Anallergenic is cost-saving when performing an elimination trial by CoreCPH

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Intro Knowledge & Respect Our signature sentence seemed appropriate for this last newsletter of the year because, as usual, fall was a period rich in congresses, and once again ROYAL CANIN® was well represented with many lectures and posters… some of which are in this edition. On the topic of scientific events in the fall, a short teaser: WINSS 2016 (WALTHAM™ International Nutritional Sciences Symposium) will take place next October… save the date! (see ad on the last page) Hélène Charles (R&D-Scientific Support)

Adverse Food Reaction Feeding ROYAL CANIN® Anallergenic is cost-saving when performing an elimination trial. The purpose of this study was to compare the cost of an elimination trial using either home-cooked diets or commercially available hydrolyzed protein-based diets. To diagnose Adverse Food Reaction (AFR), the standard procedure is to perform an elimination trial followed by provocation tests. The vet practitioner can either prescribe a home-cooked diet or a commercially available diet designed to cater for AFR, the most commonly used in France being hydrolyzed-protein diets.

Home-cooking is time consuming, but both owners and vet practitioners often think that it is the cheapest option. In this study, conducted by four boardcertified dermatologists, the ready-touse diet prescribed was ROYAL CANIN® Anallergenic (formulated with extensively hydrolyzed proteins) and the home-cooked diets were designed by a board-certified nutritionist to ensure that they were balanced. Sixty-four dogs were included in the randomised study and were fed either a home-cooked diet (30 dogs) or ROYAL CANIN® Anallergenic (34 dogs). For both diet types, all feeding costs were carefully detailed by the dog owner (grocery store invoices for home-cooked diets or buying costs for ROYAL CANIN® Anallergenic) and reported by the investigators. Two of the dogs fed the home-cooked diet were excluded from the cost comparison due to missing invoices. For the remaining 62 dogs, there were no significant differences between groups regarding age and bodyweight at inclusion or in the duration of the elimination trial. The daily cost of the home-cooked diet, standardized for a 20-kg dog, was significantly higher than the daily cost of ROYAL CANIN® Anallergenic (p=0.004) with a mean cost of 3.60 €/day (range: 1.14-8.5) and 2.60 €/day (range: 1.75-3.63) respectively.

Contrary to previous beliefs, feeding a home-cooked diet was more expensive than feeding a highly hydrolyzed protein-based diet. On top of being time-saving for the dog owner, ROYAL CANIN® Anallergenic might be the cost-saving choice when performing an elimination trial. Cadiergues M.C, Muller A, Bensignor E, Heripret D, Yaguiyan-Colliard L, Mougeot I. Cost evaluation of home-cooked and an extensively hydrolyzed diets during an elimination trial: a randomized prospective study. Proceedings of the 28th ESVD congress, Krakow (Poland), 24-26 September 2015.

Key numbers Elimination trial for a 20-kg dog

2.60 €/day with ROYAL CANIN®

Anallergenic vs 3.60 €/day with home-cooked diet

Mobility Science behind C2P+ cocktail: first in vitro study Curcuminoids extract (C), hydrolyzed collagen (O) and green tea extract (T) were added alone or combined (CT, CO, COT) at different doses to the chondrocyte cultures, and their effect on the production of “pro-OA mediators”, and on the expression of their coding genes, was measured.

The aim of this study was to assess the in vitro effects on normal and osteoarthritic chondrocytes of three promising compounds: curcuminoids extract, hydrolyzed collagen and green tea extract, either alone or combined to investigate a potential synergistic effect.

In the absence of IL-1β stimulation, there was no significant effect of any of the compounds tested on the N chondrocyte culture (NO and PGE2 were undetectable, no effect on gene expression); in OA chondrocytes none of the compounds, neither the combination, showed significant effects on NO and IL-6 production, while MMP-3 production was significantly decreased by C at the highest doses and COT at all doses (see figure1), with a synergistic effect of C, O and T in combination.

Cytokines like IL-1β play a key role in osteoarthritis (OA), by increasing the production of “pro-OA mediators” by chondrocytes: a large spectrum of proteolytic enzymes (MMP-3, ADAMTS4, ADAMTS5…) and a variety of other pro-inflammatory mediators (IL-6, NO, PGE2, COX2…). In this study, cultures of chondrocytes from either healthy or osteoarthritic articular cartilage (later referred to as N chondrocytes or OA chondrocytes respectively) were used, and the metabolic response of chondrocytes to OA was mimicked by adding IL-1β.

As expected, IL-1β significantly increased the gene expression and production of “proOA mediators” while decreasing those of aggrecans in control cultures.

Compounds effects, separately or in combination, on MMP-3 production by OA chondrocytes (without IL-1β)

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Available from: http://journals.plos.org/plosone/article?id=10.1371/journal. pone.0121654

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p<0.05 versus control p<0.001 versus control p<0.05 versus COT

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Altogether, these in vitro results indicate that the COT mixture (curcuminoids extract, hydrolyzed collagen and green tea extract) might reduce inflammation and pain in osteoarthritis by reducing the synthesis of inflammatory and catabolic mediators by chondrocytes. They provided a preclinical basis for the in vivo trial of the combination and its inclusion in the new ROYAL CANIN® Mobility C2P+ diet. Comblain F, Sanchez C, Lesponne I, Balligand M, Serisier S, Henrotin Y. Curcuminoids extract, hydrolyzed collagen and green tea extract synergically inhibit inflammatory and catabolic mediator’s synthesis by normal bovine and osteoarthritic human chondrocytes in monolayer. PLoS ONE. 2015;10(3):e0121654.

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In N chondrocytes, NO and PGE2 production and the gene expression of all “pro-OA mediators” were inhibited by C at the highest doses or in combination (COT), with a synergistic effect of COT on gene expression inhibition; at the highest dose T alone also significantly decreased IL-6 and COX2 expression. In OA chondrocytes, O significantly decreased NO production and C was once again the most efficient compound as it inhibited NO, IL-6 and MMP3 production. The COT combination inhibited all the “pro-OA mediators” and once again synergistic effects were seen.

IL-1β = interleukin-1β, NO = nitric oxide, PGE2 = prostaglandin E2, IL-6 = interleukin-6, COX2 = cyclooxygenase-2, iNOS = inducible nitric oxide synthase, MMP-3 = matrix metalloproteinase-3, ADAMTS4 = a disintegrin and metalloproteinase with thrombospondin type I motifs 4, ADAMTS5 = a disintegrin and metalloproteinase with thrombospondin type I motifs 5.

Urinary A CaOx RSS well below 1 does not allow calcium oxalate stone dissolution in vitro This study assessed the in vitro dissolution of calcium oxalate uroliths in a solution with CaOx RSS below 1. Relative Supersaturation (RSS) is considered as the gold standard methodology to measure the risk of crystal formation or dissolution in humans, and has been validated in dog and cat urine. This method is based on the saturation level of poorly soluble salts such as calcium oxalate or struvite. In cats and dogs, a struvite RSS below 1 is predictive of in vitro urolith dissolution. The aim of this study was to assess whether a calcium oxalate RSS (CaOx RSS) below 1 leads to in vitro urolith dissolution.

Over the 15 days of the study neither the canine nor the feline CaOx urolith lost any weight (see figures); although a low CaOx RSS may help prevent stone formation, further lowering CaOx RSS does not seem to be an effective lever to induce stone dissolution.

For struvite stones, the lower the RSS, the faster the dissolution; to maximize the potential effect in this study the lowest CaOx RSS possible was sought. Distilled water was chosen because, as it does not contain any electrolytes, its CaOx RSS is null (CaOx RSS = 0). One canine and one feline urolith analysed as 100% calcium oxalate were selected, their initial weights were 210 mg and 177 mg respectively. Each stone was immersed at day 0 in a bottle containing 30 mL of distilled water which was maintained at 38°C and stirred. 24 hours later, the content of the bottles was filtered to collect the stone, which was then dried and weighed. Every day the stones were placed in a new bottle with fresh distilled water and the procedure was repeated over a 15 day period to monitor the dissolution of the stones.

While a diet inducing a struvite RSS below 1 is efficient in dissolving struvite stones, the same strategy cannot be applied for calcium oxalate uroliths since even with the lowest CaOx RSS possible no dissolution occurred. CaOx stone dissolution remains an unreachable target with existing diets, hence the importance of stone prevention. Sagols E, Cuchet-Subsol C, Billy H, Biourge V. A low calcium oxalate RSS does not allow in vitro calcium oxalate stone dissolution. Proceedings of the 19th ESVCN congress, Toulouse (France), 17-19 September 2015.

Hot off the press!

Weight evolution of calcium oxalate (CaOx) stones over time with RSS=0 CANINE CaOx 250

RENAL

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Weight (mg)

New published article from the thesis of Rebecca Geddes on feline chronic kidney disease (see News from Research n°15)

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Geddes RF, Elliott J, Syme HM. Relationship between plasma Fibroblast Growth Factor-23 concentration and survival time in cats with chronic kidney disease. J Vet Intern Med. 2015 Nov 1;29(6):1494–501.

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Weight management Show dogs: not always exemplary regarding body condition

Dog owners often underestimate the body condition of their overweight (or obese) pet. Images of dogs in the media, especially of show dogs (assumed to be the “ideal” of their breed), might influence owner perception of optimal body shape. In this study, the same investigator (Dr Alex German) assessed the body condition of adult show dogs from photographs retrieved using an online search engine, as previously validated in a former study. 28 breeds were selected to be studied (14 obese-prone and 14 matched non-obese prone); a dog was eligible if it had placed between first and fifth in its class at a UK national dog show between 2001 and 2013. Of the 1120 photos retrieved, 960 were suitable for the body condition assessment: 74% of dogs scored as “ideal body condition” (BCS* 4-5/9) and 26% as “overweight” (BCS 6-9/9).

Overweight status was positively associated with dogs from the toy group and from 3 breeds: Labrador Retriever, Basset Hound and Pug; it was negatively associated with dogs from the utility group and from 6 breeds: Border Terrier, Boxer, Doberman, Hungarian Vizsla, Standard Poodle and Rhodesian Ridgeback. Disappointingly, being overweight did not seem to reduce the likelihood of a dog winning. Although overweight condition in show dogs is less prevalent than in the general pet population, these findings are still concerning given the widespread potential for dissemination of images through the media and their impact on owner perception of optimal body shape. Further efforts are now required to educate owners, breeders and show judges so that they can all better recognise an overweight condition, thus helping to prevent the development of obesity.

Key numbers

26% of the total show dog population,

80% of Pugs, 68% of Basset Hounds, and 63%

of Labrador Retrievers

are overweight

*BCS = Body Condition Score

Such ZR, German AJ. Best in show but not best shape: a photographic assessment of show dog body condition. Veterinary Record 2015;177(5):125. Available from: http://veterinaryrecord.bmj.com/content/177/5/125

Save the date 18-21 October 2016 Do you have a special interest in pet nutrition research? WINSS is a triennial symposium that combines plenary sessions from leading scientists with oral and poster free communications.

2016’s theme is ‘Growing Science in Pet Nutrition’ Scientific programme: - nutrient requirements - study methodology - growth - clinical nutrition ... and more, including workshops in the development of research careers! For more information, registration… please visit: https://www.waltham.com/events-news/winss-next-event/

WINSS

The aim of this study was to assess whether dog show winners were good examples of the ideal body condition of their breed, and determine factors associated with overweight.