Plasma glucose, insulin, free fatty acids, lactate and cortisol concentrations in dexmedetomidine-sedated dogs with or without MK-467: A peripheral α-2 adrenoceptor antagonist

Six healthy laboratory Beagles were treated IV with 10μg/kg dexmedetomidine (DEX) or 10μg/kg dexmedetomidine combined with 500μg/kg MK-467 in the same syringe (DMK) in a randomised cross-over design with a 14day washout. Blood was collected immediately before treatment and 35, 60 and 120min post-injection through a central venous catheter. The plasma concentrations of glucose, insulin, non-esterified free fatty acids (NEFAs), lactate and cortisol were determined. A repeated-measures ANOVA test was used to compare treatments and effects for each sample time point. Significant differences between treatments were found for plasma glucose (P=0.037) and insulin (P=0.009). DEX significantly increased plasma glucose at 120min, but reduced plasma insulin at 35 and 60min. NEFA decreased for both treatments at 35min. This reduction was transient for DMK, whereas it persisted during the follow up period for DEX. Plasma lactate concentrations increased at 35 and 60min with DEX. Neither treatment altered plasma cortisol concentrations. The addition of MK-467 to dexmedetomidine prevented or abolished most metabolic changes in healthy Beagles.     

Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

Background

Ketoprofen is a non-steroidal anti-inflammatory drug which has been widely used for domestic animals. Orally administered racemic ketoprofen has been reported to be absorbed well in pigs, and bioavailability was almost complete. The objectives of this study were to analyze R- and S-ketoprofen concentrations in plasma after oral (PO) and intra muscular (IM) routes of administration, and to assess the relative bioavailability of racemic ketoprofen for both enantiomers between those routes of administration in growing pigs.

Methods

Eleven pigs received racemic ketoprofen at dose rates of 4 mg/kg PO and 3 mg/kg IM in a randomized, crossover design with a 6-day washout period. Enantiomers were separated on a chiral column and their concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated and relative bioavailability (F_rel) was determined for S and R –ketoprofen.

Results

S-ketoprofen was the predominant enantiomer in pig plasma after administration of the racemic mixture via both routes. The mean (± SD) maximum S-ketoprofen concentration in plasma (7.42 mg/L ± 2.35 in PO and 7.32 mg/L ± 0.75 in IM) was more than twice as high as that of R-ketoprofen (2.55 mg/L ± 0.99 in PO and 3.23 mg/L ± 0.70 in IM), and the terminal half-life was three times longer for S-ketoprofen (3.40 h ± 0.91 in PO and 2.89 h ± 0.85 in IM) than R-ketoprofen (1.1 h ± 0.90 in PO and 0.75 h ± 0.48 in IM). The mean (± SD) relative bioavailability (PO compared to IM) was 83 ± 20% and 63 ± 23% for S-ketoprofen and R-ketoprofen, respectively.

Conclusions

Although some minor differences were detected in the ketoprofen enantiomer concentrations in plasma after PO and IM administration, they are probably not relevant in clinical use. Thus, the pharmacological effects of racemic ketoprofen should be comparable after intramuscular and oral routes of administration in growing pigs.     

Dose-response investigation of oral ketoprofen in pigs challenged with Escherichia coli endotoxin

In order to determine the effective dose, the effects of orally administered ketoprofen were evaluated in pigs following intravenous challenge with Escherichia coli endotoxin. One hour after the challenge, five groups of pigs were treated with either tap water or ketoprofen (0.5 mg/kg, 1 mg/kg, 2 mg/kg or 4 mg/kg). The body temperature was measured and a total clinical score was calculated after assessing the general behaviour, respiratory rate and locomotion of the pigs. Thromboxane B(2) and ketoprofen concentrations were analysed from blood samples. Ketoprofen treatment significantly reduced the rectal temperature and total clinical scores, and lowered blood thromboxane B(2) concentrations when compared with the control group. Ketoprofen plasma concentrations were lower than previously reported in healthy pigs after similar doses. The appropriate dose of orally administered ketoprofen in pigs in this model is 2 mg/kg, as the higher dose of 4 mg/kg failed to provide an additional benefit.     

Amazonian floodplains harbour minerotrophic and ombrotrophic peatlands

In tropical lowlands, ecosystems with peat strata are commonly reported from Southeast Asia, but hardly at all from Amazonia. In this paper, we quantify the horizontal distribution of four important plant nutrients (Ca, Mg, K and P) in five peatland sites located in Peruvian Amazonia and the vertical distribution of these nutrients in one of the sites. With this data as well as topography measurements of the peat deposit from one of the sites, we showed that minerotrophic and ombrotrophic peatlands can be detected in Amazonian floodplains. The nutrient-poor ombrotrophic bogs receive nutrients only from atmospheric deposition because of their thick peat layer and convex topography, while the minerotrophic swamps are periodically covered by nutrient-rich floodwater and/or receive nutrient input from surface waters or from groundwater with capillary rise. The existence of such peatlands in the Amazonian lowlands increases the regional habitat diversity and availability of palaeoecological information and probably has implications also for the hydrological dynamics, water quality, and carbon dynamics of the area.     

Primary gastric impaction in horses: A retrospective study of 20 cases (2005–2008)

Primary gastric impaction is an uncommon condition. Furthermore, the factors associated with gastric impaction and the optimal method of treatment are not clear. The aim of this article is to describe the clinical findings, treatment and outcome of horses with a primary gastric impaction. Medical records of horses that presented with a primary gastric impaction between 2005 and 2008 were reviewed and 20 horses with a primary gastric impaction identified. Diagnosis of a primary gastric impaction was made if the horse had been fasted for a minimum of 16 h, a concretion of ingesta precluded visualisation of the margo plicatus and there was no evidence of concurrent intestinal pathology. Thirteen of 20 (65%) horses were presented on an emergency basis. The most common complaint was inappetence (50%) followed by acute colic (35%) and recurrent colic (35%). On initial examination for colic, all horses had a normal heart rate and 7 of 20 (35%) had decreased gastrointestinal borborygmi. All horses were treated with enteral fluid therapy. The median dose of fluids administered per day was 5 doses (range 1–8 doses) of 2–10 l of isotonic electrolyte solution. The median length of treatment until resolution was 2 days (range 1–5 days). Eighteen of 20 (90%) horses survived to discharge. Primary gastric impaction appears to be a condition with clinical signs of inappetence and mild abdominal discomfort. This is the largest group of horses reported that were treated with enteral fluid therapy for a gastric impaction and it was concluded that enteral fluid therapy was of value in this study.     

Disseminated alimentary mycobacteriosis in the horse: a retrospective study of nine cases

This paper summarises the clinical findings of 9 cases of disseminated alimentary mycobacteriosis in horses presented at a Finnish referral equine hospital 2009–2014. Four of 9 horses were Standardbreds and 8/9 horses were male. The median age was 2 years, ranging from 6 months to 15 years. The duration of clinical signs before admission ranged from 2 weeks to 6 months. All horses demonstrated deterioration of the clinical signs after a protracted period of the disease and were finally subjected to euthanasia after poor response to multiple medical therapies. The most common complaints on admission were weight loss and diarrhoea (9/9), pyrexia (7/9), ventral oedema (7/9), lethargy (7/9) and inappetance (6/9). The most common clinicopathological abnormalities were hypoalbuminaemia and hyperfibrinogenaemia, which were present in all horses. Rectal biopsy specimens were examined from 5/9 horses and specimens were stained with Ziehl‐Nielsen (ZN). At rectal biopsy, mild multifocal neutrophilic or mild granulomatous proctitis was recognised in all 5 horses, but the ZN stain for mycobacteria was positive in only one biopsy. A liver biopsy was taken from one horse in which hepatomegaly was observed clinically and revealed marked granulomatous hepatitis with the presence of mycobacteria. The rectal biopsy from this horse was ZN negative. At post mortem examination, chronic, multifocal to coalescing granulomatous typhlocolitis and lymphadenitis were found in all horses with the small intestine less frequently involved. At histopathological examination of post mortem samples, a ZN stain was performed and intracellular acid‐fast bacilli were identified in macrophages and multinucleated giant cells in the large intestine, liver and lymph nodes in 9/9 horses and in the small intestine in 5/9 horses. Mycobacterium avium ssp. hominissuis was isolated in 5/9 horses from post mortem samples.     

Effect of forest management on gene pools

The influence of current forest management practices on gene pools is discussed. These forest management methods range from natural regeneration to replacing local species with exotics. Genetic changes caused by drift, alterations in the mating system, and directional selection are considered. A baseline is provided by information on genetic variation and demography of natural populations. While biochemical markers are useful for monitoring broad changes in genetic diversity or levels of inbreeding, changes of adaptive characters are likely to go undetected because of the low correlation in level and pattern of variation between biochemical and adaptive characters.     

Detomidine and the combination of detomidine and MK‐467, a peripheral alpha‐2 adrenoceptor antagonist,as premedication in horses anaesthetized with isoflurane

ObjectiveTo investigate MK-467 as part of premedication in horses anaesthetized with isoflurane.Study designExperimental, crossover study with a 14 day wash-out period.AnimalsSeven healthy horses.MethodsThe horses received either detomidine (20 μg kg⁻¹ IV) and butorphanol (20 μg kg⁻¹ IV) alone (DET) or with MK-467 (200 μg kg⁻¹ IV; DET + MK) as premedication. Anaesthesia was induced with ketamine (2.2 mg kg⁻¹) and midazolam (0.06 mg kg⁻¹) IV and maintained with isoflurane. Heart rate (HR), mean arterial pressure (MAP), end-tidal isoflurane concentration, end-tidal carbon dioxide tension, central venous pressure, fraction of inspired oxygen (FiO₂) and cardiac output were recorded. Blood samples were taken for blood gas analysis and to determine plasma drug concentrations. The cardiac index (CI), systemic vascular resistance (SVR), ratio of arterial oxygen tension to inspired oxygen (P_aO₂/FiO₂) and tissue oxygen delivery (DO₂) were calculated. Repeated measures anova was applied for HR, CI, MAP, SVR, lactate and blood gas variables. The Student's t-test was used for pairwise comparisons of drug concentrations, induction times and the amount of dobutamine administered. Significance was set at p < 0.05.ResultsThe induction time was shorter, reduction in MAP was detected, more dobutamine was given and HR and CI were higher after DET+MK, while SVR was higher with DET. Arterial oxygen tension and P_aO₂/FiO₂ (40 minutes after induction), DO₂ and venous partial pressure of oxygen (40 and 60 minutes after induction) were higher with DET+MK. Plasma detomidine concentrations were reduced in the group receiving MK-467. After DET+MK, the area under the plasma concentration time curve of butorphanol was smaller.Conclusions and clinical relevanceMK-467 enhances cardiac function and tissue oxygen delivery in horses sedated with detomidine before isoflurane anaesthesia. This finding could improve patient safety in the perioperative period. The dosage of MK-467 needs to be investigated to minimise the effect of MK-467 on MAP.