Pharmacokinetics and microsomal oxidation of praziquantel and its effects on the P450 system in three-month-old lambs infested by Fasciola hepatica

Praziquantel (PZQ) is a broadly effective trematocide and cestocide, widely employed in veterinary and human medicine. In view of several differences in both its pharmacokinetic profile in different animal species and in the cytochrome P450-dependent system between ruminant and nonruminant species, the present study was undertaken to determine the pharmacokinetics of this drug, its effects on the P450 system and the involvement of cytochrome P450 in its metabolism in 3-month-old lambs infested by Fasciola hepatica. Following both oral and i.m. administration, PZQ disposition was best described by a linear one-compartment open model with a rapid absorption and elimination. Although the PZQ dose used by the i.m. route was only half of that used by the oral route, the mean PZQ plasma concentration was higher after i.m. than after oral treatment. Oral treatment with 30 mg/kg/day of PZQ did not modify the mono-oxygenase activities tested, whilst the administration of PZQ at a dose of 60 mg/kg/day for 2 days caused a significant decrease in the P450 3A-dependent erythromycin N-demethylase and 6beta testosterone hydroxylase activities. From the incubation of microsomes from lambs not treated with PZQ, a single metabolite (PZQ 11b-OH or PZQ 1-OH) was identified by GC/MS analysis. By selective inhibition of the 3A subfamily performed with triacetyloleandromycin, the production of this metabolite declined by about 90% suggesting a prominent role of P450 3A isoforms in this oxidation. These features indicate that agents or drugs which are able to modulate P450 3A-dependent catalysis may interfere with the metabolism, bioavailability and therapeutic effects of PZQ.     

A PCR technique for the detection of Jaagsiekte sheep retrovirus in the blood suitable for the screening of ovine pulmonary adenocarcinoma in field conditions

Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring contagious lung neoplasia caused by jaagsiekte sheep retrovirus (JSRV). Although no specific circulating antibodies against the virus can be detected in infected sheep, JSRV proviral DNA sequences can be found in peripheral blood leukocytes (PBLs) in clinically affected and in a proportion of in contact animals. In this study, existing hemi-nested PCR procedure is compared with a new one-step PCR technique that was developed to minimise potential DNA contamination and reduce sample and reagent handling. Different blood preparations were assessed and the best results were achieved on DNA prepared from buffy coat. The sensitivity of this PCR was lower in JSRV infected sheep without lesions of OPA than in clinically affected sheep, which indicate that this PCR may not be not fully appropriate for screening of individual sheep, but rather to provide results at flock level. This PCR is the only currently available blood test for detection of JSRV infected sheep and may be useful in epidemiological studies and in control programmes of OPA.     

The effects of starving and feeding on Dover sole (Solea solea,Soleidae, Linnaeus, 1758) stress response and early larval development

In the view of an urgent necessity to improve the quantity and the quality of farmed fish species, there is a strong need to improve our basic knowledge on the effects of first feeding during the developmental stages of fish larvae. High mortality, mainly due to food deprivation or inappropriate food quality, has been observed in many larval fish species, but knowledge about the morphological, biochemical and molecular processes related to this topic is still poorly understood. The understanding of the early larval ontogeny as well as the larval nutritional requirements and the molecular and cellular mechanisms elicited by fish larvae during food deprivation and starvation are thus of primary importance. At this regard, this study investigates, in Dover sole larvae, the effects of starvation and starving/re‐feeding procedures at a morphological, histological, biochemical and molecular level. The results evidenced that starved larvae progressively decrease in growth, lipid content, affected their gastrointestinal tract and muscle development and increased cortisol and heat shock protein 70 levels. On the contrary, starved and re‐fed larvae showed, after the restoration of a favourable feeding condition, a compensatory growth. In conclusion, this is the first study analysing through a multidisciplinary approach the effects of food deprivation on the development of an important economic species, the Dover sole.     

Day versus night use of forest by red and roe deer as determined by Corine Land Cover and Copernicus Tree Cover Density: assessing use of geographic layers in movement ecology

Landscape Ecology - Diel use of forest and open habitats by large herbivores is linked to species-specific needs of multiple and heterogeneous resources. However, forest cover layers might deviate...     

Influence of dietary vitamin E supplementation on "heavy" pig carcass characteristics, meat quality, and vitamin E status.

Crossbred "heavy" pigs (average weight 120 kg, slaughter weight above 160 kg) were supplemented with all-rac-alpha-tocopheryl acetate during the last 60 d of late finishing at doses of 25 (control), 50, 100, 200, or 300 mg/kg of diet. At the end of this period, the pigs were slaughtered. Carcass characteristics and the meat quality of pork chops from longissimus muscle (LM) at the last lumbar vertebra were evaluated on eight barrows from each dosage group. Alpha-tocopherol levels were determined in plasma during supplementation and in LM muscle after slaughter. Thiobarbituric acid reactive substances (TBARS) and drip loss were also evaluated in meat. Plasma alpha-tocopherol levels increased (P < .005) during supplementation in treated animals compared to controls, with a peak at 40 d. Alpha-tocopherol levels were higher (P < .05) in LM from pigs treated with 300 mg/kg than in controls (8.4 vs 5.6 microg/g). Dressing percentages correlated (P < .05) with the ratio of plasma alpha-tocopherol levels to the sum of cholesterol and triglycerides. Inhibition of TBARS during storage was related (P < .005) to vitamin E supplementation level, but drip losses in chops were not related to supplementation levels. We concluded that dietary vitamin E supplementation to heavy pigs during the last 60 d of finishing improves dressing percentage, reduces lipid oxidation, and increases the alpha-tocopherol concentration of tissues.     

Immunization against bovine herpesvirus-1 infection. Preliminary tests in calves with a DNA vaccine

A bovine herpesvirus-1 (BHV-1) vaccine expressing glycoprotein D, the form with the transmembrane anchor removed, was evaluated for inducing immunity in calves. The plasmid encoding gD of BHV-1 was injected three times to nine calves, using three animals for each of the following routes: intramuscularly (i.m.), intradermally (i.d.), or intranasally (i.n.). Three additional calves were given the plasmid vector only and served as unvaccinated controls. When calves were subjected to challenge infection with BHV-1, all vaccinated calves as well as the controls developed a typical severe form of infectious bovine rhinotracheitis. However, compared to the controls, the vaccinated calves showed earlier clearance of challenge virus. Moreover, the calves given the vaccine i.m. developed neutralizing antibody to BHV-1 between 21 and 42 days following the first injection of vaccine, whereas in calves vaccinated either i.d. or i.n., as well as the controls, antibody first appeared in their sera 14 days post-challenge infection.     

A serological survey of bovine herpesvirus-1 infection in selected dairy herds in northern and central Italy

Serum samples from a total of 6979 dairy cattle from 55 herds in northern Italy (51 herds) and central Italy (4 herds), were examined by the serum neutralization test for the presence of antibody to bovine herpesvirus-1 (BHV-1). It was found that 84.31% of the farms selected in northern Italy and all the farms from central Italy had seropositive animals at titers of 1:4 or higher. The prevalence of infection was essentially the same among the cattle populations of the two selected areas of the country, being of 34.99% in the north and of 38.65% in central regions. A comparison of the data from the present study with those obtained in a serological survey conducted in Italy in 1966, shows that the rate of seropositive cattle to BHV-1 has increased by about 5.0% in the last 30 years.     

A combined bovine herpesvirus 1 gB-gD DNA vaccine induces immune response in mice

Although DNA vaccines have several advantages over conventional vaccines, antibody production and protection are often not adequate, particularly in single plasmid vaccine formulations. Here we assessed the potential for a combined vaccine based on plasmids encoding the membrane-anchored or secreted forms of bovine herpesvirus type 1 (BHV-1) glycoprotein B and D (gB and gD) to induce neutralizing and cell mediated immune responses in mice. Animals were injected by intramuscular, subcutaneous and intranasal routes. Mice immunized with the combined vaccine containing the secreted forms of BHV-1 glycoproteins developed higher titers of anti-BHV-1 neutralizing antibodies, compared to wild type gB/gD combined plasmids and to single plasmid injected groups. Cellular immunity was also developed in mice immunized with combined vaccines, whereas low or no response were observed in single plasmid injected animals. The data suggest the potential use of this combined vaccine in in vivo trials of calves, in order to evaluate its protective efficacy.     

Maedi-visna virus, a model for in vitro testing of potential anti-HIV drugs

A series of beta-D- and beta-L-cytidine analogues were evaluated for their inhibitory effect on the replication of maedi-visna virus (MVV) strains KV1772 and MV1514 cultured on sheep choroid plexus cells and the sheep chondrocyte cell line G81092, respectively. Eleven cytidine analogues were selected for the anti-viral test. Five of them belong to the family of the 2',3'-dideoxycytidine analogues, well known for their activity against human immunodeficiency virus (HIV). The others, all newly synthesized, were potential anti-viral and/or anti-leukemic agents. None of the compounds under study had a toxic effect in both anti-viral assay systems up to a 300 microM concentration. Based on the cytopathic effects (CPE), the virus replication was completely inhibited by the five 2',3'-dideoxycytidine analogues at a concentration of 50 microM, whereas the others six newly synthesized compounds induced titre reductions of 4-5 log units. The effective concentration causing 50% reduction of CPE (EC50) was of 5 microM for the five 2',3'-dideooxycytidine analogues and for beta-L-XyloFc, whereas the value of 50 microM was found for the b-L-XyloC and the four 5-azacytidine compounds tested. All these data reveal a good correlation between inhibition of MVV replication by several nucleoside cytidine analogues and their reported anti-HIV activity.