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   

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   

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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Pharmacokinetics and therapeutic efficacy of rimantadine in horses experimentally infected with influenza virus A2.     

W A Rees  J D Harkins  M Lu  R E Holland  A F Lehner  T Tobin  T M Chambers 《American journal of veterinary research》1999,60(7):888-894

OBJECTIVE: To determine pharmacokinetics of single and multiple doses of rimantadine hydrochloride in horses and to evaluate prophylactic efficacy of rimantadine in influenza virus-infected horses. ANIMALS: 5 clinically normal horses and 8 horses seronegative to influenza A. PROCEDURE: Horses were given rimantadine (7 mg/kg of body weight, i.v., once; 15 mg/kg, p.o., once; 30 mg/kg, p.o., once; and 30 mg/kg, p.o., q 12 h for 4 days) to determine disposition kinetics. Efficacy in induced infections was determined in horses seronegative to influenza virus A2. Rimantadine was administered (30 mg/kg, p.o., q 12 h for 7 days) beginning 12 hours before challenge-exposure to the virus. RESULTS: Estimated mean peak plasma concentration of rimantadine after i.v. administration was 2.0 micrograms/ml, volume of distribution (mean +/- SD) at steady-state (Vdss) was 7.1 +/- 1.7 L/kg, plasma clearance after i.v. administration was 51 +/- 7 ml/min/kg, and beta-phase half-life was 2.0 +/- 0.4 hours. Oral administration of 15 mg of rimantadine/kg yielded peak plasma concentrations of < 50 ng/ml after 3 hours; a single oral administration of 30 mg/kg yielded mean peak plasma concentrations of 500 ng/ml with mean bioavailability (F) of 25%, beta-phase half-life of 2.2 +/- 0.3 hours, and clearance of 340 +/- 255 ml/min/kg. Multiple doses of rimantadine provided steady-state concentrations in plasma with peak and trough concentrations (mean +/- SEM) of 811 +/- 97 and 161 +/- 12 ng/ml, respectively. Rimantadine used prophylactically for induced influenza virus A2 infection was associated with significant decreases in rectal temperature and lung sounds. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of rimantadine to horses can safely ameliorate clinical signs of influenza virus infection.  相似文献   

Low genetic variability in Sclerotinia sclerotiorum populations from common bean fields in Minas Gerais State,Brazil, at regional,local and micro‐scales          下载免费PDF全文

M. S. Lehner  T. J. Paula Júnior  B. T. Hora Júnior  H. Teixeira  R. F. Vieira  J. E. S. Carneiro  E. S. G. Mizubuti 《Plant pathology》2015,64(4):921-931

Sclerotinia sclerotiorum, causal agent of white mould, is the most destructive and widely distributed soilborne pathogen of common bean during the autumn–winter season in Brazil. Nevertheless, little is known about the genetic structure of the pathogen population. Microsatellite (SSR) markers and mycelial compatibility groups (MCGs) were used to characterize 118 isolates collected from 20 bean fields located in the most important growing regions of Minas Gerais State (MG). Additionally, the genetic variability among 10 isolates obtained from a single sclerotium was investigated in 10 different sclerotia. Seventy SSR haplotypes and 14 MCGs were identified among the 118 isolates. The genetic differences within bean growing areas accounted for most of the genetic variation (72%). Despite the relatively high genotypic diversity, the SSR loci were at linkage disequilibrium. Moreover, 70% of the isolates were assigned to only two MCGs, and haplotypes of a given MCG were closely related. The discriminant analysis of principal components revealed five groups. There was strong genetic differentiation between isolates collected in one municipality in southern MG when compared to other regions. Common bean resistance to white mould should be assessed with representative isolates of the five genetic groups and, if possible, of the different MCGs detected in the present study. One to five haplotypes were detected among the 10 isolates obtained from a single sclerotium. Therefore, in order to ensure genetic identity of an isolate, hyphal tip or monoascosporic isolates should be used.  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