Adenosine A2A receptor agonists inhibit lipopolysaccharide-induced production of tumor necrosis factor-alpha by equine monocytes

Adenosine is an endogenous nucleoside that regulates many physiological processes by activating one or more adenosine receptor subtypes, namely A1, A2A, A2B and A3. The results of previous studies indicate that adenosine analogues inhibit lipopolysaccharide (LPS)-induced production of reactive oxygen species (ROS) by equine neutrophils primarily through activation of A2A receptors. Because peripheral blood monocytes produce cytokines that are responsible for many of the deleterious effects of LPS, the current study was performed to evaluate the effects of an array of novel adenosine receptor agonists on LPS-induced production of tumor necrosis factor-alpha (TNF-alpha), and to assess the selectively of these agonists for equine adenosine A2A over the A1 receptor. Radioligand binding studies performed with equine tissues expressing adenosine A1 and A2A receptor subtypes yielded a rank order of affinity for the equine A2A receptor of ATL307>ATL309 approximately ATL310 approximately ATL313>ATL202 approximately ATL361 approximately ATL376>ATL372>CGS21680>NECA. Co-incubation of equine peripheral blood monocytes with LPS and these agonists resulted in inhibition of TNF-alpha production with a rank order of potency that strongly correlated with their binding affinities for equine adenosine A2A receptors. Results of experiments performed with one of the adenosine receptor agonists (ATL313) and selective adenosine receptor antagonists confirmed that inhibition of LPS-induced production of TNF-alpha occurred via stimulation of A2A receptors. Although incubation of monocytes with IB-MECA, a compound purported to act as an adenosine A3 receptor agonist, reduced LPS-induced TNF-alpha production, this effect of IB-MECA was inhibited by the A2A selective antagonist ZM241385 but not by the A3 receptor antagonist MRS1220. These results indicate that the adenosine receptor subtype responsible for regulation of LPS-induced cytokine production by equine monocytes is the A2A receptor. To address the signal transduction mechanism responsible for the anti-inflammatory effects of ATL313 in equine monocytes, production of cAMP was compared in the presence and absence of either the adenosine A2A receptor antagonist ZM241385 or the adenosine A2B receptor antagonist MRS1706. In the absence of the antagonists, ATL313 increased production of cAMP; ZM241385 inhibited this effect of ATL313, whereas MRS1706 did not. Furthermore, incubation of monocytes with either the stable analogue of cAMP, dibutyryl cAMP, or forskolin, an activator of adenylyl cyclase, also inhibited LPS-induced production of TNF-alpha production by equine monocytes. Collectively, the results of the current study indicate that adenosine analogues inhibit LPS-induced production of TNF-alpha by equine monocytes primarily via activation of adenosine A2A receptors and do so in a cAMP-dependent manner. The results of this study indicate that stable adenosine analogues that are selective for adenosine A2A receptors may be suitable for development as anti-inflammatory drugs in horses.     

Effects of feeding diets containing low crude protein and coarse wheat bran as alternatives to zinc oxide in nursery pig diets

Two experiments were conducted to determine the effects of crude protein (CP) level in diets containing coarse wheat bran (CWB) with or without pharmacological levels of Zn (provided by zinc oxide: ZnO) on growth performance and fecal DM of nursery pigs. In experiment 1, 360 barrows (Line 200 × 400, DNA, Columbus, NE, initially 5.6 kg) were allotted to 1 of 6 dietary treatments from d 0 to 21 after weaning with 5 pigs per pen and 12 pens per treatment. Treatments included a positive control diet (21% CP) with 3,000 mg/kg Zn in phase 1 and 2,000 mg/kg in phase 2; negative control (21% CP) with 110 mg/kg added Zn, and 4 diets containing 4% CWB and 110 mg/kg added Zn formulated to contain 21%, 19.5%, 18%, or 16.5% CP. The 2 control diets and 21% CP CWB diet contained 1.40% standardized ileal digestible (SID) Lys in phase 1 and 1.35% SID Lys in phase 2, while the 19.5%, 18%, and 16.5% CP diets contained 1.33, 1.25 and 1.20% Lys, respectively, in both phases. Pigs fed the positive control diet containing pharmacological ZnO had increased (P < 0.05) ADG and G:F compared with the negative control and the 21% CP CWB diet. Reducing CP (concurrently with SID Lys) in diets containing CWB decreased ADG and G:F (linear, P = 0.002); however, fecal DM increased (linear, P = 0.005). In experiment 2, two groups of 300 and 350 pigs, initially 7.0 and 6.2 kg, respectively, were used with 5 pigs per pen and 26 pens per treatment. The objective was to determine if adding back essential AA would improve growth performance of pigs fed the low CP diets. All dietary treatments were fed for 13 days, contained 4% CWB, and consisted of: (1) positive control with 2,000 mg/kg of Zn and 21% CP (1.35% SID Lys); (2) no ZnO and 21% CP; and 3 diets with no ZnO formulated to 18% CP and (3) 1.2% SID Lys; (4) 1.35% SID Lys by the addition of feed grade amino acids (AA), and (5) diet 4 with non-essential amino acids (NEAA; Gly and Glu). Pigs fed 21% CP with ZnO had increased (P = 0.001) ADG compared to those fed 18% CP (1.35% SID Lys) with high levels of feed grade amino acids or those fed the reduced SID Lys (1.2%) diet. Overall, G:F was improved (P < 0.001) for pigs fed 21% CP diets and those fed the 18% CP diet with NEAA compared to pigs fed 1.2% SID Lys and pigs fed high levels of feed grade amino acids. Fecal DM was increased for pigs fed the reduced SID Lys diet. In summary, pharmacological levels of Zn improve pig growth performance, but reducing CP (and subsequently SID Lys) decreased nursery pig growth performance.     

Use of a condylar screw plate for repair of a Salter-Harris type-III fracture of the femur in a 2-year-old horse

A 2-year-old sexually intact male Paint horse weighing 427 kg (940 lb) was admitted for examination and treatment of intermittent non-weight-bearing lameness of the right hind limb of 1 week's duration. Radiography revealed a displaced Salter-Harris type-III fracture of the right femoral condyle with the sagittal component of the fracture line located in the intercondylar space and the transverse component exiting on the medial aspect of the femur. The fracture was repaired with a condylar screw plate designed for repair of femoral condylar fractures in humans. The owner reported by telephone 9 months after surgery that the horse was sound. To our knowledge, use of this particular implant system for fixation of a Salter-Harris type-III fracture on the medial side of the femur in a horse has not been described. Results in this horse suggest that this implant can be successfully used for repair of femoral condylar fractures in selected adult horses.     

Airway inflammation is associated with mucous cell metaplasia and increased intraepithelial stored mucosubstances in horses

This study was performed to determine if a peripheral sample of lung from the site where biopsy is conducted is representative of the rest of the lung and to investigate the relationship between airway inflammation and intraepithelial mucous production in the peripheral airways. Lung parenchyma samples were collected from five different regions of the lung in five control and five heaves-affected horses. Horse groups were defined by clinical response to stabling. Tissue sections were used for semi-quantitative scoring of lesions, to count the number of airways, to quantify the amount of stored mucosubstances (Vs) within the epithelium, and to count the number of epithelial cells in terminal airways. No significant differences were found between lung regions or between groups of horses. Lack of regional differences in airway structures means that a biopsy sample can be used for diagnosis and investigation of diffusely distributed diseases. Airway inflammation was correlated with mucous cell metaplasia and Vs. Therefore, in horses, mucus accumulation is partly caused by increased number of mucous cells and is associated with airway inflammation. Therapy targeted to reduce airway inflammation will help reduce the excessive mucous accumulation in horses.     

Differential diagnosis and management of human-directed aggression in cats.

Human-directed aggression in cats should be evaluated as a multifactorial problem. It results from the combined actions of heredity, environment, learning, human social requirements (or needs), client interactions, lack of understanding of normal feline behavior, unrealistic client expectations, and lack of meeting the cat's basic ethologic needs. Managing human-directed aggression in cats encompasses the use of environmental modification, therapies, and, when and if needed, regulatory drugs so as to increase learning capabilities and adaptation and decrease danger to the human victims.     

Effect of incorporation of ground Prosopis juliflora pods in layer diet on weight gain,egg production,and natural antibody titer in KALRO genetically improved indigenous chicken

Tropical Animal Health and Production - The potential of using Prosopis juliflora pods was evaluated as a partial replacement of energy source layer’s diets. The main objective of the...     

Topical 0.1% tacrolimus for the treatment of discoid lupus erythematosus and pemphigus erythematosus in dogs

Topical 0.1% tacrolimus was used for treatment of localized lesions associated with 10 cases of discoid lupus erythematosus (DLE) and two cases of pemphigus erythematosus (PE) either as a sole therapy (n=2) or as an adjunctive treatment (n=10). Eight of 10 dogs with DLE and both dogs with PE were improved following 8 weeks of topical application. In six of the eight dogs that improved, other medications were discontinued. No adverse effects in clinical or laboratory parameters were noted throughout the study.     

Practical starter pig amino acid requirements in relation to immunity,gut health and growth performance

Immune system activation begins a host of physiological responses. Infectious agents are recognized by monocytes and macrophages which in turn stimulate cytokine production. It is the hormone-like factors called cytokines that orchestrate the immune response. The classic responses observed with immune system activation and cytokine production include: anorexia, fever, lethargy, recruitment of other immune cells, and phagocytosis. While production of immune system components is known to require some amino acids, increases in amino acid requirements are more than offset by the associated decrease in protein accretion and increased muscle protein degradation that also accompanies immune system activation. However, the biggest impact of cytokine production is a decrease in feed intake. Therefore, as feed intake decreases, the energy needed to drive protein synthesis is also decreased. This suggests that diets should still be formulated on a similar calorie:lysine ratio as those formulated for non-immune challenged pigs. The evidence is sparse or equivocal for increasing nutrient requirements during an immune challenge. Nutritionists and swine producers should resist the pressure to alter the diet, limit feed, or add expensive feed additives during an immune challenge. While immune stimulation does not necessitate changes in diet formulation, when pigs are challenged with non-pathogenic diarrhea there are potential advantages on gut health with the increased use of crystalline amino acids rather than intact protein sources (i.e., soybean meal). This is because reducing crude protein decreases the quantity of fermentable protein entering the large intestine, which lowers post weaning diarrhea. It also lowers the requirement for expensive specialty protein sources or other protein sources such as soybean meal that present immunological challenges to the gut. The objective of this review is two-fold. The first is to discuss immunity by nutrition interactions, or lack thereof, and secondly, to review amino acid requirement estimates for nursery pigs.     

Vitamin and mineral supplementation and rate of gain during the first trimester of gestation affect concentrations of amino acids in maternal serum and allantoic fluid of beef heifers

The objective of this study was to evaluate the effects of feeding vitamin and mineral (VTM) supplement and (or) rate of gain (GAIN) during early gestation on amino acid (AA) concentrations in allantoic fluid (ALF) and amniotic fluid (AMF) and maternal serum. Seventy-two crossbred Angus heifers (initial BW = 359.5 ± 7.1 kg) were randomly assigned to one of four treatments in a 2 × 2 factorial arrangement with main effects of VTM supplement (VTM or NoVTM) and rate of gain (GAIN; low gain [LG], 0.28 kg/d, vs. moderate gain [MG], 0.79 kg/d). The VTM treatment (113 g•heifer⁻¹•d⁻¹, provided macro and trace minerals and vitamins A, D, and E to meet 110% of the requirements specified by the NASEM in Nutrient requirements of beef cattle. Washington, DC: The National Academies Press. doi:10.17226/19014, 2016) was initiated 71 to 148 d before artificial insemination (AI). To complete the factorial arrangement of treatments, at breeding heifers were either maintained on the basal diet (LG), or received MG diet which was implemented by adding a protein/energy supplement to the LG diet. Thirty-five gestating heifers with female fetuses were ovariohysterectomized on d 83 of gestation and maternal serum, ALF, and AMF were collected. Samples were analyzed for concentrations of neutral AA: Ala, Asn, Cys, Gln, Gly, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, and Val; cationic AA: Arg, His, and Lys; and anionic AA: Asp and Glu. In serum, a VTM × GAIN interaction (P = 0.02) was observed for Glu, with greater concentrations for VTM-LG than VTM-MG. Concentrations of serum Cys, Met, and Trp were greater (P ≤ 0.03) for MG than LG. In ALF, concentrations of Glu were affected by a VTM × GAIN interaction, where VTM-MG was greater (P < 0.01) than all other treatments. Further, ALF from VTM had increased (P ≤ 0.05) concentrations of His, Asp, and 12 of the 14 neutral AA; whereas GAIN affected concentrations of Arg, Cys, and Asp, with greater concentrations (P ≤ 0.05) in MG heifers. In AMF, AA concentrations were not affected (P ≥ 0.10) by VTM, GAIN, or their interaction. In conclusion, increased concentrations of AA in maternal serum and ALF of beef heifers were observed at d 83 of gestation in response to VTM supplementation and rate of gain of 0.79 kg/d, which raises important questions regarding the mechanisms responsible for AA uptake and balance between the maternal circulation and fetal fluid compartments.