Vol 56, No 1 (2018)


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    Cirrhosis is associated with cardiac chronotropic and inotropic dysfunction which is known as cirrhotic cardiomyopathy. Cardiac responsiveness to adrenergic stimulation is impaired in cirrhosis. Moreover, there is vagal nerve dysfunction which is related to neuromodulatory dysfunction of the angiotensin II in the cirrhosis. This study was aimed to explore the hypothesis that administration of Losartan-angiotensin II receptor antagonist increases cardiac chronotropic response to isoproterenol in cirrhotic rats; and if so, whether this is associated with altered cardiac TGF-β receptor expression. Cirrhosis was induced by surgical ligation of the bile duct (BDL) in male Wister rats. Half of the BDL-group and control group were treated with losartan for four weeks. Four weeks after bile duct ligation or sham surgery the atria were isolated and spontaneously beating rate and chronotropic responsiveness to β-adrenergic stimulation was assessed using standard organ bath. The pathological assessment was done on the atria. Moreover, the expression of TGF-β has assessed the atria using quantitative RT-PCR. Bile duct ligation could induce a significant hypo-responsiveness to adrenergic stimulation. In cirrhotic rats, the chronotropic responses increased after chronic treatment with losartan, but it was not significant. The pathological study showed that losartan could not decrease fibrosis in atria in losartan treated cirrhotic group. TGF-β expression is markedly increased in cirrhotic rats which are significantly decreased in atria following administration of losartan. These results might be considered as angiotensin II role in cirrhotic cardiomyopathy, but further studies are required to elaborate the mechanism as well as the possible advantage of losartan. We conclude that cirrhosis in rats is associated with altered expression of TGF-β in the atrium which losartan can ameliorate it.

  • XML | PDF | downloads: 372 | views: 726 | pages: 14-20

    Organophosphates (OPs) and carbamates are acetylcholine esterase inhibitors (AChEIs), which can cause seizure and lethality. Anticonvulsant properties of potassium channel openers including cromakalim have been determined in previous studies. In the present experiment, the possible effect of cromakalim on the convulsion and death induced by OPs and carbamates was studied in mice. Dichlorvos (an OP, 50 mg/kg) and physostigmine (a carbamate, 2 mg/kg) were used to induce seizure in animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg was injected 30 min before dichlorvos and physostigmine, and 5 min before glibenclamide (a potassium channel blocker, 1 mg/kg) administration. All injections were performed intraperitoneally. After drugs administration, the onset of convulsion, death, the severity of seizure, and rate of mortality were investigated. Results revealed that both dichlorvos and physostigmine induced seizure activity and lethality in 100% of the animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg significantly increased the latency of both seizure and death (P<0.05). Also, cromakalim decreased the mortality rate induced by dichlorvos and physostigmine (P<0.05). On the other hand, glibenclamide blocked all aspects of the anticonvulsant effect of cromakalim (P<0.05). This study revealed for the first time that cromakalim (a KATP channel opener) diminishes the seizure and death induced by dichlorvos and physostigmine in mice, and introduces a new aspect to manage the patients who suffer from OPs/carbamates-induced seizure.

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    The aim of this study was to investigate whether hypermethylation of Eyes Absent 4 (EYA4) is also implicated in Iranian Colorectal Cancer (CRC) patients or not. From fresh frozen tissues, samples from 38 paired (cancer and normal) CRC tissue specimens were used in this study, the DNA was isolated, sodium bisulfite treated and analyzed by methylation-specific polymerase (MSP) chain reaction using primers specific for unmethylated or methylated promoter sequences of the EYA4 gene. We also analyzed EYA4 mRNA expression using real time RT-PCR. Demographic characteristics of these patients including age, sex, tumor grade, location, stage, and TNM classification were evaluated and the relationship between methylation status of the gene and clinicopathological features was analyzed. Current study indicated that EYA4 promoter hypermethylation has a sensitivity of 81.57% and specificity of 78.94%. Findings showed lower expression of EYA-4 in methylated samples in comparison with its normal adjacent tissue, although it was not significant (P>0.05). No significant associations were observed between EYA4 hypermethylation and the clinicopathological characteristics. Although the clinical patient outcome of our 38 CRC patients was not associated with EYA4 promoter hypermethylation, the high frequency of this methylation and its high sensitivity and specificity to neoplastic cells may qualify EYA4 promoter methylation as a potential candidate screening marker in Iranian population and may help to improve early detection of CRC.

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    Wharton`s jelly-derived mesenchymal stem cells (WJ-MSCs), have a high proliferation valency and they do not produce teratogen or carcinogen after subsequent transplantation. They are known as regenerative medicine. Thus more research is needed on the isolation and characterization of mesenchymal stem cells. In this experimental study, we obtained Wharton's jelly tissues from mothers during normal vaginal delivery, after obtaining their informed consent. Mesenchymal stem cells were isolated from cultured Wharton`s jelly, cultured, and were then examined for their proliferation, immunophenotypes, and differentiation capacities. The immunophenotypes of WJ-MSCs were analyzed by flow cytometry. Differentiation was performed resulting in osteogenic, chondrogenic and adipogenic cells. WJ-MSCs formed a homogenous monolayer of adherent spindle-shaped cells. Our results showed the high capacity of the proliferation of WJ-MSCs. Immunophenotyping further confirmed the purity of the isolated cells; their surface antigen expression showed the phenotypical properties like those of WJ-MSCs. The expanded cells were positive for CD 90, CD105, and CD44; they were negative for CD34 and HLA-DR surface markers. The cells had the adipocytic, osteocytic and chondrogenic differentiation capacity. The isolation and characterization of WJ-MSCs with high purity had been conducted, and the results were obtained in a short span. The present study has revealed the feasibility of the culture medium with high glucose and 15% FBS in isolation and proliferation of WJ-MSCs. When Wharton`s jelly pieces were put in the dry bottom of the flask, very effective separation of the MSCs was achieved.

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    Initiation of spermatogenesis in primates is triggered at puberty by an increase in gonadotropins; i.e., follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Prior to puberty, testis of the monkey contains only undifferentiated germ cells. However, sermatogonial differentiation and spermatogenesis may be initiated prior to puberty after stimulation with exogenous LH and FSH. Retinoic acid (RA) signaling is considered to be a major component that drives spermatogonial differentiation. We were interested in evaluating the relative role of LH and FSH, either alone or in combination, in regulating the retinoic acid signaling in monkey testis. Sixteen juvenile male rhesus monkeys (Macaca mulatta) were infused with intermittent recombinant single chain human LH (schLH) or recombinant human FSH (rhFSH) or a combination of both for 11 days. We then analyzed the expression of the several putative RA signaling pathway related genes; i.e. RDH10, RDH11, ALDH1A1, ALDH1A2, CYP26B1, CRABP1, CRABP2, STRA6, STRA8 in the testis after 11 days of stimulation with vehicle, LH, FSH and combination LH/FSH using quantitative real-time PCR (qPCR). The qPCR results analysis showed that administration of gonadotropins affected a significant change in expression of some RA signaling related genes in the monkey testis. The gonadotropins, either alone or in combination dramatically increased expression of CRABP2 (p≤0.001), whereas there was a decrease in ALDH1A2 expression (p≤0.001). Moreover, combined gonadotropin treatment led to the significant decrease in CRABP1 expression (p≤0.05). These findings are the first evidence that the activity of retinoic acid signaling in the monkey testis is regulated through gonadotropins (LH/FSH) levels.

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    Despite some proposed roles for the diagnostic impact of the cervical vestibular evoked myogenic potential test in the patients with Meniere’s disease, the role of this test as an objective instrument in following up the patients with Meniere’s disease who underwent. Intratympanic steroid injection is not cleared. In a prospective study, thirty-one adult patients with definite one-sided Meniere's disease with vertigo as main complaint refractory to medical treatments for three months, were selected. Patients underwent three times of intratympanic dexamethasone injection with one-week intervals. We performed cervical vestibular evoked myogenic potential test at first and four weeks after the last injection for all participants. We followed the patients for one year. The study results were analyzed with the chi-square test. Cervical vestibular evoked myogenic potential test could not be recorded in 26 patients (83.9%), and the test results were abnormal in the remaining 5 patients. The results were abnormal in the healthy ear of 32.3% of the patients. Despite the clinical improvement of the symptoms after intratympanic injection, the test results were not changed. Cervical vestibular evoked myogenic potential test could not be recorded in the majority of the patients with Meniere's disease; while it is usually recorded in normal ears. On the other hand, results of the cervical vestibular evoked myogenic potential test do not change during the early phase after treatment and could not be a good option for follow up and evaluating the response in this situation.

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    Phenylketonuria is one of the most important congenital disorders and an autosomal recessive metabolic disease that can cause irreversible brain damages, mental retardation, and cognitive disorders if left untreated. In order to reduce the genetic abnormalities caused by this metabolic disease, screening programs are implemented. The quality of the program must be properly assessed to achieve the objectives of this program if promoting children's health is of concern. The descriptive-analytic method is adopted here to assess the phenylketonuria screening program in practice in Chaharmahal and Bakhtiari province since 2012 and analyze the incidence and program coverage. The quality of the screening program is assessed through analyzing the time of diagnosis, beginning of the treatment and the healthcare centers’ facilities with checklists. The parental and the staff awareness is assessed through knowledge measuring questionnaires. Cumulative incidence of phenylketonuria in Chaharmahal and Bakhtiari province from 2012 to 2015, is 1 in every 6662 live births. The program coverage across the region is 100%. The recorded on-time sampling index before 5 days of age, indicate 84.6 % in 2015 from 80% in 2012. The treatment begun before the newborn 4 weeks was over in all cases. Program sensitivity was 100 %, and its specificity was 99.9%. Staff awareness is fair with no impact on parental awareness. General quality of the screening program is appropriate, and as to sensitivity and on-time curing specificity, higher staff and parental awareness supervision are recommended as well.

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    Pressure Ulcers (PUs) remain among the most common complications after traumatic spinal cord Injuries (SCIs). The main goal of risk factor assessment with different tools has been to provisionally estimate the chance of developing pressure ulcers in patients with Spinal Cord Injury (SCI). Braden tool has been of good predictive value and most commonly employed in hospital communities for risk assessment of pressure sore development. The objective of this study was to determine the Braden risk factors as well as the prevalence of pressure injuries in SCI patients. This cross-sectional study was performed from June 2013 to December 2015 on 163 consecutive referred outpatients with chronic traumatic SCI in our tertiary SCI rehabilitation clinic. We assessed pressure induced skin injuries as well as their Braden risk factors and analyzed their association with stage and location of Pressure Ulcer (PU) and calculated prevalence of PU. One hundred and sixty-three patients out of 580 were found to have active pressure sores, with a prevalence of 28.1%. In the multiple models, only the Braden scale had significant association with the presence of active pressure sore. Patients with severe and moderate Braden scores were 2.36 and 1.82 times, more at risk of pressure sore development, as compared with those having mild scores (P≤0.01). It may be deduced that in various stages of SCI rehabilitation, the Braden scale may be calculated, and patients with moderate and severe risks (according to Braden sale) may need more attention and/or inpatient care for PU prevention.  

Case Report(s)

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    Kleine-Levin syndrome (KLS) is a rare sleep disorder mainly affecting teenage boys in which the main features are intermittent hypersomnolence, behavioral and cognitive disturbances, hyperphagia, and in some cases hyper sexuality. Etiology is unknown, and there is no specific clinical or imaging test for this syndrome even though the illness has well-defined clinical features. Also, there is no effective treatment for KLS. KLS is self-limited, so the prognosis for these patients is not so bad. This study presents our case report and comprehensive workout that led to diagnosis which is primarily clinical. Our patient is a 20-year-old man referred to our clinic because of sleeping problems. At the age of 14, he presented with complaints of the excessive duration of sleep, increased appetite, excessive daytime sleepiness, loss of interest in social activities during attendance of high school and hallucinations. The excessive diagnostic procedure does not find pathological. Kleine-Levin syndrome (KLS) is a rare sleep disorder of unknown etiology which diagnosis is clinical and diagnostic workup is mainly to exclude other similar conditions. There is no specific therapy, but the disease is self-limited and with good prognosis.

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    Angiosarcomas of the uterine is a malignant and poor prognostic tumor and can either be a primary sarcoma or arising secondary to radiotherapy of a more complex tumor. Primary uterine angiosarcomas are exceptional and probably arise from embryonic vascular remnants, teratoma or from the rich uterine vasculature. We reported a rare case of primary angiosarcoma of uterine that at the time of diagnosis presented with sign and symptom of local and distant metastasis. The patient presented with dyspnea, chest pain, and history of vaginal bleeding and pelvic pain. The physical exam revealed pallor, prominent jugular pulse pressure, a palpable fixed mass in the pelvic however vaginal exam was unremarkable. Transthoracic echocardiography (TTE) revealed massive pericardial effusion and also a large mass in the right atrium. The abdominal ultrasound showed echogenic and poor echogenic segments in uterine mass combined with central necrosis. The patient underwent total hysterectomy and Bilateral salpingo-oophorectomy followed by radiotherapy and adjuvant chemotherapy. The patient underwent open heart surgery with resection of cardiac mass and further received a four cycle of radiotherapy (50 MG) to the mediastinum. The further follow-up (6 month) revealed no recurrence of tumor in a mediastinum. However, patient died from metastasis to the liver and its hepatic failure sequels.

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    Hallervorden-Spatz syndrome is a rare neurodegenerative disorder with hereditary properties. It usually occurs in young adolescents with extrapyramidal symptoms besides disturbed mental function. In this study, we present a 23-year-old neuropsychiatric patient who primarily misdiagnosed to have conversion disorder. She had 5-year history of progressive dysarthria and generalized abnormal movements. After detecting the pathognomonic sign of “eye of the tiger” diagnosis was confirmed. The patient was discharged. She had satisfactory condition in her follow-up. Such a rare syndrome should be considered in patients with similar presentation, and upon the diagnosis, PKAN2 gene study should be done to detect possible new mutations.