Complex Genomic Rearrangement Patterns in Malignant Pleural Mesothelioma due to Environmental Asbestos Exposure.

Malignant pleural mesothelioma (MPM) is a rare type of cancer, and its main risk factor is exposure to asbestos. Accordingly, our knowledge of the genomic structure of an MPM tumor is limited when compared to other cancers. In this study, we aimed to characterize complex genomic rearrangement patterns and variations to better understand the genomics of MPM tumors. We comparatively scanned 3 MPM tumor genomes by Whole-Genome Sequencing and High-Resolution SNP array. We also used various computational algorithms to detect both CNAs and complex chromosomal rearrangements. Genomic data obtained from each bioinformatics tool are interpreted comparatively to better understand CNAs and cancer-related Nucleotide variations in MPM tumors. In patients 1 and 2, we found pathogenic nucleotide variants of BAP1, RB1, and TP53. These two MPM genomes exhibited a highly rearranged chromosomal rearrangement pattern resembling Chromomanagesis particularly in the form of Chromoanasynthesis. In patient 3, we found nucleotide variants of important cancer-related genes, including TGFBR1, KMT2C, and PALLD, to have lower chromosomal rearrangement complexity compared with patients 1 and 2. We also detected several actionable nucleotide variants including XRCC1, ERCC2. We also discovered the SKA3-DDX10 fusion in two MPM genomes, which is a novel finding for MPM. We found that MPM genomes are very complex, suggesting that this highly rearranged pattern is strongly related to driver mutational status like BAP1, TP53 and RB1.

NLRP3-Inflammasome Gene Variations in the Risk of Type 2 Diabetes.

Inflammation is the natural immunological response of an organism against any harmful, foreign or destructive effect to heal and repair damaged tissue. The nod-like receptor pyrin domain-containing-3 (NLRP3) inflammasome is one of the main components of the inflammatory mechanism and is associated with many inflammatory diseases, but it is also closely related to metabolic abnormalities, such as type 2 diabetes mellitus (T2DM), insulin resistance and obesity. NLRP3 activates inflammation and causes interleukin-1ß release, exogenous and endogenous danger signals, as well as insulin resistance. In this direction, we focus on the gene structure of NLRP3 in diabetes and accordingly, we aim to determine the relationship between eight gene variations in the NLRP3 gene and T2DM. We investigated the rs10802501, rs10733113, rs10754558, rs10925026, rs10925027, rs35829419, rs4612666 and rs4925659 single-nucleotide polymorphisms of NLRP3 gene using the Sequenom MassARRAY system in 100 T2DM patients and 100 control individuals. There were no significant differences between T2DM risk and the genotype frequencies of rs10802501, rs10733113, rs35829419 and rs10925026 variants (p > 0.05). However, significant genotype frequencies were determined for rs10925027 (p = 0.0013) and rs4925659 (p < 0.001). For the risk allele G of the rs10754558 variant, significant differences were found in the heterozygous and dominant model (p = 0.036, p = 0.033). The genotype distribution of the rs4612666 variant was significant only in the heterozygous model (p = 0.047). In this hospital-based case-control study, rs10925027, rs4925659 and rs10754558 variants were found to be closely related to T2DM risk. The rs10925027 CC genotype, rs4925659 GG genotype, rs10754558 GG and GC+GG genotypes of the NLRP3 were determined as important risk factors for the T2DM.

Strengths and difficulties in children with specific learning disabilities.

BACKGROUND: The study aims to investigate the social, emotional, and behavioral challenges in children with a specific learning disability (SLD) and to identify the factors that accompany these problems by screening with the Strengths and Difficulties Questionnaire (SDQ). METHODS: The descriptive study was conducted on 278 children with SLD. Strengths and difficulties in children were evaluated by the SDQ applied to their mothers. The percentage of cases above the cut-off limits of the SDQ was calculated. Chi-square test and multiple logistic regression analysis were used for analysis. RESULTS: The mean (SD) total SDQ score was 15.8 (6.5). The percentage of scores of abnormal total difficulties in SLD was 47.8%. Multivariate analysis revealed that cases exposed to antenatal smoking had higher odds ratio of abnormal emotional symptoms and abnormal total difficulties; cases with poor familial income and the presence of a history of antenatal smoking exposure showed considerably higher odds ratio of conduct problems; cases with younger age at the diagnosis of SLD, dyscalculia, extreme duration of preschool screen time (≥4 h), and history of hospitalization had significantly higher odds ratio for hyperactivity-inattention problems; and cases having shorter breastfeeding duration had higher odds ratio of peer problems compared to counterparts. CONCLUSION: Children with SLD have a high score on the SDQ. Practitioners could especially give guidance and support to families with financial problems and those having a child with an early age at diagnosis, exposure to antenatal smoking, short breastfeeding period, early age of the first screen use, and long screen exposure duration during the preschool period.

Potential associations between variants of genes encoding regulators of inflammation, and mediators of inflammation in type 2 diabetes and insulin resistance.

WHAT IS KNOWN AND OBJECTIVE: Type 2 diabetes (T2DM) is a multigenic disease that develops with impaired ß-cell function and insulin sensitivity and has a high prevalence worldwide. A cause often postulated for type 2 diabetes is chronic inflammation. It has been suggested that inflammatory regulators can inhibit insulin signal transduction and that inflammation is involved in insulin resistance (IR) and the pathogenesis of type 2 diabetes. In this direction, we aimed to investigate the gene variants of MyD88 (rs1319438, rs199396), IRAK4 (rs1461567, rs4251513, rs4251559) and TRAF6 (rs331455, rs331457) and serum levels of COX-2, NF-κB, iNOS in T2DM and IR. METHODS: The MyD88, IRAK4 and TRAF6 variations were genotyped in 100 newly diagnosed T2DM patients and 100 non-diabetic individuals using The MassARRAY® Iplex GOLD SNP genotyping method. The COX-2, iNOS and NF-κB levels were measured in serum samples with the sandwich-ELISA method. Results were analysed using SPSS Statistics software and the online FINNETI program. RESULTS AND DISCUSSION: In our study, a total of the 7 variants in the MyD88, IRAK4 and TRAF6 genes were genotyped, and as a result, no relationship was found between most of these variants and the risk of type 2 diabetes and insulin resistance (p > 0.05). Only, the rs1461567 variant of the IRAK4 gene was significant in the heterozygous model (CC vs. CT), and the CT genotype was most frequent in diabetic individuals compared with the non-diabetics (p = 0.033). Additionally, COX-2 and iNOS levels were found to be associated with diabetes and insulin resistance (p < 0.05). WHAT IS NEW AND CONCLUSION: Our results show that high COX-2 and iNOS levels are associated with T2DM, besides MyD88, IRAK4 and TRAF6 gene variations may not be closely related to type 2 diabetes and insulin resistance. Nevertheless, studies in this pathway with a different population and a large number of patients are important.

Assessment of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mean platelet volume in patients with idiopathic epiretinal membrane.

PURPOSE: To assess the role of inflammation in the pathogenesis of idiopathic epiretinal membrane (iERM) using the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) as indicators of inflammation and to compare these parameter levels between iERM and control subjects. METHODS: We retrospectively analyzed the medical records of 36 patients who underwent vitrectomy-ERM peeling and 39 patients who had cataract surgery. We obtained blood samples from all individuals who participated in the study to investigate these parameters. RESULTS: Seventy-five subjects were included in this study: 36 in the iERM group and 39 in the control group. The mean neutrophil and MPV levels were significantly higher in iERM subjects than in control subjects. The mean lymphocyte level was lower in the iERM group. The mean NLR, PLR, and MPV levels were higher in iERM subjects than in control subjects. CONCLUSION: The higher NLR, PLR, and MPV levels found in patients with iERM may indicate that subclinical systemic inflammation may associate with iERM.

Optical coherence tomography parameters as predictors of treatment response to a 577-nm subthreshold micropulse laser in chronic central serous chorioretinopathy.

To determine the relation between retinal microstructural changes and the response to 577-nm subthreshold micropulse laser (SML) treatment in chronic central serous chorioretinopathy (cCSC). This retrospective study included 39 eyes of 39 patients with cCSC, treated with the 577-nm SML. The eyes were evaluated in three groups: complete remission, partial remission, and failure groups. The presence of some baseline retinal microstructural changes, thickness of the outer nuclear layer (ONL), status of the ellipsoid zone (EZ), and retinal pigment epithelium (RPE) were evaluated. The changes in central macular thickness (CMT), subretinal fluid (SRF) height, and best-corrected visual acuity (BCVA) were calculated. There were 14, 13, and 12 eyes in the complete remission, partial remission, and failure group, respectively. The baseline EZ and RPE were found intact in 71.4% and 64.3% of the eyes in the complete remission group, respectively; however, these rates were respectively 25% and 16.7% in the failure group (p < 0.05). Extrafoveal foci were present in 35.7% of the eyes in the complete remission group, but none was found in the failure group (p < 0.05). Although there was no statistically significant difference, the baseline ONL thickness was higher, and the hyperreflective dots, retinal bumps, subretinal fibrinous exudates, and PEDs were seen less in the complete remission group. The changes of the BCVA were not significant in any of the groups at the last visit (p > 0.05). The presence of baseline intact EZ and RPE, and extrafoveal foci can potentially be used as predictors of the SML treatment success in cCSC.

Common variants of genes encoding TLR4 and TLR4 pathway members TIRAP and IRAK1 are effective on MCP1, IL6, IL1ß, and TNFα levels in type 2 diabetes and insulin resistance.

OBJECTIVE AND DESIGN: Type 2 diabetes is a pandemic disease characterized by hyperglycemia, ineffective insulin use, and insulin resistance and affecting 1 in 11 people worldwide. Inflammation-related insulin resistance is thought to play an important role in the etiology of the disease. TLR4 is the central receptor of the natural immune system and has an important role as a trigger of the inflammatory response. The IRAK1 and TIRAP are members of the TLR4 pathway and involved in the TLR4-mediated inflammatory response. Genetic variants in the TLR4 gene or in the IRAK1 and TIRAP genes may have an important role in the development of insulin resistance and type 2 diabetes by disrupting the inflammatory response. In this direction, we aimed to investigate the relationship among TLR4 and IRAK1, TIRAP gene variants, and type 2 diabetes and insulin resistance, and investigate how these variants affect inflammatory factors (TNF-α, IL-6, MCP-1, and IL-1ß). SUBJECTS AND METHODS: In our study, a total of seven variations on the genes of TLR4 (rs4986790, rs4986791), IRAK1 (rs1059703, rs3027898, rs7061789), and TIRAP (rs8177374, rs8177400) were genotyped by the MassARRAY® Iplex GOLD SNP genotyping in 100 type 2 diabetic patients and 100 non-diabetic individual. The TLR4 rs4986790 and rs4986791 variation was confirmed by PCR-RFLP method also. The serum IL1-ß, IL6, MCP-1, and TNF-α levels were measured using enzyme-linked immunosorbent assay kits. RESULTS AND CONCLUSION: As a result of our study, no correlation was found among TLR4, IRAK1, and TIRAP gene variants and the risk of type 2 diabetes and insulin resistance. However, TNF-α, IL-6, MCP-1, and IL-1ß levels were also associated with diabetes and insulin resistance (p > 0.05). Although the gene variants were not significant in type 2 diabetes and insulin resistance groups, IRAK1, TLR4, and TIRAP gene variants were found to be associated with TNF-α, IL-6, MCP-1, and IL-1ß levels.

Is there any association between osteoporotic vertebral fracture and vitamin K epoxide reductase complex subunit-1 polymorphism in Turkish society? A pilot study.

OBJECTIVE: In this study, the relationship between osteoporotic vertebral fractures and 9041 Guanine/Adenine and 3673 Guanine/Adenine polymorphisms related to the vitamin K epoxide reductase complex subunit-1 (VKORC1) gene in postmenopausal women with osteoporosis was investigated. METHOD: DNA was isolated from blood samples collected from 150 women with postmenopausal osteoporosis. Genotyping of the two polymorphic regions (9041 Guanine/Adenine and 3673 Guanine/Adenine) in VKORC1 was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. The presence of radiographic fractures among the 150 patients was ascertained by using the Genant method. RESULT: At least one fracture was detected in 98 patients, and no fracture was observed in 52 patients on radiological images. We found no association between the 9041 Guanine/Adenine (p=0.283) and 3673 Guanine/Adenine (p=0.232) polymorphisms of the VKORC1 gene and the development of secondary postosteoporotic fractures in our study. CONCLUSION: There was no relationship between osteoporotic vertebral fracture and VKORC1 gene polymorphism in a postmenopausal Turkish population.

Anatomical Parameters of the Nasolacrimal Duct in Healthy Children Measured with Computed Tomography.

OBJECTIVES: This study is an evaluation of anatomical parameters at different levels of the bony nasolacrimal duct (NLD) in healthy children of different age groups using computed tomography (CT) measurements. METHODS: Bony NLD CT images of 289 patients aged 0-15 years who presented at the emergency department with various indications and underwent a brain CT scan were retrospectively evaluated. The anterior-posterior and transverse diameter at the inferior orbital margin, the narrowest diameter of the NLD, NLD length, and the orientation angle in the sagittal plane (the angle between the line connecting the distal and proximal ends of the NLD and a line drawn parallel to the nasal floor) were analyzed by age group. RESULTS: The anterior-posterior and transverse diameters at the level of the inferior orbital margin and the NLD length recorded in sagittal CT images were statistically significantly greater in patients older than 5 years of age (p<0.05). While there was an increase in the narrowest diameter of the NLD beginning at the age of 3 years, it was not statistically significant (p=0.25). The degree of the angle between the central line and the nasal floor did not change significantly between the groups. (p>0.05). CONCLUSION: A greater anterior-posterior diameter, transverse diameter, narrowest diameter of the NLD, and NLD length were observed with increasing age. The NLD anatomical parameters that we have identified in healthy children may serve as an important and useful guide in determining locations of the NLD and selecting surgical instruments of appropriate size and diameter before NLD surgery.

Is there any association between osteoporotic vertebral fracture and vitamin K epoxide reductase complex subunit-1 polymorphism in Turkish society? A pilot study

OBJECTIVE: In this study, the relationship between osteoporotic vertebral fractures and 9041 Guanine/Adenine and 3673 Guanine/Adenine polymorphisms related to the vitamin K epoxide reductase complex subunit-1 (VKORC1) gene in postmenopausal women with osteoporosis was investigated. METHOD: DNA was isolated from blood samples collected from 150 women with postmenopausal osteoporosis. Genotyping of the two polymorphic regions (9041 Guanine/Adenine and 3673 Guanine/Adenine) in VKORC1 was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. The presence of radiographic fractures among the 150 patients was ascertained by using the Genant method. RESULT: At least one fracture was detected in 98 patients, and no fracture was observed in 52 patients on radiological images. We found no association between the 9041 Guanine/Adenine (p=0.283) and 3673 Guanine/Adenine (p=0.232) polymorphisms of the VKORC1 gene and the development of secondary postosteoporotic fractures in our study. CONCLUSION: There was no relationship between osteoporotic vertebral fracture and VKORC1 gene polymorphism in a postmenopausal Turkish population.

The genetic variants of solute carrier family 11 member 2 gene and risk of developing type-2 diabetes.

Type-2 diabetes (T2DM) is a metabolic disorder characterized by long-terminsulin resistance, impaired insulin secretion from ß-cells, and loss of beta cell mass and function. Inflammation and oxidative stress play a key role in the development of diabetes and are associated with insulin resistance. Notably, recent studies have demonstrated an association between body iron stores, insulin resistance and T2DM. Free iron, a powerful pro-oxidant molecule, is involved in oxidative stress, lipid peroxidation and endothelial dysfunction via its ability to generate free radicals. Specifically, the accumulation of iron in beta cells triggers oxidative stress and DNA damage, which have been reported to be associated with ß-cell death and apoptosis. Solute carrier family-11 member-2 (SLC11A2) functions to transport ferrous iron and some divalent metal ions throughout the plasmamembrane and across endosomalmembranes. Functional polymorphisms in the SLC11A2 gene have been reported to cause excess storage of iron, resulting in iron overload. In this study, we evaluated the association between T2DM and SLC11A2 gene variants IVS4+44C/A, 1303C/A and 1254T/C by performing PCR-RFLP analysis on 100 T2DM patients and 100 healthy subjects. PCR products were digested with MnlI, MboI and SfanI restriction endonucleases and the products were then separated by 3% agarose gel electrophoresis. The genotype frequencies of the 1254T/C and 1303C/A SLC11A2 gene variants did not differ between healthy controls and T2DM patients (P > 0.05). But, inrecessive model (P = 0.037) and homozygous CC genotype (P = 0.030) for IVS4+44C/A showed significant correlation with T2DM risk. It is thought that presence of C allele of IVS4+44C/A plays pathological roles.

Genetic variant in the 3'-untranslated region of the COX2 gene is associated with type 2 diabetes: A hospital-based case-control study.

Type 2 diabetes (T2DM) is caused by the decreased ß-cell mass and insulin deficiency, and disease is characterized by hypoglycemia. The insulin resistance also plays an important role in T2DM pathogenesis. Insulin resistance is the reduced biological response to insulin at the normal concentration in the circulation and develops with the influence of environmental factors with genetic abnormalities. In recent years, it has been reported that inflammatory pathway causes activation of the insulin resistance. Chronic inflammation inhibits the insulin sensitivity through activation of signaling pathways which are directly associated with the key components of insulin signaling pathway. Cyclooxygenase (COX) enzymes are key enzymes that catalysis prostaglandin synthesis from arachidonic acid. COX2 is an inducible COX isoform and that plays an important role in inflammatory process by leading the synthesis of pro- and anti- inflammatory prostaglandins. In our study, we aimed to investigate the relationship between variants of COX-2 gene which is one of the key components of the inflammatory pathway, and T2DM risks. In this study, we evaluated rs5275 and rs689466 variants located on the COX-2 gene by PCR-RFLP in 100 T2DM patients and 100 control subjects. The interaction among COX2 variants and T2DM was analyzed using appropriate methods. The both variants were in Hardy-Weinberg equilibrium in patients and controls (p > 0.05). A significant association was observed for genotype distribution of COX2 rs5275 site between control and T2DM cases (p = 0.042). In a dominant model, the cases who had at least one copy of allele C, were at increased risk of T2DM (p = 0.016). We found no significant association for the COX2 rs689466 domain by evaluating homozygous, heterozygous, dominant, and recessive models (p > 0.05). According to our data, the rs5275 variant of the COX2 in the 3'-UTR may contribute to the etiology or modulate the risk of T2DM, whereas the rs689466 variant of the COX2 gene is not associated with T2DM risk.

miRNA-146a, miRNA-155 and JNK expression levels in peripheral blood mononuclear cells according to grade of knee osteoarthritis.

Osteoarthritis (OA) is the most common joint disease characterized by joint pain and a progressive loss of articular cartilage. OA known as a non-inflammatory disease. Despite this the recent studies are shown synovitis and low inflammation to have a role in OA pathophysiology. The aim of this study to determine the roles of a potential therapeutic targets miRNA-146a, miRNA-155 and JNK expression levels in OA patients. Peripheral mononuclear blood cells (PBMCs) were extracted from OA patients and healthy subjects. The expression levels of miRNA-146a, miRNA-155 and JNK were quantified using by real-time PCR assay. According to study results a statistically significant increase was observed only in miRNA-155 expression level (p=0,039). However, miRNA-146a and miRNA-155 expressions increased in the progressive stages (grade 3 and grade 4) in OA patients. Our data suggests that correlation of miRNAs regulating and signal pathways can play an important role in OA pathogenesis and disease progression.

Susceptiveness of Vitamin K epOxide Reductase Complex Subunit 1 Gene Polymorphism in Essential Hypertension.

BACKGROUND: Essential hypertension (EH) is defined as a worldwide public health problem and one of the important risk factors for development of human coronary artery disease. Increased peripheral arterial resistance is one of the distinguishing characteristics of EH. The extracellular deposition of calcium in the arterial wall is defined as vascular calcification, which results in aortic stiffness and elevation of blood pressure. Regulation of vascular calcification is physiologically limited by γ-carboxylated proteins that regulate mineralization. Any deficiencies related to mineralization influence vascular calcification. As a result of vitamin-K deficiency or any problem associated with the vitamin K epOxide reductase complex subunit 1 (VKORC1) gene, Glu cannot be transformed to Gla and calcification initiates in blood vessels, myocardium, and cardiac. OBJECTIVE: The aim of the study was to investigate the potential association of VKORC1 polymorphisms with the risk of EH. MATERIALS AND METHODS: There were 100 individuals diagnosed with EH and 100 healthy individuals involved in the study. 3673G/A (rs9923231) and 9041G/A (rs7294) polymorphisms in the VKORC1 gene were determined by the PCR-restriction fragment length polymorphism method. RESULTS: A significant difference was found between the rs7294 polymorphisms ratios of the case and control groups, but significant differences weren't found in distribution of the rs9923231 alleles. Finally it was determined that the GG genotype provides a 3.97-fold increased risk for EH compared to the AA genotype for the rs7294 polymorphism. CONCLUSIONS: Our results suggest that the VKORC1 gene rs7294 polymorphism is important for the development of EH.

The CYP2C19*2 and CYP2C19*17 Polymorphisms play a Vital Role in Clopidogrel Responsiveness after Percutaneous Coronary Intervention: A Pharmacogenomics Study.

Clopidogrel inhibits platelet activation and aggregation by blocking the P2Y12 receptor. Dual antiplatelet therapy with clopidogrel and aspirin is recommended treatment by current guidelines for patients undergoing percutaneous interventions. Recurrent ischaemic cardiac events after this treatment showed lack of clopidogrel responsiveness. We aimed to investigate the most noticeable variants in the genes involved in clopidogrel pharmacokinetics and pharmacodynamics. A total of 347 Turkish patients who underwent percutaneous coronary interventions with stent implantation were included in our study. Platelet reactivity (PRU) and % inhibition were measured with VerifyNow P2Y12 assay in blood samples collected from patients who took a standard dose of clopidogrel (75 mg/day) for at least 7 days. The variants in the CYP2C19, CYP3A4, CYP2B6, ABCB1, ITGB3 and PON1 genes were genotyped using the Sequenom MassARRAY system. When grouped, the patients with PRU values >208 as non-responsiveness to clopidogrel therapy; 104 (30%) patients were non-responders and 243 (70%) patients were responders. A significant association was found between the CYP2C19*2 (G636A) polymorphism and non-responsiveness to clopidogrel therapy (p < 0.001). An allele frequency of this single nucleotide polymorphism was high in non-responders; its odds ratio was 2.92 compared with G allele (p < 0.001). PRU values of CT genotypes were lower (p = 0.029) and % inhibition values of CT genotypes were higher (p = 0.008) compared with CC genotypes for the CYP2C19*17 (C806T) polymorphism. None of the other genetic variants were found to be statistically associated with non-responsiveness to clopidogrel and antiplatelet activity. Our findings suggest that the CYP2C19*2 polymorphism is associated with non-responsiveness to clopidogrel therapy and the CYP2C19*17 polymorphism enhances antiplatelet activity of clopidogrel. Depending on haplotypes of these two polymorphisms, clopidogrel-treated patients can be protected or not from stent thrombosis and ischaemic events.

miRSNPs of miR1274 and miR3202 Genes that Target MeCP2 and DNMT3b Are Associated with Lung Cancer Risk: A Study Conducted on MassARRAY Genotyping.

Genetic variants of miRNAs that target DNMTs and MBDs involved in DNA methylation were scanned with current databases, and 35 miRSNPs in 22 miRNA genes were identified. The aim of the study was to determine the association between these variants of miRNA genes and lung cancer (LC). DNA samples were isolated from blood samples and genotyped using a Sequenom MassARRAY System. An association between the rs188912830 gene variant of miR3202 that targets the MeCP2 protein and LC was indicated in both subtypes. The presence of the C-allele in patients with LC and its subtypes was significantly lower, and the absence of the C-allele was determined to increase the risk of LC by 7,429-times compared to the presence (p=0,010). The rs318039 gene variant of miR1274 that targets DNMT3b was found to be associated with LC subtypes. When allele distributions were compared, the numbers of individuals with the C-allele were significantly lower in the NSCLC and SCLC groups. No significant associations were found for the rs72563729 variant of the miR200b gene that targets DNMT3a or for the rs145416750 variant of the miR513c gene that targets TRDMT1. The other 33 variants were found to be ancestral genotypes. Consequently, rs188912830 and rs318039 variations were associated with LC subtypes. Importantly, this study is the first to indicate the functional characterisation of miRSNPs of genes that target DNA methylation.

Relationship between Peeled Internal Limiting Membrane Area and Anatomic Outcomes following Macular Hole Surgery: A Quantitative Analysis.

Purpose. To quantitatively evaluate the effects of peeled internal limiting membrane (ILM) area and anatomic outcomes following macular hole surgery using spectral domain optical coherence tomography (SD-OCT). Methods. Forty-one eyes in 37 consecutive patients with idiopathic, Gass stage 3-4 macular hole (MH) were enrolled in this retrospective comparative study. All patients were divided into 2 groups according to anatomic success or failure. Basal MH diameter, peeled ILM area, and MH height were calculated using SD-OCT. Other prognostic parameters, including age, stage, preoperative BCVA, and symptom duration were also assessed. Results. Thirty-two cases were classified as anatomic success, and 9 cases were classified as anatomic failure. Peeled ILM area was significantly wider and MH basal diameter was significantly less in the anatomic success group (p = 0.024 and 0.032, resp.). Other parameters did not demonstrate statistical significance. Conclusion. The findings of the present study show that the peeled ILM area can affect the anatomic outcomes of MH surgery.

[Drug carrier nanosystems in malignant pleural mesothelioma]. / Malign plevral mezotelyomada ilaç tasiyici nanosistemler.

Malignant pleural mesothelioma (MPM), the incidence increased with each passing day, is an important lethal disease due to the limited survive with available treatment methods and with the lack of a standard treatment. Response and survive rates of cytotoxic agents which is used in MPM treatment are not good enough. Therefore, treatment studies of MPM seem to quite important and urgent. In cancer therapy, convensional chemotherapeutic agent applications, due to the lack of selectivity, lead to systemic toxicity. Besides the limited solubility of the agent used, the distribution between the cells is weak. It is very difficult to the pass through cellular barriers, particularly, drug resistance may develop to the treatment. All of these reasons lead to failure in the treatment process. Because of the fact that cytotoxic drugs either kill the rapidly growing and dividing cells or make them disfunctional by showing toxic effect on them, to avoid the side effects and to make an inherent effect for cytotoxic drug of active ingredient given for treatment on tumor, different studies have been under investigation. At the present time, nanocarriers as one of these solutions seem to have an important place. Nanocarriers are promising for the development of therapeutic effectiveness and safety. It seems that use of the nanocarrier in the treatment of mesothelioma has a potential, as effective alternative a method, with improve of the drug efficacy and reduce of toxicity in normal tissues.

The hepatocurative effects of Cynara scolymus L. leaf extract on carbon tetrachloride-induced oxidative stress and hepatic injury in rats.

Cynara scolymus is a pharmacologically important medicinal plant containing phenolic acids and flavonoids. Experimental studies indicate antioxidant and hepatoprotective effects of C. scolymus but there have been no studies about therapeutic effects of liver diseases yet. In the present study, hepatocurative effects of C. scolymus leaf extract on carbon tetrachloride (CCl4)-induced oxidative stress and hepatic injury in rats were investigated by serum hepatic enzyme levels, oxidative stress indicator (malondialdehyde-MDA), endogenous antioxidants, DNA fragmentation, p53, caspase 3 and histopathology. Animals were divided into six groups: control, olive oil, CCl4, C. scolymus leaf extract, recovery and curative. CCl4 was administered at a dose of 0.2 mL/kg twice daily on CCl4, recovery and curative groups. Cynara scolymus extract was given orally for 2 weeks at a dose of 1.5 g/kg after CCl4 application on the curative group. Significant decrease of serum alanine-aminotransferase (ALT) and aspartate-aminotransferase (AST) levels were determined in the curative group. MDA levels were significantly lower in the curative group. Significant increase of superoxide dismutase (SOD) and catalase (CAT) activity in the curative group was determined. In the curative group, C. scolymus leaf extract application caused the DNA % fragmentation, p53 and caspase 3 levels of liver tissues towards the normal range. Our results indicated that C. scolymus leaf extract has hepatocurative effects of on CCl4-induced oxidative stress and hepatic injury by reducing lipid peroxidation, providing affected antioxidant systems towards the normal range. It also had positive effects on the pathway of the regulatory mechanism allowing repair of DNA damage on CCl4-induced hepatotoxicity.

The Effects of Monosodium Glutamate and Tannic Acid on Adult Rats.

BACKGROUND: Monosodium glutamate (MSG) is a widely-used flavor enhancer and stabilizer in ready-made or packaged foods. The excessive use of MSG has been shown to increase oxidative stress in different organ systems and causes glucose metabolism disorders, obesity, and coronary diseases. OBJECTIVES: In this study, the antioxidant activity of tannic acid was investigated experimentally with respect to its protective effects against overdosed MSG-induced oxidative stress in rats. The study took place in Turkey in August 2013. METHODS: Four groups (n = 7) of three- to four-month-old Sprague-Dawley female rats were used in this study. The first group was the control, who were administered saline. The second group received tannic acid (50 mg/kg, 3 days) intraperitoneally (i.p.). The third group received MSG (2 g/kg, 7 days) i.p., and the fourth group received both tannic acid (50 mg/kg, 3 days, pretreatment) and MSG (2 g/kg, 7 days) i.p. The animals were euthanized ten days later. Blood was collected for determining the hematological values and blood glucose levels. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were determined in the brain, liver, and kidney homogenates, and in the erythrocyte hemolysate. Histopathological examination of the brain, liver, and kidneys was conducted through hematoxylin-eosin staining. RESULTS: The data showed that the tannic acid treatment statistically decreased the MDA levels in the brain tissues of the group administered MSG and tannic acid (P < 0.001) when compared to the corresponding values of the control group. The SOD activities in the blood hemolysates of the MSG and tannic acid group increased when compared to the corresponding values for the MSG group (P < 0.01). Additionally, we found that pretreatment with tannic acid reduced blood glucose levels in comparison to the levels of the MSG group (P = 0.029). The results of our study show that tannic acid pretreatment in adult rats decreased blood glucose levels and oxidative stress. CONCLUSIONS: In the literature, it was observed that short-term MSG exposure does not cause significant histological changes in the kidneys, liver, or brain cortex. These findings should be re-evaluated in additional long-term studies.