The role of nitric oxide in dilating the fetal ductus arteriosus in rats.

Prostaglandin E is a major dilator of the fetal ductus arteriosus (DA), but the role of nitric oxide in fetal ductal dilation has not been established. We studied the effects of a potent nitric oxide synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), on the fetal DA in rats. L-NAME was injected into the dorsum of pregnant rats, and fetal DA was studied 4 h later with a rapid whole body freezing method. The inner diameters of the DA and the main pulmonary artery were measured on a freezing microtome. The inner diameter ratio of DA to main pulmonary artery (DA/PA) was 1.02+/-0.03 (mean +/- SEM; number of fetuses [n], 21) in normal near-term fetuses. The effect of prostaglandin synthesis inhibition was studied after orogastric administration of indomethacin to pregnant rats. In near-term rats on the 21st day of gestation (term, 21.5 d), a large dose of L-NAME (100 mg/kg) caused only mild ductal constriction, with DA/PA reduced to 0.83+/-0.05 (n = 20). Indomethacin (1 mg/kg) caused moderate ductal constriction, and DA/PA was decreased to 0.65+/-0.05 (n = 21). Combined administration of L-NAME (10 mg/kg) and indomethacin (1 mg/kg) caused severe ductal constriction, with DA/PA of 0.26+/-0.03 (n = 16). In preterm rats on the 19th day of gestation, a moderate dose of L-NAME (10 mg/kg) caused severe ductal constriction, with a DA/PA of 0.32+/-0.05 (n = 24). Indomethacin (1 mg/kg) alone caused only mild ductal constriction, with DA/PA 0.86+/-0.02 (n = 16). In conclusion, prostaglandin has a major role and nitric oxide has a minor role in dilating the DA in the near-term fetal rat. In contrast, nitric oxide has a major role and prostaglandin has a minor role in dilating the DA in preterm fetal rats.     

Interruption of the aortic arch associated with deletion of chromosome 22q11 is associated with a subarterial and doubly committed ventricular septal defect in Japanese patients.

OBJECTIVES: The purpose of this study was to clarify the clinical characteristics of interruption of the aortic arch associated with chromosome 22q11deletion. BACKGROUND: About half of patients with interruption of the aortic arch between the left common carotid and the left subclavian artery have deletion of chromosome 22q11. METHODS: In total, 20 patients with interruption of the aortic arch were studied with fluorescence in situ hybridization using peripheral lymphocytes and a DiGeorge syndrome chromosomal probe (Oncor N25). Cardiovascular anomalies in these patients were diagnosed by cross-sectional echocardiography and angiocardiography, and were confirmed at intracardiac repair. RESULTS: Of 13 patients with interruption between the left common carotid artery and the left subclavian artery, seven had the deletion. All 7 also showed thymic hypoplasia and hypocalcemia, together with a nasal voice and peculiar facies. Six of the seven patients had complete deficiency of the muscular outlet septum, with the defect extending to the perimembranous area. Such complete absence of the muscular outlet septum was not present in any of the patients without the deletion. CONCLUSIONS: Interruption of the aortic arch between the left common carotid and the left subclavian artery, absence of the thymus, and complete absence of the muscular outlet septum, were characteristic in Japanese patients with interruption of the aortic arch associated with deletion of chromosome 22q11.     

Brain uptake and anticancer activities of vincristine and vinblastine are restricted by their low cerebrovascular permeability and binding to plasma constituents in rat

Summary Unidirectional blood-brain barrier transfer of the lipophilic anticancer agents vincristine and vinblastine was studied in anesthetized rats, using an isolated, in situ brain perfusion technique. Drug binding to plasma constituents was also measured. Despite the high lipophilicity of these agents (the log octanol/physiological saline partition coefficient equalled 2.14 and 1.68, respectively), the cerebrovascular permeability-surface area product, PA, of vincristine in plasma was only 0.49 × 10⁻⁴ ml s⁻¹ g⁻¹ for parietal cerebral cortex, whereas that of vinblastine was too low for determination. These values are similar to those of water-soluble, poorly diffusible nonelectrolytes. The PAs were significantly higher in the absence of plasma protein, being 1.24 × 10⁻⁴ and 5.36 × 10⁻⁴ ml s⁻¹ g⁻¹, respectively. Even these values, determined by brain perfusion of protein-free buffer, were lower than would be expected from the lipophilicity of the agents. The results suggest that additional factors, such as steric hindrance and molecular charge distribution, related to the chemical and geometric structure and the large size of vincristine and vinblastine (molecular weight, 825 and 814 daltons, respectively) restrict their passage across the blood-brain barrier. As a consequence of their paradoxically low permeability at the blood-brain barrier and restrictive binding to plasma and blood constituents, doses of both agents that cause significant inhibition of extracerebral Walker 256 carcinosarcoma tumor implants in rat have no effect on tumor located in the brain.     

Early esophageal cancer: radiologic estimation of invasion into the muscularis mucosae

Background: Lymph node metastasis in squamous cell carcinoma of the esophagus is rare, and the cancer remains in the lamina propria mucosae. In cases with cancer invading the muscularis mucosae (MM), the incidence of lymph node metastasis is approximately 7%. For endoscopic treatment of mucosal cancer, it is necessary to diagnose cancer invasion into the MM. The aim of this study was to estimate cancer invasion into the MM by esophagography. Methods: One hundred ten lesions of the slightly depressed type were classified into two groups: in group A, cancer was confined to the lamina propria mucosae; in group B, the cancer invaded the MM or slightly into the submucosa. Radiologic findings of each group were studied. Results: In group A, 69% of 70 lesions showed mild depression and a smooth or undulated surface. Thickened folds were noticed in only 3%. In group B, 83% of 40 lesions showed mild or moderate depression with well-defined granules. Thickened folds were evident in 78%. In the differentiation between groups, the accuracy rates of each finding of moderate depression, well-defined granules, and thickened folds were 85%, 73%, and 90%, respectively. The overall diagnostic accuracy rate was 90%. Conclusion: Esophagography is useful for estimation of cancer invasion into the MM and, hence, the decision to apply endoscopic treatment to mucosal cancer.     

Alteration in stress distribution patterns through the elbow joint in professional and college baseball pitchers: Using computed tomography osteoabsorptiometry

Background

Long-term pitching activities change the stress distribution across the elbow joint surface in living subjects, however the influence of the different strength of stress on the stress distribution patterns remain unclear. The aims of this study were to evaluate the distribution of subchondral bone density across the elbow joint in different levels of pitchers, and to reveal the influence of the strength of stress on the elbow joint surface under long-term loading conditions of baseball pitching.