EPI-hNE4, a proteolysis-resistant inhibitor of human neutrophil elastase and potential anti-inflammatory drug for treating cystic fibrosis.

EPI-hNE4 (depelstat) is a potent inhibitor of human neutrophil elastase derived from human inter-alpha-trypsin inhibitor and designed to control the excess proteolytic activity in the sputum of cystic fibrosis patients. We analyzed its resistance to the proteolysis it is likely to encounter at inflammatory sites in vivo. EPI-hNE4 resisted hydrolysis by neutrophil matrix metalloproteases (MMPs) and serine proteases that are released from activated neutrophils in inflammatory lung secretions, including MMP-8 and MMP-9, and the elastase-related protease 3 and cathepsin G.

Beneficial effect of an inhibitor of leukocyte elastase (EPI-hNE-4) in presence of repeated lung injuries.

Persistence of alveolar neutrophil influx and activation may enhance the fibrotic process after acute lung injury. On the other hand, elastase has an antimicrobial activity and could participate in neutrophil migration, both events being critically important in host defense, explaining the controversial issue of therapeutic elastase inhibition in the setting of acute lung injury. We assessed the effect of a neutrophil elastase inhibitor, EPI-hNE-4, in single (bleomycin, 1.

Characteristics of EPI-hNE4 aerosol: a new elastase inhibitor for treatment of cystic fibrosis.

The purpose of this study was to define nebulization conditions providing delivery of aerosols of EPI-hNE4, an inhibitor of human neutrophil elastase (HNE). EPI-hNE4 was nebulized with Pari LC Star and tested at three concentrations (2.5, 5, and 10 mg/mL).

Protection against acute lung injury by intravenous or intratracheal pretreatment with EPI-HNE-4, a new potent neutrophil elastase inhibitor.

Excessive accumulation of active neutrophil elastase (NE) in pulmonary fluids and tissues of patients with cystic fibrosis (CF) is thought to act on the lungs, compromising their structure and function. The aim of this study was to investigate the in vitro and in vivo protective effect of a new, rapidly acting, potent (Ki = 5.45 x 10(-12) M and Kon = 8 x 10(6) M(-1) s(-1)) and specific human NE inhibitor, EPI-HNE-4, engineered from the Kunitz domain.

[Lethal hydrops fetalis secondary to an umbilical cord hemangioma].

We report an umbilical cord hemangioma associated with an hydrops fetalis and detected by ultrasonography at 21 week's gestation. Because of the fetal distress, a caesarean section was performed at 28 weeks'. The infant died soon after birth despite resuscitation.

Efficiency and side effects of intracavernous injections of moxisylyte in impotent patients: a dose-finding study versus placebo.

We assessed the efficiency and tolerance of the alpha-blocking agent moxisylyte in 2 double-blind studies versus placebo performed in 12 neurogenic patients with spinal cord lesions and in 61 patients presenting with either psychogenic impotence (30) or erectile dysfunction that was predominantly neither psychogenic, hormonal nor neurogenic (31). In each etiological group patients were randomized (according to latin square method) to receive 3 single doses (10, 20 and 30 mg.) of moxisylyte and a placebo.

Is the volume injected a parameter likely to influence the erectile response observed after intracavernous administration of an alpha-blocking agent?

In 12 impotent patients with spinal cord injury, we assessed the erectile response induced by intracavernous administration of 20 mg moxisylyte dissolved in 4 different volumes of solvent. We tested successively in each patient 0.4, 0.

A comparative study of controlled-release morphine (CRM) suspension and CRM tablets in chronic cancer pain.

This study compared the efficacy and the adverse effects of controlled-release morphine (CRM) suspension (SAR 213) and CRM tablets (Moscontin) in the treatment of cancer pain. This multicenter, randomized, double-blind, double-dummy, crossover study was carried out on 52 patients. Each patient received both study treatments given at an equivalent dosage of morphine during each of two 7-day periods.

[Iodized polyvidone (betadine) and prevention of postoperative infection. A multicenter study].

A multicentre study of a new preparation of povidone iodine (5% betadine) was carried out on 150 patients undergoing cataract surgery. Pre-operatively the eye was prepared by daubing the peri-ocular skin and a two-minute instillation into the conjunctival fornices. No other antiseptic was applied.

Azelastine reduces allergen-induced nasal response: a clinical and rhinomanometric assessment.

The effect of azelastine 2 mg b.d. p.