Pharmacokinetic and pharmacodynamic modelling of intravenous,intramuscular and subcutaneous buprenorphine in conscious cats

ObjectiveTo describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats.Study designRandomized, prospective, blinded, three period crossover experiment.AnimalsSix healthy adult cats weighing 4.1 ± 0.5 kg.MethodsBuprenorphine (0.02 mg kg^?1) was administered IV, IM or SC. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p < 0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the IV data was described using a model combining biophase equilibration and receptor association-dissociation kinetics.ResultsTT increased above baseline from 15 to 480 minutes and at 30 and 60 minutes after IV and IM administration, respectively (p < 0.05). Maximum increase in TT (mean ± SD) was 9.3 ± 4.9 °C at 60 minutes (IV), 4.6 ± 2.8 °C at 45 minutes (IM) and 1.9 ± 1.9 °C at 60 minutes (SC). TT was significantly higher at 15, 60, 120 and 180 minutes, and at 15, 30, 45, 60 and 120 minutes after IV administration compared to IM and SC, respectively. IV and IM buprenorphine concentration-time data decreased curvilinearly. SC PK could not be modeled due to erratic absorption and disposition. IV buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t_1/2k_e0 = 47.4 minutes) and receptor binding (k_on = 0.011 mL ng^?1 minute^?1). Persistence of thermal antinociception was due to slow receptor dissociation (t_1/2k_off = 18.2 minutes).Conclusions and clinical relevanceIV and IM data followed classical disposition and elimination in most cats. Plasma concentrations after IV administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the IV route should be preferred over the IM and SC routes when buprenorphine is administered to cats.     

The Effects of Growth Factor on Testicular Germ Cell Apoptosis in the Stallion

Apoptosis is necessary for both initiation and control of spermatogenesis; however, an increase in apoptosis can lead to subfertility/infertility in stallions, causing substantial financial loss in the equine industry. The ability of stem cell factor (SCF), leukemia-inhibiting factor (LIF), granulocyte–macrophage colony-stimulating factor (GM-CSF), and estradiol (E₂), alone or in combination, to prevent apoptosis of germ cells in short-term equine testicular cultures was examined. Testicular tissue was sectioned into approximately 2-mm cubes and placed in media-filled culture chambers. Concentrations of SCF (100 ng/mL), LIF (10 ng/mL), GM-CSF (5 ng/mL), and E₂ (10⁻⁹ mol/l) were added alone or in combination to each well. After 6 hours in culture, the tissue was fixed and immunohistochemically (terminal deoxynucleotidyl transferase-mediated nick-end labeling; TUNEL) stained for apoptosis detection. Apoptotic cells per 100 Sertoli cell nuclei within seminiferous tubules were counted until the 500^th Sertoli cell nuclei was reached. This counting procedure was used for each slide. An analysis of variance (ANOVA) with a Tukey's test was used to compare apoptotic rates. In comparison with the control, GM-CSF alone lowered apoptosis by 34.77%. GM-CSF–treated tissue combined with SCF and LIF as well as GM-CSF combined with SCF, LIF, and E₂ reduced apoptosis when compared with the control (37.45% and 44.40%, respectively) or other treatment combinations. GM-CSF alone reduced apoptosis; results suggest possible synergy for the combinations of SCF and LIF with GM-CSF and for E₂ with SCF, LIF, and GM-CSF.     

Efficacy of a collar impregnated with amitraz and pyriproxyfen for prevention of experimental tick infestations by Rhipicephalus sanguineus, Ixodes ricinus, and Ixodes scapularis in dogs

OBJECTIVE: To compare the efficacy of collars impregnated with 9% amitraz or 9% amitraz and 0.5% pyriproxyfen (PPF) for control of newly established tick infestations by Rhipicephalus sanguineus, Ixodes ricinus, and Ixodes scapularis in dogs and determine whether egg production by surviving female ticks was decreased. DESIGN: Prospective study. ANIMALS: 72 dogs. PROCEDURE: Dogs were fitted with 1 of 3 test collars impregnated with amitraz, amitraz and PPF, or only excipients (untreated controls). In 3 trials corresponding to each of the 3 tick species, dogs were infested with 150 unfed adult ticks on days 8, 10, 13, and 18. The number of feeding female ticks was recorded on days 10, 13, 18, and 28. Surviving females were weighed and permitted to oviposit under controlled conditions. RESULTS: Collars impregnated with amitraz and PPF decreased tick loads as efficiently as collars containing amitraz alone. Inclusion of PPF into the collar did not significantly decrease the efficacy of amitraz. The few female ticks that survived after feeding on dogs treated with collars containing PPF were unable to oviposit. CONCLUSIONS AND CLINICAL RELEVANCE: Collars impregnated with amitraz were efficient in preventing tick infestations in dogs but did not inhibit oviposition in the few surviving female ticks. Incorporation of PPF into the amitraz-impregnated collar resulted in impairment of the reproductive ability of ticks.     

Dairy science and health in the tropics: challenges and opportunities for the next decades

In the next two decades, the world population will increase significantly; the majority in the developing countries located in the tropics of Africa, Asia, Latin America, and the Caribbean. To feed such a population, it is necessary to increase the availability of food, particularly high-value animal protein foods produced locally, namely meat and dairy products. Dairy production in tropical regions has a lot of growth potential, but also poses a series of problems, particularly as dairy production systems were developed in temperate countries and in most cases are difficult to implement in the tropics. Drawbacks include hot weather and heat stress, the lack of availability of adequate feeds, poor infrastructure, and cold chain and the competition with cheap imports from temperate countries. This position paper reviews the major drawbacks in dairy production for the five major dairy species: cattle, water buffalo, sheep, goat, and camel, as well as the future trends in research and development. It also concerns the major trends in reproduction and production systems and health issues as well as environmental concerns, particularly those related to greenhouse gas emissions. Tropical Animal Health and Production now launches a topical collection on Tropical Dairy Science. We aim to publish interesting and significant papers in tropical dairy science. On behalf of the editorial board of the Tropical Animal Health and Production, we would like to invite all authors working in this field to submit their works on this topic to this topical collection in our journal.

     

Efficacy of alpha-cyclodextrin against experimental cryptosporidiosis in neonatal goats

The efficacy of orally administered tablets containing alpha-cyclodextrin, an excipient used in the pharmaceutical industry with demonstrated anticryptosporidial activity in vitro and in neonatal mice, was evaluated in neonatal goat kids. The formulation was evaluated for hardness and was subjected to in vitro drug release studies. Twenty goat kids were orally inoculated with 10(6) oocysts of C. parvum within the first 6 days of age. Half of the animals were treated by oral administration of four tablets of alpha-cyclodextrin/day (500 mg/kg of body weight) for six consecutive days, the treatment beginning on the day of inoculation. Infection was monitored by daily examination of faecal samples from the first day to 25 days post-inoculation. The criteria studied in evaluating efficacy were: oocyst shedding, presence of diarrhoea and weight gain at 15 and 25 days post-inoculation. alpha-cyclodextrin was effective when given at the beginning of infection: there was a longer pre-patent period, a reduction in the patent period and a decrease in the intensity of infection, these differences being statistically significant (P < 0.05) compared with untreated neonatal kids. Moreover, except in one animal, the diarrhoea was prevented in infected neonatal kids. Animals from both groups increased the body weight and no significant differences were seen between the two groups.     

Detection of Cryptosporidium oocysts in goat kid faeces: comparison of a latex agglutination test with three other conventional techniques

Detection of Cryptosporidium oocysts from goat kid faeces: comparison of a latex agglutination test with three other conventional techniques. A quantitative latex agglutination test (QLAT) with monoclonal antibodies for the detection of Cryptosporidium oocysts in faeces was compared with 3 other conventional techniques: Heine staining on faecal smears (HS) giving semi-quantitative results (scores from 1 to 5), sucrose flotation on diluted faeces (SF) with results expressed in oocysts/g of faeces (opg), direct ELISA (DE) giving qualitative results. Goat kid unconcentrated faecal samples (234) from 8 farms were processed according to the 4 techniques. Data were analyzed with Win Episcope 1.0 and Testview 1.1 softwares. The oocyst outputs ranged from 100 000 (detection limit for SF) to 200 millions opg (mean: 15.2 millions opg). A very good agreement was recorded between QLAT and HS, SF, DE: Kappa values ranged between 0.82 and 0.90. When considering the samples exhibiting oocysts (or not) as positive (or negative) using both HS and SF (n = 219), the sensitivity and specificity of QLAT were respectively 95.1 and 96.0%. The lack of sensitivity was observed in faeces harboring a few oocysts (< or = 200 000 opg, scores < or = 2) whereas the lack of specificity was only observed in 3 samples originating from the same farm. A significant correlation was calculated between the percentage of agglutination in QLAT and the number of oocysts in SF or scores in HS (Spearman correlation ranging from 0.45 to 0.48, p < 0.001). QLAT is a rapid, simple and reliable tool for routine detection of Cryptosporidium oocysts in faeces.     

Prevalence of gastrointestinal helminths,lungworms and liver fluke in sheep and goats in Norway

The present study describes the occurrence of various gastrointestinal helminths, lungworms and liver flukes in Norwegian sheep and goats as assessed from faecal samples and post mortem examinations performed between 2007 and 2010. Faecal samples for gastrointestinal nematode egg counts were collected from 77 sheep flocks and 30 dairy goat flocks from three geographical regions in Norway. Additionally, thirty-two lambs and 16 adult goats were euthanized for necropsy examination and for identification of adult gastrointestinal nematodes and tapeworms, lungworms and liver flukes. The survey showed that there was a higher mean excretion of trichostrongyle eggs in sheep than in goats at the individual level (392 EPG vs. 154 EPG, p < 0.001). For both host species, the mean prevalence and intensity of excreted trichostrongyle eggs were significantly higher in the southern coastal region compared with the inland and northern regions (p < 0.001). Third stage larvae of Trichostrongylus/Teladorsagia, Haemonchus and Nematodirus type were the most prevalent ones in the coprocultures from sheep, whereas larvae of Trichostrongylus/Teladorsagia and Nematodirus type dominated in goats. The most prevalent gastrointestinal nematode species found at necropsy was Teladorsagia circumcincta (75.0 and 81.2% respectively in sheep and goats), while the largest mean worm burdens were recorded for Haemonchus contortus in sheep (724 ± 623) and T. circumcincta in goats (377 ± 529). Other gastrointestinal nematode species were present at low prevalence or in low numbers.     

Specific proteins allow classification of pigs according to sire breed, rearing environment and gender

The present study used a proteomic data set obtained from a 2 × 2 × 2 factorial experiment on longissimus muscle of 24 pigs to identify single or couples of proteins allowing correct classification of pigs according to gender, sire breed, or rearing environment. An actin isoform, a myosin light chain 2 isoform and cytochrome Bc1 allowed each, correct classification of all pigs according to gender. Peroxiredoxin 6 allowed correct classification of 23 pigs according to indoor or outdoor rearing environment, but only if gender was also taken into account. Heat shock protein 73 allowed correct classification of 21 pigs according to sire breed, Duroc or Large White. Results show that proteins may be used as biomarkers for traceability or genetic research. Relationships between treatment factors and intracellular regulatory mechanisms associated with these proteins are discussed.     

Three-dimensional kinematics of the equine interphalangeal joints: articular impact of asymmetric bearing

The objective of this study was to assess the effects of asymmetric placement of the foot on the three-dimensional motions of the interphalangeal joints. Four isolated forelimbs were used. Trihedrons, made of three axes fitted with reflective markers, were screwed into each phalanx. They allowed to establish a local frame associated with each bone and thus to define the spatial orientation of the phalanges. The limbs were then placed under a power press, and subjected to compression with gradually increasing force (from 500 to 6 000 N). The procedure was performed in neutral position and with the lateral or medial part of the foot raised by a 12 degrees wedge. Flexion, collateromotion (passive abduction/adduction) and axial rotation of the interphalangeal joints were measured using a cardan angle decomposition according to the principle of the "Joint Coordinate System" described by Grood and Suntay. Raising the lateral or medial part of the hoof induced collateromotion (about 5.6 degrees +/- 0.8) and axial rotation (about 6.5 degrees +/- 0.5) of the distal interphalangeal joint. The proximal interphalangeal joint underwent axial rotation (about 4.7 degrees +/- 0.5 at 6 000 N) and slight collateromotion. Both interphalangeal joints underwent collateromotion in the direction of the raised part of the foot (i.e., narrowing of the articular space on the side of the wedge), whereas axial rotation occurred in the direction opposite to the raised part of the foot. These results confirm the functional importance of interphalangeal joint movements outside the sagittal plane. In particular they demonstrate the involvement of the proximal interphalangeal joint in the digital balance. These data are helpful for the identification of biomechanical factors that may predispose to interphalangeal joint injury. Also the data may be of use for the rational decision making with respect to exercise management and corrective shoeing of the lame horse.