Detection, quantification, and pharmacokinetics of furosemide and its effects on urinary specific gravity following IV administration to horses     

Dirikolu L  Lehner AF  Hughes C  Karpiesiuk W  Camargo FC  Harkins JD  Woods WE  Bosken JM  Boyles J  Troppmann A  Fisher M  Tobin T 《Veterinary therapeutics : research in applied veterinary medicine》2003,4(4):350-363

Furosemide is a potent loop diuretic used for the prevention of exercise-induced pulmonary hemorrhage in horses. This drug may interfere with the detection of other substances by reducing urinary concentrations, so its use is strictly regulated. The regulation of furosemide in many racing jurisdictions is based on paired limits of urinary SG (<1.010) and serum furosemide concentrations (>100 ng/ml). To validate this regulatory mechanism, a liquid chromatography/mass spectrometry/mass spectrometry method employing a solid-phase extraction procedure and furosemide-d5 as an internal standard was developed. The method was used to determine the pharmacokinetic parameters of furosemide in equine serum samples and its effects on urinary SG after IV administration (250 mg) to 10 horses. Pharmacokinetic analysis showed that serum concentrations of furosemide were well described by a two-compartmental open model. Based on results in this study, it is very unlikely for horses to have serum furosemide concentrations greater than 100 ng/ml or urine SG less than 1.010 at 4 hours after administration (250 mg IV). However, it should be remembered that urine SG is a highly variable measurement in horses, and even without furosemide administration, some horses might naturally have urine SG values less than 1.010.  相似文献   

禽流感病毒抗原超滤浓缩重要参数的动态变化     

张彦杰  李爱芬 《中国兽药杂志》2007,41(10):16-17

采用世界先进的切向流超滤浓缩技术，对禽流感病毒（H9N2亚型）超滤浓缩成倍体积，测定血凝价HA和半数感染量EID50。结果HA成倍增加，废液HA呈阴性，病毒回收率达100％；受宿主鸡胚系统的影响，EID50与病毒量之间不是简单的直线关系，但病毒的活性不受影响。结果表明，所用超滤系统适用于禽流感病毒抗原的浓缩。  相似文献   

Lidocaine in the horse: its pharmacological effects and their relationship to analytical findings   总被引：3，自引：1，他引：2  

Harkins  Mundy  Woods  Lehner  Karpiesiuk  Rees  Dirikolu  Bass  Carter  Boyles  & Tobin 《Journal of veterinary pharmacology and therapeutics》1998,21(6):462-476

Lidocaine is a local anaesthetic agent that is widely used in equine medicine. It is also an Association of Racing Commissioners International (ARCI) Class 2 foreign substance that may cause regulators to impose substantial penalties if residues are identified in post race urine samples. Therefore, an analytical/pharmacological database was developed for this drug. Using our abaxial sesamoid local anaesthetic model, the highest no-effect dose (HNED) for the local anaesthetic effect of lidocaine was determined to be 4 mg. Using enzyme-linked immunosorbent assay (ELISA) screening, administration of the HNED of lidocaine to eight horses yielded peak serum and urine concentrations of apparent lidocaine of 0.84 ng/mL at 30 min and 72.8 ng/mL at 60 min after injection, respectively. These concentrations of apparent lidocaine are readily detectable by routine ELISA screening tests (LIDOCAINE ELISA, Neogen, Lexington, KY). ELISA screening does not specifically identify lidocaine or its metabolites, which include 3-hydroxylidocaine, dimethylaniline, 4-hydroxydimethylaniline, monoethylglycinexylidine, 3-hydroxymonoethylglycinexylidine, and glycinexylidine. As 3-hydroxylidocaine is the major metabolite recovered from equine urine, it was synthesized, purified and characterized, and a quantitative mass spectrometric method was developed for 3-hydroxylidocaine as recovered from horse urine. Following subcutaneous (s.c.) injection of the HNED of lidocaine, the concentration of 3-hydroxylidocaine recovered from urine reached a peak of about 315 ng/mL at 1 h after administration. The mean pH of the 1 h post dosing urine samples was 7.7, and there was no apparent effect of pH on the amount of 3-hydroxylidocaine recovered. Within the context of these experiments, the data suggests that recovery of less than 315 ng/mL of 3-hydroxylidocaine from a post race urine sample is unlikely to be associated with a recent local anaesthetic effect of lidocaine. Therefore these data may be of assistance to industry professionals in evaluating the significance of small concentrations of lidocaine or its metabolites in postrace urine samples. It should be noted that the quantitative data are based on analytical methods developed specifically for this study, and that methods used by other laboratories may yield different recoveries of urine 3-hydroxylidocaine.  相似文献   

Case–control risk factor study of methicillin-resistant Staphylococcus pseudintermedius (MRSP) infection in dogs and cats in Germany     

Georg Lehner  Monika Linek  Ross Bond  David H. Lloyd  Ellen Prenger-Berninghoff  Nina Thom  Iris Straube  Kristien Verheyen  Anette Loeffler 《Veterinary microbiology》2014

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) has emerged as a highly drug-resistant small animal veterinary pathogen. Although often isolated from outpatients in veterinary clinics, there is concern that MRSP follows a veterinary-hospital-associated epidemiology. This study's objective was to identify risk factors for MRSP infections in dogs and cats in Germany. Clinical isolates of MRSP cases (n = 150) and methicillin-susceptible S. pseudintermedius (MSSP) controls (n = 133) and their corresponding host signalment and medical data covering the six months prior to staphylococcal isolation were analysed by multivariable logistic regression. The identity of all MRSP isolates was confirmed through demonstration of S. intermedius-group specific nuc and mecA. In the final model, cats (compared to dogs, OR 18.5, 95% CI 1.8–188.0, P = 0.01), animals that had been hospitalised (OR 104.4, 95% CI 21.3–511.6, P < 0.001), or visited veterinary clinics more frequently (>10 visits OR 7.3, 95% CI 1.0–52.6, P = 0.049) and those that had received topical ear medication (OR 5.1, 95% CI 1.8–14.9, P = 0.003) or glucocorticoids (OR 22.5, 95% CI 7.0–72.6, P < 0.001) were at higher risk of MRSP infection, whereas S. pseudintermedius isolates from ears were more likely to belong to the MSSP-group (OR 0.09, 95% CI 0.03–0.34, P < 0.001). These results indicate an association of MRSP infection with veterinary clinic/hospital settings and possibly with chronic skin disease. There was an unexpected lack of association between MRSP and antimicrobial therapy; this requires further investigation but may indicate that MRSP is well adapted to canine skin with little need for selective pressure.  相似文献   

Alternative HIV vaccine strategies     

Lehner T  Shearer GM 《Science (New York, N.Y.)》2002,297(5585):1276-1277

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Intravenous and intratracheal administration of trimetoquinol, a fast-acting short-lived bronchodilator in horses with 'heaves'     

Camargo FC  Robinson NE  Berney C  Eberhart S  Baker S  DeTolve P  Derksen FJ  Harkins JD  Lehner AF  Tobin T 《Equine veterinary journal》2006,38(6):563-569

REASON FOR PERFORMING STUDY: Trimetoquinol (TMQ) is a potent beta-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with 'heaves'. OBJECTIVES: To assess the pharmacodynamics of TMQ in horses with 'heaves' to determine potential therapeutic effects. METHODS: Increasing doses of TMQ were administered to horses with 'heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001-0.2 microg/kg bwt i.v. and 0.01-2 microg/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural pressure (deltaPplmax), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action to i.v. (0.2 microg/kg bwt) and i.t. (2 microg/kg bwt) TMQ was evaluated over 6 h. RESULTS: Intravenous TMQ was an exceptionally potent cardiac stimulant. Heart rate increased at 0.01 microg/kg bwt, and was still increasing after administration of highest dose, 0.2 microg/kg bwt. Airway bronchodilation, measured as a decrease in deltaPplmax, also commenced at 0.01 microg/kg bwt. By the i.t. route, TMQ was 50-100-fold less potent than by i.v. Side effects included sweating, agitation and muscle trembling. Overall, the onset of HR and bronchodilator effects was rapid, within about 3 min, but effects were over at 2 h. CONCLUSION: When administered i.v. and i.t., TMQ is a highly potent cardiac stimulant and a modest bronchodilator. It may not be an appropriate pharmacological agent by i.v. and i.t. routes for the alleviation of signs in horses with 'heaves'. Further studies of TMQ by oral and aerosol routes are necessary. POTENTIAL RELEVANCE: In horses, TMQ is a fast-acting bronchodilator with a short duration of action. It could be used as a rescue agent during an episode of 'heaves'. The i.v. and i.t. administration of TMQ is associated with side effects, similar to those reported for all other beta-agonists. However, other routes, such as aerosol and oral, may prove useful and safe for the alleviation of bronchoconstriction typical of 'heaves'.  相似文献   

Dendritic cell stimulation by mycobacterial Hsp70 is mediated through CCR5     

Floto RA  MacAry PA  Boname JM  Mien TS  Kampmann B  Hair JR  Huey OS  Houben EN  Pieters J  Day C  Oehlmann W  Singh M  Smith KG  Lehner PJ 《Science (New York, N.Y.)》2006,314(5798):454-458

An effective host immune response to mycobacterial infection must control pathogen dissemination without inducing immunopathology. Constitutive overexpression of mycobacterial heat shock protein (myHsp70) is associated with impaired bacterial persistence, but the immune-mediated mechanisms are unknown. We found that myHsp70, in addition to enhancing antigen delivery to human dendritic cells, signaled through the CCR5 chemokine receptor, promoting dendritic cell aggregation, immune synapse formation between dendritic cells and T cells, and the generation of effector immune responses. Thus, CCR5 acts as a pattern-recognition receptor for myHsp70, which may have implications for both the pathophysiology of tuberculosis and the use of myHsps in tumor-directed immunotherapy.  相似文献   

Possible parachordoma in a dog     

SF Forsyth  KG Thompson  AF French  TR Halsey 《New Zealand veterinary journal》2013,61(5):299-302

Abstract

CASE HISTORY: A 15-mm diameter mass developed in the S/C tissue overlying the right lateral gluteal muscle of a 6½-year-old female Flat-coated Retriever.

PATHOLOGICAL FINDINGS: Cytological preparations following aspiration of the mass were highly cellular and consisted of a population of large polygonal cells containing single to multiple nuclei, large prominent nucleoli, and intracytoplasmic vacuoles. Histologically, the neoplasm consisted of similar large cells surrounded by thick fibrous connective tissue trabeculae. The large polygonal cells reacted positively with antibodies against vimentin, low- and high-molecular-weight variants of cytokeratin (AE1/AE3), but not with antibodies to desmin or glial fibrillary acidic protein (GFAP).

DIAGNOSIS: The clinical, gross, histological and immunohistochemical findings are similar to those reported for parachordomas in humans. Neither recurrence nor metastases were noted 18 months after surgical excision of the mass.

CLINICAL RELEVANCE: This is the first reported case of a possible parachordoma in a dog, a benign tumour with cytological features of malignancy.  相似文献   

Strategy to identify resistance to white mould associated with high yield for irrigated common bean in Brazil     

Renan C. Lima  Pablo H. Teixeira  Ari F. F. Souza  Trazilbo J. Paula Júnior  Hudson Teixeira  Miller S. Lehner  José E. S. Carneiro  Tiago S. Marçal  Rogerio F. Vieira 《Plant pathology》2020,69(6):1172-1184

Development of common bean cultivars with partial white mould resistance through breeding techniques has been a challenge in Brazil. As yet, lines/cultivars from breeding programmes have not been investigated for resistance; therefore, this study screened 107 lines/cultivars for their reactions to white mould in 14 preliminary trials conducted under irrigation. Thirteen resistant lines/cultivars (three of Andean origin) and six Mesoamerican cultivars (three intermediately resistant and three susceptible) were selected for further investigation. These lines/cultivars and the resistant control A195 were evaluated in six advanced trials and two straw tests to assess the effectiveness of the screening procedure. In 11 preliminary trials, screenings were performed under moderate/high or higher disease pressure. These pressures occurred in two advanced trials in which, when yields were averaged across moderate/high and high pressures, 10 Mesoamerican lines/cultivars selected for resistance yielded 14%, 23%, and 38% more than intermediately resistant cultivars, A195, and susceptible cultivars, with median disease ratings (1–9 scale) of 4.5, 5.7, 5.7, and 6.7, respectively. In the straw test, three Andean lines/cultivars (A195 included) and two susceptible cultivars in the field were among those with the highest levels of physiological resistance. Thus, field rating under high disease pressure and greenhouse rating did not correlate significantly, suggesting that field trials are critical to evaluating resistance and to identifying high-yielding beans. Therefore, lines/cultivars from breeding programmes assessed in field trials may provide a low cost and fast way to identify high-yielding bean cultivars with partial resistance to white mould in the subtropical southern hemisphere.  相似文献   

Pharmacokinetics of gabapentin in horses     

Dirikolu L  Dafalla A  Ely KJ  Connerly AL  Jones CN  ElkHoly H  Lehner AF  Thompson K  Tobin T 《Journal of veterinary pharmacology and therapeutics》2008,31(2):175-177

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