1-Deoxynojirimycin containing Morus alba leaf-based food modulates the gut microbiome and expression of genes related to obesity.

BACKGROUND: Obesity is a serious disease with an alarmingly high incidence that can lead to other complications in both humans and dogs. Similar to humans, obesity can cause metabolic diseases such as diabetes in dogs. Natural products may be the preferred intervention for metabolic diseases such as obesity. The compound 1-deoxynojirimycin, present in Morus leaves and other sources has antiobesity effects. The possible antiobesity effect of 1-deoxynojirimycin containing Morus alba leaf-based food was studied in healthy companion dogs (n = 46) visiting the veterinary clinic without a history of diseases. Body weight, body condition score (BCS), blood-related parameters, and other vital parameters of the dogs were studied. Whole-transcriptome of blood and gut microbiome analysis was also carried out to investigate the possible mechanisms of action and role of changes in the gut microbiome due to treatment. RESULTS: After 90 days of treatment, a significant antiobesity effect of the treatment food was observed through the reduction of weight, BCS, and blood-related parameters. A whole-transcriptome study revealed differentially expressed target genes important in obesity and diabetes-related pathways such as MLXIPL, CREB3L1, EGR1, ACTA2, SERPINE1, NOTCH3, and CXCL8. Gut microbiome analysis also revealed a significant difference in alpha and beta-diversity parameters in the treatment group. Similarly, the microbiota known for their health-promoting effects such as Lactobacillus ruminis, and Weissella hellenica were abundant (increased) in the treatment group. The predicted functional pathways related to obesity were also differentially abundant between groups. CONCLUSIONS: 1-Deoxynojirimycin-containing treatment food have been shown to significantly improve obesity. The identified genes, pathways, and gut microbiome-related results may be pursued in further studies to develop 1-deoxynojirimycin-based products as candidates against obesity.

Nutrition and Aging in Dogs and Cats.

Aging is often associated with chronic inflammation and declining health. Both veterinarians and owners of aging dogs and cats are interested in nutritional solutions and strategies to prevent signs of age-related disease, increase longevity, and improve quality of life. Physiological decreases in muscle mass, decreased immunity, and a decrease in sense acuity are some of the changes often seen in otherwise healthy senior pets; however, there may also be an increase in risk for pathologies such as renal, cardiovascular, musculoskeletal, and neoplastic diseases. Aging may also lead to cognitive decline and even cognitive dysfunction. Some nutritional strategies that may be helpful with the prevention and treatment of age-related diseases include supplementation with ω3 polyunsaturated fatty acids and antioxidant nutrients that can help modulate inflammation and benefit osteoarthritis, renal disease, cancer, and more. Supplementation with medium-chain triglycerides shows promise in the treatment of canine cognitive dysfunction as these may be metabolized to ketone bodies that are utilized as an alternative energy source for the central nervous system. Additionally, a high intake of dietary phosphorus in soluble and bioavailable forms can lead to renal disease, which is of greater concern in senior pets. There are no published guidelines for nutritional requirements specific to senior pets and as a result, products marketed for senior dogs and cats are highly variable.

Evaluation of different substance combinations in a multiple-session mesotherapy protocol for the management of osteoarthritis in dogs: a retrospective study.

OBJECTIVE: To describe the effect of different substance combinations administered through mesotherapy in dogs with hip osteoarthritis. ANIMALS: 104 dogs. METHODS: In this retrospective study, 4 groups (dogs treated with a combination of lidocaine, piroxicam, and thiocolchicoside [MG]; dogs treated with lidocaine, piroxicam, and Traumeel [TG]; dogs treated with lidocaine, piroxicam, and glucosamine [GG]; and dogs treated with the same combination as in MG combined with a photobiomodulation session [MPG]) were set. For all groups, the same treatment frequency was followed. Response to treatment was measured with the Canine Brief Pain Inventory (divided into pain interference score and pain severity score), Liverpool Osteoarthritis in Dogs (LOAD), and Canine Orthopedic Index (divided into function, gait, stiffness, and quality of life) before treatment and 15, 30, 60, 90, and 120 days after treatment. Cox proportional hazard regression analysis was used to investigate the influence of treatment, age, sex, body weight, breed, and Orthopedic Foundation for Animals score. RESULTS: Dogs had a mean age of 7.6 ± 3.1 years and body weight of 28.6 ± 5.5 kg. Hip osteoarthritis was classified as mild (4), moderate (70), or severe (30). Greater improvements were observed in MG and MPG. Kaplan-Meier estimators showed MG and MPG had longer periods with clinically significant results. Treatment was the covariable that contributed more frequently to the outcomes observed. CLINICAL RELEVANCE: The combination used in MG, particularly combined with photobiomodulation, produced longer-lasting clinically significant results.

A placebo-controlled, double-blind study evaluating the effect of orally administered polyunsaturated fatty acids on the oclacitinib dose for atopic dogs.

BACKGROUND: Supplementation of polyunsaturated fatty acids (PUFA) enables dose reduction of prednisolone and ciclosporin in canine atopic dermatitis (cAD). OBJECTIVE: To determine if oral administration of PUFA reduces the dose of oclacitinib in cAD. ANIMALS: Twenty-two client-owned dogs with cAD receiving oclacitinib. MATERIALS AND METHODS: Dogs received a fish oil product (PUFA) or paraffin oil (placebo) for 16 weeks. Owners adjusted the oclacitinib dose according to daily pruritus assessments. On Day (D)0, D56 and D112, Canine Atopic Dermatitis Extent and Severity Index, fourth iteration (CADESI-04), pruritus Visual Analog Scale (PVAS), quality-of-life score (QoL), Global Assessment (GA), quality-of-coat (QoC) and adverse events were recorded. RESULTS: Mean daily oclacitinib dose was significantly reduced in the PUFA group from 0.51 ± 0.20 mg/kg/24 h (D0) to 0.19 ± 0.14 mg/kg/24 h (D85-112; p < 0.00001) and not in the placebo group (D0: 0.70 ± 0.33 mg/kg/24 h; D85-112: 0.53 ± 0.35 mg/kg/24 h, p = 0.5422). CADESI-04 did not change over time or differ between groups. PVAS was significantly lower in the PUFA group (2.8 ± 1.5) compared to placebo (4.2 ± 1.6) at D112 (p = 0.0375). QoL and QoC improved only in the PUFA group (QoL: D0: 20 ± 7, D112: 12 ± 5, p = 0.0057; QoC: D0: 0 ± 0.5, D112: 1 ± 0.5, p = 0.0410). GA on D112 was higher in the PUFA group (p = 0.008). No adverse events were observed. CONCLUSION: Oral supplementation of PUFA allowed dose reduction of oclacitinib and improved PVAS, QoL, QoC and GA. The use of PUFA is recommended and was safe in the atopic study dogs receiving oclacitinib.

Yeast-Derived Nucleotides Enhance Fibroblast Migration and Proliferation and Provide Clinical Benefits in Atopic Dermatitis.

Nucleotides, glycosaminoglycans, and omega-3 essential fatty acids (O3s) could be used for improving skin health, although their modes of action, alone or in combination, are not yet fully understood. To gain some insight into these mechanisms, we performed two in vitro tests and one in vivo pilot trial. The effects on human dermal fibroblast proliferation and migration were evaluated with the following compounds and combinations: 0.156 mg/mL O3s, 0.0017 mg/mL hyaluronic acid (HA), 0.0004 mg/mL dermatan sulfate (DS), 0.0818 mg/mL nucleotides, and [O3s + HA + DS] and [O3s + HA + DS + nucleotides] at the same concentrations. In both in vitro assays, adding nucleotides to [O3s + HA + DS] provided significant improvements. The resulting combination [O3s + HA + DS + nucleotides] was then tested in vivo in dogs with atopic dermatitis by oral administration of a supplement providing a daily amount of 40 mg/kg nucleotides, 0.9 mg/kg HA, 0.18 mg/kg DS, 53.4 mg/kg EPA, and 7.6 mg/kg DHA. After 30 days, the pruritus visual analog scale (pVAS) score was significantly reduced, and no adverse effects were observed. In conclusion, the combination of nucleotides plus glycosaminoglycans and O3s could serve as a useful therapeutic alternative in skin health applications.

Canine Mammary Tumors: Classification, Biomarkers, Traditional and Personalized Therapies.

In recent years, many studies have focused their attention on the dog as a proper animal model for human cancer. In dogs, mammary tumors develop spontaneously, involving a complex interplay between tumor cells and the immune system and revealing several molecular and clinical similarities to human breast cancer. In this review, we summarized the major features of canine mammary tumor, risk factors, and the most important biomarkers used for diagnosis and treatment. Traditional therapy of mammary tumors in dogs includes surgery, which is the first choice, followed by chemotherapy, radiotherapy, or hormonal therapy. However, these therapeutic strategies may not always be sufficient on their own; advancements in understanding cancer mechanisms and the development of innovative treatments offer hope for improved outcomes for oncologic patients. There is still a growing interest in the use of personalized medicine, which should play an irreplaceable role in the research not only in human cancer therapy, but also in veterinary oncology. Moreover, immunotherapy may represent a novel and promising therapeutic option in canine mammary cancers. The study of novel therapeutic approaches is essential for future research in both human and veterinary oncology.

Fibroblast growth factor-23 and Alpha-Klotho concentrations in dogs with canine Leishmaniasis.

This study aimed to assess the concentrations of Fibroblast Growth Factor-23 (FGF-23) and α-Klotho in healthy dogs and dogs at different stages of Canine Leishmaniasis (CanL), and investigate the changes of these parameters in relation to renal function and calcium­phosphorus metabolism. A total of 74 dogs (22 healthy and 52 with CanL) of varying ages, sexes, and medium-sized breeds were included. Dogs with CanL were categorized into different stages (Stage I-IV) based on Leishvet recommendations. In addition to routine hematological parameters, plasma FGF-23, serum α-Klotho, urea, creatinine, phosphorus, calcium, parathormone, vitamin D concentrations, and urine protein/creatinine ratio were measured. Data from healthy dogs were compared to dogs with CanL overall and by stage. Dogs with CanL exhibited higher concentrations of FGF-23 (p < 0.05), α-Klotho, and parathormone (p < 0.001), as well as lower concentrations of vitamin D and calcium (p < 0.001). FGF-23 concentration was particularly elevated in Stage IV compared to other stages. However, no significant differences in α-Klotho levels were observed among the stages. FGF-23 levels showed a weak positive correlation with urea and creatinine concentrations and a moderate positive correlation with urine protein/creatinine ratio. This study demonstrated increased levels of FGF-23 and α-Klotho in dogs with CanL for the first time. The increase in FGF-23 levels was more prominent in advanced stages of the disease and correlated with higher urea and creatinine concentrations. These findings may serve as a basis for future diagnostic and therapeutic investigations, contributing to the understanding of the pathophysiology of kidney disease in CanL.

A randomized double-blind clinical trial: Comparison of oclacitinib with a traditional Chinese herbal medicine product (Dihuang Guiqin capsule) in the treatment of canine atopic dermatitis.

Canine atopic dermatitis (cAD) is a common chronic inflammatory skin disease, which seriously affects the quality of life for both dogs and their owners. Currently, the common therapeutic drugs in the clinic have disadvantages such as obvious adverse effects and high prices. Traditional Chinese herbal medicine (TCHM) has great potential for the treatment of cAD. The aim of this study is to compare the effects of different doses of the TCHM product (Dihuang Guiqin capsule) and oclacitinib in the treatment of cAD through a randomized, double-blind trial. Sixty dogs diagnosed with AD were randomly and evenly divided into four groups (n = 15). The TCHM treatment group consisted of three subgroups that received three different oral doses (20, 40, and 60 mg/kg BW), while the control group received 0.5 mg/kg BW of oclacitinib. Each group was administered twice daily for 14 consecutive days. The results showed that both TCHM and oclacitinib significantly improved cAD-induced itching (evaluated by pVAS) and skin lesions (evaluated by CADESI-04), while interleukin 31 (IL-31) concentrations decreased significantly (P < 0.05) and serum biochemical indicators returned to normal. In particular, The therapeutic effects of TCHM medium- and high-dose groups were similar to those of oclacitinib (P > 0.05). The preliminary recommended dose of Dihuang Guiqin capsule for the treatment of cAD has been determined to be 40-60 mg/kg BW twice daily for 14 consecutive days, which can be reduced to once daily as appropriate. Dihuang Guiqin capsule was safe and well tolerated, which may be a new option for the treatment of cAD.

Construction of luciferase-expressing Neospora caninum and drug screening.

BACKGROUND: Neospora caninum is an apicomplexan parasite that is particularly responsible for abortions in cattle and neuromuscular disease in dogs. Due to the limited effectiveness of currently available drugs, there is an urgent need for new therapeutic approaches to control neosporosis. Luciferase-based assays are potentially powerful tools in the search for antiprotozoal compounds, permitting the development of faster and more automated assays. The aim of this study was to construct a luciferase-expressing N. caninum and evaluate anti-N. caninum drugs. METHODS: Luciferase-expressing N. caninum (Nc1-Luc) was constructed using clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9). After testing the luciferase expression and phenotype of the Nc1-Luc strains, the drug sensitivity of Nc1-Luc strains was determined by treating them with known positive or negative drugs and calculating the half-maximal inhibitory concentration (IC50). The selective pan-rapidly accelerated fibrosarcoma (pan-RAF) inhibitor TAK-632 was then evaluated for anti-N. caninum effects using Nc1-Luc by luciferase activity reduction assay and other in vitro and in vivo studies. RESULTS: The phenotypes and drug sensitivity of Nc1-Luc strains were consistent with those of the parental strains Nc1, and Nc1-Luc strains can be used to determine the IC50 for anti-N. caninum drugs. Using the Nc1-Luc strains, TAK-632 showed promising activity against N. caninum, with an IC50 of 0.6131 µM and a selectivity index (SI) of 62.53. In vitro studies demonstrated that TAK-632 inhibited the invasion, proliferation, and division of N. caninum tachyzoites. In vivo studies showed that TAK-632 attenuated the virulence of N. caninum in mice and significantly reduced the parasite burden in the brain. CONCLUSIONS: In conclusion, a luciferase-expressing N. caninum strain was successfully constructed, which provides an effective tool for drug screening and related research on N. caninum. In addition, TAK-632 was found to inhibit the growth of N. caninum, which could be considered as a candidate lead compound for new therapeutics for neosporosis.

[Anticoagulant rodenticide poisoning in dogs: Retrospective analysis of clinical and laboratory diagnostic data]. / Vergiftung mit Cumarinderivaten beim Hund: Retrospektive Analyse klinischer und labordiagnostischer Daten.

OBJECTIVE: In this retrospective study, patient records of dogs suffering from poisoning with coumarin derivatives were evaluated to characterize the clinical appearance more precisely. MATERIAL UND METHODS: Retrospective data analysis included 52 dogs with hemostaseologically proven anticoagulant rodenticide poisoning which were treated as inpatients at the Clinic for Small Animals between September 2011 and October 2018. RESULTS: In only 2 dogs (4%) the intake of poison could be observed with certainty. The most common clinical signs observed were reduced general behavior (79%), pallor of the mucosa (79%), anorexia (60%), and dyspnea/tachypnea (60%). In contrast, macroscopically visible internal and external bleedings occurred less frequently. Initially, all cases showed a highly altered prothrombin time and most patients a considerably prolonged activated partial thromboplastin time. Anemia was present in 75% of patients. All dogs included in the study received initially an intravenous treatment with 10 mg/kg vitamin K1. Pretreatment with 1 mg/kg prednisolone was given for prophylaxis of possible incompatibility reactions. No patient showed signs of anaphylactic reaction. Transfusions of whole blood or concentrated red cells were given to only 10 of the 52 animals; only one received 2 transfusions of erythrocytes. 94% of the animals could be discharged home for outpatient therapy after a median length of hospitalization of 3 days (1-9 days) with physiological or almost physiological coagulation test results. CONCLUSION: Anticoagulant rodenticide poisoning is often associated with non-specific symptoms and good prognosis if treated adequately. CLINICAL RELEVANCE: Coagulation diagnostics is always indicated in cases with unclear disorders. In life-threatening emergencies, immediate intravenous infusion of high-dose vitamin K1 is a very effective treatment and results in a rapid increase in coagulation factor activity.

Efficacy and tolerance of oral versus parenteral cyanocobalamin supplement in hypocobalaminaemic dogs with chronic enteropathy: a controlled randomised open-label trial.

OBJECTIVES: Determine comparative tolerance of daily oral and weekly parenteral cobalamin supplementation, in hypocobalaminaemic dogs with chronic enteropathy. Determine whether oral is as effective as parenteral supplementation at achieving eucobalaminaemia, in hypocobalaminaemic dogs with protein-losing enteropathy, severe hypocobalaminaemia or high canine inflammatory bowel disease activity index at inclusion. MATERIALS AND METHODS: Thirty-seven client-owned dogs with hypocobalaminaemia and clinical signs of chronic enteropathy were prospectively enrolled in three UK referral centres. Dogs were randomly allocated to daily oral for 12 weeks or weekly parenteral cobalamin supplementation for 6 weeks and one additional dose 4 weeks later. Serum cobalamin, body condition score, canine inflammatory bowel disease activity index and bodyweight were assessed at inclusion, weeks 7 and 13. Serum methylmalonic acid concentration was evaluated at inclusion and at week 13. Owners completed treatment adherence, palatability, tolerance and satisfaction questionnaires at week 13. RESULTS: Nineteen dogs completed the study. All dogs orally supplemented achieved normal or increased cobalaminaemia at weeks 7 and 13. There was no statistical difference in cobalamin concentration at week 13 in dogs treated with oral or parenteral supplementation, regardless of presence of protein-losing enteropathy, severity of hypocobalaminaemia or canine inflammatory bowel disease activity index at inclusion. Serum methylmalonic acid concentration was not significantly different between oral and parenteral groups, neither were treatment adherence, satisfaction, and tolerance scores at week 13. CLINICAL SIGNIFICANCE: Oral is as effective and as well-tolerated as parenteral cobalamin supplementation in hypocobalaminaemic dogs with chronic enteropathy and severe clinical or biochemical phenotypes, and should be considered as a suitable treatment option regardless of disease severity.

Essential oil pharmaceuticals for killing ectoparasites on dogs.

BACKGROUND: External parasites, particularly ticks and fleas, are among the most common problems affecting dogs. Chemical medicines are commonly used to prevent and eliminate such external parasites, but their improper use can cause adverse reactions, and the toxins they contain may remain in the environment. OBJECTIVES: The objective of this study was to investigate the in vitro efficacy of Zanthoxylum limonella, citronella, clove, peppermint, and ginger essential oils against dog ticks and fleas and to test the sensitivity of dogs' skin to these essential oils. METHODS: The five essential oils were tested for in vitro efficacy against ticks and fleas, and the two most effective essential oils were then tested on the dogs' skin. RESULTS: The results revealed that these five essential oils at 16% concentrations effectively inhibited the spawning of female engorged ticks. In addition, all five essential oils had a strong ability to kill tick larvae at concentrations of 2% upward. Furthermore, 4% concentrations of the five essential oils quickly eliminated fleas, especially clove oil, which killed 100% of fleas within 1 h. A 50%, 90%, and 99% lethal concentration (LC50, LC90, and LC99) for the essential oils on tick larvae in 24 h were found to be low values. LC50, LC90, and LC99 for the essential oils on flea in 1 h was lowest values. Clove oil at 16% concentration was the most satisfactory essential oil for application on dogs' skin, with a low percentage of adverse effects. CONCLUSIONS: This study confirmed the effectiveness of essential oils for practical use as tick and flea repellents and eliminators. Essential-oil-based pharmaceutical can replace chemical pesticides and provide benefits for both consumers and the environment.

Expression of the cobalamin transporters cubam and MRP1 in the canine ileum-Upregulation in chronic inflammatory enteropathy.

Chronic inflammatory enteropathy (CIE) in dogs, a spontaneous model of human inflammatory bowel disease (IBD), is associated with a high rate of cobalamin deficiency. The etiology of hypocobalaminemia in human IBD and canine CIE remains unknown, and compromised intestinal uptake of cobalamin resulting from ileal cobalamin receptor deficiency has been proposed as a possible cause. Here, we evaluated the intestinal expression of the cobalamin receptor subunits, amnionless (AMN) and cubilin (CUBN), and the basolateral efflux transporter multi-drug resistance protein 1 (MRP1) in 22 dogs with CIE in comparison to healthy dogs. Epithelial CUBN and AMN levels were quantified by confocal laser scanning microscopy using immunohistochemistry in endoscopic ileal biopsies from dogs with (i) CIE and normocobalaminemia, (ii) CIE and suboptimal serum cobalamin status, (iii) CIE and severe hypocobalaminemia, and (iv) healthy controls. CUBN and MRP1 expression was quantified by RT-qPCR. Receptor expression was evaluated for correlation with clinical patient data. Ileal mucosal protein levels of AMN and CUBN as well as mRNA levels of CUBN and MRP1 were significantly increased in dogs with CIE compared to healthy controls. Ileal cobalamin receptor expression was positively correlated with age, clinical disease activity index (CCECAI) score, and lacteal dilation in the ileum, inversely correlated with serum folate concentrations, but was not associated with serum cobalamin concentrations. Cobalamin receptor downregulation does not appear to be the primary cause of hypocobalaminemia in canine CIE. In dogs of older age with severe clinical signs and/or microscopic intestinal lesions, intestinal cobalamin receptor upregulation is proposed as a mechanism to compensate for CIE-associated hypocobalaminemia. These results support oral supplementation strategies in hypocobalaminemic CIE patients.

Phenylalanine requirements using the direct amino acid oxidation technique, and the effects of dietary phenylalanine on food intake, gastric emptying, and macronutrient metabolism in adult cats.

Despite Phe being an indispensable amino acid for cats, the minimum Phe requirement for adult cats has not been empirically defined. The objective of study 1 was to determine the minimum Phe requirement, where Tyr is in excess, in adult cats using the direct amino acid oxidation (DAAO) technique. Four adult male cats were used in an 8 × 4 Latin rectangle design. Cats were adapted to a basal diet for 7 d, top dressed with Phe to meet 140% of the adequate intake (NRC, 2006. Nutrient requirements of dogs and cats. Washington, DC: Natl. Acad. Press). Cats were randomly assigned to one of eight experimental Phe diets (0.29%, 0.34%, 0.39%, 0.44%, 0.54%, 0.64%, 0.74%, and 0.84% Phe in the diet on a dry matter [DM] basis). Following 1 d of diet adaptation, individual DAAO studies were performed. During each DAAO study, cats were placed into individual indirect calorimetry chambers, and 75% of the cat's daily meal was divided into 13 equal meals supplied with a dose of L-[1-13C]-Phe. Oxidation of L-[1-13C]-Phe (F13CO2) during isotopic steady state was determined from the enrichment of 13CO2 in breath. Competing models were applied using the NLMIXED procedure in SAS to determine the effects of dietary Phe on 13CO2. The mean population minimum requirement for Phe was estimated at 0.32% DM and the upper 95% population confidence limit at 0.59% DM on an energy density of 4,200 kcal of metabolizable energy/kg DM calculated using the modified Atwater factors. In study 2, the effects of a bolus dose of Phe (44 mg kg-1 BW) on food intake, gastric emptying (GE), and macronutrient metabolism were assessed in a crossover design with 12 male cats. For food intake, cats were given Phe 15 min before 120% of their daily food was offered and food intake was measured. Treatment, day, and their interaction were evaluated using PROC GLIMMIX in SAS. Treatment did not affect any food intake parameters (P > 0.05). For GE and macronutrient metabolism, cats were placed into individual indirect calorimetry chambers, received the same bolus dose of Phe, and 15 min later received 13C-octanoic acid (5 mg kg-1 BW) on 50% of their daily food intake. Breath samples were collected to measure 13CO2. The effect of treatment was evaluated using PROC GLIMMIX in SAS. Treatment did not affect total GE (P > 0.05), but cats receiving Phe tended to delay time to peak enrichment (0.05 < P ≤ 0.10). Overall, Phe at a bolus dose of 44 mg kg-1 BW had no effect on food intake, GE, or macronutrient metabolism. Together, these results suggest that the bolus dose of Phe used may not be sufficient to elicit a GE response, but a study with a greater number of cats and greater food intake is warranted.

Two studies were conducted to evaluate 1) the minimum requirement for dietary Phe and 2) the effects of Phe on gastric emptying (GE) and food intake in adult cats. In study 1, the minimum Phe requirement was estimated using the direct amino acid oxidation (DAAO) technique. Four cats were used and received all diets in random order in a Latin rectangle design (0.29%, 0.34%, 0.39%, 0.44%, 0.54%, 0.64%, 0.74%, and 0.84% Phe in the diet on a dry matter [DM] basis). The minimum Phe requirement, in the presence of excess of Tyr, for adult cats was estimated to be 0.59% DM on an energy density of 4,200 kcal of metabolizable energy/kg DM calculated using the modified Atwater factors; higher than current recommendations set in place by the National Research Council and the American Association of Feed Control Officials. In study 2, we first validated the use of the 13C-octanoic acid breath test (13C-OABT) in cats. Then, the effects of an oral bolus of Phe on food intake, GE, and macronutrient metabolism were evaluated. Phe supplementation did not influence food intake, macronutrient metabolism, or total GE, but tended to delay the time to peak GE.

Current evidence for non-pharmaceutical, non-surgical treatments of canine osteoarthritis.

Osteoarthritis is a progressive degenerative disease process that affects a significant proportion of the canine population, impacting these animals' quality of life. Currently, there is no cure and treatment consists of managing the clinical signs of pain and reduced mobility. There are many treatments for canine osteoarthritis and in this review we discuss the evidence base behind non-pharmaceutical, non-surgical treatments of this disease. These treatments include weight management, nutraceuticals, acupuncture, physiotherapies such as therapeutic exercise, hydrotherapy as well as other therapeutic modalities including photobiomodulation therapy, electromagnetic field therapy and others.

Therapeutic potential of low-molecular weight lignin model polymer fractions for treating skin lesions in animals: a pilot study.

Bacterial infections and resistance to antibiotics are increasingly severe problems. In recent years, Staphylococcus species have emerged as important pathogens in animals and humans. Current therapeutic methods against these species have serious disadvantages; therefore new agents with antibacterial potential, such as plant-based substances, are very important in therapy. We report a pilot study with new method of fractioning the dehydrogenate polymer DHP obtained from coniferyl alcohol and application of the low-MW fractions of 200-3000 Da for antibacterial activity in healing animal lesions. In vivo experiments were conducted on the dogs having a skin lesion. Dogs were treated with the suspension containing the low-MW DHP fractions as the active ingredient, in combination with alginate for 7 days. Cytological smears and microbiological analyses of the affected area were performed. Staphylococcus spp. was isolated from lesions in all dogs from our research. The results show that the low-MW DHP suspension in alginate promotes skin healing and reduction of the infection of the lesions in the affected animals. Pharmaceutical composition containing the low-MW DHP fractions exerts a soothing effect on the subject in wound treatment. Reduction in the number of bacteria by 30% and more were noticed in 6 dogs, while in 4 dogs this percentage is above 50%. No side effects were noticed. Synthesized lignin oligomers may have a significant place as antimicrobial and skin healing agents, especially since an increasing number of multidrug-resistant staphylococci are found on the skin lesions in animals.

Effects of a high-protein, increased-fibre, dry diet supplemented with omega-3 fatty acids on quality of life in dogs undergoing chemotherapy.

Quality of life (QOL) in dogs with cancer is a key consideration in the assessment of cancer treatment options. Despite interest in dietary strategies to improve management of oncology patients, there have been very few clinical studies showing the impact of diet on adverse effects of chemotherapy in dogs. This study was a randomised, controlled, double-blinded, multicenter clinical trial to investigate a high-protein, increased-fibre diet supplemented with omega-3 fatty acids, for dogs with cancer undergoing standard-of-care chemotherapy. Client-owned dogs with newly diagnosed grade 2 or higher mast cell tumours (or non-resectable/incompletely resected tumours) or multicentric lymphoma were randomised to receive the test diet (n = 24) or control diet (n = 21) for 8 weeks. Primary outcomes were QOL assessments, faecal scores, and blood concentrations of C-reactive protein and monocyte chemoattractant protein-1. Of 12 QOL parameters, 10 significantly improved from baseline to Week 8 in the test group compared with one in the control group. However, differences between the two groups were only statistically significant for 'frequency of signs of illness' (P = .009). There were no significant differences in the incidence of any adverse events, including gastrointestinal adverse events or clinically significant differences in laboratory parameters or faecal scores between the two groups. The absence of an observed negative impact of the test diet, combined with the magnitude of QOL improvements associated with the diet, suggest that a larger trial is warranted.

Therapeutic applications of canine platelets and their derivatives: a narrative review.

Platelets contain a multitude of growth factors and play a crucial role in physiological processes such as thrombogenesis, tissue repair, and angiogenesis. As a result, platelet-derived products have significant potential for efficient utilization in the realm of regenerative medicine due to their therapeutic and biological attributes. Numerous studies have already substantiated the therapeutic viability of platelets in various canine ailments. The existing literature indicates a substantial surge in the clinical application of canine platelets, positioning platelet-derived products as a viable alternative to conventional therapeutic agents. Platelet concentrates, including platelet-rich plasma and platelet-rich fibrin are commonly used as a therapeutic modality in clinical cases. These therapeutic derivatives exhibit effectiveness in tissue regeneration and can serve as complementary therapies. Notably, they offer a cost-effective and easily accessible therapeutic option, which has demonstrated its benefits in chronic inflammatory disorders such as osteoarthritis and tendinitis, ophthalmic conditions, wound healing, and mandibular injuries in canine patients. The broad spectrum of therapeutic effects displayed by platelets is providing researchers with novel perspectives for crafting therapeutic models in future investigations. This review centers on exploring the therapeutic potential of canine platelets across diverse disorders. Further exploration into platelet products, encompassing their preparation and applicability in canine medicine, is imperative. These inquiries hold the promise of unveiling fresh horizons for the domain of regenerative medicine.

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.

Homoharringtonine induces apoptosis of mammary carcinoma cells by inhibiting the AKT/mTOR signaling pathway.

Mammary tumour is the most common type of tumour in dogs, especially in unneutered female dogs. Homoharringtonine (HHT) is a natural alkaloid that can be used to treat various types of human tumour. However, the inhibitory effect and mechanism of HHT on canine mammary carcinomas (CMC) remain unclear. This study aimed to evaluate the inhibitory effect of HHT on CMC in vitro and determine its underlying molecular mechanism. The effects of HHT on the cytotoxicity of CMC U27 cells were evaluated by the cell counting kit-8, wound healing, and Transwell assays. HHT-induced apoptosis of U27 cells was detected by JC-1 and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Moreover, the gene expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were analysed using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and the protein expression of protein kinase B/mammalian target of rapamycin (AKT/mTOR) and mitochondrial apoptosis proteins were determined by western blotting. Furthermore, mammary tumour-bearing mouse models were established using 4T1 cells to evaluate the therapeutic effect of HHT. It was found that HHT could significantly down-regulated the protein expression of p-AKT, p-mTOR, and Bcl-2, and up-regulated the protein expression of P53, Bax, cleaved caspase-3, and cleaved caspase-9. In addition, HHT significantly suppressed both tumour volume and mass in mammary tumour mice. In conclusion, HHT damages CMC cells by inhibiting the AKT/mTOR signalling pathway and inducing mitochondrial apoptosis. Such findings lay a theoretical foundation for the clinical treatment of CMC and provide more options for clinical medication.