Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

Fertility Outcome After Renal Transplantation: A Single-Center Experience

BackgroundWomen suffering from kidney disease are more prone to fertility problems, due to uremia. Fortunately, their fertility rate increases dramatically after renal transplantation. This study analyzes the predictors/risk factors of successful pregnancy with live birth outcome while presenting an overview of the 7-year experience of a single center.MethodsThis retrospective cohort study includes 239 women of reproductive age (18–40 years) who underwent renal transplantation in a tertiary Turkish clinic between October 1, 2011, and August 24, 2017. The subjects were invited to take part in a survey questioning their obstetric characteristics and they were assessed in 2 groups: fertile and infertile. Multivariable linear regression analysis was conducted to determine the predictors of a successful pregnancy.ResultsThirty-five 35 patients wished to become pregnant: 12 got pregnant spontaneously, while 21 failed to become pregnant (spontaneously). The mean age of the patients at the survey was 34 ± 7. Regular menstrual cycles after renal transplantation, tacrolimus-mycophenolate mofetil maintenance protocol, and age at transplantation were found to be predictors of spontaneous pregnancy. The duration of peritoneal dialysis was significantly longer in the infertile group (48 vs 12 months).ConclusionEnd-stage renal disease's negative impacts, including menstrual abnormality and fertility problems, can be overcome by successful kidney transplantation with appropriate immunosuppression. Minimizing the duration of peritoneal dialysis, particularly in patients who desire future fertility, may be accepted as a logical management strategy.     

Switch From Twice-daily Tacrolimus to Once-daily,Prolonged-release Tacrolimus in Kidney Transplantation: Long-term Outcome

Background

One daily dose of tacrolimus (QDT) improves adherence in kidney transplant (KT) recipients. A switch from twice-daily tacrolimus (BDT) to QDT showed similar efficacy and safety.

神经电生理对腓总神经卡压的诊断价值

目的 观察神经电生理检测对腓总神经卡压的诊断价值。方法 对腓总神经卡压的临床特征及病因进行分析，并作神经传导速度和肌电图检测和分析。结果 21条患病神经中1条神经波形消失。其余有不同程度的传导速度减慢，尤其是跨腓骨小头段，波幅降低，传导时间延长，42块腓总神经支配的肌肉中有30块出现失神经电位。结论 神经电生理检查在腓总神经卡压的诊断中有重要意义。     

脊髓损伤大鼠的阴茎海绵体肌电图研究

目的探讨海绵体肌电图诊断脊髓性勃起功能障碍的价值。方法将24只成年雄性SD大鼠(300～400 g)分成:对照组、T9和L6损伤组(每组8只)。损伤脊髓1周后,用肌电图仪采集注射阿朴吗啡前后阴茎肌电数据,采集频率20～3 000 Hz、扫描速度5 ms／d、灵敏度10 μV／d。用t检验方法分析统计数据。结果对照组使用阿朴吗啡10 min均方根振幅为(5．60±0．89)μV, 大于T9损伤组(3．60±1．14)μV(P<0．05);使用阿朴吗啡前、使用后5 min和10 min高／低功率比均为0．05±0．03,小于L6损伤组0．13±0．04、0．15±0．07、0．13±0．07(P<0．05)。T9损伤组使用阿朴吗啡后5 min和10 min平均频率分别为(122．40±47．99)、(151．80±76．42)Hz,较L6损伤组(278．83±118．66)、(265．00±81．35)Hz低(P<0．05)。结论海绵体肌电图对脊髓性勃起功能障碍有诊断价值。     

Herzoperationen wegen Herztumoren in Deutschland – Ergebnisse eienr Umfrage für das Jahr 1996

Zusammenfassung Zahlen zur H?ufigkeit von Herztumoren im operativen Krankengut liegen bisher für die Bundesrepublik Deutschland nicht vor. Um einen entsprechenden überblick für das Jahr 1996 zu erhalten, wurde allen 77 herzchirurgischen Zentren der Bundesrepublik Deutschland ein standardisierter Fragebogen zugesandt. Daten von 65 der 77 Herzzentren (=84%) waren schlie?lich verfügbar: 187 Patienten waren wegen Myxomen, lediglich 44 wegen nichtmyxomat?sen Tumoren, davon 28 wegen malignen prim?ren oder sekund?ren Herztumoren, operiert worden. Im Jahr 1996 waren somit 0,32% (231/72 763) der Eingriffe mit Herz-Lungen-Maschine (erfa?t 72 763 von insgesamt 87 372) wegen eines Herztumors vorgenommen worden. Ausgehend von diesen operativen Daten liegt die Inzidenz ausschlie?lich der prim?ren Tumoren des Herzens zumindest bei 3 Tumoren pro 1 Million Einwohner pro Jahr (253 Tumoren/81,814 Millionen Einwohner). Wenn auch kleine Tumoren asymptomatisch und unentdeckt bleiben k?nnen, wird heute doch die Mehrzahl prim?rer kardialer Tumoren durch Echokardiographie, Computer- und Kernspintomographie bereits zu Lebzeiten des Patienten diagnostiziert, und diese Patienten werden in aller Regel einer Operation zugeführt. Somit werden gut 0,3% aller Eingriffe mit Herz-Lungen-Maschine in Deutschland wegen Herztumoren durchgeführt, wobei es sich weit überwiegend um Myxome handelt. Eingegangen: 23. September 1997, Akzeptiert: 11. Februar 1998