Expression of bcl-xL can confer a multidrug resistance phenotype

It has been suggested that genes that regulate apoptotic cell death may play an important role in determining the sensitivity of tumor cells to chemotherapy. We have recently cloned a member of the bcl-2 family, bcl- x. To test whether bcl-XL expression affects the sensitivity of tumor cells to chemotherapy, we have created stable cell lines overexpressing bcl-XL and have tested these cells for resistance to cell death induced by metabolic inhibitors and chemotherapeutic agents. Bcl-XL expression dramatically reduces the cytotoxicity of bleomycin, cisplatin, etoposide, vincristine, hygromycin B, and mycophenolic acid for up to 4 days in culture. Bcl-XL does not prevent cells from undergoing cell cycle arrest in response to these drugs, but rather prevents treated cells from undergoing apoptosis. Cell-cycle analysis on cells treated with the chemotherapeutic agents bleomycin, cisplatin, etoposide, and vincristine, show that the drugs cause growth arrest in different positions within the cell cycle. Bcl-XL expressing cells treated with chemotherapeutic drugs retain their proliferative ability after the drugs are removed. Interestingly, vincristine-treated cells expressing bcl-XL become polyploid after drug removal. These data show that bcl-XL protects cells from a wide variety of apoptotic stimuli, acts in multiple positions within the cell cycle, and confers a multidrug resistance phenotype. The ability of bcl-XL to prevent apoptotic cell death in response to chemotherapy-induced DNA damage and cell-cycle arrest may contribute to the accumulation of chromosomal aberrations within tumors. The expression of bcl-XL in tumor cells is likely to be an important indicator of chemotherapeutic efficacy.     

Prevalence and Related Risk Behaviors of HIV, Syphilis, and Anal HPV Infection Among Men who have Sex with Men from Beijing, China

Specific risk behaviors related to different sexually transmitted infections have not been widely evaluated among men who have sex with men in China. In the present study, a total of 302 MSM were recruited from Beijing with a prevalence of HIV, syphilis, and anal HPV infection as 9.9, 19.2 and 71.4%, respectively. Lower education level was observed to be related to higher infection rate of HIV and syphilis. “Ever found sexual partners in gay venues” was significantly associated with HIV infection as well. “Taking anilinction as regular sexual behavior” was observed to be a significant predictor for anal HPV infection.     

The rate of hepatic artery complications is higher in pediatric liver transplant recipients with metabolic liver diseases than with biliary atresia

Background

Liver transplantation (LT) is an excellent treatment option for patients with biliary atresia (BA) who fail portoenterostomy surgery. LT is also increasingly performed in patients with metabolic liver diseases. This study compared the outcomes in pediatric patients who underwent LT for metabolic liver diseases and BA.

Percutaneous Pinning of Fifth Carpal–Metacarpal Fracture–Dislocations: An Alternative Pin Trajectory

Traditional management of unstable fourth and fifth carpal-metacarpal (CMC) fracture-dislocations (fx-dislocs) of the hand includes closed reduction and percutaneous pinning (CRPP) versus open reduction internal fixation (ORIF). Traditional trajectory of pin placement is toward the base of the hook of the hamate. Our case series of CMC fx-dislocs treated with this trajectory led to the development of ulnar deep motor branch symptoms (sxs). We attempt to propose an alternative trajectory that could lower the chance of iatrogenic injury. Five fresh frozen cadaveric specimens underwent percutaneous pinning of the fifth CMC joint using fluoroscopic guidance. Each cadaver was dissected, and the proximity of the deep motor branch of the ulnar nerve was measured in relation to a pin that penetrated the volar cortex. Our results confirm the close proximity of the deep motor branch of the ulnar nerve to the volar cortex of the hamate and demonstrate the potential for iatrogenic injury during CRPP of the fifth CMC fx-dislocs, especially with penetration of the volar cortex. By demonstrating the close proximity of the deep motor branch to the volar cortex of the hamate in cadavers, we highlight the potential for iatrogenic injury with CRPP of CMC fx-dislocs as seen in our case series. We recommend a more midaxial starting point on the proximal metacarpal with a trajectory aimed at the midbody of the hamate to prevent penetration of the hamate volar cortex and limit the chances of iatrogenic injury.     

Childhood Pityriasis Rosea

Abstract: Pityriasis rosea (PR) is an acute, self‐limiting papulosquamous disorder of unknown etiology. Published studies of childhood PR are scarce and most are reviews. The aim of this study was to determine the demographic and clinical features of childhood PR.     

6-(αα-二苯基乙酰哌嗪基苯基)-4,5-二氢-5-甲基-3(2H)-哒嗪酮对兔血小板聚集及TXB2,cAMP的影响

6-(αα-二苯基乙酰哌嗪基苯基)-4,5-二氢-5-甲基-3(2H)-哒嗪酮(简称DMDP)是我院新合成的哒嗪酮的衍生物。DMDP可以显著抑制由花生四烯酸(AA(?),ADP和血小板活化因子(PAF)诱导的免血小板聚集,其IC₅₀分别为1.12±0.1.4.19±0.5和2.97±0.1μmol/L。实验还表明DMDP在1～500 μmol/L浓度范围内呈剂量依赖性地抑制兔血小板内血栓素B₂含量,但升高兔血小板内环腺苷酸水平,这可能是其抑制血小板聚集的作用机理之一。     

The superoxide production mediated by the redox cycling of xenobiotics in rat brain microsomes is dependent on their reduction potential

Several exogenous molecules undergo enzymatic one-electron reduction leading to radicals which can rapidly react with molecular oxygen to form superoxide anions. We have previously shown that under aerobic conditions a significant superoxide anion production occurred during the NADPH-dependent one-electron reduction of some drugs and xenobiotics by rat brain preparations. We report here for several compounds a fairly good correlation between the reduction potentials (Epc vs. SCE) which ranged between −230 and −700 mV in aqueous medium (pH 7.4) or between −700 mV and −1100 mV in the aprotic solvent N,N-dimethylformamide, and the rate of superoxide anion production during their metabolism by rat brain microsomes. The data obtained suggest that the redox potential of most of the molecules assayed was related to their ability to undergo one-electron reduction mediated by flavoenzymes in the rat brain. The main range of reduction potentials corresponding to a large superoxide anion production suggests that the redox cycling of these chemicals was mediated by NADPH-cytochrome P-450 reductase. Therefore the measurement of reduction potentials of drugs and xenobiotics able to reach the brain, and chemically related to quinones, nitroaromatics, nitroheterocyclics and iminiums, may provide information both on their electron affinity and the possibility of one-electron transfer in vivo, and thus on their possible neurotoxicity due to the production of oxygenated free radicals.