Immunohistochemical study of the innervation of pulmonary vessels and smooth muscles in the respiratory tract of two frog species.

The innervation of the respiratory tract of amphibians is still poorly understood. Therefore, the respiratory tracts of the frogs Rana esculenta and Discoglossus pictus have been investigated in order to describe non-adrenergic non-cholinergic (NANC) and adrenergic innervation, and the localization of neuromediators that are possibly involved. Immunohistochemical staining of many bioactive substances was found in neuroepithelial cells of the buccopharynx, larynx, lung septa, nerves and neurons throughout the airway system. The findings indicate the occurrence of vasoactive intestinal peptide (VIP)-immunopositive nerve fibers in fibromuscular septa and the vasculature, nitrergic innervation of the large pulmonary veins showing a plexus of nNOS-immunopositive nerve fibers that also innervate the lung wall and the localization of neuronal nitric oxide synthase (nNOS) in neurons in the lung wall. In addition, laryngeal blood vessels and small arteries in the wall of septa that form capillary networks are supplied by enkephalin-immunopositive nerve terminals. We conclude that the airway system of the two frog species studied is innervated by a parasympathetic NANC system. Adrenergic innervation was also found that was immunostained for tyrosine hydroxylase. Adrenergic fibers were mainly present in muscles in septal edges, arteries present in septa and the wall of the lung. It is suggested that nNOS-positive and leu-enkephalin-positive neurons mediate vasodilation via the release of NO, but the nature of the NANC innervation remains obscure. Despite the many pharmacological studies of the lungs of amphibians, the physiological role of pulmonary autonomic innervation remains poorly understood.

Natural leukocyte interferon alfa for the treatment of chronic viral hepatitis in heart transplant recipients.

BACKGROUND: A more rapid and aggressive course of hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related infection in organ transplant recipients has been described. Interferon alfa is the most accepted drug for treating HBV and HCV chronic infections. However, the use of interferon alfa-N3 has been contraindicated in heart transplant (HTx) recipients because of the hypothesized greater risk of triggering acute cellular rejection. The aim of this clinical pilot study was to evaluate tolerability, safety, and efficacy of natural leukocyte interferon alfa in the treatment of chronic HBV and HCV in HTx recipients. METHODS: Seven HTx recipients were enrolled in the study: two with HBV, four with HCV, and one with combined HBV-HCV chronic infection. The patients had a mean follow-up after heart transplantation of 8.5+/-3 years, before starting interferon alfa-N3 treatment at a dose of 6 MU three times per week, intramuscularly for 12 months. RESULTS: All patients completed the treatment with no major side effects. No unexpected episodes of acute cellular rejection were observed during the treatment. Mean aminotransferase serum levels were significantly lower than before transplantation at 3 (P<0.03), 6 (P<0.02), and 12 (P<0.02) months of treatment and at the 12-month follow-up (P<0.02). A complete and sustained response was achieved in all subjects with HBV-related chronic hepatitis, whereas sustained virologic response was observed in one of four HCV patients. CONCLUSIONS: The preliminary data emerging from our study indicate that natural leukocyte interferon alfa-N3 can be safely administered in HTx recipients with chronic HBV or HCV viral hepatitis. Further studies with larger numbers of patients are needed to assess the efficacy of interferon alfa-N3 on HCV virologic response.