The objective was to study oxidative status, antioxidant activities, and reactive oxygen species byproducts in whole blood and mononuclear peripherals cells and their relationship with blood pressure. Sixty-six hypertensive patients and 16 normotensive volunteers as a control group were studied. In both, whole blood and peripheral mononuclear cells oxidized/reduced glutathione ratio and malondialdehyde was significantly higher, and the activity of superoxide dismutase, catalase, and glutathione peroxidase was significantly lower in hypertensive patients when compared with normal subjects. The content of damaged base 8-oxo-2′-deoxyguanosine in nuclear and mitochondrial deoxyribonucleoproteins of hypertensive subjects was also significantly higher than that of the normotensive control subjects. No differences in these measurements were found among hypertensive subjects grouped in tertiles of 24-hour average mean blood pressure or between “white-coat” and established hypertensive subjects. Furthermore, no relationship was observed between the average of 24-hour mean blood pressure and oxidized/reduced glutathione ratio, reactive oxygen species byproducts, malondialdehide, or genomic 8-oxo-2′-deoxyguanosine. In whole blood and in mononuclear cells from hypertensive subjects, there was an increase in oxidative stress and a reduction in the activity of antioxidant mechanisms that appeared to be independent of the blood pressure values.

The human intestine is home to a diverse range of bacterial and fungal species, forming an ecological community that contributes to normal physiology and disease susceptibility. Here, the fungal microbiota (mycobiome) in obese and non-obese subjects was characterized using Internal Transcribed Spacer (ITS)-based sequencing. The results demonstrate that obese patients could be discriminated by their specific fungal composition, which also distinguished metabolically “healthy” from “unhealthy” obesity. Clusters according to genus abundance co-segregated with body fatness, fasting triglycerides and HDL-cholesterol. A preliminary link to metabolites such as hexadecanedioic acid, caproic acid and N-acetyl-L-glutamic acid was also found.Mucor racemosusandM. fuscuswere the species more represented in non-obese subjects compared to obese counterparts. Interestingly, the decreased relative abundance of theMucorgenus in obese subjects was reversible upon weight loss. Collectively, these findings suggest that manipulation of gut mycobiome communities might be a novel target in the treatment of obesity.

Prospective longitudinal studies evaluating the relevance of "Metabolically Healthy but Obese" (MHO) phenotype at risk for type 2 diabetes mellitus (T2D) and cardiovascular diseases are few and results are contradictory. As a representative of the general population, 1051 individuals were evaluated in 1997-1998 and re-evaluated after 6 years and 11 years. Subjects without known T2D were given an oral glucose tolerance test. Anthropometric and biochemical variables were measured. Four sets of criteria were considered to define MHO subjects besides body mass index ≥30 kg/m(2): A: Homeostatic Model of Assessment-Insulin Resistance Index (HOMA-IR) 40 mg/dL in men and high-density lipoprotein cholesterol >50 mg/dL in women, triglycerides <150 mg/dL, fasting glucose <110 mg/dL, and blood pressure ≤140/90 mm Hg; C: HOMA-IR <90th percentile, triglycerides <150 mg/dL, fasting glucose <110 mg/dL, and blood pressure ≤140/90 mm Hg; D: HOMA-IR <90th percentile, triglycerides <150 mg/dL, and fasting glucose <110 mg/dL. Subjects with T2D at baseline were excluded from the calculations of incidence of T2D. The baseline prevalence of MHO phenotype varied between 3.0% and 16.9%, depending on the set of criteria chosen. Metabolically nonhealthy obese subjects were at highest risk for becoming diabetic after 11 years of follow-up (odds ratio = 8.20; 95% confidence interval = 2.72-24.72; P < .0001). In MHO subjects the risk for becoming diabetic was lower than in metabolically nonhealthy obese subjects, but this risk remained significant (odds ratio = 3.13; 95% confidence interval = 1.07-9.17; P = .02). In subjects who lost weight during the study, the association between MHO phenotype and T2D incidence disappeared, even after adjusting for HOMA-IR. The results suggest that MHO is a dynamic concept that should be taken into account over time. As a clinical entity, it may be questionable.

There is increased interest in using microRNAs (miRNAs) as biomarkers in different diseases. Present in body fluids, it is controversial whether or not they are mainly enclosed in exosomes, thus we studied if urinary miRNAs are concentrated inside exosomes and if the presence of systemic lupus erythematosus with or without lupus nephritis modifies their distribution pattern. We quantified specific miRNAs in urine of patients with systemic lupus erythematosus (n = 38) and healthy controls (n = 12) by quantitative reverse-transcription PCR in cell-free urine, exosome-depleted supernatant and exosome pellet obtained by ultracentrifugation. In control group, miR-335* and miR-302d were consistently higher in exosomes than in exosome-depleted supernatant, and miR-200c and miR-146a were higher in cell-free fraction. In lupus patients, all urinary miRNAs tested were mainly in exosomes with lower levels outside them (p<0.05 and p<0.01, respectively). This pattern is especially relevant in patients with active lupus nephritis compared to the control group or to the SLE patients in absence of lupus nephritis, with miR-146a being the most augmented (100-fold change, p<0.001). Among the exosomal miRNAs tested, only the miR-146a discriminates the presence of active lupus nephritis. In conclusion, urinary miRNAs are contained primarily in exosomes in systemic lupus erythematosus, and the main increment was found in the presence of active lupus nephritis. These findings underscore the attractiveness of exosomal miRNAs in urine, a non-invasive method, as potential renal disease markers.

We screened index cases from 410 Spanish breast/ovarian cancer families and 214 patients (19 of them males) with breast cancer for germ‐line mutations in the BRCA1 and BRCA2 genes, using SSCP, PTT, CSGE, DGGE, and direct sequencing. We identified 60 mutations in BRCA1 and 53 in BRCA2. Of the 53 distinct mutations observed, 11 are novel and 12 have been reported only in Spanish families (41.5%). The prevalence of mutations in this set of families was 26.3%, but the percentage was higher in the families with breast and ovarian cancer (52.1%). The lowest proportion of mutations was found in the site‐specific female breast cancer families (15.4%). Of the families with male breast cancer cases, 59.1% presented mutations in the BRCA2 gene. We found a higher frequency of ovarian cancer associated with mutations localized in the 5′ end of the BRCA1 gene, but there was no association between the prevalence of this type of cancer and mutations situated in the ovarian cancer cluster region (OCCR) region of exon 11 of the BRCA2 gene. The mutations 187underscore;188delAG, 330A>G, 5236G>A, 5242C>A, and 589underscore;590del (numbered after GenBank U14680) account for 46.6% of BRCA1 detected mutations whereas 3036underscore;3039del, 6857underscore;6858del, 9254underscore;9258del, and 9538underscore;9539del (numbered after GenBank U43746) account for 56.6% of the BRCA2 mutations. The BRCA1 330A>G has a Galician origin (northwest Spain), and BRCA2 6857underscore;6858del and 9254underscore;9258del probably originated in Catalonia (northeast Spain). Knowledge of the spectrum of mutations and their geographical distribution in Spain will allow a more effective detection strategy in countries with large Spanish populations. Hum Mutat 22:301–312, 2003.