Donor-derived, tolerogenic dendritic cells suppress immune rejection in the indirect allosensitization-dominant setting of corneal transplantation

Significant interest has been focused on the use of ex vivo-manipulated DCs to optimally induce transplant tolerance and promote allograft survival. Although it is understood that donor-derived, tolerogenic DCs suppress the direct pathway of allosensitization, whether such DCs can similarly suppress the indirect pathway remains unclear. We therefore used the murine model of corneal transplantation to address this, as these allografts are rejected in an indirect pathway-dominant manner. Interestingly, recipients administered with donor bone marrow-derived DCregs, generated via culturing with GM-CSF, IL-10, and TGF-β1, significantly prolonged survival of corneal allografts. Correspondingly, these recipients demonstrated a potent reduction in the frequency of indirectly allosensitized T cells, as determined by ELISPOT. Examination of DCregs relative to mDCs or iDCs showed a resistance to up-regulation of MHC-II and costimulatory molecules, as well as an impaired capacity to stimulate MLRs. In vivo, DCreg administration in corneal-allografted recipients led to inhibition of CD4(+)IFN-γ(+) T cell frequencies and an associated increase in Foxp3 expression in the Treg compartment. We conclude that donor-derived, tolerogenic DCs significantly suppress the indirect pathway, thereby identifying a novel regulatory mechanism for these cells in transplantation.     

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.     

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.     

Synthesis and evaluation of in vitro anti-tuberculosis activity of N-substituted glycolamides

On the basis of the structural similarity of N-substituted glycolamides with N-glycolyl muramic acid residues of the cell wall of Mycobacterium tuberculosis, a series of these compounds were designed and synthesized by the reaction of glycolic acid acetonide 1 (2,2-dimethyl-5-oxo-1,3-dioxolane) with the proper amines. The minimum inhibitory concentration (MIC) was determined against M. tuberculosis H(37)Rv in BACTEC 12B medium, using the Microplate Alamar Blue Assay (MABA). Among the synthesized compounds, all those with disubstituted amide structure accompanied by one or two heteroatom(s) with loan pair(s) of electrons atom(s) beta to the amide nitrogen demonstrated moderate anti-tuberculosis activity and all the monosubstituted amides showed no activity at all.     

Role of Endocannabinoid System in the Ventral Hippocampus of Rats in the Modulation of Anxiety‐Like Behaviours

Abstract: The effects of unilateral intra‐ventral hippocampus injection of URB597, a fatty acid amid hydrolase inhibitor, and AM251, a selective CB₁ receptor antagonist, on anxiety‐related behaviours using elevated plus‐maze test of anxiety were evaluated in the present study. Possible involvement of GABAergic system in those effects of URB597 was also evaluated. Injection of URB597 at the doses of 0.01, 0.1 and 1 μg/rat showed significant anxiogenic‐like effects at 0.1 and 1 μg/rat. However, intra‐ventral hippocampus injection of AM251 at the doses of 0.001, 0.01 and 0.1 μg/rat did not produce any significant effect in the elevated plus‐maze. The ineffective doses of selective GABA_A receptor antagonist, bicuculline (2 μg/rat) and selective GABA_B receptor antagonist, phaclofen (1 μg/rat) on anxiety‐related behaviours were also injected with URB597 (0.1 μg/rat). The present data showed that neither bicuculline nor phaclofen affected the anxiogenic‐like effects of URB597. The results showed that injection of URB597 into the ventral hippocampus may be anxiogenic and GABAergic system may not be involved in its anxiogenic‐like effects.     

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.