Using 3D animations to teach intracellular signal transduction mechanisms: taking the arrows out of cells

Traditional methods of teaching intracellular biological processes and pathways use figures or flowcharts with the names of molecules linked with arrows. Many veterinary students, presented with such material, simply memorize the names or chemical structures of the molecules and are then likely to forget the material once the examination is completed. To address this problem, the authors designed, created, and field-tested new teaching media that incorporate realistic three-dimensional (3D) animations depicting the dynamic changes that occur in intracellular molecules during cellular activation. Testing found that veterinary students taught using traditional teaching media (e.g., lectures, handouts, textbooks) are proficient in memorizing the names and order of intracellular molecules but unable to appreciate the interactions between these elements or their spatial relationships within cells. In contrast, more than 90% of veterinary students taught using 3D animations not only recall the facts about the intracellular elements but also develop accurate mental images of the interactions among these molecules and their spatial relationships. These findings strongly suggest that the comprehension of complex biological processes by veterinary students can be enhanced by the use of dynamic 3D depictions of these processes in the classroom.     

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 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.     

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.