Pharmacodynamics of Insulin Detemir and Insulin Glargine Assessed by an Isoglycemic Clamp Method in Healthy Cats

Background: Insulin detemir and insulin glargine are synthetic long‐acting insulin analogs. In people, insulin glargine is longer acting and has a relatively flat time‐action profile, while insulin detemir has significantly less within‐subject variability. Insulin detemir is also associated with less undesired weight gain and decreased frequency of hypoglycemic events. Objectives: To compare the pharmacodynamics of insulin detemir and insulin glargine in healthy cats. Animals: Ten young, healthy, neutered, purpose‐bred cats. Methods: Randomized, cross‐over design. Pharmacodynamics of insulin detemir and insulin glargine were determined by the isoglycemic clamp method after a 0.5 U/kg SC injection. Results: The only significant difference in the pharmacodynamics of insulin detemir and insulin glargine was onset of action (1.8 ± 0.8 and 1.3 ± 0.5 hours for insulin detemir and insulin glargine, respectively, P= .03). End of action of insulin detemir was reached at 13.5 ± 3.5 hours and for insulin glargine at 11.3 ± 4.5 hours (P= .18). Time‐to‐peak action of insulin detemir was reached at 6.9 ± 3.1 hours and for insulin glargine at 5.3 ± 3.8 hours (P= .7). The time‐action curves of both insulin analogs varied between relatively flat curves in some cats and peaked curves in others. Conclusion and Clinical Importance: Insulin detemir and insulin glargine have shorter durations of action than in people when assessed by the clamp method, but in some cats these insulin analogs could be useful as once‐a‐day drugs. Peak effects of both insulin analogs are pronounced in some cats.     

The GLP-1 mimetic exenatide potentiates insulin secretion in healthy cats

The glucagon-like peptide-1 mimetic exenatide has a glucose-dependent insulinotropic effect, and it is effective in controlling blood glucose (BG) with minimal side effects in people with type 2 diabetes. Exenatide also delays gastric emptying, increases satiety, and improves β-cell function. We studied the effect of exenatide on insulin secretion during euglycemia and hyperglycemia in cats. Nine young, healthy, neutered, purpose-bred cats were used in a randomized, cross-over design. BG concentrations during an oral glucose tolerance test were determined in these cats previously. Two isoglycemic glucose clamps (mimicking the BG concentration during the oral glucose tolerance test) were performed in each cat on separate days, one without prior treatment (IGC) and the second with exenatide (1 μg/kg) injected subcutaneously 2 h before (ExIGC). BG, insulin, and exenatide concentrations were measured, and glucose infusion rates were recorded and compared in paired tests between the two experiments. After exenatide injection, insulin serum concentrations increased significantly (2.4-fold; range 1.0- to 9.2-fold; P = 0.004) within 15 min. This was followed by a mild decrease in BG concentration and a return of insulin concentration to baseline despite a continuous increase in serum exenatide concentrations. Insulin area under the curve (AUC) during ExIGC was significantly higher than insulin AUC during IGC (AUC ratio, 2.0 ± 0.4; P = 0.03). Total glucose infused was not significantly different between IGC and ExIGC. Exenatide was detectable in plasma at 15 min after injection. The mean exenatide concentration peaked at 45 min and then returned to baseline by 75 min. Exenatide was still detectable in the serum of three of five cats 8 h after injection. No adverse reactions to exenatide were observed. In conclusion, exenatide affects insulin secretion in cats in a glucose-dependent manner, similar to its effect in other species. Although this effect was not accompanied by a greater ability to dispose of an intravenous glucose infusion, other potentially beneficial effects of exenatide on pancreatic β cells, mainly increasing their proliferation and survival, should be investigated in cats.     

A retrospective study of the rate of postoperative septic arthritis following 353 elective arthroscopies

Objective : To report the rate of postoperative septic arthritis following elective diagnostic and surgical arthroscopy in small animals within a clinical setting. Methods : A retrospective case review from the case log of one veterinary surgeon. Results : Of the 353 procedures included, performed on 305 animals, there were three cases of postoperative sepsis (0·85%). Clinical Significance : Interventional arthroscopy including both diagnostic and surgical arthroscopy in small animals is a safe technique and poses a risk of postoperative sepsis of approximately 1%.     

Evaluation of diagnostic tests for Johne's disease in young cattle

OBJECTIVE: To investigate the development of immune responses in calves experimentally and naturally infected with Mycobacterium paratuberculosis and to evaluate the potential for diagnostic tests to detect infected calves. DESIGN: Sequential testing of four treatment groups of calves over a 2 year period. PROCEDURE: Twenty-nine calves were allocated to four groups. Group D calves were orally dosed with M paratuberculosis, group N calves naturally exposed to M paratuberculosis, group V calves vaccinated for M paratuberculosis, and group C were control calves (not infected or vaccinated). Blood and faecal specimens were collected from each calf at monthly intervals to 18 months of age and then every 2 months until they were slaughtered between the ages of 21 and 29 months. Specimens were tested using absorbed EIA, IFN-gamma EIA and faecal culture. The infection status of the calves was confirmed by extensive histopathological examination and tissue culture. RESULTS: M paratuberculosis infection was confirmed in 10 calves, comprising six of eight orally dosed calves, three of five naturally exposed calves and one of nine vaccinated calves. The six artificially infected calves and one naturally infected calf were detected shedding M paratuberculosis in their faeces. Results with positive absorbed EIA were obtained from one artificially infected calf, one naturally infected calf and three vaccinated calves. All calves including controls had positive results on at least one occasion using the IFN-gamma EIA. In addition, seven calves had positive bovine tuberculosis results using the IFN-gamma EIA, even though bovine tuberculosis has been eradicated from Australia. CONCLUSION: Detection of M paratuberculosis infection in young cattle continues to be difficult using current tests.     

Johne's disease in alpacas (Lama pacos) in Australia

SUMMARY: Johne's disease was diagnosed in 10 alpacas ( Lama pacos ) in Australia between February 1993 and May 1994. Eight of the animals were between 12 and 24 months of age, one was a 6-year-old female, and one was a 4-year-old male. Five, including the 6-year-old and the 4-year-old alpacas, showed weight loss and diarrhoea before death or slaughter. The other cases showed no clinical signs of Johne's disease but 4 gave a positive result on faecal culture and one gave a positive result on testing with the caprine ACID assay and had acid-fast organisms in its faeces. At necropsy, all cases had grossly enlarged mesenteric lymph nodes. Johne's disease was diagnosed after histological examination of the lymph nodes with conventional culture and polymerase chain reaction testing of tissue samples. This report outlines the clinical, epidemiological, and pathological findings in these cases.     

An effective buprenorphine analgesic protocol increases post-operative adhesions in rats after laparotomy

The use of analgesics in post‐operative adhesion (POA) research is problematic due to POA‐inhibiting effects of anti‐inflammatory agents and bowel motility‐inhibiting effects of opioids, which may increase adhesion formation. This study was conducted to assess a buprenorphine (BUP) protocol for analgesic efficacy and its effects on POA formation in a rat cecal abrasion model. The protocol was approved by the University of Florida's Institutional Animal Care and Use Committee (IACUC). Forty‐one female Sprague‐Dawley rats were randomized into two groups (n = 20 or 21 group). Body weight, food and water intake were recorded daily from 2 days before until 7 days after surgery. Treatment rats received 0.05 mg kg^–1 BUP SQ at anesthesia induction and 0.3 mg kg^–1 BUP orally in flavored gelatin 6 hours after surgery. Control rats received saline placebo injection and plain gelatin. All rats underwent laparotomy and controlled cecal abrasion. At 3, 6 and 24 hours post‐operatively rats were individually observed in 10‐minutes periods for pain related behavior incidence: ‘twitch’ (contraction of muscles along dorsum and/or head), ‘back arch’ (cat‐like position with front legs extended and pushing backward), ‘writhe’ (flank contraction), and ‘stagger/fall’ (momentary loss of balance while grooming or ambulating), using the method of Roughan and Flecknell (Pain 2001,90, 65–74). On post‐op day seven rats were euthanized by CO₂ inhalation and POA evaluated (0 to 4 scale; ³Grade 2 = clinically significant.) BUP treated rats had lower mean pain scores than control rats at 3 hours (1.6 ± 1.7 versus 20.3 ± 13.5 (mean ± SD); p < 0.001) and 6 hours (2.1 ± 2.7 versus 23.7 ± 12.9; p < 0.001) but not 24 hours (1.5 ± 1.3 versus 4.9 ± 6.6; p = 0.35) post‐operatively. Predominant pain behavior was ‘writhe’ (flank contraction) in contrast to ‘twitch,’‘back arch,’ and ‘stagger/fall’ reported as most common pain indicators in other rat strains. BUP rats had greater mean adhesion incidence (2.4 ± 1.7 versus 1.4 ± 1.8; p < 0.03) and severity (90%³Gr.2 versus 65% of controls; p < 0.05). The BUP protocol appeared to provide effective analgesia for at least 24 hours post‐operatively. Strain of rat may affect pain related behavior. BUP should be used with caution after abdominal surgical procedures having high risk of POA formation.     

The effect of different combinations of lignocaine,ketoprofen, xylazine and tolazoline on the acute cortisol response to dehorning in calves

AIMS: The aims of this study were (a) to evaluate the effect of xylazine and tolazoline, with and without lignocaine, on the cortisol response of calves following amputation dehorning and (b) to assess the effect of a non-steroidal anti-inflammatory drug (ketoprofen) and local anaesthesia on the cortisol response of calves to amputation dehorning.

METHODS: Plasma cortisol concentrations were measured in 100 dehorned or non-dehorned 3-month-old calves over an 8-h period following five different sedative/analgesic or control treatments. Sedative/analgesic treatments were: control (no anaesthesia); local anaesthesia and ketoprofen; local anaesthesia and xylazine; local anaesthesia, xylazine and tolazoline; and xylazine only. Within each sedative/analgesic treatment group, half the calves (n=10 per group) were amputation dehorned and half were not dehorned.

RESULTS: The change in plasma cortisol concentrations in calves dehorned after being given ketoprofen and local anaesthesia did not differ significantly from that of non-dehorned control calves for at least 8 h. In contrast, the cortisol response of dehorned calves not given analgesic drugs peaked 30 min after dehorning and lasted >4 h. Xylazine injected before dehorning significantly reduced but did not eliminate the peak of the cortisol response. When both xylazine and local anaesthesia were administered before dehorning the peak in the cortisol response was virtually eliminated. In the dehorned calves that received xylazine with or without local anaesthesia, cortisol concentration increased significantly 3 h after dehorning and did not return to baseline until at least 5 h later. When tolazoline was administered shortly after xylazine, it caused a marked cortisol response, higher than the response to any other treatment.

CONCLUSIONS: Combining ketoprofen and local anaesthesia minimised the cortisol response, and by inference the pain- induced distress, following amputation dehorning in calves. Xylazine reduced the initial cortisol response to dehorning but not as much as when local anaesthesia was also given. The increase in cortisol concentration from 3–8 h after dehorning in calves given xylazine alone or in combination with local anaesthesia suggests that calves experienced pain-induced distress during this time and that xylazine had no long-term analgesic effect. Tolazoline, used to reverse the sedative effects of xylazine, caused a marked cortisol response in calves via a mechanism which remains unclear.     

高效液相色谱法测定伊维菌素脂质体药物的含量及包封率

本试验旨在建立伊维菌素脂质体载体药物含量及包封率测定的高效液相色谱法。Waters surfire C18柱(150 mm×2.1 mm,5 μm),流动相为乙腈—甲醇—水(62∶30∶8),流速1 mL/min,检测波长245 nm,进样量10 μL,柱温30 ℃。采用凝胶过滤法、透析法、冷冻超速离心法、超滤离心法4种方法对脂质体与药物进行分离。结果表明,在优化色谱条件下伊维菌素与辅料及溶剂峰均得到良好分离,伊维菌素在1～50 μg/mL浓度范围内线性关系良好(r=0.9998,n=5),最终采用超速冷冻离心法可将脂质体与药物很好的分离,伊维菌素脂质载体的包封率可达98.54%±1.6%。该方法准确可靠、简单快速,可用于伊维菌素脂质体载体药物含量及包封率的测定。