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  • Author or Editor: Patrice Dubreuil x
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Objective—To study effects of in vitro exposure of bovine leukocytes to mercury, cadmium, and lead on phagocytosis, natural killer cell activity, and lymphocyte proliferation.

Sample Population—Leukocytes from 6 nonpregnant Holstein heifers.

Procedure—Leukocytes were exposed in vitro to the aforementioned metals, and leukocyte functions were assessed.

Results—Phagocytosis was suppressed by 10−5 to 10−7 M CdCl2 and by 10−5 and 10−6 M HgCl2, but not 10−7 M HgCl2 nor 10−4 to 10−6 M PbCl2. Spontaneous and concanavalin A- or phytohemagglutinin-stimulated proliferation of metal-treated bovine blood mononuclear cells was not significantly different from that of nontreated control cells, except for enhanced spontaneous proliferation in response to 10−5 M HgCl2. When proliferation was expressed as a stimulation index, a dosedependent increase of spontaneous proliferation was observed in response to exposure to HgCl2 and PbCl2. Compared with response to 10−6 or 10−7 M CdCl2, reduction of mitogen-induced and spontaneous proliferation was observed on exposure to 10−5 M CdCl2. Natural killer cell activity against yeast artificial chromosome target cells, evaluated by flow cytometry, was decreased only in cells exposed to 10−5 M HgCl2.

Conclusion and Clinical Relevance—Bovine leukocytes are susceptible to the immunomodulatory effects of in vitro exposure to heavy metals at concentrations equal to or higher than those at which similar effects are seen for leukocytes from most other animal species for which data are available for comparison. Exception is phagocytosis, which is severely affected by low concentrations of CdCl2 and HgCl2 in cattle. Reduction of defense mechanisms on exposure to metals could lead to increased susceptibility to potential pathogens.(Am J Vet Res 2000;61:339–344)

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in American Journal of Veterinary Research


Objective—To evaluate the effectiveness of masitinib for the treatment of nonresectable mast cell tumors (MCTs) in dogs at 12 and 24 months after onset of treatment.

Animals—132 dogs with nonresectable grade 2 or 3 MCTs.

Procedures—Dogs received masitinib (12.5 mg/kg/d, PO; n = 106) or a placebo (26). After 6 months, treatment was extended with tumor assessments at 3-month intervals until detection of disease progression. Endpoints were tumor response and overall survival rate and time.

Results—In dogs with nonresectable MCTs, masitinib significantly improved survival rate, compared with results for the placebo, with 59 of 95 (62.1%) and 9 of 25 (36.0%) dogs alive at 12 months and 33 of 83 (39.8%) and 3 of 20 (15.0%) dogs alive at 24 months, respectively. Median overall survival time was 617 and 322 days, respectively. Tumor control at 6 months had a high predictive value for 24-month survival, with high specificity (88%) and sensitivity (76%), whereas short-term tumor response (within 6 weeks) had a poor predictive value. Complete responses at 24 months were observed in 6 of 67 (9.0%) dogs with nonresectable MCTs treated with masitinib.

Conclusions and Clinical Relevance—Masitinib significantly increased survival rates at 12 and 24 months in dogs with nonresectable MCTs. Control of disease at 6 months, but not best response at 6 weeks, was predictive of long-term survival in dogs treated with masitinib, which suggested that short-term response may be irrelevant for assessing clinical efficacy of tyrosine kinase inhibitors for treatment of MCTs.

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in American Journal of Veterinary Research