Effect of synthetic porcine neuropeptide Y (NPY) on splanchnic blood flows and Exocrine pancreatic secretion in dogs

This study examined the effect of synthetic porcine neuropeptide Y on the splanchnic blood flows and the exocrine pancreatic secretion in dogs. Graded doses of neuropeptide Y (0.1–5 g/kg, intravenous) caused dose-dependent reduction of the secretin-stimulated exocrine pancreatic secretion and of the blood flows in the superior mesenteric artery, the portal vein, and the pancreatic tissue. Neuropeptide Y at 5 g/kg reduced the blood flows to 45.9±13.3% (superior mesenteric artery), 63.0±10.5% (portal vein), and 77.9±4.8% (pancreatic tissue), respectively. This dose also reduced secretin-stimulated pancreatic juice volume and CCK-8 plus secretin-stimulated protein output to 65.2±9.3 and 63.3±14.0%, respectively. This study shows a potent vasoconstrictor effect of neuropeptide Y on splanchnic vessels. Neuropeptide Y also inhibited exocrine pancreatic secretion in a significant correlation with the reduction in pancreatic tissue blood flow, which suggests that reduction in the blood flow may be one of the possible mechanisms of the inhibitory action of neuropeptide Y on exocrine secretion.This work was supported by a grant from the Ministry of Education, Japan (A-61440060).     

Terminal stage cardiac findings in patients with cardiac Fabry disease: an electrocardiographic, echocardiographic, and autopsy study

OBJECTIVES: Fabry disease is caused by deficiency of alpha-galactosidase A, and typically causes multi-organ dysfunction. Patients with manifestations limited to the heart, mainly left ventricular hypertrophy (LVH), have been reported as a disease variation. We have reported a 3% prevalence of this cardiac variant in men with LVH, which we designated 'cardiac Fabry disease'. The purposes of this study were to evaluate the terminal stage cardiac manifestations and autopsy findings in patients with cardiac Fabry disease. METHODS: We examined seven terminal stage patients with cardiac Fabry disease. During hospitalization, standard 12-lead electrocardiograms, Holter electrocardiograms, and echocardiograms were obtained. Autopsies were performed and macroscopic along with microscopic findings were evaluated. RESULTS: Six patients died of heart failure and one of ventricular fibrillation. Electrocardiograms revealed the presence of conduction abnormalities and nonsustained ventricular tachycardia. Echocardiograms and autopsy findings revealed LVH in all patients. Localized basal posterior wall thinning of the left ventricle was detected in the six patients who died of heart failure. All patients had severe left ventricular dysfunction. Histologically, myocardial cells, but not cardiac vascular endothelial cells, showed glycosphingolipid accumulation. No accumulation was observed in other organs or in systemic vascular endothelial cells. CONCLUSIONS: Severe left ventricular dysfunction with associated conduction disturbances and ventricular arrhythmias occur in patients with terminal stage cardiac Fabry disease. Furthermore, LVH is present and associated with thinning of the base of the left ventricular posterior wall. In contrast to typical Fabry disease, accumulation of glycosphingolipids was observed in myocardial cells but not in other organs.     

Epidemiologic analysis of the clinical features of Japanese patients with polymyositis and dermatomyositis

Objectives: This study aimed to investigate the clinical characteristics of polymyositis/dermatomyositis (PM/DM) in Japan by analyzing data from the nationwide registration system.

Methods: The data of the registration system in 2009 were analyzed to investigate patient numbers, sex, clinical symptoms, therapies, complications, and prognosis of PM/DM.

Results: The total number of PM/DM cases was approximately 17,000, and the female/male sex ratio was 2.7:1. Almost all patients improved as a result of therapy, but many suffered from sequelae such as muscle weakness.

Conclusions: The results characterize significant aspects of Japanese PM/DM patients. However, a further prospective survey is required to clarify the true epidemiology and natural history of PM/DM.     

Urinary Stones and Risk of Coronary Heart Disease and Stroke: the Japan Public Health Center-Based Prospective Study

Aim: Evidence is lacking about whether urinary stones are associated with the subsequent risk of cardiovascular diseases. Herein, we investigated the association between history of urinary stones and the risk of coronary heart disease (CHD) and stroke among middle-aged Japanese.Methods: This cohort study included 89,037 Japanese men and women (45–74 years) registered in the Japan Public Health Center-based prospective study. Cox proportional hazard models were used to calculate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for incident CHD and stroke among Japanese adults with a self-reported history of urinary stones compared with those without it. The following covariates were included in the regression models: age, sex, area, body mass index, and histories of hypertension, diabetes, hyperlipidemia, smoking habit, alcohol intake, and physical activity.Results: In total, 1.31% of Japanese adults reported a positive history of urinary stones. Throughout a median follow-up period of 12 years, 1.16% of Japanese adults developed CHD, and 4.96% developed stroke. No associations were detected between history of urinary stones and the risk of CHD (HR 1.04; 95% CI: 0.64–1.67), stroke (HR 0.92; 95% CI: 0.71–1.20), or total CVD (HR 0.95; 95% CI: 0.75–1.19). Younger urinary stone formers (45–59 years) tended to have a higher, though statistically insignificant, risk of CHD than older urinary stone formers (60–74 years): [(HR 1.15; 95% CI: 0.61–2.15) versus (HR 0.83; 95% CI: 0.40–1.76)], respectively.Conclusion: The history of urinary stones was shown to be not associated with the risk of CVD among Japanese adults.     

Clarification of the pathogenesis and development of clinical examination for allergic diseases

The incidence of allergic diseases has dramatically increased in recent decades in Japan; therefore, it is important to establish ways to diagnose allergic patients based on their pathogenesis and to treat them. Allergic diseases are complicated and diverse disorders in which various cells and mediators are involved; however, it is widely accepted that they are Th2-type inflammations triggered by the invasion of allergens. It is known that either IL-4 or IL-13, particularly the latter, has an important role in the pathogenesis of bronchial asthma among Th-2 type cytokines; however, it is unclear how IL-4 or IL-13 causes asthmatic phenotypes. We have been trying to address this question by using microarray analysis. We have recently found that periostin, identified as an IL-4/IL-13-inducible gene by microarray analysis, is a novel component of subepithelial fibrosis of bronchial asthma. This finding is important to demonstrate the significance of IL-4 and/or IL-13 as a therapeutic target to inhibit fibrosis in bronchial asthma. Furthermore, it is also important to establish a way to diagnose allergic patients in which IL-4 or IL-13 is dominantly involved, and to apply the developing IL-4/IL-13 inhibitors to these patients. In this article, we show how we are addressing this issue.     

Female reproductive factors and risk of all-cause and cause-specific mortality among women: The Japan Public Health Center–based Prospective Study (JPHC study)

Purpose

We investigated the association between reproductive history and mortality from all and major causes among Japanese women.