Canine Mucosal Artificial Colon: development of a new colonic in vitro model adapted to dog sizes.

Differences in dog breed sizes are an important determinant of variations in digestive physiology, mainly related to the large intestine. In vitro gut models are increasingly used as alternatives to animal experiments for technical, cost, societal, and regulatory reasons. Up to now, only one in vitro model of the canine colon incorporates the dynamics of different canine gut regions, yet no adaptations exist to reproduce size-related digestive parameters. To address this limitation, we developed a new model of the canine colon, the CANIne Mucosal ARtificial COLon (CANIM-ARCOL), simulating main physiochemical (pH, transit time, anaerobiosis), nutritional (ileal effluent composition), and microbial (lumen and mucus-associated microbiota) parameters of this ecosystem and adapted to three dog sizes (i.e., small under 10 kg, medium 10-30 kg, and large over 30 kg). To validate the new model regarding microbiota composition and activities, in vitro fermentations were performed in bioreactors inoculated with stools from 13 dogs (4 small, 5 medium, and 4 large). After a stabilization period, microbiota profiles clearly clustered depending on dog size. Bacteroidota and Firmicutes abundances were positively correlated with dog size both in vitro and in vivo, while opposite trends were observed for Actinobacteria and Proteobacteria. As observed in vivo, microbial activity also increased with dog size in vitro, as evidenced from gas production, short-chain fatty acids, ammonia, and bile acid dehydroxylation. In line with the 3R regulation, CANIM-ARCOL could be a relevant platform to assess bilateral interactions between food and pharma compounds and gut microbiota, capturing inter-individual or breed variabilities. KEY POINTS: • CANIM-ARCOL integrates main canine physicochemical and microbial colonic parameters • Gut microbiota associated to different dog sizes is accurately maintained in vitro • The model can help to move toward personalized approach considering dog body weight.

Bromide toxicosis (bromism) secondary to a decreased chloride intake after dietary transition in a dog with idiopathic epilepsy: a case report.

BACKGROUND: Bromide is a halide ion of the element bromine usually administered in the form of potassium salt as monotherapy or add-on treatment in epileptic dogs. It is excreted unchanged in the urine and undergoes tubular reabsorption in competition with chloride. Thus, dietary chloride content affects serum bromide concentrations. This is the first published clinical report of bromide toxicosis secondary to a dietary modification of chloride content in an epileptic dog treated with potassium bromide. CASE PRESENTATION: A 3-year-old 55-kg neutered male Tibetan Mastiff was evaluated because of a 1-month history of progressive signs including ataxia, lethargy and behaviour changes. The dog was successfully treated for idiopathic epilepsy since the age of 1-year-old with phenobarbital and potassium bromide. Two months prior to presentation, the owners decided to change the dog's diet without veterinary advice. Physical examination was unremarkable. A 12-kg weight gain was recorded since last follow-up (8 months). Neurological examination revealed severe symmetric 4-limbs ataxia with altered vigilance and intermittent episodes of hyperactivity and aggressive behaviour without significant abnormality of cranial nerves. Serum bromide concentration was high and increased by 103 % since last follow-up. Nutritional evaluation revealed a 53 % decrease of chloride content in the diet before and after dietary transition. Bromide toxicosis was suspected, due to bromide reduced clearance secondary to the decreased dietary chloride content. Potassium bromide treatment was lowered by 15 % without further dietary changes. Neurologic signs progressively improved over the next month, without any seizure. After two months, the serum bromide concentration lowered to the same level measured before dietary modification. After four months, neurological examination was unremarkable. CONCLUSIONS: Dietary chloride content can directly influence serum bromide concentrations, therefore affecting seizure control or contributing to unexpected adverse effects. In the present case, a reduction in chloride intake markedly increased serum bromide concentrations causing bromism. Dietary changes should be avoided in dogs treated with potassium bromide to maintain stable serum bromide levels.

Relationship between a plant-based 'vegan' pet food and clinical manifestation of multiple nutrient deficiencies in two cats.

A topical subject in human nutrition is the steadily growing number of people choosing to limit or completely avoid all animal-derived food products either for moral dilemma, health concerns or both. To meet people's will of applying their dietary choices to their domestic animals, the pet food industry answered by launching on the market some plant-based diets. This leads to concerns about whether these diets are adequately formulated to satisfy the target species nutritional requirements, especially for cats which are still considered strict carnivores. This case report follows a 2-year-old male neutered Main Coon and a 1-year-old female spayed Domestic Shorthair cat, presented to the nutrition service of the University of Toulouse, France. Reason for consultation was lethargy with in anamnesis a recent dietary transition to a plant-based pet food. Dysorexia, lethargy and muscle waste were present at first consultation. Progressive weight loss developed during follow-ups. A macrocytic, non-regenerative anaemia with serum folates below reference were the main clinical features. Analysis of pet food showed multiple nutrients below minimum recommendation at the average daily intake of both cats. Folic acid supplementation improved dysorexia, and subsequent reintroduction of animal-derived ingredients in the diet restored appetite, weight and a normal mentation in both cases.

Dietary regimen of the woodpigeon (Columba palumbus).

Recently, new agricultural policies and European Directives brought to important changes in farming practice, some of which could affect food availability for the wild bird population endangering biodiversity. This study aims to evaluate the consequences of such agricultural changes in France on the woodpigeon's dietary regimen. A total of 1,093 woodpigeons were collected over a four-year period (2014-2017). Voluntary sampling was performed in six regions in the south-west of France by local hunters during this species' autumnal migration and wintering. Ingluvies contents were recovered, macroscopically and microscopically identified, and then weighed before and after drying. Five food groups were identified: acorns, corn, green plant material, cultivated seeds and others. ANOVA testing followed by Tukey's test for multiple comparison were performed (R version 3.5.2). Significance was set at p < .05. A total of 762 woodpigeons met the study's inclusion criteria. Mean weight of total crop contents was less of 9 grams of dry matter. Most frequent food groups were "green plant material" (70.3%), acorns (42.3%) and corn (27.2%). In terms of grams of dry matter, the most important food in the crop content were acorns (62%): these were eaten more during the first two hunting seasons (p < .001), and in region A, lower amount was consumed compared to all other regions. On the contrary, corn intake peaked during the third year (p < .001), and in region A, birds had an increasing intake of this cereal. Cultivated seeds contributed to the diet more during migration (p = .007), while "green plant material" and others more during wintering (p = .011; p = .004). In conclusion, results confirm the opportunistic nature of the woodpigeon, balancing its diet according to food availability. Corn was eaten more in areas where the winter burying of chopped maize stover (mulching), provided by the Nitrate's directive, was in derogation.

Characterization of GMO or glyphosate effects on the composition of maize grain and maize-based diet for rat feeding.

INTRODUCTION: In addition to classical targeted biochemical analyses, metabolomic analyses seem pertinent to reveal expected as well as unexpected compositional differences between plant genetically modified organisms (GMO) and non-GMO samples. Data previously published in the existing literature led to divergent conclusions on the effect of maize transgenes on grain compositional changes and feeding effects. Therefore, a new study examining field-grown harvested products and feeds derived from them remains useful. OBJECTIVES: Our aim was to use a metabolomics approach to characterize grain and grain-based diet compositional changes for two GMO events, one involving Bacillus thuringiensis toxin to provide insect resistance and the other one conferring herbicide tolerance by detoxification of glyphosate. We also investigated the potential compositional modifications induced by the use of a glyphosate-based herbicide on the transgenic line conferring glyphosate tolerance. RESULTS: The majority of statistically significant differences in grain composition, evidenced by the use of 1H-NMR profiling of polar extracts and LC-ESI-QTOF-MS profiling of semi-polar extracts, could be attributed to the combined effect of genotype and environment. In comparison, transgene and glyphosate effects remained limited in grain for the compound families studied. Some but not all compositional changes observed in grain were also detected in grain-based diets formulated for rats. CONCLUSION: Only part of the data previously published in the existing literature on maize grains of plants with the same GMO events could be reproduced in our experiment. All spectra have been deposited in a repository freely accessible to the public. Our grain and diet characterization opened the way for an in depth study of the effects of these diets on rat health.

Low doses of bisphenol A induce gene expression related to lipid synthesis and trigger triglyceride accumulation in adult mouse liver.

UNLABELLED: Changes in lifestyle are suspected to have strongly influenced the current obesity epidemic. Based on recent experimental, clinical, and epidemiological work, it has been proposed that some food contaminants may exert damaging effects on endocrine and metabolic functions, thereby promoting obesity and associated metabolic diseases such as nonalcoholic fatty liver disease (NAFLD). In this work, we investigated the effect of one suspicious food contaminant, bisphenol A (BPA), in vivo. We used a transcriptomic approach in male CD1 mice exposed for 28 days to different doses of BPA (0, 5, 50, 500, and 5,000 µg/kg/day) through food contamination. Data analysis revealed a specific impact of low doses of BPA on the hepatic transcriptome, more particularly on genes involved in lipid synthesis. Strikingly, the effect of BPA on the expression of de novo lipogenesis followed a nonmonotonic dose-response curve, with more important effects at lower doses than at the higher dose. In addition to lipogenic enzymes (Acc, Fasn, Scd1), the expression of transcription factors such as liver X Receptor, the sterol regulatory element binding protein-1c, and the carbohydrate responsive element binding protein that govern the expression of lipogenic genes also followed a nonmonotonic dose-response curve in response to BPA. Consistent with an increased fatty acid biosynthesis, determination of fat in the liver showed an accumulation of cholesteryl esters and of triglycerides. CONCLUSION: Our work suggests that exposure to low BPA doses may influence de novo fatty acid synthesis through increased expression of lipogenic genes, thereby contributing to hepatic steatosis. Exposure to such contaminants should be carefully examined in the etiology of metabolic diseases such as NAFLD and nonalcoholic steatohepatitis.

The Perception of the Body Condition of Cats and Dogs by French Pet Owners and the Factors Influencing Underestimation.

Managing pet obesity relies heavily on the active involvement of owners; however, a key challenge arises from misperceptions about their own pet's body condition. Given evolving societal dynamics like the body positivity movement, understanding owners' perceptions is increasingly pivotal. To evaluate the differences in owners' perception, this study compared the use of verbal and visual body condition score scales versus the established nine-point body condition score system. The factors linked to underestimation were further specifically investigated. Owners of healthy adult dogs and cats attending vaccination consultations in Veterinary Hospitals in France between 2020 and 2022 were recruited. They were required to assess their pets' body condition initially using an oral description and then with the nine-point BCS visual scale. Their assessments were then compared with the BCS determined by veterinary health care personnel, considered the primary investigator. A total of 304 dogs and 270 cats were included in the study. It was observed that 27% of dog owners and 24% of cat owners underestimated their pets' body condition. Among dog and cat owners, factors associated with the underestimation of body condition were the pets' overweight status and having children. This discovery emphasizes the need for a holistic One Health approach that prioritizes the health and well-being of both humans and their pets. When it comes to pet owners evaluating their pets' body condition, underestimation proved to be the predominant misperception. Addressing this issue requires comprehensive education to empower owners to recognize and comprehend their pets' overweight status, a critical step for the overall well-being of companion animals.

Two Cases of Suspected Poisoning With Goat's Rue (Galega officinalis L.) in Horses.

The present report describes two novel cases of suspected intoxication with Galega officinalis in 6- and 21-year-old Arabian mares displaying acute respiratory signs. Both animals showed signs of pulmonary edema at physical examination, with the oldest of the two also manifesting severe dyspnea and foamy nasal discharge. The mares were grazing on the same meadow with hay available ad libitum. Botanical analysis of the latter showed traces of the toxic plant Galega officinalis (L.), which has been daily ingested at a dose of around 14 g of dry matter for three days. Based on the respiratory signs and the presence of goat's rue in the mares' feed, a presumptive diagnosis of plant poisoning was assumed. Dietary change and treatment allowed the 6-year-old mare to fully recover in 3 days while a longer period of about 2 weeks was necessary for the older horse. Horses avoid eating fresh goat's rue as its palatability is low, yet poisoning may still happen in these species when the plant is found in dried and processed feed material.

In vitro models of the canine digestive tract as an alternative to in vivo assays: Advances and current challenges.

Dogs occupy a full place in the family, and their well-being is of paramount importance to their owners. Digestion, a complex process involving physicochemical, mechanical, and microbial parameters, plays a central role in maintaining canine health. As in vivo studies in dogs are increasingly restricted by ethical, regulatory, societal, and cost pressures, an alternative option is the use of in vitro models simulating the different compartments of the canine gastrointestinal tract. This review introduces digestion and gut microbiota as key factors in dog nutrition and health under both healthy and diseased conditions (obesity and inflammatory bowel disease) and highlights similarities and differences between the human and canine digestive tract and processes. We provide the first in-depth description of currently available models of the canine digestive tract, discuss technical and scientific challenges that need to be addressed, and introduce potential applications of in vitro gut models in the food and veterinary fields. Even if the development of some in vitro models is still limited by a lack of in vivo data in dogs that is necessary for relevant configuration and validation, translation of long-term expertise on human in vitro gut models to dogs opens avenues for model optimization and adaptation to specific canine digestive conditions associated with various dog ages, sizes, breeds and/or diets, in both physiological and diseased states.

From Chihuahua to Saint-Bernard: how did digestion and microbiota evolve with dog sizes.

Health and well-being of dogs are of paramount importance to their owners. Digestion plays a key role in dog health, involving physicochemical, mechanical and microbial actors. However, decades of breeding selection led to various dog sizes associated with different digestive physiology and disease sensitivity. Developing new products requires the consideration of all the multi-faceted aspects of canine digestion, the evaluation of food digestibility, drug release and absorption in the gut. This review paper provides an exhaustive literature survey on canine digestive physiology, focusing on size effect on anatomy and digestive parameters, with graphical representation of data classified as "small", "medium" and "large" dogs. Despite the huge variability between protocols and animals, interesting size effects on gastrointestinal physiology were highlighted, mainly related to the colonic compartment. Colonic measurements, transit time permeability, fibre degradation, faecal short-chain fatty acid concentration and faecal water content increase while faecal bile acid concentration decreases with body size. A negative correlation between body weight and Proteobacteria relative abundance was observed suggesting an effect of dog body size on faecal microbiota. This paper gathers helpful in vivo data for academics and industrials and supports the development of new food and pharma products to move towards canine personalized nutrition and health.

Managing Feline Idiopathic Hypercalcemia With Chia Seeds (Salvia hispanica L.): A Case Series.

Background: We describe for the first time the use of chia seeds (Salvia hispanica L.) as a non-pharmacological solution in managing feline idiopathic hypercalcemia when dietary change alone fails. Case Summary: Over a 2-year period of time, three female spayed, middle-aged, Domestic Shorthair cats were diagnosed with idiopathic hypercalcemia. Reason for consultation were lethargy and dysorexia, with a single episode of vomiting described in one cat and dysuria in another. Thorough diagnostic work-up included complete blood count, serum biochemistry, urinalysis, ionized calcium, calcemic hormones, parathyroid hormone-related protein, and imaging of chest and abdomen. Based on different nutritional reasons, each cat was switched to a different high-moisture pet food as first-step in managing the disorder: a high-fiber diet, a diet formulated for chronic kidney disease management and a diet designed to prevent calcium oxalate urolithiasis. In the three cats, 6 weeks of dietary change alone did not result in normocalcemia. Before resorting to any pharmacological solution, supplementation to the diet of chia seeds (2 g/cat/day) was started. After 4 weeks from the introduction of Salvia hispanica L., all cats achieved normalization of ionized calcium concentration. Conclusion: Chia seeds (Salvia hispanica L.) supplementation could be a useful tool in managing feline idiopathic hypercalcemia.

Appetite-stimulating effect of gabapentin vs mirtazapine in healthy cats post-ovariectomy.

OBJECTIVES: The aim of the study was to evaluate the appetite-stimulating effect of gabapentin by comparing it with mirtazapine in healthy cats in the first 8 h after ovariectomy surgery. METHODS: This double-masked, placebo-controlled, prospective clinical trial included 60 healthy cats presented to the hospital for ovariectomy: 20 received gabapentin, 21 received mirtazapine and 19 received a placebo immediately before and 6 h after surgery. Food was offered at 2, 4, 6 and 8 h post-ovariectomy. After each meal, food intake was measured. Data were analysed using repeated-measure ANOVA and a linear mixed-model analysis. Post-hoc Tukey's honest significant difference test was performed for multiple comparisons. RESULTS: Food intake increased in both treatment groups vs placebo. No statistically significant difference was found between cats treated with gabapentin or mirtazapine. CONCLUSIONS AND RELEVANCE: Cats receiving gabapentin ate more than cats in the placebo group. Thirty percent of cats in the gabapentin group covered their resting energy requirements, while none of the cats in the placebo group did. Gabapentin and mirtazapine produced similar effects on food intake.

Cotoneaster sp. poisoning in a llama (Lama glama).

A case of poisoning with a Cotoneaster sp. is described in a llama (Lama glama). The clinical signs were dyspnea, with congested mucous membranes, chewing, recumbency, and opisthotonos. Several hours after ingestion of the plant, the llama died, despite treatment with sodium thiosulfate and nitrite. Necropsy revealed approximately 676 g of leaves and fruit of Cotoneaster in the first compartment of the stomach. The blood was light red and did not clot. Because Cotoneaster sp. contains low concentrations of cyanogenic glycosides, toxicosis occurs only following massive ingestion of plant material.

Orthologous metabonomic qualification of a rodent model combined with magnetic resonance imaging for an integrated evaluation of the toxicity of Hypochoeris radicata.

In the present study, we have used metabonomics combined with magnetic resonance imaging (MRI) to investigate an orphan neurological disease, Australian stringhalt, described in horse-ingesting inflorescences of Hypochoeris radicata (HR), without any knowledge on the toxic principle and without any practical possibility to perform experiments on the target species. To get valuable candidate biomarkers, we have chosen the mouse species as a "metabolically competent" laboratory animal model. Metabonomics has been applied as a holistic approach to obtain some pertinent metabolic information about the target organs and biomarker metabolites involved in the HR-induced disruptive events. From urine, liver, and brain metabolic fingerprints, HR ingestion induced a very significant effect on the general metabolism, which is proportional to the HR dose administered and to the HR intoxication duration. The main metabolic biomarker in the mouse model of an intoxication specifically induced by HR feeding has been unambiguously identified as scyllo-inositol. A significant increase of this metabolic marker has been measured in urine and in hydrosoluble liver or brain extracts with a very significant canonical link between these two organs. MRI results obtained in the thalamus have confirmed the involvement of scyllo-inositol, a metabolite found in many neurodegenerative diseases, in some specific metabolic disruptions involved in both neuronal and glial dysfunctions as awaited from etiology of this horse disease. This brain metabolic biomarker has been clearly associated with changes in N-acetyl-aspartate, lactate, and choline cerebral concentration found in both neuronal and glial dysfunctions. Scyllo-inositol is a valuable candidate biomarker of the Australian stringhalt disease that needs now to be clinically validated in the target species.

A new model for evaluating maintenance energy requirements in dogs: allometric equation from 319 pet dogs.

Reports concerning maintenance energy requirements (MER) in dogs are common but most of the data cover laboratory or utility dogs. This study establishes those of healthy adult pet dogs and the factors which cause these energy requirements to vary. Within the framework of a nutrition teaching exercise, each student followed a pet from his entourage and gathered accurate records of its feeding habits. Data have been restricted to healthy adult dogs with an ideal body weight (BW) which did not vary more than 5 % during the study period. A total of 319 eligible records were analysed using multiple linear regression. Variation factors such as ownership, breed, sex and neutered status, bedding location, temperament and feeding habits were then analysed individually using a non-parametric model. Two models result from this study, one excluding age (r2 0·813) and a more accurate one which takes into consideration the age in years (r2 0·816). The second model was assessed with the main variation factors and shows that: MER (kcal) = k1 × k2 × k3 × k4 × k5 × 128 × BW0·740 × age-0·050/d (r2 0·836), with k1 the effect of the breed, k2 the effect of sex and neutered status, k3 the effect of bedding location, k4 the effect of temperament and k5 the effect of the type of feed. The resulting model is very similar to the recommendations made by the National Research Council (2006) but a greater accuracy was obtained using age raised to a negative power, as demonstrated in human nutrition.

Evaluation of total body water in canine breeds by single-frequency bioelectrical impedance analysis method: specific equations are needed for accuracy.

BACKGROUND: Equations based on single-frequency bioelectrical impedance analysis at 50 kHz for determination of total body water content (TBW) have been previously validated in healthy non-sedated beagle dogs. We investigated whether these equations are predictive of TBW in various canine breeds by comparing the results of these equations with TBW values evaluated directly by deuterium oxide (D2O) dilution. METHODS: Total body water content of 13 healthy adult pet dogs of various breeds was determined directly using D2O dilution and indirectly using previous equations based on values obtained with a portable bioelectric impedance device. Paired Student's t-tests were used to compare TBW obtained by single-frequency bioelectrical impedance analysis and D2O dilution. A p-value of <0.05 was considered statistically significant for all analyses. RESULTS: Significant differences were observed between TBW determined by the reference method and the values obtained with both predictive equations. CONCLUSIONS: The proposed equations including single-frequency bioelectrical impedance analysis parameters validated at 50 kHz in healthy adult beagles need to be modified including morphological parameters such as body size and shape in a first approach. As in humans, morphological-specific equations have to be developed and validated.

Indirect prediction of total body water content in healthy adult Beagles by single-frequency bioelectrical impedance analysis.

OBJECTIVE: To develop equations for prediction of total body water (TBW) content in unsedated dogs by combining impedance (resistance and reactance) and morphological variables and to compare the results of those equations with TBW content determined by deuterium dilution (TBW(d)). ANIMALS: 26 healthy adult Beagles. PROCEDURES: TBW content was determined directly by deuterium dilution and indirectly with equations developed from measurements obtained by use of a portable bioelectric impedance device and morphological variables including body length, height, weight, and thoracic and abdominal circumferences. RESULTS: Impedance and morphological data from 16 of the 26 dogs were used to determine coefficients for the following 2 equations: TBW(1) = -0.019 (BL(2)/R) + -0.199 (RC + AC) + 0.996 W + 0.081 H + 12.31; and TBW(2) = 0.048 (BL(2)/R) + -0.144 (RC + AC) + 0.777 W + 0.066 H + 0.031 X + 7.47, where AC is abdominal circumference, H is height, BL is body length, R is resistance, RC is rib cage circumference, W is body weight, and × is reactance. Results for TBW(1) (R(2)(1) = 0.843) and TBW(2) (R(2)(2) = 0.816) were highly correlated with the TBW(d). When the equations were validated with data from the remaining 10 dogs, the respective mean differences between TBW(d) and TBW(1) and TBW(2) were 0.17 and 0.11 L, which equated to a nonsignificant underestimation of TBW content by 2.4% and 1.6%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that impedance and morphological data can be used to accurately estimate TBW content in adult Beagles. This method of estimating TBW content is less expensive and easier to perform than is measurement of TBW(d), making it appealing for daily use in veterinary practice.

Dietary polyunsaturated fatty acids and heme iron induce oxidative stress biomarkers and a cancer promoting environment in the colon of rats.

The end products of polyunsaturated fatty acid (PUFA) peroxidation, such as malondialdehyde (MDA), 4-hydroxynonenal (HNE), and isoprostanes (8-iso-PGF2α), are widely used as systemic lipid oxidation/oxidative stress biomarkers. However, some of these compounds have also a dietary origin. Thus, replacing dietary saturated fat by PUFAs would improve health but could also increase the formation of such compounds, especially in the case of a pro-oxidant/antioxidant imbalanced diet. Hence, the possible impact of dietary fatty acids and pro-oxidant compounds was studied in rats given diets allowing comparison of the effects of heme iron vs. ferric citrate and of ω-6- vs. ω-3-rich oil on the level of lipid peroxidation/oxidative stress biomarkers. Rats given a heme iron-rich diet without PUFA were used as controls. The results obtained have shown that MDA and the major urinary metabolite of HNE (the mercapturic acid of dihydroxynonane, DHN-MA) were highly dependent on the dietary factors tested, while 8-iso-PGF2α was modestly but significantly affected. Intestinal inflammation and tissue fatty acid composition were checked in parallel and could only explain the differences we observed to a limited extent. Thus, the differences in biomarkers were attributed to the formation of lipid oxidation compounds in food or during digestion, their intestinal absorption, and their excretion into urine. Moreover, fecal extracts from the rats fed the heme iron or fish oil diets were highly toxic for immortalized mouse colon cells. Such toxicity can eventually lead to promotion of colorectal carcinogenesis, supporting the epidemiological findings between red meat intake and colorectal cancer risk. Therefore, the analysis of these biomarkers of lipid peroxidation/oxidative stress in urine should be used with caution when dietary factors are not well controlled, while control of their possible dietary intake is needed also because of their pro-inflammatory, toxic, and even cocarcinogenic effects.

Influence of feeding and analytical method on the bioequivalence of a racemic drug undergoing enantioselective enterohepatic recycling.

Two crossover bioequivalence trials of an enantioselectively enterohepatic recycled drug, carprofen, were conducted in dogs with the same racemic oral formulation to determine: (i) the influence of feeding patterns, and (ii) the effect of the analytical method (enantioselective vs non-enantioselective) on the statistical power of the trials. The first trial was conducted with a standard feeding protocol and the second with a special feeding protocol selected to ensure constant biliary flow into the duodenum. Using a non-enantioselective technique, 90% confidence intervals provided conclusions of bioequivalence in 100% of the cases for both area under the plasma concentration versus time curve (AUC) and maximum plasma drug concentration (Cmax) with the special feeding protocol, but only 50% for AUC and 13% for Cmax with the standard feeding protocol, suggesting that a feeding pattern that diminishes plasma drug concentration rebound for an enterohepatically recycled drug increases the power of a bioequivalence trial. Whatever the feeding protocol, an enantioselective method decreased the power of the trials for AUC but increased the power of the trials for Cmax. For an enterohepatically recycled drug, feeding pattern can influence the power of a bioequivalence trial, and the analytical technique that provides the greatest power depends on the assessed bioequivalence parameter and the feeding pattern.

Mining the brain metabolome to understand behavioural disruptions induced in mouse fed Hypochoeris radicata (L.), a neurotoxic plant for horse.

Mining the brain metabolome to understand behavioural disruptions induced in mouse fed Hypochoeris radicata (L.), a neurotoxic plant for horse. C57BL/6J mice orally exposed to 9% H. radicata (HR) are metabolically competent laboratory animals which can be used as model of Australian stringhalt, a neurological horse disease induced by HR ingestion. So, the present study was conducted to assess the brain metabolome and the behavioural performances of mice fed with a 9%-HR-based diet for 21 days. By the end of the period of exposure, mice were investigated for motor activity and coordination, anxiety level, learning and memory performances, social behaviour and rewarding properties of for the plant. Thus, the animals were sacrificed and the brain metabolome was studied using (1)H NMR spectroscopy. HR-exposed mice displayed a motor hyperactivity in several tasks, a less resignation in the forced swimming test, and paradigm place preference for the plant. A bootstrap-based regularized canonical analysis performed on merged behavioural and metabolic datasets showed a clear relationship in HR-treated mice between an increase in cerebral scyllo-inositol, an increased motor activity, and seemingly rewarding properties of HR. These results underlie the interest of such a dual approach to characterize functional end-points of a pathophysiological model of the Australian stringhalt in equine species.