Acute Moderate Hypoxia in Conscious Rabbits: Effect on Hepatic Cytochrome P450 and on Reactive Oxygen Species

This study aimed to document whether acute moderate hypoxia modifies the amount and activity of hepatic cytochrome P450 and in addition, induces changes in the production or the ability to neutralize oxygen reactive species (ORS). Rabbits were exposed to a low partial pressure of oxygen (12%) for 8 or 24 h, killed, and the amount and activity of cytochrome P450, lipid peroxidation, microsomal chemiluminescence and enzymatic scavenger activity were assessed in the liver. After 8 h of hypoxia, total amount but not the activity of cytochrome P450 was decreased, although after 24 h of hypoxia, both the amount and the activity of cytochrome P450 were decreased. Hypoxia for 8 h increased the activity of glutathione peroxidase. However, after 24 h of hypoxia, lipid peroxidation, microsomal chemiluminescence and superoxide dismutase activity were increased, while hepatic glutathione and glutathione peroxidase activity were reduced, modifications that suggest an enhanced presence of ORS. In in-vitro studies, an ORS generating system reduced the activity of cytochrome P450 and enhanced lipid peroxidation of hepatic microsomal membranes, supporting the view that ORS can impair cytochrome P450. The results of the present study show that hypoxia induces changes in the amount and activity of cytochrome P450, as well as in the production or the ability to neutralize ORS, and that these changes are time-dependent.     

The "Long-Sheath" Technique in Percutaneous Aortic Balloon Valvuloplasty

A new 100 cm long 16.5 French valvuloplasty introducer was used in 12 consecutive patients (mean age 73 years, five males and seven females) undergoing aortic balloon valvuloplasty for severe aortic stenosis. The long-sheath was introduced into the ascending aorta along the stiff part of an exchange guidewire. The valvuloplasty procedure, which included a complete diagnostic catheterization in three patients, lasted 113 ± 47 min (211 ± 81 min in the previous 18 procedures performed with a conventional approach, P < 0.05). Introduction of balloon catheters (3 × 12 mm trefoil balloon in the 12 cases and 2 × 19 mm bifoil balloon in 2 of these cases) was possible in all patients and an increased stability of the balloon during inflation was observed. No systemic embolization or vascular complications occurred at the puncture site. The long-sheath technique appears to be a valuable adjunct for aortic valvuloplasty in that it provides easier and quicker access for even the largest balloons and additional support and stability during balloon inflation. In our experience, this reduced the practical difficulties and the duration of the procedure.     

Cross–reactivity of antibody against an epitope of the Plasmodium falciparum second merozoite surface antigen

Monoclonal antibodies directed against the 51 kD merozoite surface antigen of Plasmodium falciparum also bind to other antigens within the infected cell. The sizes of these cross-reacting antigens have been characterized. Immunofluorescence due to the reaction of one of the monoclonal antibodies with these cross-reacting antigens was localized in the intra-erythrocytic parasite and in granules in the infected red cell cytoplasm. This immunofluorescence could be distinguished from the merozoite surface antigen in parasite lines with a variant serotype of the merozoite surface antigen which fails to react with the monoclonal antibodies. It was found that the in-vitro growth inhibition caused by the presence of one of the monoclonal antibodies, 8G10/48, was dependent on the expression of the corresponding serotype of merozoite surface antigen, a finding consistent with the inhibitory effect of this antibody being primarily directed against the merozoite surface antigen and not the cross-reacting antigens. Analysis of the frequency at which epitopes occur suggests that such cross-reacting proteins will be commonly seen in malaria, without the need to postulate a selective advantage for such cross-reacting specificities.     

Immunohistochemical Localization of Gap Junction Protein Channels in Hamster Sinoatrial Node in Correlation with Electrophysiologic Mapping of the Pacemaker Region

Gap Junction Proteins in the Sinoatrial Node. Introduction: Gap junction proteins are thought to form the low resistance pathways that connect neighboring cells within the sinoatrial node, and to mediate pacemaker synchronization.
Methods and Results: We have carried out microelectrode mapping experiments of the hamster sinoatrial region to localize the primary pacemaker area for subsequent light, electron, and immunofluorescence microscopic studies aimed at testing the hypothesis that the major cardiac gap junction protein (connexin43) is present in such an area. The site of earliest activation is unifocal and the pattern of activation, obtained In multiple sequential microelectrode recordings of the Sinoatrial region, is qualitatively similar to that previously described for other species. However, quantitatively, the impulse transmission time from the primary pacemaker area to the crista (sulcus) terminal's in the hamster sinoatrial node is about 50% briefer than that of the guinea pig and five times faster than that of the rabbit. Immunolocalization studies in the hamster sinoatrial node using anti-connexin43 antisera demonstrated specific staining at the areas of cell-to-cell apposition and suggested that the apparently high degree of electrical coupling in this tissue is the result of abundant connexin43 expression. The immunofluorescence data were supported by light microscopic studies, which demonstrated the typical morphologic characteristics of sinus nodal cells in the pacemaker area. In addition, an electron microscopic study of the sinoatrial region revealed the presence of gap junctions in the junctional complex at areas of cell-to-cell contact.
Conclusion: Our results demonstrate that cells in the sinoatrial region of the hamster heart are electrically well coupled and strongly suggest that such coupling is mediated by gap junctional channels formed by connexin43.     

Peptic ulcer in the elderly—a double-blind, short-term study comparing nizatidine 300 mg with ranitidine 300 mg

This was a randomized, double-blind, multicentre, short-term study comparing ranitidine and nizatidine at the standard dosages of 300 mg at bedtime. In 49 centres in Italy, all peptic ulcer patients aged over 65 years and with endoscopically documented acute disease were considered eligible for the study. Clinical check-ups were repeated every 3 weeks, while the endoscopic and biochemical assessments were scheduled at 6 and (in unhealed patients) 12 weeks. Statistics: chi-squared test, Fisher's exact test, Student t-test for unpaired data. The study included 170 duodenal ulcer and 75 gastric ulcer patients. Of these, 83/17 duodenal ulcer and 38/75 gastric ulcer patients were treated with nizatidine 300 mg and the remainder with ranitidine 300 mg. The groups were well-matched for common clinical data. Eight patients dropped out. Healing rates at 6 and 12 weeks were 81.9% and 91.5% for nizatidine-treated duodenal ulcer patients versus 78.1% and 94.2% for ranitidinetreated duodenal ulcer cases (P: N.S.); 6 and 12-week healing rates were 76.3% and 89.5% for nizatidinetreated gastric ulcer patients versus 67.6% and 83.8% for ranitidine-treated gastric ulcer patients (P: N.S.). No slow healing risk factors were found. Only minor adverse events were registered. In conclusion: ranitidine 300 mg and nizatidine 300 mg both proved effective and safe in the treatment of acute peptic ulceration in the elderly.     

Characterization of Conduction in the Ventricles of Normal and Heterozygous Cx43 Knockout Mice Using Optical Mapping

INTRODUCTION: Gap junction channels are important determinants of conduction in the heart and may play a central role in the development of lethal cardiac arrhythmias. The recent development of a Cx43-deficient mouse has raised fundamental questions about the role of specific connexin isoforms in intercellular communication in the heart. Although a homozygous null mutation of the Cx43 gene (Cx43-/-) is lethal, the heterozygous (Cx43+/-) animals survive to adulthood. Reports on the cardiac electrophysiologic phenotype of the Cx43+/- mice are contradictory. Thus, the effects of a null mutation of a single Cx43 allele require reevaluation. METHODS AND RESULTS: High-resolution video mapping techniques were used to study propagation in hearts from Cx43+/- and littermate control (Cx43+/+) mice. Local conduction velocities (CVs) and conduction patterns were quantitatively measured by determining conduction vectors. We undertook the characterization of ECG parameters and epicardial CVs of normal and Cx43+/- mouse hearts. ECG measurements obtained from 12 Cx43+/+ and 6 Cx43+/- age matched mice did not show differences in any parameter, including QRS duration (14.5 +/- 0.9 and 15.7 +/- 2.3 msec for Cx43+/+ and Cx43+/-, respectively). In addition, using a sensitive method of detecting changes in local CV, video images of epicardial wave propagation revealed similar activation patterns and velocities in both groups of mice. CONCLUSION: A sensitive method that accurately measures local CVs throughout the ventricles revealed no changes in Cx43+/- mice, which is consistent with the demonstration that ECG parameter values in the heterozygous mice are the same as those in wild-type mice.