BACKGROUND: Reoxygenation of hypoxic myocardium during repair of congenital heart defects results in poor ventricular function and cellular injury. Endothelin-1 (ET-1), a potent vasoconstrictor that increases during hypoxia, may suppress myocardial function and activate leukocytes. The objective was to determine whether administration of an endothelin receptor antagonist could improve ventricular function and decrease cardiac injury after hypoxia and reoxygenation. METHODS: Fourteen piglets underwent 90 minutes of ventilator hypoxia, 1 hour of reoxygenation on cardiopulmonary bypass, and 2 hours of recovery (controls). Nine additional animals received an infusion of Bosentan, an ET(A/B) receptor antagonist, (5 mg/kg per hour) during hypoxia and reoxygenation. RESULTS: Right and left ventricular dP/dt in controls decreased to 78% and 52% of baseline, respectively, after recovery (p < 0.05). In contrast, Bosentan-treated animals had complete preservation of RV dP/dt and less depression of LV dP/dt. Bosentan reduced the hypoxia and reoxygenation-induced elevation of ET-1 and iNOS mRNA at the end of recovery (p < 0.05). Bosentan-treated animals had diminished myocardial myeloperoxidase activity and lipid peroxidation compared with controls (p < 0.05). Myocardial apoptotic index, elevated by hypoxia and reoxygenation, was lower in the Bosentan-treated animals (p < 0.05). CONCLUSIONS: Endothelin-1 receptor antagonism improved functional recovery and decreased leukocyte-mediated injury after reoxygenation. The reduction in cardiac cell death might also improve long-term outcome after reoxygenation injury. 相似文献
Background : Recent studies suggest that coeliac disease (CD) is one of the commonest, life-long disorders in Italy. The aims of this multicentre work were: (a) to establish the prevalence of CD on a nationwide basis; and (b) to characterize the CD clinical spectrum in Italy. Patients and methods : Fifteen centres screened 17201 students aged 6–15 years (68.6% of the eligible population) by the combined determination of serum IgG- and IgA-antigliadin antibody (AGA) test; 1289 (7.5%) were IgG and/or IgA-AGA positive and were recalled for the second-level investigation; 111 of them met the criteria for the intestinal biopsy: IgA-AGA positivity and/or AEA positivity or IgG-AGA positivity plus serum IgA deficiency. Results : Intestinal biopsy was performed on 98 of the 111 subjects. CD was diagnosed in 82 subjects (75 biopsy proven, 7 not biopsied but with associated AGA and AEA positivity). Most of the screening-detected coeliac patients showed low-grade intensity illness often associated with decreased psychophysical well-being. There were two AEA negative cases with associated CD and IgA deficiency. The prevalence of undiagnosed CD was 4.77 × 1000 (95% CI 3.79–5.91), 1 in 210 subjects. The overall prevalence of CD, including known CD cases, was 5.44 × 1000 (95% CI 4.57–6.44), 1 in 184 subjects. The ratio of known to undiagnosed CD cases was 1 in 7. Conclusions : These findings confirm that, in Italy, CD is one of the most common chronic disorders showing a wide and heterogeneous clinical spectrum. Most CD cases remain undiagnosed unless actively searched. 相似文献
Background: Previous studies have found subtle slowing of responses in tests of addition and digit-symbol substitution during acute severe isovolemic anemia to a hemoglobin concentration of 5 g/dl in healthy unmedicated humans. In this study, the authors tested the hypothesis that such changes relate to the slowing of afferent neural traffic.
Methods: The median nerve was stimulated at the wrist in seven healthy unmedicated volunteers before and after induction of acute isovolemic anemia to a nadir hemoglobin concentration of 5.1 +/- 0.3 g/dl (mean +/- SD). Times for neural impulses to travel from the stimulus site to the brachial plexus, cervical spinal cord, and cerebral cortex were measured using somatosensory evoked potentials. Tests were repeated during acute anemia with the subject breathing oxygen. As a control for time and intrasubject variation, the testing was repeated on a separate day when anemia was not produced at times equivalent to those on the experimental day.
Results: Induced acute severe isovolemic anemia decreased nerve conduction latencies from the wrist to the contralateral cerebral cortex (i.e., to the N20 peak) by 2.3 +/- 1.6% compared with values at a mean hemoglobin concentration of 12.7 g/dl (P < 0.01). These decreased latencies were due solely to an increased peripheral conduction velocity, from the wrist to the brachial plexus (P < 0.05), and were not altered when subjects breathed oxygen (P > 0.05). Conduction velocity from the brachial plexus or cervical spinal cord to the cerebral cortex did not change with acute anemia (P > 0.05). Latencies did not differ on the control day among the times of testing (all P > 0.05), nor did they differ at baseline between the control and experimental days (all P > 0.05). 相似文献
Summary An autopsy case with clinical features of progressive parkinsonism and dementia of presenile occurrence was characterized by the following neuropathologic findings: (1) severe degeneration in the striationigral system and (2) widespread occurrence of numerous senile plaques and Alzheimer's neurofibrillary tangles in the cerebral cortex. We believe this to be a very rare case of striatonigral degeneration combined with Alzheimer's disease, because, as far as we know, only two similar cases have been reported and they had not such typical characteristics of Alzheimer's disease as ours did. In addition, in our case the biochemical examination revealed that the activity of one of the dopamine-synthesizing enzymes, tyrosine hydroxylase, was greatly decreased in the nigro-striato-pallidal system. 相似文献
The capacity of diazepam to counteract cardiac arrhythmias was studied in barbiturate-anesthetized cats treated with digitalis (i.e., deslanoside, 25 μg/kg given every 15 min iv). Diazepam dissolved in commercial propylene glycol solvent was administered in repeated doses of 10 mg iv at approximately 45-sec intervals to five animals exhibiting deslanoside-induced ventricular arrhythmias. Conversion of the arrhythmia to sinus rhythm was observed in two animals, while development of more serious rhythm changes was observed in the other three animals. One explanation for the deleterious effect seen with diazepam in the three animals is that the solvent itself may produce significant cardiocirculatory changes. To test this possibility, seven animals were intoxicated with deslanoside and the diazepam solvent was administered in doses of 1.0 ml every 45 sec until a total dose of 5.0 ml was given. In each animal, the administration of the solvent was associated with the development of more serious rhythm changes. Ventricular fibrillation (VF) developed 10.8 ± 1.6 min after the onset of deslanoside-induced ventricular tachycardia (VT). The corresponding time interval between deslanoside-induced VT and VF was 26.7 ± 5.0 min when no solvent was administered. These results indicate that propylene glycol solvent is deleterious to cardiac rhythm and should not be employed as a vehicle for antiarrhythmic drugs. 相似文献