Postprandial modulation of dietary and whole-body nitrogen utilization by carbohydrates in humans

BACKGROUND: Sucrose exerts a sparing effect on whole-body protein metabolism, mainly during the absorptive phase. OBJECTIVE: We aimed to characterize the acute postprandial effect of addition of sucrose on deamination of dietary and endogenous nitrogen, with particular consideration being given to the effects of bioavailability. DESIGN: Twenty-one subjects equipped with ileal tubes ingested (15)N-labeled soy protein combined with [(13)C]glycine, with (n = 10) or without (n = 11) sucrose. Dietary and endogenous ileal flow of nitrogen were determined from the ileal effluents. The kinetics of dietary amino acid transfer to the blood were characterized by (13)CO(2) enrichment in breath and (15)N enrichment in plasma amino acids. Deamination of dietary and endogenous amino acid was determined from body urea, urinary nitrogen, and (15)N enrichment. RESULTS: (13)CO(2) recovery in breath and (15)N plasma amino acid enrichments were highly correlated (R:(2) >/= 0.95, P: < 0.001, for both meals) and markedly delayed by sucrose (half-(13)CO(2) recovery: 274 min compared with 167 min), whereas exogenous and endogenous ileal nitrogen kinetics and balances remained unchanged. Addition of sucrose halved the early (0-2 h) deamination peak of dietary nitrogen and reduced endogenous nitrogen oxidation over the first 4 h. Both were reduced by 18-24% over the 8-h period after the meal. CONCLUSIONS: Without changing the nitrogen absorptive balance, sucrose markedly affected the bioavailability profile, which is governed by gastric emptying. Endogenous and dietary nitrogen were not spared in the same way and over the same periods, showing that the metabolism of endogenous and dietary nitrogen may be affected differently by nutritional modulation, even if the effects are of a similar magnitude over the entire postprandial period.     

Deficient mismatch repair phenotype is a prognostic factor for colorectal cancer in elderly patients

ObjectiveAbout 15% of colorectal adenocarcinomas have a deficient DNA mismatch repair phenotype. The frequency of deficient DNA mismatch repair tumours increases with age due to the hypermethylation of hMLH1 promoter. The study aimed to determine the prognostic value of deficient DNA mismatch repair phenotype in elderly patients.DesignMismatch repair phenotype was retrospectively determined by molecular analysis in consecutive resected colorectal adenocarcinoma specimens from patients over 75 years of age from 4 Oncology centres.Results231 patients (median age: 81, range: 75–100) were enrolled from 2005 to 2008. Mean prevalence of deficient DNA mismatch repair phenotype was 22.5%, and 36% for patients over 85 years. Deficient DNA mismatch repair status was significantly associated with older age, female sex, proximal colon primary and high grade tumour. For stage II tumours no deficient DNA mismatch repair tumours had a recurrence at end of follow-up compared to 17% for tumours with proficient phenotype. The proficient phenotype status was significantly associated with worse age-adjusted overall survival [HR 2.60; 95% CI 1.05–6.44; p = 0.039]. For stage III tumours a trend for less recurrence was observed for deficient DNA mismatch repair phenotype (16%) compared to proficient phenotype (36%).Conclusiondeficient DNA mismatch repair phenotype is a prognostic factor in stage II colorectal tumour in elderly patients. Our results suggest that mismatch repair phenotype should be taken in consideration for adjuvant chemotherapy decision in elderly patients.     

Efficacy of pantoprazole 20 mg daily compared with esomeprazole 20 mg daily in the maintenance of healed gastroesophageal reflux disease: a randomized, double-blind comparative trial - the EMANCIPATE study

OBJECTIVES: To compare the efficacy and tolerability of pantoprazole 20 mg once daily with that of esomeprazole 20 mg once daily for 6 months as maintenance therapy in patients with previously healed gastroesophageal reflux disease. METHODS: In an initial open-label acute phase, outpatients with endoscopically confirmed gastroesophageal reflux disease (Los Angeles grades A-D) received pantoprazole 40 mg once daily for 4 or 8 weeks. Those healed (defined as the absence of esophagitis, and 'no' or 'mild' heartburn and acid regurgitation) were randomized in the double-blind manner for maintenance therapy with pantoprazole 20 mg once daily or esomeprazole 20 mg once daily for 6 months. RESULTS: In the acute healing phase, 1452 patients were recruited to receive pantoprazole 40 mg once daily. Healing success was 91% (intent-to-treat analysis). A total of 1303 patients entered the maintenance phase of the study. Pantoprazole 20 mg once daily and esomeprazole 20 mg once daily were equally effective at maintaining patients in remission; 84 and 85% of pantoprazole and esomeprazole recipients remained in combined endoscopic and symptomatic remission at 6 months (intent-to-treat analysis). The confidence interval of the difference was (-5.7; +infinity), showing that pantoprazole is as effective as esomeprazole with a noninferiority margin of 5.8%. Combined endoscopic and symptomatic remission was independent of Helicobacter pylori status. Both treatments were well tolerated and safe. CONCLUSION: Treatment with pantoprazole 20 mg once daily or esomeprazole 20 mg once daily provides similarly effective and well-tolerated maintenance of previously healed gastroesophageal reflux disease irrespective of baseline H. pylori status.     

Celecoxib leads to G2/M arrest by induction of p21 and down-regulation of cyclin B1 expression in a p53-independent manner

A unique in vitro system has been developed in our lab that consists of normal enterocytes derived from the rat ileum (IEC-18 cells) and their transformed derivatives with c-K-ras (R1 cells), anti-sense bak (B3 cells) and cyclin D1 (D1 cells). R1 and B3 cells express high level of COX-2 protein and PGE2. IEC 18 and D1 cells express negligible amount of COX-2, and produce very low level of PGE2. A relatively low dose of celecoxib (5-10 microM) induced G2/M arrest, followed by induction of apoptosis in the transformed but not in the normal cells. Down-regulation of cyclin B1 and up-regulation of p21 expressions independent of p53 might have cause this cell cycle block. Growth inhibition was related to COX-2 function with 90-95% reduction in PGE2 production. These findings may be of clinical importance, since low concentration of celecoxib can be achieved in human serum following standard anti-inflammatory (100-200 mg bid) regime.     

Buerger's disease or thromboangiitis obliterans revealed by an enteric ischemia. Case report and literature review

Thromboangiitis obliterans or Buerger's disease is a rare arteritis affecting mainly young male smokers. Distal limb symptoms are well-known. Digestive manifestations, especially when inaugural, are less known and sometimes misdiagnosed. We report the case of a 37-year-old man who developed a large mesenteric infarct with diffuse ischemic colitis and ischemia in the hepatic artery field. Histopathological findings were consistent with thromboangiitis obliterans. Unexplained abdominal pain, even if inaugural, in young male smokers, should evoke the possibility of Buerger's disease.