مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال هفتاد و سوم شماره 1 (پیاپی 169، فروردین 1394)

Metastasis associated miRNA (metastamiR) opened a new field of anti-metastatic therapy which have a great potential of treatment for the most lethal aspect of cancer، metastasis. The pleiotropic nature of gene regulation exhibited by certain miRNAs that showed that miRNAs might be endowed with a capacity to function as crucial modulators of tumor metastasis. MiR-31 is a pleiotropic anti-metastatic miRNA whose expression decreased significantly in metastatic breast cancer cells. MiR-31 has multiple roles in metastasis cascade. Therefore، using the miR-31-restoration based therapy could be an efficient anti-metastatic strategy for cancer therapy. This research was performed from May 2014 to October 2015 in Tarbiat Modares University in Tehran، Iran. The double-strand oligo of mature miR-31 was cloned into pcDNA 6. 2gw/EmGFP according to the manufacturer instruction. The MDA-MB231، MCF-7 breast cancer cell lines were cultured and their miRNAs have been extracted. The expression of miR-31 has been quantified by Real time-PCR be-fore transfection of construct contained miR-31 into two cell lines and in normal breast cells. Then the constructs contain miR-31 have been transfected in to two cell lines. The expression of miR-31 has been quantified after 48 hours. Scratch and invasion as-say have been carried out for assessing the level of migration and invasion. The result of Real time-PCR before transfection of constructs contained miR-31 have been shown 4 fold and more than 100 fold reduction in expression of miR-31 in MCF-7 and MDA-MB231 respectively in comparison to miR-31 expression in nor-mal breast cells، but after transfection of miR-31 construct to MDA-MB231 the quan-tification of expression showed the significant increase in mir-31 expression and 20 fold reduction in invasive and 10 fold reduction in migratory characteristics of MDA-MB231 in comparison to MCF-7. Metastasis associated miRNA have been represented a promising candi-dates in the field of anti-metastatic therapy and miR-31 as a powerful member of this family can function very effectively in order to inhibit the metastasis and introduce the new possibility of metastasis inhibition.

The molecular studies indicate some of the genes in the promoter region itself, will undergo methylation. Methylation of CpG islands in the promoter region of that cause silence or reduced expression of genes involved in cell growth pathways, which are colorectal cancer causing agents. Detection of methylation status can be used as a marker for cancer diagnosis and prediction of disease. CDKN2A tumor suppressor gene encodes a protein, which inhibit CDK 4/6 and loss of retinoblastoma protein phosphorylation (pRb) is involved. The purpose of this study was to investigate the molecular hypermethylation in exon 1 of CDKN2A gene in patients with colorectal cancer and normal subjects. In this case-control study, the study population consisted of 20 patients with colorectal cancer and 10 healthy persons. Samples in paraffin blocks were prepared in pathology department of Mehr Hospital, Tehran, Iran, from December 2010 to June 2012. Then, specific primers were designed for the methylation and Non-methylation of CDKN2A gene. To determine the level of exon 1 methylation of CDKN2A gene, methylation-specific polymerase chain reaction (MSP) method was performed. In this study, hypermethylation in exon 1 of CDKN2A gene were observed in 80% of tumor tissues (16 cases) and 20% of normal tissues (2 cases). The patients aged older than 50 years, had a higher CDKN2A gene methylation and frequency than patients younger than 50 years old (66% vs 34%) (P<0/001). The result of this study has been confirmed the role of CDKN2A gene promoter methylation of CpG sites of colorectal cancer as the leading cause of colorectal cancer. These data suggest that epigenetic silencing via aberrant methylation of the CDKN2A promoter plays a critical role in the inactivation of this tumor suppressor gene in colorectal cancer and can be used as a marker for early detection and identification of potential applications.

Breast cancer is the second most common cancer in the world after lung cancer also is the fifth cause of cancer mortality. About 90 percent of cancer mortality is because of metastasis and devastating between cell attachments, especially tight cell junctions. Epithelial mesenchymal transition is a phenomena involved in metastasis and starts with cell detachment. Occludin is the integral membrane protein which is located in tight junctions. Obviously distressing tight junction, which facilitates the stages of metastasis in cancer cells are very critical step. The aim of this study was to demonstrate the importance of occludin expression and its relationship with invasiveness in human breast cancer. In a cross sectional study we evaluated 30 patients who were referred to Caner Institute of Imam Khomeini Hospital Complex, Tehran, Iran, from March 2013 to April 2013. Samples were derived from fresh frozen tumor of patients suffering from breast cancer after inform consent assignment in the Tumor Bank of Iran (TBI). RNA was extracted from tumor tissue followed by reverse transcription, polymerase chain reaction (PCR), conventional Real-time PCR and data analysis for the occludin gene expression. Data were analyzed based on clinical staging of breast cancer patients which were cited in data bank of TBI. Results of this study have demonstrated that the occludin gene expression was increased with the advanced stage. In 22 of patients the expression of gene was elevated compared with normal samples. On the other hand, the expression was significantly increased in stage II in comparison with stage I. The expression of occludin has increased by elevation of stage compared with normal tissue. It is suggested that alteration in the expression of this gene might be a possible factor which could affect on patient’s prognosis the same as other factors which are belonging to the same family. Increasing in expression of this gene might be considered as one of the possible markers which predict the possibility of invasion and metastasis.

Staphylococcus aureus is the most important cause of nosocomial infections acquired in the community. Protein A is a major component of Staphylococcus aureus cell wall. In analysis of the nucleotide sequence Protein A encoding spa, locus x consists of 24 base pairs which repeat with high polymorphism. In this study, the spa gene of Staphylococcus aureus isolated from clinical specimens were obtained from patients admitted to the hospital and healthy carriers. In a cross-sectional study, a total of 200 samples were collected. One hundred fifty samples were obtained from hospitalized patients and 50 samples obtained from staff nasal swabs in Hamadan University Hospitals from October 2013 to August 2014. Disk diffusion antibiotic susceptibility tests performed. The antibiotics studied were Vancomycin (30 µg), Cefoxitin (15 µg) Gentamicin (10 µg), Tetracycline (30 µg), Trimethoprim/sulfamethoxazole (25 µg), Ciprofloxacin (5 µg), Erythromycin (15 µg), Clindamycin (2 µg), Rifampin (5 µg). The tests performed according to the guidelines of clinical and laboratory standards institute (CLSI). It also detect the mecA gene of Methicillin-resistant Staphylococcus aureus strains (MRSA) and genes spa which encodes the protein A by polymerase chain reaction (PCR). The PCR products using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method with enzyme Rsa I (Afa I) were prepared. This methicillin-resistant Staphylococcus aureus strain (MRSA) had the highest sensitivity and resistance to ciprofloxacin and clindamycin. Totally, 8 amplicon with different sizes for the spa gene were identified. A total of 9 patterns polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) were found. Some of these patterns between Staphylococcus aureus isolated from clinical specimens and nasal carriers were common. There is a similar pattern of spa gene among patients admitted to the hospital and staff, according to our findings. Analysis of the patterns can reduced transmission of infection in both hospital staff and patients. Also it can help the physicians for correct management of infections.

Last decades, we have observed major improvements in treating infertility by using microinjection. However, reduction in abortion or increase in fertility has not been significant. It seems use of corticosteroids improves clinical outcomes during assisted reproductive technology (ART) techniques. Therefore, this study tried to show how corticosteroids therapy improves the results of intracytoplasmic sperm injection (ICSI). This semi clinical trial study without control group was included infertile women with more than one year’s infertility and were candidate to ICSI which were referred to Kosar Infertility Center, Urmia University of Medical Sciences from April 2011 to September 2013. Patients received prednisolone which was started 20 mg/day from one day before embryo transfer to 7 days, then for 2 days more 1 tablet and stopped. Pregnancy outcomes were chemical and clinical pregnancy, ectopic pregnancy, multiple pregnancy and rate of abortion before 20 weeks. Beta human chorionic gonadotropin (HCG) test was performed. Patients with positive pregnancy test were followed by sonography in 6, 12 weeks and 20 weeks of pregnancy. One hundred and eighty one patients entered to the study. The mean± SD of age and fertility duration were 30.42± 6.07 and 7.69± 5.54 years. The mean± SD of transferred embryo was 4.60± 1.10 and embryo grading was 138 (44.7%) grade A, 124 (40.1%) grade B, 47 (15.2%) grade C, respectively. There were no significant difference between fresh/frozen embryo transfer in pregnancy outcomes (P> 0.05) in all of outcomes comparison). The incidence rate of biochemical pregnancy was 48.1% (87), clinical pregnancy rate with appearance of fetal heart was 44.2% (80), incidence rate of abortion before appearance of fetal heart (6 weeks) in women with intra-uterine pregnancy was 5.9% (5), incidence rate of abortion before 20 weeks was 12.9% (11). Incidence rate of ectopic pregnancy was 2.3% (2) and rate of multiple pregnancies was 32.5% (26). Our study suggests that the infertile patients who receive prednisolone in ICSI cycle, had improved pregnancy outcomes. Additional confirmatory studies are needed.

Orthopedic trauma is a common type of injury in children and may cause deep and permanent psychological and physical damage both for the patient and the parents. This study aimed to analyze the epidemiology age, gender distribution and the mechanism of injury in patients presenting to a level I trauma center in urban population of Tehran. In this prospective descriptive study, the patients under 19 years old with orthopedic trauma who were hospitalized in Tehran Shafa University Hospital were entered. This hospital is the main orthopedic referral center in Iran. The patients were prospectively evaluated from April 2013 to March 2014. The data were collected and analyzed. The study included 1081 patients under 19 years old. There was a male predominance (76.8% n= 830). The boys had a higher mean age 11.04±5.06 year, versus girls with mean age 8.67±4.63 year (P< 0.05). The peak age of boys was 18 and the girls had two peaks at three and nine. The fractures occurred in upper limb in 70.8% (n= 621) and 29.2% (n= 256) in lower limb of patients. There were 27 cases with joint dislocation, 5 cases with knee ligamentous injuries, 128 cases with soft tissue injuries and 44 cases with spine injuries. The most frequent mechanism in both gender were falls from standing position (48.5%). The most common fractures were foreman both bone fractures (n: 146 16.7%), elbow supracondylar fractures (n: 134, 15.3%) and distal radius fractures (n: 84, 9.6%). The most fractures occurred in summer (30.1%) and the least in winter (18.1%). Evaluation of epidemiologic factors can lead to the best prediction and treatment planning of trauma. Early recognition of injury, even minor, and expected care using specialized teams will help to improve outcomes for these patients. This study determines the most at risk children for trauma and fractures and may help the parents to prevent damage.

One of the toxins accumulated in the body of hemodialysis patients is beta-2 microglobulin which is caused and increased by various factors. The one of this factors that can affect beta-2 macroglobulin is of membrane type that using in hemodialysis. In the present study, we examined the impact of C-reactive protein (CRP) as an inflammatory factor on beta-2 microglobulin in high-flux membrane hemodialysis patients. This cross-sectional study was done in 44 hemodialysis patients that have been dialyzed in two academic centers; Sina and Amir Alam Hospitals, Tehran, Iran from 2013 to 2014. The patients were hemodialyzed via fistula or permanent catheters three times a week for 4 hours for more than three months. Patients with known infectious disease, hemodialysis with low-flux membrane and dialysis less than three times a week were excluded. All patients were hemodialyzed using Fresenius biocompatible high-flux membrane (FX 100, Fresenius, Massachusetts, USA). Arterial blood sampling was performed. beta-2 microglobulin, CRP, BUN and creatinine tests were conducted for all patients. Forty-four patients among the chronic hemodialysis patients were selected for final analysis. 20 males (44.5%) and 24 females (54.5%) were included in this study. The frequencies of underlying disease in patients participating in the study were as follows: hypertension, 23 cases (52.3%); diabetes mellitus, 11 cases (25%); hypertension and diabetes mellitus, 2 cases (4.5%); obstructive disorder, 2 cases (4.5%). In 23 patients (52.3%), beta-2 macroglobulin was >12 mg/l and in 21 (47.7%), it was <12 mg/l. 29 cases (65.9%) had CRP values less than or equal 6 mg/l. However, there was no significant differences between beta-2 microglobulin and CRP levels (P= 0.460). Also regression analysis of data showed no relationship between beta-2 microglobulin and CRP levels (r= -047, P= 0.763). Although it seems that inflammatory factors can be effective in increasing beta-2 microglobulin, the present study did not find such a relationship between CRP and beta-2 microglobulin.

Ondansetron is a 5-hydroxytryptamine receptor antagonist which is a highly effective antiemetic for postoperative and chemotherapy induced nausea and vomiting. It is an off-label drug to treat nausea and vomiting of pregnancy but availa-ble data about its safety is limited. In this study our purpose was to evaluate neonatal outcomes in women who received this treatment. This study is a descriptive retrospective case series study, included 22 preg-nant women who treated with ondansetron due to repeated nausea and vomiting unre-sponsive to our center's protocol, at Mahdiyeh Hospital, Tehran, Iran from May 2006 to September 2014. We investigated neonatal factors including: gestational age at birth, stillbirth, neonatal birth weight, apgar score, need to NICU admission and major birth defects. The outcomes of 22 pregnancies and 22 newborns are presented here. We had two twin pregnancies and two abortions. Ondansetron was initiated in 18 cases (72%) on average gestational age of 9 weeks, during organogenesis. In 8 cases (32%) on-dansetron continued till third trimester of pregnancy. In primary evaluation, all the pa-tients had ketonuria, 15 cases (60%) had hypokalmia (K< 3.5), 3 cases (12%) had ab-normal TSH that all of them were hyperthyroidism and 5 cases (20%) had abnormal liver function test (LFT) Three patients (12%) had positive urine culture, one patient had hypercalcemia and one patient who was known a case of hypocalcemia had low serum calcium. The mean time of admission due to hyperemesis gravidarum (HG) was 5 days (2-10 sd=1.92). In this study we had only one preterm birth and the mean neo-natal birth weight was 3110 gram, one newborn was low birth weight due to preterm birth. Finally none of newborns had low apgar score, no one needed to NICU admis-sion and no congenital anomaly was seen in neonates. Ondansetron taken during pregnancy was not associated with increased risk of adverse fetal outcomes.

Enuresis is the inability to control urination during sleep. It is one of the most common childhood urologic disorders. Nocturnal enuresis refers to the occurrence of involuntary voiding at night after 5 years. Persistent nocturia can decrease self-esteem, increase anxiety and other emotional problems in children. The aim of this study is to evaluate the factors affecting nocturia amongst school-aged children. This cross- sectional study was conducted on 200 children over a period of 3 months from 21 April to 22 July 2014 (. Subjects of this study included 200 children (100 boy and 100 girl) aged 6 to 12 years that referred to the urology clinic. Following the written consent, patients under study were divided into two groups according to gender. A questionnaire concerning the personal data was completed for each patient. Questionnaires were completed by interviewing parents. Our investigation revealed that 32% of children had nocturnal enuresis. The Chi-square test demonstrated significant differences between the case and control groups in terms of gender (P= 0.002), positive family history (P= 0.004), deep sleep (P= 0.005) and high fluid intake (P= 0.00). Significant differences were not observed among enuretic children with parent's education level, income, number of family members, birth order, history of injury and hospitalization, birth of a new baby, moving house, problems at school and home, snoring, mouth breathing, urinary tract infections, constipation (P> 0.05). In order to control enuresis it seems essential to provide information about nocturia and its etiologic factors to the children and their parents by the physician.

The effects of consumption of nutrients on coronary artery disease (CAD) are widely observed. The aim of this study is to assess the exclusive Iranian dietary pattern on coronary artery diseases (CAD) and its risk factors. In this description-cross sectional study, 801 inhabitants of Borujerd City were included by random stratification method and a questionnaire regarding micro- and macronutrients for subjects over 35 years old from March 2011 to February 2012 was filed out. Of all the subjects consent to participate were prepared by volunteers. The complete description and a standard questionnaire to record demographic and socioeconomic status of people were taken. The prevalence of coronary artery disease and its risk factors determined Based on rose questionnaire and Monica questionnaire respectively. In this study mean age of the subjects were 54.8±1.2 years, 388 male and 413 female. There was no meaningful relation between red meat consumption and coronary artery disease (P= 0.117). Nut consumption was higher in patients with CAD (P= 0.028). Use of fresh and cooked vegetables, dried fruit, animal oils cakes, french fries and some dairies are correlated with CAD (P< 0.05). However, artificially flavored soda in contrast to ordinary soda was not associated with coronary artery disease. Although there are some differences between dietary pattern in patient with coronary artery disease, nutritional attitudes are not significantly different in normal and CAD patients. However, according to the importance of diet in CAD, balancing these attitudes should be on the educational system high priority.