Search

Myelofibrosis (MF) is characterized by a presence of an extra fibrous tissue in the bone marrow and additional hematopoiesis. The somatic mutation in the Janus kinase 2 (JAK2) gene (V617F) occurs gradually and is detected in about 50.0% of myelofibrosis or essential thrombo-cytopenia (ET) patients. Our aim was to determine the genotype status according to the carriers of the V617F mutation in patients with MF at the Hematology Ward of the University Hospital "Ivan Rilski" in Sofia, Bulgaria. DNA samples were isolated from venous blood of patients with various hematological disorders. DNA was amplified by polymerase chain reaction (PCR) and subsequent restriction analysis was performed using a BsaXI restriction enzyme. The genotype status was determined on 2.0% agarose gel. We analyzed 38 patients initially suspected of carrying MF or osteomyelofibrosis (OMF). After trepanobiopsy, 20 out of 38 patients were confirmed as myelofibrotic (52.6%), 5/38 (13.2%) were diagnosed as ET, 1/38 (2.6%) was diagnosed as myeloproliferative neoplasm (MPN), 6/38 (15.8%) had polycythemia vera (PV). In six patients, the presence of disease was rejected. Patients with MF were divided into three groups according to the JAK2 V617F genotype status: homozygous for the mutation (3/20 or 15.0%), heterozygous (9/20 or 45.0%) and homozygous for the wild type allele (8/20 or 40.0%). The triggering factor of MF is still unknown. It was considered that this factor could have a genetic nature. Mutations in three genes were mainly accepted as an actual predisposing events to this disease: point mutations leading to amino acid substitutions in JAK2 (V617F) and in MPL (W515L, W515K), as well as insertion or deletion in CALK We have proven that carriers of the V617F mutation prevailed in the group of patients with MF (altogether 12 patients or 60.0%). Previous studies also showed that JAK2 V617F is present in more than half of MF patients within their blood-forming cells. Therefore, the risk of evolution to MF could be associated with V617F-mutant allele burden in patients with MPN. [ABSTRACT FROM AUTHOR]

Mutations in the receptor of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are used as biomarkers for predicting the response of treatment with EGFR tyrosine kinase inhibitors (EGFR TKIs). Non-small cell lung cancer patients usually have activating EGFR mutations that leads to a very good response when they are treated with EGFR TKIs. Our tumor samples were examined for the presence of sensitive mutations in the EGFR gene, resistant mutations or the absence of mutations. To identify the types of the mutation, we used a real-time polymerase chain reaction (RT-PCR) method. Additionally, we evaluated the frequency of EGFR mutations and their association with smoking status, gender and histology. The tumor samples (n = 551) were tested for 29 somatic mutations in the EGFR gene. Sensitive mutations in the EGFR genes were found in 55 NSCLC samples (10.0%). The prevalence of EGFR mutations was much higher for females than for males (27.1 vs. 3.9%, p <0.001). The prevalence of EGFR mutations was greater in subjects who had never smoked than in smokers (15.0 vs. 6.08%, p <0.003). Additionally, the frequency of EGFR mutations was higher in adenocarcinomas than in other histological types (14.9 vs. 5.1%; p <0.001). Our results show that activating mutations on the EGFR gene are more frequent in females than in males, in adenocarcinoma than other histological types and in non smokers than smokers. [ABSTRACT FROM AUTHOR]

The behavioral responses of male mound-building mice Mus spicilegus to odours from males of their own species and odors from males of another species - house mouse Mus musculus musculus and yellow-necked mouse Apodemus flavicollis were studied in an attraction-avoidance test in order to clarify the role of odour in their relationships in wild populations in agricultural land. The experiments were carried out in the breeding season. M. spicilegus males showed attraction to conspecific odours from the same sex, but indifference to heterospecific odours of male M. m. musculus, and avoidance to odours of male A. flavicollis. The behavioural responses to conspecific and heterospecific odours are discussed in terms of attractiveness of odour cues, according to their significance in social relationships and spacing behaviour. [ABSTRACT FROM AUTHOR]

Background The progression of hepatic fibrosis into cirrhosis is a main prognostic factor for survival in people with alcoholic liver disease. The range of cut-off values characterising the stage of hepatic fibrosis seems to be dependent on the aetiology of the liver disease. Aims To determine the diagnostic accuracy of transient elastography (the index test) for diagnosis of fibrosis in alcoholic liver disease when compared with liver biopsy (the reference standard), using the METAVIR scoring system. To establish the optimal cut-off values for the hepatic fibrosis stages. Methods We followed Cochrane Methodology for diagnostic test accuracy reviews. We identified 14 studies. Among the study participants with alcoholic liver disease, 834 provided numerical data for analysis (August 2014). Only half of the studies were monoaetiology studies. We used the bivariate model and estimated the summary sensitivities and summary specificities. Hence, we calculated the summary likelihood ratios ( LRs) to rule in or rule out hepatic fibrosis. We investigated pre-defined sources of heterogeneity. Results Severe fibrosis (F3 or worse): summary (95% CI) sensitivity 0.92(0.89-0.96) and specificity 0.70(0.61-0.79); LR+ 3.1(2.1-4.1), LR− 0.11(95% CI 0.06-0.16). Cirrhosis (F4): summary (95% CI) sensitivity of 0.95(0.87-0.98) and specificity 0.71(0.56-0.82); LR+ 3.3(2.1-5.0); LR− 0.07(0.03-0.19). Conclusions Transient elastography may be used as a diagnostic method to exclude cirrhosis or severe fibrosis when the test is negative. Cut-off values of around 12.5 kPa for cirrhosis may be used in clinical practice, but caution is needed, as the values reported in the review are not yet prospectively validated. [ABSTRACT FROM AUTHOR]

Lung cancer is the most common cause of cancer death worldwide, and its prognosis and treatment response rate as well as the survival rate remain poor. In our study, we performed next generation sequencing (NGS) with cancer panel (Illumina) for 19 Bulgarian patients with both non-small cell lung cancer (NSCLC; 18 patients) and neuroendocrine tumor (1 patient) and focused on common polymorphisms which define proven or reported sensitivity to platinum-based therapy. We report reference SNP (rs)1042522 (TP53), rs2228001 (XPC), rs2227983 (EGFR), rs1799793, and rs13181 (ERCC2) single nucleotide polymorphism variants which have been detected in our patients in homozygous and/or heterozygous state. Therefore, we give important information to confirm the role of those polymorphisms in tumor resistance and recurrence after chemotherapy treatment. The results reveal that TruSight Cancer Panel could be a useful clinical tool for determining pharmacogenetic variants associated with the effect of chemotherapy. [ABSTRACT FROM AUTHOR]

Investigation was conducted in order to elucidate the possibility of using perlite as support for preparation of nickel based precursor catalyst, potentially applicable in vegetable oil hydrogenation process. On three differently prepared expanded perlite, nickel catalyst precursors with identical Ni/SiO = 1.1 and Ni/Mg = 10/1 ratios were synthesized by precipitation-deposition method. Different techniques, SEM micrography, He-pycnometry, calcimetry, Hg-porosimetry, N-physisorption, H-chemisorption and temperature programmed reduction, were used for characterization of obtained samples. Determining the precursor texture, morphology and reducibility shows a successfully deposited nickel phase on perlite support with promising properties for vegetable oil hydrogenation. Chosen precursor was reduced and passivated in paraffin oil and the obtained catalyst showed significant catalytic activity in the test of sunflower oil hydrogenation. [ABSTRACT FROM AUTHOR]

Epigenetic changes, in particular DNA methylation processes, play a role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM) linking genetic and environmental factors. To clarify this role, we have analyzed in patients with different duration of T2DM: (i) expression levels of methyl- CpG-binding domain protein 2 (MBD2) as marker of DNA methylation, and ii) methylation changes in 22 genes connected to cellular stress and toxicity. We have analyzed MBD2 mRNA expression levels in 16 patients and 12 controls and the methylation status of stress and toxicity genes in four DNA pools: (i) controls; (ii) newly-diagnosed T2DM patients; (iii) patients with T2DM duration of <5 years and (iv) of >5 years. The MBD2 expression levels were 10.4-times increased on average in T2DM patients compared to controls. Consistent increase in DNA methylation fraction with the increase in T2DM duration was observed in Prdx2 and SCARA3 genes, connected to oxidative stress protection and in BRCA1 and Tp53 tumor-suppressor genes. In conclusion, increased MBD2 expression in patients indicated general dysregulation of DNA methylation in T2DM. The elevated methylation of Prdx2 and SCARA3 genes suggests disturbance in oxidative stress protection in T2DM. The increased methylation of BRCA1 and Tp53 genes unraveled an epigenetic cause for T2DM related increase in cancer risk. [ABSTRACT FROM AUTHOR]

Ni-Al layered double hydroxides with Ni/Al molar ratios of 1.5 and 3.0 have been synthesized by co-precipitation and studied as catalyst precursors for purification of CO-containing gas-mixtures by means of CO oxidation to CO and conversion of CO by water vapor (water-gas shift reaction). The influence of the alkali additives (K ions) on the water-gas shift activity has been also examined. It was established that the catalytic activity of both reactions increases with the temperature and the nickel content. Hypothetic schemes are proposed about activation of the catalysts in the WGSR and CO oxidation including redox Ni ↔ Ni transition on the catalyst surface. The activity in WGSR is positively affected by the presence of potassium promoter, depending on its amount. The sample with higher nickel loading is the most effective catalyst as for CO oxidation as well as for WGSR at intermediate temperatures after potassium promotion. [ABSTRACT FROM AUTHOR]

This paper is treating the problem of reducing energy consumption through heat integration system of bioreactors for antibiotics production. A scheme for heat integration with two heat tanks providing work in different time intervals is proposed. A practically feasible method for managing the processes of heat integration is designed. The task is formulated in terms of continuous nonlinear programming (NLP). The method has been applied to a real industrial process for the production of antibiotics. [ABSTRACT FROM AUTHOR]

The effect of the type of the silica gel pore structure on the surface properties of the Ni-silica gel catalyst precursors for the vegetable oil hydrogenation process has been examined applying N sorption and X-ray photoelectron spectroscopy techniques. The nickel catalyst precursors with identical composition (SiO/Ni = 1.0) has been synthesized by precipitation of Ni(NO) · 6HO solution with NaCO solution on the three types of silica gel with different pore structures. It is shown that the usage of the silica gel supports with different texture as source of SiO causes different location of Ni-species into the support pores and on the external surface area. The XPS data confirm the formation of surface species with different strength of interaction and different dispersion. These surface characteristics of the precursors will predetermine the formation of the active nickel metallic phase as well as the mass transfer of the reactants and products to and from the catalytic sites. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2010; 32: 356–367 Background Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal. Aim To assess the benefits and harms of antioxidant supplements for patients with liver diseases. Methods We identified trials through electronic and manual searches until August 2009. We included randomized trials comparing antioxidant supplements (beta-carotene, vitamin A, C, E and selenium) vs. placebo or no intervention for autoimmune liver diseases, viral hepatitis, alcoholic liver disease and cirrhosis (any aetiology). Random-effects and fixed-effect meta-analyses were conducted. Results were presented as relative risks (RR), or mean difference (MD), both with 95% confidence intervals (CI). Results Twenty randomized trials with 1225 participants were included. The trials assessed beta-carotene (3 trials), vitamin A (2 trials), vitamin C (9 trials), vitamin E (15 trials) and selenium (8 trials). The majority of the trials had high risk of bias and showed heterogeneity. Overall, the assessed antioxidant supplements had no significant effect on all-cause mortality [relative risk (RR) 0.84, 95% confidence interval (CI) 0.60–1.19, I2 = 0%] or liver-related mortality (RR 0.89, 95% CI 0.39–2.05, I2 = 37%). Stratification according to the type of liver disease assessed did not affect the conclusions. Antioxidant supplements significantly increased the activity of gamma glutamyl transpeptidase (MD 24.21 IU/L, 95% CI 6.67–41.75, I2 = 0%). Conclusions We found no evidence to support or refute antioxidant supplements in patients with liver disease. Antioxidant supplements may increase liver enzymes. [ABSTRACT FROM AUTHOR]

Two series of silver modified Ni-Mg materials were synthesized by precipitation-deposition on SiO2 support derived from two silica sources: diatomite activated at 800°C ( Series a; Mg/Ni = 0.1 and SiO2/Ni = 1.07) and synthetic water glass ( Series b; Mg/Ni = 0.1 and SiO2/Ni = 1.15). The modification with silver was made at three molar Ag/Ni ratios, namely 0.0025, 0.025, and 0.1. The effects of the source of the silica support and the silver presence and content on the nickel state in the silver modified reduced-passivated NiMg/SiO2 precursors of the vegetable oil hydrogenation catalyst were established by X-ray diffraction and X-ray photoelectron spectroscopy techniques. The passivation procedure was applied in order to protect the metallic nickel particles from further oxidation. The crystallization of the formed nickel hydrosilicate phases depends on the source of the silica support, more expressed in the diatomite supported samples. It was shown that the silver modification of the NiMg/SiO2 precursors enhances the reduction of the nickel hydrosilicates accompanied by formation of relatively smaller metallic nickel particles, more pronounced in the water glass supported precursors. The increase of the silver content in the water glass deposited samples is responsible for the metallic nickel dispersion increase. The higher content of the Ni0 particles on the surface of the diatomite deposited samples is in accordance with the higher stability of the larger metallic nickel crystallites to oxidation during the passivation step. On contrary, higher dispersed Ni0 particles on the surface of the water glass supported samples are more susceptible to the oxida [ABSTRACT FROM AUTHOR]

The article focuses on the efficiency of practicing meta-analysis of randomized clinical trials (RCTs) in detecting patients' diseases in Great Britain. Conducting meta-analysis is important because it determines whether patients were able to receive the appropriate medical care. The randomization and binding process derived from Cochrane Hepato-Biliary module was used in assessing patient's treatment.

Background The evidence on whether antioxidant supplements prevent gastrointestinal cancers is contradictory. Aim To assess the beneficial and harmful effects of antioxidant supplements in preventing gastrointestinal cancers. Methods Using the Cochrane Collaboration methodology, we reviewed the randomized trials comparing antioxidant supplements with placebo or no intervention on the occurrence of gastrointestinal cancers. We searched electronic databases and reference lists until October, 2007. Our outcome measures were gastrointestinal cancers, overall mortality and adverse events. Outcomes were reported as relative risks (RR) with 95% confidence intervals (CI) based on random-effects and fixed-effect models meta-analyses. Results We identified 20 randomized trials (211 818 participants) assessing beta-carotene, vitamin A, vitamin C, vitamin E, and selenium. The trial quality was generally high. The antioxidant supplements were without a significant effect on the occurrence of gastrointestinal cancers (RR 0.94, 95% CI 0.83–1.06, I 2 = 54.0%). The heterogeneity seemed to be explained by bias risk (low-bias risk trials RR 1.04, 95% CI 0.96–1.13 compared to high-bias risk trials RR 0.59, 95% CI 0.43–0.80, test of interaction P < 0.0005) and type of antioxidant supplement (beta-carotene potentially increasing and selenium potentially decreasing cancer risk). Antioxidant supplements had no significant effect on mortality in a random-effects model meta-analysis (RR 1.02, 95% CI 0.97–1.07, I 2 = 53.5%) but significantly increased mortality in a fixed-effect model meta-analysis (RR 1.04, 95% CI 1.02–1.07). Conclusions We could not find evidence that the studied antioxidant supplements prevented gastrointestinal cancers. On the contrary, they seem to increase overall mortality. [ABSTRACT FROM AUTHOR]

Tumor-suppressor Pdcd4 inhibits transformation and invasion and is downregulated in cancers. So far, it has not been studied as to whether miRNAs, suppressing target expression by binding to the 3′-UTR, regulate Pdcd4 or invasion. The present study was conducted to investigate the regulation of Pdcd4, and invasion/intra-vasation, by miRNAs. A bioinformatics search revealed a conserved target-site for miR-21 within the Pdcd4-3′-UTR at 228–249 nt. In 10 colorectal cell lines, an inverse correlation of miR-21 and Pdcd4-protein was observed. Transfection of Colo206f-cells with miR-21 significantly suppressed a luciferase-reporter containing the Pdcd4-3′-UTR, whereas transfection of RKO with anti-miR-21 increased activity of this construct. This was abolished when a construct mutated at the miR-21/nt228–249 target site was used instead. Anti-miR-21-transfected RKO cells showed an increase of Pdcd4-protein and reduced invasion. Moreover, these cells showed reduced intra-vasation and lung metastasis in a chicken–embryo–metastasis assay. In contrast, overexpression of miR-21 in Colo206f significantly reduced Pdcd4-protein amounts and increased invasion, while Pdcd4-mRNA was unaltered. Resected normal/tumor tissues of 22 colorectal cancer patients demonstrated an inverse correlation between miR-21 and Pdcd4-protein. This is the first study to show that Pdcd4 is negatively regulated by miR-21. Furthermore, it is the first report to demonstrate that miR-21 induces invasion/intravasation/metastasis.Oncogene (2008) 27, 2128–2136; doi:10.1038/sj.onc.1210856; published online 29 October 2007 [ABSTRACT FROM AUTHOR]

Context: Antioxidant supplements are used for prevention of several diseases.Objective: To assess the effect of antioxidant supplements on mortality in randomized primary and secondary prevention trials. DATA SOURCES AND TRIAL SELECTION: We searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention were included in our analysis. Randomization, blinding, and follow-up were considered markers of bias in the included trials. The effect of antioxidant supplements on all-cause mortality was analyzed with random-effects meta-analyses and reported as relative risk (RR) with 95% confidence intervals (CIs). Meta-regression was used to assess the effect of covariates across the trials.Data Extraction: We included 68 randomized trials with 232 606 participants (385 publications).Data Synthesis: When all low- and high-bias risk trials of antioxidant supplements were pooled together there was no significant effect on mortality (RR, 1.02; 95% CI, 0.98-1.06). Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.04[corrected]-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality.Conclusions: Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study. [ABSTRACT FROM AUTHOR]

Background Colorectal cancer may be prevented by reducing the development of adenomatous polyps. Aim To assess the benefits and harms of antioxidant supplements in preventing colorectal adenoma. Methods Using the Cochrane Collaboration methodology we reviewed all randomized clinical trials comparing antioxidant supplements with placebo or no intervention. We searched electronic databases and the reference lists until October 2005. Outcome measures were development of colorectal adenoma adverse events. We analysed dichotomous outcomes with fixed- and random-effects model meta-analyses and calculated the relative risk with 95% confidence interval. Results We identified eight randomized trials (17 620 participants). Neither fixed-effect (relative risk: 0.93, 95% CI: 0.81–1.1) nor random-effect model meta-analyses (0.82, 0.60–1.1) showed statistically significant effects of supplementation with β-carotene, vitamins A, C, E and selenium alone or in combination. Antioxidant supplements seemed to increase the development of colorectal adenoma in three low-bias risk trials (1.2, 0.99–1.4) and significantly decrease its development in five high-bias risk trials (0.59, 0.47–0.74). The estimates difference is significant ( P < 0.0001). There was no significant difference between the intervention groups regarding adverse events, including mortality (0.82, 0.47–1.4). Conclusion We found no convincing evidence that antioxidant supplements have significant beneficial effect on primary or secondary prevention of colorectal adenoma. [ABSTRACT FROM AUTHOR]

The Wnt signaling pathway is activated by mutations in the adenomatous polyposis coli (APC) or β-catenin genes in most colon cancers, leading to the transactivation of promoters containing binding sites for the Tcf/LEF family of transcription factors. We have previously shown that it is possible to confer colon cancer specificity on autonomous parvoviruses by inserting Tcf sites into the viral P4 promoter. The mutant Tcf promoters were responsive to activation of the Wnt pathway but the viruses replicated poorly. We show here that reduction of the number of Tcf sites from four to two leads to an increase in the efficiency of replication and toxicity of the viruses in Co115 colon cancer cells, with only a small reduction in selectivity for cells with an active Wnt signaling pathway. Despite this improvement, virus production by most colon cancer cells remained low. Analysis of parental phH1 virus infection of SW480 colon cancer cells showed that the nonstructural and capsid proteins were expressed, but single stranded DNA and progeny virus were not produced. This defect reflects the dependence of autonomous parvoviruses on host functions for many steps in their replication cycle and represents a major limitation to the use of selectively replicating parvoviruses for colon cancer therapy.Cancer Gene Therapy (2006) 13, 273–280. doi:10.1038/sj.cgt.7700904; published online 9 September 2005 [ABSTRACT FROM AUTHOR]

We study two-variable Engel-like relations and identities characterizing finite-dimensional solvable Lie algebras and, conjecturally, finite solvable groups and introduce some invariants of finite groups associated with such relations. Bibliography: 29 titles. [ABSTRACT FROM AUTHOR]

The case of a 72-year-old woman with a bleeding tumour in the region of the left knee is described. The clinical diagnosis was angiosarcoma. The histological examination showed an infiltrating tumour, consisting of two types of cells : stromal cells, resembling young connective tissue cells, and multinucleated giant cells. On the basis of the histological findings the tumour was classified as an osteoclastoma. The authors stress the fact that the tumour developed autochtoneously in the skin, rejecting the theory that the giant-cell tumour results from abnormal hyperplasia of osteoclasts. [ABSTRACT FROM AUTHOR]

The authors discuss their response on the comments regarding their article on transient elastography for staging liver fibrosis in alcoholic liver disease. They agree that their article is based on their Cochrane systematic review but stress that including data from the two studies will not influence the results of the meta-analyses. They argue against the comment that the mixed aetiology in the 50% of the included studies is a limitation of their review.

A response by the G. Bjelakovic and colleagues to a letter to the editor on their article "Metaanalysis: antioxidant supplements for liver disease: the Cochrane Hepato-Biliary Group" in the 2010 issue is presented.