Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1

Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.     

Comparison Between Phenylephrine and Dopamine in Maintaining Cerebral Oxygen Saturation in Thoracic Surgery: A Randomized Controlled Trial

Fluid is usually restricted during thoracic surgery, and vasoactive agents are often administered to maintain blood pressure. One-lung ventilation (OLV) decreases arterial oxygenation; thus oxygen delivery to the brain can be decreased. In this study, we compared phenylephrine and dopamine with respect to maintaining cerebral oxygenation during OLV in major thoracic surgery.Sixty-three patients undergoing lobectomies were randomly assigned to the dopamine (D) or phenylephrine (P) group. The patients’ mean arterial pressure was maintained within 20% of baseline by a continuous infusion of dopamine or phenylephrine. Maintenance fluid was kept at 5 mL/kg/h. The depth of anesthesia was maintained with desflurane 1MAC and remifentanil infusion under bispectral index guidance. Regional cerebral oxygen saturation (rScO₂) and hemodynamic variables were recorded using near-infrared spectroscopy and esophageal cardiac Doppler.The rScO₂ was higher in the D group than the P group during OLV (OLV 60 min: 71 ± 6% vs 63 ± 12%; P = 0.03). The number of patients whose rScO₂ dropped more than 20% from baseline was 0 and 6 in the D and P groups, respectively (P = 0.02). The D group showed higher cardiac output, but lower mean arterial pressure than the P group (4.7 ± 1.0 vs 3.9 ± 1.2 L/min; 76.7 ± 8.1 vs 84.5 ± 7.5 mm Hg; P = 0.02, P = 0.02). Among the variables, age, hemoglobin concentration, and cardiac output were associated with rScO₂ by correlation analysis.Dopamine was superior to phenylephrine in maintaining cerebral oxygenation during OLV in thoracic surgery.     

Steep Decrease of Gender Difference in DSM-IV Alcohol Use Disorder: A Comparison of Two Nation-wide Surveys Conducted 10 Years Apart in Korea

While decreasing trend in gender differences in alcohol use disorders was reported in Western countries, the change in Asian countries is unknown. This study aims to explore the shifts in gender difference in alcohol abuse (AA) and dependence (AD) in Korea. We compared the data from two nation-wide community surveys to evaluate gender differences in lifetime AA and AD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Face-to-face interviews using the Composite International Diagnostic Interview (CIDI) were applied to all subjects in 2001 (n=6,220) and 2011 (n=6,022). Male-to-female ratio of odds was decreased from 6.41 (95% CI, 4.81-8.54) to 4.37 (95% CI, 3.35-5.71) for AA and from 3.75 (95% CI, 2.96-4.75) to 2.40 (95% CI, 1.80-3.19) for AD. Among those aged 18-29, gender gap even became statistically insignificant for AA (OR, 1.59; 95% CI, 0.97-2.63) and AD (OR, 1.18; 95% CI, 0.80-2.41) in 2011. Men generally showed decreased odds for AD (0.55; 95% CI, 0.45-0.67) and women aged 30-39 showed increased odds for AA (2.13; 95% CI 1.18-3.84) in 2011 compared to 2001. Decreased AD in men and increased AA in women seem to contribute to the decrease of gender gap. Increased risk for AA in young women suggests needs for interventions.     

Was kann der Sonotrainer-Ultraschallsimulator?

In obstetrics and gynaecology, as well as in many other fields of medicine, ultrasound has become an indispensable diagnostic tool. Ultrasound training, however, still lacks proper quality assessment and control. In fact, in prenatal diagnostics most fetal anomalies requiring diagnosis during pregnancy are extremely rare. Therefore, effective training opportunities are limited to the very few medical centres which treat many such cases. Ultrasound simulator-based training, as performed with the Sonofit Sonotrainer, has been demonstrated to partly overcome this dilemma. In this article, the authors summarize their experience in using and evaluating various teaching concepts after the implementation of the ultrasound simulator under different conditions. Furthermore, an overview of the advantages of the Sonotrainer-based ultrasound training and its acceptance among trainees is provided. The authors also focus on aspects of quality assessment in gynaecological and prenatal ultrasound.