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Biomedical subjects

W Wurst

Publications and source records attributed to W Wurst.

106 records · Page 6Linked to original sources
PubMed1989

Evidence for normal thymic export of lymphocytes and an intact RT6a gene in RT6 deficient diabetes prone BB-rats.

Diabetes prone BB-rats develop an insulin-dependent diabetes mellitus between postnatal day 60 and 120 in a high incidence. Moreover, even before onset of the diabetes, these animals are deficient in the RT6+ subset of T lineage cells. We here put forward evidence that the export of cells from the thymus is normal in these rats, suggesting a maturational block in the periphery. We show furthermore by Southern blot analysis that diabetes prone BB-rats possess the RT6a gene which is not grossly altered in comparison to that of diabetes resistant strains.

Animals↗
PubMed1989

Improved orthostatic dysregulation record after administration of a sustained-release form of urapidil.

The efficacy and safety of urapidil has been demonstrated in a long-term treatment. However, a relatively good record of side effects has been marred by reports of orthostatic dysregulation. This study was designed to examine the blood pressure lowering effect, tolerability and pharmacokinetics of a sustained-release formulation of urapidil. Twelve patients received either 60 mg of sustained-release urapidil (Ebrantil 60) or 50 mg urapidil for experimental reference as a fast-release tablet in single or multiple doses in a randomized, double-blind fashion. To ensure the double blind-character of the study, the tablets were encapsulated. Blood samples for the determination of urapidil (HPLC) were drawn before and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h post application. Blood pressure was measured at 0.5, 1.5, 3, 8, 10 and 12 h post application. An orthostatic test was performed before and at 1, 2, 4 and 6 h post application. Twelve h after the first application, patients received a second capsule or encapsulated tablet and continued medication for two days. On day four, the same procedure as on day one was repeated, except that patients received no evening medication and blood samples and blood pressure were measured at 24, 28 and 32 h post application on the fifth day. The Cmax of sustained-release urapidil was 44% lower than for the single tablet dose and 37% lower after multiple dosing. The peak-trough fluctuation of the steady-state serum concentrations was 29% lower for the sustained-release capsule (138 +/- 45%) compared to the tablet (195 +/- 83%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Acute haemodynamic effects of urapidil in patients with chronic left ventricular failure.

Urapidil, a new alpha 1-adrenoceptor blocking drug, has been shown to be effective in the treatment of hypertension. Ten normotensive patients with severe congestive heart failure were given Urapidil 25 mg i.v. twice in 15 min and the haemodynamic effects were measured. There was a significant fall in systolic blood pressure (-16%), mean blood pressure (-13%), left ventricular end-diastolic pressure (-38%), mean pulmonary artery pressure (-31%) and wedge pressure (-40%). Total peripheral resistance fell by 25%, whereas pulmonary arteriolar resistance did not change significantly. Cardiac output increased by 22%. The increase in cardiac output with decreasing peripheral resistance and LV pressures suggests that urapidil may be useful in the therapy of congestive heart failure.

Adult↗
PubMed1988

Treatment of mild hypertension with urapidil or captopril.

The aim of this study was to compare the efficacy (lowering diastolic blood pressure to 90 mm Hg or less) of urapidil, a postsynaptic alpha-blocker with central action with that of captopril in a randomized, double-blind, multicenter study. Two hundred ninety-five essential hypertensives (WHO I/II) (140 male, 155 female, age 56-60 years) were treated for 12 weeks with either 30 to 90 mg urapidil bid or 12.5 to 50 mg captopril bid. Supine blood pressure values (mmHg, mean +/- SD) at the end of the 12-week treatment dropped for the urapidil group (n = 142) from 175/103 +/- 19/6 to 154/89 +/- 17/9 (P less than 0.001), and in the captopril group (n = 153) from 175/103 +/- 19/6 to 154/90 +/- 19/9 (P less than 0.001), corresponding to 62% urapidil and 58% captopril responder rates. The results demonstrate that the two antihypertensive medications with different modes of action control blood pressure with equal efficacy at three dose levels. A dose decrease was possible in 20% of each group, but a dose increase was necessary in 39% of urapidil and 44% of captopril group.

Adult↗
PubMed1988

Efficacy of urapidil in the management of essential hypertension. A comparison with captopril.

In a multicentre study by general practitioners, the antihypertensive efficacy of urapidil, a postsynaptic alpha-blocker with central action, was compared with that of the angiotensin-converting enzyme inhibitor captopril. The study was of a double-blind, randomised parallel-group design. Following a 2-week washout and placebo phase, 295 essential hypertensives (WHO I/II) were treated for 12 weeks with either urapidil or captopril, initially with urapidil 60 mg twice daily or captopril 25mg twice daily, with the possibility of adjusting the dose according to blood pressure response after 2 weeks of treatment [diastolic blood pressure (DBP) 90 mm Hg or less: reduction of urapidil to 30 mg twice daily or captopril to 12.5mg twice daily; DBP 91 to 99 mm Hg: dose unchanged; DBP 100 mm Hg or more: dose increased to urapidil 90 mg twice daily or captopril 50 mg twice daily]. Blood pressure values at the end of the 12-week treatment period dropped significantly in the urapidil group (n = 142; all dosages) from 175/103 mm Hg to 154/89 mm Hg (p less than 0.001) and in the captopril group (n = 153; all dosages) blood pressure decreased from 175/103 mm Hg to 154/90 mm Hg (p less than 0.001), corresponding to 62% and 58% urapidil and captopril responder rates (DBP less than or equal to 90 mm Hg), respectively. The responder rate at 12 weeks under urapidil therapy was 30% for the initial, 17% for the lower and 15% for the higher dose; the respective values for captopril were 28, 16 and 14%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Analysis of the rat major histocompatibility system by Southern blot hybridization.

The organization of the rat major histocompatibility complex, RT1, was studied at the DNA level by Southern blot hybridization. Genomic DNA from eight different RT1 congenic rat strains was digested by various restriction enzymes and was hybridized under stringent conditions with probes of mouse class I and class II H-2 genes. Few cross-hybridizing DNA fragments, showing no polymorphism, were seen with class II A alpha and A beta probes. The class I probes allowed for the distinction of about 8 to 19 cross-hybridizing bands, which exhibited extensive polymorphism. With the use of five RT1 recombinants, about 20% of the DNA fragments could be mapped to the RT1.A region, which codes for the ubiquitously expressed class I antigens, and about 80% to the RT1.C region-determining class I-like antigens, which are different from RT1.A antigens with respect to tissue distribution, restriction function in immune responses, and allograft rejection. The number of class I genes present in the rat genome and the possible relationship of RT1.C to H-2Qa, Tla of the mouse are discussed.

Animals↗
PubMed1985

Functional and molecular genetic analysis of a group of rat class I major histocompatibility genes which might be homologous to H-2Qa.

Studies on the major histocompatibility complex of the rat (RT1) will be summarized, which demonstrate the existence of a cluster of class I-like genes differing in expression, function and complexity of their organization from the "classical" class I genes, the gene products of which restrict antigen recognition by T lymphocytes. The characterization of the respective gene region (RT1.C) and its products is based on data obtained with classical genetic, molecular genetic, biochemical and immunological methods. It turns out that the RT1.C region and RT1.C antigens are in many aspects homologous to the H-2Qa region and H-2Qa antigens, respectively, of the mouse.

Animals↗
PubMed1984

Cytotoxic T lymphocytes of the rat are predominantly restricted by RT1.A and not RT1.C-determined major histocompatibility class I antigens.

Two types of biochemically defined class I major histocompatibility complex (MHC) antigens are found in the rat, RT1.A antigens that are ubiquitously expressed and RT1.C antigens which so far are detectable only on certain cell types, notably B and T lymphocytes. It is shown that the cytotoxic T lymphocyte response to minor H antigens of the LEW strain, including the H-Y antigen, and to TNP-modified syngeneic lymphoid cells is restricted by RT1.A but not RT1.C gene products. This conclusion is based on bulk culture assays including cold target inhibition tests and limiting dilution experiments using recombinants between the RT1a and RT1u haplotypes. The possibility that class I MHC antigens exist which have no major restriction function is discussed.

Animals↗
PubMed1979

Antibacterial active components in human urine after administration of penicillins.

Four-hourly urine from volunteers and patients who had received penicillins orally or intravenously was investigated by means of thin layer chromatography and bioautography. Antibacterially active metabolites were not detected with only two of 12 penicillins, namely amoxicillin and mezlocillin. In the case of the other penicillins the metabolites possessed variable antibacterial activity as could be demonstrated using different test microorganisms. After administration of carbenicillin esters three antibacterially active spots were detected, one of which corresponded to penicillin G; the other two were active against Pseudomonas aeruginosa. The bioautogram after treatment with azlocillin showed two components which were active against Bacillus subtilis, Staphylococcus aureus and Escherichia coli; only the rapid moving component was active against P. aeruginosa, however. The formation and chemical nature of these additional active components is still to a large extent not understood. It is quite possible, however, that they affect the bio-availability of an antibiotic.

Administration, Oral↗
PubMedDate not supplied

Molecular characterisation of antidepressant effects in the mouse brain using gene expression profiling.

Antidepressants are widely used for the treatment of psychiatric disorders, including depression and anxiety. Although they are efficient drugs, there are several unsolved questions regarding their clinical pharmacology. Furthermore, the molecular mechanisms of action of antidepressants are still poorly understood and the molecular targets and pathways remain to be identified. To address these issues, we performed a gene expression analysis in mice treated with two commonly used antidepressants with differing pharmacology (paroxetine or mirtazapine) for 1, 7 or 28 days. We quantified the effects of these treatments on gene expression in the mouse brain with cDNA-microarrays containing 3624 expressed sequence tags (ESTs) representing murine genes expressed in the brain. We found that both drugs led to downregulation of four common genes. In addition, although it was possible to identify common targets for the two drugs, the expression profiles of the drugs differed in a fundamental manner, and the longer the treatment duration, the greater the difference in the profiles. These findings suggest that antidepressants with different pharmacologies can share molecular targets even though the primary pathways at which they act are different.

Animals↗
PubMedDate not supplied

Optimizing the intragastric pH as a supportive therapy in upper GI bleeding.

Acid inhibitory therapy has long been considered of no benefit for upper GI bleeding. The reason was that achlorhydria in the stomach could not be achieved with any single or combination of acid inhibitory drugs. The introduction of proton pump inhibitors has, for the first time, allowed the physician to temporarily achieve achlorhydria by large doses of intravenously applied proton pump inhibitors. The first placebo-controlled clinical trials have shown that, indeed, an intragastric pH of near 7 can significantly improve the clinical outcome of upper GI bleeding. Pharmacokinetic studies with proton pump inhibitors have shown that a bolus of 80 mg pantoprazole or omeprazole followed by immediate continuous infusion of eight mg per hour will result in an intragastric pH of 7 within 20 minutes. This intragastric pH optimizes the different steps of hemostasis in the stomach.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMedDate not supplied

Current status of acid pump antagonists (reversible PPIs).

The introduction of H2-receptor antagonists in the mid-1970s provided, for the first time, acceptable medical therapy for acid-related diseases. Their short duration of action and single receptor targeting, however, limited satisfactory treatment of patients. Today the control of gastric acid secretion can be effectively achieved by direct inhibition of the H+, K(+)-ATPase. Inhibition of the proton pump suppresses acid secretion independent of the route of stimulation. Two classes of drugs are able to inhibit the proton pump. First, the substituted benzimidazoles (proton pump inhibitors [PPIs]), which, due to their pKa of about 4, accumulate in the acidic secretory canaliculus of the stimulated parietal cell. Following conversion to a cationic sulfenamide, they react with cysteines on the extracytoplasmatic face of the H+, K(+)-ATPase subunit. Second, acid pump antagonists (APAs) acting by K(+)-competitive and reversible binding to the gastric proton pump, which is the final step for activation of acid secretion in the parietal cell. One possible class of APAs are imidazopyridines. BY841 was selected from this class and is chemically a (8-(2-methoxycarbonylamino-6-methyl-phenylmethylamino )-2,3-dimethyl-imidazo [1,2-a]-pyridine). In pharmacological experiments such as pH-metry in the conscious, pentagastrin-stimulated fistula dog, BY841 proved to be superior to both ranitidine and omeprazole by rapidly elevating intragastric pH up to a value of 6. The duration of this pH elevation in the dog was dose-dependent. As was predicted by the above-mentioned dog model, available clinical phase I data confirm dose-dependent pharmacodynamics of BY841 in man. Using both acid output and continuous 24-hr pH measurements, a pronounced antisecretory effect of BY841 has been found. Actually, a single 50 mg oral dose of BY841 immediately elevated intragastric pH to about 6. Higher doses caused a dose-dependent increase in duration of the pH-elevation, without any further increase in maximum pH values. Twice daily administration was more effective than once a day administration of the same daily dose. With both regimens, the duration of the pH-elevating effect of BY841 further increased upon repeated daily administration. This demonstrates lack of tolerance development, the latter being a well-known disadvantage of H2-receptor antagonists. In comparison with the standard dose of omeprazole, BY841 administered at a dose of 50 mg or 100 mg twice daily is markedly more effective on Day one of treatment, and both doses are at least as potent as omeprazole following repeated daily administration.

Administration, Oral↗