Enhanced Expression of CXCL13 in Human <Emphasis Type="Italic">Helicobacter pylori</Emphasis>-Associated Gastritis

Background and Aims

Chemokine CXC ligand 13 (CXCL13) and CXC receptor type 5 (CXCR5) are constitutively expressed in tertiary lymphoid follicles where the CXCL13/CXCR5 system regulates B lymphocytes homing. In this study, we sought to examine CXCL13 expression in the H. pylori-infected and -uninfected gastric mucosa and to elucidate the implication in the pathogenesis of HAG in humans.

Methods

Using endoscopic biopsies taken from the gastric antrum of 29 subjects infected with Helicobacter pylori and 22 uninfected subjects, mucosal CXCL13 mRNA and protein levels were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.

Results

The CXCL13 expression levels were significantly more elevated in H. pylori-positive patients than uninfected ones. The CXCL13 expression levels correlated with the degree of chronic gastritis and bacterial colonization. Immunohistochemistry and in vitro infection assay showed that CXCL13 was not produced by the gastric epithelium, but the α-smooth muscle antigen expressing mesenchymal cells were the possible source of CXCL13 within H. pylori-infected gastric mucosa. CXCR5 immunostaining was seen in the CD20-positive lymphoid aggregates.

Conclusions

The enhanced induction of CXCL13 may be involved in the pathogenesis of H. pylori-associated gastritis.

     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection: New Facts in Clinical Management

Purpose

The global prevalence of Helicobacter pylori remains high in spite of its significant downwards trajectory in many regions. The clinical management of H. pylori infection merits guidance to meet ongoing challenges on whom and how to test, prevent, and cure related diseases.

Recent findings

Several international guidelines and consensus reports have updated the management strategies for cure of the H. pylori infection. The definition of H. pylori gastritis as an infectious disease independent of whether or not presenting with clinical manifestations and symptoms has broadened the use of the test and treat strategy. Patients on selected long-term medications, such as aspirin, other anti-platelet agents, NSAIDs, and PPIs should be considered for H. pylori test and treat. Important progress is made with initiatives in primary and secondary gastric cancer prevention. Uncertainties persist in the interpretation of the role of H. pylori in association with extragastric diseases. Selection of therapies needs to address individual antibiotic resistance and regional surveillance of resistance for the adoption of an effective treatment algorithm.

Conclusion

Clinical aspects of H. pylori infection have evolved over time and the therapeutic management requires continuous adaptation. A vaccine is still a non-fulfilled promise. The future will tell us more about the role of H. pylori in interactions with the gut microbiome.

     

Association of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> with hepatobiliary stone disease,a prospective case control study

Background

Hepatobiliary stone disease is one of the most common surgical conditions worldwide. There are multiple causative agents responsible for the formation of hepatobiliary stones, and bacterial infection is one of them. The presence of Helicobacter DNA species has been investigated in the biliary epithelium of patients with biliary diseases. However, conflicting results have been observed that may have been due to the small number of subjects studied, difficulty in obtaining a healthy control group, absence of controlling for confounding factors, or ethical and regional differences among populations.

Methods

We investigated the presence of Helicobacter pylori species by PCR of 26-kDa surface antigen specific to H. pylori in bile samples from 50 cases with hepatobiliary stones and 25 controls without hepatobiliary stones. The control group comprised of 20 patients of hydatid cyst disease of liver and 5 patients of right colonic growth.

Result

H. pylori was present in 20 bile samples among cases and was absent in 30 bile samples among cases. Among controls, H. pylori could not be detected. A significant association of the presence of H. pylori with hepatobiliary stone disease was seen (p < 0.001).

Conclusion

There is an association between bile infection with H. pylori and hepatobiliary stone disease.

     

The association between <Emphasis Type="Italic">Helicobacter pylori</Emphasis> seropositivity and risk of new-onset diabetes: a prospective cohort study

Aims/hypothesis

Previous studies have suggested a possible connection between Helicobacter pylori (H. pylori) infection and diabetes risk. However, prospective studies examining direct associations between these two factors are relatively lacking. In this prospective cohort study, we aimed to evaluate the association between H. pylori infection and risk of developing diabetes.

Methods

We performed a population-based prospective study, recruiting participants aged 45–74 years and without diabetes from the Chinese Multi-provincial Cohort Study in 2002, with a 10 year follow-up to investigate development of diabetes. H. pylori serostatus was determined by measuring serum H. pylori antibodies. H. pylori seropositivity was defined as the antibody concentration ≥ 10 U/ml. To examine the association between H. pylori seropositivity and diabetes risk, modified Poisson regression was performed.

Results

Of 2085 participants without diabetes, 1208 (57.9%) were H. pylori seropositive in 2002. After multivariate adjustment of possible diabetes risk factors, H. pylori seropositivity was associated with lower risk of diabetes (RR 0.78 [95% CI 0.63, 0.97], p = 0.022). Of the 1275 participants with H. pylori antibody measurements in both 2002 and 2007, 677 (53.1%) were persistently seropositive. A lower risk of diabetes was also observed in participants with persistent H. pylori seropositivity (RR 0.61 [95% CI 0.41, 0.93], p = 0.020), compared with those persistently seronegative.

Conclusions/interpretation

H. pylori seropositivity was associated with lower risk of diabetes in this prospective cohort study. Extrapolation of these results and the mechanism underlying the observed association require further investigation.

     

Gastric adenocarcinoma in a patient re-infected with <Emphasis Type="Italic">H. pylori</Emphasis> after regression of MALT lymphoma with successful anti-<Emphasis Type="Italic">H. pylori</Emphasis>therapy and gastric resection: a case report

Background

Helicobacter pylori (H. pylori) has been etiologically linked with primary gastric lymphoma (PGL) and gastric carcinoma (GC). There are a few reports of occurrence of both diseases in the same patient with H. pylori infection.

Case presentation

We report a patient with PGL in whom the tumor regressed after surgical resection combined with eradication of H. pylori infection. However, he developed GC on follow up; this was temporally associated with recrudescence / re-infection of H. pylori. This is perhaps first report of such occurrence.

Conclusions

Possible cause and effect relationship between H. pylori infection and both PGL and GC is discussed. This case also documents a unique problem in management of PGL in tropical countries where re-infection with H. pylori is supposed to be high.

     

Primary Antibiotic Resistance of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> in China

Background and Aims

Antibiotic resistance is the most important factor leading to the failure of eradication regimens; thus, it is important to obtain regional antibiotic resistance information. This review focuses on the prevalence of Helicobacter pylori primary resistance to clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and furazolidone in China.

Methods

We searched the PubMed, EMBASE, the China National Knowledge Infrastructure, and Chinese Biomedical databases from the earliest date of each database to October 2016. The search terms included the following: H. pylori, antibiotic (including clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and furazolidone) resistance with or without China or different regions of China. The data analysis was performed using MedCalc 15.2.2. Each article was weighted according to the number of isolated H. pylori strains. A pooled proportion analysis was performed.

Results

Twenty-three studies (14 studies in English and 9 in Chinese) were included in this review. A total of 6274, 6418, 3921, 5468, 2802, and 275 H. pylori strains were included in this review to evaluate the prevalence of H. pylori primary resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, tetracycline, and furazolidone, respectively. Overall, the primary resistance rates of clarithromycin, metronidazole, levofloxacin, amoxicillin, tetracycline, and furazolidone were 28.9, 63.8, 28.0, 3.1, 3.9, and 1.7%, respectively.

Conclusions

In China, the prevalence of H. pylori primary resistance to clarithromycin, metronidazole, and levofloxacin was high and increased over time, whereas the resistance rates to amoxicillin, tetracycline, and furazolidone were low and stable over time.

     

CRISPR-like sequences in <Emphasis Type="Italic">Helicobacter pylori</Emphasis> and application in genotyping

Background

Many bacteria and archaea possess a defense system called clustered regularly interspaced short palindromic repeats (CRISPR) associated proteins (CRISPR-Cas system) against invaders such as phages or plasmids. This system has not been demonstrated in Helicobacter pylori. The numbers of spacer in CRISPR array differ among bacterial strains and can be used as a genetic marker for bacterial typing.

Results

A total of 36 H. pylori isolates were collected from patients in three hospitals located in the central (PBH) and southern (SKH) regions of Thailand. It is of interest that CRISPR-like sequences of this bacterium were detected in vlpC encoded for VacA-like protein C. Virulence genes were investigated and the most pathogenic genotype (cagA vacA s1m1) was detected in 17 out of 29 (58.6%) isolates from PBH and 5 out of 7 (71.4%) from SKH. vapD gene was identified in each one isolate from PBH and SKH. CRISPR-like sequences and virulence genes of 20 isolates of H. pylori obtained in this study were analyzed and CRISPR-virulence typing was constructed and compared to profiles obtained by the random amplification of polymorphic DNA (RAPD) technique. The discriminatory power (DI) of CRISPR-virulence typing was not different from RAPD typing.

Conclusion

CRISPR-virulence typing in H. pylori is easy and reliable for epidemiology and can be used for inter-laboratory interpretation.

     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection status had no influence on upper gastrointestinal symptoms: a cross-sectional analysis of 3,005 Japanese subjects without upper gastrointestinal lesions undergoing medical health checkups

Background

This study aimed to evaluate the influence of Helicobacter pylori infection and its eradication on the upper gastrointestinal symptoms of relatively healthy Japanese subjects.

Methods

A total of 3,005 subjects (male/female: 1,549/1,456) undergoing medical health checkups were enrolled in the present study, at five hospitals in Saga, Japan, from January to December 2013. They had no significant findings following upper gastrointestinal endoscopy. All subjects completed a questionnaire that addressed a frequency scale for symptoms of gastroesophageal reflux disease. The questionnaire comprised seven questions regarding reflux symptoms and seven regarding acid-related dyspepsia, which were answered with a score based on the frequency of symptoms. Helicobacter pylori infection was identified by a rapid urease test and/or H. pylori antibody titer, and an eradication history was confirmed by the subjects’ medical records.

Results

Helicobacter pylori infection was positive in 894 subjects out of 3,005 (29.8%). Eradication of Helicobacter pylori was successfully achieved in 440 subjects of 458 treated. Helicobacter pylori infection had no influence on the acid-related dyspepsia evaluated by the questionnaire, whereas the mean reflux score was relatively high in the Helicobacter pylori native negative subjects compared to Helicobacter pylori native positive. Eradication of Helicobacter pylori and time span after the eradication had no effect on the upper gastrointestinal symptoms evaluated by the questionnaire.

Conclusion

Helicobacter pylori infection and history of eradication did not affect acid-related dyspepsia symptoms in Japanese healthy subjects.

     

Applicability of a short/rapid <Superscript>13</Superscript>C-urea breath test for <Emphasis Type="Italic">Helicobacter pylori</Emphasis>: retrospective multicenter chart review study

Background

Carbon labeled urea breath tests usually entail a two point sampling with a 20 to 30-minute gap. Our aim was to evaluate the duration of time needed for diagnosing Helicobacter pylori by the BreathID^® System.

Methods

This is a retrospective multicenter chart review study. Test location, date, delta over baseline, and duration of the entire test were recorded. Consecutively ¹³C urea breath tests results were extracted from the files over a nine year period.

Results

Of the 12,791 tests results, 35.1% were positively diagnosed and only 0.1% were inconclusive. A statistically significant difference in prevalence among the countries was found: Germany showing the lowest, 13.3%, and Israel the highest, 44.1%. Significant differences were found in time to diagnosis: a positive diagnosis had the shortest and an inconclusive result had the longest. Overall test duration averaged 15.1 minutes in Germany versus approximately 13 minutes in other countries. Diagnosis was achieved after approximately 9 minutes in Israel, Italy and Switzerland, but after 10 on average in the others. The mean delta over baseline value for a negative diagnosis was 1.03 ± 0.86, (range, 0.9 - 5), versus 20.2 ± 18.9, (range, 5.1 - 159.4) for a positive one.

Conclusions

The BreathID^® System used in diagnosing Helicobacter pylori can safely shorten test duration on average of 10-13 minutes without any loss of sensitivity or specificity and with no test lasting more than 21 minutes.

     

A <Emphasis Type="Italic">Tbc1d1</Emphasis><Superscript>Ser231Ala</Superscript>-knockin mutation partially impairs AICAR- but not exercise-induced muscle glucose uptake in mice

Aims/hypothesis

TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) is a Rab GTPase-activating protein (RabGAP) that has been implicated in regulating GLUT4 trafficking. TBC1D1 can be phosphorylated by the AMP-activated protein kinase (AMPK) on Ser²³¹, which consequently interacts with 14-3-3 proteins. Given the key role for AMPK in regulating insulin-independent muscle glucose uptake, we hypothesised that TBC1D1-Ser²³¹ phosphorylation and/or 14-3-3 binding may mediate AMPK-governed glucose homeostasis.

Methods

Whole-body glucose homeostasis and muscle glucose uptake were assayed in mice bearing a Tbc1d1 ^Ser231Ala-knockin mutation or harbouring skeletal muscle-specific Ampkα1/α2 (also known as Prkaa1/2) double-knockout mutations in response to an AMPK-activating agent, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR). Exercise-induced muscle glucose uptake and exercise capacity were also determined in the Tbc1d1 ^Ser231Ala-knockin mice.

Results

Skeletal muscle-specific deletion of Ampkα1/a2 in mice prevented AICAR-induced hypoglycaemia and muscle glucose uptake. The Tbc1d1 ^Ser231Ala-knockin mutation also attenuated the glucose-lowering effect of AICAR in mice. Glucose uptake and cell surface GLUT4 content were significantly lower in muscle isolated from the Tbc1d1 ^Ser231Ala-knockin mice upon stimulation with a submaximal dose of AICAR. However, this Tbc1d1 ^Ser231Ala-knockin mutation neither impaired exercise-induced muscle glucose uptake nor affected exercise capacity in mice.

Conclusions/interpretation

TBC1D1-Ser²³¹ phosphorylation and/or 14-3-3 binding partially mediates AMPK-governed glucose homeostasis and muscle glucose uptake in a context-dependent manner.

     

A multicenter prospective study on the diagnostic performance of a new liquid rapid urease test for the diagnosis of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection

Background

Helicobacter pylori (H. pylori) causes a diversity of gastric diseases. Rapid urease tests (RUT) are well established for the point-of-care, invasive diagnosis of H. pylori infection. The study aimed to evaluate the diagnostic performance of a new liquid RUT, the preOx-HUT, within a prospective cohort of treatment-naïve patients.

Methods

The multicenter prospective clinical trial was conducted at nine Austrian centers for gastrointestinal endoscopy. Patients referred for a diagnostic upper gastrointestinal endoscopy underwent gastric biopsy sampling for routine histological evaluation, and in parallel, the preOx-HUT. Histology served as reference standard to evaluate the diagnostic performance of the preOx-HUT.

Results

From January 2015 to January 2016, a total of 183 consecutive patients (54 males and 129 females, median age 50 years) were included. Endoscopy revealed pathological findings in 149/183 cases (81%), which were mostly gastritis (59%) and gastro-esophageal reflux disease (27%). H. pylori infection was detected by histology in 41/183 (22%) cases. In relation to histology, the preOx-HUT had a sensitivity of 85%, a specificity of 94%, a positive predictive value of 80% and a negative predictive value of 96%. Performance of preOx-HUT was not affected significantly by concomitant PPI-use as present in 15% of cases (P = 0.73).

Conclusions

This was the first study evaluating the preOx-HUT in a prospective, multicenter clinical setting. We found a high diagnostic accuracy for the point-of-care, invasive diagnostic test of H. pylori infection. Hence, this test may be a valuable diagnostic adjunct to the clinical presentation of patients with suspected H. pylori infection. Trial registration number EK 1548/2014, Name of registry: Register der Ethikkommission der Medizinischen Universität Wien, URL of registry: https://ekmeduniwien.at/core/catalog/2012/, Date of registration: 24.09.2014, Date of enrolment of the first participant to the trial: 15.01.2015

     

Oncogenic miR-23a in Pancreatic Ductal Adenocarcinogenesis Via Inhibiting <Emphasis Type="Italic">APAF1</Emphasis>

Background

miR-23a, which participates in invasion of pancreatic ductal adenocarcinoma cells into the mesothelial barrier, is a critical regulator in many cancers. It, however, is still unknown whether miR-23a regulates pancreatic cell proliferation and apoptosis or not.

Aims

We sought to investigate the role of miR-23a in regulation of pancreatic cell proliferation and apoptosis.

Methods

miRNA, mRNA, and protein expressions were determined by qRT-PCR and Western blot, respectively. Dual-luciferase reporter assay was used in detection for binding ability of miR-23a to APAF1. Ectopic miR-23a and APAF 1 were introduced to pancreatic cells, and their roles in proliferation and apoptosis were detected by MTT, colony formation, and apoptosis assays, respectively.

Results

Up-regulation of miR-23a and down-regulation of APAF 1 were found in pancreatic ductal cancer, respectively. miR-23a significantly inhibited the luciferase activity by targeting APAF 1 3′UTR. Ectopic miR-23a significantly suppressed the APAF 1 gene expression in pancreatic cancer cells. Similar to siAPAF1, miR-23a significantly promoted pancreatic cancer cell proliferation and repressed apoptosis. Furthermore, miR-23a inhibitor and exogenous APAF 1 could recover the effects.

Conclusions

It is suggested that miR-23a, acting as an oncogenic regulator by directly targeting APAF 1 in pancreatic cancer, is a useful potential biomarker in diagnosis and treatment of pancreatic cancer.

     

<Emphasis Type="Italic">Gcg</Emphasis><Superscript><Emphasis Type="Italic">CreERT2</Emphasis></Superscript> knockin mice as a tool for genetic manipulation in pancreatic alpha cells

Aims/hypothesis

The Cre/loxP system, which enables tissue-specific manipulation of genes, is widely used in mice for diabetes research. Our aim was to develop a new Cre-driver mouse line for the specific and efficient manipulation of genes in pancreatic alpha cells.

Methods

A Gcg ^CreERT2 knockin mouse, which expresses a tamoxifen-inducible form of Cre from the endogenous preproglucagon (Gcg) gene locus, was generated by homologous recombination. The new Gcg ^CreERT2 mouse line was crossed to the Rosa26 ^tdTomato (R26 ^tdTomato ) Cre reporter mouse line in order to evaluate the tissue specificity, efficiency and tamoxifen dependency of Gcg ^CreERT2 -mediated recombination. Cell types of pancreatic islets were identified using immunohistochemistry. Biochemical and physiological data, including blood glucose levels, plasma glucagon and glucagon-like peptide (GLP)-1 levels, and pancreatic glucagon content, were collected and used to assess the overall effect of Gcg gene targeting on Gcg ^CreERT2/w heterozygous mice.

Results

Tamoxifen-treated Gcg ^CreERT2/w ;R26 ^tdTomato/w mice displayed Cre reporter activity, i.e. expression of tdTomato red fluorescent protein (RFP) in all known cells that produce proglucagon-derived peptides. In the adult pancreas, RFP was detected in 94–97% of alpha cells, whereas it was detected in a negligible (~ 0.2%) proportion of beta cells. While more than 98% of cells labelled with tamoxifen-induced RFP were glucagon-positive cells, 14–25% of pancreatic polypeptide (PP)-positive cells were also positive for RFP, indicating the presence of glucagon/PP bihormonal cell population. Tamoxifen-independent expression of RFP occurred in approximately 6% of alpha cells. In contrast to alpha cells and GLP-1-producing neurons, in which RFP expression persisted for at least 5 months after tamoxifen administration (presumably due to rare neogenesis in these cell types in adulthood), nearly half of RFP-positive intestinal L cells were replaced with RFP-negative L cells over the first 2 weeks after tamoxifen administration. Heterozygous Gcg ^CreERT2/w mice showed reduced Gcg mRNA levels in islets, but maintained normal levels of pancreatic and plasma glucagon. The mice did not exhibit any detectable baseline physiological abnormalities, at least in young adulthood.

Conclusions/interpretation

The newly developed Gcg ^CreERT2 knockin mouse shows faithful expression of CreER^T2 in pancreatic alpha cells, intestinal L cells and GLP-1-producing neurons. This mouse line will be particularly useful for manipulating genes in alpha cells, due to highly specific and efficient CreER^T2-mediated recombination in this cell type in the pancreas.

     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis>in apparently healthy children aged 0-12 years in urban Kampala,Uganda: a community-based cross sectional survey

Background

Helicobacter pylori is one of the most common causes of bacterial infection in human beings. Studies have showed a high prevalence of Helicobacter pylori among people in low-income countries and colonization early in life. A monoclonal antigen test, performed on faeces, HpSA^®ImmunoCardSTAT, has a high sensitivity, specificity and accuracy and the faecal test can be performed in all ages, also in resource-limited settings. The main objective of this study was to determine the prevalence and factors associated with Helicobacter pylori colonization in apparently healthy children aged 0-12 years in urban Kampala, Uganda.

Method

We tested 427 apparently healthy children, age 0-12 years (211 males, 216 females), in a cross sectional survey for Helicobacter pylori colonization using HpSA ^®ImmunoCardSTAT. A short standardized interview with socio-demographic information and medical history was used to assess risk factors.

Results

The overall prevalence of Helicobacter pylori in the 427 children was 44.3% (189 out of 427). Early colonization was common, 28.7%, in children younger than 1 year of age. The age specific rates were 46.0% in children age 1- < 3 years, 51.7% in children age 3- < 6 years, 54.8% in children age 6- < 9 years and 40.0% in children age 9- < 12 years. There was a significant difference in prevalence by gender; female 38.5% versus male 49.8% and by type of housing; permanent house 38.5% versus semi-permanent house 48.6%. Congestive living and education level of the female caretaker showed a clear trend for a difference in prevalence. Factors independently associated with Helicobacter pylori colonization included: drugs taken last three months, using a pit latrine, sources of drinking water and wealth index.

Conclusion

The prevalence of Helicobacter pylori colonization among urban Ugandan children is high at an early age and increases with age. The impact of Helicobacter pylori colonization on children's health in Uganda needs to be further clarified.

     

Genome characterization of bile-isolated <Emphasis Type="Italic">Shewanella algae</Emphasis> ACCC

Background

Shewanella algae has been recognized as an emerging human pathogen. However, not much is known about the mechanism of its pathogenesis and its adaptation to a special niche such as the hepatobiliary tract.

Results

In this study, we isolated the S. algae ACCC strain from human bile and performed whole genome sequencing. S. algae ACCC consists of a circular 4,743,354-bp chromosome with a GC content of 53.08%, within 4080 protein coding sequences. The genome of strain ACCC contains a number of candidate genes which have been reported to be associated with bile adaption, including htpB, exbBD, wecA, galU, adeFGH and phoPQ regulon.

Conclusions

Our results highlight the association of S. algae with a rare disease profile. Further studies are needed to shed light on the evolution of pathogenesis and the niche adaptation of S. algae.

     

Influence of <Emphasis Type="Italic">TGFB1</Emphasis>+<Emphasis Type="Italic">869T</Emphasis>>C functional polymorphism in non-small cell lung cancer (NSCLC) risk

Purpose

Lung cancer is the third most common type of cancer in Europe and is the first cause of death by cancer worldwide. Non-small cell lung cancer accounts for 75–85% of all histological types of LC. The transforming growth factor beta 1 is a multifunctional regulatory polypeptide that controls many aspects of cellular function (cellular proliferation, differentiation, migration, apoptosis, immune surveillance). TGFB1+869T>C is a functional polymorphism described in TGFB1 gene and this transition has been associated with higher circulating levels of TGFß1 that may modulate cellular microenvironment and consequently LC development and prognosis.

Methods

We studied TGFB + 869T > C functional polymorphism by allelic discrimination using 7300 real-time polymerase chain reaction system in 305 patients with NSCLC and 380 healthy individuals.

Results

We found an increased risk for C carriers to develop NSCLC, both epidermoid NSCLC and non-epidermoid NSCLC (odds ratio (OR) = 2.03, P < 0.0001, OR = 2.37, P < 0.001 and OR = 1.83, P = 0.001, respectively). TGFB1+869T>C functional polymorphism may influence NSCLC susceptibility with impact in cellular microenvironment.

Conclusions

Our results suggest that individual differences influence the susceptibility to LC and tumoral behavior. This genetic profiling may help define higher risk groups for an individualized chemoprevention strategy and therapy.

     

First case of <Emphasis Type="Italic">E. meningoseptica</Emphasis> in Italy in a patient with necrotic hemorrhagic pancreatitis

Introduction

Elizabethkingia meningoseptica can frequently colonizes the respiratory tract, but its pathogenetic role and its clinical significance are frequently questioned. However, recent data reported E. meningoseptica outbreaks in particular settings, as hospitalized patients.

Case Report

We report here the first case of Elizabethkingia meningoseptica infection in Italy in a patient with necrotic-hemorrhagic pancreatitis. E. meningoseptica was isolated from respiratory tract and treated with combination antibiotic therapy.

Conclusion

We discuss here the role of isolation of E. meningoseptica in hospitalized patients as a sign of patient’s frailty.

     

<Emphasis Type="Italic">SOCS2</Emphasis> polymorphisms are not associated with clinical and biochemical phenotypes in acromegalic patients

Purpose

Suppressor of cytokine signaling 2 (SOCS2) is a STAT5b-regulated gene and one of its functions is to influence growth and development through negative regulatory effects on GH/IGF-1 pathway. So, we evaluate the potential influence of SOCS2 single nucleotide polymorphisms (SNPs) on clinical and laboratorial characteristics of a large cohort of Brazilian patients with acromegaly.

Methods

Four SOCS2 SNPs (rs3782415, rs3816997, rs3825199 and rs11107116) were selected and genotyped by real-time PCR using specific Taqman probe assays. A total of 186 patients (116 women, age range 26–88 years) were evaluated.

Results

No association of SOCS2 genotypes was observed with none of the following clinical and laboratorial characteristics: age, sex, body mass index, comorbidities, basal GH, oral glucose tolerance test GH nadir, IGF-I, ULNR-IGF-I.

Conclusion

Despite of the key role of SOCS2 in the regulation of GH receptor signaling, we did not find any significant association between SOCS2 polymorphisms and acromegaly.