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.     

Sex-related differences in pain

This article provides an overview of sex-related differences in musculoskeletal pain and the role sex hormones and response to analgesic drugs may play in these differences. Some common pain conditions that include temporomandibular disorders, rheumatoid arthritis, fibromyalgia syndrome and tension-type and migraine headaches, show fairly marked sex-related differences in their occurrence, however, with the exception of rheumatoid arthritis, these pain conditions are also characterized by a lack of understanding of their basic underlying pathophysiology. The association of pain symptoms of these musculoskeletal pain conditions with the reproductive cycle of women is strongly suggestive of a role of the estrogens and/or progesterones, the main female sex hormones, in sex-related differences in pain. Nevertheless, an alternative suggestion that testosterone, the major male sex hormone, protects men from these chronic musculoskeletal pain conditions, has also been made. Indeed, emerging evidence suggests that both male and female sex hormones may contribute to the marked sex-related differences in the occurrence of certain musculoskeletal pain conditions. Men and women also appear to differ in response to pain treatment with certain analgesic drugs. The mechanistic basis for these sex-related differences is not entirely understood but sex hormones are thought to be one of the influencing factors. An improved understanding of mechanisms which underlie sex-related differences in musculoskeletal pain and response to analgesic drugs should permit improved pain management strategies for male and female musculoskeletal pain patients in the clinical setting.     

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.     

Activation of p38 mitogen-activated protein kinase is critical step for acquisition of effector function in cytokine-activated T cells, but acts as a negative regulator in T cells activated through the T-cell receptor

Peripheral blood CD4⁺ CD45RO⁺ T cells activated in vitro are able to induce expression of tumour necrosis factor‐α (TNF‐α) in monocytes via a contact‐dependent mechanism. Activation is achieved either with interleukin‐2 (IL‐2)/IL‐6/TNF‐α over an 8‐day period or cross‐linking CD3 using anti‐CD3 antibody for 48 hr. In this paper, we show that the p38 mitogen‐activated protein kinase (MAPK) signalling pathway played different roles in the generation of effector function in these two types of activated T cells. In anti‐CD3 activated T cells, p38 MAPK is a negative regulator for anti‐CD3 induced cell proliferation and has no significant effect on the acquisition of either the effector function (induction of monocyte‐derived TNF‐α) or production of T‐cell cytokines. In contrast, the p38 MAPK signalling pathway is required for the acquisition of cytokine‐induced effector function and promotes cell proliferation and cytokine production.