bluuebunny/crossref_metadata_2025 huggingface dataset:
Resuscitation with Lipid versus Epinephrine in a Rat Model of Bupivacaine Overdose
Authors: Weinberg Guy L. , Di Gregorio Guido , Ripper Richard , Kelly Kemba , Massad Malek , Edelman Lucas , Schwartz David , Shah Nirali , Zheng Sophie , Feinstein Douglas L.
Published: April 2008

Background

Lipid emulsion infusion reverses cardiovascular compromise due to local anesthetic overdose in laboratory and clinical settings. The authors compared resuscitation with lipid, epinephrine, and saline control in a rat model of bupivacaine-induced cardiac toxicity to determine whether lipid provides a benefit over epinephrine.

Methods

Bupivacaine, 20 mg/kg, was infused in rats anesthetized with isoflurane, producing asystole in all subjects. Ventilation with 100% oxygen and chest compressions were begun immediately, along with intravenous treatment with 30% lipid emulsion or saline (5-ml/kg bolus plus continuous infusion at 0.5 ml . kg . min) or epinephrine (30 microg/kg). Chest compressions were continued and boluses were repeated at 2.5 and 5 min until the native rate-pressure product was greater than 20% baseline. Electrocardiogram and arterial pressure were monitored continuously and at 10 min, arterial blood gas, central venous oxygen saturation, and blood lactate were measured. Effect size (Cohen d) was determined for comparisons at 10 min.

Results

Lipid infusion resulted in higher rate-pressure product (P < 0.001, d = 3.84), pH (P < 0.01, d = 3.78), arterial oxygen tension (P < 0.05, d = 2.8), and central venous oxygen saturation (P < 0.001, d = 4.9) at 10 min than did epinephrine. Epinephrine treatment caused higher lactate (P < 0.01, d = 1.48), persistent ventricular ectopy in all subjects, pulmonary edema in four of five rats, hypoxemia, and a mixed metabolic and respiratory acidosis by 10 min.

Conclusions

Hemodynamic and metabolic metrics during resuscitation with lipid surpassed those with epinephrine, which were no better than those seen in the saline control group. Further studies are required to optimize the clinical management of systemic local anesthetic toxicity.
Infection of neonates with murine gammaherpesvirus 68 results in enhanced viral persistence in lungs and absence of infectious mononucleosis syndrome
Authors: Ptaschinski Catherine , Rochford Rosemary
Published: April 2008

We used the murine gammaherpesvirus 68 (γHV-68), which serves as a model for human gammaherpesvirus infection, to determine whether age at infection altered the pattern of gammaherpesvirus pathogenesis. We infected mice intranasally at 8 days old (pups) and 6 weeks old (adults) to investigate differences inγHV-68 pathogenesis. There was no difference between adults or pups in acute infection in the lungs at 6 days post-infection (p.i.). However, mice infected as pups exhibited a more disseminated viral infection with viral DNA detected in the spleen, liver and heart as measured by quantitative PCR (Q-PCR). In addition, viral DNA was detected in the lungs of mice infected as pups until 60 days p.i. Three viral transcripts (M2, M3 and M9) were expressed at both 30 and 60 days p.i. In contrast, no viral DNA or mRNA expression was detected in lungs of mice infected as adults at 30 or 60 days p.i. Mice infected as adults experienced a peak in latent infection in the spleen at 16 days p.i., corresponding with an increase in splenic weight and expansion of the Vβ4+CD8+T-cell population, similar to infectious mononucleosis observed following infection of young adults with Epstein–Barr virus. However, the increase in splenic weight of infected pups was not as pronounced and no significant increase in Vβ4+CD8+T-cell expansion was observed in infected pups. Together, these data suggest that the pathogenesis of murine gammaherpesvirusγHV-68 is age-dependent.
Molecular epidemiology of the African horse sickness virus S10 gene
Authors: Quan Melvyn , van Vuuren Moritz , Howell Peter G. , Groenewald Daleen , Guthrie Alan J.
Published: April 2008

Between 2004 and 2006, 145 African horse sickness viruses (AHSV) were isolated from blood and organ samples submitted from South Africa to the Faculty of Veterinary Science, University of Pretoria. All nine serotypes were represented, with a range of 3–60 isolates per serotype. The RNA small segment 10 (S10) nucleotide sequences of these isolates were determined and the phylogeny investigated. AHSV, bluetongue virus (BTV) and equine encephalosis virus (EEV) all formed monophyletic groups and BTV was genetically closer to AHSV than EEV. This study confirmed the presence of three distinct S10 phylogenetic clades (α, β and γ). Some serotypes (6, 8 and 9 in α; 3 and 7 in β; 2 in γ) were restricted to a single clade, while other serotypes (1, 4 and 5) clustered into both the α and γ clades. Strong purifying selection was evident and a constant molecular clock was inappropriate. The S10 gene is the second most variable gene of the AHSV genome and the use of S10 in molecular epidemiology was illustrated by an AHS outbreak in the Western Cape in 2004. It was shown that two separate AHSV were circulating in the area, even though AHSV serotype 1 was the only isolate from the outbreak. The small size of the gene (755–764 bp) and conserved terminal regions facilitate easy and quick sequencing. The establishment of an S10 sequence database is important for characterizing outbreaks of AHS. It will be an essential resource for elucidating the epidemiology of AHS.
Complete genome analysis of hepatitis C virus subtypes 6t and 6u
Authors: Noppornpanth Suwanna , Poovorawan Yong , Lien Truong Xuan , Smits Saskia L. , Osterhaus Albert D. M. E. , Haagmans Bart L.
Published: April 2008

Hepatitis C virus (HCV) genomes exhibit high nucleotide sequence diversity. In this study, we performed complete genome sequence analysis of 11 HCV genotype 6 samples from Vietnam and Thailand. We identified nine HCV complete genomes belonging to subtypes 6a (D9), 6e (D42 and D88), 6f (TH52), 6i (TH24), 6l (D33), 6n (TH22 and TH31) and 6o (D85). Phylogenetic analysis of the core/E1 and NS5B regions from unclassified genotype 6 isolates from Asian immigrants in Canada revealed that two other viruses (D49 and D83) could be classified as novel candidates of HCV subtypes 6t and 6u.
Two GATA Transcription Factors Are Downstream Effectors of Floral Homeotic Gene Action in Arabidopsis
Authors: Mara Chloe D. , Irish Vivian F.
Published: April 2008

Floral organogenesis is dependent on the combinatorial action of MADS-box transcription factors, which in turn control the expression of suites of genes required for growth, patterning, and differentiation. In Arabidopsis (Arabidopsis thaliana), the specification of petal and stamen identity depends on the action of two MADS-box gene products, APETALA3 (AP3) and PISTILLATA (PI). In a screen for genes whose expression was altered in response to the induction of AP3 activity, we identified GNC (GATA, nitrate-inducible, carbon-metabolism-involved) as being negatively regulated by AP3 and PI. The GNC gene encodes a member of the Arabidopsis GATA transcription factor family and has been implicated in the regulation of chlorophyll biosynthesis as well as carbon and nitrogen metabolism. In addition, we found that the GNC paralog, GNL (GNC-like), is also negatively regulated by AP3 and PI. Using chromatin immunoprecipitation, we showed that promoter sequences of both GNC and GNL are bound by PI protein, suggesting a direct regulatory interaction. Analyses of single and double gnc and gnl mutants indicated that the two genes share redundant roles in promoting chlorophyll biosynthesis, suggesting that in repressing GNC and GNL, AP3/PI have roles in negatively regulating this biosynthetic pathway in flowers. In addition, coexpression analyses of genes regulated by AP3, PI, GNC, and GNL indicate a complex regulatory interplay between these transcription factors in regulating a variety of light and nutrient responsive genes. Together, these results provide new insights into the transcriptional cascades controlling the specification of floral organ identities.
Clinical relevance of serum levels of matrix metallopeptidase‐2, and tissue inhibitor of metalloproteinase‐1 and ‐2 in patients with malignant melanoma
Authors: YOSHINO Yuichiro , KAGESHITA Toshiro , NAKAJIMA Motowo , FUNAKUBO Minako , IHN Hironobu
Published: April 2008

The interaction and/or balance between matrix metallopeptidase (MMP)‐2 and tissue inhibitor of metalloproteinase (TIMP)‐2 in vivo may play important roles in the process of tumor growth, invasion and metastasis of malignant melanoma. In this study, we investigated the serum levels and immunohistochemical expression of MMP‐2, TIMP‐1 and TIMP‐2 in patients with melanoma and analyzed the correlation with clinicopathological parameters. The level of serum MMP‐2 in patients was significantly higher than that of the control. Moreover, the level of MMP‐2 was significantly higher than that of the control in patients who were: (i) female; (ii) pT1 and pT4; (iii) with and without lymph node (LN) metastasis; (iv) in stage I and stage IV; (v) with and without recurrence; and (v) alive and dead. The level of serum TIMP‐1 in patients with melanoma was significantly higher than that of the control. Among melanoma patients, the level of TIMP‐1 with pT4 was significantly higher for patients who were: (i) pT1 and pT3; (ii) with LN metastasis (vs those without); (iii) in stage IV (vs those in stages I, II and III); and (iv) dead (vs those alive). The level of serum TIMP‐2 in patients with melanoma was not different from the control. However, the level of TIMP‐2 in patients with pT4 was significantly higher than for patients who were: (i) pT1, pT3 and control; (ii) with LN metastasis (vs those without metastasis and control); (iii) with stage IV (vs those in stages I and II and control); (iv) in recurrence (vs control); and (v) dead (vs those alive and control). These results suggest that increased serum levels of TIMP‐1 and TIMP‐2 reflected the extent of metastatic melanoma lesions, and that serum levels of TIMP‐1 may be a new useful marker for melanoma progression.
Childhood and adolescent predictors of heavy drinking and alcohol use disorders in early adulthood: a longitudinal developmental analysis
Authors: Englund Michelle M. , Egeland Byron , Oliva Elizabeth M. , Collins W. Andrew
Published: April 2008

Aims  To identify childhood and adolescent factors differentiating heavy alcohol users in early adulthood from more moderate users or abstainers.

Design  Low‐income participants followed from birth to age 28 years.

Participants  A total of 178 adults (95 males) who were first‐born children of low‐income mothers recruited in Minneapolis, Minnesota, during their third trimester of pregnancy.

Measurements  Maternal hostility (24/42 months), externalizing and internalizing behavior problems (9 years), peer acceptance and academic achievement (12 years), maternal alcohol use and participants' drinking behavior (16 years), quantity of alcohol use per occasion (19, 23 and 26 years), alcohol use disorders (28 years).

Findings  For men: (i) higher amounts of alcohol consumption at age 16 increased the odds of being a heavy drinker compared to an abstainer (age 19) and a moderate drinker (ages 23 and 26); (ii) lower achievement scores at age 12 and having a mother who drank more when the participant was age 16 increased the odds of being a heavy drinker compared to moderate drinker (age 26). Higher levels of externalizing behavior problems at age 9 and drinking more when the participants were age 16 increased the odds that men would have a current alcohol use disorder at age 28. For women: (i) drinking more at age 16 increased the odds of being a heavy drinker compared to being either an abstainer or a moderate drinker (age 26); (ii) having higher levels of achievement at age 12 increased the odds of being a heavy drinker compared to an abstainer at age 23. Adolescent alcohol use mediated the relation between externalizing behavior at age 9 and alcohol use at age 26 for women.

Conclusions  Problem drinking may be the result of a long‐term developmental process wherein childhood externalizing behavior problems sets a pathway leading to heavy drinking during and after adolescence.
The effect of flurbiprofen, a potent non‐steroidal anti‐inflammatory agent, upon Trypanosoma vivax infection in goats
Authors: MIERT A.S.J.P.A.M. VAN , DUIN C. Th. VAN , BUSSER F.J.M. , PERIEA N. , INGH T. S. G. A. M. VAN DEN , NEYS‐BACKERS M. H. H. DE
Published: April 2008

Platelet aggregation leading to a decreased number of thrombocytes and reduced blood serotonin levels can be correlated with parasitaemia as has been observed in goats and cattle infected with T. vivax Y58. Flurbiprofen is a potent anti‐inflammatory agent with antipyretic activity. In vitro, this agent inhibits platelet aggregation and blocks serotonin release. The results of the present study demonstrated that flurbiprofen inhibited the febrile reactions during the acute phase of T. vivax infection, but the drug did not prevent or reverse the associated drop in blood serotonin level during this period. Moreover, it was apparent that flurbiprofen had a deleterious effect on goats infected with T. vivax Y58. The infection in the untreated animals (sixteen out of seventeen goats) followed a rather mild and prolonged course with peaks of parasitaemia during the febrile episodes, whereas in flurbiprofen‐treated goats (five animals), inoculated with the same number of trypanosomes, the parasitaemia was progressive and terminated in early death with disseminated intravascular coagulation at post mortem examination. These observations would seem to confirm the work of previous investigators, suggesting that anti‐inflammatory agents have an aggravatory effect on the course of infection in animals inoculated with various strains of trypanosomes. Important differences exist, however, in the relationship between prostaglandin synthesis in the platelets of the goat and in those of other species.
Mammary and renal excretion of chlorpromazine in goats
Authors: NAWAZ MUHAMMAD , RASMUSSEN FOLKE
Published: April 2008

In experiments on goats it was found that the binding of chlorpromazine (Cpz) to the proteins in plasma and milk ranged between 91–99 and 91–97 %, respectively, and was independent of the drug concentration in the samples. The in vitro binding of chlorpromazine in whole milk (96%) was significantly higher (P<0.01) than the protein binding in skim milk (91%) because the drug was concentrated in the butterfat. The concentration of Cpz was always higher in the milk than in the corresponding plasma samples. The renal clearance of Cpz in goats with normal urine pH was very small (0.16 ml min‐1) due to the high degree of plasma protein binding and of back diffusion. The mechanisms involved during the renal excretion of Cpz in goats included glomerular filtration, probably active tubular secretion and pH dependent back diffusion.
Comparative plasma kinetics of orally administered sulfamethazine in clinically parasitized and parasitism‐treated lambs
Authors: RIGHTER H. F. , SHOWALTER D. H. , TESKE R. H.
Published: April 2008

Sulfamethazine was administered at a dosage of 99 mg/kg body weight to lambs with a naturally acquired parasitism and again at 37 days following treatment with an anthelmintic. Blood samples were analyzed for sulfonamides over a 72 h period following sulfamethazine administration in both phases of the study. Pharmacokinetic parameter estimates of the sulfonamide blood data demonstrated significantly lower peak levels, longer times to peak and higher blood levels of the drug as time after dosing increased, in the parasitized as compared with the parasitism‐treated lambs.
Some physiological and biochemical effects of acetazolamide in the dog
Authors: ROSE R.J. , CARTER J.
Published: April 2008

Acetazolamide was administered at a dose rate of 10 mg/kg intravenously every 8 h to twelve dogs for a period of 7 days. Before administration of the acetazolamide and every second day during the period of administration, values of PaO2, PaCO2, pH, base excess, bicarbonate, systolic and diastolic arterial pressure, central venous pressure, packed cell volume, haemoglobin and total plasma protein were measured. Plasma concentrations of sodium, potassium, chloride, creatinine, urea, glucose, bilirubin, iron, calcium, phosphate and triglycerides were also determined. These values were also measured in a similar control group of dogs not given acetazolamide. Acetazolamide produced significant elevations in PaO2 and chloride values and significant decreases in PaCO2, pH, base excess, bicarbonate, potassium and calcium. There were no significant changes in any of the other parameters measured. The non‐respiratory acidosis produced by acetazolamide makes it a useful model to enable the investigation of therapeutic regimes for treating acidosis of this type.
Correlation of serum phenytoin (diphenylhydantoin) with the administration of oral and intravenous phenytoin in dogs
Authors: KOWALCZYK D. F.
Published: April 2008

The concentration of serum phenytoin was determined in normal dogs following the administration of phenytoin by either the intravenous or oral route. An intravenous dose of 11 and 33 mg/kg of body weight was given to six dogs and a further dose of 44 mg/kg was given to two dogs. Serial blood samples were taken following the three doses for determination of pharmacokinetic parameters. The mean half‐life was 3.35, 3.84 and 4.57 h as the dose was increased. Signs of toxicity occurred immediately following the infusion of phenytoin (emesis, ataxia and seizures). In the first oral studies, serial blood samples were taken for 2 consecutive days following a dose of 11 and 88 mg/kg, t.i.d. The time—concentration profiles of phenytoin varied significantly from one day to the next in the same dog. In the second oral study, blood samples were taken at 3 and 7 h following a dose of 11, 22, 44, 66 and 88 mg/kg, t.i.d. There was a poor correlation between the size of the oral dose and the concentration of serum phenytoin. Due to the short half‐life and poor absorption of phenytoin in dogs, it was concluded that the oral administration of phenytoin in dogs produces sub‐therapeutic and erratic serum concentrations of phenytoin which makes its efficacy as an anti‐convulsant questionable.
Plants used in traditional veterinary medical practice in Nigeria
Authors: NWUDE N. , IBRAHIM M. A.
Published: April 2008

Ninety‐two species of plants used in traditional veterinary medical practice in Nigeria are presented. The vernacular names, animal species in which they are used, indications/uses and comments on the plants are given. The importance of integrating traditional veterinary medicine with modern orthodox veterinary medicine is discussed.
Oxytetracycline hydrochloride in the horse: serum, synovial, peritoneal and urine concentrations after single dose intravenous administration
Authors: BROWN MURRAY P. , STOVER SUSAN M. , KELLY ROBIN H. , FARVER THOMAS B. , KNIGHT HUMPHREY D.
Published: April 2008

Six adult mares were given a single intravenous injection of oxytetracycline HCl (50 mg/ml) at a dosage of 5 mg/kg. Serum, synovial fluid, peritoneal fluid, and urine oxytetracycline concentrations were measured serially over a 48‐h period. The highest measured serum oxytetracycline concentration was 8.01 mcg/ml at 1/2 h. Oxytetracycline was detected in synovial fluid and peritoneal fluid, which obtained mean peak oxytetracycline concentrations of 4.43 mcg/ml and 4.20 mcg/ml, at 1/2 h and 1 h, respectively. These concentrations steadily declined in parallel with serum concentrations and were not measurable at 48 h. Urine oxytetracycline concentration was relatively high, with a peak concentration of 1565.2 mcg/ml at 1/2 h after drug administration.
Cardiovascular effects of intravenous administration of tetracycline in cattle
Authors: GYRD‐HANSEN N. , RASMUSSEN FOLKE , SMITH MOGENS
Published: April 2008

Tetracycline chloride dissolved in saline was injected intravenously to seven cows. Two doses of tetracycline were used: 5 and 10 mg/kg b.wt, and the injections were given over a period of either 10, 60 or 300 sec.

A number of the cows collapsed shortly after the injection was completed, usually when the 10 mg dosage was given in 60 sec. When the same dose was given over a period of 5 min none of the cows collapsed. A more or less pronounced drop in blood pressure could be detected during or shortly after the injection; in those cows which collapsed the blood pressure fell almost to zero. The predominant change in pulse rate in connection with the tetracycline administration was a decrease which could be quite marked, pulse rates falling as low as 10–20 per min. Simultaneously with these changes in blood pressure and pulse rate severe abnormalities in ECG could be observed. Pre‐treatment with a normal therapeutic dose of calcium borogluconate intravenously prevented collapse in the cows and diminished the drop in blood pressure associated with an ensuing tetracycline injection.

It is concluded that intravenous injection of tetracycline is hazardous, but that collapse can be avoided by giving the injection very slowly over a period of no less than 5 min.
Emetic action of xylazine on the chemoreceptor trigger zone for vomiting in cats
Authors: COLBY E. D. , McCARTHY L. E. , BORISON H. L.
Published: April 2008

Xylazine is an effective sedative analgesic that induces vomiting in the cat. A consistently effective intramuscular emetic dose of xylazine was established in normal cats in this laboratory. Animals in which the area postrema of the medulla oblongata had been chronically destroyed did not exhibit emesis in response to the standard test dose of xylazine but continued to show sedation. By contrast, sham‐operated cats responded normally. Refractoriness to deslanoside, a known specific emetic drug, was used as functional proof for successful ablation of area postrema, and the lesions were also validated histologically. We conclude that xylazine exerts its emetic action on the chemoreceptor trigger zone of the area postrema. It is suggested that this action may be mediated by an opiate type of molecular receptors.
Physicochemical methods for pharmacokinetic and residue analysis of chloramphenicol and degradation products in dairy cows
Authors: LEE J. J. VAN DER , NOUWS J. F. M. , BLOEMENDAL F. W. R.
Published: April 2008

The disposition of chloramphenicol after intramammary and intravenous administration was followed through determinations of chloramphenicol in blood and milk by means of high‐performance differential pulse polarography. The concentration‐time curves obtained reflected the different modes of administration, and allowed calculation of some pharmacokinetic parameters. The results of the polarographic determination in blood agreed fairly well with those of the microbiological assay in serum. Several body fluids and tissues of the cows were examined for residues of chloramphenicol and degradation products, both by the microbiological method and by high‐performance liquid chromatography with ultraviolet detection. In urine, chloramphenicol and chloramphenicol glucuronide were found; in the other fluids and tissues only now and then a trace of chloramphenicol or a degradation product was detected. From these results it appears that chloramphenicol and degradation products are eliminated rapidly and completely after intravenous or intrammary application. No accumulation of degradation products occurred.
Xylazine hydrochloride‐induced hyperglycemia and hypoinsulinemia in thoroughbred horses
Authors: THURMON JOHN C. , NEFF‐DAVIS CAROL , DAVIS LLOYD E. , STOKER ROBERT A. , BENSON G. JOHN , LOCK THEODORE F.
Published: April 2008

The effects of intravenous xylazine (1.1 mg/kg) were studied in six thoroughbred horses (five mares and a stallion). Plasma glucose concentration increased to 168% of control at 45 min and decreased to 112% of control at 180 min. Insulin had decreased to 31% of control at 15 min. Thereafter, insulin concentration increased, reaching its highest concentration at 150 min. The mechanism for these changes is not fully understood and further investigation is indicated.
Pharmacological aspects of metaldehyde poisoning in mice
Authors: HOMEIDA A. M. , COOKE R. G.
Published: April 2008

Metaldehyde, when administered orally to mice at a dose of 1 g kg‐1, produced convulsions and death within 2 h. Brain concentrations of noradrenaline (NA) 5‐hydroxytryptamine (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA) were significantly reduced in these animals relative to controls. Treatment with either intraperitoneal clonidine or diazepam 20 min after administration of metaldehyde reduced the mortality rate and in mice surviving for 5 h, the decrease in brain NA and 5‐HT concentrations were significantly reduced.
Pharmacokinetics of sulphadimidine in normal and febrile dogs
Authors: RIFFAT SUALEHA , NAWAZ MUHAMMAD , REHMAN ZIA‐UR‐
Published: April 2008

Pharmacokinetic parameters which describe the distribution and elimination of sulphadimidine were determined in normal dogs and dogs in which fever was produced by an intravenous injection of escherichia and staphylococcal species of bacteria. Sulphadimidine was injected as a single intravenous bolus at the dose of 100 mg/kg and the kinetics of the drug were described in terms of the bi‐exponential expression: Cp=Ae‐αt+Be‐βt. The distribution half‐times of the drug were 1.52 h in the normal and 0.81 h in the febrile dogs. The drug distribution was significantly more rapid (P < 0.05) in febrile than in normal dogs. Average ± SD values for the half‐lives of the drug were 16.2 ± 5.7 h in normal and 16.7 ± 4.7 h in the febrile dogs. The apparent volume of distribution (V'd(area)) was 628 ± 251 ml/kg in the normal dogs, and was not statistically different from 495 ± 144 ml/kg in the febrile dogs. The volume of the central compartment (V'c) was 445 ± 55 ml/kg in normal dogs and this was significantly higher (P < 0.01) than the V'c of 246 ± 72 ml/kg in the febrile dogs. The body clearance was 22.4 ± 4.8 and 20.2 ± 3.6 ml/hour. kg in the normal and febrile dogs, respectively. The investigation revealed that the dosage regimen of sulphadimidine did not differ significantly between normal and febrile dogs.
Selective blockade of the responses of reticuloruminal muscle to 5‐HT in sheep
Authors: RUCKEBUSCH Y. , OOMS L.
Published: April 2008

The effects of intravenous administration of 5‐HT on the patterns of reticulorumen contractions were studied in conscious sheep. Contractions were measured by strain gauges applied to the external wall of the reticulum and the ventral and/or dorsal sac of the rumen. The responses to 5‐HT comprised (i) a shortlived contraction followed by (ii) a sustained increase in muscle tone and (iii) a concomitant inhibition of the extrinsic reticulo‐rumen contractions. The corresponding blockades produced by (i) atropine, (ii) 5‐HT antagonists and (iii) chemical sympathectomy suggest involvement of a peripheral cholinergic mechanism in the initial contractile response and a central adrenergic mechanism in the reflex inhibition of extrinsic reticulo‐rumen contractions.
Pharmacokinetics of digoxin in cattle
Authors: KORITZ G. D. , ANDERSON K. L. , NEFF‐DAVIS C. A. , WILCKE J. R. , DAVIS L. E.
Published: April 2008

Digoxin was administered as a single intravenous injection of 22 μg/kg to six cattle. The resulting serum concentrations were fitted by both a bi‐ and tri‐exponential equation with the latter providing the best fit to the data of a majority of the animals. The biological half‐life of digoxin in cattle was found to be 7.8 h. This relatively short half‐life in comparison to other animal species dictates that digoxin should be administered more frequently to cattle to provide therapeutic concentrations in serum without broad fluctuations in serum concentrations. Computer simulations of various intravenous dosage regimens suggested that a loading dose of 22 μg/kg followed by an infusion of 0.86 μg/kg/h would offer the greatest safety and efficacy in bovine patients.
Pharmacokinetics of lidocaine and its active metabolites in dogs
Authors: WILCKE J. R. , DAVIS L. E. , NEFF‐DAVIS C. A. , KORITZ G. D.
Published: April 2008

The pharmacokinetics of lidocaine in dogs were investigated following the intravenous and intramuscular administration of single doses of lidocaine hydrochloride. The mean elimination rate constant and the mean specific clearance determined for the intravenous portion of the study were 0.786 h‐1 and 2.40 1/kg/h, respectively. Following intramuscular administration the mean absorption rate constant was 7.74 h‐1. Absorption was nearly complete as the percentage of an intramuscular dose absorbed averaged 91.9%. Concentrations of two N‐deethylated metabolites, determined following the administration of lidocaine suggest that monoethylglycinexylidide is eliminated rapidly while glycinexylidide is more slowly eliminated. The relative contribution of these metabolites to the therapeutic and toxic effects of lidocaine and the potential for glycinexylidide accumulation during lidocaine administration remain to be investigated.
Pharmacokinetics of erythromycin in foals and in adult horses
Authors: PRESCOTT J. F. , HOOVER D. J. , DOHOO I. R.
Published: April 2008

The pharmacokinetic parameters of erythromycin in foals were determined following intravenous administration of 5.0 mg/kg to animals aged 1, 3, 5 and 7 weeks. The distribution of the drug was described by a two‐compartment open model, and no significant differences were observed between coefficients on which the parameters were based. Pharmacokinetic values were also determined for four mares given 5.0 mg/kg intravenously and for six 10–12 week‐old foals given 20.0 mg/kg intravenously. The half‐life of erythromycin for all groups of animals (foals less than 7 weeks, mares, foals 10–12 weeks) was 1.0–1.1 h; the apparent volume of distribution was between 2.3 and 7.2 l/kg, and the clearance of the drug from the body was between 1.9 and 5.0 mg/kg/h. No drug could be detected in the serum following oral administration of 5.0 mg/kg erythromycin estolate; detectable levels were found for 5 h in mares given 12.5 mg/kg, and for 8 h in foals given 20.0 mg/kg orally. Peak levels in foals given the drug orally were 0.42 μg/ml at 120 min after administration. Foals given 10.0 mg/kg of erythromycin base intramuscularly had serum concentrations detectable 12 h later, the peak level achieved was 1.44 μg/ml serum 90 min after administration and concentrations exceeded 0.25 μg/ml for 6 h. In the mares the milk concentrations were approximately twice those in serum. Recommendations were made for drug dosage to be used in the treatment of Corynebacterium equi pneumonia of foals.
A pharmacokinetic study of digoxin in the horse
Authors: BRUMBAUGH GORDON W. , THOMAS WILLIAM P. , ENOS L. REED , KANEKO JIRO J.
Published: April 2008

Digoxin was administered orally and intravenously to seven healthy adult mares and geldings in two separate trials. At a dose of 44 μg digoxin/kg body weight, the oral study was characterized by an absorption phase with a mean (± 1 standard deviation) peak serum digoxin concentration of 2.21 ng/ml (± 0.45) at a mean of 2.29 h (± 1.52) after administration. A second rise in serum digoxin concentration started about 6–8 h after administration and extended to about 20 h after administration. The mean bioavailability (F) was 23.38% (± 5.96).

At a dose of 22 μg digoxin/kg body weight, the intravenous study was characterized by a two‐compartment model with the following mean pharmacokinetic measurements: distribution rate constant (α), 1.391 h‐1 (± 0.1909); zero‐time serum digoxin concentration determined from the distribution phase (A), 21.247 ng/ml (± 5.6614); elimination rate constant (β), 0.0409 h‐1 (± 0.0069); zero‐time serum digoxin concentration determined from the elimination phase (B), 3.82 ng/ml (± 0.433); apparent specific volume of distribution uncorrected for protein binding (Vdβ), 5.003 1/kg (± 0.5177). The mean β corresponded to a biological half‐life (t1/2 ±) of 16.9 h.

Based upon results of this study, theoretically achievable steady‐state serum digoxin concentrations were calculated for maintenance doses given by oral and intravenous routes of administration with appropriate two‐compartment, multiple‐dose formulae. Loading doses were also calculated for each route. It is the opinion of the authors that the oral route of administration of digoxin is effective in the horse and may preclude the potential risks posed by the high serum digoxin concentrations immediately following intravenous administration.
Pharmacokinetics of imidocarb in normal dogs and goats
Authors: ABDULLAH A. SALAM , BAGGOT J. DESMOND
Published: April 2008

The pharmacokinetics of imidocarb were studied in seven mongrel dogs and eight crossbred goats. An intravenous bolus dose (4 mg/kg) of 12% imidocarb dipropionate solution wasinjected into the cephalic vein in dogs and the jugular vein in goats. The plasma concentration of imidocarb was measured by spectro‐photometry. The experimental data were analysed using a two‐compartment open model. The apparent volume of the central compartment was significantly higher (P<0.01) in dogs than in goats. The significantly larger (P<0.05) apparent specific volume of distribution in goats than in dogs may be attributed to passive diffusion followed by ion trapping of the drug in rumen fluid. Neither the half‐life nor body clearance differed significantly between dogs (t1/2, 207 ± 45 min; ClB, 1.47 ± 0.38 ml/min kg) and goats (t1/2, 251 ± 94 min; ClB, 1.62 ± 0.50 ml/min kg). While almost 80% of the dose had been eliminated at 8 h in. both species, the high ratio of the imidocarb level in the peripheral‐to‐central compartment in goats suggests that a prolonged period may be required for complete elimination of the drug.
Thiopentone pharmacokinetics and electrocorticogram pattern in sheep
Authors: TOUTAIN P. L. , BRANDON R. A. , ALVINERIE M. , BAGGOT J. D.
Published: April 2008

Thiopentone pharmacokinetics and electrocorticogram patterns were studied in a group of six sheep given thiopentone intravenously (20 mg/kg). Plasma concentrations were determined using a high‐performance liquid chromatography method. A three‐compartment open model was selected to describe the disposition kinetics of thiopentone. The drug had an apparent volume of distribution of 1005 ± 196 ml/kg; body clearance was 3.5 ± 0.8 ml/minkg and the half‐life, based on the slope of the terminal portion of the curve, was 196 ± 64 min. From the electrocorticogram pattern, it seems likely that the highest concentrations in brain occurred between 47 and 217 sec after commencing administration and a brain penetration half‐time of 26.5 ± 2.87 sec was calculated. At the time of awakening (36.6 ± 6.36 min) 24.1 ± 6.3% of the dose was located in the central compartment, 12.6 ± 8.2 was in the shallow peripheral compartment, 38.8 ± 14.1 was in the deep peripheral compartment and 24.6 ± 10.3 had been eliminated. Using simulated curves, it appeared that suppression of the shallow peripheral compartment (muscle) did not change the time of awakening; in contrast when elimination‐rate constant was decreased, awakening was delayed. It was suggested that the relatively short duration of thiopentone anaesthesia in sheep should be attributed mainly to elimination of the drug by hepatic metabolism and uptake by body fat. This hypothesis, which differs from the widely accepted view that the duration of thiopentone anaesthesia is independent of the rate of hepatic metabolism, is discussed in terms of differences in regional blood flow between sheep and monogastric species.
Population distributions of phenylbutazone and oxyphenbutazone after oral and i.v. dosing in horses
Authors: CHAY S. , WOODS W. E. , NUGENT T. E. , WECKMAN T. , HOUSTON T. , SPRINKLE F. , BLAKE J. W. , TOBIN T. , SOMA L. R. , YOCUM J. , SMITH J. D.
Published: April 2008

Experiments to determine the residual plasma concentrations of phenylbutazone and its metabolites found in horses racing on a ‘no‐race day medication’ or 24‐h rule were carried out. One dosing schedule (oral‐i.v.) consisted of 8.8 mg/kg (4g/1000 lbs) orally for 3 days, followed by 4.4 mg/kg (2g/1000 lbs) intravenously on day 4. A second schedule consisted of 4.4 mg/kg i.v. for 4 days. The experiments were carried out in Thoroughbred and Standardbred horses at pasture, half‐bred horses at pasture, and in Thoroughbred horses in training.

After administering the i.v. schedule for 4 days to Thoroughbred and Standard‐bred horses at pasture, the mean plasma concentrations of phenylbutazone increased from 0.77 μg/ml on day 2 to 2.5 μg/ml on day 5. The shape of the frequency distribution of these populations was log‐normal. These data are consistent with one horse in 1,000 yielding a plasma level of 8.07 μg/ml on day 5.

After administration of the oral‐i.v. schedule to Thoroughbred and Standard‐bred horses at pasture, the mean plasma concentrations of phenylbutazone were 3.4 μg/ml on day 2 and 3.5μg/ml on day 5. The range on day 5 was from 1.4 to 8.98 μg/ml and the frequency distribution was log‐normal. These data are consistent with one horse in 1000 having a plasma level of 15.8 μg/ml on day 5.

In a final experiment, the oral dosing schedule was administered to 62 Thoroughbred horses in training. Plasma concentrations on day 5 in these horses averaged 5.3 μg/ml. The range was from 1.3 to 13.6 μg/ml and the frequency distribution was log‐normal. Statistical projection of these values suggests that following this oral dosing schedule in racing horses about one horse in 1000 will yield a plasma level of 23.5 μg/ml of phenylbutazone 24h after the last dose.
Effect of probenecid on the pharmacokinetics of cefotaxime in sheep
Authors: GUERRINI V. H. , FILIPPIGH L. J. , ENGLISH P. B. , CAO G. R. , BOURNE D. W. A.
Published: April 2008

Guerrini, V.H., Filippich, L.J., English, P.B., Cao, G.R. &: Bourne, D.W.A. Effect of probenecid on the pharmacokinetics of cefotaxime in sheep. J. vet. Pharmacol. Therap. 8, 38–46.

The effect of probenecid given by intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) injection on the pharmacokinetics of cefotaxime was studied in six Merino ewes. When given intravenously, probenecid increased significantly (P < 0.05) the plasma half‐life of cefotaxime three‐fold (to 0.94 ± 0.32 h) and the area under the curve (AUG) approximately two‐fold (to 41.1 ± 16.8 μg.h/ml), and decreased plasma cefotaxime clearance (ClB) 45% (to 0.648 ± 0.191 1/h/kg). When given with probenecid intravenously, renal clearance (ClR), volume of the central compartment (VC), volume of distribution steady slate (Vd(ss)). and the amount excreted in urine unchanged did not alter significantly.

When given by i.m. injection, probenecid and cefotaxime were well tolerated and cefotaxime was well absorbed (101 ± 45%). When given by s.c. injection, only 40 ± 25% cefotaxime was absorbed. When given intramuscularly or subcutaneously, probenecid appeared to reduce the ClB and ClR of cefotaxime, probably because plasma probenecid concentrations are prolonged. Probenecid did not appear to affect the distribution of cefotaxime.

Dr D.W.A. Bourne, Department of Pharmacy, University of Queensland, St Lucia, QLD 4067, Australia.
Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison
Authors: SCHWARTZ‐PORSCHE DOROTHEA , LÖSCHER W. , FREY H.‐H.
Published: April 2008

Schwartz‐Porsche, D., Löscher, W. & Frey, H.‐H. Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison. J. vet. Pliannacol. Therap. 8, 113–119.

The efficacy of phenobarbital and primidone against canine epilepsy was compared in a controlled study. Thirty‐five dogs showing generalized tonic‐clonic seizures (grand mal), treated for a minimum of 6 months, were included in the study; fifteen of these were treated with phenobarbital, the other twenty with primidone. Both drugs were dosed according to the clinical requirement; the daily doses ranged from 5‐17mg/kg phenobarbital and from 17‐70mg/kg primidone. The plasma concentrations of phenobarbital, or of primidone and its metabolites phenobarbital and phenylethylmalondiamide (PEMA), were routinely monitored. Complete control of tonic‐clonic seizures for 6 months, at least, was attained in six out of fifteen dogs of the phenobarbital group, and in five out of twenty dogs in the primidone group. A further six dogs on phenobarbital, and seven dogs on primidone, were classified as ‘improved’, i.e. the rate of seizures was reduced by at least 50%. The rest of the dogs were not improved by the treatment. The difference between the efficacy of phenobarbital and primidone was not significant, but primidone gave rise to signs of liver toxicity in fourteen out of twenty dogs, as indicated by considerable elevations of liver enzyme values (alanine transferase, glutamate dehydrogenase, alkaline phosphatase). Phenobarbital is, therefore, regarded as the drug of first choice for the treatment of canine epilepsy.

Dr H.‐H. Frey, Laboratory of Pharmacology and Toxicology, School of Veterinary Medicine, Free University of Berlin, Koserstrafie 20, D‐1000 Berlin‐West 33, Germany.
Cefadroxil in the horse: pharmacokinetics and in vitro antibacterial activity
Authors: WILSON W. DAVID , BAGGOT J. DESMOND , ADAMSON PETER J. W. , HIRSH DWIGHT C. , HIETALA SHARON K.
Published: April 2008

Wilson, W.D., Baggot, J.D., Adamson, P.J.W., Hirsh, D.C. & Hietala, S.K. Cefadroxil in the horse: pharmacokinetics and in vitro antibacterial activity. J. vet. Pharmacol. Therap. 8, 246–253.

Sodium cefadroxil was administered as a single intravenous dose (25 mg/kg) to six healthy adult mares. Plasma samples were collected over a 24‐h period and cefadroxil concentrations were measured by microbiological assay. The pharmacokinetic behavior of the drug was appropriately described in terms of a one‐compartment open model. Values for the major pharmacokinetic terms were: extrapolated initial plasma concentration = 59.2 ± 15.0 μg/ml; half‐life = 46 ± 20 min; apparent volume of distribution = 462 ± 191 ml/kg; and body clearance = 7.0 ± 0.6 ml/min.kg. In a subsequent study, a suspension of cefadroxil monohydrate was administered intragastrically (25 mg/kg) to the same six horses. Plasma concentrations of the drug peaked at 1–2 h but, in general, absorption was both poor and inconsistent. The data were unsuitable for determination of cefadroxil bioavailability from this oral dosage form.

Ninety‐nine isolates of eleven bacterial species obtained from clinically ill horses were tested for susceptibility to cefadroxil. All strains of Streptococcus equi, Streptococcus zooepidemicus, coagulase‐positive staphylococci, Corynebciclerium pseudotuberculosis and five out of six strains of Actinobacillus suis were highly susceptible to the drug (MIC<4 μg/ml). Escherichia coli, Klebsiella pneumoniae and Salmonella sp. showed intermediate susceptibility (MIC 4–16 μg/ml), while all isolates of Corynebacteriuin (Rhodococcus) equi, Enterobacter cloacae and Pseudomonas aeruginosa proved to be highly resistant to cefadroxil (MIC > 128 μg/ml).

Dr W. Dcvid Wilson, Department of Medicine, School of Veterinary Medicine, Universily of California, Davis, CA 95616, U.S.A.
Some dynamic and toxic effects of theophylline in horses
Authors: ERRECALDE J. O. , BUTTON C. , MÜLDERS M. S. G.
Published: April 2008

Errecalde, J.O., Button, C. & Mülders, M.S.G, Some dynamic and toxic effects of theophylline in horses. J. vet. Plmrmacol. Therap. 8, 320–327.

A single intravenous administration of theophylline as aminophylline at 10 mg/kg to four mares induced a diuresis in which maximal urine production was more than seven times the control volume. The diuretic effect was maximal within the first hour post‐administration, and lasted approximately 6 h. Theophylline resulted in dose‐related tachycardia, polypnoea and nervous symptoms (tactile, visual and auditory hypersensitivity, muscle tremor, sweating) in normal mares, but had only minor effects on arterial and central venous blood pressures, intrapleural pressure, red blood cell variables and plasma proteins. The upper limit of safe plasma theophylline concentration in horses is approximately 15 μg/ml. Whenever feasible, the oral or intragastric route of administration should be used as it is safer than the intravenous route.

Dr C. Button, Regional Veterinary Laboratory, PO Box 388, Benalla, Victoria 3672, Australia.
Dermal reactivity to histamine, serotonin and bradykinin in relation to allergic skin reactions of the horse
Authors: MORROW ALEX , QUINN PATRICK J. , BAKER KENNETH P.
Published: April 2008

The reactivity of horse skin to intradermal inoculation of histamine, serotonin and bradykinin was investigated, and the resulting reactions compared with those produced in the same horses by a 1% whole‐body extract of Cnliroides. Both histamine and bradykinin produced large reactions, but there was no significant correlation between the dermal responsiveness to insect allergen and either histamine or bradykinin. Two anti‐hislamine drugs (promethazine hydrochloride and tripelennaniine hydrochloride) were effective in reducing the reaction produced by the insect extract.
Phenylbutazone and oxyphenbutazone distribution into tissue fluids in the horse
Authors: LEES P. , TAYLOR J. B. O. , HIGGINS A.J. , SHARMA S. C.
Published: April 2008

The clinically recommended dose rate of phenylbutazone (4.4 mg/kg) was administered intravenously as a single dose to five Welsh Mountain ponies. Distribution of phenylbutazone and its active metabolite oxyphenbutazone into body fluids was studied by measuring concentrations in plasma, tissue‐cage fluid, peritoneal fluid and acute inflammatory exudate harvested from a polyester sponge model of inflammation. The ready penetration of phenylbutazone into inflammatory exudate was demonstrated by the relatively high mean value for Cmax of 12.4 μg/ml occurring at a time of 4.6 h and a mean AUQ)_24 of 128 μg‐h/ml. A high mean exudate: plasma AUCo_24 ratio of 0.83 was recorded. Plasma: exudate concentration ratios for phenylbutazone were initially greater than and subsequently less than one; the slower clearance from exudate was indicated by approximate t½β values of 4.8 and 24 h for plasma and exudate, respectively. These findings may help to explain the relatively long duration of action of phenylbutazone, in spite of a plasma elimination half‐life of less than 5 h. Lower values of Cmax and AUC0–24 for phenylbutazone passage into peritoneal fluid (6.3 μg/ml and 45 (μh/ml) were recorded, and a limited number of sampling times indicated a similar degree of penetration as into tissue cage fluid. Mean concentrations of oxyphenbutazone in all fluids were lower than phenylbutazone concentrations at all times, but ready penetration of the metabolite into body fluids, especially into inflammatory exudate, occurred suggesting that oxyphenbutazone may contribute to the anti‐inflammatory effect. The hyperaemia of acute inflammation and the high protein levels in inflammatory exudate may both assist passage of phenylbutazone and oxyphenbutazone into exudate. The slower clearance of both compounds from exudate, periton̆ceal fluid and tissue cage fluid than from plasma is similar to previous reports for other drugs.