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 persistence of foot-and-mouth disease virus on wool

SUMMARY Five Suffolk sheep, held in a high-security isolation room, were exposed for 2 hours to the aerosol of 3 mature pigs that had been infected with foot-and-mouth disease virus (FMDV), strain O₁-BFS. The fleeces of 3 of the sheep were contaminated with FMDV at 2 days post exposure (dpe), while at 5 dpe the fleeces of all 5 sheep were more extensively, and more heavily, contaminated. The persistence of FMDV on contaminated wool was examined in vitro using multiple 0.5 g samples of Merino wool that were each contaminated with one of 3 strains of FMDV in tissue-culture medium: O₁-BFS, O-Morocco (O-MOR 9/91) or an Asia 1 strain (TAI 1/90). Wool samples were held at either 4°C, 18°C or 37°C, and decay curves were established for each virus at each temperature. These curves predicted that O₁-BFS, O-MOR 9/91 and TAI 1/90 would fall below detect-able levels at 72, 70 and 48 days post contamination (pc), respectively, for wool stored at 4°C; at 11, 12 and 12 days pc, respectively, for wool stored at 18°C; and at 57, 68 and 33 hours pc, respectively, for wool stored at 37°C. For wool contaminated with O₁-BFS-infected sheep faeces, urine or blood, or with O₁-BFS-infected cattle saliva, decay curves predicted virus to persist for 5 to 11 days pc at 18°C. We demonstrated that the simulated scouring of FMDV-contaminated wool at 60° to 70°C would usually reduce virus to below detectable levels. The detergent component of the scouring process had little, if any, antiviral activity, and scouring at 20°C or 50°C had limited impact on FMDV titres . We recommend that either (1) simple storage of FMDV-contaminated wool for 4 weeks at temperatures of 18°C or higher, or (2) scouring of contaminated wool at 60° to 70°C would be sufficient to remove the threat of FMDV-contaminated wool being infectious to other animals .     

Characteristics of in-shell Brazil nuts and their relationship to aflatoxin contamination: criteria for sorting

External characteristics of in-shell Brazil nuts were evaluated for dimensions (length and face width), weight, chromaticity, and shell thickness. The internal characteristics evaluated were moisture content (mc), aflatoxin contamination (analyzed by LC-MS/MS), and shell/nut ratio. According to their length, Brazil nuts were classified in three groups: I, II, and III, corresponding to large, medium, and small sizes, respectively. It was possible to establish the following parameters as standards for normal/healthy nuts: length (53.2, 43.9, and 36.6 mm), weight (12.9, 8.8, and 6.3 g), and shell chromaticity components (L*, 38.3, 39.5, and 41.6; a*, 8.0, 7.9, and 7.8; and b*, 17.6, 18.0, and 18.7), for the three groups, respectively. The mean of shell thicknesses were 1.92 and 2.68 mm taken from each face and nut top. The nuts, classified as small (Group III), presented aflatoxin B1 contamination at a level of 5.62 microg/kg. The Groups shell/nut ratios were 1.2, 1.2, and 1.3 for normal whole and healthy nuts. No aflatoxin was detected in Groups I and II. The data obtained from the Brazil nut measured characteristics can help to distinguish healthy/safe and deteriorated nuts and will be useful for Brazil nut sorting and machine development.     

Selenium and aflatoxin levels in raw Brazil nuts from the Amazon basin

Whereas selenium (Se) is an important antioxidant in human metabolism to prevent cancer, aflatoxins are highly carcinogenic. Brazil nuts from Eastern and Western Amazon regions were evaluated to find any relationship between Se and aflatoxins levels. A total of 80 (in-shell and shelled) nuts samples were collected directly from different forest sites and analyzed for Se by atomic emission spectrometry and aflatoxins by liquid chromatography tandem mass spectrometry. The limit of quantitation (LOQ) for Se was 2.0 mg/kg, and LOQ for total aflatoxins was 0.390 microg/kg. Nut Se levels from the Eastern region were higher than the Western, in addition to the aflatoxins. The moisture content (mc) and water activity (aw) of the raw nuts from the two regions did not present a significant difference, for either in-shell or shelled. The mc was 24.5% (minimum of 20.1% and maximum of 30.4%) and 22.1% (minimum of 14.6% and maximum of 28.9%) and a w of 0.85 for both regions. Further studies need to be carried out to discover the role of Se on fungi growth stress and aflatoxin production mechanisms.     

Assessment of postoperative pain after unilateral mastectomy using two different surgical techniques in dogs

Background

There are few studies reporting pain and postoperative analgesia associated with mastectomy in dogs. The aim of this study was to evaluate postoperative pain after unilateral mastectomy using two different surgical techniques in the dog.

Findings

Twenty female dogs were assigned (n=10/group) to undergo unilateral mastectomy using either the combination of sharp and blunt dissection (SBD) or the modified SBD (mSBD) technique, in which the mammary chain is separated from the abdominal wall entirely by blunt (hand and finger) dissection except for a small area cranial to the first gland, in a prospective, randomized, clinical trial. All dogs were premedicated with intramuscular acepromazine (0.05 mg/kg) and morphine (0.3 mg/kg). Anesthesia was induced with intravenous ketamine (5 mg/kg) and diazepam (0.25 mg/kg), and maintained with isoflurane. Subcutaneous meloxicam (0.2 mg/kg) was administered before surgery. Postoperative pain was evaluated according to the University of Melbourne pain scale (UMPS) by an observer who was blinded to the surgical technique.. Rescue analgesia was provided by the administration of intramuscular morphine (0.5 mg/kg) if pain scores were >14 according to the UMPS. Data were analyzed using t-tests and ANOVA (P>0.05). There were no significant differences between the groups for age, weight, extubation time, and duration of surgery and anesthesia (P>0.05). There were no significant differences for postoperative pain scores between groups. Rescue analgesia was required in one dog in each group.

Conclusions

The two surgical techniques produced similar surgical times, incidence of perioperative complications and postoperative pain. Multimodal analgesia is recommended for treatment of postoperative pain in dogs undergoing unilateral mastectomy.