St John's wort extract (Ze 117) does not alter the pharmacokinetics of a low-dose oral contraceptive.

Purpose: St John's wort (Hypericum perforatum) is an herbal remedy that is widely used in the treatment of depression. Recent clinical data have demonstrated that St John's wort extracts interfere with the action of various drugs and possibly also with combined oral contraceptives. Therefore, we investigated the effects of a St John's wort extract (Ze 117) with low hyperforin content on the pharmacokinetics of ethinylestradiol and 3-ketodesogestrel.

Safety of cyproterone acetate: report of active surveillance.

Concern about a potentially increased risk of liver cancer associated to cyproterone acetate (CPA) treatment led to a postmarketing long-term surveillance study with historic accural of four groups of patients with sexual-hormonal disorders under treatment with CPA. The aim of the study was to provide a description of potential ADRs under CPA treatment with special emphasis on liver cancer. A long-term follow-up of 2506 patients was conducted.

4-(4-Guanidinobenzoyl)-2-imidazolones and related compounds: phosphodiesterase inhibitors and novel cardiotonics with combined histamine H2 receptor agonist and PDE III inhibitor activity.

A series of new positive inotropic agents was synthesized with the aim of combining the pharmacophores of the imidazolone-type phosphodiesterase (PDE) inhibitor enoximone and guanidine-type histamine H2 receptor agonists such as arpromidine. All compounds are para-substituted 4-benzoyl-5-alkyl-2-imidazolones. H2 agonism was incorporated by p-(hetero)arylalkyl substituents, in particular by an imidazolylpropyl guanidine group.

Immunocytochemical studies of the Gi protein mediated muscarinic receptor-adenylyl cyclase system.

The localization of three key signal transduction components was indicated in rat heart tissue by immunocytochemical and histochemical experiment. It was shown that: 1. The M2 muscarinic receptors are localized along outer cell membranes and T-tubule membranes of cardiomyocytes but additionally at membranes of endothelial cells and fibroblasts.

Pituitary adenylate cyclase activating peptides are endothelium-independent dilators of human and porcine coronary arteries.

The PACAPs have been shown to be potent vasodilators in different animal species. Data in humans are still lacking. Therefore we investigated the effects of PACAP 38, PACAP 27 and VIP on isolated human and porcine coronary arteries (HCA and PCA).

Comparative immunocytochemical demonstration of G proteins in rat heart tissue.

Localization of G proteins in the rat heart tissue was investigated using primary affinity-purified antibodies against synthetic peptides with amino acid sequences corresponding to alpha-subunits (alpha i common and alpha i 1, 2) of G proteins. Detection of immunoreactivity was performed with the peroxidase-anti-peroxidase complex (PAP), avidin-biotin complex (ABC) and fluorescein-labelled secondary antibodies for light microscopy and the protein A-gold technique for electron microscopy. In ventricles and atria, immunostaining for G proteins was detected in the sarcolemma and perinuclear space of cardiomyocytes.

Diltiazem prevents the depression of adenylyl cyclase activity induced by the calcium paradox in rat.

In isolated rat hearts the calcium paradox, induced by perfusion for 3 minutes in the absence of calcium followed by perfusion for 10 minutes in the presence of calcium, depressed the activation of adenylyl cyclase by l-isoproterenol, NaF and forskolin. The characteristics of the beta-adrenoceptors and the activation of adenylyl cyclase by guanylyl imidodiphosphate were not changed. The findings suggest an uncoupling of beta-adrenoceptors from the catalytic site of the adenylate cyclase complex.

[Clinical and hemodynamic results of surgical correction of hypertrophic obstructive cardiomyopathy].

The value of transaortal subvalvular myectomy after Morrow remains unclarified. We therefore analysed our results with HOCM with particular attention to the operation risk and the longterm results. 56 patients were treated at the Leipzig Heart Centre between January 1984 and August 1990 using the transaortic myectomy.

Comparison of myectomy alone or in combination with mitral valve repair for hypertrophic obstructive cardiomyopathy.

Unlabelled: Between 1/84 and 6/91 56 patients were treated for hypertrophic obstructive cardiomyopathy (HOCM): the Morrow technique alone was performed on 40 patients (group 1), in 16 patients (group 2) an additional replacement (n = 13) or reconstruction (n = 3) of the mitral valve was indicated. In a total of 14 cases coronary artery bypass grafting and aortic valve replacement was performed in addition. Postoperatively (mean follow-up 4.

In vitro effects of reactive O2 species on the beta-receptor-adenylyl cyclase system.

The irreversible loss of activity of the sarcolemma-localized beta-receptor-adenylyl cyclase system (beta-RAS) in myocardial ischemia is a well documented phenomenon. Alterations in the sarcolemma (SL) induced by reactive O2 species could be responsible for this loss. Therefore the influence of oxidation of SH-groups and lipid peroxidation induced by Fe2+/Vit.

G protein function in the ischaemic myocardium.

The activity of adenylyl cyclase (AC) is controlled by its interaction with receptor-regulated G proteins. The efficiency to form cyclic AMP is strongly influenced by the amount, the subspecies and function of these regulatory proteins. An impairment of AC function has been shown to occur in sarcolemmal preparations (SL) of hearts exposed to either local or global ischaemia.

Immunocytochemical localization of G-proteins (alpha subunits) in rat heart tissue.

The subcellular localization of peptide antibodies against G-protein alpha subunits was studied by the indirect immunogold technique with Lowicryl K4M embedded rat cardiac tissue. Two antibodies were used. The alpha common peptide antibody recognizes the alpha subunits of Gs, Gi and Go.

Free radical-induced damage of cardiac sarcolemma (SL) and activity loss of beta-receptor adenylate cyclase system (beta-RAS). A comparison of the time courses.

In vitro studies have demonstrated that free radicals generated by Fe2+/Vit. C alter the beta-RAS function. SH-oxidation, peroxidation of sarcolemmal lipids and reaction of aldehydes (formed by lipid peroxidation) with the beta-RAS may contribute to this effect.

Investigations on the mechanism of a diminished inotropic isoprenaline effect in isolated rat hearts after high linoleic acid diet.

Male Wistar rats were fed on a diet rich (13.3 J%) or poor (0.5 J%) in linoleic acid for 10 weeks.

Altered effect of BAY K 8644 after exposure of the rat aorta to IBMX or Db cAMP.

The development of isometric tension of aortic rings from rats was tested after cumulative administration of BAY K 8644 before and after exposure of the aortic preparations for 15 or 60 minutes to IBMX (10(-4) M) or Db cAMP (3.10(-4) M). BAY K 8644 exhibits dose-dependent contractions of those aortic rings which have not been exposed or have been exposed for only 15 minutes to IBMX or Db cAMP.

Responsiveness of cardiac adenylate cyclase in the normal and ischemic myocardium. Role of oxygen free radicals.

Cyclic AMP has been shown to play a significant regulatory role in a number of myocardial cell functions. The cAMP-forming adenylate cyclase complex is localized in the sarcolemmal membrane which is the major site of lipid peroxidation by oxygen-derived free radicals known to be increased in the ischemic myocardium. Adenylate cyclase function was found to be depressed in the ischemic myocardium but the specific biochemical mechanism responsible for this effect is still unknown.

Decreased contractile response after exposure of the rat aorta to Db cAMP or IBMX.

Isometric tension developed by different receptor agonists was found to be decreased after pretreatment of rat aortic rings with IBMX or Db cAMP and only partially restored by CaCl2 and A 23187. The contraction produced by Bay k 8644 was converted into dose-dependent relaxation after pretreatment of the aorta rings with Db cAMP or IBMX. An alteration of the calcium channel is assumed to play a common role in the cAMP-dependent inhibition of the smooth muscle contraction.

Cytochemical localization of adenylate cyclase activity in heart tissue with cerium.

Adenylate cyclase (AC) activity showed a doses depending inactivation of the basal activity and of the sodium fluoride stimulation by cerium in homogenates of unfixed and fixed guinea pig hearts. The isoproterenol and guanine nucleotide stimulation was not more than two times of the basal activity in glutaraldehyde-prefixed heart homogenates in the presence of 2 mmol/l CeCl3. The inactivation of the AC (activity) by cerium was less than in the presence of lead.

Adrenergic regulation of the acute ischaemic myocardium: facts, interpretations and consequences.

Anoxic stress is accompanied by activation of the central and peripheral sympathetic nervous system resulting in a high local catecholamine concentration. The authors studied how myocardial cells cope with the high level of catecholamines under ischaemic conditions. The beta-adrenoceptor-adenylate cyclase system (AC) was investigated in different models of ischaemia and anoxia (global ischaemia, low-perfused hearts, coronary artery ligation) in rat hearts.

Developmental changes of Ca++ transport systems in chick heart.

Sarcolemma (SL) Na+/Ca++ exchange, binding of the Ca++ channel antagonist [3H]nitrendipine and sarcoplasmic reticulum (SR) Ca++ uptake were studied in crude membranes from developing chick heart. Energy-linked Ca++ uptake of mitochondria (MT) was measured in tissue homogenates. When reckoned per unit of heart mass Na+/Ca++ exchange increases linearly (20-fold) from embryonic day 4 to postnatal day 10.

Signal transfer in cardiac muscle. Alteration of the beta-adrenoceptor adenylate cyclase system in the hypertrophied myocardium.

The beta-adrenoceptor adenylate cyclase complex (beta ACR), located in the sarcolemmal membrane, is one of the most effective signal transduction systems regulating function and metabolism of heart muscle primarily via cyclic AMP. It is thought to play an important role in adaptive mechanisms of the heart as to pressure load and stressful stimuli. Present knowledge about composition and function of beta ARC enable us to clear up which of the single components of this system contributes to pathophysiological alterations of heart function.

Putative Ca2+ channels in cardiac membranes. Subcellular distribution of [3H]nitrendipine receptors.

The binding of Ca2+ channel blocking drug nitrendipine was studied in purified sarcolemma (SL), fragmented sarcoplasmic reticulum (SR), and crude membranes isolated from porcine left ventricle. The density of specific [3H]nitrendipine binding sites was compared to Na+/Ca2+ exchange and (Na+, K+)ATPase activities of each membrane preparation. Enrichment of [3H]nitrendipine binding sites in purified SL correlates excellently with the purification of the two studied sarcolemmal marker activities.

Reversible inhibition of adenylate cyclase activity in the ischemic myocardium.

Adenylate cyclase (AC) function was studied in homogenate and particulate preparations of ischemic rat heart obtained from three models: anoxic-ischemic incubations, coronary artery ligation, and global low-flow perfusion of isolated hearts. Both basal activity and the function of AC measured in the presence of NaF (8 X 10(-3)M), Gpp(NH)p (10(-5)M), and L-(-)-isoprenaline (10(-8)-10(-4)M) were reduced to 50% of the control value in homogenates of hearts incubated under anoxic-ischemic conditions for 10 min. Comparable results were obtained with homogenates from the ischemic area 20 min after coronary artery ligation in anesthetized open-chest rats with artificial ventilation.

[Behavior of adenylate cyclase in ischemic and necrotic myocardial tissue].

The adenylate cyclase activity was determined in the left ventricles of rat hearts up to 60 min after severe ischemia and 24 hours after injection of a high dose of isoproterenol. The quantitative data show a progressive decline in the activity after 20 min of ischemia. Isoproterenol- and fluoride-stimulated activities were influenced in the same manner.