The underlying mechanism by which anti-VEGF agents prolong cancer patient survival is poorly understood. We show that in a mouse tumor model, VEGF systemically impairs functions of multiple organs including those in the hematopoietic and endocrine systems, leading to early death. Anti-VEGF antibody, bevacizumab, and anti-VEGF receptor 2 (VEGFR-2), but not anti-VEGFR-1, reversed VEGF-induced cancer-associated systemic syndrome (CASS) and prevented death in tumor-bearing mice. Surprisingly, VEGFR2 blockage improved survival by rescuing mice from CASS without significantly compromising tumor growth, suggesting that “off-tumor” VEGF targets are more sensitive than the tumor vasculature to anti-VEGF drugs. Similarly, VEGF-induced CASS occurred in a spontaneous breast cancer mouse model overexpressing neu . Clinically, VEGF expression and CASS severity positively correlated in various human cancers. These findings define novel therapeutic targets of anti-VEGF agents and provide mechanistic insights into the action of this new class of clinically available anti-VEGF cancer drugs.

The results of this study support and extend those in several earlier reports and show that cats in New Zealand are, in many respects, similar to cats in Europe and North America in terms of their susceptibility to hyperthyroidism. The finding that female cats are predisposed to hyperthyroidism is at variance with most previously published work. It remains unclear which, if any, of the identified disease associations are causal, so further studies of this increasingly prevalent feline endocrinopathy are warranted.

Summary The interrelationships between clinical, clinicopathological and morphological findings were studied in 17 cases of equine granulomatous enteritis (GE) and 19 cases of equine eosinophilic granulomatosis (EG) in order to define criteria for clinical diagnosis and to elucidate pathophysiological events in these disorders. Both diseases were marked by progressive wasting and hypoalbuminaemia. They occurred sporadically and showed a predilection for 1‐ to 4 year‐old standardbreds. Excessive protein loss into the gastrointestinal tract was demonstrable by 51Cr‐albumin in both disorders. Serum immunoglobulin levels varied greatly. Significant deviations of mean levels included low IgG(T) in both groups, low IgM in GE and low IgG in EG. D‐xylose absorption was poor in GE, reflecting the villous atrophy of the small bowel in the disease, whereas it was quantitatively unimpaired but tended to be delayed in EG. Diarrhoea was common in EG (14 out of 19 cases) and less frequent in GE (4/17), a difference partly explained by differing major disease sites in the gut (large bowel in EG, small bowel in GE). Marked cholangitis and cholangiohepatitis often occurred in EG, being reflected in some animals by high levels of gammaglutamyltranspeptidase and the appearance of a bile duct isoenzyme of alkaline phosphatase in the serum. Several horses in the EG group showed severe dermatopathy, often including coronitis and loss of chestnuts, whereas severe skin lesions were only occasionally found in the GE series. Anaemia was often present in GE (11/17) but rare in EG (1/19). The study indicated that, although clinical and laboratory findings in EG and GE show much overlap, several features that help to distinguish between the two disorders in the live animal do exist. The results are discussed in the light of possible pathophysiological and pathogenetic mechanisms. Zusammenfassung Klinische und pathophysiologische Merkmale der granulomatösen Enteritis und der eosinophilen Granulomatose beim Pferd Die wechselseitigen Beziehungen zwischen klinischen, klinisch‐pathologischen und morphologischen Befunden wurden in 17 Fällen von equiner granulomatöser Enteritis (GE) und in 19 Fällen von equiner eosinophiler Granulomatose (EG) untersucht, um Kriterien für die klinische Diagnose zu definieren und um die pathophysiologischen Abläufe bei diesen Störungen zu klären. Beide Krankheiten waren gekennzeichnet durch eine progressive Verschlechterung und Hypoalbuminämie. Sie traten sporadisch auf und zeigten eine Prädilektion für ein bis vier Jahre alte Traber. Mit Hilfe von 51Cr‐albumin ließ sich bei beiden Störungen ein exzessiver Proteinverlust in den Gastrointestinaltrakt nachweisen. Die Serumimmunglobulinkonzentrationen variierten erheblich. Signifikante Abweichungen von durchschnittlichen Konzentrationen betrafen in beiden Gruppen die erniedrigten IgG(T), sowie die niedrigen IgM bei der GE und die niedrigen IgG bei der EG. Die schlechte d‐Xylose‐Absorption bei der GE widerspiegelt die Atrophie der Darmzotten im Dünndarm. Bei der EG war di...

Serum from 82 individual cats was analyzed for decabromobiphenyl (BB-209), polybrominated diphenyl ethers (PBDEs), hydroxylated PBDEs (OH-PBDEs), and 2,4,6-TBP in order to study differences in body burden between healthy and sick cats diagnosed with Feline Hyperthyroidism (FH). Within the study group, 60 of these cats had a euthyroid (n = 23) or hyperthyroid (n = 37) status, all of which were used in the comparison. This study shows that hyperthyroid compared to euthyroid cats have higher serum concentrations for some of the investigated PBDEs (BDE-99, BDE-153, and BDE-183) and CB-153 on a fat weight basis. Further, it is intriguing, and beyond explanation, why the flame retardant BB-209 (discontinued in 2000) is present in all of the cat serum samples in concentrations similar to BDE-209. Median BDE-47/-99 ratios are 0.47 and 0.32 for healthy and euthyroid cats, respectively, which differs significantly from Swedes, where the ratio is 3.5. Another important finding is the occurrence of very low levels or the absence of hydroxylated PBDE metabolites in the cats. In addition, the major OH-PBDE, 6-OH-BDE47, is likely of natural origin, probably ingested via cat food. The statistics indicate an association between elevated PBDE concentrations in the cats and FH.

Pet cats may be used as a biomarker for assessing exposures to organohalogen compounds (OHCs) adsorbed to household dust in home environments. This study explores two exposure routes of OHCs, ingestion of OHCs (i) via house dust and (ii) via cat food. House dust from 17 Swedish homes and serum from the participating families' pet cats were collected, and cat food was purchased matching the diet reported. Paired samples of cat serum, house dust, and cat food were analyzed for brominated flame retardants/natural products (polybrominated diphenyl ethers (PBDEs), decabromobiphenyl (BB-209), decabromodiphenyl ethane (DBDPE), 2,4,6-tribromophenol (2,4,6-TBP), OH-PBDEs) and organochlorines (polychlorinated biphenyls (PCBs), 1,1-bis(4,4'-dichlorodiphenyl)-2,2,2-trichloroethane (4,4'-DDT), 1,1-bis(4,4'-dichlorodiphenyl)-2,2-dichloroethene (4,4'-DDE), hexachlorobenzene (HCB), pentachlorophenol (PCP)). Significant correlations were found between serum and dust samples from the living rooms for BDE-47 (p < 0.035), BDE-99 (p < 0.035), and BDE-153 (p < 0.039), from the adult's bedroom for BDE-99 (p < 0.019) and from all rooms for BDE-99 (p < 0.020) and BB-209 (p < 0.048). This is the first time a correlation between cat serum levels and household dust has been established, a finding that supports the hypothesis that dust is a significant exposure route for cats. Serum levels were also significantly correlated with concentrations found in cat food for 6-OH-BDE47 (p < 0.002), 2,4,6-TBP (p < 0.035), and BB-209 (p < 0.007). DBDPE was found in high concentrations in all dust (median 154 pmol/g) and food samples (median 0.7 pmol/g lw) but was below detection in serum samples, suggesting low or no bioavailability for DBDPE in cats.

Carprofen administered IV before or during anesthesia did not cause detectable significant adverse effects on renal function or results of serum biochemical and hematologic analyses in healthy Beagles with low blood pressure during anesthesia.

The incidence of cats being diagnosed with feline hyperthyroidism (FH) has increased greatly since it was first described in 1979. The cause of FH has not been established. Hypothetically, there is a link between increasing FH and exposure to brominated flame retardants. Much greater polybrominated diphenyl ethers (PBDE) concentrations have been reported in cat serum compared with human serum, likely due to cat licking behaviour. This study aimed to extend the present identification of brominated compounds in cat serum, with a focus on hydroxylated metabolites of PBDE, to improve the understanding of feline metabolism of PBDEs. A pooled serum sample from 30 Swedish pet cats with FH was analysed, and brominated species were identified. The results showed exposure to the discontinued flame retardant decabromobiphenyl (BB-209) and technical penta- and octa-BDEs. Altogether 12 PBDE congeners were identified along with 2'-MeO-BDE68. Furthermore, 2,4-dibromophenol, 2,4,6-, 2,4,5- and 2,3,4-tribromophenol plus 2'-OH-BDE68, 6-OH-BDE47, 5-OH-BDE47, 4'-OH-BDE49 were identified. 2,4,6-tribromophenol and 6-OH-BDE47 were the most prominent species in cat serum. Considering that these are natural products, it can be concluded that metabolism of PBDEs to OH-PBDEs is not a major route of PBDE elimination in cats. It is notable that BB-209, 6-OH-BDE47, and 2,4,6-tribromophenol all suggested that endocrine-disrupting chemicals were present in high concentrations in cat serum.

No abstract