The Effect of Antihypertensive Therapy on Skeletal Muscle Mass and Bone Mineral Density in Patients With End-Stage Kidney Disease.

OBJECTIVE: Sarcopenia and osteoporosis substantially influence health and lifespan. However, the variables affecting skeletal muscle mass (SMM) or bone mineral density (BMD) remain unknown. DESIGN AND METHODS: From August 1, 2018 to July 31, 2019, we conducted a single-center, observational cohort study with 291 Japanese adult patients on maintenance hemodialysis due to end-stage kidney disease, who had their femoral neck BMD measured using dual-energy X-ray absorptiometry. After 1-year follow-up, we measured annual changes of BMD (ΔBMD) and SMM (ΔSMM), which were calculated through a modified creatinine index (mg/kg/day) using age, sex, serum creatinine, and single-pooled Kt/V for urea. The factors associated with ΔSMM/ΔBMD or progressive loss of SMM/BMD, defined as ΔSMM/ΔBMD < 0 per year, respectively, were analyzed with multivariable, linear regression or logistic regression models. RESULTS: The median age of the patients was 66 years and 33% were female. Dialysis vintage and ß-blocker-use were inversely correlated to ΔSMM. In comparison to nonusers, ß-blockers users had 2.5-fold higher SMM loss odd ratios [95% confidence interval, 1.3-4.8]. The risk for SMM loss caused by ß-blockers was not increased in users of renin-angiotensin system inhibitors. The ΔBMD was negatively correlated to the usage of calcium channel blockers. The risk of developing osteosarcopenia, which was defined as annual loss of both SMM and BMD, increased in calcium channel blockers users. CONCLUSIONS: The use of ß-blockers is associated with an elevated risk of developing sarcopenia, whereas renin-angiotensin system inhibitors may minimize this effect in patients with end-stage kidney disease. Use of calcium channel blocker therapy was associated with a faster decline of BMD.

Pump Exchange from a Left Ventricular Assist Device to a Jarvik 2000 with a Postauricular Cable Due to Abdominal Driveline Infection.

Driveline infection in patients with implantable left ventricular assist devices (LVAD) remains common and crucial. Once a driveline exit-site infection reaches the LVAD component, radical treatment such as LVAD exchange may become necessary, although the clinical results are unsatisfactory. The Jarvik 2000 device, which utilizes a postauricular cable, allows the driveline to exit the body behind the ear (postauricular) instead of through an abdominal site. Here, we report the case of a patient who had awaited heart transplantation for more than 6 years and had a critical driveline infection that almost reached the LVAD pump. The patient underwent a pump exchange using the Jarvik 2000 with a postauricular cable, with excellent results. It is a useful replacement option for patients with abdominal driveline infections, owing to its small pump pocket and the availability of an alternative pathway for the driveline.

[Minimally Invasive Cardiac Surgery-Coronary Artery Bypass Grafting by Left Small Intercostal Thoracotomy for Very Elderly Patients:Report of Two Cases].

The increase in the age of patients undergoing operations has become more prominent in recent years. We report our experience of minimally invasive cardiac surgery-coronary artery bypass grafting (MICS-CABG) by left small intercostal thoracotomy for very elderly patients. Case 1:The patient was a 91-year-old woman with a history of percutaneous coronary intervention (PCI) for left anterior descending artery (LAD) and right coronary arteries at different timings. Due to her contrast media allergy, we performed MICS-CABG to treat 75% stenosis of LAD. Blood transfusion was not required. She was discharged on the 13th day. Case 2:The patient was a 92-year-old man. We performed MICS-CABG for 75% stenosis of the left main trunk and 90~99% stenosis of the LAD with severe calcification. Blood transfusion was not required. He was discharged on the 21th day. MICS-CABG can be performed with less invasiveness in comparison to the conventional method and therefore seems to be an effective method of surgery for very elderly patients.

Zinc Deficiency via a Splice Switch in Zinc Importer ZIP2/SLC39A2 Causes Cystic Fibrosis-Associated MUC5AC Hypersecretion in Airway Epithelial Cells.

Airway mucus hyperproduction and fluid imbalance are important hallmarks of cystic fibrosis (CF), the most common life-shortening genetic disorder in Caucasians. Dysregulated expression and/or function of airway ion transporters, including cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC), have been implicated as causes of CF-associated mucus hypersecretory phenotype. However, the contributory roles of other substances and transporters in the regulation of CF airway pathogenesis remain unelucidated. Here, we identified a novel connection between CFTR/ENaC expression and the intracellular Zn2+ concentration in the regulation of MUC5AC, a major secreted mucin that is highly expressed in CF airway. CFTR-defective and ENaC-hyperactive airway epithelial cells specifically and highly expressed a unique, alternative splice isoform of the zinc importer ZIP2/SLC39A2 (ΔC-ZIP2), which lacks the C-terminal domain. Importantly, ΔC-ZIP2 levels correlated inversely with wild-type ZIP2 and intracellular Zn2+ levels. Moreover, the splice switch to ΔC-ZIP2 as well as decreased expression of other ZIPs caused zinc deficiency, which is sufficient for induction of MUC5AC; while ΔC-ZIP2 expression per se induced ENaC expression and function. Thus, our findings demonstrate that the novel splicing switch contributes to CF lung pathology via the novel interplay of CFTR, ENaC, and ZIP2 transporters.

Time-resolved Fluorescent Detection for Glucose Using a Complex of Luminescent Layered Titanates and Enzymes.

Luminescent europium-doped layered titanates (Eu-TiOx) were synthesized and complexed with horseradish peroxidase (HRP) and glucose oxidase (GOx). The emission of a resultant Eu-TiOx/HRP/GOx complex decreased upon the addition of glucose in the presence of guaiacol. The emission decrease was dependent on the concentrations of glucose, and the detection limit for glucose was 3.1 µM. The proposed system would be promising as a new detection method for glucose.

Pharmacological and genetic reappraisals of protease and oxidative stress pathways in a mouse model of obstructive lung diseases.

Protease-antiprotease imbalance and oxidative stress are considered to be major pathophysiological hallmarks of severe obstructive lung diseases including chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), but limited information is available on their direct roles in the regulation of pulmonary phenotypes. Here, we utilized ßENaC-transgenic (Tg) mice, the previously established mouse model of severe obstructive lung diseases, to produce lower-mortality but pathophysiologically highly useful mouse model by backcrossing the original line with C57/BL6J mice. C57/BL6J-ßENaC-Tg mice showed higher survival rates and key pulmonary abnormalities of COPD/CF, including mucous hypersecretion, inflammatory and emphysematous phenotypes and pulmonary dysfunction. DNA microarray analysis confirmed that protease- and oxidative stress-dependent pathways are activated in the lung tissue of C57/BL6J-ßENaC-Tg mice. Treatments of C57/BL6J-ßENaC-Tg mice with a serine protease inhibitor ONO-3403, a derivative of camostat methylate (CM), but not CM, and with an anti-oxidant N-acetylcystein significantly improved pulmonary emphysema and dysfunction. Moreover, depletion of a murine endogenous antioxidant vitamin C (VC), by genetic disruption of VC-synthesizing enzyme SMP30 in C57/BL6J-ßENaC-Tg mice, exaggerated pulmonary phenotypes. Thus, these assessments clarified that protease-antiprotease imbalance and oxidative stress are critical pathways that exacerbate the pulmonary phenotypes of C57/BL6J-ßENaC-Tg mice, consistent with the characteristics of human COPD/CF.

Sagace: a web-based search engine for biomedical databases in Japan.

BACKGROUND: In the big data era, biomedical research continues to generate a large amount of data, and the generated information is often stored in a database and made publicly available. Although combining data from multiple databases should accelerate further studies, the current number of life sciences databases is too large to grasp features and contents of each database. FINDINGS: We have developed Sagace, a web-based search engine that enables users to retrieve information from a range of biological databases (such as gene expression profiles and proteomics data) and biological resource banks (such as mouse models of disease and cell lines). With Sagace, users can search more than 300 databases in Japan. Sagace offers features tailored to biomedical research, including manually tuned ranking, a faceted navigation to refine search results, and rich snippets constructed with retrieved metadata for each database entry. CONCLUSIONS: Sagace will be valuable for experts who are involved in biomedical research and drug development in both academia and industry. Sagace is freely available at http://sagace.nibio.go.jp/en/.