A proton nuclear magnetic resonance-based metabolomic approach in IgA nephropathy urinary profiles

Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. Both one-dimensional NOESY and transverse-relaxation filter CPMG NMR spectra were recorded to investigate the urine metabolome of 24 IgAN patients and to detect altered metabolic profiles in comparison with 68 healthy matched controls. The spectral data were analyzed using multivariate statistical techniques. The analysis revealed that the NMR spectra of IgAN patients were statistically different from those of the controls (P = 4 × 10^?7 for 1D-NOESY and P = 2 × 10^?7 for CPMG). The robustness of the determined statistical model was confirmed by its predictive performance (for the 1D-NOESY dataset: sensitivity = 67 %, specificity = 95 %; for the CPMG dataset sensitivity = 60 %, specificity = 94 %). For the first time we found metabolites, including betaine and citrate, that are differentially modulated in IgAN patients compared to controls and that may be directly involved in the pathogenesis of IgAN. These metabolites may influence, directly or indirectly, the TNF-α, a regulating factor of the Th1/Th2 cell balance that is relevant in the pathology. The involvement of metabolites such as betaine and citrate in TNF-α regulation supports the power of the identified metabolic profiles to discern IgAN from controls.     

Length and GC Content Variability of Introns among Teleostean Genomes in the Light of the Metabolic Rate Hypothesis

A comparative analysis of five teleostean genomes, namely zebrafish, medaka, three-spine stickleback, fugu and pufferfish was performed with the aim to highlight the nature of the forces driving both length and base composition of introns (i.e., bpi and GCi). An inter-genome approach using orthologous intronic sequences was carried out, analyzing independently both variables in pairwise comparisons. An average length shortening of introns was observed at increasing average GCi values. The result was not affected by masking transposable and repetitive elements harbored in the intronic sequences. The routine metabolic rate (mass specific temperature-corrected using the Boltzmann''s factor) was measured for each species. A significant correlation held between average differences of metabolic rate, length and GC content, while environmental temperature of fish habitat was not correlated with bpi and GCi. Analyzing the concomitant effect of both variables, i.e., bpi and GCi, at increasing genomic GC content, a decrease of bpi and an increase of GCi was observed for the significant majority of the intronic sequences (from ∼40% to ∼90%, in each pairwise comparison). The opposite event, concomitant increase of bpi and decrease of GCi, was counter selected (from <1% to ∼10%, in each pairwise comparison). The results further support the hypothesis that the metabolic rate plays a key role in shaping genome architecture and evolution of vertebrate genomes.     

Oxygen therapy at low flow causes oxidative stress in chronic obstructive pulmonary disease: Prevention by N-acetyl cysteine

Exposure to high oxygen concentration produces toxicity by free radical release. We aimed to study: whether stable chronic obstructive pulmonary disease (COPD) patients present an unbalance in the blood redox status; the effect of oxygen administration on blood redox balance; the efficacy of N-acetyl-cysteine (NAC) treatment against the oxidative stress-induced by oxygen administration and whether it is dose-related. To this, 45 stable state III COPD patients were recruited and reduced glutathione (GSH) and oxidised glutathione (GSSG) in erythrocytes and thiol proteins (P-SH) and carbonyl proteins (PC) in both erythrocytes and plasma were evaluated. All COPD patients underwent 2 l/m oxygen for 18 h and NAC at 1200 or 1800 mg/day or placebo for 48 h starting with oxygen administration. Blood samples were collected at basal conditions, after 8 and 18 h of oxygen administration and 24 h after oxygen withdrawal. Results: COPD patients present an unstable redox equilibrium mainly due to plasma sulphydryl protein depletion. Oxygen administration oxidize erythrocyte GSH, decrease P-SH and increase PC levels in both plasma and erythrocytes. NAC administration counteract the oxidative stress and at the highest dose completely prevent protein oxidation. In conclusion, stable state III COPD patients present an unstable redox balance; long term low flow oxygen administration induces systemic oxidative stress, which is prevented by NAC treatment.     

Factors Affecting Elevated Arsenic and Methyl Mercury Concentrations in Small Shield Lakes Surrounding Gold Mines near the Yellowknife,NT, (Canada) Region

Gold mines in the Yellowknife, NT, region—in particular, the Giant Mine—operated from 1949–99, releasing 237,000 tonnes of waste arsenic trioxide (As₂O₃) dust, among other compounds, from gold ore extraction and roasting processes. For the first time, we show the geospatial distribution of roaster-derived emissions of several chemical species beyond the mine property on otherwise undisturbed taiga shield lakes within a 25 km radius of the mine, 11 years after its closing. Additionally, we demonstrate that underlying bedrock is not a significant source for the elevated concentrations in overlying surface waters. Aquatic arsenic (As) concentrations are well above guidelines for drinking water (10 μg/L) and protection for aquatic life (5 μg/L), ranging up to 136 μg/L in lakes within 4 km from the mine, to 2.0 μg/L in lakes 24 km away. High conversion ratios of methyl mercury were shown in lakes near the roaster stack as well, with MeHg concentrations reaching 44% of total mercury. The risk of elevated exposures by these metals is significant, as many lakes used for recreation and fishing near the City of Yellowknife are within this radius of elevated As and methyl Hg concentrations.     

Focus: Sex and Gender Health: Women and Chest Pain: Recognizing the Different Faces of Angina in the Emergency Department

Emergency departments (ED) in the United States see over eight million cases of chest pain annually. While a cardinal symptom of acute coronary syndrome (ACS), multiple emergent and non-emergent causes can attribute to chest pain. This case-based perspective describes the different sex-specific causes of angina seen in ED patients. Once coronary artery disease (CAD) is ruled out with standard protocols, microvascular dysfunction is perhaps the most prevalent but under-diagnosed cause of non-CAD related angina in ED patients. Additional causes include coronary artery spasm, coronary artery dissection, coronary artery endothelial dysfunction and myocardial bridging. Non-CAD related angina is associated with persistent chest pain causing poor function, quality of life, and recidivism. Clinicians should consider additional diagnostics to routinely screen for non-CAD related causes of angina in patients with recurrent chest pain. Future work is needed to better define the epidemiological, clinical, biological, and genetic correlates of microvascular dysfunction in these patients.     

Bifidobacterium longum CECT 7347 modulates immune responses in a gliadin-induced enteropathy animal model

Coeliac disease (CD) is an autoimmune disorder triggered by gluten proteins (gliadin) that involves innate and adaptive immunity. In this study, we hypothesise that the administration of Bifidobacterium longum CECT 7347, previously selected for reducing gliadin immunotoxic effects in vitro, could exert protective effects in an animal model of gliadin-induced enteropathy. The effects of this bacterium were evaluated in newborn rats fed gliadin alone or sensitised with interferon (IFN)-γ and fed gliadin. Jejunal tissue sections were collected for histological, NFκB mRNA expression and cytokine production analyses. Leukocyte populations and T-cell subsets were analysed in peripheral blood samples. The possible translocation of the bacterium to different organs was determined by plate counting and the composition of the colonic microbiota was quantified by real-time PCR. Feeding gliadin alone reduced enterocyte height and peripheral CD4+ cells, but increased CD4+/Foxp3+ T and CD8+ cells, while the simultaneous administration of B. longum CECT 7347 exerted opposite effects. Animals sensitised with IFN-γ and fed gliadin showed high cellular infiltration, reduced villi width and enterocyte height. Sensitised animals also exhibited increased NFκB mRNA expression and TNF-α production in tissue sections. B. longum CECT 7347 administration increased NFκB expression and IL-10, but reduced TNF-α, production in the enteropathy model. In sensitised gliadin-fed animals, CD4+, CD4+/Foxp3+ and CD8+ T cells increased, whereas the administration of B. longum CECT 7347 reduced CD4+ and CD4+/Foxp3+ cell populations and increased CD8+ T cell populations. The bifidobacterial strain administered represented between 75-95% of the total bifidobacteria isolated from all treated groups, and translocation to organs was not detected. These findings indicate that B. longum attenuates the production of inflammatory cytokines and the CD4+ T-cell mediated immune response in an animal model of gliadin-induced enteropathy.     

Three new species of Antricola (Acari: Argasidae) from Brazil, with a key to the known species in the genus

Three new species of Antricola (Acari: Argasidae) are described from adult specimens collected on bat guano in different caves in Brazil. The female of Antricola guglielmonei n. sp. is easily determined by the presence of 2 smooth, depressed areas lacking setae in the posterolateral portions of the dorsum of the idiosoma, together with the partial fusion of the tubercles in the anteromedian portion of the idiosoma. The male of this species has a small spiracular plate surrounded by a pattern of tubercles disposed concentrically in its dorsal portion. Both sexes have cervical grooves very slightly marked. Antricola delacruzi n. sp. represents the only Antricola species with the dorsum of the idiosoma devoid of tubercles in both sexes and with scarce and minute setae placed over the smooth cuticle. The female of A. inexpectata n. sp. is known only from a few specimens. In this species, lines of smooth cuticle lacking setae separate the tubercles of the dorsum. In addition, there are 3 clumps of plumose setae close to the spiracular plate, in the ventrolateral portions of the idiosoma, in 3 well-delimited regions over cuticular thickenings. These 3 species share the peculiarity of a Haller's organ with the anterior pit bearing only 7 + 2 setae. The collection of these new species in Brazilian caves greatly expands the known range of the genus. A key to the adults of all known species of the genus is provided.     

Effect of homologous series of n-alkyl sulfates and n-alkyl trimethylammonium bromides on low molecular mass protein tyrosine phosphatase activity

The effect of anionic and cationic surfactants on acid phosphatase denaturation has been extensively studied. Low molecular mass (LMr) protein tyrosine phosphatase (PTP), a key regulatory enzyme involved in many different processes in the cell, was distinctly affected by anionic (homologous series of n-alkyl sulfates (C8-C14)) and cationic (n-alkyl trimethylammonium bromides (C12-C16)) surfactants. At concentrations 10-fold lower critical micellar concentration (cmc) values, the enzyme was completely inactivated in the presence of anionic surfactants, in a process independent of the pH, and dependent on the chain length of the surfactants. Under the same conditions, the effect of cationic surfactants on the enzyme activity was pH-dependent and only at pH 7.0 full inactivation was observed at concentrations 10-fold higher cmc values. In contrast to cationic surfactants the effect of anionic surfactants on the enzyme activity was irreversible and was not affected by the presence of NaCl. Inorganic phosphate, a known competitive inhibitor of PTP, protected the enzyme against inactivation by the surfactants. Our results suggest that the inactivation of the LMr PTP by anionic and cationic surfactants involved both electrostatic and hydrophobic interactions, and that the interactions enzyme-surfactants probably occurred at or near the active site.