Copper-associated chronic hepatitis in Cavalier King Charles spaniels.

BACKGROUND: Copper-associated chronic hepatitis (CuCH) is poorly characterised in Cavalier King Charles spaniels (CKCS). METHODS: Hepatic copper accumulation was qualitatively and quantitatively assessed, and blood samples were used for genetic testing to screen for known CuCH-associated genetic variants. RESULTS: The study included 13 CKCS with CuCH and eight unaffected controls. Increased transaminase activities, elevated biliary enzyme concentrations and portal hypertension were documented in 100%, 73% and 38% of dogs with CuCH, respectively. Five dogs had three or more abnormalities in measures of liver function. All 11 dogs with CuCh that underwent genetic testing were homozygous negative for the COMMD1 deletion and ATP7A variant but homozygous positive (n = 7) or heterozygous (n = 4) for the ATP7B variant. Liver histology often demonstrated marked architectural distortion by severe, bridging fibrosis and regenerative nodules with lymphoplasmacytic inflammation. Centrilobular copper accumulation characterised early cases with minimal fibrosis. When fibrosis was significant, copper was often differentially concentrated within regenerative nodules. Chelation therapy resolved laboratory derangements and portal hypertension in five of seven dogs. Of the 7 non-surviving dogs with CuCH, 6 had not received chelation therapy. LIMITATIONS: Limitations include a small cohort size and the lack of pedigree analyses to corroborate heritability. CONCLUSIONS: CuCH should be considered in CKCS with suspected liver disease. Long-term prognosis seems favourable in dogs receiving chelation therapy, notwithstanding the presence of previously reported negative prognostic markers.

ß-Alanine Supplementation Attenuates the Neurophysiological Response in Animals Exposed to an Acute Heat Stress.

The effect of 30 days of ß-alanine supplementation on neurophysiological responses of animals exposed to an acute heat stress (HS) was examined. Animals were randomized to one of three groups; exposed to HS (120 min at 40-41 °C) and fed a normal diet (EXP; n = 12); EXP and supplemented with ß-alanine (EXP + BA; n = 10); or not exposed (CTL; n = 10). Hippocampal (CA1, CA3 and DG) and hypothalamic (PVN) immunoreactive (ir) cell numbers of COX2, IBA-1, BDNF, NPY and HSP70 were analyzed. Three animals in EXP and one in EXP-BA did not survive the HS, however no significant difference (p = 0.146) was noted in survival rate in EXP + BA. The % change in rectal temperature was significantly lower (p = 0.04) in EXP + BA than EXP. Elevations (p's < 0.05) in COX-2, IBA-1 and HSP70 ir-cell numbers were noted in animals exposed to HS in all subregions. COX-2 ir-cell numbers were attenuated for EXP + BA in CA1 (p = 0.02) and PVN (p = 0.015) compared to EXP. No difference in COX-2 ir-cell numbers was noted between CTL and EXP + BA at CA1. BDNF-ir cell numbers in CA1, DG and PVN were reduced (p's < 0.05) during HS compared to CTL. No difference in BDNF-ir cell numbers was noted between EXP + BA and CTL in CA3 and PVN. NPY-ir density was reduced in exposed animals in all subregions, but NPY-ir density for EXP-BA was greater than EXP in CA3 (p < 0.001) and PVN (p = 0.04). ß-Alanine supplementation attenuated the thermoregulatory and inflammatory responses and maintained neurotrophin and neuropeptide levels during acute HS. Further research is necessary to determine whether ß-alanine supplementation can increase survival rate during a heat stress.

Astaxanthin supplementation impacts the cellular HSP expression profile during passive heating.

Astaxanthin is a powerful carotenoid antioxidant prevalent in marine organisms and approved as a food supplement. Recent studies have demonstrated Astaxanthin's beneficial attributes in various health states. Following initial reports of potential heat protective properties in Astaxanthin supplemented rats, we present here results of a novel study examining the effect of Astaxanthin supplementation on the heat shock response in rats in relation to core temperature (Tc) and the ensuing physiological strain. Two hours of heat stress at 41 °C during which rats developed their thermoregulatory hyperthermic plateau resulted in progressive increases in HSP72 and HSP27 in the Astaxanthin (Oleoresin)-treated group but not in the control (Olive oil) group. Enhanced elevation in HSPs suggests that Astaxanthin supplementation may augment the cellular stress protective response to heat stress.