Elucidating the spectrum of alpha-thalassemia mutations in Iran

Alpha thalassemia (alpha-thal) is one of the most common hemoglobin (Hb) disorders in the world. Alpha-globin genes are located on chromosome 16. The majority of alpha-thal mutations are deletions but point mutations are found as well. Since the Iranian population is a mixture of different ethnic groups, frequency and distribution of alpha-globin mutations in various regions of the country need to be clarified. These findings can contribute to a wider understanding of this disorder.     

CB1 receptor activation in the basolateral amygdala produces antinociception in animal models of acute and tonic nociception

1. Recent studies have suggested that the basolateral nucleus of the amygdala (BLA) participates in the processing of pain information, especially noxious somatic information. Cannabinoid receptors or CB1 mRNA are expressed more in the BLA than in other nuclei of the amygdala. Thus, the aim of the present study was to examine whether CB1 receptors in the BLA may be involved in modulating acute and/or tonic nociceptive processing. 2. Adult rats were exposed to intra-BLA microinjection of the cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo [1,2,3,-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate [WIN 55,212-2 (1, 2.5, 5 or 10 microg/side)] and subjected to the tail flick and formalin tests. 3. The rats demonstrated a dose-dependent increase in latency to withdraw from a thermal noxious stimulus in the tail flick test and a decrease in formalin-induced pain behaviours. The antinociceptive effects of the CB1 receptor agonist WIN 55,212-2 (10 microg/side) in both tests were attenuated in the presence of the selective CB1 receptor antagonist, N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamide (AM251; 0.55 ng/side). Administration of the CB1 receptor antagonist AM251 (0.55, 5.5, or 55.5 ng/side) alone did not alter the nociceptive thresholds in either test. Bilateral microinjection of the selective CB2 receptor antagonist N-[(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528; 1 microg/side) had no effect on the antinociception produced by WIN 55,212-2, suggesting that the antinociceptive actions of WIN 55,212-2 are mediated by CB1 receptors. 4. The findings suggest the existence of a CB1-mediated inhibitory system in the BLA that, when activated, can diminish responsivity to acute and tonic noxious stimuli, but that normally has no tonic effect on the response threshold of these stimuli.     

Impaired periamygdaloid-cortex prodynorphin is characteristic of opiate addiction and depression

Negative affect is critical for conferring vulnerability to opiate addiction as reflected by the high comorbidity of opiate abuse with major depressive disorder (MDD). Rodent models implicate amygdala prodynorphin (Pdyn) as a mediator of negative affect; however, evidence of PDYN involvement in human negative affect is limited. Here, we found reduced PDYN mRNA expression in the postmortem human amygdala nucleus of the periamygdaloid cortex (PAC) in both heroin abusers and MDD subjects. Similar to humans, rats that chronically self-administered heroin had reduced Pdyn mRNA expression in the PAC at a time point associated with a negative affective state. Using the in vivo functional imaging technology DREAMM (DREADD-assisted metabolic mapping, where DREADD indicates designer receptors exclusively activated by designer drugs), we found that selective inhibition of Pdyn-expressing neurons in the rat PAC increased metabolic activity in the extended amygdala, which is a key substrate of the extrahypothalamic brain stress system. In parallel, PAC-specific Pdyn inhibition provoked negative affect–related physiological and behavioral changes. Altogether, our translational study supports a functional role for impaired Pdyn in the PAC in opiate abuse through activation of the stress and negative affect neurocircuitry implicated in addiction vulnerability.     

Cell damage through pentose phosphate pathway in fetus fibroblast cells exposed to methyl mercury

Methylmercury (MeHg) is a global pollutant that causes malformations. There has been no direct evidence for the effect of MeHg on pentose phosphate pathway (PPP). In embryonic development, PPP is much more active. This pathway produces ribose for DNA/RNA production. It is possible that one of teratogenicity mechanisms of MeHg is through PPP. The fetus fibroblast cells were incubated with different concentrations of MeHg (0.1–100 μm ). A dose–response dependence was observed in MTT assay. Transketolase activity and DNA content were determined in cell exposed to MeHg. A defect at the level of DNA content was observed. This amount of DNA was highly correlated with transketolase activity (r = 0.76). This study has demonstrated that the potential teratogenic action of MeHg is through PPP. To assess the protective effects of thiamin, the infected cells were incubated with different concentrations of thiamin. The obtained results show that thiamin pyrophosphate supplementation correlated with the toxicity. This finding confirms that thiamin therapy is suitable for the prevention of MeHg toxicity. Our study provides basic data for prevention and treatment of MeHg toxicity via boosting PPP. Copyright © 2011 John Wiley & Sons, Ltd.     

Development of viral vectors for use in cardiovascular gene therapy

Cardiovascular disease represents the most common cause of mortality in the developed world but, despite two decades of promising pre-clinical research and numerous clinical trials, cardiovascular gene transfer has so far failed to demonstrate convincing benefits in the clinical setting. In this review we discuss the various targets which may be suitable for cardiovascular gene therapy and the viral vectors which have to date shown the most potential for clinical use. We conclude with a summary of the current state of clinical cardiovascular gene therapy and the key trials which are ongoing.     

Imaging Bone Morphogenetic Protein 7 Induced Cell Cycle Arrest in Experimental Gliomas

Bone morphogenetic protein 7 (BMP-7) belongs to the superfamily of transforming growth factor β-like cytokines, which can act either as tumor suppressors or as tumor promoters depending on cell type and differentiation. Our investigations focused on analyzing the effects of BMP-7 during glioma cell proliferation in vitro and in vivo. BMP-7 treatment decreased the proliferation of Gli36ΔEGFR-LITG glioma cells up to 50%through a cell cycle arrest in the G₁ phase but not by induction of apoptosis. This effect was mediated by the modulation of the expression and phosphorylation of cyclin-dependent kinase 2, cyclin-dependent kinase inhibitor p21, and downstream retinoblastoma protein. Furthermore, in vivo optical imaging of luciferase activity of Gli36ΔEGFR-LITG cells implanted intracranially into nude mice in the presence or absence of BMP-7 treatment corroborated the antiproliferative effects of this cytokine. This report clearly underlines the tumor-suppressive role of BMP-7 in glioma-derived cells. Taken together, our results indicate that manipulating the BMP/transforming growth factor β signaling cascade may serve as a new strategy for imaging-guided molecular-targeted therapy of malignant gliomas.     

Patellofemoral pain syndrome in Iranian female athletes

Patellofemoral pain syndrome (PFPS) is the most common overuse syndrome in athletes. It is one of the causes of anterior knee pain in athletic population who come to the sports medicine clinic. Patellofemoral pain is more common among female athletes especially adolescents and young adults. Symptoms include: persistent pain behind the patella or peripatella. Pain increases on ascending and descending stairs and squatting and prolonged sitting. The aim of this study was to evaluate the prevalence of PFPS in Iranian female athletes. 418 female athletes aged 15-35 years were examined in five sports: Soccer (190), volleyball (103), running (42), fencing (45) and rock climbing (38). The athletes who had non- traumatic onset anterior knee pain of at least 3 months that increased in descending and ascending stairs and squatting, had no other causes of anterior knee pain such as ligament instability, bursitis, meniscal injury, tendonitis and arthritis and no history of knee surgery during the one past year were diagnosed as PFPS. 26/190 (13.68 %) soccer players, 21/103(20.38 %) volleyball players, 7/42 (16.66 %) runners, 6/45(13.33 %) fencers and 10/38 (26.31%) rock climbers had patellofemoral pain. Among the 418 female athletes who were evaluated 70 had PFPS. Rock climbers were the most common athletes with PFPS followed by volleyball players and runners.