Serum levels and mesenteric fat tissue expression of adiponectin and leptin in patients with Crohn's disease.

Crohn's disease (CD) is characterized by inflammation and an aetiology that is still unknown. Hypertrophy of mesenteric fat is a reflection of disease activity, as this fat covers the entire length of the affected area. Adipocytes synthesize leptin and adiponectin, adipocytokines responsible for pro- and anti-inflammatory effects. Therefore, we evaluated serum levels of adiponectin and leptin, as well as mesenteral expression of adiponectin in active CD and those in remission. Sixteen patients with ileocaecal CD followed at the Outpatient Clinic, Coloproctology Unit of University of Campinas Clinical Hospital, participated in the study. Analysis of serum adiponectin and leptin by enzyme-linked immunosorbent assay was performed in patients with active CD (ACD group), remission CD (RCD group) and in six healthy controls. Ten patients with active ileocaecal CD (FCD group) and eight patients with non-inflammatory disease selected for surgery were also studied. The specimens were snap-frozen and the expression of adiponectin was determined by immunoblot of protein extracts. Serum C-reactive protein levels were higher in the ACD group when compared to the others and no difference of body mass index was observed between the groups. Serum adiponectin was lower in the ACD group when compared to control, but no differences were seen when comparing the ACD and RCD groups. Mesenteric adiponectin expression was lower in the FCD group when compared to the FC group. Serum leptin was similar in all groups. The lower levels of serum and mesenteric adiponectin in active CD suggest a defective regulation of anti-inflammatory pathways in CD pathogenesis.

Chronic exercise reduces platelet activation in hypertension: upregulation of the L-arginine-nitric oxide pathway.

Nitric oxide (NO) inhibits platelet function and plays a key role in the regulation of cardiovascular homeostasis. Essential hypertension is characterized by an increased risk of thrombus formation, and by an inhibition of intraplatelet NO bioactivity. We have previously shown that membrane transport of L-arginine is a rate-limiting step for platelet-derived NO synthesis. This study examined the effects of exercise on the platelet L-arginine-NO pathway and aggregation and systemic inflammation markers in 13 sedentary hypertensive patients subjected to 60 min of training activity (exercise group), predominantly aerobic, three times a week for a period of 12 weeks. Six sedentary hypertensive patients participated in the control group. After 12 weeks, L-arginine transport was significantly increased and associated with increased platelet NO synthase activity and cGMP levels and reduced platelet aggregation. Moreover, exercise training reduced plasma concentrations of fibrinogen and C-reactive protein and blood pressure. The control group did not change their previous intraplatelet L-arginine-NO results and systemic inflammatory markers levels. Thus, exercise training reduces inflammatory responses, restores NO synthesis in platelets and thereby contributes to the beneficial effects of exercise in hypertension. The present study adds exercise as a new tool to reduce morbidity and mortality associated with platelet activation in hypertension.

Role of nitrites in the genesis of adenocarcinoma associated with Barrett's esophagus.

BACKGROUND: Barrett's esophagus (BE) is one of the complications of gastroesophageal reflux disease (GERD) and a premalignant condition. It consists of a process of replacement of the squamous epithelium of the esophagus by intestinal columnar epithelium containing goblet cells, known as specialized intestinal metaplasia with goblet cells, and several factors have been related to its pathogenesis. The objective of this study was to evaluate an experimental model of duodenogastroesophageal reflux and the effect of ingestion of sodium nitrite solution on the genesis of adenocarcinoma associated with Barrett's esophagus. MATERIALS AND METHODS: Sixty male Wistar rats were divided into four groups. Twenty were not submitted to surgery and served as controls (10 animals ingesting only water and 10 ingesting water plus a solution of sodium nitrite), while the remaining 40 animals were submitted to side-to-side duodenogastroesophageal anastomosis (20 animals ingesting only water and 20 ingesting water plus the sodium nitrite solution). The Vienna classification for dysplasia and adenocarcinoma was used in the analysis of results. RESULTS: After 42 weeks of observation, Barrett's esophagus was found in 26.3% (5/19) of the animals submitted to surgery that had not ingested nitrites compared to 72.3% (13/18) of the animals in the group submitted to surgery and given nitrites. Six cases of adenocarcinoma (33.3%) were also found in this latter group. Barrett's esophagus was not found in any of the animals that were not submitted to surgery. Categories 2, 3 and 5 of the Vienna classification were only found in the animals submitted to surgery that also received sodium nitrite (66.7%). CONCLUSION: The ingestion of sodium nitrite associated with duodenogastroesophageal reflux plays an important role in the genesis of adenocarcinoma associated with Barrett's esophagus.

The role of exercise on L-arginine nitric oxide pathway in chronic heart failure.

Chronic heart failure (CHF) is a pathological state with high morbidity and mortality and the full understanding of its genesis remain to be elucidated. In this syndrome, a cascade of neurohormonal and hemodynamic mechanisms, as well as inflammatory mediators, are activated to improve the impaired cardiac function. Clinical and experimental observations have shown that CHF is associated with a generalized disturbance in endothelium-dependent vasodilation, which may contribute to the progression of ventricular and vascular remodelling in this syndrome. There is also accumulating evidence that disturbances in nitric oxide (NO) availability is involved in the development of heart failure at the systemic and cardiac levels. NO is a ubiquitous signalling molecule which causes potent vasodilation, inhibits platelet activation and regulates the contractile properties of cardiac myocytes. It is generated from the amino acid L-arginine via constitutive and inducible isoforms of the enzyme NO synthase (NOS). There is evidence that exercise, a nonpharmacological tool, improves symptoms, fitness (VO(2peak)), quality of life and NO bioavailability in CHF population. This review examines different aspects of the L-arginine-NO pathway and inflammation in the physiopathology of CHF and highlights the important beneficial effects of exercise in this disease.