The effect of capromorelin on glycemic control in healthy dogs.

Capromorelin is a ghrelin-receptor agonist widely used as an appetite stimulant in dogs. Capromorelin disrupts glucose homeostasis in cats but information regarding its effects on canine glucose homeostasis is lacking. The study objective was to evaluate the effect of capromorelin on glucose homeostatic mechanisms in healthy dogs. Eight clinically healthy client-owned adult dogs were enrolled in this prospective, cross-over, placebo-controlled study. Dogs were randomized to receive capromorelin (Entyce, 3 mg/kg) or placebo, q24h for 3 d. A wk later, treatments were crossed over. Interstitial glucose (IG) concentrations were measured using a flash glucose monitoring system throughout. On d 1 of each treatment, blood glucose (BG), insulin, glucagon, glucose-dependent insulinotropic peptide (GIP), and glucagon-like peptide-1 (GLP-1) concentrations were measured before drug administration, then before and 30-120 min after feeding a glucose-rich diet (Ensure Plus, 21 kcal/kg). Data were analyzed as a 2-period crossover design using generalized least squares estimation. Capromorelin administration increased mean 48 h IG by10% and mean BG by 20% at 90 and 120 min post-prandially (P < 0.0001). Post-prandially, there was a time-by-treatment effect for insulin (P = 0.03) and GIP (P = 0.0002) because capromorelin doubled geometric mean insulin concentrations at 120 min and increased geometric mean GIP concentrations more rapidly than after placebo. There were no differences in glucagon or GLP-1 concentrations between treatment groups. The increase in post-prandial blood glucose was not the result of overt suppression of incretin hormone secretion. There was also no suppressive effect of capromorelin on insulin.

In vitro effects of Yunnan Baiyao on canine hemangiosarcoma cell lines.

Yunnan Baiyao is a Chinese herbal medicine that has been utilized for its anti-inflammatory, haemostatic, wound healing and pain relieving properties in people. It has been utilized in the veterinary profession to control bleeding in dogs with hemangiosarcoma (HSA) and has been anecdotally reported to prolong survival times in dogs with this neoplasm. This study evaluated the in vitro activity of Yunnan Baiyao against three canine HSA cell lines after treatment with increasing concentrations of Yunnan Baiyao (50, 100, 200, 400, 600 and 800 µg mL(-1) ) at 24, 48 and 72 h. Mean half maximum inhibitory concentration (IC50 ) at 72 h for DEN, Fitz, SB was 369.9, 275.9 and 325.3 µg mL(-1) , respectively. Caspase-3/7 activity increased in correlation with the IC50 in each cell line which was confirmed by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL, APO-BRDU Kit; BD Biosciences, San Jose, CA, USA) assay. VEGF in cell supernatant was also quantified. Overall, the study found that Yunnan Baiyao causes dose and time dependent HSA cell death through initiation of caspase-mediated apoptosis, which supports future studies involving Yunnan Baiyao.

In vitro effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine hemangiosarcoma cell lines.

This study evaluated the in vitro activity of masitinib mesylate against canine hemangiosarcoma (HSA) cell lines after treatment with increasing concentrations of masitinib mesylate (0.01-100 µM) for 24, 48 and 72 h. Results indicated that masitinib mesylate caused a dose- and time-dependent decrease in HSA cell proliferation. The 50% inhibitory concentration (IC(50) ) at 72 h for three HSA cell lines (DEN, Fitz and SB) was found to be 8.56, 9.41 and 10.65 µM, respectively. Further investigation demonstrated that masitinib mesylate induced apoptosis in all HSA cell lines, including activation of caspase-3/7. Measurement of VEGF levels in cell supernatant found a statistically significant increased VEGF in close proximity to the IC(50) of each cell line followed by a decline back towards baseline. These findings indicate that masitinib mesylate causes dose-dependent HSA cell death in vitro and supports future clinical trials of masitinib for canine HSA.

Radiosensitivity and capacity for radiation-induced sublethal damage repair of canine transitional cell carcinoma (TCC) cell lines.

Understanding the inherent radiosensitivity and repair capacity of canine transitional cell carcinoma (TCC) can aid in optimizing radiation protocols to treat this disease. The objective of this study was to evaluate the parameters surviving fraction at 2 Gy (SF(2) ), α/ß ratio and capacity for sublethal damage repair (SLDR) in response to radiation. Dose-response and split-dose studies were performed using the clonogenic assay. The mean SF(2) for three established TCC cell lines was high at 0.61. All the three cell lines exhibited a low to moderate α/ß ratio, with the mean being 3.27. Two cell lines exhibited statistically increased survival at 4 and 24 h in the dose-response assay. Overall, our results indicate that the cell lines are moderately radioresistant, have a high repair capacity and behave similarly to a late-responding normal tissue. These findings indicate that the radiation protocols utilizing higher doses with less fractionation may be more effective for treating TCC.

Performance of serologic tests used to detect heartworm infection in cats.

OBJECTIVE: To compare heartworm serum antibody (Ab) and antigen (Ag) test results, using commercial laboratories and in-house heartworm test kits, with necropsy findings in a population of shelter cats. DESIGN: Prospective study. ANIMALS: 330 cats at an animal shelter. PROCEDURE: Between March and June 1998, 30 ml of blood was collected from the cranial and caudal venae cavae of 330 cats that were euthanatized at a local animal shelter. Results of heartworm Ab and Ag serologic tests for heartworm infection were compared with necropsy findings in this population of cats, using commercial laboratories and in-house test kits to measure serum Ab and Ag concentrations. RESULTS: On necropsy, adult Dirofilaria immitis were found in 19 of 330 (5.8%) cats. Combining results from serum Ab and Ag tests achieved higher sensitivities than using serum Ab and Ag test results alone (i.e., maximum sensitivities of 100% vs 89.5%, respectively, whereas use of serum Ag and Ab test results alone achieved higher specificities compared with the use of a combination of serum Ab and Ag results (i.e., maximum specificities of 99.4% vs 92.9%, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of our findings, if a cat has clinical signs that suggest heartworm disease despite a negative heartworm serum Ab test result, an alternative heartworm Ab test, a heartworm Ag test, thoracic radiography, or two-dimensional echocardiography should be performed.

Relationship between endometrial oxytocin receptors and oxytocin-induced prostaglandin F2 alpha release during the oestrous cycle and early pregnancy in pony mares.

The effect of transcervical endometrial biopsy on the concentrations of plasma immunoreactive oxytocin and 15-keto-13,14-dihydro-prostaglandin F2 alpha (PGFM) was studied in 18 pony mares on days 8, 12 and 14 after ovulation, days 12 and 14 of early pregnancy and at oestrus. Five biopsy specimens were taken within 15 min and consecutive specimens from each mare were pooled two (A) and three (B) together for measurement of the number of oxytocin receptors. Blood samples were collected at intervals of 5 min for 15 min beginning just before the initial biopsy. Biopsy procedure elicited prompt oxytocin release in all mares. Pregnancy did not affect the response but day after ovulation had a significant influence on oxytocin release. The greatest increase in plasma oxytocin was observed on day 12 in both nonpregnant and pregnant mares and the lowest on day 8. The concentration of plasma PGFM rose linearly over the 15 min period in nonpregnant mares. This response increased progressively with time after ovulation and was greatest on day 14. There was no increase in circulating PGFM in pregnant mares. Endometrial oxytocin receptor concentration was lowest in mares at oestrus and highest in nonpregnant mares on day 14. Oxytocin receptor density in pregnant mares was similar to that in nonpregnant mares on day 12 but was significantly attenuated on day 14. The affinity of oxytocin receptors was lower in pregnant than in nonpregnant mares. Because of the positive correlation between PGF2 alpha release, endometrial oxytocin receptor density, and plasma oxytocin concentrations in nonpregnant mares, it is assumed that the release of PGF2 alpha was induced by oxytocin and was mediated by oxytocin receptors. Pregnancy-induced inhibition of PGF2 alpha release was not associated with suppression of oxytocin release or oxytocin receptor density. An embryo-derived factor is therefore the most likely cause for the suppression of PGF2 alpha release and interruption of the oxytocin-PGF2 alpha interaction in mares during early pregnancy.