Hepatitis C Virus Infection is Highly Correlated with Hepatocellular Apoptosis and Transforming Growth Factor‐β1 MRNA Expression in Patients with Chronic Hepatitis C

Introduction:  The cellular phases (granulation, reepithelialization, and dermal remodelling) of the healing process involve many cell types. Fibroblasts and myofibroblasts are the key cells in granulation tissue formation and wound contraction.
Objective:  To compare the effects on cultured human fibroblasts of a new nonadhesive lipidocolloid wound dressing, Urgotul^®, with five other wound dressings including impregnated gauzes and some other modern wound dressings.
Method:  Cultures in monolayer were used to study the morphology and growth of fibroblasts. The Bell model of cultured dermis equivalents was used to investigate myofibroblast differentiation. These cultures were labelled α‐SM actin and F‐actin.
Results:  Two of the tested dressings induced cytotoxic effects on the fibroblasts. They were found to inhibit cell growth (greater than 60%) and to disturb cell shape and cytoskeletal differentiation. Urgotul^® and the remaining three dressings showed no effect on proliferation. However some of them modified fibroblast morphology and affected F‐actin distribution.
Conclusion:  Depending on their nature and components, wound dressings may respect or affect in vitro fibroblast behaviour (proliferation, morphology, and α‐SM actin and F‐actin distribution). The observed in vitro findings require further investigations.     

Impairment of Cardiac β-Adrenoceptor Cellular Signaling by Decreased Expression of Gsα in Septic Rabbits

Background: Abnormalities in the [beta]-adrenergic control of cardiac function play a role in the pathogenesis of several disease states. Because circulatory failure in patients with septic shock is known to be less responsive to catecholamines, we investigated whether the [beta]-adrenoceptor-linked signal transduction mechanisms are altered in the heart of a septic animal model.

Methods: Rabbits were rendered endotoxemic by an intravenous injection of 100 [mu]g/kg Escherichia coli lipopolysaccharide. Three and 6 h later, the myocardial tissues were used for the experiments.

Results: The positive inotropic response to isoproterenol was significantly impaired in papillary muscles isolated from septic rabbits compared with those from controls. The impaired inotropic responsiveness to isoproterenol was not prevented by the nitric oxide synthase inhibitor NG-nitro-l-arginine, indicating no involvement of nitric oxide overproduction. Adenylate cyclase activity stimulated with isoproterenol and 5'-guanylyl imidodiphosphate was markedly reduced in septic myocardium. The contractile and adenylate cyclase responses to colforsin daropate, a direct adenylate cyclase activator, were unaffected by sepsis. Radioligand binding experiments with (-)[125I]iodocyanopindolol revealed no significant alteration in myocardial [beta]-adrenoceptor density or affinity in sepsis. Determination of cardiac Gs[alpha] level by Western blotting showed a reduction of approximately 50% in sepsis. The relative content of Gs[alpha] messenger RNA in septic myocardium also was reduced from the control level by about 50%, as determined by Northern blot analysis. Little change was found in protein and messenger RNA levels of Gi[alpha] in septic myocardium.     

Attenuation of Ascending Nociceptive Signals to the Rostroventromedial Medulla Induced by a Novel α2-Adrenoceptor Agonist, MPV-2426, following Intrathecal Application in Neuropathic Rats

Background: In the current study, the potency and spread of the antinociception induced by MPV-2426, a novel [alpha]2-adrenoceptor agonist, was characterized in neuropathic and non-neuropathic animals.

Methods: Neuropathy was induced by unilateral ligation of two spinal nerves in the rat. After lumbar intrathecal or systemic administration of MPV-2426, thermally and mechanically evoked responses of nociceptive neurons of the rostroventromedial medulla were recorded during pentobarbitone anesthesia. To obtain a behavioral correlate of neurophysiologic findings, nocifensor reflex responses evoked by thermal and mechanical stimuli were assessed in unanesthetized neuropathic and control animals.

Results: After intrathecal administration, MPV-2426 and dexmedetomidine produced a dose-related antinociceptive effect, independent of the submodality of the noxious test stimulus or the pathophysiologic condition. This antinociceptive effect was spatially restricted to the inputs from the lower half of the body, and it was reversed by atipamezole, an [alpha]2-adrenoceptor antagonist. After systemic administration in non-neuropathic animals, MPV-2426 had no antinociceptive effect on responses to rostroventromedial medulla neurons, whereas systemically administered dexmedetomidine produced a dose-related suppression of nociceptive signals to the rostroventromedial medulla, independent of the site of test stimulation. In a behavioral study, intrathecal MPV-2426 produced a dose-dependent suppression of nocifensor responses evoked by noxious mechanical or heat stimuli, whereas systemic administration of MPV-2426 had no effects.