Tehran University Medical Journal

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Background: Mycosis fungoides (MF) is the commonest T-Cell lymphoma (CTCL) involving skin and its appendages to variable degrees. Nail involvement is one of multiple dermatologic manifestation of this disorder and could have negative impact on psychological status of patients and producing therapeutic challenge to physician. We aimed to evaluate prevalence and subtypes of nail involvement in MF patients attending dermatology clinic, Razi Hospital in Tehran, Iran. Methods: All patients having MF confirmed via histopathology, visiting Razi Hospital Dermatology Clinic, Phototherapy and follow-up on inpatient wards from 2010 to 2011, were included. Patients examined by dermatologist researcher focusing on nail changes and all detected nail changes including onycholysis, longitudinal ridges and 11 more other changes, recorded in appropriated questionnaires. Treatment regimen prescribed to the patients also recorded as well as clinical CTCL staging. Results: A total of 60 patients, including 28 (46.7%) males and 32 (53.3%) females entered the study. 18 patients (12 males and 6 females) had different nail changes including longitudinal ridging, leukonychia, pitting and nine more morphological changes in decrescendo order. Ten patients had smoking history including four patients with nail changes. The commonest used treatment was local bath Psoralen and UVA light therapy (PUVA). Overall nail involvement in our study was approximately 30%. There was no significant relationship between prevalence of nail changes, demographic and clinical specification of underlying CTCL disorder especially tumor stage. Also, no significant relationship between prevalence and type of nail involvement with prescribed therapeutic regimen was found. Conclusion: We found about 30% prevalence that is a little higher than previously shown. It seems that nail changes in CTCL have no relationship to CTCL staging or other specifications including demographic specifications.

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Background: Vesicoureteral reflux (VUR) is the retrograde flow of urine from the bladder into the ureter and toward the kidney. Vesicoureteral reflux is the most com-mon inherited disease in urogenital system. Primary VUR is the most common urologi-cal anomaly in children and it has been reported in 30-50% of those who present with urinary tract infection (UTI). The association of vesicoureteral reflux, urinary tract in-fection and renal damage is well known. ‍Current methods for vesicoureteral reflux di-agnosis are unpleasant. Therefore, human leukocyte antigen system not only might help to detect causative gene but also would assists to establish better prognoses tests of this disease. In this study, the relationship between vesicoureteral reflux and HLA-DRB1 and HLA-DQB1 genes were investigated. Methods: This study applied on forty vesicoureteral reflux confirmed children from Kerman province, Iran. These children have been admitted to the Afzalipour Hospital for UTI and primary VUR for them was proved by voiding cystourethrogram (VCUG). Also, forty children without any VUR sign as control group. DNA was extracted from the whole blood sample and was amplified using sequence-specific priming polymerase chain reaction (PCR-SSP) method. Finally PCR products were evaluated by electropho-resis in 1.5% agarose gel and frequency of alleles and haplotypes were compared by Chi-square test. Significance level was assumed at P< 0.05. Results: Low-resolution HLA typing showed the frequency of the HLA-DR17 antigen was significantly increased in vesicoureteral reflux children compared to control group (P= 0.039). On the other hand HLA-DR16 was significantly decreased in vesicoureteral reflux group. Also, frequency of HLA-DQ2 was significantly higher in patients com-pared to control group (P= 0.002). DRB1 (11, 17) and DQ (2, 7) haplotypes were also higher in vesicoureteral reflux patients (P= 0.027, P= 0.01). Conclusion: The HLA cluster might affect on susceptibility to vesicoureteral reflux es-pecially by locus which located close to HLA-DRB1 and HLA-DQB1 genes. This study demonstrates for the first time in Iran. However, further extensive researches with a large number of samples from different populations and ethnicities are required to val-idate the results obtained in this study.

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Background: Uterine myomas are benign tumors of the uterus and the most common solid pelvic tumors causing symptoms in approximately 25% of women in their reproductive years. However, its etiology and pathogenesis remain obscure there is increasing evidence that endometriosis is inherited as a complex genetic trait. Recent studies indicated the involvement of glutathione S-transferase M1 (GSTM1) gene in the pathogenesis of this disease and current investigations are devoted to the other members of phase II detoxification system genes such as glutathione S-transferase T1 (GSTT1). Therefore, current study was carried out to investigate the distribution of GSTM1 and GSTT1polymorphisms in Iranian population in order to estimate possible impact of null-alleles of each gene in development of this disease. Methods: In this study, 50 patients with endometriosis diagnosed by both pathology and laparoscopic findings according to the revised American Fertility Society classification of endometriosis were recruited from subjects referred to the Pasteur Institute of Iran between November 2012 to September 2013. Accordingly, controls (n=50) were subjects without any of aforementioned gynecologic conditions. The genomic DNA was extracted from peripheral blood leucocytes using the salting out method and GSTM1 and GSTT1 genotyping for gene deletions were carried out using Gap-polymerase chain re-action. Logistic regression analysis was applied to assess whether there was any significant risk increase between the case group with higher null genotypes compared to control group. The level of statistical significance was set at 0.05 and all analyses were conducted using the SPSS version 18.0 (SPSS Inc., Chicago, IL). Results: There was significant evidence that the distribution of the GSTM1 and GSTT1 genotypes differed between the patients and the controls with an allelic odds ratio (OR) of 3.56 (95%CI: 1.35-9.37, P=0.01) and 3.92 (95%CI: 1.4-10 P=0.009) respectively. Data analysis also revealed that individuals with both GSTM1 and GSTT1 null genotypes (-/-) had higher risk to develop the disease in comparison to the people with the both present (+/+) genotype (OR:19.23, P=0.007). Conclusion: The findings suggest that the GSTM1 and GSTT1 genetic polymorphisms are associated with the development of endometriosis in Iranian women which is in agreement with previous results obtained in other populations. However, the ethnic variations of polymorphisms should be evaluated in detail and differences should be incorporated into investigations of susceptibility variants for this disease.

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Background: Biosynthesis of nanoparticles has attracted the attention of the scientific community in nanotechnology and biotechnology due to their extensive application in the area of material sciences and medicine. Nowadays, despite a various application of nanomaterial’s, there is a little information about their impact on human health. In this study, we investigated the comparative study on cytotoxicity effect of biological and commercial synthesized nanosilver on human gastric carcinoma (AGS) and normal lung fibroblast (MRC-5) cell lines. Methods: The current experimental study was carried out in Islamic Azad University, East Tehran Branch, from April to November 2014. The biological synthesis of nanosilver was obtained from Eucalyptus plant extract as a reducing agent. Further to more analysis, morphological study on size and shape of developed biological nanosilver was characterized by performing scanning electron microscopy and dynamic light scattering. AGS and MCR-5 cell lines were treated with various concentration of nanosilver for 24, 48 and 72 hours. Finally, the cell viability was evaluated by using MTT assay. Results: The results show that the nanosilver exerts a dose-dependent inhibitory effect on viability of cells. At 100µg/mL of commercial and biological synthesized nanosilver, the viability of AGS was reduced to 7.47±0.002% (P=0.002) and 3.65±0.01% (P=0.003) after 72 hours, respectively. In addition, the viability of MRC-5 at the same condition was reduced to 10.27±0.19% (P=0.001) and 9.16±1.53% (P=0.002), respectively. Conclusion: Based on a thorough literature surveys, the present study is the first research about biosynthesis of nanosilver using Eucalyptus plant extract. This eco-friendly and cost effective method can be used for large scale production of silver nanoparticle. In addition, based on the current obtained data, commercial and biological synthesized nanosilver can more inhibitory effect on cancer cells compared to the normal cells. Hence, silver nanoparticles might be used as a new strategy for treating many human cancers. However, further studies are necessary to ascertain their potential as anticancer agents.

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Background: Inguinal hernia is a common surgical problem which increases with aging especially in men. A common method for treatment is surgical repair using prosthesis, Lichtenstein technique. One frequent complication after inguinal herniorrhaphy is soft tissues seroma. There are several methods to prevent or to drain seroma. Some surgeons suggest the insertion of closed suction drainage system but others disagree. Methods: In this clinical trial study, 42 patients who are candidate for hernia repairing (Lichtenstein technique), referred to Amir Al-Momenin Hospital in Semnan, Iran, from 2011 to 2012, were randomly divided into two groups. So that, the list of eligible patients in the study, were numbered, and then using the patients' code, patients, who assigned an odd number in the registration list, were allocated to group 1, the remainder were placed in group two. The two first numbers in registration list (1 or 2), were randomly assigned to groups. Group 1 underwent hernia surgery without closed suction drainage and the second group underwent hernia surgery with closed suction drainage. The patients were evaluated for seroma, hematoma or wound infection after 24 hours, during days 4 to 7 and days 10 to 15 following surgery. Results: No adverse event including hematoma, seroma or wound infection occurred in either group with or without closed suction drainage in the first 10 days after surgery. Only one patient carried wound infection during days 10 to 15 following operation who was in the group with closed drainage (P=1.00). Conclusion: In this study, Seroma and hematoma was not observed in patients with and without closed suction drainage. To avoid drains' complications, indiscriminate use of antibiotics, prolonged hospital stay, we do not recommend the use of drains in this type of surgery.

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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. Methods: 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. Results: 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 parents' 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). Conclusion: 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.

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Background: The incidence of Patent Ductus Arteriosus (PDA) in premature infants whose birth weight is less than 1500 grams is approximately 30-60%, most of them need medical or surgical interventions. The purpose of this study is to determine the efficacy of prophylactic treatment with oral paracetamol (Acetaminophen- Hakim® Oral Drops 100 mg/ml, Hakim Pharmaceutical Co., Tehran, Iran) for PDA in preterm infants. Methods: A randomized clinical trial conducted from March 2012 to March 2013. Thirty-two preterm newborns whose gestational age was under 32 weeks and birth weight was 1500 grams or less, admitted in neonatal intensive care unit (NICU) of Vali-Asr Hospital, Tehran were studied prospectively. They were randomly assigned in two groups. The prophylaxis group received oral paracetamol for a period of two days starting during first 24 hours of life. No placebo was given to the control group. Echocardiography was performed 24-36 hours after the last given dose in prophylaxis group and on the 4th and 5th day in control group. A p-value less than 0.05 are considered significant. Results: There were 16 newborns in each group (20 boys and 12 girls). In 12 newborns of prophylaxis group the ductus arteriosus was closed although in control group in 8 newborns the duct was closed. No significant difference was observed in sex, gestational age, birth weight, mode of delivery, multifetal gestation and birth order between two groups. The rate of ductal closure was 75% and 50% in prophylaxis group and control group respectively (P=0.27). Conclusion: Our study demonstrated that prophylactic paracetamol is ineffective in PDA closure, although the rate of ductal closure between two groups seems remarkable. Paracetamol as a new strategy for PDA closure because of cost effectiveness and harmlessness may be used in future. However, we presume larger sample size studies are needed to show the efficacy of paracetamol, side effects, and complications in PDA prophylaxis treatment.

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Background: Pregnancy is a phenomenon that antigens of semi allogenic fetus are in direct contact with mother's immune system. Immune dysregulation can cause fetus rejection by mother's immune system responses. Human leukocyte antigen-G1, as an immunotolerant molecule has a major role to induce tolerance during pregnancy by suppression of natural killer cells through inhibitor receptors on these cells. Natural killer cells have an important role in immune surveillance and these cells can be reaction with HLA-G molecules on the trophoblast cells surface. This function prevents natural killer cell invasion against fetus trophoblast cells. The purpose of this study was determination of natural killer cells percent and human leukocyte antigen-G1 expression in peripheral blood of threatened-abortion pregnant women in comparison with control group. Methods: This case-control study was conducted from, February 2014 to October, 2014 in Baghban Clinic in Sari City, Mazandaran province. We investigated 21 threatened-abortion women with light bleeding or spotting less than twenty weeks of pregnancy in comparison with 21 normal pregnant women as control group. Peripheral blood mononuclear cell was isolated by ficoll histopaque (1.077) and natural killer cells percent were evaluated by flow cytometry. Furthermore, we assessed the human leukocyte antigen-G1 isoforms expression by real-time polymerase chain reaction (PCR) in case and control groups. Results: The results of this study was shown that natural killer cells percent in threatened-abortion pregnant women was significantly higher than normal pregnant women (P=0.03). In addition, human leukocyte antigen-G1 isoform had a lower expression in threatened-abortion pregnant women in comparison with control group (P=0.004). Conclusion: Decreasing of human leukocyte antigen-G1 expression with increasing of natural killer cells level in threatened-abortion pregnant women is an indicator of mother's immune system dysregulation in comparison with control group. Therefore, it is concluded that in the threatened-abortion pregnant women, human leukocyte antigen-G1 expression level with natural killer cells percent as diagnostic marker must be determine.

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Background: The aim of this study was to investigate interaction between vanillin and alpha-, beta- and gamma-cyclodextrin carriers for targeted drug delivery and compare the performance between them using theoretical methods. Methods: All theoretical calculations were performed on a Intel® Core™ i5 Processors computer at Kerman University using Gaussian 09 program package (Gaussian, Inc., Wallingford, USA) in a three month period (February 2014 to May 2014). Starting geometries were generated employing GaussView software, version 5 (Gaussian, Inc., Wallingford, USA) and then the resulting coordinates were optimized using density functional theory (DFT) calculations. The natural bond orbital method (NBO program, under Gaussian 09 program package) was carried out to study charge transfer energy associated with the intermolecular interactions. The quantum theory of atoms in molecules was applied for DFT results to get insight in the nature of interaction existing in the investigated systems. The calculations were carried out with AIM2000 program and AIMAll 14.10.27 package (Todd A. Keith, TK Gristmill software, Overland Park KS, USA) to find and characterize bond critical points. Results: The vanillin molecule is adsorbed on the surface of carriers by hydrogen bonding between its oxygen atom and hydrogen atoms of cyclodextrin. The hydrogen of -OH group on the cyclodextrin can form hydrogen bond to the oxygen atom of carbonyl group of vanillin molecule. This study indicates a decrease of total energy with increasing surface of cyclodextrin. So gamma-cyclodextrin and its complex with the maximum surface in between carriers have the highest stabilities. The gamma-cyclodextrin shows the strongest interaction with vanillin. In all complexes of vanillin-cyclodextrin, the direction of charge transfer is from drug to carrier. Conclusion: Due to the high solubility of gamma-cyclodxtrin and its stronger interaction with the molecule vanillin, it can be the best option as drug carrier.

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Despite the valuable results achieved in identification of genes and genetic changes associated with type 2 diabetes (T2D), lack of consistency and reproducibility of these results in different populations is one of the challenges lie ahead in introduction of T2D candidate genes. Therefore, the present review article aimed to provide an overview of the most important genes and genetic variations associated with development of T2D based on a systematic search in well-known genetic databases. For this purpose, the National Center for Biotechnology Information, Database of Genotypes and Phenotypes (NCBI dbGaP) and Human Genome Epidemiology Network (HuGENet) database were searched to find the most important genes associated with T2D. In addition, a gray literature search was conducted to collect any available information released by laboratories offering genetic tests such as deCODE genetics and 23andMe. Candidate genes were selected among the results of all databases based on the highest level of similarity. Subsequently, without any time restriction, PubMed, Scopus and Google scholar databases were searched using relevant Medical Subject Headings (MeSH) terms to access related articles. The relevant articles were screened to make a conclusion about the genes and genetic variations associated with T2D. The results revealed that four selected candidate genes, in order of importance, were TCF7L2, CDKAL1, KCNJ11, and FTO. The most significant single nucleotide polymorphism (SNP) associated with T2D in the TCF7L2 gene was rs7903146 however, the results showed a wide range of variation from slight association in the Amish (P= 5.0×10^-2) to strong association in European descent populations (P= 2.0×10^-51). Then, rs10440833 mapping to the intronic region of the CDKAL1 gene showed significant association with T2D (P= 2.0×10^-22). In the KCNJ11 gene, a missense variation (rs5215) in exon one was found to have the highest association with T2D compared with other SNPs discovered in this gene (P= 5.0×10^-11). Finally, rs8050136 located in the first intron of the FTO gene had the strongest association with T2D (P= 2.0×10^-17). On the basis of these results, it can be concluded that the current study can be introduced as a model for achieving well-documented results among spectrum of information available in genetic databases based on a systematic search strategy. The candidate genes and genetic variations presented in this review article might be applied for early diagnosis, prevention, and treatment of T2D.

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Background: Human papilloma virus is a DNA virus from the papillomavirus family that is most prevalent in human cervical cancers and many studies showed the E6 and E7 proteins are present in the majority of cervical cancer cases. Development of universal HPV peptide-based vaccine with more serotypes coverage has considerable value. The aim of the study was to design a multi-epitope universal vaccine for major HPV based on E6 and E7 proteins and optimization the expression of polytopic construct contains E6 and E7 genes from different genotypes of human papilloma virus as a candid vaccine.

Methods: In this experimental study that was carried out in Pasteur Institute of Iran, Virology Department from October 2013 to November 2014. In order to design the polytypic construct, we predicted the most probable immunogenic epitopes of E6 and E7 from common high risk HPV16, 18, 31, 45 along with high prevalent type 6 and 11 using bioinformatics methods. The synthetic pET28a expression vector harboring E6 and E7 protein was transformed into Escherichia coli hosts and its expression was analyzed by SDS-PAGE and western blotting. Finally, in order to expression optimization of recombinant protein, cell density, induction time, growth temperature, IPTG (Isopropyl &beta-D-1-thiogalactopyranoside) concentration and cultures media were studied.

Results: In the present study the recombinant fusion protein was expressed successfully and the highest expression of target protein was achieved in super broth medium containing 0.1% glucose and 0.2% L-arabinose. In Super broth medium, the optimum condition for recombinant protein expression was occurred at OD600 of 0.8, 0.1mM IPTG, one hour’s incubation time at 37 °C and BL21 (A1) host.

Conclusion: The results of this study show that the optimum expression of E6 and E7 proteins from different genotypes of human papilloma virus can be performed. Moreover, by purification of recombinant protein and evaluation of its immunogenicity in mice, it can be used as a vaccine candidate against the human papilloma virus.

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Background: This study investigated compatibility between post chemoradiation magnetic resonance images and histologic findings after operation and chemoradiation in patients with locally advanced rectal cancer.

Methods: In this prospective study, 63 patients referred to Cancer Institute of Emam Khomeini Hospital, Tehran, Iran, from October 2011 to October 2013 with locally advanced rectal cancer receiving neoadjuvant chemoradiation (50.4 Gy external beam radiation with concomitant capecitabine 825 mg/m2 PO twice a day with or without 60 mg/m2 oxaliplatin weekly). Patients had an MRI before chemoradiation and MRI assessment were used to identify Tumor (T) and lymph node (N) staging by an experienced radiologist. Patients were recommended to repeat MRI after surgery but it was not obligatory. Findings of post chemoradiation MRI and histopathologic reports were compared. Downstaging was defined as at least one stage decrease in T or N in histopathologic report comparing to their first MRI, on condition of no sign of disease progression.

Results: 32 patients (50.79%) had T downstaging and 36 of them (57.14%) showed N downstaging: none had disease progression. In this study MRI had an accuracy of 55.5% for rectal tumor (T) restaging after chemoradiation comparing to pathology. MRI sensitivity for T restaging was 33.3% to 83.3%.  There was a higher possibility to have errors in restaging of T1-2 stages. Specificity of MRI for T restaging was higher than its sensitivity, 66.6%. In this study lymph node involvement (N) was determined according to morphology and size. MRI has an accuracy of 42.8% for detecting lymph node involvement. Its sensitivity and specificity for N restaging were 50% and 66.6% respectively. All patients had MRI before chemoradiation, although 21 of them repeated MRI after chemoradiation since it was not mandatory. 19 of these 21 patients underwent surgery.

Conclusion: Although MRI is a suitable imaging for staging locally advanced rectal cancer its use for restaging after chemoradiation is under question. According to this study, MRI accuracy rates for both T and N restaging were below the rates of previous studies.

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Background: Congenital hypothyroidism is a major but preventable cause of mental backwardness in infants. In case of hypothyroidism in fetuses, certain complications will occur in vital organs like the central nervous system and the skeleton. Before screening programs were introduced, congenital hypothyroidism was diagnosed with delay due to its few and non-specific symptoms during the first days of life. Given the difference in reference range for various races and populations, this study was aimed to determining a natural range for thyroid hormones used in the screening of infants.

Methods: In a descriptive cross-sectional study at Vali-asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran, from March 2013 to 2014. The level of T4, FT4 and TSH hormones was measured in all natural childbirth, without any complications and with one-minute Apgar score above 7 while this study was underway.

Results: A group of 249 infants (male and female), including 35 (14.1%) aged between 0 and 4 days, 102 (41%) aged between 5 and 7 days and 112 (45%) aged between 7 and 30 days, were examined. The average TSH, T4 and FT4 amounts in infants, aged 0 to 30 days, were respectively 5.35 µU/ml, 10.77 µg/dl and 1.33 ng/dl. The interval was 4.76-6.01 µU/ml for TSH, 10.36-11.17 µg/dl for T4 and 1.29-1.37ng/dl for FT4. The difference between age groups with average TSH concentration is not meaningful (P=0.7) and the average T4 amount in different age groups was meaningfully different (P=0.05). The average FT4 in different age groups is meaningfully different (P=0.007). The thyroid hormone amounts calculated for males and females were not significantly different.

Conclusion: Given the difference in the reference range in race, population and geographical zones, it is necessary to determine a range for screening in Iran. According to the findings of the present study, lower cut-offs, compared with western countries, should be envisaged for TSH in congenital hypothyroidism screening programs that could speed up the diagnosis of minor cases of the disease and prevent complications.

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Background: Over the last two decades invasive candidiasis has become an increasing problem in neonatal intensive care units (NICUs). Colonization of skin and mucous membranes with Candida spp. is important factor in the pathogenesis of neonatal infection and several colonized sites are major risk factors evoking higher frequencies of progression to invasive candidiasis. The aim of this study was to detect Candida colonization in NICU patients.

Methods: This cross-sectional study was conducted on 93 neonates in NICUs at Imam Khomeini and Children Medical Center Hospitals in Tehran. Cutaneous and mucous membrane samples obtained at first, third, and seventh days of patients’ stay in NICUs during nine months from August 2013 to May 2014. The samples were primarily cultured on CHROMagar Candida medium. The cultured media were incubated at 35°C for 48h and evaluated based on colony color produced on CHROMagar Candida. In addition, isolated colonies were cultured on Corn Meal Agar medium supplemented with tween 80 for identification of Candida spp. based on their morphology. Finally, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed for definite identification of isolated species.

Results: Colonization by Candida spp. was occurred in 20.43% of neonates. Fifteen and four patients colonized with one and two different Candida spp., respectively. Isolated Candida spp. identified as; C. parapsilosis (n: 10), C. albicans (n: 7), C. tropicalis (n: 3), C. guilliermondii (n: 2), and C. krusei (n: 1). In present study non-albicans Candia species were dominant (69.56%) and C. parapsilosis was the most frequent isolate (43.47%). Using Fisher's exact test, the correlation between fungal colonization with low birth weight, low gestational age, and duration of hospital stay was found to be statistically significant (P=0.003).

Conclusion: The results of this study imply to the candida species colonization of neonates. Neonates in NICU are at the highest risk for severe infection with Candida parapsilosis. Therefore, isolation of C. parapsilosis as the most common species (43.47%) in present study was noteworthy.

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Background: Major platelet adhesive receptors that contribute significantly to thrombus formation include platelet receptor glycoprotein Ibα (GPIbα) of the GPIb-IX-V complex and platelet glycoprotein VI (GPVI). GPIbα plays a crucial role in platelet tethering to sub-endothelial matrix, which initiates thrombus formation at arterial shear rates, whereas GPVI is critically involved in platelets firm adhesion to the site of injury regardless of shear condition. During storage, platelets experience some changes that deleteriously affect the expression levels of platelet receptors, which in turn can alter platelet functional behaviors. Considering the important roles of GPIbα and GPVI in platelet adhesion, it seems that any dramatic changes in the expression levels of these receptors can influence adhesive function of transfused platelets. Thereby examining GPIbα and GPVI expression during the storage of platelet concentrates may provide some useful information about the functional quality of these products after transfusion.

Methods: In our experimental study, 5 PRP-platelet concentrates were randomly obtained from Iranian Blood Transfusion Organization (IBTO). All the platelet products met the standard quality assessment based on AABB (American Association of Blood Banks) guidelines. Washed platelets were subjected to flowcytometry analysis for the evaluation of GPIbα and GPVI receptor expression in day 1, 3 and 5 after storage. Data were presented as mean fluorescence intensity (MFI) and analyzed by Kruskal-Wallis test with Dunn’s multiple comparison test.

Results: The GPIbα expression on first day (MFI=86±5.9) was reduced three days after storage (MFI= 69±6.9). The expression levels continued to reduce until day 5 in which GPIbα expression was markedly decreased to (MFI= 61±7.7) (P= 0.0094). GPVI expression on the days 1, 3 and 5 after storage were 20.6±3.3, 24±2.5 and 14±4.9, respectively. The results showed a significant decrease of expression on day 5, compared to that in day 3 after storage (P= 0.0213).

Conclusion: Our study showed significant decreases in the expression of platelet receptors GPIbα and GPVI after 5 days storage, suggesting a major defect in adhesive function of platelets during this term.

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Background: Platelet adhesion typically occurs by the critical role of GPIb-V-IX in capturing free-flowing platelets to the injured vessel wall where its rapid binding kinetics enables platelet tethering even under conditions of high shear through the interaction of the major ligand-binding subunit of GPIb-V-IX, GPIbα with subendothelial-bound vWF. During storage, platelet undesired activation may lead to platelet storage lesion (PSL) which changes the expression levels of platelet functional receptors including GPIbα. This study investigates the levels of expression and ectodomain shedding of platelet adhesive receptor GPIbα during the storage of platelet rich plasma (PRP) concentrates (PRP- PCs).

Methods: Five PRP-platelet concentrates were obtained from Iranian Blood Transfusion Organization (IBTO). The GPIbα expressions of platelets were analyzed on day 1, 3 and 5 after storage using flowcytometry. To examine the ectodomain shedding of this receptor the microparticle free supernatants obtained from stored platelets were subjected to western blot analysis. For control study, blood specimens was drawn from healthy consenting individuals and resting platelets were isolated while resuspended in Tyrode buffer.

Results: Our results indicated a continuous decrease of GPIbα expression during storage where the expression from fist day (Mean fluorescence intensity=86±5.9) was significantly reduced compared to that of fifth day (mean fluorescence intensity=61±7.7) after storage (P=0.0094). Conversely, shed GPIbα (Glycocalicin) demonstrated continuous elevation during five-day storage (P=0.0098). According to the results the shedding levels for the first day were increased from 0.31± 0.3 to 1.5± 0.4 by the day 5 after storage.  

Conclusion: Our study has demonstrated significant loss of platelet GPIbα during storage mostly due to receptor ectodomain shedding that leads to significant increase of soluble GPIbα in stored platelets. Considering the high levels of shed GPIbα in long stored platelets whether the transfusion of such products might be associated with defective adhesive function of platelets or possible proinflammatory effects could be of interests for future investigation.

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Background: Aloysia citrodora belongs to the Verbenaceae family of plants, a well-known herbal medicine in Iran. The aim of the present study was to investigate the chemical composition, antioxidant, antibacterial, cytotoxic and apoptotic effect of A. citrodora extract against human colon cancer (HT29) cells by using real-time polymerase chain reaction and flow-cytometry methods.

Methods: This experimental study was carried out in Islamic Azad University, East Tehran Branch, from March to September of 2014. At first, the A. citrodora chemical constituents were analyzed by gas chromatography-mass spectrometry (GC-MS) technique. In addition, antioxidant assay, antibacterial and anti-cancer effect was performed using 1,1-diphenyl-2-picrylhydrazyl (DPPH), disk diffusion and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods, respectively. The half maximal inhibitory concentration (IC50) value was calculated. We extracted total RNA molecules by using RNX solution, after which cDNA was synthesized. Finally, the pro-apoptotic (Bax) and anti-apoptotic (Bcl2) gene expression was performed by real-time polymerase chain reaction and apoptotic effects were analyzed using Flow-cytometry method.

Results: GC-MS analysis of Aloysia citrodora extract was shown 37 major components and the most frequent component was belonged to Spathulenol (17.57%) and Caryophyllene oxide (15.15%) The antioxidant activity of the extract was IC50= 0.6±0.03 mg/ml. The maximum and minimum antibacterial effects of extract were belonged to gram-negative and gram-positive bacteria, respectively. Cytotoxic results revealed that the A.citrodora extract have IC50= 20.1±0.78 mg/ml against colon cancer (HT29) cell line and real-time polymerase chain reaction results showed the expression level of Bax and Bcl2 was increased and decreased respectively in colon cancer cell line (3.470±0.72 (P< 0.05), 0.43±0.35 (P< 0.05)). In addition, the flow-cytometry results indicated the 38.66% apoptosis in colon cancer cell line.

Conclusion: According to the results, it seems that A. citrodora extract has potential antioxidant, antibacterial and anticancer effects and it suggested that further studies were performed for A. citrodora pharmaceutical importance.

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Background: The primary manifestation of cardiac tumors in embryonic period is a very rare condition. Cardiac rhabdomyomas most frequently arise in the ventricular myocardium, they may also occur in the atria and the epicardial surface. In spite of its benign nature, the critical location of the tumor inside the heart can lead to lethal arrhythmias and chamber obstruction. Multiple rhabdomyomas are strongly associated with tuberous sclerosis which is associated with mental retardation and epilepsy of variable severity. Ultrasonography as a part of routine prenatal screening, is the best method for the diagnosis of cardiac rhabdomyomas. In the review of articles published in Iran, fetal cardiac rhabdomyoma was not reported.

Case presentation: We report a case of cardiac rhabdomyoma on a 24-year-old gravid 1, referred to Day Medical Imaging Center for routine evaluation of fetal abnormalities at 31 weeks of her gestational age. Ultrasonographic examination displayed a homogenous echogenic mass (13×9mm), originating from the left ventricle of the fetal heart. It was a normal pregnancy without any specific complications. Other organs of the fetus were found normal and no cardiac abnormalities were appeared. No Pericardial fluid effusion was found. The parents did not have consanguineous marriage. They did not also have any specific disease such as tuberous sclerosis.

Conclusion: The clinical features of cardiac rhabdomyomas vary widely, depending on the location, size, and number of tumors in the heart. Although cardiac rhabdomyoma is a benign tumor in many affected fetuses, an early prenatal diagnosis of the tumor is of great significance in making efficient planning and providing adequate follow up visits of the patients and the complications such as, heart failure and outlet obstruction of cardiac chambers.

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Background: Human leukocyte antigen E is a member of non-classical HLA class I. Interaction between HLA-E molecule on the target cells and inhibitory CD94/NKG2A receptor on the cell surface of natural killer (NK) cells has an important role in the regulation of immune system against pathogens; therefore different cell surface expression of HLA-E molecule plays an important role in host resistance against viral infections as well as host response to treatment. Considering this fact, we analyzed the frequency of different HLA-E genotypes (HLA-E*01010101, HLA-E*01030103, HLA-E*01010103) in major thalassemic patients who underwent frequent transfusion therapy and are thus more susceptible to infectious diseases.

Methods: This study was a cross-sectional study of 104 major thalassemic patients who referred to Tehran Thalassemia Clinic between the years 2015 to 2016. Blood DNA was extracted and proliferated by sequence-specific primer polymerase chain reaction (SSP PCR). The PCR product was subjected to electrophoresis on 1.5 percent agarose gel then DNA fragment bands on the gel were detected by exposing to UV light. Furthermore, PCR products were also subjected to sequencing analysis for further confirmation.

Results: From 104 patients in this study, 49 (47.1%) were man and 55 (52.9%) were women. These patients were in the age range of 16 to 43 years (mean+SD; 31.03±4.7 year). The frequency of HLA-E*01010103 genotype (64.4 percent) was significantly (P= 0.001) higher than the genotypes of HLA-E*01010101 (15.4%) and HLA-E*01030103 (20.2%) whereas there was no difference between the frequency of HLA-E*0103 allele (52.4%) and HLA-E*0101 (47.6%).

Conclusion: This is the first study that examined the HLA-E polymorphisms in Iranian thalassemic patients referred to Tehran Thalassemia Clinic. This study has shown that the frequency of HLA-E*01010103 genotype was significantly higher than other genotypes of HLA-E whereas there was no difference between the frequency of HLA-E*0103 allele and HLA-E*0101 allele. Whether different frequencies of HLA-E genotype may affect thalassemic patients’ susceptibility to blood-borne infections will be of interest for future studies.

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Background: Obesity is one of the most important problems in developed countries and cause cardiovascular diseases, diabetes and hypertension. The complex phenotype influenced by both genetic and the environment factors. One of the most important genes which is effective in this phenotype is peroxisome proliferator-activated receptor gamma (PPAR-γ). This study was carried out of investigate the association of Pro12Ala (rs1801282) polymorphism in mentioned gene with obesity in Tehran Lipid and Glucose Study (TLGS).

Methods: The present study done in September 2014 in Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences. For the present case-control study 239 subjects with excess weight and body mass index more than 30 kg/m2 as a case and 240 subjects with normal weight and body mass index less than 25 kg/m2 as a control were selected. The rs1801282 was proliferated, detected and genotyped using tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method.

Results: The results indicated that there was significant association between the presence of risk allele G of rs1801282 and obesity disease in the TLGS population (P=0.000). Genotype and allelic frequencies of rs1801282 in patient and healthy group were: 55.2% and 23.8% for GG, 24.3% and 30.4% for GC, 20.5% and 45.8% for CC, 67% and 39% for G, 33% and 61% for C, respectively.

Conclusion: The results of study indicated that the presence of G allele could be increase 1.7 the risk of obesity. These differences in patient and healthy group lead us to select this marker as a genetic marker to predict the risk of obesity. There are statistical differences between the distribution of mentioned polymorphism in Tehranian population and other populations. However, replicating the study in a larger population of Tehranian people with more affected cases is suggested to generalize the results of this study.