In this investigation, we report a relationship between the terbium (Tb3+) binding protein and the accumulation of cisplatin in human ovarian cancer cells. The number of Tb3+ binding sites in cisplatin-resistant C13+ cells is significantly greater by 79% than those in cisplatin-sensitive 2008 cells. Exposure to Tb3+ also increased the cellular accumulation of cisplatin. The accumulation of cisplatin as a function of the Tb3+ concentration in the C13+ cells (0.85%/microM Tb3+) was significantly greater than the accumulation of cisplatin in 2008 cells with respect to Tb3+ (0.46%/microM Tb3+). The number of Tb3+ binding sites in revertant RH4 cells was similar to that in 2008 cells. The RH4 cells were less sensitive to the stimulatory effects of Tb3+ than the C13+ cells. Our results show that the Tb3+ binding protein correlates with cisplatin resistance, and the receptor binding of Tb3+ increases the accumulation of cisplatin in cisplatin-resistant cells.
A quarter of men with obesity or type 2 diabetes have hypogonadotropic hypogonadism. Animal studies and in vitro data have shown that insulin action and insulin responsiveness in the brain are necessary for the maintenance of the functional integrity of the hypothalamo-hypophyseal-gonadal axis. We conducted a randomized, placebo-controlled trial to evaluate the effect of one dose of intranasal insulin (40 IU of regular insulin) or saline on LH concentrations in 14 men (8 with type 2 diabetes and 6 healthy lean men). Insulin or saline was administered intranasally on two different occasions, at least one week apart. Blood samples were collected to measure LH concentrations every 15 minutes for 5 hours. Study drug was administered intranasally after a 2-hour baseline sampling period. Patients remained fasting throughout the procedure. The primary endpoint of the study was to compare the change in LH concentrations after intranasal insulin as compared to placebo (intranasal saline). Change was defined as the difference between baseline LH concentrations (average of the 9 samples collected in two hours prior to drug administration) and average LH concentrations following drug administration (average of the 12 samples collected in 3 hours). There was no change in LH concentrations following insulin administration as compared to placebo in men with diabetes or in lean men. We conclude that one dose of 40 IU of regular insulin administered intranasally does not change LH concentrations acutely in men.
Background and Objectives: Cardioplegia is one of the most significant components used to protect the myocardium during cardiac surgery. There is a paucity of evidence regarding the utilization of whole-blood Del Nido cardioplegia (WB-DNC) on clinical outcomes in coronary artery bypass grafting (CABG). The purpose of this retrospective cross-sectional study is to compare the effectiveness of diluted (blood to crystalloid; 1:4) Del Nido cardioplegia (DNC) with WB-DNC in patients who underwent elective CABG in a tertiary care hospital in Lahore-Pakistan. Materials and Methods: This was a retrospective descriptive study conducted at the Department of Cardiovascular Surgery, King Edward Medical University, Lahore. The medical database of all consecutive patients admitted from January 2018 to March 2020 and who fulfilled the inclusion criteria were reviewed. Results: Out of 471 patients admitted during the study period, 450 underwent various elective cardiac surgeries. Out of 450, 321 patients (71.33%) were operated on for CABG. Only 234/321 (72.89%) CABG patients fulfilled our inclusion criteria; 120 (51.28%) patients received WB-DNC, while 114 (48.71%) patients were administered with DNC. The former group presented with better clinical outcomes compared with the latter in terms of lesser requirements of inotropic support, low degree of hemodilution, shorter in-hospital stay, improved renal function, and cost-effectiveness. Peak values of serum Troponin-T (Trop-T), creatine kinase-myocardial band (CK-MB) release, and activated clotting time (ACT) were also lower in the WB-DNC group compared with the DNC group. Conclusions: The WB-DNC conferred better myocardial protection, improved early clinical outcomes, and also proved to be economical for patients undergoing elective CABG compared with classical crystalloid cardioplegia solution.
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