Clinical efficacy of nutraceutical diet for cats with clinical signs of cutaneus adverse food reaction (CAFR).

Food allergies and food intolerances are clinically difficult to discriminate. Most often, along with cutaneous adverse food reactions or CAFR, they are classified as adverse food reactions, whose causes are numerous, including toxic compounds. Eighteen indoor-housed domestic cats with evident clinical symptoms related to CAFR (drooling, back and neck intense itching, neck eczema, chronic conjunctivitis and stomatitis) involving skin lesions were studied. Cytological evaluations of ear, skin and gingival swabs revealed an increased turnover of keratinocytes while the oxytetracycline ELISA determination showed an unexpected high amount of oxytetracycline in all cats at the first visit. All cats were then randomly assigned to receive a standard (SD group) or a nutraceutical diet (ND group) for 60 days. In the ND group a significant reduction of the mean serum concentration of oxytetracycline, pruritus intensity and skin lesion severity (**p<0.01, ***p<0.001, and ***p<0.001, respectively) was observed after 60 days, and associated with a significant improvement in the clinical picture. Although a direct correlation between oxytetracycline presence within cat sera and CAFR-related symptoms has never been described, this study highlights the benefit of a specific nutraceutical diet supplementation in improving clinical symptoms and skin lesions in cats with CARF.

Serum concentration dynamic of energy homeostasis hormones, leptin, insulin, thyroid hormones, and cortisol throughout canine pregnancy and lactation.

Pregnancy and lactation represent critical periods of canine reproductive life and different hormones are required to maintain homeostasis and the correct energy requirements. The aim of this study was to evaluate leptin, insulin, triiodotyronine (T3), thyroxin (T4) and cortisol serum concentrations to better describe the canine maternal energy metabolism. Twelve Bloodhound bitches that had at least one litter and were considered to be healthy submitted blood samples every 15 days starting from day 0 (ovulation) throughout pregnancy up to the end of lactation (day 120). We found that leptin concentrations increased from day 0 to reach maximum value at day 45 (P < 0.001), decreased at day 60 (P < 0.05) and rose again at day 105 and day 120 (P < 0.05 and P < 0.01 respectively). Insulin concentrations significantly increased during pregnancy peaking at day 60 (P < 0.05). After parturition dropped and reached progressively lower values similar to those at day 0 at the end of lactation. During pregnancy Body Weight was in low correlation with leptin (r = 0.32, P < 0.01) and there was no correlation with insulin (r = 0.13, P > 0.1); moreover, no correlation was found during lactation. T3 concentrations showed a U-shaped trend with a significant reduction at day 75 (P < 0.05). T4 concentrations fluctuated without any significant change (ranging from 27.0 ± 1.6 nmol/l to 32.1 ± 1.9 nmol/l). Cortisol concentrations ranged within the reference values (minimal value at day 30 (49.8 ± 6.3 nm/L) and maximal value at day 45 (72.5 ± 16.1 nm/L)). Our study states that canine pregnancy and lactation evoke many hormonal changes necessary to mother and fetuses. In particular, this is the first report regarding the pattern of leptin during whole pregnancy and lactation. The present work lays the groundwork for further studies on endocrine homeostatic mechanisms using the dog as a model for human medicine.

Effects in dogs with behavioural disorders of a commercial nutraceutical diet on stress and neuroendocrine parameters.

The well-being of dogs can be affected by changes in human lifestyle, eating habits and increased stressors that lead to behavioural disorders including fear, hyperactivity and anxiety, followed by negative affective moods and poor welfare. This randomised, controlled clinical evaluation involved 69 dogs, 38 males and 31 females, of different breeds, with behavioural disorders related to anxiety and chronic stress. They were fed a control diet or a nutraceutical diet (ND group) for 45 days. Neuroendocrine (serotonin, dopamine, ß-endorphins, noradrenaline and cortisol) and stress (derivatives of reactive oxygen metabolites (dROMs) and biological antioxidant potential (BAP)) parameters related to behavioural disorders were evaluated at the beginning and end of the study period. Results showed a significant increase in serotonin, dopamine and ß-endorphins plasma concentrations (*P<0.05, *P<0.05 and **P<0.01, respectively) and a significant decrease in noradrenaline and cortisol plasma concentrations in the ND group (*P<0.05). dROMs significantly decreased in the ND group (*P<0.05) while BAP was not affected. This study demonstrated for the first time that a specific diet significantly and positively affected neuroendocrine parameters and dROMs. These results open significant perspectives concerning the use of diet and nutraceuticals in the treatment of behavioural disorders.

Toxicological Implications and Inflammatory Response in Human Lymphocytes Challenged with Oxytetracycline.

Antibiotics are widely used in zoo technical and veterinary practices as feed supplementation to ensure wellness of farmed animals and livestock. Several evidences have been suggesting both the toxic role for tetracyclines, particularly for oxytetracycline (OTC). This potential toxicity appears of great relevance for human nutrition and for domestic animals. This study aimed to extend the evaluation of such toxicity. The biologic impact of the drug was assessed by evaluating the proinflammatory effect of OTC and their bone residues on cytokine secretion by in vitro human peripheral blood lymphocytes. Our results showed that both OTC and OTC-bone residues significantly induced the T lymphocyte and non-T cell secretion of interferon (IFN)-γ, as cytokine involved in inflammatory responses in humans as well as in animals. These results may suggest a possible implication for new potential human and animal health risks depending on the entry of tetracyclines in the food-processing chain.

Cytotoxic effects of oxytetracycline residues in the bones of broiler chickens following therapeutic oral administration of a water formulation.

Tetracyclines, which represent one of the most commonly used antibiotics for poultry, are known to be deposited in bones, where they can remain, despite the observation of appropriate withdrawal times. The aim of the study was to determine the concentration of oxytretracycline (OTC) residues in the bone and muscle of chickens, following the oral administration of a commercially available liquid formulation, and to test their cytotoxic effects on an in vitro cell culture model. Seventy-two 1-day-old broiler chickens were randomly allotted into 2 groups (control and treated animals). OTC (40 mg/kg BW) was administered via drinking water during the 1 to 5 and 20 to 25 days of life periods. At the end of the trial, the birds were slaughtered and the OTC residues in the target tissues were measured by means of liquid chromatography (LC) - tandem mass spectrometry (MS/MS). Cytotoxicity was assessed by evaluating the pro-apoptotic effect of the bone residues on the K562 erythroleukemic line and on the peripheral blood mononuclear cells (PBMC). In all the animals, the OTC residues in the muscle were far below the established MRL of 100 µg/kg. The OTC levels in the bones of the treated animals were instead found in the parts per million (ppm) range. Cell cytotoxicity was assessed by evaluating the pro-apoptotic effect of OTC bone residues on the haematopoietic cell system. This in vitro system has revealed a significant pro-apoptotic effect on both the K562 cell line and PBMC cultures. This result suggests potential human and animal health risks due to the entry of tetracycline residues contained in the bones of treated livestock into the food-chain. This could be of concern, particularly for canine and feline diets, as meat, bone meal, and poultry by-products represent some of the main ingredients of pet foods, especially in the case of dry pet food. Further studies are needed to define the underlying mechanisms of cytotoxicity and to evaluate the in vivo toxicological implications due to the observed in vitro effects.