平面性を有するコアシェル型逆相カラム-HPLCでのジルチアゼム類の分離選択性と迅速製剤分析法の開発

　Recently UHPLC, where smaller particle (2～3 μm) packing materials are employed, is progressing rapidly. Higher performance (higher theoretical plate number, lower theoretical plate height) and fast analysis can be obtained by the UHPLC, compared with the conventional HPLC with the usual size packing materials (5 μm). In this study, core-shell (CS) type packing materials (particle size 2.6 μm, column length 10 cm) are used for the separation of diltiazem (DIL), 8-chlorodilitiazem, and those related substances such as trans-form and deacetyl-form (DIL-OH). Four CS type reversed-phase columns, including a phenyl column and a phenylhexyl column both having a planar moiety, are investigated with the mobile phase containing acetonitrile as an organic solvent. Among four CS type columns, a Cholestyer column gave large Rs values for the separation between isomers such as cis-form (DIL) and its trans-form, n-propyl paraben and isopropyl paraben. On the other hand, separation of DIL and DIL-OH was successful by employing a phenyl column and a phenyl-hexyl column. For the separation of 8-chlorodilitiazem and its related substances, the tendency was the same as in DIL. Finally, assay and content uniformity testing of DIL formulations such as tablets and injections, purity testing (related substances) of DIL drug substances and formulations were successfully performed within 100 s, showing the usefulness of this type column as a tool of high through put analysis

Blocking of P2X7r Reduces Mitochondrial Stress Induced by Alcohol and Electronic Cigarette Exposure in Brain Microvascular Endothelial Cells

Studies in both humans and animal models demonstrated that chronic alcohol/e-cigarette (e-Cig) exposure affects mitochondrial function and impairs barrier function in brain microvascular endothelial cells (BMVECs). Identification of the signaling pathways by which chronic alcohol/e-Cig exposure induces mitochondrial damage in BMVEC is vital for protection of the blood–brain barrier (BBB). To address the issue, we treated human BMVEC [hBMVECs (D3 cell-line)] with ethanol (ETH) [100 mM], acetaldehyde (ALD) [100 μM], or e-cigarette (e-Cig) [35 ng/mL of 1.8% or 0% nicotine] conditioned medium and showed reduced mitochondrial oxidative phosphorylation (OXPHOS) measured by a Seahorse analyzer. Seahorse data were further complemented with the expression of mitochondrial OXPHOS proteins detected by Western blots. We also observed cytosolic escape of ATP and its extracellular release due to the disruption of mitochondrial membrane potential caused by ETH, ALD, or 1.8% e-Cig exposure. Moreover ETH, ALD, or 1.8% e-Cig treatment resulted in elevated purinergic P2X7r and TRPV1 channel gene expression, measured using qPCR. We also demonstrated the protective role of P2X7r antagonist A804598 (10 μM) in restoring mitochondrial oxidative phosphorylation levels and preventing extracellular ATP release. In a BBB functional assay using trans-endothelial electrical resistance, we showed that blocking the P2X7r channel enhanced barrier function. In summary, we identified the potential common pathways of mitochondrial injury caused by ETH, ALD, and 1.8% e-Cig which allow new protective interventions. We are further investigating the potential link between P2X7 regulatory pathways and mitochondrial health

Changes in Brain Metabolite Concentrations after Neonatal Hypoxic-ischemic Encephalopathy.

Purpose To investigate the time-course changes and predictive utility of brain metabolite concentrations in neonatal hypoxic-ischemic encephalopathy (HIE). Materials and Methods Sixty-eight neonates (age, 35-41 gestational weeks) with HIE were admitted to a neonatal intensive care unit between September 2009 and March 2016 and examined by using proton MR spectroscopy at 18-96 hours (n = 25) and 7-14 days (n = 64) after birth (35-43 postmenstrual weeks) to estimate metabolite concentrations in the deep gray matter. Adverse outcome was defined as death or neurodevelopmental impairment at 18-22 months of age. Areas under the receiver operating characteristic curves were calculated to evaluate the prognostic values of metabolites. Results At 18-96 hours, N-acetylaspartate and creatine concentrations were lower, whereas lactate, and glutamate and glutamine (Glx) concentrations were higher in neonates with adverse outcomes than in those with favorable outcomes. Metabolite concentrations at 18-96 hours decreased during days 7-14 in neonates with adverse outcomes but did not change in those with favorable outcomes. For N-acetylaspartate, creatine, lactate, and Glx concentrations measured at 18-96 hours to predict adverse outcomes, areas under the receiver operating characteristic curve were 0.98, 0.89, 0.96, and 0.88, respectively, whereas at 7-14 days, the areas under the receiver operating characteristic curve were 0.97, 0.97, 0.59, and 0.36, respectively. Conclusion Time-dependent reductions in N-acetylaspartate and creatine concentrations at both 18-96 hours and 7-14 days accurately predicted adverse outcomes. However, higher lactate and glutamate and glutamine concentrations were often transient

Resultados tempranos y a medio plazo de la reparación quirúrgica endovascular y abierta del aneurisma del arco aórtico no disecado

OBJECTIVES: With the introduction of endovascular stent graft technology, a variety of surgical options are available for patients with aortic aneurysms. We sought to evaluate early-term and mid-term outcomes of patients undergoing endovascular and open surgical repair for non-dissected aortic arch aneurysm. METHODS: Overall, 200 patients underwent treatment for isolated non-dissected aortic arch aneurysm between January 2008 and February 2016: 133 patients had open surgery and 67, endovascular repair. Early-term and mid-term outcomes were compared. RESULTS: Seventy percent (n?=?47) needing endovascular repair underwent fenestrated stent graft and 30% (n?=?20) underwent the debranched technique. Patients in the open surgery group were younger (71 vs 75 years, P?<?0.001) and had a lower prevalence of ischaemic heart disease (11% vs 35%, P?<?0.001). Intensive care unit stay (1 vs 3 days, P?<?0.001), hospital stay (11 vs 17 days, P?<?0.001) and surgical time (208 vs 390?min, P?<?0.001) were lower in the endovascular repair group than in the open surgery group. There were 3 in-hospital deaths each in the open surgery and endovascular groups (2% vs 5%, respectively, P?=?0.40). Mid-term survival (P?<?0.001) and freedom from reintervention (P?=?0.009) were better in the open surgery than in the endovascular repair group. No aneurysm-related deaths were observed. The propensity-matched comparison (n?=?58) demonstrated that survival was better in the open surgery group (P?=?0.011); no significant difference was seen in the reintervention rate (P?=?0.28). CONCLUSIONS: Close follow-up for re-intervention may reduce the risk for aneurysm-related deaths and provide acceptable outcomes in patients undergoing endovascular repair

Resultados tempranos y a medio plazo de la reparación quirúrgica endovascular y abierta del aneurisma del arco aórtico no disecado

OBJECTIVES: With the introduction of endovascular stent graft technology, a variety of surgical options are available for patients with aortic aneurysms. We sought to evaluate early-term and mid-term outcomes of patients undergoing endovascular and open surgical repair for non-dissected aortic arch aneurysm. METHODS: Overall, 200 patients underwent treatment for isolated non-dissected aortic arch aneurysm between January 2008 and February 2016: 133 patients had open surgery and 67, endovascular repair. Early-term and mid-term outcomes were compared. RESULTS: Seventy percent (n?=?47) needing endovascular repair underwent fenestrated stent graft and 30% (n?=?20) underwent the debranched technique. Patients in the open surgery group were younger (71 vs 75 years, P?<?0.001) and had a lower prevalence of ischaemic heart disease (11% vs 35%, P?<?0.001). Intensive care unit stay (1 vs 3 days, P?<?0.001), hospital stay (11 vs 17 days, P?<?0.001) and surgical time (208 vs 390?min, P?<?0.001) were lower in the endovascular repair group than in the open surgery group. There were 3 in-hospital deaths each in the open surgery and endovascular groups (2% vs 5%, respectively, P?=?0.40). Mid-term survival (P?<?0.001) and freedom from reintervention (P?=?0.009) were better in the open surgery than in the endovascular repair group. No aneurysm-related deaths were observed. The propensity-matched comparison (n?=?58) demonstrated that survival was better in the open surgery group (P?=?0.011); no significant difference was seen in the reintervention rate (P?=?0.28). CONCLUSIONS: Close follow-up for re-intervention may reduce the risk for aneurysm-related deaths and provide acceptable outcomes in patients undergoing endovascular repair

Correction: Physical, social, and psychological characteristics of community-dwelling elderly Japanese dog and cat owners.

[This corrects the article DOI: 10.1371/journal.pone.0206399.]

Physical, social, and psychological characteristics of community-dwelling elderly Japanese dog and cat owners.

ObjectivesPrevious studies examined the physical characteristics of older dog owners. However, associations of health-related factors with dog/cat ownership have not been comprehensively evaluated. This cross-sectional study examined physical function, physical activity, social function, and psychological function of a population of community-dwelling older Japanese dog and cat owners after controlling for important confounders.MethodsThe analysis included data from 11,233 community-dwelling adults aged 65 years or older (51.5% women; 52.3% aged 75-84), in Ota City, Tokyo, Japan. Pet ownership experience and pet species owned were determined by self-reported questionnaire, and current, past, and never dog/cat ownership was analyzed.ResultsAnalysis of variables related to physical function and physical activity showed that motor fitness scale and walking activity were significantly associated with experience of dog ownership, after adjustment for important sociodemographic and health characteristics. Analysis of social function showed that interaction with neighbors, social isolation, and trust in neighbors were significantly associated with experience of dog ownership and cat ownership.ConclusionsAs compared with respondents with no history of pet ownership, motor fitness and walking activity are greater for dog owners and social function is higher for dog and cat owners. Caring for a dog or cat might be an effective health promotion strategy to increase physical activity and facilitate social participation among older adults