The pregnane X receptor (PXR) is the main transcriptional regulator of many enzymes that metabolize xenobiotics such as P450s and drug transporters. Polymorphisms in the PXR gene contribute to population variability in CYP3A4 and P-glycoprotein levels. Single nucleotide polymorphisms (SNPs) have been reported in Caucasian, African-American and Japanese populations. In the present study, we identified the known SNP, V140M and a novel SNP, Q158K, in Chinese subjects. We developed an allele-specific polymerase chain reaction method to detect the novel allele and found its frequency in 451 Chinese subjects to be 2.2%. CYP3A4-luciferase reporter assays revealed that the Q158K variant gave rise to much lower levels of CYP3A4 promoter activity in LS174T and HepG2 cells exposed to the PXR ligands, rifampin and paclitaxel, than did wild-type PXR. The SNP had less effect on promoter activity in response to clotrimazole or nifedipine.
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. carbon dioxide 30 [27][28][29][30][31][32][33][34][35] mmHg and median temperature 37.1 [36.8-37.3]°C. After removal of artefacts, the mean monitoring time was 22 h08 (8 h54). All patients had impaired cerebral autoregulation during their monitoring time. The mean IAR index was 17 (9.5) %. During H 0 H 6 and H 18 H 24 , the majority of our patients; respectively 53 and 71 % had an IAR index > 10 %. Conclusion According to our data, patients with septic shock had impaired cerebral autoregulation within the first 24 hours of their admission in the ICU. In our patients, we described a variability of distribution of impaired autoregulation according to time. ReferencesSchramm P, Klein KU, Falkenberg L, et al. Impaired cerebrovascular autoregulation in patients with severe sepsis and sepsis-associated delirium. Crit Care 2012; 16: R181. Aries MJH, Czosnyka M, Budohoski KP, et al. Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury. Crit. Care Med. 2012.
OBJECTIVES: Diabetes is a serious, costly metabolic disorder with a rising prevalence worldwide. Chromium has long been shown to improve insulin sensitivity, lipid profiles, and blood glucose in insulin resistance and type-2 diabetic patients. METHODS: All relevant databases were searched up to December 2011 limited to human studies in English language. Clinical studies in newly onset patients with type-2 diabetes reporting use of chromium at least for 4 weeks and outcomes of fasting blood glucose (FBG), hemoglobin A1C (HbA1c), triglyceride (TG), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL) and body mass index (BMI) were identified. Data of before and after use of chromium intake were compared. RESULTS: The functional outcome data from clinical studies revealed that our of 834 studies, 39 met inclusion criteria. Seventy present of articles demonstrated a decrease in FBS while 23% showed an increase. Forty-seven percent of studies showed an increase in HbA1c, while 15% a decrease. TG in 60% of studies showed an increase while in 15% a reduction was reported. LDL cholesterol in 60% of studies showed a decrease and in the rest there was no report of increase. Forty percent of studies showed a decrease in HDL cholesterol while 30% showed an increase. BMI in 40% of studies decreased and in 7% of cases increased. CONCLUSIONS: In clinical studies, average of mentioned parameters were improved significantly after administration of chromium in patients with type 2 diabetes in a dose-dependent manner with no side effects. This systematic review indicates beneficial effects of chromium in diabetic patients.
OBJECTIVES:This study examined the opioid-sparing effectiveness, analgesic efficacy and tolerability of postoperative administration of parecoxib in total knee arthroplasty (TKA) patients. METHODS: We performed a retrospective study of enrollees received patient-controlled analgesia (PCA, consisted of morphine 1 mg/ml and fentanyl 30 mcg/ml) with or without single-dose of intravenous 40 mg parecoxib following TKA from November 2010 through April 2011. Effect was assessed by the amount of PCA used, pain intensity, length of hospital stay (LOS), satisfaction score and adverse events. RESULTS: Nine patients under PCA with parecoxib as the parecoxib group and 73 patients without parecoxib as the controlled group were evaluated. PCA consumption was observed to be reduced in the parecoxib group by 17.2 %, 25.5 % and 39.8 % less than the controlled group at 24 h, 48 h, and 72 h after surgery. Pain at movement improved significantly at 48 h and 72 h for the parecoxib group with visual analogue score (VAS). There were no significant differences in pain scores at rest and LOS, however, between those who received parecoxib or not. Satisfaction was described as "good, fair, and poor" by 0 %, 89 %, and 11 % in the parecoxib group, respectively, compared with 4 %, 81 %, and 15 % of the controlled group. The overall incidences of adverse events were reported for 78 % of patients with parecoxib and 71 % of patients without parecoxib. CONCLUSIONS: In this study, postoperative administration of parecoxib demonstrated benefit in terms of PCA consumption and VAS score at movement. Therefore, it seemed that parecoxib provided opioid-sparing and analgesic effect. Also, the parental preparation of parecoxib may be especially useful when patients were unable to take oral medication or were experiencing nausea and vomiting.
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