Tehran University Medical Journal

The role of cytokines in systemic lupus erythematosis: review article

Nima Rezaei

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, involves almost all organs such as skin, heart, kidneys and central nervous system. The disease is characterized by vascular and connective tissue inflammation in a recurring pattern of remission and flare. Although the exact pathophysiology of disease has not been fully understood yet, the fundamental defect in SLE is attributed to dysfunction of T lymphocytes in controlling of B-cell that leads to polyclonal activation of B lymphocytes and production a large quantity of autoantibodies against nuclear and cytoplasmic components. These autoantibodies can damage tissues either directly or as a result of immune complex deposits. Several factors are involved in pathogenesis of SLE which can be divided into three major groups, environmental factors, genetic components, and immunological disturbances. They could breakdown body tolerance towards endogenous antigens and cause abnormal immunologic response to the healthy tissue, resulting in tissue damage. SLE occurs more frequently in female than male. It seems that immunological factors have important role in SLE. Inflammation and vascular endothelium irregularities are a number of main pathologies seen in SLE. Cytokines are protein mediators that play an essential role as regulator of innate and adaptive immune response against microbial agents or self-antigens. Influences of cytokines in autoimmune diseases such as SLE are poorly understood. Studies in both experimental animal models of lupus and patients with SLE have revealed a number of cytokine pathways that are important in the disease process. These studies showed that overexpression of inflammatory cytokines increases the proliferation of auto reactive B-cells and results in higher production of autoantibodies. Among them, the role of B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), TNF-α, IFN-α, IL-6, IFN-γ, IL-23/IL-17, IL-10, IL-21 are prominent, which is associated with the generation of pathogenic autoantibodies and formation of immune complexes. In this paper, the role of cytokines and their encoding genes are described, while therapeutic applications are also briefly presented.

Germline mutation of exon 19 of RET proto-oncogene in an Iranian population with Medullary thyroid cancer

Mehdi Hedayati

Background: Medullary thyroid cancer (MTC), includes 5-10% of all the thyroid cancers. RET proto-oncogene mutations have been found in association with MTC development. Therefore, identification of the mutations in RET can allow early diagnosis of the families who are at the risk of the disease. The goal of this study was to investigate existence and association between mutations in exon 19 of the RET proto-oncogene in an Iranian population medullary thyroid cancer patients and their family members. Methods: This study was run in the research laboratory of Research Institute for Endocrine Research Center Shahid Beheshti University of Medical Sciences from May, 2013 to May, 2014. In this study, 110 patients with confirmed medullary thyroid carcinoma were selected and examined. At first, the genomic DNA content of the peripheral white blood cells (WBC) of the samples were extracted using a saturated salting out and proteinase K standard method. Exon 19 of the RET proto-oncogene using polymerase chain reaction (PCR) method was amplified. Then the desired PCR products formation was confirmed by electrophoresis technique for true amplification, and finally the amplified samples were used for direct sequenced for finding and assessing any possible mutations Results: In this study, two nucleotide changes at position rs2075912 (Y: T/C) and position rs2075913 (W: T/A) exon 19 RET proto-oncogene were found in the patients with medullary thyroid cancer. The frequency of both nucleotide changes were higher in men than women with medullary thyroid cancer. The frequency of the rs2075912 and rs2075913 were 11.2 and 6.3% higher in men than women. But in statistical analysis, there was no association between age, sex and the founded two mutations. Conclusion: In addition to mutations in other exons of proto-RET, mutations in exon 19 can also be used for early detection and confirmation of medullary thyroid carcinomas.

UBD role of gene expression in patients with breast cancer

Elham Moslemi

Background: Breast cancer is the most common non- skin cancer among women and it’s the second leading cause of cancer related death in women. Ubiquitin and ubiquitin like proteins are member of signal transduction pathways which have several cellular functions. It has shown that Ubiquitin like protein D (UBD) has accelerated the cancer progress. The aims of this study is evaluation of UBD gene expression in women suffering from breast cancer and its correlation with disease progression. Methods: In this study 30 FFPE (Formalin-fixed, paraffin-embedded) samples 20 cases from breast cancer and 10 cases from mammoplasty were collected from Parsian and Kasra Hospitals in Tehran after confirmation by pathologist. For each sample collection characters included ER-positive, lymph node negative, tumor size less than 5 cm in diameter were considered. Samples belonged to May 2010 up to April 2012. At first paraffin was removed by adding xylene then xylene removed with replacing ethanol 98%. After removing ethanol, RNA was extracted from samples by using RNX plus solution and cDNA synthesis were performed by using Moloney murine leukemia virus (M-MuLV) enzyme. UBD gene expression were examined in all samples cDNA by relative Real Time PCR. In this study GAPDH gene expression was also used as internal control. Results: UBD gene expression was obtained by calculating ΔΔCT and RQ. The average incensement of UBD gene expression in comparison of normal samples was 11 times. The results have shown that the level of UBD expression was related to the development and extend of the disease. In patients with stage 1 of disease, UBD gene expression had 2.73 times increase (P=0.001) compared to the control samples. However in stage 4 of disease, this number has increased up to 19.4 times (P=0.0005) more than normal. Conclusion: Considering the results of this study, it could be said that UBD gene expression as useful biomarker has an important role in detection of breast cancer. In addition as UBD gene expression levels increased stages of disease increased too. So that evaluation of UBD gene expression can be useful in early detection of disease.

The effect of varicocelectomy on serum testosterone level in infertile men with varicocele: an interventional study

Meysam Jangkhah

Background: Varicocele is recognized as the most common cause of male factor infertility and is found in 15% of the general population. This prevalence increases to 35% in men presenting with primary infertility and between 70 to 80% in men presenting with secondary infertility. The effect of varicocele on Leydig cell function and testosterone production has been always a question. In this study we examined the effect of varicocelectomy on serum testosterone. Methods: This research protocol was approved by the institutional review board at Royan Institute in infertility department and also this study has been done in Royan Institute (Tehran, Iran) during one year since September 2012 till October 2013. In this cross-sectional study, Serum levels of total testosterone in 79 men with clinical varicocele and in 70 fertile men who served as a control group were compared. Men aged 23–46 years with clinically palpable varicoceles as determined by physical examination were studied. Three to 6 months, testosterone levels were measured again after varicocelectomy, then testosterone levels were compared before and after varicocelectomy. Results: The mean of serum testosterone levels before surgery in infertile men with varicocele and fertile men were 590(230) vs. 583(237) ng/dl respectively. No statistically significant changes were noted in serum testosterone levels for any groups. Three month after varicocelectomy mean serum testosterone levels were significantly increased in infertile men with varicocele compared with preoperative levels from 590 (230) to 663 (242) ng/dl (P=0.009). Also the testis volume of patients were examined, which were divided into two groups included the men with testis volume less than 16 ml (<16) and more than 16 ml (≥16). Conclusion: In infertile men affected with clinical varicocele, varicocelectomy seems to have caused positive impact on the level of serum testosterone increase. It is thought that positive effect is probably caused by improvement of the Leydig cell functions which induce the increase of serum testosterone level.

Clinical outcome of Induction therapies in patients undergoing renal transplantation

Javad Zeynali

Background: The goal of Induction therapy is to prevent acute rejection during the early posttransplantation period by providing a high degree of Immunosuppression at the time of transplantation. Induction therapy is often considered essential to optimize outcomes, especially in patients at high risk for poor short-term outcomes. The optimal prophylactic induction immunosuppressive therapy to prevent kidney transplant rejection remains controversial and historically, immunosuppressant selection was solely based on efficacy in preventing rejection. Methods: In a cross-sectional retrospective study, 410 cases of renal graft recipients were reviewed in the Hasheminejad Hospital, Tehran, Iran from March 2008 to March 2011. The adult patients with induction therapy with age over 18 years were studied for the indication, results and adverse effects of Induction therapy. Results: From 66 transplanted patients with induction therapy, 44(66.7%) patients were male. The mean age±SD of patients with induction therapy was 39.9±13.2 years. The most common cause of Induction therapy was cadaveric transplantation (45.5%), other causes was the prior history of transplantation (24.2%), without risk factor of rejection, panel reactivity test (PRT)>20% and delay graft function. Anti-thymocyte globulin (rabbit) is the most commonly used agent (97%) for induction therapy. The rate of acute rejection was 16.7% percent (11 patients), that the most of them related to the panel positive patients. The most common adverse effect of anti-thymocyte globulin was thrombocytopenia (15.2%) and the rate of New Onset Diabetes mellitus After transplantation (NODAT) and leukopenia was 10.6%, 1.5%, respectively. The urine culture was positive in 6 (9.1%) patients with induction therapy and positive blood culture was seen in one patient (1.5%). The viral and fungal infections were not seen. Conclusion: No standard Induction immunosuppressive regimen exists for patients undergoing renal transplantation. Anti-thymocyte globulin with low dose regimen is the most commonly used agent. The PRT>20% had the most association with acute allograft rejection. The most common side effect of induction therapy was thrombocytopenia.

Specification of requirements for health social-network as Personal Health Record (PHR) system

Ali Asghar Safaei

Background: Patient-centered care improves the quality of life and health care, and reduces the costs of care. The advent of new technologies such as health social networks, and personal health records (PHR), have significant impact on the patient-centered care. The aim of this article is to analyze and provide a set of features and requirements needed by the users of health social network serving as a PHR (Personal Health Record) system. The combination of capabilities offered by PHRs and social networks providing better delivery of patient-centered care. Methods: In this paper, after a brief study of capabilities and features of existing health social networks and based on a comparative study, a set of requirements which are necessary to create a comprehensive health social network as a PHR system are proposed. Identification of such a systems stakeholders and users e.g. healthcare professionals, patients, and healthcare organizations is important for categorizing the requirements. Also, classifying relatively vast range of existing systems is needed to have a better analyze and design. Results: The proposed health social network can be used by different user groups in healthcare e.g. healthcare professionals, patients, and healthcare organizations. According to the each user group’s requirements, it provides separate facilities for them. The users of this integrated health social network can optionally share some of their information with other users in their group or with users in the other groups and interact with them. Studies show that the proposal requirements and capabilities for health social network not only cover the capabilities of similar systems but also satisfactory provide the requirements of a PHR system to deliver the patient-centered care. Conclusion: The proposed set of requirements are qualitatively compared with the other similar systems. Using the proposed health social network that provides PHR capabilities for its users will have an irrefutable impact on quality and efficiency of patient-centered care, and play an important role in improving the health of society.

Vitamin D deficiency and mode of delivery: a study in Tehran Women General Hospital

Mojgan Asadi

Background: Vitamin D deficiency is a widespread problem especially in the developing countries like Iran. The prevalence of vitamin D deficiency differs from moderate to severe among Iranian women, particularly among pregnant women, and it can cause some problems such as preeclampsia, gestational diabetes mellitus (GDM), premature labor and primary cesarean section. The aim of this study was to evaluate whether the mode of delivery is related to serum vitamin D levels or not and if there is any difference in the percentage of cesarean section between vitamin D-deficient and vitamin D-insufficient women. Methods: This cross-sectional study was carried out between the April 2012 and April 2014 in a woman university hospital, Tehran, Iran. One hundred and eighty-six women aged between 17 and 52 years old (Mean age 28.46 and SD5.97) were surveyed in this study. The study group comprised of (N=186) consecutive cases attending Tehran Women General Hospital Clinic for normal vaginal delivery or cesarean section. Women who underwent cesarean section due to previous cesarean delivery were not recruited for the study. The participants were divided into two groups: women with vaginal delivery and women with cesarean section. Serum vitamin D concentration (25(OH) Vitamin D) was measured for each patient. Concentration of serum vitamin D was compared between these 2 groups. Results: One hundred and twenty-eight (68.8%) women had cesarean section and 58 (32.2%) had vaginal delivery. Median and inter-quartile range (IQR) of serum 25(OH) D were 13.64 and 12.47 ng/ml respectively, among women with cesarean section, compared to 11.68 and 12.59 ng/ml in those with vaginal delivery. No statistically significant difference was detected in serum vitamin D between these 2 groups (P=0.72). In addition, no statistically significant difference was detected between women with vitamin D deficiency and women who were vitamin D insufficient (P=0.8). Conclusion: In this study, there was no association between serum vitamin D levels and delivery mode.

Vitamin D deficiency in population with BMI greater than 25 kg/m2 and its association with demographic and anthropometric indices

Zahra Alizadeh

Background: Today obesity and overweightness are the major health problem all over the world. The relation between decreasing serum level of vitamin D and some chronic diseases such as diabetes and obesity was shown in the available studies. The aim of this study was to determine the prevalence of vitamin D deficiency among obese and overweight Iranian population and its relation with age, sex, occupation, body fat percentage and body weight according to body mass index. Methods: In a descriptive cross-sectional study, all patients who were referred to obesity clinic of Imam Khomeini Hospital, Tehran, for weight management throughout one year were included to the study. The prevalence of vitamin D deficiency with serum level lower than 30 ng/ml among 107 subjects was evaluated. The data were analyzed by SPSS, ver. 19 (SPSS, Inc., Chicago, IL, USA). Quantitative variables were presented as mean±SD and qualitative variables were presented as relative frequency. The groups were compared with independent samples t-test and Chi-square test. The level of significance for comparing the groups was considered at P<0.05. Results: In 107 participants, vitamin D deficiency in 81 subjects (75.7%) was reported. The prevalence of deficiency in participants with body mass index between 25 to 29.9, 30 to 34.9 and equal or greater than 35 kg/m2 was 77.3%, 83.7% and 69.4%, respectively. However, the differences between overweight and obese groups were not significant (P=0.193). The prevalence of moderate and severe vitamin D deficiencies among the participants was 50.5% and 25.2 %, respectively. Vitamin D deficiency was more common in participants below 50 years of age compared with those older than fifty (P=0.001). Conclusion: The prevalence of vitamin D deficiency was high in obese and overweight population especially among individuals younger than 50 years. It seems that, it is necessary to add prevention and management of this deficiency to obesity treatment protocols especially in the young adults.

Measurement of subcutaneous adipose tissue thickness by infrared images during liposuction surgery: brief report

Fatemeh Valipoori Goodarzi

Background: Currently, there are many techniques to measure subcutaneous body fat but these methods have many limitations. In this study, we tried to provide a clustering algorithm to measure the thickness of subcutaneous fat in thermography images. Methods: For the detection of subcutaneous adipose tissue in the midline area (from pubis to the xiphoid process), imaging takes place in the right or left lateral sides of the concerned person and to detect this tissue at the left and right flank (from ribs to the iliac crest), imaging takes place from the front. This study was done on 100 subjects (50 female, 50 male) of patients referred to the Shahid Mobini Hospital of Sabzevar since April 2013/4 to December, 2013 and the thickness of their subcutaneous fat in midline abdomen from pubis to the xiphoid process and flank from ribs to the iliac crest were measured based on thermal model and using K-Means and Fuzzy c-means (FCM) clustering methods and also recursive connected components algorithm. Results: Subcutaneous fat tissue can quickly appear in the thermogram as an area of low temperature and since in the thermal images, temperature is characterized by the color, as a result, subcutaneous fat tissue must have lower levels of color (temperature) relative to internal body tissues. All the measurements based-on thermal images to determine the maximum thickness of subcutaneous fat were compared with ultrasound. The results of our method were similar to the results of ultrasound method done by a radiologist, with the acceptable approximation. Conclusion: The method presented in this paper is considered as a noninvasive and cost-effective method to measure the thickness of subcutaneous body fat.

A patient with isolated pancreatic tuberculosis: case report

Davod Tasa

Background: Although Tuberculosis (TB) is prevalent in developing countries, visceral TB is rare. Most cases of pancreatic tuberculosis are seen in association with disseminated TB (miliary) but isolated pancreatic infection is very rare. Especially when present in immunocompetent hosts. In clinical and radiological evaluation, pancreatic TB may present as a pancreatic abscess, acute or chronic pancreatitis, and cystic or solid pancreatic masses, so can confused with neoplasm in most cases. Case presentation: In winter of 2013, a 52-year-old woman was admitted to this hospital with epigastric pain. She also mentioned a history of weight loss during previous three months. Liver transaminases and total bilirubin were within normal range. Chest X-ray performed was negative for any cardiopulmonary process, and lung fields were noted to be clear. A purified protein derivative (PPD) skin test for tuberculosis yielded an induration of less than 1 centimeter. An abdominal CT- scan with IV and oral contrast was done. A 2×2 cm mass was seen in the pancreatic head. A diagnostic laparotomy was done. Conclusion: During surgery, a completely necrotic mass was in the pancreatic head. samples were sent for frozen section. The tuberculosis granuloma was diagnosed. Four drug anti-tuberculosis medication was started and continued for six months. Repeat imaging of the abdomen performed 6-months after the initiation of anti-TB therapy revealed complete resolution of the pancreatic mass, and antitubercular therapy was discontinued after a 6-month duration. Pancreatic tuberculosis can present with a variable spectrum of imaging findings. Furthermore, TB should be considered as a cause of any suspicious pancreatic lesion, especially in patients from areas where the infection is endemic.