Pharmacokinetics of clomipramine in dogs following single-dose intravenous and oral administration

OBJECTIVE: To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs after IV or oral administration of a single dose. ANIMALS: 6 male and 6 female Beagles. PROCEDURES: Clomipramine was administered IV (2 mg/kg), PO (4 mg/kg) after food was withheld for 15 hours, and PO (4 mg/kg) within 25 minutes after dogs were fed. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method. RESULTS: Time to peak plasma concentrations of clomipramine and desmethylclomipramine following oral administration was 1.2 hours. For clomipramine, after IV administration, elimination half-life was 5 hours, mean residence time was 3 hours, and plasma clearance was 1.4 L/h/kg. Values for mean residence time and terminal half-life following oral administration were similar to values obtained following IV administration, and systemic bioavailability was approximately 20% for clomipramine and 140% for desmethylclomipramine, indicating fast absorption of clomipramine from the gastrointestinal tract and extensive first-pass metabolism. Administration of clomipramine with food did not alter the area under the concentration versus time curve for desmethylclomipramine but resulted in a 25% increase for clomipramine. Clomipramine and desmethylclomipramine were extensively bound (> 96%) to serum proteins. There were no significant differences in area under the concentration versus time curve between male and female dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that there should not be any clinically important differences in efficacy regardless of whether clomipramine is administered with or without food.     

Pathogenicity of 21 newly described Phytophthora species against seven Western Australian native plant species

The pathogenicity of some Phytophthora species recently described from Western Australia, together with P. cinnamomi as a control, was tested against seven Western Australian native plant species in the glasshouse. Host species were Banksia grandis, B. littoralis, B. occidentalis, Casuarina obesa, Corymbia calophylla, Eucalyptus marginata and Lambertia inermis. Twenty‐two Phytophthora species were grown on a vermiculite, millet seed and V8 substrate and used as soil inoculum when the plant hosts were approximately 3 months old. Pathogenicity was assessed after 6 weeks and plants were scored for death, root damage, and percentage reduction of shoot growth compared with control plants. The pathogenicity of P. cinnamomi was confirmed. Phytophthora niederhauserii was shown to be similar to P. cinnamomi in pathogenicity and of concern ecologically. Other species that killed one or more hosts were P. boodjera, P. constricta, P. elongata, P. moyootj and P. rosacearum, while P. condilina, P. gibbosa, P. gregata, P. litoralis and P. ‘personii’ caused significant reduction to shoot and/or root growth, but did not kill plants. Host species susceptible to the highest number of Phytophthora species were B. grandis, B. littoralis, B. occidentalis and E. marginata. No Phytophthora species tested killed C. calophylla.     

Variation in Occurrence of Dematiaceous Hyphomycetes on Forage Bermudagrass over Years, Sampling Times, and Locations

ABSTRACT Leaf samples of forage bermudagrass with symptoms of infection by species of Bipolaris, Curvularia, and Exserohilum (dematiaceous hyphomycetes) were collected from three swine waste application sites in Mississippi at eight sampling times during each of 3 years. Samples were assayed for pathogens by observing sporulation on plated leaf tissue. Among 3,600 leaves assayed, eight species of the three genera were observed. Features and criteria for the practical identification of species on plated leaf samples are described. Sporulation by dematiaceous hyphomycetes was observed on 97% of leaves; a single pathogen was observed on 20% and two to five pathogens were observed on 77% of leaves. Distributions of leaves among classes with one to five pathogens per leaf, for sites within years, always differed significantly (P = 0.01) from a Poisson distribution and usually included fewer leaves than expected with four or five pathogens. Significant (P = 0.05) variation in frequencies of occurrence of pathogens among 72 samples of 50 leaves each was attributed to pathogen species, sampling times, and species-time interactions. Exserohilum rostratum, Curvularia lunata, and Bipolaris cynodontis were the most frequent pathogens across years and sites; B. spicifera and C. geniculata were intermediate; and B. hawaiiensis, B. sorokiniana, and B. stenospila were least frequent. For the five most common pathogens, significant differences in frequency among locations were commonplace. Six pathogens exhibited significant (P = 0.05) positive and negative correlations with others in overall frequencies of occurrence across years, sampling times, and sites. However, chi(2) tests of dual occurrence indicated that interactions between specific pairs of pathogens in or on leaves are not likely to be major causes for overall frequency correlations. Results indicate that dematiaceous hyphomycetes typically infect forage bermudagrass on swine waste application sites in complexes rather than as individual species; that E. rostratum, C. lunata, and B. cynodontis are the predominant pathogens; and that frequencies of pathogens often differ significantly between locations.     

Recovery from adverse effects of heat stress on slow-growing chicks in the tropics 1: Effect of ascorbic acid and different levels of betaine

Three hundreds, 21 d-old slow-growing chicks were randomly divided among 5 treatments, of 5 replicates each. Each replicate contained 12 unsexed chicks housed in (1 × 1) a floor pen. A group was kept under thermoneutral condition at 28 ± 4°C and RH was 55 ± 3% during 21–84 d of age (positive control) and fed corn-soybean meal diet. The other four groups were kept for three successive days per week under heat stress (HS) at 38 ± 1.4°C and 49 ± 2% RH from 12.00 to 16.00 pm. Chicks in HS treatments were fed corn-soybean meal diet without (negative control) or with 250 mg AA/kg diet and Bet at 0.5 and 1 g/kg diet. HS decreased productive performance, increased (P < 0.05) meat dry matter, plasma triglyceride and serum calcium whereas decreased (P > 0.05) plasma glucose, serum total protein and water holding capacity (WHC) of meat. AA and 1 g of Bet/kg diet was equally potent for partial relief (P < 0.05) of the negative effect of HS on growth, increased (P < 0.05) feed intake, protein digestibility (P < 0.05), dressing out percentage, liver and giblets, whilst improved (P < 0.05) feed conversion ratio (FCR). Also, a complete recovery from the negative effect (P < 0.05) of HS shown on plasma glucose and partial recovery (P < 0.05) observed in total protein, triglyceride, blood pH, packed cell volume (PCV), hemoglobin (Hgb), rectal temperature (RT) and respiration rate (RR) and improved humoral immune competence to sheep red blood cell (SBRCs) test.     

Comparison of larval thermal maxima between <Emphasis Type="Italic">Fundulus heteroclitus</Emphasis> and <Emphasis Type="Italic">F. grandis</Emphasis>

Fundulus heteroclitus and F. grandis are resident salt marsh fishes that overlap in distribution over a narrow range in northeastern Florida. The objective of the present study was to examine whether the limits of the species’ ranges could be explained by differences in thermal tolerance. Two populations of each species were collected and then spawned in the laboratory, and 9-day-old larvae were used for critical thermal maxima trials. Mean LOE temperatures of larvae ranged from 43.04 to 43.65°C and showed little difference between species. Therefore, differences in high temperatures experienced cannot account for the differences of the distributions of the two species. Condition-specific competition may play a greater role in determining the observed range of the two species.     

Detection of bovine viral diarrhea virus (BVDV) in seropositive cattle

Detection of bovine virus diarrhoea virus (BVDV) in one vaccinated beef cattle and three non-vaccinated dairy herds was investigated on peripheral blood leukocytes (PBL) with or without previous treatment followed by a capture ELISA (cELISA). Using the combination of PHA and polycation treatment, PBL from 229 seropositive cattle were studied and could be classified in four different states of BVDV infection. Lysed PBL from four animals were directly positive in cELISA (Category I), PBL of 17 animals were positive after PHA stimulation (Category II), 15 animals were positive only after PHA stimulation plus polycation treatment (Category III), while virus could not be detected in 193 seropositive cattle. Wild-type BVDV strains were isolated by co-culture on polycation-treated MDBK cells from 11 of these seropositive animals. BVDV antibodies of these same animals were able to neutralize their own virus, indicating that virus persists in PBL in spite of strain-specific antibodies. No apparent change of leukocyte subpopulations could be detected in any category of virus-positive animals. Thus, BVDV may be present in the PBL of some cattle, even in the presence of a specific active immune response.     

An evaluation of an oral formulation of moxidectin against selected anthelmintic-resistant and -susceptible strains of nematodes in lambs

The efficacy of an oral formulation of the newly developed parasiticide, moxidectin, was tested against benzimidazole-resistant Haemonchus contortus, Trichostrongylus colubriformis, and Nematodirus spathiger, levamisole-resistant Ostertagia circumcincta, and susceptible Cooperia curticei infections in weaned lambs. Thirty-two lambs were experimentally infected with mixed doses of the above strains of nematodes. They were allocated into four treatment groups by stratified randomisation using liveweights and faecal egg counts 28 days later. One group received moxidectin at 0.2 mg/kg liveweight, one group oxfendazole at 4.5 mg/kg liveweight, one group levamisole at 7.5 mg/kg liveweight and the last group remained untreated as the control. Worm burdens in the lambs at slaughter 10 days after oral treatment confirmed the resistance status of the nematode strains used, and showed that moxidectin had a greater than 99.9% efficacy (p<0.01) against all of them. No adverse effects due to treatment with moxidectin were observed in any of the animals.     

Anticipating the species jump: surveillance for emerging viral threats

Zoonotic disease surveillance is typically triggered after animal pathogens have already infected humans. Are there ways to identify high‐risk viruses before they emerge in humans? If so, then how and where can identifications be made and by what methods? These were the fundamental questions driving a workshop to examine the future of predictive surveillance for viruses that might jump from animals to infect humans. Virologists, ecologists and computational biologists from academia, federal government and non‐governmental organizations discussed opportunities as well as obstacles to the prediction of species jumps using genetic and ecological data from viruses and their hosts, vectors and reservoirs. This workshop marked an important first step towards envisioning both scientific and organizational frameworks for this future capability. Canine parvoviruses as well as seasonal H3N2 and pandemic H1N1 influenza viruses are discussed as exemplars that suggest what to look for in anticipating species jumps. To answer the question of where to look, prospects for discovering emerging viruses among wildlife, bats, rodents, arthropod vectors and occupationally exposed humans are discussed. Finally, opportunities and obstacles are identified and accompanied by suggestions for how to look for species jumps. Taken together, these findings constitute the beginnings of a conceptual framework for achieving a virus surveillance capability that could predict future species jumps.