Urate Oxidase Purification by Salting-in Crystallization : Towards an Alternative to Chromatography

Background: Rasburicase (FasturtecH or ElitekH, Sanofi-Aventis), the recombinant form of urate oxidase from Aspergillus flavus, is a therapeutic enzyme used to prevent or decrease the high levels of uric acid in blood that can occur as a result of chemotherapy. It is produced by Sanofi-Aventis and currently purified via several standard steps of chromatography. This work explores the feasibility of replacing one or more chromatography steps in the downstream process by a crystallization step. It compares the efficacy of two crystallization techniques that have proven successful on pure urate oxidase, testing them on impure urate oxidase solutions

Genetic structure and variability within and among populations of the fat-tailed Barbarine sheep breed using microsatellites markers

This study investigates the genetic diversity and the structure of the most dominant native fat-tailed Tunisian sheep breed (Barbarine, BAR) using microsatellite markers. Blood samples from 183 BAR animals, belonging to 4 subpopulations according to phenotypic traits, were collected across all regions in Tunisia. BAR animals and 31 Appenninica Italian sheep breed (APP) used as an out-group were genotyped at 17 microsatellites loci. A total of 270 alleles were identified with average gene diversity equal to 0.812. The mean observed heterozygosity (0.745) and allelic richness (8.09) estimates were high within BAR breed highlighting notable levels of genetic diversity. The low FIS (0.078) and FIT (0.084) values indicate low level of inbreeding within this breed while a low FST estimate (0.007) shows that the subpopulations are not genetically differentiated. The clustering analysis performed with ‘structure’ detected the absence of substructures and the clear uniqueness of the BAR. Tomiuk and Loeschcke’s DTL genetic distance values confirmed the distinction between APP and BAR breeds. Results arising from our microsatellites analysis represent a starting point for the valorization of this indigenous Tunisian sheep breed. A suggestion was made to monitor its genetic variability and for the preservation of this breed for the next generations.Keywords: Tunisian Barbarine sheep breed, microsatellite markers, genetic variability, population structureAfrican Journal of Biotechnology, Vol. 13(1), pp. 44-54, 1 January, 201

Stuctural And Magnetic Characterization Of CoxZn1-x/Cu Multilayers Obtained by Electrodeposition

We present the experimental results of (CoxZn1-x/Cu)n multilayers (3<x<10) grown using the electrochemical dual bath method. The X-ray diffraction patterns have shown that the CoZn structural lattice parameters are close to those of the monoclinic CoZn13 compound. We have developed an analytical model in the X-ray kinematical theory adapted to the electrodeposited (CoxZn1-x/Cu) multilayers. We have shown that the model can give interesting structural information about the multilayer components, and reproduces the position of the satellite peaks around the main diffraction peak. Thus we have deduced the multilayer period and performed comparison between experimental results and the analytical model. The magnetic properties at room temperature reveal both superparamagnetic and ferromagnetic features. The inclusion of Zn into the magnetic layer and the existence of CoZnCu based alloy at the interfacial regions explain the magnetic properties. The magnetoresistance (MR) loop displays a broad , rounded maximum and the saturation is not observed even at high applied fields. The MR(H) behaviour and its small ratio can be attributed to interfacial effects.We present the experimental results of (CoxZn1-x/Cu)n multilayers (3<x<10) grown using the electrochemical dual bath method. The X-ray diffraction patterns have shown that the CoZn structural lattice parameters are close to those of the monoclinic CoZn13 compound. We have developed an analytical model in the X-ray kinematical theory adapted to the electrodeposited (CoxZn1-x/Cu) multilayers. We have shown that the model can give interesting structural information about the multilayer components, and reproduces the position of the satellite peaks around the main diffraction peak. Thus we have deduced the multilayer period and performed comparison between experimental results and the analytical model. The magnetic properties at room temperature reveal both superparamagnetic and ferromagnetic features. The inclusion of Zn into the magnetic layer and the existence of CoZnCu based alloy at the interfacial regions explain the magnetic properties. The magnetoresistance (MR) loop displays a broad , rounded maximum and the saturation is not observed even at high applied fields. The MR(H) behaviour and its small ratio can be attributed to interfacial effects

Synchronous Primary Tumors of the Kidney and Pancreas: Case Report

The simultaneous presence of primary carcinomas in the same patient is uncommon and synchronous primary tumors involving the kidney and pancreas are extremely rare. There are a few reports in the English literature of synchronous primary malignancies of the kidney and pancreas. We present a 62-year-old man who had weight loss of 9 kg and epigastric pain. Findings showed a Furhman grade II renal papillary carcinoma confined to the kidney and a synchronous well differentiated pancreatic ductal adenocarcinoma.Key Words: Synchronous double cancer, renal cell carcinoma, pancreatic carcinom

Association of Mediterranean diet with survival after breast cancer diagnosis in women from nine European countries: results from the EPIC cohort study

BACKGROUND: The Mediterranean diet has been associated with lower risk of breast cancer (BC) but evidence from prospective studies on the role of Mediterranean diet on BC survival remains sparse and conflicting. We aimed to investigate whether adherence to Mediterranean diet prior to diagnosis is associated with overall and BC-specific mortality. METHODS: A total of 13,270 incident breast cancer cases were identified from an initial sample of 318,686 women in 9 countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Adherence to Mediterranean diet was estimated through the adapted relative Mediterranean diet (arMED), a 16-point score that includes 8 key components of the Mediterranean diet and excludes alcohol. The degree of adherence to arMED was classified as low (score 0-5), medium (score 6-8), and high (score 9-16). Multivariable Cox proportional hazards models were used to analyze the association between the arMED score and overall mortality, and Fine-Gray competing risks models were applied for BC-specific mortality. RESULTS: After a mean follow-up of 8.6 years from diagnosis, 2340 women died, including 1475 from breast cancer. Among all BC survivors, low compared to medium adherence to arMED score was associated with a 13% higher risk of all-cause mortality (HR 1.13, 95%CI 1.01-1.26). High compared to medium adherence to arMED showed a non-statistically significant association (HR 0.94; 95% CI 0.84-1.05). With no statistically significant departures from linearity, on a continuous scale, a 3-unit increase in the arMED score was associated with an 8% reduced risk of overall mortality (HR3-unit 0.92, 95% CI: 0.87-0.97). This result sustained when restricted to postmenopausal women and was stronger among metastatic BC cases (HR3-unit 0.81, 95% CI: 0.72-0.91). CONCLUSIONS: Consuming a Mediterranean diet before BC diagnosis may improve long-term prognosis, particularly after menopause and in cases of metastatic breast cancer. Well-designed dietary interventions are needed to confirm these findings and define specific dietary recommendations

Activating Transcription Factor 4 Confers a Multidrug Resistance Phenotype to Gastric Cancer Cells through Transactivation of SIRT1 Expression

BACKGROUND: Multidrug resistance (MDR) in gastric cancer remains a major challenge to clinical treatment. Activating transcription factor 4 (ATF4) is a stress response gene involved in homeostasis and cellular protection. However, the expression and function of ATF4 in gastric cancer MDR remains unknown. In this study, we investigate whether ATF4 play a role in gastric cancer MDR and its potential mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that ATF4 overexpression confered the MDR phenotype to gastric cancer cells, while knockdown of ATF4 in the MDR variants induced re-sensitization. In this study we also showed that the NAD(+)-dependent histone deacetylase SIRT1 was required for ATF4-induced MDR effect in gastric cancer cells. We demonstrated that ATF4 facilitated MDR in gastric cancer cells through direct binding to the SIRT1 promoter, resulting in SIRT1 up-regulation. Significantly, inhibition of SIRT1 by small interfering RNA (siRNA) or a specific inhibitor (EX-527) reintroduced therapeutic sensitivity. Also, an increased Bcl-2/Bax ratio and MDR1 expression level were found in ATF4-overexpressing cells. CONCLUSIONS/SIGNIFICANCE: We showed that ATF4 had a key role in the regulation of MDR in gastric cancer cells in response to chemotherapy and these findings suggest that targeting ATF4 could relieve therapeutic resistance in gastric cancer

Comparison of diet consumption, body composition and lipoprotein lipid values of Kuwaiti fencing players with international norms

<p>Abstract</p> <p>Background</p> <p>No published data is currently available that describes the dietary patterns or physiological profiles of athletes participating on the Kuwaiti national fencing team and its potential impact on health and physical performance. The purpose of this investigation was to: 1) collect baseline data on nutrient intake 2) collect, analyze and report baseline for body composition, plasma lipid and lipoprotein concentrations during the competitive season, 3) compare the results with the international norms, 4) and provide necessary health and nutritional information in order to enhance the athletes' performance and skills.</p> <p>Methods</p> <p>Fifteen national-class fencers 21.5 ± 2.6 years of age participated in this study. Food intake was measured using a 3-day food record. Body composition was estimated using both the BOD POD and Body Mass Index (BMI). Total blood lipid profiles and maximum oxygen consumption was measured for each of the subjects during the competitive season.</p> <p>Results</p> <p>The results of the present study showed significant differences in dietary consumption in comparison with the recommended dietary allowances (RDA). The blood lipids profile and body composition (BMI and % body fat) were in normal range in comparison with international norms However, the average VO_{2 max}value was less than the value of the other fencers.</p> <p>Conclusion</p> <p>Due to the results of the research study, a dietary regimen can be designed that would better enhance athletic performance and minimize any health risks associated with nutrition. Percent body fat and BMI will also be categorized for all players. In addition, the plasma blood tests will help to determine if any of the players have an excessive level of lipids or any blood abnormalities. The outcomes of present study will have a direct impact on the players health and therefore their skills and athletic performance.</p

The Renin Angiotensin System (RAS) mediates bifunctional growth regulation in melanoma and is a novel target for therapeutic intervention

Despite emergence of new systemic therapies, metastatic melanoma remains a challenging and often fatal form of skin cancer. The renin–angiotensin system (RAS) is a major physiological regulatory pathway controlling salt–water equilibrium, intravascular volume and blood pressure. Biological effects of the RAS are mediated by the vasoactive hormone angiotensin II (AngII) via two receptor subtypes, AT1R (encoded by AGTR1) and AT2R (encoded by AGTR2). We report decreasing expression and increasing CpG island methylation of AGTR1 in metastatic versus primary melanoma and detection in serum of methylated genomic DNA from the AGTR1 CpG island in metastatic melanoma implying that AGTR1 encodes a tumour suppressor function in melanoma. Consistent with this hypothesis, antagonism of AT1R using losartan or shRNA-mediated knockdown in melanoma cell lines expressing AGTR1 resulted in acquisition of the ability to proliferate in serum-free conditions. Conversely, ectopic expression of AGTR1 in cell lines lacking endogenous expression inhibits proliferation irrespective of the presence of AngII implying a ligand-independent suppressor function for AT1R. Treatment of melanoma cell lines expressing endogenous AT2R with either AngII or the AT2R-selective agonist Y6AII induces proliferation in serum-free conditions whereas the AT2R-specific antagonists PD123319 and EMA401 inhibit melanoma growth and angiogenesis and potentiate inhibitors of BRAF and MEK in cells with BRAF V600 mutations. Our results demonstrate that the RAS has both oncogenic and tumour suppressor functions in melanoma. Pharmacological inhibition of AT2R may provide therapeutic opportunities in melanomas expressing this receptor and AGTR1 CpG island methylation in serum may serve as a novel biomarker of metastatic melanoma