Helicobacter pylori infection upregulates endothelial nitric oxide synthase expression and induces angiogenesis in gastric mucosa of dyspeptic patients

BACKGROUND: Helicobacter pylori (H. pylori) infection induces nitric acid (NO) overproduction through inducible NO synthase (NOS) expression, subsequent DNA damage and enhanced antiapoptosis signal transduction sequence in the human gastric mucosa, whereas its possible effect on endothelial nitric oxide synthase (eNOS) expression has not as yet been investigated. The aim of this study was to evaluate the effect of H. pylori infection in the expression of eNOS in gastric mucosa. PATIENTS AND METHODS: We prospectively studied 30 nonsmoking dyspeptic patients (12 men, 18 women, mean age 54.26+/-12.89 years). The diagnosis of H. pylori infection was based mainly on histology. The histological grading of H. pylori infection was evaluated according to the modified Sydney classification. Histological grading of eNOS expression and microvessel density as estimated by CD34 expression were determined by immunohistochemistry (degree 0-3) and correlated with H. pylori infection and histological degree of gastritis. RESULTS: Twelve patients were H. pylori-positive and 18 patients were H. pylori-negative. The two groups were matched for age (P=0.139), sex (P=0.342) and similar degree of gastritis. Intensity of eNOS and CD34 expression in the corpus and antrum were significantly correlated (P<0.001). eNOS expression was correlated with H. pylori infection in the mucosa of the body and antrum (P=0.013 and 0.037, respectively) but not with gastric inflammation and activity (P=0.848 and 0.871, respectively, for the corpus and P=0.565 and 0.793, respectively, for the antrum). H. pylori-positive patients showed higher expression of CD34-positive blood vessels in the mucosa of the antrum (P=0.048). CD34 expression was correlated with gastric inflammation and activity (P=0.03 and 0.044, respectively) in the mucosa of the antrum of H. pylori-positive patients. CONCLUSION: H. pylori infection upregulates eNOS, and induces angiogenesis, contributing to H. pylori-associated pathophysiology in gastric mucosa.     

A breaker of advanced glycation end products attenuates diabetes-induced myocardial structural changes

The formation of advanced glycation end products (AGEs) on extracellular matrix components leads to accelerated increases in collagen cross linking that contributes to myocardial stiffness in diabetes. This study determined the effect of the crosslink breaker, ALT-711 on diabetes-induced cardiac disease. Streptozotocin diabetes was induced in Sprague-Dawley rats for 32 weeks. Treatment with ALT-711 (10 mg/kg) was initiated at week 16. Diabetic hearts were characterized by increased left ventricular (LV) mass and brain natriuretic peptide (BNP) expression, decreased LV collagen solubility, and increased collagen III gene and protein expression. Diabetic hearts had significant increases in AGEs and increased expression of the AGE receptors, RAGE and AGE-R3, in association with increases in gene and protein expression of connective tissue growth factor (CTGF). ALT-711 treatment restored LV collagen solubility and cardiac BNP in association with reduced cardiac AGE levels and abrogated the increase in RAGE, AGE-R3, CTGF, and collagen III expression. The present study suggests that AGEs play a central role in many of the alterations observed in the diabetic heart and that cleavage of preformed AGE crosslinks with ALT-711 leads to attenuation of diabetes-associated cardiac abnormalities in rats. This provides a potential new therapeutic approach for cardiovascular disease in human diabetes.     

Short-term treatment with ezetimibe, simvastatin or their combination does not alter circulating adiponectin, resistin or leptin levels in healthy men

Objective Statin therapy decreases cardiovascular morbidity and mortality, and ezetimibe, a novel cholesterol absorption inhibitor has both lipid‐lowering and anti‐atherosclerotic effects in animal models. As several adipokines, that is, adiponectin, high molecular weight (HMW) adiponectin, leptin and/or possibly resistin are involved in the pathogenesis of insulin resistance (IR), dyslipidaemia and atherosclerosis, we investigated whether ezetimibe and/or statin treatment may modulate serum concentrations of these four major adipokines. Research design and methods One‐centre, randomized, parallel three‐group study in 72 healthy men [mean age 32 ± 9 years, mean body mass index (BMI) 25·7 ± 3·2 kg/m²]. Patients Seventy‐two healthy men. Each group of 24 subjects received a 14‐day treatment with either ezetimibe (10 mg/day), simvastatin (40 mg/day) or their combination. Blood was drawn before and after the 14‐day treatment period. Measurements Lipid levels, IR indices, serum leptin, adiponectin, HMW adiponectin and resistin concentrations. Results Neither ezetimibe nor simvastatin or their combination had any effect on serum leptin, adiponectin, HMW adiponectin and resistin concentrations. Baseline leptin levels correlated positively, while adiponectin and HMW adiponectin negatively, with BMI. Leptin concentrations correlated negatively while adiponectin and HMW adiponectin positively with plasma high‐density lipoprotein‐cholesterol concentrations. Resistin concentrations were not associated with BMI, lipid levels or indicators of IR. Conclusions Treatment with ezetimibe, simvastatin or their combination does not alter circulating levels of adiponectin, leptin or resistin in adult healthy men.     

Reproducible lactulose hydrogen breath test as a measure of mouth-to-cecum transit time

Breath hydrogen monitoring after oral lactulose syrup is a conventional measure of mouth-to-cecum transit time (MCTT), but its reproducibility has been questioned. We compared the reproducibility of five measurements of MCTT after a conventional breakfast (380 kcal) taken with tea containing 20 g lactulose to five measurements of MCTT after 20 g lactulose in water in eight normal volunteers. Individual mean breakfast transit time was not significantly different from lactulose transit time in each of the seven subjects, but one had a breakfast transit time of 151±15 min and a lactulose transit time of 86±22 minutes (¯X ±sd, P<0.001). The coefficient of variation of breakfast transit time (11.6±5.3%, range: 6.9–24.2%) was less than that of lactulose transit time (30.7±7.8%, range: 22.1–50.0%, P<0.001). In a second set of experiments, the liquid phase marker ( ^99m Technetiumdiethylene triamine pentaacetic acid) emptied from the stomach more rapidly after the lactulose solution (T1/2 16.3±5.4) than after the breakfast (33.9±10.9 min, P<0.01) and MCTT was shorter after lactulose (77±32 vs 104±40 min, trespectively, P<0.05). There was no correlation between MCTT of lactulose and breakfast and between half-time gastric emptying and MCTT of either lactulose or breakfast. We conclude that the ingestion of inert lactulose induces an abnormally rapid MCTT and that breakfast MCTT is a much more reproducible investigation and should be employed in studies requiring serial measurements.     

Common and Dissociable Dysfunction of the Reward System in Bipolar and Unipolar Depression

Unipolar and bipolar depressive episodes have a similar clinical presentation that suggests common dysfunction of the brain’s reward system. Here, we evaluated the relationship of both dimensional depression severity and diagnostic category to reward system function in both bipolar and unipolar depression. In total, 89 adults were included, including 27 with bipolar depression, 25 with unipolar depression, and 37 healthy comparison subjects. Subjects completed both a monetary reward task and a resting-state acquisition during 3T BOLD fMRI. Across disorders, depression severity was significantly associated with reduced activation for wins compared with losses in bilateral ventral striatum, anterior cingulate cortex, posterior cingulate cortex, and right anterior insula. Resting-state connectivity within this reward network was also diminished in proportion to depression severity, most notably connectivity strength in the left ventral striatum. In addition, there were categorical differences between patient groups: resting-state connectivity at multiple reward network nodes was higher in bipolar than in unipolar depression. Reduced reward system task activation and resting-state connectivity therefore appear to be a brain phenotype that is dimensionally related to depression severity in both bipolar and unipolar depression. In contrast, categorical differences in reward system resting connectivity between unipolar and bipolar depression may reflect differential risk of mania. Reward system dysfunction thus represents a common brain mechanism with relevance that spans categories of psychiatric diagnosis.     

The diagnosis of Gestational Diabetes Mellitus and its impact on In Vitro Fertilization pregnancies. A pilot study

BackgroundIn Vitro Fertilization (IVF) is increasingly becoming a necessary mode of reproduction. This high risk group is prone to Gestational Diabetes Mellitus (GDM) which further exposes these pregnancies to an increased risk of adverse outcomes. In light of the limited data in the current literature, further investigation is needed regarding the time of GDM diagnosis in IVF pregnancies as well as the outcome of IVF pregnancies complicated by GDM.MethodsIn this three center pilot cross sectional study, the data of 101 singleton IVF pregnancies complicated by GDM were analyzed. Prompt GDM diagnosis in IVF pregnancies was accomplished by self-blood glucose monitoring (SMBG) from the first antenatal visit and confirmed by an OGTT. To evaluate pregnancy outcome, maternal and fetal complications in the 101 GDM IVF group was compared to 101 IVF as well as 101 spontaneous conceptions (SC). The three groups were matched by age. The effect of demographic and glycemic parameters on the outcome of GDM IVF pregnancies was investigated.ResultsGDM diagnosis was made before the 24th week in 37.6% of the GDM IVF group. The week of delivery was earlier for the GDM IVF group (37 ± 1.7) relative to the IVF (37.9 ± 0.9, p < 0.001) and the SC group (38.1 ± 0.8, p < 0.001). GDM IVF pregnancies exhibited greater preeclampsia rates and 84.8% underwent caesarian section. No significant difference regarding LGA and SGA birth weights was found. Complications of GDM IVF pregnancies were associated with the 1-h postprandial BG (r = 0.267, p = 0.007).ConclusionGDM screening in IVF pregnancies may be considered earlier than the 24th week. IVF pregnancies affected by GDM are prone to increased maternal and fetal complications which are associated with 1-h postprandial BG.     

Locoregional immunochemotherapy in primary and metastatic liver disease: meta-analysis and review of literature

BACKGROUND/AIMS: Primary and metastatic liver tumors are the most common malignancies that resist conventional chemotherapy and radiotherapy. Several immunotherapies have been attempted for cancer treatment on the basis of stimulating host immune response to tumors and recent development of combined targeting locoregional immunochemotherapy reported with promising results. However, the efficacy of this therapeutic modality is not yet widely established. METHODOLOGY: We reviewed the medical literature for publications dealing with the value of locoregional immunochemotherapy in patients with primary or metastatic liver tumors. RESULTS: We found that 5 and 7 studies have been controlled and inadequately controlled, respectively. Among 131 patients with primary liver cancer, 40 were treated with combined locoregional immunochemotherapy, and 20 with systemic immunochemotherapy, and 71 with systemic chemotherapy served as two control groups. Complete or partial response was observed in 32 out of 40 (80%) patients who received combined locoregional therapy, and in 10 out of 20 (50%) systemic immunochemotherapy controls (P = 0.03). Survival was three times higher in the patients who received combined locoregional therapy compared with systemic chemotherapy controls (18 vs. 5.6 months). Recurrence of tumor was higher in systemic immunochemotherapy controls (P = 0.003). Among 286 patients with metastatic liver disease, 180 patients were treated with combined locoregional immunochemotherapy and 106 patients with systemic immunochemotherapy. Response (complete or partial) was observed in 65 out of 98 (66.3%) patients who received combined therapy, and in 4 out of 26 (15.4%) controls (P < = 0.001). Survival was two-fold higher in the patients treated with combined therapy (21 vs. 10.5 months). Tumor recurrence was higher in the systemic immunochemotherapy controls (P < = 0.001). CONCLUSIONS: The observational studies indicate a plausible therapeutic rationale for the introduction of locoregional immunotherapy in patients with primary and metastatic liver disease.