Bioaccumulation of copper nanoparticle in gill, liver, intestine and muscle of Siberian sturgeon (Acipenser baerii) juvenile

Copper (Cu) is an essential element required by all living organisms, since at least 30 enzymes are known to use Cu as a cofactor. Cu is also toxic in excess and liver and gills are known to be target organs for it. In the present study, 240 Siberian sturgeon juvenile (with initial weight 29.2 ± 3.1 g and initial length 21.8 ± 1.4 cm) were randomly distributed in 12 fiberglass tanks at 4 different copper nanoparticle (Cu-NPs) treatments with 3 replicates. Treatments included control (T0 = no added Cu-NPs), 50 (T50), 100 (T100), 200 (T200) µg.l -1 Cu-NPs (mean primary particle size of 2 - 6 nm) in a semi-static waterborne exposure regime. Water exchanged were 20% daily with redosing after each change. The experimental period lasted 28 days, 14 days exposure to Cu-NPs and 14 days as recovery time. Fish liver, gill, intestine and muscle were sampled at days 0, 7, 14, 21 and 28. Samples were weighed, dried (100 ◦C for 48 h) then digested in concentrated nitric acid in a water bath, cooled, and analyzed for Cu concentration in the tissues with graphite furnace atomic absorption spectroscope. Most of the Cu-NPs were accumulated in the intestine, gill, liver and muscle. The accumulation of NPs in tissues was increased in all treatments from day 7 through 14. In the recovery period, Cu-NPs in tissues decreased but it was still higher than the control treatment. The current findings indicate that preventing the entry of Cu-NPs into the aquatic environment would seem to be essential

Dietary administration of vitamin C and Lactobacillus rhamnosus in combination enhanced the growth and innate immune response of the rainbow trout, Oncorhynchus mykiss

The effects of dietary vitamin C and Lactobacillus rhamnosus on immunity and growth performance were investigated in Oncorhynchus mykiss. For this purpose, 480 rainbow trout (68±5g) were obtained from a local farm and acclimated to laboratory conditions for 10 days and then divided into four groups in three replicates. During 30 days, juvenile rainbow trout were fed diets supplemented with vitamin C (1g/kg) and L. rhamnosus (at 5 × 107 CFU/g) or a control diet. Biometry was done at day -30 and blood samples were taken by caudal vein after fish anesthesia with clove powder at day 0, 15, 30 and 45. Serum lysozyme activity, alternative complement activity and total plasma immunoglobulin level were assayed as innate immune response of rainbow trout. Results showed fish fed with vitamin c and L. rhamnosus (group 3) statistically could improve fish growth performance. Also lysozyme activity and alternative complement activity of serum significantly were higher in group three than other groups, but total plasma level of immunoglobulin only was higher than all groups at day 30. In conclusion dietary administration of vitamin C and L. rhamnosus in rainbow trout diet could enhance the growth and innate immune response, but these properties need further studies on the field applications

Effects of dietary Bacillus subtilis on growth performance and immune responses, in rainbow trout, Oncorhynchus mykiss (Walbaum, 1792)

Four hundred and eighty five rainbow trout (76 ± 6.44 g mean weight) were acclimated to laboratory conditions and then randomly divided into four groups of tanks in triplicate. The first group (Group 1) was fed on a commercial diet (control) without Bacillus subtilis supplementation. The second, third and fourth groups (Group 2, Group 3 and Group 4, respectively) were given a diet supplemented with 1, 5 and 10 g probiotic powder (containing 8×10^7 CFU g^-1 Bacillus subtilis) per kg commercial feed. Growth performance, immune responses and glucose levels were analyzed on days 0, 22 and 44. The results showed that dietary Bacillus subtilis supplementation significantly (p0.05) was observed in weight gain rate (WGR) between the control and group 2. On the effect of dietary Bacillus subtilis on serum lysozyme, it was observed that group 3 and group 4 did not show any significant differences in serum lysozyme activity and serum total antibody on day 44. Results of alternative complement activity, showed significant increase during the experimental days (p<0.05). Results on glucose assay showed that group 3 had the lowest glucose level (13.71 mg/dL) which was not significantly different than that in other groups on day 44. Fish diet supplementation with 5 g probiotic powder (Group 3) is preferable for immune system responses; however, high dose of Bacillus subtilis may be helpful to improve growth performance in rainbow trout, Oncorhynchus mykiss (Walbaum, 1792)

Factors influencing the geographic distribution of physicians in Iran: A qualitative study

Introduction: The uneven geographic distribution of physicians has been a longstanding important issue worldwide. Different policies have been recently employed in Iran, with the aim of bridging the gap. This study aimed to explore factors influencing the distribution of specialist physicians in Iran and investigate the effects of newly established policies on attracting and retaining physicians in rural and remote areas. Methods: This qualitative study was conducted in 2012. Qualitative data were obtained through an open-ended questionnaire and by reviewing relevant documents. Participants were 82 key officials from medical universities, who were directly involved in the distribution of physicians across the country, including vice chancellors for treatment affairs, managers for treatment affairs, and human resources experts. Thematic analysis was used to analyse qualitative data. Results: Four main factors influencing the distribution of physicians were explored, namely external, contextual, individual, and organizational factors. The decision to practice in rural areas was mainly influenced by socioeconomic characteristics of the designated areas and personal attributes of physicians, including sex, income expectations, and rural background. Participants also asserted that the implemented policies had a major positive influence on the distribution of physicians. In addition, participants believed that the improvement in the distribution of physicians had both positive economic and health impacts in underdeveloped areas. Conclusions: It seems that the regional distribution and supply of physicians have been improved in the light of the implemented policies in recent years. The study also revealed that a number of factors influence physician choices to stay and practice in rural and underdeveloped areas. Policies such as providing more financial and non-financial incentives, reducing disparities between physicians' income in rural and metropolitan areas, selection of students with rural background, and supportive measures for physicians working in underserved areas were recommended. © H Ravaghi, E Taati, Z Abdi, A Meshkini, S Sarvarizadeh, 2015

Communities that thrive in extreme conditions captured from a freshwater lake

Organisms that can grow in extreme conditions would be expected to be confined to extreme environments. However, we were able to capture highly productive communities of algae and bacteria capable of growing in acidic (pH 2), basic (pH 12) and saline (40 ppt) conditions from an ordinary freshwater lake. Microbial communities may thus include taxa that are highly productive in conditions that are far outside the range of conditions experienced in their host ecosystem. The organisms we captured were not obligate extremophiles, but were capable of growing in both extreme and benign conditions. The ability to grow in extreme conditions may thus be a common functional attribute in microbial communities.</jats:p

The Incidence Rate of Vasovagal Reactions and Its Effective Factors among Blood Donors in Mashhad Blood Transfusion Centers

Aims: Vasovagal reaction is one of the most common complications of blood donation, this study was conducted to determine the prevalence of vasovagal reactions and its effective factors among blood donors in Mashhad blood transfusion centers. Materials & Methods: This case-control study was performed on 657 blood donors in Mashhad's four blood transfusion centers during 6 months. The donors who had vasovagal reactions were in the case group (218 cases), and 439 donors who did not respond to vasovagal were in the control group. The age, BMI, blood pressure, pulse rate, hematocrit and vasovagal response variables were studied. Data were analyzed by SPSS 11.5 using Chi-square and Mann-Whitney tests. Findings: The incidence of vasovagal reactions in the six months was 2.16%. The mean age in the case group was significantly lower than the control group (p<0.001). Vasovagal reactions were significantly higher in women and in first-time donors, as well as in those with anxiety and in subjects with lower BMI (p<0.001). The mean reduction in arterial pressure after blood donation was significantly higher in the case group than in the control group (p<0.001). Conclusion: The incidence of vasovagal reactions is dependent on several factors, including age, sex, BMI, and blood pressure, and with more care from high-risk donors, it can be approximately prevented from vasovagal reaction and increased the possibility of returning to blood donation

Aid conditionalities, international Good Manufacturing Practice standards and local production rights: a case study of local production in Nepal

© 2015 Brhlikova et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This work was supported by the Economic and Social Research Council and the Department for International Development [RES-167-25-0110] through the collaborative research project Tracing Pharmaceuticals in South Asia (2006 – 2009). In addition to the authors of this paper, the project team included: Soumita Basu, Gitanjali Priti Bhatia, Erin Court, Abhijit Das, Stefan Ecks, Patricia Jeffery, Roger Jeffery, Rachel Manners, and Liz Richardson. Martin Chautari (Kathmandu) and the Centre for Health and Social Justice (New Delhi) provided resources drawn upon in writing this paper but are not responsible for the views expressed, nor are ESRC or DFID. Ethical review was provided by the School of Social and Political Science at the University of Edinburgh, and ethical approval in Nepal for the study granted by the Nepal Health Research Council (NHRC)

Cost-effectiveness analysis of adding low dose ribavirin to peginterferon alfa-2a for treatment of chronic hepatitis C infected thalassemia major patients in Iran

Background: The prevalence of hepatitis C in Iran is 1 and 18 in general population and thalassemia patients respectively. The cost effectiveness analysis of adding Ribavirin to Peginterferon alfa-2a (PEG IFN alfa-2a) as a combination treatment strategy of chronic hepatitis C in thalassemia patients in comparison with monotherapy could help clinicians and policy makers to provide the best treatment for the patients. Objectives: In this study we aimed to assess whether adding Ribavirin to PEG IFN alfa-2a is a cost effective strategy in different genotypes and different subgroups of 280 patients with chronic hepatitis C infection from the perspective of society in Iranian setting. Patients and Methods: A cost effectiveness analysis including all costs and outcomes of treatments for chronic hepatitis C infected thalassemia major patients was conducted. We constructed a decision tree of treatment course in which a hypothetical cohort of 100 patients received "PEG IFN alfa-2a" or "Peg IFN alfa-2a plus Ribavirin." The cost analysis was based on cost data for 2008 and we used 9300 Iranian Rials (IR Rial) as exchange rate declared by the Iranian Central Bank on that time to calculating costs by US Dollar (USD). To evaluate whether a strategy is cost effective, one time and three times of GDP per capita were used as threshold based on recommendation of the World Health Organization. Results: The Incremental Cost Effectiveness Ratio (ICER) for combination therapy in genotype-1 and genotypes non-1 subgroups was 2,673 and 19,211 US dollars (USD) per one Sustain Virological Response (SVR), respectively. In low viral load and high viral load subgroups, the ICER was 5,233 and 14,976 USD per SVR, respectively. The calculated ICER for combination therapy in subgroup of patients with previously resistant to monotherapy was 13,006 USD per SVR. Combination therapy in previously resistant patients to combination therapy was a dominant strategy. Conclusions: Adding low dose of Ribavirin to PEG IFN alfa-2a for treatment of chronic hepatitis C patients with genotype-1 was "highly cost effective" and in patients with low viral load and in previous monotherapy resistant patients was "cost effective." © 2013, Kowsar Corp

Generation of Reactive Oxygen Species by Polyenylpyrroles Derivatives Causes DNA Damage Leading to G2/M Arrest and Apoptosis in Human Oral Squamous Cell Carcinoma Cells

10.1371/journal.pone.0067603PLoS ONE86-POLN

Induction of Erythroid Differentiation in Human Erythroleukemia Cells by Depletion of Malic Enzyme 2

Malic enzyme 2 (ME2) is a mitochondrial enzyme that catalyzes the conversion of malate to pyruvate and CO2 and uses NAD as a cofactor. Higher expression of this enzyme correlates with the degree of cell de-differentiation. We found that ME2 is expressed in K562 erythroleukemia cells, in which a number of agents have been found to induce differentiation either along the erythroid or the myeloid lineage. We found that knockdown of ME2 led to diminished proliferation of tumor cells and increased apoptosis in vitro. These findings were accompanied by differentiation of K562 cells along the erythroid lineage, as confirmed by staining for glycophorin A and hemoglobin production. ME2 knockdown also totally abolished growth of K562 cells in nude mice. Increased ROS levels, likely reflecting increased mitochondrial production, and a decreased NADPH/NADP+ ratio were noted but use of a free radical scavenger to decrease inhibition of ROS levels did not reverse the differentiation or apoptotic phenotype, suggesting that ROS production is not causally involved in the resultant phenotype. As might be expected, depletion of ME2 induced an increase in the NAD+/NADH ratio and ATP levels fell significantly. Inhibition of the malate-aspartate shuttle was insufficient to induce K562 differentiation. We also examined several intracellular signaling pathways and expression of transcription factors and intermediate filament proteins whose expression is known to be modulated during erythroid differentiation in K562 cells. We found that silencing of ME2 leads to phospho-ERK1/2 inhibition, phospho-AKT activation, increased GATA-1 expression and diminished vimentin expression. Metabolomic analysis, conducted to gain insight into intermediary metabolic pathways that ME2 knockdown might affect, showed that ME2 depletion resulted in high orotate levels, suggesting potential impairment of pyrimidine metabolism. Collectively our data point to ME2 as a potentially novel metabolic target for leukemia therapy