Tehran University Medical Journal

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Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with presumed autoimmune origin. T cells are considered to play a pivotal role in orchestrating the self-reactive immune responses in multiple sclerosis (MS). This study was performed to investigate the role of polymorphisms of the programmed cell death 1 (PD-1) gene on susceptibility to ankylosing spondylitis.This gene codes an immunoreceptor named PD-1, which has a cytoplasmic domain containing two tyrosine residues located within immunoreceptor tyrosine-based inhibitory and switch motifs (ITIM and ITSM), suggesting that PD-1 is predominantly inhibitory which responsible for the negative regulation in T cell activation and peripheral tolerance. We investigated whether PD-1 gene polymorphism is a genetic modifier for risk and progression of MS.Methods: Blood samples from 150 Iranian Relapsing-Remitting MS patients (mean age, 34.98 years) and 202 healthy controls (mean age, 30 years) were enrolled in this study.The PD-1.3 (7146 G/A Intron 4) and PD-1.9 (7625 C/T Exon 5) polymorphisms were detected by Polymerase Chain Reaction and Restriction Enzyme digestion or Restriction Fragment Length Polymorphism (PCR-RFLP). Results: No significant association of the mutated alleles with the disease were detected. Because of the ethnic group genetic variation, our data is not like some of Asian population such as Korea and China.Conclusions: Our data suggest that PD-1 polymorphisms are not act as genetic modifiers of the progression of MS, possibly these polymorphisms don't induce a partial defect in PD-1 mediated inhibition of T-cell activation.

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Background: Uterine environment and fetal period can profoundly affect health of the neonat. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that regulates cellular stress responses and its activity is essential in both embryogenesis and postnatal life. The aim of the present study was to investigate the effects of maternal swimming on rat pups' HIF-1α levels as a key regulator of oxygen in lungs.

Methods: Sixteen female Wistar rats weighing 180- 200 grams were acclimated to a new environment consisting of equal light-darkness cycle and ad lib access to chow and adapted to the stress caused by water for two weeks. The rats were divided into two swimming and control groups. Swimming training began on the first day of pregnancy in a pool and continued for 3 weeks (1 h/day, 5 days/wk). Pups' lungs were removed two days after birth and their HIF-1α concentration was determined with enzyme-linked immunosorbent assay (ELISA). Statistical analysis of the data was done using independent t-test. A p-value smaller than 0.05 was considered statistically significant.

Results: Swimming lead to a significant (P<0.001) increase in the pups' lung HIF-1α levels compared with the control group. Although 3-wk period of swimming training, showed no significant increase in weight and also lung weight of newborns. Thus it can be concluded that swimming endurance training in pregnancy, can be considered as appropriate alternative in order to embryos development.

Conclusion: Our research suggests that HIF-1α level is an essential element for the development of the lungs of embryos. Moreover, further studies on the lung HIF-1α levels at post-natal period with different modes of exercise will provide more clear insight into the mechanisms of the findings resulting from this study.