Pharmacokinetics of an injectable long‐acting parenteral formulation of doxycycline hyclate in pigs

Based on its ideal PK/PD ratios, doxycycline hyclate (DOX‐h), a time‐dependant antibacterial, is ideally expected to achieve sustained plasma drug concentrations at or slightly above the MIC level for as long as possible between dosing intervals. Pursuing this end, a poloxamer‐based matrix was used to produce a 10% long‐acting injectable preparation (DOX‐h‐LA) and its serum concentrations vs. time profile investigated after its injection to pigs in the pericaudal s.c. by parallel design. Results were compared with the forced oral bolus dose and i.v. pharmacokinetics of DOX‐h. For this study, 12 recently weaned pigs per group were included in this trial, and a dose of 20 mg/kg was injected in all cases. DOX‐h‐LA showed the greatest values for bioavailability (115.38%); maximum serum concentration (Cmax) value was 1.5 ± 0.2 with a time to reach Cmax of 3.41 ± 0.04 h and an elimination rate constant of 70.93 ± 0.87 h. Considering minimum effective serum concentration of 0.5 μg/mL, a dose interval of at least 5 days can be achieved for DOX‐h‐LA, whereas p.o. and i.v. dosing of DOX‐h may only last 11 and 15 h, respectively. Pigs were slaughtered on day 30 after this trial, and no visible remnants of the preparation were detected neither fibrosis was observed after a thorough macroscopic and histopathological analysis.     

A study of inherited short tail and taillessness in Pembroke Welsh corgi

OBJECTIVES: To study whether natural short tail in adult Pembroke Welsh corgi is associated with congenital spinal defects. To report anatomical defects in two newborn tailless puppies from short-tailed parents, and to check whether they were homozygous for the dominant mutation in the T-gene (C295G). METHODS: The vertebral column of 19 adult dogs with natural short tail, from short-tail x long-tail crossings, was radiographically examined. Two tailless puppies were radiographed and submitted for necropsy. Samples from the puppies, their parents and five siblings were analysed for the mutation of the T-gene. RESULTS: No congenital spinal defects were diagnosed in any of the short-tailed dogs. The tailless puppies had anorectal atresia, had multiple spinal defects and were homozygous for the mutation in the T-gene. CLINICAL SIGNIFICANCE: As tail docking is forbidden in many countries, breeding Pembroke Welsh corgis with natural short tail is becoming increasingly common. Previous studies indicated that the mutation in homozygotes is lethal in early fetal life. It is of clinical significance that natural short tail is probably not associated with congenital spinal defects, as is known from studies of other species, and that homozygotes for this mutation with serious anatomical defects may be born.     

Lomustine for treatment of mast cell tumors in cats: 38 cases (1999-2005)

OBJECTIVE: To determine clinical activity and toxic effects of lomustine when used to treat cats with mast cell tumors (MCTs). DESIGN: Retrospective case series. ANIMALS: 38 cats with measurable, histologically or cytologically confirmed MCTs treated with lomustine at a dosage > or = 50 mg/m(2). PROCEDURES: Medical records were reviewed to determine response to treatment and evidence of drug toxicoses. The Kaplan-Meier method was used to estimate remission duration. RESULTS: 26 cats had cutaneous MCTs, 7 had MCTs of the mesenteric lymph nodes, 2 had gastrointestinal tract MCTs, 2 had hepatic MCTs, and 1 had MCTs involving multiple organs. Targeted lomustine dosage was 50 mg/m(2) in 22 cats and 60 mg/m(2) in 16 cats. Median administered dosage of lomustine was 56 mg/m(2) (range, 48 to 65 mg/m(2)), and median number of doses administered was 2 (range, 1 to 12). Seven cats had a complete response and 12 had a partial response, for an overall response rate of 50%. Median response duration was 168 days (range, 25 to 727 days). The most common toxicoses were neutropenia and thrombocytopenia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that lomustine had activity against MCTs in cats and was well tolerated. Further, findings suggested that treatment with lomustine should be considered for cats with MCTs for which local treatment is not an option.     

The effect of dietary supplementation with 9-cis:12-trans and 10-trans:12-cis conjugated linoleic acid (CLA) for nine months on serum cholesterol, lymphocyte proliferation and polymorphonuclear cells function in Beagle dogs

Conjugated linoleic acids (CLA), 9-cis:11-trans and 10-trans:12-cis, have been shown to be able to modify some immune cells parameters and plasma lipids in a variety of experiment models. Since lymphocytes and polymorphonuclear cells (PMNC) have a large spectrum functions in the immune response, the knowledge in this field has to be expanded. Beagle dogs were fed a control diet or a CLA supplemented diet for nine months. Blood was collected for biochemical analysis and lymphocyte and PMNC isolation. PMNC were assayed for lysosome content, phagocytic activity and superoxide anion production. A lymphocyte proliferation capacity assay was done. The CLA fed dogs had a 34% reduction in total cholesterol (P < 0.05), 28% in LDL (P < 0.05) and 28% non-HDL-cholesterol (P < 0.05). Neither of the PMNC parameters evaluated demonstrated significant alteration. Lymphocytes from CLA group increased by 45% their mitotic capacity (P < 0.05). Our study demonstrates that CLA can successfully modify the lipid profile of dogs (monogastrics) when fed at reasonable levels, but did not significantly alter inflammatory function as would generally predicted. Further, we had some indication that CLA modulated T cell responsiveness.     

Estimating exposed pulp lengths of tusks in the African elephant (Loxodonta africana africana)

Captive and wild African elephants frequently suffer tusk fractures. Several institutions shorten the tusks of captive elephants to reduce fractures and injury as a result of behaviour within enclosures. Fracturing or coronal amputations that expose pulp lead to pain for the elephant. Estimating coronal pulp lengths may thus help to minimise the risk of pulp exposure during amputations. We aimed to determine the length of the pulp beyond the lip margin from an external tusk characteristic. Tusks collected from elephants in Namibia and the Kruger National Park had similar morphological relationships. This statistical property allowed us to correct for missing data in our data sets. Pulp volume and pulp length correlated with tusk circumference at the lip. Even so, the circumference at the lip could not predict the length of the pulp in the crown external to the lip. Our findings suggest that tusks, irrespective of sex or age, amputated further than 300 mm from the lip should not expose pulp.     

Response to dietary phosphorus deficiency is affected by genetic background in growing pigs

Concern over the environmental effect of P excretion from pig production has led to reduced dietary P supplementation. To examine how genetics influence P utilization, 94 gilts sired by 2 genetic lines (PIC337 and PIC280) were housed individually and fed either a P-adequate diet (PA) or a 20% P-deficient diet (PD) for 14 wk. Initially and monthly, blood samples were collected and BW recorded after an overnight fast. Growth performance and plasma indicators of P status were determined monthly. At the end of the trial, carcass traits, meat quality, bone strength, and ash percentage were determined. Pigs fed the PD diet had decreased (P < 0.05) plasma P concentrations and poorer G:F (P < 0.05) over the length of the trial. After 4 wk on trial, pigs fed the PD diet had increased (P < 0.05) plasma 1,25(OH)(2)D(3) and decreased (P < 0.05) plasma parathyroid hormone compared with those fed the PA diet. At the end of the trial, pigs fed the PD diet had decreased (P < 0.05) BW, HCW, and percentage fat-free lean and tended to have decreased LM area (P = 0.06) and marbling (P = 0.09) and greater (P = 0.12) 10th-rib backfat than pigs fed the PA diet. Additionally, animals fed the PD diet had weaker bones and also decreased (P < 0.05) ash percentage and increased (P < 0.05) concentrations of 1alpha-hydroxylase and parathyroid hormone receptor mRNA in kidney tissue. Regardless of dietary treatment, PIC337-sired pigs consumed more feed and gained more BW than their PIC280-sired counterparts (P < 0.05) during the study. The PIC337-sired pigs also had greater (P < 0.05) HCW, larger (P < 0.01) LM area, and tended to have (P = 0.07) greater dressing percentage. Meat from the PIC337-sired pigs also tended to have greater (P = 0.12) concentrations of lactate but decreased (P = 0.07) concentrations of total glucose units 24 h postslaughter. Although plasma 1,25(OH)(2)D(3) concentrations were elevated (P < 0.05) in all the animals fed the PD diet, this elevation due to P deficiency tended (P = 0.09) to be greater in the PIC337-sired pigs after 12 wk on the treatment. The PIC337-sired pigs had stronger (P < 0.01) bones with greater ash percentage than the PIC280-sired pigs. The difference in the strength of the radii between the PIC337-sired pigs fed the PA and PD diets was greater than their PIC280-sired counterparts, which resulted in sire line x treatment interactions (P < 0.05). These data indicate differing mechanisms of P utilization between these genetic lines. Elucidating these mechanisms may lead to strategies to increase efficiency of growth in a more environmentally friendly manner.     

Pharmacokinetics and bioavailability of cefquinome in healthy piglets

A study on bioavailability and pharmacokinetics of cefquinome in piglets was conducted after intravenous (i.v.) and intramuscular (i.m.) administrations of 2.0 mg/kg of body weight, respectively. Plasma concentrations were measured by high‐performance liquid chromatography assay with UV detector at 268‐nm wavelength. Plasma concentration–time data after i.v. administration were best fit by a two‐compartment model. The pharmacokinetic values were distribution half‐life 0.27 ± 0.21 h, elimination half‐life 1.85 ± 1.11 h, total body clearance 0.26 ± 0.08 L/kg·h, area under curve 8.07 ± 1.91 μg·h/mL and volume of distribution at steady state 0.46 ± 0.10 L/kg. Plasma concentration–time data after i.m. administration were also best fit by a two‐compartment model. The pharmacokinetic parameters were distribution half‐life 0.88 ± 0.42 h, elimination half‐life 4.36 ± 2.35 h, peak concentration 4.01 ± 0.57 μg/mL and bioavailability 95.13 ± 9.93%.     

Dose titration of sericea lespedeza leaf meal on Haemonchus contortus infection in lambs and kids

The objective of three experiments was to determine the impact of supplementing sericea lespedeza (Lespedeza cuneata; SL) in three concentrations in a loose or pelleted diet on gastrointestinal nematodes (GIN) in small ruminants. Experiments on lambs were conducted at the USDA, Agricultural Research Service in Booneville, AR (Exp. 1) and at Louisiana State University in Baton Rouge, LA (Exp. 2); an experiment on goat kids occurred at University of Maryland-Eastern Shore (Exp. 3). Exp. 1 used crossbred hair sheep lambs naturally infected with GIN that were randomly allocated to diets containing 0, 25, 50, and 75% SL diets (n=11 or 12/diet). Exp. 2 consisted of Haemonchus contortus-inoculated crossbred wool breed lambs that were blocked by gender and FEC and randomly assigned to 0, 25, 50, or 75% SL diet (n=8/diet). Fecal egg counts (FEC) and blood packed cell volume (PCV) were not influenced by SL supplementation in Exp. 1 and 2. Exp. 3 consisted of naturally GIN infected Boer crossbred goat kids in individual pens. Kids were blocked by FEC and randomly allotted to treatments of 0, 20, 40, or 60% SL with 9-13 goats/diet. The more SL fed, the greater the reduction in FEC (P<0.001). There was an increase in PCV in SL fed goats (P<0.001). Larval speciation at the end of the experiment indicated that feces from control animals produced 43% H. contortus larva while 20, 40 and 60% SL resulted in 39%, 35% and 31% H. contortus larvae, respectively. Feeding dried SL may be less effective in lambs than kids, though concurrent studies must be conducted to confirm this.