A randomized, controlled, double-blind, multi-center trial to evaluate the efficacy and safety of a liquid containing ivy leaves dry extract (EA 575®) vs. placebo in the treatment of adults with acute cough.

This randomized, placebo-controlled, double-blind trial was conducted to assess the efficacy and safety of ivy leaves cough liquid in the treatment of acute cough. A total of 181 adult patients with acute cough were treated with either ivy leaves cough liquid containing EA 575® or with placebo three times a day for one week. The primary efficacy outcome was cough severity (CS) assessed by Visual Analogue Scale (VAS) over the whole treatment period (area-under-the-curve (AUC0-168 h) over 7 days (visit (V)1, V2, V3, V4, and V5). The secondary endpoints were defined as the CS assessed by VAS over the whole observation period (V1 - V6) and by Bronchitis Severity Score (BSS) and Verbal Category Descriptive (VCD) score. The evaluation of the VAS, BSS and VCD score revealed that subjects treated with ivy leaves cough liquid showed statistically significant and clinically relevant reductions in CS, severity of symptoms associated with cough and bronchitis compared to the placebo group. Furthermore, a remarkable early onset of efficacy was observed as significant reductions of cough severity were detected within 48 hours after the first drug intake. At all following visits and even 7 days after the end of treatment (V6) this significant treatment advantage was detected in comparison to placebo. All adverse events (AEs) in this clinical trial were non-serious, mild or of moderate severity and not drug-related. This clinical trial proved consistent superiority of the ivy leaves cough liquid treatment versus placebo and confirmed the EA 575® preparation to be a safe and efficacious option for the treatment of acute cough.

Efficacy and safety of comfrey root extract ointment in the treatment of acute upper or lower back pain: results of a double-blind, randomised, placebo controlled, multicentre trial.

OBJECTIVE: The objective was to show the superiority of comfrey root extract ointment to placebo ointment in patients with acute upper or lower back pain. DESIGN: The study was conducted as a double-blind, multicentre, randomised clinical trial with parallel group design over a period of 5 days (SD 1). The patients (n = 120, mean age 36.9 years) were treated with verum or placebo ointment three times a day, 4 g ointment per application. The trial included four visits. MAIN OUTCOME MEASURES: The primary efficacy variable was the area under the curve (AUC) of the visual analogue scale (VAS) on active standardised movement values at visits 1 to 4. The secondary efficacy variables were back pain at rest using assessment by the patient on VAS, pressure algometry (pain-time curve; AUC over 5 days), global assessment of efficacy by the patient and the investigator, consumption of analgesic medication and functional impairment measured using the Oswestry disability index. RESULTS: There was a significant treatment difference between comfrey extract and placebo regarding the primary variable. In the course of the trial the pain intensity on active standardised movement decreased on average (median) approximately 95.2% in the verum group and 37.8% in the placebo group. CONCLUSIONS: The results of this clinical trial were clear-cut and consistent across all primary and secondary efficacy variables. Comfrey root extract showed a remarkably potent and clinically relevant effect in reducing acute back pain. For the first time a fast-acting effect of the ointment (1 h) was also witnessed.

Integrated effects of the vasodilating beta-blocker nebivolol on exercise performance, energy metabolism, cardiovascular and neurohormonal parameters in physically active patients with arterial hypertension.

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.

An examination of the hemodynamic and metabolic effects of carteolol during different workloads on a bicycle ergometer.

The influence of 10 mg carteolol/day on the serum concentrations of insulin, C-peptide, glucagon, free fatty acids, adrenaline, noradrenaline, blood glucose, blood lactate levels, on heart rate and systolic blood pressure was investigated during different workloads on a bicycle ergometer in a placebo-controlled randomised double-blind study involving twelve male volunteers. The subjects performed standardized increasing exercises until subjective exhaustion as well as three 40-minute endurance exercises of varying intensity, corresponding to a lactate concentration of 1.0 to 2.0 mmol/l, 2.5 to 3.5 mmol/l and more than 3.5 mmol/l in the region of the anaerobic threshold, each exercise being followed by one rest day. The most important findings are: --the ISA of carteolol is of significance for the influence on the heart rate at rest but plays a minor role with respect to the degree of reduction in the heart rate and blood pressure under exercise; --carteolol exerts a minor influence on the metabolic parameters investigated in this study. This can be partly ascribed to the pronounced ISA of carteolol. In the case of endurance exercises, which lead to blood lactate concentrations of more than 3 mmol/l, the blood glucose levels showed a tendency to decrease. However, this was not statistically significant.

[High-dose trospium chloride in therapy of detrusor hyperreflexia]. / Hochdosierte Applikation von Trospiumchlorid zur Therapie der Detrusorhyperreflexie.

The efficacy and tolerance of a high-dose treatment with trospium chloride (20 mg twice daily) were investigated in pilot studies carried out in three trial centres and involving a total of 29 patients suffering from reflex bladder due to transverse lesions of the spinal cord with paraplegia. In all three centres the trial procedure was the same. Urodynamic measurements (maximum bladder capacity, bladder compliance, maximum detrusor pressure during micturition, urinary flow and residual urine) were taken both before and after treatment with trospium chloride for a period of at least 2 weeks. In almost all patients there was a clear rise in maximum bladder capacity, a marked decrease in maximum detrusor pressure and an increase in bladder compliance. As a result the frequency of micturitions was lowered. In the majority of patients, urinary incontinence caused by detrusor hyperreflexia was brought under control through depression of detrusor activity, and urinary continence was achieved. If necessary, intermittent catheterization was continued to empty the bladder. Tolerance of the test preparation was good, and side-effects were rare and mild.

Effect of trospium chloride on urodynamic parameters in patients with detrusor hyperreflexia due to spinal cord injuries. A multicentre placebo-controlled double-blind trial.

In a multicentre placebo-controlled double-blind study 61 patients with spinal cord injuries and detrusor hyperreflexia were treated: 20 mg trospium chloride was given twice daily over a period of 3 weeks. Pre- and posttreatment urodynamic measurements demonstrated large improvements in maximum cystometric capacity (mean = 138.1 ml), decreased maximum detrusor pressure (mean = -37.8 cm H2O) and an increase in compliance (mean = 12.1 ml/cm H2O) in the treatment group. Urodynamic parameters in the placebo group remained substantially unchanged. Comparisons between the two groups revealed highly significant differences for these parameters (all, p less than 0.001). No effect on maximum flow rate and residual urine was detected in either group. The incidence of spontaneously reported side-effects was extremely low and comparable for both groups.

Effect of diacetylrhein on the phagocytosis of polymorphonuclear leucocytes and its influence on the biosynthesis of hyaluronate in synovial cells.

1. The influence of diacetylrhein on the luminol-induced chemiluminescence of zymosan-activated polymorphonuclear leucocytes (PMNL) was investigated. At a concentration of 4 x 10(-5) mol/l diacetylrhein an inhibition of about 40% was found. 2. A model for the degradation of hyaline cartilage by frustrated phagocytosis was developed, in which human polymorphonuclear leucocytes cause a release of glycosaminoglycan peptides from hyaline cartilage slices (bovine nasal septum). We observed a 20% inhibition of this release at a concentration of 10(-4) mol/l diacetylrhein. 3. Human synovial fibroblasts synthesize the glycosaminoglycan hyaluronate. As a parameter of the rate of hyaluronate synthesis we measured the incorporation of 14C-glucosamine into hyaluronate. At a concentration of 2 x 10(-4) mol/l diacetylrhein a 4-fold increase of 14C-glucosamine incorporation in the membrane fraction of the synovial cells (tryptic fraction) and a 1.6-fold elevation of glucosamine release into the medium was measured. The synovial fibroblasts show a higher (1.5-fold) glucose consumption and lactate production in the presence of diacetylrhein (2 x 10(-4) mol/l).

Antibiotics from basidiomycetes. XVII. The effect of marasmic acid on nucleic acid metabolism.

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.

Antibiotics from basidiomycetes. XIII. The alliacols A and B from Marasmius alliaceus (Jacq. ex Fr.) Fr.

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.

[Antibiotics from basidiomycetes, VI. Merulinic acids A, B, and C, new antibiotics from Merulius tremellosus and Phlebia radiata (author's transl)]. / Antibiotika aus Basidiomyceten, VI. [1] Merulinsäuren A, B und C, neue Antibiotika aus Merulius tremellosus Fr. und Phlebia radiata Fr.

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 beta-resorcylic and salicylic acid, carrying monounsaturated C17-alkyl side chains in 6-position. The merulinic acids are mixtures of the delta8'-compounds with minor amounts of the corresponding delta10'-, dehydro, and dihydro derivatives, separable only by means of HPLC. delta8'-Merulinic acid A (I) 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 microgram/ml of merulinic acid B and C or by 73 microgram/ml of merulinic acid A.

Antibiotics from Basidiomycetes. V merulidial, a new antibiotic from the Basidiomycete Merulius tremellosus Fr.

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.