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.     

Mineralized paraprostatic cyst as a potential contributing factor in the development of perineal hernias in a dog

Perineal hernias almost exclusively affect male dogs (sexually intact or castrated). Factors that may contribute or predispose a dog to perineal hernias include tenesmus, pelvic musculature variations (male vs female), and gonadal hormone influence. In dogs with perineal hernias and tenesmus it is important to include rectal and prostatic diseases, including paraprostatic cysts, in the differential list of potential underlying causes. Surgical correction of the perineal hernia with a perineal herniorrhaphy is indicated. Successful treatment depends on the degree of preexisting neurologic alterations, meticulous surgical technique, and identification and correction of underlying contributing factors. Paraprostatic cysts develop predominantly in sexually intact medium to large breed dogs. These cysts are thin-walled structures often attached to the prostatic dorsal midline. Osseous metaplasia of paraprostatic cysts may occur. Clinical signs of tenesmus often result from compression on adjacent structures (urinary bladder and colon), and tenesmus may contribute to the development of perineal hernias. Preferred treatment of a paraprostatic cyst is surgical removal and castration. This report describes a dog with bilateral perineal hernias and a large mineralized paraprostatic cyst that was identified as a possible contributing factor to the hernias.     

A retrospective study of 11 cases of lungworm (Didelphostrongylus hayesi) infection in opossums (Didelphis virginiana).

A juvenile, female North American opossum (Didelphis virginiana) died of verminous pneumonia caused by Didelphostrongylus haysei despite aggressive treatment with oral fenbendazole, corticosteroids, and antibiotics. This prompted a retrospective study of lungworm infection in opossums, during which 19 additional necropsy reports from opossums were reviewed. Including the subject of this report, a total of 11 (55%) of these cases included a diagnosis of lungworm infection. This diagnosis was considered to have contributed to death in eight out of the 11 cases (73%). Histologically, 10 of the 11 (91%) opossums had granulomatous bronchopneumonia with small to moderate numbers of adult nematodes in the airways and parenchyma. Four of the 11 (36%) opossums had free larvae within the parenchyma or terminal airways. Inflammation was usually associated with larvae, degenerating parasites, and nonintact adult nematodes. Superimposed bacterial pneumonia was evident in three animals, and sections of lung examined from all the opossums were characterized by moderate to severe smooth-muscle hyperplasia in airways, including terminal respiratory bronchioles and alveolar ducts. Nine animals had prominent medial smooth-muscle hyperplasia in small- and medium-sized arterioles. Lesions in other organs, particularly in liver, heart, and gastrointestinal tract, were frequently identified. Three animals had concomitant septicemia or bacterial bronchopneumonia (or both), which contributed to the cause of death. Seven animals had gastric nematodosis (Physaloptera sp.), although three of them had been treated with a 14-day course of fenbendazole.     

A review of phosphorus homeostasis and the impact of different types and amounts of dietary phosphate on metabolism and renal health in cats

Elevated concentrations of serum phosphate are linked with progression and increased case fatality rate in animals and humans with chronic kidney disease. Elevated concentrations of serum phosphate can be a risk factor for development of renal and cardiovascular diseases or osteoporosis in previously healthy people. In rodents, an excess intake of dietary phosphorus combined with an inverse dietary calcium : phosphorus ratio (<1 : 1) contributes to renal calcification. Renal injury also has occured in cats fed experimental diets supplemented with highly soluble phosphate salts, especially in diets with inverse calcium : phosphorus ratios. However, not all phosphorus sources contribute similarly to this effect. This review, which focuses on cats, summarizes the published evidence regarding phosphorus metabolism and homeostasis, including the relative impact of different dietary phosphorus sources, and their impact on the kidneys. No data currently shows that commercial cat foods induce renal injury. However, some diets contain high amounts of phosphorus relative to recommendations and some have inverse Ca : P ratios and so could increase the risk for development of kidney disease. While limiting the use of highly soluble phosphates appears to be important, there are insufficient data to support a specific upper limit for phosphate intake. This review also proposes areas where additional research is needed in order to strengthen conclusions and recommendations regarding dietary phosphorus for cats.     

Efficacy of fenbendazole against inhibited larvae of Ostertagia ostertagi in yearling cattle

Efficacy of fenbendazole, at doses of 7.5 and 10.0 mg/kg of body weight, against inhibited early 4th-stage larvae of Ostertagia ostertagi and other nematodes of the abomasum and intestinal tract, was investigated in naturally infected yearling heifers in late May 1982. In Louisiana, this is near the end of the period (March to May) in which maximal numbers of inhibition-prone larvae are acquired. The mean numbers of O ostertagi in 10 untreated control cattle were: adults, 4,880; developing 4th-stage larvae, 12,546; and inhibited early 4th-stage larvae, 167,931. At the 7.5 mg/kg dose level (10% liquid suspension) in 10 cattle, percentage reduction of O ostertagi in comparison with controls was: adults, 95.7%; developing 4th stages, 91.1%; and inhibited 4th stage, 55.0%. Percentage reductions of other genera were as follows: abomasum--Trichostrongylus axei, 99.6%; Haemonchus sp, 95.1%; intestinal tract--Cooperia spp, 97.8%; Trichostrongylus colubriformis, 100.0%; and Oesophagostomum radiatum 4th stage and adults, 100.0%. At the 10.0 mg/kg dose (10% liquid suspension) in 11 cattle, the percentage reduction of O ostertagi in comparison with controls was: adults, 98.6%; developing 4th stages, 92.9%; and inhibited 4th stage, 80.0%. Percentage reductions of other genera were: abomasum--T axei, 99.9%; Haemonchus sp, 98.8%; intestinal tract--Cooperia spp, 99.3%; T colubriformis, 100.0%; and Oes radiatum 4th stage and adults, 100.0%. Variability of efficacy against inhibited larvae was observed, particularly at the 7.5 mg/kg dose; at this dose, 7 of the 10 heifers in the group yielded in excess of 54,000 surviving larvae.(ABSTRACT TRUNCATED AT 250 WORDS)     

Variations in muscle fiber composition between successfully and unsuccessfully raced quarter horses

Muscle biopsy samples were removed from the m gluteus medius of 47 retired running Quarter Horse (QH) mares. Horses were separated based on bloodline, past racing history and percentage Thoroughbred (TB). The bred to run and raced (BRRA) and bred to run and not raced (BRNR) groups possessed a lower percentage (P<.01) of fast-twitch low oxidative (FT) fibers (BRRA 38.6 and BRNR 36.2±2.54 respectively). These horses also possessed a higher percentage (P<.01) of fast-twitch high oxidative (FTH) fibers (BRRA 52.5 and BRNR 48.5±2.54, respectively) than not bred to run and not raced (NBNR) horses. Horses that were bred to run had higher (P<.05) FTH to FT fiber ratios (1.44) than horses that were not bred to run (.94). Successful racehorses possessed a lower percentage (P<.05) of slow-twitch (ST) fibers and a higher percentage (P<.05) of FT fibers than unsuccessful racehorses. Success or failure was determined by Speed Index. No differences (P>.05) were found in the percentage FTH fibers between successful and unsuccessful horses.