Urate-induced epigenetic modifications in myeloid cells.

OBJECTIVES: Hyperuricemia is a metabolic condition central to gout pathogenesis. Urate exposure primes human monocytes towards a higher capacity to produce and release IL-1ß. In this study, we assessed the epigenetic processes associated to urate-mediated hyper-responsiveness. METHODS: Freshly isolated human peripheral blood mononuclear cells or enriched monocytes were pre-treated with solubilized urate and stimulated with LPS with or without monosodium urate (MSU) crystals. Cytokine production was determined by ELISA. Histone epigenetic marks were assessed by sequencing immunoprecipitated chromatin. Mice were injected intraarticularly with MSU crystals and palmitate after inhibition of uricase and urate administration in the presence or absence of methylthioadenosine. DNA methylation was assessed by methylation array in whole blood of 76 participants with normouricemia or hyperuricemia. RESULTS: High concentrations of urate enhanced the inflammatory response in vitro in human cells and in vivo in mice, and broad-spectrum methylation inhibitors reversed this effect. Assessment of histone 3 lysine 4 trimethylation (H3K4me3) and histone 3 lysine 27 acetylation (H3K27ac) revealed differences in urate-primed monocytes compared to controls. Differentially methylated regions (e.g. HLA-G, IFITM3, PRKAB2) were found in people with hyperuricemia compared to normouricemia in genes relevant for inflammatory cytokine signaling. CONCLUSION: Urate alters the epigenetic landscape in selected human monocytes or whole blood of people with hyperuricemia compared to normouricemia. Both histone modifications and DNA methylation show differences depending on urate exposure. Subject to replication and validation, epigenetic changes in myeloid cells may be a therapeutic target in gout.

Hyaluronic acid versus albumin in human embryo transfer medium.

We compared the implantation and pregnancy rate through in vitro fertilization (IVF) using hyaluronic acid and albumin as transfer medium in 60 women randomly allocated to 2 groups. In treatment group A (n = 30), embryos were transferred to medium supplemented with hyaluronic acid. In the control group B (n = 30), embryos were transferred to medium containing albumin. There were no significant differences between the groups in terms of mean age of the females, mean duration of infertility and mean number of embryos. The pregnancy rate in groups A and B were 81.8% and 71.4% respectively, a non-statistically significant difference. Hyaluronic acid can successfully replace albumin as transfer medium.

Semen parameters of non-infertile smoker and non-smoker men.

INTRODUCTION: According to the world Health organization, approximately one third of the world` population older than 15 years are smokers. Evidences indicate that both in men and in women, cigarette smoking affects reproductive health more than the consumption of caffeine or alcohol in comparable doses. The mechanisms according to which tobacco affects spermatozoa are poorly understood. Some of the studies focused on the relation between cigarette smoking and the principal semen analysis, variable such as concentration, Morphology and Motility. In this study, we compared the sperm parameters between smokers and non-smokers. MATERIAL AND METHODS: This case control study was done on men from infertile couples who were referred to Yazd research and clinical center for infertility but the cause of infertility was not the male factor. The semen analysis was compared between the smokers and non-smokers. RESULTS: 151 infertile men were enrolled in the present study. 98 non-smokers and 53 smokers the mean age of patients was not significantly different between groups. There were no significant differences among groups according to sperm concentration (P-Value 0.108), Morphology (P-Value 0.138) and Motility (P-Value 0.082). Also there were no significant relationship between sperm parameters and the amount of cigarettes people had used (based on Pack/year scale). CONCLUSION: Semen parameters (Morphology, Motility and concentration) were lower in smokers but there were no significant differences between groups.

Pregnancy outcomes in asthmatic women.

Asthma is considered to be the most common respiratory disorder complicating pregnancy. Seventy-six asthmatic and 152 non-asthmatic pregnant women were studied. Maternal asthma was significantly associated with adverse infant outcomes, including prematurity, low birth weight and the need for Cesarean delivery. The results of this study could indicate that pregnant women with asthma were at substantially increased risk for adverse infant outcomes and suggest the need for extra attention to mothers with asthma before and during pregnancy.