Effects of high‐fat and high‐carbohydrate diets on fat and carbohydrate oxidation and plasma metabolites in healthy cats

High‐fat (HF) or high‐carbohydrate (HC) diets (30% fat, 18.9% carbohydrate; HF and 10% fat, 46.3% carbohydrate; HC) and lengths of adaptation were investigated in cats (Felis catus; 10 ± 2 months, 3.6 ± 0.3 kg). Cats randomly received each treatment for 14 days in a crossover design with a 14‐day washout period between each diet. Three 22‐h indirect calorimetry studies were conducted after acute (day 0), semichronic (day 4) and chronic (day 13) dietary exposure. Blood samples were collected after a 24‐h fast on days 1, 5 and 14. When cats consumed the HC and HF diet, oxidation of the restricted nutrient exceeded intake while oxidation of the nutrient in excess matched intake. Mean max energy expenditure (EE) of cats consuming the HF and HC diet were 107 and 102 kcal/kg^0.67/day and occurred at a mean of 4 and 12 h post‐feeding respectively. Maximal fat (0.90 g/h) and carbohydrate (carbohydrate; 1.42 g/h) oxidation were attained at 26 min and 10.4 h post‐feeding respectively. The changes observed in macronutrient oxidation and EE suggest that cats adapt whole‐body nutrient metabolism in response to changes in dietary macronutrient content, but may require longer than 14 day to adapt to a macronutrient that is present at a lower concentration in the diet.     

Effect of feeding a high‐carbohydrate or a high‐fat diet on subsequent food intake and blood concentration of satiety‐related hormones in dogs

Although studies in rodents and humans have evidenced a weaker effect of fat in comparison to carbohydrates on the suppression of food intake, very few studies have been carried out in this field in dogs. This study investigates the effects of a high‐carbohydrate (HC ) and a high‐fat (HF ) diets on subsequent food intake and blood satiety‐related hormones in dogs. Diets differed mainly in their starch (442 vs. 271 g/kg dry matter) and fat (99.3 vs. 214 g/kg dry matter) contents. Twelve Beagle dogs received the experimental diets at maintenance energy requirements in two experimental periods, following a cross‐over arrangement. In week 7 of each period, blood concentrations of active ghrelin, glucagon‐like peptide (GLP ‐1), peptide YY , insulin, and glucose were determined before and at 30, 60, 120, 180, and 360 min post‐feeding. The following week, intake of a challenge food offered 180 min after the HC and HF diets was recorded over two days. In comparison to the dogs on the HC diet, those on the HF diet had a higher basal concentration of GLP ‐1 (p  = .010) and a higher total area under the curve over 180 min post‐prandial (tAUC _0–180) (p  = .031). Dogs on the HC diet showed a higher elevation of ghrelin at 180 min (p  = .033) and of insulin at 360 min (p  = .041), although ghrelin and insulin tAUC _0–180 did not differ between the two diets (p  ? .10). Diet had no effect on challenge food intake (p  ? .10), which correlated with the tAUC _0–180 of ghrelin (r = .514, p  = .010), insulin (r = ?.595, p  = .002), and glucose (r = ?.516, p  = .010). Feeding a diet high in carbohydrate or fat at these inclusion levels does not affect the feeding response at 180 min post‐prandial, suggesting a similar short‐term satiating capacity.     

ORIGINAL ARTICLE: Application of soybean meal,soy protein concentrate and isolate differing in α‐galactosides content to low‐ and high‐fibre diets in growing turkeys

The aim of this experiment was to investigate the physiological and growth response of young turkeys (up to 8 weeks of age) to dietary replacement of soybean meal (SBM) by soy protein concentrate (PC) or protein isolate (PI). This replacement resulted in a differentiated dietary concentration of α‐galactosides of over 2.5% in the SBM diet, approximately 2% with a mixture SBM and PC, 1% with a PC diet and 0.1% with a PI diet. Each treatment was applied in two ways: with lower (3.5%) or higher (5.3%) dietary crude fibre content, made by supplementation with soybean hulls. The highest and lowest body weight of turkeys was recorded both after the first and second 4‐week half of the study in the PC and PI‐type diets respectively. A gradual withdrawal of α‐galactosides from a diet was accompanied by a decline in ileal tissue mass, ileal viscosity and activity of endogenous maltase (the latter was found to be significant at 4 weeks of age). At the same time, two‐way anova revealed that an elevated level of crude fibre (HF treatment) caused an increase in ileal tissue mass (p < 0.05 after 4 weeks of feeding) as well as a decrease in activity level of intestinal sucrase and maltase. The presence of raffinose family oligosaccharides in a diet, in contrast to dietary crude fibre level, significantly affected the caecal metabolism. The rate of bacterial production of short‐chain fatty acids in the caeca was distinctly diminished by dietary withdrawal of α‐galactosides. In conclusion, the soy protein concentrate, in contrast to the protein isolate preparation, exerted positive effects on the turkeys’ growth and gastrointestinal tract physiology and should be considered as an effective SBM substitute.     

Patient characteristics,prognostic factors and outcome of dogs with high‐grade primary mediastinal lymphoma

The goals of this retrospective study were to determine the patient characteristics of dogs with high‐grade primary mediastinal lymphoma and to determine outcome and associated prognostic factors. A total of 42 dogs were identified, in which 36 received treatment and had follow‐up information available. The most common clinical signs included lethargy, anorexia and polyuria/polydipsia. Hypercalcemia and pleural effusion were common findings at diagnosis. The phenotype was almost exclusively T‐cell, most often in association with lymphoblastic cytomorphology as defined by the World Health Organization (WHO) lymphoma classification scheme. The overall progression‐free survival (PFS) and overall survival (OS) were 133 and 183 days, respectively. Treatment with a CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) protocol was associated with an improved PFS (144 days) and OS (194 days) when compared with dogs that received other medical therapies (P = .005 and P = .002, respectively); the absence of pleural effusion at diagnosis was associated with an increased OS but not PFS. These results suggest that while the prognosis for dogs with mediastinal lymphoma is poor, survival may be improved with treatment using a CHOP‐based protocol.     

Prognostic value of pretreatment plasma D‐dimer level in dogs with intermediate to high‐grade non‐Hodgkin lymphoma

Pretreatment D‐dimer levels have been reported to predict survival in several types of malignancies in human patients. The objective of this study was to evaluate the prognostic value of pretreatment D‐dimer level in dogs with intermediate to high‐grade non‐Hodgkin lymphoma (NHL). In a prospective, randomized, double‐blind study of F14512 vs etoposide phosphate, we assessed the prognostic value of pretreatment plasma D‐dimer level in 48 client‐owned dogs diagnosed with intermediate to high‐grade NHL. The correlation between pretreatment plasma D‐dimer level and various clinical features, progression‐free survival (PFS) and overall survival (OS) was analysed. The median value of pretreatment plasma D‐dimer level was 0.4 μg/mL (range: 0.1‐14.3 μg/mL). High pretreatment plasma D‐dimer level (>0.5 μg/mL) was detected in 44% (21/48) of dogs. High D‐dimer levels were not correlated with naive vs relapsed lymphoma, clinical stage, substage, immunophenotype or treatment group. D‐dimer levels >0.5 μg/mL were significantly associated with inferior median PFS (54 vs 104 days, P = .011) and OS (93 vs 169 days, P = .003). In the multivariate analysis, high D‐dimer levels remained an independent predictor for worse PFS (HR: 3.21, 95% CI: 1.57‐6.56, P = .001) and OS (HR: 3.87, 95% CI: 1.88‐7.98; P < .001). This study suggests that pretreatment plasma D‐dimer level can serve as a predictor of prognosis in dogs with intermediate to high‐grade NHL. Further studies are warranted to confirm these findings.     

Prognostic significance of Ki67 evaluated by flow cytometry in dogs with high‐grade B‐cell lymphoma

Ki67 can discriminate between high‐ and low‐grade canine lymphomas, but its prognostic role in specific subtypes of the neoplasm is unknown. We assessed the prognostic significance of Ki67% (percentage of Ki67‐positive cells), evaluated by flow cytometry, in 40 dogs with high‐grade B‐cell lymphoma, treated with a modified Wisconsin–Madison protocol (UW‐25). The following variables were investigated for association with lymphoma specific survival (LSS) and relapse free interval (RFI): Ki67%, breed, sex, age, stage, substage, complete remission (CR). By multivariate analysis, Ki67% (P = 0.009) and achievement of CR (P = 0.001) were independent prognostic factors for LSS. Dogs with intermediate Ki67% (20.1–40%) presented longer LSS and RFI (median = 866 and 428 days, respectively) than dogs with low (median = 42 days, P < 0.001; median = 159 days, P = 0.014) or high (median = 173 days, P = 0.038; median = 100 days, P = 0.126) values. Determination of Ki67 is a prognostic tool that improves the clinical usefulness of flow cytometric analysis in canine high‐grade B‐cell lymphoma.     

Macronutrient intake of dogs,self‐selecting diets varying in composition offered ad libitum

The diet of the domestic dog has changed significantly from that of its wolf ancestor, with to date only two studies having examined macronutrient self‐selection in dogs. Whilst the first focused solely on protein intake, determining an intake of 30% metabolisable energy (ME ), the second investigated dietary protein, fat and carbohydrate (PFC ), indicating an intake ratio of 30:63:7% by energy. This study's aim was to further elucidate macronutrient intake by providing greater macronutrient range, energy content, and to investigate over a longer duration than previous studies. Fifteen adult dogs were given access to three wet diets providing 500% of daily ME , twice daily over 10 days. The diets were nutritionally complete and formulated using the same four ingredients in different proportions to supply high levels of protein (58% ME ), fat (86% ME ) or carbohydrate (54% ME ). Overall fat and carbohydrate consumption significantly declined from 6,382 to 917 kcals per day (p  < 0.001) and 553 to 214 kcals day^?1 (p  < .01) respectively. Protein intake, however, remained constant over the study and ranged from 4,786 to 4,156 kcals day^?1. Such results impacted on percentage total energy intake, with fat decreasing from 68% to 52% (p  < .001) and protein increasing from 29% to 44% (p  < .01). Our findings suggest that dogs still possess a “feast or famine” mentality, wherein energy dense fat is prioritised over protein initially. With continued feeding over 10 days, a transition to a more balanced energy contribution from both macronutrients is evident. The study also shows that given the option, dogs do not select carbohydrate to be a significant portion of the diet. The health implications of such dietary selection are of interest.     

Effects of high‐sulphur water on hepatic gene expression of steers fed fibre‐based diets

Sulphur‐induced polioencephalomalacia (sPEM), a neurological disorder affecting ruminants, is frequently associated with the consumption of high‐sulphur (S) water and subsequent poor performance. Currently, there is no economical method for S removal from surface water sources, and alternative water sources are typically neither readily available nor cost‐effective. Determination of genes differentially expressed in response to high‐S water consumption may provide a better understanding of the physiology corresponding to high dietary S and ultimately lead to the development of treatment and prevention strategies. The objective of this study was to determine changes in gene expression in the liver, an organ important for S metabolism, of fibre‐fed steers consuming high‐S water. For this study, liver tissues were collected on the final day of a trial from yearling steers randomly assigned to low‐S water control (566 mg/kg SO₄; n = 24), high‐S water (3651 mg/kg SO₄; n = 24) or high‐S water plus clinoptilolite supplemented at either 2.5% (n = 24) or 5.0% (n = 24) of diet dry matter (DM). Microarray analyses on randomly selected healthy low‐S control (n = 4) and high‐S (n = 4; no clinoptilolite) steers using the Affymetrix GeneChip Bovine Genome Array revealed 488 genes upregulated (p < 0.05) and 154 genes downregulated (p < 0.05) in response to the high‐ vs. low‐S water consumption. Real‐time RT‐PCR confirmed the upregulation (p < 0.10) of seven genes involved in inflammatory response and immune functions. Changes in such genes suggest that ruminant animals administered high‐S water may be undergoing an inflammation or immune response, even if signs of sPEM or compromised health are not readily observed. Further study of these, and other affected genes, may deliver new insights into the physiology underlying the response to high dietary S, ultimately leading to the development of treatments for high S–affected ruminant livestock.     

Serum metabolites,ghrelin and leptin are modified by age and/or diet in weanling kittens fed either a high‐ or moderate‐protein diet

The objective of this study was to evaluate the effects of in utero and postnatal exposure of a high‐protein (HP; n = 9) or moderate‐protein (MP; n = 16) diet on growth, and serum metabolite, ghrelin and leptin concentrations during the first 4 months of life in kittens. It was hypothesized that blood indices would be modified due to diet. Blood samples were collected from kittens at 4, 8, 12 and 16 weeks of age. Kittens were weaned at 8 weeks of age onto the same diet as the dam. Body weight was measured weekly from birth and daily food intake for each litter was recorded post‐weaning. Serum concentrations of urea nitrogen, total protein and triglycerides were greater (P < 0.05) in kittens fed the HP diet. Serum cholesterol concentrations were greater (P < 0.05) in MP‐fed kittens at 4 weeks of age. Moderate‐protein fed kittens tended to have greater (P < 0.10) serum ghrelin concentrations. Leptin concentrations were not affected by diet, but changed over time (P < 0.05). Our data indicate that diet and age of kittens affect circulating concentrations of peptides important in appetite regulation. Further research testing the effects of in utero and early postnatal nutrient exposure on feline obesity risk in adulthood is needed.     

Correlations between circulating leptin concentrations and growth performance,carcass traits,and meat quality indexes in finishing Simmental × Luxi bulls fed high‐concentrate diets

Circulating leptin concentrations could potentially be used as a predictor of production traits in cattle. This study aimed to clarify the correlations between circulating leptin concentrations and growth performance, carcass traits, and meat quality indexes in finishing bulls fed high‐concentrate diets (concentrate‐to‐forage ratio 70:30). Fifty‐seven Simmental × Luxi F1 crossbred bulls were used for 112‐day finishing experiment. Circulating leptin concentrations and relevant indexes of growth performance, and carcass traits and meat quality were measured during or after finishing trail. The results indicated that the leptin concentrations tended to be negatively correlated with dry matter intake (DMI) (r = ?.233, p = .081), and were positively correlated with 12th‐rib fat thickness (r = .330, p = .012), marbling score (r = .336, p = .011), and intramuscular fat content (r = .368, p = .021). Moreover, the leptin concentrations were negatively correlated with cholesterol content (r = ?.339, p = .037) and were not correlated with sensory indexes including tenderness, juiciness, and like flavor (p > .05). In conclusion, circulating leptin concentrations may potentially be used as a predictor of carcass traits related to content of fat and beef quality traits related to content of cholesterol in finishing bulls fed high‐concentrate diets.     

Retrospective outcome evaluation for dogs with surgically excised,solitary Kiupel high‐grade,cutaneous mast cell tumours

Published outcomes for dogs with specifically high‐grade mast cell tumours (MCTs), controlled for clinical stage, are few. Clinical outcomes for 49 dogs with Kiupel high‐grade, clinical stage I, cutaneous MCTs were evaluated. Median survival time (MST) was 1046 days; 1 and 2‐year survival rates were 79.3% and 72.9%, respectively. At study end 24 dogs had died, 23 dogs were alive (median follow‐up 980 days) and 2 dogs were lost to follow‐up. Death was considered MCT‐related in 14 of 20 dogs with a known cause of death. Local tumour recurrence developed in nine dogs (18.4%); regional lymph node metastasis occurred in six dogs (12.2%); and a new MCT developed in 15 dogs (30.1%). Tumour location, histologic margin size and use of chemotherapy did not affect MST; increasing mitotic count (P = .001) and increasing tumour diameter (P = .024) were independently negatively prognostic. Six dogs that developed lymph node metastasis after surgery had worse MST (451 days) than 42 dogs that did not develop metastasis (1645 days); (P < .001). Our study suggests that dogs with local surgical control of clinical stage I histologically high Kiupel grade cutaneous MCT may have a long survival time; especially those with smaller tumours and a lower mitotic count. Our results suggest that evaluation of staging information and mitotic count may be equally helpful as histologic grading when making a prognosis; and highlight the importance of not relying on histologic grade alone when predicting survival for dogs with MCT.     

Use of low carbohydrate, high protein diets in cats with diabetes mellitus

The goal of this randomized, double‐blind study was to compare the effects of feeding a low carbohydrate, high protein diet versus a maintenance diet in a group of cats with diabetes mellitus treated with insulin glargine twice daily. All cats with naturally occurring diabetes mellitus not currently treated with insulin glargine or diabetogenic drugs or being fed a low carbohydrate, high protein diet were eligible for inclusion. Baseline testing included a physical examination, complete blood count, serum biochemistry profile, urinalysis and urine culture, serum thyroxine concentration, and serum fructosamine concentration. All cats were treated with insulin glargine (starting dose of 0.25 U/kg) twice daily. Insulin was adjusted as needed for glucose regulation. Cats were randomized to receive either a low carbohydrate, high protein diet or a feline maintenance diet. Re‐evaluations were performed on all cats at weeks 1, 2, 4, 6 and 10, and included an assessment of clinical signs, physical examination, 12‐h blood glucose curve, and serum fructosamine concentrations. Changes in continuous variables over the course of the study were analyzed using analysis of variance with repeated measures. p < 0.05 was considered statistically significant. Ten cats have completed the study. There were no significant differences between diet groups at baseline for age, gender, weight, body condition score, serum glucose or fructosamine concentrations. Although there was not a significant difference over time in clinical signs, insulin doses, or peak or nadir glucose concentrations between diet groups, diet did have a significant effect on serum fructosamine concentrations (p = 0.01). Six of the 10 cats that have completed the study achieved complete remission by the end of the study period, with no statistical difference between diets. The study's results indicate that diet can have significant effects on glucose regulation in cats receiving insulin glargine for treatment of feline diabetes mellitus.     

A dose‐finding study with a novel water‐soluble formulation of paclitaxel for the treatment of malignant high‐grade solid tumours in dogs

A new formulation of water‐soluble paclitaxel (Paccal® Vet) has been developed for canine cancer patients, without the need for pre‐medication (traditionally required in non‐water‐soluble paclitaxel formulations). The objective of the study was to determine a clinically safe and efficacious dose of Paccal Vet and to estimate progression‐free and overall survival and to evaluate single‐dose pharmacokinetics in tumour‐bearing dogs. A positive risk:benefit ratio was established for Paccal Vet administered at 150 mg m^–2 intravenous (IV) for three or more treatment cycles. Preliminary efficacy was demonstrated by best objective response rate (86%), median time to response (14 days) and median progression‐free survival (131 days). Paccal Vet was associated with expected adverse events (AE) (e.g. myelosuppression), however the majority were transient, clinically silent and manageable. This is the first clinical report of a water‐soluble formulation of paclitaxel suggesting successful administration and being safely used without pre‐medication in dogs.     

Prognostic significance of hypermethylation of death‐associated protein kinase (DAPK) gene CpG island in dogs with high‐grade B‐cell lymphoma

Death‐associated protein kinase (DAPK) is a serine/threonine kinase and a tumour suppressor gene. Diffuse large B‐cell lymphomas with inactivated DAPK through hypermethylation of a CpG island is known to result in a biologically aggressive phenotype in humans. This retrospective study was carried out to analyse the prognostic significance of DAPK CpG island hypermethylation in canine lymphoma. We hypothesized that DAPK CpG island hypermethylation can be a negative prognostic indicator in dogs with nodal high‐grade B‐cell lymphoma. Forty‐seven dogs with high‐grade B‐cell lymphoma, according to the updated Kiel classification, were evaluated after being treated with a CHOP (vincristine, cyclophosphamide, doxorubicin and prednisolone)‐based chemotherapy protocol. The methylation status of the DAPK CpG island was examined by methylation‐specific PCR. Progression‐free survival (PFS) and overall survival (OS) were compared using the Kaplan‐Meier analysis and log‐rank test. The cox proportional hazard regression model was used to evaluate the effect of multiple variables. Hypermethylation of the DAPK CpG island was detected in 21 of the 47 dogs. The PFS and OS in dogs with the hypermethylation (median: 220 and 266 days, respectively) were significantly shorter than those of dogs without hypermethylation (median: 301 and 412 days, respectively) (PFS, P = .036; OS, P = .007). In the multivariate analysis, hypermethylation of the DAPK CpG island remained an independent prognostic factor in predicting shortened PFS (P = .047) and OS (P = .021) as well as clinical substage b. Overall, hypermethylation of the DAPK CpG island was a negative prognostic factor in canine high‐grade B‐cell lymphoma.     

A retrospective review of treatment and response of high‐risk mast cell tumours in dogs

This retrospective case series evaluates survival outcome of 94 dogs with high metastatic risk mast cell tumours (MCT). Patients were treated with a cytotoxic chemotherapy protocol or the tyrosine kinase inhibitor masitinib, in the presence of gross disease or as an adjunct to surgical resection of the primary tumour. In patients presenting with metastatic disease, surgical resection of the primary tumour with adjunctive therapy with any chemotherapy incurred a significant survival advantage [median survival time (MST): 278 days] compared to patients receiving chemotherapy without surgical excision of the primary tumour (MST: 91 days, P < 0.0001). Patients with a surgically excised Patnaik grade II tumour and high Ki‐67 in the absence of metastatic disease treated with vinblastine and prednisolone showed a significantly longer survival (MST: 1946 days) than those treated with masitinib (MST: 369 days, P = 0.0037). Further prospective case‐controlled clinical trials of high‐risk MCTs are required to make precise evidence‐based treatment decisions for individual patients.