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ABSTRACT 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. [ABSTRACT FROM AUTHOR]

Vaccines are utilized within the poultry industry to minimize disease-associated losses and spray vaccination is a commonly utilized means for the mass application of poultry vaccines. During this process, vaccine-laden particles are deposited upon target areas (e.g., eyes, nares, and oral cavity) resulting in the direct internalization of the vaccine. However, particles are also deposited on nontarget areas such as the exterior of the subject and its surrounding environment. To better determine the fate of particles deposited upon nontarget areas and the impact of deposition site on the efficiency of vaccine application, a live bacterial poultry vaccine (AviPro®MG F) was applied via spray using a spray cabinet with a slotted partition allowing for head-only, body-only, and whole-bird spray application. At 11 wk age, Hy-Line® W-36 pullets (n = 280) were allocated equally among 7 treatments including: nonvaccinated controls, pullets spray-vaccinated at the manufacturer's recommended dose (1X) in a site-specific manner (head-only, body-only, and whole-bird), pullets spray-vaccinated at 5X the recommended level (bodyonly), pullets vaccinated by manual eye-drop application (1X), and pullets eye-drop vaccinated at a level approximating that achieved during the spray vaccination process (1/700X). At 6 to 7 wk postvaccination, vaccination efficiency was assessed via serologicalbased assays [serum plate agglutination (SPA) and ELISA] and the detection of vaccine-derived in vivo populations. Results indicate an additive contribution of the vaccine deposited on the body to the overall vaccination efficiency of this live bacterial live poultry vaccine. [ABSTRACT FROM AUTHOR]

Conduction system pacing (CSP) encompassing His bundle (HBP) and left bundle branch area pacing (LBBAP) is gaining increasing attention in the electrophysiology community. These relatively novel physiological pacing modalities have the potential to outperform conventional pacing approaches with respect to clinical endpoints, although data are currently still limited. While HBP represents the most physiological form of cardiac stimulation, success rates, bundle branch correction, and electrical lead performance over time remain a concern. LBBAP systems may overcome these limitations. In this review article, we provide a comprehensive overview of the current evidence, implantation technique, device programming, and follow-up considerations concerning CSP systems. Moreover, we discuss ongoing technical developments and future perspectives of CSP.

Background: Tetracyclines' use in intensive animal farming has raised some concerns regarding the biosafety for humans. Increasing evidences have revealed the presence of these drugs in processed animal by-products, such as bone, throughout the food chain. A potential off-target of tetracyclines is the bacterial-like mitochondrial translational machinery, thereby causing proteostatic alterations in mitochondrial DNA-encoded components of the oxidative phosphorylation system., Methods: The Seahorse methodology, confocal microscopy imaging of mitochondrial potential and reactive oxygen species, and q-RT-PCR analysis of the expression of genes involved in mitochondrial biogenesis and mitophagy were carried out on human lymphoblast derived K562 cell line challenged with bone powder derived from chicken treated with or without oxytetracycline and pure oxytetracycline., Results: A complex dose-dependent profile was attained with a low dosage of bone powder extracts causing a metabolic adaptation hallmarked by stimulation of the mitochondrial respiration and enhanced expression of mitochondriogenic factors in particular in cells challenged with oxytetracycline-free bone extract. Conversely, a higher dosage of bone powder extracts, regardless of their source, caused a progressive inhibition of mitochondrial respiration and glycolysis, ultimately leading to cell death. No significant effects of the pure oxytetracycline were observed., Conclusion: Bone powder, regardless of chicken treatment, contains and releases factors/chemicals responsible for the observed effects on energy metabolism. Quantitative differential effects appear to depend on biochemical alterations in the bone matrix caused by antibiotics rather than antibiotics themselves.

Male dog infertility may represent a serious concern in the canine breeding market. The aim of this clinical evaluation was to test the efficacy of a commercially available nutraceutical diet, enriched with Lepidium meyenii, Tribulus terrestris, L-carnitine, zinc, omega-3 (N-3) fatty acids, beta-carotene, vitamin E, and folic acid, in 28 male dogs suffering from infertility associated with hypospermia. All dogs received the diet over a period of 100 days. At the end of the evaluation period, no adverse effects, including head and tail anomalies percentage onset, were reported. Interestingly, motility percentage, semen volume and concentration, and total number of sperms per ejaculation significantly increased. Further investigations on a wider cohort of dogs might be useful to better correlate the presence of oxytetracycline in pet's diet and the onset of infertility and clearly assess the action mechanism of an oxytetracycline-free nutraceutical diet.

In the last decades, adverse food reactions have increased considerably in dogs and cats. In this study we report on the possible onset of food intolerances symptoms, including otitis, diarrhoea, generalised anxiety, and dermatitis in a cohort of 8 dogs consuming commercial diets. All dogs received an organic chicken-based diet for 15 days. We performed analysis of blood biochemical parameters, kibble composition, and oxytetracycline (OTC) serum concentration before and after 15 days of organic chicken-based diet supplementation. We hypothesised that a chronic intake of contaminated food enhanced by the presence of nanoparticle aggregates might be at the base of the onset of pharmacologic or idiopathic food intolerances. At the end of the evaluation period, an overall significant reduction of otitis, diarrhoea, generalised anxiety, and dermatitis was observed. Biochemical analyses indicate a significant increase in the alkaline phosphatase, from 41 to 52.5 U/L, after 15 days (••p <0.01), while a significant decrease in Gamma-glutamyl transferase and urea, from 9.37 to 6.25 U/L and from 32.13 ± 8.72 to 22.13 ± 7.8 mg/dL, respectively, was observed (•p <0.05). A significant decrease, from 0.22 to 0.02 μg/mL, in mean OTC serum concentration was also observed (••p <0.01). Composition analysis revealed the presence of OTC, calcium, aluminium, silicon, and phosphorous nanoparticle aggregates. Further research on a wider sample size would help to confirm the hypothesis proposed here.

Chronic kidney disease is characterized by structural and/or functional impairment of one or both kidneys persisting for more than 3 months. In cats, chronic kidney disease can frequently occur in animals aged over 9 years with an incidence of approximately 10%. Thirty-four client-owned, neutered cats, suffering from stage II-III chronic kidney disease and diagnosed according to the International Renal Interest Society guidelines were randomly assigned to receive either a control diet (n = 17) or a nutraceutical diet (ND; n = 17) for 90 days. Both diets were commercialized for management of CKD symptoms. The diets were identical except that the ND contained tablets that consisted of 60-80% hydrolysed proteins, 20-40% minerals and active substances, that are, Lespedeza spp. 0.0588%, Vaccinium macrocarpom 0.0371%, and Taraxacum officinale 0.0231%. No adverse effects were reported during this study. Both diets resulted in an improvement in CKD symptoms. After a 90-day evaluation, creatinine, blood urea nitrogen, total proteins, and aspartate aminotransferase significantly decreased in cats that received the ND. A significant decrease was also observed in urine turbidity score, color score, and total proteins in cats that received the ND. We have found that a ND based on Lespedeza spp., Vaccinium macrocarpon, and Taraxacum officinale improves key indicators of renal failure in cats affected by chronic kidney disease., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

The aim of this study was to evaluate the prevalence of hip and elbow dysplasia in a group of growing Labrador retrievers fed a fish-based diet enriched with nutraceuticals with chondroprotective properties. The puppies ranged from 3 to 12 mo of age and were divided into 2 groups, each fed a different diet. The control diet consisted of a high quality, chicken-based dog food, while the test diet was a fish-based dog food, enriched with nutraceuticals. Hip and elbow joints were radiographed and scored at 6 and 12 mo of age. Overall, 42 dogs completed the study. At 12 mo of age, no differences were found between the groups in the prevalence of hip and elbow dysplasia, although dogs fed the fish-based food enriched with nutraceuticals had a less severe grade of osteoarthritis at 12 mo. It was concluded that the fish-based diet with nutraceuticals did have beneficial effects on the development of severe osteoarthritis.

Mechanical properties of living cells can be used as reliable markers of their state, such as the presence of a pathological state or their differentiation phase. The mechanical behavior of cells depends on the organization of their cytoskeletal network and the main contribution typically comes from the actomyosin contractile system, in both suspended and adherent cells. In the present study, we investigated the effect of a pharmaceutical formulation (OTC - Ossitetraciclina liquida 20%) used as antibiotic, on the mechanical properties of K562 cells by using the Micropipette Aspiration Technique (MAT). This formulation has been shown to increase in a time dependent way the inflammation and toxicity in terms of apoptosis in in vitro experiments on K562 and other types of cells. Here we show that by measuring the mechanical properties of cells exposed to OTC for different incubation times, it is possible to infer modifications induced by the formulation to the actomyosin contractile system. We emphasize that this system is involved in the first stages of the apoptotic process where an increase of the cortical tension leads to the formation of blebs. We discuss the possible relation between the observed mechanical behavior of cells aspirated inside a micropipette and apoptosis.

Background: Oxytetracycline (OTC), which is largely employed in zootechnical and veterinary practices to ensure wellness of farmed animals, is partially absorbed within the gastrointestinal tract depositing in several tissues. Therefore, the potential OTC toxicity is relevant when considering the putative risk derived by the entry and accumulation of such drug in human and pet food chain supply. Despite scientific literature highlights several OTC-dependent toxic effects on human and animal health, the molecular mechanisms of such toxicity are still poorly understood., Methods: Here, we evaluated DNA damages and epigenetic alterations by quantitative reverse transcription polymerase chain reaction, quantitative polymerase chain reaction, chromatin immuno-precipitation and Western blot analysis., Results: We observed that human peripheral blood mononuclear cells (PBMCs) expressed DNA damage features (activation of ATM and p53, phosphorylation of H2AX and modifications of histone H3 methylation of lysine K4 in the chromatin) after the in vitro exposure to OTC. These changes are linked to a robust inflammatory response indicated by an increased expression of Interferon (IFN)- γ and type 1 superoxide dismutase (SOD1)., Discussion: Our data reveal an unexpected biological in vitro activity of OTC able to modify DNA and chromatin in cultured human PBMC. In this regard, OTC presence in foods of animal origin could represent a potential risk for both the human and animal health., Competing Interests: None of the authors have financial or personal relationships with other people or organisations that could inappropriately influence or bias the content of the paper. This research was performed in collaboration with some scientists from the Division of Research and Development, Sanypet SpA, Padova, Italy (as indicated in the authors’ affiliation) according to scientific and ethical principles of the scientific community. No financial funding was obtained from Sanypet Industry for this research study.

In dogs, diets are often used to modulate behavioral disturbances related to chronic anxiety and stress caused by intense and restless activity. However, the traditional ways to monitor behavioral changes in dogs are complicated and not efficient. In the current clinical evaluation, a new, simple monitoring system was used to assess the effectiveness of a specific diet in positively modulating the intense and restless activity of 24 dogs of different ages and breeds. This protocol describes how to easily and rapidly evaluate improvement in a set of symptoms related to generalized anxiety by using a specific sensor, a mobile phone app, a wireless router, and a computer. The results showed that dogs treated with specific diets showed significant improvement in the times spent active and at rest after 10 days (p < 0.01 and p < 0.05, respectively). These dogs also showed an overall significant improvement in clinical and behavioral symptoms. A specific sensor, along with its related hardware, was demonstrated to successfully monitor behavioral changes relating to movement in dogs.

Background: Canine keratoconjunctivitis sicca (cKCS) is an inflammatory eye condition related to a deficiency in the tear aqueous fraction. Etiopathogenesis of such disease is substantially multifactorial, combining the individual genetic background with environmental factors that contribute to the process of immunological tolerance disruption and, as a consequence, to the emergence of autoimmunity disease. In this occurrence, it is of relevance the role of the physiological immune-dysregulation that results in immune-mediated processes at the basis of cKCS. Current therapies for this ocular disease rely on immunosuppressive treatments. Clinical response to treatment frequently varies from poor to good, depending on the clinical-pathological status of eyes at diagnosis and on individual response to therapy. In the light of the variability of clinical response to therapies, we evaluated the use of an anti-inflammatory/antioxidant nutraceutical diet with potential immune-modulating activity as a therapeutical adjuvant in cKCS pharmacological treatment. Such combination was administered to a cohort of dogs affected by cKCS in which the only immunosuppressive treatment resulted poorly responsive or ineffective in controlling the ocular symptoms., Results: Fifty dogs of different breeds affected by immune-mediated cKCS were equally distributed and randomly assigned to receive either a standard diet (control, n = 25) or the nutraceutical diet (treatment group, n = 25) both combined with standard immunosuppressive therapy over a 60 days period. An overall significant improvement of all clinical parameters (tear production, conjunctival inflammation, corneal keratinization, corneal pigment density and mucus discharge) and the lack of food-related adverse reactions were observed in the treatment group (p < 0.0001)., Conclusions: Our results showed that the association of traditional immune-suppressive therapy with the antioxidant/anti-inflammatory properties of the nutraceutical diet resulted in a significant amelioration of clinical signs and symptoms in cKCS. The beneficial effects, likely due to the presence of supplemented nutraceuticals in the diet, appeared to specifically reduce the immune-mediated ocular symptoms in those cKCS-affected dogs that were poorly responsive or unresponsive to classical immunosuppressive drugs. These data suggest that metabolic changes could affect the immune response orchestration in a model of immune-mediated ocular disease, as represented by cKCS.

The aim of this evaluation study was to assess the possible role of a specific nutraceutical diet in relieving main clinical symptoms of chronic bilateral otitis externa (occlusion of ear canal, erythema, discharge quantity, and odor) in 30 adult dogs. Thirty dogs of different breeds (mean age ± SEM; 6.03 ± 0.15 years and mean weight ± SEM; 32.01 ± 1.17 Kg; 53.3% males, 46.6% females) with evident chronic clinical otitis symptoms were equally divided and randomly assigned to receive either the nutraceutical diet (ND group) or a standard diet (SD group) over a period of 90 days. In all cases a topical pharmacological treatment was given. The nutraceutical diet, also endowed with anti-inflammatory and antioxidant activities, significantly decreased the mean score intensity of all symptoms after 90 days of intervention (P < 0.0001) with the exception of Malassezia pachydermatis infection which was only slightly reduced. Our investigation is one of the few evidence-based results where a commercial nutraceutical diet has been proven effective, in combination with drugs, in relieving otitis externa-related symptoms. This study opens new insights into otitis externa clinical management providing evidence of efficacy of a combined therapy with drugs and a specific nutraceutical diet.

Methods: Ninety-six cobb race chickens were equally divided in 4 groups and randomly assigned to receive a standard treatment feed + homeopathic concentrations of Symphytum (S.) officinalis (9CH), or standard treatment feed + homeopathic concentrations of Tricalcarea (4CH), or standard treatment feed + homeopathic concentrations of Calcarea (C.) carbonica (30CH) or a placebo (the same feed but without any homeopathic compound) in order to assess the ability of the homeopathic compounds to increase the concentration of calcium hydroxyapatite in the sternal spongy bone tissue. We measured the concentration of calcium hydroxyapatite in the sternal spongy bone tissue of all chickens by means of a computed tomography (CT)., Results: 30%, 36% and 63% increase of sternum spongy-bone mineralization was observed after a 2 years period in the treatment groups with S. officinalis (9CH), Tricalcarea (4CH) (*P < 0.05) and C. carbonica (30CH) (***P < 0.001) respectively., Conclusion: Bone mineralization is usually low in battery chickens reared in commercial poultry-sheds, creating a weakness of the whole animal supporting apparatus. Homeopathic preparations with bone-tissue tropism may improve their health quality., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Several extrinsic factors, like drugs and chemicals, can foster autoimmunity. Tetracyclines, in particular oxytetracycline (OTC), appear to correlate with the emergence of immune-mediated diseases. Accumulation of OTC, the elective drug for gastrointestinal and respiratory infectious disease treatment in broiler chickens, was reported in chicken edible tissues and could represent a potential risk for pets and humans that could assume this antibiotic as residue in meat or in meat-derived byproducts. We investigated the in vitro anti-inflammatory properties of a pool of thirteen botanicals as a part of a nutraceutical diet, with proven immunomodulatory activity. In addition, we evaluated the effect of such botanicals in contrasting the in vitro proinflammatory toxicity of OTC. Our results showed a significant reduction in interferon- (INF-) γ production by human and canine lymphocytes in presence of botanicals ((⁎) p < 0.05). Increased INF-γ production, dependent on 24-hour OTC-incubation of T lymphocytes, was significantly reduced by the coincubation with Haematococcus pluvialis, with Glycine max, and with the mix of all botanicals ((⁎) p < 0.05). In conclusion, the use of these botanicals was shown to be able to contrast OTC-toxicity and could represent a new approach for the development of functional foods useful to enhance the standard pharmacological treatment in infections as well as in preventing or reducing the emergence of inflammatory diseases.

Background: Clinical appearance and evolution of Canine Leishmaniosis (CL) are the consequence of complex interactions between the parasite and the genetic and immunological backgrounds. We investigated the effect of an immune-modulating diet in CL. Dogs were treated with anti- Leishmania pharmacological therapy combined with standard diet (SD Group) or with the immune-modulating diet (IMMD Group). CD3+ CD4+ Foxp3+ Regulatory T cells (Treg) and CD3+ CD4+ IFN-γ + T helper 1 (Th1) were analyzed by flow cytometry., Results: All sick dogs showed low platelet number at diagnosis (T0). A platelet increase was observed after six months (T6) SD Group, with still remaining in the normal range at twelve months (T12). IMMD Group showed an increase in platelet number becoming similar to healthy dogs at T6 and T12. An increase of CD4/CD8 ratio was revealed in SD Group after three months (T3), while at T6 and at T12 the values resembled to T0. The increase in CD4/CD8 ratio at T3 was maintained at T6 and T12 in IMMD Group. A reduction in the percentage of Treg of all sick dogs was observed at T0. A recovery of Treg percentage was observed only at T3 in SD Group, while this effect disappeared at T6 and T12. In contrast, Treg percentage became similar to healthy animals in IMDD Group at T3, T6 and T12. Sick dogs showed an increase of Th1 cells at T0 as compared with healthy dogs. We observed the occurrence of a decrease of Th1 cells from T3 to T12 in SD Group, although a trend of increase was observed at T6 and T12. At variance, IMMD Group dogs showed a progressive decrease of Th1 cells, whose levels became similar to healthy controls at T6 and T12., Conclusion: The immune-modulating diet appears to regulate the immune response in CL during the standard pharmacological treatment. The presence of nutraceuticals in the diet correlates with the decrease of Th1 cells and with the increase of Treg in sick dogs. Therefore, the administration of the specific dietary supplement improved the clinical response to the standard treatment in a model of CL.

Halitosis is a common complaint involving social and communicational problems in humans and also affects the pet-owner relationship. In this randomized placebo-controlled crossover clinical evaluation, we assessed the effectiveness of a dedicated dietary supplement to improve chronic halitosis in 32 dogs of different breeds and ages. This protocol describes how to evalute the presence of oral volatile suphur compunds, e.g. methyl mercaptan, hydrogen sulfide and dimethyl sulfide, by means of a portable gas chromatograph device coupled with a syringe, which was used to collect the breath, and a dedicated software, which allows the operator to monitor each compound concentration during each measurement, in a relatively short time (8 min). A significant modification of halitosis parameters was observed after 30 days since the beginning of treatment (p <0.05), while a long-lasting effect was still observed even 20 days after the suspension of the treatment. Portable gas chromatograph, which is also widely used in clinical practice, can be therefore used to confirm and control halitosis in humans and animals. Even though human and animal species present some differences, this innovative and alternative therapy for halitosis management might be extended to human clinical practice as an adjuvant dietary approach.

Biological aging is characterized by a progressive accumulation of oxidative damage and decreased endogenous antioxidant defense mechanisms. The production of oxidants by normal metabolism damages proteins, lipids, and nucleotides, which may contribute to cognitive impairment. In this study 36 dogs were randomly divided into four groups and fed croquettes of different compositions for 6 months. We monitored derivatives of reactive oxygen metabolites (dROMs) and biological antioxidant potential (BAP) levels in dogs' plasma samples as well as brain-derived neurotrophic factor (BDNF) serum levels at the beginning and at the end of the dietary regime. Our results showed that a dietary regime, enriched with antioxidants, induced a significant decrease of plasma levels of dROMs (p < 0.005) and a significant increase in BDNF serum levels (p < 0.005) after six months. Thus, we hypothesized a possible role of the diet in modulating pro- and antioxidant species as well as BDNF levels in plasma and serum, respectively. In conclusion the proposed diet enriched with antioxidants might be considered a valid alternative and a valuable strategy to counteract aging-related cognitive decline in elderly dogs.

Introduction: Great interest is raising in food intolerances due to the lack, in many cases, of a particular sensitizing agent., Objective: We investigated the serum level of possible new haptens in 15 heavy meat consumers for sport fitness affected by various kinds of food intolerance and who had ever been administered antibiotics in their life for clinical problems., Methods: Forty ml of blood were drawn from each patient and analyzed, by means of an ELISA test, in order to possibly identify the presence of an undue contaminant with hapten properties., Results: Four out of fifteen subjects (26%) showed a serum oxytetracycline amount > 6 ng/g (which is considered the safety limit), 10 of 15 (66%) a serum doxycycline amount > of 6 ng/g and 3 out of 15 (30%) subjects had high serum level of both molecules., Conclusions: Although a direct ratio between body antibiotics remnant storage in the long run and chronic gut dysfunctions and/or food allergy did not reached the evidence yet, the blood traces of these compounds in a food intolerant otherwise healthy population might be considered the preliminary putative step of a sensitizing pathway. Our next goals foresee a deeper insight into the sensitizing trigger from human chronic antibiotic exposure via the zootechnical delivery of poultry food., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)