A single preoperative oral dose of pregabalin 150 mg is an effective method for reducing postoperative pain and fentanyl consumption in patients undergoing laparoscopic cholecystectomy.

Our laboratory has delineated that the phosphatidylinositol 3 0 kinase (PI3K)/AKT/IjB kinase (IKK) pathway positively regulates NFjB and b-catenin, both important transcriptional regulators in colorectal cancer (CRC). Therefore, we investigated the effect of inhibiting the PI3K/AKT/IKKa pathway in regulating the inappropriate constitutive activation of NFjB and b-catenin in CRC cell lines. SW480 and RKO CRC cell lines demonstrate constitutive activation of AKT as well as both NFjB-and b-catenin-dependent transcription. The constitutive activation of NFjB-and b-catenin-dependent transcription is inhibited by transiently transfecting either kinase dead (KD) IKKa, which blocks IKKa kinase activity, KD AKT, which blocks AKT activity, or wildtype (WT) PTEN, which inhibits PI3K and AKT activity. The ability of KD IKKa, KD AKT or WT PTEN to decrease b-catenindependent transcription is independent of their effects on NFjB. Inducible expression of either KD IKKa or WT PTEN strongly inhibits both the constitutive NFjB-and b-catenin-dependent promoter and endogenous gene activation. Targeted array-based gene expression analysis of this inducible system reveals that many of the genes downregulated upon inhibition of this pathway are involved in tumor angiogenesis and metastasis. The activation of this pathway and the expression of the three most repressed genes was further analysed in samples of CRC. These results indicate a role of this pathway in controlling gene expression important in tumor progression and metastasis.

Tramadol 1.5 mg kg(-1) administered i.v. 30 min before extubation decreases the incidence and severity of CRBD and postoperative fentanyl requirement.

Research question:What is the prevalence of dysmenorrhea severity and its associated symptoms among adolescent girls?Objectives:(1) To study the prevalence of dysmenorrhea in high school adolescent girls of Gwalior. (2) To study the evidence of severity of the problem with associated symptoms and general health status.Study design:An explorative survey technique with a correlational approach.Setting and Participants:Nine hundred and seventy adolescent girls of age 15 to 20 years, studying in the higher secondary schools (Pre-University Colleges) of Gwalior.Statistical analysis:Percentages, Chi-square test, and Test-Retest Method.Results:The prevalence of dysmenorrhea in adolescent girls was found to be 79.67%. Most of them, 37.96%, suffered regularly from dysmenorrhea severity. The three most common symptoms present on both days, that is, day before and first day of menstruation were lethargy and tiredness (first), depression (second) and inability to concentrate in work (third), whereas the ranking of these symptoms on the day after the stoppage of menstruation showed depression as the first common symptoms. Negative correlation had found between dysmenorrhea and the General Health Status as measured by the Body surface area.

In vitro incubation and centrifugation is known to decrease human sperm quality. In the human body, besides its antioxidant effects, L-carnitine (LC) facilitates the transport of activated fatty acids from the cytosol to the mitochondrial matrix. In this study, we investigated the effect of LC on human sperm motility, viability and DNA oxidation after incubation and centrifugation, following the sperm preparation protocols of assisted reproduction. Normozoospermic semen samples (n = 55) were analysed according to the World Health Organization (WHO) guidelines. LC concentrations that are not toxic to spermatozoa as determined by sperm motility and viability were standardised after 2 and 4 h of incubation at 37 °C. Semen samples to which the optimal LC concentrations were added were also centrifuged for 20 min at 300 g and analysed for sperm motility, viability and DNA oxidation. Sperm motility was improved at 0.5 mg ml(-1) LC after incubation and centrifugation with 5 × 10(6) sperm ml(-1). Higher concentration of LC (50 mg ml(-1)) significantly decreased sperm motility and viability. LC did not alter the baseline of sperm DNA oxidation during both incubation and centrifugation. In conclusion, LC may enhance sperm motility following incubation and centrifugation, while it might not affect sperm viability and DNA oxidation.

I B kinase (IKK), discovered as the major activator of NF-B, plays additional roles in signaling. By using mouse embryo fibroblasts (MEFs) lacking both the ␣ and ␤ subunits of IKK, we find that these proteins are required for induction of a major subset of IFN␥-stimulated genes and that this requirement is independent of NF-B activation. Furthermore, there is no defect in IFN␥-stimulated signal transducer and activator of transcription 1 (Stat1) activation or function in the IKK␣͞␤-null MEFs. Therefore, although activated Stat1 dimers are necessary for the activation of these genes in response to IFN␥, they are not sufficient. These results reveal an important additional pathway for IFN␥-stimulated gene expression in which an NF-B-independent function of IKK is required.

The identification of agents that preferentially kill cancer cells while protecting normal cells offers the potential to overcome toxicities found in many existing chemotherapeutic agents. Because p53 is frequently inactivated in cancer, agents that preferentially kill p53-null cells and protect wild-type p53-expressing cells are highly desirable chemotherapeutic agents. By using pairs of isogenic colon cancer cell lines that differ only in p53 expression (RKO and HCT116), securinine was found to exhibit these properties. Securinine (30 microM) induces apoptosis in 73% of p53-null HCT116 cells (LD(50) 17.5 microM) as opposed to 17.6% of HCT116 parental cells (LD(50) 50 microM) at 72 h after treatment. The mechanism of securinine-mediated death in p53-deficient cells involves the induction of the p53 family member, p73. Interestingly, the proapoptotic protein p73 is down-regulated in colon cancer cells expressing p53. This differential regulation of p73 in a p53-dependent fashion reveals a novel pathway for preferentially targeting cancer cells. In contrast to p53-deficient cells, cells expressing p53 are protected from cell death through the p53-mediated up-regulation of p21. These studies reveal a novel approach to specifically target colon cancer cells lacking p53 as well as identify a novel clinically relevant pathway to selectively induce p73 in p53-null cells.

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