Effect of aldosterone on collagen steady state levels in primary and subcultured rat hepatic stellate cells.

BACKGROUND/AIMS: Activation of the renin-angiotensin-aldosterone system can lead to collagen accumulation and reactive myocardial fibrosis. This study aims at evaluating the effect of aldosterone on extracellular matrix synthesis by rat hepatic stellate cells. METHODS: Cultured cells were treated with different concentrations of aldosterone (10(-6)-10(-10) M) and metabolically labeled with 35S-methionine/35S-cysteine. Procollagen types I, III and IV, laminin and fibronectin were specifically immunoprecipitated and quantified by phosphor imaging. Using the reverse transcription-polymerase chain reaction, we investigated the expression of the mineralocorticoid receptor in hepatic stellate cells. RESULTS: Quantitation showed that 10(-6) M aldosterone induced procollagen type I synthesis significantly, whereas procollagen type IV expression was significantly affected by 10(-9) and 10(-10) M aldosterone, both in primary hepatic stellate cells. RT-PCR experiments clearly demonstrated a lack of expression of the mineralocorticoid receptor in hepatic stellate cells. CONCLUSION: We demonstrated that aldosterone altered moderately procollagen type I and IV synthesis by primary hepatic stellate cells, but not by activated stellate cells which are the principal cellular sources of extracellular matrix proteins in chronic liver disease. Moreover, hepatic stellate cells do not express the mineralocorticoid receptor, suggesting that the observed modest changes of extracellular matrix synthesis are probably due to mineralocorticoid receptor unrelated mechanisms.

Comparative study of the efficacy and safety of trazodone versus clorazepate in the treatment of adjustment disorders in cancer patients: a pilot study.

The efficacy of trazodone (mean once-daily dose 111.5 +/- 36.3 mg) versus clorazepate (mean once-daily dose 17.5 +/- 7.5 mg) to relieve anxious and depressive symptoms in 18 patients undergoing treatment for breast cancer was investigated in a 28-day randomized, double-blind study. Efficacy was evaluated using the Hospital Anxiety and Depression Scale, the Revised Symptom Checklist and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. A successful response to treatment was achieved in 91% (10/11) of patients who received trazodone and 57% (four of seven) of patients who were administered clorazepate (P = 0.1373). Bayesian analysis revealed that the prior probability of making a wrong decision in prescribing trazodone rather than clorazepate reduced from 26% to 8%. Assessment of the clinical scales suggested a benefit of trazodone compared with clorazepate, although the differences were not significant. Safety of both treatments was similar. Trazodone is devoid of an abuse risk and dependence and, therefore, could be a valuable alternative to clorazepate in the treatment of adjustment disorders in cancer patients.

Efficacy and safety of trazodone versus clorazepate in the treatment of HIV-positive subjects with adjustment disorders: a pilot study.

The efficacy of trazodone and clorazepate to relieve anxiety and depressive symptoms in 21 HIV-positive subjects with adjustment disorders was determined in a 28-day single-centre, randomized, double-blind study. Subjects were evaluated using the Hospital Anxiety and Depression Scale, the Revised Symptom Checklist, the European Organization for Research and the Treatment of Cancer Quality of Life Questionnaire, and a binary criterion based on the Clinical Global Impression. The incidence of successful treatment was 80% for trazodone compared with 64% for clorazepate; the sample number was too small to establish a significant difference. Bayesian analysis revealed the probability of making a wrong decision in prescribing trazodone rather than clorazepate reduced from 35% to 18% in this small sample. Clinical evaluations using the different scales suggest some benefit from trazodone, although this was not significant. Safety of both treatments was similar. Trazodone is devoid of the risk of abuse and dependence, and may be a valuable alternative to benzodiazepines for the treatment of HIV-related adjustment disorders.

Effects of spironolactone-altizide on left ventricular hypertrophy.

OBJECTIVE: To investigate the effects of the association spironolactone (25 mg)/altizide (15 mg) as monotherapy on left ventricular hypertrophy (LVH) in patients with mild to moderate hypertension. Additionally, to study the correlation between left ventricular mass (LVM) index and electrocardiographic (ECG) criteria for LVH. METHODS AND RESULTS: This was an open, prospective study of 6 months. Patients with mild to moderate essential hypertension were treated with spironolactone/altizide for two months and were included in the study if their blood pressure (BP) at the end of this first treatment period was normalised according to protocol criteria (systolic BP < 160 mm Hg and diastolic BP < 95 mm Hg). Patients then entered a second 4-month treatment period. LVM was determined by echocardiography performed at the beginning of treatment and after 6 months. LVH was defined as LVM > or = 100 g/m2 in women and LVM > or = 131 g/m2 in men. Echocardiograms were interpreted blindly by two echocardiography reading laboratories. Seventy-one patients with a normalised BP after two months of treatment, were enrolled in the study. Changes in LVM index were studied in 31/71 patients with LVH (25 women and 6 men, mean LVM index +/- (SD) 119.9 +/- 16.4 g/m2 in women and 147.8 +/- 10.9 g/m2 in men). Spironolactone/altizide significantly reduced LVM index by 10%, from 125.3 +/- 22.5 to 114.2 +/- 25.1 g/m2 (p < 0.005). Posterior and septal wall thickness decreased by 4% (p = 0.06) and 5% (p = 0.026), respectively. End-diastolic dimension was reduced by 3%, from 50.3 +/- 3.3 to 48.9 +/- 3.4 mm (p = 0.006). The posterior wall thickness to end-diastolic dimension ratio remained unchanged. Complete regression of LVH according to mass criteria occurred in 11 patients out of 31 (34.5%). The observed changes in ECG voltage criteria were in accordance with a decrease of LVM index. CONCLUSION: In this open study, the potassium-sparing diuretic spironolactone/altizide decreases LVM index in hypertensive patients, who were selected for follow-up because they had echocardiographic LVH and because their BP had normalised during an initial 2-month treatment period.

Cibenzoline in the prevention of recurrence of supraventricular arrhythmias.

Hundred and twenty-three outpatients were treated with oral cibenzoline for 3 months in order to test the efficacy and safety of the compound in the prevention of the recurrence of supraventricular arrhythmias. The dose was 260-390 mg/day for those under 70 and 130-260 mg/day for those over 70 years. All patients were converted to sinus rhythm before entry to the study and 95 patients had previously been treated with one or more drugs which had been discontinued due to lack of effect and/or poor tolerability. In 21 patients (17%) recurrence was documented by ECG or Holter monitoring, cibenzoline thus being effective in 83%. In 35 other patients there was a return of symptoms but no confirmation of recurrence. There were no relevant changes in blood pressure or heart rate. PR, QT and QTc intervals were stable but mean QRS interval increased slightly during the first week before stabilizing. Cibenzoline was discontinued because of adverse events in only 10 patients (8.1%). The most frequent complaints were nausea, vertigo and faintness. Seventy-two per cent of patients rated their well-being as "well/very well" at month one compared with 84% at month three. Cibenzoline is an appropriate first line choice in this indication.