Human T lymphocytes express both ionotropic and metabotropic glutamate receptors that control immune responses, cell activation, maturation and death. In this study, we examined the effect of N-methyl-D-aspartate (NMDA) and σ1-receptor ligands on the secretion of the proinflammatory chemokine interleukin 8 (IL-8) and the anti-inflammatory cytokine interleukin 10 (IL-10) in human leukemia Jurkat cells and peripheral blood lymphocytes (PBLs). We have shown that NMDA increased IL-8 and decreased IL-10 secretion and that σ-ligands modulated the action of NMDA. Moreover, the effects of NMDA and σ-ligands were interrelated with the nitric oxide (NO) content, suggesting that the intracellular concentration of NO could play a major role in the synthesis of cytokines. Western blots against the NR2A and NR2B subunits of the NMDA glutamate receptor revealed that long-term (48 h) treatment of PBLs with glutamate at concentrations within normal plasma levels (1 × 10–5M), in contrast to low concentrations (0.3 × 10–6M), downregulates the NR2A subunit, probably by internalization. Furthermore, we found that PBLs with noninternalized NR2A secreted less IL-10 than lymphocytes with downregulated NR2A; under these conditions, the transcriptional activity of NF-κB was increased whereas the transcriptional activity of c-Fos was decreased. These findings implicate that the activities of NF-κB and c-Fos control the expression of the IL8 and IL10 genes, depending on the subunit composition of the NMDA receptor. In conclusion, we suggest that lymphocytes express an active NMDA receptor only in a low-glutamate milieu.

The aim of this study was to investigate the frequency of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in Georgian females with hypothyroidism. Thirty-four patients and 29 healthy individuals were recruited in this study. Polymerase chain reaction-restriction fragment length polymorphism analyses were used for genotyping of MTHFR polymorphisms. The results of this study suggest that the MTHFR C677T variant was significantly associated with hypothyroidism. In addition, in individuals with T allele risk of hypothyroidism significantly increased. Combination of CT/AA genotypes was more prevalent in the hypothyroid patients than in the control group. Thus, C677T polymorphism could be a possible genetic factor contributing to the pathophysiology of hypothyroidism, possibly through hyperhomocysteinemia.

Nager syndrome (MIM #154400) is a rare acrofacial dysostosis syndrome predominantly characterized by malformations in craniofacial and preaxial limb bones. Most cases are sporadic and present with significant clinical heterogeneity. Although autosomal recessive and autosomal dominant modes of inheritance have been reported, most cases of Nager syndrome are spontaneous. Heterozygous variants in SF3B4 on chromosome 1q21 are found in approximately 60% of patients. Here, we report a first patient from Georgia diagnosed with Nager syndrome with detailed description of its clinical manifestations and diagnosis.