ABSTRACT
Chronic nitroglycerin (GTN) anti-ischemic therapy induces side effects such as nitrate tolerance and endothelial dysfunction. Both phenomena could be based on a desensitization/oxidation of the soluble guanylyl cyclase (sGC). Therefore, the present study aims at investigating the effects of the therapy with the sGC activator BAY 60-2770 and the sGC stimulator BAY 41-8543 on side effects induced by chronic nitroglycerin treatment. Male Wistar rats were treated with nitroglycerin (100mg/kg/d for 3.5days, s.c. in ethanol) and BAY 60-2770 (0.5 or 2.5mg/kg/d) or BAY 41-8543 (1 and 5mg/kg/d) for 6days. Therapy with BAY 60-2770 but not with BAY 41-8543 improved nitroglycerin-triggered endothelial dysfunction and nitrate tolerance, corrected the decrease in aortic nitric oxide levels, improved the cGMP dependent activation of protein kinase I in aortic tissue and reduced vascular, cardiac and whole blood oxidative stress (fluorescence and chemiluminescence assays; 3-nitrotyrosine staining). In contrast to BAY 41-8543, the vasodilator potency of BAY 60-2770 was not impaired in isolated aortic ring segments from nitrate tolerant rats. sGC activator therapy improves partially the adverse effects of nitroglycerin therapy whereas sGC stimulation has only minor beneficial effects pointing to a nitroglycerin-dependent sGC oxidation/inactivation mechanism contributing to nitrate tolerance.
Subject(s)
Guanylate Cyclase/metabolism , Nitrates/metabolism , Nitroglycerin/pharmacology , Receptors, Cytoplasmic and Nuclear/metabolism , Animals , Aorta/drug effects , Aorta/metabolism , Benzoates/pharmacology , Biphenyl Compounds/pharmacology , Enzyme Activation/drug effects , Enzyme Activation/physiology , Hydrocarbons, Fluorinated/pharmacology , Male , Morpholines/pharmacology , Organ Culture Techniques , Oxidative Stress/drug effects , Oxidative Stress/physiology , Pyrimidines/pharmacology , Rats , Rats, Wistar , Soluble Guanylyl CyclaseABSTRACT
The estimated lifetime risk of acquiring a dermatophyte infection is between 10 and 20 percent. Recognition and appropriate treatment of these infections reduces both morbidity and discomfort and lessens the possibility of transmission. Dermatophyte infections are classified according to the affected body site, such as tinea capitis (scalp), tinea barbae (beard area), tinea corporis (skin other than bearded area, scalp, groin, hands or feet), tinea cruris (groin, perineum and perineal areas), tinea pedis (feet), tinea manuum (hands) and tinea unguium (nails). To determine the best treatment approach, the physician must consider several factors: (1) the anatomic locations of the infection, (2) the safety, efficacy and cost of treatment options and (3) the likelihood that the patient will comply with treatment. Newer medications in both oral and topical forms, including imidazoles and allylamines, have greatly increased the cure rate for tinea infections. Certain types of tinea may be treated with "pulse" regimens; these innovative therapies lower treatment costs and improve patient compliance.
Subject(s)
Antifungal Agents/therapeutic use , Tinea , Administration, Cutaneous , Administration, Oral , Antifungal Agents/administration & dosage , Diagnosis, Differential , Humans , Patient Education as Topic , Teaching Materials , Tinea/diagnosis , Tinea/drug therapyABSTRACT
OBJECTIVE: The disappearance kinetic of human chorionic gonadotropin (hCG) follows a biexponential decay with a rapid initial fall followed later by a slow disappearance. This kinetic is characterised by two half-lives: an early and a late. The objective of this study was to determine if and which half-life could be used clinically to detect persistent trophoblast after conservative surgery in patients with ectopic pregnancy. DESIGN: Retrospective analysis of patients having undergone salpingostomy by laparoscopy for an ectopic tubal pregnancy between January 1990 and October 1993. SETTING: Gynaecology Department of an University Hospital. PATIENTS: 104 women with diagnosed tubal ectopic pregnancy were treated by salpingostomy performed under laparoscopy. In seven cases, persistent trophoblast was diagnosed on the basis of plateauing or increasing peripheral hCG values. MAIN RESULTS: From the individual disappearance curves of hCG we calculated the early half-life (early T0.5, from samples obtained between 0 and 48 h postsurgery) and the late half-life (late T0.5, from samples obtained between 2 and 7 days postsurgery). Late T0.5 but not early T0.5 were significantly (P<0.0001 and P=0.416 respectively) longer in women (n =7) in whom a persistent trophoblast was diagnosed. Early T0.5 was dependant on the preoperative value of hCG, whereas late T0.5 was independent. We propose to use late T0.5 as a parameter to follow ectopic pregnancies after treatment.
