Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic β-Cell Injury

BackgroundGlucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic β-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic β-cells from high glucose-induced apoptosis.MethodsReverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations.ResultsCoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP.ConclusionOur data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored

Alcoholic and non-alcoholic fatty liver disease and associations with coronary artery calcification- Evidence from the Kangbuk Samsung Health Study

Objective Recent evidence suggests that alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) may differentially affect risk of cardiovascular mortality. To investigate whether early liver disease due to AFLD or NAFLD have similar or dissimilar effects on risk of early coronary artery atherosclerosis, we have investigated the associations between AFLD and NAFLD and coronary artery calcium (CAC). Design A cross-sectional study was performed in 105 328 Korean adults who attended a health check-up programme. CAC score was assessed using CT, daily alcohol intake was recorded as grams/day and liver fat by ultrasound. Logistic regression model was used to calculate ORs with 95% CIs for prevalent CAC. Results Both NAFLD and AFLD were positively associated with CAC score. After adjusting for potential confounders, multivariable-adjusted OR (95% CIs) for CAC >0 comparing NAFLD and AFLD to the reference (absence of both excessive alcohol use and fatty liver disease) were 1.10 (95% CI 1.05 to 1.16) and 1.20 (95% CI 1.11 to 1.30), respectively. In post hoc analysis, OR (95% CI) for detectable CAC comparing AFLD to NAFLD was 1.09 (95% CI 1.01 to 1.17). Associations of NAFLD and AFLD with CAC scores were similar in both non-obese and obese individuals without significant interaction by obesity (p for interaction=0.088). After adjusting for homeostasis model assessment of insulin resistance and high-sensitivity C reactive protein, the associations between fatty liver disease and CAC scores remained statistically significant. Conclusion In this large sample of young and middle-aged individuals, early liver disease due to NAFLD and AFLD were both significantly associated with the presence of coronary artery calcification

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Human papillomavirus 16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in 15-25 years old healthy Korean women

OBJECTIVE: The study assessed the immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Korean women aged 15-25 years. METHODS: Phase IIIB, double-blind, randomised (2:1), multi-centre trial was conducted in Korea from June 2007 to March 2008. The study enrolled 225 women in the HPV (N=149) and placebo (N=76) groups who received three doses of HPV-16/18 AS04-adjuvanted vaccine or placebo (aluminium hydroxide) administered intramuscularly at 0, 1, and 6 months and were followed until one month post-dose 3. Serum samples were collected pre-vaccination and one month post-dose 3. Safety and reactogenicity data were collected throughout. RESULTS: In this trial, 208 women completed the study (141 in HPV group; 67 in placebo group). At month 7, all initially seronegative women had seroconverted for HPV-16 and HPV-18 antibodies with anti-HPV-16 and anti-HPV-18 geometric mean titres of 9,351.4 El.U/mL (95% CI, 8,145.5 to 10,735.8) and 4204.1 El.U/mL (95% CI, 3,626.5 to 4,873.6), respectively. Initially seropositive women showed similar increase in geometric mean titre levels. Compliance to the three dose vaccination course was 95.3% in HPV and 89.5% in placebo group. Solicited local (pain) and general (fatigue, myalgia or headache) symptoms were commonly reported in both groups. Three serious adverse events were reported (two in HPV group; one in placebo group), all unrelated to vaccination by the investigator; all recovered. CONCLUSION: The HPV-16/18 AS04-adjuvanted vaccine was highly immunogenic with a clinically acceptable safety profile in Korean women. This study was in line with previous global studies in Europe, North America, and Brazil. (ClinicalTrials.gov number, NCT 00485732.).ope

Treatment of high-risk neuroblastoma

Although high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) have improved the prognosis for patients with high-risk neuroblastoma (NB), event-free survival rates remain in the range of 30 to 40%, which is unsatisfactory. To further improve outcomes, several clinical trials, including tandem HDCT/autoSCT, high-dose 131I-metaiodobenzylguanidine treatment, and immunotherapy with NB specific antibody, have been undertaken and pilot studies have reported encouraging results. Nonetheless, about half of high-risk NB patients still experience treatment failure and have no realistic chance for cure with conventional treatment options alone after relapse. Therefore, a new modality of treatment is warranted for these patients. In recent years, several groups of investigators have examined the feasibility and effectiveness of reduced-intensity allogeneic stem cell transplantation (RI alloSCT) for the treatment of relapsed/progressed NB. Although a graft-versus-tumor effect has not yet been convincingly demonstrated in the setting of relapsed NB, the strategy of employing RI alloSCT has provided hope that treatment-related mortality will be reduced and a therapeutic benefit will emerge. However, alloSCT for NB is still investigational and there remain many issues to be elucidated in many areas. At present, alloSCT is reserved for specific clinical trials testing the immunomodulatory effect against NB