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.

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.

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.

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.

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.

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.

Determination of the Relationship Between rs4986790 and rs4986791 Variants of TLR4 Gene and Lung Cancer.

Chronic inflammation triggers DNA damage and oncogenic mutations and causes tumor formation and tumor progression. One of the important components of the inflammatory response is Toll-like receptor (TLR) family. The objective of our study is to determine the relationship between rs4986790(+896A/G) and rs4986791(+1196C/T) gene polymorphisms and lung cancer risk. PCR-RFLP technique was carried out to identify the genotypes in 100 control individuals and 160 lung cancer patients. DNA extracted from peripheral blood samples were amplified and digested with NcoI and HinfI then visualized. We did not find any difference between genotype frequencies between controls and patients (p > 0.05) in rs4986790. But a significant difference between control group and patients with lung cancer as for genotype frequencies (χ (2) = 4.19, p = 0.041) in rs4986791 variants was found. Our data indicate that any correlation was not found between rs4986790 polymorphism and lung cancer, while a correlation between rs4986791 and lung cancer has been determined and found to be associated with lung cancer risk.

The role of NOD1/CARD4 and NOD2/CARD15 genetic variations in lung cancer risk.

BACKGROUND AND AIM: NOD1/CARD4 and NOD2/CARD15 are members of the Nod-like receptor (NLR) family, and they contain a caspase recruitment domain (CARD). NLRs are located in the cytosol where they bind bacterial and viral ligands and play a key role in the innate and adaptive immune response, apoptosis, autophagy, and reactive oxygen species generation. NLR gene polymorphisms may shift the balance between pro- and anti-inflammatory cytokines and modulate the risk of infection, chronic inflammation, and cancer. NOD1/CARD4 and NOD2/CARD15 gene polymorphisms may also be associated with altered risks for many cancer types. The aim of our study was to evaluate the potential associations between lung cancer and NOD1/CARD4 and NOD2/CARD15 polymorphisms. METHOD: The NOD1/CARD4 (rs5743336) and NOD2/CARD15 (rs2066847) SNPs were analyzed by PCR restriction fragment-length polymorphism analysis (PCR-RFLP) in 260 subjects (lung cancer patients: n = 160; healthy controls: n = 100) of Turkish origin. PCR products were digested with AvaI for rs5743336 and ApaI for rs2066847 and then visualized. RESULTS: Comparisons of the genotypes between control and lung cancer patients were performed by Chi-square tests. We found a significant difference in the genotypic distribution of the rs5743336 variant of NOD1/CARD4 between lung cancer patients and controls (p = 0.010, χ (2) = 9.220). However, we did not identify any statistically significant difference for the p.Leu1007fsX1008 (rs2066847) genotype of NOD2/CARD15 between groups (p > 0.05). CONCLUSION: According to our data, the rs5743336 variant of the NOD1/CARD4 gene may influence the diagnosis and treatment of lung cancer, whereas the rs2066847 variant of the NOD2/CARD15 gene is not associated with lung cancer risk in the Turkish population.

Is the 1254T>C polymorphism in the DMT1 gene associated with Parkinson's disease?

Parkinson's disease (PD) is a late-onset neurodegenerative disorder with both familial and sporadic presentation. The main pathological characteristic of PD is the death of dopaminergic neurons in the substantia nigra (SN) pars compacta. PD is the second most common neurodegenerative disease worldwide, after Alzheimer's disease. Recent studies have suggested increased levels of iron and iron-binding proteins in the brains of patients with PD. Divalent metal transporter 1 (DMT1) is one protein responsible for iron transport. Postmortem studies have shown an important increase in DMT1 levels in the SN of patients with PD. Our aim is to determine whether there is an association between DMT1 polymorphisms and PD. We analyzed two single nucleotide polymorphisms (1254T>C and IVS4+44C>A) in the DMT1 gene in patients with 97 Parkinson's disease and in 100 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No association was found between the IVS4+44C>A polymorphism and PD, but the TT genotype and T allele of the 1254T>C polymorphism in the DMT1 gene were associated with PD (P=0.002 and P=0.012, respectively). In contrast to a previous study, our results suggest that the TT genotype and T allele of the 1254T>C polymorphism may be a risk factor for PD.

Impact of tannic acid on blood pressure, oxidative stress and urinary parameters in L-NNA-induced hypertensive rats.

Hypertension is a major health problem with increasing prevalence around the world. Tannic acid is water-soluble polyphenol that is present in tea, green tea, coffee, red wine, nuts, fruits and many plant foods. It has been reported to serve as an antioxidant or a pro-oxidant depending on the type of cells and its concentration. The purpose of our study was to evaluate the effect of tannic acid on systolic blood pressure, oxidative stress and some urinary parameters in the rat model of essential hypertension. Blood pressures of all rats were measured using the tail-cuff method. The nitric oxide synthase inhibitor N (omega)-nitro-L-arginine was administered orally at a dose of 0.5 g/l/day for 15 days to rats in order to create an animal model of hypertension. Tannic acid was intraperitoneally injected at a dose of 50 mg/kg for 15 days. Superoxide dismutase, catalase activity and the concentration of malondialdehyde (MDA) were determined in blood plasma and homogenates of heart, liver and kidney. In order to evaluate renal functions, urine pH, urine volume, urine creatine, uric acid, and urea nitrogen values were measured. Compared with the hypertension group, a decrease in MDA concentrations of heart tissue (p < 0.01), urea nitrogen values (p < 0.01) and urine volumes (p < 0.001) were established in hypertension + tannic acid group. There was also a decrease in blood pressure values (20th and 30th days) of this group, but there was no a statistical difference according to hypertension group. The findings of our research show the effect of tannic acid in lowering blood pressure in hypertensive rats.

Association between I/D polymorphism in the ACE gene and sarcoidosis in Turkish patients.

Sarcoidosis is a chronic inflammatory disease with a complex pathogenesis and unknown etiology characterized by noncaseating granulomas that invade the lungs, eyes, liver and other organs. Insertion (I)/deletion (D) polymorphism in the gene encoding the angiotensin-converting enzyme (ACE) has been studied to examine the genetic predisposition to sarcoidosis in different populations, but the results have been inconsistent and inconclusive. This study aimed to determine the frequencies of the genotypes and alleles of I/D polymorphism in the ACE gene in Turkish patients as a distinct ethnic group and to investigate whether such polymorphism is associated with predisposition to sarcoidosis. Genomic DNA samples obtained from 154 individuals (70 patients with sarcoidosis and 84 healthy controls) were used in the study. The DNA was amplified using polymerase chain reactions using allele-specific primers. The amplified products were analyzed by 2 % agarose gel electrophoresis followed by UV transillumination. The allele frequencies and genotype distribution of the groups were analyzed using the Chi square test. There were no significant differences between the controls and sarcoidosis cases with respect to genotype distribution (χ(2) = 4.202, p = 0.122) and allele frequencies (χ(2) = 1.358, p = 0.244). Our results suggest that I/D polymorphism in the ACE gene does not cause a genetic predisposition to sarcoidosis in Turkish patients.

Preventive role of gallic acid on hepatic ischemia and reperfusion injury in rats.

There is little information about the hepatoprotective effects of gallic acid against ischemia-reperfusion (I/R) damage. Animals were subjected to I/R. Gallic acid at doses of 50 and 100 mg/kg body weight (bw) were injected as a single dose prior to ischemia. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels. At the same time alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed in serum samples and compared statistically. While the ALT, AST, LDH activities and MDA levels were significantly increased, CAT and GPx activities significantly decreased in only I/R-induced control rats compared to normal control rats (P < 0.05). Treatment with gallic acid at a dose of 100 mg/kg bw significantly decreased the ALT, AST, LDH activities and MDA levels, and markedly increased activities of CAT and GPx in tissue homogenates compared to I/R-induced rats with no treatment group (P < 0.05). In oxidative stress generated by hepatic ischemia-reperfusion, gallic acid contributes partially an alteration in the delicate balance between the scavenging capacity of antioxidant defense systems and free radicals in favour of the antioxidant defense systems in the body.

Angiotensin II type 1 receptor (AT1) gene A1166C is associated with the risk of hypertension.

AIM: This study was performed on primary hypertension patients in a Turkish population to determine the frequency of the A1166C polymorphism in the angiotensin II type 1 receptor (AT1) gene and to examine the role of this polymorphism in hypertension development. MATERIALS AND METHODS: In this study, 250 genomic DNA samples were collected (from 142 hypertension patients and 108 healthy subjects), randomized, and analyzed. Genomic DNA was prepared from peripheral blood using the salt extraction method. The presence of the A1166C polymorphism in the AT1 gene was determined using the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. PCR products were separated by 2% agarose gel electrophoresis and visualized by a charge-coupled device camera. RESULTS: Genotype distribution and allele frequency A1166C genotype frequency was determined as AA 96.3% and AC 3.7% for controls and as AA 86.6% and AC 13.4% for patients. A statistically significant difference was found between the control group and patients in terms of genotype and allele frequency. CONCLUSION: Our results suggest that an interaction exists between the AT1 gene polymorphism and hypertension in the Turkish population.

Protective effects of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate on experimental testicular torsion and detorsion injury.

Testicular torsion results with the damage of the testis and it is a surgical emergency. Pyrrolidine dithiocarbamate (PDTC) is a low-molecular-weight antioxidant and potent inhibitor of nuclear factor kappa B (NF-κB) activation. In this study, we aimed to investigate the effects of PDTC to testicular torsion-detorsion (T/D) injury. Forty adult male Sprague-Dawley rats were separated into four groups. A sham operation was performed in group I. In group II, torsion is performed 2 hours by 720 degree extravaginally testis. In group III, 4 h reperfusion of the testis was performed after 2 h of testicular torsion. In group IV, after performing the same surgical procedures as in group III, PDTC (100 mg/kg, intravenous's) was administered before 30 min of detorsion. The testes tissue malondialdehyde (MDA), superoxide dismutase (SOD) catalase (CAT) level was evaluated. Histological evaluations were performed after hematoxylin and eosin staining. Testicular tissue MDA levels were the highest in the T/D groups compared with treatment group. Administration of PDTC prevented a further increase in MDA levels. Significant decrease occurred in CAT and SOD levels in treatment group compared with the control group. The rats in the treatment group had normal testicular architecture. The results suggest that PDTC can be a potential protective agent for preventing the biochemical and histological changes related to oxidative stress in testicular injury caused by testis torsion.