Body composition estimation in vivo and on the carcass of pigs raised on pastures

To compare the prediction of body composition in vivo and in slaughtered animals, a pig population with a broad genetical background, was used to determine the extent on which that prediction was affected by different characters (sex, slaughter body weight and lean percentage). Seventy-two barrows and 57 gilts were measured firstly ultrasonically (PigLog 105 - P) in vivo and then their carcasses were evaluated with a Fat-O-Meater apparatus (FOM) at the abattoir. Data were analysed by means of the Student t test for paired observations and subjected to linear correlation studies with the correlation coefficient. P and FOM measurements of lean percentage were positively and significantly associated (r = 0.68, P<0.01). Sensitivity, specificity, positive and negative predictive values of in vivo evaluations were also assessed. P measurements underestimated both muscle depth and fat thickness and did not show significant differences in lean percentage when compared to FOM values. As live evaluation showed a low sensitivity, lean percentage estimated in vivo with P can not be considered a good individual estimator of the same trait when measured in the carcass using FOM, notwithstanding its usefulness as an estimator of the average lean percentage of the group as a whole

Linagliptin Improves Insulin Sensitivity and Hepatic Steatosis in Diet-Induced Obesity

Linagliptin (tradjenta™) is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor. DPP-4 inhibition attenuates insulin resistance and improves peripheral glucose utilization in humans. However, the effects of chronic DPP-4 inhibition on insulin sensitivity are not known. The effects of long-term treatment (3–4 weeks) with 3 mg/kg/day or 30 mg/kg/day linagliptin on insulin sensitivity and liver fat content were determined in diet-induced obese C57BL/6 mice. Chow-fed animals served as controls. DPP-4 activity was significantly inhibited (67–89%) by linagliptin (P<0.001). Following an oral glucose tolerance test, blood glucose concentrations (measured as area under the curve) were significantly suppressed after treatment with 3 mg/kg/day (–16.5% to –20.3%; P<0.01) or 30 mg/kg/day (–14.5% to –26.4%; P<0.05) linagliptin (both P<0.01). Liver fat content was significantly reduced by linagliptin in a dose-dependent manner (both doses P<0.001). Diet-induced obese mice treated for 4 weeks with 3 mg/kg/day or 30 mg/kg/day linagliptin had significantly improved glycated hemoglobin compared with vehicle (both P<0.001). Significant dose-dependent improvements in glucose disposal rates were observed during the steady state of the euglycemic–hyperinsulinemic clamp: 27.3 mg/kg/minute and 32.2 mg/kg/minute in the 3 mg/kg/day and 30 mg/kg/day linagliptin groups, respectively; compared with 20.9 mg/kg/minute with vehicle (P<0.001). Hepatic glucose production was significantly suppressed during the clamp: 4.7 mg/kg/minute and 2.1 mg/kg/minute in the 3 mg/kg/day and 30 mg/kg/day linagliptin groups, respectively; compared with 12.5 mg/kg/minute with vehicle (P<0.001). In addition, 30 mg/kg/day linagliptin treatment resulted in a significantly reduced number of macrophages infiltrating adipose tissue (P<0.05). Linagliptin treatment also decreased liver expression of PTP1B, SOCS3, SREBP1c, SCD-1 and FAS (P<0.05). Other tissues like muscle, heart and kidney were not significantly affected by the insulin sensitizing effect of linagliptin. Long-term linagliptin treatment reduced liver fat content in animals with diet-induced hepatic steatosis and insulin resistance, and may account for improved insulin sensitivity

Protective efficacy of a live attenuated vaccine against Argentine hemorrhagic fever. AHF Study Group

Fil: Maiztegui, Julio I. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: McKee Jr, K. T. Womack Army Medical Center, Fort Bragg, North Carolina; Estados Unidos.Fil: Barrera Oro, J G. ANLIS Dr.C.G.Malbrán; Argentina.Fil: Harrison, L H. University of Pittsburgh Graduate School of Public Health,Pittsburgh, Pennsylvania; Estados Unidos.Fil: Gibbs, P H. Division of Disease Assessment, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21701; Estados Unidos.Fil: Feuillade, María Rosa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Enria, Delia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Briggiler, Ana M. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Levis, Silvana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Ambrosio, Ana María. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Halsey, N A. Department of International Health, Johns Hopkins Medical Institutions, Baltimore, Maryland; Estados Unidos.Fil: Peters, C J. Special Pathogens Branch, Centers for Disease Control, Atlanta, Georgia; Estados Unidos.Argentine hemorrhagic fever (AHF), caused by the arenavirus Junin, is a major public health problem among agricultural workers in Argentina. A prospective, randomized, double-blind, placebo-controlled, efficacy trial of Candid 1, a live attenuated Junin virus vaccine, was conducted over two consecutive epidemic seasons among 6500 male agricultural workers in the AHF-endemic region. Twenty-three men developed laboratory-confirmed AHF during the study; 22 received placebo and 1 received vaccine (vaccine efficacy 95%; 95% confidence interval [CI], 82%-99%). Three additional subjects in each group developed laboratory-confirmed Junin virus infection associated with mild illnesses that did not fulfill the clinical case definition for AHF, yielding a protective efficacy for prevention of any illness associated with Junin virus infection of 84% (95% CI, 60%-94%). No serious adverse events were attributed to vaccination. Candid 1, the first vaccine for the prevention of illness caused by an arenavirus, is safe and highly efficacious

Development of a New Tacaribe Arenavirus Infection Model and Its Use to Explore Antiviral Activity of a Novel Aristeromycin Analog

Background A growing number of arenaviruses can cause a devastating viral hemorrhagic fever (VHF) syndrome. They pose a public health threat as emerging viruses and because of their potential use as bioterror agents. All of the highly pathogenic New World arenaviruses (NWA) phylogenetically segregate into clade B and require maximum biosafety containment facilities for their study. Tacaribe virus (TCRV) is a nonpathogenic member of clade B that is closely related to the VHF arenaviruses at the amino acid level. Despite this relatedness, TCRV lacks the ability to antagonize the host interferon (IFN) response, which likely contributes to its inability to cause disease in animals other than newborn mice. Methodology/Principal Findings Here we describe a new mouse model based on TCRV challenge of AG129 IFN-α/β and -γ receptor-deficient mice. Titration of the virus by intraperitoneal (i.p.) challenge of AG129 mice resulted in an LD50 of ∼100 fifty percent cell culture infectious doses. Virus replication was evident in the serum, liver, lung, spleen, and brain 4–8 days after inoculation. MY-24, an aristeromycin derivative active against TCRV in cell culture at 0.9 µM, administered i.p. once daily for 7 days, offered highly significant (P\u3c0.001) protection against mortality in the AG129 mouse TCRV infection model, without appreciably reducing viral burden. In contrast, in a hamster model of arenaviral hemorrhagic fever based on challenge with clade A Pichinde arenavirus, MY-24 did not offer significant protection against mortality. Conclusions/Significance MY-24 is believed to act as an inhibitor of S-adenosyl-L-homocysteine hydrolase, but our findings suggest that it may ameliorate disease by blunting the effects of the host response that play a role in disease pathogenesis. The new AG129 mouse TCRV infection model provides a safe and cost-effective means to conduct early-stage pre-clinical evaluations of candidate antiviral therapies that target clade B arenaviruses

Inhibition of Lassa Virus Glycoprotein Cleavage and Multicycle Replication by Site 1 Protease-Adapted α1-Antitrypsin Variants

The virus family Arenaviridae includes several hemorrhagic fever causing agents such as Lassa, Guanarito, Junin, Machupo, and Sabia virus that pose a major public health concern to the human population in West African and South American countries. Current treatment options to control fatal outcome of disease are limited to the ribonucleoside analogue ribavirin, although its use has some significant limitations. The lack of effective treatment alternatives emphasizes the need for novel antiviral therapeutics to counteract these life-threatening infections. Maturation cleavage of the viral envelope glycoprotein by the host cell proprotein convertase site 1 protease (S1P) is critical for infectious virion production of several pathogenic arenaviruses. This finding makes this protease an attractive target for the development of novel anti-arenaviral therapeutics. We demonstrate here that highly selective S1P-adapted α1-antitrypsins have the potential to efficiently inhibit glycoprotein processing, which resulted in reduced Lassa virus replication. Our findings suggest that S1P should be considered as an antiviral target and that further optimization of modified α1-antitrypsins could lead to potent and specific S1P inhibitors with the potential for treatment of certain viral hemorrhagic fevers

A Multivalent and Cross-Protective Vaccine Strategy against Arenaviruses Associated with Human Disease

Arenaviruses are the causative pathogens of severe hemorrhagic fever and aseptic meningitis in humans, for which no licensed vaccines are currently available. Pathogen heterogeneity within the Arenaviridae family poses a significant challenge for vaccine development. The main hypothesis we tested in the present study was whether it is possible to design a universal vaccine strategy capable of inducing simultaneous HLA-restricted CD8+ T cell responses against 7 pathogenic arenaviruses (including the lymphocytic choriomeningitis, Lassa, Guanarito, Junin, Machupo, Sabia, and Whitewater Arroyo viruses), either through the identification of widely conserved epitopes, or by the identification of a collection of epitopes derived from multiple arenavirus species. By inoculating HLA transgenic mice with a panel of recombinant vaccinia viruses (rVACVs) expressing the different arenavirus proteins, we identified 10 HLA-A02 and 10 HLA-A03-restricted epitopes that are naturally processed in human antigen-presenting cells. For some of these epitopes we were able to demonstrate cross-reactive CD8+ T cell responses, further increasing the coverage afforded by the epitope set against each different arenavirus species. Importantly, we showed that immunization of HLA transgenic mice with an epitope cocktail generated simultaneous CD8+ T cell responses against all 7 arenaviruses, and protected mice against challenge with rVACVs expressing either Old or New World arenavirus glycoproteins. In conclusion, the set of identified epitopes allows broad, non-ethnically biased coverage of all 7 viral species targeted by our studies

Habitat Associations and Relative Densities of Rodent Populations in Cultivated Areas of Central Argentina

Small mammals were livetrapped during 12 months in crop fields and weedy borders at 18 sites in central Argentina. A total of 1,652 mammals of 14 species was captured during3 3,060 trap-nights. Six species of rodents comprised \u3e 95% of captures. Periodically disturbed fields of crops were dominated by Calomys musculinus and C. laucha, and to a lesser extent Mus musculus. A second group composed of Akodon azarae, Bolomys obscures, and Oligoryzomys flavescens primarily inhabited the more stable, weedy borders of cultivated fields. Peaks in relative densities of C. musculinus, C. laucha, and M . musculus were observed in summer and early autumn ,and populations declined to low numbers in winter, following harvest. In contrast, maxima for A. azarae, B . obscures, and O. flavescens were in late autumn and early winter ,and numbers never declined to low values seen for the other species. These characteristic differences in habitat associations and relative densities of pampas rodents may reflect colonizing potential, as both Calomys and Mus potentially are highly opportunistic genera

Reproductive Characteristics of Rodent Assemblages in Cultivated Regions of Central Argentina

Small mammals were trapped for 2 years at 16 localities on the central-Argentine pampa. Six species (Akodon azarae, Calomys musculinus, C. laucha, Bolomys obscurus, Oligory-zomys flavescens and Mus musculus) accounted for \u3e95% of captures. The major breeding season, as assessed by pregnancies, was September or October through April or May. Mild weather in late autumn and winter of the second season resulted in a relatively longer breeding season during the 2nd year of the study. Females of all six species comprised significantly 50% of captures during the height of the breeding season. For most species, there was a negative correlation between embryo size and embryos per pregnancy; females with large embryos were poorly represented. C. musculinus had the longest breeding season; C. musculinus and Mus had the highest number of embryos per pregnancy; the two species of Calomys and Oligoryzomys had the highest percentages of pregnant females during the breeding season. The predominance of animals of smaller mass classes during the winter is thought to represent seasonal weight loss rather than juvenile recruitmen