Objective: The present study was designed to investigate the integrated effects of the beta-1-selective blocker with vasodilator properties, nebivolol, on systemic haemodynamics, neurohormones and energy metabolism as well as oxygen uptake and exercise performance in physically active patients with moderate essential hypertension (EH). Design and methods: Eighteen physically active patients with moderate EH were included: age: 46.9 ± 2.38 years, weight: 83.9 ± 2.81 kg, blood pressure (BP): 155.8 ± 3.90/102.5 ± 1.86 mm Hg, heart rate: 73.6 ± 2.98 min −1 . After a 14-day wash-out period a bicycle spiroergometry until exhaustion (WHO) was performed followed by a 45-min submaximal exercise test on the 2.5 mmol/l lactate-level 48 h later. Before, during and directly after exercise testing blood samples were taken. An identical protocol was repeated after a 6-week treatment period with 5 mg nebivolol/day. Results: Nebivolol treatment resulted in a significant ( P < 0.01) decrease in systolic and diastolic BP and heart rate at rest and during maximal and submaximal exercise. Maximal physical work performance, blood lactate and rel. oxygen uptake (rel. VO 2 ) before and after nebivolol treatment at rest and during maximal and submaximal exercise remained unaltered. Free fatty acid, free glycerol, plasma catecholamines, beta-endorphines and atrial natriuretic peptide (ANP) increased before and after treatment during maximal and submaximal exercise but remained unaltered by nebivolol treatment. In contrast, plasma ANP levels at rest were significantly higher in the presence of nebivolol, endothelin-1 levels were unchanged. Conclusions: Nebivolol was effective in the control of BP at rest and during exercise in patients with EH. Furthermore, nebivolol did not negatively affect lipid and carbohydrate metabolism and substrate flow. The explanation for the effects on ANP at rest remain elusive. This pharmacodynamic profile of nebivolol is potentially suitable in physically active patients with EH.

The structures of the antibiotically active sesquiterpenoids hypnophilin, pleurotellic acid and pleurotellol have been elucidated by spectral investigations. Pleurotellic acid and pleurotellol contain a rearranged hirsutane skeleton which may be derived biosynthetically from hypnophilin by a Wagner-Meerwein type rearrangement.

From submerged cultures of Lachnella villosa, Lachnella sp. 541, and Peniophora laeta we isolated marasmic acid (1), a metabolite first described from surface cultures of Marasmius conigenus. The sesquiterpenoid exhibits potent antimicrobial and cytotoxic properties. In cells of the ascitic form of Ehrlich carcinoma RNA and DNA syntheses are preferentially inhibited. Marasmic acid inhibits RNA synthesis in isolated nuclei, but does not interfere with the transport of nucleoside precursors into the cells. RNA polymerase II and capping enzyme (mRNA guanylyltransferase), two enzymes of nucleic acid metabolism, are markedly affected after preincubation with marasmic acid. We assume that marasmic acid acts on nucleic acid syntheses by direct inhibition of some of the enzymes involved. This mode of action would also explain its mutagenic properties. The preparation and testing of two derivatives, 2 and 3, revealed that the alpha,beta-unsaturated aldehyde is essential for the antimicrobial and cytotoxic activity of marasmic acid.

Two antimicrobial and cytotoxic metabolites were isolated from fermentation broth of Marasmius alliaceus. The structures of the two crystalline antibiotics, alliacols A (6) and B (1) were elucidated by spectroscopic methods and chemical correlation with alliacolide (3). The alliacols show weak antibacterial and antifungal activity. Both antibiotics strongly inhibit DNA synthesis in cells of the ascitic form of Ehrlich carcinoma at concentrations of 2 approximately 5 microgram/ml. Both alliacols A and B react with cysteine to form adducts with strongly reduced biological activities.

Abstract Three new antibiotics, merulinic acids A, B, and C, have been isolated from fruiting bodies of Merulis tremellosus and Phlebia radiata. They are closely related derivatives of β-resorcylic and salicylic acid, carrying monounsaturated C17-alkyl side chains in 6-position. The merulinic acids are mixtures of the Δ8′-compounds with minor amounts of the corresponding Δ10′-, dehydro, and dihydro derivatives, separable only by means of HPLC. Δ8′-Merulinic acid A (1) was synthesized via a biomimetic cyclization of a linear precursor. The merulinic acids inhibit a variety of bacteria and are not active against fungi. RNA, DNA, and protein synthesis in Bacillus brevis and Ehrlich carcinoma ascites cells are inhibited shortly after the addition of the antibiotics. Almost complete hemolysis of human erythrocytes is caused by 25 μg/ml of merulinic acid B and C or by 73 μg/ml of merulinic acid A.

Merulidial, a new antibiotic, was isolated from the culture fluid of the Basidiomycete Merulius tremellosus Fr., strain No. WQ 568. Merulidial inhibits a variety of bacteria and fungi. In cells of the ascitic form of EHRLICH carcinoma, DNA synthesis is inhibited at lower concentration as compared to RNA and protein synthesis. Merulidial shows mutagenicity when incubated with the his-mutant TA 100 for Salmonella typhimurium (B.N.AMES). The molecular formula as determined by high resolution mass spectrometry is C15H20O3.