Actinomycin D for Reinduction of Remission in Dogs With Resistant Lymphoma

Twenty-five dogs with malignant lymphoma refractory to chemotherapy were treated with actinomycin D at a median dose of 0.7 mg/m² (range, 0.5 to 0.9 mg/m²) every 3 weeks. The dogs treated had received between 2 and 8 chemotherapeutic agents (median 7), for a median of 266 days before being treated with actinomycin D. For 23 of the 25 dogs, previous chemotherapy included doxorubicin. No dog responded to actinomycin D chemotherapy.     

Congenital ocular anomalies and ventricular septal defect in a dromedary camel (Camelus dromedarius).

A 5-wk-old female dromedary camel (Camelus dromedarius) was clinically diagnosed with bilateral corneal dermoids, incomplete congenital cataracts, a left persistent hyaloid artery (PHA), and a ventricular septal defect (VSD). The corneal dermoids were removed by lamellar keratectomy, and vision improved in the left eye. Thirteen months after dermoid surgery, the calf was presented for enlargement of the right eye. Glaucoma was confirmed in the right eye, and corneal fibrosis and cataract were noted in the left eye. Persistence of the VSD was confirmed by cardiac ultrasonography. The calf was euthanized, and necropsy findings confirmed VSD. Histopathologic examination revealed bilateral corneal thinning and fibrosis, cataracts with retrolental fibroplasia, and retinal dysplasia. Additional changes in the right globe were anterior segment dysgenesis, ruptured lens capsule, chronic phacoclastic uveitis, and retinal separation. The PHA was confirmed in the left eye.     

Anthropogenic effects on soil quality of ancient agricultural systems of the American Southwest

Soil studies of ancient agricultural fields contribute to research on long-term human–environmental relationships and land use sustainability. This kind of research is especially applicable in desert landscapes of the American Southwest because: (1) soil formation is slow enough that cultivation effects persist for centuries to millennia; (2) many ancient fields in valley margins have remained uncultivated since they were abandoned, so long-term soil properties reflect ancient agricultural use; and (3) agricultural features (e.g., terraces, rock alignments and rock piles, and irrigation canals) provide clues for identifying and sampling ancient cultivated and uncultivated soils. Surficial remnants of these field systems persist and remain intact in many cases. Soil studies of ancient and modern American Indian agricultural systems across the Southwest indicate that soil changes are highly variable, ranging from degradation (e.g., organic matter/nutrient decline, compaction), to minimal net change, to enhanced soil quality. Soil changes caused by cultivation can be inferred by comparing soils in agricultural fields relative to reference uncultivated areas in similar landscape settings (that is, space-for-time substitution). Soil response trajectories vary for a number of reasons, such as variability in initial ecosystem conditions, diversity in agricultural methods, variability in the mix of crops and cropping intensity, and environmental sensitivity to alteration (varying resistance and resilience). Studies of rock mulch soils indicate enhanced fertility, with elevated organic carbon, nitrogen, and available phosphorus levels, increased infiltration rates and moisture retention, and no evidence of compaction. By contrast, cultivation effects vary widely for terraced soils. Although numerous studies have focused on irrigation canals, irrigated soils have received far less attention. Soil studies of irrigation systems along the Gila and Santa Cruz rivers of Arizona now underway will help fill this research gap.     

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.     

Canine X-linked severe combined immunodeficiency.

Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma (gamma c) subunit of the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors. The most striking clinical feature is a failure to thrive or 'stunted' growth. Recurrent or chronic infections begin at the time of decline of maternal antibody, usually between six and eight weeks of age. Affected dogs rarely survive past three to four months of age. The major pathologic feature of canine XSCID is a small, dysplastic thymus. Grossly identifiable lymph nodes, tonsils, and Peyer's patches are absent in XSCID dogs. During the neonatal period, XSCID dogs have few, if any, peripheral T cells and increased number of peripheral B cells. Some XSCID dogs do develop phenotypically mature, nonfunctional T cells with age, however, the absolute number of peripheral T cells remain significantly decreased compared to age-matched normal dogs. An interesting finding is that as soon as T cells begin to appear in XSCID dogs they rapidly switch from a CD45RA+ (naive) phenotype to a CD45RA- (activated or memory phenotype). One of the characteristic findings in XSCID dogs is an absent or markedly depressed blastogenic response of T cells in response to stimulation through the T cell receptor and when the necessary second messengers for cellular proliferation are directly provided that by-pass signals delivered through ligand-receptor interaction. The proliferative defect is due to the inability of T cells to express a functional IL-2 receptor. Canine XSCID B cells do not proliferate following stimulation with T cell-dependent B cell mitogens, however, they proliferate normally in response to T cell-independent B cell mitogens. Canine XSCID B cells are capable of producing IgM but are incapable of class-switching to IgG antibody production following immunization with the T cell-dependent neoantigen, bacteriophage phiX174. The number of thymocytes in the XSCID thymus is approximately 0.3% of the thymocytes present in the thymus of age-matched normal dogs. The proportion of CD4-CD8- thymocytes in XSCID dogs is increased 3.5-fold and the CD4+CD8+ population is decreased 2.3-fold. These findings demonstrate that (1) a functional gamma c is required for normal B and T cell function, (2) early T cell development is highly dependent upon a functional gamma c, and (3) B cell development can occur through a gamma c-independent pathway.     

Ear temperatures in the horse during recovery from anesthesia

Ear temperatures were measured during and after halothane anesthesia in 16 horses and ponies. Aural hypothermia developed during recovery and persisted for more than one hour following standing. The decreased ear temperature was attributed to decreased peripheral perfusion and was considered to be related to other cardio-pulmonary and neuro-endocrine derangements that occur during recovery.