ISSN:0165-2176    

DOI:10.1080/01652176.2000.9695014

出版商:Taylor & Francis Group    

年代:2000

数据来源: Taylor

摘要:

Veterinary pharmacology has undergone a gradual development in the Netherlands during this century. Starting from a historical perspective the paper aims to provide an overview of future trends and important issues in the area of veterinary pharmacology and toxicology. It is pointed out that this discipline comprises several subdisciplines as the comparative aspect of both, pharmacology and toxicology, is inherent to veterinary medicine which has to address a broad variety of animal species. Thus, the comparison of drug effects, side effects, and drug disposition as well as the comparison of the species‐specific susceptibility to xenobiotics are obvious challenges in this discipline. Several areas in clinical pharmacology are highlighted to indicate future research needs. Finally, the principles of Good Veterinary Practice are presented as the ‘golden standard’ in veterinary clinical pharmacology.

ISSN:0165-2176    

DOI:10.1080/01652176.2000.9695015

出版商:Taylor & Francis Group    

年代:2000

数据来源: Taylor

摘要:

The selective control of inflammatory reactions will continue to be a major issue in the development of new drugs. Many new molecular targets are coming up. This paper highlights a few key mediators that are nowadays considered as interesting therapeutic intervention points. Cytokines play an important regulatory role in the initiation, maintenance and termination of inflammatory reactions. More than 50 cytokines have been identified, and more and more has become known about their receptors and signal transduction pathways. Tumour necrosis factor‐α (TNF‐α) is still regarded as one of the initial cytokines of the cascade, and different approaches are followed to control its synthesis, release or effects. Lipopolysaccharide (LPS) is a one of the triggers that is able to induce a strong TNF‐response. Inhibitors of cyclic nucleotide phosphodiesterases (PDEs), including rolipram and pentoxifylline suppress the LPS‐induced TNF‐α production in monocytes/ macrophages. In our laboratory it has been shown that the alternative way to increase cAMP levels, via stimulation of ß‐adrenergic receptors, also provides an effective way, bothin vitroandin vivo, to inhibit TNF‐α release. Other therapeutic ways include the use of antibodies directed to cytokines, TNF receptor fused to IgG, antibody therapy against TNF, the use of MAP kinase inhibitors. The different signal transduction pathways, including the NF‐κB activation route may provide alternative pharmacological tools.

ISSN:0165-2176    

DOI:10.1080/01652176.2000.9695016

出版商:Taylor & Francis Group    

年代:2000

数据来源: Taylor

摘要:

Diseases are a major cause of variation in drug response. Although many different diseases are known that have an effect on the pharmacokinetics or sometimes the pharmacodynamics of a drug, disorders associated with a so‐called acute phase response (APR) are the most important in this respect. During APR, for example caused by tissue damage or invasion of a pathogen, a group of symptoms can be observed that often include fever, lassitude, inhibition of gastric function and synthesis of acute phase proteins. All phases that together determine the pharmacokinetic profile of a drug, absorption, distribution, metabolism and excretion, can be affected during APR. From a clinical point of view however, the effects on absorption and metabolism are the most relevant. For drugs that are given orally, a slower absorption rate is often observed during APR due to a delayed gastric emptying. Even more important from a clinical point of view is the depression of biotransformation capacity in the liver during APR, especially affecting the enzymes of the cytochrome P450 (CYP450) complex. Although much has become known about the mechanism of this effect, a number of questions remain. Cytokines, nitric oxide and possibly the enzyme heme oxygenase are playing a role in a complex process that depends on a mutual interaction between Kupffer cells (macrophages) and hepatocytes in the liver. The clinician should be aware of unexpected changes in drug effects or residue levels due to cumulation of the compound during disease or after vaccination. In these situations, drugs that are excreted unchanged may be better alternatives.

ISSN:0165-2176    

DOI:10.1080/01652176.2000.9695017

出版商:Taylor & Francis Group    

年代:2000

数据来源: Taylor

摘要:

In this study primary hepatocyte cultures (HC cultures) and cocultures comprised of hepatocytes and Kupffer cells (HC/KC cocultures) were compared to investigate the inflammatory response induced by lipopolysaccharide (LPS). In addition both culture types were compared to study the hepatotoxic effects of two frequently used drugs: tiamulin and chlorpromazine.

ISSN:0165-2176    

DOI:10.1080/01652176.2000.9695018

出版商:Taylor & Francis Group    

年代:2000

数据来源: Taylor

摘要:

During infection and inflammation drug disposition and hepatic metabolism are markedly affected in mammals. Pro‐inflammatory mediators play an important role in the suppression of (cytochrome‐P450‐mediated) drug metabolism. Inflammatory mediators like cytokines, nitric oxide (NO), reactive oxygen species (ROS) and eicosanoids are released by activated macrophages from various sources, including liver and lung.

ISSN:0165-2176    

DOI:10.1080/01652176.2000.9695019

出版商:Taylor & Francis Group    

年代:2000

数据来源: Taylor

摘要:

It is well known that cattle ingesting aflatoxin B1contaminated feed commodities excrete aflatoxin M1into their milk. As aflatoxin M1originates from hepatic metabolism, measures to prevent aflatoxin M1formation need to be directed to either the immobilization of aflatoxin B1in the gastrointestinal tract or the modification of hepatic metabolism of aflatoxin B1. Here we studied the influence of oltipraz and a second dithiolthione, (1,2) dithiolo (4,3‐c)‐1,2‐dithiole‐3,6 dithione (DDD) on bovine hepatic aflatoxin B1biotransformation. Oltipraz inhibited aflatoxin B1metabolism as no aflatoxin M1and no aflatoxin B1‐dihydrodiol, the second metabolite found in bovine hepatocytes, was formed. DDD did not significantly inhibit aflatoxin B1metabolism. It could be demonstrated that the inhibition of aflatoxin B1metabolism was due to the inhibition of several cytochrome P450 enzyme activities by oltipraz. In contrast, DDD inhibited only ethoxyresorufinO‐deethylation activity. These findings suggest a high efficacy of oltipraz in inhibiting aflatoxin M1contamination of milk from dairy cows exposed to aflatoxin B1contaminated feeds.

ISSN:0165-2176    

DOI:10.1080/01652176.2000.9695020

出版商:Taylor & Francis Group    

年代:2000

数据来源: Taylor

摘要:

A stochastic simulation model to investigate the transmission of classical swine fever (CSF) virus within an infected farm is described. The model is structured according to the processes that occur within and between management groups (pig units or houses). It uses the individual pig as the unit of interest and estimates the number of animals in the states ‘susceptible’, ‘infected’, ‘infectious’, and ‘removed’ for each day of the disease incident. Probabilities are assigned to the transitions between states. The probability of a pig becoming infected is made dependent on the probability of contact between a susceptible and an infectious pig as well as the probability of transmission. The more pigs become infected in one unit, the more likely is subsequent spread to another management group on the farm. Ultimately, the probability that a shipment of pigs from the farm will include at least one infected pig can be estimated in order to identify high‐risk movements during a CSF epidemic. The model results were compared with experimental data on CSF transmission within one pig unit (management group). It could be shown that the model was capable of reproducing the experimentally observed infection and mortality rates. To improve the input parameters and for further model validation, more experimental data and field data from CSF outbreaks are needed.

ISSN:0165-2176    

DOI:10.1080/01652176.2000.9695021

出版商:Taylor & Francis Group    

年代:2000

数据来源: Taylor

摘要:

Disease‐induced variations of plasma albumin (ALB) and alph1‐acid glycoprotein (AAG) levels were investigated in dogs. Lower ALB (sometimes >50% reduction) and higher AAG (sometimes >10‐fold increase) levels were observed in dogs with various diseases. Drug binding was determined at therapeutic concentrations using normal, low‐ALB and high‐AAG dog plasma. The binding percentages of the ALB‐binding drugs decreased in low‐ALB plasma, resulting in a large increase in unbound drug, particularly for naproxen (a 13‐fold increase). The binding percentages of all AAG‐binding drugs investigated in this study increased in high‐AAG plasma, resulting in a large decrease in unbound drug, particularly for quinidine (99% decrease). The fluctuation in the unbound fraction of drugs could affect their efficacy or could cause side‐effects. Veterinary clinicians should monitor the ALB and AAG levels in the plasma of patients and correct dosage regimens according to these levels, where field conditions permit this, in order to ensure the proper usage of drugs with high affinity for ALB or AAG.

ISSN:0165-2176    

DOI:10.1080/01652176.2000.9695022

出版商:Taylor & Francis Group    

年代:2000

数据来源: Taylor

摘要:

Since visual observation is the most commonly used way of detecting oestrus and is supposed to be as effective as detection with technical devices, we evaluated a recently developed oestrus detection scoring system in daily dairy practice. In this scoring system nine signs of oestrus are scored with points, ranging 3 to 100.

ISSN:0165-2176    

DOI:10.1080/01652176.2000.9695023

出版商:Taylor & Francis Group    

年代:2000

数据来源: Taylor