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Background: Chlamydia trachomatis is one of the most common diseases as sexually transferred in world. According to the World Health Organization statistics, approximately 92 million new Chlamydia trachomatis infection occur in the world. Chlamydia trachomatis (CT) is the cause of tubal obstruction, ectopic pregnancy and infertility in women. The aim of this study is prevalence evaluation of Chlamydia Trachomatis by PCR in female infertile referred to Montasarieh study center of infertility in Mashhad. Materials and Methods: The cervical swab specimens were collected from 100 infertile (as case) and 30 fertile (as control group) women attending to the infertility center of Mash-had Medical University. DNA extraction was performed from clinical specimens using DNA extraction kit. In this study, in addition to PCR reaction by commercial kit, PCR test was performed using specific primers and probe for CTCP gene. Results: The results of PCR reaction using the kit was match with PCR test and showed that the prevalence of Chlamydia trachomatis is 21% in infertile women and 3.3% in normal fertile women that was statistically significant (p=0.024). Conclusion: Considering the high sensitivity of PCR method for diagnosis of Chlamydia trachomatis infection, this method can be useful for routine screening. [ABSTRACT FROM AUTHOR]

Objective: Yao syndrome (YAOS) is formerly called nucleotide-binding oligomerization domain containing 2 ( NOD2) -associated autoinflammatory disease.We report a large cohort of YAOS., Methods: We conducted a retrospective analysis of a cohort of adult patients with systemic autoinflammatory diseases (SAIDs). All patients underwent testing for a periodic fever syndrome gene panel., Results: A total of 194 patients carried NOD2 variants, 152 patients were diagnosed with YAOS, and 42 had mixed autoinflammatory diseases with combined variants in NOD2 and other SAID-associated genes. Demographic, clinical and molecular data were summaried. In sub-group analysis of the 194 patients, individual patients were often identified to carry two or more variants that usually included IVS8 + 158/R702W, IVS8 + 158/L1007fs, IVS8 + 158/V955I, IVS8 + 158/other, or NOD2/ variants in other SAID genes. Ninety-nine patients carried single variants. Taken together, these variants contribute to the disease in combination or individually., Conclusion: This largest cohort has provided comprehensive clinical and genotyping data in YAOS. Variants in the NOD2 gene can give rise to a spectrum from inflammatory bowel disease to autoinflammatory disease.This report further raises awareness of the underdiagnosed disease in the medical community., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Nomani, Wu, Saif, Hwang, Metzger, Navetta-Modrov, Gorevic, Aksentijevich and Yao.)

Objectives: Cryopyrin-associated periodic syndrome or NLRP3-associated autoinflammatory disease (NLRP3-AID) and NLRP12-AID are both Mendelian disorders with autosomal dominant inheritance. Both diseases are rare, primarily reported in the pediatric population, and are thought to be phenotypically indistinguishable. We provide the largest cohort of adult-onset patients and compared these diseases and the gene variant frequency to population controls., Methods: A cohort of adult patients with AIDs were retrospectively studied. All underwent molecular testing for periodic fever syndrome gene panels after extensive and negative workups for systemic autoimmune and other related diseases. Patients were divided into Group 1- NLRP3-AID patients with NLRP3 variants (N=15), Group 2- NLRP12-AID with NLRP12 variants (N=14) and Group 3- both NLRP3 and NLRP12 (N=9) variants. Exome sequence data of two large control populations including the ARIC study were used to compare gene variant distribution and frequency., Results: All 38 patients were Caucasian with women accounting for 82%. Median age at diagnosis was 41 ± 23 years and the disease duration at diagnosis was 14 ± 13 years. We identified statistically significant differences between the groups, notably that gastrointestinal symptoms as well as evaluations for same were significantly more frequent in patients with NLRP12 variants, and headaches/dizziness were less common among the NLRP12 patients. Livedo reticularis was noted in four patients, exclusively among NLRP12 carriers. Over 50% of patients in Groups 1 and 2 carry low-frequency disease-associated variants, while the remaining carry rare variants. We unprecedently identified digenic variants, i.e., the coexistence of NLRP3 and NLRP12, which were either both low frequency or low frequency/rare. Allele frequencies of all variants identified in our cohort were either absent or significantly lower in the control populations, further strengthening the evidence of susceptibility of these variants to SAID phenotypes., Conclusion: Our comparative study shows that both NLRP3-AID and NLRP12-AID share similar clinical phenotypes, yet there are significant differences between them with regard to gastrointestinal and neurological symptoms. A spectrum of high to low genetic variations in both genes can contribute to SAID individually or in combination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yun, Deng, Navetta-Modrov, Xin, Yang, Nomani, Aroniadis, Gorevic and Yao.)

NOD-like receptors (NLRs) are intracellular sensors associated with systemic autoinflammatory diseases (SAIDs). We investigated the largest monocentric cohort of patients with adult-onset SAIDs for coinheritance of low frequency and rare mutations in NOD2 and other autoinflammatory genes. Sixty-three patients underwent molecular testing for SAID gene panels after extensive clinical workups. Whole exome sequencing data from the large Atherosclerosis Risk in Communities (ARIC) study of individuals of European-American ancestry were used as control. Of 63 patients, 44 (69.8%) were found to carry combined gene variants in NOD2 and another gene (Group 1), and 19 (30.2%) were carriers only for NOD2 variants (Group 2). The genetic variant combinations in SAID patients were digenic in 66% ( NOD2/MEFV , NOD2/NLRP12, NOD2/NLRP3 , and NOD2/TNFRSF1A) and oligogenic in 34% of cases. These variant combinations were either absent or significantly less frequent in the control population. By phenotype-genotype correlation, approximately 40% of patients met diagnostic criteria for a specific SAID, and 60% had mixed diagnoses. There were no statistically significant differences in clinical manifestations between the two patient groups except for chest pain. Due to overlapping phenotypes and mixed genotypes, we have suggested a new term, "Mixed NLR-associated Autoinflammatory Disease ", to describe this disease scenario. Gene variant combinations are significant in patients with SAIDs primarily presenting with mixed clinical phenotypes. Our data support the proposition that immunological disease expression is modified by genetic background and environmental exposure. We provide a preliminary framework in diagnosis, management, and interpretation of the clinical scenario., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nomani, Deng, Navetta-Modrov, Yang, Yun, Aroniadis, Gorevic, Aksentijevich and Yao.)

Competing Interests: Conflicts of interest None disclosed.

Background: Polycystic ovary syndrome (PCOS) causes anovulation and hyperandrogenism. Hormonal imbalance is known to contribute to systemic autoimmune diseases., Objective: To examine the frequency of certain rheumatic diseases in PCOS., Methods: This retrospective study utilized and analyzed electronic medical records from January 2004 through February 2020. A diagnosis of PCOS and specified rheumatic diseases was searched using ICD-9 and ICD-10 codes. A total of 754 adult patients with PCOS and 1,508 age- and body mass index-matched patients without PCOS were included. Frequencies of the rheumatic diseases were compared between PCOS and non-PCOS subjects or literature data., Results: The prevalence of rheumatoid arthritis (RA) was found to be 2.25% (17/737) in the PCOS patients, numerically higher than 1.26% (19/1489) in the non-PCOS subjects. The difference was significant with a confidence level of 90% (1.04-3.15) but not at 95% with an odds ratio of 1.808 (95% CI = 0.934-3.4, p = 0.0747). When compared with the literature data from the US female population, the prevalence of RA in PCOS patients was significantly higher (2.25% vs. 1.40%, p < 0.0001). Among the autoimmune diseases examined, both systemic sclerosis (0.40% vs. 0.0%, p = 0.0369) and undifferentiated connective tissue disease (0.53% vs. 0.0%, p = 0.0123) were significantly more frequent in the PCOS patients than the non-PCOS. Additionally, PCOS patients had a significantly higher frequency of osteoarthritis than non-PCOS patients (5.44% vs. 2.92%, p = 0.0030) with an odds ratio of 1.913 (95% CI = 1.239-2.955)., Conclusion: We have shown unprecedentedly that certain rheumatic diseases are more prevalent in PCOS. This study provides important insight into autoimmunity in association with PCOS. Key Points • Polycystic ovary syndrome is postulated to cause systemic autoimmune disease due to its hormonal imbalance. • We conducted the first epidemiologic assessment of the prevalence of systemic autoimmune diseases. • Certain autoimmune and rheumatic diseases are more prevalent in polycystic ovary syndrome., (© 2021. International League of Associations for Rheumatology (ILAR).)

Competing Interests: The authors declare no conflict of interest.

Background: Atrial fibrillation (AF) occurring after cardiac surgery, post-operative AF (POAF), is a serious and common complication of this treatment. POAF may be life-threatening and the available preventive strategies are insufficient or are associated with significantly increased risk of adverse effects, especially in long-term use. Therefore, more appropriate treatment strategies are needed., Methods: In this paper, the efficacy, safety, and other aspects of using statins in the prevention of POAF focusing on their anti-inflammatory effects are reviewed., Results: Recent studies have suggested that inflammation has a significant role in POAF, from the first AF episode to its serious complications including stroke and peripheral embolism. On the other hand, statins, the most widely used medications in cardiovascular patients, have pleiotropic effects, including anti-inflammatory properties. Therefore, they may potentially be effective in POAF prevention. Statins, especially atorvastatin, appear to be an effective option for primary prevention of POAF, especially in patients who had coronary artery bypass grafting (CABG), a cardiac surgery treatment associated with inflammation in the heart muscle. However, several large studies, particularly with rosuvastatin, did not confirm the beneficial effect of statins on POAF. One large clinical trial reported higher risk of acute kidney injury (AKI) following high-dose rosuvastatin in Chinese population. In this study, rosuvastatin reduced the level of C-reactive protein (CRP) but did not reduce the rate of POAF., Conclusion: Further studies are required to find the most effective statin regimen for POAF prevention with the least safety concern and the highest health benefits.

Several studies have indicated an association between inflammation and the recurrence of Atrial Fibrillation (AF), especially after ablation, which is a therapeutic option leading to local inflammation. On the other hand, each AF can lead to another AF, as a general rule. Thus, preventing recurrences of AF is extremely important for patient outcomes. In this paper, we attempted to review the effect of medicinal agents with anti-inflammatory properties on the prevention of AF recurrence. There are several randomized controlled trials (RCTs) and meta-analyses on the prevention of AF recurrence using agents with anti-inflammatory properties, which include steroids, colchicine, statins, and n-3 fatty acids (n-3 FA). Clinical trials evaluating the efficacy of anti-inflammatory drugs in preventing the recurrence of AF led to inconsistent results for corticosteroids, statins and n-3 FAs. These results may be related to the fact that inflammation is not the only factor responsible for triggering recurrences of AF. For example, the presence of structural, mechanical and electrical remodeling could potentially be the most important factors that trigger recurrences of AF but these factors have not been addressed in most of the reported studies. Therefore, future clinical trials are needed to compare the efficacy of anti-inflammatory drugs in AF patients with, or without other factors. For colchicine, a potent anti-inflammatory drug, there are limited studies. However, all the studies investigating colchicine in the context of AF were consistent and promising, especially when colchicine was used on a short-term basis following ablation in patients with paroxysmal AF. Therefore, colchicine could be a promising candidate for further clinical studies involving recurrent AF., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: The present study was designed to evaluate the association of transporters associated with antigen processing (TAP2) polymorphisms TAP2-379Ile > Val (rs1800454), TAP2-665Thr > Ala (rs241447) and TAP2-565Ala > Thr (rs2228396) as a candidate gene with susceptibility to the Systemic Lupus Erythematosus (SLE)., Methods: To analyze these three polymorphic variants, 88 patients with SLE and 100 healthy controls from northeastern Iran were enrolled from May 2018 to July 2019. Genomic DNA polymorphisms were performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. Data were analyzed by SPSS software., Results: In this cross-sectional study, there was a stratification between patients and controls. The distribution of the frequency of Ala73 (41.5%) allele at TAP2/665 and Ile 19 (10.8%) allele at TAP2/379 was higher in patients. Additionally, the Ala/Ala 13(14.8%) and Ala/Thr 49(55.7%) genotypes distributions at 665 positions were higher in SLE patients compared to the controls. Furthermore, frequencies of TAP2*H allele significantly increased in SLE patients 10(5.71%) (P=0.01). Frequency of TAP2*A allele in the control group was 120(60%) (p=0.06) due to the dominant genetic model. This allele has a protective effect against SLE. There was no relationship between TAP2*D, TAP2*E, TAP2*F and TAP2*G alleles with the outbreak of SLE., Conclusion: Our data indicated that genetic variants in TAP2 gene may be associated with SLE disease. A correlation between Ala allele at TAP2/665 and Ile allele at TAP2/379 polymorphisms and pathogenesis of SLE was observed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Atrial fibrillation (AF) is a serious and common complication following heart surgery. Cardiac surgery triggers inflammation in the heart and makes it susceptible to the incidence of AF. Therefore, anti-inflammatory drugs may reduce the rate of AF incidence in the post-surgery conditions. Immunosuppressant agents, steroidal anti-inflammatory drugs (corticosteroids), non-aspirin non-steroid anti-inflammatory drugs (NSAIDs), colchicine and omega-3 unsaturated fatty acids (n-3 UFA) are drugs with well-known anti-inflammatory properties. The efficacy, safety and other aspects of using these drugs in the prevention of post-operative AF (POAF) have been reviewed here. Studies evaluating the efficacy of colchicine have shown that it could be effective in the prevention of POAF. However, there is a need for additional studies to find a colchicine regimen with optimal efficacy and higher tolerability. The use of corticosteroids may also be of value based on the most of meta-analyses. In the case of n-3 polyunsaturated fatty acids and NSAIDs, current data fail to support their efficacy in POAF prevention. Moreover, perioperative administration of NSAIDs may be associated with some severe safety considerations. Immunosuppressant agents have not been used for the prevention of POAF. Further studies are needed to find the most effective strategy for POAF prevention with the least safety considerations and the highest health benefits.

Objective: This study aimed to systematically investigate whether anti-androgens could significantly reduce Obsessive-Compulsive Disorder (OCD) symptoms compared to placebo or usual care in OCD patients., Methods: PubMed, EMBASE, CENTRAL and International Clinical Trials Registry Platform (ICTRP) databases were searched up to October 2018 using relevant keywords. All randomized and if not available non-randomized studies conducted on a population including OCD patients who were administered with anti-androgen, which reported changes in their symptoms, were included. The studies on compulsive hypersexuality were excluded. Required data were extracted from full-text of the included articles by two independent authors. One randomized and four non-randomized trials were found., Results: The only randomized trial showed that flutamide, an anti-androgen agent, was effective in reducing compulsion scores in male OCD patients with comorbid Tourette syndrome, compared to placebo. Three out of four non-randomized trials showed that different anti-androgens including finasteride, cyproterone acetate and triptorelin were effective in reducing OCD symptoms. The only study, which failed to show the efficacy of an anti-androgen agent, administered OCD patients with flutamide. Despite the positive results, available studies provide the evidence with low quality based on the Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) approach., Conclusion: Available studies are not sufficient for a precise answer to our study question. There is still a need for further large randomized blinded clinical trials to evaluate the effectiveness of antiandrogens in OCD patients. It is recommended that gender, comorbidities and subscales of Yale- Brown Obsessive-Compulsive Score (Y-BOCS) should be considered in designing the studies and interpreting their results., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Antipsychotic (AP) medications are the cornerstone treatment for schizophrenia and some other psychiatric diseases. However, some observational studies suggest that these medications might increase the risk of venous thromboembolism (VTE) and pulmonary embolism (PE)., Objectives: The aim of this study was to assess whether AP medications are associated with the development of VTE or PE, and to assess the risk based on any type of AP drugs, quality of studies and after adjustment of risk factors., Data Sources: To identify relevant studies, we searched PubMed and EMBASE databases up to February 2019. We also searched the reference lists of relevant articles for related studies., Study Selection: Twenty studies fulfilled the eligibility criteria and were included in our meta-analysis after screening relevant observational cohort and case-control studies., Primary Outcome: The primary outcome of our meta-analysis was the occurrence of all VTE or PE only attributed to exposure to AP medications compared with non-exposure to AP medications., Results: Exposure to AP drugs was associated with a significant increase in the risk of VTE (RR 1.53, 95% CI 1.30-1.80, I2 = 85%) and PE (RR 3.69, 95% CI 1.23-11.07, I2 = 90%). In the subgroup metaanalysis, the use of low-potency AP drugs was associated with a higher risk of VTE, (RR 1.90, 95% CI 1.04-3.47, I2 = 78%)., Conclusion: AP exposure was associated with a 1.5-fold increase in the risk of VTE and a 3.7-fold increase in the risk of PE. Low-potency AP drugs were associated with a higher risk of VTE. However, high heterogeneity among studies limits the generalizability of the results., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cola-containing drinks (CCDs) are among the most common drinks in the world. There are some reports on interactions between CCDs and some drugs. However, there is no review on reported and possible interactions of CCDs. Thus, this paper attempted to provide a comprehensive review on this subject. It is well-accepted that CCDs are acidic and contain caffeine. It has been suggested that these two properties potentiate interactions of CCDs with different drugs in the context of both pharmacodynamics and pharmacokinetic, which includes drug absorption, metabolism, and renal excretion of drugs. It has been shown that serum concentrations of MTX, clozapine, carbamazepine, phenytoin, and ibuprofen increased following CCD consumption; these interactions can be toxic. Additionally, it has been reported that serum levels of lithium and warfarin were decreased and their efficacy reduced when simultaneously administered with CCDs. Serum concentrations of erlotinib and different azoles, including itraconazol, posaconazole, and ketoconazole, have been shown to increase when these drugs were co-administered with a CCD. As proposed and discussed here, CCDs have the potential for interactions with numerous other drugs and thus clinicians should be aware of reported and potential interactions of CCDs with various medications in order to avoid adverse reactions and achieve expected clinical response., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Diabetes mellitus (DM) and cancer are global problems carrying huge human, social, and economic impact. Type 2 diabetes (T2DM) is associated with an increased risk for a number of cancers, including breast, pancreatic, and liver cancer. Moreover, adverse drug reactions are higher in paitents with cancer with T2DM compared to cancer patients without T2DM. Cellular mechanisms of hyperglycemia and chemotherapy efficacy may be different depending upon the particular cancer type and the condition of the patient. This review evaluates the effect of DM on the pharmacokinetic, pharmacodynamic, and adverse drug reactions of commonly used anticancer drugs such as cisplatin, methotrexate, paclitaxel, doxorubicin, and adriamycin in both clinical and animal models. A literature search was conducted in scientific databases including Web of Science, PubMed, Scopus, and Google Scholar including the relevant keywords. The results of the effectiveness of anticancer therapies in patients with DM are, however, inconsistent because DM can negatively impact multiple diverse entities including nerves and vascular structures, insulin-like growth factor 1, the function of the innate immune system, drug pharmacokinetics, the expression levels of hepatic CYP 450 , Mdr 1b and enzymes that then lead to drug toxicity. However, in a few circumstances, DM led to attenuation of the toxicity of anticancer drugs secondary to attenuation of the energy-dependent renal uptake process. Overall, the impact of DM on patients with cancer is variable because of the diverse types of cancers and the spectrum of anticancer drugs. With respect to the evidence for cancer involvement in DM pathophysiology and the response to anticancer treatment in patients with DM, many questions still remain and further clinical trials are needed., (© 2019 Wiley Periodicals, Inc.)

Cardiac complications including arrhythmia and especially atrial fibrillation (AF) are common causes of death in β-thalassemia patients. The main factor in the etiopathogenesis of these complications is iron overload, which results in increased oxidative stress. Although there is a known association between cardiac complications and iron overload in β-thalassemia patients, there is no comprehensive review on AF and excessive iron with a focus on oxidative stress in these patients. The aim of this article was to review the different aspects of AF in β-thalassemia patients with a focus on the prevention and treatment of AF by using iron chelators and/or anti-oxidants. AF in β-thalassemia patients is more common than in the general population. One of the most important causes of AF is cardiac iron overload and the harmful effects of increased oxidative stress. Iron-induced AF can be reversed by using an intensive iron chelation regimen. Based on a few experimental studies, the combination of iron chelators with some anti-oxidants, including NAC, vitamin C, and acetaminophen, can lead to improved cardiac protection. However, the effect of such combinations on cardiac arrhythmias should be further evaluated with animal and human studies., (© 2018 Wiley Periodicals, Inc.)

Malignancy is a significant cause of mortality after organ transplantation. There is an increased rate of malignancy following heart transplantation (HTx) compared to the general population and other organ transplant recipients. Post-HTx patients with a history of malignancy are also at a higher risk of developing new malignancies or exacerbation of their existing malignancies. Mammalian target of Rapamycin inhibitors (mTORIs) are newly introduced immunosuppressive drugs with a unique mechanism of action. By changing the immunosuppressive regimen from classic drugs, especially calcineurin inhibitors (CNIs) to mTORIs, the rate of developing de novo malignancies and the relapse of former malignancies is significantly reduced. However, issues like allograft function, total surveillance of patients, and post-transplantation complications should be considered during the conversion of drug regimens utilizing CNIs to drug regimens employing mTORIs. We reviewed different post-heart transplant maintenance immunosuppressive regimens and their effect on post-HTx malignancies with a focus on mTORIs, compared safety against effectiveness, and gathered conclusions based on our review of the literature, which may lead clinicians to make a better evidence-based decision regarding post-HTx maintenance immunosuppressive drug regimens. Overall, CNI to mTORI conversion in post-HTx maintenance immunosuppressive drug regimens was associated with a reduced rate of developing malignancy in post-HTx patients. Furthermore, nephrotoxicity decreased significantly while using mTORIs in combination with lower doses of CNIs and the rejection rate was equivalent to CNI-only regimens. In conclusion, mTORI-based maintenance immunosuppressive drug regimens seem to be safe and beneficial when considering efficacy vs. adverse effects, and all-cause mortality rates are significantly lower in patients switched to mTORIs when compared to CNI recipients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Adipose tissue, an endocrine organ, secretes bioactive factors including adiponectin. Adiponectin is a protein hormone that enhances insulin sensitivity through increased fatty acid oxidation and inhibition of hepatic glucose production. We assessed the association of the adiponectin promoter region polymorphisms -11391 G/A and -11377 C/G with susceptibility to type 1 (T1DM) and type 2 (T2DM) diabetes mellitus in the population of west Iran. Also, we investigated the effect of adiponectin level and lipid profile on T1DM and T2DM development. In this case-control study, we recruited 189 patients with diabetes (100 T2DM and 89 T1DM) and 161 sex and age-matched unrelated healthy controls. Adiponectin mutations were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the protein level was measured by the enzyme-linked immunosorbent assay. Other biochemical parameters were determined by routine laboratory methods. The G allele of adiponectin gene at -11377 position (C/G) significantly increased the risk of T1DM. With respect to genotype models, codominant (2.97 times), dominant (3.6-fold), and over-codominant (2.9-fold) patients with T1DM who carried -11377 C > G single-nucleotide polymorphisms were significantly susceptible to the development of the disease. A significantly higher level of adiponectin in T1DM was oberved compared with the control group. In contrast, patients with T2DM had lower adiponectin levels compared with healthy controls. The genotype distributions of -11391 G/A polymorphisms were the same for patients with diabetes and control groups. The presence of G allele at -11377 C/G adiponectin gene significantly increased serum adiponectin level and may be a risk factor for T1DM susceptibility among the western Iranian population., (© 2018 Wiley Periodicals, Inc.)

Introduction: End-stage renal disease (ESRD) is associated with critical kidney illness that seriously affects the lifespan. Genetic factors and oxidative stress could play critical role in the development of ESRD. We assessed the association between chemerin rs17173608 T/G and vaspin rs2236242 T/A genes variants with the risk of ESRD and their correlation with plasma malondialdehyde (MDA) level., Materials and Methods: In a case-control study, 131 gender and age-matched unrelated healthy controls and 110 ESRD patients were enrolled. The chemerin rs17173608 T/G and vaspin rs2236242 T/A were detected by Tetra primer-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). The MDA concentration was determined by HPLC., Results: Our findings for the first time revealed that in codominant genetic model (T/G vs. T/T genotype), the T/G genotype of chemerin gene significantly had a protective role against ESRD susceptibility. Also, in the presence of chemerin G allele, the risk of ESRD decreased by 0.79-fold (p = .048) in Kurdish population of Iran. The MDA serum levels in ESRD patients carrying the chemerin T/G + G/G genotype of rs17173608 T/G and also in carriers of A/A + T/A genotype of vaspin rs2236242 T/A were significantly higher compared to those in control subjects. The overall distribution of vaspin rs2236242 T/A genotypes and alleles comparing ESRD patients and healthy subjects were not statistically significant., Conclusion: We found that the G allele of chemerin rs17173608 compared to T allele decreased the risk of ESRD, and there was a significant association between chemerin and vaspin variants with plasma MDA level in a sample of the Iranian population.

Competing Interests: All authors declare no conflicts of interests.

The variants of angiotensin converting enzyme ( ACE ) and matrix metalloproteinases (MMPs) genes might be involved in the pathogenesis of end stage renal disease (ESRD) and hypertension. We studied the ACE insertion/deletion (I/D) and MMP-7 A-181G variants in 99 unrelated ESRD patients and 117 individuals without renal complications from Western Iran with Kurdish ethnic background. The frequency of ACE I/D variants was not significantly different between ESRD patients and controls. However, the presence of ACE D allele increased the risk of hypertension in ESRD patients by 2.14-fold (P=0.036). The MMP-7 -181 AG genotype increased the risk of ESRD by 2.04 times (P=0.026). The present study indicated the absence of an association between the ACE I/D polymorphism with the risk of ESRD. However, the ACE D allele increased the risk of hypertension in ESRD patients. Also, the present study suggests a role for MMP-7 AG genotype in the pathogenesis of ESRD., Competing Interests: The authors report no conflicts of interest.

The cytotoxic T lymphocyte antigen-4 (CTLA-4) also known as CD152 (cluster of differentiation 152) is a crucial negative regulator of the immune system. This protein receptor provides negative signals in order to suppress T-cell activation and immune attack against self-antigens, although its role is unclear.  The ability of CTLA-4 to limit T cell-mediated immune response has made it a major target in treatment of tumors and autoimmune diseases such as systemic lupus erythematosus (SLE). In this study, we investigated whether CTLA-4 G-1661A and CTLA-4 T-1722C mutations are associated with SLE. So one hundred nine SLE patients and 101 gender and age-matched unrelated healthy controls were recruited for this case-control study. The promoter mutations were detected by PCR-RFLP, neopterin, malondialdehyde (MDA) and serum lipid concentration were determined by HPLC and enzyme assay, respectively., Result: We found that both codominant (AA vs. GG) and recessive (AA vs. GA+GG) CTLA-4 G-1661A mutation significantly decreased the risk of SLE by 1.7 and 3.7 times, respectively.  Interestingly, SLE patients with AA genotypes of CTLA-4 G-1661A have lower neopterin and MDA concentration compared with GA+GG genotypes. The overall distribution of CTLA-4 T-1722C genotypes and alleles in SLE patients were similar to those in control group. In conclusion, our findings showed, that there is an association between systemic inflammatory markers, oxidative stress and the CTLA-4 G-1661A GG+AG genotypes, MDA and neopterin which are the most conventional risk factors for coronary heart disease, therefore these mutations may be consider as a risk factor for susceptibility to heart disease in SLE patients.

Introduction: There are some evidences indicating DNA damage by oxidant and mutant agents has an essential role in the chronic renal failure and end stage renal disease (ESRD). To investigate the possible association of GSTs variants with ESRD, we investigated the frequency of GST- T1, M1, and P1 genotypes, and the level of malondialdehyde (MDA) in patients with ESRD., Materials and Methods: The present case-control study consisted of 136 ESRD patients treated with maintenance hemodialysis and 137 gender- and age-matched, unrelated healthy controls from the population of west of Iran. The GST- T1, M1, and P1 genotypes were determined in all individuals using multiplex-PCR and PCR-RFLP. The level of MDA was measured by high-performance liquid chromatography (HPLC)., Results: We found that GSTM1 and GSTT1 null genotypes (GSTT1-/GSTM1-) increased the risk of ESRD by 1.8 times (p < 0.001) and the increased risk of ESRD for GSTM-null (T1+-M1-) genotype was 3.04 times (p = 0.002). ESRD patients carriers the GST (GSTM1-null + GSTT1-null + GST-null) genotypes compared to GST normal genotype increased the risk of ESRD by 3.3 (p < 0.001) times. ESRD patients carriers of GST-null, GSTM1-null, and GSTT1-null genotypes had greater MDA concentration compared with the same genotypes of control subjects. Our results indicated that the GST-null allele (GSTT1-null/GSTM1-null) is a risk factor for ESRD and carriers of this allele have high levels of MDA., Conclusion: Our findings indicate that oxidative stress, impairment of the antioxidant system and abnormal lipid metabolism may play a role in the pathogenesis and progression of ESRD and its related complications. These data suggest that patients with ESRD are more susceptible to vascular diseases.

Background: Previous studies using cell culture systems for the replication of hepatitis C virus have opened new research dimensions, and paved the ways for further and detailed studies of the virus in vitro., Objectives: The purpose of the present study was to cultivate hepatitis C virus in a cell culture system and evaluate viral amplification., Materials and Methods: In order to propagate hepatitis C virus, cloned whole genome of virus, JFH-1, was used. JFH-1 cDNA was introduced into strain JM109 of Escherichia coli and plasmid, containing the viral genome was purified from transformed bacteria. After XbaI digestion, RNA synthesis was induced using T7 RNA polymerase enzyme. Next, eukaryotic cell line Huh 7.5 was transfected by the purified RNA. Finally, Huh-7.5 cell line was infected with replicated virus and viral load was determined using real-time PCR (Polymerase Chain Reaction)., Results: The amount of viral load, which was measured using real-time PCR was 17592 IU/mL., Conclusions: In the present study, using cell culture, a high titer (in acceptable range) of infectious hepatitis C virus was produced. This method could be used in future studies.

Background: Hepatitis delta virus (HDV) is dependent on the hepatitis B virus for transmission and propagation. Based on isolated HDV sequences from different parts of the world, at least three major different genotypes with different geographic distributions are suggested. Studies have shown that genotype 1 is the predominant genotype of HDV in different parts of Iran; however, the genotype distribution of this virus has not been identified in Mashhad, northeast Iran., Objectives: This current study determines the frequency of HDV major genotypes in Mashhad, Iran., Patients and Methods: Twenty-five participants were enrolled in this study. All samples were positive for HBsAg (determined by Enzyme-linked immunosorbent assay (ELISA)) and anti-HDV. RNA extraction and cDNA synthesis was performed. Then, PCR was performed and HDV genotypes were determined by restriction fragment length polymorphism (RFLP)., Results: Of 25 patients, 12 (48%) were positive for HDV RNA. Genotype analysis of HDV RNA revealed that the prevalence of HDV genotypes I and II was 83.3% (n = 10) and 16.7% (n = 2), respectively., Conclusions: This study showed that the most prevalent genotype of HDV in Mashhad was genotype I. It was of interest that in contrast to other provinces of Iran, HDV genotype 2 was observed in Mashhad. Similar studies with larger sample sizes could provide valuable information regarding the molecular epidemiology and geographical distribution. It may also help control and prevent the spread of hepatitis D virus infections. In addition, the genotyping of HDV may predict the severity of the disease.

Mannitol is commonly used to lower intracranial and intraocular pressures. Large doses/massive infusions of mannitol have been found to be associated with acute renal failure (MI-ARF), that is, osmotic nephrosis. While many researchers have reported individual experiences with this pathology, we felt that there is need of an updated comprehensive review of all reported cases with elaboration of etiology, pathogenesis, diagnosis and management plan for MI-ARF. The purpose of the present communication is to share our own experience with MI-ARF, to review the effect of mannitol on kidney function and to highlight the dynamics of MI-ARF with considerations for the cautious use of mannitol in patients with risk factors for kidney diseases.

Background: Neonatal herpes infection is the most serious complication of Herpes Simplex Virus (HSV) infection during pregnancy and perinatal period. Few studies have reported neonatal HSV infection in developing countries., Objectives: The aim of this study was to detect the HSV infection among neonates and infants with sepsis., Materials and Methods: In a cross sectional study all infants aged less than 3 months, admitted to neonatal intensive care unit and pediatric emergency ward of Ghaem Hospital (a university hospital with 900 beds) in Mashhad (Northeast of Iran) with clinical diagnosis of sepsis and at least one inclusion criteria during one year from November 2009 to October 2010, were enrolled in the study. Polymerase chain reaction (PCR) was done on clinical samples obtained from patients., Results: Among 150 neonates and infants younger than 3 months old with sepsis, the PCR results for detecting the HSV DNA, were positive in 6 samples of 5 patients (3.3 %). None of the mothers had symptomatic HSV infection during delivery. The mean age of the patients was 18 days. Two of them died due to shock and disseminated intravascular coagulation (DIC)., Conclusions: In neonates and infants with primary diagnosis of sepsis, HSV infection should be considered especially if the clinical condition does not improve after 48 hours of antibiotic therapy, and sepsis still exists with elevated liver enzymes.

Background/aim: Several types of the hepatitis C virus (HCV), with variations in different parts of the genome, have been isolated from different regions of the world. Based on heterogenic sequences in the isolated genome, HCV is classified into different genotypes and subtypes. Data on distribution of HCV genotypes in a certain region could be important to patient management. Therefore, this study was conducted to determine the distribution of HCV in Mashhad, Northeast Iran., Materials and Methods: This cross-sectional study was conducted on 103 patients with HCV infections in Mashhad. Among the participants, at least 22 (21.4%) were intravenous drug users. HCV seropositivity was determined by an enzyme-linked immunosorbent assay and was confirmed by reverse transcriptase polymerase chain reaction. HCV-positive samples were selected for HCV genotyping using genotype specific primers., Results: Of 103 subjects, 43 (41.7%) and 34 (33.0%) had genotypes 1a and 3a, respectively. Other genotypes including 1b, 2a, 2b, 3b, and 5a were found in 4 (3.9%), 1 (1.0%), 3 (2.9%), 4 (3.9%), and 1 (1.0%), respectively. Coinfections with 2 genotypes were also observed in 11 (10.7%) patients. Genotyping for 2 (1.9%) of 103 samples did not produce any results., Conclusion: Genotypes la and 3a were found to be the most prevalent HCV genotypes in Mashhad, Iran.

The insulin and insulin-like growth factor-1 (IGF-1) are considered to play important roles in brain development; and their cognate receptors -InsR and IGF-1R- localized within distinct brain regions including cerebellum. Using Real-Time PCR and western blot analysis, we compared the expression of InsR and IGF-1R in male and female developing rat cerebellum at P0, P7, and P14. At all time points studied, the cerebellar expression of IGF-1R, both at mRNA and protein levels was higher than that of InsR. The lowest InsR and IGF-1R mRNA and protein levels were measured in the neonate cerebellum, independent of gender. In males, the highest InsR and IGF-1R mRNA and protein expression were found at P7. InsR and IGF-1R expression increased significantly between P0 and P7, followed by a marked downregulation at P14. In contrast, in females, mRNA and protein levels of InsR and IGF-1R remain unchanged between P0 and P7, and are upregulated at P14. Therefore, peaked InsR and IGF-1R expression in female cerebelli occurred at P14. Interestingly, changes in mRNA expression and in protein levels followed the same developmental pattern, indicating that InsR and IGF-1R transcription is not subject to modulatory effects during the first 2 weeks of development. These findings indicate that there are prominent sexual differences in InsR and IGF-1R expression in the developing rat cerebellum, suggesting a probable mechanism for the control of gender differences in development and function of the cerebellum.

Background: Hepatitis C virus (HCV) infection is a significant health problem throughout the world. Chronic form of the disease is found in about 75% to 85% of the newly infected individuals. The chronic infection may lead to severe forms including chronic liver disease, cirrhosis and with a higher mortality rate, hepatocellular carcinoma. Since no vaccine has yet been developed against HCV, there is an increasing need to take measures to control the spread of the infection. Therefore, epidemiologic study of the virus is important to manage and monitor the spread of the virus in the community., Objectives: The aim of this study was to determine the prevalence of hepatitis C seropositivity in the general population of Mashhad, northeast of Iran., Patients and Methods: Three thousand, eight hundred and seventy (3870) individuals living in the city of Mashhad were recruited using cluster sampling method. HCV seropositivity was determined with HCV antibody detection ELISA kit and was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) method., Results: In this study the overall seroprevalence of hepatitis C was founded to be 0.2% by using ELISA method. However, the overall Hepatitis C virus infection prevalence was found to be 0.13% with RT-PCR method., Conclusions: Our study suggested that the prevalence rate of Hepatitis C virus is below 1% in the general population of Mashhad.

Background: Hepatitis B virus (HBV) infection is the most common and serious liver infection in the world. An estimated 350 million people are chronic carriers of this virus, of whom, more than 620,000 die from liver-related diseases annually. Due to the vaccination program, prevalence of HBV, particularly among the younger generation, is reported to have declined in recent years in Iran., Objectives: The aim of this study was to evaluate the prevalence of HBV infection in Mashhad, North-East of Iran., Patients and Methods: Three thousand one hundred and ninety eight (3198) individuals living in Mashhad were studied using cluster sampling method. HBV infection was determined by HBsAg ELISA commercial kit. Positive results were subjected for PCR using HBV-specific primers. HBeAg, HBeAb, and HBcAb-IgM ELISA tests were performed for HBsAg-positive samples., Results: Patients' age ranged from 15 to 65 years (Mean = 35.54 ± 14.85). Thirty four (1.0%) of the subjects were positive for HBsAg, of whom, 2.9 % (1 of 34 cases) were also positive in PCR-based screening. ELISA tests for HBeAg, HBeAb, and HBcAb IgM were positive in one (2.9 %), 27 (79.4%) and one (2.9 %) cases, respectively., Conclusions: According to our results, HBsAg was positive in 0.53 of the total population. The prevalence of HBV infection was seemingly low in Mashhad; however, an upward trend was observed in older subjects probably due to successful HBV vaccination coverage in the younger generation. Continuous surveillance and periodic population-based studies are essential to monitor the prevalence of HBV infection in Mashhad in the future.

DNA damage which occurred by the effect of oxidant and mutant agents has an essential role in the development of atherosclerosis. To investigate the possible association between GSTs polymorphism with coronary artery disease (CAD), we investigated the frequency of GSTT1, M1, and P1 genotypes in patients with CAD compared to controls. The genotypes of GSTT1, M1, and P1 were determined in 209 angiographically documented CAD patients and 108 normal coronary artery cases (as controls) by Multiplex Polymerase Chain Reaction and PCR-RFLP. In CAD patients, the frequency of GSTT1-null genotype was significantly (P = 0.025) lower than that in control. The presence of this genotype was associated with 2.2-fold increased risk of CAD. However, the frequency of GSTM1 and GSTP1 genotypes were not significantly different comparing both groups (P = 0.405 and P = 0.521, respectively). Moreover, non smokers patients had a lower frequency of GSTM1-null genotype (29.2%) compared to non smoker controls (43.5%, P = 0.043). Also, the frequency of both GSTT1-null and GSTM1-null genotypes in patients (3.8%) was significantly lower compared to controls with the same genotypes (10.2%, P = 0.014). Our results indicated that a reduction in the frequency of GSTT1-null and GSTM1-null genotypes that observed in our study might be involved in the pathogenesis of CAD in our population.

Objective: The role of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in early onset coronary artery disease age < 55years (ECAD) is controversial. The aim of this study was to further evaluate the role of this ACE(I/D) gene polymorphism on the risk of premature CAD in patients from western Iran., Methods: The ACE(I/D) genotypes were detected by PCR-RFLP in 323 individuals undergoing their first coronary angiography. Patients were placed into two groups: ECAD and late onset CAD age ≥ 55years (LCAD)., Results: We found a statistically significant association of the ACE D allele, as homozygous or ACE ID plus DD genotypes (ID+DD), only in the ECAD subjects OR=1.35, p=0.015, OR=3.27, p=0.014, and OR=2.8, p=0.013, respectively. In addition, there was a significant association after adjustment for the absence of history of diabetes, presence of normolipidemia and absence of history of blood pressure [OR 1.38, p=0.017 and 2.35, p=0.02]. Our results indicated that the ACE D allele is a risk factor for early onset of CAD even after correcting for conventional risk factors. The incidence of triple vessel disease was significantly higher in individuals carrying ACE(D/D) genotype in ECAD patients compared to those who carried ACE(I/I) genotype (OR 3.38; p=0.019; 57.5% vs. 42.5%; p=0.013)., Conclusion: The presence of D allele of ACE can be important independent risk factor in the onset of CAD patients less than 55 years old in a west population of Iran. Larger collaborative studies are needed to confirm these results., (Copyright © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

There are controversial results related to the contribution of factor V Leiden G1691A, prothrombin gene G20210A and methylentetrahydrofolate reductase (MTHFR) C677T mutations in the development of coronary artery disease (CAD) and their association with diabetes. To assess the distribution of these thrombophilic mutations in CAD patients with and without type 2 diabetes mellitus (T2DM), we studied 117 CAD patients [65 CAD patients with diabetes (CAD/T2DM) and 52 CAD patients without diabetes (CAD/ND)] and 59 age-matched and sex-matched healthy individuals without CAD from population of western Iran. Genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism using Mnl I, Hind III and Hinf I for factor V Leiden, prothrombin G20210A and MTHFR C677T, respectively. The prevalence of prothrombin G20210A variant in CAD/T2DM, CAD/ND and control individuals was 3.1, 1.9 and 0%, respectively. Factor V Leiden G1691A was found in 4.6% of patients with CAD/T2DM, 3.8% of patients with CAD/ND and 3.4% of healthy individuals. The prevalence of MTHFR C677T was found to be 49.2, 32.7 and 44.1% in CAD/T2DM, CAD/ND and control group, respectively. Our results indicate that there is no significant difference between the prevalence of thrombophilic mutations of factor V Leiden, prothrombin G20210A variant and MTHFR C677T in CAD patients with or without diabetes compared with controls. Although a higher prevalence of these thrombophilic mutations was observed in CAD patients, especially in those patients with diabetes, it seems that these variants may not be considered as independent risk factors for CAD or diabetes in our sample. These findings are discussed in relation to available literature.

Objective: It has been suggested that there is a relationship between apolipoprotein E polymorphism and the severity of coronary artery disease in type II diabetes mellitus (T2DM). The current study specifically aimed to examine whether APOE polymorphism in association with serum lipids-lipoproteins level is a risk factor for developing coronary artery disease (CAD) in diabetic patients living in western of Iran., Methods: The APOE genotypes were detected by PCR-RFLP in 152 angiographically documented diabetic CAD patients, 262 non-diabetic (ND) individuals with CAD and 300 unrelated controls (normal coronary artery cases without diabetes) and serum lipid level was measured enzymatically., Results: The APOE-epsilon4 and epsilon2 allele frequencies were significantly higher in the CAD/T2DM and CAD/ND patients than in the control group (p<0.001). Our study demonstrated a significant association between APOE polymorphism and the level of plasma lipids with CAD/T2DM (p=0.001) and CAD/ND (p=0.026) patients. The CAD subjects with T2DM and ND patients carrying APOE-epsilon4 allele had lower plasma HDL-C level (p<0.001), (p=0.008) but had higher plasma LDL-C (p=0.01), total cholesterol (p=0.002), (p=0.03) and TG (p<0.001), (p=0.042) than that of the APOE-epsilon3 carriers, respectively. However, carriers of APOE-epsilon2 had significantly higher levels of plasma TG only. OR of APOE-epsilon4 and epsilon2 alleles in CAD/T2DM and CAD/ND patients were found to be 2.98 (p=0.001),1.86 (p=0.001), 2 (p=0.001), and 1.65 (p=0.001), respectively., Conclusions: The major finding of the present case-control study is that T2DM patients carrying APOE-epsilon2 and epsilon4 alleles have a higher risk of developing CAD than ND patients in the western population of Iran, with APOE-epsilon4 being more closely associated with CAD than the APOE-epsilon2 allele. These results indicated that carriers of APOE-epsilon4 allele have a distinct plasma lipids profile and carrier of this allele with low levels of HDL-C and with high levels of LDL-C may be susceptible to CAD and myocardial infarction specially in diabetic patients. This suggests that a therapeutic modality should be considered for these patients.

Objectives: The glutathione S-transferases (GSTs) play a critical role in protecting the colorectal mucosa. We investigated the efficacy of using the GSTs activity of plasma as a biomarker of risk for colorectal cancer., Methods: GSTs activity was measured in the plasma of control individuals (n=39) and in the plasma, tumor tissue and normal tissue adjacent to a tumor of patients with colorectal cancer taken at colonoscopy (n=60)., Results: Mean GSTs activity was significantly (P< 0.01) higher in tumors (242+/- 45 nmol/min mg protein) as compared to normal tissues adjacent to a tumor (84+/- 49 nmol/min mg protein). A significant correlation between normal tissues adjacent to a tumor GSTs with those in malignant tissues was observed (r=0.61). Plasma GSTs activity was significantly (P<0.0001) higher in colorectal cancer patients (164+/-11 nmol/min mL) than those obtained from normal individuals (92+/- 23 nmol/min mL)., Conclusions: GSTs measurement may be useful as a colorectal cancer marker in colorectal cancer, and biopsies obtained at colonoscopy can be used to measure tumor markers.