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.     

Inheritance of cataracts and primary lens luxation in Jack Russell Terriers

OBJECTIVE: To characterize heritability and mode of inheritance of cataracts and primary lens luxation in Jack Russell Terriers. ANIMALS: 872 Jack Russell Terriers from which buccal epithelial cells were collected and phenotypes for cataracts and lens luxation were determined and an additional 1,898 Jack Russell Terriers without phenotypic information used to complete pedigree relationships and that were included in the analyses. PROCEDURES: Narrow-sense heritabilities and genetic correlation for cataracts and lens luxation were modeled by use of threshold analysis, whereas complex segregation analysis was used to characterize mode of inheritance. For the analyses, dogs < 6 years old, unless confirmed as having cataracts or lens luxation, were classified as an unknown phenotype. The possible involvement of an HSF4 mutation in cataracts was determined by DNA sequencing. RESULTS: Cataracts and primary lens luxation were highly heritable and genetically correlated, and neither was controlled by a single gene. Cataracts were not associated with an HSF4 mutation. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of the data indicated that concerted selection against both cataracts and primary lens luxation when choosing breeding animals can be used to improve ocular health in Jack Russell Terriers.     

Malignant mediastinal extra-adrenal paraganglioma with spinal cord invasion in a dog.

A 1.5-year-old castrated, male, mixed-breed dog was evaluated because of a 2-week history of lethargy, stiffness, and progressive paraparesis. Spinal radiographs, myelography, and computed tomography of the region showed a locally invasive mass involving the thoracic wall. Upon necropsy, an encapsulated, fluctuant mass was noted attached to the right dorsal body wall in the region of the fifth to seventh thoracic vertebra. Churukian-Schenk staining revealed positive granules within the neoplastic cell cytoplasm and immunohistochemistry was positive for expression for cytoplasmic neuron-specific enolase and synaptophysin. Chromogranin A and S100 expression were found to be negative. Immunohistochemistry and silver staining did not allow further differentiation of the tumor, and the diagnosis remains consistent with either a chromaffin paraganglioma or a nonchromaffin paraganglioma (chemodectoma) with some production of catecholamines. Extra-adrenal paragangliomas are rare neoplasms in dogs but should be considered as a possible differential diagnosis for a primary paraspinal thoracic mass.     

Validation of the FAMACHA eye color chart for detecting clinical anemia in sheep and goats on farms in the southern United States

Recent studies on sheep and goat farms in the southern United States indicate that multiple-anthelmintic resistance in Haemonchus contortus is becoming a severe problem. Though many factors are involved in the evolution of resistance, the proportion of the parasite population under drug selection is believed to be the single most important factor influencing how rapidly resistance develops. Therefore, where prevention of resistance is an important parallel goal of worm control, it is recommended to leave a portion of the animals untreated. Recently, a novel system called FAMACHA was developed in South Africa, which enables clinical identification of anemic sheep and goats. When H. contortus is the primary parasitic pathogen, this system can be applied on the farm level to reduce the number of treatments administered, thereby increasing the proportion of the worm population in refugia. Since most studies validating the FAMACHA method have been performed in South Africa, it is important that the method be tested in other regions before its use is broadly recommended. We performed a validation study of FAMACHA by testing the system in sheep (n = 847) and goats (n = 537) of various breeds and ages from 39 farms located in Arkansas, Georgia, Louisiana, Florida, and the US Virgin Islands. The color of the ocular conjunctiva of all animals were scored on a 1-5 scale using the FAMACHA card, and blood samples were collected from each animal for determination of packed cell volume (PCV). Fecal samples were also collected from a majority of the animals tested for performance of fecal egg counts (FEC). Correlations between PCV and eye scores, PCV and FEC, and FEC and eye scores were all highly significant for both sheep and goats (P < 0.001). Data for both FAMACHA scores and PCV were evaluated using two separate criteria for anemia: eye score values of 3, 4 and 5 or 4 and 5, and PCV values of < or =19 or < or =15 were considered anemic. Specificity was maximized when eye score values of 4 and 5 were considered anemic and PCV cut off for anemia was < or =19, but sensitivity was low. In contrast, sensitivity was 100% for both sheep and goats when eye score values of 3, 4 and 5 were considered anemic and PCV cut off was < or =15, but specificity was low. In both sheep and goats, predictive value of a negative was greater than 92% for all anemia and eye score categories, and was greater than 99% for both eye score categories when an anemia cutoff of < or =15 was used. Predictive value of a positive test was low under all criteria indicating that many non-anemic animals would be treated using this system. However, compared to conventional dosing practices where all animals are treated, a large proportion of animals would still be left untreated. These data indicate that the FAMACHA method is an extremely useful tool for identifying anemic sheep and goats in the southern US and US Virgin Islands. However, further studies are required to determine optimal strategies for incorporating FAMACHA-based selective treatment protocols into integrated nematode control programs.     

Comparison of homeopathy, placebo and antibiotic treatment of clinical mastitis in dairy cows - methodological issues and results from a randomized-clinical trial

Based on the widespread use of homeopathy in treatment of animal disease and the poor documentation of its possible effects and consequences, a clinical trial was carried out in order to evaluate the efficacy of homeopathy in treatment of clinical mastitis in dairy cows and a design for clinical studies on homeopathic treatment, taking into account the guidelines for randomized-clinical trials (RCT) as well as the basic principles of homeopathy. A three-armed, stratified, semi-crossover design comparing homeopathy, placebo and a standardized antibiotic treatment was used. Fifty-seven dairy cows were included. Evaluation was made by two score scales, with score I measuring acute symptoms and score II measuring chronic symptoms, and by recording the frequencies of responders to treatment based on four different responder definitions. Significant reductions in mastitis signs were observed in all treatment groups. Homeopathic treatment was not statistically different from either placebo or antibiotic treatment at day 7 (P = 0.56, P = 0.09) or at day 28 (P = 0.07, P = 0.35). The antibiotic treatment was significantly better than placebo measured by the reduction in score I (P < 0.01). Two-thirds of the cases both in the homeopathy and placebo groups responded clinically within 7 days. The outcome measured by frequencies of responders at day 28 was poor in all treatment groups. Evidence of efficacy of homeopathic treatment beyond placebo was not found in this study, but the design can be useful in subsequent larger trials on individualized homeopathic treatment.     

The Effect of Sedation on Gastric Emptying of a Liquid Marker in Ponies

OBJECTIVE: The effect of sedation on gastric emptying was evaluated in six ponies by monitoring serum concentrations of acetaminophen (AP) after intragastric administration. EXPERIMENTAL DESIGN: Prospective randomized experimental study. ANIMALS: Six adult ponies, 135 to 275 kg. METHODS: Fifteen minutes after the intravenous administration of xylazine (1 mg/kg), butorphanol (0.05 mg/kg), acepromazine (0.05 mg/kg) or saline, ponies were given AP (20 mg/kg in 350 mL water) by stomach tube. Blood for AP analysis was collected at baseline and 15, 30, 45, 75, 90, 105, and 120 minutes after AP administration. The time (Tmax) to reach peak serum concentration (Cmax), and the area under the AP serum concentration versus time curve (AUC) were determined for each treatment group. RESULTS: Tmax was 31 mins in the control group, and this increased significantly (P<.05) after sedation. Cmax decreased (P<.05) after xylazine administration, and AUC decreased (P<.05) after acepromazine. CONCLUSIONS: This study indicated that sedation has a significant effect on the gastric emptying rate of a liquid in ponies.     

An investigation of Salmonella Fluntern illnesses linked to leopard geckos—United States, 2018

Reptile contact can result in zoonotic non‐typhoidal salmonellosis. In April 2018, Oregon Public Health Division contacted CDC about a cluster of four Salmonella serovar Fluntern (SF) illnesses in four states (OR, CA, IA, NY); patients reported contact with geckos, a popular reptile pet. PulseNet, the national molecular subtyping network of food‐borne disease surveillance, subsequently identified additional SF clinical isolates. Twelve cases in 11 states were identified; median age was 5 years (range: <1–58 years). Three patients were hospitalized; no deaths were reported. Of those with exposure information (n = 10), all reported reptile exposure; 9 (90%) specified contact with leopard geckos. No common source of geckos was identified from reported purchase locations. Los Angeles County (LAC) health officials isolated SF from one patient's leopard gecko. Five reptile/gecko isolates were identified from the USDA National Veterinary Services Laboratories (NVSL) from 2015 to 2018. Five countries responded to an Epidemic Intelligence Information System post by PulseNet; reptile isolate sequence data were received from Czech Republic. A clinical case from England was identified through the National Center for Biotechnology Information pathogen detection pipeline; the patient did not report contact with leopard geckos. Whole genome sequencing analysis revealed substantial genetic diversity between clinical and animal isolates; however, gecko and clinical isolates from LAC were highly related (1 allele difference). This investigation linking SF illnesses to leopard geckos highlights an important public health risk from pets. A better understanding of how geckos are distributed by the pet industry in the United States could improve traceability to points of origin and mitigate Salmonella transmission at gecko breeders. Earlier NVSL reports of SF isolates from geckos suggest the risk of human SF infection from geckos is not new. This investigation demonstrates a need to educate gecko breeders, retailers and gecko owners about the continued Salmonella infection risk from pet geckos.     

Stable carbon isotopes accurately predict diet selection by sheep fed mixtures of C3 annual pastures and saltbush or C4 perennial grasses

The stable carbon isotope technique has been widely used to infer the dietary ecology of a range of animal species; however calibration of the technique with animals fed known diets is essential for accurate back-calculation of dietary preferences. The aim of this study was to identify suitable samples and back-calculation methods to predict short-term (2 to 3 week) dietary selection by sheep among plants with C₃ and C₄ photosynthetic pathways. Variation in integration time of dietary carbon into plasma and faeces; diet-tissue discrimination of carbon isotopes (fractionation) and the importance of accounting for the digestible or indigestible components of the diet was investigated. The results indicate that faecal and rumen samples provided the most accurate prediction of short term dietary changes in sheep selecting between C₃ and C₄ plants. The most accurate back-calculation method for these samples used δ¹³C of the C₃ and C₄ plants and accounted for both diet-tissue discrimination and differences in the indigestibility between the C₃ and C₄ forage. For faecal samples, the organic matter content of the diet originating from C₄ plants could be predicted with a mean error as low as 2.7%. Wool and plasma samples were not conducive to predicting proportion of C4 forage in the diet within 18 days after a change in diet; however plasma could be used to discriminate between animals fed 100% C₃ and C₄ diets after 3 days. The δ¹³C technique provides a valuable tool for researchers when designing pastures for dual environmental and production purposes. An understanding of what sheep select allows for development of appropriate grazing management strategies to optimise productivity and/or persistence of target species.     

饲料颗粒：家禽生长不可忽视的基础

编者按:在家禽养殖中,饲料是支撑家禽生长的最基本元素.除去营养需要外,高度加工处理的饲料从一开始着眼于提高家禽的生产性能,以达到效率最优化.