Bis(triphenyl­guanidinium) tetra­chlorido­cuprate(II)

The structure of the title compound, (C19H18N3)2[CuCl4], consists of square-planar [CuCl4]2− anions and triphenyl­guanidinium cations. The CuII ion occupies a crystallographic inversion centre. In the cation, the dihedral angles between the phenyl rings and the plane defined by the central guanidinium fragment are in the range 51.9 (4)–64.4 (3)°. N—H⋯Cl hydrogen bonds assemble the ions into infinite chains running along the b axis

Intracoronary infusion of mononuclear cells after PCI-treated myocardial infarction and arrhythmogenesis: is it safe?

To reduce long-term morbidity after revascularised acute myocardial infarction, different therapeutic strategies have been investigated. Cell therapy with mononuclear cells from bone marrow (BMMC) or peripheral blood (PBMC) has been proposed to attenuate the adverse processes of remodelling and subsequent heart failure. Previous trials have suggested that cell therapy may facilitate arrhythmogenesis. In the present substudy of the HEBE cell therapy trial, we investigated whether intracoronary cell therapy alters the prevalence of ventricular arrhythmias after 1 month or the rate of severe arrhythmogenic events (SAE) in the first year. In 164 patients of the trial we measured function and infarct size with cardiovascular magnetic resonance (CMR) imaging. Holter registration was performed after 1 month from which the number of triplets (3 successive PVCs) and ventricular tachycardias (VT, ≥4 successive PVCs) was assessed. Thirty-three patients (20%) showed triplets and/or VTs, with similar distribution amongst the groups (triplets: control n = 8 vs. BMMC n = 9, p = 1.00; vs. PBMC n = 10, p = 0.67. VT: control n = 9 vs. BMMC n = 9, p = 0.80; vs. PBMC n = 11, p = 0.69). SAE occurred in 2 patients in the PBMC group and 1 patient in the control group. In conclusion, intracoronary cell therapy is not associated with an increase in ventricular arrhythmias or SAE

Body mass index related electrocardiographic findings in healthy young individuals with a normal body mass index

IntroductionAn increased body mass index (BMI) (>25 kg/m2) is associated with a wide range of electrocardiographic changes. However, the association between electrocardiographic changes and BMI in healthy young individuals with a normal BMI (18.5–25 kg/m2) is unknown. The aim of this study was to evaluate the association between BMI and electrocardiographic parameters.MethodsData from 1,290 volunteers aged 18 to 30 years collected at our centre were analysed. Only subjects considered healthy by a physician after review of collected data with a normal BMI and in sinus rhythm were included in the analysis. Subjects with a normal BMI (18.5–25 kg/m2) were divided into BMI quartiles analysis and a backward multivariate regression analysis with a normal BMI as a continuous variable was performed.ResultsMean age was 22.7 ± 3.0 years, mean BMI was 22.0, and 73.4% were male. There were significant differences between the BMI quartiles in terms of maximum P-wave duration, P-wave balance, total P-wave area in lead V1, PR-interval duration, and heart axis. In the multivariate model maximum P-wave duration (standardised coefficient (SC) = +0.112, P P-wave balance in lead V1 (SC = +0.072, P P P ConclusionIncreased BMI was related with discrete electrocardiographic alterations including an increased P-wave duration, increased P-wave balance, a leftward shift of the heart axis, and decreased Sokolow-Lyon voltage on a standard twelve lead electrocardiogram in healthy young individuals with a normal BMI.Medicinal Chemistr

N,N′,N′′-Triphenyl­guanidinium 5-nitro-2,4-dioxo-1,2,3,4-tetra­hydro­pyrimidin-1-ide

In the title compound, C19H18N3 +.C4H2N3O4 −, the dihedral angles between the phenyl rings and the plane defined by the central guanidinium fragment are in the range 41.3 (1)–66.6 (1)°. The pyrimidine ring of the anion is distorted towards a boat conformation and the nitro group is rotated 11.4 (2)° out of the uracil plane. Hydrogen bonds assemble the ions in infinite helical chains along the b axis

Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis

The desmosomal cadherin desmoglein-1 (DSG1) is an essential intercellular adhesion molecule that is altered in various human cutaneous disorders; however, its regulation and function in allergic disease remains unexplored. Herein, we demonstrate a specific reduction in DSG1 in esophageal biopsies from patients with eosinophilic esophagitis (EoE), an emerging allergic disorder characterized by chronic inflammation within the esophageal mucosa. Further, we show that DSG1 gene silencing weakens esophageal epithelial integrity, and induces cell separation and impaired barrier function (IBF) despite high levels of desmoglein-3 (DSG3). Moreover, DSG1 deficiency induces transcriptional changes that partially overlap with the transcriptome of inflamed esophageal mucosa; notably, periostin, a multipotent pro-inflammatory extracellular matrix molecule, is the top induced overlapping gene. We further demonstrate that IBF is a pathological feature in EoE, which can be partially induced through the downregulation of DSG1 by interleukin-13 (IL-13). Taken together, these data identify a functional role for DSG1 and its dysregulation by IL-13 in the pathophysiology of EoE and suggest that the loss of DSG1 may potentiate allergic inflammation through the induction of pro-inflammatory mediators such as periostin

Age influence on effectiveness of a novel 3-phytase in barley-wheat based diets for pigs from 12 to 108 kg under commercial conditions

[EN] The main objective of this study was to evaluate the influence of pig's age on the effectiveness of a new microbial 3-phytase, produced by Komagataella phaffii, under commercial conditions in barley-wheat based diets. Two experiments were conducted in weaned, growing and finishing pigs; firstly, to determine phytase efficacy on dry matter, organic matter, energy, protein and mineral (phosphorus, P and calcium, Ca) digestibility (n = 48; Experiment 1), and secondly, to evaluate the effect of phytase on growth performance and bone mineralization (n = 312; Experiment 2). In each experiment, three barley-wheat based diets were formulated following the recommendations for each animal age, of which two versions were manufactured, including 0 and 1000 phytase units (FTU)/kg of feed of the new 3-phytase to be tested. Results showed the new phytase had the potential to increase the digestibility of Ca and P (on av. + 0.05 and +0.06, respectively; P < 0.01), especially P digestibility in growing pigs (+0.10; P < 0.001), consequently decreasing P and Ca excretion. Digestible energy (DE) of the diet increased with the addition of phytase in weaned pigs (+0.69 MJ/kg of dry matter (DM); P < 0.001). Dietary inclusion of new 3-phytase enhanced average daily gain from 46 to 94 days of age (+0.07 kg/d; P < 0.05) and decreased feed conversion ratio from 46 to 154 days of age (on av. -0.13; P < 0.05), although no significant effect was observed from 154 to 185 days of age. Addition of the new 3-phytase also promoted bone mineralization, increasing the weight of the bones (+3.99 and +3.64 g of tibia at 95 days and metacarpus at 100 days of age, respectively; P < 0.05) and the ash, Ca and P content in these bones (e.g. + 0.46 and +0.33 g of P in tibia at 95 days and metacarpus at 100 days of age, respectively; P < 0.001). In conclusion, pig age affected the efficacy of a new 3-phytase on P and Ca digestibility both in weaned and growing diets and DE content of the weaned diets, which also resulted in improvements in growth, feed conversion and bone development until 154 days of age. These effects seem to be reduced during the finishing period, although the advantages of the new 3-phytase on bone mineralization were maintained until 185 days of age.We thank the technical staff at the experimental farms of the Research and Technology Animal Centre (CITA-IVIA), the Institute of Animal Science and Technology (Universitat Politècnica de Valencia) and Javier Gómez (Crianzas Campovivo) for expert technical assistance and experimental support.Cambra López, M.; Cerisuelo, A.; Ferrer, P.; Ródenas Martínez, L.; Aligué, R.; Moset, V.; Pascual Amorós, JJ. (2020). Age influence on effectiveness of a novel 3-phytase in barley-wheat based diets for pigs from 12 to 108 kg under commercial conditions. Animal Feed Science and Technology. 267:1-13. https://doi.org/10.1016/j.anifeedsci.2020.114549S113267Adeola, O., & Cowieson, A. J. (2011). BOARD-INVITED REVIEW: Opportunities and challenges in using exogenous enzymes to improve nonruminant animal production. 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Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in European EoE cases and subsequently in a multi-site cohort with local and out-of-study control subjects. In addition to replication of the 5q22 locus (meta-analysis p = 1.9×10−16), we identified association at 2p23 (encoding CAPN14, p = 2.5×10−10). CAPN14 was specifically expressed in the esophagus, dynamically upregulated as a function of disease activity and genetic haplotype and after exposure of epithelial cells to IL-13, and located in an epigenetic hotspot modified by IL-13. There was enriched esophageal expression for the genes neighboring the top 208 EoE sequence variants. Multiple allergic sensitization loci were associated with EoE susceptibility (4.8×10−2 < p < 5.1×10−11). We propose a model that elucidates the tissue specific nature of EoE that involves the interplay of allergic sensitization with an EoE-specific, IL-13–inducible esophageal response involving CAPN14