The Clastogenic effect of Pyrimethamine (Daraprim) on human chromosomes in lymphocyte cultures

In this study the clastogenic effect of pyrimethamine (Daraprim), a folic acid antagonist used for the treatment of toxoplasmosis and malaria on human chromosomes, was investigated. Pyrimethamine was added to in vitro lymphocyte cultures at six different concentrations: 0.05 (normal therapeutic dose), 0.1, 0.2, 0.4, 0.8, and 1.6 mg/ml. No proliferation was observed in any of the cultures containing 1.6 mg/ml pyrimethamine. The results of the cytogenetic evaluations show that the frequency of breaks and gaps increase significantly in dose-dependent manner. Thus, pyrimethamine has a clastogenic effect on human chromosomes.Abbreviations PHAM Phytohemagglutinin M - M Metaphase - G Gap - B break - R Rearrangement - NCA Number Chromosome Abnormalities - FA Folic acid - SCE Sister Chromatid Exchange     

Effect of pioglitazone on the expression of ubiquitin proteasome system and autophagic proteins in rat pancreas with metabolic syndrome

The metabolic syndrome (MetS) and pathologies associated with metabolic dysregulations a worldwide growing problem. Our previous study demonstrated that pioglitazone (PGZ) has beneficial effects on metabolic syndrome associated disturbances in the heart. However, mechanism mediating the molecular alterations of Ubiquitin proteasome system (UPS) and autophagy has not been investigated in rat pancreas with metabolic syndrome. For this reason, we first aimed to detect whether MetS effects on the expression of UPS (p97/VCP, SVIP, Ubiquitin) and autophagic (p62, LC3) proteins in rat pancreas. The second aim of the study was to find impact of pioglitazone on the expression of UPS and autophagic proteins in MetS rat pancreas. To answer these questions, metabolic syndrome induced rats were used as a model and treated with pioglitazone for 2 weeks. Pancreatic tissue injuries, fibrosis and lipid accumulation were evaluated histopathologically in control, MetS and MetS-PGZ groups. Apoptosis and cell proliferation of pancreatic islet cells were assessed in all groups. UPS and autophagic protein expressions of pancreas in all groups were detected by using immunohistochemistry, double-immunfluorescence and Western blotting. Compared with the controls, the rat fed with high sucrose exhibited signs of metabolic syndrome, such as higher body weight, insulin resistance, higher triglyceride level and hyperglycaemia. MetS rats showed pancreatic tissue degeneration, fibrosis and lipid accumulation when their pancreas were examined with Hematoxilen-eozin and Mallory trichrome staining. Metabolic, histopathologic parameters and cell proliferation showed greater improvement in MetS-PGZ rats and pioglitazone decreased apoptosis of islet cells. Moreover, SVIP, ubiquitin, LC3 and p62 expressions were significantly increased while only p97/VCP expression was significantly decreased in MetS-rat pancreas compared to control. PGZ treatment significantly decreased the MetS-induced increases in autophagy markers. Additionally, UPS and autophagy markers were found to colocalizated with insulin and glucagon. Colocalization ratio of UPS markers with insulin showed significant decrease in MetS rats and PGZ increased this ratio, whereas LC3-insulin colocalization displayed significant increase in MetS rats and PGZ reversed this effect. In conclusion, PGZ improved the pancreatic tissue degeneration by increasing the level of p97/VCP and decreasing autophagic proteins, SVIP and ubiquitin expressions in MetS-rats. Moreover, PGZ has an effect on the colocalization ratio of UPS and autophagy markers with insulin.

     

Molecular dynamics simulation of helium–argon gas mixture under various wall conditions

As computational capabilities increase, molecular dynamics (MD) simulations become important tools of simulating reality. These simulations are especially useful for compressible gas mixture problems. In this study, binary diffusion of helium and argon was examined using a hard-sphere MD simulation method. For the sake of computational speed, low spacing ratios were chosen. Binary mass diffusion of gases in two equally sized halves of a box was simulated for identical initial kinetic energies and number densities. It has been noted that a purely mass diffusion mechanism of different gases is not physically possible. The resultant gas mixtures of several diffusion simulations were used as initial conditions for combined heat transfer – Couette flow, and heating and cooling experiments. The results showed the interesting behaviour of the mixture, which was subjected to various wall conditions. Energy of heavier molecules is found to be more sensitive to the wall velocities and less sensitive to the wall temperatures than lighter molecules. Diffusion, heat transfer, viscosity and heat capacity coefficients are deduced as well.     

Is emotion recognition the only problem in ADHD? effects of pharmacotherapy on face and emotion recognition in children with ADHD

The objectives of this study were to evaluate both face and emotion recognition, to detect differences among attention deficit and hyperactivity disorder (ADHD) subgroups, to identify effects of the gender and to assess the effects of methylphenidate and atomoxetine treatment on both face and emotion recognition in patients with ADHD. The study sample consisted of 41 male, 29 female patients, 8–15 years of age, who were diagnosed as having combined type ADHD (N = 26), hyperactive/impulsive type ADHD (N = 21) or inattentive type ADHD (N = 23) but had not previously used any medication for ADHD and 35 male, 25 female healthy individuals. Long-acting methylphenidate (OROS-MPH) was prescribed to 38 patients, whereas atomoxetine was prescribed to 32 patients. The reading the mind in the eyes test (RMET) and Benton face recognition test (BFRT) were applied to all participants before and after treatment. The patients with ADHD had a significantly lower number of correct answers in child and adolescent RMET and in BFRT than the healthy controls. Among the ADHD subtypes, the hyperactive/impulsive subtype had a lower number of correct answers in the RMET than the inattentive subtypes, and the hyperactive/impulsive subtype had a lower number of correct answers in short and long form of BFRT than the combined and inattentive subtypes. Male and female patients with ADHD did not differ significantly with respect to the number of correct answers on the RMET and BFRT. The patients showed significant improvement in RMET and BFRT after treatment with OROS-MPH or atomoxetine. Patients with ADHD have difficulties in face recognition as well as emotion recognition. Both OROS-MPH and atomoxetine affect emotion recognition. However, further studies on the face and emotion recognition are needed in ADHD.     

2D Representation of Transcriptomes by t-SNE Exposes Relatedness between Human Tissues

The GTEx Consortium reported that hierarchical clustering of RNA profiles from 25 unique tissue types among 1641 individuals accurately distinguished the tissue types, but a multidimensional scaling failed to generate a 2D projection of the data that separates tissue-subtypes. In this study we show that a projection by t-Distributed Stochastic Neighbor Embedding is in line with the cluster analysis which allows a more detailed examination and visualization of human tissue relationships.     

Antioxidant and antimicrobial actions of the clubmoss <Emphasis Type="Italic">Lycopodium clavatum</Emphasis> L.

Purpose of the present study was to evaluate antioxidant, antibacterial, antifungal, and antiviral activities of the petroleum ether, chloroform, ethyl acetate and methanol extracts as well as the alkaloid fraction of Lycopodium clavatum L. (LC) from Lycopodiaceae growing in Turkey. Antioxidant activity of the LC extracts was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging method at 0.2 mg/ml using microplate-reader assay. Antiviral assessment of LC extracts was evaluated towards the DNA virus Herpes simplex (HSV) and the RNA virus Parainfluenza (PI-3) using Madin-Darby Bovine Kidney (MDBK) and Vero cell lines. Antibacterial and antifungal activities of the extracts were tested against standard and isolated strains of the following bacteria; Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Acinobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, Bacillus subtilis as well as the fungi; Candida albicans and C. parapsilosis. All of the extracts possessed noteworthy activity against ATCC strain of S. aureus (4 μg/ml), while the LC extracts showed reasonable antifungal effect. On the other hand, we found that only the chloroform extract was active against HSV (16–8 μg/ml), while petroleum ether and alkaloid extracts inhibited potently PI-3 (16–4 μg/ml and 32–4 μg/ml, respectively). However, all of the extracts had insignificant antiradical effect on DPPH. In addition, we also analyzed the content of the alkaloid fraction of the plant by capillary gas chromatography-mass spectrometry (GC-MS) and identified lycopodine as the major alkaloid.     

Effect of fish oil supplementation on plasma oxidant/antioxidant status in rats

The aim of this study was to investigate effect of dietary omega-3 fatty acid supplementation on the indices of in vivo lipid peroxidation and oxidant/antioxidant status of plasma in rats. The plasma thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO) levels, and activities of xanthine oxidase (XO), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were studied in male Wistar Albino rats after ingestion of 0.4 g/kg fish oil (rich in omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid) for 30 days and compared to untreated control rats. The rats in the treated group had significantly higher SOD activity (P < 0.001), NO levels (P < 0.01) and decreased TBARS levels (P < 0.05) with respect to controls whereas GSH-Px and XO activities were not significantly different between the groups. None of the measured parameters had significant correlation with each other in both groups. We conclude that dietary supplementation of omega-3 fatty acids may enhance resistance to free radical attack and reduce lipid peroxidation. These results support the notion that omega-3 fatty acids may be effective dietary supplements in the management of various diseases in which oxidant/antioxidant defence mechanisms are decelerated.