248 research outputs found

    Effects of Extracellular Acidification on Intracellular pH and ATP-Induced Calcium Mobilization in Rabbit Lens Epithelial Cells

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    Effects of extracellular acidification on intracellular pH (pHi) and ATP-induced calcium mobilization were investigated in rabbit lens epithelial cells. Primary-cultured lens epithelial cells of Japanese white rabbits were used. Intracellular calcium ([Ca2+]i) and pHi were measured by using fluorescent dyes, fura-2 acetoxymethylester (fura-2 AM) and 2',7'-bis (carboxyethyl)-5,6-carboxyfluorescein acetoxymethylester (BCECF AM), respectively. The addition of 10 ?mol/L ATP produced an initial peak followed by a sustained increase in [Ca2+]i in a standard artificial aqueous humor at extracellular pH (pH0) 7.40. The initial peak was abolished by pretreatment with 1 ?mol/L thapsigargin, whereas the sustained increase was attenuated in a Ca2+-free solution or by pretreatment with 100 ?mol/L verapamil. Acidification of the pH0 from 7.40 to 6.80 decreased the pHi from 7.21 to 7.03, and enhanced both the initial peak and sustained increase in [Ca2+]i. These results suggest that acidification of pH0 significantly affects the pHi and modifies the ATP-induced [Ca2+]i transient in rabbit lens epithelial cells

    Association of liver enzyme levels and alveolar bone loss : a cross-sectional clinical study in Sado Island

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    The interaction of periodontopathic bacteria with host immune system induces the production of inflammatory mediators which leads to alveolar bone loss (ABL), the essential feature of periodontitis. Concurrently, periodontal diseases cause the elevation of blood cytokine levels, the alteration of gut microbiota and the dissemination of enterobacteria to the liver. Owing to these mechanisms, periodontal disease might be a risk for liver dysfunction. Several epidemiological studies have reported associations between periodontal diseases and liver dysfunction, although the association between ABL and liver dysfunction has not been investigated. This cross-sectional study determined if elevated serum liver enzyme levels were associated with ABL in Japanese adults. Japanese adults living on Sado Island who visited Sado General Hospital were invited to participate in the study. Participants over 40 years of age who underwent dental panoramic radiography and blood tests were included. Drinking and smoking habits were self-administered. After excluding patients with edentulous jaw, diagnosed liver diseases, and those on dialysis, data from 44 men and 66 women with a mean age of 73 years were analyzed. The average percentage of ABL for each participant was calculated for mesial and distal sites of all remaining teeth. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were determined. Univariate analyses were performed to select covariates to be put in multivariate analyses. The association between elevated serum liver enzyme levels and the highest quartile of ABL were assessed by multiple logistic regression analysis. After adjusting for covariates, no significant association was found between elevated serum AST, ALT, or GGT levels as dependent variables and the highest quartile of ABL as an explanatory variable. There was no significant association between the elevation of serum liver enzyme levels and ABL in Japanese adults

    ERRγ agonist under mechanical stretching manifests hypertrophic cardiomyopathy phenotypes of engineered cardiac tissue through maturation

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    iPS細胞から成熟した人工心筋組織の作製方法の開発 肥大型心筋症の治療法開発への利用に期待. 京都大学プレスリリース. 2023-10-06.Stretching and stimulating engineered heart tissues to accurately portray hypertrophic cardiomyopathy. 京都大学プレスリリース. 2023-10-17.Engineered cardiac tissue (ECT) using human induced pluripotent stem cell-derived cardiomyocytes is a promising tool for modeling heart disease. However, tissue immaturity makes robust disease modeling difficult. Here, we established a method for modeling hypertrophic cardiomyopathy (HCM) malignant (MYH7 R719Q) and nonmalignant (MYBPC3 G115∗) pathogenic sarcomere gene mutations by accelerating ECT maturation using an ERRγ agonist, T112, and mechanical stretching. ECTs treated with T112 under 10% elongation stimulation exhibited more organized and mature characteristics. Whereas matured ECTs with the MYH7 R719Q mutation showed broad HCM phenotypes, including hypertrophy, hypercontraction, diastolic dysfunction, myofibril misalignment, fibrotic change, and glycolytic activation, matured MYBPC3 G115∗ ECTs displayed limited phenotypes, which were primarily observed only under our new maturation protocol (i.e., hypertrophy). Altogether, ERRγ activation combined with mechanical stimulation enhanced ECT maturation, leading to a more accurate manifestation of HCM phenotypes, including non-cardiomyocyte activation, consistent with clinical observations

    Fluvoxamine for aripiprazole-associated akathisia in patients with schizophrenia: a potential role of sigma-1 receptors

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    <p>Abstract</p> <p>Background</p> <p>Second-generation antipsychotic drugs have been reported to cause fewer incidences of extrapyramidal side effects (EPSs) than typical antipsychotic drugs, but adverse events such as akathisia have been observed even with atypical antipsychotic drugs. Although understanding of the pathophysiology of akathisia remains limited, it seems that a complex interplay of several neurotransmitter systems might play a role in its pathophysiology. The endoplasmic reticulum protein sigma-1 receptors are shown to regulate a number of neurotransmitter systems in the brain.</p> <p>Methods</p> <p>We report on two cases in which monotherapy of the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the akathisia of patients with schizophrenia treated with the antipsychotic drug aripiprazole.</p> <p>Results</p> <p>The global score on the Barnes Akathisia Scale in the two patients with schizophrenia treated with aripiprazole decreased after fluvoxamine monotherapy.</p> <p>Conclusion</p> <p>Doctors may wish to consider fluvoxamine as an alternative approach in treating akathisia associated with antipsychotic drugs such as aripiprazole.</p
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