Auranofin modulates gelatinase release from rat neutrophils

We have examined the effects of auranofin and some nonsteroidal anti-inflammatory drugs (NSAID) on the release of gelatinase from rat neutrophils. Two preparations of neutrophils were used, one derived from normal blood and the other from the inflamed pleural fluids of carrageenin-elicited pleurisy. Both neutrophil preparations released gelatinase in response to stimulation by serum-treated zymosan (STZ) or concanavalin A (Con A). Control, blood-derived neutrophils exposed to STZ produced more than a four-fold increase in the release of gelatinase, a response significantly inhibited by the presence of auranofin at 10(-5) and 10(-4) M. Inflamed, pleural neutrophils exposed to STZ produced a doubling in gelatinase release and this was also inhibited by auranofin at 10(-5) and 10(-4) M. The release of gelatinase by control neutrophils (no stimulation) or by neutrophils exposed to Con A was enhanced by 10(-6) M auranofin. In contrast, the NSAIDs aspirin, piroxicam, sulindac, indomethacin and naproxen had no inhibitory action on neutrophil gelatinase release. We conclude that auranofin is an effective inhibitor of gelatinase release from neutrophils and this property may represent a contributory factor assigned to the beneficial therapeutic action of gold salts.     

A rare case of nasopharyngeal angiofibroma in an elderly female

Nasopharyngeal angiofibromas occur predominantly in males in their puberty and adolescence; the incidence in other age groups and in women is exceptional. This report describes a case of a 57-year-old woman with nasopharyngeal angiofibroma presenting typical radiological findings in computed tomography, MR imaging and angiography. The tumour was successfully removed and histopathological examination confirmed the diagnosis. In 6 years follow-up the patient is free of symptoms.     

Activity of erythrocytic glycoxalases I and II in bearers of certain neoplasms

Activity of red cell glycoxalase I and glyoxalase II was investigated in 92 cancer-bearing subjects. This parameter was either higher or lower than in the control group consisting of blood donors, and changed in the course of disease. Its initial rise was followed by the fall.     

Long-term effect of antidepressant drugs and electroconvulsive shock on brain alpha 1-adrenoceptors following destruction of noradrenergic or serotonergic nerve terminals

Antidepressant drugs and electroconvulsive shock (ECS) given repeatedly increase the density of brain alpha 1-adrenoceptors. However, the mechanism involved in this effect is unknown. To study the role of presynaptic noradrenaline (NA) and 5-hydroxytryptamine (5-HT) nerve terminals in the above phenomenon we examined the density of [3H]prazosin binding sites in the rat cerebral cortex following a prolonged treatment with imipramine and citalopram (10 mg/kg po, twice daily for 14 days) or ECS (once daily for 8 days) in animals pretreated with DSP-4 (62.5 mg/kg ip) and p-chloroamphetamine (PCA, 2 x 10 mg/kg ip). In normal rats imipramine, citalopram and ECS increased the density (Bmax) of [3H]prazosin binding sites by 30, 25 and 19%, respectively. DSP-4 pretreatment abolished the effect of imipramine and citalopram but not that of ECS. Pretreatment with PCA influenced the effect of neither antidepressant drugs nor ECS. Our results indicate that the "up-regulation" of alpha 1-adrenoceptors induced by imipramine and citalopram, but not by ECS, depends on intact NA nerve terminals. They also show that the 5-HT system is not involved in the above phenomenon.     

Causal relationship between a tumour growth and the changes in histamine metabolism in tissues of sarcoma-bearing rat

The relationship between malignancy and histamine metabolism in the liver and the small intestine has been examined in sarcoma-bearing Wistar rats two weeks after subcutaneous implantation of a transplantable methylcholanthrene sarcoma Sa1828 and on the 3, 7 and 14th days after tumour extirpation. Two weeks after tumour implantation, the histamine level was increased by 100% and 50% in the liver and the small intestine, respectively. On the 3rd day after extirpation of the tumour the level of histamine had returned to the control values and remained unchanged during the next 10 days. Neither of the histamine catabolizing enzymes, diamine oxidase with a putrescine as a substrate or histamine methyltransferase were influenced by the existing tumour or by its extirpation except on the 14th day where a high increase in diamine oxidase activity was found. Some changes in the distribution of histamine metabolites suggest an involvement of an oxidative pathway of histamine catabolism as well as the aldehyde catabolizing enzymes in tumour development.     

Hepatitis C virus (HCV) genotype 1 NS5A resistance-associated variants are associated with advanced liver fibrosis independently of HCV-transmission clusters

Objectives

The aim of the study was to characterize the differences in the frequencies of NS3 and NS5A resistance-associated variants (RAVs) among Polish therapy-naive genotype 1 (G1) hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients including clustering patterns and association of RAV frequency with liver fibrosis.