مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال هفتاد و سوم شماره 7 (پیاپی 175، مهر 1394)

The spread of influenza viruses in multiple bird and mammalian species is a worldwide serious threat to human and animal population's health and raise major concern for ongoing pandemic in humans. Direct transmission of the avian viruses which have sialic acid specific receptors similar to human influenza viruses are a warning to the emergence of a new mutant strain that is likely to share molecular determinants to facilitate their replication in human host. So the emerge virus can be transmitted easily through person to person. The genetic variations of the influenza viruses, emerge and re-emerge of new antigenic variants, and transmission of avian influenza viruses to human may raise wide threat to public health and control of pandemic influenza. Vaccination, chemoprophylaxis with specific antiviral drugs, and personal protective non-pharmacological measures are tools to treat influenza virus infection. The emergence of drug resistant strains of influenza viruses under drug selective pressure and their limited efficacy in severe cases of influenza infections highlight the need to development of new therapies with alternative modes. In recent years several studies have been progressed to introduce components to be act at different stages of the viral life cycle with broad spectrum reactivity against mammalian and bird influenza subtypes. A wide variety of different antiviral strategies include inhibition of virus entry, blocking of viral replication or targeting of cellular signaling pathways have been explored. The current inactivated influenza vaccines are eliciting only B-cell responses. Application of the vaccines has been limited due to the emergence of the new virus antigenic variants. In recent decade development of gene vaccines by targeting various influenza virus proteins have been interested because significant potential for induction of both humoral and cell mediated immunity responses. Enhanced and directed immune responses to viral vaccine can be achieved by using adjuvant. The ability of biological molecular adjuvant such as cytokines, interlukines, and bacterial derivatives to improve the immunogenicity of vaccines as a novel strategy is under evaluation, however, and immune system regulator proteins have additional considerations.

Cancer and obesity are two major public health concerns. More than 12 million cases of cancer are reported annually. Many reports confirmed obesity as a risk factor for cancer. The molecular relationship between obesity and breast cancer has not been clear yet. The purpose of this study was to investigate priorities of effective genes in the molecular relationship between obesity and breast cancer. In this study, computer simulation method was used for prioritizing the genes that involved in the molecular links between obesity and breast cancer in laboratory of systems biology and bioinformatics (LBB), Tehran University, Tehran, Iran, from March to July 2014. In this study, ENDEAVOUR software was used for prioritizing the genes and integrating multiple data sources was used for data analysis. Training genes were selected from effective genes in obesity and/or breast cancer. Two groups of candidate genes were selected. The first group was included the existential genes in 5 common region chromosomes (between obesity and breast cancer) and the second group was included the results of genes microarray data analysis of research Creighton, et al (In 2012 on patients with breast cancer). The microarray data were analyzed with GER2 software (R online software on GEO website). Finally, both training and candidate genes were entered in ENDEAVOUR software package. The candidate genes were prioritized to four style and five genes in ten of the first priorities were repeated twice. In other word, the outcome of prioritizing of 72 genes (Product of microarray data analysis) and genes of 5 common chromosome regions (Between obesity and breast cancer) showed, 5 genes (TNFRSF10B, F2, IGFALS, NTRK3 and HSP90B1) were the priorities in the molecular connection between obesity and breast cancer. There are some common genes between breast cancer and obesity. So, molecular relationship is confirmed. In this study the possible effect of gene F2 polymorphism in making breast cancer associated with obesity risk factor was confirmed, the fact that past studies have not been reported.

Ovarian sex cord-stromal tumors (SCST) account for rare ovarian malignancy. These tumors are 5-8% of all ovarian neoplasms. The most common type of sex cord ovarian tumors is granulosa cell tumor (GCT). In this study our purpose was to have a look at some of clinicopathologic aspects and treatment results of these tumors. In a retrospective study, all documents of patients with SCST was referred to tumor clinics of Ghaem and Omid Hospitals, from 1998 to 2008. The data of patients were collected and analyzed. In 39 (5.9) of the 398 cases, ovarian malignancies was present in SCST. Eight Patients omitted from the study because there were not enough data for them. The commonest pathology was adult granulosa cell tumor in 25 patients (80.6%). Two patients (8.33%) had juvenile granulosa cell tumor, they were 25 and 38 years old. At time of diagnosis, 27 cases (87.1%) were in early stages (stage I). Mean age of patients was 41 years (range 16-76 years) at time of diagnosis of disease. Surgical staging of cancer was performed in 14 patients (46.7%). We did fertility sparing surgery in 12 patients (40%). Two patients were pregnant after surgery. 17 patients (54.80%) did not receive chemotherapy. Three patients (9.7%) received radiotherapy. Overall survival rates were 95% at both 2 years and 5 years. Longer survival had correlation with early stages of disease (P= 0.002). Age, conservative surgery and chemotherapy had no correlations with survival. The prognosis of SCST is almost good. Most of the patients were diagnosed in early stage of disease. In sex cord ovarian tumor, the only factor that have a full effect on survival, is stage of the disease. If the patients desire to preserve fertility, we can do fertility sparing surgery with minimal effect on survival.

Magnetic resonance imaging (MRI) is widely applied for examination and diagnosis of brain tumors based on its advantages of high resolution in detecting the soft tissues and especially of its harmless radiation damages to human bodies. The goal of the processing of images is automatic segmentation of brain edema and tumors, in different dimensions of the magnetic resonance images.

The proposed method is based on the unsupervised method which discovers the tumor region, if there is any, by analyzing the similarities between two hemispheres and computes the image size of the goal function based on Bhattacharyya coefficient which is used in the next stage to detect the tumor region or some part of it. In this stage, for reducing the color variation, the gray brain image is segmented, then it is turned to gray again. The self-organizing map (SOM) neural network is used the segmented brain image is colored and finally the tumor is detected by matching the detected region and the colored image. This method is proposed to analyze MRI images for discovering brain tumors, and done in Bu Ali Sina University, Hamedan, Iran, in 2014.

The results for 30 randomly selected images from data bank of MRI center in Hamedan was compared with manually segmentation of experts. The results showed that, our proposed method had the accuracy of more than 94% at Jaccard similarity index (JSI), 97% at Dice similarity score (DSS), and 98% and 99% at two measures of specificity and sensitivity.

The experimental results showed that it was satisfactory and can be used in automatic separation of tumor from normal brain tissues and therefore it can be used in practical applications. The results showed that the use of SOM neural network to classify useful magnetic resonance imaging of the brain and demonstrated a good performance.

Low density lipoprotein (LDL) particles have shown to be heterogeneous structures with distinctive electrical charges. Alteration in the fatty acids content of the LDL particles is known to affect their structural features, electrical charges, and ultimately physiologic properties and, in this way, may play a role in the pathology of coronary artery disease (CAD). On the basis of evidences, in the present study, the relationship of fatty acids content of LDL particles and their electrical charge was assessed in patients with CAD in comparison with control subjects.

In the current case- control study, from subjects who referred to the Mostafa Khomeini Hospital in Ilam during a time period from December 2013 to October 2014, 40 CAD patients and 40 control subjects were selected based on the clinical and angiographic parameters. The fatty acids content and electrical charges of LDL particles were measured by using a gas chromatography system, equipped with a flame ionization detector GC-FID, Acme 6000 M (Young Lin Co., Korea) as well as a Zetasizer (Malvern Instruments Ltd., UK), respectively.

In the present study, CAD patients and control subjects were matched for age, sex, and body mass index (BMI). The electrical charge amounts of LDL particles in the patients group was significantly lower than those in the control subjects (P= 0.0001). There was an inverse correlation between the electrical charge amounts of the LDL particles and the saturated fatty acids as well as linoleic acid contents of them in CAD patients group. However, we found a direct correlation between the unsaturated fatty acids (monounsaturated fatty acids and some of the polyunsaturated ones) content of the LDL particles and their electrical charge amounts (P= 0.02).

Results of the present study demonstrated that the increased saturated fatty acids as well as the linoleic acid contents of the LDL particles are associated with decreased electrical charge amounts of these particles and this situation may engage in pathogenesis of CAD.

Convulsion is one of the common cause of hospital admission in children. Idiopathic seizure is when no anatomic, electrolytic, metabolic or hemorrhagic causes are found. Recently, lead poisoning, which is considered when serum lead levels are higher than the normal levels (previously 10 μg/dl changed to 5 μg/dl). Even lower levels of lead inflict harmful consequences in central nervous system (CNS) development in pediatric group. Due to air pollution and high lead level in air of Tehran, investigation the probable role of lead in producing or predisposing convulsion in children is very important. To determine the cerebrospinal fluid (CSF) lead level in children with idiopathic convulsion in compare with nonconvulsive ones (control). A case-control study upon 60 children (30 convulsive and 30 nonconvulsive control) admitted in Rasoul Akram and Ali Asghar University Hospitals, Tehran, from 2012 to 2013 had done. One ml of CSF obtained and lead level determined by atomic absorption test. The mean age between cases and controls was not different (mean= 30.18+27.36 vs 25.46±20.56 months, P= 0.1). The CSF lead level (μg/dl) had not meaningful difference between 2 groups (3.43+3.07 vs 2.78+2.77, P= 0.3), and no related to type of convulsion in cases (P= 0.7), the area under the curve (AUC) was 0.588; 1-0.433, P= 0.2). The CSF lead cutoff was 1.65 μg/dl; sensitivity of 70%, specificity of 46%, PPV and NPV was 56% and 60% respectively. The toxic blood level for lead is 3.5 μg/dl. The CSF lead level; even in little amount (1.65 μg/dl) is an acceptable sensitivity but lower specificity for differentiation the convulsive from nonconvulsive children. Although the role of genetic and other causes should be considered in idiopathic convulsion, probably, the high level of lead in CSF could predispose those children to convulsion. It can effect CNS development in children even in small amounts. Indeed, long-term effects of lead which continue to adulthood should be considered as well. Hence, it is paramount to rectify the ambient air lead pollution in Tehran.

Smoking is known as the most important preventable risk factor for morbidity and premature death. It is the fourth risk factor attributable to burden of disease globally. Because of the misconception that waterpipe is less harmless than cigarette and also less socially prohibited, people smoke waterpipe more. Studies showed that tobacco consumption rate is increasing among adolescents and it`s initiation age has been declined. The aim of current study was the assessment of the prevalence of different types of tobacco use among students aged between 14 to 18 year old in Tehran. Also we had a comparison with similar studies. In this cross-sectional study 2877 students between May and July 2014 have been assessed. Samples were collected from language institutes and “Farhangsara”s according to stratified cluster sampling based on the educational zones in Tehran. A structured questionnaire was used for different types of tobacco use habit assessment. Because of sampling method, data analysis was done with complex sample survey analysis in SPSS, ver. 20 (Chicago, IL, USA) and Stata, ver. 12 (College Station, TX, USA) software. P-values less than 0.05 considered as statistically significance. Among participants 11.5% (10.8%-13.3%) had cigarette smoking experience. The prevalence of current cigarette smoking was 4.4% (3.7%-5.3%). 1.4% (0.9%-2.2%) of girls and 7% (5.7%-8.5%) of boys were current cigarette smokers (P< 0.001). Waterpipe smoking experience prevalence was 41.5% (39.7%-43.4%) in total, 41.7% (39.2%-44.2%) in girls and 41.4% (39.2%-44.2%) in boys. Current waterpipe smoking was reported in 25.7% (24.1%-27.4%) of students with no statistically significant difference between boys and girls. Pipe smoking experience prevalence was 3.9% (3.2%-4.7%) and it was more frequent in boys. Cigarette smoking was significantly higher among boys than girls, while waterpipe smoking prevalence showed no difference. In addition, smoking prevalence was higher among students who had smoker parents or smoker friends and also had a bad economic status. It seems that specific interventions should be considered to reduce tobacco burden in adolescents specially in regard to cigarette and waterpipe smoking.

To reduce cesarean section rate, we need complex interventions to modify related behavior. We aimed to identify the effectiveness of a community-based intervention on prenatal care status, delivery and decline of cesarean section rate. A quasi-experimental study was carried out on mothers residing in Khak Sefid and Javadiyeh in Tehran from January 2011 to September 2014. Study population was 274 mothers; attending in health centers for first vaccination of their neonates. Mother's demographic data were recorded in some questionnaires. One year interventions including; consultation, distribution of educational package and training courses (for mothers, fathers and their families, educational programs for midwives, obstetricians and gynecologist, residents, medical students), accomplishment of 10 steps baby-friendly principles and provision adequate personnel in labor-delivery room were implemented in community, hospitals and health centers. After intervention, 250 mothers who were attending in health centers for vaccination of 2 months aged neonates were assessed and their data were recorded in the same questionnaires. The effectiveness of intervention on cesarean section rate and cesarean tendency in before and after intervention groups were compared. P< 0.05 was considered as level of significance. Of 274 mothers in "before intervention" group 193 (70.44%) and of 250 mothers in "after intervention", 169 subjects (67.6%) had cesarean section. Although a significant decline was seen in cesarean tendency in "after intervention" group (P= 0.034), no significant difference was seen between 2 group's cesarean section rates (P= 0.48). In "after intervention" group episiotomy, induction of labor rate and maternal morbidity were significantly lower than "before intervention" group (P= 0.0001, 0.0001, 0.01). Although no significant difference was seen between two groups neonatal birth weight (P= 0.69), a significant difference was seen between two group's gestational age (P= 0.007). After intervention, in spite of no decline in cesarean section rate, NVD tendency and morbidity rate were raised and improved respectively. It seems that cesarean section rate was influenced by other important factors.

The influenza virus is one of the most important factors for higher morbidity and mortality in the world. Recently, researchers have been focused on influenza conserved antigenic proteins such as hemagglutinin stalk domain (HA2) for vaccine production and serological studies. The HA2 plays a major role in the fusion of the virus with host cells membrane. The immunity system enables to produce antibody against HA2. The aim of this study is polyclonal antibody production against influenza HA2.

This study was done in the Influenza Research Lab, Pasteur Institute of Iran, Tehran for one year from September 2013 to October 2014. In the present study, recombinant HA2 protein was produced in prokaryotic system and purified using Nickel affinity chromatography. The purified HA2 was mixed with Freund’s adjuvant (complete and incomplete) and injected into two New Zealand white rabbits by intramuscularly and subcutaneously routes. Immunization was continued for several months with two weeks interval. Before each immunization, blood was drawn by venous puncture from the rabbit ear. Function of rabbit's sera was evaluated using radial immunodiffusion (RID) in both forms, Single RID (SRID) and Double RID (DRID). Finally, antiserum activity against HA2 was evaluated using western blotting as serological assay.

Sedimentary line and zone was observed in RID assays (SRID and DRID) represent interaction between HA2 protein and anti- HA2 antibody. As well as, western blotting results was positive for HA2 protein. Therefore, these results showed that polyclonal antibody produced against HA2 protein can identify HA2 protein antigenic sites.

These findings show that humoral immune responses have properly been stimulated in rabbits and these antibodies can identify HA2 protein and may be suitable for other serological methods.

Standard treatment of Gestational Trophoblastic Disease (GTD) is chemotherapy. Single-agent chemotherapy regime including Methotrexate (MTX) or Actinomycin. Single-agent is widely used in treatment of persistent trophoblastic disease. We reported an uncommon toxicity of low-dose single-agent methotrexate in a patient.

A 20-year-old woman, primary gravid after two months missed period and spotting with diagnosis of incomplete abortion with uterine size equivalent of ten weeks pregnancy (8-10 cm) underwent evacuation curettage. In serial follow-up, based on rise of beta-hCG titer and absence of metastatic disease, it was categorized as low-risk persistent trophoblastic disease. She was referred to gynecology oncology center of Ghaem Hospital, Mashhad University of Medical Sciences in May 2014. Because of rise of beta-hCG titer, after complete metastatic work-up and lack of disease in other sites, persistent disease was diagnosed and candidate for chemotherapy (single agent low-dose). The patient received first course of therapy with MTX (50 mg/m², intra muscular). Unfortunately, after two days of treatment she developed uncommon severe toxicity, fever, severe nausea and vomiting, tachycardia, and generalized weakness. Also, we found hematologic abnormality (WBC: -14000-15000 µI, platelet- 540 µI and sever neutropenia), and abnormal rising in liver function test (SGOT, SGPT) (three to four times) and renal function test (BUN and Creatinine) (two times). In addition, she had disseminated erosive lesion in all of body especially in face. Due to the fatal side effects of chemotherapy, she was admitted to intensive care unit (ICU). Fortunately, after two to three weeks, she was improved by conservative management. After few weeks beta-hCG titer was in normal limit. However she had normal serial beta-hCG in one year of follow-up.

It is important to emphasis unpredictable side effects of chemotherapy with low-dose methotrexate.