Conservative approach in Peutz-Jeghers syndrome: Single-balloon enteroscopy and small bowel polypectomy

AIM: To assess the usefulness of the balloon assisted enteroscopy in preventing surgical intervention in pa-tients with Peutz-Jeghers syndrome (PJS) having a small bowel large polyps. METHODS: Seven consecutive asymptomatic pts(age 15-38 years) with PJS have been collected; six under-went polypectomy using single balloon enteroscopy(Olympus SIF Q180) with antegrade approach using push and pull technique. SBE system consists of the SIF-Q180 enteroscope, an overtube balloon control unit(OBCU Olympus Balloon Control Unit) and a dispos-able silicone splinting tube with balloon(ST-SB1). All procedures were performed under general anesthesia. Previously all pts received wireless capsule endos-copy(WCE). Prophylactic polypectomy was reservedmainly in pts who had polyps 15 mm in diameter. The balloon is inflated and deflated by a balloon control unit with a safety pressure setting range from-6.0 kPa to +5.4 kPa. Informed consent has been obtained from pts or parents for each procedure.RESULTS: Six pts underwent polypectomy of small bowel polyps; in 5 pts a large polyp 15 mm(range 20-50 mm in diameter) was resected; in 1 patient with WCE negative, SBE was performed for previous surgi-cal resection of gastrointestinal stromal tumors. In 2 pts endoscopic clips were placed due to a polypectomy. No surgical complication have been reported. SBE with resection of small bowel large polyps in PJS pts was useful to avoid gastrointestinal bleeding and emergency laparotomy due to intestinal intussuscep-tions. No gastrointestinal tumors were found in sub-sequent enteroscopic surveillance in all seven pts. In order surveillance, all pts received WCE, upper en-doscopy, ileocolonoscopy every 2 years. No pts had extraintestinal malignant lesions. SBE was performed when WCE was positive for significant polyps( 15 mm).CONCLUSION: The effective of prophylactic polyp-ectomy of small bowel large polyps( 15 mm) could be the first line treatment for conservative approach in management of PJS patients.     

Rural and urban microbiota: To be or not to be?

A multitude of metagenomic studies has brought to light an enormous richness of human gut microbiota compositions. In this space of possible configurations, clinical specialists are trying to mine the markers of healthy microbiota via case-control and longitudinal studies. We have discovered potentially beneficial communities while examining the microbial diversity in rural Russians in comparison with the urban dwellers. In this addendum, we further examine the data by elaborating on some of the less common types and suggesting the possible co-metabolism of their drivers. In the light of the first validated clinically effective bacterial transplantation, we discuss the concept of a reference healthy microbiota, outline the problems encountered on the way to its restoration in the developed world, and speculate if rural communities can serve as a source for its prototype.     

Oxidative and nitrosative stress enzymes in relation to nitrotyrosine in Helicobacter pylori-infected humans

AIM: To compare a possible relation between Helicobacter pylori(H. pylori) and the oxygen- and nitrogen radical system in humans. METHODS: Mechanisms for H. pylori to interfere with the oxygen and nitrogen radical system is of great importance for understanding of the H. pylori persistence and pathogenesis. Biopsies were obtained from the gastric wall of 21 individuals. Ongoing infection with H. pylori was detected using direct analyze from the biopsies using campylobacter-like organism test(CLO-test) and/or by using 14C-urea breath test. The individuals were divided in a negative H. pylori and a positive H. pylori group. Expression in the gastric mucosa of induc-ible nitric oxide syntase(iNOS), nicotinamide adenine dinucleotide phosphate-oxidase(NADPH-oxidase) myeloperoxidase(MPO), and nitrotyrosine were assessed by Western blotting.RESULTS: The individuals who undervent gastroscopy were divided in a H. pylori neg. [n = 13, m/f = 7/6, age(mean) = 39] and a H. pylori pos. group [n = 8, m/f = 5/3, age(mean) = 53]. Using western blot analysis iNOS was detected as a 130 kDa band. The iNOS expression was upregulated in the antrum of H. pylori infected individuals in comparison to the controls, mean ± SD being 12.6 ± 2.4 vs 8.3 ± 3.1, P 0.01. There was a markedly upregulated expression of MPO in the antrum of H. pylori infected individuals in comparison to the control group without infection. In several of noninfected controls it was not possible to detect any MPO expression at all, whereas the expression was high in all the infected subjects, mean ± SD being 5.1 ± 3.4 vs 2.1 ± 1.9, P 0.05. The NADPH-oxidase expression was analysed by detecting the NADPH-oxidase subunit p47-phox expression. P47-phox was detected as a 47 kDa band using Western blot, and showed a significantly higher expression of p47-phox in the antrum of the H. pylori infected individuals compared to the controls, mean ± SD being 3.1 ± 2.2 vs 0.3 ± 0.2, P 0.01. Regarding nitrotyrosine formation, Western blot did not show any significant increase or decrease compared to controls, 7.0 ± 0.9 vs 6.9 ± 1.1, not significant.CONCLUSION: iNOS, MPO and NADPH-oxidase was up-regulated among H. pylori infected. Regarding nitrotyrosine no difference was found. This support an H. pylori related inhibition of radical formation.     

Interactions between chromosomal and nonchromosomal elements reveal missing heritability

The measurement of any nonchromosomal genetic contribution to the heritability of a trait is often confounded by the inability to control both the chromosomal and nonchromosomal information in a population. We have designed a unique system in yeast where we can control both sources of information so that the phenotype of a single chromosomal polymorphism can be measured in the presence of different cytoplasmic elements. With this system, we have shown that both the source of the mitochondrial genome and the presence or absence of a dsRNA virus influence the phenotype of chromosomal variants that affect the growth of yeast. Moreover, by considering this nonchromosomal information that is passed from parent to offspring and by allowing chromosomal and nonchromosomal information to exhibit nonadditive interactions, we are able to account for much of the heritability of growth traits. Taken together, our results highlight the importance of including all sources of heritable information in genetic studies and suggest a possible avenue of attack for finding additional missing heritability.A fundamental problem in genetics is unraveling the link between genotype and phenotype. Ascertaining the heritability of a trait is a key step toward harnessing the predictive capacity of genetic information for human disease risk assessment and therapy (1). Knowledge of all of the elements contributing to heritability would facilitate the establishment of a causal relationship between the information that is passed down from generation to generation and the resulting phenotype. Genome-wide association studies (GWASs) have successfully identified many human polymorphisms that are associated with traits such as height, eye color, or susceptibility to common diseases, but these variants typically explain only a small proportion of the observed heritability of a trait (2, 3).A number of explanations for missing heritability have been suggested (2), including the existence of many weak variants with effects too small to achieve statistical significance (4), interactions between variants that cannot be identified with current studies (5), rare variants that were not identified by GWAS, and epigenetic effects (6–8). The contribution of nonchromosomal information to the missing heritability is rarely considered, despite the fact that there is a long history documenting the effect in many organisms of diverse cytoplasmic elements on phenotype. Recent work on a mouse model of Crohn disease supports a combinatorial model of complex disease traits in which the pathology requires the interaction between a specific mutation in the mouse and a specific strain of virus (9). Another recent study showed strong effects on the plant metabolome stemming from variation in mitochondrial and chloroplast genomes (10). In humans, the importance of nonchromosomal information has been supported by targeted analyses, but these studies have not analyzed its impact on heritability in a well-controlled context (11–13). Such nonchromosomal interactions might help explain why shared mutations in humans do not always produce the same phenotype, thus reducing the apparent heritability of a trait (14, 15).We sought to characterize explicitly how nonchromosomal modifiers collectively influence the heritability of a trait, colony size, in a system unique to yeast where we use a defined chromosomal genotype and vary the cytoplasmic genetic information. Yeast has at least four well-studied sources of inherited, nonchromosomal information: mitochondrial DNA, an endogenous dsRNA virus (16, 17), prions (18, 19), and a 2µ plasmid (20, 21).Our results show that the nonchromosomal contribution to heritability can be large, adding another dimension to the estimation of heritability in wild populations. Nonchromosomal information is not under the usual constraints of the nuclear genome. These nonchromosomal elements are extremely unstable: they mutate at higher frequencies than the DNA of the chromosomal genome, may be lost at high frequencies without loss of viability, and can vary in copy number from cell to cell. Thus, careful controls and measurements are necessary to characterize the effects of nonchromosomal modifiers.