Tehran University Medical Journal

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Background: Fumonisins, a family of mycotoxins, are mainly found in wheat, corn and their products. Previous studies have shown that fumonisin B1 (FB1), the most abundant and toxic of known fumonisins, has been associated with many animal and human diseases including cancer. In the present study, the effects of FB1 were examined on the production of inflammatory cytokines in intestine and stomach cell lines.

Methods: This study was performed in the Cancer Research Center of Tehran University of Medical Sciences in 2010. The cell lines of colon adenocarcinoma (SW742) and gastric epithelium (AGS) were purchased from the Pasteur Institute of Iran. The cells were pretreated with different concentrations of FB1 (0 to 100 µM) for 3 days. The cells were later stimulated by lipopolysaccharides. Twenty-four hours after cell induction, the cytokines including tumor necrosis factor-alpha (TNF-α), interlukin-1 beta (IL-1β) and interlukin-8 (IL-8) were measured by ELISA.

Results: Treatment with FB1 induced a dose-dependent decrease in IL-8 production (P<0.05). This decrease was seen in both SW742 and AGS cell lines. Moreover, FB1 induced a dose-dependent increase in the production of TNF-α and IL-1β in both cell lines (P<0.05).

Conclusion: The results of this study indicated that FB1 could increase the inflammatory cytokines including TNF-α and IL-1β in gastric and intestinal celllines. These effects might result in the development of inflammatory responses and subsequent mucosal atrophy in in-vivo conditions.

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Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood, characterized by excess lymphoblasts, and immature white blood cells that are continuously multiplying and overproducing in the bone marrow. The aim of this investigation was to measure the sensitivity of lymphocytes against gamma irradiation in patients with acute lymphoblastic leukemia, and also find out the effect of such irradiations in causing chromosomal abnormalities.
Methods: In this investigation performed between April 2010 and July 2011, at the Department of Genetics, Cancer Institute of Iran, we studied the effects of gamma irradiation on the lymphocytes of 20 children with acute lymphoblastic leukemia. The lymphocytes of 30 healthy donors were used to establish as a normal response to gamma irradiation and seven age-matched ataxia telangiectasia patients were recruited as positive control. The chromosomal radiosensitivity was assessed with the G2- and the G0-assay. We compared the mean number of chromosomal abnormalities such as chromosome and chromatid breakages, chromosome and chromatid gaps, and chromatid exchanges in one-hundred metaphases of patients and control groups.
Results: The frequency of chromosomal aberrations was statistically higher among patients with acute lymphoblastic leukemia than the normal controls (P<0.01). In total, 65% of the patients were sensitive to gamma irradiation, but the remaining 35% were similar to the normal controls. Patients with ataxia telangiectasia showed the highest sensitivity to gamma irradiation (P=0.001).
Conclusion: Our results showed that a high percentage of patients with acute lymphoblastic leukemia were sensitive to irradiation, meaning that maximum care should be taken during their treatment to avoid unnecessary X-rays or radiotherapies.

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Background: Previous studies indicate that morphine dependent and withdrawal from chronic opiates enhanced anxiety-related behaviours in novel and stressful conditions in rats. Recent studies have shown that exposure to a stressor generates a wide variety of adaptive responses, while enhancing abilities to adopt with the stressor. Therefore, the aim of this study was to examine the effect of chronic restraint stress and acute water immersion (WI) stress on the anxiety profile in morphine-dependent rats.
Methods: Thirty two rats were injected with twice daily doses (10 mg/kg, subcutaneous, at 12 hour intervals) of morphine over a period of 10 days in the presence or absence chronic restraint stress (1 hour/day). On day 11, two hour after morphine injection, anxiety-like behaviours were tested in the elevated plus-maze model in the presence or absence acute water immersion stress. Rats were divided into four groups: dependent- No restraint stress (D/NRS), dependent- restraint stress (D/RS), dependent- restraint stress+ water immersion stress (D/RS+WI), dependent- water immersion stress (D/WI).
Results: Finding have shown that D/RS+WI rats exhibited an increase in the elevated plus-maze open arm entries and time as compared with the control groups (P=0.018 and P=0.037, respectively). Also, this measure was significantly lower in the WI rats than the D/RS+WI rats (P=0.049 and P=0.031, respectively).
Conclusion: Our findings indicate that chronic restraint stress followed by acute water immersion stress decreases the severity of the anxiogenic-like behaviours in morphine dependent rats thus it may have a therapeutic application in the treatment of the asso-ciated disorders in addiction.

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Background: Rotational deformity after intramedullary nailing is a well-known complication. Femoral malrotation is the most common form of mal::::union:::: but it is underrecognized in part because of the difficulty in accurately assessing rotation as well as the variation that exists in normal anatomy. The aim of this study was to evaluate femoral malrotation following intramedullary nailing of the femur. Methods: We studied 70 patients who had referred to Imam Khomeini Hospital and had undergone antegrade intramedullary fixation for isolated femoral shaft fracture during 3-year period from 2008 to 2011. Inclusion criteria including isolated femoral shaft fracture that had undergone antegrade intramedullary nailing. Exclusion criteria including spontaneous ipsilateral tibial fracture or pelvic fracture, contralateral femoral fracture, femoral fracture that had fixed using plate or external fixator or retrograde intramedullary nailing. During operation, the patients were assessed clinically for rotational deformity and then in the postoperative follow-up period, degree of rotation was identified with CT scan. Postoperative computed tomography measurements of rotation were compared with the opposite side. Results: There were 70 patients, 56 men and 14 women. The average age of the patients was 28.21±14.39 patients (55/7%) had external rotation and 31 patients (44/3%) had internal rotation. The mean of malrotation degree in physical examination was 4/67 and The mean of malrotation degree in CT scan was 7. Degree of malrotation deformity, less of 5º, 5 to 10º and 10 to 15º was less of 8.6%, 75.7% and 15.7% respectively. Degree of malrotation didn’t relate to age, sex, fracture location and activity of the patients (P> 0.05). Conclusion: Rotational deformity in 28% of the patients was equal to more 15º. This complication didn’t relate to fracture location. The patients with external rotation deformity had more symptoms than the patients with internal rotational deformity but there isn’t significant relation in this study.

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Background: Uterine leiomyoma is one of the most common benign smooth muscle tumors occurring in 20-40% of women worldwide in their reproductive years. Recent studies revealed that estrogen plays an important role in the pathogenesis of this disease. Since glutathione S-transferase (GST) gene family are involved in the biosynthesis of estrogen, the prior probability that variants at this locus are associated with uterine leiomyoma is likely to be above the null. Therefore, this study was carried out to examine whether GSTP1 polymorphism (Ile105Val) is associated with increased risk of uterine leiomyoma in Iranian population. Methods: In this case-control study, 50 women diagnosed with uterine leiomyoma and 50 healthy controls were recruited from subjects referred to the Pasteur Institute of Iran from November 2012 to September 2013. The genomic DNA was extracted from peripheral blood leucocytes using the standard phenol-chloroform method and subsequently the GSTP1 polymorphism was genotyped using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Logistic regression analysis was applied to estimate odds ratios and 95% confidence intervals after age adjustment using the SPSS statistical software package, version 18.0. Results: The results showed significant differences between case and control groups in terms of genotype frequency (P<0.0001). In addition, the results indicated that the presence of the valine allele significantly increased risk of uterine leiomyoma about three times more in individuals carrying the mutant allele compared to control group (Odds Ratio: 3.34 95%CI: 1.82-6.15 P<0.0001). Conclusion: To our knowledge, this is the first study performed in Iranian population assessing the association between GSTP1 Ile105Val polymorphism and risk of uterine leiomyoma. However, further extensive studies with a large number of samples from different populations and ethnicities are required to validate the results obtained in this study.

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Background: Helicobacter pylori vacA (vacuolating toxin A) gene is comprised of mid- (m), intermediate- (i) and signal-regions. Recently, the vacA-i region genotype has been suggested to be a better predictor of disease severity than either the s- or m-region. The main aim of the present study was to determine the associations of i region poly-morphisms of vacA gene with gastric cancer (GC) and peptic ulcer disease (PUD) in Azerbaijan Province patients. Methods: A number of 89 patients were enrolled. The biopsy samples were taken from patients referring to the endoscopy units of Imam Reza and Shahid Madani Hospitals, Tabriz, Iran from August 2012 to May 2013. The genotype frequencies of vacA-i1 and i2 in were studied using polymerase chain reaction (PCR). Results: The frequency of vacA-i1 and i2 was 51.68% and 48.31%, respectively. The genotypic frequency of vacA-i1 in patients with GC (21/24, 87.5%) was significantly higher than in those with non-atrophic gastritis, NAG (19/48, 39.58%). In contrast, the genotypic frequency of vacA-i2 in patients with NAG, PUD, and GC was 60.42%, 64.70%, and 14.28%, respectively. The results of multiple linear and logistic regression analyses confirmed the intensity of correlation of vacA-i1 allele with GC compared with control group (NAG). No significant correlation was found between the vacA-i-region alleles and PUD risk. Conclusion: We have proposed that the H. pylori vacA-i1 genotype could be an im-portant biomarker for predicting the gastric cancer risk in Azerbaijan Province in Iran. However, due to the difference in the allelic frequency of this gene in H. pylori strains from different parts of the world, the vacA-i1 genotype usefulness in predicting the gas-trointestinal diseases is dependent to the geographic origin of the strains.

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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: The major issue to address in endometriosis etiology is to identify the genetic changes in the disease and their occurrence in different populations. Uncovering these genetic changes may be important in developing potential biomarkers for early diagnosis and prognosis of endometriosis. Among all endometriosis susceptibility genes studied before, convincing association has been found with variants in the estrogen receptor alpha (ESR1) gene and this disease however, the contributions of these genetic variants in different populations and ethnic groups are not similar. Accordingly, this study was carried out to replicate the previous findings to assess whether this polymorphism is associated with endometriosis in Iranian women. Methods: A case-control study was designed to determine the possible association between ESR1-351A>G variant and occurrence of endometriosis. The study group consisted of 100 subjects diagnosed with endometriosis as case group and 100 fertile women without endometriosis as controls recruited from subjects referred to the Tehran Women’s General Hospital between January to September 2013. All subjects were genotyped for this marker using amplification refractory mutation system- polymerase chain reaction (ARMS-PCR). Association of risk allele (G) with endometriosis was as-sessed using PLINK software after age adjustment. Results: The results showed that the genotype frequencies were in Hardy-Weinberg Equilibrium (HWE) in both case (F=0.04, P:0.67) and control (F=0.02, P:0.83) groups. In addition, there were no significant differences between case and control groups in terms of genotype frequencies (P=0.17). Moreover, the results indicated that the presence of risk allele (G) did not significantly increase risk of endometriosis (OR: 1.43, 95%CI: 0.96-2.13, P=0.07). Conclusion: The results do not support the previous findings of an association between -351A>G genetic polymorphism in ESR1 gene and endometriosis. Therefore, comprehensive genetic approaches including linkage analyses and family-based tests, together with a number of replication studies with large sample size, are needed to make conclusive claims about the role of this genetic polymorphism in susceptibility to endometriosis.

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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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HIV/AIDS is among the leading causes of morbidity and mortality in world. There are more than 35 million people living with HIV/AIDS in the world. Although the annual incidence of HIV infection is decreasing globally, HIV prevalence is rising due to development of more effective treatment and higher survival. Iran suffers from concentrated HIV epidemics among injecting and non-injecting drug users. There are more than 27 thousand registered cases of HIV infection and it is estimated that there are above seventy eight thousand cases in the country. Regarding the burden of disease, it is projected that HIV/AIDS will have the highest growth during the next 10 years. The outcome of this epidemics will be determined by human behavior. HIV, psychiatric disorders and substance use disorders are closely correlated and are accompanied by similar risk factors. They also share common consequences such as stigma and discrimination. Correlation of psychiatric disorders, as one of the most influential determinants of our behavior, and HIV/AIDS infection is reviewed in this narrative article. Psychiatric disorders are associated with greater risk of HIV acquisition. Substance use disorders, both injecting and non-injecting, as well as severe mental illnesses put the individual at higher risk of acquiring HIV infection. Impaired judgment, diminished inhibition and control over behaviors, lack of insight and poor self-care have been proposed as the underlying mechanisms. On the other hand, HIV infection may put the individual at greater risk of developing a mental illness. Coping with a chronic and life-threatening illness, fear of stigma and discrimination, CNS invasion of the virus as well as the adverse neuropsychiatric side effects of anti-retroviral medications may all contribute to establishment of a psychiatric disorder. Although there exists a bi-directional correlation between mental health problems and HIV/AIDS infection, this reciprocity goes beyond. Psychiatric disorders can affect the patient’s adherence, access to treatment and care and can worsen the course and clinical outcome of the infection. The clinical importance, underlying mechanism and other implications of this correlation are reviewed in this article.

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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: Cervical cancer is known to be preventable because of long period of pre-invasive stage, availability of screening tools, and effective treatments for early invasive cervical lesions. Screening is main measures to prevent the disease and Pap smear is a screening strategy for cervical cancer. Current paper aimed to evaluate levels of awareness and practice regarding Pap smear screening among women aged between 20 to 65 years in Tehran (Iran). Methods: This was a descriptive-analytical study conducted in Tehran City of Iran in 2015 at Firoozgar Hospital. The research population included all married, widowed and divorced women aged 20-65 years. Data analysis was performed using the Pearson correlation and Student’s t-tests in SPSS, ver. 23 (Chicago, IL, USA). Results: Among 90 individuals who have fill questionnaire completely, 66.6% subjects had Pap smear tests. 40% of the individuals aged between 30 to 39 and the education level is distributed equally between Intermediate, Diploma and graduate and only 3 percent of them, continue their education to higher level. There was a significant relationship between the awareness of Pap smear and educational level (of both wives and husbands). The people who have graduate degree, have the best awareness. Working women revealed higher level of awareness about Pap smear. Shame and fear of taking the cancer were the most common reasons which lead to avoidance in doing the test by the women, while the most encouraging factors for performing the test were the information mostly provided by physicians and after that, the information provided by friends. Conclusion: The awareness of Pap smear test which was measured by weighting different questions in the questionnaire by experts, prove that the women aged above 39, have an average level of awareness of Pap smear test. Due to high prevalence of cervical cancer and prolonged pre invasive course, role of Pap smear for early diagnosis necessitate the use of proper and inexpensive instructional methods to increase awareness in women about cervical cancer and preventive strategies.

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Results: The patients included 42 (75%) men and 14 (25%) women with the mean age of 49.5 years (9 to 90 years). Positive culture was observed in 9 cases but, only in one of these patients direct examination was positive and fungal elements were seen in 10% KOH preparation. Though, fungal keratitis was confirmed in 9 (16%) patients including seven (77.8%) men and two (22.2%) women. The majority of cases (88.9%) had a history of corneal trauma with plants and they were mainly farmer. According to statistical analysis, there was a significant association between corneal trauma and keratomycosis (P=0.007). The most common etiologic agents were Fusarium spp. (n: 4, 44.4%), followed by Aspergillus flavus (n: 2, 22.2%), Penicillium sp. (n: 1, 11.1%), Acremonium sp. (n: 1, 11.1%), and Cladosporium sp. (n: 1, 11.1%) respectively. Conclusion: In the presence of sufficient predisposing factors such as corneal injuries caused by plants, keratomycosis could be caused by a variety of fungi. Furthermore, low sensitivity of direct examination in this study, revealed the necessity of culture in diagnosis of keratomycosis.

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Results: According to results, of the 661 patients who were studied, 462 ones had positive and 273 had significant prick test results. The grasses group with 293 positive (44.3%) and weeds group with 259 positive results (39.2%) were more common than the other categories. Among the significant positive tests, these two categories with 161 and 142 significant positive tests were indicated as the most common allergens. Respiratory allergens were also more common in patients with a family history of allergies in weeds and trees categories, but there was no significant difference in sensitization pattern according to the history of tonsillectomy. Conclusion: Patients in Ardabil with allergic rhinitis and asthma were more sensitized to weeds and grass mixtures. It is recommended to provide preventive recommendations to allergic patients and the development of localized skin testing packages and additional studies should be conducted focusing on these two categories of allergens.

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Background: Traumatic Spinal Cord Injury (TSCI) is one of the catastrophic events, the rate of which has been growing compared to the past decades. Complications caused by TSCI have a wide spectrum and can range from complete paralysis to numbness of the limbs. Additional to the injury severity and disability of the patient, the recovery rate depends on the treatment strategies. Despite extensive efforts and research in this field, there are still few treatment options for TSCI patients. Controversial results have been reported, however, spinal cord decompression is the only certainty for the treatment of these patients. In the present study, patients with thoracic and lumbar fractures were undergone decompression, less and more than 24 hours, and the recovery rate (RR) was compared after 6 months.
Methods: In this study, patients with lumbar and thoracic fractures who were referred to the neurosurgery department of Ahvaz Golestan Hospital during May 2019 to December 2021 were included. Decompression was performed at the fracture level as a total and at the upper and lower levels of the fracture as a partial decompression. To evaluate fine motor movements, picking up a small object with toes and following a rectangular path were used. Also, the gross motor movements, upper and lower proximal and distal muscle forces were measured. Conclusion: This study showed that decompression<24 hours in TSCI is associated with a significant improvement in lower fine movements.
 

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