Platinum-resistance in ovarian cancer cells is mediated by IL-6 secretion via the increased expression of its target cIAP-2

Ovarian carcinoma patients are initially responsive to platinum-based therapy, but eventually become refractory to treatment due to the development of platinum chemoresistance. Elevated levels of interleukin-6 (IL-6) in the sera and ascites of these patients predict poor clinical outcome. Our goal was to analyze the interaction between cisplatin and cisplatin-resistant ovarian cancer cells, and to identify means of circumventing platinum resistance. We studied ovarian carcinoma cell lines and cells drawn from ovarian carcinoma patients. Gene array analyses were performed on ovarian carcinoma cells upon treatment with cisplatin, and the results were validated by ELISA and Western blotting (WB). Cytotoxicity assays were performed on anti-IL-6 Ab-, IL-6-, and cellular inhibitor of apoptosis 2 (cIAP-2) siRNA-treated cells, following cisplatin addition. Our results revealed a highly significant increase in IL-6 and cIAP-2 mRNA and protein levels upon treatment with cisplatin. WB analysis of cisplatin-treated cells exhibited decreased cIAP-2 expression level following anti-IL-6 Ab addition. Furthermore, IL-6 by itself, significantly increased cIAP-2 levels in ovarian carcinoma cells. Finally, cytotoxicity assays showed sensitization to cisplatin following the addition of IL-6 and cIAP-2 inhibitors. In conclusion, cisplatin treatment of ovarian carcinoma cells upregulates IL-6 and cIAP-2 levels while their inhibition significantly sensitizes them to cisplatin. Here, we present cIAP-2 as a novel inducer of platinum resistance in ovarian carcinoma cells, and suggest an axis beginning with an encounter between cisplatin and these cells, mediated sequentially by IL-6 and cIAP-2, resulting in cisplatin resistance. Consequently, we propose that combining IL-6/cIAP-2 inhibitors with cisplatin will provide new hope for ovarian carcinoma patients by improving the current treatment.     

Emblica officinalis improves glycemic status and oxidative stress in STZ induced type 2 diabetic model rats

Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats were divided into nine groups including control groups receiving water,type 2 diabetic controls,type 2 diabetic rats treated with glibenclamide(T2GT)and type 2diabetic rats treated with aqueous extract of fruit pulp of E.officinalis.They were fed orally for8 weeks with a single feeding.Blood was collected by cutting the tail tip on 0 and 28 days and by decapitation on 56 day.Packed red blood cells and serum were used for evaluating different biochemical parameters.Results:Four weeks administration of aqueous extract of E.officinalis improved oral glucose tolerance in type 2 rats and after 8 weeks it caused significant(P0.007)reduction in fasting serum glucose level compared to 0 day.Triglycerides decreased by 14%but there was no significant change in serum ALT,creatinine,cholesterol and insulin level in any group.Furthermore,reduced erythrocyte malondialdehyde level showed no significant change(P0.07)but reduced glutathione content was found to be increased significantly(P0.05).Conclusions:The aqueous extract of E.officinalis has a promising antidiabetic and antioxidant properties and may be considered for further clinical studies in drug development.     

Patient-controlled epidural analgesia for labor pain: effect on labor, delivery and neonatal outcome of 0.125% bupivacaine vs 0.2% ropivacaine

The objective was to evaluate the influence of patient-controlled epidural analgesia (PCEA) using low doses of bupivacaine vs. ropivacaine, on labor pain, motor blockade, progression of labor, delivery and neonatal outcome. This randomized double blind study included 565 parturients. All received a 5-mL/h infusion and PCEA (5-mL boluses with a 20-min lockout, maximum volume 20 mL/h) of either 0.125% bupivacaine (n = 313: 165 nulliparous, 148 parous) or 0.2% ropivacaine (n = 252: 113 nulliparous, 139 parous). Pain score, lower limb motor block, sensory levels, local analgesic doses required, hemodynamic parameters, side effects and complications were assessed. Obstetric variables included cervical dilation at epidural insertion, incidence of ruptured membranes and their duration, use of oxytocin, fetal heart rate changes, duration of labor, mode and outcome of delivery, and use of invasive and non-invasive fetal monitoring. Neonatal characteristics included birth weight, Apgar scores, umbilical artery pH, serum bilirubin, hypoglycemia, need for assisted ventilation, sepsis or sepsis study, feeding difficulties and respiratory distress syndrome. Ropivacaine 0.2% was equianalgesic with 0.125% bupivacaine, but produced less motor block (P < 0.0001). There were no significant differences, however, in duration of labor, delivery type or neonatal outcome.     

Similar incidence of hypotension with combined spinal-epidural or epidural alone for knee arthroplasty

BACKGROUND: We hypothesized that the incidence of hypotension during total knee replacement (TKR) surgery is lower in patients given combined spinal-epidural (CSE) anesthesia vs those receiving epidural anesthesia alone. METHODS: In a prospective study, 80 American Society of Anesthesiologists I-II patients (aged 40-80 yr), undergoing elective TKR surgery were randomly assigned to either CSE anesthesia (CSE, n = 40) or epidural anesthesia alone (Epidural, n = 40). Hemodynamic measurements included oscillometric mean arterial blood pressure (MAP), heart rate (HR), and cardiac index (CI) as determined by thoracic bioimpedance; systemic vascular resistance (SVR) was calculated. Our primary endpoint (outcome) was the number of hypotension episodes (defined as MAP < 70 mmHg). RESULTS: Using univariate analysis, we found no differences between the groups in regards to MAP, HR, CI, or SVR during the perioperative period. The incidence of hypotension was similar in both groups (two patients in each group), as was the incidence of bradycardia (12 patients in CSE, 7 in Epidural; P = 0.2). There were no differences between groups in other hemodynamic measurements including CI and calculated SVR. Analgesia supplementation with fentanyl was more frequently required in the Epidural group (20 vs 6 patients - P = 0.03). CONCLUSION: Combined spinal-epidural anesthesia and epidural anesthesia alone during TKR surgery are associated with the same incidence of hypotension with statistically and clinically similar hemodynamic responses.     

Pulmonary complications following endotracheal intubation for anesthesia in breech extraction

A 28-year-old, healthy pregnant patient developed bilateral pneumothorax, subcutaneous emphysema, pneumomediastinum, pneumoretroperitoneum and pneumoperitoneum following endotracheal intubation and manual ventilation during general anesthesia for breech extraction. It is likely that positive-pressure ventilation was the cause for this very rare combination of complications. Early recognition and treatment may prevent such a catastrophe.