Higher PBDE serum concentrations may be associated with feline hyperthyroidism in Swedish cats.

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.

Decabromobiphenyl, polybrominated diphenyl ethers, and brominated phenolic compounds in serum of cats diagnosed with the endocrine disease feline hyperthyroidism.

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.

Anti-VEGF agents confer survival advantages to tumor-bearing mice by improving cancer-associated systemic syndrome.

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.

Per- and polyfluoroalkyl substances (PFASs) in Swedish household dust and exposure of pet cats.

Per- and polyfluoroalkyl substances (PFASs) are used in a wide range of products and have been found ubiquitously in our indoor environment, and there is evidence that exposure to PFAS can lead to adverse endocrine effects, such as thyroid hormone disruption. Pet cats have a high dust intake due to their grooming behavior and have been shown to be a suitable sentinel species for assessment of toddler's exposure. Here we used paired household dust (n=46) and cat serum (n=27) samples to establish whether dust is a relevant exposure pathway to PFASs. An analytical method for PFAS analysis was optimized using a low volume of cat serum samples, combining solid-phase extraction and online sample cleanup. Dust was extracted with methanol by sonication and cleaned up by addition of active carbon. In total, 27 PFASs were analyzed by liquid chromatography/mass spectrometry analysis. The correlation between PFAS levels in dust and serum, serum lipids and thyroid hormone levels, and PFAS levels in dust between different rooms were statistically evaluated. PFOS and PFDA could be quantified in all cat serum samples (median 2300 pg/mL and 430 pg/mL, respectively), followed by PFOA (median 1100 pg/mL), quantified in 96% of the samples. The levels of 6:2 and 8:2 diPAPs were determined in 65% and 92% of the serum samples, respectively, and were an order of magnitude lower (1.4-160 pg/mL). Household dust on the other hand was dominated by 6:2 and 8:2 diPAPs, with a median of 65 ng/g dust and 49 ng/g dust, respectively. PFOS (median 13 ng/g dust) and PFOA (median 9 ng/g dust) were quantified in 93% of the dust samples. Only eight PFASs were detected (>LOD) in at least 50% of the samples of both matrices and could be paired. Significant correlations between cat serum and dust were found for PFOA (rS=0.32, p<0.049) and PFUnDA (rS=0.55, p<0.001). Significant positive correlations were found between serum total thyroxine (rS=0.11, p<0.05) and PFNA and between serum cholesterol and PFHpA (rS=0.46, p<0.01), PFUnDA (rS=0.40, p<0.05), PFDoDA (rS=0.44, p<0.01), and sum PFAS (rS=0.48, p<0.01). In conclusion, this study confirmed that dust is a relevant exposure pathway for the ingestion of some PFASs for cats, and the serum levels of PFASs could be of relevance for the cat's health.

Are persistent organic pollutants important in the etiology of feline hyperthyroidism? A review.

Feline hyperthyroidism is a rather new disease, first reported from the North American east coast in 1979. The prevalence is increasing, especially in older cats, and hyperthyroidism is now reported worldwide as the most common feline endocrinopathy. Several studies have been performed trying to identify important etiological factors such as exposure to persistent organic pollutants, and especially brominated flame retardants, have been suggested to be of importance for the development of the disease. Recent studies have shown higher concentrations of these contaminants in serum of hyperthyroid cats in comparison to cats with normal thyroid status. However, other still unknown factors are most probably of importance for the development of this disease.

Effects of carprofen on renal function and results of serum biochemical and hematologic analyses in anesthetized dogs that had low blood pressure during anesthesia.

OBJECTIVE: To investigate effects of IV administered carprofen on indices of renal function and results of serum biochemical and hematologic analyses in dogs anesthetized with acepromazine-thiopentone-isoflurane that had low blood pressure during anesthesia. ANIMALS: 6 healthy Beagles. PROCEDURE: A randomized crossover study was conducted, using the following treatments: saline (0.9% NaCl solution)-saline, saline-carprofen, and carprofen-saline. Saline (0.08 ml/kg) and carprofen (4 mg/kg) were administered IV. The first treatment was administered 30 minutes before induction of anesthesia and immediately before administration of acepromazine (0.1 mg/kg, IM). Anesthesia was induced with thiopentone (25 mg/ml, IV) and maintained with inspired isoflurane (2% in oxygen). The second treatment was administered 30 minutes after onset of inhalation anesthesia. Blood gases, circulation, and ventilation were monitored. Renal function was assessed by glomerular filtration rate (GFR), using scintigraphy, serum biochemical analyses, and urinalysis. Hematologic analysis was performed. Statistical analysis was conducted, using ANOVA or Friedman ANOVA. RESULTS: Values did not differ significantly among the 3 treatments. For all treatments, sedation and anesthesia caused changes in results of serum biochemical and hematologic analyses, a decrease in mean arterial blood pressure to 65 mm Hg, an increase of 115 pmol/L in angiotensin II concentration, and an increase of 100 seconds in time required to reach maximum activity counts during scintigraphy. CONCLUSIONS AND CLINICAL RELEVANCE: 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.

Validation of an enzyme-linked immunosorbent assay for measurement of feline serum insulin.

BACKGROUND: Feline insulin has been measured previously using assays developed for measuring human insulin. As feline insulin differs from human insulin, it is important to validate the assay before use. OBJECTIVES: The aims of this study were to validate an ELISA, the Mercodia Feline Insulin ELISA, intended for measuring feline insulin and to determine the stability of feline insulin in serum. METHODS: Validation of the ELISA, which uses monoclonal antibodies that recognize both human and feline insulin, included evaluation of coefficients of variation (CVs), patterns of variation, and consistency after dilution and spiking with feline insulin. Stability was evaluated by measuring insulin in feline serum samples stored at 20°C, 2-8°C, and -80°C. RESULTS: The intra-assay CV in 14-20 adjacent replicates (excluding position effects) was 2.0-4.2% and the inter-assay CV was 7.6-14%. The systematic and random position effect yielded a CV of 6.2-10%. When 3 feline serum samples were set at fixed positions and analyzed on 8 plates, microplate effects and interaction were significant for all 3 samples. Recovery upon dilution and spiking was 78-105% and 86-126%, respectively. Feline serum insulin concentration was stable for 24 hours at 20°C, for 4 days at 2-8°C, and for 15 months at -80°C. CONCLUSIONS: The Mercodia Feline Insulin ELISA can be used for measuring serum feline insulin. Recovery after spiking and dilution was acceptable. As in many ELISAs, intra-assay CV for adjacent replicates was low, whereas the position and between-assay CVs were considerably higher.

Low cortisol levels in blood from dairy cows with ketosis: a field study.

BACKGROUND: An elevated plasma glucose concentration has been considered to be a potential risk factor in the pathogenesis of left-displaced abomasums (DA). Therefore the present study was performed to investigate if spontaneous disease (parturient paresis, metritis, ketosis etc) in dairy cows results in elevated concentrations of glucose and cortisol in blood as cortisol is the major regulator of glucose in ruminants. METHODS: Cortisol, insulin, beta-hydroxybutyric acid (BHBA), non esterified fatty acids (NEFA), and serum calcium were analyzed in blood serum and glucose, in whole blood, from 57 spontaneously diseased cows collected at different farms. The cows were grouped according to the disease; parturient paresis, recumbent for other reasons, mastitis, metritis, ketosis, inappetance and others. RESULTS: No elevated concentrations of cortisol or glucose were found in cows with metritis and mastitis but both cortisol and glucose were elevated in cows stressed by recumbency. Cows with ketonemia (BHBA > 1.5 mmol/l) did not have low concentration of glucose in blood but significantly low levels of cortisol. Some of these cows even had cortisol concentrations below the detection limit of the analysing method (< 14 nmol/l). CONCLUSIONS: The study gives patho-physiological support to the treatment strategies of ketosis, recommending glucocorticoids, insulin etc. However further studies of this problem are needed to understand why cows with ketosis have low levels of cortisol and normal levels of glucose. To what extent elevated cortisol and glucose levels in hypocalcemic and recumbent cows are involved in the ethiology and /or the pathogenesis of DA also will need further research.

Subchronic toxicity of Baltic herring oil and its fractions in the rat II: Clinical observations and toxicological parameters.

This study aimed to increase the knowledge about the toxicity of fish-derived organohalogen pollutants in mammals. The strategy chosen was to separate organohalogen pollutants derived from Baltic herring (Clupea harengus) fillet, in order to obtain fractions with differing proportions of identified and unidentified halogenated pollutants, and to perform a subchronic toxicity study in rats, essentially according to the OECD guidelines, at three dose levels. Nordic Sea lodda (Mallotus villosus) oil, with low levels of persistent organohalogen pollutants, was used as an additional control diet. The toxicological examination showed that exposure to Baltic herring oil and its fractions at dose levels corresponding to a human intake in the range of 1.6 to 34.4 kg Baltic herring per week resulted in minimal effects. The spectrum of effects was similar to that, which is observed after low-level exposure to pollutants such as chlorinated dibenzo-p-dioxins and dibenzofurans (CDD/F) and chlorinated biphenyls, despite the fact that these contaminants contribute to a minor part of the extractable organically bound chlorine (EOCI). The study confirmed previous findings that induction of hepatic ethoxyresorufin deethylase (EROD) activity takes place at daily intake levels 0.15 ng fish-derived CDD/F-TEQs/kg body weight. The study also demonstrated that hepatic vitamin A reduction takes place at somewhat higher daily exposure levels, i.e. 0.16-0.30 ng fish-derived CDD/F-TEQs/kg body weight. Halogenated fatty acids, the major component of EOCI, could not be linked to any of the measured effects. From a risk management point of view, the study provides important new information of effect levels for Ah-receptor mediated responses following low level exposure to organohalogen compounds from a matrix relevant for human exposure.