bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of estrogen receptor β in normal skin, melanocytic nevi and malignant melanomas
Authors: OHATA Chika , TADOKORO Taketsugu , ITAMI Satoshi
Published: April 2008

Sex hormones are known to be associated with increases of melanocytes and melanin production in human skin. However, the expression of estrogen receptor (ERα) in melanocytic lesions has been controversial. In 1996, a new subset of estrogen receptor was cloned, and named estrogen receptor β (ERβ). We used immunohistochemical staining to characterize the expression of ERα and ERβ in normal skin and in melanocytic lesions. Normal sebaceous glands and hair follicles were positive for ERα and ERβ. Other adnexal structures and constituents in the skin were positive for ERβ, but not for ERα. Melanocytic nevi and malignant melanomas were negative for ERα, but both were positive for ERβ. The ubiquitous expression of ERβ may play a fundamental role in various normal skin cells and melanocytic tumors.
Childhood and adolescent predictors of alcohol use and problems in adolescence and adulthood in the National Child Development Study
Authors: Maggs Jennifer L. , Patrick Megan E. , Feinstein Leon
Published: April 2008

Aims  To identify childhood and adolescent predictors of alcohol use and harmful drinking in adolescence and adulthood.

Design  Longitudinal data from childhood to mid‐life from the National Child Development Study (NCDS) were used, including predictors collected at ages 7, 11, 16 years and alcohol outcomes collected at ages 16, 23, 33 and 42 years.

Setting  The NCDS is an ongoing longitudinal study of a cohort of 1 week's births in Britain in 1958.

Participants  Childhood and adolescent predictors and alcohol use data from at least one adolescent or adult wave were available from 7883 females and 8126 males.

Measurements  Social background, family, academic and behavioural predictors measured at ages 7, 11 and 16 years were entered into hierarchical multiple and logistic regressions to predict quantity of alcohol use at ages 16, 23, and 33 years and harmful drinking [i.e. Cut‐down, Annoyed, Guilt, Eye‐opener (CAGE) questionnaire score] by age 42 years.

Findings  Previous drinking was controlled in final models to predict change. Drinking was heavier among those with greater childhood and adolescent social advantage (especially females), less harmonious family relationships, more social maladjustment, greater academic performance, less internalizing problems, more truancy and earlier school‐leaving plans.

Conclusions  Alcohol use and problems in adulthood can be predicted by indicators of social background, adjustment and behaviour in childhood and adolescence. Results demonstrate that the early roots of adolescent and adult alcohol use behaviours begin in childhood.
Clinical decision‐making: predictors of patient participation in nursing care
Authors: Florin Jan , Ehrenberg Anna , Ehnfors Margareta
Published: April 2008

Aim.  To investigate predictors of patients’ preferences for participation in clinical decision‐making in inpatient nursing care.

Background.  Patient participation in decision‐making in nursing care is regarded as a prerequisite for good clinical practice regarding the person’s autonomy and integrity.

Design.  A cross‐sectional survey of 428 persons, newly discharged from inpatient care.

Methods.  The survey was conducted using the Control Preference Scale. Multiple logistic regression analysis was used for testing the association of patient characteristics with preferences for participation.

Results.  Patients, in general, preferred adopting a passive role. However, predictors for adopting an active participatory role were the patient’s gender (odds ratio = 1·8), education (odds ratio = 2·2), living condition (odds ratio = 1·8) and occupational status (odds ratio = 2·0). A probability of 53% was estimated, which female senior citizens with at least a high school degree and who lived alone would prefer an active role in clinical decision‐making. At the same time, a working cohabiting male with less than a high school degree had a probability of 8% for active participation in clinical decision‐making in nursing care.

Conclusions.  Patient preferences for participation differed considerably and are best elicited by assessment of the individual patient.

Relevance to clinical practice.  The nurses have a professional responsibility to act in such a way that patients can participate and make decisions according to their own values from an informed position. Access to knowledge of patients’ basic assumptions and preferences for participation is of great value for nurses in the care process. There is a need for nurses to use structured methods and tools for eliciting individual patient preferences regarding participation in clinical decision‐making.
Endocannabinoids and the Regulation of Bone Metabolism
Authors: Bab I. , Ofek O. , Tam J. , Rehnelt J. , Zimmer A.
Published: April 2008

In mammals, including humans, bone metabolism is manifested as an ongoing modelling/remodelling process whereby the bone mineralised matrix is being continuously renewed. Recently, the main components of the endocannabinoid system have been reported in the skeleton. Osteoblasts, the bone forming cells, and other cells of the osteoblastic lineage, as well as osteoclasts, the bone resorbing cells, and their precursors, synthesise the endocannabinoids anandamide and 2‐arachidonoylglycerol (2‐AG). CB1 cannabinoid receptors are present in sympathetic nerve terminals in close proximity to osteoblasts. Activation of these CB1 receptors by elevated bone 2‐AG levels communicates brain‐to‐bone signals as exemplified by traumatic brain injury‐induced stimulation of bone formation. In this process, the retrograde CB1 signalling inhibits noradernaline release and alleviates the tonic sympathetic restrain of bone formation. CB2 receptors are expressed by osteoblasts and osteoclasts. Their activation stimulates bone formation and suppresses bone resorption. CB2‐deficient mice display a markedly accelerated age‐related bone loss. Ovariectomy‐induced bone loss can be both prevented and rescued by a CB2 specific agonist. Hence, synthetic CB2 ligands, which are stable and orally available, provide a basis for developing novel anti‐osteoporotic therapies, free of psychotropic effects. The CNR2 gene (encoding CB2) in women is associated with low bone mineral density, offering an assay for identifying females at risk of developing osteoporosis.
Endogenous Cannabinoids: Structure and Metabolism
Authors: Bisogno T.
Published: April 2008

The finding of specific binding sites for Δ9‐tetrahydrocannabinol, the psychoactive component of Cannabis sativa, has led to the discovery of the endocannabinoid system and has emphasised the physiological and pathological relevance of endocannabidoid lipid signalling. Subsequently, an increasing number of papers have been published on the biochemistry and pharmacology of endocannabinoids. An overview of the current understanding of structure and metabolism of the best studied endocannabinoids is provided, with a focus on the mechanisms responsible for their biosynthesis and inactivation.
The Cannabinoid System and Male Reproductive Functions
Authors: Rossato M. , Pagano C. , Vettor R.
Published: April 2008

Cannabinoids, the main active components of marijuana, have been shown to exert different adverse effects on male reproduction both in vertebrates and invertebrates. In vivo, cannabinoids exert negative effects on hypothalamic–hypophyseal reproductive hormone secretion and testicular endocrine and exocrine functions. Furthermore, a large amount of experimental data obtained in vitro have clearly shown that cannabinoids negatively influence important sperm functions, including motility and acrosome reaction, two fundamental processes necessary for oocyte fertilisation. These inhibitory effects are mediated by the direct action of cannabinoids on sperm through the activation of the cannabinoid receptor subtype CNR1 that has been shown to be expressed in mature sperm. In the present paper, we briefly review the effects of cannabinoids and endocannabinoids, a particular group of endogenously produced cannabinoids, on male reproductive function.
Cannabinoid Type 1 Receptor: Another Arrow in the Adipocytes’ Bow
Authors: Bellocchio L. , Cervino C. , Vicennati V. , Pasquali R. , Pagotto U.
Published: April 2008

The endocannabinoid system has recently emerged as an important modulator of several functions of adipose tissue, including cell proliferation, differentiation and secretion. Here, we will review the effects of cannabinoid type 1 (CB1) receptor activation/blockade in adipocytes by summarising the data in the literature since the discovery of the presence of this receptor in adipose tissue. We will also discuss our original data obtained in mouse 3T3‐L1 adipocyte cells using WIN55 212, a CB1/CB2 receptor agonist and SR141716 (rimonabant), a specific CB1 receptor antagonist, respectively, in different experimental settings.
A Saturated N‐Acylethanolamine Other than N‐Palmitoyl Ethanolamine with Anti‐inflammatory Properties: a Neglected Story…
Authors: Dalle Carbonare M. , Del Giudice E. , Stecca A. , Colavito D. , Fabris M. , D’Arrigo A. , Bernardini D. , Dam M. , Leon A.
Published: April 2008

N‐acylethanolamines, which include the endocannabinoid anandamide and the cannabinoid receptor‐inactive saturated compounds N‐palmitoyl ethanolamine and N‐stearoyl ethanolamine, are ethanolamines of long‐chain fatty acids degraded by fatty acid amide hydrolase (FAAH) known to accumulate in degenerating tissues and cells. Whilst much evidence supports a protective anti‐inflammatory role of both anandamide and N‐palmitoyl ethanolamine, very little information is available with regard to the bioactivity of N‐stearoyl ethanolamine. Employing a murine model of passive IgE‐induced cutaneous anaphylaxis, we have found that N‐stearoyl ethanolamine is endowed with marked anti‐inflammatory properties in vivo, supporting the hypothesis that endogenous N‐stearoyl ethanolamine is, in analogy to N‐palmitoyl ethanolamine, a bioactive signalling lipid capable of downregulating allergic inflammation in the skin. This effect, although mimicked by synthetic, non‐selective, CB1/CB2 receptor agonists, such as WIN55, 212‐2, was not sensitive to CB1 or CB2 receptor antagonists, but rather was fully reversed by capsazepine, a competitive antagonist of the TRPV1 receptor. Moreover, CB1 receptor antagonists, although effective in antagonising the WIN55,212‐2‐induced hypothermia, did not reduce the anti‐inflammatory effect of WIN55,212‐2, whilst CB2 receptor antagonists, per se inactive, potentiated the WIN55,212‐2 effect, suggesting an involvement of non‐CB1/CB2 receptors in the anti‐inflammatory action of WIN55,212‐2. All this, together with demonstration of FAAH as a major regulator of the in vivo concentrations of saturated N‐stearoyl ethanolamine, in addition to N‐palmitoyl ethanolamine, raise the speculation that pharmacological treatments with saturated N‐acylethanolamines such as N‐stearoyl ethanolamine, or alternatively FAAH inhibitors able to increase their local concentration, rather than selective CB receptor agonists, might be of promising therapeutic benefit in reducing allergic inflammation in the skin.
Endocannabinoids, Adipose Tissue and Lipid Metabolism
Authors: Pagano C. , Rossato M. , Vettor R.
Published: April 2008

Endoannabinoids regulate energy balance by modulating hypothalamic circuits controlling food intake and energy expenditure. However, convincing evidence has accumulated indicating that the endocannabinoid system is present also in peripheral tissues, in particular in adipose tissue. Fat cells produce (and are targets of) endocannabinoids. Adipogenesis, lipogenesis and glucose uptake are stimulated by endocannabinoids through CB1 receptors and these effects are blocked by the CB1 receptor antagonist rimonabant, suggesting that the weight‐lowering effect of CB1 receptor blockade is partly due to peripheral mechanisms. This review will focus on the role of endocannabinoids in adipose tissue metabolism, adipokine production and interactions between endocannabinoids and peroxisome proliferator activated receptors during adipogenesis.
Sulphadoxine and trimethoprim in goats and cows: absorption fraction, half‐lives and the degrading effect of the ruminal flora
Authors: NIELSEN POUL , ROMVARY ATTILA , RASMUSSEN FOLKE
Published: April 2008

Oral administration of sulphadoxine to adult goats (100 mg/kg body weight) resulted in absorption of about two thirds from the gastrointestinal tract. The absorption rate was lowest in newborn kids and increased with increasing age. Following administration of sulphadoxine (40 mg/kg body weight) through a rumen fistula about 80% was absorbed in cows. Also the elimination rate for sulphadoxine was lower in newborn kids than in adult goats and increased with the age. Oral administration of the trimethorpim (TMP) to kids, goats (20 mg/kg body weight) and cows (8 mg/kg body weight) resulted in higher plasma concentrations in newborn kids than in the older age groups and the maximal concentration of TMP in the blood of adult goats and cows was lower than 0.2 μg/ml. In vitro experiments showed that trimethoprim may be degraded by ruminal microorganisms, but from experiments with oral administration of trimethoprim to cows it is concluded that metabolism in the cow's liver is at least as important as ruminal degradation.
Neuromuscular blocking effects of certain antibacterial agents in pigs and lambs
Authors: MATHEW BABU P. , TESKE RICHARD H. , ROBINSON JEAN A. , ADAMS H. RICHARD
Published: April 2008

The neuromuscular blocking effects of several antibacterial agents were examined in young pigs and lambs using a sciatic nerve‐gastrocnemius muscle preparation. Intravenous administration of streptomycin, neomycin or tetracycline produced a decrease in indirectly stimulated contractions of the gastrocnemius muscle; whereas, chloramphenicol, sulphadiazine and penicillin‐G had no discernible neuromuscular blocking effects. Present findings confirm the neuromuscular blocking activity of certain antibiotic agents, and indicate the potential for this adverse side effect in food‐producing animal species.
The disposition and excretion of ethanol by the horse
Authors: CHAPMAN D. I. , RUDRAM D. A.
Published: April 2008

The disposition and excretion of ethanol in horses has been studied after oral administration. Ethanol was rapidly absorbed from the gastrointestinal tract. The highest concentration of ethanol in blood and in parotid saliva occurred within 1 h of administration. The concentrations were dose dependent. The mean rate of disappearance of ethanol from blood was 6.3 mg/100 ml/h. The ratio of the concentration of ethanol in parotid saliva to that in venous blood was 1.16:1. The mean rate of elimination was 51 mg/kg body weight/h. The proportion of ethanol excreted in the urine was 0.7% of the dose.
Pharmacokinetic studies of phenylbutazone in cattle
Authors: EBERHARDSON BO , OLSSON GERT , APPELGREN LARS‐ERIK , JACOBSSON STEN‐OLOF
Published: April 2008

The disposition kinetics and systemic availability of phenylbutazone were studied in healthy dairy cows. The same dose (6mg/kg) of phenylbutazone was administered by the i.v., i.m. and oral routes. The elimination half time after intravenous administration ranged from 32.4 to 60.8h. The result suggested that the distribution of phenylbutazone in cows can be described by a two‐compartment open model. Total body clearance of the drug had a mean value of 0.0016 ml/kg‐h. The overall tissue to plasma level ratio (k12/k21‐β), after distribution equilibrium had been attained was 0.64. Phenylbutazone was shown, by an equilibrium dialysis method, to be highly bound to plasma proteins (93%) at serum levels of 100 μ/ml. The systemic availability of phenylbutazone was 69% and 89% when administered orally and intramuscularly respectively. Animals receiving half the dose of phenylbutazone (3 mg/kg) intravenously did not differ from cows receiving 6 mg/kg in elimination half‐life and other distribution and elimination kinetic parameters. Based on the experimental data obtained, a dosage regimen is proposed, consisting of a priming oral dose of 9 mg/kg and maintenance doses of 4.5 mg/kg of phenylbutazone orally administered at 48 h intervals. The relatively long half‐life in cattle, however, complicates the use of phenylbutazone because of the drug residue problem.
The influence of the rumen on the absorption of drugs: studies using meclofenamic acid administered by various routes to sheep and cattle
Authors: MARRINER S. , BOGAN J. A.
Published: April 2008

As part of a general study of the pharmacokinetics of drugs in the ruminant animal, the absorption and distribution kinetics of meclofenamic acid between the gastro‐intestinal tract and plasma of sheep and cattle were investigated. Meclofenamic acid is a non‐steroidal anti‐inflammatory drug which has been shown to possess anti‐anaphylactic activity in cattle (Aitken & Sanford, 1969; 1972; Wells, Eyre & Lumsden, 1973) and sheep (Alexander, Eyre, Head & Sanford, 1970) and although marketed only for the horse in the United Kingdom (Arquel, Warner‐Lambert) is known to be used in ruminant animals as an anti‐inflammatory drug, for its inhibitory effects on prostaglandin synthesis (Smith G. G. A. 1977, personal communication) and for its anti‐pyretic action (Van Miert, Van der Wal‐Komproe & Van Duin, 1977). The aims of the study were first to evaluate the contribution of reticular (oesophageal) groove closure in directing orally administered drug directly to the abomasum and to assess the rate of absorption through the ruminal epithelium. Second, since Aitken & Sanford (1975) have described the plasma levels of meclofenamate after administration of sodium meclofenamate to cattle by the oral, intravenous and intra‐ruminal routes, it was decided to complement their study and to measure the plasma levels after intra‐muscular injection of sodium meclofenamate. This route is more convenient in cattle than the oral and intravenous routes examined by them. Lastly, the biphasic pattern of plasma levels of meclofenamate observed by Aitken & Sanford (1975) following oral administration of sodium meclofenamate to cattle was further examined using weaned and unweaned calves in an attempt to confirm their view that some of the drug is delivered to the abomasum directly, by‐passing the rumen, by closure of the reticular groove.
Plasma chloramphenicol concentrations in cats after parenteral administration of chloramphenicol sodium succinate
Authors: WATSON A. D. J.
Published: April 2008

Five cats were dosed on five occasions with 20 mg chloramphenicol/kg body weight. The drug was given three times as chloramphenicol sodium succinate (by intravenous, intramuscular and subcutaneous injections) and twice as crystalline chloramphenicol in capsules. Plasma chloramphenicol concentrations were determined at fixed intervals after administration. Parenteral injection of the ester usually produced highest plasma levels at the initial sampling, 0.5 h after dosing. When capsules were given, there was greater variation between cats: highest plasma levels were recorded usually at 0.5‐2 h after dosage but delayed absorption was evident in some cases. There were no statistically significant differences between the different routes with regard to mean plasma antibiotic levels at each sampling or mean area under the curve of plasma level versus time, except that mean plasma levels at 0.5 h were higher with intravenous or intramuscular injection than with oral administration.
Pharmacokinetics and urinary excretion of sulphadimidine in sheep and goats
Authors: NAWAZ MUHAMMAD , KHAN F. H.
Published: April 2008

Pharmacokinetics and urinary excretion of sulphadimidine were determined in sheep and goats following a single intravenous injection (100 mg/kg). The disposition of the drug was described in terms of exponential expression: Cp=Be‐βt. Based on total (free and bound) sulphonamide level in plasma, pseudo‐distribution equilibrium was rapidly attained and the half‐life for elimination was 3.88 ± 0.64 h and 4.00 ± 0.34 h in sheep and goats, respectively. Body clearance, which is the sum of all clearance processes was 88 ± 19 and 55 ± 4 ml/kg/h in sheep and goats. Based on this study a satisfactory intravenous dosage regimen might consist of 100 and 60 mg sulphadimidine/kg body wt for sheep and goats and should be repeated at 12 h intervals. The influence of disease conditions on predicted plasma levels remain to be verified experimentally. Three‐quarters of an intravenously injected dose of sulphadimidine was excreted in the urine of sheep and goats within 24 h of administration. The drug was mainly excreted as free amine while acetylated drug constituted 7 and 8% of total drug content in the urine of sheep and goats, respectively.
The selection of prostaglandin‐F2α analogues for luteolysis in cattle
Authors: VRIES H. DE , FEENSTRA H.
Published: April 2008

The effects of newly synthesized PG‐F2α analogues, mainly belonging to the 13‐thia‐ and Δ 9, 10‐analogues, were investigated using the isolated rate uterus test, the pregnancy interruption test in rats and the pregnancy interruption test in hamsters. The luteolytic action was investigated in cattle. Several compounds were many times more active than PG‐F2α. There appeared to be a differentiation between luteolytic and uterotonic potency in the test models used. Some compounds appeared to be good candidates for veterinary clinical use. One compound demonstrated a good luteolytic effect in lactating cows.
Pharmacokinetics of sulphadoxine and trimethoprim in horses. Half‐life and volume of distribution of sulphadoxine and trimethoprim and cumulative excretion of [14C]‐trimethoprim
Authors: RASMUSSEN FOLKE , GELSÅ HANS , NIELSEN POUL
Published: April 2008

A proprietary combination product containing sulphadoxine and trimethoprim was administered to horses by intravenous injection. Protein‐binding of sulphadoxine was dependent on the concentration in plasma and decreased from 72% at 50 μg/ml to 14% at 450 μg/ml. Sulphadoxine is eliminated from plasma in accordance with a three compartment open model. The elimination half‐life was on average 14 h while the volume of distribution was found to be 0.39 1/kg. Trimethoprim was eliminated from plasma in accordance with a two compartment open model. The elimination half‐life was on an average 3 h. Experiments in which trimethoprim was administered alone showed that the elimination half‐life was not dependent on the simultaneous administration of sulphadoxine. About 50% of trimethoprim was bound to plasma proteins, but in contrast to sulphadoxine there was no dependence between plasma concentration and protein binding. The protein binding of trimethoprim was independent of the presence of sulphadoxine and vice versa. Experiments with 14C‐labelled trimethoprim showed that it was excreted in almost equal amounts in urine and faeces. 97% of the administered dose was recovered in urine and faeces during the course of the first 4 days after administration.
Susceptibility of clinical isolates of Pseudomonas aeruginosa to antimicrobial agents
Authors: HIRSH DWIGHT C. , WIGER NINA , KNOX SUSAN J.
Published: April 2008

One hundred and eighteen isolates of Pseudomonas aeruginosa obtained from clinical material were tested for susceptibility to antimicrobial agents. Regardless of species of animal from which the isolate was obtained, 75% of the isolates were inhibited by ≤ 4 μg of gentamicin/ml, 100% by ≤ 4 μg of tobramycin/ml, 97% by ≤ 128 μg of carbenicillin/ml, and 2% by ≤ 64 μg of chloramphenicol/ml.
Force plate studies on the effect of exogenous hyaluronic acid on joint function in equine arthritis
Authors: GINGERICH D. A. , AUER J. A. , FACKELMAN G. E.
Published: April 2008

A pressure sensitive force plate was used to measure the degree of lameness in arthritic horses as a test system for studying the effect of exogenous hyaluronic acid on joint function. Intra‐articular injection of hyaluronic acid resulted in a measurable reduction of lameness in experimentally induced osteoarthritis and septic arthritis as well as in naturally occurring equine osteoarthritis.
The role of calcium in the mechanical performance of cattle ruminal muscle
Authors: BÜRGIN H.
Published: April 2008

A viable preparation from the external muscle coat of cattle rumen for in vitro studies of contractility is described. The threshold Ca2+ concentration for contractile response in glycerol treated ruminal muscle was found to be pH dependent. At physiological pH it is situated between 10‐8 and 10‐7 M. Strips with intact membranes were studied in the depolarized state. In this preparation contraction to acetylcholine or histamine requires Ca2+ in the medium. However, contractility persists for several minutes in Ca2+‐free solution at rest but disappears rapidly during stimulation. Recovery in a Ca2+‐containing medium is much faster than the decline of responsiveness in a Ca2+‐free medium. Tetracaine and D600 seem to inhibit contraction by blocking release of Ca2+ from and uptake of Ca2+ into hypothetical Ca stores inside the cell. The results are interpreted by assuming cellular Ca stores and two Ca pumps, one extruding Ca2+ into the medium and one accumulating Ca in the stores. Acetylcholine and histamine act by increasing Ca2+ permeability of both the membranes of the stores and the plasma membrane. The stimulator‐induced and possibly the resting Ca2+ permeability in the depolarized state is reduced by tetracaine and D600 at both sites. The pumps are assumed not to be affected by stimulators and the mentioned drugs.
Pharmacokinetic disposition and plasma protein binding (in vitro) of chloramphenicol in Bubalus bubalis I*
Authors: VARMA K. J. , PAUL B. S. , GUPTA R. C.
Published: April 2008

Eleven buffalo calves (Bubalus bubalis) of 1‐1 1/2 years of age and weighing between 64 and 174 kg were given chloramphenicol at the dose rates of 10 and 20 mg/kg body weight. Pharmacokinetic parameters were determined from the plasma levels. The median elimination half‐life was estimated to be 2.95 h and the median volumes of distribution were 1.1667 litres/kg with the 10 mg/kg dose and 0.9699 litres/kg with the 20 mg/kg dose. The median metabolic clearance rates were 288.30 and 234.13 ml/h/kg, respectively. From the average plasma concentrations obtained with the 20 mg/kg i.v. dose, it was considered necessary to repeat the drug by the i.m. route with the same dose (four calves) which resulted in prolonging the therapeutic concentration (> 5 μg/ml) until 18 h. At therapeutic concentrations, about 60% of the drug was bound to plasma proteins. Using the overall elimination rate constant (0.2354 h‐1) and the apparent specific volume of distribution (0.97 litres/kg), different dosage regimens were calculated so as to obtain plasma concentrations (Cp min) of 2, 5 and 10 μg/ml.
Pharmacokinetics of chloramphenicol in Chinese spot‐billed ducks (Anas poecilorhyncha)*
Authors: DEIN F. JOSHUA , MONARD DRU F. , KOWALCZYK DAVID F.
Published: April 2008

The pharmacokinetic behavior of chloramphenicol in Chinese spot‐billed ducks (Anas poecilorhyncha) was investigated. Single doses of chloramphenicol were given by the intravenous (22 mg/kg), intramuscular (22 mg/kg), and oral route (55 mg/kg) to six, seven and six ducks, respectively. Serum samples were collected at various times and analyzed for chloramphenicol by a radio‐enzymatic procedure. The time—concentration curves after intravenous administration were described by one‐compartment kinetics. The mean half‐lives for the intravenous, intramuscular, and oral route were 102.5, 104.5 and 151.4 min, respectively. There was little individual variation in the time—concentration plots for either the intravenous or intramuscular route. However, following oral administration, there was considerable individual variation indicating erratic absorption. From the intravenously derived, pharmacokinetic parameters, dosage regimens applicable to either the intravenous or intramuscular route, were developed.
A pharmacokinetic basis for the administration of digoxin to puppies
Authors: BUTTON C. , GROSS D. R.
Published: April 2008

The pharmacokinetics of digoxin were investigated in five 15‐day‐old puppies. Following administration of 30 μg/kg digoxin intravenously, multiple serum samples were collected and assayed by radioimmunoassay. Data was analysed by non‐linear least squares regression analysis.

The mean biological half‐life of digoxin in puppies was 22.7 h and the mean volume of distribution by extrapolation was 14.4 litres/kg. The data collected along with data from the literature was applied to standard pharmacokinetic equations to formulate tentative doses of digoxin. The maintenance doses calculated for puppies were, in μg/kg/24 h, 15 for the intravenous injection, 18 for the pediatric elixir and 22 for the tablet.

When the above doses of digoxin were administered to six 31‐day‐old Beagle pups, resultant plasma digoxin concentrations measured over 12 days were mostly lower than expected but were nevertheless within the proposed therapeutic, non‐toxic range of 0.5 to 2.5 ng/ml.
Effects of sodium acetate, bicarbonate and lactate on acid‐base status in anaesthetized dogs
Authors: HARTSFIELD SANDEE M. , THURMON JOHN C. , CORBIN J. E. , BENSON G. JOHN , AIKEN T.
Published: April 2008

Equal doses of sodium acetate, bicarbonate and lactate (6.6 mEq/L) infused intravenously over 30 min into three groups of halothane‐anaesthetized dogs caused changes in acid‐base status. Arterial carbon dioxide tension (PaCO2), pHa, base excess (BE) and standard bicarbonate (SB) increased. Sodium bicarbonate caused the most rapid and greatest changes. The bicarbonate group was significantly different (P<0.05) from the other groups at 15 and 30 min after the start of infusion for pHa, BE and SB. The greater effects of bicarbonate are due to its production of alkalinization without a requirement for metabolism; acetate and lactate require oxidation to be effective. The acetate and bicarbonate groups were not statistically different at 45 min after the onset of drug infusion, but both had significantly higher SB and BE mean values than the lactate group. AH measurements made after 45 min revealed no significant differences among groups. Thus, after the earlier differences noted above, the three alkalinizers caused similar effects on acid‐base status. PaCO2 was elevated in all groups, but there were no differences among groups. Cardiovascular effects caused by infusion of the three drugs were minimal.
Some pharmacokinetic and biochemical aspects of sulphadiazine and sulphadimidine in ewes
Authors: YOUSSEF S. ABDEL HAMID , EL‐GENDI A. Y. I. , EL‐SAYED M. G. A. , ATEF M. , SALAM S. A. ABDEL
Published: April 2008

Eight experiments were carried out on eight clinically healthy non‐pregnant ewes. Each animal was injected intravenously with either sulphadiazine or sulphadimidine at a dose rate of 100 mg/kg body weight. A two‐compartment pharmacokinetic model was developed to describe the disposition of these drugs. The elimination half‐lives were 7.15 ± 0.58 h and 9.51 ± 0.59 h and the distribution half‐lives were 0.56 ± 0.07 h and 0.42 ± 0.05 h for sulphadiazine and sulphadimidine, respectively. The apparent specific volumes of distribution were less than 1 litre/kg (0.410 and 0.501 litres/kg for sulphadiazine and sulphadimidine, respectively) which indicates a relatively lower distribution of these drugs to tissues than in plasma in sheep. The degree of plasma protein binding was similar for both drugs (19.15 ± 0.55% and 23.12 ± 0.32%) for sulphadiazine and sulphadimidine, respectively). Serum concentrations of ketone bodies, total lipids and calcium were significantly reduced, and blood glucose concentration significantly increased following administration of both of these sulphonamides, whilst serum total protein concentration was unaltered. The serum cholesterol concentration was significantly reduced following sulphadiazine administration, but not after sulphadimidine.
Xylazine‐induced mydriasis: possible involvement of a central postsynaptic regulation of parasympathetic tone
Authors: HSU W. H. , BETTS D. M. , LEE P.
Published: April 2008

Intravenous injection of xylazine (0.01 – 1 mg/kg) produced a dose‐dependent mydriasis associated with a depression of tonic ciliary nerve activity in anesthetized cats. Xylazine‐induced mydriasis was apparent in the sympathectomized iris but was absent in the parasympathectomized, physostigmine‐treated iris. Epinephrine (30 μg/kg, i.v.) produced a slighdy greater mydriasis in the sympathectomized iris than in the parasympathectomized, physostigmine‐treated iris. The α2‐adrenergic blocking agent, yohimbine (0.5 mg/kg, i.v.) antagonized the pupillary dilation and reversed the depression of ciliary nerve activity induced by xylazine administration.

In rats pretreated with reserpine (7.5 mg/kg, s.c., 20 h) and α‐methyl‐p‐tyrosine (250 mg/kg, i.p., 5 h), intravenous injection of xylazine (0.01 – 1 mg/kg) resulted in mydriasis of similar magnitude as control animals. However, xylazine induced bradycardia in the control group but not in die pretreated animals.

The results suggest that pupillary dilation produced by i.v. xylazine is primarily die result of a central inhibition of parasympathetic tone to the iris. It also appears that xylazine produces this effect via postsynaptic α2‐adrenergic mechanisms, while it produces bradycardia through a presynaptic α2‐adrenergic mechanism.
Digoxin‐quinidine interaction in the dog
Authors: RICK A. DE , BELPAIRE F.
Published: April 2008

In seven healthy dogs, digoxin was given as an oral loading dose (0.05 mg/kg/day) on the first day, followed by an oral maintenance dose (0.02 mg/kg/day) during the next 14 days. On the sixth day of digoxin treatment, oral quinidine (200 mg b.i.d.) was added until the tenth day. Plasma concentrations of digoxin and quinidine were measured; in three of the seven dogs ECG and physical signs of digitalis toxicity were evaluated. The average steady state plasma concentration of digoxin increased significantly (P<0.01) during quinidine administration (from 1.4 to 2.3 ng/ml). On the days that digoxin was administered without quinidine, none of the dogs vomited nor was anorectic; the PQ‐interval increased significantly (P<0.01) between 0.01 and 0.03 s. When quinidine was added, vomiting and anorexia occurred but no further increases in die PQ‐interval were seen.
Pharmacokinetics of theophylline in swine: a potential model for human drug bioavailability studies
Authors: KORITZ G. D. , BOURNE D. W. A. , HUNT J. P. , PRASAD V. I. , BEVILL R. F. , GAUTAM S. R.
Published: April 2008

The pharmacokinetics of theophylline in swine were investigated following die oral and intravascular administration of single doses of theophylline free base. The mean half‐life of theophylline following intravascular administration was 11.0 h, and the apparent specific volume of distribution was 0.61 liter/kg. Following oral administration, theophylline in solution was absorbed quite rapidly with a bioavailability of 79%. The similarity of the pharmacokinetics of theophylline in swine and humans suggests that swine may provide a useful model for the study of the bioequivalency of theophylline dosage forms intended for human use. The pharmacokinetic characteristics of theophylline also favor its consideration for usage as a therapeutic agent in swine.
The pharmacokinetics and tissue levels of polymyxin B, colistin and gentamicin in calves
Authors: ZIV G. , NOUWS J. F. M. , VAN GINNEKEN C. A. M.
Published: April 2008

Following a single intravenous injection of polymyxin B, colistin (5 mg/kg, each) and gentamicin (3 mg/kg) to calves, the decline in serum antibiotic concentration generally suggested a three‐compartment (open system) pharmacokinetic model. Tissue binding is a dominant factor in the distribution and elimination kinetics of the drugs. Less than 65% of the dose of polymyxin B and colistin was recovered in the urine during 48 h after treatment. Concentrations of nonbound polymyxin B and colistin in the kidney, liver, lung, heart, and skeletal muscles were similar to total (free and bound) serum drug levels, but considerably higher concentrations were found, in bound form, in chloroform‐ethanol extracts of these organs.

At 24 h after treatment, more than 50% of the doses of polymyxin B and colistin were present bound to the tissues; the largest amount was in the skeletal muscles. Gentamicin was concentrated in the kidney, predominantly in the free form. At 48 h after treatment the amount of gentamicin in the kidney was 6.3% of the administered dose, being more than five times greater than the corresponding amounts of polymyxin B and colistin.

The extent of tissue uptake of polymyxin B and colistin limits the usefulness of kinetic values, which are derived from the analysis of serum drug levels, for the purpose of designing dosage schedules. The strong affinity of the polymyxins to the muscle tissue, and gentamicin to the kidney, can result in drug residues persisting in the body for several weeks.
Autonomic and autacoid activity in antigen‐sensitized and control ovine pulmonary vein and artery
Authors: MIRBAHAR K. B. , EYRE P.
Published: April 2008

Spirally cut strips of ovine pulmonary vein and artery were studied in isolated organ baths and their responses to selected autacoid and autonomic agents were compared. In addition blood vessels taken from horse plasma‐sensitized sheep were compared with their respective controls. Pulmonary vein and artery exhibited qualitative and quantitative differences in their autacoid and autonomic reactivity. Veins were more sensitive in responding with contractions to histamine (HIST) and carbachol (CARB) when compared with arteries. Responses of these vessels differed qualitatively to 5‐Hydroxytryptamine (5HT); phenylephrine (PE) and adrenaline (ADR): arteries responded with strong contraction and veins with relaxations. Isoproterenol (ISOP) effectively relaxed veins but was either without effect or produced 10%–15% relaxations of precontracted arterial strips. Phentolamine competitively antagonized ADR and PE‐induced contractile responses of arteries while on veins, ISOP and PE dose—response curves (DRCs) were shifted to the right in the presence of propranolol. Mepyramine inhibited venous and arterial responses to HIST.

Comparisons between sensitized and non‐sensitized sheep vasculature revealed a significant (P < 0.05) decrease in the activity of spasmolytic agonists on veins, i.e. relaxant actions of 5HT, PE and ISOP were significantly impaired. In addition the activity of 5HT to contract pulmonary artery was significantly (P < 0.05) increased when compared with controls. Present investigation suggests: (i) the predominance of H1‐histaminergic receptors in ovine pulmonary vasculature; (ii) the preponderance of α and β‐adrenergic receptors in pulmonary artery and vein, respectively; (iii) that antigenic sensitization exaggerates the pathological state by causing a decrease in spasmolytic activity with a parallel increase in spasmogenic activity.
Clinical pharmacology and pharmacokinetics of flumequine after intravenous, intramuscular and oral administration in pigeons (Columba livid)
Authors: DORRESTEIN G. M. , GOGH H. VAN , BUITELAAR M. N. , NOUWS J. F. M.
Published: April 2008

Dorrestein, G.M., Gogh, H. van, Buitelaar, M.N. & Nouws, J.F.M. Clinical pharmacology and pharmacokinetics of flumequine after intravenous, intramuscular and oral administration in pigeons (Columba livia). J. vet. Pharmacol. Therap. 6, 281–292.

The in‐vitro activity of flumequine against 157 strains of bacteria isolated from birds was determined. The minimum inhibitory concentration (MIC) of 96.3% of the Enterobacteriaceae, Proteus spp. and Yersinia pseudotuberculosis studied (n = 135) was ≤1 μg/ml. Pharmacokinetics of flumequine in pigeons (Columbalivia) was investigated after intravenous, intramuscular and oral administration. From the blood disappearance curves after i.v. bolus injection (10 mg/kg body weight) clearance rate, blood half‐time and distribution volume were calculated. The recovery of unchanged flumequine from the droppings in 24 h was 37 ± 10% of the administered dose. Flumequine was also given i.m. at two dose levels, 10 and 60 mg/kg body weight. The availability of flumequine as intact drug was 22 and 23%, respectively, in 24 h. Therapeutic blood levels were maintained for 4 and 10 h, respectively. After an oral dose of flumequine (60 mg/kg body weight) an availability of 6.7 ± 2.5% and a peak blood concentration of 2.68 ± 0.92 μg/ml at 2 h after administration were found. The recovery of unchanged flumequine from the droppings in 24 h was 1.55 ± 0.79% of the administered dose. With the exception of the i.m. dose of 10 mg/kg, all flumequine administrations made the pigeons vomit. It appears that blood concentrations below 3 μg/ml will not induce vomiting. On the basis of the present data, a dosage regimen for flumequine in pigeons of a priming dose of 30 mg/kg i.m., followed after 8 h by oral administration of 30 mg/kg, this dose being repeated every 8–12 h, would be expected to give blood concentrations between 1.44 and 2.88 μg/ml.
Comparison of pharmacokinetic parameters for two oxytetracycline preparations in pigs
Authors: XIA WENJIANG , GYRD‐HANSEN NILS , NIELSEN POUL
Published: April 2008

Pharmacokinetics of oxytetracycline (OTC) were studied in 10 pigs after administration of 20 mg/kg body weight of either a conventional (OTC‐C) or a long‐acting (OTC‐LA) preparation.

After intravenous administration of OTC‐C the elimination half‐life for OTC was 3.75 h, with approximately 75% of the dose being excreted in the urine in 1 week. Intramuscular (i.m.) injection of OTC‐C resulted in plasma peak values after 4 h, while OTC‐LA after i.m. administration produced the highest plasma levels within 1 h, although these were lower than with OTC‐C.

For both preparations the bioavailability after i.m. administration was 95–100% and about 70% of the dose was excreted in the urine during the first week.

With OTC‐C given i.m., plasma concentrations above 0.5 μg/ml were maintained for 28 h and with OTC‐LA for 35 h indicating a weak retard effect of the latter.

Pronounced tissue damage at the injection site was seen 1 and 2 weeks after the administration of OTC‐LA, while OTC‐C produced very little irritation. OTC could be found at the injection site for 2 weeks, the concentrations being higher for OTC‐LA than for OTC‐C.
Encapsulated forms of slow‐release dry cow products of rapidly absorbed antibiotics
Authors: LINDER C. , ZIV G.
Published: April 2008

The persistence of chloramphenicol, cephacetrile, and clindamycin in the udders of dry cows was studied after drying‐off therapy with salts of these antibiotics suspended in conventional oil bases. Antibiotic activity was not found in dry udder secretions collected 3–5 days after treatment. After equivalent doses of encapsulated formulations of chloramphenicol were suspended in the same oil bases and infused at drying‐off, most of the drug remained bound within the microcapsules; chloramphenicol concentrations higher than 10 μg/ml secretion were maintained for 3–4 weeks, but upon release from the microcapsule, the free drug was very quickly absorbed from the udder. Microcapsulated formulations of cephacetrile and clindamycin were infused at drying‐off, suspended in the same type of oil base and at similar doses to the non‐capsulated preparations. The concentrations of free drug in the secretions remained constant over a period of 2–3 weeks, although total drug (bound and free) concentrations in the udder, which were much higher than free drug levels, were progressively and markedly reduced. It appeared that after infusion of the microcapsulated preparations of cephacetrile and clindamycin, rates of drug release from the depot were equal to the rates of absorption of free drug from the udder.
Dispersion of a fluorescein dye‐ampicillin mixture after intratracheal administration in calves
Authors: LONG PATRICIA E. , FURROW ROBERT D.
Published: April 2008

The pulmonary and systemic dispersion of a dye mixture after intratracheal (i.t.) administration was characterized in young dairy calves. Five calves were given i.t. injections of a fluorescein and ampicillin mixture, and were then killed at 2, 5 or 15 min after treatment. The respiratory system, nasal pharynx area, nose, liver, kidney, stomach and esophagus were removed and examined. Sections were taken from lung areas for histopathological examinations and all tissues were photographed, using floodlight and ultraviolet light. There was uniform low‐grade fluorescence throughout the lung, but the greatest fluorescence followed an anterior ventral dispersion. The dye was readily absorbed from the lung into the bloodstream, causing fluorescence in the liver, bile, kidney and urine. Coughing of the calves during the injection caused some of the mixture to be expectorated and swallowed, resulting in fluorescence in the esophagus, stomach contents, and nasal pharanges, turbinates and nostrils.
Pharmacokinetic analysis of plasma concentration and urinary excretion of sulphamonomethoxine and its metabolite in Goettingen minipigs
Authors: TSUBOI TAKAMITSU , KOKUE EI‐ICHI , SHIMODA MINORU , HAYAMA TOYOAKI
Published: April 2008

The plasma concentration and renal excretion after a bolus intravenous injection of a low (10 mg/kg) or high (100 mg/kg) dose of sulphamonomethoxine (SMM) were studied in five Goettingen minipigs. The time data of plasma concentration after a low dose decreased rapidly and appeared to be linear on semilog graph paper. On the other hand, a decrease in the plasma concentration after a high dose was slow at first, gradually accelerated, then became rapid, showing that SMM disposition after a high dose (100 mg/kg) seemed to be non‐linear with capacity‐limited elimination. A large amount of the acetyl derivative of SMM (AcSMM), which was determined to be the main excretory product of SMM in urine, was detected in the plasma after SMM injection. As the ratios of the area under plasma concentration‐time curve of AcSMM to that of SMM were not significantly different at either dose, the acetylation of SMM may be unsaturable by injection of 100 mg/kg of SMM. Immediately after the injection of a low dose, a rapid hyperbolic increase of the fraction of the cumulative amount of the excretory products in urine was observed. On the other hand, the fraction curve at the high dose rose slowly at first, then rapidly and hyperbolically. These results suggested that the non‐linear drug disposition after a high dose (100 mg/kg) of SMM in pigs may be the result of a limited capacity for renal excretion of SMM and excretory products, especially the acetyl derivative.