Pharmacokinetics and pharmacodynamics of three formulations of firocoxib in healthy horses          下载免费PDF全文

B. Holland  C. Fogle  A. T. Blikslager  A. Curling  B. M. Barlow  J. Schirmer  J. L. Davis 《Journal of veterinary pharmacology and therapeutics》2015,38(3):249-256

The objectives of this study were to compare the pharmacokinetics and COX selectivity of three commercially available formulations of firocoxib in the horse. Six healthy adult horses were administered a single dose of 57 mg intravenous, oral paste or oral tablet firocoxib in a three‐way, randomized, crossover design. Blood was collected at predetermined times for PGE₂ and TXB₂ concentrations, as well as plasma drug concentrations. Similar to other reports, firocoxib exhibited a long elimination half‐life (31.07 ± 10.64 h), a large volume of distribution (1.81 ± 0.59L/kg), and a slow clearance (42.61 ± 11.28 mL/h/kg). Comparison of the oral formulations revealed a higher C_max, shorter T_max, and greater AUC for the paste compared to the tablet. Bioavailability was 112% and 88% for the paste and tablet, respectively. Maximum inhibition of PGE₂ was 83.76% for the I.V. formulation, 52.95% for the oral paste formulation, and 46.22% for the oral tablet formulation. Pharmacodynamic modeling suggests an IC₅₀ of approximately 27 ng/mL and an IC₈₀ of 108 ng/ mL for COX2 inhibition. Inhibition of TXB₂ production was not detected. This study indicates a lack of bioequivalence between the oral formulations of firocoxib when administered as a single dose to healthy horses.  相似文献   

Faecal bile loss in horses following small intestinal resection     

Little D  White CE  Young KM  Blikslager AT 《Equine veterinary journal》2005,37(1):92-94

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Detection of differentially regulated genes in ischaemic equine intestinal mucosa     

Tschetter JR  Blikslager AT  Little D  Howard RD  Woody SL  Beex LM  Crisman MV 《Equine veterinary journal》2005,37(4):319-324

REASONS FOR PERFORMING STUDY: Colic is a serious disease syndrome in horses. Much of the mortality is associated with ischaemic-injured intestine during strangulating obstruction, yet there is limited understanding of the associated molecular events. Identification of differentially expressed genes during ischaemic injury should expand our understanding of colic and may lead to novel targeted therapeutic approaches in the future. OBJECTIVE: To isolate and identify differentially expressed genes in equine jejunum following a 2 h ischaemic event compared to normally perfused jejunum. METHODS: Suppressive subtractive hybridisation was used to clone genes that are differentially expressed in equine jejunum injured by 2 h of complete ischaemia as compared to time-matched control jejunal tissues. Expression of selected clones was further evaluated by northern blot analysis. RESULTS: Of the 384 clones selected, 157 were confirmed to possess cDNAs corresponding differentially expressed genes by dot blot analysis. Two genes, fatty acid binding protein 2 and calcium-activated chloride channel 4 were further confirmed to be differentially expressed by northern blot analysis. CONCLUSIONS: Suppressive subtractive hybridisation can be used to detect changes in expression of a broad array of genes, as confirmed by northern blot analysis of selected genes. POTENTIAL RELEVANCE: These initial results have identified a pool of equine intestinal epithelial genes that are differentially expressed following a 2 h ischaemic event. In particular, genes indicative of deranged metabolic activity and those potentially involved in early repair events were identified and may ultimately provide clues as to the nature of epithelial ischaemic injury in horses.  相似文献   

Interactions between lipopolysaccharide and the intestinal epithelium     

Tomlinson JE  Blikslager AT 《Journal of the American Veterinary Medical Association》2004,224(9):1446-1452

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Cyclooxygenase expression in the early stages of equine laminitis: a cytologic study     

Blikslager AT  Yin C  Cochran AM  Wooten JG  Pettigrew A  Belknap JK 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2006,20(5):1191-1196

BACKGROUND: Recent reports indicate increased amounts of mRNA from inflammation-related genes in the prodromal stage of laminitis. HYPOTHESIS: Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) undergo distinct patterns of expression in equine laminae in the developmental stage (DEV) and acute clinical stage (LAM) of laminitis. ANIMALS: Horses selected from an outbred population were placed into 1 of 4 groups: DEV (n = 5), CON-3h (control group for DEV, n = 5), LAM (n = 5) and CON-10h (control group for LAM, n = 5). METHODS: Laminar and skin samples were obtained from (1) animals either undergoing leukopenia (DEV) or the onset of clinical signs of laminitis (LAM) after black walnut extract (BWE) administration and (2) animals either 3 (CON-3h) or 10 (CON-10h) hours after administration of water. Real-time quantitative polymerase chain reaction (RT-qPCR), immunoblotting, and immunohistochemical analysis were performed for COX-1 and COX-2. RESULTS: Upon immunohistochemical analysis of all 4 groups, COX-2 was expressed by most viable epithelial cells in both laminae and skin. COX-1 exhibited similar epithelial expression to COX-2 in skin epidermis, but was expressed exclusively in the basal layer of laminar epidermis. COX-1 protein was not detectable in dermal vasculature of equine skin or laminae, whereas COX-2 was present in endothelial and vascular smooth muscle cells of dermal vasculature in both skin and laminae in all groups. A marked increase in laminar COX-2 protein concentrations was detected on immunoblotting in the DEV group, although a lesser increase was observed in the LAM group. CONCLUSIONS AND CLINICAL IMPORTANCE: COX-2 protein expression is markedly increased in the resident laminar cell types in the developmental stage of BWE-induced laminitis.  相似文献   

Characterization of turkey inducible nitric oxide synthase and identification of its expression in the intestinal epithelium following astrovirus infection     

Meyerhoff RR  Nighot PK  Ali RA  Blikslager AT  Koci MD 《Comparative immunology, microbiology and infectious diseases》2012,35(1):63-69

The inducible nitric oxide synthase (iNOS) enzyme has long been recognized as a key mediator of innate immune responses to infectious diseases across the phyla. Its role in killing or inactivating bacterial, parasitic, and viral pathogens has been documented in numerous host systems. iNOS, and its innate immune mediator NO has also been described to have negative consequence on host tissues as well; therefore understanding the pathogenesis of any infectious agent which induces iNOS expression requires a better understanding of the role iNOS and NO play in that disease. Previous studies in our laboratory and others have demonstrated evidence for increased levels of iNOS and activity of its innate immune mediator NO in the intestine of turkeys infected with astrovirus. To begin to characterize the role iNOS plays in the innate immune response to astrovirus infection, we identified, characterized, developed tkiNOS specific reagents, and demonstrated that the intestinal epithelial cells induce expression of iNOS following astrovirus infection. These data are the first to our knowledge to describe the tkiNOS gene, and demonstrate that astrovirus infection induces intestinal epithelial cells to express iNOS, suggesting these cells play a key role in the antiviral response to enteric infections.  相似文献   

Retrospective analysis of detomidine infusion for standing chemical restraint in 51 horses     

DV Wilson BVSc  MS  Dipl ACVA    GV Bohart DVM    AT Evans DVM  MS  Dipl ACVA    S Robertson BVMS  PhD  Dipl ACVA  Dipl ECVA    Y Rondenay†DVM 《Veterinary anaesthesia and analgesia》2002,29(1):54-57

Objective To assess the effectiveness of a detomidine infusion technique to provide standing chemical restraint in the horse. Design Retrospective study. Animals Fifty‐one adult horses aged 9.5 ± 6.9 years (range 1–23 years) and weighing 575 ± 290.3 kg. Methods Records of horses presented to our clinic over a 3‐year period in which a detomidine infusion was used to provide standing chemical restraint were reviewed. Information relating to the types of procedure performed, duration of infusion, drug dosages and adjunct drugs administered was retrieved. Results Detomidine was administered as an initial bolus loading dose (mean ± SD) of 7.5 ± 1.87 µg kg^?1. The initial infusion rate was 0.6 µg kg^?1 minute^?1, and this was halved every 15 minutes. The duration of the infusion ranged from 20 to 135 minutes. Twenty horses received additional detomidine or butorphanol during the procedure. All horses undergoing surgery received local anesthesia or epidural analgesia in addition to the detomidine infusion. A wide variety of procedures were performed in these horses. Conclusions Detomidine administered by infusion provides prolonged periods of chemical restraint in standing horses. Supplemental sedatives or analgesics may be needed in horses undergoing surgery. Clinical relevance An effective method that provides prolonged periods of chemical restraint in standing horses is described. The infusion alone did not provide sufficient analgesia for surgery and a significant proportion of animals required supplemental sedatives and analgesics.  相似文献   

Ovariectomy as treatment for ovarian bacterial granulomas in a Duvaucel's gecko (Hoplodactylus duvaucelii)     

AT Le Souëf  M Barry  DH Brunton  R Jakob-Hoff  B Jackson 《New Zealand veterinary journal》2013,61(6):340-344

CASE HISTORY: An adult female Duvaucel's gecko (Hoplodactylus duvaucelii) from a threatened species breeding programme presented due to a prolonged gestation period and distended abdomen.

CLINICAL AND PATHOLOGICAL FINDINGS: The gecko was in lean body condition with an irregularly shaped, firm mass in the coelomic cavity. Radiographically there was a diffuse radio-opacity within the coelomic cavity with cranial displacement of the right lung field. Ultrasonography revealed a round homogenous abdominal mass of medium echogenicity with an echogenic capsule. Haematology showed a leucocytosis with a moderate left shift in heterophils and toxic changes. Bilateral ovariectomy was performed to remove two ovarian granulomas and Salmonella enterica subspecies houtenae (IV) was cultured from the ovarian tissue. The gecko recovered well from the surgery, regained weight and remained in good health 3 years following the surgery.

DIAGNOSIS: Pre-ovulatory stasis and ovarian granulomas associated with infection with Salmonella enterica subsp. houtenae.

CLINICAL RELEVANCE: The surgery described in this case resulted in recovery of the gecko, which despite its loss of reproductive capability is of value as an education animal. This is the first report of pre-ovulatory stasis and ovarian granulomas associated with infection with Salmonella enterica in a Duvaucel's gecko and is also the first reported case of pre-ovulatory stasis in a viviparous lizard species. The case adds to knowledge regarding potential reproductive pathology in lizards, which is particularly important information for managers of captive lizard breeding programmes.  相似文献   

Assessment of insecticidal effects and selectivity of CAPA‐PK peptide analogues against the peach‐potato aphid and four beneficial insects following topical exposure     

Shun‐Hua Gui  Clauvis NT Taning  Kristof De Schutter  Qun Yang  Pengyu Chen  Mohamad Hamshou  Ronald J Nachman  Aniruddha A Pandit  Julian AT Dow  Shireen Davies  Guy Smagghe 《Pest management science》2020,76(10):3451-3458

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Letter to the Editor: Bias in statistics or bias in equine veterinary medicine?     

A. L. Ziegler  C. A. Fogle  M. Burke  A. T. Blikslager 《Equine veterinary journal》2019,51(3):423-423

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