Evaluation of performance metrics for high energy density rechargeable lithium-oxygen batteries.

The demand for practical implementation of rechargeable lithium-oxygen batteries (LOBs) has grown owing to their extremely high theoretical energy density. However, the factors determining the performance of cell-level high energy density LOBs remain unclear. In this study, LOBs with a stacked-cell configuration were fabricated and their performance evaluated under different experimental conditions to clarify the unique degradation phenomenon under lean-electrolyte and high areal capacity conditions. First, the effect of the electrolyte amount against areal capacity ratio (E/C) on the battery performance was evaluated, revealing a complicated voltage profile for an LOB cell operated under high areal capacity conditions. Second, the impact of different kinds of gas-diffusion layer materials on the "sudden death" phenomenon during the charging process was investigated. The results obtained in the present study reveal the importance of these factors when evaluating the performance metrics of LOBs, including cycle life, and round-trip energy efficiency. We believe that adopting a suitable experimental setup with appropriate technological parameters is crucial for accurately interpreting the complicated phenomenon in LOBs with cell-level high energy density.

Criteria for evaluating lithium-air batteries in academia to correctly predict their practical performance in industry.

Although the market share for Li-ion batteries (LiBs) has continuously expanded, the limited theoretical energy density of conventional LiBs will no longer meet the advanced energy storage requirements. Lithium-air batteries (LABs) are potential candidates for next-generation rechargeable batteries because of their extremely high theoretical energy density. However, the reported values for the actual energy density of LABs are much lower than those for LiBs, mainly due to the excess amount of electrolyte in the cell. In the present review article, the practical energy density is estimated for the representative LABs reported in academia, and the critical factors for improving the energy density of LABs are summarized. The criteria for evaluating LABs in laboratory-based experiments are also proposed for accurately predicting the performance of practical cells in industry.

An enteric polymer mitigates the effects of gastric pH on oral absorption of poorly soluble weak acid drugs from supersaturable formulations: A case study with dantrolene.

This study demonstrated that an enteric polymer can mitigate the effects of gastric pH on the oral absorption of a poorly water-soluble weak acid drug, dantrolene (DNT). An amorphous solid dispersion (ASD) of DNT with hydroxypropyl methylcellulose (HPMC) acetate succinate (ASD-HPMCAS) was prepared as the enteric released ASD (ER-SF). ASD with HPMC (ASD-HPMC) and DNT sodium salt were also used as immediate-release supersaturable formulations (IR-SFs) with and without water-soluble polymer, respectively. In vivo study with rats and in vitro study with a dissolution/permeation (D/P) system were performed to evaluate oral DNT absorption from each formulation under normal and high gastric pH conditions in rats and humans, respectively. The oral absorption of DNT from both IR-SFs in rats with a high gastric pH was significantly higher than that in rats with a normal gastric pH. In contrast, ASD-HPMCAS attenuated the difference in oral absorption between normal and high gastric pH conditions with significant improvement of DNT absorption. In vivo results implied that an enteric polymer delayed the onset of dissolution until after gastric emptying. ASD-HPMCAS generated supersaturation in the small intestine irrespective of gastric conditions, which was supported bythe in vitrostudy using the D/P system. This study suggested that an enteric polymer is useful to mitigate the inter- and intra-individual differences in oral absorption of poorly water-soluble weak acid drugs.

Intracranial growing teratoma syndrome observed at 44 months after initial treatment; a case presentation and literature review.

Intracranial growing teratoma syndrome (iGTS) is rare phenomenon which is observed in non-germinomatous germ cell tumor (NGGCT) after chemotherapy. The clinical features of iGTS are rapidly increasing in size compared with relapse, no elevation of tumor marker in spite of tumor regrowth, multiple cystic lesions in cranial imaging, and histopathologically diagnosed as mature teratoma. Here we present a 14-year-old man with iGTS which was revealed at 44 months after initial chemotherapy. He was diagnosed as pineal immature teratoma by histopathological specimen, and we performed chemotherapy and radiation therapy. After this treatment, we found growing cystic lesion in tumor removal cavity at 26 months after surgery. The histopathological findings showed dermoid cyst in first salvage surgery. Following this result, we observed him without adjuvant chemotherapy. However he had continuous headache, abnormal eye movement at 44 months after initial treatment. Cranial MRI showed regrowing cyst. In second salvage surgery, mature teratoma was demonstrated on histopathological specimen, and we diagnosed as iGTS. Although most reported iGTSs show rapid increasing after initial chemotherapy, few reported cases show regrowth at chronic phase as our case. In long-term follow-up of germ cell tumor, iGTS is important as differential diagnosis.

[Predictive Factors for Gastrointestinal Bleeding Following Hemorrhagic Stroke: A Hospital-Based Cohort Study].

BACKGROUND AND PURPOSE: Gastrointestinal bleeding is an important complication in the acute phase of hemorrhagic stroke. In this study, we aimed to identify the risk factors for gastrointestinal bleeding in patients with hemorrhagic stroke despite the administration of antiulcer drugs. METHODS: We conducted a retrospective cohort study of our hemorrhagic stroke cases. We analyzed the background factors associated with gastrointestinal bleeding in the study population and their outcomes. RESULTS: The study included 837 patients: 598 with intracerebral hemorrhages and 239 with subarachnoid hemorrhages. Among them, 22 patients developed gastrointestinal bleeding. Intraventricular hemorrhage (P=0.0019) and ongoing oral anticoagulant use (P=0.0177) were significantly associated with gastrointestinal bleeding. Gastrointestinal bleeding was significantly associated with severe disability at discharge (P=0.0333) and number of days of hospitalization (P=0.0190). CONCLUSIONS: The risk factors of poorly controlled gastrointestinal bleeding during the acute phase of hemorrhagic strokes were intraventricular hemorrhage and use of anticoagulant drugs. Patients with a high risk for gastrointestinal bleeding need to be identified and to be given effective prophylactic therapy. (Received October 12, 2017; Accepted March 29, 2018; Published August 1, 2018).

New Prediction Score for Hematoma Expansion and Neurological Deterioration after Spontaneous Intracerebral Hemorrhage: A Hospital-Based Retrospective Cohort Study.

OBJECTIVE: To ensure hematoma expansion and neurological deterioration in the management of acute spontaneous intracerebral hemorrhage, accurate prediction is crucial for initial assessment on admission. We conducted this study to develop a new clinical prediction score using only noncontrast computed tomography image and simply measurable variables. METHODS: This study was a retrospective cohort analysis. The study took place in a single academic medical center in Japan. Development of the prediction score was conducted based on patients who presented between October 2010 and June 2015, using univariate and multivariate logistic regression. We then validated the results in a second cohort between July 2015 and April 2017. The primary outcome was hematoma expansion and the secondary outcome was neurological deterioration up to 14 days after onset. RESULTS: In total, 622 patients were included in the analysis after excluding unsuitable cases. Of these, 457 patients were included in the development cohort and 165 were included in the validation cohort, with 10.8% meeting the criteria for hematoma expansion and 8.8% showing neurological deterioration. In the multivariate analysis, predictors of expansion or deterioration were as hematoma heterogeneity on computed tomography, niveau formation, peripheral edema, hematoma volume of more than 30 mL, and anticoagulant use. We then created the HEAVN score based on the univariate regression coefficients. The C-statistics for the hematoma expansion scores were .81 and .80 in the development and validation cohorts, respectively. Similar results were obtained for neurological deterioration. CONCLUSIONS: The HEAVN score is simple and useful for predicting hematoma expansion and neurological deterioration based on imaging and background data.

Specific Factors to Predict Large-Vessel Occlusion in Acute Stroke Patients.

BACKGROUND: The effectiveness of thrombectomy for acute ischemic stroke has been established, and earlier treatment produces better outcomes. If possible to identify large-vessel occlusion (LVO) at the prehospital phase, eligible patients can be shipped directly to a hospital that can perform thrombectomy. The purpose of this study was to determine factors that are specific to LVO and can be known before hospital arrival. METHODS: The subjects were stroke patients during the period between July 2014 and June 2016, who had a National Institutes of Health Stroke Scale (NIHSS) score of 8 or higher and came to our hospital within 6 hours of onset. These patients were divided into an LVO group and a non-LVO group, and background factors, mode of onset, individual NIHSS item scores, and blood pressure at the time of the visit were retrospectively investigated. The selected factors were compared with LVO prediction scales reported in the past. RESULTS: There were 196 stroke patients who had NIHSS scores of 8 or higher and arrived at the hospital within 6 hours. Of these 196 patients, 56 had LVO. This LVO group included a significantly higher number of patients with the 2 items of atrial fibrillation (odds ratio [OR], 11.5: 95% confidence interval [CI], 4.04-32.9; P < .0001) and systolic blood pressure of 170 mm Hg or lower (OR, 2.99: 95% CI, 1.33-6.71, P = .008). These 2 items predicted LVO equally to existing LVO prediction scales. CONCLUSIONS: The 2 items of atrial fibrillation and systolic blood pressure of 170 mm Hg or lower were significantly correlated with LVO.

Preparation of antibodies against a novel immunosuppressant, FTY720, and development of an enzyme immunoassay for FTY720.

FTY720 (1) is a novel immunosuppressant (immunomodulator), derived from ISP-I (2: myriocin and thermozymocidin). To clarify the pharmacokinetic properties of 1, antibodies against 1 were prepared and a competitive enzyme immunoassay (EIA) was developed. Two kinds of haptens, 3 and 4, for 1 were synthesized and coupled to ovalbumin (OVA). Rabbits were immunized with 3-OVA or 4-OVA, and corresponding antibodies were obtained. Both antibodies recognized the 2-amino-2-(2-phenylethyl)propane-1,3-diol moiety in 1. Using the anti-3-OVA antibody, a competitive EIA for 1 was developed and evaluated. The range of quantification by the EIA was 0.06-10 ng/mL. The application of the EIA has enabled us to measure the FTY720 concentration in serum after oral administration of 1 (1mg/kg) to rats.

Involvement of the drug transporters p glycoprotein and multidrug resistance-associated protein Mrp2 in telithromycin transport.

The present study aims to investigate the role of P glycoprotein and multidrug resistance-associated protein (Mrp2) in the transport of telithromycin, a newly developed ketolide antibiotic, in vitro and in vivo. The in vitro experiments revealed that the intracellular accumulation of telithromycin in adriamycin-resistant human chronic myelogenous leukemia cells (K562/ADR) overexpressing P glycoprotein was significantly lower than that in human chronic myelogenous leukemia cells (K562/S) not expressing P glycoprotein. Cyclosporine significantly increased the intracellular accumulation of telithromycin in K562/ADR cells. When telithromycin was coadministered intravenously with cyclosporine in Sprague-Dawley (SD) rats, cyclosporine significantly delayed the disappearance of telithromycin from plasma and decreased its systemic clearance to 60% of the corresponding control values. Hepatobiliary excretion experiments revealed that cyclosporine almost completely inhibited the biliary clearance of telithromycin, suggesting that telithromycin is a substrate of P glycoprotein and a potential substrate of Mrp2. Moreover, the biliary clearance of telithromycin was significantly decreased by 80% in Eisai hyperbilirubinemic mutant rats with a hereditary deficiency in Mrp2, indicating that Mrp2, as well as P glycoprotein, plays an important role in the biliary excretion of telithromycin. When the effect of telithromycin on the biliary excretion of doxorubicin, a substrate of P glycoprotein and Mrp2, was examined in SD rats, telithromycin significantly decreased the biliary clearance of doxorubicin by 80%. Results obtained from this study indicate that telithromycin is a substrate of both P glycoprotein and Mrp2, and these transporters are involved in the hepatobiliary transport of telithromycin.