Endogenous peripheral hydrogen sulfide is propyretic: its permissive role in brown adipose tissue thermogenesis in rats.

NEW FINDINGS: What is the central question of this study? In fever, the most striking response in the acute phase reaction of systemic inflammation, plasma H2 S concentration increases. However, the role of endogenous peripheral H2 S in fever is unknown. What is the main finding and its importance? Endogenous peripheral H2 S is permissive for increased brown adipose tissue thermogenesis to maintain thermal homeostasis in cold environments as well as to mount fever. This finding expands the physiological role of the gaseous modulator as a key regulator of thermal control in health (thermal homeostasis) and disease (fever in systemic inflammation). ABSTRACT: In recent years, hydrogen sulfide (H2 S) has been reported as a gaseous modulator acting in several tissues in health and disease. In animal models of systemic inflammation, the plasma H2 S concentration increases in response to endotoxin (bacterial lipopolysaccharide, LPS). The most striking response in the acute phase reaction of systemic inflammation is fever, but we found no reports of the peripheral action of H2 S on this thermoregulatory response. We aimed at investigating whether endogenous systemic H2 S modulates LPS-induced fever. A temperature datalogger capsule was inserted in the abdominal cavity of male Wistar rats (220-270 g) to record body core temperature. These animals received an i.p. injection of a systemic H2 S inhibitor (propargylglycine; 50 or 75 mg kg-1 ), immediately followed by an i.p. injection of LPS (50 or 2500 µg kg-1 ), and were exposed to different ambient temperatures (16, 22 or 27°C). At 22°C, but not at 27°C, propargylglycine at 75 mg kg-1 significantly attenuated (P < 0.0001) the fever induced by LPS (50 µg kg-1 ), indicating a modulatory (permissive) action of endogenous peripheral H2 S on brown adipose tissue (BAT) thermogenesis. Evidence on the modulatory role of peripheral H2 S in BAT thermogenesis was strengthened when we discarded (i) the possible influence of the gas on febrigenic signalling (when measuring plasma cytokines), and (ii) its interaction with the nitric oxide pathway, and mainly when (iii) we carried out physiological and pharmacological activations of BAT. Endogenous peripheral H2 S modulates (permits) BAT activity not only in fever but also during maintenance of thermal homeostasis in cold environments.

Association between leukaemia inhibitory factor gene polymorphism and pregnancy outcomes after assisted reproduction techniques.

Certain gene polymorphisms are associated with implantation failure and pregnancy loss. Studies of leukaemia inhibitory factor (LIF) gene polymorphisms are scarce. The LIF single nucleotide polymorphism (SNP) thymine (T)/guanine (G) (rs929271) was studied in women to determine whether an association existed with pregnancy outcomes after intracytoplasmic sperm injection (ICSI); 411 women who underwent ICSI were recruited. DNA was extracted from the peripheral blood, and the LIF gene SNP T/G (rs929271) was genotyped using real-time polymerase chain reaction. Participants were divided into three groups according to their LIF genotype: T/T (n = 168), T/G (n = 202) and G/G (n = 41). All IVF and ICSI procedures were carried out under the same clinical and laboratory conditions. The ICSI cumulative results (from fresh plus frozen cycles) of each genotype group were analysed. The G/G genotype in women was associated with a higher implantation rate (T/T: 15.9%, T/G: 16.2%, G/G: 27.0%; P < 0.05), ongoing pregnancy rate/patient (T/T: 31.5%, T/G: 36.1%, G/G: 53.7%; P < 0.05) and ongoing pregnancy rate/transfer (T/T: 18.5%, T/G: 20.2%, G/G: 36.7%; P < 0.05). LIF SNP T/G (rs929271) seems to be a susceptibility biomarker capable of predicting implantation efficiency and pregnancy outcomes.

The Relationship between Vascular Endothelial Growth Factor 1154G/A Polymorphism and Recurrent Implantation Failure.

OBJECTIVE: The aim of this study was to investigate the relationship between herpesvirus-associated ubiquitin-specific protease (HAUSP A/G, rs1529916), tumor protein p53 (TP53 Arg/Pro, rs1042522), leukemia inhibitory factor (LIF G/T, rs929271), glycoprotein 130 (gp130 A/T, rs1900173) and vascular endothelial growth factor (VEGF G/A, rs1570360) polymorphisms and recurrent implantation failure (RIF) in Brazilian women. SUBJECTS AND METHODS: A total of 120 women with RIF (i.e. those with ≥5 cleaved embryos transferred and a minimum of 2 failed in vitro fertilization/intracytoplasmic sperm injection attempts) were included. The control group involved 89 women who had experienced at least 1 live birth (without any infertility treatment). DNA was extracted from the peripheral blood of all participants, and the abovementioned single-nucleotide polymorphisms (SNPs) were genotyped by real-time polymerase chain reaction. The data were evaluated using Fisher's test. RESULTS: A significant difference between the RIF and control groups was found in the VEGF gene where the GG genotype showed a 2.1-fold increased chance of not being included in the RIF group, while the presence of an A allele increased this risk 1.6-fold. No significant differences were found for the other polymorphisms. CONCLUSION: This study showed an association between the VEGF -1154G/A polymorphism and RIF in Brazilian women.

Cellular bioenergetics changes in magnocellular neurons may affect copeptin expression in the late phase of sepsis.

We investigated whether inflammatory mediators during cecal ligation and puncture (CLP)-induced sepsis may diminish copeptin expression in magnocellular neurons, thus affecting arginine-vasopressin (AVP) synthesis. The transcript abundance of IL-1ß, IL-1R1, iNOS and HIF-1α was continuously elevated. IL-1ß, iNOS and cytochrome c protein levels progressively increased until 24h. Immunostaining for these proteins was higher at 6 and 24h, as also seen in the annexin-V assay, while copeptin was continuously decreased. This suggests that increased IL-1ß and NO levels may cause significant bioenergetics changes in magnocellular neurons, affecting copeptin expression and compromising AVP synthesis and secretion in the late phase of sepsis.