Pedro Ximenez sun-dried grape must: a dietary supplement for a healthy longevity.

Polyphenols in red wine are bioactive compounds with positive effects on health and disease prevention. White grape musts and wines have a lower concentration of phenolic compounds compared to the red ones and are therefore considered less beneficial to health. In Andalucía, a region located in the South West of Spain, Pedro Ximenez white grapes are desiccated under the sun for a week before they are pressed and the juice (must) is obtained. This ancient procedure increases the variety and content of polyphenols present in the Pedro Ximenez must (PXM). We incorporated PXM into the daily diet of aged Mus spretus mice (24 months) and investigated their properties by comparing several parameters determined in these old mice with those measured in young mice (two months old). Biochemical, histological, and transcriptional analyses indicated that PXM exhibited potent antioxidant properties, promoted the normalization of the biotransforming ability of several cytochromes, i.e., the P450 family, in the liver, and regularized hepatic apoptosis, promoting proliferation instead. Our data indicated that PXM possesses a profound ability to promote liver regeneration in terms of both the structure and the function, thus contributing to a healthy aging process.

First outbreak of bovine haemorrhagic septicaemia caused by Pasteurella multocida type B in Spain - Short communication.

This paper describes the first documented outbreak of haemorrhagic septicaemia (HS) caused by Pasteurella multocida type B in cattle in Spain. This acute, highly fatal septicaemia causes major economic losses in cattle and buffaloes in many areas of Asia and Africa. In other species and in European countries it is an infrequently reported disease. Acute septicaemic pasteurellosis occurred in a free-range farm of 150 cattle and 70 beef calves in Southern Spain. Twenty-one calves and one cow were affected, of which three calves and the adult cow died. Postmortem examination revealed characteristic oedema in the ventral area of the neck and the brisket region, and widespread haemorrhages in all organs. Pure cultures of P. multocida were obtained from all tissues and organs studied. The aetiological agent was further confirmed by molecular and biochemical analysis as P. multocida capsular type B, biovar 3. Although the source of infection could not be determined, wildlife may play an important role. The use of tulathromycin in the initial stage of the disease might be related to the low morbidity and mortality of this outbreak. After using an autogenous vaccine no more cases of HS were observed.

Characterization of dendritic cells and follicular dendritic cells in the hepatic lymph nodes and liver of sheep experimentally infected with Fasciola hepatica.

Fasciola hepatica has been shown to have a high capacity for immunomodulation of the host response, making the development of protective vaccines extremely difficult. One of these immunomodulation mechanisms is the impairment of dendritic cells (DC) maturation and, therefore, suppression of antigenic presentation. The aim of this study was to evaluate the pathological changes as well as the characterization of two antigen presenting cells, DC (CD1b, CD83 and MHC-II positive) and follicular dendritic cells (FDC) (CNA.42, S100 and CD83 positive) by immunohistochemistry in the hepatic lymph nodes (HLN) and livers of sheep during the early stages of infection with F. hepatica [9 and 18 days post-infection (dpi)], compared with an uninfected group (UC) as a control. The results revealed a marked hyperplasia of HLN germinal centres at 9 and, in particular, 18 dpi, with respect to the UC group, with coincidental increased expression of CNA.42 in FDC of lymphoid follicles and CD1b in the DC of paracortical areas at 18 dpi. However, the expression of MHC-II and CD83 decreased at 9 and, particularly, at 18 dpi in HLN compared with that in the UC group. Since both markers are related to active presentation of antigens by DC and FDC, the results of the present study suggest that, despite the marked hyperplasia of HLN and increase in DC and FDC numbers during early stages of infection, the DC and FDC antigenic presentation capacity, as suggested by the expression of the markers MHC-II and CD83, is suppressed by the parasite. This suppression was not observed in the liver, probably because of the low number of DC. This is the first study of the immunophenotype of DCs and FDC in sheep infected with F. hepatica.

Protective effect of Pedro-Ximénez must against p,p'-DDE-induced liver damages in aged Mus spretus mice.

Aging is characterized by deterioration of biomolecules and impaired stress responses that make the elderly especially vulnerable to environmental pollutants. The pesticide p,p'-DDE is a DDT derivative that generates great concern because of its wide distribution and its harmful effects on both human health and the environment. We analyzed here the biological responses elicited by p,p'-DDE exposure in the liver of aged Mus spretus mice. Data demonstrate that the elderly constitute a population especially sensitive to this noxious environmental pollutant. We also demonstrated here that the daily consumption of sun-dried Pedro Ximénez (PX) white-grape must (PXM) protects the liver of aged mice from both the age and the damages caused by p,p'-DDE exposure. The PXM activity was exerted through the restoration of the hepatic metabolisms of lipids and carbohydrates and, probably, is a consequence of the ability of this polyphenol-rich mixture to avoid oxidative stress. Nutritional interventions including PXM, which ameliorates the effects of unavoidable exposure to pesticides in our food, are helpful tools that can help elderly populations to enjoy a healthy and expanded lifetime.

Comparative dynamics of peritoneal cell immunophenotypes in sheep during the early and late stages of the infection with Fasciola hepatica by flow cytometric analysis.

BACKGROUND: The peritoneal cell populations (PCP) are thought to play a crucial role during the early immune response in Fasciola hepatica infection while newly excysted juveniles (NEJ) are migrating in the peritoneal cavity (PC) towards the liver. In this study, we aimed to determine the immunophenotypes of the PCP and to analyse the dynamics of the recruitment of the PCP during the early and late stage of the infection in sheep infected with F. hepatica. METHODS: Thirty-seven sheep were divided into three groups: Group 1 (n = 20) and 2 (n = 10) were challenged with F. hepatica, Group 3 (n = 7) was not infected and remained as uninfected control (UC). After the slaughtering, peritoneal lavages were carried out to isolate peritoneal cell populations at 1, 3, 9 and 18 days post-infection (dpi) for Group 1 and at 14 weeks post-infection (wpi) for Group 2 and 3. Flow cytometry was conducted to assess the dynamics of peritoneal cavity cell populations. RESULTS: TCD4 cells showed a significant decrease at 1 and 18 dpi when compared to UC; no statistical differences were detected for TCD8 and WC1+γδ during the early stage of the infection with respect to the UC. CD14 cells exhibited a decreasing trend, with a significant decrease at 9 and 18 dpi when compared to the UC. The dynamics of MHCII and CD83 cells showed a similar increasing pattern from 3 to 18 dpi. During the chronic stage, both TCD4 and TCD8 cells showed no significant differences when compared to the UC, although a slight but statistically significant higher level of WC1+γδ cells was observed. A lower percentage of antigen-presenting cells (APCs) was detected with respect to the UC. CONCLUSIONS: The recruitment of the lymphocytes subsets did not show a significant increase during the course of the infection and only WC1+γδ cells displayed a significant increase at the chronic stage. For the CD14, a decreasing trend was observed during the early stage, which was statistically significant at the chronic stage of the infection. Peritoneal CD83 and MHCII cells developed an increasing trend during the early stage of infection, and showed a significant decrease at the late stage of the infection.

Fasciola hepatica induces Foxp3 T cell, proinflammatory and regulatory cytokine overexpression in liver from infected sheep during early stages of infection.

The expression of T regulatory cells (Foxp3), regulatory (interleukin [IL]-10 and transforming growth factor beta [TGF-ß]) and proinflammatory (tumor necrosis factor alpha [TNF-α] and interleukin [IL]-1ß) cytokines was quantified using real time polymerase chain reaction (qRT-PCR) in the liver of sheep during early stages of infection with Fasciola hepatica (1, 3, 9, and 18 days post-infection [dpi]). Portal fibrosis was also evaluated by Masson's trichrome stain as well as the number of Foxp3+ cells by immunohistochemistry. Animals were divided into three groups: (a) group 1 was immunized with recombinant cathepsin L1 from F. hepatica (FhCL1) in Montanide adjuvant and infected; (b) group 2 was uniquely infected with F. hepatica; and (c) group 3 was the control group, unimmunized and uninfected. An overexpression of regulatory cytokines of groups 1 and 2 was found in all time points tested in comparison with group 3, particularly at 18 dpi. A significant increase of the number of Foxp3+ lymphocytes in groups 1 and 2 was found at 9 and 18 dpi relative to group 3. A progressive increase in portal fibrosis was found in groups 1 and 2 in comparison with group 3. In this regard, group 1 showed smaller areas of fibrosis than group 2. There was a significant positive correlation between Foxp3 and IL-10 expression (by immunohistochemistry and qRT-PCR) just as between portal fibrosis and TGF-ß gene expression. The expression of proinflammatory cytokines increased gradually during the experience. These findings suggest the induction of a regulatory phenotype by the parasite that would allow its survival at early stages of the disease when it is more vulnerable.