Prevalencia de alteraciones del metabolismo hidrocarbonado en una población infanto-juvenil con obesidad grave

IntroductionThere is currently a disproportionate increase in childhood and adolescent obesity worldwide, together with other disorders involving substantial cardiometabolic risk in adulthood, such as alterations in carbohydrate metabolism.ObjectiveTo establish the prevalence of prediabetes, defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) after an oral glucose tolerance test, and the prevalence of type 2 diabetes mellitus (DM-2) in a pediatric population with severe obesity. Additionally, we aimed to assess clinical metabolic differences between prediabetic obese patients and obese subjects without prediabetes.Material and methodsA cross-sectional study was carried out in children and adolescents with severe obesity (>97th percentile). The variables studied were age, sex, height, weight, body mass index, waist circumference, fasting plasma glucose and oral glucose tolerance test, insulinemia, insulin resistance assessed by the homeostasis model assessment (HOMA) index, glycated hemoglobin (HbA_1c), triglycerides, high-density lipoprotein cholesterol (HDL), and systolic and diastolic blood pressure.ResultsA total of 133 patients were included: 67 boys (50.4%) and 66 girls (49.6%), with a mean age of 12.17±3.27 years. Fourteen patients (10.52%) had prediabetes (10 IFG, 3 IGT, 1 IFG+IGT): 7 girls and 8 boys, with a mean age of 13.2±3.3 years. One patient had DM2 (0.75%). Patients with prediabetes had significantly higher concentrations of fasting glucose (98±10.76 vs 88.53±6.3 mg/d; p=0.001), insulinemia (35.38±14.22 vs 22.95±14.30 μU/ml; p=0.009) and HOMA index (8.10±3.24 vs 4.89±3.27; p=0.004) than patients without impaired carbohydrate metabolism. These patients also had higher values of HbA_1c, triglycerides, blood pressure and HDL concentrations, although differences were not statistically significant.ConclusionsThe prevalence of prediabetes (IFG/IGT) in children with severe obesity was high (10.52%). These patients should therefore be investigated to establish early diagnosis and appropriate treatment. Obese patients with prediabetes have significantly higher levels of insulin and insulin resistance than individuals without impaired carbohydrate metabolism.     

Cross-priming of T cell responses by synthetic microspheres carrying a CD8+ T cell epitope requires an adjuvant signal

Controlling the cross-presentation of exogenous Ags to CD8+ T cells represents a major step for designing new vaccination strategies. Whereas several recombinant pseudo-viral particles have been used as delivery systems for triggering potent CTL responses to heterologous exogenous Ags, the adjuvant properties of virus-like particles (VLPs) themselves were little questioned. Here, we analyzed the contribution of the porcine parvovirus (PPV)-VLPs to the induction of protective cellular responses to exogenous Ags carried by an independent delivery system. Microspheres, which are known to transfer exogenous Ags into the MHC class I pathway, were chosen for delivering the immunodominant OVA(257-264) CD8+ T cell epitope (B-OVAp). This delivery system fulfills the requirements in terms of cross-presentation, but fails to induce cross-priming of specific CD8+ T cells. Coinjection of PPV-VLPs with B-OVAp results in the priming of potent CTL responses and type 1-biased immunity in a CD4- and CD40-independent manner, as efficiently as the recombinant PPV-VLPs carrying the same epitope (PPV-OVAp). Furthermore, vaccination with PPV-VLPs and B-OVAp was fully efficient to protect mice against the development of OVA-bearing melanoma. These findings indicate that PPV-VLPs act not only as a delivery system but also as a strong adjuvant when independently provided with exogenous Ag. Thus, dissociation between delivery system and adjuvant would provide a more flexible and reliable system to induce potent and protective CTL.     

Cyclo-oxygenase 2 expression impairs serum-withdrawal-induced apoptosis in liver cells

We have investigated the mechanism of COX-2 (cyclo-oxygenase 2)-dependent inhibition of apoptosis in liver, a key pathway underlying proliferative actions of COX-2 in liver cancers, cirrhosis, chronic hepatitis C infection and regeneration after partial hepatectomy. Stable expression of COX-2 in CHL (Chang liver) cells induced proliferation, with an increase in the proportion of cells in S-phase, but no other significant changes in cell-cycle distribution. This was associated with a marked inhibition of the apoptotic response to serum deprivation, an effect mimicked by treating empty-vector-transfected control cells (CHL-V cells) with prostaglandin E2 and prevented in COX-2-expressing cells (CHL-C cells) treated with selective inhibitors of COX-2. Serum-deprived CHL-V cells displayed several indicators of activation of intrinsic apoptosis: caspases 9 and 3 activated within 6 h and caspase 8 within 18 h, Bax expression was induced, cytochrome c was released to the cytosol, and PARP-1 [poly(ADP-ribose) polymerase 1] cleavage was evident in nuclei. COX-2 expression blocked these events, concomitant with reduced expression of p53 and promotion of Akt phosphorylation, the latter indicating activation of survival pathways. CHL cells were resistant to stimulation of the extrinsic pathway with anti-Fas antibody. Moreover, in vivo expression of GFP (green fluorescent protein)-labelled COX-2 in mice by hydrodynamics-based transient transfection conferred resistance to caspase 3 activation and apoptosis induced by stimulation of Fas.     

Biogeography and Genetic Structure in Populations of a Widespread Lichen (Parmelina tiliacea,Parmeliaceae, Ascomycota)

The genetic diversity and population structure of the foliose lichenized fungus Parmelina tiliacea has been analyzed through its geographical range, including samples from Macaronesia (Canary Islands), the Mediterranean, and Eurosiberia. DNA sequences from the nuclear ribosomal internal transcribed spacer, the mitochondrial large subunit ribosomal RNA gene, and the translation elongation factor 1-α were used as molecular markers. The haplotypes of the three markers and the molecular variance analyses of multilocus haplotypes showed the highest diversity in the Canary Islands, while restricted haplotypes occurred at high frequencies in Mediterranean coastal samples. The multilocus haplotypes formed three unevenly distributed clusters (clusters 1-3). In the Canary Islands all the haplotypes were present in a similar proportion, while the coastal Mediterranean sites had almost exclusively haplotypes of cluster 3; cluster 2 predominated in inland Mediterranean sites; and cluster 1 was more abundant in central and northern Europe (Eurosiberian area). The distribution of clusters is partially explained by climatic factors, and its interaction with local spatial structure, but much of the variation remains unexplained. The high frequency of individuals in the Canary Islands with haplotypes shared with other areas suggests that could be a refugium of genetic diversity, and the high frequency of individuals of the Mediterranean coastal sites with restricted haplotypes indicates that gene flow to contiguous areas may be restricted. This is significant for the selection of areas for conservation purposes, as those with most genetic variation may reflect historical factors and biological properties of the species.     

Hyperuricemia and metabolic syndrome in children with overweight and obesity

ObjectiveTo study the prevalence of hyperuricemia in children with overweight or obesity and analyze the relation with metabolic syndrome and the diseases that define it.Materials and methodsThis is a cross-sectional prevalence study in 148 children recruited from pediatric endocrinology consultation, with overweight or obesity (12 ± 3 years, 48% boys, BMI 31.8 ± 6.1). We measured BMI, waist-height, waist circumference, blood pressure with standard instrumentation and glucose (fasting and after overload with 75 g), insulin resistance, cholesterol HDL, triglycerides and uric acid.ResultsThe prevalence of hyperuricemia was 53%. Patients with hyperuricemia had greater BMI (33.9 vs 30.6, p = 0.003), plus waist circumference (101.4 vs 91.1 cm, p < 0.001), higher blood pressure: systolic (123.4 vs 111.9 mm Hg, p < 0.001), diastolic (78.2 vs 68.7 mm Hg, p < 0.001). They presented greater blood glucose after overload oral glucose (107.5 vs 100.7 mg/dl, p = 0.03), insulin was higher (29.2 vs 20.7 mg/dl, p = 0.001) as well as HOMA IR (6.5 vs 4.4, p < 0.001) and HDL levels were lower (49.5 vs 54.4 mg/dl, p = 0.02).Uric acid's level which most is the likely diagnosis of metabolic syndrome corresponds to 5.4 mg/dl in our sample (sensitivity: 64% and specificity 62%).ConclusionThe prevalence of hyperuricemia in children with overweight and obesity is high. In the group of patients with obesity and hyperuricemia, we found out that the parameters measured to diagnose with metabolic syndrome were less favorable. Uric acid's level from where there is a higher possibility to see metabolic syndrome is 5.4 mg/dl.     

Potentiation of protein kinase C zeta activity by 15-deoxy-delta(12,14)-prostaglandin J(2) induces an imbalance between mitogen-activated protein kinases and NF-kappa B that promotes apoptosis in macrophages

Activation of the macrophage cell line RAW 264.7 with lipopolysaccharide (LPS) transiently activates protein kinase C zeta (PKC zeta) and Jun N-terminal kinase (JNK) through a phosphoinositide-3-kinase (PI3-kinase)-dependent pathway. Incubation of LPS-treated cells with the cyclopentenone 15-deoxy-Delta(12,14)-prostaglandin J(2) (15dPGJ(2)) promoted a sustained activation of PKC zeta and JNK and inhibited I kappa B kinase (IKK) and NF-kappa B activity. Accordingly, 15dPGJ(2) induced an imbalance between JNK and IKK activities by increasing the former signaling pathway and inhibiting the latter signaling pathway. Under these conditions, apoptosis was significantly enhanced; this response was very dependent on PKC zeta and JNK activation. The effect of 15dPGJ(2) on PKC zeta activity observed in LPS-activated macrophages was not dependent on a direct action of this prostaglandin on the enzyme but was due to the activation of a step upstream of PI3-kinase. Moreover, LPS promoted the redistribution of activated PKC zeta from the cytosol to the nucleus, a process that was enhanced by treatment of the cells with 15dPGJ(2) that favored a persistent and broader distribution of PKC zeta in the nucleus. These results indicate that 15dPGJ(2) and other cyclopentenone prostaglandins, through the sustained activation of PKC zeta, might contribute significantly to the process of resolution of inflammation by promoting apoptosis of activated macrophages.     

Evaluation of MycAssay? Aspergillus for Diagnosis of Invasive Pulmonary Aspergillosis in Patients without Hematological Cancer

Methods based on real-time polymerase chain reaction (PCR) can speed up the diagnosis of invasive aspergillosis but are limited by a lack of standardization. We evaluated the commercially available MycAssay™ Aspergillus test for the diagnosis of invasive aspergillosis in patients without hematological cancer. We prospectively collected 322 lower respiratory tract samples (November 2009–January 2011) from 175 patients with lower respiratory tract infection and the following predisposing conditions: solid cancer (16.8%), cirrhosis (16.8%), corticosteroid therapy (71.7%), HIV infection (15.6%), chronic obstructive pulmonary disease (COPD, 52.6%), solid organ transplantation (kidney [1.2%], heart [3%], liver [4.6%]), or none (3.5%). Specimens were obtained when clinically indicated and analyzed in the microbiology laboratory. Aspergillus DNA was extracted and amplified by means of MycXtra® and MycAssay™ Aspergillus. Aspergillus spp. was isolated from 65 samples (31 patients). According to the European Organization for Research and Treatment of Cancer and Bulpa''s criteria (for patients with COPD), 15 had probable invasive aspergillosis. MycAssay™ Aspergillus results were negative (n = 254), positive (n = 54), or indeterminate (n = 14). The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic odds ratio of the MycAssay™ (first sample/any sample) were 86.7/93, 87.6/82.4, 34.1/34.1, 92.2/100, and 48/68.75. The differences between the proportion of samples with positive PCR determinations (63%) and the proportion of samples with Aspergillus spp. isolation (75%) did not reach statistical significance (P = 0.112). The median time from sample culture to visualization of fungal growth was 3 days, compared with ∼4 hours for MycAssay™ Aspergillus PCR. MycAssay™ Aspergillus showed high sensitivity for the diagnosis of invasive aspergillosis in patients without hematological cancer. Sensitivity increased when multiple samples were used. Compared with fungal culture, PCR significantly reduced the time to diagnosis.