Progression of lipase activity and pancreatic lipase immunoreactivity in dogs hospitalized for acute pancreatitis and correlation with clinical features.

BACKGROUND: Lipase activity and pancreatic lipase immunoreactivity (PLI) have not been compared in dogs hospitalized for acute pancreatitis (AP). OBJECTIVES: To describe the progression of lipase activity and PLI, and correlations with clinicopathologic features in dogs with AP. ANIMALS: Thirty-nine dogs with AP based on clinical signs and lipase activity >350 U/L (reference interval [RI], 24-108 U/L). METHODS: Retrospective study. Lipase activity (LIPC Roche), PLI (SpecPL), and clinical signs were recorded daily. Admission (d1) data (clinical, laboratory, and ultrasound [US] findings), and clinical signs during hospitalization (d2-d3) were assessed for correlation with lipases. RESULTS: Median (range) duration of clinical signs before presentation was 2 days (1-7 days). Median (range) lipase activity and PLI at d1 were 1070 U/L (range, 357-1500 U/L) and 1111 µg/L (range, 292-1500 µg/L). Strong correlation between assays at d1 (rs 0.96; P < .0001; n = 39), remained equally strong on d2 (rs 0.964; P < .0001; n = 39), and d3 (rs 0.966; P < .0001; n = 22). On d2, lipase activity and PLI were within RI in 13/39 (33%) and 18/39 (46%) of cases. Lipase activities were minimally increased (median, 124 U/L) in 5 dogs with d2 PLI <200 µg/L. On d3, 4 more dogs had normal lipase activity and PLI, and the nature and magnitude of change were always the same for both assays. Clinical signs were not associated with lipases. Only a hyperechoic mesentery, but not an US diagnosis of AP, correlated significantly with lipase activity and PLI. CONCLUSIONS AND CLINICAL IMPORTANCE: Lipase decreases rapidly to near or within RI within 2 days of treatment in the majority of dogs with AP. Both lipase assays yielded virtually identical results. Mesenteric echogenicity may be an early marker of AP in dogs.

Methadone does not potentiate the effect of doxorubicin in canine tumour cell lines.

Opioid receptor activation was shown to enhance the efficacy of anti-neoplastic drugs in several human cancer cell lines. In these cell lines, doxorubicin increased the number of opioid receptors and methadone concurrently enhanced cellular doxorubicin uptake. Triggered through lay press and media, animal owners started to challenge veterinary oncologists with questions about methadone use in anti-cancer therapy. Especially in veterinary medicine, where side effects of chemotherapy are tolerated to a lesser extent and hence smaller doses are given, agents potentiating chemotherapeutic agents would be an optimal approach to treatment. Canine transitional cell carcinoma cells (TCC, K9TCC), canine osteosarcoma cells (OSA, Abrams) and canine hemangiosarcoma cells (HSA, DAL-4) were incubated with different combinations of methadone, buprenorphine and doxorubicin, in order to test inhibition of cell proliferation. Opioid receptor density was assessed with fluorescence-activated cell sorting in drug native and doxorubicin pretreated cells. In TCC and OSA cell lines opioid receptor density increased after doxorubicin pretreatment. In combination treatment, however, we did not find significant potentiation of doxorubicin's inhibitory effect on proliferation in these cell lines. Neither was there a significant increase of the effect of doxorubicin when the opioids were added 24 hr before doxorubicin. Hence, we could not confirm the hypothesis that opioids increase the anti-proliferative effect of the anti-neoplastic drug doxorubicin in any of these canine tumour cell lines. The lack of effect on a cellular level does not warrant a clinical approach to use opioids together with doxorubicin in dogs with cancer.