Biological activity of immunostimulatory CpG DNA motifs in domestic animals

Bacterial DNA contains a much higher frequency of CpG dinucleotides than are present in mammalian DNA. Furthermore, bacterial CpG dinucleotides are often not methylated. It is thought that these two features in combination with specific flanking bases constitute a CpG motif that is recognized as a "danger" signal by the innate immune system of mammals and therefore an immune response is induced when these motifs are encountered. These immunostimulatory activities of bacterial CpG DNA can also be achieved with synthetic CpG oligodeoxynucleotides (ODN). Recognition of CpG motifs by the innate immune system requires engagement of Toll-like receptor 9 (TLR-9), which induces cell signaling and subsequently triggers a pro-inflammatory cytokine response and a predominantly Th1-type immune response. CpG ODN-induced innate and adaptive immune responses can result in protection in various mouse models of disease. Based on these observations, clinical trials are currently underway in humans to evaluate CpG ODN therapies for cancer, allergy and infectious disease. However, potential applications for immunostimulatory CpG ODN in species of veterinary importance are just being explored. In this review, we will highlight what is presently known about the immunostimulatory effects of CpG ODN in domestic animals.     

Prepartum teat apex colonization with Staphylococcus chromogenes in dairy heifers is associated with low somatic cell count in early lactation

A high number of dairy heifers freshen with udder health problems. The prevalence of teat apex colonization (TAC) with Staphylococcus chromogenes, one of the most widespread coagulase-negative staphylococci (CNS) in milk samples from freshly calved dairy heifers, was measured cross-sectionally in non-lactating heifers on eight commercial dairy farms in Belgium. The influence of age on this prevalence, and the association between teat apex colonization with S. chromogenes prepartum and quarter milk somatic cell count (SCC) in early lactation were studied. In total, 492 teat apices were sampled from 123 heifers. The age of the heifers varied from 8 to 34 months. Overall, 20% of the heifers had at least one teat apex colonized with S. chromogenes. Of all teats sampled, 10% were colonized with S. chromogenes. The chance of having at least one teat apex colonized with S. chromogenes increased with age of the heifer. The presence of prepartum teat apex colonization with S. chromogenes was not associated with intramammary infection (IMI) early postpartum with the same bacterium. On the contrary, teat apex colonization with S. chromogenes prepartum appeared to protect quarters in the first few days of lactation from having somatic cell count >or=200000cells/ml milk, commonly accepted as the threshold for intramammary infection.     

核桃优良早实新品系云新90301、云新90303的选育

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Associations between dry dietary factors and canine calcium oxalate uroliths

OBJECTIVE: To identify factors in dry diets associated with the occurrence of calcium oxalate (CaOx) uroliths in dogs. ANIMALS: 600 dogs with CaOx uroliths and 898 dogs without urinary tract diseases. PROCEDURE: Univariate and multivariate logistic regression were performed. RESULTS: Compared with diets with the highest concentrations of sodium, dry diets with the lowest concentrations of sodium, phosphorus, calcium, chloride, protein, magnesium, or potassium were linearly associated with increased risk of CaOx urolith formation. Significant nonlinear associations between increased occurrence of CaOx uroliths and urine acidifying potential and low moisture content were observed. Significant nonlinear associations between decreased occurrence of CaOx uroliths and carbohydrate and fiber contents were observed. A significant association between the occurrence of CaOx uroliths and dietary fat was not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that dry diets formulated to contain high concentrations of protein, calcium, phosphorus, magnesium, sodium, potassium, and chloride may minimize formation of CaOx uroliths. In addition, comparison of risk and protective factors of various diet ingredients fed to dogs with CaOx uroliths suggests that although similar findings were observed in canned and dry formulations, in general, greater risk is associated with dry formulations. However, before these hypotheses about dietary modifications are adopted by food manufacturers, they must be investigated by use of appropriately designed clinical studies of dogs with CaOx urolithiasis.     

Associations between dietary factors in canned food and formation of calcium oxalate uroliths in dogs

OBJECTIVE: To identify dietary factors in commercially available canned foods associated with the development of calcium oxalate (CaOx) uroliths in dogs. ANIMALS: 117 dogs with CaOx uroliths and 174 dogs without urinary tract disease. PROCEDURE: Case dogs were those that developed CaOx uroliths submitted to the Minnesota Urolith Center for quantitative analysis between 1990 and 1992 while fed a commercially available canned diet. Control dogs were those without urinary tract disease evaluated at the same veterinary hospital just prior to or immediately after each case dog. A content-validated multiple-choice questionnaire was mailed to each owner of case and control dogs with the permission of the primary care veterinarian. Univariate and multivariate logistic regressions for each dietary component were performed to test the hypothesis that a given factor was associated with CaOx urolith formation. RESULTS: Canned foods with the highest amount of protein, fat, calcium, phosphorus, magnesium, sodium, potassium, chloride, or moisture were associated with a decreased risk of CaOx urolith formation, compared with diets with the lowest amounts. In contrast, canned diets with the highest amount of carbohydrate were associated with an increased risk of CaOx urolith formation. CONCLUSIONS AND CLINICAL RELEVANCE: Feeding canned diets formulated to contain high amounts of protein, fat, calcium, phosphorus, magnesium, sodium, potassium, chloride, and moisture and a low amount of carbohydrate may minimize the risk of CaOx urolith formation in dogs.     

Effects of short-term trimethoprim-sulfamethoxazole administration on thyroid function in dogs

OBJECTIVE: To determine how rapidly trimethoprim-sulfamethoxazole affects serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in euthyroid dogs and how quickly hormone concentrations return to reference values following discontinuation of administration. DESIGN: Prospective study. ANIMALS: 7 healthy euthyroid dogs. PROCEDURE: Dogs were given trimethoprim-sulfamethoxazole (26.5 to 31.3 mg/kg [12 to 14.2 mg/lb], PO, q 12 h) for a maximum of 6 weeks. A CBC and Schirmer tear test were performed and serum total T4 and TSH concentrations were measured weekly. Administration of trimethoprim-sulfamethoxazole was discontinued if total T4 concentration was less than the lower reference limit and TSH concentration was greater than the upper reference limit or if persistent neutropenia developed. RESULTS: Six dogs had total T4 concentrations less than the lower reference limit within 3 weeks; T4 concentration was decreased after 1 week in 3 of these 6 dogs. In these 6 dogs, TSH concentration was greater than the upper reference limit within 4 weeks. In 1 dog, T4 and TSH concentrations were not affected, despite administration of trimethoprim-sulfamethoxazole for 6 weeks. Neutropenia developed in 4 dogs. In 1 dog, the neutropenia resolved while trimethoprim-sulfamethoxazole was still being administered. In the other 3, neutrophil counts returned to reference values 1 week after drug administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of trimethoprim-sulfamethoxazole at a dosage of 26.5 to 31.3 mg/kg, PO, every 12 hours can substantially alter serum total T4 and TSH concentrations and neutrophil counts in dogs within as short a time as a few weeks.     

Massive transfusion in dogs: 15 cases (1997-2001)

OBJECTIVE: To determine clinical characteristics of dogs that received massive transfusion and identify the underlying diseases, complications, and outcomes. DESIGN: Retrospective study. ANIMALS: 15 dogs. PROCEDURE: Medical records of dogs receiving a massive blood transfusion were evaluated for transfusion volume, underlying disease process or injury, benefits and complications of transfusion, and outcome. A massive transfusion was defined as transfusion of a volume of blood products in excess of the patient's estimated blood volume (90 ml/kg [40 ml/lb]) in a 24-hour period or transfusion of a volume of blood products in excess of half the patient's estimated blood volume in a 3-hour period. RESULTS: Six dogs had intra-abdominal neoplasia resulting in hemoabdomen, 3 had suffered a traumatic incident resulting in hemoabdomen, and 6 had non-traumatic, non-neoplastic blood loss. Mean volumes of packed RBC and fresh-frozen plasma administered were 66.5 ml/kg (30 ml/lb) and 22.2 ml/kg (10 ml/lb), respectively. All dogs evaluated developed low ionized calcium concentrations and thrombocytopenia. Transfusion reactions were recognized in 6 dogs. Four dogs survived to hospital discharge. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that massive transfusion is possible and potentially successful in dogs. Predictable changes in electrolyte concentrations and platelet count develop.     

Circulating cortisol, tumor necrosis factor-alpha interleukin-1beta, and interferon-gamma in pigs infected with Actinobacillus pleuropneumoniae

This study evaluated the time course of systemic cytokine concentrations in an acute model of pneumonia in pigs challenged intranasally with Actinobacillus pleuropneumoniae. Feed intake and serum cortisol were measured as overt clinical and systemic markers of disease onset, respectively, and serum tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma as representative systemic inflammatory markers. Crossbred barrows (n = 15), approximately 5 wk of age, were used in the study. Pigs were housed in an environmentally controlled facility at 25 degrees C and under continuous illumination in pens measuring approximately 1.5 m2. Pigs had free access to water and an unmedicated diet. Approximately 1 wk prior to disease challenge, pigs were fitted nonsurgically with venous catheters. At challenge, pigs were given 5 x 10(8) CFU Actinobacillus pleuropneumoniae intranasally (n = 8) or a similar volume of sterile growth media intranasally (Control; n = 7). Feed intake was estimated by the change in feeder weight at 12-h intervals from -12 to 72 h relative to the time of disease challenge. Blood sampling began 12 h prior to challenge and continued until 72 h after challenge. Pigs were sampled at -12, -6, and 0 h, then at 90-min intervals until 12-h post-challenge, continuing at 3-h intervals until 24-h post-challenge, then again at 6-h intervals until 72 h after challenge. Serum was harvested and frozen until assayed for cortisol, tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma. Feed intake was reduced in Actinobacillus pleuropneumoniae pigs during the intervals 0 to 12 h (P < 0.001), 24 to 36 h (P < 0.001), 48 to 60 h (P <0.05), and 60 to 72 h (P < 0.05). TheActnobacillus pleuropneumoniae-challenged pigs had elevated serum cortisol from 180-min to 18-h post-challenge (P < 0.001) and also at 36 (P < 0.05), 42 (P < 0.001), and 60 (P < 0.05) h following infection. Circulating cytokines were not affected by disease challenge. Thus, in this experimental model of pneumonia, weaned pigs demonstrated expected behavioral and endocrine characteristics of disease in the absence of significant changes in circulating inflammatory cytokines.     

Effects of supplementation on intake, digestion, and performance of beef cattle consuming fertilized, stockpiled bermudagrass forage

Experiments were conducted to determine the effects of increasing supplement protein concentration on performance and forage intake of beef cows and forage utilization of steers consuming stockpiled bermudagrass forage. Bermudagrass pastures were fertilized with 56 kg of N/ha in late August. Grazing was initiated during early November and continued through the end of January each year. Treatments for the cow performance trials were: no supplement or daily equivalents of 0.2, 0.4, and 0.6 g of supplemental protein per kilogram of BW. Supplements were formulated to be isocaloric, fed at the equivalent of 0.91 kg/d, and prorated for 4 d/wk feeding. Varying the concentration of soybean hulls and soybean meal in the supplements created incremental increases in protein. During yr 1, supplemented cows lost less weight and condition compared to unsupplemented animals (P < 0.05). During yr 2, supplemented cows gained more weight (P = 0.06) and lost less condition (P < 0.05) compared to unsupplemented cows. Increasing supplement protein concentration had no affect on cumulative cow weight change or cumulative body condition score change. Forage intake tended to increase (P = 0.13, yr 1 and P = 0.07, yr 2) in supplemented cows. Supplement protein concentration did not alter forage intake. In a digestion trial, four crossbred steers were used in a Latin square design to determine the effects of supplement protein concentration on intake and digestibility of hay harvested from stockpiled bermudagrass pasture. Treatments were no supplement; or 0.23, 0.46, and 0.69 g of supplemental protein per kilogram of BW. Forage intake increased (P < 0.05) 16% and OM intake increased (P < 0.01) 30% in supplemented compared to unsupplemented steers. Diet OM digestibility increased (P = 0.08) 14.5% and total digestible OM intake increased (P < 0.05) 49% in supplemented compared to unsupplemented steers. Supplement protein concentration did not alter forage intake, total digestible OM intake, or apparent digestibility of OM or NDF. During the initial 30 d after first killing frost, beef cows did not respond to supplementation. However, later in the winter, supplementation improved utilization of stockpiled bermudagrass forage.