Analysis of the Influences of Short-Term Levosimendan Exposure on Oxidant/Antioxidant Status and Trace-Element Levels in the Physiological Status of the Thoracic Aorta of Rats

The objective of this study was to evaluate the effect of levosimendan (chemical formula C₁₄H₁₂N₆O) exposure on oxidant/antioxidant status and trace-element levels in the thoracic aorta of rats. Eighteen male Wistar albino rats were randomly divided into two groups of eight animals each. Group 1 was not exposed to levosimendan and served as a control. Levosimendan (12???g/kg) diluted in 10 ml 0.5?% dextrose was administered intraperitoneally to group 2. Animals of both groups were killed after 3?days, and their thoracic aortae were harvested for determination of changes in tissue oxidant/antioxidant status and trace-element levels. The animals in both groups were killed 72?h after levosimendan exposure, and thoracic aortae were harvested for determination of the lipid peroxidation product MDA and antioxidant GSH levels and the activities of antioxidant enzymes such as SOD, GSH-Px and CAT. It was found that MDA, GSH and CAT enzyme levels increased in thoracic aortae of rats after levosimendan administration. SOD and CA enzyme activities and the level of antioxidant GSH decreased in thoracic aortae of rats after levosimendan treatment. Pb, Cd and Fe levels of thoracic aortae were significantly higher (P?<?0.001) and Mg, Mn, Zn and Cu were significantly lower (P?<?0.001) in the levosimendan group compared to the control group. These results suggest that short-term levosimendan treatment caused an increase in free radical production and a decrease in antioxidant enzyme activity in thoracic aortae of levosimendan-treated rats. It also causes a decrease or increase in many mineral levels of the thoracic aorta, which is an undesirable condition for normal pharmacological function.     

Whole genome sequencing of Turkish genomes reveals functional private alleles and impact of genetic interactions with Europe,Asia and Africa

Background

Turkey is a crossroads of major population movements throughout history and has been a hotspot of cultural interactions. Several studies have investigated the complex population history of Turkey through a limited set of genetic markers. However, to date, there have been no studies to assess the genetic variation at the whole genome level using whole genome sequencing. Here, we present whole genome sequences of 16 Turkish individuals resequenced at high coverage (32 × -48×).

Results

We show that the genetic variation of the contemporary Turkish population clusters with South European populations, as expected, but also shows signatures of relatively recent contribution from ancestral East Asian populations. In addition, we document a significant enrichment of non-synonymous private alleles, consistent with recent observations in European populations. A number of variants associated with skin color and total cholesterol levels show frequency differentiation between the Turkish populations and European populations. Furthermore, we have analyzed the 17q21.31 inversion polymorphism region (MAPT locus) and found increased allele frequency of 31.25% for H1/H2 inversion polymorphism when compared to European populations that show about 25% of allele frequency.

Conclusion

This study provides the first map of common genetic variation from 16 western Asian individuals and thus helps fill an important geographical gap in analyzing natural human variation and human migration. Our data will help develop population-specific experimental designs for studies investigating disease associations and demographic history in Turkey.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-963) contains supplementary material, which is available to authorized users.     

Determination of intracellular efficacies of azithromycin against Leishmania major infection in human neutrophils in vitro

Azithromycin is one of a new class of antibiotics known as azalides. Azithromycin has high tissue affinity and this feature is thought to be due to the presence of two basic tertiary amine groups. Leishmania major, one of the causative agents of cutaneous leishmaniosis, is an obligate intracellular parasite. In this in vitro study, the potential anti-leishmanial effect of azithromycin upon intracellular forms namely the amastigote of L. major in mice peritoneal macrophages was investigated. L. major promastigotes were propagated in RPMI-1640 supplemented with 20% fetal calf serum in the log phase. The percentage of phagocytosis and microbiacidal activity of azithromycin on macrophages was assessed in the control and study groups by fluorescence microscopy, using acridine orange. Our results showed that at all the concentrations used (0.05, 0.1, 0.3, 0.6 microg ml(-1)) azithromycin had no inhibitory effect on the phagocytic capacity of mouse peritoneal macrophages. Although no significant difference was observed for leishmaniacidal activity between the study and the control groups at a concentration of 0.05 microg ml(-1) (p>0.05), a significant (p<0.05) increase in leishmaniacidal activity was detected at 0.1, 0.3 and 0.6 microg ml(-1). As a result, azithromycin does not provide any contribution to the phagocytosis of L. major promastigotes in macrophages in vitro, but it increases the intracellular killing rates of amastigotes. These results suggest that it has a potential anti-leishmanial effect, and may provide a significant advantage in the treatment of the disease.     

Frequency and risk factors of dermatophytosis in students living in rural areas in Eskişehir,Turkey

Mycopathologia - Our study included 2384 students from five villages around Eski?ehir, Turkey. We asked every student for their personal identification and also for their sanitation in order...     

Critical role for the tapasin-docking site of TAP2 in the functional integrity of the MHC class I-peptide-loading complex

The transporter associated with Ag processing (TAP) translocates antigenic peptides into the endoplasmic reticulum for binding onto MHC class I (MHC I) molecules. Tapasin organizes a peptide-loading complex (PLC) by recruiting MHC I and accessory chaperones to the N-terminal regions (N domains) of the TAP subunits TAP1 and TAP2. To investigate the function of the tapasin-docking sites of TAP in MHC I processing, we expressed N-terminally truncated variants of TAP1 and TAP2 in combination with wild-type chains, as fusion proteins or as single subunits. Strikingly, TAP variants lacking the N domain in TAP2, but not in TAP1, build PLCs that fail to generate stable MHC I-peptide complexes. This correlates with a substantially reduced recruitment of accessory chaperones into the PLC demonstrating their important role in the quality control of MHC I loading. However, stable surface expression of MHC I can be rescued in post-endoplasmic reticulum compartments by a proprotein convertase-dependent mechanism.     

Free oxygen radical-induced lipid peroxidation and antioxidant in infants receiving total parenteral nutrition

OBJECTIVE: Increased oxygen-derived free radical activity has been reported during total parenteral nutrition (TPN) in infants particularly linked to the fat infusion. It is possible that partial enteral feeding can ameliorate some of the complications of TPN. By this study we aimed to investigate free radical formation and antioxidant activity in term and preterm infants during TPN and/or enteral feeding. STUDY DESIGN: We had 6 groups of term and preterm infants made up of 10 patients each. Group I had only enteral feeding, Group II enteral plus parenteral feeding, Group III only parenteral feeding. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), vitamin E and vitamin C levels were measured in all infants. Blood samples of infants receiving only TPN and TPN plus enteral feeding were measured on the 1st and 5th days, and 3h after the end of lipid infusion. RESULTS: There was no difference between the term and preterm infants in terms of MDA, SOD, vitamin C and E levels taken baseline and after parenteral, and enteral plus parenteral feeding on the 1st and 5th days. When 3 groups of both term and preterm infants were compared with each other none of the parameters showed a statistically significant difference. In addition, we compared baseline and 1st and 5th days of TPN therapy in both term and preterm infants fed only parenterally and enteral plus parenteral feedings. In term infants fed both parenterally and parenteral plus enterally, the MDA levels before TPN were significantly higher than that of the levels of patients on parenteral nutrition on the 5th day. On the 1st and 5th days of TPN therapy, the levels of vitamin C was significantly decreased, in term and preterm infants fed only parenterally, levels of vitamin E was increased, in term and preterm infants fed both parenterally and parenteral plus enterally. Also, when compared to their base line the SOD levels of the term infants detected on the 1st and 5th days were significantly high. CONCLUSION: Free radical production is increased by the administration of TPN and may be linked to its adverse effects. It may be assumed that long-term complications of preterm infants receiving TPN may be reduced by further strengthening the antioxidant capacities of the TPN solutions.