bluuebunny/crossref_metadata_2025 huggingface dataset:
Clavus detected incidentally by positron emission tomography with computed tomography
Authors: DAINICHI Teruki , HONMA Yutaka , HASHIMOTO Takashi , FURUE Masutaka
Published: April 2008

This is the first report showing that positron emission tomography with computed tomography (PET/CT) can detect clavus. A 37‐year‐old woman diagnosed with epithelioid sarcoma on her left inguinal region was investigated by whole‐body PET/CT. The imaging showed some 18F‐fluorodeoxyglucose uptake at the right lateral foot. There had been a clavus in exactly the same region. Every dermatologist, radiologist and oncologist needs to know about this finding for making an accurate diagnosis.
Overexpression of snakin‐1 gene enhances resistance to Rhizoctonia solani and Erwinia carotovora in transgenic potato plants
Authors: ALMASIA NATALIA I. , BAZZINI ARIEL A. , HOPP H. ESTEBAN , VAZQUEZ‐ROVERE CECILIA
Published: April 2008

Snakin‐1 (SN1), a cysteine‐rich peptide with broad‐spectrum antimicrobial activity in vitro, was evaluated for its ability to confer resistance to pathogens in transgenic potatoes. Genetic variants of this gene were cloned from wild and cultivated Solanum species. Nucleotide sequences revealed highly evolutionary conservation with 91–98% identity values. Potato plants (S. tuberosum subsp. tuberosum cv. Kennebec) were transformed via Agrobacterium tumefaciens with a construct encoding the S. chacoense SN1 gene under the regulation of the ubiquitous CaMV 35S promoter. Transgenic lines were molecularly characterized and challenged with either Rhizoctonia solani or Erwinia carotovora to analyse whether constitutive in vivo overexpression of the SN1 gene may lead to disease resistance. Only transgenic lines that accumulated high levels of SN1 mRNA exhibited significant symptom reductions of R. solani infection such as stem cankers and damping‐off. Furthermore, these overexpressing lines showed significantly higher survival rates throughout the fungal resistance bioassays. In addition, the same lines showed significant protection against E. carotovora measured as: a reduction of lesion areas (from 46.5 to 88.1% with respect to the wild‐type), number of fallen leaves and thickened or necrotic stems. Enhanced resistance to these two important potato pathogens suggests in vivo antifungal and antibacterial activity of SN1 and thus its possible biotechnological application.
EMBRYO YELLOW gene, encoding a subunit of the conserved oligomeric Golgi complex, is required for appropriate cell expansion and meristem organization in Arabidopsis thaliana
Authors: Ishikawa Takaaki , Machida Chiyoko , Yoshioka Yasushi , Ueda Takashi , Nakano Akihiko , Machida Yasunori
Published: April 2008

We identified an embryo yellow (eye) mutation in Arabidopsis that leads to the abnormal coloration and morphology of embryos. The eye mutant formed bushy plants, with aberrant organization of the shoot apical meristem (SAM) and unexpanded leaves with irregular phyllotaxy. The epidermal cells of the eye mutant were much smaller than that of the wild‐type. Thus, EYE is required for expansion of cells and organs, and for formation of the organized SAM. Hydrophobic layers of epidermal cells were also disrupted, suggesting that EYE might be involved in the generation of the extra‐cellular matrix. The mutated gene encoded a protein that is homologous to Cog7, a subunit of the conserved oligomeric Golgi (COG) complex, which is required for the normal morphology and function of the Golgi appratus. The eye mutation caused mislocalization of a Golgi protein. In addition, the size of the Golgi apparatus was also altered. Thus, EYE might be involved in transport or retention of Golgi‐localized proteins and in maintenance of Golgi morphology. We propose that some Golgi‐localized proteins, distributions of which are controlled by EYE, play important roles in expansion of cells and organs, and in formation of the properly organized SAM in plants.
Expression of inhibitors of apoptosis family protein in 7,12‐dimethylbenz[a]anthracene‐induced hamster buccal‐pouch squamous‐cell carcinogenesis is associated with mutant p53 accumulation and epigenetic changes
Authors: Hsue Shui‐Sang , Wang Wen‐Chen , Chen Yuk‐Kwan , Lin Li‐Min
Published: April 2008

Fifty outbred Syrian golden hamsters were equally divided into three experimental groups and two control groups. The pouches of the experimental groups were painted bilaterally with a 0.5% 7,12‐dimethylbenz[a]anthracene (DMBA) solution thrice a week for 3, 7 and 14 weeks. One of the control groups was applied with mineral oil while another control group remained untreated throughout the experiment. Neither survivin nor cIAP2 could be detected in any of the control tissues, whereas survivin and cIAP2 were found to be significantly increased in 3‐, 7‐ and 14‐week DMBA‐treated pouches compared with the control pouches. Expression of XIAP, cIAP1 and NAIP were noted for both the control and 3‐, 7‐ and 14‐week DMBA‐treated pouches, but levels were found to be significantly elevated in the experimental groups compared with the control pouches. p53 was not detected in any control tissues, but was significantly increased in 3‐, 7‐ and 14‐week DMBA‐treated pouches. Direct sequencing revealed a point mutation (C→G) of p53 for pouch tissues treated with DMBA for 3 and 7 weeks, and there was a wide variation in the p53 sequence of the 14‐week DMBA‐treated pouch tissues, as compared with the control tissues. The control tissues had a survivin‐ and cIAP2‐methylated allele, whereas the DMBA‐treated tissues showed no evidence of survivin‐ and cIAP2‐methylation. Neither the control nor DMBA‐treated pouches showed evidence of XIAP‐, cIAP1‐ or NAIP‐methylation. Our results suggest that the expression of inhibitors of apoptosis family in DMBA‐induced hamster buccal‐pouch squamous‐cell carcinogenesis may be modulated by both genetic (mutant p53) and epigenetic mechanisms.
Endocannabinoids: Some Like it Fat (and Sweet Too)
Authors: Matias I. , Cristino L. , Di Marzo V.
Published: April 2008

There is growing interest in the commercialisation of the CB1 receptor antagonist Rimonabant in Europe for the treatment of obesity and the metabolic syndrome. Clinical trials have shown that CB1 receptor blockers are able to reduce not only food intake but also abdominal adiposity and its metabolic sequelae. Accordingly, CB1 receptors, and tissue concentrations of endocannabinoids sufficient to activate them, are present in all brain and peripheral organs involved in the control of energy balance, including the hypothalamus, nucleus accumbens, pancreas, adipose tissue, skeletal muscle and liver. At the central level, the endocannabinoid system seems to play a dual role in the regulation of food intake by hedonic and homeostatic energy regulation. At the peripheral level, the endocannabinoid system seems to behave as a system that reduces energy expenditure and directs energy balance towards energy storage into fat. The emerging role of the endocannabinoid system in energy balance at both central and peripheral levels will be discussed in this review.
The Role of the Endocannabinoid System in Atherosclerosis
Authors: Mach F. , Steffens S.
Published: April 2008

Our current understanding of the pathophysiology of atherosclerosis suggests a prominent role for immune responses from its initiation through its complications. Given the increasing prevalence of cardiovascular risk factors worldwide, there is an urgent need to better understand the underlying mechanisms to improve current treatment protocols. A growing body of evidence suggests that endocannabinoid signalling plays a critical role in the pathogenesis of atherogenesis and its clinical manifestations. Blocking CB1 receptors has been shown to mediate not only weight reduction, but also several cardiometabolic effects in rodents and humans, indicating a potential relevance for the process of atherosclerosis. Activation of CB2 receptors with Δ9‐tetrahydrocannabinol (THC) has been shown to inhibit atherosclerotic plaque progression in mice, mainly by inhibiting macrophage recruitment. Endocannabinoids released from endothelial cells, macrophages or platelets, reduce hypertension in rodents, a major risk factor for atherosclerosis. In addition, anandamide inhibits inflammatory gene expression in endothelial cells, and consequently monocyte adhesion. Conversely, endocannabinoids might also mediate pro‐atherosclerotic effects by inducing platelet activation. In conclusion, the precise role of the endocannabinoid system during atherosclerosis is not yet understood. Whether increased endocannabinoid signalling is associated with disease progression and increased risk of acute thrombotic events remains to be determined.
The Endocannabinoid System and the Control of Glucose Homeostasis
Authors: Nogueiras R. , Rohner‐Jeanrenaud F. , Woods S. C. , Tschöp M. H.
Published: April 2008

Blockade of the CB1 receptor is one of the promising strategies for the treatment of obesity. The first selective CB1 receptor antagonist, rimonabant, which has already successfully completed phase III clinical trials, led to sustained weight loss and a reduction in waist circumference. Patients treated with rimonabant also demonstrated statistically significant improvement in high‐density lipoprotein cholesterol levels, triglyceride levels and insulin resistance, as well as a reduced overall prevalence of metabolic syndrome. Currently, one of the most discussed aspects of endocannabinoid system function is to what extent the endocannabinoid system might affect metabolism independently of its control over body weight and food intake. Specifically, a food‐intake‐ and body‐weight‐independent role in the regulation of glucose homeostasis and insulin sensitivity could have major impact on the potential of drug candidates targeting the endocannabinoid system for the prevention and treatment of metabolic syndrome. This review summarises the effects of the endocannabinoid system on glucose homeostasis and insulin sensitivity.
Some aspects of clinical pharmacokinetics in veterinary medicine. I
Authors: BAGGOT J. DESMOND
Published: April 2008

This series of two review articles deals with general aspects of the mechanisms which govern absorption and distribution of drugs within the body, and the kinetics of drug metabolism and excretion. Emphasis is given to the verification of pharmacokinetic principles in domestic animals, and the clinical applications which proceed therefrom. In the first part, the concept of the two compartment and three compartment models for drug disposition are introduced and developed to demonstrate the mathematical models which may be derived to describe the kinetics of drug distribution and elimination. In the second part bioavailability and drug dosage will be considered.
Residues of azaperone and azaperol in slaughter pigs
Authors: RAUWS A. G. , OLLING M.
Published: April 2008

An investigation was carried out to determine the residues of azaperone in slaughter pigs and pig meat products. The butyrophenone tranquillizer azaperone is frequently administered to pigs by intramuscular injection in order to reduce mortality and loss of meat quality resulting from transportation from the farm to the slaughter house. In the pig, following administration of azaperone as recommended by the manufacturer (0.4 mg/kg i.m.) residue concentrations of about 0.05 μg/g azaperone, and 0.20 μg/g azaperol (the main biotransformation product in the pig) were found in the kidneys; the kidneys proving to be the sampling organs of choice. Pasteurization and other technological procedures did not influence residues measurably. Toxicological evaluation suggests that the residues found do not per se constitute a danger to public health. None the less, the presence of any drug residue in meat or meat products is undesirable, and alternative, non‐pharmacological approaches to the problems arising from transportation prior to slaughter should be considered.
The non‐absorption of chloramphenicol after oral administration in adult ruminants: a tentative explanation from in vitro studies
Authors: CORTE‐BAETEN K. DE , DEBACKERE M.
Published: April 2008

The biotransformation of chloramphenicol in the ruminant forestomachs was studied by incubating the antibiotic with ovine rumen contents in vitro. Differential centrifugation of rumen contents showed that rapid reduction of the aromatic nitro group of chloramphenicol to an arylamine occurred in those fractions containing ciliates, and this activity was not inhibited by penicillin or streptomycin. It is concluded that in adult ruminants, chloramphenicol is metabolised by rumen microfauna more rapidly than it is absorbed, when administered orally.
Comparative study of chloramphenicol absorption in calves after oral, intra‐ruminal and intra‐abomasal administration
Authors: BACKER P. DE , DEBACKERE M.
Published: April 2008

The mechanisms responsible for the rapid decline of chloramphenicol plasma levels after oral administration in young calves during their first weeks of life were investigated. Chloramphenicol was administered by stomach tube, to four 2 week old calves on three consecutive days at a dose of 50 mg/kg. The plasma levels increased daily to a peak value on the third day. The minimum therapeutic concentration of 5 μg/ml, however, was barely obtained. Simultaneous estimation of the ruminal contents showed a parallel increase in chloramphenicol concentration. Thus it can be assumed that there is an inefficient absorption of chloramphenicol from the forestomachs of young calves. Chloramphenicol was not metabolized by the ruminal contents until the calves were 9 weeks old. Finally chloramphenicol was administered to 7 week old calves by the intra‐abomasal route, intraruminal route and by mouth. Only with the intra‐abomasal method could a therapeutically effective level be reached. This indicates that the rapid decline of chloramphenicol plasma levels in calves during their first weeks of life could be attributed to the delayed reticulo‐rumen emptying and to inefficient absorption from the forestomachs.
Effect of the injection site on the bioavailability of amoxycillin trihydrate in dairy cows
Authors: RUTGERS L. J. E. , VAN MIERT A. S. J. P. A. M. , NOUWS J. F. M. , VAN GINNEKEN C. A. M.
Published: April 2008

The pharmacokinetic behaviour of amoxycillin sodium and amoxycillin trihydrate‐20% aqueous suspension was studied in a group of five dairy cows. Amoxycillin sodium was administered intravenously and amoxycillin trihydrate‐20% by four different routes of administration: subcutaneously in the dewlap, intramuscularly in the lateral neck, M. triceps, and buttock (M. semitendineus). The dose level for both drug formulations was 3.83 ± 0.47 mg/kg.

The mean plasma concentration–time curve(Cp)for intravenous amoxycillin sodium administration could be described mathematically by the biexponential equation Cp= 15.6 e‐0.033t+ 1.04 e‐0.0091t. The areas under the plasma concentration–time curve (AUC's) obtained after the intravenous injections of sodium amoxycillin were used as references for the bioavailability studies of the four routes of amoxycillin trihydrate administration.

Intramuscular injections into the lateral neck or into the M. triceps resulted in similar systemic bioavailabilities, being at 12 h post injection (p.i.) 76.2 and 79.2% of the administered dose. The biological half‐lives (t1/2) were similar, being 6.2 and 6.9 h, respectively. After subcutaneous injection into the dewlap or intramuscular injection into the buttock lower bioavailabilities at 12 h p.i. were observed (24.1 and 49.2%, respectively). The plasma amoxycillin concentration was persistently low. The half‐lives of plasma amoxycillin disposition after the buttock and dewlap injections were 13.2 and 44 h, respectively.

The plasma concentrations obtained were compared with minimal inhibitory concentrations (MIC) against pathogenic bacteria with respect to the theoretical design of effective antibacterial therapy. The differences observed serve to emphasize the fact that more attention should be paid to the effect of the route of administration on the biological bioavailability of a drug, with particular reference to studies on clinical efficacy. Pre‐slaughter withdrawal times were suggested for the different routes of injection of these two drug formations.
Hyperglycaemic effect of xylazine
Authors: FELDBERG W. , SYMONDS H. W.
Published: April 2008

In cats, xylazine, an analogue of clonidine, produced hyperglycaemia when injected intravenously. The effect was obtained in unanaesthetized cats and in pentobarbitone sodium anaesthesia. The hyperglycaemia was not a central effect, nor due to adrenaline release from the adrenals, nor to a direct action of xylazine on the liver. It resulted from a fall in plasma insulin produced by an action of xylazine on the pancreas, inhibiting insulin secretion without affecting glucagon secretion. The increase in the glucagon/insulin ratio, by stimulating glucose production in the liver, was probably responsible for the xylazine‐induced hyperglycaemia.
Serum chloramphenicol concentrations in preruminant calves: a comparison of two formulations dosed orally
Authors: HUFFMAN E. M. , CLARK C. H. , OLSON J. D. , BALL L.
Published: April 2008

Serum concentrations of chloramphenicol were determined after oral doses (55 mg/kg body weight) were administered to 7–9 day old Holstein‐Friesian calves. Chloramphenicol in an oral solution produced greater serum concentrations than did an equivalent dose of chloramphenicol in capsules (P<0.005). A second dose of each formulation administered 12 h after the first dose elevated serum chloramphenicol concentrations significantly (P<0.001). The average serum chloramphenicol concentration exceeded 5 μg/ml of serum 1 h after administration of the solution compared with 4 h for the capsules. Average serum chloramphenicol concentration was greater than 5 μg/ml for at least 12 h after the dose was administered for both formulations. Of the eight calves receiving repeat doses of chloramphenicol, seven (87.5%) developed diarrhea in 76 ± 8.6 h. Six of the eight calves (75%) died during or shortly after the period of chloramphenicol administration.
The efficacy of berenil (diminazene aceturate) against Trypanosoma evansi infection in mice
Authors: ELAMIN E. A. , HOMEIDA A. M. , ADAM S. E. I. , MAHMOUD M.M.
Published: April 2008

The efficacy of berenil (diminazene aceturate) was studied in experimental Trypanosoma evansi infection in albino mice. The criteria used for the assessment of the anti‐trypanosomal effect of berenil included the examination of the blood and tissues for T. evansi and the clinical, pathological and enzyme histochemical changes seen in the lungs, heart, liver, kidney and spleen at intervals after treatment. Single doses of 10 and 20 mg/kg of berenil given intraperitoneally or intramuscularly to infected mice produced a complete elimination of the protozoon and caused a slow tissue recovery mirrored in the persistence of lesions in different organs. Single doses of 3.5 mg/kg of berenil were less effective and none of the three dose levels of the drug used induced toxic effects in albino mice.
The pharmacokinetics, pharmacological responses and behavioral effects of acepromazine in the horse
Authors: BALLARD S. , SHULTS T. , KOWNACKI A. A. , BLAKE J. W. , TOBIN T.
Published: April 2008

After intravenous (i.v.) injection, acepromazine was distributed widely in the horse (Vd= 6.6 litres/kg) and bound extensively (>99%) to plasma proteins. Plasma levels of the drug declined with an α phase half‐life of 4.2 min, while the β phase or elimination half‐life was 184.8 min. At a dosage level of 0.3 mg/kg acepromazine was detectable in the plasma for 8 h post dosing. The whole blood partitioning of acepromazine was 46% in the plasma phase and 54% in the erythrocyte phase.

Penile prolapse was clearly evident at doses from 0.01 mg/kg to 0.4 mg/kg i.v., and the duration and extent of protrusion were dose related. Hematocrit levels were significantly lowered by administration of 0.002 mg/kg i.v. (about 1 mg to a 500 kg horse) and increasing dosages resulted in greater than 20% lowering of the hematocrit from control levels. Pretreatment of horses with acepromazine also reduced the variable interval (VI 60) responding rate in all horses tested.

These data show that hematocrit changes are the most sensitive pharmacological responses to acepromazine, followed by changes in penile extension, respiratory rate, VI responding and locomotor responses. Acepromazine is difficult to detect in plasma at normal clinical doses. However, because of its large volume of distribution, its urinary elimination is likely prolonged, and further work on its elimination in equine urine is required.
Comparative efficacy of santonin and piperazine against Neoascaris vitulorum in buffalo calves
Authors: AKHTAR M. S. , CHATTHA M. I. , CHAUDHRY A. H.
Published: April 2008

An investigation was undertaken to evaluate the comparative efficacy of single dose treatment with santonin and piperazine against naturally acquired Neoascaris vitulorum in sixty‐two buffalo calves of 20–60 days of age. Santonin was administered orally in doses of 5 mg, 10 mg and 15 mg/kg body weight to thirteen, eighteen, and sixteen buffalo calves, respectively. As a control, piperazine (88 mg/kg) was given by drench to a group of fifteen infected buffalo calves. Pretreatment and post treatment faecal eggs per gram (EPG) counts were determined by the Stoll's technique. The percentage reductions in EPG counts on the third and seventh days after administration of the two drugs were calculated. The percentage reduction in EPG counts in the piperazine treated group on the third day was 82 ± 15, 90.2 ± 3 and 91.3 ± 2.3% while on the seventh day these values were 88 ± 16, 97 ± 3, and 98 ± 2% in high, moderate and heavy infection calves, respectively. Treatment with santonin at 5, 10 and 15 mg/kg body weight also reduced the EPG counts. The percentage reduction in EPG counts in the calves treated with 15 mg/kg of santonin on the third day was 92.3 ± 18, 95.8 ± 7 and 93.5 ± 4% while on the seventh day these values were 100 ± 0, 100 ± 0 and 99.7 ± 2% in high, moderate and heavily infected calves, respectively. Both piperazine and santonin were associated with some side effects like diarrhoea, restlessness, etc. but their percentage incidence was not significantly different from each other. These findings suggest that santonin in a 15 mg/kg dose has an efficacy similar to piperazine given at the 88 mg/kg dose level for the treatment of ascariasis in buffalo calves.
Influence of dopamine on rumino‐reticular motility and rumination in sheep
Authors: BUÉNO L. , SORRAING J. M. , FIORAMONTI J.
Published: April 2008

The effects of intracerebroventricular (i.c.v.) and intravenous (i.v.) administration of dopamine and its antagonists (domperidone and metoclopramide) on forestomach motility were investigated in four sheep fitted with Nichrome electrodes and strain gauges implanted on the reticulum and the caudo‐dorsal sac of the rumen.

Infused by the i.c.v. route at a rate of 2 μg·kg‐1·min‐1, dopamine inhibited the phasic contractions of the reticulo‐rumen. A similar effect was obtained following i.v. administration of doses which were 10 times higher, but the effect was associated with an increased tone of the rumen wall. Prior i.v. administration of domperidone (0.5 μg·kg‐1) blocked these effects and a selective blockade of the dopamine‐induced inhibition of phasic contractions was obtained with higher dose of domperidone (2.5 μg·kg‐1) administered centrally.

When dopamine was infused alone ventricularly or intravenously after metoclopramide (40 μg·kg‐1), it induced a transient (6–8 min) period of rumination, which could be blocked by a prior i.c.v. administration of tolazoline.

It was concluded that dopamine acts on rumino‐reticular motility in sheep through specific dopamine receptors (i) centrally by inhibiting the frequency of reticular contraction and (ii) peripherally by increasing the muscular tone of the rumen, and its effects on rumination involved α2 adrenergic receptors located in the central nervous system.
Influence of acepromazine maleate on the equine haematocrit
Authors: PARRY B. W. , ANDERSON G. A.
Published: April 2008

The effect of acepromazine maleate (ACP) on the equine venous haematocrit and total plasma protein concentration was studied in six clinically normal horses. Total plasma protein concentration was not appreciably influenced by ACP. However, the haematocrit decreased with the duration, but not the degree, of the decrease being dose‐related. Mean haematocrit values returned to control levels by 12 h after 0.05 mg ACP/kg body weight and 21 h after 0.15 mg ACP/kg body weight.
Pharmacokinetics of phenytoin (diphenylhydantoin) in horses
Authors: KOWALCZYK DAVID F. , BEECH JILL
Published: April 2008

The pharmacokinetics of the anti‐convulsant phenytoin were investigated in clinically healthy horses after oral (p.o.) and intravenous (i.v.) administration. A single dose of phenytoin (8.8 mg/kg body weight) was given i.v. as a bolus to nine horses and one horse received 13.2 mg/kg. A two‐compartment open model was used to describe the disposition of phenytoin. Four of the horses that received an i.v. dose (three at 8.8 mg/kg and one at 13.2 mg/kg) were then given the same dose 3 days later by the oral route. Phenytoin achieved a peak concentration in serum within 1–4 h after p.o. administration and was poorly absorbed with a bioavailability of 34.5 ± 8.6%. Oral dosage regimens were calculated on the basis of a dosing interval of 8 h to provide average serum steady‐state concentrations of 5 and 10 μg/ml for phenytoin.
The effect of polyethylene glycol‐200 on metabolic acidosis induced by chloralose anaesthesia
Authors: SHUKLA RAJNI , SHUKLA S. B.
Published: April 2008

Chloralose may be used in a 10% solution as an anaesthetic in dogs. The solubility of chloralose was found to be much higher in polyethylene glycol‐200 (PEG‐200) than in either warm (body temperature) or cold saline (0.9% NaCl). The intravenous (i.v.) administration of chloralose in warm saline solution induced acidosis as a result of the increase in the level of metabolic acids. The acidity generated by chloralose in almost neutral saline was probably the result of increase in the base deficit in the animal. The infusion of PEG‐200 (almost neutral) significantly reduced the base deficit without disturbing the PaO2 or PaCO2 in the arterial blood. The base deficit value was significantly lower after administration of chloralose solution in PEG‐200 (almost neutral) than after administration in saline. The use of PEG‐200 as a solvent for chloralose was advantageous in two ways. Firstly, it prevented the production of acids in anaesthetic solution and neutralized the blood metabolic acids generated by chloralose administration in saline. Secondly, the solubility of chloralose (10% w/v solution) in PEG‐200 was very much higher than in warm or cold saline.
Effect of age on the acetylation and deacetylation reactions of sulphadimidine and N4‐ acetylsulphadimidine in calves
Authors: NOUWS J. F. M. , VREE T. B. , BAAKMAN M. , TIJHUIS M.
Published: April 2008

Following intravenous (i.v.) or intramuscular (i.m.) adminstration of sulphadimidine (SDM), the pharmacokinetics of SDM and N4‐acetylsulphadimidine (N4‐SDM) were studied in plasma of calves from the first day of life to the age of about 6 months. An obvious age dependency was observed for the elimination half‐life (t1/2) of SDM: the first day of life the t1/2 ranged between 13.5 and 17 h, and decreased in approximately 3 weeks to 4–6 h and remained constant from this time. The metabolite N4‐SDM, as a percentage of the total concentration of the sulphonamide measured in plasma of neonatal calves, ranged between 21.6 and 25.5% at the first day of life, declined in 3 weeks to approximately 12.8%, and at 5 till 9 weeks the final percentage was about 6.8%. Following administration of N4‐SDM, the elimination half‐life of N4‐SDM was 3 h in an 8‐day‐old calf declined to 1.4–1.7 h in 4‐week‐old calves, and was 0.9 h in calves older than 11 weeks. The percentage of SDM (a metabolite of N4‐SDM) in plasma increased with time after injection from 5.5 to 62.8% of the total sulphonamide plasma concentration. This value was age‐related. The total body clearance of N4‐SDM was three‐ to five‐fold higher than that of SDM.
Concentrations of methicillin in blood, normal milk and mastitic milk of cows after intramuscular injection of methicillin and tamethicillin
Authors: ZIV G. , SOBACK S. , BOR A.
Published: April 2008

Tamethicillin (TAM) is a basic ester pro‐drug of methicillin (MET) which is converted in the body by non‐specific esterases to MET. Equal doses of MET and TAM were administered intramuscularly in a crossover trial involving four dairy cows. Acute mastitis was induced in each cow by infusing two quarters of the udder with Escherichia coli endotoxin 3 h before antibiotic administration.
Radioimmunoassay of the anabolic agent zeranol. II. Zeranol concentrations in urine of sheep and cattle implanted with zeranol (Ralgro)
Authors: DIXON S. N. , RUSSELL K. L.
Published: April 2008

A radioimmunoassay for zeranol has been validated and used to measure the concentration of zeranol in the urine of sheep and cattle treated with zeranol (Ralgro). The assay uses an antibody raised against zeranol‐16‐carboxy‐propyl ether conjugated to human serum albumin. In sheep and cattle urine the limits of detection were approximately 2 ng/ml and 2.5 ng/ml, respectively.

In two trials 13 sheep were implanted with 12 mg zeranol at the base of the ear. The mean maximum concentrations of zeranol observed in urine were 45 ng/ml (Trial I) on day 35 and 90 ng/ml (Trial II) on day 56, and had declined to 26 ng/ml 42 days after implantation (Trial I) and 11.7 ng/ml 70 days after implantation (Trial II). In four cattle implanted with 36 mg zeranol the concentrations of zeranol in urine reached a mean maximum concentration of 13.5 ng/ml 22 days after implantation and had declined to 2.9 ng/ml 69 days after implantation.
Comparison of pharmacokinetics of sodium and lysine cephalexin in calves
Authors: CARLI S. , PERRETTA G. , BRUSA T. , INVERNIZZI A. , FAUSTINI R.
Published: April 2008

The pharmacokinetics of sodium and lysine cephalexins were investigated after intravenous and intramuscular administration of a single dose rate of 30 mg.kg‐1 body weight in calves.

The data for the two salts administered intravenously were pooled, the resulting pharmacokinetic disposition of cephalexin indicating a distribution half‐time (t1/2α) and an elimination half‐time (t1/2β) of 9.78 and 62.0 min, respectively.

Following intramuscular administration some pharmacokinetic differences were recorded between the cephalexin preparations: lysine cephalexin was more rapidly eliminated (t1/2kel= 55.2 min) than sodium cephalexin (t1/2kel= 89.8 min), although the peak blood level was higher and attained after a longer time with lysine cephalexin.
Responses of pulmonary vasculature of cattle to dopamine and apomorphine
Authors: BAKUNZI F. R. , EYRE P.
Published: April 2008

Both dopamine and apomorphine caused concentration‐dependent contractions of the bovine pulmonary artery from rest. Both of these compounds caused relaxation of histamine‐precontracted arterial and venous strips after α‐adrenoceptor blockade. Arterial contraction elicited by dopamine was inhibited either by phentolamine (α‐blocker) or by the dopamine‐selective antagonists, spiperone and butaclamol. Apomorphine in the highest concentration (<10‐5 M) inhibited dopamine‐induced contractions. Dopamine‐ and apomorphine‐induced vascular relaxations were attenuated by propranolol but not by spiperone or butaclamol. These data suggest that dopamine‐ and apomorphine‐induced relaxation in these preparations is most likely mediated through β‐adrenergic mechanisms, whereas dopamine‐induced contractions seem to involve both α‐adrenergic and dopa‐minergic receptors.
Arachidonic acid metabolites in carrageenin‐induced equine inflammatory exudate
Authors: HIGGINS A. J. , LEES P.
Published: April 2008

The presence of cyclooxygenase products of arachidonic acid metabolism in carrageenin‐induced inflammatory exudate was investigated in ponies using two models. In the first model, an inflammatory response was stimulated by injecting carrageenin into subcutaneously implanted polypropylene tissue cages and exudates were collected at five predetermined times between 3 and 48 h. In the second model, exudates were harvested at 6, 12 and 24 h from carrageenin‐impregnated polyester sponges which had also been inserted beneath the skin. Prostaglandin (PG) E2, thromboxane (TX) B2 and the stable breakdown‐product of prostacyclin (PGI2), 6‐keto‐PGF1α, in exudates were measured by radioimmunoassay (RIA); PGE2‐like and PGF2α‐like activities were bioassayed following an acid‐lipid extraction technique which provided a recovery rate of 78%. Agreement between RIA and bioassay was within acceptable limits. In Model 1, using RIA, mean PGE2 concentration reached 197 ng‐ml‐1 at 12 h decreasing to < 12 ng‐ml‐1 at 24 h. Mean TXB2 and 6‐keto‐PGF1α levels were highest at 48 h (22.3 and 34.2 ng‐ml‐1, respectively) after considerable fluctuations and with wide standard errors prior to this time. In the sponge model, however, PGE2 levels were surprisingly low for each group (mean 12.8 ng‐ml‐1 at 12 h) and TXB2 and 6‐keto‐PGF1α were similarly lower (means of 3.3 and 8.1 ng‐ml‐1 respectively at 12 h). Mean total leucocyte counts and total protein concentrations were increased in both models after carrageenin stimulus. PGF2α was not detected in measurable quantities in any exudate. It is concluded that PGE2, TXB2 and PGI2 could be regarded as possible mediators of acute inflammatory reactions to carrageenin in ponies.
The pharmacokinetics of ketamine administered intravenously in calves and the modifying effect of premedication with xylazine hydrochloride
Authors: WATERMAN A.E.
Published: April 2008

Ketamine hydrochloride was administered intravenously to unpremedicated and xylazine‐treated calves. The plasma concentrations of ketamine and norketamine were measured at several time intervals after drug administration and the data were fitted to a two‐compartment open model. In unpremedicated female calves the distribution and elimination half‐lives averaged 6.9 and 60.5 min, respectively. The volume of the central compartment was 1.21 1/kg and the peripheral compartment was 4.04 1/kg. Total body clearance of ketamine averaged 40.4 ml/ min/kg. Premedication with xylazine, whilst not affecting the half‐lives signifi‐candy, reduced volumes of distribution and the clearance rate of the drug by approximately 50%. The results for the male calves which were premedicated were intermediate between the two groups of female calves.
Effects of dipyrone on endotoxininduced fever, central nervous depression and hypoglycaemia in sheep
Authors: NAYLOR J. M. , CATANZARRO C. A. , KRONFELD D. S.
Published: April 2008

Sixteen sheep were divided into four groups and were given saline, Escherichia coli endotoxin at 35 μg/kg0.75, dipyrone at 88 mg/kg0.75, or endotoxin and dipyrone intravenously. Plasma glucose concentrations, rectal temperature and depression of central nervous function were assessed at hourly intervals for 10 h and again at 24 h. Dipyrone had no effect on normal sheep but in sheep given endotoxin, it blocked the febrile response and partially blocked the depression effect upon the central nervous system without affecting the hypoglycaemic response.
Pharmacokinetics and bioavailability of theophylline in horses
Authors: ERRECALDE J. O. , BUTTON C. , BAGGOT J. D. , MULDERS M. S. G.
Published: April 2008

The pharmacokinetics and bioavailability of theophylline in horses were investigated following both intravenous and intragastric administration of aminophyllinc solutions at doses, corresponding to 15 and 10 mg/kg theophylline base. A rapid distributive phase with a half‐life of approximately 15‐30 min was followed by a slower elimination half‐life averaging 15‐17h. The apparent volume of distribution averaged 850‐900 ml/kg. Theophylline, administered as aminophylline solution, was both rapidly and completely absorbed from the equine digestive tract. Based on the bioavailability and disposition kinetics of theophylline, an intragastric dosage regimen for aminophylline consisting of the administration of 5 mg/kg at 12h intervals would be expected to maintain plasma theophylline concentrations within the therapeutic range.
Studies on the influence of non‐steroidal anti‐inflammatory drugs upon trypanosomiasis in goats and sheep
Authors: DWINGER R. H. , VOS J. , NIEUWENHUIJS J. , ZWART D. , van MIERT A. S. J. P. A. M.
Published: April 2008

The non‐steroidal anti‐inflammatory drug (NSAID) flurbiprofen caused a rise in parasitaemia in goats infected with Trypanosoma vivax, Trypanosoma congolense and Trypanosoma brucei. All trypanosome‐infected goats treated with flurbiprofen showed many dividing trypanosomes. This also included the short‐stumpy forms of T. brucei. In T. vivax‐infected goats flurbiprofen treatment resulted in 100% mortality in the acute and chronic stages of the infection. The increase in parasitaemia of T. brucei infected goats, treated with flurbiprofen, was not associated with an increase in mortality. The increase in parasitaemia of T. congolense‐intected goats, treated with flurbiprofen, tended to be associated with a somewhat higher mortality but this was statistically not significant. The significant rise in parasitaemia could be reproduced in T. brucei‐infected sheep without, however, killing the animals. Two other NSAIDs were also studied. Suprofen caused a rise in parasitaemia and 100% mortality when given to goats in the acute stage of T. vivax infection. Results with flunixin meglumine, when tested in T. brucei infected goats, were not conclusive.
Distribution of oxytetracycline into ocular tissues and tears of calves
Authors: GEORGE LISLE W. , SMITH J. A. , KASWAN RENEE
Published: April 2008

George, L., Smith, J. & Kaswan, R. Distribution of oxytetracycline into ocular tissues and tears of calves. J. vet. Pharmacol. Therap. 8, 47–54.

A long‐acting oxytetracycline formulation was administered (20 mg/kg of body weight) intramuscularly to calves, and the concentrations of the drug in serum, ocular tissues and tears were measured. The drug was distributed selectively to the epithelium of the conjunctiva and to the lacrimal gland ductules, and reached concentrations in each tissue that exceeded those in serum. The drug did not penetrate into the aqueous humour, and produced mean peak lacrimal fluid concentrations <1 μg/ml after i.m. administration. When given subconjunctivally, however, concentrations > 2.0 μg/ml were observed in tears for 72 h. Severe local reactions occurred in all calves that were given the drug subconjunctivally.

Lisle W. George, Department of Medicine, School of Veterinary Medicine, University of California, Davis, CA 95616, U.S.A.
Apramycin: minimal inhibitory concentrations for avian Escherichia coli and serum levels after intramuscular injection in turkeys
Authors: FREIDLIN P. J. , BOCK R. , BERNATH A. , HOEXTER S. , ZIV G. , FROMER A. , PERLSTEIN Z. , TOMER S. , SAMBERG Y.
Published: April 2008

Freidlin, P.J., Bock, R., Bernath, A., Hoexter, S., Ziv, G., Fromer, A., Perlstein, Z., Tomer, S. & Samberg, Y. Apramycin: minimal inhibitory concentrations for avian Esclierichia coli and serum levels after intramuscular injection in turkeys. J. vet. Pharmacol. Therap. 8, 105–109.

The minimal inhibitory concentrations (MIC) of apramycin, a unique amino‐cyclitol antibiotic, for 100 Escherichia coli isolates recovered from clinical cases of avian colibacillosis were determined using the agar dilution method. All isolates were inhibited at apramycin concentration of 8.0 μg/ml; 90 and 50% of the isolates were inhibited at 6.6 and 3.4 μg/ml, respectively.

A commercial injectable product containing 200 mg apramycin/ml was administered intramuscularly (i.m.) to groups of 6‐and 12‐week‐old turkeys at 10, 15 and 20 mg/kg. Apramycin was quickly absorbed from the i.m. injection site. Mean peak serum drug concentrations were reached 1 h after treatment and were 19.5, 27.5 and 36.0 μg/ml, respectively. The serum elimination half‐life (1/2) of the drug ranged between 1.75 h for the 10 mg/kg dose and 2.5 h for the 20 mg/kg dose. Very low concentrations of the drug were found 24 h after treatment. Duration of serum apramycin concentrations in relation to the MIC, dose, and age of birds was determined.

Dr G. Ziv, Ministry of Agriculture, Kimron Veterinary Institute, P.O. Box 12, Bet‐Dagan, Israel.
Pharmacokinetics of probenecid in sheep
Authors: GUERRINI V. H. , FILIPPICH L. J. , ENGLISH P. B. , SCHNEIDER JENNY , CAO G. R. , BOURNE D. W. A.
Published: April 2008

Guerrini, V.H., Filippich, L.J., English, P.B., Schneider, J., Cao, G.R. & Bourne, D.W.A. Pharmacokinetics of probenecid in sheep. J. vet. Pharmacol. Therap. 8, 128–135.

Six Merino ewes were given 1g (27g/kg) probenecid by the intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes. After i.v. injection, the biological half‐life was 1.55 h and apparent volume of distribution at the steady state (Vdss) 0.18l/kg. Body clearance (ClB)and renal clearance (ClR) were 0.12l/h/kg and 0.03l/h/kg, respectively. Approximately 28% of unchanged probenecid was excreted in urine. Plasma probenecid concentrations after i.v., i.m. and s.c. injections were 133, 37, and 31 μg/ml, respectively, at 15 min; 76, 36, and 34μg/ml at 1 h; and 43, 23 and 34μg/ml at 2 h. The average bioavailability of probenecid given by i.m. and s.c. injection was 46% and 34%, respectively. However, after 2 h, probenecid plasma concentrations remained higher when it was given subcutaneously than when it was given intramuscularly.

Urine output was correlated positively (P < 0.05) with kel and ClB. Urine pH increased significantly (P < 0.01) for the first 2 h, and then steadily declined over the subsequent 6 h. The results suggested that probenecid in sheep was rapidly eliminated because it was rapidly excreted in the normal but alkaline urine. Subcutaneous administration of probenecid in animals may be a useful alternative to oral or i.v. administration.

Dr V. H. Guerrini, Department of Pharmacy, University of Queensland, St Lucia, Queensland 4067, Australia.
Effects of phenylbutazone and oxyphenbutazone on basic drug detection in high performance thin layer chromatographic systems*,†
Authors: WOODS W. E. , CHAY S. , HOUSTON T. , BLAKE J. W. , TOBIN T.
Published: April 2008

Woods, W.E., Chay, S., Houston, T., Blake, S.W. & Tobin, T. Effects of phenylbutazone and oxyphenbutazone on basic drug detection in high performance thin layer chromatographic systems. J. vet. Pharmacol. Therap. 8, 181–189.

Interference or ‘masking’ in thin layer chromatography occurs when the presence of one drug on a thin layer plate physically obscures or interferes with the detection of another drug. We investigated the ability of phenylbutazone and oxyphenbutazone to mask or interfere with the detection by high performance thin layer chromatography (HPTLC) of basic drugs used illegally in horse racing. Of fifty‐five basic drugs called ‘positive’ since 1981 by laboratories affiliated with the Association of Official Racing Chemists (AORC), forty did not comigrate with phenylbutazone or oxyphenbutazone and could not, therefore, be masked. When 75μg/ml of oxyphenbutazone was spiked into urine samples, subjected to an extraction procedure for basic drugs, and then run in our routine HPTLC systems, no ‘spots’ due to oxyphenbutazone appeared. ‘Masking’ by oxyphenbutazone, therefore, did not and could not occur in our test systems. When phenylbutazone at a concentration of 30μg/ml was spiked into urine samples and run in the routine HPTLC system, phenylbutazone spots were visible under ultraviolet light and after certain specific oversprays were used to visualize basic drugs. These spots, however, did not interfere with routine thin layer testing for basic drugs. It was concluded that phenylbutazone and oxyphenbutazone had no significant ability to interfere with detection of the parent forms of these basic drugs under the conditions described in these experiments.

T. Tobin, Kentucky Equine Drug Research and Testing Programs, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546‐0076, U.S.A.
Low‐dose ethanol in the treatment of ethylene glycol poisoning
Authors: TARR BRYAN D. , WINTERS LORA J. , MOORE MICHAEL P. , COWELL RICK L. , HAYTON WILLIAM L.
Published: April 2008

Tarr, B.D., Winters, L.J., Moore, M.P., Cowell, R.L. & Hayton, W.L. Low‐dose ethanol in the treatment of ethylene glycol poisoning. J. vet. Pharmacol. Therap. 8, 254–262.

pharmacokinetic study was conducted to determine the effectiveness of lower doses of ethanol in the treatment of ethylene glycol (EG) poisoning. Four dogs were maintained at serum ethanol concentrations of 0, 35 and 140 mg/dl prior to EG (i.v., 2 ml/kg) administration. The serum EG concentration‐time data showed that the 35 mg/dl ethanol level provided as effective an inhibition of EG metabolism as did the 140 mg/dl level. The average urinary excretion rate of oxalic acid post EG administration was reduced to control levels by ethanol. The 35 mg/dl serum ethanol level reduced the total body clearance of EG from 93.9 to 50.0 ml/h/kg and increased the effective half‐life from 5.78 to 11.4 h.

Clinical‐testing was accomplished by giving the dogs 12 ml EG/kg body weight orally. One hour later, the dogs were either not treated or treated with a sodium bicarbonate‐ethanol solution to obtain a serum ethanol concentration of 50 mg/dl. The clinical test performed in the ethanol‐treated dogs showed little change from normal limits. Urine calcium oxalate crystals were seldom found. The dogs given EG (12 ml/kg) but not treated with ethanol were in a coma at 13 h and showed severe metabolic acidosis, dehydration, mild hepatocellular disease and acute renal damage. Urine calcium oxalate crystals were found in high numbers. The rapid death associated with EG poisoning appeared to be due to metabolic acidosis in combination with dehydration.

Bryan D. Tarr, College of Pharmacy, Washington Slate University, Pullman, WA 99164, U.S.A.
Intramuscular treatment of subclinical staphylococcal mastitis in lactating cows with penicillin G, methicillin and their esters
Authors: ZIV G. , STORPER M.
Published: April 2008

Ziv, G. &: Storper, M. Intramuscular treatment of subclinical staphylococcal mastitis in lactating cows with penicillin G, methicillin and their esters. J. vet. Pharmacol. Therap. 8, 276–283.

The relationship between antibiotic milk concentrations and bacteriological efficacy was investigated in groups of lactating cows with subclinical mastitis due to either penicillin G‐sensitive or penicillin G‐resistant Staphylococcus aureus. Treatments consisted of the intramuscular injection of procaine penicillin G, or its weak base ester penethamate hydriodide, and sodium methicillin, or its weak base ester tamethicillin. Antibiotics were administered once daily for 2 or 4 days at accepted dosages.

After four daily, treatments with procaine penicillin G and penethamate hydriodide, infections were eliminated from 56.5% and 68.8%, respectively, of quarters infected with penicillin G‐sensitive staphylococci, and from 14.3% and 7.7%, respectively, of quarters infected with penicillin G‐resistant staphylococci. After four daily treatments with sodium methicillin and tamethicillin, infections were eliminated from 32.4% and 48.6%, respectively, of quarters infected with penicillin G‐resistant staphylococci. The better efficacy of penethamate hydriodide and tamethicillin was considered to be linked to the higher milk drug concentrations obtained with these drugs as opposed to the lower concentrations measured in the milk after treatment with the parent drugs. Cure rates were generally higher after treatment for 4 days than after the 2‐day course of therapy. Treatment efficacy decreased progressively with increasing age of the cows.

Intramuscular treatment of subclinical staphylococcal mastitis in lactating cows can serve as a useful model for screening existing and new antibacterial agents and drug products intended for the parenteral treatment of clinical staphylococcal mastitis.

Dr G. Ziv, Ministry of Agriculture, Kimron Veterinary Institute, Bet‐Dagan, Israel.