Dual Infection with Hepatitis B Virus and Hepatitis C Virus Correlated with Type 2 Diabetes Mellitus.

BACKGROUND: Conflicting data exist regarding the relationship between dual infection of hepatitis B virus (HBV) and hepatitis C virus (HCV) with type 2 diabetes mellitus (T2DM). We assessed dual infection of HBV and HCV with the levels of blood glucose and development of DM. METHODS: A total of 9621 participants in a community-based study were enrolled from 18 towns in Maoli county of Taiwan. Blood samples were collected and tested for hepatitis B surface antigen (HBsAg) and antibodies (HBsAb), antibodies against hepatitis C virus (anti-HCV) and fasting plasma glucose. DM was defined as fasting plasma glucose≥126 mg per 100 ml. RESULTS: Only 0.7% of total participants had HBV/HCV coinfection. The prevalence of HBV and HCV monoinfection were 9.9 and 5.7%, respectively. Adjusted blood glucose levels and development risk of T2DM (odds ratio [OR], 2.55; p<0.001) were significantly high among HBV/HCV coinfection group using multivariate linear regression adjusted for age, gender, education, race and BMI. Furthermore, using multivariate logistic regression models adjusted for covariates, HCV mono-and HBV/ HCV coinfection significantly increased on blood glucose levels. CONCLUSIONS: Our study shows HBV/HCV coinfection was significantly correlated with blood glucose levels. A significant proportion (28%) of participants with HBV/HCV coinfection developed T2DM. Although the precise mechanisms of dual positive infection of HBV and HCV are unclear, there is increasing evidence that dual infection of HCV and HBV is strongly associated with the development of T2DM.

Ethnic Disparities in Blood Pressure: A Population-based Study.

Taiwan's indigenous population exhibits a higher mortality of cardiovascular disease, but current research has not reported any associations among ethnicities on the blood pressure (BP). We randomly selected representative samples in this population-based study. We measured height, weight, hip and waist circumferences, and blood pressure in a screening survey. Systolic BP and diastolic BP were significantly higher in the indigenous population. Among women, prevalence rates of DBP > 90 mmHg among indigenes (32.9 %) were significantly high than those in Han Chinese (17.4 %). Based on multivariate analysis adjusted for covariates, the results showed gender and ethnicity to be significantly correlated with systolic and diastolic BP. Gender was a modifier between ethnicity and BP. Furthermore, we found an additive effect between ethnicity and age on systolic and diastolic BP by gender. Our study showed independent additive effects on systolic BP and diastolic BP between ethnicity and age by gender.

Compared to Sleeve Gastrectomy, Duodenal-Jejunal Bypass with Sleeve Gastrectomy Gives Better Glycemic Control in T2DM Patients, with a Lower ß-Cell Response and Similar Appetite Sensations: Mixed-Meal Study.

BACKGROUND: Functional studies of how duodenal-jejunal exclusion (DJE) brings a superior glycemic control when added to sleeve gastrectomy in duodenal-jejunal bypass with sleeve gastrectomy (DJB-SG) patients, are lacking. To study this, we compared the appetite sensations and the ß-cell response following a standard mixed meal in patients with DJB-SG, versus those with sleeve gastrectomy (SG) alone. METHODS: Twenty one patients who underwent DJB-SG and 25 with SG, who participated in mixed-meal tests (MMTT) preoperatively and at 1 year, with complete data were included and compared. Blood glucose, C-peptide, and insulin levels were estimated, along with the visual analogue scale (VAS) scoring of the six appetite sensations, as a part of the MMTT. RESULTS: At 1 year following surgery, compared to SG group, DJB-SG group had greater complete remission rates (HbA1C <6.0 %) of 62 versus 32 % (p < 0.05), with similar total body weight loss (25.7 vs. 22 %). There were significantly lower post-prandial blood glucose and lower C-peptide levels during the MMTT in the patients with DJB-SG compared to SG group. There were no significant differences in the appetite sensations (mean VAS) scores between the groups. CONCLUSION: The addition of DJE component to SG, as in DJB-SG, was associated with higher diabetes remission rates, lower glycemic fluctuations, and lower C-peptide levels. This may point to a ß-cell preserving glucose control which could result in longer remission of type 2 diabetes mellitus (T2DM). This effect also may be unrelated to food intake as there were no significant differences in the appetite sensations.

Improved renal function 12 months after bariatric surgery.

BACKGROUND: Obesity is a risk factor for developing chronic kidney disease (CKD) that may be improved with bariatric surgical weight reduction. The objective of this study was to investigate changes in the glomerular filtration rate (GFR) in severely obese patients 1 year after bariatric surgery. METHODS: GFR was measured in 233 severely obese patients before and more than 12 months after bariatric surgery. Patients were separated by baseline GFR: hyperfiltration (GFR>125 mL/min), normal (GFR 125-90 mL/min), CKD stage 2 (GFR 89-60 mL/min), and CKD stage 3 (59-30 mL/min). The groups were reanalyzed 12 months after bariatric surgery. RESULTS: Of the 233 patients, 61 (26.2%) had hyperfiltration, 127 (54.5%) were normal, 39 (16.7%) had CKD stage 2, and 6 (2.6%) had CKD stage 3. The mean GFR was 146.4±17.1 mL/min in the hyperfiltration group, 105.7±9.6 mL/min in the normal group, 76.8±16.7 mL/min in the CKD stage 2 group, and 49.5±6.6 mL/min in the CKD stage 3 group. The mean GFR 1 year after weight loss surgery decreased to 133.9±25.7 mL/min in the hyperfiltration group, increased to 114.2±22.2 mL/min in the normal group, increased to 93.3±20.4 mL/min in the CKD stage 2 group, and increased to 66.8±19.3 mL/min in the CKD stage 3 group. CONCLUSIONS: Abnormal renal function was common in severely obese patients. Bariatric surgery-induced weight loss had positive effects on renal function at 1 year after surgery.

An outbreak of methicillin-resistant Staphylococcus aureus infections related to central venous catheters for hemodialysis.

OBJECTIVES: To determine risk factors for hemodialysis catheter-related bloodstream infections (HCRBSIs) and investigate whether use of maximal sterile barrier precautions would prevent HCRBSIs. SETTING: Tertiary-care medical center hemodialysis unit. DESIGN: Open trial with historical comparison and case-control study of risk factors for HCRBSIs. METHODS: Prospective surveillance was used to compare HCRBSI rates for 1 year before and after implementation of maximal sterile barrier precautions. A case-control study compared 50 case-patients with HCRBSI with 51 randomly selected control-patients. RESULTS: The HCRBSI rate was 1.6% per 100 dialysis runs (CI95, 1.1%-2.3%) in the first year and 0.77% (CI95, 0.5%-1.1%) in the second year (P = .0106). The most frequent cause of HCRBSI was MRSA in the first year (15 of 32) and MSSA in the second year (13 of 18). Ten MRSA blood isolates in the first year were identical by PFGE. Diabetes mellitus was a risk factor for HCRBSI. Age, gender, site of hemodialysis central venous catheter (CVC), other underlying diseases, coma score, APACHE II score, serum albumin level, and cholesterol level were not associated with HCRBSI and did not change between the 2 years. Hospital stay was prolonged for case-patients (32.78 +/- 20.96 days) versus control-patients (22.75 +/- 17.33 days), but mortality did not differ. CONCLUSIONS: Use of maximal sterile barrier precautions during the insertion of CVCs reduced HCRBSIs in dialysis patients and seemed cost-effective. Diabetes mellitus was associated with HCRBSI. An outbreak of MRSA in the first year was likely caused by cross-infection via medical personnel.

Uncoupling of photoreceptor peripherin/rds fusogenic activity from biosynthesis, subunit assembly, and targeting: a potential mechanism for pathogenic effects.

Inherited defects in the RDS gene cause a multiplicity of progressive retinal diseases in humans. The gene product, peripherin/rds (P/rds), is a member of the tetraspanin protein family required for normal vertebrate photoreceptor outer segment (OS) architecture. Although its molecular function remains uncertain, P/rds has been suggested to catalyze membrane fusion events required for the OS renewal process. This study investigates the importance of two charged residues within a predicted C-terminal helical region for protein biosynthesis, localization, and interaction with model membranes. Targeted mutagenesis was utilized to neutralize charges at Glu(321) and Lys(324) individually and in combination to generate three mutant variants. Studies were conducted on variants expressed as 1) full-length P/rds in COS-1 cells, 2) glutathione S-transferase fusion proteins in Escherichia coli, and 3) membrane-associated green fluorescent protein fusion proteins in transgenic Xenopus laevis. None of the mutations affected biosynthesis of full-length P/rds in COS-1 cells as assessed by Western blotting, sedimentation velocity, and immunofluorescence microscopy. Although all mutations reside within a recently identified localization signal, none altered the ability of this region to direct OS targeting in transgenic X. laevis retinas. In contrast, individual or simultaneous neutralization of the charged amino acids Glu(321) and Lys(324) abolished the ability of the C-terminal domain to promote model membrane fusion as assayed by lipid mixing. These results demonstrate that, although overlapping, C-terminal determinants responsible for OS targeting and fusogenicity are separable and that fusogenic activity has been uncoupled from other protein properties. The observation that subunit assembly and OS targeting can both proceed normally in the absence of fusogenic activity suggests that properly assembled and targeted yet functionally altered proteins could potentially generate pathogenic effects within the vertebrate photoreceptor.

Cultured retinal neuronal cells and Müller cells both show net production of lactate.

Glucose has long been considered the substrate for energy metabolism in the retina. Recently, an alternative hypothesis (metabolic coupling) suggested that mitochondria in retinal neurons utilize preferentially the lactate produced specifically by Müller cells, the principal glial cell in the retina. These two views of retinal metabolism were examined using confluent cultures of photoreceptor cells, Müller cells, ganglion cells, and retinal pigment epithelial cells incubated in modified Dulbecco's minimal essential medium containing glucose or glucose and lactate. The photoreceptor and ganglion cells represented neural elements, and the Müller and pigment epithelial cells represented non-neural cells. The purpose of the present experiments was two-fold: (1) to determine whether lactate is a metabolic product or substrate in retinal cells, and (2) to examine the evidence that supports the two views of retinal energy metabolism. Measurements were made of lactic acid production, cellular ATP levels, and cellular morphology over 4 h. Results showed that all cell types incubated with 5 mM glucose produced lactate aerobically and anaerobically at linear rates, the anaerobic rate being 2-3-fold higher (Pasteur effect). Cells incubated with both 5 mM glucose and 10 mM lactate produced lactate aerobically and anaerobically at rates similar to those found when cells were incubated with glucose alone. Anaerobic ATP content in the cells was maintained at greater than 50% of the control, aerobic value, and cellular morphology was well preserved under all conditions. The results show that the cultured retinal cells produce lactate, even in the presence of a high starting ambient concentration of lactate. Thus, the net direction of the lactic dehydrogenase reaction is toward lactate formation rather than lactate utilization. It is concluded that retinal cells use glucose, and not glial derived lactate, as their major substrate.

Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells.

We have shown previously with in vivo and in vitro animal models that the lens epithelium, in contrast to the nucleus, is remarkably resistant to hyperoxia. The main purpose of this study was to investigate the mRNA response of cultured human lens epithelial cells (LECs) to challenge by a high level of hyperbaric oxygen. Cells were treated for 3 hr with 50 atm of 99% O2, and then cultured normally for various times up to 11 days. Although the cells appeared normal immediately after the O2-treatment, they failed to grow and suffered 50% cell loss, as well as significant mitochondrial damage, during normal post-culture. Growth of the cells resumed after 3 days and by day 11, the number of O2-treated cells was the same as the controls. Remarkably, the 3 hr O2-treatment produced no immediate effects on either the cellular level of GSH, or on the activities of a number of antioxidant enzymes including glyceraldehyde-3-phosphate dehydrogenase, which is generally regarded as being highly sensitive to oxidation. In contrast, the activity of thioredoxin reductase (TrxR) was severely affected by the O2, decreasing by 51% after the 3 hr exposure. O2-induced death of the cells appeared to be caused by loss of ATP since a 31% decrease in ATP level occurred immediately after the O2-treatment, in spite of a 46% increase in lactate production. Analysis with real-time PCR showed a maximum 3-6-fold increase in mRNA levels 9 hr after the 3 hr O2-exposure for the enzymes heme oxygenase-1 (HO-1), MnSOD and TrxR1 (the cytoplasmic form of TrxR). These results were confirmed with the use of one-step RT-PCR and Northern blotting. Initial upregulation of message for HO-1 occurred a few hours before any upregulation of MnSOD could be detected, suggesting that release of free iron from the degradation of heme by HO-1 may have played a role in the upregulation of the dismutase. No significant changes in mRNA levels were observed for the antioxidant enzymes catalase, CuZnSOD, glutathione reductase and glutathione peroxidase, or for the antioxidant protein thioredoxin. Recovery of TrxR activity over a 4-day period appeared to parallel the return of the cells to a normal rate of growth. The results indicate that damaging effects of hyperoxia on cultured LECs occur primarily in the mitochondria, rather than in the cytoplasm. Cells avoid O2-induced cell death, and return to a normal rate of proliferation by upregulating mRNA levels for HO-1, MnSOD and TrxR1. It appears that full activity of TrxR1, an enzyme required for the production of deoxyribonucletides for DNA synthesis, is essential for the normal growth of O2-challenged LECs.