The Effects of Vitamin E, Silymarin and Carnitine on the Metabolic Abnormalities Associated with Nonalcoholic Liver Disease.

The obesity epidemic has resulted in an increase in the incidence of metabolic syndrome, and liver disease. Studies indicate that antioxidant supplementation may improve abnormal liver chemistries, glucose control, and hyperlipidemia, in patients with nonalcoholic fatty liver disease (NAFLD). The primary objective of the study was to determine the normalization of abnormalities in hepatic function testing in patients with NAFLD when treated with vitamin E 200 IU, Silymarin 750 mg, and l-carnitine 1 gram (VSC) for 18 weeks in comparison to a placebo-controlled group. Secondary objectives were to evaluate changes in blood glucose level, insulin, total cholesterol, triglycerides, high-density lipoproteins (HDL), low-density lipoproteins (LDL), C-reactive protein (CRP), hemoglobin A1C (HgA1c), and homeostatic models assessment (HOMA) in patients treated with VSC vs placebo. Findings showed that VSC caused a significant reduction in serum glucose, insulin, and HOMA levels. While there were downtrends in the other measured values these were not statistically significant. In this 18-week study, the ability of this supplement in reducing markers of liver inflammation, glucose, insulin, and triglycerides indicate that this supplement could play an important role in the treatment of nonalcoholic fatty liver disease, diabetes, and the metabolic syndrome.

Propofol compared with combination propofol or midazolam/fentanyl for endoscopy in a community setting.

This retrospective cohort study evaluated procedural efficiency and patient satisfaction in patients who had received propofol, midazolam/fentanyl/propofol (MFP), or midazolam/fentanyl, as sedation for either esophagogastroduodenoscopy or colonoscopy. Questionnaires about procedural times and patient satisfaction were administered. Use of propofol for colonoscopy resulted in shorter time (minutes) from induction to start of procedure (mean +/- standard deviation: propofol, 1.3 +/- 0.57; MFP, 3.2 +/- 2.2; midazolam/fentanyl, 3.8 +/- 2.7; P < .04) and shorter procedure time (propofol, 13 +/- 0.36; MFP, 15 +/- 0.004; midazolam/fentanyl, 75 +/- 0.005 minutes; P < .05). Recovery time was less for patients receiving propofol for their colonoscopy compared with the other groups (propofol, 9 +/- 8; MFP, 15 +/- 9; midazolam/ fentanyl, 18 +/- 117 minutes; P < .05). Patients undergoing esophagogastroduodenoscopy who received propofol had a shorter recovery time (9 +/- 7 minutes vs MFP, 14 +/- 9 minutes, and midazolam/fentanyl, 19 +/- 11 minutes; P < .05). Patients receiving propofol felt less discomfort and need for adjustment in the sedation, and remembered less of the procedure compared with the MFP group. Propofol resulted in less time in the endoscopy unit, quicker recovery and discharge, and greater patient satisfaction than did balanced or conscious sedation.

Duodenal carcinoma at the ligament of Treitz. A molecular and clinical perspective.

BACKGROUND: There is very small occurrence of adenocarcinoma in the small bowel. We present a case of primary duodenal adenocarcinoma and discuss the findings of the case diagnostic modalities, current knowledge on the molecular biology behind small bowel neoplasms and treatment options. CASE: The patient had a history of iron deficiency anemia and occult bleeding with extensive workup consisting of upper endoscopy, colonoscopy, capsule endoscopy, upper gastrointestinal series with small bowel follow through and push enteroscopy. Due to persistent abdominal pain and iron deficiency anemia the patient underwent push enteroscopy which revealed adenocarcinoma of the duodenum. The patient underwent en-bloc duodenectomy which revealed T3N1M0 adenocarcinoma of the 4th portion of the duodenum. CONCLUSIONS: Primary duodenal carcinoma, although rare should be considered in the differential diagnosis of occult gastrointestinal bleeding when evaluation of the lower and upper GI tract is unremarkable. We discuss the current evaluation and management of this small bowel neoplasm.

Accumulation of oxidatively induced clustered DNA lesions in human tumor tissues.

Increased levels of oxidatively induced DNA damage have been reported in various cases of human pathogenesis like age-related and chronic diseases. Advances in experimental carcinogenesis associate high oxidative stress with genome instability and oncogenic transformation. Cancer biomarkers are helpful for early tumor diagnostics, prediction of tumor development, and analysis of individual tumors' response to therapy as well as recurrence. The repair resistant oxidatively induced clustered DNA lesions (OCDLs) could serve as a common indicator of oxidative stress in human malignant cells or tissues. To test this hypothesis, we assessed the levels of endogenous OCDLs in several human tumor and adjacent normal tissues from patients with liver, ovary, kidney, breast and colon cancer. These tumor tissues have already been shown to accumulate higher endogenous levels of gamma-H2AX foci. For the detection of clustered DNA lesions we used the human repair enzymes APE1, OGG1 and NTH1 as well as the Escherichia coli homologue Endonuclease III. In the majority of cases we detected higher levels of OCDLs in tumor vs. normal tissues but not always with a statistically significant difference and not with uniform tissue dependence. These data suggest for the first time the importance of endogenous non-DSB clusters in human cancer and their potential use as cancer biomarkers.

Induction and processing of complex DNA damage in human breast cancer cells MCF-7 and nonmalignant MCF-10A cells.

Oxidatively induced stress and DNA damage have been associated with various human pathophysiological conditions, including cancer and aging. Complex DNA damage such as double-strand breaks (DSBs) and non-DSB bistranded oxidatively induced clustered DNA lesions (OCDL) (two or more DNA lesions within a short DNA fragment of 1-10 bp on opposing DNA strands) are hypothesized to be repair-resistant lesions challenging the repair mechanisms of the cell. To evaluate the induction and processing of complex DNA damage in breast cancer cells exposed to radiotherapy-relevant gamma-ray doses, we measured single-strand breaks (SSBs), DSBs, and OCDL in MCF-7 and HCC1937 malignant cells as well as MCF-10A nonmalignant human breast cells. For the detection and measurement of SSBs, DSBs, and OCDL, we used the alkaline single-cell gel electrophoresis, gamma-H2AX assay, and an adaptation of pulsed-field gel electrophoresis with E. coli repair enzymes as DNA damage probes. Increased levels for most types of DNA damage were detected in MCF-7 cells while the processing of DSBs and OCDL was deficient in these cells compared to MCF-10A cells. Furthermore, the total antioxidant capacity of MCF-7 cells was lower compared to their nonmalignant counterparts. These findings point to the important role of complex DNA damage in breast cancer and its potential association with breast cancer development especially in the case of deficient BRCA1 expression.

Induction and processing of oxidative clustered DNA lesions in 56Fe-ion-irradiated human monocytes.

Space and cosmic radiation is characterized by energetic heavy ions of high linear energy transfer (LET). Although both low- and high-LET radiations can create oxidative clustered DNA lesions and double-strand breaks (DSBs), the local complexity of oxidative clustered DNA lesions tends to increase with increasing LET. We irradiated 28SC human monocytes with doses from 0-10 Gy of (56)Fe ions (1.046 GeV/ nucleon, LET = 148 keV/microm) and determined the induction and processing of prompt DSBs and oxidative clustered DNA lesions using pulsed-field gel electrophoresis (PFGE) and Number Average Length Analysis (NALA). The (56)Fe ions produced decreased yields of DSBs (10.9 DSB Gy(-1) Gbp(-1)) and clusters (1 DSB: approximately 0.8 Fpg clusters: approximately 0.7 Endo III clusters: approximately 0.5 Endo IV clusters) compared to previous results with (137)Cs gamma rays. The difference in the relative biological effectiveness (RBE) of the measured and predicted DSB yields may be due to the formation of spatially correlated DSBs (regionally multiply damaged sites) which result in small DNA fragments that are difficult to detect with the PFGE assay. The processing data suggest enhanced difficulty compared with gamma rays in the processing of DSBs but not clusters. At the same time, apoptosis is increased compared to that seen with gamma rays. The enhanced levels of apoptosis observed after exposure to (56)Fe ions may be due to the elimination of cells carrying high levels of persistent DNA clusters that are removed only by cell death and/or "splitting" during DNA replication.