Lisa M. Freeman

Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells

The functions of dendritic cells (DCs) are tightly regulated such that protective immune responses are elicited and unwanted immune responses are prevented. 1α25-dihydroxyvitamin D3 (1α25(OH)2D3) has been identified as a major factor that inhibits the differentiation and maturation of DCs, an effect dependent upon its binding to the nuclear vitamin D receptor (VDR). Physiological control of 1α25(OH)2D3 levels is critically dependent upon 25-hydroxyvitamin D3-1α-hydroxylase (1αOHase), a mitochondrial cytochrome P450 enzyme that catalyzes the conversion of inactive precursor 25-hydroxyvitamin D3 (25(OH)D3) to the active metabolite 1α25(OH)2D3. Using a human monocyte-derived DC (moDC) model, we have examined the relationship between DC VDR expression and the impact of exposure to its ligand, 1α25(OH)2D3. We show for the first time that moDCs are able to synthesize 1α25(OH)2D3 in vitro as a consequence of increased 1αOHase expression. Following terminal differentiation induced by a diverse set of maturation stimuli, there is marked transcriptional up-regulation of 1αOHase leading to increased 1αOHase enzyme activity. Consistent with this finding is the observation that the development and function of moDCs is inhibited at physiological concentrations of the inactive metabolite 25(OH)D3. In contrast to 1αOHase, VDR expression is down-regulated as monocytes differentiate into immature DCs. Addition of 1α25(OH)2D3 to moDC cultures at different time points indicates that its inhibitory effects are greater in monocyte precursors than in immature DCs. In conclusion, differential regulation of endogenous 1α25(OH)2D3 ligand and its nuclear receptor appear to be important regulators of DC biology and represent potential targets for the manipulation of DC function.

AAHA Nutritional Assessment Guidelines for Dogs and Cats

Donald Ostwald, Jr., DVM, DABVP (Canine & Feline) Introduction The American Animal Hospital Association recommends these nutritional assessment guidelines because good nutrition enhances pets’ quality and quantity of life, and is integral to optimal animal care. Incorporating nutritional assessment into regular animal care is critical for maintaining pets’ health, as well as their response to disease and injury. It requires little to no additional time or cost. The specific goals of this article are to provide:

Pet feeding practices of dog and cat owners in the United States and Australia

Most pet dogs and cats in developed countries are fed commercial foods, but there is growing interest in the use of noncommercial foods for pets, including homemade and raw food diets. A survey of dog and cat owners in the United States and Australia revealed that > 90% of pets were fed commercial foods, but that noncommercial foods comprised at east 25% of the diet for 17.3% of dogs and 6.3% of cats.

Cachexia and Sarcopenia: Emerging Syndromes of Importance in Dogs and Cats

Cachexia is the loss of lean body mass (LBM) that affects a large proportion of dogs and cats with congestive heart failure (CHF), chronic kidney disease (CKD), cancer, and a variety of other chronic diseases. Sarcopenia, the loss of LBM that occurs with aging, is a related syndrome, although sarcopenia occurs in the absence of disease. As many of the diseases associated with muscle loss are more common in aging, cachexia and sarcopenia often are concurrent problems. Both cachexia and sarcopenia have important clinical implications because they are associated with increased morbidity and mortality. The pathophysiology of these 2 syndromes is complex and multifactorial, but recent studies have provided new information that has helped to clarify mechanisms and identify potential new targets for treatment. Newly identified mechanisms and pathways that mediate cachexia appear to act by increasing energy requirements, decreasing energy intake, impairing nutrient absorption, and causing metabolic alterations. Whereas cachexia and sarcopenia are important areas of research for drug development in people, they are only beginning to be recognized in veterinary medicine. Greater awareness and earlier diagnosis will help provide practical approaches to managing body weight and lean tissue in dogs and cats, as well as more directed targets for treatment.

Origin and subset distribution of peripheral blood dendritic cells in patients with chronic Graft-Versus-Host disease

Background. After allogeneic hematopoietic stem cell transplantation, donor T cells interact with an antigen-presenting cell environment that is distorted in number, level of activation, and origin. The role of antigen presentation in the development of chronic graft-versus host disease (cGVHD) is unknown. Methods. The number and origin of peripheral blood immature myeloid (CD19− CD1c+) and plasmacytoid (BDCA-2+) dendritic cells (DCs) was determined in 30 patients at more than 100 days after allogeneic hematopoietic stem cell transplantation. Results. Patients with cGVHD had significantly higher plasmacytoid DC numbers than individuals without this complication (9.1±2.0×106/L versus 3.8±0.6×106/L, P =0.025). Chimerism studies demonstrated that DCs in patients with cGVHD were exclusively of donor origin, whereas persistence of host DCs was observed in some control patients. Conclusions. The antigen-presenting cell environment in patients with cGVHD, as represented by immature blood DCs, is of donor origin but distorted in terms of subset distribution.

Chronic Hepatitis in Labrador Retrievers: Clinical Presentation and Prognostic Factors

BACKGROUND An increased incidence of chronic hepatitis has been reported in Labrador Retrievers. HYPOTHESIS A breed associated hepatopathy occurs in Labrador Retrievers. ANIMALS Twenty-four client-owned Labrador Retrievers. METHODS Medical records of dogs with histopathologic confirmation of chronic hepatitis were retrospectively reviewed. A clinical score based on clinical signs and the results of biochemical tests was generated for each dog. Hepatic biopsy specimens were scored for disease activity, fibrosis, and copper accumulation. RESULTS The median age was 9.3 years (range, 3.9-14.0 years). Clinical signs included inappetence, vomiting, lethargy, and weight loss. All dogs had increases in serum activity of one or more hepatobiliary enzyme. Hyperbilirubinemia and hypoalbuminemia were present in 45% and 21% of dogs, respectively. The median clinical score was 2.9, with a range of 0-8. The median histopathology activity and the fibrosis scores were 3.5 (range, 1-6) and 3.0 (range, 0-4), respectively. Rhodanine-positive copper staining was present in 15 of 17 biopsy specimens, with a median score of 2.0 (range, 0-3). Median survival was 374 days (range, 1-2645 days). A prolonged prothrombin time (P = .013) and thrombocytopenia (P = .041) were associated with survival < 2 months. The presence of anorexia (P = .049), hypoglobulinemia (P = .045), or prolonged partial thromboplastin time (P = .033) were associated with shorter overall survival times. The clinical score correlated with survival time (P = .030) and histopathologic staging (P = .049). CONCLUSIONS AND CLINICAL IMPORTANCE A progressive hepatopathy in Labrador Retrievers in this study was marked by chronic inflammation, fibrosis, and copper accumulation. A clinical scoring system that correlates with survival time may be useful as a noninvasive method to predict prognosis.

Relationship among plasma amino acids, C-reactive protein, illness severity, and outcome in critically ill dogs.

BACKGROUND Alterations in circulating amino acids have been documented in animal models and in critically ill people but have not been evaluated in dogs with spontaneously occurring disease. HYPOTHESIS/OBJECTIVES To compare amino acid concentrations in critically ill dogs and healthy controls and to investigate potential relationships among amino acids, markers of inflammation, illness severity, and clinical outcome. ANIMALS Forty-eight critically ill dogs and 24 healthy control dogs. METHODS Plasma was analyzed for amino acids and C-reactive protein (CRP) was measured in serum. The Fischer ratio (the molar ratio of branched chain amino acids [BCAA] to aromatic amino acids [AAA]) and survival prediction index (SPI2) were calculated. RESULTS Median CRP concentrations were significantly higher in the critically ill dogs compared with controls (P < .001). Critically ill dogs had significantly lower concentrations of alanine (P= .001), arginine (P < .001), citrulline (P < .001), glycine (P < .001), methionine (P < .001), proline (P < .001), and serine (P= .001) but significantly higher concentrations of lysine (P= .02) and phenylalanine (P < .001; Table 1). This pattern resulted in a significantly lower Fischer ratio (P= .001) in the critically ill group. Median SPI2 score was significantly higher in dogs that survived (P= .03). Concentrations of arginine (P= .02), isoleucine (P= .01), leucine (P= .04), serine (P= .04), valine (P= .04), total BCAA (P= .03), and the Fischer ratio (P= .03) were significantly higher in survivors compared with nonsurvivors. CONCLUSIONS AND CLINICAL IMPORTANCE Critically ill dogs have altered amino acid profiles and additional research to investigate potential benefits of amino acid supplementation is warranted.

Evaluation of vehicular trauma in dogs: 239 cases (January-December 2001)

OBJECTIVE To describe a population of dogs with vehicular trauma and to determine whether age, type and severity of injury, or preexisting disease were associated with outcome. DESIGN Retrospective case series. ANIMALS 239 dogs evaluated at a university referral hospital after vehicular trauma over a 12-month period. PROCEDURES Patient characteristics, including age, outcome, animal trauma triage (ATT) score, treatments performed, hospital stay, cost, and preexisting disease, were recorded from medical records of dogs that had vehicular trauma. Dogs were assigned to a young, middle-aged, or geriatric age group. Categoric and continuous variables were compared between survivors and nonsurvivors to identify possible associations. RESULTS 239 dogs (126 males and 113 females) were evaluated following vehicular trauma during 2001: young (n = 149), middle-aged (68), and geriatric (22). The median ATT score was 3 (range, 0 to 15). Sixteen dogs had preexisting disease. Hospital stay ranged from < 1 to 28 days (median, 3 days). Cost ranged from

Current knowledge about the risks and benefits of raw meat-based diets for dogs and cats

77 to

Association of Body Weight and Body Condition with Survival in Dogs with Heart Failure

10,636 (median,