Association of the p53 Arg72Pro polymorphism with esophageal cancer in Chinese populations: a meta-analysis.

Although many epidemiologic studies have investigated the p53 codon 72 polymorphism and its association with esophageal cancer (EC) in China, definite conclusions could not be drawn. To clarify the effects of p53 codon 72 polymorphism on the risk of EC, we performed a meta-analysis on the Chinese population. A total of 13 studies including 3308 patients and 5115 controls were involved in this meta-analysis. Our results suggested that the Pro/Pro genotype was associated with an increased risk of EC in the Chinese population (Pro vs Arg: odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.01-1.34; Pro/Pro vs Arg/Arg+Arg/Pro: OR = 1.32, 95%CI = 1.06-1.66; Pro/Pro vs Arg/Arg: OR = 1.35, 95%CI = 1.03-1.78; Pro/Pro vs Arg/Pro: OR = 1.32, 95%CI = 1.06-1.65). In subgroup analyses by geographical location and ethnicity, significant association was also found in south China in both the Han Chinese population and in the population group with no stated ethnicity. Sensitivity analysis confirmed the reliability and stability of the meta-analysis. No publication bias was found among studies using the Egger test. In conclusion, this meta-analysis provides supporting evidence that the Pro/Pro genotype might contribute to the development of EC in the Chinese population, especially in Southern China.

Influence of cyclophilin D protein expression level on endothelial cell oxidative damage resistance.

We examined the influence of cyclophilin-D (CypD) protein expression level on endothelial cell oxidative damage resistance. A model of CypD protein expression or high expression in endothelial cells was established through gene silencing or cloning. The comparable groups were normal endothelial cells cultured in phosphate-buffered solution in liquid handling cells containing 500 mM H2O2 for 90 or 120 min, and then the medium was replaced with common nutrient solution and cultured again for 24 h. The apoptosis rate and nitric oxide (NO) levels of each group were tested. The cell apoptosis rate of the CyPD low expression group (32.51 ± 6.6 %) was significantly lower than that of the control group (52.57 ± 5.84%, P = 0.001), and total NO production was 24.06 ± 3 and 13.03 ± 3.55 µM. The apoptosis rate of the CyPD high expression group (24.24 + 3.08%) was significantly higher than that of the control group (7.7 + 0.68%, P < 0.001); total NO production was 3.55 ± 1.53 and 8.46 ± 0.77 µM, which was significantly different (P = 0.008). CypD protein could increase oxidative stress and cause endothelial cell injury and apoptosis.

Voluntary weight loss: systematic review of early phase body composition changes.

Weight loss follows when adult humans enter a phase of negative energy balance brought about by reducing energy intake and/or increasing energy expenditure. The weight loss period is usually viewed as a continuous process, ending when energy equilibrium is achieved at a lower weight or with death following depletion of fuel stores. However, growing evidence supports the expanded view that induction of negative energy balance leads to well-defined physiological effects characterized by three discrete phases (I-III). At present there are no comprehensive reviews of the 'early' phase of weight loss, a gap highlighted by recent interest in rapidly testing new treatments with short-term protocols. Herein we show from earlier reports and with new data that weight loss during phase I is: mathematically quantifiable with a t(1/2) < 1-week and 4- to 6-week duration; includes well-defined rapidly evolving body composition and energy expenditure changes; and is moderated by multiple factors including subject sex and activity level, nutrients ingested at baseline and during the negative energy balance period, and hormone and pharmacologic treatments. Our in depth review collectively characterizes phase I as a distinct weight loss period while revealing important knowledge gaps that can be filled with appropriately designed future studies.

Eradication of Helicobacter pylori infection reverses E-cadherin promoter hypermethylation.

BACKGROUND: E-cadherin methylation is important in gastric carcinogenesis. Reversing hypermethylation may halt the carcinogenic process. We have previously reported that Helicobacter pylori infection is associated with E-cadherin methylation in chronic gastritis patients. AIM: To examine if eradication of H pylori could reverse E-cadherin methylation. METHODS: Patients with dyspepsia and positive for H pylori infection, with a mucosal biopsy showing chronic active gastritis, were randomised to receive H pylori eradication therapy (group 1, n = 41) or no treatment (group 2, n = 40), and were followed up prospectively. Gastric mucosae were taken for methylation assay at week 0 (before treatment) and week 6 (after treatment). Archived specimens of intestinal metaplasia with H pylori infection (n = 22) and without (n = 19) were retrieved for methylation analysis. Methylation was assessed using methylation specific polymerase chain reaction and sequencing. RESULTS: Methylation at E-cadherin was detected in 46% (19/41) and 17% (7/41) of patients at weeks 0 and 6, respectively, in group 1 (p = 0.004); 78.9% (15/19) of specimens were unmethylated after eradication of H pylori. Mucosal biopsy showed chronic inactive gastritis in 35 patients, intestinal metaplasia in one, and normal mucosa in five at week 6. Methylation was detected in 47.5% (19/40) and 52.5% (21/40) of patients at weeks 0 and 6, respectively, in group 2 (P = 0.5). Gastric mucosal biopsy showed persistent chronic active gastritis in all cases. Methylation frequency did not differ in H pylori positive or negative intestinal metaplastic specimens (72.7% v 63%; p = 0.5). CONCLUSION: H pylori eradication therapy could reverse methylation in patients with chronic gastritis. This demonstrates an environmental effect on methylation.

Effect of Helicobacter pylori on apoptosis and apoptosis related genes in gastric cancer cells.

BACKGROUND/AIMS: Helicobacter pylori induces the apoptosis of gastric epithelial cells in vivo and in vitro. However, the molecular mechanism has not been clarified. The aim of this study was to investigate the effect of H pylori on the apoptosis of gastric epithelial cells and the expression of apoptosis related genes in vitro. METHODS: Human gastric adenocarcinoma SGC-7901 cells were co-cultured with a cytotoxic H pylori strain, NCTC 11637, at various densities ranging from 3.2 x 10(4) to 1.0 x 10(8) colony forming units (CFU)/ml for 48 hours. Apoptosis in gastric cells was determined by transmission electron microscopy, Hoechst 33258 fluorochrome staining, and flow cytometry. The expression of apoptosis related proteins, Bcl-2, Bax, and c-Myc, was measured by an immunohistochemical method, and c-Myc mRNA expression was determined by the reverse transcription-polymerase chain reaction. RESULTS: Helicobacter pylori induces morphological changes typical of apoptosis. Both fluorochrome staining and flow cytometry showed that the apoptotic index began to increase when H pylori were at a density of > 1.6 x 10(4) CFU/ml, and in a density dependent manner (p < 0.01; one way ANOVA). The expression of the Bax and c-Myc proteins and of c-Myc mRNA was increased, whereas Bcl-2 expression was decreased after co-culture for 48 hours. CONCLUSIONS: Helicobacter pylori induced apoptosis in gastric epithelial cells is mediated by altered expression of the products of the Bcl-2, Bax, and c-Myc genes.

[Cardiovascular effects of lateral intracerebroventricular injection of L-securinine].

To investigate cardiovascular effects of changed GABAergic tonic activation in periventricular forebrain, arterial pressure (AP), heart rate (HR) and renal sympathetic nerve discharge (RSND) were recorded in anesthetized rats when L-securinine (L-Sec) was administered into the lateral intracerebroventricle. L-Sec elicited dose-dependent increases in RSND, AP and HR, which were much weaker than those of bicuculline. L-Sec antagonized the sympatho-inhibitory and depressor effects evoked by both muscimol and baclofen. These results indicate that GABAergic inhibition originating from periventricular forebrain may suppress tonically sympathetic outflow to cardiovascular system which is disinhibited by L-Sec, and L-Sec is likely an unselective GABA receptor antagonist.

Effect of intracerebral injection of pirenzepine on electroencephalography and convulsions in conscious rabbits.

Intracerebroventricular (icv) injection of pirenzepine (Pir) 2 mg.kg-1 caused EEG spike discharges, which first appeared in amygdala or hippocampus and then in midbrain reticular formation and cortex. After that rabbits developed clonic convulsions. Injection (300 micrograms) into amygdala or hippocampus also produced EEG spike discharges Hemicholinium 3 (HC-3) 50-150 micrograms.kg-1 icv inhibited the EEG spike and seizure discharges in varying degrees produced by Pir. It is suggested that Pir has a central stimulatory action which is related to cholinergic mechanism.

[Sites of seizure discharges after intracerebroventricular injection of anisodamine and the antagonism by diazepam in rabbits].

Anisodamine is a tropine alkaloid isolated from Scopolia tangutica Maxim. To determine the original sites of anisodamine seizure discharge, permanent electrodes were implanted into different parts of the brain in rabbits and the electrical activities were continuously recorded by monopolar leads. Injection of anisodamine 1.5 mg/kg into the lateral ventricle of conscious rabbits always produced abnormal discharges. The spike discharges appeared first in the amygdala and consisted of rhythmic large surface-positive spikes. Multiple spikes then appeared in the hippocampus, caudate nucleus, midbrain reticular formation and frontal cortex. Diazepam 1.5-2.5 mg/kg did not inhibit the spike discharges from the amygdala, but did inhibit the discharges from other sites as well as clonic convulsions. When the dosage of diazepam was increased to 4.5 mg/kg, the spike discharges from the amygdala were also inhibited. The above findings indicate that the site of origin of anisodamine seizure discharges in rabbits is the amygdala. The seizure discharges then spread to the mesencephalic reticular formation, the hippocampus, the caudate nucleus and the cortex. Diazepam was shown to be an effective antagonist against central stimulation induced by anisodamine.