Studies by various investigators have indicated that elevated levels of plasma homocyst(e)ine are strongly associated with the occurrence of occlusive vascular diseases. With the eventual aim of determining whether or not elevated plasma homocyst(e)ine concentrations are directly causative of cardiovascular diseases, we have generated mice that are moderately and severely homocyst(e)inemic. Homologous recombination in mouse embryonic stem cells was used to inactivate the cystathionine 13-synthase [L-serine hydrolyase (adding homocysteine), EC 4.2.1.22] gene. Homozygous mutants completely lacking cystathionine 13-synthase were born at the expected frequency from matings ofheterozygotes, but they suffered from severe growth retardation and a majority of them died within 5 weeks after birth. Histological examination showed that the hepatocytes of homozygotes were enlarged, multinucleated, and filled with microvesicular lipid droplets. Plasma homocyst(e)ine levels of the homozygotes were "40 times normal. These mice, therefore, represent a model for severe homocyst(e)inemia resulting from the complete lack of cystathionine 18-synthase. Heterozygous mutants have 509o reduction in cystathionine 8-synthase mRNA and enzyme activity in the liver and have twice normal plasma homocyst(e)ine levels. Thus, the heterozygous mutants are promising for studying the in vivo role of elevated levels of homocyst(e)ine in the etiology of cardiovascular diseases.Homocysteine is an intermediate amino acid in methionine metabolism and is either converted to cysteine by transsulfuration or methylated to form methionine. A decreased rate of metabolism through either of these pathways can lead to homocyst(e)inemia and homocystinuria.The of elevated homocyst(e)ine in the formation of thrombi or in the acceleration of atherogenesis is not well understood, various experiments suggest that homocysteine is a mediator of disease. For example, homocysteine damages cultured human venous and arterial endothelial cells (9, 10). Furthermore, DeGroot et al. (11) showed that cells grown from obligate heterozygotes for CBS deficiency were much more sensitive to methionine-mediated injury than were control cells. Other in vitro studies have demonstrated that homocysteine enhances autooxidation of low density lipoproteins (12), enhances biosynthesis of thromboxane (13), inhibits cell-surface thrombomodulin expression (14), promotes vascular smooth muscle cell growth (15), and enhances binding of lipoprotein(a) to fibrin (16). In vivo, long-term infusion of homocystine in baboons leads to endothelial desquamation, to an increase in platelet consumption, and to arterial lesions (17). However, there are also conflicting data indicating that an increased incidence of vascular diseases was not found in individuals heterozygous for homocystinuria (18,19). Determining whether elevated plasma homocyst(e)ine levels are causative of cardiovascular disease or are a consequence of the disease has been difficult because of the lack of an experimental animal mo...

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Traditional biomedical models are easy to manage in experimental facilities and allow fast and affordable basic genetic studies related to human disorders, but in some cases they do not always represent the complexity of their physiology. Translational medicine demands selected models depending on the particularities of the human disease to be investigated, reproducing as closely as possible the evolution, clinical symptoms and molecular pathways, cells or tissues involved in the dysfunction. Thus, pig models offer an alternative because of their anatomical and physiological similarities to humans and the availability of genomic, transcriptomic and, progressively more, proteomic tools for analysis of this species. Furthermore, there is a wide range of natural, selected and transgenic porcine breeds. The present review provides a summary of the applications of the pig as a model for metabolic, cardiovascular, infectious diseases, xenotransplantation and neurological disorders and an overview of the possibilities that the diverse proteomic techniques offer to study these pathologies in depth.

Ejaculated ram spermatozoa, freed from seminal plasma by a dextran/swim-up procedure and exposed to cold shock, were incubated with ram seminal plasma proteins and analyzed by fluorescence markers and scanning electron microscopy. Seminal plasma proteins bound to the sperm plasma membrane modified the functional characteristics of damaged spermatozoa, reproducing those of live cells. Scanning electron microscopy showed that the dramatic structural damage induced by cooling reverted after incubation with seminal plasma proteins. Assessment of membrane integrity by fluorescence markers also indicated a restoration of intact-membrane cells. This protein adsorption is a concentration-dependent process that induces cell surface restoration in relation to the amount of protein in the incubation medium. Fractionation of ram seminal plasma proteins by exclusion chromatography provided three fractions able to reverse the cold shock effect. Scanning electron microscopy also confirmed the high activity of one fraction, because approximately 50% of cold-shocked sperm plasma membrane surface was restored to its original appearance after incubation. Differences in composition between the three separated fractions mainly resulted from one major band of approximately 20 kDa, which must be responsible for recovering the sperm membrane permeability characteristic of a live cell.

The Mediterranean diet is considered as the foremost dietary regimen and its adoption is associated with the prevention of degenerative diseases and an extended longevity. The preeminent features of the Mediterranean diet have been agreed upon and the consumption of olive oil stands out as the most peculiar one. Indeed, the use of olive oil as the nearly exclusive dietary fat is what mostly characterizes the Mediterranean area. Plenty of epidemiological studies have correlated that the consumption of olive oil was associated with better overall health. Indeed, extra virgin olive oil contains (poly)phenolic compounds that are being actively investigated for their purported biological and pharma-nutritional properties. On 18 and 19 May 2018, several experts convened in Jaen (Spain) to discuss the most recent research on the benefits of olive oil and its components. We reported a summary of that meeting (reviewing several topics related to olive oil, not limited to health) and concluded that substantial evidence is accruing to support the widespread opinion that extra virgin olive oil should, indeed, be the fat of choice when it comes to human health and sustainable agronomy.