Baja ingesta de yodo durante la gestación: Relación con el desarrollo placentario y el perímetro cefálico del recién nacido

IntroductionIodine is considered to be an essential micronutrient in pregnant women. Iodine placental transport to the embryo-fetus is essential for hormone synthesis and is crucial for nervous system development. However, the relationship between iodine intake and placental weight and its potential implications for the newborn have not been studied.Material and methodsIodine intake was analyzed in 77 pregnant women based on urinary iodine excretion (UIE) levels, measured using Pinós modified method (normal value, ≥ 150 μg/L). Placental weight was measured (PW: normal, ≥500 g). In the newborn, weight, height, and head perimeter (HP) were also measured. Placental index (PI: placental weight/newborn weight) was calculated, and was considered normal if ≥0.15.ResultsUIE was normal in 50 pregnant women (mean ± SD, 279 μg/L ± 70.22 μg/L) and decreased in 27 (94 μg/L ± 31.49 μg/L). Newborns of mothers with low UIE had a similar weight (3357 g ± 416.30 g; n: 27) to those of mothers with normal UIE (3489 g ± 560.59 g; n: 50). Forty-four percent of mothers with low UIE had PW <500 g, and statistically lower HPs were found in newborns of mothers with low PW (PW³500 g: 36.05 cm ± 0.55 cm, n: 54; PW <500 g: 33.93 cm ± 15 cm, n:23, p < 0.019). Similar results were found with PI, but they did not reach statistical significance (0,17 ± 0,04; p = 0.066). No differences were seen in all other parameters.ConclusionThe study suggests the existence of a relationship between PW and HP. This finding may be related to iodine intake during pregnancy.     

Impaired pro-inflammatory cytokine production and increased Th2-biasing ability of dendritic cells exposed to Taenia excreted/secreted antigens: A critical role for carbohydrates but not for STAT6 signaling

In cysticercosis, a parasitic disease caused by cestodes, the details of early interactions between parasite antigens and innate cells from the host are not well understood. In this study, the role of cestode-conditioned dendritic cells (DCs) in priming Th1 versus Th2 responses to bystander antigen was examined by using CD11c⁺ DCs as antigen-presenting cells and naive CD4⁺ DO11.10 lymphocytes specific to ovalbumin (OVA) as responding cells. No conventional maturation was induced in DCs exposed to Taenia crassiceps excreted/secreted antigens (TcES). The ability of TcES to affect Toll-like receptor (TLR)-mediated maturation and the pro-inflammatory response was analyzed by co-pulsing DCs with TcES and TLR ligands. DCs exposed to TcES blocked TLR4, TLR9 and Toxoplasma soluble antigen-induced phenotypic maturation. TcES-exposed DCs also blocked secretion of pro-inflammatory cytokines and alloreactive T cell proliferation, while preserving IL-10 production. DCs pulsed with TcES + OVA suppressed IFN-γ, whereas they induced greater IL-4 production by CD4⁺ DO11.10 cells. TcES with chemically-altered glycans failed to modulate TLR-mediated activation of DCs and their Th1-inhibitng ability, which was STAT6-independent. Our results reflect the capacity of TcES glyco-antigens to modulate Th1-type and inflammatory responses mediated through DC activation.     

Taxonomic and Functional Metagenomic Profiling of the Microbial Community in the Anoxic Sediment of a Sub-saline Shallow Lake (Laguna de Carrizo, Central Spain)

The phylogenetic and functional structure of the microbial community residing in a Ca(2+)-rich anoxic sediment of a sub-saline shallow lake (Laguna de Carrizo, initially operated as a gypsum (CaSO(4)?×?2 H(2)O) mine) was estimated by analyzing the diversity of 16S rRNA amplicons and a 3.1?Mb of consensus metagenome sequence. The lake has about half the salinity of seawater and possesses an unusual relative concentration of ions, with Ca(2+) and SO (4) (2-) being dominant. The 16S rRNA sequences revealed a diverse community with about 22% of the bacterial rRNAs being less than 94.5% similar to any rRNA currently deposited in GenBank. In addition to this, about 79% of the archaeal rRNA genes were mostly related to uncultured Euryarchaeota of the CCA47 group, which are often associated with marine and oxygen-depleted sites. Sequence analysis of assembled genes revealed that 23% of the open reading frames of the metagenome library had no hits in the database. Among annotated genes, functions related to (thio) sulfate and (thio) sulfonate-reduction and iron-oxidation, sulfur-oxidation, denitrification, synthrophism, and phototrophic sulfur metabolism were found as predominant. Phylogenetic and biochemical analyses indicate that the inherent physical-chemical characteristics of this habitat coupled with adaptation to anthropogenic activities have resulted in a highly efficient community for the assimilation of polysulfides, sulfoxides, and organosulfonates together with nitro-, nitrile-, and cyanide-substituted compounds. We discuss that the relevant microbial composition and metabolic capacities at Laguna de Carrizo, likely developed as an adaptation to thrive in the presence of moderate salinity conditions and potential toxic bio-molecules, in contrast with the properties of previously known anoxic sediments of shallow lakes.     

Longitudinal Study of a Human Drug-Induced Model of Autoantibody to Cytoplasmic Rods/Rings following HCV Therapy with Ribavirin and Interferon-α

Background

A novel pattern in the indirect immunofluorescence antinuclear antibody assay on HEp-2 cells (IIF-HEp-2) characterized by cytoplasmic rods and rings (RR) was reported in HCV patients, but stringent disease specificity studies and longitudinal analysis are lacking. We investigated the clinical significance of anti-RR in an HCV cohort with up to a 12-month treatment follow up.

Methodology/Results

597 patients (342 HCV, 55 HCV/HIV, 200 non-HCV) were screened and titered for anti-RR. Serial samples were available from 78 of 176 treated and 27 of 166 untreated patients. Anti-RR was detected in 14.1% of 342 HCV patients, 9.1% of 55 HCV/HIV, 3.4% of 29 Hepatitis B, and none of 171 non-HCV (p<0.0001; HCV versus non-HCV). Anti-RR was present in 38% of 108 patients receiving interferon-α/ribavirin, but none in 26 receiving either interferon-α or ribavirin, or 166 untreated patients (p<0.0001). Other IIF-HEp-2 patterns were more frequently associated with interferon-α treatment alone (52.2%) as compared to interferon-α/ribavirin (25%), ribavirin alone (33.3%), and no therapy (26.5%). Anti-RR frequency was not associated with sex, age, ethnicity, HCV genotype or viral load. Anti-RR occurred only after initiation of treatment, beginning as early as 1 month (6%), but by the sixth month >47% tested positive for anti-RR. The anti-RR titer generally increased with sustained treatment and remained high in 53% of patients. After treatment, anti-RR titer was negative in 41%. Non-responders to HCV therapy were 77% in anti-RR-positive versus 64% in anti-RR-negative patients. Response to treatment was not associated with anti-RR titer or the dynamics of anti-RR reactivity during and after treatment.

Conclusions

The exquisite association of anti-RR reactivity with combined interferon-α/ribavirin therapy in HCV patients represents a unique model for drug-induced autoantibody generation in humans as demonstrated by the fact that a significant fraction of patients who have anti-RR during therapy becomes anti-RR-negative after completion of therapy.     

3-(2-Benzyloxyphenyl)isoxazoles and isoxazolines: synthesis and evaluation as CFTR activators

A novel class of activators for chloride conductance in the cystic fibrosis transmembrane conductance regulator (CFTR) protein has been identified. These 3-(2-benzyloxyphenyl)isoxazoles and 3-(2-benzyloxyphenyl)isoxazolines were synthesized employing the 1,3-dipolar cycloaddition of nitrile oxides with various alkene and alkyne dipolarophiles. Utilizing a fluorescence cell-based assay of halide transport, the best compounds increased CFTR-dependent chloride transport with half-maximal stimulation at 20-50 microM.     

Lovastatin inhibits the extracellular-signal-regulated kinase pathway in immortalized rat brain neuroblasts

Arachidonic acid is a potential paracrine agent released by the uterine endometrial epithelium to induce PTGS2 [PG (prostaglandin)-endoperoxide synthase 2] in the stroma. In the present study, bovine endometrial stromal cells were used to determine whether PTGS2 is induced by arachidonic acid in stromal cells, and to investigate the potential role of PPARs (peroxisome-proliferator-activated receptors) in this effect. Arachidonic acid increased PTGS2 levels up to 7.5-fold within 6 h. The cells expressed PPARalpha and PPARdelta (also known as PPARbeta) (but not PPARgamma). PTGS2 protein level was increased by PPAR agonists, including polyunsaturated fatty acids, synthetic PPAR ligands, PGA1 and NSAIDs (non-steroidal anti-inflammatory drugs) with a time course resembling that of arachidonic acid. Use of agonists and antagonists indicated PPARalpha (but not PPARdelta or PPARgamma) was responsible for PTGS2 induction. PTGS2 induction by arachidonic acid did not require PG synthesis. PTGS2 levels were increased by the PKC (protein kinase C) activators 4beta-PMA and PGF(2alpha), and the effects of arachidonic acid, NSAIDs, synthetic PPAR ligands and 4beta-PMA were blocked by PKC inhibitors. This is consistent with PPAR phosphorylation by PKC. Induction of PTGS2 protein by 4beta-PMA in the absence of a PPAR ligand was decreased by the NF-kappaB (nuclear factor kappaB) inhibitors MG132 and parthenolide, suggesting that PKC acted through NF-kappaB in addition to PPAR phosphorylation. Use of NF-kappaB inhibitors allowed the action of arachidonic acid as a PPAR agonist to be dissociated from an effect through PKC. The results are consistent with the hypothesis that arachidonic acid acts via PPARalpha to increase PTGS2 levels in bovine endometrial stromal cells.     

Loss of phylogenetic and functional originalities of woody cerrado species in simulated extinction scenarios

Originality measures how different a given species is from all other co‐occurring species regarding either their phylogenetic history or functional traits. Since it is important to preserve the various aspects of diversity and original species carry more phylogenetic or functional information, originality may be used to assign conservation priorities. Our goal was to evaluate the relationships between phylogenetic and functional originalities, and their simulated losses under extinction scenarios based on abundance, fire tolerance and habitat preference. We placed 100 plots in a cerrado reserve located in central Brazil, sampled all woody plants species within the plots, measured 14 functional traits and measured fire history. We assembled a phylogenetic tree and a functional dendrogram, with which we calculated the originalities. Phylogenetic‐ and functional‐based originalities were correlated. However, the loss of functional originality was different from random extinctions on the abundance and fire tolerance scenarios, whereas the loss of phylogenetic originality was not. When compared with phylogenetic originality, functional originality brought more information to be used in conservation strategies because it was sensitive to differences in species abundance and fire tolerance. Thus, the extinction of rare or fire‐sensitive species would result in important functional changes due to loss of distinctive traits.     

Phospholipid sources for adrenic acid mobilization in RAW 264.7 macrophages. Comparison with arachidonic acid

Cells metabolize arachidonic acid (AA) to adrenic acid (AdA) via 2-carbon elongation reactions. Like AA, AdA can be converted into multiple oxygenated metabolites, with important roles in various physiological and pathophysiological processes. However, in contrast to AA, there is virtually no information on how the cells regulate the availability of free AdA for conversion into bioactive products. We have used a comparative lipidomic approach with both gas chromatography and liquid chromatography coupled to mass spectrometry to characterize changes in the levels of AA- and AdA-containing phospholipid species in RAW 264.7 macrophage-like cells. Incubation of the cells with AA results in an extensive conversion to AdA but both fatty acids do not compete with each other for esterification into phospholipids. AdA but not AA, shows preference for incorporation into phospholipids containing stearic acid at the sn-1 position. After stimulation of the cells with zymosan, both AA and AdA are released in large quantities, albeit AA is released to a greater extent. Finally, a variety of phosphatidylcholine and phosphatidylinositol molecular species contribute to AA; however, AdA is liberated exclusively from phosphatidylcholine species. Collectively, these results identify significant differences in the cellular utilization of AA and AdA by the macrophages, suggesting non-redundant biological actions for these two fatty acids.