Tehran University Medical Journal
Year:2017 | Volume:75 | Issue:6|Papers Count:15

Cutaneous leishmaniasis (CL) is an endemic parasitic disease of major health impact in many parts of the world and is caused by several species of the protozoan parasite Leishmania. Antimonial compounds (i.e glucantime and pentostam) are the first-line treatment for cutaneous leishmaniasis with emerging drug resistance as a problem. The control of Leishmania is further complicated by the emergence of drugresistant parasites. In the clinical settings, resistance to SbV containing drugs is now well established and it was found to occur in South America, Europe, the Middle East and most notably in India. Clinical resistance to organic pentavalent antimonials, in the form of sodium stibogluconate (pentostam) or N-methylglucamine antimoniate (glucantime), has long been recognized. However, it is unknown whether the clinical failure of chemotherapy is attributable to the development of drug resistance mechanisms in the parasite or to a variety of host factors that might also contribute to low drug response. Reported rate of drug-resistance to antimonial compounds in Iran varies from 9.4% to 94.2% and there is not any comprehensive study on this issue.Indeed, in the endemic region treatment with SbV fails in more cases; thus, in general patients infected with resistant parasites are unresponsive although exceptions have been reported. This article aims to review the mechanisms of drug resistance to these compounds. The main resistance factors include genetical, enzymatic, intracellular (such as apoptosis and cytoskeleton changes) and resistance proteins. Also, mechanisms related to drug transport and intracellular activation are discussed. Various methods of drug resistance detection such as culture and molecular methods (i.e polymerase chain reaction) are reviewed. Although the exact mechanism of action glucantime is not clear, it seems that protein and gene factors involved in cellular drug entry are the main causes of drug resistance. Cross-sectional studies on meglumine antimoniate resistance in endemic areas of cutaneous leishmaniasis in Iran are highly recommended. Also, studies for evaluation of alternatives therapies for antimonial resistant cases are required.

Background: Aberrant pre-mRNA alternative splicing is a common event in cancer cells. Many abnormally spliced RNA variants have been observed in tumor cells and they can be used as biomarkers or therapeutic targets in new drug design. Increasing our knowledge in understanding the mechanisms of alternative pre-mRNA splicing for cancer-related genes and determination of cancer specific isoforms are important for the development of new strategies in cancer therapy. The aim of this study was isoforms identification and expression of PIK3CA, FGFR3 and FGFR1 genes in bladder cancer by RNA Sequencing and Real-Time PCR.Methods: This cross-sectional study was conducted at Urology Research Center of Sina Hospital, Tehran University of Medical Sciences, Tehran, from September 2014 to October 2016. Paired tumor and adjacent normal tissues samples were obtained from 30 bladder cancer subjects. Total RNAs were extracted from bladder tumor and normal tissues. Quantitative and qualitative examinations have been done. After quality control, fragmentation of RNAs and cDNA library construction, next-generation RNA sequencing was performed. Resulting raw data were analyzed with different bioinformatics software. Differential expression was confirmed by Real-Time PCR.Results: RNA sequencing results showed the number of PIK3CA (1 vs 3), FGFR3 (7 vs 6) and FGFR1 (9 vs 12) isoforms and their expression were different in bladder normal tissues in comparison to tumor tissues. Overexpression of PIK3CA gene have been observed in 42% of tumor samples but statistically was not significant. Increased FGFR3 gene (P=0.01) and decreased FGFR1 (P=0.01) expression were significant.There was an association with overexpression of FGFR3 and cigarette smoking ((P=0.037) and family history (P=0.004).Conclusion: RNA sequencing make possible to do the accurate assessment of transcript abundance and identification of different isoforms resulted from aberrant pre-mRNA alternative splicing, which is a crucial process for the maturation of transcripts of multiexon genes. Regarding the differences in isoforms expression in tumor and normal tissues of bladder cancer, they have potential to be used as biomarkers and sensitive targets for cancer therapy.

Background: Post-acrosomal sheath WW domain binding protein (PAWP) is one of sperm factors related to oocyte activation and is expressed in elongating spermatid.Previously, the effect of high of testicular temperature in infertile men with varicocele on semen quality, sperm DNA damage, expression of genes and proteins were reported.In this study, expression of PAWP at RNA and protein levels, and also sperm DNA damage were compared between fertile and infertile men with varicocele.Methods: In this case-control study, semen samples were collected from 35 infertile men with varicocele (grade II & III) and 20 fertile men referring to Isfahan Fertility and Infertility Center from January 2016 to September 2016. Ejaculated semen was obtained by masturbation into a sterile plastic container after 3-5 days of abstinence and was allowed to liquefy at room temperature. Briefly, sperm concentration, motility and morphology were evaluated using a sperm chamber (Sperm meter; Sperm Processor, Aurangabad, India), Computer Assisted Semen Analysis (CASA, Video Test, ltd: version Sperm 2.1, Russia) and Papanicolaou staining, respectively. In addition, DNA fragmentation, expression of PAWP at RNA and protein levels were assessed by realtime PCR, and Western blot technique, respectively. Microsoft Excel 2013 (Microsoft Corp., Redmond, WA, USA) and Package for the Social Studies were used to analyze data. We used independent-samples t-test to compare the mean value between different groups. Differences with values of P<0.05 were considered as statistically significant.Results: Mean of semen volume, sperm concentration, percentage of sperm motility, and expression of PAWP at both RNA (P=0.0001) and protein (P=0.03) levels were significantly lower in infertile men with varicocele in comparison with fertile men. In addition, mean percentage of sperm abnormal morphology and sperm DNA fragmentation were significantly higher in infertile men with varicocele in comparison with fertile men (P<0.05).Conclusion: Expression of PAWP as a protein involved in spermatogenesis and fertilization process, has decreased in infertile men with varicocele. In addition, sperm DNA integrity was disrupted in these individuals that can be considered as a main etiology of infertility.

Background: Thyroid carcinoma is the most common endocrine malignancy and approximately accounts 2% of all cancer cases. Medullary thyroid cancer (MTC) is an endocrine tumor with differentiation of Parafollicular or C-cells and is categorized into hereditary or sporadic types. Medullary thyroid carcinoma approximately accounts for 5-10% of all thyroid carcinoma. Germ-line and somatic mutations in exons 10 and 11 RET (Rearranged during Transfection) proto-oncogene are responsible for the occurrence of the familial and sporadic types, respectively. Calcitonin is a key marker in MTC diagnose and has been demonstrated to be highly sensitive for differential diagnosis prognostic assessment, follow-up and evaluation of MTC treatment. The aim of this study was to investigate the relationship between plasma levels of calcitonin in MTC patients with or without RET mutation.Methods: In this cross-sectional study, the population consist of MTC patients who have referred to the endocrine and metabolism research center of Shahid Beheshti University of medical sciences since October 2013 till October 2016. Genomic DNA was extracted from peripheral blood leucocytes using the standard salting out/proteinase K method. Nucleotide change detection in exons 10 and 11 was performed using polymerase chain reaction (PCR) and direct DNA sequencing methods. Participants were then divided into two groups with or without mutation (43 individuals in each group). Plasma calcitonin levels were determined by enzyme-linked immunosorbent assay (ELISA) method in both groups.Results: Evaluation of the level of plasma calcitonin in 43 patients with a molecular mutation in RET proto-oncogene (mean age 31 years) and 43 patients without molecular mutations in RET proto-oncogene (mean age 43 years) were 7.6 pmol/mL and 3.07 pmol/mL respectively. This difference is statistically significant (P=0.0014).Conclusion: Routine measurement of calcitonin has been investigated as a screening method for the diagnosis of medullary thyroid carcinoma patients. Nevertheless, additional data are required to definitely support routine measurement of calcitonin due to the role of RET proto-oncogene.

Background: Urinary tract infections are very common in patients with high blood pressure. Hypertensive patients experience an average of three times of urinary tract infection per year. Blood pressure control is very important for preventing complications and also for identifying high-risk groups. Since, there is no national related study in this regard, the present study was conducted to investigate the effect of chronic hypertension on the incidence and recurrence of urinary tract infections.Methods: In this case-control study, the required data were collected from outpatient cases referring to Taleghani Hospital and Sina Hospital related to Tabriz University of Medical Sciences in Tabriz city, Iran. Data needed for the control group included patients accompanying patients who had no symptoms of urinary tract infection and with no history of blood pressure.Results: 60 patients with urinary tract infections were examined: 57 (47.5%) of the subjects were men and 63 (52.5%) women. There was a significant relationship between the rate of red blood cell deposition in the first hour and systolic blood pressure. There was no significant correlation between the numerical value of white blood cell count and systolic or diastolic blood pressure in the studied patients.Conclusion: According to the results of the present study, there was a significant difference in systolic blood pressure in patients ESR 1 hour (red blood cell deposition rate in the first hour) with hypertension in case and control groups. There was a significant correlation between the ESR of the first hour and systolic blood pressure in the study, so that with an increase in ESR 1h, the systolic blood pressure increased in the examined patients, however, no significant correlation was found between ESR 1hour and diastolic blood pressure. Also, there was no meaningful correlation between the numerical value of white blood cell count and systolic or diastolic blood pressure in the studied patients. There was no significant correlation between systolic and diastolic blood pressure and age.

Background: The prevalence of gestational diabetes is increasing among pregnant women. It is associated with an increased risk of congenital heart disease, including hypertrophic cardiomyopathy. The aim of this study was to evaluate the effect of maternal diabetes control (based on HbA1c) on their hypertrophic cardiomyopathy in newborns.Methods: This case-control study was performed on 60 neonates born in Afzalipour Hospital (Kerman University of Medical Sciences) from May to November 2014 in two groups of eligible infants using the convenience sampling method. Information about the age, sex, weight, gestational age, maternal age, obstetric history, gestational diabetes through the checklist were collected. Then Doppler echocardiography, MMode, Doppler tissue was conducted on two groups. Echocardiographic criteria including ventricular septal thickness and blood HbA1c mothers in both groups were compared. To compare quantitative and qualitative variables between the two groups’Independent samples t‐test and Chi-square test was used. A significant level of 0.05 was considered in all of the statistical samples and SPSS software, ver.20 (IBM, Armonk, NY, USA) was used to analyze the data.Results: In this study, the birth weight of infants and the age of mothers did not differ between two groups (Respectively P=0.56, P=0.08) However, HbA1c was significantly higher in the infants of mothers with impaired glucose tolerance test (GTT) (P<0.001).In infants of mothers with impaired GTT, ventricular septal thickness was significantly higher than the healthy controls (P=0.03), Also there was a significant difference between two groups in tissue Doppler criteria (Ea) (P=0.04), In other echocardiographic criteria, no significant differences were reported (The LA/AO, LVPWT, LVEF, LVEF, LVFS, LVFS, LVEDd, LVESd, Sa and Aa, All P-values were ≥ 0.05).Conclusion: Diabetes mellitus of mothers causes several complications in their infants.The prevalence of cardiomyopathy hypertrophy is higher in babies whose mothers have higher levels of HbA1c and a sign of poor control of blodd glucose level during pregnancy.

Background: Sleep quality may be directly related with vitamin D serum level. Some studies found that people with lower vitamin D serum level experienced a lower sleep quality. Consequently, this study aimed at determining the effect of vitamin D supplements on sleep point and quality in 20-50 year-old people with sleep disorders.Methods: This double-blind, clinical trial was performed in Golestan Hospital of Ahvaz Jundishapur Medical Sciences University from November 2015 to February 2016 on 89 people with sleep disorders based on Pittsburgh Sleep quality index (PSQI).Participants of the study were selected based on inclusion and exclusion criteria.Patients under study were divided into two groups of vitamin D supplement and placebo recipients by random allocation. At the end of the study, the data on 89 subjects (44 in intervention group and 45 people in placebo group) were examined. Participants in intervention group received four edible pearls, each 50000 IU vitamin D, one in a fortnight. To placebo group, a placebo capsule (edible paraffin) was given one in a fortnight. Before and after intervention, Petersburg’s sleep quality questionnaire, Depression Anxiety Stress Scale (DASS-21) questionnaire, international physical activity questionnaire, general information questionnaire, sun exposure, vitamin D serum level and three-day food record questionnaire were assessed and recorded for all participants. To analyze data, Student's t-test, Chi-square test, ANCOVA, Mann-Whitney U test and Wilcoxon statistical tests were used.Results: Mean score of Pittsburgh sleep quality questionnaire before and after intervention was 9.45±2.44 and 6.75±2.97 respectively (P=0.001) in interventional group and 10.51±3.14 and 9.73±3.04 respectively (P=0.18) in controls. Based on the results of the present study, at the end of the study score of Pittsburgh sleep quality questionnaire reduced significantly in vitamin D recipients as compared with placebo recipients (P=0.001).Conclusion: This study shows that the use of vitamin D supplement reduced sleep score (PSQI) or improved sleep score, reduced sleep latency, increased sleep duration and increased subjective sleep quality after modifying confounding variables in adult people with sleep disorder.

Background: Brucellosis is a systemic infection caused by gram-negative coccobacilli and facultative intracellular bacteria of the genus brucella. Brucellosis is a bacterial disease common to humans and livestock. Infection with Brucella spp. continues to pose a human health risk globally despite strides in eradicating the disease from domestic animals. The humoral and cellular immunity plays an important role in brucellosis. The effect of phagocytosis and cellular immunity has been demonstrated in brucellosis. The effect of cupping as a therapeutic method on bacterial diseases has been demonstrated. By considering this fact that cupping is an effective method on host immune system functions and has potential effect to regulate the inflammatory reactions.Methods: This experimental study was carried out on 48 rats in 6 groups (48 rats were divided into 6 groups) during the first 6 months from January 2015 to July 2016 in the laboratory of microbiology and animal of Hamedan University of Medical Sciences.The rats were infected through the injection ofBrucella melitensis with plenty 5×105 (cfu/ml) of bacteria. After a week, in order to approve the accuracy of the infection in the studied rats inoculated with coombosBrucella melitensis, Wright test, 2-Mercaptoethanol test and Coombs' Wright test were used. The rats were then treated with cupping method in their sacral area. IFN-gwas measured using enzyme-linked immunosorbent assay. And the study of tissues using hematoxylin and eosin (H& E) Staining.Results: The results of this study showed that cupping leads to an increase in the mean serum level of interferon-gamma. The histopathological study of liver tissue showed that the radial arrangement was not observed in the infected group with brucellosis and the cells were acidophilus. While, the radial arrangement was observed in treated rats with cupping, but it was not complete. The number of enlarged sinusoids were reduced.But, cell infiltration was observed.Conclusion: This study showed that cupping can increase serum level of IFN-g, and thus help to the clearance of disease and improvement of injury in the brucellosis animals lab.

Background: The death certificate is a document consisting of the deceased individual’s basic information and identification which is filled out, registered and signed by a doctor. the World health organization’s policies in their health planning, provide a suitable database with knowledge of the required elements for planners and other authorized information demanders. During a multi-year cooperation between various organizations, the first uniformed death certificate according the ICD-10 standard got published in the country in the year 2004.Methods: This is a retrospective study which is about all of the deceased individuals in Tajrish and Modares Tehran hospitals from april 2013 until the march 2014 who had death certificates. In this study the data related to 777 individual’s death certificates and medical files was analyzed. The sampling method was census and all the cases in the study’s time period who had death certificates were studied. The cases that had a gap in their required information were ruled out of the study. The data that included age, sex, place of death, issuing doctor’s expertise, general information and the cause of death was extracted from the archived files.Results: The cases studied, 421 people died in Tajrish Hospital and 356 in Modarres Hospital. The highest number of deaths in both hospitals were in the internal wards (336 cases) and surgery (168 people).45.6% of death certificates have been issued by a forensic expert.64.8% cases correctly inserted ICD-10 code.Conclusion: Training of physicians for the importance of death certificate and how it should be completed is very important. This research showed that in the cases which the death certificates were completed by the hospital forensic medicine specialists were more useful and accurate.

Background: Pyoderma gangrenosum (PG) (ulcerating neutrophilic dermatosis) is a rare disease that about of half of these patients have a systemic disorder, particularly Crohn's and ulcerative colitis. In addition, inflammatory lesions play key role in its pathogenesis. In early diagnosis of disease, we will further prevent of serious consequences of the disease. In this report, a case of PG after the vaginal surgery with history of ulcerative colitis was introduced.Case presentation: A 37-years old woman was admitted in an University Hospital of Mashhad University of Medical Sciences, Iran, in 2016 two weeks after genital surgery.The chief complaints were fever, painful tenderness, ulcerative lesion and inflammatory papule on surgical site and thigh. She suffered of fever despite received oral and then wide spectrum intravenous antibiotic therapy. Blood cultures and wound culture were negative. In addition to two deferent intravenous antibiotics, topical wound debridement was performed. Despite this course of treatment which did not improve the lesion, biopsy was performed. Histopathology features of biopsy specimen indicated prominent neutrophils mixed inflammation and lymphocytic vasculitis indicated as pyoderma gangrenous. The patient's medical history included associated ulcerative colitis from 18 years ago and she was under irregular oral receiving of Asacol (mesalamine). Intravenous corticosteroid therapy was administered which led to response of skin of right thigh and surgical site inflammation. After 6-months followup, the patient is still in good condition.Conclusion: Based on major variable clinical manifestations and no diagnostic serologic test of pyoderma gangrenosum, diagnosis of this disease is difficult. Increased awareness about PG and exclusion of other etiologies such as inflammatory and immunologic disease will aid in prompting of pyoderma gangrenosum diagnosis and proper management of the disease.