The effect of opium addiction on arrhythmia following acute myocardial infarction

The effect of opium addiction on the appearance of different types of arrhythmias after acute myocardial infarction (AMI) has been assessed in few studies. This study is aimed to determine the effect of opium on post-MI arrhythmia and also to address the differences in the appearance of different types of arrhythmias after AMI between opium addicted and non-addicted patients. In this comparative study, participants were classified into two groups with opium addiction (n=94) and without opium addiction (n=106). Post-MI arrhythmias were determined among each group. Study populations were included all patients with first AMI admitted within 6 hours of the onset of chest pain to coronary care units (CCU) of two teaching hospitals affiliated to Kerman University of Medical Sciences (KUMS) in the city of Kerman, Iran. Opium addicted subjects had significantly more frequency of arrhythmia than non-opium addicted subjects (80.9 vs. 22.6, respectively; P<0.001). Opium addiction was a strong predictor for the occurrence of post-MI arrhythmias in two models of crude analysis (crude OR=14.4, P<0.001) and after adjusting for potential confounder factors (adjusted OR = 21.9, P<0.001). The prevalence of sinus tachycardia, sinus bradycardia and atrial fibrillation in opium addicts were significantly higher than non opium addicts (P<0.05). The results of our study showed that opium addiction is a potential and strong risk for occurring post-MI arrhythmias. © 2012 Tehran University of Medical Sciences. All rights reserved

Comprehensive genotype‐phenotype correlation in AP‐4 deficiency syndrome; Adding data from a large cohort of Iranian patients

Mutations in adaptor protein complex‐4 (AP‐4) genes have first been identified in 2009, causing a phenotype termed as AP‐4 deficiency syndrome. Since then several patients with overlapping phenotypes, comprised of intellectual disability (ID) and spastic tetraplegia have been reported. To delineate the genotype‐phenotype correlation of the AP‐4 deficiency syndrome, we add the data from 30 affected individuals from 12 out of 640 Iranian families with ID in whom we detected disease‐causing variants in AP‐4 complex subunits, using next‐generation sequencing. Furthermore, by comparing genotype‐phenotype findings of those affected individuals with previously reported patients, we further refine the genotype‐phenotype correlation in this syndrome. The most frequent reported clinical findings in the 101 cases consist of ID and/or global developmental delay (97%), speech disorders (92.1%), inability to walk (90.1%), spasticity (77.2%), and microcephaly (75.2%). Spastic tetraplegia has been reported in 72.3% of the investigated patients. The major brain imaging findings are abnormal corpus callosum morphology (63.4%) followed by ventriculomegaly (44.5%). Our result might suggest the AP‐4 deficiency syndrome as a major differential diagnostic for unknown hereditary neurodegenerative disorders

Evolving evidence on a link between the ZMYM3 exceptionally long GA-STR and human cognition

The human X-linked zinc finger MYM-type protein 3 (ZMYM3) contains the longest GA-STR identified across protein-coding gene 5� UTR sequences, at 32-repeats. This exceptionally long GA-STR is located at a complex string of GA-STRs with a human-specific formula across the complex as follows: (GA)8-(GA)4-(GA)6-(GA)32 (ZMYM3-207 ENST00000373998.5). ZMYM3 was previously reported among the top three genes involved in the progression of late-onset Alzheimer�s disease. Here we sequenced the ZMYM3 GA-STR complex in 750 human male subjects, consisting of late-onset neurocognitive disorder (NCD) as a clinical entity (n = 268) and matched controls (n = 482). We detected strict monomorphism of the GA-STR complex, except of the exceptionally long STR, which was architecturally skewed in respect of allele distribution between the NCD cases and controls F (1, 50) = 12.283; p = 0.001. Moreover, extreme alleles of this STR at 17, 20, 42, and 43 repeats were detected in seven NCD patients and not in the control group (Mid-P exact = 0.0003). A number of these alleles overlapped with alleles previously found in schizophrenia and bipolar disorder patients. In conclusion, we propose selective advantage for the exceptional length of the ZMYM3 GA-STR in human, and its link to a spectrum of diseases in which major cognition impairment is a predominant phenotype. © 2020, The Author(s)

Iranome: A catalogue of genomic variations in the Iranian population

Considering the application of human genome variation databases in precision medicine, population-specific genome projects are continuously being developed. However, the Middle Eastern population is underrepresented in current databases. Accordingly, we established Iranome database (www.iranome.com) by performing whole exome sequencing on 800 individuals from eight major Iranian ethnic groups representing the second largest population of Middle East. We identified 1,575,702 variants of which 308,311 were novel (19.6%). Also, by presenting higher frequency for 37,384 novel or known rare variants, Iranome database can improve the power of molecular diagnosis. Moreover, attainable clinical information makes this database a good resource for classifying pathogenicity of rare variants. Principal components analysis indicated that, apart from Iranian-Baluchs, Iranian-Turkmen, and Iranian-Persian Gulf Islanders, who form their own clusters, rest of the population were genetically linked, forming a super-population. Furthermore, only 0.6% of novel variants showed counterparts in "Greater Middle East Variome Project", emphasizing the value of Iranome at national level by releasing a comprehensive catalog of Iranian genomic variations and also filling another gap in the catalog of human genome variations at international level. We introduce Iranome as a resource which may also be applicable in other countries located in neighboring regions historically called Greater Iran (Persia)

Investigation of Response to Angiotensin II (Ang II) and its Receptor Subtypes in Acutely Inflamed Joint Blood Vessels in Rabbit

Abstract: Introduction: Inflammatory joint diseases are common in elderly, and regulation of joint blood flow (JBF) is important in these conditions. The aim of this study was to investigate the response of inflamed joint blood vessels to angiotensin II (Ang II), a vasoconstrictor factor which has been shown to be produced in inflamed joints locally. Identification of Ang II receptor subtypes in joint blood vessels was the second goal of this study. Methods: The present study was performed on 12 Newzland white rabbits. Acute knee joint inflammation was produced by intraarticular injection of 0.5 ml of a 2% of carrageenan solution 24 hours before the experiment. On experiment day, animals were anaesthetized by thiopental sodium (50mg/kg ip) and carotid artery was cannulated for recording blood pressure. JBF was recorded by laser Doppler flow meter. Joint vascular resistance (JVR) was calculated by dividing arterial blood pressure by JBF. Results: Based on Ang II dose/ response curve of joint blood vessels, the constrictor response was started from 10-12 M and reached to maximum at 10-5 M.Losartan completely inhibited this response with no vasodilation left behind, therefore the receptor subtypes are AT1. No evidence of presence of AT2 receptor subtype was observed in joint blood vessels. Conclusion: The comparison of the results of this study with a previous study on normal joints showed that the Ang II receptor subtypes did not change due to the process of acute inflammation. Keywords: Acute inflammation, Joint blood flow, Angiotensin II, Angiotensin receptor, rabbi

Role of Angiotensin II in Reactive Oxygen Species Production and Modulatory Role of Nitric Oxide (NO) in Vessel Responses to AngII in Acute Joint Inflammation in the Rabbit

Abstract: Introduction: It has been approved that in most tissues NO production increases during acute inflammation and Angiotensin II has a role in production of reactive oxygen species (ROS). As regulation of joint blood flow (JBF) is important in this situation, this study was performed to investigate the interaction of local Ang II and ROS production and the modulatory role of NO on regulation of JBF during acute inflammation. Methods: The study was performed on 24 Newzealand white rabbits divided into three experimental and one control groups. Acute knee joint inflammation was produced by intraarticular injection of 0.5 ml of a 2% solution of carrageenan in knee joint. In the first group after 24 hours animals were anesthetized by thiopental sodium and carotid artery, jugular vein and saphenous artery were cannulated for recording blood pressure, injection of L-NAME and local injection of AngII and losartan respectively. Blood flow was recorded by laser Doppler flow meter. Joint vascular resistance (JVR) was calculated by dividing arterial blood pressure (ABP) by JBF. In the second group, knee joint tissue was used for homogenization and ROS measurement .In the third group, Losartan (10mg/kg) was administrated orally 2 hours before induction of inflammation. Results: L-NAME increased JVR significantly. JVR in response to AngII was significantly increased. This response was significantly potentiated by L-NAME (P<0.01). Losartan completely blocked the effect of AngII on JVR. Data showed that total amount of antioxidant and catalase activity nonsignificantly increased in inflamed group. Losartan significantly returned the catalase activity of the inflamed joint to the control level (P<0.01). Conclusion: NO plays a role in the regulation of joint vascular tone and modulates theAT1receptor response to AngII in acutely inflamed joints. Ang II increased the production of ROS and as a result the amount of antioxidants in acutely inflamed joints and this is via angiotensin II and through AT1 receptors. Keywords: Angiotensin II, Nitric oxide, Reactive oxygen species , acute inflammation, Carragenan, knee joint, Rabbi

The Effect of Intra-Articular Injection of Two Anti TNFα Drugs on Histopathology and Effect of Local Infusion of these Drugs on Blood Flow of Chronically Inflamed Joints in Rabbit

Abstract: Background & Aims: The anti TNFα drugs are new line treatment for articular inflammatory diseases which are used systemically, but due to expensiveness and some systemic adverse effects have limited usage. The aims of this study were to investigate the effect of intra-articular (local) injection of Etanercept and Infliximab as two anti TNFα drugs on histopathology and also due to the important role of joint blood flow on joint performance, to investigate the effect of local infusion of these drugs on blood flow of chronically inflamed joints. Method: Forty two NZW rabbits, underwent chronic knee joint inflammation by antigen induced arthritis method and then were randomly assigned into histopathology and blood flow groups. Each group was divided into 3 subgroups: vehicle (normal saline), Etanercept and Infliximab. In the first group, 2 weeks after intraarticular injection of antigen either 4 mg Etanercept, 16 mg Infliximab or o.5 ml vehicle was injected into the joint and after 2 weeks microscopic sections of knee joints were assessed for synovial membrane hyperplasia, villus hyperplasia, inflammatory cell infiltration and pannus formation. In the second group, 4 weeks after intraarticular injection of antigen, either 4 mg Etanercept, 16 mg Infliximab or vehicle was locally infused into articular atrery. Systemic blood pressure via carotid artery canulla and joint blood flow (JBF) by Laser Doppler Flowmeter were recorded. Results: Intraarticular injection of Etanercept and Infliximab had no significant effect on histopathological indices of inflammation. Etanercept increased JBF by 63.8±16.1% and decreased JVR by 42.2±4.4%. Infliximab, too, increased JBF by 70.6±16.1.1% and decreased JVR by 38.7 ±6.3%. The drugs had no effect on arterial blood pressure. Conclusion: Although not significantly effective on histopathlogical indices, Etanercept and Infliximab seems to improve prognosis of chronic joint diseases such as rheumatoid arthritis through blood flow enhancement and hypoxia diminution. Keywords: Arthritis, Infliximab, Etanercept, Blood flow velocity, Pathology, Rabb

The Effect of Enalapril on Brain Edema and Cytokine Production Following Transient Focal Cerebral Ischemia in Mice

Abstract: Introduction: Cytokines production as one of the inflammatory pathways in CNS is responsible for most brain damages following ischemia. On the other hand, during inflammation and brain ischemia, most of the renin- angiotensin components (RAS) increase locally. While it is established that blockade of RAS especially AT1 receptors has a protective effect on ischemia, the interaction of cytokines and angiotensin II is not well understood. This study was designed to investigate the effect of angiotensin II inhibitor on cytokine production as well as brain edema. Method: Fifty-four male mice were randomly divided into 5 groups of normal, Sham operated, ischemia, Pretreatment with enalapril (high dose), and Pretreatment with enalapril (low dose) for the measurement of IL-IB and TNF-β in the brain and blood serum by ELIZA method. Results: Ischemia caused a significant increase in water content and neurological deficit scores as well as cytokine levels. Treatment with enalapril had paradoxical effect on ischemia. In high dose, 85% of the animals showed convulsion after reperfusion. The IL-1β in serum and neurological deficit scores of this group were high, in accordance with clinical signs. In contrast, the low dose of enalapril, had protective effect on ischemia. It caused a significant reduction in brain concentration of both IL-1β and TNF-α (P<0.05) and improved significantly the neurological deficit scores and brain water content as well. (P<0.05). Conclusion: Enalapril as an ACE inhibitor, has a dual effect on stroke. At low dose, it has a protective role at least in part by suppressing the local production of pro-inflammatory cytokines while, at high dose, it increases the inflammation by an unknown mechanism. Keywords: Ischemia, Cytokines, ACE inhibitors, Mic

CYTOGENETIC ANALYSIS IN WOMEN WITH PRIMARY AND SCONDARY AMENORRHEA IN IRAN: RETROSPECTIVE STUDY ON 110 PATIENTS

The absence of menstrual periods for one or more periods is called amenorrhea. Primary amenorrhea means the lack of its occurrence until the age of 16 years. Secondary amenorrhea refers to situations that a person has experienced menstruation periods in the past and then stops its occurrence. Amenorrhea is a symptom, not a disease that can cause due to disorders of hypothalamus and pituitary glands, disorders of sexual glands and deformities of the uterus and ovaries. Due to the clinical importance of reproductive in life and non-reproductive of women amenorrhea due to ovarian function, this study has been conducted in order to determine the prevalence and type of chromosomal abnormalities in women referred to the Cytogenetic Laboratory of Cellular and Molecular Research Center, in University of Medical Sciences of Qazvin. Karyotype analysis and its relationship with phenotype were performed on 110 Iranian female patients with primary and secondary amenorrhea. Metaphase chromosomes were prepared and analyzed by G-banding technique and were evaluated to examine the mosaicism of 100 cells of lymphocytes cells