مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال هفتاد و پنجم شماره 12 (پیاپی 204، اسفند 1396)

Thyroid cancer is one of the most common endocrine malignancies and in the last two decades the number of involved people in the world has been increased. Thyroid cancer in Iran is the seventh most common cancer in women and 14th in men. In recent years many achievements regarding to molecular pathogenic factors such as the substantial role of signaling pathways and molecular abnormalities have been made. Nowadays there is no efficient treatment for progressed thyroid cancer that does not respond to radioiodine therapy which are included poorly differentiated, anaplastic and metastatic or recurrent differentiated thyroid cancer. Although the results of some clinical trials in phase II for treatment of progressed thyroid cancer are rewarding but none of the treated patients responded to treatment and only a few of them responded partially to the treatment which indicates that the treatment can only control the condition of patients with advanced disease, therefore it is needed to consider other alternative solutions which would be helpful in controlling the disease. Epigenetic is referred to study of heritable changes in gene expression without changes in primary DNA sequence. The main mechanisms of genetic and epigenetic alterations are including mutations, increasing the gene copy number and aberrant gene methylation. Epigenetic defects are prevalent in different types of cancers. Aberrant methylation of genes that control cell proliferation and invasion (p16INK4A, RASSF1A, PTEN, Rap1GAP, TIMP3, DAPK, RARβ2, E-cadherin, and CITED1), as well as specific genes involved in differentiation of thyroid cancer (Na symport, TSH receptor, pendrin, SL5A8, and TTF-1) in association with genetic alterations, leads to tumor progression. Growing evidence shows that acquired epigenetic abnormalities participate with genetic alterations to cause altered patterns of gene expression or function. Many of these molecular changes can be used as molecular markers for prognosis, diagnosis and new therapeutic targets for thyroid cancer. This article is about the most common genetic and epigenetic alterations in thyroid cancer which can be complementary together in recognition of new treatments for the disease.

Infertility influences an estimated 20% of couples worldwide. The factors that can affect the fertility potential are equally distributed between men and women. Despite extensive research in male infertility, the etiology in majority of infertile men is unknown. In 2010, there was an opinion published in Nature asking a selection of leading researchers and policy-makers about what their future focuses will be in 2020. Metabolomics was mentioned as the leading omics technology by them. The word metabolomics has been defined almost 20 years ago. However, the clinical metabolomics history goes back to more than 1,000 years ago. The great Persian physician and philosopher Avicenna observed an individual urine changes during illness. Today, the color or smell changes are known to be caused by metabolites deregulation indicating metabolic diseases. Metabolomics approach is a systematic analysis of the unique pattern followed by a specific biochemical pathway that uses a biological material, e.g. spermatozoa or human seminal plasma. For the diagnosis of infertile men, the typical parameters of semen analysis are: sperm motility, sperm morphology, concentration and count. Human seminal plasma is a valuable biological source which was not used in the diagnosis of infertile men, unfortunately. To the best of our knowledge, there is no parameter for analysis of the human seminal plasma. Thus, the need for a novel parameter to diagnose infertile men is urgently needed. We recommend the use of seminal plasma in order to diagnose infertile men according to our previous research. Only a handful studies have used metabolomics approaches in the male infertility. In this study, we summarize the current research and our contribution to the field of male infertility and metabolomics. One of our main contributions has been to use metabolic profiling of seminal plasma from non-obstructive azoospermia to find 36 potentials biomarkers for detection of spermatogenesis. A search in the PubMed using keywords “metabolomics” and “infertility” shows only 59 publications. This demonstrates how newborn the metabolomics in its application for male infertility is. In this review article we have tried to have a comprehensive and specific approach to male infertility from a metabolomics perspective and related techniques.

Cardiovascular diseases are the leading cause of human mortality worldwide. Myocardial ischemia is a type of cardiovascular disease that increases with age spread. Therefore, the purpose of this study was to compare non-invasive myocardial ischemia in patients with heart problems in different age groups.
This study is a causal-comparative study was conducted from July to October 2016 in the University of Mazandaran. One hundred and seventy-five (age=45-59 years) and 124 (age=60-77 years) men with heart problem participated in this study. The questionnaires of Rose angina pectoris (for assessing the risk of ischemic myocardium), lifestyle and physical activity level were completed by the participants. In addition, the anthropometric characteristics, blood pressure and peak oxygen uptake (VO2peak) of the participants were measured.
The risk of myocardial ischemia in men aged 60-77 years was significantly higher than men aged 45-59 years (P=0.049). Men aged 60-77 years were significantly lower in good indices (physical activity level, VO2peak and more lifestyle indices) and higher in bad indicators (waist/hip ratio, body shape index, ankle systolic blood pressure, brachial systolic and diastolic blood pressure) than men aged 45-59 years (P It seems that the higher risk of myocardial ischemia in men aged 60-77 years, as compared to men aged 45-59 years, might be related to aging process and imbalance in the risk factors. Promoting physical activity can favorably affect the risk of myocardial ischemia in the middle-aged or elderly men. It is concluded that physical activity effectively decreased the risk of myocardial ischemia.

The main causes and difficulties of cancer are the imbalance between cell growth and cell death. This event is the results of changes in the expression level of genes related to these mechanisms. Among genes including in this case, death-associated protein kinase (DAPK) can be mentioned. Studies have shown that the expression of genes is influenced by the methylation of promoter regions. The purpose of this research was to evaluate the expression of the mentioned gene and the effect of methylation on the expression of this gene and its relationship with developing breast cancer in women.
Eighty patients with breast cancer and 80 healthy individuals participated in this case-control study which has been referred to Shahid Faghihi and Namazi hospitals, Shiraz city, from August 2014 to March 2017. This study was carried out at the Genetic Research Center of Islamic Azad University, Kazerun Branch, Iran. Peripheral blood lymphocytes were lysed and the mRNAs were extracted using the InViSorb™ RNA preparation kit II (Cat#1062100300, Invitek GmbH, Berlin, Germany) and cleaned up with Qiagen RNeasy spin columns. The first-strand cDNA was synthesized affording to the high capacity cDNA reverse transcription kit procedure. For DAPK gene expression, (Thermo Fisher Scientific, Waltham, MA, USA) PCR technique combines the quantitative performance of SYBR® Green-based real-time PCR, used. This technique is gainful, easy-to-use, and emphases only on the genes that you want. We designated 18S-rRNA gene, as our house-keeping gene. For determine of methylation, methylation-specific polymerase chain reaction (MS-PCR) method was used.
The achieved results from this research show that the levels of DAPK gene expression have a significant difference. The rate of expression in patients was significantly reduced compared with the control group (P=0.0156). Also, the relationship between expression of DAPK factor and lymph node involvement was investigated. The results show the relationship between the factors studied. On the other hand, there was no significant relationship between the expression level of this gene and its promoter methylation (P=0.13).
This research shows that reduction in the rate of DAPK gene expression plays an effective role in the patients with breast cancer.

The benefits of aspirin have been proven by repeated examinations, especially in secondary prevention in cardiac infarction, stroke, and after interventional angiography and stent insertion.
This is a retrospective study on all patients who underwent non-cardiac surgeries between June 2005 and March 2013 in Ghaem hospital in Mashhad and aspirin continued due to many reasons. Most frequent surgeries included laparoscopic appendectomy and cholecystectomy. Information such as bleeding and its amount both during surgery and post-operative, hematoma after surgery, requiring re-operation due to bleeding and cardiovascular events in hospital were recorded and analyzed. Moreover, all patients were followed within one month after discharge from hospital to check whether any cardiovascular events had been happened. Furthermore, bruising in the skin, and bleeding after discharge were evaluated. Data were analyzed using SPSS Version 16 (SPSS, Chicago, IL, USA).
One hundred seventy patients enrolled in the study and all of them underwent general anesthesia. Of all patients 37.06% were male and 62.94% were female. The mean age was 52.78±5.01 years. Majority of operations included laparoscopic cholecystectomy (41.62%). Also in most of the patients (58.38%) surgery were emergency and discontinuation of aspirin were impossible. 91.37% of patients were taking less than 80 mg aspirin per day. Mean bleeding amount during surgery was 100 ml. 13 patients (6.59%) who undergo laparoscopic cholecystectomy and one patients in appendectomy group had bleeding more than 110 ml due to inadequate artery ligation and they underwent conversion to open surgery and bleeding were controlled successfully. Other eight patients (4.06%) treated conservatively without need to conversion to open surgery. In 7.61% of patients, ecchymosis happened which were healed within one month. No patient underwent reoperation due to post-operative hemorrhage. No vascular event and hematoma had been reported during one month follow up after surgery.
Continuing aspirin in perioperative period of non-cardiac surgeries were without additional risk of bleeding and it also helped to reduce risk of vascular evets post-operatively.

Bronchiolitis is one of the most common diseases of the lower respiratory tract in infants. Vitamin D has been shown to be protective against lower respiratory infections; however, there are limited and contradictory results in relation to serum vitamin D level and the incidence of bronchiolitis in children. The aim of this study was to compare serum levels of this vitamin in healthy infants and infants with acute bronchiolitis.
This case-control study conducted at Abuzar hospital in Ahvaz city, during October to March of 2014. Three groups of 45 eligible infants including control, low and high intensity of bronchiolitis enrolled to study. The severity of bronchiolitis classified according to scores derived from the respiratory distress assessment index. One to eight scores considered as low intensity and 9 to 17 scores considered as high intensity of bronchiolitis. Subsequently, 3 ml of venous blood sample were taken from them and the serum levels of 25(OH)D were measured by using an enzymatic kit.
60 (44.4%) infants were girls. The mean age of the control, low and high intensity of bronchiolitis groups were 11.2±5.2, 10±5.8 and 9.8±4.7 months, respectively (P=0.1). The mean of 25(OH)D concentrations in the control, low and high intensity bronchiolitis groups were 28.3±19.4, 17.7±11.7 and 13.6±5.7 nm/l, respectively. There was a significant difference in levels of 25(OH)D between the control-low intensity bronchiolitis groups (P=0.001) and the control-high intensity bronchiolitis groups (P=0.002), this difference was not significant between the two groups of bronchiolitis. There was a direct and significant correlation between serum level of 25(OH)D and age (r=0.2, P=0.005), breast milk consumption (r=0.3, P=0.001), and vitamin D supplementation (r=0.6, P=0.000).
In the present study, levels of 25(OH)D were significantly lower in infants with bronchiolitis than control group. In addition, 25(OH)D levels did not affect the severity of bronchiolitis.

Vaginal candidiasis is common in during pregnancy. It may lead to complications like abortions, premature birth, low birth weight, chorioamnionitis and fungal systemic neonatal infection. The aim of present study was identification of Candida species by mycological and molecular methods in pregnant women with vaginal candidiasis.
This cross-sectional study was performed on 80 pregnant women with or without clinical symptoms of vulvovaginal candidiasis referred to Shahid Noorani Talesh Hospital, Gilan University of Medical Sciences, Iran, from April to December 2015 (8 months). All specimens were examined by direct microscopy and culture on CHROMagar Candida medium for isolation and differentiation of major clinical-significant Candida species (spp.). Cultured media were incubated at 35 °C for 48 hours and evaluated based on color and number of grown colonies. If no growth was observed, the media were incubated for several additional days. Subcultures were done on Sabouraud dextrose agar (Merck, Germany) and Corn meal agar with Tween 80 media (Micromedia, Hungary) for further study. Identification of Candida spp. carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
In this study, vulvovaginal candidiasis was observed in 20 (25%) patients. Twenty-two isolates were obtained from culture of specimens on CHROMagar Candida medium (Paris, France). The most common isolated species was Candida albicans 16 (72.8%) and followed by Candida glabrata 5 (22.7%), Candida tropicalis 3 (13.6%) and Candida krusei 1 (4.5%) cases. Two patients had mixed infection with 2 different Candida species (C. albicans and C. glabrata) While using PCR-RFLP method, the Candida species were identified as 13 (59.1%) Candida albicans, 5 (22.7%) Candida glabra, 3 (13.6%) Candida tropicalis and 1 (4.5%) Candida krusei cases, respectively. In direct examination were seen yeast budding cells and pseudohyphae in 8 culture positive specimens. In the present study, results of conventional mycological method in differentiation of Candida spp. were consistent with molecular results in 80% of cases. There was also significant correlation between vulvovaginal candidiasis with clinical symptoms (P PCR-RFLP was able to identify correctly the Candida spp. as a complementary method.

Bloodstream infections are the most important causes of morbidity and mortality in hospitalized patients. Blood culture plays an important role in identifying most of bacterial agents of bloodstream infections. Knowledge about bacterial agents of bloodstream infections and also antibiotic resistance of these bacteria are important. Antibiotic resistance among bacterial agents of bloodstream infection including Acinetobacter, Klebisella, Pseudomonas, Escherichia coli, Enterobacter, Enterococcus, Staphylococcus aureus and Staphylococcus coagulase negative (CoNS) is one of the major challenges faced by physicians in treating. Therefore, this study was aimed to determine the frequency and antibiotic resistant patterns of bacterial isolates from hospitalized patient's blood cultured samples in the hospital, Tehran, Iran.
This research is a descriptive and retrospective study based on recorded data in Shariati hospital laboratory and under the supervision of Tehran University of Medical Sciences. The bacterial isolates were collected from positive blood cultures from October 2013 to March 2014. The frequency of bacterial isolates were determined by phenotypic and biochemical tests. The antibiotic resistance patterns of isolated bacteria were found by disk diffusion agar method. The diameters of inhibition zone were recorded and interpreted according to Clinical and Laboratory Standards Institute (CLSI) 2013.
The frequency of bacterial isolates was determined among 595 positive blood cultures as followed: 41% Pseudomonas, 20% Staphylococcus epidermidis, 10% Escherichia coli, 6% Acinetobacter lwoffii, 6% Staphylococcus aureus, 5% Stenotrophomonas, 3% Acinetobacter baumannii. The antibiogram test showed that 96.2% of Acinetobacter lwoffii, 92.8% of Acinetobacter baumannii, 66% of Pseudomonas aeruginosa, 85.7% of Staphylococcus epidermidis, 65% of Staphylococcus aureus, 75% of Klebsiella, 73.7% of Escherichia coli, and 50% of Stenotrophomonas were resistant to imipenem, piperacillin, piperacillin, erythromycin, erythromycin, ciprofloxacin, trimethoprim-sulfamethoxazole, and ceftazidime respectively.
The most prevalent bacterial isolate among the blood cultures of patients was Pseudomonas. The patients more than 50 years were more susceptible to blood stream infections. The most bacteria were isolated from the internal medicine department of hospital. The antibiotic resistance was also increasing especially in Acinetobacter, Staphylococcus coagulase negative, Escherichia coil and Klebsiella

Air pollution PM exposure associated with increased inflammation and decreased cellular immune function. The innate immune system is one of the first lines of defense against inhaled air pollution and is characterized by activation of lung key signaling pathways. One pathway is initiated by the activation of toll-like receptors (TLRs) that associated with airway cells culminates in the translocation of nuclear factor-kappa B and other transcription factors to the nucleus, and therefore initiation of altered signaling of pro-inflammatory mediators such as IL-1β and TNF-α. The purpose of this study was to investigate the effect of 4 weeks of aerobic training after long-term inhalation of black carbon black particulate matter on IL-β lung tissue in male rats.
The present study was conducted experimentally in October and November 2015 at the Sport Physiology Laboratory of Tarbiat Modares University of Tehran. 12 adult male Wistar rats (279.29±26.97) were divided to two groups: A: Daily, two hours inhalation of carbon black PM10, n=6), B: 60 minutes aerobic exercise activity, 50 percent average peak velocity, 15 minutes after inhalation of carbon black PM10. The gene expression of IL-1β was analyzed in lung tissue by real-time-PCR and Pfaffl formula. In order to determine the significant differences between groups independent t-test were used.
Although, there were no significant differences among the A and B groups, however, the mean of relative gene expression of IL-1β in group B was slightly lower than group A.
Four weeks regular aerobic exercise activity did not worsen lung tissue inflammation after long-term inhalation of carbon black PM10. It seems regular exercise training mitigate pulmonary inflammatory responses and in part, decrease the risk of pulmonary diseases.

Grave's disease is the most common cause (85% of all cases) of thyrotoxicosis in women in childbearing age. Many of the symptoms are similar to hyper-metabolic status during pregnancy. The cause of the disease is autoantibodies that stimulate the thyroid-stimulating hormone (TSH) receptor. Hyperthyroidism is uncommon in pregnancy and its prevalence is 0.1-%0.4. In this paper we introduce a patient who was admitted with a primary diagnosis of pulmonary embolism and treatment with final diagnosis of thyroid storm and was discharged with good condition.
In the first pregnancy of a 29-year-old woman with gestation age of 31 weeks was referred to obstetric emergency unit Ghaem Hospital, Mashhad, Iran in March 2015. She had Grave’s disease in her past medical history which was treated with methimazole before pregnancy and propylthiouracil (PTU) during pregnancy. In admission, she presented with tachycardia and tachypnea and hypertension and lower extremity edema. During pregnancy, she used propantheline instead of propylthiouracil due to pharmacy mistake. She admitted in Intensive care unit. After rule out of pulmonary embolism, ultrasonography showed a fetus with 30 weeks of gestational age with an approximate weight of 1680 grams. The amniotic fluid was reduced. She was treated with thyroid storm diagnosis due to a medication error. In serial obstetric visits fetal heart rate was not detected. Due to the fetal death, the pregnancy was terminated. Hyperthyroid therapy continued with PTU after delivery. She was discharged with a good general condition.
Despite the rarity of thyroid storm during pregnancy, in the event of unstable hemodynamic condition and cardiac dysfunction in pregnant women, rule out of thyroid disorders should be considered. Clinician should be paid attention to past drug history and underline disease of patient.