Limited sampling pharmacokinetics of subcutaneous ondansetron in healthy geriatric cats, cats with chronic kidney disease, and cats with liver disease.

Ondansetron, a 5-HT3 receptor antagonist, is an effective anti-emetic in cats. The purpose of this study was to compare pharmacokinetics of subcutaneous (SQ) ondansetron in healthy geriatric cats to cats with chronic kidney disease (CKD) or liver disease using a limited sampling strategy. 60 cats participated; 20 per group. Blood was drawn 30 and 120 min following one 2 mg (mean 0.49 mg/kg, range 0.27-1.05 mg/kg) SQ dose of ondansetron. Ondansetron concentrations were measured by liquid chromatography coupled to tandem mass spectrometry. Drug exposure represented as area under the curve (AUC) was predicted using a limited sampling approach based on multiple linear regression analysis from previous full sampling studies, and clearance (CL/F) estimated using noncompartmental methods. Kruskal-Wallis anova was used to compare parameters between groups. Mean AUC (ng/mL·h) of subcutaneous ondansetron was 301.4 (geriatric), 415.2 (CKD), and 587.0 (liver). CL/F (L/h/kg) of SQ ondansetron was 1.157 (geriatric), 0.967 (CKD), and 0.795 (liver). AUC was significantly higher in liver and CKD cats when compared to geriatric cats (P < 0.05). CL/F in liver cats was significantly decreased (P < 0.05) compared to geriatric cats. In age-matched subset analysis, AUC and CL/F in liver cats remained significantly different from geriatric cats.

Oral, subcutaneous, and intravenous pharmacokinetics of ondansetron in healthy cats.

Ondansetron is a 5-HT3 receptor antagonist that is an effective anti-emetic in cats. The purpose of this study was to evaluate the pharmacokinetics of ondansetron in healthy cats. Six cats with normal complete blood count, serum biochemistry, and urinalysis received 2 mg oral (mean 0.43 mg/kg), subcutaneous (mean 0.4 mg/kg), and intravenous (mean 0.4 mg/kg) ondansetron in a cross-over manner with a 5-day wash out. Serum was collected prior to, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18, and 24 h after administration of ondansetron. Ondansetron concentrations were measured using liquid chromatography coupled to tandem mass spectrometry. Noncompartmental pharmacokinetic modeling and dose interval modeling were performed. Repeated measures anova was used to compare parameters between administration routes. Bioavailability of ondansetron was 32% (oral) and 75% (subcutaneous). Calculated elimination half-life of ondansetron was 1.84 ± 0.58 h (intravenous), 1.18 ± 0.27 h (oral) and 3.17 ± 0.53 h (subcutaneous). The calculated elimination half-life of subcutaneous ondansetron was significantly longer (P < 0.05) than oral or intravenous administration. Subcutaneous administration of ondansetron to healthy cats is more bioavailable and results in a more prolonged exposure than oral administration. This information will aid management of emesis in feline patients.

Topoisomerase IIα mediates TCF-dependent epithelial-mesenchymal transition in colon cancer.

Aberrant T-cell factor (TCF) transcription is implicated in the majority of colorectal cancers (CRCs). TCF transcription induces epithelial-mesenchymal transition (EMT), promoting a tumor-initiating cell (TIC) phenotype characterized by increased proliferation, multidrug resistance (MDR), invasion and metastasis. The data presented herein characterize topoisomerase IIα (TopoIIα) as a required component of TCF transcription promoting EMT. Using chromatin immunoprecipitation (ChIP) and protein co-immunoprecipitation (co-IP) studies, we show that TopoIIα forms protein-protein interactions with ß-catentin and TCF4 and interacts with Wnt response elements (WREs) and promoters of direct target genes of TCF transcription, including: MYC, vimentin, AXIN2 and LEF1. Moreover, both TopoIIα and TCF4 ChIP with the N-cadherin promoter, which is a new discovery indicating that TCF transcription may directly regulate N-cadherin expression. TopoIIα N-terminal ATP-competitive inhibitors, exemplified by the marine alkaloid neoamphimedine (neo), block TCF activity in vitro and in vivo. Neo effectively inhibits TopoIIα and TCF4 from binding WREs/promoter sites, whereas protein-protein interactions remain intact. Neo inhibition of TopoIIα-dependent TCF transcription also correlates with significant antitumor effects in vitro and in vivo, including the reversion of EMT, the loss of TIC-mediated clonogenic colony formation, and the loss of cell motility and invasion. Interestingly, non-ATP-competitive inhibitors of TopoIIα, etoposide and merbarone, were ineffective at preventing TopoIIα-dependent TCF transcription. Thus, we propose that TopoIIα participation in TCF transcription may convey a mechanism of MDR to conventional TopoIIα inhibitors. However, our results indicate that TopoIIα N-terminal ATP-binding sites remain conserved and available for drug targeting. This article defines a new strategy for targeted inhibition of TCF transcription that may lead to effective therapies for the treatment of CRC and potentially other Wnt-dependent cancers.

The effects of insulin on the turnover of glucose-6-phosphate dehydrogenase in epididymal adipose tissue of the rat.

The effects of insulin on the turnover of glucose-6-phosphate dehydrogenase in rat epididymal adipose tissue were studied by immunochemical technique in in vitro incubations. Insulin increased the relative rate of synthesis of glucose-6-phosphate dehydrogenase by two-fold in tissue obtained from normal rats. Insulin also had an effect on the rate of degradation of this enzyme. In the absence of insulin in the incubation medium the rate constant of degradation was 0.11 h-1 (half-life, 6.3 h). When insulin was added to the medium degradation of this enzyme was slowed. The new rate constant of degradation was 0.04 h-1 (half-life, 17 h). In the presence of insulin, the rate constant of degradation of total protein in adipose tissue was unchanged; therefore the effects of insulin on the degradation of glucose-6-phosphate dehydrogenase are specific to that protein and perhaps to a few other specific proteins.

Effects of glucose and nitrogen source on the levels of proteinases, peptidases, and proteinase inhibitors in yeast.

In Saccharomyces cerevisiae harvested from early exponential growth on glucose-containing media, the specifc activities of proteinases A and B, carboxypeptidase Y, and the inhibitors IA, IB, IC of these three proteinases, respectively, are found to be 10-30% of the specific activities observed in media without glucose, containing acetate as a carbon source; the activities of two aminopeptidases in glucose-grown cells were 30-50% of those in acetate-grown cells. In contrast to fructose-biphosphatase, phosoenolpyruvate carboxykinase, and cytoplasmic malate dehydrogenase, which are inactivated after the addition of glucose to derepressed cells, the proteinases and inhibitors are not inactivated after glucose addition, but appear to be repressed. Growth of the yeast on poor nitrogen sources or starvation for nitrogen results in 2-3 fold increases in the levels of most proteinases and peptidases, but this effect is not observed with glucose as the carbon source.

Preliminary crystallographic study of glucose-6-phosphate dehydrogenase from rat liver.

Crystals of D-glucose-6-phosphate: NADP+ oxidoreductase were obtained with the hanging drop, vapor diffusion and batch methods from ammonium sulfate-containing solutions. X-ray diffraction photographs indicate that the crystals belong to the orthorhombic space groups I222 or I2(1)2(1)2(1) with unit cell dimensions of a = 66.0 A, b = 140.8 A and c = 177.8 A. These data, together with results from sodium dodecyl sulfate/polyacrylamide gel electrophoresis and crystal density experiments, indicate that there is one 116,000 Mr dimer per asymmetric unit. The crystals diffract to at least 2.2 A and are suitable for X-ray crystallographic structure determination.

Effects of short-term use of nicotine gum in pregnant smokers.

OBJECTIVES: To compare blood concentrations of nicotine and cotinine and maternal and fetal hemodynamic effects resulting from use of nicotine gum versus cigarette smoking in pregnant smokers. METHODS: Pregnant women (24 to 36 weeks' gestation) who smoked chronically were randomly assigned with a 1:2 randomization scheme to either a group that smoked cigarettes (n = 10) or to a group that stopped smoking and chewed at least six pieces of nicotine gum (2 mg nicotine per piece) per day (n = 19). Blood nicotine and cotinine concentrations, maternal heart rate and blood pressure, uterine resistance index, and fetal heart rate and umbilical artery resistance index were obtained before and after one cigarette was smoked at baseline and after 5 continuous days of either chewing gum or smoking. RESULTS: A significant reduction from baseline in nicotine (p < 0.0001) and cotinine (p < 0.0025) concentrations was observed in those who chewed nicotine gum compared with those who smoked cigarettes. No significant differences in the changes in maternal or fetal hemodynamic parameters from baseline to estimated time of peak nicotine exposure were observed between those who smoked cigarettes and those who chewed nicotine gum. CONCLUSION: Short-term use of nicotine gum delivers less nicotine than usual cigarette smoking in pregnant women.

Sensitivity of a S. cerevisiae RAD27 deletion mutant to DNA-damaging agents and in vivo complementation by the human FEN-1 gene.

We have investigated the sensitivity to DNA-damaging agents of a strain of Saccharomyces cerevisiae containing a deletion of the RAD27 gene. The mutant strain is sensitive to a number of alkylating agents that modify DNA at a variety of positions, including one that produces primarily phosphotriesters. In contrast, the mutant strain is not sensitive to the oxidizing agent hydrogen peroxide. The introduction of a plasmid containing the FEN-1 gene (the human ortholog of the RAD27 gene) can substantially complement the sensitivity to alkylating agents observed in the mutant strain.

Comparative effects of thermal and surgical trauma on rat muscle protein metabolism.

A modified intraperitoneal pool flooding technique, employing L-3H-tyrosine, was developed for measuring muscle protein synthetic rates following traumatic injury. Sufficient radiolabeled tyrosine was injected intraperitoneally to effect a six-fold increase in plasma tyrosine concentration (124-800 microM) resulting in constant, sustained specific radioactivities in plasma- and intracellular-free tyrosine pools. Localized vs systemic effects of thermal and surgical trauma on gastrocnemius muscle protein turnover were assessed 2 and 4 days postinjury. Thermal trauma increased total, myofibrillar, and sarcoplasmic muscle protein synthesis (44%) and protein degradation (300%). Conversely, surgical trauma decreased synthesis of total (24%), myofibrillar (14%), and sarcoplasmic (43%) muscle proteins without altering protein degradation. Short-term restriction of pair-fed controls did not affect either aspect of protein turnover.

Muscle protein metabolism of rats in surgical trauma.

The effects of decreased food intake and degree of surgical trauma on total, myofibrillar and sarcoplasmic muscle protein synthesis and degradation were assessed in two experiments (A and B). Trauma consisted of an abdominal incision with or without hysterectomy. The degree of trauma in experiment B was increased relative to that in experiment A by extending the length of the incision, operative manipulation and time required to perform the surgery. To account for postoperative diminutions in food intake on protein turnover, a group of nonoperated rats were pair-fed to the level of food consumed by hysterectomized rats. Traumatized rats in experiment B lost more weight, ate less, and had a lower muscle total protein concentration than corresponding rats in experiment A, confirming a more severe trauma in experiment B. In both experiments, trauma depressed total protein content of muscle. Synthesis was measured by the incorporation of L-[U-14C] tyrosine from a single meal into total, sarcoplasmic and myofibrillar proteins of gastrocnemius muscle. Degradation was calculated as the difference between the growth rate and the synthetic rate. Synthetic rate (ks) of total protein was depressed by surgical trauma; the more severe the trauma, the greater the depression. In mild trauma, the depression in ks was due only to a decrease in sarcoplasmic protein synthesis (ke), whereas with more severe trauma, synthetic rates of both sarcoplasmic (kes) and myofibrillar (kem) proteins were decreased. Protein degradation (kd,) was increased on day 2 in experiments A and B, had returned to control values on day 4 in experiment A and had decreased below control values in experiment B.(ABSTRACT TRUNCATED AT 250 WORDS)

Postsurgical muscle protein turnover in perfused hindquarters of the rat.

Skeletal muscle protein synthesis and degradation were measured simultaneously in perfused hindquarters of adult female rats 0, 2, and 4 days after surgical trauma. In order to explore the role of decreased postoperative nutrient intake on muscle protein turnover, a group of rats were pair-fed to the level of food consumed by surgical traumatized animals. Protein synthesis was measured by the incorporation of 3H-L-phenylalanine into the myofibrillar (contractile) and sarcoplasmic (soluble) proteins of gastrocnemius muscle. Protein degradation rates were calculated from the release of myofibrillar 3-methyl histidine (3MH) during the perfusion. Surgical trauma significantly depressed myofibrillar and sarcoplasmic protein synthetic rates by 33 and 29%, respectively. Protein degradation, as assessed by 3MH release into perfusate, increased 25% on the second postoperative day but returned to control levels by the 4th day after surgery. Food restriction of the pair-fed control rats did not alter protein synthesis, however, protein degradation decreased significantly. In conclusion, the effect of trauma on protein turnover appears not to be due to decreased nutrient consumption.

Plasma lipoprotein changes in hens (Gallus domesticus) during an induced molt.

Blood plasma lipoproteins were studied during food and light deprivation or prolactin injection-induced involution of ovarian follicles (molt) of laying hens. Egg laying stopped 3 days after initiation of either treatment. Food and light-deprived hens lost 29% of initial body weight during the 10-day experiment (P < 0.05), whereas prolactin-treated hens lost 9% of body weight. Yolk-directed very low density lipoprotein (VLDLy) concentration in plasma decreased in both groups, but declined more rapidly in food and light-deprived hens. Very low density lipoprotein triacylglycerol decreased 40% in food and light-deprived hens by day 2 compared with a 13% decrease in the prolactin-treated hens. By day 5, a lipoprotein particle 21-22 nm in diameter appeared in the d = 1.019-1.046 g/ml density fraction of plasma in both groups. A similar lipoprotein particle, termed HDLR, developed in overfed hens with involuting ovarian follicles. In conclusion, hens undergoing ovarian regression due to food and light deprivation, prolactin treatment or overfeeding display marked decreases in plasma yolk-directed very low density lipoproteins and the appearance of HDLR. Other lipoprotein populations varied depending on whether the hens continued to feed or not.

An ELISA for quantification of murine IgG in rat plasma: application to the pharmacokinetic characterization of AP-3, a murine anti-glycoprotein IIIa monoclonal antibody, in the rat.

An enzyme-linked immunosorbent assay (ELISA) has been developed to determine concentrations of murine IgG in rat plasma. Specifically, the assay was developed to measure a murine anti-glycoprotein IIIa antibody (AP-3) in rat plasma to facilitate future investigations of AP-3 pharmacokinetics and pharmacodynamics in the rat. The working range of the assay is 15-100 ng ml(-1), corresponding to a limit of quantification of 1.5 microg ml(-1) in rat plasma. The assay was validated with respect to accuracy, precision, and cross-reactivity with both pooled rat and mouse IgG. Intra-assay recoveries of AP-3 in rat plasma ranged from 93 to 103%, with CV% values ranging from 5.2 to 8.5%. Inter-assay recoveries of the plasma AP-3 samples ranged from 107 to 119% with CV% values ranging from 17.7 to 25.1%. The assay has no appreciable cross reactivity with pooled rat IgG and full cross reactivity with pooled mouse IgG, making this an ideal assay to determine plasma pharmacokinetics of mouse antibodies in the rat. The assay was used to determine the pharmacokinetics of AP-3 in a Sprague-Dawley rat.

Current and future trends in demographics of veterinary medicine in California.

OBJECTIVE: To evaluate the present and future supply of veterinarians in California, in light of changing trends in animal ownership. DESIGN: Database analysis. SAMPLE POPULATION: Human and animal populations, including populations of veterinarians, throughout the United States. PROCEDURES: Data on animal and human populations were compiled from a number of sources, including the US Census Bureau, American Veterinary Medical Association, State of California Department of Finance, and State of California Veterinary Medical Board. The distribution of veterinarians in California was contrasted with other health professionals in California and with that of veterinarians in other states. Recent changes in veterinary medical demographics in California were quantified and used to develop in-state projections about the supply of veterinarians for the next 20 years. RESULTS: Although California is the most populous of the 50 states, only 7 states had fewer veterinarians per capita. Furthermore, California ranked next to last among states in increase of number of veterinarians between 1990 and 1995. Los Angeles County had the smallest per-capita number of veterinarians among 9 populous California counties. During that period, California had a net gain of only 6 veterinarians who were exclusively or predominantly large-animal or mixed-animal practitioners. CONCLUSIONS AND CLINICAL RELEVANCE: If current trends continue, the per-capita number of veterinarians will continue to decrease in California. To maintain the current ratio of 17.8 veterinarians/100,000 people in California in the future, we estimate that an additional 50 veterinarians above the currently predicted increase will be required annually.

Fatty liver hemorrhagic syndrome in hens overfed a purified diet. Selected enzyme activities and liver histology in relation to liver hemorrhage and reproductive performance.

A nutritionally adequate, purified diet was developed and used in studies to characterize selected aspects of laying hens in which fatty liver hemorrhagic syndrome (FLHS) was induced by overfeeding. Hens consuming the diet ad libitum or intubated with the diet in quantities equivalent to usual daily energy intake maintained normal rates of lay, did not become obese, and did not develop liver hemorrhage. Overfed hens had a 33% incidence of FLHS, as indicated by the presence of severe liver hemorrhage score, and displayed the full range of symptoms associated with spontaneous outbreaks of FLHS, including definitive lesions of hepatic reticulin. Among four groups of hens clinically classified according to rates of liver hemorrhage and egg production, there were no differences noted in total liver fat, liver fat concentration, or final body weight. Liver hemorrhage was associated with the degree of induction of liver lipogenic accessory enzymes. Serum enzyme activities indicate that overfed hens, unlike the overfed goose, retain hepatocellular membrane integrity. Overfeeding caused altered reproductive performance in 72% of hens. Alterations included erratic laying, increased incidence of double ovulations, shell defects, follicular collapse, and oviduct involution. Pattern of lay preceding necropsy seemed to influence follicle weight at necropsy. The data presented re-emphasize the interdependence among liver, ovary, and oviduct function in the etiology of FLHS.

Transfection of avian LMH-2A hepatoma cells with cationic lipids.

LMH-2A is an estrogen-responsive avian hepatoma cell line whose susceptibility to cationic-lipid-mediated transfection is poorly described. 3 beta[N-N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DCC) requires a one-step synthesis, and can be used to formulate transfection-grade liposomes when combined with dioleoylphosphatidyl-ethanolamine (DOPE) 1/1 (wt/wt). Luciferase activities in LMH-2A cells were 8.5-fold and 87.5-fold greater than those in HepG2 and FTO2B cells, respectively, following DCC-liposome-mediated transfection with a reporter consisting of the human cytomegalovirus immediate-early promoter (CMV), joined to Photinus pyralis luciferase (L) cDNA, designated pCMVL. Using pCMVL, N-(2-bromoethyl)-N,N-dimethyl-2,3-bis(9-octadecenyloxy)-propana minimun bromide) (BMOP)/DOPE 1/1 (wt/wt), at a 7.5:1 ratio with DNA, produced luciferase activities that were 2.9-fold higher than those of DCC-liposomes, at an optimal 10:1 lipid:DNA ratio. At optimal lipid:DNA ratios, commercially available liposomes, Transfectam, Lipofectamine, and Lipofectin, produced luciferase activities that were 1.39, 1.03, and 0.47-fold those of DCC-liposomes. The effect of 0, 10, 100, or 500 nM/L 17 beta-estradiol on the expression of pCMVL and a second luciferase reporter containing the -593/+48 promoter region of the estrogen-responsive avian apo VLDL-II gene, designated pApoL, was tested in cells cultured in the presence or absence of 10% chicken serum. The CMV promoter supported a high level of expression in LMH-2A cells that was unaffected by serum alone, but was weakly responsive to estrogen. Estrogen responses of both reporters reached a plateau at 10 nM/L. Estrogen increased the expression of pApoL 24-fold and 79-fold in the absence and presence of serum, respectively. The -593/+48 region of the apo VLDL-II promoter may not contain previously reported negative insulin response elements, but chicken serum contains factors that enhance estrogen responsiveness of this region.

Effect of divergent selection for total plasma phosphorus on plasma and yolk very low density lipoproteins and plasma concentrations of selected hormones in laying Japanese quail.

Japanese quail lines were divergently selected over 32 generations for laying hen plasma yolk precursor, as measured by total plasma phosphorus (TPP). The high (HP) and low (LP) lines were developed from a randombred control population (R1) that was maintained without conscious selection. The purpose of the present study was to characterize the composition of very low density lipoproteins (VLDL) in laying Japanese quail hens (VLDLy) and the concentration of selected hormones in laying hens from the HP, LP, and R1 lines. The changes in TPP because of genetic selection in the Japanese quail lines were associated with large alterations in plasma VLDLy concentration (HP > R1 > LP), but only minor changes in lipid composition and size (HP > LP = R1; P< or =0.01) of plasma VLDLy particles. Basal plasma levels of hormones associated with reproduction and lipid metabolism were also different among lines, with luteinizing hormone (LH) ranking HP >R1 = LP and triiodothyronine (T3), thyroxine (T4), and 17beta-estradiol ranking HP > R1 > LP (P< or =0.05). The results suggest possible increased rates of hepatic lipogenesis, hepatic VLDLy assembly and secretion, and plasma VLDLy concentration in association with increases in concentrations of plasma LH, T3, T4, and 17beta-estradiol. Concentrations of total lipids in yolk VLDL were not different among lines, and only minor line differences in the concentration of different classes of yolk VLDL neutral lipids were detected. The data indicate a preferential uptake of a specific plasma VLDLy subpopulation into rapidly growing ovarian follicles, resulting in a constant composition of yolk VLDL of laid eggs among lines of Japanese quail with large differences in plasma VLDLy concentration.

Innovations in mission architectures for exploration beyond low Earth orbit.

Through the application of advanced technologies and mission concepts, architectures for missions beyond Earth orbit have been dramatically simplified. These concepts enable a stepping stone approach to science driven; technology enabled human and robotic exploration. Numbers and masses of vehicles required are greatly reduced, yet the pursuit of a broader range of science objectives is enabled. The scope of human missions considered range from the assembly and maintenance of large aperture telescopes for emplacement at the Sun-Earth libration point L2, to human missions to asteroids, the moon and Mars. The vehicle designs are developed for proof of concept, to validate mission approaches and understand the value of new technologies. The stepping stone approach employs an incremental buildup of capabilities, which allows for future decision points on exploration objectives. It enables testing of technologies to achieve greater reliability and understanding of costs for the next steps in exploration.

Pharmacokinetics of cyclophosphamide after oral and intravenous administration to dogs with lymphoma.

BACKGROUND: Cyclophosphamide is an alkylating chemotherapeutic drug administered i.v. or p.o.. It is currently assumed that exposure to the active metabolite, 4-hydroxycyclophosphamide (4-OHCP), is the same with either route of administration. OBJECTIVES: To characterize the pharmacokinetics of cyclophosphamide and 4-OHCP in dogs with lymphoma when administered p.o. or i.v.. ANIMALS: Sixteen client-owned dogs with substage A lymphoma were enrolled in the study. Eight dogs received cyclophosphamide i.v. and 8 received it p.o.. METHODS: Prospective randomized clinical trial was performed. Blood was collected from each dog at specific time points after administration of cyclophosphamide. The serum was evaluated for the concentration of cyclophosphamide and 4-OHCP with mass spectrometry and liquid chromatography. RESULTS: Drug exposure to cyclophosphamide measured by area under the curve (AUC)(0-inf) is significantly higher after intravenous administration (7.14 ± 3.77 µg/h/mL) compared with exposure after oral administration (P-value < .05). No difference in drug exposure to 4-OHCP was detected after i.v. (1.66 ± 0.36 µg/h/mL) or p.o. (1.42 ± 0.64 µg/h/mL) administered cyclophosphamide. CONCLUSIONS AND CLINICAL IMPORTANCE: Drug exposure to the active metabolite 4-OHCP is equivalent after administration of cyclophosphamide either p.o. or i.v..

Induction of VEGF by tepoxalin does not lead to increased tumour growth in a canine osteosarcoma xenograft.

The purpose of this study was to determine the impact of the non-steroidal anti-inflammatory drug tepoxalin on canine tumour cell growth and describe the changes associated with tepoxalin treatment. In vitro experiments were performed to assess tepoxalin-associated alterations in tumour cell growth. Clinically achievable tepoxalin concentrations did not significantly alter tumour cell growth in vitro. Vascular endothelial growth factor (VEGF) production and hypoxia-inducible factor-1α dose-dependently increased in vitro in the presence of tepoxalin. A canine osteosarcoma xenograft was used to determine in vivo effects of tepoxalin on tumour growth and angiogenesis. Despite increased VEGF in vitro, there was a significant growth delay associated with tepoxalin treatment. Normal dogs were administered tepoxalin to assess effects on systemic VEGF production, but not found to have significantly increased VEGF. These data suggest that tepoxalin may moderately inhibit tumour growth and may be administered as an analgesic to tumour-bearing dogs.