effect, therefore the number of phosphate groups critically changes receptor affinity. 9. Additional experiments using permanent perfusion with alpha, beta-methylene ATP (alpha,beta-meATP) and the selective P(2x1)-receptor antagonist NF023 showed that the newly discovered human dinucleoside polyphosphates activated the vascular P(2x1)-receptor and an recently identified new P(2x)-receptor subtype. 10. The differential effects of dinucleoside polyphosphates allow a fine tuning of local perfusion via composition of Xp(n)Xs.

Adenosine↗
PubMed2001

Increased vascular growth in hemodialysis patients induced by platelet-derived diadenosine polyphosphates.

BACKGROUND: Enhanced vascular smooth muscle cell (VSMC) growth is one hallmark of atherosclerosis. One mechanism responsible for stimulating arterial smooth muscle cell growth is the release of growth factors from platelets aggregating at endothelial lesions. Since in end-stage renal failure (ESRF) atherogenesis is markedly accelerated, the release of VSMC growth factors on aggregation of platelets from hemodialysis patients, ESRF patients in the predialysis stage, and healthy subjects was examined. METHODS: Platelets were activated by thrombin, and the supernatant was tested for growth stimulation in VSMCs from rat aorta. The cell proliferation rate was determined by [(3)H]-thymidine incorporation in VSMCs. The diadenosine polyphosphate (Ap(n)A with N = 3 to 6) content in the supernatant and in intact platelets was determined using a chromatographic assay established on the basis of affinity- and reversed-phase chromatographic methods. RESULTS: The thrombin-activated platelet supernatant from hemodialysis patients (N = 15) increased the [(3)H]-thymidine incorporation rate in VSMC s in comparison to the supernatant of healthy control subjects (N = 17, counts/supernatant of 10(6) stimulated platelets +/- SEM, 604 +/- 71 vs. 364 +/- 45, P < 0.05). The addition of the selective P2-receptor blocker pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid to supernatants inhibited the stimulatory effects of Ap(n)A on the growth of vascular smooth muscle cells (219 +/- 53 vs. 156 +/- 71 counts/supernatant of 106 stimulated platelets +/- SEM). The Ap(n)A (N = 3 to 6) amount of thrombin-activated platelet supernatants from hemodialysis patients was significantly higher than in platelets from 10 healthy control subjects (Ap(3)A, 119 +/- 32 vs. 12 +/- 3; Ap(4)A, 154 +/- 59 vs. 43 +/- 20; Ap(5)A, 39 +/- 14 vs. 13 +/- 6; Ap(6)A, 42 +/- 19 vs. 2 +/- 1 fg/platelet +/- SEM, each P < 0.05, N = 10). The intracellular Ap(n)A (N = 3 to 6) amount of intact platelets from hemodialysis patients (N = 61) was significantly higher than that from healthy control subjects [N = 30, Ap(n)A amount (fg/platelet +/- SEM): Ap(3)A, 366 +/- 68 vs. 14.7 +/- 1; Ap(4)A, 336 +/- 48 vs. 19 +/- 2; Ap(5)A, 227 +/- 35 vs. 10 +/- 1; Ap(6)A, 141 +/- 45 vs. 4 +/- 1; each P < 0.01]. CONCLUSIONS: The increased amount of dinucleoside polyphosphate in platelets from hemodialysis patients may be an important additional atherogenic factor.

Animals↗