Genotype and allele frequency of CYP2C19*17 in a healthy Iranian population

Background: Cytochrome P450 2C19 (CYP2C19) is important in metabolism of wide range of drugs. CYP2C19*17 is a novel variant allele which increases gene transcription and therefore results in ultra-rapid metabolizer phenotype (URM). Distribution of this variant allele has not been well studied worldwide. The aim of present study was to investigate allele and genotype frequencies of CYP2C19*17 in a healthy Iranian population and compare them with other ethnic groups. Methods: One hundred eighty healthy unrelated Iranian volunteer took part in this study and were genotyped for CYP2C19 *2, *3, *17 (-3402) by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and CYP2C19*17 (-806) by a nested-PCR assays. The distribution of CYP2C19*17 polymorphism in Iranian population was then compared with other ethnic groups. Results: The CYP2C19*17 allele frequency was 21.6 in Iranian population. Among studied subjects 5.5 were homozygous for CYP2C19*17 and phenotyped as ultra-rapid metabolizers; 28.8 were genotyped as CYP2C19*1*17 (extensive metabolizers) and 3.3 as CYP2C19*2*17 (intermediate metabolizers). Conclusion: The CYP2C19*17 genetic distribution in Iranian population is similar to Middle East or European countries. The high frequency of CYP2C19*17 in Iranian population highlights the importance of this new variant allele in metabolism of CYP2C19 substrates. Thus, future association studies are required to reveal clinical consequence of this genetic polymorphism in carrier individuals

Cornual Polyps of the Fallopian Tube Are Associated with Endometriosis and Anovulation

Background. The relationship between tubal cornual polyps and endometriosis and ovulatory disorders in infertile women is unclear. Our objective was to determine such an association from our database and review the literature. Methods. Twenty-two infertile women with tubal cornual polyps were assessed for coexistence of oligoovulation/anovulation and endometriosis with stratification for polyp diameter (large: ≥5 mm diameter, small <5 mm diameter). Result(s). Oligoovulation/anovulation was more prevalent in women with large versus small tubal cornual polyps (P = 0.0048). Endometriosis was associated with both large and small polyps. Conclusion(s). This case series confirms the association of tubal cornual polyps with oligoovulation/anovulation and endometriosis in infertile women. This case series is limited by a lack of controls

Down-regulation of miR-135b in colon adenocarcinoma induced by a TGF-β receptor i kinase inhibitor (SD-208)

Objective(s): Transforming growth factor-β (TGF-β) is involved in colorectal cancer (CRC). The SD-208 acts as an anti-cancer agent in different malignancies via TGF-β signaling. This work aims to show the effect of manipulation of TGF-β signaling on some miRNAs implicated in CRC. Materials and Methods: We investigated the effects of SD-208 on SW-48, a colon adenocarcinoma cell line. The cell line was treated with 0.5, 1 and 2 μM concentrations of SD-208. Then, the xenograft model of colon cancer was established by subcutaneous inoculation of SW-48 cell line into the nude mice. The animals were treated with SD-208 for three weeks. A quantitative real-time PCR was carried out for expression level analysis of selected oncogenic (miR-21, 31, 20a and 135b) and suppressormiRNAs (let7-g, miR-133b, 145 and 200c). Data were analyzed using the 2-��CT method through student�s t-test via the GraphPad Prism software. Results: Our results revealed that SD-208 could significantly down-regulate the expression of one key onco-miRNA, miR-135b, in either SW-48 colon cells (P=0.006) or tumors orthotopically implanted in nude mice (P=0.018). Our in silico study also predicted that SD-208 could modulate the expression of potential downstream tumor suppressor targets of the miR135b. Conclusion: Our data provide novel evidence that anticancer effects of SD-208 (and likely other TGF-β inhibitors) may be owing to their ability to regulate miRNAs expression. © 2015, Mashhad University of Medical Sciences. All rights reserved

Behavioral and neural markers of cigarette-craving regulation in young-adult smokers during abstinence and after smoking

Cigarette craving contributes substantially to the maintenance of tobacco use disorder. Behavioral strategies to regulate craving may facilitate smoking cessation but remain underexplored. We adapted an emotion-regulation strategy, using proximal/distal self-positioning, to the context of cigarette craving to examine craving regulation in 42, daily smokers (18-25 years old). After overnight abstinence from smoking, before and after smoking their first cigarette of the day, participants viewed videos of natural scenes presenting young adults who were either smoking cigarettes ("smoke") or not ("non-smoke"). Before each video, participants were instructed to imagine themselves either immersed in the scene ("close") or distanced from it ("far"). They rated their craving after each video. Task-based fMRI data are presented for a subsample of participants (N = 21). We found main effects of smoking, instruction, and video type on craving-lower ratings after smoking than before, following the "far" vs. "close" instructions, and when viewing non-smoke vs. smoke videos. Before smoking, "smoke" vs. "non-smoke" videos elicited activation in, orbitofrontal cortex, anterior cingulate, lateral parietal cortex, mid-occipital cortex, ventral striatum, dorsal caudate, and midbrain. Smoking reduced activation in anterior cingulate, left inferior frontal gyrus, and bilateral temporal poles. Activation was reduced in the ventral striatum and medial prefrontal cortex after the "far" vs. the "close" instruction, suggesting less engagement with the stimuli during distancing. The results indicate that proximal/distal regulation strategies impact cue-elicited craving, potentially via downregulation of the ventral striatum and medial prefrontal cortex, and that smoking during abstinence may increase cognitive control capacity during craving regulation

Cytotoxic Effect of Titanium Dioxide-Hydroxyurea Nanocamposit on Hela Cancer Cell Line

BACKGROUND AND OBJECTIVE: The use of nanotechnology in drug delivery Not only increase the efficacy and ease of drug penetration, but also they decrease their adverse effects. In this study, TiO2 nanoparticle was used as Hydroxyl Urea carrier to increase the contact surface of the drug and cells, and with pegylation of nanoparticle surface decrease immunogenicity, hence to increase drug solubility and penetration to cells. The goal of this study was to investigate cytotoxicity of synthesized TiO2-Poly Ethylene Glycol-Hydroxy Urea (TiO2-PEG-HU) nanocomposite on Hela cell-line and apoptosis induction of treated cells compared to the control group to determine the effective dose of nanodrug. METHODS: In this laboratory study, the effect of TiO2-PEG-HU nano-drug was evaluated on cells bioactivity by MTT method at concentrations of 200, 400, 800, and 1800 µg/ml in 48 and 120 hours. Annexin-V/PI flowcytometry method was used to analyze apoptosis induction. Data were analyzed using uni-directional variance and independent T-test. FINDINGS: Higher concentrations of TiO2-PEG-HU nanocomposite decreased cells bioactivity dependent on dosage and time. As the concentration of 1600 µg/ml of nanocomposite reduced amount of bioavailability by 1.52 times over a 120-hour period compared to the 48-hour time-effect. For both times, this reduced cell survival was `significantly different from that of the control group at the level of p <0.0001. In addition, nano-drug significantly increased apoptosis induction 2.5 times in treated Hela cells (p=0.0114). CONCLUSION: Nano-composite TiO2-PEG-HU on the Hela cell line is cytotoxic and induces apoptosis and can be a promising drug for cancer treatment

A comparison of maladaptive early schemas and appearance schemas in obese and normal weight control subjects

The purpose of this study was to compare early maladaptive and appearance schemas in obse and and normal-weight subjects. Materials and Methods: The method of the study was causal- comparative and groups were included 30 obese (BMI�35) and 30 normal-weight adults (BMI<25). All participants completed Young Schema Questionnaire�Short Version (YSQ-S) and appearance schema Inventory (ASI) questionnaire. Results: Obse subjects showed significantly higher scores in compare to control group in self-sacrifice and emotional inhibition schemas. In addition, severity of appearance schemas in body- image vulnerability and self- investment subscales were significantly greater in obese subjects than in control group. Conclusion: The results of this study suggest that some early maladaptive and appearance schemas are associated with obesity and therefore, theoretical conceptualizations and psychological interventions should address the above thesis constructs. © 2015, Semnan University of Medical Sciences. All rights reserved

The Prevalence of the Genetic Polymorphism of GSTM1, GSTT1 and GSTP1 and Its Relationship with Clinical Criteria of Multiple Sclerosis (MS) Patients in Tehran

BACKGROUND AND OBJECTIVE: Multiple Sclerosis is the chronic inflammation of central nervous system with demyelinated lesions in the brain and spinal cord. The genetic polymorphisms associated with glutathione S-transferase enzymes involved in antioxidant defense in Iranian patients have not been investigated. Therefore, in the present study, the prevalence of the genetic polymorphism of glutathione S-transferase M1, P1 and T1 and its relationship with clinical criteria of MS patients with has been examined. METHODS: In this case-control study, 69 patients who referred to Sina Hospital in Tehran and had no panic attack within the last three months and 74 healthy subjects were interviewed. After examination by neurologist and blood sampling, DNA extraction was performed using Roche kit. Then, the genotypic variations of the samples were evaluated using RFLP-PCR and its prevalence was analyzed in relation with age, birth weight, malignancy (EDSS) and gender using GraphPad Prism software. FINDINGS: Most malignancies were observed in men (3.1±5.9) and the highest incidence rate was observed in those born in May (30%). Although the results of genotyping between the studied groups and their gender did not show any significant difference (OR: 2-4, p>0.05), patients with GSTM1 deficiency developed the disease at a lower age (32.8±2.6 years) compared with other patients (29.5±8.9 years) (CI-95%: 20.3–26.4, p=0.009). In addition, people with a rare GSTM1 allele who smoked cigarette had higher EDSS (CI-95%: 2.1–3.7, p=0.03). CONCLUSION: Based on the results of this study, the effect of GSTM1 on malignancy is indicative of its role in detoxification of tobacco products and can be used as an agent for early diagnosis of disease in people who are susceptible to this disease