Serum vascular endothelial growth factor concentrations and postsurgical outcome in dogs with osteosarcoma

Vascular endothelial growth factor (VEGF) is a key angiogenic growth factor, playing putative roles in both tumour growth and metastasis. The purpose of this study was to correlate pretreatment serum concentrations of VEGF in dogs with osteosarcoma (OSA) with disease‐free interval (DFI) and overall survival (OS). Additionally, the effect of serum from dogs with OSA on ex vivo canine endothelial cell (EC) growth was determined. Pretreatment platelet‐corrected serum VEGF levels correlated significantly with DFI. No other examined variable predicted outcome. The ability of sera from dogs with OSA to stimulate canine EC proliferation did not correlate with VEGF concentration or outcome. These data support a role for VEGF in the development or progression of metastatic disease in dogs with OSA. The VEGF concentration in tested sera was not a major determinant of ex vivo canine EC proliferation in this study.     

Serum C-reactive protein concentrations in dogs with multicentric lymphoma undergoing chemotherapy

OBJECTIVE: To determine whether serum C-reactive protein (CRP) concentration is high in dogs with multicentric lymphoma, whether CRP concentration changes in response to chemotherapy, and whether CRP concentration can be used as a marker for relapse in dogs with multicentric lymphoma. DESIGN: Cohort study. ANIMALS: 20 dogs with multicentric lymphoma and 8 healthy control dogs undergoing chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP) or with vincristine, cyclophosphamide, methotrexate, and L-asparaginase (VCMA) and 20 other healthy dogs. PROCEDURES: Serum CRP concentration was measured weekly during the first month of chemotherapy and then at 3-week intervals until relapse in dogs with multicentric lymphoma, weekly for 16 weeks in healthy dogs undergoing chemotherapy, and once in the healthy dogs not undergoing chemotherapy. RESULTS: For both groups of dogs with lymphoma, mean serum CRP concentration during week 1 (prior to treatment) was significantly higher than mean concentrations following induction of chemotherapy and at the time of relapse. Mean serum CRP concentration in the healthy dogs undergoing chemotherapy was not significantly different at any time from mean concentration for the healthy dogs not undergoing chemotherapy. No significant differences were observed between dogs treated with CVP and dogs treated with VCMA. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that serum CRP concentration is high in dogs with multicentric lymphoma but that serum CRP concentration is not a useful marker for relapse and that chemotherapy itself does not affect serum CRP concentration.     

Serum alpha 1-acid glycoprotein concentrations before and after relapse in dogs with lymphoma treated with doxorubicin

OBJECTIVE: To determine whether serum alpha 1-acid glycoprotein (AGP) concentration was a useful marker of relapse in dogs with lymphoma that were in clinical remission following treatment with doxorubicin. DESIGN: Cohort study. ANIMALS: 12 dogs with lymphoma and 10 healthy dogs. PROCEDURE: Serum AGP concentration was measured in the healthy dogs and in the dogs with lymphoma before treatment, 3 weeks after the first dose of doxorubicin was administered, and every 3 weeks thereafter until relapse (i.e., recurrence of clinically detectable disease such as palpable enlargement of peripheral lymph nodes). Serum AGP concentrations were determined by use of a radial immunodiffusion kit. RESULTS: Mean serum AGP concentration in healthy dogs was significantly less than concentration in dogs with lymphoma prior to treatment. Mean serum AGP concentrations after the first and each subsequent dose of doxorubicin were not significantly different from concentration in healthy dogs. However, mean serum AGP concentrations 3 weeks prior to and at the time of relapse were significantly higher than concentration measured after the first dose of doxorubicin, and were not significantly different from concentration measured before treatment. CLINICAL IMPLICATIONS: Results suggest that measuring serum AGP concentration may be a useful method of predicting relapse before recurrence of clinically detectable disease in dogs with lymphoma undergoing treatment with doxorubicin.     

Effect of octreotide on plasma concentrations of glucose, insulin, glucagon, growth hormone, and cortisol in healthy dogs and dogs with insulinoma

The inhibitory effect of the somatostatin analogue octreotide on the secretion of insulin could be used in the treatment of insulinoma. However, current information on the effectiveness of octreotide in dogs is conflicting. Therefore, the endocrine effects of a single subcutaneous dose of 50 microg octreotide were studied in healthy dogs in the fasting state (n=7) and in dogs with insulinoma (n=12). Octreotide did not cause any adverse effects. In healthy dogs in the fasting state, both plasma insulin and glucagon concentrations declined significantly. Basal (non-pulse related) GH and ACTH concentrations were not affected. A slight but significant decrease in the plasma glucose concentrations occurred. Dogs with insulinoma had significantly higher baseline insulin concentrations and lower baseline glucose concentrations than healthy dogs in the fasting state. Plasma glucagon, GH, ACTH, and cortisol concentrations did not differ from those in healthy dogs. Baseline plasma insulin concentrations decreased significantly in dogs with insulinoma after octreotide administration, whereas plasma concentrations of glucagon, GH, ACTH, and cortisol did not change. In contrast to the effects in the healthy dogs, in the dogs with insulinoma plasma glucose concentrations increased. Thus, the consistent suppression of plasma insulin concentrations in dogs with insulinoma, in the absence of an suppressive effect on counter-regulatory hormones, suggests that further studies on the effectiveness of slow-release preparations in the long-term medical treatment of dogs with insulinoma are warranted.     

Erythrocytic antioxidant defense, lipid peroxides level and blood iron, zinc and copper concentrations in dogs naturally infected with Babesia gibsoni

Babesiosis is a common tick borne disease of dogs in tropical and subtropical regions of the world caused by different species of Babesia. The present study aimed to examine erythrocyte lipid peroxide and erythrocytic antioxidant levels in dogs with clinical babesiosis, caused by Babesia gibsoni, and impact of the disease on blood iron, zinc and copper levels. The study was conducted on 10 naturally occurring cases of canine babesiosis with the history of tick infestation, erratic pyrexia, and prolonged illness. Microscopic examination of Giemsa stained peripheral blood smears confirmed B. gibsoni infection in the erythrocytes. Six apparently healthy dogs of different age, sex and breeds, brought for either health checkup or vaccination were used for comparison. Levels of erythrocytic antioxidant enzymes were significantly (P<0.01) higher in sick dogs than those of cytologically negative dogs (catalase: 0.192+/-0.024 units/mg Hb vs 0.074+/-0.004 units/mg Hb; superoxide dismutase: 0.014+/-0.0009 units/mg Hb vs 0.006+/-0.0008 units/mg Hb and lipid peroxide: 6.01+/-0.30 nmol MDA/mg Hb vs 1.89+/-0.10 nmol MDA/mg Hb). The levels of blood micronutrients were significantly low in these dogs (iron: 89.87+/-8.12 microg/g vs 126.44+/-14.65 microg/g; zinc: 3.67+/-1.85 microg/g vs 5.62+/-1.83 microg/g and copper: 0.55+/-0.63 microg/g vs 0.65+/-0.04 microg/g). The study demonstrated oxidative damage in dogs naturally infected with B. gibsoni. Low level of blood iron, zinc and copper seems to have an additional role in the genesis of anaemia and oxidative stress.     

Oral chromium picolinate and control of glycemia in insulin-treated diabetic dogs

Chromium is an essential dietary trace mineral involved in carbohydrate and lipid metabolism. Chromium is required for cellular uptake of glucose, and chromium deficiency causes insulin resistance. Chromium supplementation may improve insulin sensitivity and has been used as adjunct treatment of diabetes mellitus in humans. In this study, 13 dogs with naturally acquired diabetes mellitus were treated with insulin for 3 months, then with insulin and chromium picolinate for 3 months. Dogs weighing <15 kg (33 lb: n = 9) were administered 200 microg of chromium picolinate PO once daily for I month, then 200 microg of chromium picolinate twice daily for 2 months. Dogs weighing >15 kg (n = 4) received 200 microg of chromium picolinate once daily for 2 weeks, then 200 microg twice daily for 2 weeks, then 400 microg twice daily for 2 months. Type of insulin, frequency of insulin administration, and diet were kept constant, and insulin dosage was adjusted, as needed, to maintain optimal control of glycemia. Mean body weight, daily insulin dosage, daily caloric intake, 10-hour mean blood glucose concentration, blood glycated hemoglobin concentration, and serum fructosamine concentration were not markedly different when dogs were treated with insulin and chromium picolinate, compared with insulin alone. Adverse effects were not identified with chromium picolinate administration. Results of this study suggest that, at a dosage range of 20-60 microg/kg/d, chromium picolinate caused no beneficial or harmful effects in insulin-treated diabetic dogs.     

Prophylactic trimethoprim-sulfadiazine during chemotherapy in dogs with lymphoma and osteosarcoma: a double-blind, placebo-controlled study

BACKGROUND: The administration of chemotherapy is associated with risk for morbidity. Management of chemotherapy-related morbidity in veterinary oncology has been primarily supportive. HYPOTHESIS: The purpose of this study was to evaluate the effect of prophylactic antimicrobial use on chemotherapy-associated morbidity in dogs with lymphoma or osteosarcoma. ANIMALS: Dogs presenting with histologically confirmed osteosarcoma or lymphoma were eligible. METHODS: Patients were randomized to receive placebo or trimethoprim-sulfadiazine for 14 days after their first doxorubicin chemotherapy. Both owner and clinician were blinded with respect to treatment. Patient assessment included CBC, physical examination and performance, and toxicosis grading on days 7 and 14. Investigated outcomes were hospitalization, suspicion of infection, gastrointestinal toxicity, neutropenia, nonhematologic toxicity, and quality of life. RESULTS: Seventy-three dogs were enrolled; 34 had osteosarcoma, and 39 had lymphoma. Dogs receiving trimethoprim-sulfadiazine (n = 36) had a significantly reduced hospitalization rate (P = .03), nonhematologic toxicity (P = 0.039), grade 2-4 nonhematologic toxicity (P < .0001), grade 2-4 gastrointestinal toxicity (P = .007). and altered performance (P = .015). By group, dogs with osteosarcoma (n = 34) that received the antimicrobial experienced fewer occurrences of nonhematologic toxicity (P = .02) and less severe nonhematologic toxicity (P = .038). Dogs with lymphoma (n = 39) had significant reductions in the occurrence of hospitalization (P = .035), severity of nonhematologic toxicity (P = .036), and alterations of performance (P = .015). CONCLUSIONS: The use of prophylactic trimethoprim-sulfadiazine has benefit in reducing morbidity in dogs with osteosarcoma or lymphoma during the first 14 days after treatment with doxorubicin.     

Serum concentrations of immunoglobulins G, A, and M in dogs with neoplastic disease

The concentrations of the three major classes of immunoglobulins (Ig) were determined in canine serum by single radial immunodiffusion against calibrated standards. Serum samples were collected from 121 dogs categorized into 3 groups: normal dogs (n = 34), those with lymphosarcoma (n =41), and those with malignant, solid neoplasms other than lymphosarcoma (n = 46). The mean value for serum IgM concentration in the group of dogs with lymphosarcoma was significantly (P less than or equal to 0.02) higher than was the mean IgM concentration of the normal dogs. Dogs with neoplasms other than lymphosarcoma had significantly increased serum concentrations of IgG and IgM antibodies. There was no significant difference in serum IgA concentration among the three groups. A wide range of Ig concentrations was in the serum of clinically normal dogs, as well as in dogs with neoplastic diseases. Although individual dogs with neoplasms had low serum Ig concentrations, the 81 dogs with neoplastic disease were generally able to synthesize Ig.     

Serum 17-alpha-hydroxyprogesterone and corticosterone concentrations in dogs with nonadrenal neoplasia and dogs with suspected hyperadrenocorticism

OBJECTIVE: To assess serum 17-alpha-hydroxyprogesterone (17OHP) and corticosterone concentrations in dogs with nonadrenal neoplasia and dogs being screened for hyperadrenocorticism. DESIGN: Prospective study. ANIMALS: 16 clinically normal dogs, 35 dogs with nonadrenal neoplasia, and 127 dogs with suspected hyperadrenocorticism. PROCEDURE: ACTH stimulation tests were performed in all dogs. Baseline serum cortisol and corticosterone concentrations were measured in the healthy dogs; baseline serum cortisol concentration and ACTH-stimulated cortisol, corticosterone, and 17OHP concentrations were measured in all dogs. Endogenous plasma ACTH concentration was also measured before administration of ACTH in dogs with neoplasia. RESULTS: In 35 dogs with neoplasia, 31.4% had high serum 17OHP concentration and 22.9% had high serum corticosterone concentration. Of the 127 dogs with suspected hyperadrenocorticism, 59 (46.5%) had high ACTH-stimulated cortisol concentrations; of those, 42 of 59 (71.2%) and 32 of 53 (60.4%) had high serum 17OHP and corticosterone concentrations, respectively. Of dogs with serum cortisol concentration within reference range after ACTH administration, 9 of 68 (13.2%) and 7 of 67 (10.4%) had high serum 17OHP and corticosterone concentrations, respectively. In the dogs with neoplasia and dogs suspected of having hyperadrenocorticism, post-ACTH serum hormone concentrations were significantly correlated. CONCLUSIONS AND CLINICAL RELEVANCE: Serum concentrations of 17OHP or corticosterone after administration of ACTH may be high in dogs with nonadrenal neoplasia and no evidence of hyperadrenocorticism. Changes in serum 17OHP or corticosterone concentrations after administration of ACTH are proportionate with changes in cortisol concentration.     

Serum free and total iodothyronine concentrations in dogs with hyperadrenocorticism.

Serum concentrations of total and free thyroxine (T4 and FT4, respectively), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3) were measured in 42 dogs with hyperadrenocorticism, and were compared with values determined in clinically normal dogs. Mean total T4 concentration in dogs with hyperadrenocorticism (14.3 nmol/L) was significantly (P less than 0.001) lower than the normal value (25.7 nmol/L), with 38% of the dogs having low serum T4 concentration. Although 16 (38%) of the 42 dogs with hyperadrenocorticism had a high FT4 fraction, indicative of diminished serum T4 binding, normal FT4 concentration was found in only 6 of the 16 dogs (38%) with low total T4 values. Mean serum T3 concentration in dogs with hyperadrenocorticism (0.79 nmol/L) was also significantly (P less than 0.001) lower than the normal value (1.16 nmol/L), with 39% of the dogs having T3 values below the normal range. Individual T3-to-T4 and T3-to-FT4 ratios, indices of T3 production and/or clearance, were above the normal range in 29 and 24% of dogs with hyperadrenocorticism, respectively. Mean reverse T3 concentration in dogs with hyperadrenocorticism (0.17 nmol/L) was also significantly (P less than 0.001) lower than the normal mean value (0.39 nmol/L), with 48% of the dogs having reverse T3 values below the normal range. Of the 21 dogs in which all iodothyronines were measured, 6 (29%) had undetectable values for all hormones.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum cobalamin concentrations in dogs with leishmaniosis before and during treatment

Hypocobalaminemia in dogs is most commonly associated with gastrointestinal disorders leading to impaired absorption and utilization of cobalamin. The objectives of this study were to compare serum cobalamin concentrations between dogs with leishmaniosis and clinically healthy dogs, and to assess possible alterations of serum cobalamin concentrations in dogs with leishmaniosis at different timepoints during treatment. Fifty-five dogs with leishmaniosis and 129 clinically healthy dogs were prospectively enrolled. Diagnosis of leishmaniosis was based on clinical presentation, positive serology and microscopic detection of Leishmania amastigotes in lymph node aspiration smears. Twenty of the dogs with leishmaniosis were treated with a combination of meglumine antimonate and allopurinol for 28 days and serum cobalamin concentrations were measured in blood samples that were collected before initiation of treatment (timepoint 0) and on days 14 and 28. In order to estimate alterations of serum cobalamin concentrations during treatment, cobalamin concentrations were measured in blood samples from 20 out of 55 dogs with leishmaniosis at all timepoints. Serum cobalamin concentrations were significantly lower in dogs with leishmaniosis before treatment (median: 362 ng/L; IQR: 277−477 ng/L) compared to clinically healthy dogs (median: 470 ng/L; IQR: 367−632 ng/L; P = 0.0035). Serum cobalamin concentrations increased significantly in dogs with leishmaniosis on day 14 of treatment compared to timepoint 0 (P = 0.02).In the present study, serum cobalamin concentrations were significantly lower in dogs with leishmaniosis compared to clinically healthy dogs. In addition, there was an increase in serum cobalamin concentrations during treatment. The clinical significance of hypocobalaminemia in dogs with leishmaniosis remains to be determined.     

Canine liver iron, copper, and zinc concentrations and association with histologic lesions.

Concentrations of iron, copper, and zinc were measured in livers of 95 dogs that were suspected of having liver disease. Iron concentrations ranged from 177 to 7,680 ppm (dry weight basis); 54 dogs had iron concentrations greater than the normal concentration of 1,200 ppm. Iron stores were present in Kupffer cells and macrophages but not hepatocytes. The dogs did not have lesions of hemochromatosis. Dogs with high liver iron tended to have high liver copper and inflammatory lesions. High liver copper concentrations usually were associated with hepatocellular necrosis and fibrosis. High liver zinc was found in only 5 animals and was accompanied by histologic inflammatory lesions in one. In humans, increased iron concentration in the liver exacerbates liver damage caused by a variety of insults, and the same may be true for dogs.     

Polycythemia and inappropriate erythropoietin concentrations in two dogs with renal T-cell lymphoma

Two dogs presented with suspected renal disease and polycythemia. Abdominal ultrasound examinations performed on both dogs revealed coalescing masses causing bilateral renomegaly. Serum erythropoietin (EPO) concentrations were physiologically inappropriate. Postmortem examinations revealed renal T-cell lymphoma in both dogs. One of the two dogs also had involvement of the liver and mesentery. EPO-immunohistochemistry on tissue samples demonstrated positive staining in tumor cells and occasional normal renal cells. This report illustrates that paraneoplastic EPO production may induce polycythemia. The pattern of EPO-immunohistochemistry staining suggested that the mechanism of production was due to tumor production of EPO and local hypoxia-induced EPO production from compression of normal renal cells and vasculature.     

Trace metals and animal health: Interplay of the gut microbiota with iron,manganese, zinc,and copper

Metals such as iron, manganese, copper, and zinc are recognized as essential trace elements. These trace metals play critical roles in development, growth, and metabolism, participating in various metabolic processes by acting as cofactors of enzymes or providing structural support to proteins. Deficiency or toxicity of these metals can impact human and animal health, giving rise to a number of metabolic and neurological disorders. Proper breakdown, absorption, and elimination of these trace metals is a tightly regulated process that requires crosstalk between the host and these micronutrients. The gut is a complex system that serves as the interface between these components, but other factors that contribute to this delicate interaction are not well understood. The gut is home to trillions of microorganisms and microbial genes (the gut microbiome) that can regulate the metabolism and transport of micronutrients and contribute to the bioavailability of trace metals through their assimilation from food sources or by competing with the host. Furthermore, deficiency or toxicity of these metals can modulate the gut microenvironment, including microbiota, nutrient availability, stress, and immunity. Thus, understanding the role of the gut microbiota in the metabolism of manganese, iron, copper, and zinc, as well as in heavy metal deficiencies and toxicities, and vice versa, may provide insight into developing improved or alternative therapeutic strategies to address emerging health concerns. This review describes the current understanding of how the gut microbiome and trace metals interact and affect host health, particularly in pigs.     

Serum concentrations of cortisol and cortisone in healthy dogs and dogs with pituitary-dependent hyperadrenocorticism treated with trilostane

The serum concentrations of cortisol and cortisone were measured in 19 healthy dogs and in 13 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and one hour after an injection of synthetic adrenocorticotropic hormone (ACTH). In the dogs with pdh, the cortisol and cortisone concentrations were measured before and after one to two weeks and three to seven weeks of treatment with trilostane. The dogs with PDH had significantly higher baseline and poststimulation concentrations of cortisol and cortisone, and higher baseline cortisol:cortisone ratios than the healthy dogs. During the treatment with trilostane, the poststimulation cortisol, the baseline and poststimulation cortisone concentrations, and the baseline and poststimulation cortisol:cortisone ratios decreased significantly. The decrease in poststimulation cortisone was significantly smaller than the decrease in cortisol.