Αρχειοθήκη ιστολογίου

Παρασκευή 1 Απριλίου 2016

IJMS, Vol. 17, Pages 485: Do Variants in GSTs Modify the Association between Traffic Air Pollution and Asthma in Adolescence?

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Polymorphisms in genes involved in the oxidative stress response may partially explain the documented heterogeneous associations between traffic-related air pollution (TRAP) exposure and asthma and allergies in children. We investigated whether the GSTT1, GSTM1 and GSTP1 gene polymorphisms modified the associations between TRAP exposure during the first year of life and asthma, wheeze and hay fever in adolescence. We used a birth cohort of 620 high risk infants from the Melbourne Atopy Cohort Study. TRAP exposure during the first year of life was defined as the cumulative length of major roads within 150 m of each participant's residence during the first year of life. Wheeze, asthma and hay fever were measured at ages 12 (n = 370) and 18 (n = 434) years. The associations and interactions with glutathione S-transferases (GST s) were investigated using regression models. Overall, there was no relationship between TRAP exposure during the first year of life and current asthma, wheeze and hay fever at ages 12 or 18 years. However, in GSTT1 null carriers, every 100 m increase in cumulative lengths of major road exposure during the first year of life was associated with a 2.31-fold increased risk of wheeze and a 2.15-fold increased risk of asthma at 12 years. TRAP is associated with some respiratory outcomes in carriers of genetic polymorphisms in oxidative stress metabolism genes.

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IJMS, Vol. 17, Pages 484: KRAS G12V Mutation Detection by Droplet Digital PCR in Circulating Cell-Free DNA of Colorectal Cancer Patients

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KRAS mutations are responsible for resistance to anti-epidermal growth factor receptor (EGFR) therapy in colorectal cancer patients. These mutations sometimes appear once treatment has started. Detection of KRAS mutations in circulating cell-free DNA in plasma ("liquid biopsy") by droplet digital PCR (ddPCR) has emerged as a very sensitive and promising alternative to serial biopsies for disease monitoring. In this study, KRAS G12V mutation was analyzed by ddPCR in plasma DNA from 10 colorectal cancer patients and compared to six healthy donors. The percentage of KRAS G12V mutation relative to wild-type sequences in tumor-derived DNA was also determined. KRAS G12V mutation circulating in plasma was detected in 9 of 10 colorectal cancer patients whose tumors were also mutated. Colorectal cancer patients had 35.62 copies of mutated KRAS/mL plasma, whereas in healthy controls only residual copies were found (0.62 copies/mL, p = 0.0066). Interestingly, patients with metastatic disease showed a significantly higher number of mutant copies than M0 patients (126.25 versus 9.37 copies/mL, p = 0.0286). Wild-type KRAS was also significantly elevated in colorectal cancer patients compared to healthy controls (7718.8 versus 481.25 copies/mL, p = 0.0002). In conclusion, KRAS G12V mutation is detectable in plasma of colorectal cancer patients by ddPCR and could be used as a non-invasive biomarker.

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IJMS, Vol. 17, Pages 496: Characterization of Virulence Properties of Aeromonas veronii Isolated from Diseased Gibel Carp (Carassius gibelio)

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Aeromonas veronii is a kind of opportunistic pathogen to fish and humans, significantly impending aquaculture production. Recently, we isolated two A. veronii strains, named GYC1 and GYC2, from diseased Gibel carp (Carassius gibelio) in China. Based on gyrB (DNA gyrase B subunit) genes of GYC1 and GYC2, the constructed phylogenetic tree showed that the two strains were clustered with A. veronii. Sixteen virulence genes related to the pathogenicity of Aeromonas spp. were subjected to PCR assay. The genes of ompAI, ompAII, lafA, act, aer, fla, gcaT and acg were detected in the two strains, while genes of hly, ahp, lip, ast and alt were not detected. Additionally, genes eprCAI, ela and exu were only detected in the strain GYC1. Furthermore, the results of extracellular enzyme analysis revealed that the two isolates can produce hemolysin, caseinase, esterase, amylase and lecithinase, which were closely related to the pathogenicity of the two strains. However, the results showed that there was no gelatinase activity in either strain. According to the antibiotic resistant assay, the two strains were sensitive to cephalosporins and aminoglycosides, while they were resistant to penicillins and quinolones. Through this study, the virulence characteristics, including virulence genes and extracellular enzymes, the pathogenicity of A. veronii was clarified, enhancing the understanding about this pathogenic bacterium and providing the theoretical basis in disease control.

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Transforming Healthcare with the Internet of Things



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Cardiac autonomic dysfunction in patients with gastroesophageal reflux disease.

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Cardiac autonomic dysfunction in patients with gastroesophageal reflux disease.

World J Gastroenterol. 2015 Jun 14;21(22):6982-9

Authors: Milovanovic B, Filipovic B, Mutavdzin S, Zdravkovic M, Gligorijevic T, Paunovic J, Arsic M

Abstract
AIM: To investigate autonomic nervous function in patients with a diagnosis of gastroesophageal reflux disease (GERD).
METHODS: The investigation was performed on 29 patients (14 men), aged 18-80 years (51.14 ± 18.34), who were referred to our Neurocardiology Laboratory at the Clinical and Hospital Center "Bezanijska Kosa" with a diagnosis of GERD. One hundred sixteen healthy volunteers matched in age and sex with the examinees served as the control group. The study protocol included the evaluation of autonomic function and hemodynamic status, short-term heart rate variability (HRV) analysis, 24 h ambulatory ECG monitoring with long-term HRV analysis and 24 h ambulatory blood pressure monitoring.
RESULTS: Pathologic results of cardiovascular reflex test were more common among patients with reflux compared to the control group. Severe autonomic dysfunction was detected in 44.4% of patients and in 7.9% of controls (P < 0.001). Parameters of short-term analysis of RR variability, which are the indicators of vagal activity, had lower values in patients with GERD than in the control group. Long-term HRV analysis of time-domain parameters indicated lower values in patients with reflux disease when compared to the control group. Power spectral analysis of long-term HRV revealed lower low- and high-frequency values. Detailed 24 h ambulatory blood pressure analysis showed significantly higher values of systolic blood pressure and pulse pressure in the reflux group than in the control group.
CONCLUSION: Patients with GERD have distortion of sympathetic and parasympathetic components of the autonomic nervous system, but impaired parasympathetic function appears more congruent to GERD.

PMID: 26078576 [PubMed - indexed for MEDLINE]



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Esomeprazole regimens for reflux symptoms in Chinese patients with chronic gastritis.

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Esomeprazole regimens for reflux symptoms in Chinese patients with chronic gastritis.

World J Gastroenterol. 2015 Jun 14;21(22):6965-73

Authors: Sun J, Yuan YZ, Hou XH, Zou DW, Lu B, Chen MH, Liu F, Wu KC, Zou XP, Li YQ, Zhou LY

Abstract
AIM: To compare symptom control with esomeprazole regimens for non-erosive reflux disease and chronic gastritis in patients with a negative endoscopy.
METHODS: This randomized, open-label study was designed in line with clinical practice in China. Patients with typical reflux symptoms for ≥ 3 mo and a negative endoscopy who had a Gastroesophageal Reflux Disease Questionnaire score ≥ 8 were randomized to initial treatment with esomeprazole 20 mg once daily either for 8 wk or for 2 wk. Patients with symptom relief could enter another 24 wk of maintenance/on-demand treatment, where further courses of esomeprazole 20 mg once daily were given if symptoms recurred. The primary endpoint was the symptom control rate at week 24 of the maintenance/on-demand treatment period. Secondary endpoints were symptom relief rate, success rate (defined as patients who had symptom relief after initial treatment and after 24 wk of maintenance treatment), time-to-first-relapse and satisfaction rate.
RESULTS: Based on the data collected in the modified intention-to-treat population (MITT; patients in the ITT population with symptom relief after initial esomeprazole treatment, n = 262), the symptom control rate showed a small but statistically significant difference in favor of the 8-wk regimen (94.9% vs 87.3%, P = 0.0473). Among the secondary endpoints, based on the data collected in the ITT population (n = 305), the 8-wk group presented marginally better results in symptom relief after initial esomeprazole treatment (88.3% vs 83.4%, P = 0.2513) and success rate over the whole study (83.8% vs 72.8%, P = 0.0258). The 8-wk regimen was found to provide a 46% reduction in risk of relapse vs the 2-wk regimen (HR = 0.543; 95%CI: 0.388-0.761). In addition, fewer unscheduled visits and higher patient satisfaction supported the therapeutic benefits of the 8-wk regimen over the 2-wk regimen. Safety was comparable between the two groups, with both regimens being well tolerated.
CONCLUSION: Chinese patients diagnosed with chronic gastritis achieved marginally better control of reflux symptoms with an 8-wk vs a 2-wk esomeprazole regimen, with a similar safety profile.

PMID: 26078574 [PubMed - indexed for MEDLINE]



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The Role of Gastroesophageal Reflux and Other Factors during Progression to Esophageal Adenocarcinoma.

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The Role of Gastroesophageal Reflux and Other Factors during Progression to Esophageal Adenocarcinoma.

Cancer Epidemiol Biomarkers Prev. 2015 Jul;24(7):1012-23

Authors: Hazelton WD, Curtius K, Inadomi JM, Vaughan TL, Meza R, Rubenstein JH, Hur C, Luebeck EG

Abstract
BACKGROUND: U.S. esophageal adenocarcinoma (EAC) incidence increased over 5-fold between 1975 and 2009. Symptomatic gastroesophageal reflux disease (sGERD) elevates the risk for EAC. However, a simple calculation suggests that changes in sGERD prevalence can explain at most approximately 16% of this trend. Importantly, a mechanistic understanding of the influence of sGERD and other factors (OF) on EAC is lacking.
METHODS: A multiscale model was developed to estimate temporal trends for sGERD and OF, and their mechanistic role during carcinogenesis. Model calibration was to Surveillance, Epidemiology, and End Results (SEER) incidence and age-dependent sGERD data using maximum likelihood and Markov chain Monte Carlo (MCMC) methods.
RESULTS: Among men, 77.8% [95% credibility interval (CI), 64.9%-85.6%] of the incidence trend is attributable to OF, 13.4% (95% CI, 11.4%-17.3%) to sGERD, and 8.8% (95% CI, 4.2%-13.7%) to sGERD-OF interactions. Among women, 32.6% (95% CI, 27.0%-39.9%) of the trend is attributable to OF, 13.6% (95% CI, 12.5%-15.9%) to sGERD, and 47.4% (95% CI, 30.7%-64.6%) to interactions. The predicted trends were compared with historical trends for obesity, smoking, and proton pump inhibitor use. Interestingly, predicted OF cohort trends correlated most highly with median body mass index (BMI) at age 50 (r = 0.988 for men; r = 0.998 for women).
CONCLUSIONS: sGERD and OF mechanistically increase premalignant cell promotion, which increases EAC risk exponentially with exposure duration.
IMPACT: Surveillance should target individuals with long-duration sGERD and OF exposures.

PMID: 25931440 [PubMed - indexed for MEDLINE]



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