bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastrointestinal Regulation of Food Intake: General Aspects and Focus on Anandamide and Oleoylethanolamide
Authors: Capasso R. , Izzo A. A.
Published: April 2008

The gastrointestinal tract plays a pivotal role in the regulation of food intake and energy balance. Signals from the gastrointestinal tract generally function to limit ingestion in the interest of efficient digestion. These signals may be released into the bloodstream or may activate afferent neurones that carry information to the brain and its cognitive centres, which regulates food intake. The rate at which nutrients become systemically available is also influenced by gastrointestinal motility: a delay in gastric emptying may evoke a satiety effect. Recent evidence suggests that the endocannabinoid anandamide and the related acylethanolamide oleoylethanolamide are produced in the intestine and might regulate feeding behaviour by engaging sensory afferent neurones that converge information to specific areas of the brain. The intestinal levels of these acylethanolamides are inversely correlated to feeding, as food deprivation increases intestinal levels of anandamide (which acts in the gut as a ‘hunger signal’), while it decreases the levels of oleoylethanolamide (which acts in the gut as a ‘satiety signal’). Additionally, these acylethanolamides, whose gastric levels change in response to diet‐induced obesity, alter gastrointestinal motility, which might contribute to their effect on food intake and nutrient absorption.
Blood Pressure Lowering Effects of Rimonabant in Obesity‐related Hypertension
Authors: Grassi G. , Quarti‐Trevano F. , Seravalle G. , Arenare F. , Brambilla G. , Mancia G.
Published: April 2008

Obesity‐related hypertension represents a common clinical condition characterised by complex pathophysiological and therapeutic features. From a pathophysiological view point, results of experimental and animal studies have led to the hypothesis that neurogenic mechanisms participate in the development and progression of the disease. The hypothesis is based on the evidence that metabolic (i.e. insulin‐resistance) and neural (sympathetic activation) alterations frequently co‐exist in the obese hypertensive patient and that they reciprocally potentiate each other. From a therapeutic view point, the 2007 European Society of Hypertension/European Society of Cardiology emphasised the importance in this clinical condition of treatment not only through antihypertensive drugs but also via lifestyle changes and drug‐induced interventions that reduce body weight. The fourRimonabant In Obesity(RIO) studies have shown that rimonabant can decrease body weight. A recent meta‐analysis, based on the RIO results, showed that rimonabant, particularly in obese hypertensive patients, can also decrease − although modestly (2.8 mmHg for systolic and 2.2 mmHg for diastolic) − blood pressure. These effects, which appear to be triggered by the weight reduction induced by the drug, are clinically relevant because they contribute favourably to lower the elevated cardiovascular risk profile of the obese hypertensive patient.
Obligate anaerobes in clinical veterinary medicine: susceptibility to antimicrobial agents
Authors: KIMSEY PAUL B. , HIRSH DWIGHT C.
Published: April 2008

Ninety‐nine isolates of obligate anaerobic bacteria obtained from clinical material were tested for susceptibility to ten antimicrobial agents. Regardless of the species of animal from which the isolates were obtained 90–95% were inhibited by ≤4 μg of ampicillin/ml, ≤4 μg of chloramphenicol/ml, ≤1 μg clindamycin/ml, ≤2 μg metronidazole/ml, ≤8 μg minocycline/ml, ≤16 μg penicillin Gyml, and ≤16 μg tetracycline/ml. All the aminoglycoside antibiotics tested (gentamicin, kanamycin, neomycin, and streptomycin) were shown to be relatively ineffective requiring ≥128 μg/ml for the inhibition of >50%of the isolates. The minimal inhibitory concentration of penicillin G and tetracycline tended to be higher for isolates from non‐human primates (penicillin G) and ruminants (tetracycline).
The influence of ketamine and other intravenous anaesthetic agents on cerebral blood flow in the sheep
Authors: WATERMAN A. , LIVINGSTON A.
Published: April 2008

Cerebral blood flow (CBF) was measured in sheep by measuring clearance of directly injected 133 Xenon from the cerebral cortex. The influence of ketamine at various dose levels on the CBF was measured and compared to the effects produced by pentobarbitone and CT1341. It was found that ketamine caused an initial depression of CBF followed by a rise, pentobarbitone produced a profound long lasting depression whilst CT1341 caused an initial depression which was rapidly followed by a return to control values.
In vitro inactivation of endotoxin by polymyxin B and colistin in mastitic milk
Authors: ZIV G. , HARTMAN I. , TORTEN M.
Published: April 2008

The in vitro inactivation of crude endotoxins (lipopolysaccharides) of four Escherichia coli strains by polymyxin B and colistin in mastitic milk was investigated utilizing the Limulus amebocyte lysate test. Although minor differences were observed among the endotoxins in respect to susceptibility to inactivation, activity of each was markedly reduced by both drugs.
Intra‐uterine absorption of sodium benzylpenicillin in the cow
Authors: AYLIFFE T. R. , NOAKES D. E.
Published: April 2008

Twenty‐six experiments were performed on six healthy, non‐lactating cows with normal oestrous cycles. Absorption of sodium benzylpenicillin from the uterus in oestrus and on day 12 following oestrus was compared with intravenous injection. Absorption, as shown in plasma from the uterus of six cows in oestrus, occurred to a greater extent (mean peak 12.80 ± S.E.M. 3.36 i.u./ml) than from the uterus in the luteal phase on nine occasions (mean peak 3.92±0.75 i.u./ml.). Intrauterine infusion of 10% Lugol's iodine solution before the administration of antibiotic did not significantly alter absorption on day 12 in six cases (mean peak 5.07±1.51 i.u./ml).
Comparison between diffusion and dilution methods for testing antimicrobial susceptibility of Staphylococcus aureus cultures derived from bovine mastitis
Authors: FERREIRO L. , BIBERSTEIN E. L.
Published: April 2008

One hundred Staphylococcus aureus strains from bovine mastitis were tested for susceptibility to eight antimicrobials by the paper disc diffusion method (Kirby‐Bauer) and a commercially prepared dilution system. Except in the case of penicillin and possibly ampicillin, comparison of the two methods showed excellent correlation. Agreement was perfect with methicillin, chloramphenicol, gentamicin, and kanamycin.
Serum digoxin concentrations in healthy dogs treated without a loading dose
Authors: PEDERSOLI W. M.
Published: April 2008

Healthy dogs were treated once‐a‐day for 20 days, with a liquid oral dosage form of digoxin (0.022 mg/kg). Serum digoxin concentrations, measured by radio immunoassay technique, were in the therapeutic range 8 h after the second daily dose of digoxin had been administered. Of the ten dogs treated, four had digoxin serum concentrations above those accepted to be moderately toxic. Results of a blood urea nitrogen and a phenolsulfonphthalein test, determined at days 0, 5, 8, 12, 15 and 19 after the beginning of the investigation all were within normal limits. Serum osmolality, calcium, potassium, and sodium, determined daily, evidenced no significant difference from control values. Lengthening of the PR interval and a decrease in the heart rate were observed. Digitalization of dogs can be achieved without the use of a loading dose and within a much shorter time than was previously reported.
Disposition of sulfonamides in food‐producing animals: pharmacokinetics of sulfamerazine in cattle
Authors: KORITZ GARY D. , BOURNE DAVID W. A. , DITTERT LEWIS W. , BEVILL RICHARD F.
Published: April 2008

The disposition of sulfamerazine in the plasma and urine of cattle was determined following single intravenous and oral doses. The averaged and the individual animal data were described by a two‐compartment pharmacokinetic model. The drug was eliminated with a biological half‐life of 6.2 h, primarily by renal excretion of unchanged sulfamerazine and metabolism to acetylsulfamerazine. Sulfamerazine (in solution) was absorbed with a half‐life 6.7 h and with relative completeness (68%) following oral administration.
Effect of toxic hepatitis on pharmacokinetics of salicylate in dogs
Authors: ABBITT LAUREN E. , DAVIS LLOYD E. , DAVIS CAROL A. NEFF
Published: April 2008

The effect of carbon tetrachloride (CT) induced toxic hepatitis on the pharmacokinetics of sodium salicylate was studied in beagle dogs. Plasma concentrationtime profiles were determined for sodium salicylate in ten healthy dogs and in the same dogs after CT administration. Laboratory tests for liver disease were performed before and after liver injury in order to examine the feasibility of using commonly employed laboratory tests as a guide for determining dosage regimens of sodium salicylate in the presence of liver dysfunction. The disappearance of sodium salicylate from the plasma of dogs was a first‐order process through 8 h in both the normal and liver disease states. After CT, there was an alteration in the kinetic behavior between 8 and 24 h after salicylate administration. This change was linked to the decreased ability of the damaged liver to form glucuronides. The changes observed in the pharmacokinetics of salicylate before and after CT induced liver dysfunction were minimal and not statistically significant. The majority of the dogs, however, demonstrated a slightly decreased half‐life after CT administration. This was due to an increase in the urinary excretion of unchanged salicylate. It was not possible to correlate laboratory parameters with pharmacokinetic parameters. Therefore, dosage alterations could not be based upon laboratory data. Data from this investigation, however, did not suggest the need to routinely alter the dosage of salicylate in the presence of CT induced toxic hepatitis.
Pharmacokinetics of propranolol in the dog
Authors: KATES ROBERT E. , KEENE BRUCE W. , HAMLIN ROBERT L.
Published: April 2008

The pharmacokinetics of propranolol were investigated in dogs following intravenous, single oral, and multiple oral doses. Mean half‐life of the compound following single intravenous administration was 1.09 h, following single oral dose 1.58 h, and 2.14 h after chronic oral dosing. Half‐life values previously reported in dogs for the levo and dextro isomers were 0.77 and 1.08h, respectively. The bioavailability of oral propranolol was low (2–17% available) following a single oral dose, but increased substantially after chronic oral dosing, suggesting saturation of the disposition processes for propranolol with multiple dosing regimens.
α‐Adrenergic control of gonadotropin secretion in the ewe
Authors: NARAYANA K. , DOBSON HILARY
Published: April 2008

The effect of the centrally acting α‐adrenoceptor agonist, clonidine, on plasma LH and FSH was studied in oestradiol‐primed and unprimed ewes and in oestrous ewes. In unprimed anoestrous ewes, clonidine stimulated LH and FSH release after a lag period of 18 h, and noradrenaline intracarotid injection or i.v. infusions immediately stimulated LH release. In oestradiol‐infused anoestrous ewes, clonidine produced either a delay or inhibition of the gonadotrophin surge and noradrenaline i.v. infusion advanced the LH surge. In oestrous ewes treated with clonidine, there was marked delay in the LH surge, but the magnitude of the LH and FSH surges were unaffected. Intravenous administration of α‐adrenoceptor blockers, phentolamine and phenoxybenzamine, blocked the oestradiol‐induced gondotrophin surge in anoestrous ewes. The effect of phenoxybenzamine on gonadotrophin surge was dose dependent in oestrous ewes. Small doses (4 mg/kg i.v.) of phenoxybenzamine delayed the synchronous LH and FSH surges. There was complete blockade of the LH surge and partial blockade of FSH surges in ewes given phenoxybenzamine (8 mg/kg i.v.) before the expected synchronous gonadotrophin surges. After this experiment, the initial rise of plasma progesterone concentrations did not occur until day 6 of oestrous cycle. Administration of phenoxybenzamine before the expected second FSH surge had no effect on the second FSH surge. Gonadotrophin release induced by gonadotrophin‐releasing hormone was attenuated by phenoxybenzamine, but not by clonidine. The results suggest that the LH surge is under α‐adrenergic control and the first FSH surge is under partial α‐adrenergic control, but the second FSH surge is not under α‐adrenergic control. The results also suggest oestradiol modulation of α‐adrenergic receptor action.
The effect of flurbiprofen upon fever and ruminal stasis induced by Escherichia coli endotoxin, Poly I: Poly C and sodium nucleinate from yeast in conscious goats
Authors: MIERT A.S.J.P.A.M. VAN , DUIN C.Th.M. VAN
Published: April 2008

Intravenous injection of endotoxin from Escherichia coli (0.01 μg and 0.1 μg per kg body weight), sodium nucleinate from yeast (5 mg and 10 mg per kg body weight) or Poly I: Poly C (15 μg and 30 μg per kg body weight) caused fever, changes in heart rate and stasis of the extrinsic ruminal contractions in conscious goats. It appears that ruminal stasis is associated with clinical and experimental fever. The febrile responses were abolished by the prior intravenous administration of flurbiprofen (2 mg per kg body weight), a potent non‐steroidal anti‐inflammatory and antipyretic agent. This agent, however, only had a partial antagonistic influence upon pyrogen‐induced ruminal stasis. The secondary changes in heart rate were not prevented by the drug. It seems unlikely that the inhibition of the extrinsic ruminal contractions by exogenous pyrogens is due simply to a release of prostaglandins.
Pharmacological evaluation of sheep lung strip
Authors: CHAND N.
Published: April 2008

Isolated sheep lung parenchymal strips responded to histamine > carbachol > PGF2a > 5‐HT with contractions, and to isoproterenol (Isop), and to large doses of epinephrine (E), norepinephrine (NE) and phenylephrine (PE) with relaxations. PGF2a‐contracted lung strip responded to PGE1 and PGE2 with relaxation. The strips which were partially contracted to histamine, PGF2a, 5‐HT and carbachol also responded to isop, E and NE with relaxations. Histamine responses were not modified by metiamide (an H2‐receptor antagonist). Mepyramine and atropine selectively antagonized contractions to histamine and carbachol, respectively. After β‐blockade with propranolol, lung strips responded to NE > E > PE > isop with contractions, which were inhibited or reversed by phentolamine and dibenzyline. It is concluded that H1 receptors are present in sheep peripheral airway smooth muscles, and that a‐ and β‐adrenoceptors mediate contraction and relaxation, respectively, in sheep lung strips.
Pharmacological basis of immediate hypersensitivity in the domestic fowl: a review
Authors: CHAND N.
Published: April 2008

This review discusses the mechanisms of immediate hypersensitivity and their putative relationship to clinical syndromes in the fowl. The general features of these mechanisms are outlined, in terms of the pharmacological mediators involved, the anaphylactic antibodies, and the distribution and relative significance of the immune target cells — the mast cells and basophils. Emphasis is given to the ways in which these features are similar to or differ from those occurring in mammals. Consideration is given to the immunological release of histamine and of SRS‐A in the fowl. The results of work on the mechanisms of in vitro anaphylaxis (Schultz‐Dale phenomenon) in the chicken are discussed. The roles of several potential mediators of acute systemic anaphylaxis are discussed in some detail, with reference to the activities of antagonists to each of these potential mediators. A major role for the vasoactive lipids and peptides is suggested.
Enhancement of ampicillin bioavailability in pigs
Authors: GALTIER P. , ALVINERIE M.
Published: April 2008

Biliary excretion of Na‐ampicillin was studied in 40–50 kg male castrated pigs fitted with a bile duct re‐entrant cannula. There is a low recovery of antibiotic in the bile after an extraduodenal administration. The injection of sodium de‐hydrocholate increased the bioavailability of ampicillin and decreased the volumes of distribution in the drug. The simultaneous administration of probenecid led also to an increased ampicillin bioavailability. The use of such regimes to obtain longer ampicillin dosage intervals is discussed.
The renal clearance of inulin, creatinine, trimethoprim and sulphadoxine in horses
Authors: GELSÅ HANS
Published: April 2008

The clearance of inulin and creatinine were almost identical in horses, indicating that creatinine clearance can be used for estimation of the glomerular filtration rate in horses. Trimethoprim (TMP) is excreted in urine by glomerular filtration, active tubular secretion and back‐diffusion. The clearance of TMP is highly influenced by urine pH, but also by the plasma concentration of the drug and by the degree of diuresis. The results indicate self‐depression of the active tubular secretion of TMP at plasma concentrations above 1–2 μg/ml. The renal excretion of sulphadoxine in horses involves glomerular filtration and a pronounced back‐diffusion. The clearance of sulphadoxine is dependent on urine pH and increases with increasing pH. The clearance of N4‐acetyl sulphadoxine was higher than the clearance of the parent compound. The renal excretion of N4‐acetyl sulphadoxine was shown to involve glomerular filtration, active tubular secretion and back‐diffusion.
Effects of lithium on aggressive behaviour in domestic pigs
Authors: DANTZER ROBERT , MORMEDE PIERRE
Published: April 2008

Lithium carbonate (0.75 and 1 mEq/kg daily) mixed with food was chronically administered to growing pigs. Control animals received equivalent amounts of sodium carbonate. Added lithium decreased intra‐group aggression occurring when access to food was restricted but did not prevent aggression and fighting observed after mixing pigs from different origins. The results are discussed in relation to the current interpretations of the psychopharmacological activity of lithium, and the prospective value of using lithium in pig intensive husbandry for controlling behavioural disorders is examined.
Plasma chloramphenicol concentrations in cats following intramuscular administration of three different chloramphenicol preparations
Authors: WATSON A. D. J.
Published: April 2008

Five adult cats were given 30 mg chloramphenicol/kg by intramuscular injection on three separate occasions, using a different preparation on each occasion. The preparations were an aqueous suspension of chloramphenicol, a solution of chloramphenicol in methylpyrrolidone, and an aqueous solution of chloramphenicol sodium succinate. Plasma chloramphenicol concentrations were determined chemically at fixed intervals after dosing. Chloramphenicol sodium succinate solution gave higher and more rapidly attained plasma chloramphenicol concentrations than the other two preparations. The extent of chloramphenicol absorption up to 8 h after administration was greater with the succincate ester than with chloramphenicol dissolved in methylpyrrolidone. There was no difference in bioavailability between the aqueous suspension and the solution in methylpyrrolidone.
Influence of food intake on the absorption of lysine‐acetylsalicylate in dogs
Authors: RICHEZ P. , REGNIER A. , RUCKEBUSCH Y.
Published: April 2008

The influence of food intake on the absorption of a water‐soluble aspirin, lysine‐acetylsalicylate, was examined in six healthy adult mongrel dogs. Single‐dose kinetics were determined following ingestion of 90 mg/kg of lysine‐acetylsalicylate in dogs either fasted for 12 h or following a standard meal of either dry food or the same meal containing 20% of olive oil. Concurrent intake of food both reduced the serum salicylate concentration for 3 h after administration, and reduced the total amount of drug absorbed as reflected by the area under the plasma concentration/time curve(AUC). The effects were more pronounced following the fatty meal. Data from this investigation suggest that lysine‐acetylsalicylate is therapeutically effective, without side effects when taken at the rate of 80 mg/kg at 12 h intervals, during or after feeding rather than before feeding.
Oral chloramphenicol dosage regimens in cats
Authors: WATSON A. D. J.
Published: April 2008

Five adult domestic cats were each given three separate 3‐day courses of chloramphenicol, using a different oral‐dosage regimen each time. The regimens were: 120 mg/kg/day divided 8‐hourly, 60 mg/kg/day divided 8‐hourly, and 50 mg per cat every 12 h (25–40 mg/kg/day). The interval between successive courses was 3 weeks. On the third day of each course plasma samples were obtained at fixed intervals after dosing and were assayed chemically for chloramphenicol. The ranges from peak to trough chloramphenicol concentrations with each regimen were (values are means ± SEM): 63.8 ± 4.60 to 43.0 ± 3.32 μg/ml (120 mg/kg/day), 42.0 ± 3.63 to 24.7 ± 1.83 μg/ml (60 mg/kg/day), and 24.3 ± 1.72 to 7.5 ± 0.85 μg/ml (50 mg per cat 12‐hourly). Because of these findings, previous toxicity studies, and the proposed therapeutic (effective and safe) concentration for chloramphenicol of 5–15 μg/ml, it is suggested that a regimen of 50 mg per animal every 12 h could be adequate for chloramphenicol therapy in cats of average size (2.5‐3.9 kg) and should be evaluated clinically.
Radioimmunoassay of the anabolic agent zeranol I. Preparation and properties of a specific antibody to zeranol
Authors: DIXON S. N.
Published: April 2008

A highly specific antibody has been raised in sheep to an antigen prepared by coupling zeranol hemisuccinate to bovine serum albumin. An assay procedure is described and has been used to measure the cross‐reactivity of the antiserum, and evaluate the sensitivity of the assay method. The only compounds which reacted with the antibody were zeranol 100%, zearalanone 100%, zearalenone 19% and zearalenol 19%. The sensitivity of the assay procedure allows the determination of zeranol and/or its main metabolite zearalanone between 100 and 1000 pg.
Intravenous fluid therapy for non‐respiratory acidosis in dogs: a comparison of a balanced electrolyte solution with a fluid rich in potassium and bicarbonate
Authors: ROSE R. J. , CARTER R. J.
Published: April 2008

To assess the efficacy in dogs of an experimental solution (Solution A) containing high concentrations of bicarbonate and potassium, for the treatment of acidosis, acetazolamide was used to create a stable non‐respiratory acidosis. A total of 24 dogs was used, being divided into two control groups and two groups receiving acetazolamide. One control group and a group receiving acetazolamide had a balanced electrolyte solution (Normosol R) administered at a flow rate of 38.2 ml/kg/h for 2 h, and the other control and acetazolamide groups received Solution A. Blood‐gas, acid‐base, electrolyte and various biochemical measurements, as well as arterial and central venous pressure measurements were performed before fluid administration and up to 24 h after administration.

Both fluids resulted in partial correction of the acidosis. Solution A returned acid‐base balance closer to the values of control dogs by the end of 2 h of fluid administration than did Normosol R. Despite the high concentration of potassium in Solution A (20 mmol/1) there were only marginal elevations in plasma potassium values. Administration of an average of 80 mmol of bicarbonate to normal dogs resulted in an average increase of only 2.7 mmol/1, whereas in dogs with acidosis the increase was 6.4 mmol/1.
Levels of the isoxazolyl penicillins, cloxacillin and flucloxacillin, in serum and synovia of horses
Authors: MARTIN IAN C. A. , LOVE DARIA N. , ROSE REUBEN J.
Published: April 2008

Cloxacillin and flucloxacillin were administered to horses by single intravenous dose (25, 33 or 44 mg/kg). Levels of these compounds were assayed biologically from serum and synovia of the carpal and tibio‐tarsal joints at intervals up to 360 min. Serum levels of cloxacillin at 30 min were all in excess of 48 μg/ml and were equal to, or higher than, those given by the equivalent doses of flucloxacillin. Highly significant differences (P<0.001) between doses and between sampling times (30, 60, 90, 120, 180, 240, 360 min) were detected for both compounds. Although the rates of elimination of cloxacillin and flucloxacillin from blood did not differ significantly, the early establishment of higher levels of cloxacillin in blood meant that it regularly persisted longer than flucloxacillin in both serum and synovia. The rate of elimination from serum was significantly steeper (P<0.001) than that computed for synovia. The slower rate of loss of cloxacillin or flucloxacillin from the synovia than the blood appears to fit the model of transfer between serum and synovium proposed by Howell, Sutherland & Rolinson (1972). The persistence of cloxacillin and flucloxacillin in synovia beyond the time when effective minimum inhibitory concentrations (4 μg/ml) were present in the blood, indicates a practical advantage in equine therapeutics where septic arthritis is the major indication for use of these compounds. In these situations, cloxacillin has a further clinical advantage in persisting in synovia for a longer time than flucloxacillin.
Effects of chlorpromazine on plasma concentrations of long chain fatty acids and glucose in sheep
Authors: BRUSS MICHAEL L.
Published: April 2008

Intravenous chlorpromazine was found to cause rapid increases in plasma concentrations of glucose and long chain fatty acids in adult sheep of both sexes. α‐adrenergic blockade with phentolamine suppressed the increase in glucose concentration but not the increase in concentration of long chain fatty acids caused by chlorpromazine. β‐adrenergic blockade with propranolol suppressed the increase in concentration of long chain fatty acids but not the increase in glucose concentration caused by chlorpromazine. These results were consistent with the hypothesis that chlorpromazine caused a systemic release of epinephrine.
Prolonged depression of thermoregulation after xylazine administration to cats
Authors: PONDER S. W. , CLARK W. G.
Published: April 2008

Xylazine administered subcutaneously (s.c.; 1–4 mg/kg) or intravenously (i.v.; 0.5‐2 mg/kg) to cats consistently caused dose‐related decreases in body temperature which were maximal 3–4 h after injection and lasted for at least 12 h. Otherwise the animals appeared to have recovered fully from the central nervous system effects of the drug within 1.5–3.5 h. Xylazine‐induced hypothermia developed more rapidly in cats placed in a 4°C environment and, in contrast, was replaced by a hyperthermic response in cats placed in a 32°C environment. These changes in body temperature were not opposed by compensatory thermoregulatory effector activity such as shivering or tachypnea. This pattern of responses at varied environmental temperatures is indicative of a general depression of the thermo‐regulation. Thus, animals given xylazine should not be exposed to extreme heat or cold for several hours to avoid development of hyper‐ or hypothermia.
The selection in vitro of antibiotics with activity against intracellular S. aureus
Authors: CRAVEN N. , ANDERSON J. C.
Published: April 2008

The activity of a range of antibiotics on intracellular Staphylococcus aureus was examined using an in vitro system in which staphylococci survived within bovine neutrophils and extracellular organisms were killed by lysostaphin. Cloxacillin in the presence of lysostaphin caused a reduction in the number of viable intracellular S. aureus but cloxacillin alone failed to reduce such bacteria significantly. The cloxacillin appeared to sensitize the staphylococci to lysis by extracellular traces of lysostaphin following neutrophil disruption. Extracellular staphylococci which remained viable after exposure to cloxacillin in the absence of lysostaphin were subsequently killed more rapidly by neutrophils, but this was not found with bacteria exposed to cloxacillin while inside cells. Vancomycin with lysostaphin produced a similar but smaller sensitization effect but this antibiotic also appeared to increase survival of intracellular staphylococci when compared with controls, possibly by impeding neutrophil bactericidal mechanisms. The only other antibiotic to show significant intracellular killing was rifampicin, and in this case the action was independent of lysostaphin.
Susceptibility of Clostridium perfringens of animal origin to fifteen antimicrobial agents
Authors: DUTTA G. N. , DEVRIESE L. A.
Published: April 2008

The minimal inhibitory concentrations of fifteen antibacterial agents were determined by agar‐dilution method against 121 strains of Clostridium perfringens isolated from pigs, cattle and poultry. All strains, regardless of host of origin, were susceptible to avoparcin, furazolidone, monensin, nitrovin, penicillin G, ronidazole and tiamulin and resistant to flavomycin. Poultry strains were also susceptible to carbadox, chloramphenicol, erythromycin and virginiamycin. Bacitracin‐resistant poultry strains were susceptible to all tested antibacterial agents except tetracycline, but the bacitracin‐resistant cattle strains were polyresistant. Porcine strains were susceptible to bacitracin and bovine strains to carbadox. Carbadox‐resistant porcine strains were resistant to erythromycin, lincomycin and tetracycline and susceptible to chloramphenicol. Resistance to erythromycin was associated with resistance to lincomycin. High level erythromycin‐lincomycin‐resistant strains were susceptible to virginiamycin, but the intermediate level erythromycin‐lincomycin‐resistant cattle strains were resistant to virginiamycin. Resistance to chloramphenicol or erythromycin‐lincomycin was always associated with resistance to tetracycline but the reverse was not always true.
A radioimmunoassay method for the measurement of residues of the anabolic agent, hexoestrol, in tissues of cattle and sheep
Authors: HARWOOD D. J. , HEITZMAN R. J. , JOUQUEY A.
Published: April 2008

A radioimmunoassay (RIA) method for hexoestrol using an antiserum against hexoestrol‐carboxypropyl ether‐BSA and H3‐hexoestrol was used to measure the concentrations of residues of hexoestrol in 0.1 ml biological fluids and 1 g edible tissues of implanted cattle and sheep. A preliminary ether extraction of biological fluids was necessary before RIA. The ether extract from tissues was further purified by solvent partition and silica gel column chromatography before RIA. Conjugates of hexoestrol were measured after enzymatic hydrolysis to free hexoestrol. In untreated animals residues were either not detected or very low in all tissues except urine from sheep. The method has a lower limit of detection of approximately 0–10 pg/ml for biological fluids in cattle and 20–100 pg/g for tissues in both sheep and cattle but the lower limit of detection in sheep urine was 70–294 pg/ml urine.

In two heifers implanted with 60 mg hexoestrol and slaughtered 2 and 7 days after implantation, residues of hexoestrol were detected in all tissues except muscle with highest concentrations between 2 ‐ 17 ng/g in urine, bile and kidney. The concentration of residues in steers which had been implanted with 45 mg or 60 mg hexoestrol and slaughtered at 90 days after implantation were 0, < 50, 46–96 and 200 pg/ml or g of plasma, muscle, liver and urine, respectively. The concentrations of hexoestrol in sheep implanted with 15 ml hexoestrol and slaughtered after 60 days were 70, 0, 964, 3100 and 4074 pg/g or ml of muscle, fat, liver, kidney and urine, respectively. No hexoestrol was found in control untreated cattle and sheep. It was concluded that some residues of hexoestrol were present in the excretory fluids and tissues of cattle and sheep which had been implanted with hexoestrol at the recommended dose and slaughtered after the recommended withdrawal periods. However, the concentrations of hexoestrol in muscle and fat were extremely low or not detectable. The method could be used for the routine screening of animals for treatment with hexoestrol.
Residue profile of phenylbutazone in the rabbit. A comparative evaluation by tissue kinetics prior to and post mortem
Authors: TOUTAIN P. L. , ALVINERIE M. , RUCKEBUSCH Y.
Published: April 2008

The disposition kinetics and residue levels of phenylbutazone (8 mg/kg) were studied in rabbit. The result suggested that distribution of phenylbutazone can be described by a two open compartment. Elimination half‐time is short (2 h) and estimation of residue levels in muscle, liver and kidney did not differ significantly before and after bleeding. These results suggest that biopsy can be used to determine the phenylbutazone concentration in tissues of larger species. Moreover, using a pharmacokinetic approach based on drug concentrations in plasma, it appears that the mean resting quantity in the peripheral compartment was very close to the experimental data for the muscle.
The in vitro resistance of canine staphylococci to trimethoprim and sulphamethoxazole alone and in combination
Authors: HINTON M. , MARSTON M. , CRISFIELD JULIA
Published: April 2008

The in vitro resistance of 40 strains of Staphylococcus aureus isolated from dogs to trimethoprim, sulphamethoxazole and co‐trimoxazole (SXT) was assessed using the disc diffusion technique on Diagnostic Sensitivity Test Agar (DSTA), DSTA with 5% lysed horse blood (DSTA + B), IsoSensitest Agar (ISTA) and Wellcotest Sensitivity Test Agar (WSTA).

When sensitivity was based on a zone width of ≥4 mm all 40 strains were sensitive to SXT on DSTA + B and ISTA, 39 were sensitive on WSTA while only 31 (77.5%) were sensitive on DSTA.

A comparison of the results obtained for each strain for trimethoprim and sulphamethoxazole with those obtained with the Oxford strain of S. aureus and using a scheme for interpretation recommended by Garrod & O'Grady (1971) indicated that the proportion of strains classed as sensitive for therapeutic purposes was 5%, 55%, 47.5% and 15% respectively on DSTA, DSTA + B, ISTA and WSTA.
The pharmacokinetics of xylazine hydrochloride: an interspecific study
Authors: GARCIA‐VILLAR R. , TOUTAIN P. L. , ALVINERIE M. , RUCKEBUSCH Y.
Published: April 2008

The pharmacokinetic disposition of xylazine hydrochloride is described after both intravenous and intramuscular injection of a single dose, in four domestic species: horse, cattle, sheep and dog, by an original high performance liquid chromatographic technique. Remarkably small interspecific differences are reported. After intravenous administration, systemic half‐life (t1/2 β) ranged between 22 min (sheep) and 50 min (horse) while the distribution phase is transient with half‐life (t1/2 α) ranging from 1.2 min (cattle) to 5.9 min (horse). The peak level of drug concentration in the plasma is reached after 12–14 min in all the species studied following intramuscular administration. Xylazine bioavailability, as measured by the ratios of the areas under the intravenous and intramuscular plasma concentration versus time curves, ranged from 52% to 90% in dog, 17% to 73% in sheep and 40% to 48% in horse. The low dosage in cattle did not permit calculation. Kinetic data are correlated with clinical data and the origins of interspecific differences are discussed.
Metronidazole: a method for its determination in biological fluids and its disposition kinetics in the dog
Authors: NEFF‐DAVIS CAROL A. , DAVIS LLOYD E. , GILLETTE EDWARD L.
Published: April 2008

A method for the analytical determination of metronidazole concentrations in biological tissues was developed using high performance liquid chromatography. The procedure was employed to investigate the pharmacokinetics of metronidazole in dogs following intravenous and oral administration (44 mg/kg). The overall elimination rate constant β was 0.0027 ± 0.0005 min‐1, the apparent specific volume of distribution (V'd) was 0.948 ± 0.096 L/kg overall clearance (ClB) was 2.49 ± 0.54 ml/kg/min and the rate constant for absorption Kab was 0.0456 ± 0.0353 min‐1. Oral bioavailability was high but variable (59%–100%). Implications of these data for chemotherapy of infections caused by anaerobic bacteria, trichomonads, and Giardia and for the sensitization of hypoxic neoplastic cells to radiotherapy are discussed.
Lidocaine plasma concentrations obtained with a standardized infusion in the awake and anaesthetized dog
Authors: RICK A. DE , ROSSEEL M.‐T. , BELPAIRE F. , BOGAERT M.
Published: April 2008

Lidocaine was administered intravenously on several occasions to three healthy mongrel dogs. The lidocaine treatment consisted of an infusion of 0.8 mg/kg/ min over 10 min, followed by an infusion of 0.085 mg/kg/min over 3 h. This lidocaine treatment was given once in the awake state and on two other occasions the infusion was started before or during the following anaesthetic regimen: atropine‐meperidine premedication, thiopental induction and maintenance nitrous oxide‐methoxyflurane anaesthesia.

In most instances plasma levels were somewhat higher at the end of the loading infusion (>5 μg/ml) than subsequendy, but steady‐state values were obtained soon after starting the 3‐h infusion. There were no striking differences between the plasma profiles and half‐lives found in the three series of experiments: mean plasma concentrations of lidocaine during steady state were between 3.5 and 5.0 μg/ml and the half‐life of lidocaine was 1 to 2 h.

Signs of intoxication were not seen in any of the dogs at any stage of the procedures. It is concluded that with the loading and maintenance doses used in this study steady‐state values, probably within the therapeutic range, are obtained within a few minutes. The plasma concentrations are not influenced by the anaesthetic regimen used.
Pharmacokinetics of warfarin in rabbits during short‐term and long‐term uraemia
Authors: TVEDEGAARD ERLING , LADEFOGED JØRGEN , LADEFOGED OLE
Published: April 2008

Warfarin was administered intravenously twice at an interval of six months to rabbits with surgically‐induced impairment of renal function and to control animals. Pharmacokinetic analysis showed that the elimination rate of warfarin was significantly decreased in the uraemic group after 2 weeks duration of uraemia and was even further decreased at the second examination 6 months later. No significant changes in the volumes of distribution were found. Renal function tests indicated stable renal function between the two examinations.
The pharmacokinetics of meclofenamic acid in the horse
Authors: SNOW D. H. , BAXTER P. , WHITING B.
Published: April 2008

The pharmacokinetics of meclofenamic acid were studied in Thoroughbred horses and in ponies. After intravenous (i.v.) administration of either 2 mg/kg or 4 mg/kg sodium meclofenamate the elimination half‐life was of the order of 0.9 h while the volume of distribution was found to be 0.128 litre/kg. Elimination was in accordance with a one‐compartment model. Following oral administration of either meclofenamic acid (4 mg/kg) or sodium meclofenamate (4 mg/kg) a much longer terminal half‐life than that calculated for Kel from i.v. data was found. This anomaly indicated that the ‘flip‐flop’ phenomenon was present, i.e. Ka exceeded Kel. More rapid and higher peak levels occurred following sodium meclofenamate than meclofenamic acid, although total bioavailability was similar. Studies in ponies with meclofenamic acid showed a lower absorption than that found in Thoroughbreds. Overnight fasting before meclofenamic acid administration did not alter the rate or extent of absorption. Intramuscular administration of sodium meclofenamate resulted in low plasma concentrations and after 25 h only 46% of the drug had been absorbed.
Three compartment model for pyrimethamine disposition in the pig
Authors: SHIMODA MINORU , KOKUE EI‐ICHI , KUREBAYASHI YOICHI , HAYAMA TOYOAKI
Published: April 2008

Plasma concentration and urine excretion of pyrimethamine (Py) after intravenous (i.v.) administration (10 mg/kg) were determined in four pigs, using NP‐FID gas chromatography. A three‐compartment model system adequately fitted the observed plasma data. Py may undergo an extensive extravascular distribution, because of the ratio of total volume of distribution to volume of the central compartment was extremely large (about 10). From the calculation of theoretical distribution, only 30% of the dose appears to remain in the central compartment 15 min after administration. Within 2 h of administration the proportion of drug within the two identified peripheral compartments exceeded the proportion remaining in the central compartment. Calculation of cumulative drug excretion showed that up to 90% of an administered dose is excreted within 24 h of administration, although only about 3% of the dose could be detected in urine in an unchanged form during the 24 h period.
Effects of Caerulein on exocrine pancreatic secretion in sheep
Authors: BERETTA C. , ORMAS P. , BELLOLI C. , INVERNIZZI A. , FAUSTINI R.
Published: April 2008

Caerulein administered by slow intravenous infusion at increasing dosage rates (0.1, 1.0, 5.0 and 10.0 ng/kg/min ± 30 min) stimulated pancreatic juice production in sheep as well as the protein content, the amylolytic, the lipolytic and proteolytic activities of pancreatic juice samples collected at 30 min intervals.

A long lasting (300 min) infusion of a high dose of Caerulein by subcutaneous route elicited stimulatory effects with reduced intensities, slower onsets but more sustained durations than those produced by the same dose level administered intravenously.
‘Lactate type’ response of ruminal fermentation to chloral hydrate, chloroform and trichloroethanol
Authors: AMGARTEN M. , SCHATZMANN H. J. , WÜTHRICH A.
Published: April 2008

In ruminal fluid, taken from a cow 2 h after cereal feeding and supplemented with powdered grass, chloral hydrate diminished die rate of acetate, butyrate and propionate production. Instead, a considerable increase in lactate production was elicited by the drug. Chloroform and trichloroethanol had the same effect. Chloral hydrate and chloroform rendered the redox potential more negative which indicates inhibition of methane production. A concentration of chloral hydrate (2 mM), giving complete methane inhibition, reduced volatile fatty acid production by 30%. The findings are explained by assuming that chloral hydrate blocks methane production but in addition is inhibitory at a step below lactate in the reductive pathway to propionate and that the conditions chosen resulted in substrate saturation of one of the enzymes in the succinate pathway to propionate.
The pharmacokinetics of some aminoglycoside antibiotics in the horse
Authors: BAGGOT J. D. , LOVE DARIA N. , ROSE R. J. , RAUS J.
Published: April 2008

The disposition kinetics and bioavailability of streptomycin, kanamycin and neomycin were determined following their administration as parenteral preparations to horses. Single doses (10 mg/kg) of each aminoglycoside were given by the intravenous (i.v.) and intramuscular (i.m.) routes and, at a later time, seven intramuscular doses were injected at 12‐h intervals. The pharmacokinetic behaviour of the three aminoglycosides was similar, in that a rapid distribution phase was followed by a relatively short half‐life. The half‐life (mean ± SD, n= 6) of kanamycin (1.80 ± 0.17 h) was significantly (P<0.01; t test, 10 d.f.) shorter than that of streptomycin (3.40 ± 0.42 h), while neomycin half‐life (2.10 ± 0.97 h) was of an intermediate length. The apparent volume of distribution of neither kanamycin nor neomycin varied significantly (P > 0.05) from that of streptomycin and numerically (V1 d = 230 ml/kg) was the same as the extracellular fluid volume. The body clearance of kanamycin (88.5 ± 11.3 ml/kg.h) was significantly (P < 0.01) larger than that of streptomycin (47.5 ± 7.9 ml/kg.h), while a significant difference in this parameter did not exist (P > 0.05) between neomycin and streptomycin. Following intramuscular injection, each aminoglycoside was rapidly and completely absorbed from the injection site, although neomycin showed wide individual variation in the fraction absorbed. The administration of multiple doses did not change either the bioavailability or the apparent half‐life from the values obtained after a single dose. The only pharmacokinetic difference between these aminoglycosides that is of clinical importance lies in the rate of their elimination. A dosage interval of 8 h would be appropriate for kanamycin compared with a 12‐h interval for streptomycin. The dosage interval for neomycin based on half‐life should be 8 h but, due to the relatively greater toxicity of this aminoglycoside, an interval of 12 h might be recommended. The height of the peak serum concentration is determined by the size of the dose.
A study on renal function in the Indian buffalo (Bubalus bubalis)
Authors: VARMA KANWAL J. , PAUL BALBIR S. , POWERS THOMAS E. , POWERS JEAN D.
Published: April 2008

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in buffalo species (Bubalus bubalis) were estimated using a single injection technique. The total body clearances of inulin and para‐aminohippuric acid (PAH) served as estimates of GFR and ERPF, respectively. Inulin and PAH were administered to animals as a single i.v. bolus. The time—concentration curves were determined for each compound. Three mathematical models were applied to the data. The two compartment model gave the best fit to the data. The single compartment model gave slightly higher values, but could be used in clinical and certain research situations to estimate renal functions when it is not practical to take large number of samples.
The reticular groove and drug absorption
Authors: COOKE R. G. , NICHOLSON T.
Published: April 2008

The young ruminant animal makes use of the reflex mechanism causing closure of the reticular (sometimes called oesophageal) groove to channel swallowed milk from the oesophagus to the omasal canal. Water drunk to satisfy thirst does not activate this reflex and therefore passes to the rumen. It has been known for a long time that the operation of the reticular groove reflex may persist to a varying degree in the adult ruminant (Schalk & Amadon. 1928), the variability of this response, and the factors affecting it, having been most thoroughly investigated and reviewed by Watson (1944)
Failure of naloxone to prevent the emetic activity of apomorphine in dogs
Authors: KEITH J. C. , WILSON R. C. , BOOTH N. H. , KEMPPAINEN R.J.
Published: April 2008

Apomorphine is derived from morphine by acid hydrolysis (DiChiara & Gessa, 1978), and for many years has been used in both human and veterinary medicine as an effective agent for induction of emesis, primarily in cases of poisoning. Since apomorphine is derived from morphine, it was initially thought that it was an opiate receptor agonist similar to morphine. As a result, several medical and veterinary medical pharmacology textbooks recommend reversal of the emetic activity of apomorphine hydrochloride by administration of naloxone hydrochloride, a narcotic antagonist (Klaassen, 1980; Meyers, Jawetz & Goldfien, 1980).