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In vivo and in vitro evaluation of the effects of domperidone on the gastrointestinal tract of healthy horses
2013
Nieto, Jorge E. | Maher, Omar | Stanley, Scott D. | Larson, Richard | Snyder, Jack R.
Objective-To determine the effects of domperidone on in vivo and in vitro measures of gastrointestinal tract motility and contractility in healthy horses. Sample-18 adult horses and tissue samples from an additional 26 adult horses. Procedures-Domperidone or placebo paste was administered to healthy horses in a 2-period crossover study. Gastric emptying was evaluated after oral administration of domperidone paste (1.1 or 5.0 mg/kg) or placebo paste by means of the acetaminophen absorption test in 12 horses. Frequency of defecation, weight of feces produced, fecal moisture, and stomach-to-anus transit time of microspheres were evaluated after administration of domperidone paste (1.1 mg/kg) or placebo paste in 6 horses. The effect of domperidone on smooth muscle contractile activity in samples of duodenum, jejunum, ileum, or colon obtained from 26 horses immediately after euthanasia (for nonsystemic medical problems) was investigated. Results-Oral administration of 5.0 mg of domperidone/kg increased peak plasma acetaminophen concentration and area under the curve, indicating increased gastric emptying. Administration of 1.1 mg of domperidone/kg had no effect on gastric emptying, transit time, defecation frequency, or amount and moisture of excreted feces. Contractile activities of circular and longitudinal muscle strips from the duodenum, jejunum, ileum, or colon were not altered by domperidone. Dopamine increased contractile activity of longitudinal muscle strips but not that of circular muscle strips from the midjejunum. Domperidone decreased the dopamine-induced contractile activity of midjejunal longitudinal muscle strips. Conclusions and Clinical Relevance-The potential beneficial effects of domperidone in horses with ileus need to be evaluated in horses with decreased gastric emptying or adynamic ileus.
显示更多 [+] 显示较少 [-]Effects of pneumoperitoneum induced at various pressures on cardiorespiratory function and working space during laparoscopy in cats
2013
Mayhew, Philipp D. | Pascoe, Peter J. | Kass, Philip H. | Shilo-Benjamini, Yael
Objective—To evaluate the effect of pneumoperitoneum on cardiorespiratory variables and working space during experimental induction of 3 intra-abdominal pressures (IAPs) in cats. Animals—6 healthy young adult neutered male domestic shorthair cats. Procedures—All cats were anesthetized through use of a standardized protocol. A catheter was placed in the right femoral artery for blood pressure and blood gas monitoring. A thermodilution catheter was placed in the right jugular vein via fluoroscopic guidance. Cardiopulmonary variables were measured before (baseline) and 2 and 30 minutes after initiation of pneumoperitoneum at IAPs of 4, 8, and 15 mm Hg; these were created through the use of a mechanical insufflator. At each IAP, abdominal dimensions (height, width, and circumference) were measured at a standardized location. Results—At 4 mm Hg and 8 mm Hg IAP, no clinically important changes were identified in cardiorespiratory values. Heart rate, cardiac index, and stroke volume index remained unchanged throughout the study at all IAPs. Mean arterial blood pressure began to increase at 8 mm Hg and was significantly higher, compared with baseline, at both time points at 15 mm Hg. At 15 mm Hg, Paco2 was significantly higher and cats were more acidotic than at baseline. Working space was subjectively greater at 8 mm Hg than at 4 mm Hg IAP; however, at 15 mm Hg, no clinically important enlargement of the working space was identified, compared with at 8 mm Hg. Conclusions and Clinical Relevance—Values of cardiopulmonary variables were largely unchanged by induction of pneumoperitoneum in healthy cats up to an IAP of 8 mm Hg, and no clinically important increases in working space were evident at an IAP of 15 versus 8 mm Hg. These findings provide little justification for use of IAPs > 8 mm Hg in healthy cats undergoing laparoscopic procedures; however, whether the situation is similar in diseased or elderly cats remains to be determined.
显示更多 [+] 显示较少 [-]Effect of delayed exposure of cattle to Mycobacterium avium subsp paratuberculosis on the development of subclinical and clinical Johne's disease
2013
Espejo, Luis A. | Kubat, Noel | Godden, Sandra M. | Wells, Scott J.
Objective—To evaluate the effect of delayed exposure of dairy cattle to Mycobacterium avium subsp paratuberculosis (MAP) on the incidence of those cows testing positive for MAP and developing clinical Johne's disease (CJD). Animals—79 cows not exposed to MAP as calves (unexposed cohort) and 260 cows exposed to MAP as calves (exposed cohort). Procedures—Cows in the unexposed cohort were born into 5 MAP-uninfected herds and introduced at various ages into 5 MAP-infected herds where the exposed cohort cows were born and raised. Beginning when each cow was 24 months old, fecal and serum samples were collected annually from 2003 through 2006. Feces were cultured for MAP, and an ELISA was used to analyze serum samples for antibodies against MAP. Date and reason for culling were obtained from herd records. Incidence of positive culture and ELISA results and CJD was compared between unexposed and exposed cohort cows with Cox regression. Results—Compared with exposed cohort cows, the hazard ratios for unexposed cohort cows having positive culture results, having positive ELISA results, and developing CJD were 0.12, 0.03, and 0.001, respectively, and those ratios increased by 2%, 6%, and 17%, respectively, for each month spent in an MAP-infected herd. Conclusions and Clinical Relevance—Delayed exposure of cows to MAP resulted in lower incidences of positive culture and ELISA results and CJD in those cows, compared with incidences of cows exposed to MAP since birth. The hazard of testing positive for MAP or developing CJD increased with time, regardless of cohort.
显示更多 [+] 显示较少 [-]Pharmacokinetics and safety of silibinin in horses
2013
Hackett, Eileen S. | Mama, Khursheed R. | Twedt, David C. | Gustafson, Daniel L.
Objective—To determine the oral bioavailability, single and multidose pharmacokinetics, and safety of silibinin, a milk thistle derivative, in healthy horses. Animals—9 healthy horses. Procedures—Horses were initially administered silibinin IV and silibinin phospholipid orally in feed and via nasogastric tube. Five horses then consumed increasing orally administered doses of silibinin phospholipid during 4 nonconsecutive weeks (0 mg/kg, 6.5 mg/kg, 13 mg/kg, and 26 mg/kg of body weight, twice daily for 7 days each week). Results—Bioavailability of orally administered silibinin phospholipid was 0.6% PO in feed and 2.9% via nasogastric tube. During the multidose phase, silibinin had nonlinear pharmacokinetics. Despite this, silibinin did not accumulate when given twice daily for 7 days at the evaluated doses. Dose-limiting toxicosis was not observed. Conclusions and Clinical Relevance—Silibinin phospholipid was safe, although poorly bio-available, in horses. Further study is indicated in horses with hepatic disease.
显示更多 [+] 显示较少 [-]Effects of subtherapeutic concentrations of antimicrobials on gene acquisition events in Yersinia, Proteus, Shigella, and Salmonella recipient organisms in isolated ligated intestinal loops of swine
2013
Brewer, Matt T. | Xiong, Nalee | Anderson, Kristi L. | Carlson, Steve A.
Objective-To assess antimicrobial resistance and transfer of virulence genes facilitated by subtherapeutic concentrations of antimicrobials in swine intestines. Animals-20 anesthetized pigs experimentally inoculated with donor and recipient bacteria. Procedures-4 recipient pathogenic bacteria (Salmonella enterica serotype Typhimurium, Yersinia enterocolitica, Shigella flexneri, or Proteus mirabilis) were incubated with donor bacteria in the presence of subinhibitory concentrations of 1 of 16 antimicrobials in isolated ligated intestinal loops in swine. Donor Escherichia coli contained transferrable antimicrobial resistance or virulence genes. After coincubations, intestinal contents were removed and assessed for pathogens that acquired new antimicrobial resistance or virulence genes following exposure to the subtherapeutic concentrations of antimicrobials. Results-3 antimicrobials (apramycin, lincomycin, and neomycin) enhanced transfer of an antimicrobial resistance plasmid from commensal E coli organisms to Yersinia and Proteus organisms, whereas 7 antimicrobials (florfenicol, hygromycin, penicillin G, roxarsone, sulfamethazine, tetracycline, and tylosin) exacerbated transfer of an integron (Salmonella genomic island 1) from Salmonella organisms to Yersinia organisms. Sulfamethazine induced the transfer of Salmonella pathogenicity island 1 from pathogenic to nonpathogenic Salmonella organisms. Six antimicrobials (bacitracin, carbadox, erythromycin, sulfathiazole, tiamulin, and virginiamycin) did not mediate any transfer events. Sulfamethazine was the only antimicrobial implicated in 2 types of transfer events. Conclusions and Clinical Relevance-10 of 16 antimicrobials at subinhibitory or subtherapeutic concentrations augmented specific antimicrobial resistance or transfer of virulence genes into pathogenic bacteria in isolated intestinal loops in swine. Use of subtherapeutic antimicrobials in animal feed may be associated with unwanted collateral effects.
显示更多 [+] 显示较少 [-]Efficacy of decontamination and sterilization of a single-use single-incision laparoscopic surgery port
2013
Coisman, James G. | Case, J Brad | Clark, Nadia D. | Wellehan, James F.X. | Ellison, Gary W.
Objective-To determine the efficacy of decontamination and sterilization of a disposable port intended for use during single-incision laparoscopy. Sample-5 material samples obtained from each of 3 laparoscopic surgery ports. Procedures-Ports were assigned to undergo decontamination and ethylene oxide sterilization without bacterial inoculation (negative control port), with bacterial inoculation (Staphylococcus aureus, Escherichia coli, and Mycobacterium fortuitum) and without decontamination and sterilization (positive control port), or with bacterial inoculation followed by decontamination and ethylene oxide sterilization (treated port). Each port underwent testing 5 times; during each time, a sample of the foam portion of each port was obtained and bacteriologic culture testing was performed. Bacteriologic culture scores were determined for each port sample. Results-None of the treated port samples had positive bacteriologic culture results. All 5 positive control port samples had positive bacteriologic culture results. One negative control port sample had positive bacteriologic culture results; a spore-forming Bacillus sp organism was cultured from that port sample, which was thought to be an environmental contaminant. Bacteriologic culture scores for the treated port samples were significantly lower than those for the positive control port samples. Bacteriologic culture scores for the treated port samples were not significantly different from those for negative control port samples. Conclusions and Clinical Relevance-Results of this study indicated standard procedures for decontamination and sterilization of a single-use port intended for use during singleincision laparoscopic surgery were effective for elimination of inoculated bacteria. Reuse of this port may be safe for laparoscopic surgery of animals.
显示更多 [+] 显示较少 [-]Failure of a VapA/CpG oligodeoxynucleotide vaccine to protect foals against experimental Rhocococcus equi pneumonia despite induction of VapA-specific antibody and interferon-γ response
2013
Lohmann, Katharina L. | Lopez, A Marianela | Manning, Stephen T. | Marques, Fernando J. | Brownlie, Robert | Allen, Andrew L. | Sangster, Anna E. | Mutwiri, George | Gerdts, Volker | Potter, Andrew | Townsend, Hugh G.G.
We evaluated the immunogenic and protective potential of a recombinant VapA/CpG oligodeoxynucleotide (ODN) 2395 vaccine in neonatal foals undergoing experimental Rhodococcus equi challenge. Foals (n = 8) were vaccinated by intramuscular injection on days 1 and 15 of the study; control foals (n = 7) received a phosphate-buffered saline (PBS) solution. All foals were challenged by intrabronchial administration of 5 × 106R. equi 103+ on day 29. Bronchoalveolar lavages were done on days 15, 29, and 36 and total cell count, differential cell count, rVapA-stimulated cell proliferation and interferon (IFN)-γ mRNA expression determined. Clinical examination, complete blood (cell) counts, serology for VapA-specific antibodies, and culture of nasal and fecal swabs were done on days 1, 15, 29, 36, 43, and 50. Foals were humanely euthanized on day 50 and severity of pneumonia scored on a 4-point scale. Vaccination resulted in a significant increase in VapA-specific immunoglobulin (Ig) production, with total IgG and IgG(T) being increased by day 15. Expression of VapA-specific IFN-γ mRNA by BAL cells was increased in the vaccinated foals following challenge. Postmortem lung severity scores did not differ between groups. Two foals shed virulent R. equi in feces; however, real-time polymerase chain reaction (PCR) revealed the isolates to be different from the challenge strain.
显示更多 [+] 显示较少 [-]Antinociceptive effects of long-acting nalbuphine decanoate after intramuscular administration to Hispaniolan Amazon parrots (Amazona ventralis)
2013
Sanchez-Migallon Guzman, David | Braun, Jana M. | Steagall, Paulo V.M. | Keuler, Nicholas S. | Heath, Timothy D. | Krugner-Higby, Lisa A. | Brown, Carolyn S. | Paul-Murphy, Joanne R.
Objective: To evaluate the thermal antinociceptive effects and duration of action of nalbuphine decanoate after IM administration to Hispaniolan Amazon parrots (Amazona ventralis). Animals: 10 healthy adult Hispaniolan Amazon parrots of unknown sex. Procedures: Nalbuphine decanoate (33.7 mg/kg) or saline (0.9% NaCl) solution was administered IM in a randomized complete crossover experimental design (periods 1 and 2). Foot withdrawal threshold to a noxious thermal stimulus was used to evaluate responses. Baseline thermal withdrawal threshold was recorded 1 hour before drug or saline solution administration, and thermal foot withdrawal threshold measurements were repeated 1, 2, 3, 6, 12, 24, 48, and 72 hours after drug administration. Results: Nalbuphine decanoate administered IM at a dose of 33.7 mg/kg significantly increased thermal foot withdrawal threshold, compared with results after administration of saline solution during period 2, and also caused a significant change in withdrawal threshold for up to 12 hours, compared with baseline values. Conclusions and Clinical Relevance: Nalbuphine decanoate increased the foot withdrawal threshold to a noxious thermal stimulus in Hispaniolan Amazon parrots for up to 12 hours and provided a longer duration of action than has been reported for other nalbuphine formulations. Further studies with other types of nociceptive stimulation, dosages, and dosing intervals as well as clinical trials are needed to fully evaluate the analgesic effects of nalbuphine decanoate in psittacine birds.
显示更多 [+] 显示较少 [-]Myocardial cytokine expression in dogs with systemic and naturally occurring cardiac diseases
2013
Fonfara, Sonja | Hetzel, Udo | Tew, Simon R. | Cripps, Peter | Dukes-McEwan, Joanna | Clegg, Peter D.
Objective: To compare myocardial cytokine expression in dogs with naturally occurring cardiac or systemic diseases and dogs without cardiac or systemic diseases (control dogs). Sample: Myocardial tissue samples from 7 systemic disease-affected dogs (SDDs), 7 cardiac disease-affected dogs (CDDs), and 8 control dogs. Procedures: mRNA expression of interleukin (IL)-1, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, and growth differentiation factor-15 in myocardial tissue samples obtained from CDDs, SDDs, and control dogs were analyzed via quantitative PCR assays. Results: In control dogs, only mRNA for TNF-α, TGF-β1, and TGF-β3 was detected; concentrations were significantly higher in male than in female dogs. In SDDs and CDDs, all cytokines, growth factors, and growth differentiation factor-15 were expressed. Compared with findings in SDDs, IL-1, IL-6, IL-8, IL-10, TNF-α, and IFN-γ expression was significantly increased in CDDs; specifically, IL-1, IL-8, TNF-α, TGF-β1, and TGF-β3 expression was increased in the atria and IL-8, IL-10, TNF-α, and IFN-γ expression was increased in the ventricles of CDDs. Conclusions and Clinical Relevance: Data suggested that the alterations in cytokine expression in SDDs and CDDs, compared with control dog findings, were a result of inflammatory system activation. The differences in cytokine expression in atria and ventricles between SDDs and CDDs were suggestive of different remodeling processes. A better knowledge of myocardial involvement in SDDs and of immune regulation in CDDs might beneficially affect morbidity and mortality rates and provide new treatment approaches.
显示更多 [+] 显示较少 [-]Evaluation of the efficacy and safety of single administration of 4.7-mg deslorelin acetate implants on egg production and plasma sex hormones in Japanese quail (Coturnix coturnix japonica)
2013
Petritz, Olivia A. | Sanchez-Migallon Guzman, David | Paul-Murphy, Joanne | Fecteau, Kellie | Mete, Asli | Kass, Philip H. | Hawkins, Michelle G.
Objective: To evaluate the effects of 4.7-mg deslorelin acetate implants on egg production and plasma concentrations of 17β-estradiol and androstenedione in Japanese quail (Coturnix coturnix japonica) over 180 days and assess safety of the implants in quail via gross and histologic examination. Animals: 20 female Japanese quail. Procedures: Following a 7-day period of consistent egg laying, quail were anesthetized and received a 4.7-mg deslorelin implant (treatment group; n = 10) or identical placebo implant (control group; 10) SC between the scapulae. Egg production was monitored daily. Plasma concentrations of 17β-estradiol and androstenedione were measured on days 0 (immediately prior to implant injection), 14, 29, 62, 90, 120, 150, and 180 via radioimmunoassay. Birds were weighed periodically and euthanized at day 180 for complete necropsy. Results: Egg production was significantly decreased in the treatment group, compared with the control group, from 2 to 12 weeks after implant injection. Egg production ceased in 6 of 10 quail in the treatment group (mean duration of cessation, 70 days). Plasma androstenedione and 17β-estradiol concentrations were significantly lower on day 29 in the treatment group than in the control group. Plama androstenedione and 17β-estradiol concentrations were significantly lower on day 29 in the treatment group then in the control group. Conclusions and Clinical Relevance: 4.7-mg deslorelin acetate implants reversibly decreased egg laying for approximately 70 days in most of the Japanese quail evaluated. Further studies evaluating implants containing different concentrations of the drug are needed in quail and other avian species.
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