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Effects of sodium valproate on corticotropin-releasing factor systems in rat brain.


Despite no Food and Drug Administration (FDA) indication and little safety data, over one-third of premature infants in our population were exposed to a diuretic, many with minimal respiratory support.

The causes of chronic heart failure at the end of the 20th century are quite different from those 30 or 50 years ago. The last data from the Framingham study indicate that ischaemic heart disease and/or hypertension are the main cause in as many as 90% patients. The prevalence of chronic heart failure in European countries, 0.4-2%, implies 40-200,000 patients in the Czech Republic. Pharmacological treatment during the last 15 years revealed clearly that the drugs of choice which prolong life are inhibitors of the angiotensin converting enzyme (ACE-I) which are combined with other drugs as needed by the patient. A combination of five drug groups (ACE-I, digitalis, diuretics, beta-blockers, and spironolactone) are nowadays the basic treatment. In the 4S study (Scandinavian Simvastatin Survival Study--4,444 patients with ischaemic heart disease followed up for 5.4 years) 412 (9.2%) developed chronic heart failure requiring treatment, i.e. 228 (10.3%) in the placebo group and 184 (8.3%) patients in the group treated with simvastatin (p < 0.015). In the group of patients with signs of heart failure 73 of 228 died the placebo group and 47 of 184 in the simvastatin group (reduction of the relative risk by 19%, p = 0.014), to save one life (NNT) it was necessary to treat 15 patients for a period of 5 years. From the aspect of the number of patients it was necessary to treat six times as many patients without heart failure than with heart failure to save one life in five years. Hypolipidaemic treatment should be an obvious part of treatment of heart failure due to ischaemic heart disease. Hyperlipoproteinaemia is described in 60-80% patients after transplantation of the heart. Treatment involves diet, reduction or discontinuation of corticoids, maintenance of cyclosporin at the lowest effective level and treatment wit statins.

Adrenal incidentaloma are usually found during the assessment of non adrenal disease. In this paper we report the association between a bilateral adrenal hyperplasia and a macronodule of adrenal cortex (adrenal incidentaloma) which is a rare and misleading cause of primary aldosteronism. In the light of this association even if it is likely to remain rare and of those previously published, its existence is an additional reason for suggesting surgical treatment of primary aldosteronism only to patients who satisfy the following criteria: 1) satisfactory control with spironolactone; 2) poor spironolactone tolerance and poor control with other drugs; 3) accept to be operated on and the risk of a possible error.

Orally administered eplerenone attenuated collagen accumulation within the neointima, thereby inhibiting neointimal hyperplasia after stent implantation.

The pharmacological activity of single oral doses of a new aldosterone antagonist, prorenoate potassium, has been compared with spironolactone and placebo in a balanced double-blind crossover study in six healthy subject. Endogenous mineralocorticoids were stimulated by administration of frusemide followed by dietary sodium restriction, and the urinary excretion of electrolytes in response to prorenoate potassium, spironolactone and placebo was measured over a 24 hour period. Significant activity of prorenoate potassium and spironolactone was observed between 2 - 24 hours after medication, with peak activity at 6 - 8 hours. The active drugs significantly increased sodium excretion and the sodium : potassium (Na/K) ratio, but changes in potassium excretion were not significant. The total urine Na/K response to prorenoate potassium 45 mg was significantly greater than to spironolactone 100 mg.

A comprehensive evaluation of the benefits of mineralocorticoid receptor antagonists on cardiac remodeling is lacking. We aimed to evaluate the impact of mineralocorticoid receptor antagonists on changes in cardiac structure and function of left ventricular dysfunction.

Ald potentiates Ang II-induced ERK-1/2 and JNK phosphorylation. Oxygen radicals, the MR, and the EGFR play a role in early signaling induced by Ang II and Ald in VSMCs. These in vitro data may help explain the effects of MR blockade on Ang II-induced end-organ damage in vivo.

A prospective register was implemented in 17 secondary or tertiary hypertension centres. The inclusion criterion was one of the following: onset of hypertension before 40 years of age; history of hypokalaemia; drug-resistant hypertension (resistant to three drugs); or spironolactone efficiency on BP.

CYP11B1 was detected in the human adrenal cortex and in human adenomas by in situ-hybridization methods. Specific riboprobes were generated and hybridized to sections of an Aldosterone Producing Adenoma (APA), the non-tumour portion of the corresponding adrenal gland and two adenomas not related to hyperaldosteronism. P45011B1 mRNA was clearly localized in the zona fasciculata/reticularis. Semi-quantitative analysis has been performed and seems to be applicable for a further classification of adrenal tumours. Stable expression of CYP11B1 cDNA was performed in V79 cells. The interference of different substances (metyrapone, spironolactone and different imidazole derivatives) with CYP11B1 activity was studied using this cell line. The cell line revealed to be suitable for analysis of the active site of CYP11B1 as well as for analysis of side effects of drugs on steroidogenesis.