Quality of life in chronic NSAID users: a comparison of the effect of omeprazole and misoprostol

OBJECTIVE: To compare the impact on quality of life (QoL) of omeprazole and misoprostol during healing, and omeprazole, misoprostol, and placebo during maintenance treatment in chronic NSAID users with NSAID-associated gastroduodenal lesions. METHODS: Validated baseline and follow-up QoL questionnaires were completed by 610 patients (healing: after 4/8 weeks; maintenance: after 6 months). RESULTS: Patients with arthritis being treated with NSAIDs have a poor QoL. Rheumatoid arthritis causes more joint problems and physical mobility limitations than osteoarthritis. Chronic NSAID use causes heartburn and dyspepsia. QoL improved on both treatments (about equally on two general QOL scales), but omeprazole relieved gastrointestinal symptoms more than misoprostol, particularly reflux, abdominal pain and indigestion symptoms. During maintenance, both treatments maintained QoL, but misoprostol induced diarrhoea. CONCLUSION: QoL in arthritis patients on chronic NSAID treatment is destroyed. Omeprazole is superior to misoprostol for relief and prevention of NSAID-associated gastrointestinal symptoms allowing continued NSAID treatment without compromising the patients' QoL.     

The influence of the polyphenols of cider on plasmin and plasminogen activators

Preliminary findings suggested that the inhibitory activity on fibrinolysis produced by most varieties of cider is due to their content of polyphenols. In particular, the inhibitory activity co-eluted with the brown coloration on gel filtration, was removed by adsorption with polyvinylpyrrolidine, and was greatly reduced in a type of cider with a low concentration of phenolic compounds. The individual polyphenols of apple juice and ciders were examined for their ability to inhibit tissue activator, urokinase and plasmin. Neither phloridzin nor chlorogenic acid had any inhibitory activity at concentrations of 500 micrograms/ml while epicatechin had only a slight inhibitory effect at this concentration. The procyanidin fractions were markedly inhibitory on urokinase-induced clot lysis, the amidolytic activity of plasmin and on the fibrinolytic activities of plasmin, urokinase and tissue activator on fibrin plates: inhibition was noted at concentrations as low as 0.25 micrograms/ml. The order of inhibition was polymer greater than oligomer greater than trimer greater than dimer.     

Transformation of human androgen receptors to the deoxyribonucleic acid-binding state

The transformation of [3H]dihydrotestosterone-androgen receptor complexes to the nuclear binding state was studied in fibroblasts cultured from human genital skin, using binding of the androgen-receptor complex to DNA-cellulose as a measure of transformation. Transformation of cytosolic dihydrotestosterone-receptor complexes proceeded slowly at 0 C, and heating to 25 C caused rapid transformation that was essentially complete within 15 min. Sodium molybdate (up to 10 mM) slowed the rate of transformation in a concentration-dependent fashion; low concentrations of molybdate (0.5-1 mM) prevented transformation at 0 C, but transformation of up to 70% of the total cytosolic hormone-receptor complexes could be achieved in the presence of high concentrations of molybdate by appropriately prolonged heating at 25 C. Molybdate appeared to exhibit a dual effect, increasing the total amount of androgen-receptor complex recoverable in cytosol and prolonging the time course of heat-induced transformation. Treatment of cytosolic dihydrotestosterone-receptor complexes with 0.5 M NaCl caused a degree of transformation similar to that seen after heat treatment but was unaffected by 10 mM molybdate. Transformation was accompanied by disappearance of the 7S form of the receptor on sucrose density gradients, but there was no reciprocal increase in a smaller size binding moiety on low ionic strength sucrose density gradients. The heat-transformed receptor could be detected, however, as a 3S binding peak on gradients containing 0.3 M NaCl, suggesting that transformation was accompanied by a structural alteration of the hormone-receptor complex.     

Formation of 5alpha-androstane-3alpha,17beta-diol by normal and hypertrophic human prostate.

The 3-keto reduction of [1,2-3H]dihydrotestosterone to 3alpha- and 3beta-androstanediols was assessed in homogenates of 40 prostates obtained either at surgery or at medicolegal autopsy from men who had died suddenly. Formation of both androstanediols was demonstrable in cytosol and in microsomes, and both NADH and NADPH were effective cofactors for the two reactions. Formation of the two steroids was not influenced by storage of the gland for up to 8 h prior to processing. When NADPH was cofactor, the formation of 3alpha- and 3beta-androstanediol was significantly higher in microsomes and cytosol from hypertrophic than from normal glands.     

Bmp15 mutations and ovarian function

BMP15, also known as growth and differentiation factor 9B (GDF9B), is a member of the transforming growth factor beta superfamily (TGFbeta) which in humans, rodents and sheep is expressed exclusively in the oocyte. BMP15 is closely related to GDF9, another oocyte-specific member of this superfamily which has been shown to be essential for early ovarian folliculogenesis. Inactivation of the BMP15 gene in mice has shown only minor effects on fertility. However, Inverdale and Hanna lines of sheep carry naturally occurring mutations in BMP15 which highlight differences in the action of this gene between mice and other mammals. Sheep which are heterozygous show an increase in ovulation rate whereas homozygotes are infertile. The granulosa cell receptor which mediates the BMP15 response has not yet been identified, but the discovery that a point mutation in the BMP1B receptor in Booroola sheep is responsible for increased ovulation rate highlights the importance of the TGFbeta signalling molecules in early folliculogenesis.     

Clinical, haemodynamic, and antiarrhythmic effects of long term treatment with amiodarone of patients in heart failure

Twenty two patients with heart failure were studied in a double blind crossover trial to compare amiodarone (200 mg/day) with placebo. Each agent was given for three months. Extrasystoles and complex ventricular arrhythmias were common during ambulatory electrocardiographic monitoring and during exercise testing at entry to the study. Breathlessness and tiredness as assessed by visual analogue scores and duration of treadmill exercise did not become worse during amiodarone treatment. During the placebo and amiodarone phases of the study left ventricular ejection fraction and cardiac index determined by first pass radionuclide ventriculography were similar, both at rest and during upright bicycle exercise. Exercise induced ventricular tachycardia was abolished and simple and complex ventricular arrhythmias observed on 24 hour ambulatory monitoring were greatly diminished during amiodarone treatment. Three patients died, all suddenly, during the placebo phase. In two patients amiodarone was withdrawn after a further myocardial infarction in one and a worsening of symptoms of ventricular arrhythmia in the other. In contrast with other antiarrhythmic agents amiodarone is effective in suppressing ventricular arrhythmias in heart failure without causing adverse haemodynamic effects. Because frequent ventricular arrhythmias are known to be associated with a poor prognosis in heart failure, these data suggest that amiodarone may improve the poor prognosis in patients with heart failure.     

The effects of a prostaglandin endoperoxide analogue on canine gastric acid and mucus secretion

The effects of U-46619, a stable analogue of the prostaglandin endoperoxide PGH2, were studied on canine gastric acid secretion, gastric mucosal blood flow, and secretion of mucus into gastric juice and compared to those of PGE2. U-46619 was approximately four and three times as potent as PGE2 in inhibiting acid secretion and stimulating mucus secretion, respectively. When infused at a low dose, U-46619 inhibited acid secretion directly without causing a decrease in the ratio of mucosal blood flow to volume rate of secretion (R), this effect being similar to that observed for PGE2. However, unlike PGE2, U-46619 when administered in a higher dose caused a decline in R while decreasing acid secretion and mucosal blood flow, suggesting a primary restriction of blood flow. The antisecretory effects of arachidonic acid may be due in part to the endogenous formation of prostaglandin endoperoxides as opposed solely to prostaglandin formation. Considering the antisecretory and mucogenic actions of U-46619, nontoxic analogues of prostaglandin endoperoxides may be of value as antiulcer agents.