21 research outputs found
Mao-to Prolongs the Survival of and Reduces TNF-α Expression in Mice with Viral Myocarditis
Goal of this study was to evaluate effects of Mao-to on development of myocarditis induced by encephalomyocarditis (EMC) virus in mice. Mice were randomly divided into five groups. Group N included uninfected controls (n = 18), while group A, B and C underwent intraperitoneal injection of EMC virus. Group A was administered oral saline from day 0 to day 4. Group B was administered oral Mao-to (500 mgâ1 kgâ1 dayâ1) from day 0 to day 4. Group C was administered Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10. Treated mice were followed for survival rates during 2 weeks after infection. Body weight (BW) and organ weights including heart (HW), lungs, thymus and spleen were examined on days 4, 6 and 14. Survival rate of group C (36.4%) was significantly improved compared with group A, B or D (0% of each, P < 0.05). HW and HW/BW ratio in group C was significantly (P < 0.05) lower than those in group A, B or D. Viral titers of hearts were significantly different among groups A, B and C. Cardiac expression in tumor necrosis factor-α (TNF-α) was significantly reduced in group C in comparison with group A, B or D on day 6 by immunohistochemical study. Administration of Mao-to starting on day 2 improves mortality resulting from viral myocarditis in mice with reduced expression of cardiac TNF-α. These findings suggest that timing of Mao-to is crucial for preventing cardiac damage in mice with viral myocarditis
Association of severe hypertension with pneumonia in elderly patients with acute ischemic stroke
Pneumonia is one of the most frequent complications in elderly patients with acute ischemic stroke. Although severe hypertension is often observed in the early phase of acute stroke, there are few studies of acute hypertension as a factor influencing the incidence of stroke-associated pneumonia (SAP) in elderly subjects with acute ischemic stroke. To assess the association of acute phase blood-pressure elevation with the incidence of SAP, we compared 10 elderly patients with acute ischemic stroke complicated with severe hypertension (â©Ÿ200/120âmmâHg) with 43 patients with moderate hypertension (160â199/100â119âmmâHg), as well as with 65 control normotensive or mildly hypertensive (<160/100âmmâHg) controls on admission. Data were collected on known risk factors, type of ischemic stroke and underlying chronic conditions. The significance of differences in risk factors was analyzed using univariate and multivariate comparisons of 38 SAP cases and others, 8 SAP death cases and others, and 28 patients with poor outcome associated with in-hospital death or artificial feeding at discharge and others. After adjustment for potential confounding factors, the relative risk estimates for SAP, SAP death and poor outcome were 2.83 (95% confidence interval 1.14â7.05), 5.20 (1.01â26.8) and 6.84 (1.32â35.4), respectively, for severe hypertension relative to normotensive or mildly hypertensive controls. We conclude that severe hypertension on admission is an independent predictive factor for SAP in elderly patients with acute ischemic stroke
Linagliptin ameliorated cardiac fibrosis and restored cardiomyocyte structure in diabetic mice associated with the suppression of necroptosis
ABSTRACT Aims/Introduction Linagliptin is a selective dipeptidyl peptidase (DPP)â4 inhibitor capable of successfully regulating blood glucose levels. The cardiovascular protective effects of several DPPâ4 inhibitors have been shown in preclinical studies; however, the detailed influence of DPPâ4 inhibitors on diabetic pathological alterations in cardiac tissue has not yet been elucidated. Materials and Methods We combined laboratoryâbased experiments and bioinformatics techniques to identify suitable candidate targets with significant biological pathways. Mice with streptozotocinâinduced insulin deficiency diabetic model were utilized for inâvivo experiments. Mice were euthanized at 24âweeks after the induction of diabetes; linagliptin intervention was carried out for 4âweeks before euthanasia. Microarray analysis of heart samples was carried out. Results Mice with streptozotocinâinduced diabetes, but not control mice, showed cardiac fibrosis with an endothelialâmesenchymal transition program, and myocardial fiber and sarcomere disruption; linagliptin alleviated these diabetesâassociated pathological alterations without altering blood glucose levels. Bioinformatics analysis utilizing a microarray dataset identified 10 hub genes that were confirmed to have human disease relevance by Gene Expression Omnibus analysis. Among these hub genes, we focused on the Sox9ânecroptosis axis as a therapeutic target in diabetic hearts. Indeed, diabetic mice showed the induction of necroptosisâassociated genes and the phosphorylation of RIP3 and mixed lineage kinase domainâlike protein. Conclusions Linagliptin showed excellent heart protection in mice with streptozotocinâinduced diabetes associated with alterations in human diseaseârelevant hub genes. Further investigation is required to determine why DPPâ4 inhibitors do not show similar superior organâprotective effects in the clinical setting
Mao-to Prolongs the Survival of and Reduces TNF-a Expression in Mice with Viral Myocarditis
Goal of this study was to evaluate effects of Mao-to on development of myocarditis induced by encephalomyocarditis (EMC) virus in mice. Mice were randomly divided into five groups. Group N included uninfected controls (n = 18), while group A, B and C underwent intraperitoneal injection of EMC virus. Group A was administered oral saline from day 0 to day 4. Group B was administered oral Mao-to (500 mg Ă1 kg Ă1 day Ă1 ) from day 0 to day 4. Group C was administered Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10. Treated mice were followed for survival rates during 2 weeks after infection. Body weight (BW) and organ weights including heart (HW), lungs, thymus and spleen were examined on days 4, 6 and 14. Survival rate of group C (36.4%) was significantly improved compared with group A, B or D (0% of each, P < 0.05). HW and HW/BW ratio in group C was significantly (P < 0.05) lower than those in group A, B or D. Viral titers of hearts were significantly different among groups A, B and C. Cardiac expression in tumor necrosis factor-a (TNF-a) was significantly reduced in group C in comparison with group A, B or D on day 6 by immunohistochemical study. Administration of Mao-to starting on day 2 improves mortality resulting from viral myocarditis in mice with reduced expression of cardiac TNF-a. These findings suggest that timing of Mao-to is crucial for preventing cardiac damage in mice with viral myocarditis