bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycated Lysine Residues: A Marker for Non-Enzymatic Protein Glycation in Age-Related Diseases
Authors: Ansari Nadeem A. , Moinuddin  , Ali Rashid
Published: June 2013

Nonenzymatic glycosylation or glycation of macromolecules, especially proteins leading to their oxidation, play an important role in diseases. Glycation of proteins primarily results in the formation of an early stage and stable Amadori-lysine product which undergo further irreversible chemical reactions to form advanced glycation endproducts (AGEs). This review focuses these products in lysine rich proteins such as collagen and human serum albumin for their role in aging and age-related diseases. Antigenic characteristics of glycated lysine residues in proteins together with the presence of serum autoantibodies to the glycated lysine products and lysine-rich proteins in diabetes and arthritis patients indicates that these modified lysine residues may be a novel biomarker for protein glycation in aging and age-related diseases.
Genetic Polymorphism of the Glutathione S-Transferase M1 and T1 Genes in Three Distinct Arab Populations
Authors: Salem Abdel Halim , Yaqoob Alaeddin , Ali Muhalab , Handu Shailandra , Fadel Raouf , Abu-Hijleh Marwan , Almawi Wassim
Published: June 2013

Deletion polymorphisms for the glutathione S-transferase (GST) gene are associated with increased risk of cancer, and are implicated in detoxifying mutagenic electrophilic compounds. GST Polymorphic variants were reported for different populations. The aim of this study was to investigate the frequencies ofGSTM1andGSTT1null genotypes among Bahraini, Lebanese and Tunisian Arabs. GST genotyping was done by multiplex PCR-based methods. Study subjects comprised 167 Bahrainis, 141 Lebanese and 186 Tunisians unrelated healthy individuals.GSTM1deletion homozygosity of 49.7%, 52.5% and 63.4% were recorded for Bahraini, Lebanese and Tunisians, respectively. Among Bahrainis, the prevalence ofGSTT1null homozygotes was 28.7%, while in higher rates were seen in Lebanese (37.6%) and Tunisians (37.1%). Our results indicate that there are no major differences in allelic distribution ofGSTM1and GSTT1 genes between the three Arab populations investigated except between Bahrainis and Tunisians regarding the allelic distribution ofGSTM1gene (P= 0.013). Combined analysis of both genes revealed that 14.4% of Bahrainis, 16.3% of Lebanese and 21.0% of Tunisians harbor the deleted genotype of both genes. This is the first study that addressesGSTgene polymorphism in Bahraini and Lebanese Arabs, and will help genetic studies on the association ofGSTM1andGSTT1polymorphisms with disease risks and drug effects in Arab populations.
Associations of −308G/APolymorphism ofTumor Necrosis Factor(TNF)–αGene and Serum TNF-αLevels with Measures of Obesity, Intra-Abdominal and Subcutaneous Abdominal Fat, Subclinical Inflammation and Insulin Resistance in Asian Indians in North India
Authors: Vikram Naval K. , Bhatt Surya Prakash , Bhushan Bharat , Luthra Kalpana , Misra Anoop , Poddar Pawan K. , Pandey Ravindra M. , Guleria Randeep
Published: June 2013

Objectives:Obesity is associated with high levels proinflammatory cytokines like tumour necrosis factor alpha (TNF-α), which may play an important role in the genesis of insulin resistance. We evaluated the relationship of −308G/Apolymorphism ofTNF-αgene with obesity and insulin resistance in Asian Indians in north India.

Methods:This cross-sectional study included 151 apparently healthy individuals (79 males, 72 females) 18–50 yrs of age from New Delhi, India. Body composition by dual-energy x-ray absorptiometry (DEXA) and abdominal fat by magnetic resonance imaging (MRI) were measured. Biochemical measurements included OGTT, lipids, fasting insulin, hs-CRP and TNF-αlevels. We analysed −308G/Apolymorphism ofTNF-αgene and studied its association with obesity and biochemical parameters.

Results:At comparable BMI, abdominal obesity was more prevalent in females (50%) as compared to males (20%). The wild genotype (GG) was present in 78.8%, GA in 17.9%, andAAin 3.3% subjects. Measures of body composition, abdominal fat distribution, lipids, insulin, hs-CRP and TNF-αlevels were not influenced by the presence of −308G/Apolymorphism. Serum TNF-αlevels correlated significantly with fasting insulin in both genders.

Conclusion:TNF-αlevels correlate with fasting insulin but not with indicators of body composition in Asian Indians. The −308G/Apolymorphism ofTNF-αgene is not associated with differences in the serum levels of TNF-αin Asian Indians.
Absence of kl-vs Variant of Klotho Gene in Iranian Cardiac Patients (Comparison to the World Populations)
Authors: Tavakkoly-Bazzaz Javad , Tabatabaei-Malazy Ozra , Tajmir-Riahi Mohammad , Javidi Daryoosh , Izadi Manizhe , Shahrabi-Farahani Maryam , Amiri Parvin , Amoli Mahsa M.
Published: June 2013

Objective:Klotho has an important role in development of coronary artery (CAD) disease. A functional variant of klotho gene (kl-vs) has been found as an independent risk factor for early-onset occult coronary artery disease (CAD) in previous studies. The Frequency of this variant was not known in Iranian population. We have examined the allele frequency of the kl-vs variant in a case-control study in an Iranian population.

Methods and results:Genotyping for kl-vs variant was carried out inN= 107 individuals includingN= 54 cases andN= 53 control who all underwent coronary angiogram for CAD evaluation. Patients with >50% stenosis in vessels considered as case groups (or CAD+) and patients with normal vessels (or CAD−) as controls. The frequency of kl-vs variant was determined in these patients using PCR-RFLP technique. None of the individual was carrying the kl-vs mutation in our samples. The frequency of kl-vs mutation was significantly different from previous studies in different populations.

Conclusion:The kl-vs variant seems to be scare found in the Iranian population in comparison to other populations reported previously. Klotho gene might be a candidate gene of atherosclerosis in some populations but not in Iranian population. Further studies are required to examine the frequency of kl-vs variant in other populations from the Middle East.
Prognostic values of serum IP-10 and IL-17 in Patients with Pulmonary Tuberculosis
Authors: Chen Yung-Che , Chin Chien-Hung , Liu Shih-Feng , Wu Chao-Chien , Tsen Chia-Cheng , Wang Yi-Hsi , Chao Tung-Ying , Lie Chien-Hao , Chen Chung-Jen , Wang Chin-Chou , Lin Meng-Chih
Published: June 2013

Objective:To identify patients at high risk of relapse after anti-tuberculosis (TB) therapy or with poor long-term outcomes.

Methods:Fifty-one patients with pulmonary TB: 7 were classified as high association with both cavitations on initial chest radiography and positive sputum smear/cultures after two months of anti-TB treatment (HA group); 19 medium association (MA, one risk alone); and 25 low association (LA, neither risk). Serum interferon (IFN)-γ-inducible protein 10 (IP-10), interleukin-17 (IL-17), and C-reactive protein levels were investigated.

Results:There was a trend towards higher serum IP-10 levels (p= 0.042) for HA patients throughout the 6-month treatment period. Month-2 IP-10 levels were higher in the HA than in the MA/LA group (656.2 ± 234.4 vs. 307.6 ± 258.5 pg/ml, adjustedp= 0.005). Receiver operating characteristic curves showed that the risk of relapse was well-captured by month-2 IP-10 levels at a cut-off value of 431 pg/ml (AUC=0.857, 95% CI 0.75–0.97,p= 0.003). Month-2 serum IL-17 levels were lower in non-survivors than survivors (15.7 ± 2.9 pg/ml vs. 24.6 ± 8.2 pg/ml,p= 0.001). Multivariate analysis demonstrated that a month-2 serum IL-17 level of ≤ 17 pg/ml (p= 0.026) was independently associated with all-cause mortality.

Conclusions:Serum IP-10 and IL-17 levels after 2 months of anti-TB treatment may be biomarkers for estimating risk of both cavitation and delayed sputum conversion, and for predicting long-term mortality, respectively.
SREBP-2 1784G/CGenotype is Associated with Non-Alcoholic Fatty Liver Disease in North Indians
Authors: Bhatt Surya Prakash , Nigam Priyanka , Misra Anoop , Guleria Randeep , Luthra Kalpana , Vaidya M. , Jain S. K. , Pasha M. A. Qadar
Published: June 2013

Background:Genetics of non-alcoholic fatty liver (NAFLD) in Asian Indians has been inadequately investigated. This study aims to determine the association of the1784G > Cpolymorphism in the SREBP-2 gene with NAFLD in Asian Indians in north India.

Methods:In this study, (n= 335); 162 obese with NAFLD, 91 obese without NAFLD and 82 non-obese without NAFLD subjects were recruited. Abdominal ultrasound, clinical profile, anthropometry, metabolic profile, serum levels of alanine aminotransferase, aspartate aminotransferase, fasting insulin and high sensitivity C-reactive protein (hs-CRP) were analysed. Polymerase chain reaction and restriction fragment length polymorphism were used to identify individual genotypes, and the association of this polymorphism with clinical and biochemical parameters was assessed.

Results:The observed frequency of G allele was 0.73 and C allele was 0.27. Frequency ofC/Cgenotype was higher in NAFLD as compared to obese and non-obese subjects (p= 0.003). In NAFLD subjects 57.4% wereG/Ghomozygous, 31.5%G/Cheterozygous and 11.1% wereC/Chomozygous. The SREBP-2 genotype frequencies deviated from the Hardy Weinberg Equilibrium (X2= 6.39,p = 0.0114). Mean values of TG (p= 0.002), TC (p= 0.002), ALT (p= 0.04) and AST (p=0.03) levels were significantly higher in NAFLD subjects withG/Cgenotype as compared toG/Ggenotypes in obese and non-obese groups. Fasting insulin (p= 0.03), HOMA (p= 0.009) and hs-CRP levels were significantly higher in NAFLD subjects withG/Cgenotype as compared to obese and non obese subjects withG/Ggenotypes.

Conclusion:In this study, conducted for the first time in Asian Indians,SREBP-21784G > Cgenotype was associated with NAFLD.
Evaluation of Serum Resistin Levels in Periodontal Health and Disease and Effects of Non Surgical Periodontal Therapy on Its Levels
Authors: Devanoorkar Archana , Dwarakanath C.D. , Gundanavar Gayatri , Kathariya Rahul , Patil Sudhir R
Published: June 2013

Background: Resistin and adiponectin are the adipokines secreted by adipocytes and various inflammatory cells. These adipokines are known to play an important role in insulin resistance. The aim of this study was to determine the serum resistin levels in periodontal health and disease and also, to determine the effect of nonsurgical periodontal therapy on its levels.

Methods: A total of 40 patients (20 Males and 20 Females; age range 20–50 years) participated in the study. Subjects were categorized as healthy (group 1; Controls) and chronic periodontitis (group 2; Study) groups based on their periodontal status. Periodontal parameters (Plaque index (PI), Gingival index (GI), Bleeding index (BI), Probing pocket depth (PPD), Clinical attachment loss (CAL)) together with serum resistin levels were assessed at baseline and between 6–8 weeks following nonsurgical periodontal therapy for subjects in group~2 and only at baseline in group 1. Sera were tested in duplicate (single run), and the results were averaged.

Results: Study group showed higher (1.89 ± 1.83 ng/ml) serum resistin levels, compared to control group (1.35 ± 0.70 ng/ml). However, this difference was not statistically significant (P=0.227). Also, resistin levels decreased following nonsurgical periodontal therapy but, this decrease failed to show any statistical significance, with pretreatment levels being 1.89 ± 1.83 ng/ml and post treatment levels being 1.59 ± 1.01 ng/ml (P=0.386).

Conclusion: Observations of the present study revealed that there was not much difference in the serum resistin levels between the cases and the controls. Also the decrease in the resistin levels following nonsurgical periodontal therapy did not show any statistical significance.
Exon Dosage Variations in Brazilian Patients with Parkinson’s Disease: Analysis ofSNCA,PARKIN,PINK1andDJ-1Genes
Authors: Moura Karla Cristina Vasconcelos , Junior Mário Campos , de Rosso Ana Lúcia Zuma , Nicaretta Denise Hack , Pereira João Santos , Silva Delson José , Santos-Rebouças Cíntia Barros , Pimentel Márcia Mattos Gonçalves
Published: June 2013

Parkinson’s disease is one of the most common neurodegenerative disorders associated with aging, reaching ∼ 2% of individuals over 65 years. Knowledge achieved in the last decade about the genetic basis of Parkinson’s disease clearly shows that genetic factors play an important role in the etiology of this disorder. Exon dosage variations account for a high proportion of Parkinson’s disease mutations, mainly forPARKINgene. In the present study, we screened genomic rearrangements inSNCA,PARKIN,PINK1andDJ-1genes in 102 Brazilian Parkinson’s disease patients with early onset (age of onset ≤ 50 years), using the multiplex ligation-dependent probe amplification method. Family history was reported by 24 patients, while 78 were sporadic cases. Screening of exon dosage revealedPARKINandPINK1copy number variations, but no dosage alteration was found inSNCAandDJ-1genes. Most of the carriers harbor heterozygous deletions or duplications in thePARKINgene and only one patient was found to have a deletion inPINK1exon 1. Data about dosage changes are scarce in the Brazilian population, which stresses the importance of including exon dosage analysis in Parkinson’s disease genetic studies.
Association of MTHFR Polymorphisms and Chromosomal Abnormalities in Leukemia
Authors: Sinthuwiwat Thivaratana , Poowasanpetch Phanasit , Wongngamrungroj Angsana , Soonklang Kamonwan , Promso Somying , Auewarakul Chirayu , Tocharoentanaphol Chintana
Published: June 2013

Genetic variation in MTHFR gene might explain the interindividual differences in the reduction of DNA repaired and the increase of chromosome breakage and damage. Nowadays, chromosomal rearrangement is recognized as a major cause of lymphoid malignancies. In addition, the association of MTHFR polymorphisms with aneuploidy was found in several studies, making the MTHFR gene as a good candidate for leukemia etiology. Therefore, in this study, we investigated the common sequence variation, 677C>T and 1298A>C in the MTHFR gene of 350 fixed cell specimens archived after chromosome analysis. The distribution of the MTHFR polymorphisms frequency was compared in leukemic patients with structural chromosome abnormality and chromosome aneuploidy, as well as in those with no evidence of chromosome abnormalities. We observed a significant decrease in the distribution of T allele in 677C>T polymorphisms among patients with chromosomal abnormalities including both structural aberration and aneuploidy. The same significance result also found in patients with structural aberration when compare with the normal karyotype patients. Suggesting that polymorphism in the MTHFR gene was involved in chromosome abnormalities of leukemia. However, further investigation on the correlation with the specific types of chromosomal aberrations is needed.
Decrease in Antioxidant Status of Plasma and Erythrocytes from Geriatric Population
Authors: Kumawat Manjulata , Sharma Tarun Kumar , Singh Ishwar , Singh Neelima , Singh Sanjeev Kumar , Ghalaut Veena Singh , Shankar Vijay , Vardey Satish Kumar
Published: June 2013

Background: Ageing is associated with an accumulation of free radical damage, which leads to physiological and clinical modifications. The study aims to find out the status of lipid profile, antioxidant enzymes, malondialdehyde in geriatric population.

Patients/methods: The study was conducted on 150 subjects (75 healthy control between the ages of 20–30 years and 75 elderly subjects between ages of 50–70 years as cases). The following parameters were analyzed using the standard reference methods: lipid profile, reduced glutathione, glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase and malondialdehyde.

Results: The present study was conducted to estimate the oxidative stress parameters in geriatric population. Highly significant increase in total cholesterol (TC), triglyceride (TG), LDL-cholesterol (LDL-C), VLDL-cholesterol (VLDL-C), malondialdehyde, catalase and decrease in high density lipoprotein cholesterol (HDL-C), reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase was observed in geriatrics when compared with their younger counterparts.

Conclusion: This study concluded that there is enhanced oxidative stress and decreased antioxidant defence in geriatrics as compared to younger subjects which could play an important role in ageing. Dyslipidemia has become one of the important risk factors for the increasing prevalence of cardiovascular diseases. There is lack of awareness on the relationship between blood lipids and the risk of cardiovascular diseases in geriatric population. The strategy of early prevention should be adopted against dyslipidemia.
Genetic Association and Gene-gene interaction ofHAS2,HABP1andHYAL3Implicate Hyaluronan Metabolic Genes in Glaucomatous Neurodegeneration
Authors: Basu Kaustuv , Sen Abhijit , Ray Kunal , Ghosh Ilora , Datta Kasturi , Mukhopadhyay Arijit
Published: June 2013

Hyaluronan (HA) plays a significant role in maintaining aqueous humor outflow in trabecular meshwork, the primary ocular tissue involved in glaucoma. We examined potential association of the single nucleotide polymorphisms (SNPs) of the HA synthesizing gene – hyaluronan synthase 2 (HAS2), hyaluronan binding protein 1 (HABP1) and HA catabolic gene hyaluronidase 3 (HYAL3) in the primary open angle glaucoma (POAG) patients in the Indian population. Thirteen tagged SNPs (6 forHAS2, 3 forHABP1and 4 forHYAL3) were genotyped in 116 high tension (HTG), 321 non-high tension glaucoma (NHTG) samples and 96 unrelated, age-matched, glaucoma-negative, control samples. Allelic and genotypic association were analyzed by PLINK v1.04; haplotypes were identified using PHASE v2.1 and gene-gene interaction was analyzed using multifactor dimensionality reduction (MDR) v2.0. An allelic association (rs6651224;p= 0.03; OR: 0.49; 95% CI: 0.25–0.94) was observed at the second intron (C>G) ofHAS2both for NHTG and HTG. rs1057308 revealed a genotypic association (p= 0.03) at the 5’ UTR ofHAS2with only HTG. TCT haplotype (rs1805429 – rs2472614 – rs8072363) inHABP1and TTAG and TTGA (rs2285044 – rs3774753 – rs1310073 – rs1076872) inHYAL3were found to be significantly high (p< 0.05) both for HTG and NHTG compared to controls. Gene-gene interaction revealedHABP1predominantly interacts withHAS2in HTG while it associates with bothHYAL3andHAS2in NHTG. This is the first genetic evidence, albeit from a smaller study, that the natural polymorphisms in the genes involved in hyaluronan metabolism are potentially involved in glaucomatous neurodegeneration.
Association of the PGC-1αrs8192678 Variant with Microalbuminuria in Subjects with Type 2 Diabetes Mellitus
Authors: Prior Sarah L. , Clark Amy R. , Jones Danielle A. , Bain Steve C. , Hurel Steve J. , Humphries Steve E. , Stephens Jeffrey W.
Published: June 2013

PPAR-γ co-activator-1α (PGC-1α) is a tissue-specific transcriptional co-activator involved in the regulation of antioxidant enzymes. The A-allele of thers8192678 PGC-1α} (G>A) gene variant has previously been associated with nephropathy in Korean and Indian-Asian type 2 diabetes mellitus (T2DM) samples. Our aim was to examine the association between this variant and urine albumin exccretion in European subjects with T2DM. Genotyping was performed on 583 European subjects with T2DM and examined in relation to urinary albumin, plasma oxidized-LDL and small dense-LDL percentage. We observed a significant association between genotype (GG/GA/AA) and urinary albumin (normoalbuminuria v micro/macroalbuminuria: 48.6/39.7/11.7% v 38.2/51.2/10.5%,p=0.02; for GG v GA/AA,p=0.01). The odds ratio for micro/macroalbuminuria in GA and AA subjects relative to GG were 1.70 [1.15–2.50],p=0.008 and 1.20 [0.66–2.16],p=0.56 respectively (for GA/AA v GG: 1.58 [95% CI: 1.09–2.27],p=0.02). There was a significant association between the A allele and a higher percentage of small dense-LDL particles (GG v GA v AA: 70.8 [58.01–81.06] % v 72.8 [56.18–81.19] % v 78.9 [67.16–85.33] %,p=0.03). In European subjects with T2DM the GA relative to the GG genotype is associated with a 70% increase in the risk of micro/microalbuminuria. Furthermore, homozygosity for the A-allele is also associated with a preponderance of small dense-LDL particles.
Antioxidant Effects of Potassium Ascorbate with Ribose Therapy in a Case with Prader Willi Syndrome
Authors: Anichini C. , Lotti F. , Longini M. , Proietti F. , Felici C. , Perrone S. , Buonocore G.
Published: June 2013

Oxidative stress (OS) is involved in several human diseases, including obesity, diabetes, atherosclerosis, carcinogenesis, as well as genetic diseases. We previously found that OS occurs in Down Syndrome as well as in Beckwith-Wiedemann Syndrome (BWS). Here we describe the clinical case of a female patient with Prader Willi Syndrome (PWS), a genomic imprinting disorder, characterized by obesity, atherosclerosis and diabetes mellitus type 2, pathologies in which a continuous and important production of free radicals takes place. We verified the presence of OS by measuring a redox biomarkers profile including total hydroperoxides (TH), non protein-bound iron (NPBI), thiols (SH), advanced oxidation protein products (AOPP) and isoprostanes (IPs). Thus we introduced in therapy an antioxidant agent, namely potassium ascorbate with ribose (PAR), in addition to GH therapy and we monitored the redox biomarkers profile for four years. A progressive decrease in OS biomarkers occurred until their normalization. In the meantime a weight loss was observed together with a steady growth in standards for age and sex.
Associations of Killer Cell Immunoglobulin-Like Receptor Genes with Rheumatoid Arthritis
Authors: Ramírez-De los Santos S. , Sánchez-Hernández P. E. , Muñoz-Valle J. F. , Palafox-Sánchez C. A. , Rosales-Rivera L. Y. , García-Iglesias T. , Daneri-Navarro A. , Ramírez-Dueñas M. G.
Published: June 2013

Objective: Rheumatoid Arthritis (RA) is an autoimmune and chronic inflammatory disease of unknown etiology. Killer cell immunoglobulin-like receptors are expressed on the surface of natural killer cells and CD28nullT-cells, both present in synovial membrane of RA. Therefore we evaluated the associations ofKIRgenes with RA.

Methods: 16KIRgenes were genotyped in 100 healthy subjects (HS) and 100 RA patients from Western Mexico using PCR-SSP. Differences inKIRgenotypes and gene frequencies were assessed using theX2test.

Results: Gene frequency ofKIR2DL3was lower in RA than in HS (p= 0.0019), whereasKIR2DL2andKIR2DS2were higher in RA than HS (p= 0.0004 andp= 0.0487, respectively). In addition were identified 38 genotypes (from G1-G38) in both studied groups, and the genotype frequencies of G1, G6 and G14 showed significant differences (p= 0.0001,p= 0.0208 andp= 0.0300, respectively).

Conclusions: The presence ofKIR2DL2,KIR2DS2and absence ofKIR2DL3are associated with RA. Moreover, two genotypes BX are associated with RA. These results suggest thatKIRscan be involved in RA susceptibility.
Antibodies against 4-Hydroxy-2-nonenal Modified Epitopes Recognized Chromatin and Its Oxidized Forms: Role of Chromatin, Oxidized Forms of Chromatin and 4-Hydroxy-2-nonenal Modified Epitopes in the Etiopathogenesis of SLE
Authors: Al-Shobaili Hani A. , Al Robaee Ahmad A. , Alzolibani Abdullateef A. , Rasheed Zafar
Published: June 2013

Objectives:This study was undertaken to investigate the role of lipid oxidative-by-product 4-hydroxy-2-nonenal (HNE)-modified human serum albumin (HSA), chromatin, reactive oxygen species (ROS)-modified chromatin and nitric oxide (NO)-modified chromatin in systemic lupus erythematosus (SLE).

Methods:HSA was modified by HNE. Immunogenicity of modified HSA was probed by inducing polyclonal antibodies in rabbits. Chromatin was isolated from goat liver and modified by ROS or NO. Immunocross-reactions of Protein-A purified anti-HNE-HSA-IgG with chromatin, ROS-chromatin and NO-chromatin were determined. Autoantibodies from 74 SLE patients were screened. HSA was isolated from SLE patients (SLE-HSA) and immunocross-reactions of isolated SLE-HSA with HNE-specific antibodies were investigated.

Results:HNE-HSA was found to be highly immunogenic in rabbits. The notable feature of anti-HNE-HSA-IgG showed cross-reactions with chromatin, ROS-chromatin and NO-chromatin (p< 0.01). High degree of specific binding to HNEHSA, chromatin, ROS-chromatin or NO-chromatin was observed with antibodies from 55% of SLE patients. SLE anti-native/oxidized chromatin antibodies showed specificity towards HNE-HSA. Furthermore, SLE-HSAshowed binding with HNE-specific antibodies.

Conclusions:This is the first study to demonstrate that chromatin and its oxidized forms have been recognized by antibodies against HNE modified epitopes. Our results provide an important insight into the immunological basis of the reported HNE-modified epitopes in SLE.
Susceptibility to Toxoplasmic Retinochoroiditis Is Associated with Hla Alleles Reported to Be Implicated with Rapid Progression to Aids
Authors: Demarco Ana Lúcia G. , Rodrigues Maria de Lourdes V. , Figueiredo José Fernando C. , Deghaide Neifi Hassam S. , de Menezes Marcelo Bezerra , Demarco Luís A. , Fernandes Ana Paula M. , Donadi Eduardo A.
Published: June 2013

Background/aims: The frequency of HLA markers associated with rapid progression to AIDS was evaluated in Brazilian patients with AIDS exhibiting or not toxoplasmic retinochoroiditis (TRC).

Methods: 98 AIDS patients (25 with TRC, 43 with anti-T. gondii antibodies but without TCR, and 30 without anti-T. gondii antibodies and without TCR) were studied.

Results: The HLA-B35 was significantly increased in TRC group (p= 0.0038).

Conclusion: The presence of HLA-B35 may simultaneously predispose to progression to AIDS and TRC.
IL-23 Gene Expression in PBMCs of Patients with Coronary Artery Disease
Authors: Khojasteh-Fard Maryam , Abolhalaj Milad , Amiri Parvin , Zaki Majid , Taheri Zahra , Qorbani Mostafa , Bazzaz Javad Tavakkoly , Amoli Mahsa M.
Published: June 2013

Objective: Both adaptive and innate immune systems are involved in coronary artery disease (CAD). The aim of this study was to evaluate TH17 cytokines expression profiles in un-stimulated peripheral blood lymphocytes (PBMCs) of patients with coronary artery disease. Methods: Expression profiles of IL-17, IL-23, and TGF-β1 were determined in individuals with and without CAD using Real-time PCR. Results: A significant decrease in IL-23 gene expression in un-stimulated PBMCs of patients with CAD compared to those without CAD was found (p=0.003, OR=0.045, 95% CI: 0.006–0.355). Conclusion: Our data reinforce the potential role of the IL-23 as a critical regulatory molecule that bridges the innate and adaptive arms of the immune system in the complex mechanisms associated with the development of atherosclerosis.
Effect of Nonsurgical Periodontal Therapy on Crevicular Fluid and Serum Glutathione Peroxidase Levels
Authors: Patel Swati Pradeep , Rao Nishanth S. , Pradeep A. R.
Published: June 2013

Background: Plasma glutathione peroxidase (eGPx) is an important selenium containing antioxidant in human defense against oxidative stress. While crevicular fluid (GCF) eGPx levels and its association with periodontal disease is well documented, there is no data on correlation of GCF and serum eGPx levels in chronic periodontitis. Hence this study was undertaken to further probe into the role of oxidative stress in periodontal diseases and effect of nonsurgical periodontal therapy (NSPT) by correlating GCF and serum levels of eGPx.

Materials and methods: Thirty subjects (16-Males and 14-Females; age: 30–38 years) participated in the study. The subjects were divided, based on gingival index, probing pocket depth and clinical attachment level into: Healthy (group-1,n=10), Gingivitis (group-2,n=10) and Periodontitis (group-3,n=10). Chronic periodontitis patients after NSPT constituted group 4. GCF and serum samples collected from each subject were quantified for eGPx levels using Enzyme linked Immunosorbent Assay.

Results: The mean eGPx concentrations increased from health (14.01 ng/μl and 78.26 ng/ml) to gingivitis (22.86 ng/μl and 90.44 ng/ml) and then to periodontitis (29.89 ng/μl and 103.43 ng/ml), in GCF and serum respectively. After NSPT, there was statistically significant reduction in eGPx concentration in GCF and serum (19.41 ng/μl and 85.21 ng/ml). Further, all the GCF eGPx values showed a positive correlation to that of serum eGPx level.

Conclusion: Thus, increased eGPx concentration in GCF can be considered as an indicator of local increase in oxidative stress. While, increase in serum eGPx levels indicates that periodontal disease can also lead to increased oxidative stress at the systemic level.
KPNA3Variation Is Associated with Schizophrenia, Major Depression, Opiate Dependence and Alcohol Dependence
Authors: Morris Charles P. , Baune Bernhard T. , Domschke Katharina , Arolt Volker , Swagell Christopher D. , Hughes Ian P. , Lawford Bruce R. , McD Young Ross , Voisey Joanne
Published: June 2013

KPNA3is a gene that has been linked to schizophrenia susceptibility. In this study we investigated the possible association betweenKPNA3variation and schizophrenia. To investigate a wider role ofKPNA3across psychiatric disorders we also analysed major depression, PTSD, nicotine dependent, alcohol dependent and opiate dependent cohorts. Using a haplotype block-based gene-tagging approach we genotyped sixKPNA3single nucleotide polymorphisms (SNPs) in 157 schizophrenia patients, 121 post-traumatic stress disorder patients, 120 opiate dependent patients, 231 alcohol dependent patients, 147 nicotine dependent patients and 266 major depression patients. One SNP rs2273816 was found to be significantly associated with schizophrenia, opiate dependence and alcohol dependence at the genotype and allele level. Major depression was also associated with rs2273816 but only at the allele level. Our study suggests that KPNA3 may contribute to the genetic susceptibility to schizophrenia as well as other psychiatric disorders.
GSTT1 Null Genotype Is a Risk Factor for Diabetic Retinopathy in Caucasians with Type 2 Diabetes, whereas GSTM1 Null Genotype Might Confer Protection against Retinopathy
Authors: Cilenšek Ines , Mankoč Sara , Petrovič Mojca Globočnik , Petrovič Daniel
Published: June 2013

Aim: Substantial data indicate that oxidative stress is involved in the development of diabetic retinopathy (DR). The aim of the present study was to investigate whether the genetic polymorphisms: polymorphic deletions of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and Ile105Val of the GSTP1 are associated with DR in Slovenian patients with type 2 diabetes.

Methods: In this cross sectional case-control study 604 unrelated Slovene subjects (Caucasians) with type 2 diabetes mellitus were enrolled: 284 patients with DR (cases) and the control group of 320 subjects with type 2 diabetes of more than 10 years’ duration who had no clinical signs of DR. Genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).

Results: In our study, the deletion of the GSTM1 was found less frequent in cases with DR than in the controls (27.5% versus 44.4%;P< 0.001), whereas the deletion of GSTT1 was found significantly more often in cases than in the controls (49.3% versus 29.7%;P< 0.001). We did not find statistically significant differences in the genotype distribution in GSTP1 (Ile105Val) polymorphism between cases and controls (40.5% versus 46.0%).

Conclusions: We may conclude that individuals homozygous for the deletion of GSTT1 are at an ≈ 2-fold-greater risk of DR, whereas the GSTM1 deficiency is associated with lower frequency of DR in type 2 diabetics.
Plasma Seprase and DPP4 Levels as Markers of Disease and Prognosis in Cancer
Authors: Javidroozi Mazyar , Zucker Stanley , Chen Wen-Tien
Published: June 2013

Seprase (fibroblast activation protein α) has been examined as an invasion biomarker for various types of solid tumors. We studied whether plasma levels of seprase and homologous protease, DPP4 in cancer might serve as tumor biomarkers. We developed sensitive and specific Enzyme-Linked Immunosorbent Assays (ELISAs) to measure these proteases. In 747 plasma samples (from 139 healthy volunteers and 561 cancer patients), mean seprase and DPP4 levels were 0.51 ± 0.30 and 4.65 ± 6.37 μg/mL, respectively, and they were correlated with each other (R2= 0.382). Plasma DPP4 and seprase levels were significantly lower in cancer patients compared with healthy subjects (4.38 versus 5.65 μg/mL,p< 0.001 for DPP4; 0.46 versus 0.66 μg/mL,p< 0.001 for seprase). Higher DPP4 was associated with better survival in all cancers combined (n= 346) as well as in head and neck malignancies (n= 38). Higher seprase was associated with better survival in all non-metastatic cancers combined (n= 151) as well as head and neck malignancies, but worse survival in colorectal cancers (n= 47). This study demonstrates that in contrast to the high expression in solid tumors, plasma concentrations of seprase and DPP4 are reduced and correlate inversely with survival in most types of cancer, suggesting that these circulating proteases represent useful tumor markers.
A Songbird Animal Model for Dissecting the Genetic Bases of Autism Spectrum Disorder
Authors: Panaitof S. Carmen
Published: June 2013

The neural and genetic bases of human language development and associated neurodevelopmental disorders, including autism spectrum disorder (ASD), in which language impairment represents a core deficit, are poorly understood. Given that no single animal model can fully capture the behavioral and genetic complexity of ASD, work in songbird, an experimentally tractable animal model of vocal learning, can complement the valuable tool of rodent genetic models and contribute important insights to our understanding of the communication deficits observed in ASD. Like humans, but unlike traditional laboratory animals such as rodents or non-human primates, songbirds exhibit the capacity of vocal learning, a key subcomponent of language. Human speech and birdsong reveal important parallels, highlighting similar developmental critical periods, a homologous cortico-basal ganglia-thalamic circuitry, and a critical role for social influences in the learning of vocalizations. Here I highlight recent advances in using the songbird model to probe the cellular and molecular mechanisms underlying the formation and function of neural circuitry for birdsong and, by analogy, human language, with the ultimate goal of identifying any shared or human unique biological pathways underscoring language development and its disruption in ASD.
Urinary Chiro- and Myo-Inositol Levels as a Biological Marker for Type 2 Diabetes Mellitus
Authors: Hong Jun Hwa , Jang Hye Won , Kang Yea Eun , Lee Ju Hee , Kim Koon Soon , Kim Hyun Jin , Park Kyu Ri , Ku Bon Jeong
Published: June 2013

Background: The aim of this study was to investigate the role of the urinary chiro- and myo-inositol levels in predicting type 2 diabetes mellitus (T2DM).

Subjects and methods: A total of 212 normal controls and 101 type 2 diabetic patients were enrolled this study. The concentrations of urinary chiro- and myo-inositol were measured by high performance liquid chromatography/mass spectrometry.

Results: The concentration of urinary chiro-inositol was significantly higher in the diabetic subjects (2.24 ± 5.18 ng/L) than those in the control group (0.38 ± 0.62 ng/L;p< 0.001). The urinary myo-inositol level of the diabetic subjects (36.95 ± 37.77 ng/L) was also significantly higher than that of the controls (8.17 ± 13.29 ng/L;p< 0.001). The urinary chiro-inositol multiplied by myo-inositol level of the diabetic subjects (148.10 ± 544.91) was significantly higher than in the controls (5.12 ± 24.15;p< 0.001). The area under the receiver operating characteristic curve for the urinary chiro-inositol multiplied by myo-inositol level to predict T2DM was 0.840 (confidence interval 0.789–0.891,p< 0.001). The cut-off value for the urinary chiro-inositol multiplied by myo-inositol level to predict T2DM was 2.20 (sensitivity 81.3%, specificity 70.3%).

Conclusions: The urinary chiro- and myo-inositol concentrations were increased in the type 2 diabetic patients and the urinary chiro- times the myo-inositol was considered to be a sufficient marker in predicting T2DM.
Limited Value of KAI1/CD82 Protein Expression as a Prognostic Marker in Human Gastric Cancer
Authors: Knoener Maximilian , Krech Till , Puls Florian , Lehmann Ulrich , Kreipe Hans , Christgen Matthias
Published: June 2013

The cell surface glycoprotein KAI1/CD82 suppresses tumor growth and metastasis in animal models. This study aimed to evaluate the prognostic relevance of KAI1/CD82 protein expression in human gastric cancer. Primary gastric carcinomas (n= 271) with amean clinical follow-up time of 48months were immunostained using the monoclonal anti-KAI1/CD82 antibody G2. Staining was evaluated as negativeversuspositive for statistical analysis. KAI1/CD82 immunoreactivity was absent in 103/271 (38%) cases. There was a trend towards KAI1/CD82 negativity in poorly differentiated cases (p= 0.0679). Moreover, KAI1/CD82-negative carcinomas were associated with a higher pT status (p= 0.0222), metastatic lymph node involvement (p= 0.0018) and a higher clinical tumor stage (p= 0.0050). The median overall survival times of KAI1/CD82-negative and KAI1/CD82-positive gastric carcinomas were 20 and 37 months, respectively (p= 0.2305). These results are in line with the proposed function of KAI1/CD82 as a suppressor of tumor growth and metastasis. However, these data suggest that KAI1/CD82, as detected by immunohistochemistry, is of limited value as a prognostic marker for gastric cancer in routine histological workup.
Association of the Wild-Type A/A Genotype of MBL2 Codon 54 with Asthma in a North Indian Population
Authors: Birbian Niti , Singh Jagtar , Jindal Surinder Kumar , Joshi Amit , Batra Navneet , Singla Neha
Published: June 2013

Background: High serumMBL level as well as polymorphisms in the mannose-binding lectin 2 (MBL2) gene resulting in MBL deficiency are involved in the mechanism of a number of non-infectious diseases such as asthma, conferring either risk or protection in different population studies. MBL being the first reactant of the MBL pathway is also a major determinant of the fate of the anaphylatoxins such as C3a and C5a, which are also pro-inflammatory mediators. The MBL2 gene polymorphisms thus control the serum levels of MBL as well as C3a and C5a.

Objective: This is the first case-control study conducted in India, investigating the role of MBL2 codon 54 A/B polymorphism in asthma pathogenesis.

Methods: A case-control study was performed with a total of 992 adult subjects, including 410 adult asthmatics and 582 healthy controls from regions of North India. The MBL2 codon 54 A/B polymorphism was genotyped by PCR-RFLP.

Results: Statistical analysis for the codon 54 polymorphism revealed that the wild (A) allele was significantly associated with asthma with OR = 1.9, 95% CI (1.4–2.4), and p < 0.001.

Conclusion: The MBL2 codon 54 A/B polymorphism is significantly associated with asthma and its phenotypic traits as the wild (A/A) genotype confers a significant risk towards the disease in the studied North Indian population.
Matrix Metalloproteinase 13 Genotype in rs640198 Polymorphism Is Associated with Severe Coronary Artery Disease
Authors: Vašků Anna , Meluzín Jaroslav , Blahák Jan , Kincl Vladimír , Pávková Goldbergová Monika , Sitar Jan , Zlámal Filip , Bienertová-Vašků Julie , Vítovec Jiří
Published: June 2013

Atherosclerosis as a main etiopathogenetic source for coronary artery disease (CAD) development is intimately related to dynamic changes in the extracellular matrix (ECM). Elevated levels of MMP-13 have been observed in human atherosclerotic plaques which could also involve variability in MMP-13 gene. The aim of the study was to associate rs640198 polymorphism with CAD and/or with its severity.

The study comprised 1071 consecutive patients with suspected or known coronary artery disease (CAD), confirmed by coronary angiography.

Genotyping for the rs640198 polymorphism in MMP-13 gene was performed using Taqman® assay. The TT and TG genotypes of rs640198 polymorphism in MMP-13 gene confer the significantly increased risk of triple vessel disease compared to patients without atherosclerotic lesions in coronary arteries (odds ratio = 1.64, Pcorr = 0.05). Furthermore, an increased risk of having 5 and more stenoses (odds ratio = 1.90, Pcorr = 0.004) was observed in TT and TG carriers (sensitivity of 0.613 and a specificity of 0.544; power of the test is 0.87).

The T allele of MMP-13 intron polymorphism rs640198 is associated with the severity of coronary artery disease, represented by the number of affected arteries as well as by the number of stenoses confirmed by coronarography.
Aurora a Overexpression and pVHL Reduced Expression Are Correlated with a Bad Kidney Cancer Prognosis
Authors: Ferchichi Imen , Kourda Nadia , Sassi Samia , Romdhane Khaled Ben , Balatgi Sarra , Cremet Jean Yves , Prigent Claude , Elgaaied Amel Benammar
Published: June 2013

We investigate the expression and localization of the tumor suppressor protein pVHL as well as the oncoprotein Aurora A kinase in kidney cancer. Both Aurora A kinase and pVHL protein status were evaluated using immunohistochemistry. The Aurora A expression is correlated with the Fuhrman grade and the TNM stage, while the pVHL expression is correlated with the capsule rupture and the TNM stage. Aurora A kinase expression increases in malignant tissue comparing to the non-malignant one. And there is a decrease in pVHL expression from the adjacent healthy tissues to the tumor`s ones. The two kinds of opposite tumor profiles display significant distribution difference according to TNM stages. It could be proposed that the absence of Aurora A protein associated with a strong expression of pVHL in clear cells kidney carcinoma are of good prognosis for the disease.
Apo Lipoprotein A1 Gene Polymorphisms Predict Cardio-Metabolic Risk in South Asian Immigrants
Authors: Dodani Sunita , Henkhaus Rebecca , Dong Lei , Butler Merlin G.
Published: June 2013

Objectives: Coronary artery disease (CAD) is a leading cause of death globally with increasing burden in South Asians in the US. Specific genetic variants that influence CAD have not been fully assessed in South Asian Immigrants. The goal is to identify Apo lipoprotein A1 (APOA1) gene polymorphisms and their association with CAD risk factors, metabolic syndrome and dysfunctional HDL (Dys-HDL).

Methods: A community-based study on South Asians aged 35-65 years without CAD was conducted.APOA1gene sequencing was performed and genotypes compared with cardiovascular findings.

Results: The prevalence of metabolic syndrome and dysfunctional-HDL was 29.7% and 26%, respectively. Six novelAPOA1gene single nucleotide peptides (SNPs) were analyzed. Three of the six SNPs (G2, G3, and G5) were found to be associated with metabolic syndrome; G2 (T655C) (p=0.044), G3 (T756C) (p=0.037) and G5 (T1001C) (p=0.037).APOA1gene SNP G1 (T319C) was highly correlated with low HDL levels (p=0.001). In our study, both associations ofAPOA1SNPs with metabolic syndrome and low HDL remained after age-adjustment.

Conclusion: Discovery of novel gene polymorphisms will help to understand further the causes of excess CAD risk in South Asians so that preventative strategies targeted to high-risk group can be developed.
Evaluation of the Role of LRRK2 Gene in Parkinson’s Disease in an East Indian Cohort
Authors: Sadhukhan Tamal , Vishal Mansi , Das Gautami , Sharma Aanchal , Mukhopadhyay Arijit , Das Shyamal K , Ray Kunal , Ray Jharna
Published: June 2013

Leucine rich repeat kinase 2 (LRRK2)gene defects cause Parkinson's disease (PD). Recently,LRRK2has also been shown by genome wide association (GWA) studies to be a susceptibility gene for the disease. In India mutations inLRRK2is a rare cause of PD. We, therefore, genotyped 64 SNPs acrossLRRK2in 161 control samples and finally studied 6 haplotype tagging SNPs for association-based study on 300 cases and 446 ethnically matched controls to explore the potential role ofLRRK2as a susceptibility gene in PD for East Indians. We did not find any significant allele/ genotype or haplotype associations with PD suggesting that common genetic variants withinLRRK2play limited role in modulating PD among East Indians. In addition, we also screened for the common mutations (viz. p.R1441C, p.R1441G, p.R1441H, p.Y1699C, p.G2019S), and a risk variant common among Asians (p.G2385R) but did not observe any of the above mentioned variants in our cohort. Our study, therefore, strongly suggests thatLRRK2has minimal role as a candidate and susceptibility gene in PD pathogenesis among East Indians.
Analyzing the Impact of Ambient Temperature Indicators on Transformer Life in Different Regions of Chinese Mainland
Authors: Bai Cui-fen , Gao Wen-Sheng , Liu Tong
Published: June 2013

Regression analysis is applied to quantitatively analyze the impact of different ambient temperature characteristics on the transformer life at different locations of Chinese mainland. 200 typical locations in Chinese mainland are selected for the study. They are specially divided into six regions so that the subsequent analysis can be done in a regional context. For each region, the local historical ambient temperature and load data are provided as inputs variables of the life consumption model in IEEE Std. C57.91‐1995 to estimate the transformer life at every location. Five ambient temperature indicators related to the transformer life are involved into the partial least squares regression to describe their impact on the transformer life. According to a contribution measurement criterion of partial least squares regression, three indicators are conclusively found to be the most important factors influencing the transformer life, and an explicit expression is provided to describe the relationship between the indicators and the transformer life for every region. The analysis result is applicable to the area where the temperature characteristics are similar to Chinese mainland, and the expressions obtained can be applied to the other locations that are not included in this paper if these three indicators are known.
Control of Bleeding in Endoscopic Skull Base Surgery: Current Concepts to Improve Hemostasis
Authors: Thongrong Cattleya , Kasemsiri Pornthep , Carrau Ricardo L. , Bergese Sergio D.
Published: June 2013

Hemostasis is critical for adequate anatomical visualization during endoscopic endonasal skull base surgery. Reduction of intraoperative bleeding should be considered during the treatment planning and continued throughout the perioperative period. Preoperative preparations include the optimization of comorbidities and cessation of drugs that may inhibit coagulation. Intraoperative considerations comprise anesthetic and surgical aspects. Controlled hypotension is the main anesthetic technique to reduce bleeding; however, there is controversy regarding its effectiveness; what the appropriate mean arterial pressure is and how to maintain it. In extradural cases, we advocate a mean arterial pressure of 65–70 mm Hg to reduce bleeding while preventing ischemic complications. For dealing intradural lesion, controlled hypotension should be cautious. We do not advocate a marked blood pressure reduction, as this often affects the perfusion of neural structures. Further reduction could lead to stroke or loss of cranial nerve function. From the surgical perspective, there are novel technologies and techniques that reduce bleeding, thus, improving the visualization of the surgical field.