Effects of urodilatin on natriuresis in cirrhosis patients with sodium retention

BACKGROUND: Sodium retention and ascites are serious clinical problems in cirrhosis. Urodilatin (URO) is a peptide with paracrine effects in decreasing sodium reabsorption in the distal nephron. Our aim was to investigate the renal potency of synthetic URO on urine sodium excretion in cirrhosis patients with sodium retention and ascites. METHODS: Seven cirrhosis patients with diuretics-resistant sodium retention received a short-term (90 min) infusion of URO in a single-blind, placebo-controlled cross-over study. In the basal state after rehydration the patients had urine sodium excretion < 50 mmol/24 h. RESULTS: URO transiently increased urine sodium excretion from 22 ± 16 μmol/min (mean ± SD) to 78 ± 41 μmol/min (P < 0.05) and there was no effect of placebo (29 ± 14 to 44 ± 32). The increase of URO's second messenger after the receptor, cGMP, was normal. URO had no effect on urine flow or on blood pressure. Most of the patients had highly elevated plasma levels of renin, angiotensin II and aldosterone and URO did not change these. CONCLUSION: The short-term low-dose URO infusion increased the sodium excretion of the patients. The increase was small but systematic and potentially clinically important for such patients. The small response contrasts the preserved responsiveness of the URO receptors. The markedly activated systemic pressor hormones in cirrhosis evidently antagonized the local tubular effects of URO

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Stimulation of renin secretion by potassium-channel activation with cromakalim

The cardiovascular and endocrine profile of cromakalim has been studied in 8 healthy men (age 25 +/- 2 years: means SEM) and its influence on renin release from cultured rat juxtaglomerular cells in vitro has also been examined. According to a double-blind, randomized sequence the subjects received placebo or cromakalim 1 mg as a single daily oral dose for 5 days. Compared to placebo, cromakalim significantly increased plasma renin activity (+ 122%; from 1.73 to 3.87 ng AI.ml-1.h-1), angiotensin II (+ 105%; from 5.1 to 10.5 pg.ml-1), and norepinephrine (+ 61%) levels, and heart rate (+ 8%). Plasma aldosterone, blood pressure and indices of the electrolyte-fluid volume state were unchanged. Cromakalim in vitro stimulated renin release, from 9.9 to 36.5 ng AI.h-1.30 min.mg cell protein, from juxtaglomerular cells. It appears that the presumed K+-channel activator cromakalim increases renin release in vivo at least in part by direct stimulation of renal juxtaglomerular cells

Use of drugs with more than a twenty-four-hour duration of action

AIM: To assess compliance with a drug regimen of two doses a day compared with one a day. PATIENTS AND METHODS: A prospective crossover study was set up in a general practice environment to compare compliance on a drug regimen of once a day versus twice a day. Data were collected by electronic monitoring in 113 patients with hypertension or angina pectoris. All patients were prescribed slow-release nifedipine twice a day during the first month and then crossed to a single daily dose of amlodipine for another month. RESULTS: Compliance, defined as the proportion of days on which the correct dose was taken, improved in 30% of patients (95% confidence interval 19-41%; P &lt; 0.001) when the patients were switched from twice a day to once a day, but at the same time there was a 15% increase (95% confidence interval 5-25%; P &lt; 0.02) in the number of patients with one or more no-dose days. Approximately 8% of patients displayed low compliance, irrespective of the dose regimen. Actual dose intervals were used to estimate the extent and timing of periods with unsatisfactory drug activity for various hypothetical drug durations of action. CONCLUSIONS: The apparent advantage of a single daily dose in terms of compliance appears to be clinically meaningful only when the duration of activity extends beyond the dose interval in all patients

Zeitpunkt der Medikamenten-einnahme bei Hypertonie und Angina pectoris. Eine kontrollierte Uberwachungsstudie. [Time of drug intake in hypertension and angina pectoris. A controlled monitoring study]

A prospective cross-over study was performed in a general practice environment to assess and compare compliance data obtained by electronic monitoring on a BID or QD regimen in 113 patients with hypertension or angina pectoris. All patients were on a BID regimen (nifedipine SR) during the first month and switched to QD regimen (amlodipine) for another month. Taking compliance (i.e. the proportion of days with correct dosing) improved in 30% of patients (95% confidence interval 19 to 41%, p &lt; 0.001), when switching from a BID to a QD regimen, but at the same time there was a 15% increase (95% confidence interval 5 to 25%, p &lt; 0.02) in the number of patients with one or more no-dosing days. About 8% of patients had a low compliance rate, irrespective of the dosage regimen. Actual dosage intervals were used to estimate extent and timing of periods with unsatisfactory drug activity for various hypothetical drug durations of action, and it appears that the apparent advantage of QD regimen in terms of compliance is clinically meaningful only, when the duration of activity extents beyond the dosage interval in all patients