TEHRAN UNIVERSITY MEDICAL JOURNAL (TUMJ)
Year:2009 | Volume:67 | Issue:1|Papers Count:14

The prostate is a small gland located below the bladder and upper part of the urethra. In developed countries prostate cancer is the second common cancer (after skin cancer), and also the second leading cause of cancer death (after lung cancer) among men. The several studies have been shown prostate cancer familial aggregation. The main reason for this aggregation is inheritance included genes. The family history is an important risk factor for developing the disease. The genes AR, CYP17, SRD5A2, HSD3B1 and HSD3B2 are all intimately involved in androgen metabolism and cell proliferation in the prostate. Each shows intraspecific polymorphism and variation among racial-ethnic groups that is associated with the risk of prostate cancer. Some of genes expressed in the prostate are in association with the production of seminal fluid and also with prostate cancer. Epigenetic modifications, specifically DNA hypermethylation, are believed to play an important role in the down-regulation of genes important for protection against prostate cancer. In prostate cancer numerous molecular and genetic aberrations have been described. It is now well established that cancer cells exhibit a number of genetic defects in apoptotic pathways. In this review article, the most recent data in molecular genetic, prevention and especially gene therapy in prostate cancer are introduced.

Background: Adenosine receptors play an important role in the treatment of paroxysmal supraventricular tachycardia in cardiovascular system. This effect is through interaction with A1 type of G-protein-coupled adenosine receptors. The effect of N6-cyclopentyladenosine (CPA), an A1-selective adenosine agonist, was studied on ouabain-induced toxicity in spontaneously beating isolated guinea pig atria.Methods: The isolated guinea pig atria were mounted on the organ bath containing modified krebs and contractile responses in the four groups (sham, CPA, ouabain, CPAouabain) were measured.Results: CPA significantly increased the time of onset of arrhythmia (toxicity) induced by ouabain (1.2μM) when it was administered 10 min before ouabain was added in organ bath. CPA (2-16nM) produced a dose-dependent decrease in the force of contractions (34%-51%) and in the rate of contractions (22%-48%). Ouabain (1.2mM) alone produced arrhythmia at 7 min and either asystole or standstill at 22 min. CPA alone did not prduce any arrhythmogenic effect but CPA (8nM) increased the time required to produce arrhythmia to 27.5 min and prolonged beating atria to more than 63 min and prevented the occurrence of asystole.Conclusion: CPA produces direct cardiac action, probably due the inhibition of cardiac Ca2+ channel and membrane hyperpolarization of atrium cells in guinea pig atria. Moreover, our results suggest that CPA may reduce the membrane conduction through inhibition of ionic channels, which decrease ouabain- induced toxicity.

Background: Type I diabetes is an autoimmune disease characterized by T-cell Mediated destruction of pancreatic b-cells. A variety of environmental, genetic and Immunologic factors are involved in the development of the disease. IL18 is a cytokine secreted by macrophage and monocytes and play an important role in the pathogenesis of diabetes Type I through inducing IFN-g production. It is shown to be strongly associated with the development of diabetes in NOD mice. It is also shown to have increased level in the subclinical stage of diabetes mellitus (type 1). Genetic polymorphisms in the IL-18 gene influence production and secretion of cytokine and are considered as a risk factor in auto-Immune diseases.Methods: In this case control study, 75 type I diabetic patients and 88 healthy controls studied for polymorphism at positions -137 and -607. DNA extraction from the whole blood was performed according to the standardized method and polymorphism was determines by SSP-PCR. Data were analyzed by SPSS- 12 using Chi-Square Test with 95% Confidence interval.Results: A statistical significant difference in GG genotype (53%) and CC genotype (16%) at the -137 position of IL18 gene was found, as compared to the control subjects (p=0.000) whereas we have not shown any statistical significance at the position -607. Conclusion: IL18 is a key cytokine secreted by macrophages and monocytes and stimulate the Th1 lymphocyte. This cytokine can activate cytotoxic T lymphocytes(CTL) and destroy the pancreatic b cell. Our results show that the frequency of GG and CC genotypes at the position -137 may be associated with susceptibility to diabetes.

Background: Anti-dsDNA antibodies frequently found in the sera Systemic Lupus Erythematosus patients, particularly in active disease stage. Nowadays exploit different eukaryotic and prokaryotic dsDNA as antigen source and different reagents as binder. The aim of this study to compared two dsDNA different sources and tow different kinds of reagents for binder in ELISA test.Methods: In this study bacterial genomic DNA from E.coli (ATCC 25922) and genomic DNA from calf thymus extracted with high purity and were used as antigens for IgG anti-dsDNA detection by ELISA. To coat dsDNA in microtiter wells, tow different kinds of reagents including methylated –BSA and poly-l-lysine (for pre-coating) are used. Sera from systemic lupus erythematosus patients and from normal blood donors are used to assess sensitivity and specificity of our ELISA test in compared with IF test and commercial kits.Results: Our results displayed pre-coating of microtiter plates with methylated –BSA reduce nonspecific binding reaction and the relative sensitivity and specificity of ELISA increased when calf thymus DNA is employed as antigenic source in compared with IF test and commercial kits 80%, 88% and 100%, 98% respectively, but when E.coli DNA is used 73%, 69% and 85%, 79%, respectively.Conclusion: The genomic DNA from calf thymus is a potentially useful source of antigen for detection of anti-dsDNA by ELISA. Also the use of methylatted- BSA could have an effective role in reducing of nonspecific binding reactions.

Background: Plasminogen has a central role in fibrinolyrtic system can activate through various activators (PAs) to its active form plasmin and perfoem its vital function that is fibrin clot lysis. Furthermore the fibrinolyrtic system plays a major role in angiogenesis. The fibrinolyrtic system activation control cell migration and invasion. In addition to this, plasmin regulates tumor growth. Monoclonal antibodies, as biological tools, play an important role in basic researches.Methods: In the first step the effects of antibodies on the activation of fibrinolyrtic system with PAs were evaluated with several methods including macroscopic observation, quantitative measurement of DD/E fragments by D-dimer assay and activation of plasminogen by S-2251 synthetic substrate (ELISA method), subsequently we studied the effect of antibodies on angiogenesis process in an in- vitro model. Results: Results showed that MC2B8 that is an inhibitor of plasminogen activation in presence of plasminogen activators can inhibit angiogenesis process: A1D12 that is against N-terminal domain of Glu-plasminogen, in addition to activation of fibrinolyrtic system in presence of plasminogen activators, can activate in vitro angiogenesis process.Conclusion: Plasmin formation is a critical step in invasion and migration of endothelial cells to form new vessels. Plasmin directly participates in angiogenesis by direct fibrin and other matrix components degradation, and indirectly by activating matrix degrading metalloproteinase and angiogenic growth factors. According to the in- vitro results, MC2B8 and A1D12 monoclonal antibodies play roles in this process in a dose dependent manner.

Background: Leukemia is one of the most common pediatric malignancies. T-cell Acute Lymphoblastic Leukemia (T-ALL) accounts for 15% of hematopoetic cancers. It has been well understood that identification of genetic alterations associated with leukemias is very critical. The molecular genetic techniques have promoted the identification of leukemia-associated genetic changes that may characterize the most accurate predictors of clinical outcome. These considerations reinforce the requirement for rapid identification of the abnormalities.Methods: Multiplex RT-PCR, a highly sensitive and specific method applied to screen simultaneously three most frequent transcription factors, TLX1/HOX11, TLX3/HOX11L2 and TAL1/SCL which are associated with T-cell Acute Lymphoblastic Leukemia (TALL).Results: We describe here our efforts to establish a multiplex RT-PCR analysis system that facilitates the detection of these transcription factors which are specifically expressed in Peer, HPB-ALL and K562 cell lines, respectively. Conclusion: The multiplex RT-PCR technique is a sensitive, valuable and costeffective diagnostic tool which could improve our ability to accurately and rapidly riskstratification of patients with childhood T-ALL. In order to perform multiplex RT-PCR technique researchers do not need bone marrow samples and they can employ this method using peripheral blood samples. Therefore, the status of treatment could be followed by assessment of the level of mRNA expression of oncogenic transcriptional factor using peripheral blood sample. Use of this procedure not only provides the best results in short term for specialist, but also clinicians could have opportunities to choose suitable treatment strategies with decrement of drug side effects.

Background: Transitional Cell Carcinoma (TCC) of bladder is the second most common urogenital malignancy and because of its high rate of recurrence (two third of tumors recur) vigilant surveillance is necessary. There have been a lot of efforts to find a proper biomarker for detecting urothelial cancers because available methods are expensive and invasive (like cystoscopy) or have a low degree of sensitivity (like urine cytology). Urothelial malignancies, like other cancers tend to express a large amount of telomerase. The aim of this study was to evaluate the possible application of voided urine human telomerase reverse transcriptase (hTERT) mRNA assay in detecting lowgrade bladder carcinoma in comparison with urine cytology.Methods: Voided urine samples were collected from 49 patients who were supposed to go under operation. Samples were examined by both Quantitative Real-time RT-PCR (for measuring hTERT mRNA level) and cytology; the results were then compared to the final pathologic studies.Results: Regardless of clinical stage and or pathological grade of tumor, sensitivity of telomerase test and urine cytology was 74% and 16% respectively. There was a strong correlation between results of urine cytology and stage and/or grade of tumor; however, sensitivity of telomerase test was acceptable regardless of stage and or grade of tumor. There was a statistically significant difference between sensitivity of urine cytology and telomerase test (p<0.001). Conclusion: Detection of hTERT- mRNA can potentially be used as a non-invasive method for diagnosis and follow up of bladder carcinoma instead of urine cytology.

Background: Visual, brain stem auditory and somatosensory evoked potentials (EPs) have been traditional paraclinical tests to evaluate the competency of sensory tracts in multiple sclerosis (MS) patients. It seems that only one of these EPs could be sufficient, at least as a screening test. The objective of this paper is to evaluate the frequency of these three evoked potentials in definite MS patients.Methods: This descriptive cross-sectional study involved was 25 definite relapsing remitting MS patients who referred to our university hospital. Twenty five individuals from normal population without any neurologic, visual, auditory or sensory disorders have been evaluated as well to determine the standard values in our electrophysiology lab. Values more than mean+2.5SD for latencies and less than mean-2.5SD for amplitudes were considered as abnormal.Results: Fifteen (60%), 13 (52%), and 13 (52%) had abnormal visual, auditory and somatosensory EPs respectively. The latency of P100 in visual EP (VEP) had the most sensitivity among all of the parameters. It was determined that the possibility of abnormality in each of auditory and somatosensory EPs in the presence of normal VEP could be 30.8%. In other words 30.8% of patients with negative VEP could have a positive auditory brain stem or somatosensory EPs.Conclusion: In our study, a VEP abnormality was more frequent than auditory brain stem and somatosensory EPs. Thus it is not logical to perform triple EP tests in all suspected MS patients, but auditory and somatosensory EPs could be considered in patients with normal VEP.

Background: Previous studies have suggested the presence of a relationship between the increase of Nucleated RBC (NRBC) and the duration and intensity of asphyxia. The purpose of this study was to evaluate the relationship of fetal heart rate pattern and the number of NRBC’s in umbilical cord blood sample at birth.Methods: We enrolled 322 pregnant women with healthy, term fetuses who referred to Mirza Kouchak Khan Hospital for pregnancy termination in 2005 in a case-control study. All patients underwent continuous FHR monitoring and based on their FHR pattern, they were divided into two groups with normal FHR pattern and at least one abnormality in FHR pattern (including absence of beat to beat variability; absence of proper acceleration; and early, late, variable and prolonged deceleration). Samples of umbilical cord blood were evaluated for NRBC count and pH immediately after birth.The variables were compared in these two groups.Results: The mean NRBC count was significantly higher in patients with any kind of deceleration (late, variable, early or prolonged) in comparison with controls (respectively 11.88±4.406, 8.32±4.64, 10.58±5.366, and 4.11±4.913 vs. 0.93±1.790 in controls). Furthermore the mean NRBC count was significantly higher in patients with absence of acceleration or beat to beat variability (10.73±5.07 and 13.73±3.58 vs. 1.47±2.50). There was a negative correlation between 5th minute Apgar score and umbilical cord blood sample with mean NRBC count of umbilical cord blood sample. Conclusion: Any abnormality in FHR pattern is associated with a significant increase in mean NRBC count of umbilical cord blood sample. There is also a significant relationship between the 5th minute Apgar score and umbilical cord blood sample pH, and mean NRBC count in umbilical cord blood sample.

Background: Uric acid as a final product of purine metabolism has a role of risk factor for cardiovascular disease with less clear mechanism in general population. The aim of this study was Assessing and finding association between uric acid levels and CAD as a risk factor in renal transplant candidates and if we can predict need to revascularization according to uric acid level as an important measure.Methods: This is a cross-sectional study that has been studied since April 2007 up to December 2008, in imam Khomeini and pars hospitals in Tehran. Inclusion criteria were patients with ESRD, more than 40 years who were candidates for renal transplantations. They underwent coronary angiography without regarding clinical cardiac symptom or results of noninvasive tests (for avoiding referral bias) and simultaneous analysis of serum uric acid level and results of this two producers were analyzed. Excluding criteria were patients who didn’t tend to coronary angiography, those who hadn’t adequate artery access, or potential comorbidity so that angiography was impossible and life expectancy less than 6 month.Results: 56 (24 females and 32 males) were constituted. 89.3% (50) of patients had coronary artery disease. The average of uric acid level was significantly different in patients with and without CAD [7.62±1.07mg/dl and 5.95±1.29mg/dl respectively] (p=0.0024). Moreover, there was statistically significant difference in serum uric level between patients who were candidate for revascularization and the others [7.89±0.79mg/dl and 6.2±1.27mg/dl respectively] (p<0.001). Conclusion: It seems that serum uric acid can be considered as a cardiovascular risk factor in renal transplant candidates and also as a predictor for related treatment.

Background: The long-term effects of poliomyelitis are known in many of countries. In despite of one accrue title for these signs and symptoms; there are similarity aspects in patients' problems. In the signs of explained, absence of strength and endurance, musculoskeletal difficulties, respiratory dysfunction, sleep disorders are more generalized. Prevalence of post polio syndrome (PPS) is aim of this study.Methods: 150 subjects with history of poliomyelitis (80 male and 70 female) in Tehran city contributes in this study and complete question forms. Results: Muscle pain was reported in 88% of subjects. Thigh muscle weakness was at 42/28%, also muscle spasm indicated at 66%. Recurrent falling of subjects appeared in 74/7%. Early fatigue reported 86%. Above five signs selected for PPS. In this study 85 subjects had four signs of above criteria or 56.66% of subjects had PPS. Conclusion: Depended of evaluation and observation there is post polio syndrome in Tehran. Recommended for physical therapy of post polio syndrome attend to stages of progression of this syndrome. In aim to this procedure, physical treatment of these patients must limit to muscle fatigue and also severe physical and exercise activities must be reduce, also some mild aerobic activities without fatigue can be useful.

Background: Anterior Cruciate Ligament (ACL) is one of the main knee stabilizing ligaments. Because of high incidence of ACL tearing especially in young athletes its reconstruction is very important. The aim of this study was to evaluate short-term results of anterior cruciate ligament ruptures using four strand hamstring auto graft and Bone patellar tendon autograph.Methods: The study group included 96 patients (3 female and 93 male) with ACL teared who had been referred to our center in 5 years period (2002-2007). The subject which were Accessed in this study included meniscal injury concomitant chondral injury, determine the most common cause of ACL tearing, comparision of IKDC and lysholm score in all patients before and after surgery, and limitation of rang ofmotion of knee  post operation. Results: Involvement was in the right knee in 38 patients and in the left knee in 58 patients. Mean age of patients was 27.6 years (19-48). Mean surgical delay was 18 month (1-77). The most common cause of tear was playing soccer. Meniscal injury was in 78 patients. (Medial meniscus in 63 patients, lateral meniscus in 29 patients) Concommitent chondral injury was in 54 patients (56.25%). 68% of patients returned to preoperative functions sport activity. There was no limitation in extension and there was 6 patients limitation in flexion about 20º. In last visit of patients IKDS in class A and B was 96. Conclusion: It is seem that arthroscopic reconstruction of ACL is a safe and good method in treatment of Knee stability. Use of IKDC and lysholm score for comparision of patients before and after surgery is helpful. The operation should be done early after injury. Reconstruction of ACL in older patients in the abscense of DJD is effective.

Background: Reflex Sympathetic Dystrophy Syndrome (RSDS) is a rarely described complication which characterized by pain, edema, movement and vasomotor disorders, trophic changes in the skin and patchy demineralization of bone in extremities. There are numerous risk factors such as trauma, surgery, myocardial infraction and drugs. Cyclosporine (CsA) is one of the drugs which can induce RSDS.Case report: Herein we described a 33- years old man (known case of ALL) with severe painful and edematous extremities, which was being treated with cyclosporine because of Graft Versus Host Disease (GVHD) after bone marrow transplantation. His laboratory tests were normal except for AST and ALT. With impression of Reflex Sympathetic Dystrophy Syndrome triple-phase bone scan was done, Increased uptake and delayed wash-out in vascular and bony phase is considered typical for RSDS. Due to clinical and triple-phase bone scan findings the diagnosis was established. Symptoms of RSDS improved when CsA was discontinued. Conclusion: According to this case report and the other ones, Cyclosporine could be considered as the etiology of Reflex Sympathetic Dystrophy Syndrome.