Effect of inhaled furosemide and torasemide on bronchial response to ultrasonically nebulized distilled water in asthmatic subjects.

Inhaled furosemide has been shown to reduce the bronchoconstriction induced by several indirect stimuli, including ultrasonically nebulized distilled water (UNDW). Because the protective effect could be due to the inhibition of the Na(+)-2Cl(-)-K+ cotransport system of bronchial epithelium, we have compared the protective effect of inhaled furosemide with that of inhaled torasemide, a new and more potent loop diuretic, on UNDW-induced bronchoconstriction in a group of 12 asthmatic subjects. UNDW challenge was performed by constructing a stimulus-response curve with five increasing volume outputs of distilled water (from 0.5 to 5.2 ml/min) and the bronchial response expressed as the provocative output causing a 20% fall in FEV1 (PO20UNDW). On different days, each subject inhaled an equal dose (28 mg) of furosemide and torasemide in a randomized, double-blind, placebo-controlled study 5 min prior to an UNDW challenge. Furosemide and torasemide had no significant effect on resting lung function. The geometric mean value of PO20UNDW measured after placebo was 1.73 ml/min. This was significantly lower than that recorded after furosemide (4.25 ml/min; p < 0.025), but not after torasemide (3.05 ml/min; p = 0.07). Inhaled furosemide totally blocked bronchial response to UNDW in five subjects. In two of five subjects the response was also blocked by inhaled torasemide. A remarkable increase in diuresis was noted only after torasemide in most subjects. We conclude that inhaled furosemide has a better protective effect than does inhaled torasemide against UNDW-induced bronchoconstriction. However, the protective effect of furosemide is variable, with some asthmatic patients showing no change in bronchial response to UNDW.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduction in transmission of hepatitis C after the introduction of a heat-treatment step in the production of C1-inhibitor concentrate

BACKGROUND: The transmission of viral infections via protein concentrates made from a large pool of plasma depends on the selection of donors, fractionation process, and virucidal methods. To date, no data are available on the infectivity risk of plasma concentrates of the inhibitor of the first component of complement (C1-INH). STUDY DESIGN AND METHODS: The prevalence of blood-borne viral infections and levels of transaminases were evaluated in patients treated with a large- pool plasma concentrate of the inhibitor of C1-INH before and after the introduction of virucidal methods. The study included 85 patients with hereditary angioedema and 4 with acquired angioedema. The patients were divided into three groups: 1) 48 untreated patients; 2) 22 patients treated with non-virus-inactivated C1-INH concentrates; and 3) 19 patients treated with virus-inactivated concentrates. Serum samples obtained at various times after the infusion of concentrate were assayed for alanine amino-transferase and tested for hepatitis B surface antigen and antibodies to hepatitis C virus (anti-HCV) and human immunodeficiency virus (anti-HIV); anti-HCV-negative subjects exposed to the concentrate were also tested for HCV RNA. RESULTS: Prevalences of HCV infection and elevated alanine aminotransferase are significantly lower in patients treated with virus-inactivated concentrates than in those exposed to non-virus-inactivated concentrates. No patients were anti-HIV positive. CONCLUSION: This study suggests that C1-INH concentrates transmitted HCV, but that the virucidal methods adopted are effective in reducing the infectivity.     

The effect of adrenoceptor agonists and antagonists on histamine-induced wheal response in the skin of normal subjects and atopic patients

The role of the adrenergic mechanism in the pathogenesis of atopic diseases is controversial. Recent experimental and clinical reports have suggested that beta-2 adrenergic stimulation impairs and beta-2 adrenergic blockade enhances the histamine effect on vascular permeability. This led us to study the effect of salbutamol and of propranolol on histamine-induced cutaneous response in 13 healthy subjects and in 16 patients with allergic oculo-rhinitis. Both in normal subjects and in atopic patients salbutamol attenuated the whealing response to histamine and the protective effect of salbutamol was counteracted by propranolol. The ability, however, of salbutamol to inhibit histamine-induced response was significantly reduced in 50% of atopic patients. These findings suggest that beta-2 adrenergic hyporesponsiveness is present in some allergic patients.     

NK and NKT-like cells in granulomatous and fibrotic lung diseases

Clinical and Experimental Medicine - Background The pathogenetic and regulatory roles of natural killer (NK) and natural killer T-like cells in interstitial lung diseases (ILDs), fibrotic and...     

Effect of oral losartan potassium administration on intraocular pressure in normotensive and glaucomatous human subjects

The effects of the type 1 angiotensin II receptor antagonist Losartan potassium on intraocular pressure (IOP) were studied. Four groups of subjects were analysed: group A, ten controls; group B, ten patients with essential arterial hypertension and with IOP within the normal range; group C, ten patients with primary open angle glaucoma (POAG), but without essential arterial hypertension; group D, ten patients with arterial hypertension and POAG. The study design was held in a randomized crossover double-blind fashion. Systolic and diastolic arterial pressure, heart rate, pupil diameter, IOP and total outflow facility were recorded at baseline and at 1 hr intervals up to 6 hr, following the oral administration of 50 mg of Losartan potassium and/or placebo. The alternative treatment was given a week later. Drug administration significantly reduced IOP in all subjects. No variation in heart rate and pupil diameter was observed during the follow-up period. Blood pressure dropped only in arterial hypertensive patients (groups B and D). Total outflow facility increased significantly in all groups. Placebo did not induce any variation in all groups. These findings demonstrate that the mechanism by which Losartan potassium reduces intraocular pressure is not mediated by a decrease in blood pressure, but rather it is more specific, confirming the role of the renin-angiotensin system also in the regulation of intraocular pressure in man.     

Myopia onset and progression: can it be prevented?

Myopia is the commonest ocular abnormality and the high and growing prevalence of myopia, especially but not only in Asian populations, as well as its progressive nature in children, has contributed to a recent surge in interest. Such worldwide growing prevalence seems to be associated with increasing educational pressures, combined with life-style changes, which have reduced the time that children spend outdoors. Highly nearsighted people are at greater risk for several vision-threatening problems such as retinal detachments, choroidal neovascularization, cataracts and glaucoma, thus the potential benefits of interventions that can limit or prevent myopia progression would be of remarkable social impact. Our understanding of the regulatory processes that lead an eye to refractive errors is undoubtedly incomplete but has grown enormously in the last decades thanks to the animal studies, observational clinical studies, and randomized clinical trials recently published. In this review we assess the effects of several types of life-style and interventions, including outdoor activities, eye drops, undercorrection of myopia, multifocal spectacles, contact lenses, and refractive surgery on the onset and progression of nearsightedness.     

Effect of tecarfarin,a novel vitamin K epoxide reductase inhibitor,on coagulation in beagle dogs

Background and purpose:

Tecarfarin (ATI-5923) is a novel vitamin K epoxide reductase inhibitor that is metabolized by esterase (mainly human carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The objective of this study was to test and compare the efficacy of tecarfarin with that of warfarin, when administered either intravenously or once a day orally, to produce stable anticoagulation in beagle dogs.

Experimental approach:

Effects on coagulation were assessed by measuring the activity levels of Factor VII and Factor X and thromboplastin-induced coagulation times, reported as prothrombin time (PT).

Key results:

Continuous intravenous infusions and oral administration of tecarfarin and warfarin caused a dose-dependent decrease in activity of Factor VII and Factor X, and associated increase in PT. Intravenous fresh frozen canine plasma or subcutaneous vitamin K₁ treatment reversed the anticoagulant effects of orally administered tecarfarin. Consistent with the inhibitory effects of amiodarone on CYP2C9, co-administration of amiodarone significantly increased the anticoagulation effect of warfarin and plasma warfarin concentrations. In contrast, amiodarone had no effect on the anticoagulation induced by tecarfarin or tecarfarin plasma concentrations in this model.

Conclusions and implications:

Overall, the data presented herein indicate that tecarfarin, via a vitamin K-dependent mechanism, causes changes in key parameters of haemostasis in beagle dogs that are consistent with effective anticoagulation. Compared to warfarin it has a decreased potential to interact metabolically with drugs that inhibit CYP450 enzymes and, therefore, may offer an improved safety profile for patients.