Objective—To assess expression pattern and subcellular compartmentalization of 5-lipoxygenase in cutaneous, UV radiation–induced, and oral squamous cell carcinomas (SCCs) in cats and determine the effects of cyclooxygenase or 5-lipoxygenase inhibition on proliferation or apoptosis in a feline oral squamous cell carcinoma (SCCF1) cell line. Sample—60 archived paraffin-embedded samples of SCCs from 60 cats and SCCF1 cells. Procedures—Retrospective immunohistochemical analysis of the archived samples of SCCs (20 cutaneous, 20 UV radiation–induced, and 20 oral tumors) was performed. Cell culture proliferation assays involving SCCF1 cells were performed, and tepoxalin-induced apoptosis and signaling were examined via western blotting and annexin V staining. Results—Immunohistochemically, staining for 5-lipoxygenase was most frequently of greatest intensity in oral SCCs, whereas staining of cutaneous and UV radiation–induced lesions had less consistent 5-lipoxygenase expression. Exposure of SCCF1 cells to the 5-lipoxygenase inhibitor tepoxalin resulted in apoptosis; the effect appeared to be mediated via alteration of cell signaling rather than via suppression of lipid mediators that are typically produced as a result of 5-lipoxygenase activity. Conclusions and Clinical Relevance—In cats, expression of 5-lipoxygenase in SCCs appeared to differ depending on tumor location. The influence of tepoxalin-induced 5-lipoxygenase inhibition on a poxygenase–expressing cell line coupled with the notable expression of 5-lipoxygenase in oral SCCs suggested that 5-lipoxygenase inhibition may have therapeutic benefits in affected cats. Although the safety of tepoxalin in cats has yet to be investigated, 5-lipoxygenase inhibitors should be evaluated for use as a potential treatment for SCCs in that species.

Objective—To investigate whether plasma activity of matrix metalloproteinase (MMP)-2 and -9 was associated with severity of myxomatous mitral valve disease (MMVD) in dogs and to assess potential associations between MMP activity and dog characteristics, echocardiographic variables, systolic arterial blood pressure (SAP), heart rate, cardiac troponin I (cTnI) concentration, and C-reactive protein concentration. Animals—75 client-owned dogs. Procedures—Severity of MMVD was assessed by use of echocardiography. Plasma activity of latent (pro-MMP) and active MMP-2 and -9 was analyzed via zymography. Plasma concentration of cTnI was analyzed with a high-sensitivity cTnI assay, and C-reactive protein concentration was analyzed with a canine-specific ELISA. Results—Pro-MMP-9, active MMP-9, and pro-MMP-2 were detected, but active MMP-2 was not. No significant differences were found in MMP concentrations among the 4 MMVD severity groups. Activity of pro-MMP-9 decreased with decreases in SAP and was higher in male dogs than in female dogs. Activity of MMP-9 decreased with increases in left ventricular end-systolic dimension and with decreases in SAP and cTnI concentration. Left ventricular end-systolic dimension was the variable most strongly associated with MMP-9 activity. No associations were found between the activity of pro-MMP-2 and investigated variables. Conclusions and Clinical Relevance—Plasma MMP-9 activity decreased with increases in the end-systolic left ventricular internal dimension and decreases in SAP. Hence, evaluation of MMP-9 activity has the potential to provide unique information about the myocardial remodeling process in dogs with MMVD.

Objective—To determine the pharmacokinetics of tramadol and its metabolites O-desmethyltramadol (ODT) and N-desmethyltramadol (NDT) in adult horses. Animals—12 mixed-breed horses. Procedures—Horses received tramadol IV (5 mg/kg, over 3 minutes) and orally (10 mg/kg) with a 6-day washout period in a randomized crossover design. Serum samples were collected over 48 hours. Serum tramadol, ODT, and NDT concentrations were measured via high-performance liquid chromatography and analyzed via noncompartmental analysis. Results—Maximum mean ± SEM serum concentrations after IV administration for tramadol, ODT, and NDT were 5,027 ± 638 ng/mL, 0 ng/mL, and 73.7 ± 12.9 ng/mL, respectively. For tramadol, half-life, volume of distribution, area under the curve, and total body clearance after IV administration were 2.55 ± 0.88 hours, 4.02 ± 1.35 L/kg, 2,701 ± 275 h•ng/mL, and 30.1 ± 2.56 mL/min/kg, respectively. Maximal serum concentrations after oral administration for tramadol, ODT, and NDT were 238 ± 41.3 ng/mL, 86.8 ± 17.8 ng/mL, and 159 ± 20.4 ng/mL, respectively. After oral administration, half-life for tramadol, ODT, and NDT was 2.14 ± 0.50 hours, 1.01 ± 0.15 hours, and 2.62 ± 0.49 hours, respectively. Bioavailability of tramadol was 9.50 ± 1.28%. After oral administration, concentrations achieved minimum therapeutic ranges for humans for tramadol (> 100 ng/mL) and ODT (> 10 ng/mL) for 2.2 ± 0.46 hours and 2.04 ± 0.30 hours, respectively. Conclusions and Clinical Relevance—Duration of analgesia after oral administration of tramadol might be < 3 hours in horses, with ODT and the parent compound contributing equally.

Antimicrobial susceptibilities and toxin types were determined for 275 Clostridium perfringens isolates collected in Ontario in the spring of 2005. Minimal inhibitory concentrations (MICs) of C. perfringens isolates for 12 antimicrobials used in therapy, prophylaxis, and/or growth promotion of cattle (n = 40), swine (n = 75), turkeys (n = 50), and chickens (n = 100) were determined using the microbroth dilution method. Statistical analyses and MIC distributions showed reduced susceptibility to bacitracin, clindamycin, erythromycin, florfenicol, and tetracycline for some isolates. Reduced susceptibility to bacitracin was identified in chicken (64%) and turkey (60%) isolates. Swine isolates had predominantly reduced susceptibility to clindamycin (28%) and erythromycin (31%), whereas bovine isolates had reduced susceptibility to clindamycin (10%) and florfenicol (10%). Reduced susceptibility to tetracycline was spread across all species. No clear reduced susceptibility, but elevated MIC50 for virginiamycin was found in chicken isolates in comparison with isolates from other species. Toxin typing revealed that C. perfringens type A is the dominant toxin type isolated in this study across all 4 host species.

Objective—To compare values of urodynamic measurements of cats with idiopathic cystitis (IC) with previously published data for healthy female cats. Animals—11 female cats with IC. Procedures—2 sequential cystometrograms and 2 urethral pressure profiles were obtained for each cat. All tracings were evaluated for evidence of overactive urinary bladder (OAB). Maximum urethral pressure (MUP), maximum urethral closure pressure (MUCP), and functional profile length were recorded. Results—Only 3 cats had obvious micturition events. None of the 11 cats had evidence of OAB. Although not significant, threshold pressure was lower in cats with IC than in healthy cats (mean ± SD, 89.0 ± 12.0 cm H2O vs 75.7 ± 16.3 cm H2O, respectively); however, the total volume infused was significantly lower in cats with IC (4.8 ± 2.1 mL/kg vs 8.3 ± 3.2 mL/kg). The MUCP was significantly higher in cats with IC than in healthy cats (158.0 ± 47.7 cm H2O vs 88.9 ± 23.9 cm H2O, respectively). The MUP was also significantly higher in all portions of the urethra in cats with IC. Conclusions and Clinical Relevance—No evidence of OAB was identified in any cat evaluated; therefore, medications used to target this abnormality did not appear justified. The high MUCP in cats with IC suggested that α1-adrenoceptor antagonists or skeletal muscle relaxants may be useful in this disease, and if these data were applicable to male cats, then α1-adrenoceptor antagonism may help prevent recurrent obstructive IC. Further studies are indicated to determine the effects, if any, these drugs might have in cats with IC.

Objective—To evaluate the effects of carprofen and meloxicam on conductance and permeability to mannitol and on the histologic appearance of sections of canine gastric mucosa. Sample—Gastric mucosa from 6 mature mixed-breed dogs. Procedures—Sections of gastric mucosa were mounted in Ussing chambers, and carprofen (40 or 400μg/mL [CAR40 and CAR400, respectively]), meloxicam (8 or 80μg/mL [MEL8 and MEL80, respectively]), or no drug (controls) was added to the bathing solution. For all sections, conductance was calculated every 15 minutes for 240 minutes and flux of mannitol was calculated for 3 consecutive 1-hour periods; histologic examination was performed after the experiment. The area under the conductance-time curve for each chamber was calculated. Values of conductance × time, flux of mannitol, and the frequency distribution of histologic findings were analyzed for treatment effects. Results—For CAR400- and MEL80-treated sections, conductance X time was significantly higher than that for control and MEL8-treated sections. The effect of CAR40 treatment was not different from that of any other treatment. Over the three 1-hour periods, mannitol flux increased significantly in MEL80-, CAR40-, and CAR400-treated sections but not in MEL8- treated or control sections. Major histologic changes including epithelial cell sloughing were limited to the CAR400-treated sections. Conclusions and Clinical Relevance—In the gastric mucosa of dogs, carprofen and meloxicam increased in vitro conductance and permeability to mannitol. At a concentration of 400 μg/mL, carprofen caused sloughing of epithelial cells. Carprofen and meloxicam appear to compromise gastric mucosal integrity and barrier function in dogs.

Objective—To evaluate effects of cyclosporine, dexamethasone, and the immunosuppressive agent human CTLA4-Ig on cytokine production by feline lymphocytes in vitro and to assess patterns of cytokine production for 5 immunosuppressed renal transplant recipient cats. Animals—21 clinically normal cats and 5 immunosupressed renal transplant recipient cats. Procedures--Peripheral blood mononuclear cells were isolated from clinically normal cats and stimulated with concanavalin A (Con A; 10 μg/mL) alone or Con A with cyclosporine (0.05 μg/mL), dexamethasone (1 × 10−7M), a combination of cyclosporine-dexamethasone, or human CTLA4-Ig (10 g/mL). Cells from transplant recipients were stimulated with Con A alone. An ELISA was performed to measure production of interferon (IFN)-γ, granulocyte macrophage–colony stimulating factor (GM-CSF), interleukin (IL)-2, IL-4, and IL-10. Proliferation of CD4+ and CD8+T cells from immunosuppressed cats were also evaluated. Pairwise comparisons were performed via a Wilcoxon signed rank test or Wilcoxon rank sum test. Results—Cyclosporine, dexamethasone, cyclosporine-dexamethasone combination, and CTLA4-Ig caused a significant decrease in IL-2, IFN-γ, and GM-CSF production. Cyclosporine and cyclosporine-dexamethasone, but not human CTLA4-Ig, caused a significant decrease in IL-10 production. High basal concentrations of IL-2 and IL-10 were identified in transplant recipients, and IL-10 was significantly increased in stimulated cultures. In immunosuppressed cats, there was a decrease in frequency of responders and proliferative capacity of CD4+ and CD8+T cells. Conclusions and Clinical Relevance—CTLA4-Ig successfully inhibited proinflammatory cytokines while sparing cytokines critical for allograft tolerance. These data may be useful for developing better strategies to prevent rejection while sparing other immune functions

This study investigated the sedative, cardiopulmonary, and gastrointestinal effects produced by buprenorphine and xylazine given in combination to horses. Six healthy adult horses underwent 4 randomized treatments, with an interval of 1 wk between treatments. A control group was given a saline solution intravenously (IV) and the experimental groups received buprenorphine [10 μg/kg bodyweight (BW)] in combination with 1 of 3 different doses of xylazine: 0.25 mg/kg BW (BX25), 0.50 mg/kg BW (BX50), or 0.75 mg/kg BW (BX75), all of them by IV. Cardiopulmonary parameters were evaluated for 120 min after the drugs were administered and intestinal motility was observed for 12 h after treatment. Sedation was found to be dose-dependent in all groups receiving buprenorphine and xylazine and it was observed that the heart rate decreased in the first 5 min and increased at the end of the sedation period. Arterial blood gas tension analyses showed minimal alterations during the experiment. Gastrointestinal hypomotility was observed for up to 8 h. The combination of buprenorphine and 0.50 mg/kg BW of xylazine (BX50) provided a 30-minute period of sedation without intense ataxia and maintained cardiopulmonary parameters within acceptable limits for the species.

A study was conducted to investigate the efficacy of fosfomycin in controlling streptococcosis in Nile tilapia (Oreochromis niloticus). The minimum inhibitory concentrations (MICs) of fosfomycin against multiple S. iniae isolates showed a sensitivity range of 12.5- 25 'g/mL. The fosfomycin dose levels tested were 40, 60, and 80 mg of active ingredient per kilogram fish per day. Administration of medicated feed started one day after infection by immersion exposure to S. iniae and continued for eight days. Survival rates of fosfomycin treated groups were 90, 100 and 96.6% with an average survival of 95. 53 %. On contrary, survival rates of infected non treated groups were 3.3%. All survivors and negative control groups showed no clinical signs, no gross pathology together with negative S. iniae re-isolation.

The objective of this study is to elicit the destructive effect of lead on the tissues of liver and kidney of mice and if vitamin C is capable of repairing the damage caused by lead. In this study, 40 male mice were used and divided into three groups as: Control group which consists of 16 mice; 8 of them were injected intraperitoneally with (0.9 % N.S.) for 15 days daily then they were sacrificed and the remainder 8 mice were injected intraperitoneally with (0.9 % N.S.) for additional 15 days daily then they were sacrificed, First treated group (T1 group) which consists of 8 mice only; they were injected intraperitoneally with (80 mg/kg) lead acetates then with (400 mg/kg) vitamin C after one hour of lead acetates injection for 15 days daily then they were sacrificed, Second treated group(T2 group) which consists of 16 mice; they were injected intraperitoneally with (80 mg/kg) lead acetates for 15 days daily then 8 of them were sacrificed and called as (T2a) and the remainder 8 mice were injected with (400 mg/kg) vitamin C for additional 15 days daily and called as (T2b). Histologically, the kidneys of the lead acetates treated group indicated undefined epithelial cell lining and also the presence of giant-like cells. When vitamin C offered, it decreased the damage that caused by lead where the kidneys indicated the presence of cuboidal epithelial cells with disrupted epithelial cell lining, and increased intracellular space in the lumen. The livers of the lead acetates treated group indicated the presence of abnormal hepatocytes with distorted shape and undefined epithelial cell lining enlarged nucleus with vacuolations. The incidence of changes and severity were less in the vitamin C treated group. The effect of vitamin C was similar if it is offered after one hour of lead injection or for additional 15 days after lead injection. Hence acute exposure to lead causes morphological changes in the liver and kidney of mice. Hence acute exposure of lead may be toxic and is associated with various pathological conditions such as hepatic and renal dysfunction and cancers.