Knockdown of iPLA2γ enhances cisplatin-induced apoptosis by increasing ROS-dependent peroxidation of mitochondrial phospholipids in bladder cancer cells.

Cisplatin (CDDP) is a platinum-based drug with anti-cancer activity and is widely used as a standard therapy for bladder cancer. It is well known that CDDP causes cell death by increasing the generation of reactive oxygen species (ROS) and lipid peroxidation, but the mechanism of its anti-cancer effects has not been fully elucidated. There are still some problems such as chemoresistance in CDDP therapy. In the present study, we found the expression of Ca2+-independent phospholipase A2γ (iPLA2γ), which has been reported to regulate cellular redox homeostasis by inhibiting lipid peroxide accumulation, in human bladder cancer tissues. Thus, we investigated the effect of iPLA2γ knockdown on CDDP-induced bladder cancer cell death. As a result, we found that iPLA2γ knockdown significantly enhanced CDDP-induced apoptosis, intracellular and mitochondrial ROS production, cytochrome c release and caspase activation in bladder cancer cells. Moreover, mitochondrial membrane potential was decreased and peroxidation of mitochondrial phospholipids was increased by iPLA2γ knockdown. It was also shown that co-treatment of bromoenol lactone, an iPLA2 inhibitor, increased CDDP-induced apoptosis. These results indicated that iPLA2γ plays an important role in protecting bladder cancer cells from CDDP-induced apoptosis, and that iPLA2γ inhibitors might represent a novel strategy in CDDP-based multi-drug therapy.

All-Optical Rapid Formation, Transport, and Sustenance of a Sessile Droplet in a Two-Dimensional Slit with Few-Micrometer Separation.

We present a sessile droplet manipulation platform that enables the formation and transport of a droplet on a light-absorbing surface via local laser-beam irradiation. The mechanism relies on solutocapillary Marangoni flow arising from a concentration gradient in a binary mixture liquid. Because the mixture is strongly confined in a two-dimensional slit with a spacing of a few micrometers, the wetting film is stably sustained, enabling the rapid formation, deformation, and transport of a sessile droplet. In addition, to sustain the droplet in the absence of laser irradiation, we developed a method to bridge the droplet between the top and bottom walls of the slit. The bridge is stably sustained because of the hydrophilicity of the slit wall. Splitting and merging of the droplet bridges are also demonstrated.

Cardiac arrest during hemodialysis: a survey of five Japanese hospitals.

AIM: Intraprocedural cardiac arrest is a serious complication among patients receiving hemodialysis. However, the frequency and reaction to these events remain unclear. This study aimed to explore the clinical picture of cardiac arrest during hemodialysis. METHODS: Ten cardiac arrests that had occurred during 217,984 hemodialysis treatments in five Japanese hospitals, between 2008 and 2017, were reviewed. We investigated the underlying disease, vital signs, emergency responses, and outcomes using patient medical records. RESULTS: The cardiac arrest rate ranged from 1.1 to 7.5 per 100,000 hemodialysis sessions. All included cases of cardiac arrest occurred in a hemodialysis unit and had been witnessed and reported by supervising clinicians. The initial rhythm was ventricular fibrillation/ventricular tachycardia in six patients (60%) and pulseless electrical activity/asystole in four patients (40%). Seven (70%) patients showed a return of spontaneous circulation (ROSC), and two (20%) patients were discharged with a cerebral performance category score of 1. There was a statistically significant difference in the ROSC rate (P = 0.048) only in the event of an emergency call. The SpO2 and respiratory rates had not been recorded in six patients. There was no significant difference in ROSC between initial rhythms of ventricular fibrillation/ventricular tachycardia and pulseless electrical activity/asystole. CONCLUSION: We evaluated the frequency of cardiac arrest during hemodialysis. Overall assessment including respiratory status is needed at initiation of hemodialysis. In case of a sudden change in a patient's status, high-quality resuscitation treatment that includes an emergency call can improve prognosis.

Near-infrared spectroscopy monitoring during out-of-hospital cardiac arrest: can the initial cerebral tissue oxygenation index predict ROSC?

STUDY OBJECTIVES: Near-infrared spectroscopy is a modality that can monitor tissue oxygenation index (TOI) and has potential to evaluate return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation (CPR). This study's objectives were to evaluate whether TOI could be associated with ROSC and used to help guide the decision to either terminate CPR or proceed to extracorporeal CPR (ECPR). METHODS: In this observational study, we assessed the patients with out-of-hospital cardiac arrest with non-traumatic cause receiving CPR on arrival at our ED between 2013 and 2016. TOI monitoring was discontinued either on CPR termination after ROSC was reached or on patient death. Patients were classified into two groups: ROSC and non-ROSC group. RESULTS: Out of 141 patients, 24 were excluded and the remaining 117 were classified as follows: ROSC group (n=44) and non-ROSC group (n=73). ROSC group was significantly younger and more likely to have their event witnessed and bystander CPR. ROSC group showed a higher initial TOI than non-ROSC group (60.5%±17.0% vs 37.9%±13.7%: p<0.01). Area under the curve analysis was more accurate with the initial TOI than without it for predicting ROSC (0.88, 95% CI 0.82 to 0.95 vs 0.79, 95% CI 0.70 to 0.87: p<0.01). TOI cut-off value ≥59% appeared to favour survival to hospital discharge whereas TOI ≤24% was associated with non-ROSC. CONCLUSIONS: This study demonstrated an association between higher initial TOI and ROSC. Initial TOI could increase the accuracy of ROSC prognosis and may be a clinical factor in the decision to terminate CPR and select patients who are to proceed to ECPR.

A retrospective study of in-hospital cardiac arrest.

Aim: In-hospital cardiac arrest is an important issue in health care today. Data regarding in-hospital cardiac arrest in Japan is limited. In Australia and the USA, the Rapid Response System has been implemented in many institutions and data regarding in-hospital cardiac arrest are collected to evaluate the efficacy of the Rapid Response System. This is a multicenter retrospective survey of in-hospital cardiac arrest, providing data before implementing a Rapid Response System. Methods: Ten institutions planning to introduce a Rapid Response System were recruited to collect in-hospital cardiac arrest data. The Institutional Review Board at each participating institution approved this study. Data for patients admitted at each institution from April 1, 2011 until March 31, 2012 were extracted using the three keywords "closed-chest compression", "epinephrine", and "defibrillation". Patients under 18 years old, or who suffered cardiac arrest in the emergency room or the intensive care unit were excluded. Results: A total of 228 patients in 10 institutions were identified. The average age was 73 ± 13 years. Males represented 64% of the patients (82/146). Overall survival after in-hospital cardiac arrest was 7% (16/228). Possibly preventable cardiac arrests represented 15% (33/228) of patients, with medical safety issues identified in 8% (19/228). Vital sign abnormalities before cardiac arrest were observed in 63% (138/216) of patients. Conclusions: Approximately 60% of patients had abnormal vital signs before cardiac arrest. These patients may have an improved clinical outcome by implementing a Rapid Response System.

Quantitative and pattern analyses of continuous-wave Doppler-derived pulmonary regurgitant flow velocity for the diagnosis of constrictive pericarditis.

BACKGROUND: Many echocardiographic features of constrictive pericarditis (CP) have been reported, but each alone has a limitation either in sensitivity or in specificity. Continuous-wave Doppler-derived flow velocity of pulmonary regurgitation can reflect the diastolic right ventricular pressure pattern characteristic of CP and be useful for its detection. METHODS: Fifteen patients with CP, 18 patients with restrictive cardiomyopathy, and 20 normal subjects were studied retrospectively. Using continuous-wave Doppler echocardiography, pulmonary regurgitation velocities were measured at the early diastolic peak (VMAx), mid-diastolic inflection point (VIFL), and late diastolic minimal point (VMIN). RESULTS: VIFL, VIFL/VMAx, VMIN, and VMIN/VMAx were significantly lower in the CP group compared with the restrictive cardiomyopathy and normal groups. Prevalence rates of patients with early mid-diastolic inflection, VIFL/VMAx < 0.5, VMIN < 50 cm/sec, and VMIN/VMAx < 0.33 were significantly greater in the CP group compared with the other groups. Sensitivity and specificity for the diagnosis of CP were 93% and 74%, respectively, for the presence of early mid-diastolic inflection, 73% and 100% for VIFL/VMAx < 0.5, 73% and 97% for VMIN < 50 cm/sec, and 93% and 92% for VMIN/VMAx < 0.33. CONCLUSIONS: The quantitative and pattern analyses of continuous-wave Doppler-derived pulmonary regurgitation velocity could enhance the accuracy of echocardiographic detection of CP.

A new method to detect cerebral blood flow waveform in synchrony with chest compression by near-infrared spectroscopy during CPR.

OBJECTIVE: The objective of the study is to demonstrate the utility of near-infrared spectroscopy (NIRS) in evaluating chest compression (CC) quality in cardiac arrest (CA) patients as well as determine its prognosis predictive value. METHODS: We present a nonconsecutive case series of adult patients with CA whose cardiopulmonary resuscitation (CPR) was monitored with NIRS and collected the total hemoglobin concentration change (ΔcHb), the tissue oxygen index (TOI), and the ΔTOI to assess CC quality in a noninvasive fashion. RESULTS: During CPR, ΔcHb displayed waveforms monitor, which we regarded as a surrogate for CC quality. Total hemoglobin concentration change waveforms responded accurately to variations or cessations of CCs. In addition, a TOI greater than 40% measured upon admission appears to be significant in predicting patient's outcome. Of 15 patients, 6 had a TOI greater than 40% measured upon admission, and 67% of the latter were in return of spontaneous circulation after CPR and were found to be significantly different between return of spontaneous circulation and death (P = .047; P < .05). CONCLUSION: Near-infrared spectroscopy reliably assesses the quality of CCs in patients with CA demonstrated by synchronous waveforms during CPR and possible prognostic predictive value, although further investigation is warranted.