Predictors of the Response to Tolvaptan Therapy and Its Effect on Prognosis in Cirrhotic Patients with Ascites

Aims: The vasopressin V2 receptor antagonist, tolvaptan, has been reported to be effective in cirrhotic patients with ascites. Here, we evaluated predictors of the response to tolvaptan. Methods: A total of 97 patients with cirrhosis (60 males; median age, 63 years) who had been treated for ascites with oral tolvaptan were enrolled. Tolvaptan efficacy was defined as urine volume increase of ≥500 mL or a urine volume ≥2000 mL/day on the day following treatment. Normalization of the serum sodium (Na) level after 1 week of treatment and the posttreatment survival rate was analyzed. Results: Tolvaptan therapy resulted in effective urination in 67% of patients. A multivariate analysis revealed that the blood urea nitrogen/creatinine (BUN/Cr) ratio and urinary Na/potassium (Na/K) ratio were predictive of the tolvaptan response (p <0.05). The serum Na level was 135 (121–145) mEq/L, and normal levels were recovered in 50.0% of the patients with an initial Na level of <135 mEq/L. The posttreatment survival rate was significantly higher in patients who responded to tolvaptan therapy (p <0.05). Conclusions: The combination of the initial BUN/Cr and urine Na/K ratios and a normalized serum Na level after 1 week was predictive of a favorable outcome to tolvaptan therapy

高齢者の認知機能向上とITヘルスケアシステム

IT（Information Technology）ヘルスケアシステムが高齢者の認知機能の向上に影響をもたらすか，その効果を測定するため，デイサービス事業所５か所において調査を行った．効果測定は，認知機能評価スケールMini Mental State Examination（MMSE）を用い，介入前後に測定できた４９人（介入群４０人，対照群９人）のデータを分析し比較検討した．結果，ITヘルスケアシステム（ITHCS）介入前後のMMSE得点，および認知機能の変化（前後差）において，介入群の方が有意に高い得点を示す項目はなかった．しかし，介護度別にみると介入後の方が有意に高い認知機能の変化を示した項目（即時想起，物品呼称，自発書字）もあった．そのためITヘルスケアシステムの効率性を高めるには，利用者への個別的対応を組み合わせるなどのアプローチが必要であると結論付けられた．This article examines how effective IT（Information Technology）health care system is in improving cognitive functioning for the elderly people. We have organized a small project for health promotion among elderly people at five day-care centers and evaluated its effectiveness in the cognitive abilities of the service users. Mini Mental State Examination （MMSE） is used to assess the project’s efficacy, including the impact of the IT health care system. Eleven types of cognitive abilities are tested on ４９ people （４０ within intervention group and ９ within contrast group） prior the intervention and after. The result doesn’t show significant improvement on the score, however, some improvement on cognitive abilities such as short-term memory, calculation, identifying objects, and following simple directions, was seen in some group according to their care requirement level. Therefore, we concluded that the program with IT health care system combined with some individualized approach is necessary in order to improve its effectiveness

Involvement of SIK3 in Glucose and Lipid Homeostasis in Mice

Salt-inducible kinase 3 (SIK3), an AMP-activated protein kinase-related kinase, is induced in the murine liver after the consumption of a diet rich in fat, sucrose, and cholesterol. To examine whether SIK3 can modulate glucose and lipid metabolism in the liver, we analyzed phenotypes of SIK3-deficent mice. Sik3−/− mice have a malnourished the phenotype (i.e., lipodystrophy, hypolipidemia, hypoglycemia, and hyper-insulin sensitivity) accompanied by cholestasis and cholelithiasis. The hypoglycemic and hyper-insulin-sensitive phenotypes may be due to reduced energy storage, which is represented by the low expression levels of mRNA for components of the fatty acid synthesis pathways in the liver. The biliary disorders in Sik3−/− mice are associated with the dysregulation of gene expression programs that respond to nutritional stresses and are probably regulated by nuclear receptors. Retinoic acid plays a role in cholesterol and bile acid homeostasis, wheras ALDH1a which produces retinoic acid, is expressed at low levels in Sik3−/− mice. Lipid metabolism disorders in Sik3−/− mice are ameliorated by the treatment with 9-cis-retinoic acid. In conclusion, SIK3 is a novel energy regulator that modulates cholesterol and bile acid metabolism by coupling with retinoid metabolism, and may alter the size of energy storage in mice

A Semidominant Mutation in an Arabidopsis Mitogen-Activated Protein Kinase Phosphatase-Like Gene Compromises Cortical Microtubule Organization

Reversible protein phosphorylation regulates many cellular processes, including the dynamics and organization of the microtubule cytoskeleton, but the events mediating it are poorly understood. A semidominant phs1-1 allele of the Arabidopsis thaliana PROPYZAMIDE-HYPERSENSITIVE 1 locus exhibits phenotypes indicative of compromised cortical microtubule functions, such as left-handed helical growth of seedling roots, defective anisotropic growth at low doses of microtubule-destabilizing drugs, enhancement of the temperature-sensitive microtubule organization1-1 phenotype, and less ordered and more fragmented cortical microtubule arrays compared with the wild type. PHS1 encodes a novel protein similar to mitogen-activated protein kinase (MAPK) phosphatases. In phs1-1, a conserved Arg residue in the noncatalytic N-terminal region is exchanged with Cys, and the mutant PHS1 retained considerable phosphatase activity in vitro. In mammalian MAPK phosphatases, the corresponding region serves as a docking motif for MAPKs, and analogous Arg substitutions severely inhibit the kinase–phosphatase association. Transgenic studies indicate that the phs1-1 mutation acts dominant negatively, whereas the null phs1-2 allele is recessive embryonic lethal. We propose that the PHS1 phosphatase regulates more than one MAPK and that a subset of its target kinases is involved in the organization of cortical microtubules