Plasma vascular endothelial growth factor concentrations in healthy dogs and dogs with hemangiosarcoma

Vascular endothelial growth factor (VEGF) is a dimeric glycosylated polypeptide growth factor with potent angiogenic, mitogenic, and vascular permeability-enhancing properties specific for endothelial cells. In humans, VEGF seems to play a major role in tumor growth, and plasma concentrations correlate with tumor burden, response to therapy, and disease progression. This study compared plasma VEGF concentrations in healthy client-owned dogs (n = 17) to dogs with hemangiosarcoma (HSA; n 16). Dogs with HSA were significantly more likely to have detectable concentrations of plasma VEGF (13/17) compared to healthy dogs (1/17; P < .001). The median plasma VEGF concentration for dogs with HSA was 17.2 pg/mL (range, < 1.0-66.7 pg/mL). Plasma VEGF concentrations in dogs with HSA did not correlate with stage of disease or tumor burden, but 1 dog had undetectable VEGF during chemotherapy that subsequently increased with disease progression.     

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 growth hormone and insulin-like growth factor-1 concentrations in Japanese black cattle with growth retardation

Serum concentrations of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) were determined in 5 calves in the same lineage with growth retardation. They had normal appetites, activities, body proportion, and laboratory test results. Calves with growth retardation had higher serum GH concentrations and lower serum IGF-I concentrations. These findings suggested defects in the GH-IGF-1 axis, such as in the GH-receptor.     

Endostatin and vascular endothelial growth factor concentrations in healthy dogs, dogs with selected neoplasia, and dogs with nonneoplastic diseases

To evaluate the relationship between endostatin and vascular endothelial growth factor (VEGF) in cancers of dogs, circulating concentrations of these 2 tumor-associated markers were measured prospectively in healthy dogs (n = 44), dogs with tumors (n = 54), and dogs with nonneoplastic diseases (n = 42 for endostatin; n = 16 for VEGF). A canine-directed enzyme-linked immunosorbent assay kit was used for determination of endostatin, and a human-directed kit was validated for detection of canine VEGF. Concentrations of endostatin for all dogs were 28-408 ng/mL. Increasing serum endostatin concentration was associated with increasing age (P = .0396). Concentrations of endostatin were not different among groups of dogs (P = .1989) when adjusted for age. Mean endostatin concentrations for all dogs were higher in dogs (P = .0124) with detectable VEGF concentrations. Endostatin concentrations, when corrected for age, were related to decreasing PCV (P = .032) but not white blood cell count (P = .225) or platelet count (P = .1990). Measurable VEGF (> or = 2.5 pg/mL) was detected in 3 (7.0%) of 43 healthy dogs. Dogs with tumors had detectable VEGF in 24 (44%) of 54 dogs, with concentrations ranging from 2.5-274 pg/mL; only 1 dog with a nonneoplastic disease process had detectable VEGF. VEGF concentrations for all dogs after correcting for age, endostatin, and disease categories were associated with increased white blood cell count (P = .0032) and platelet counts (P = .0064) and decreased PCV (P = .0017). Linkage between increased endostatin and VEGF concentrations suggests that similar factors may influence concentrations of these markers. Further evaluation of endostatin and VEGF associations in dogs with tumors may provide information on the extent and progression of the disease.     

Thyrotropin-releasing hormone-induced growth hormone secretion in dogs with primary hypothyroidism

Primary hypothyroidism in dogs is associated with increased release of growth hormone (GH). In search for an explanation we investigated the effect of intravenous administration of thyrotropin-releasing hormone (TRH, 10 microg/kg body weight) on GH release in 10 dogs with primary hypothyroidism and 6 healthy control dogs. The hypothyroid dogs had a medical history and physical changes compatible with hypothyroidism and were included in the study on the basis of the following criteria: plasma thyroxine concentration < 2 nmol/l and plasma thyrotropin (TSH) concentration > 1 microg/l. In addition, (99m)TcO(4)(-) uptake during thyroid scintigraphy was low or absent. TRH administration caused plasma TSH concentrations to rise significantly in the control dogs, but not in the hypothyroid dogs. In the dogs with primary hypothyroidism, the mean basal plasma GH concentration was relatively high (2.3+/-0.5 microg/l) and increased significantly (P=0.001) 10 and 20 min after injection of TRH (to 11.9+/-3.5 and 9.8+/-2.7 microg/l, respectively). In the control dogs, the mean basal plasma GH concentration was 1.3+/-0.1 microg/l and did not increase significantly after TRH administration. We conclude that, in contrast to healthy control dogs, primary hypothyroid dogs respond to TRH administration with a significant increase in the plasma GH concentration, possibly as a result of transdifferentiation of somatotropic pituitary cells to thyrosomatotropes.     

Circulating concentrations of insulin-like growth factor-1 in dogs with naturally occurring mitral regurgitation

Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth hormone, has effects on cardiac mass and function, and plays an important role in the regulation of vascular tone. In humans, an inverse relationship between degree of heart failure (HF) and circulating IGF-1 concentrations has been found in several studies. In dogs with HF, few studies have focused on IGF-1. We examined circulating IGF-1 concentrations in dogs with mitral regurgitation (MR) caused by myxomatous mitral valve disease. Study 1 included 88 Cavalier King Charles Spaniels (CKCSs) with a broad range of asymptomatic MR (median serum IGF-1: 76.7 microg/L; 25-75 percentile, 59.8-104.9 microg/L). As expected, standard body weight and percentage under- or overweight correlated directly with IGF-1. MR (assessed in 4 different ways) did not correlate with IGF-1. In study 2, 28 dogs with severe MR and stable, treated congestive HF had similar serum IGF-1 concentrations (median, 100.8 g/L; 25-75 percentile, 74.9-156.5 microg/L) as 11 control dogs (79.6 microg/L; 25-75 percentile, 64.1-187.4 microg/L; P = .84). In study 3, the plasma IGF-1 concentration of 15 untreated CKCSs with severe MR was 16.4 +/- 24.2 microg/L lower (P = .02) at the examination when decompensated HF had developed (80.8 +/- 30.9 microg/L) than at a visit 1-12 months earlier (97.2 +/- 39.8 microg/L), possibly in part due to an altered state of nutrition. The studies document that circulating IGF-1 concentrations are not altered before development of congestive HF in dogs with naturally occurring MR, but decrease by approximately 20% with the development of untreated HE In treated HF, circulating IGF-1 concentrations apparently return to within the reference range.     

Serum antiprotease concentrations in dogs with spontaneous and experimentally induced acute pancreatitis

A significant decline (P = 0.047) in serum antiprotease concentration was detected in dogs with experimentally induced acute pancreatitis. Decreased serum antiprotease concentrations, similar in magnitude to those documented in the experimental dogs, were present in dogs with spontaneous, acute pancreatitis. These findings suggest that significant amounts of proteolytic enzymes escape into the systemic circulation during acute pancreatitis in dogs. These circulating enzymes may be involved in the extrapancreatic complications of acute pancreatitis.     

Serial thyroid hormone concentrations in healthy euthyroid dogs, dogs with hypothyroidism, and euthyroid dogs with atopic dermatitis.

Serum thyroxine (T4) and 3,5,3'-triiodothyronine (T3) concentrations were determined every 3 h for 12 h beginning at 8 a.m. in 20 healthy euthyroid dogs, 19 dogs with hypothyroidism, and 18 euthyroid dogs with atopic dermatitis. Status of thyroid function was based on history, physical findings, results of thyrotropin response testing, and requirement for thyroid hormone replacement therapy. Mean serum T4 and T3 concentrations did not vary significantly between blood samplings within each of the three groups of dogs. Between groups of dogs, mean serum T4 concentration was significantly (P less than 0.05) higher at each blood sampling time in healthy euthyroid dogs and euthyroid dogs with atopic dermatitis when compared to dogs with hypothyroidism. There was no significant difference in mean serum T4 concentration at any blood sampling time between healthy euthyroid dogs and euthyroid dogs with atopic dermatitis or in mean serum T3 concentrations at any blood sampling time between any of the three groups of dogs. Random fluctuation in serum T4 and T3 concentrations was found in dogs in all three groups. Random fluctuations were more common with serum T3 versus T4 concentrations. Consequently, sensitivity (0.88 versus 0.52), specificity (0.73 versus 0.45), predictive value for a positive test (0.75 versus 0.32), predictive value for a negative test (0.87 versus 0.65), and accuracy (0.80 versus 0.47) were better for serum T4 concentration than serum T3 concentration, respectively, when all blood samples were analysed. Measurement of serum T4 concentration was more accurate than serum T3 concentration in assessing the status of thyroid gland function.     

Serum growth hormone and insulin-like growth factor-1 concentrations in Japanese black cattle with renal tubular dysplasia

To elucidate the cause of growth retardation, 14 cattle with renal tubular dysplasia (RTD) were investigated by determining serum growth hormone (GH) and insulin-like growth factor (IGF)-1 concentrations. Compared with 6 healthy cattle, the baseline, maximum, area under the curve and peak amplitude of serum GH concentrations were higher or tended to be higher. Serum IGF-1 concentrations were lower normal or lower in cattle with RTD than in healthy cattle. Serum IGF-1 concentrations correlated significantly with body weight and chest girth, but not with serum GH and creatinine concentrations. Growth retardation in RTD might be associated partially with GH resistance.     

Serum C-reactive protein concentrations in healthy Miniature Schnauzer dogs

Background: C‐reactive protein (CRP) is a sensitive marker for inflammation in people and dogs. In people, an association between CRP concentration and atherosclerosis has been reported. Atherosclerosis is rare in dogs, but the Miniature Schnauzer breed may be at increased risk for developing this vascular disease. It is not known if CRP concentrations in Miniature Schnauzer dogs differ from those in other dog breeds. Objectives: Our objectives were to validate an automated human CRP assay for measuring CRP in dogs and compare CRP concentrations in healthy Miniature Schnauzer dogs with those in non‐Miniature Schnauzer breeds. Methods: Sera from 37 non‐Miniature Schnauzer dogs with inflammatory disease were pooled and used to validate a human CRP immunoturbidimetric assay for measuring canine CRP. Blood was collected from 20 healthy Miniature Schnauzer dogs and 41 healthy dogs of other breeds. Median serum CRP concentration of healthy Miniature Schnauzer dogs was compared with that of healthy non‐Miniature Schnauzer dogs. Results: The human CRP assay measured CRP reliably with linearity between 0 and 20 mg/L. CRP concentration for healthy Miniature Schnauzer dogs (median 4.0 mg/L, minimum–maximum 0–18.2 mg/L) was significantly higher than for the healthy non‐Miniature Schnauzer dogs (median 0.1 mg/L, minimum–maximum 0–10.7 mg/L); 17 of the 20 Miniature Schnauzer dogs had values that overlapped with those of the non‐Miniature Schnauzer dogs. Conclusions: Median CRP concentration of Miniature Schnauzer dogs was slightly higher than that of other breeds of dogs. A relationship between higher CRP concentration in Miniature Schnauzer dogs and idiopathic hyperlipidemia, pancreatitis, and possible increased risk for atherosclerosis remains to be determined.     

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.     

Serum concentrations of the third component of complement in healthy dogs and dogs with protein-losing nephropathy

OBJECTIVE: To develop a method for determining the concentration of the third component of complement (C3) in canine serum, to establish a reference range for C3 in healthy dogs, and to evaluate dogs with protein-losing nephropathy (PLN) to determine whether PLN is associated with decreased serum C3 concentrations. ANIMALS: 30 healthy dogs and 49 dogs with PLN. PROCEDURES: Serum samples were obtained from healthy dogs at the time of examination, whereas serum samples were obtained from dogs with PLN at the time of diagnosis. All samples were frozen at -70 degrees C until analyzed. Serum C3 concentrations were determined by use of a sandwich ELISA. Concentrations were expressed as the number of dilutions in which C3 could be detected. RESULTS: C3 was detectable in healthy control dogs (range, 1,920,000 to 15,400,000 dilutions; median, 9,600,000 dilutions). This represented a range of four 2-fold serum dilutions. In addition, C3 was detectable in dogs with PLN (range, 1,460,000 to 30,070,000 dilutions; median, 7,680,000 dilutions), which represented a range of six 2-fold serum dilutions. There was no significant difference in C3 concentrations between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: C3 is a critical part of the immune defense system that has not been extensively examined in veterinary medicine. An ELISA was developed for measuring C3 concentrations, and a reference range for healthy dogs was established. Significant decreases in C3 concentrations were not detected in any dog with PLN. Additional studies will be required to definitively determine the importance of serum C3 concentrations in PLN.     

Serum concentrations of monocyte chemoattractant protein‐1 in healthy and critically ill dogs

Background: The chemokine monocyte chemoattractant protein‐1 (MCP‐1) is a primary regulator of monocyte mobilization from bone marrow, and increased concentrations of MCP‐1 have been associated with sepsis and other inflammatory disorders in critically ill people. The relationship between MCP‐1 and disease in dogs has not been evaluated previously. Objective: The purpose of this study was to assess serum concentrations of MCP‐1 in healthy dogs, dogs in the postoperative period, and critically ill dogs. We hypothesized that MCP‐1 concentrations would be significantly increased in critically ill dogs compared with postoperative or healthy dogs. Methods: Serum concentrations of MCP‐1 were measured in 26 healthy control dogs, 35 postoperative dogs, and 26 critically ill dogs. Critically ill dogs were further subgrouped into dogs with sepsis, parvovirus gastroenteritis, immune‐mediated hemolytic anemia, and severe trauma (n=26). MCP‐1 concentrations were determined using a commercial canine MCP‐1 ELISA. Associations between MCP‐1 concentrations and disease status were evaluated statistically. Results: MCP‐1 concentration was significantly higher in critically ill dogs (median 578 pg/mL, range 144.7–1723 pg/mL) compared with healthy dogs (median 144 pg/mL, range 4.2–266.8 pg/mL) and postoperative dogs (median 160 pg/mL, range 12.6–560.4 pg/mL) (P<.001). All subgroups of critically ill dogs had increased MCP‐1 concentrations with the highest concentrations occurring in dogs with sepsis. However, differences among the 4 subgroups were not statistically significant. Conclusion: Critically ill dogs had markedly increased serum concentrations of MCP‐1 compared with postoperative and healthy dogs. These results indicate that surgery alone is not sufficient to increase MCP‐1 concentrations; thus, measurement of MCP‐1 may be useful in assessing disease severity in critically ill dogs.     

Endostatin concentrations in healthy dogs and dogs with selected neoplasms

Endostatin prevents angiogenesis and tumor growth by inhibiting endothelial cell proliferation and migration. The purpose of this study was to determine serum endostatin concentrations in 53 healthy dogs and in 38 dogs with confirmed malignant neoplasms. Endostatin concentration was determined with a competitive enzymatic immunoassay (EIA) with rabbit polyclonal antibody generated against a recombinant canine endostatin protein. Both the presence of cancer and increasing age were associated with increased serum concentration of endostatin. Endostatin concentration in healthy dogs was 87.7 +/- 3.5 ng/mL. Upper and lower limits of the reference range for serum endostatin concentration in healthy dogs were 60 and 113 ng/mL. Dogs with lymphoma (LSA) and hemangiosarcoma (HSA) had endostatin concentrations of 107 +/- 9.3 ng/mL. In conclusion, this study demonstrates that endostatin can be quantified in dogs and that endostatin concentrations are high in dogs with HSA and LSA.     

Serum vascular endothelial growth factor in dogs with haemangiosarcoma and haematoma

Splenic haemangiosarcomas are frequently seen in dogs. Because of their bad prognosis differentiation from other benign splenic lesions are of prognostic importance.     

Serum digoxin concentrations in healthy dogs treated without a loading dose

Healthy dogs were treated once-a-day for 20 days, with a liquid oral dosage form of digoxin (0.022 mg/kg). Serum digoxin concentrations, measured by radio immunoassay technique, were in the therapeutic range 8 h after the second daily dose of digoxin had been administered. Of the ten dogs treated, four had digoxin serum concentrations above those accepted to be moderately toxic. Results of a blood urea nitrogen and a phenolsulfonphthalein test, determined at days 0, 5, 8, 12, 15 and 19 after the beginning of the investigation all were within normal limits. Serum osmolality, calcium, potassium, and sodium, determined daily, evidenced no significant difference from control values. Lengthening of the PR interval and a decrease in the heart rate were observed. Digitalization of dogs can be achieved without the use of a loading dose and within a much shorter time than was previously reported.     

Active immunization of pigs against growth hormone-releasing factor: effect on concentrations of growth hormone and insulin-like growth factor 1

Cyclic gilts (96 +/- 1 kg) were used to determine the effect of active immunization against growth hormone-releasing factor GRF(1-29)-NH2 on concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Gilts were immunized against GRF conjugated to human serum albumin (GRF-HSA, n = 5) or HSA alone at 180 d of age (wk 0). Booster doses were administered at wk 9 and 13. Seven days after the second booster (wk 14), blood samples were collected at 15-min intervals for 6 h before feeding and 30, 60, 120, 180 and 240 min after feeding. Eight days after the second booster, all gilts were administered a GRF analog, [desNH2Tyr1,Ala15]-GRF(1-29)-NH2, followed by an opioid agonist, FK33-824. Blood samples were collected at 15-min intervals from -30 to 240 min after injection. Immunization against GRF-HSA resulted in antibody titers, expressed as dilution required to bind 50% of [125I]GRF, ranging from 1:11,000 to 1:60,000 (wk 11 and 14); binding was not detectable or was less than 50% at 1:100 in HSA gilts (P less than .05). Episodic release of GH was abolished by immunization against GRF-HSA (P less than .05). Mean GH was decreased (P less than .07), but basal GH concentrations were not altered (P greater than .15) by immunization against GRF-HSA. Serum concentrations of IGF-1 were similar at wk 0, but concentrations were lower in GRF-HSA than in HSA gilts (P less than .05) at wk 14.(ABSTRACT TRUNCATED AT 250 WORDS)