ABSTRACT
The clinical spectrum of hypertensive disorders of pregnancy (HDP) is determined by the interplay between environmental and genetic factors, most of which remains unknown. ERAP1, ERAP2 and LNPEP genes code for multifunctional aminopeptidases involved with antigen processing and degradation of small peptides such as angiotensin II (Ang II), vasopressin and oxytocin. We aimed to test for associations between genetic variants in aminopeptidases and HDP. A total of 1282 pregnant women (normotensive controls, n = 693; preeclampsia, n = 342; chronic hypertension with superimposed preeclampsia, n = 61; eclampsia, n = 74; and HELLP syndrome, n = 112) were genotyped for variants in LNPEP (rs27300, rs38034, rs2303138), ERAP1 (rs27044, rs30187) and ERAP2 (rs2549796 rs2927609 rs11135484). We also evaluated the effect of ERAP1 rs30187 on plasma Ang II levels in an additional cohort of 65 pregnant women. The genotype C/C, in ERAP1 rs30187 variant (c.1583 T > C, p.Lys528Arg), was associated with increased risk of eclampsia (OR = 1.85, p = 0.019) whereas ERAP2 haplotype rs2549796(C)-rs2927609(C)-rs11135484(G) was associated with preeclampsia (OR = 1.96, corrected p-value = 0.01). Ang II plasma levels did not differ across rs30187 genotypic groups (p = 0.895). In conclusion, ERAP1 gene is associated with eclampsia whereas ERAP2 is associated with preeclampsia, although the mechanism by which genetic variants in ERAPs influence the risk of preeclampsia and eclampsia remain to be elucidated.
Subject(s)
Aminopeptidases/genetics , Eclampsia/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Minor Histocompatibility Antigens/genetics , Pre-Eclampsia/genetics , Alleles , Brazil/epidemiology , Eclampsia/diagnosis , Eclampsia/epidemiology , Female , Gene Frequency , Genotype , HELLP Syndrome/diagnosis , HELLP Syndrome/epidemiology , HELLP Syndrome/genetics , Haplotypes , Humans , Linkage Disequilibrium , Models, Genetic , Odds Ratio , Phenotype , Population Surveillance , Pre-Eclampsia/diagnosis , Pre-Eclampsia/epidemiology , Pregnancy , Reproducibility of ResultsABSTRACT
OBJECTIVE: This study investigated the acute effects of high-intensity interval (HIIE) and moderate-intensity continuous (MICE) exercise on ghrelin levels in obese men. METHODS: A total of 10 obese men (age 27.6 ± 1.8 years, body mass index 35.4 ± 4.5 kg/m2, body fat 39.9 ± 2.1%) performed two exercise sessions in a randomized order: HIIE (10 × 1 min intervals at 90% of the maximal heart rate [HRmax] interspersed by 1 min of active recovery) and MICE (20 min at 70% of the HRmax). Ghrelin levels were assessed pre-, post- and 1h post-exercise, and energy intake was assessed 1h post-exercise through an ad libitum meal. RESULTS: HIIE and MICE showed a trend to decrease ghrelin levels immediately post-exercise (-14.1 ± 21.6% and -9.6 ± 23.8%, respectively, p = 0.07) and decreased 1h post-exercise (-12.7 ± 31.8% and -13.8 ± 21.7%, respectively, p < 0.05). No changes were observed for post-exercise energy intake (p > 0.05). There was a positive correlation between the change in ghrelin levels and post-exercise energy intake only for HIIE (r = 0.63, p = 0.05). CONCLUSION: In summary, a single session of HIIE and MICE elicits a reduction on ghrelin levels without changing post-exercise energy intake in obese men.
Subject(s)
Exercise , Ghrelin , High-Intensity Interval Training , Obesity/blood , Energy Intake , Ghrelin/blood , Humans , MaleABSTRACT
Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2) were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection.