709 research outputs found

    An amino acids mixture improves the hepatotoxicity induced by acetaminophen in mice

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    Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but at high dose it leads to undesirable side effects, such as hepatotoxicity and nephrotoxicity. The aim of this study was to evaluate the protective role of DDM-GSH, a mixture of L-cysteine, L-methionine, and L-serine in a weight ratio of 2\u2009:\u20091\u2009:\u20091, in comparison to N-acetylcysteine (NAC), against acetaminophen- (APAP-) induced hepatotoxicity in mice. Toxicity was induced in mice by the intraperitoneal (ip) administration of low dose (2\u2009mmol/kg) or high dose (8\u2009mmol/kg) of APAP. DDM-GSH (0.4 to 1.6\u2009mmol/kg) was given ip to mice 1\u2009h before the APAP administration. The same was done with NAC (0.9 to 3.6\u2009mmol/kg), the standard antidote of APAP toxicity. Mice were sacrificed 8\u2009h after the APAP injection to determine liver weight, serum alanine aminotransferase (ALT), and total glutathione (GSH) depletion and malondialdehyde (MDA) accumulation in liver tissues. DDM-GSH improved mouse survival rates better than NAC against a high dose of APAP. Moreover, DDM-GSH significantly reduced in a dose-dependent manner not only APAP-induced increases of ALT but also APAP-induced hepatic GSH depletion and MDA accumulation. Our results suggest that DDM-GSH may be more potent than NAC in protecting the liver from APAP-induced liver injury

    Genetic analysis of rennet coagulation time, curd-firming rate, and curd firmness assessed over an extended testing period using mechanical and near-infrared instruments

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    Abstract The aims of this study were (1) to analyze rennet coagulation time (RCT), curd-firming rate, and curd firmness obtained by extending the standard 30-min testing time to 45min; (2) to estimate heritabilities of the aforementioned traits determined by mechanical (Formagraph; Foss Electric, Hillerod, Denmark) and near-infrared optical (Optigraph; Ysebaert, Frepillon, France) instruments, and to assess the statistical relevance of their genetic background by using the Bayes factor procedure, the deviance information criterion, and the mean squared error; (3) to estimate phenotypic and genetic relationships between instruments within trait and between traits within instrument; and (4) to obtain correlations for sire rankings based on the used instruments. Individual milk samples were collected from 913 Brown Swiss cows reared in 63 herds located in Trento Province (Italy). Milk coagulation properties (MCP) were measured using 2 different instruments: Formagraph and Optigraph. Both instruments were housed in the same laboratory and operated by the same technician. Each sample was analyzed simultaneously on each instrument. All experimental conditions (milk temperature and the concentration and type of rennet) were identical. For the analysis, univariate and bivariate animal models were implemented using Bayesian methods. Univariate analyses were conducted to test the hypothesis that the traits showed additive genetic determination. Deviance information criterion, Bayes factor, and mean squared error were used as model choice criteria. The main results were that (1) RCT could be measured on all samples by extending the observation time to 45min, and its genetic parameters ( h 2 =0.23) and breeding values could be estimated while avoiding the bias of noncoagulating samples; (2) curd-firming rate could be measured on almost all milk samples, and its genetic parameters could be estimated for the first time on a field data set ( h 2 =0.21); (3) for the first time, genetic parameters of curd firmness 45min after rennet addition ( h 2 =0.12) were estimated, and they were compared with curd firmness 30min after rennet addition ( h 2 =0.17); and (4) MCP estimated using the Optigraph appeared to be genetically different from those determined by Formagraph, with the partial exception of RCT (genetic correlation=0.97). Breeding strategies for the improvement of MCP must be planned with caution. Currently, the high throughput, ease of use, and reduced costs of analysis make predictions obtained from mid-infrared spectroscopy (MIRS) on untreated milk samples a promising alternative to produce relevant data at the population level. The use of mechanical lactodynamographs to establish reference data for MIRS calibrations have been already studied, whereas the use of near-infrared optical lactodynamographs as a reference method for MIRS calibrations needs to be investigated

    Dissecting the Physiological Function of Plant Glyoxalase I and Glyoxalase I-Like Proteins

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    The Arabidopsis genome annotation include 11 glyoxalase I (GLXI) genes, all encoding for protein members of the vicinal oxygen chelate (VOC) superfamily. The biochemical properties and physiological importance of three Arabidopsis GLXI proteins in the detoxification of reactive carbonyl species has been recently described. Analyses of phylogenetic relationships and conserved GLXI binding sites indicate that the other eight GLXI genes (GLXI-like) do not encode for proteins with GLXI activity. In this perspective article we analyse the structural features of GLXI and GLXI-like proteins, and explore splice forms and transcript abundance under abiotic stress conditions. Finally, we discuss future directions of research on this topic with respect to the substrate identification of GLXI and GLXI-like proteins and the need of reliable quantitative measurements of reactive carbonyl species in plant tissues

    Short communication: Characterization of a monoclonal antibody for κ-casein B of cow's milk1

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    A monoclonal antibody (antik-B) against an oligopeptide of 23 AA corresponding to the region 131-153 of bovine kappa-casein (kappa-CN) B was generated using the Human Combinatorial Antibody Library (HuCAL) technology. Both AA substitutions distinguishing kappa-CN A and B are located in that region (positions 136 and 148). In this study, the reactivity of antik-B to milk samples collected from cows previously genotyped as CSN3*AA, CSN3*AB, and CSN3*BB was tested. According to Western blot results, antik-B recognized kappa-CN B and it showed no cross-reactivity toward kappa-CN A and other milk proteins. Furthermore, a modified Western blot method, urea-PAGE Western blot, was set up to assess the reactivity of antik-B toward all isoforms of kappa-CN B. In conclusion, antik-B was specific to kappa-CN B in milk and it seemed to be reactive toward all its isoforms

    Endothelial Dysfunction In Cardiovascular And Endocrine-metabolic Diseases: An Update.

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    The endothelium plays a vital role in maintaining circulatory homeostasis by the release of relaxing and contracting factors. Any change in this balance may result in a process known as endothelial dysfunction that leads to impaired control of vascular tone and contributes to the pathogenesis of some cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived nitric oxide (NO) bioavailability and increased production of thromboxane A2, prostaglandin H2 and superoxide anion in conductance and resistance arteries are commonly associated with endothelial dysfunction in hypertensive, diabetic and obese animals, resulting in reduced endothelium-dependent vasodilatation and in increased vasoconstrictor responses. In addition, recent studies have demonstrated the role of enhanced overactivation of β-adrenergic receptors inducing vascular cytokine production and endothelial NO synthase (eNOS) uncoupling that seem to be the mechanisms underlying endothelial dysfunction in hypertension, heart failure and in endocrine-metabolic disorders. However, some adaptive mechanisms can occur in the initial stages of hypertension, such as increased NO production by eNOS. The present review focuses on the role of NO bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro-inflammatory factors on the endothelial dysfunction that occurs in hypertension, sympathetic hyperactivity, diabetes mellitus, and obesity. These are cardiovascular and endocrine-metabolic diseases of high incidence and mortality around the world, especially in developing countries and endothelial dysfunction contributes to triggering, maintenance and worsening of these pathological situations.44920-3

    Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an update

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    The endothelium plays a vital role in maintaining circulatory homeostasis by the release of relaxing and contracting factors. Any change in this balance may result in a process known as endothelial dysfunction that leads to impaired control of vascular tone and contributes to the pathogenesis of some cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived nitric oxide (NO) bioavailability and increased production of thromboxane A2, prostaglandin H2 and superoxide anion in conductance and resistance arteries are commonly associated with endothelial dysfunction in hypertensive, diabetic and obese animals, resulting in reduced endothelium-dependent vasodilatation and in increased vasoconstrictor responses. In addition, recent studies have demonstrated the role of enhanced overactivation of β-adrenergic receptors inducing vascular cytokine production and endothelial NO synthase (eNOS) uncoupling that seem to be the mechanisms underlying endothelial dysfunction in hypertension, heart failure and in endocrine-metabolic disorders. However, some adaptive mechanisms can occur in the initial stages of hypertension, such as increased NO production by eNOS. The present review focuses on the role of NO bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro-inflammatory factors on the endothelial dysfunction that occurs in hypertension, sympathetic hyperactivity, diabetes mellitus, and obesity. These are cardiovascular and endocrine-metabolic diseases of high incidence and mortality around the world, especially in developing countries and endothelial dysfunction contributes to triggering, maintenance and worsening of these pathological situations449920932CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informaçã

    The genetic heritage of Alpine local cattle breeds using genomic SNP data

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    Background: Assessment of genetic diversity and population structure provides important control metrics to avoid genetic erosion, inbreeding depression and crossbreeding between exotic and locally-adapted cattle breeds since these events can have deleterious consequences and eventually lead to extinction. Historically, the Alpine Arc represents an important pocket of cattle biodiversity with a large number of autochthonous breeds that provide a fundamental source of income for the entire regional economy. By using genotype data from medium-density single nucleotide polymorphism (SNP) arrays, we performed a genome-wide comparative study of 23 cattle populations from the Alpine Arc and three cosmopolitan breeds. Results: After filtering, we obtained a final genotyping dataset consisting of 30,176 SNPs for 711 individuals. The local breeds showed high or intermediate values of genetic diversity compared to the highly selected cosmopolitan breeds. Patterns of genetic differentiation, multidimensional scaling, admixture analysis and the constructed phylogenetic tree showed convergence, which indicates the presence of gene flow among the breeds according to both geographic origin and historical background. Among the most differentiated breeds, we identified the modern Brown cattle. In spite of admixture events, several local breeds have preserved distinctive characteristics, which is probably due to differences in genetic origin and geographic location. Conclusions: This study represents one of the most comprehensive genome-wide analysis of the Alpine cattle breeds to date. Using such a large dataset that includes the majority of the local breeds found in this region, allowed us to expand knowledge on the evaluation and status of Alpine cattle biodiversity. Our results indicate that although many of the analyzed local breeds are listed as endangered, they still harbor a large amount of genetic diversity, even when compared to some cosmopolitan breeds. This finding, together with the reconstruction of the phylogeny and the relationships between these Alpine Arc cattle breeds, provide crucial insights not only into the improvement of genetic stocks but also into the implementation of future conservation strategies
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