Potential interactions between non-steroidal anti-inflammatory drugs and other drugs

Objective: The objective of this review is to summarize what is known in human and veterinary patients regarding the potential interactions of non‐steroidal anti‐inflammatory drugs (NSAIDs) with clinically important drugs. Data sources: Relevant articles as identified through searches of Medline, 1985 to present. Human data synthesis: Hemodynamic drug interactions are most likely to cause clinically relevant problems in humans, in which NSAIDs blunt the response to anti‐hypertensive agents and diuretics in patients with cardiovascular disease, or cause renal decompensation in patients with hypovolemia. In addition, NSAIDs enhance the ulcerogenic effects of glucocorticoids or other recently administered NSAIDs, and can increase bleeding from anti‐coagulant drugs or from herbs with platelet inhibitory activities. Veterinary data synthesis: Although there are numerous studies examining the safety and efficacy of various NSAIDs in healthy or arthritic dogs, there are very few studies that address the safety of these agents in veterinary patients receiving medication for other acute or chronic conditions. Conclusions: Based upon what is known in humans, more studies are needed in veterinary patients to assess the safety of NSAIDs in those animals being treated with anti‐hypertensive, diuretic or anti‐coagulant drugs.     

Macrolide antibiotics, drug interactions and microsomal enzymes: implications for veterinary medicine

The macrolide group of antibiotics includes natural members, pro-drugs and semi-synthetic derivatives, thus named because they are composed of a large aglycone ring (from 14 to 16 carbon atoms), to which are attached several sugars. Some of them are amino-sugars, containing a diethylamino, tertiary amine function. A number of antibiotics, including erythromycin, oleandomycin, triacetyl-oleandomycin (troleandomycin), carbomycin, spiramycin, tylosin, rosamicin, azithromycin, clarithromycin, dirithromycin and others, are members of this group. On a comparative basis, erythromycin and oleandomycin are similar, with the same basic 14-carbon lactone ring and side chain sugars. The remaining compounds contain a basic 15- or 16-carbon lactone ring and one or two side-chain sugars. Most of the macrolides are produced by Streptomyces spp bacteria. An exception is rosamicin, which is produced by Micromonospora. Clarithromycin and azithromycin are new semi-synthetic derivatives of erythromycin.     

GxE interactions for growth and carcass leanness: Re-ranking of boars in organic and conventional pig production

The objective of this study was to evaluate genotype by environment interactions for growth rate and carcass leanness in organic and conventional pig production environments. Organic breeding values for fattening traits were estimated for 37 Hampshire AI-boars based on slaughter records registered for 1805 crossbred offspring raised in an organic environment. The offspring were born and raised in herds certified for organic production. The statistical model included the fixed effects of sex, litter size at 2 weeks and herd. It also included the random effects of herd-year-season, birth litter and animal. Conventional breeding values for the same boars were captured from the breeding organization’s genetic evaluation. In the organic environment h² was estimated to 0.30 and 0.37 for growth rate and carcass leanness, respectively (r_g = − 0.11). Spearman rank correlations between organic and conventional breeding values, based on 29 boars with ≥ 20 progenies, were 0.48 for growth rate and 0.42 for carcass leanness. Both correlations were significantly different from 0 and 1. In conclusion, the results of the present study indicate weak genotype by environment interactions for both growth rate and carcass leanness in organic and conventional pig production environments, and there is some re-ranking of boars’ breeding values between environments.     

Alternatives to conventional antimicrobial drugs: a review of future prospects

BACKGROUND: Growing antimicrobial resistance poses the threat that before long no suitable drugs will be available for treatment of common infections. This review examines promising new strategies for treatment and control of microbial diseases, with an emphasis on staphylococcal infection. NEW DRUGS AND TARGETS: Advances in microbial genomics have provided tools identifying many new targets for antimicrobial drugs. Of particular interest amongst these are inhibition of microbial efflux pump activity, interruption or diversion of riboswitches controlling bacterial metabolism, and metagenomics, which allows analysis of genes from unculturable organisms. BIOLOGICAL APPROACHES: Advances are also being made in biological systems for disease control, with the exploitation of antimicrobial peptides to attack micro-organisms and modulate immune responses, and the use of bacteriophages or their lysins to eliminate bacteria. There are new approaches in the development and targeting of vaccines and immunoglobulin preparations based on advanced knowledge of microbial physiology and immunoregulation. WORKING WITH THE BIOME: With increasing recognition of the value of the normal microbiota in modulating immunity and the establishment of pathogens, there is growing interest in understanding the mammalian microbiome. Strategies are being developed to promote or maintain the normal microbiota, including the use of probiotics, and there is re-evaluation of the potential of bacterial interference. LOOKING AHEAD: Whilst these approaches are likely to generate new methods of disease control, few will yield usable products within the near future. There will be a continuing need for careful use of existing drugs based on firm diagnosis, rigorous hygiene and prudent antimicrobial stewardship.     

Adenosine receptor modulation: potential implications in veterinary medicine

Adenosine is a purine nucleoside whose concentration increases during inflammation and hypoxia and the many roles of this molecule are becoming better understood. Increased reactivity to adenosine of the airways of asthmatic but not of normal subjects underlines the role of adenosine in airway inflammation. The identification and pharmacological characterisation of different adenosine receptors have stimulated the search for subtype-specific ligands able to modulate the effects of this molecule in a directed way. Several compounds of different chemical classes have been identified as having potential drawbacks, including side effects resulting from the broad distribution of the receptors across the organism, have prevented clinical application. In this article, the effects of adenosine's different receptors and the intracellular signalling pathways are reviewed. The potential of adenosine receptor modulation as a therapeutic target for chronic airway inflammation is considered, taking equine recurrent airway disease and feline asthma as examples of naturally occurring airway obstructive diseases. Other potential applications for adenosine receptor modulation are also discussed. As the intrinsic molecular events of adenosine's mechanism of action become uncovered, new concrete therapeutic approaches will become available for the treatment of various conditions in veterinary medicine.     

New perspectives in cardiovascular medicine: the calcium channel blocking drugs

Calcium channel blocking drugs reduce the influx of calcium (Ca++) through cell membrane passageways in excitable tissues. This unique pharmacodynamic action represents an important new addition to cardiovascular therapeutics. Clinically available members of this diverse group of compounds are verapamil, nifedipine, and diltiazem. Beneficial responses to these drugs can be explained by vasodilatation and resulting hemodynamic improvement in tissue perfusion-oxygen demand relationships, by suppression of Ca++-dependent arrhythmogenic mechanisms, by direct reduction of pathologic Ca++ overload in ischemic injured cells, or by a combination of these effects. Calcium channel blockade already has become a therapeutic mainstay in human medicine for management of ischemic heart disease and some forms of cardiac dysrhythmias. Relative to veterinary medicine, Ca++ channel blocking drugs may provide a clinical option for controlling supraventricular tachyarrhythmias. Other indications might include obstructive cardiomyopathies, shock-trauma, and congestive heart failure. Importantly, however, essential issues about adverse cardiovascular side effects of Ca++ channel blocking drugs remain unresolved and controversial. Recent studies especially have raised questions about the tendency for Ca++ channel blockade to exacerbate preexisting or occult myocardial contractile failure. Such pharmacodynamic complexities should be assessed judiciously as the Ca++ channel blocking drugs are appraised for entry into veterinary internal medicine.     

The coxib NSAIDs: potential clinical and pharmacologic importance in veterinary medicine

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to control acute and chronic pain as well as to manage oncologic and neurologic diseases in human and veterinary patients. Despite ongoing research and efforts to improve the safety and efficacy of existing drugs, adverse effects such as gastrointestinal irritation, renal and hepatic toxicity, interference with hemostasis, and reproductive problems persist. The true incidence of NSAID-induced adverse effects in animals is unknown, but is likely underestimated, because cats and dogs may be more sensitive than humans to NSAIDs due to alterations in drug metabolism, absorption, and enterohepatic recirculation. NSAIDs produce both analgesia and toxic adverse effects primarily by inhibiting cyclooxygenase (COX), thereby decreasing the production of prostaglandins that signal inflammation and pain as well as mediate physiologic functions such as platelet aggregation, gastric protection, and electrolyte balance in the kidney. The presence of at least 2 COX isoforms may account for variability in NSAID efficacy and toxicity both within and among species. This paper reviews and evaluates the published literature on the safety, pharmacology, uses, and complications of a subclass of COX-1-sparing drugs, the coxibs, in veterinary medicine. Coxibs and other COX-1-sparing drugs provide a clinically useful improvement over traditional NSAIDs, but data are incomplete and more in vivo species-specific, target-tissue, and clinical studies are needed.     

Transesophageal echocardiography: principles, technique and potential indications in veterinary medicine

Transesophageal echocardiography (TEE) is a recent ultrasound technique using an endoscopic transducer to image the heart from within the esophagus. TEE avoids the anatomical structures that may affect the quality of the conventional transthoracic echocardiography. The quality of cardiovascular images obtained with TEE is therefore superior to transthoracic views. The potential indications of TEE in veterinary medicine include analysis of specific abnormalities (thrombosis, aneurism, cardiac tumors), cardiac monitoring during anesthesia or catheterization, and evaluation of cardiovascular surgical procedures.     

Defining and using behavioral competencies to manage performance and careers: potential applications and implications for veterinary medicine

Recent studies have highlighted concerns regarding the skills, career prospects, and economic prosperity of veterinarians. Human resource departments in a wide variety of organizations and industries have adopted a competency-based approach to managing the selection, training, placement, and ongoing development of their staff. This paper defines competencies, characterizes their typical use in industry, and examines the potential applications of a competency-based approach for veterinary medicine. It is argued that the competency-based approaches honed in the private sector promise to assist veterinary colleges, employers of veterinarians, and professional societies in influencing the state of the profession through the selection, education, and development of veterinarians.     

A review of neuroendoscopy and potential applications in veterinary medicine

The endoscope was first developed over 200 yr ago. Endoscopy has since been applied to many disciplines of medicine. Its application to the nervous system was initially slow and not widely accepted and mainly involved the biopsy of tumors and the treatment of hydrocephalus. Several reasons for neuroendoscopy's limited use include inadequate endoscope technology, high skill level required, the advent of the surgical microscope, and the development of other treatments such as ventricular shunting. Over the past 50 yr, improvements in optical glass lenses, fiber optics, and electrical circuitry has led to better equipment and a revival of neuroendoscopy. Neuroendoscopy is now used in many diseases in human medicine including hydrocephalus, neoplasia, and intracranial cysts. This review presents the history of neuroendoscopy, the equipment and technology used, and the possible translation of techniques currently used in human medicine to veterinary medicine.     

Maedi-visna virus, a model for in vitro testing of potential anti-HIV drugs

A series of beta-D- and beta-L-cytidine analogues were evaluated for their inhibitory effect on the replication of maedi-visna virus (MVV) strains KV1772 and MV1514 cultured on sheep choroid plexus cells and the sheep chondrocyte cell line G81092, respectively. Eleven cytidine analogues were selected for the anti-viral test. Five of them belong to the family of the 2',3'-dideoxycytidine analogues, well known for their activity against human immunodeficiency virus (HIV). The others, all newly synthesized, were potential anti-viral and/or anti-leukemic agents. None of the compounds under study had a toxic effect in both anti-viral assay systems up to a 300 microM concentration. Based on the cytopathic effects (CPE), the virus replication was completely inhibited by the five 2',3'-dideoxycytidine analogues at a concentration of 50 microM, whereas the others six newly synthesized compounds induced titre reductions of 4-5 log units. The effective concentration causing 50% reduction of CPE (EC50) was of 5 microM for the five 2',3'-dideooxycytidine analogues and for beta-L-XyloFc, whereas the value of 50 microM was found for the b-L-XyloC and the four 5-azacytidine compounds tested. All these data reveal a good correlation between inhibition of MVV replication by several nucleoside cytidine analogues and their reported anti-HIV activity.     

Pathophysiology of acute pancreatitis: potential application from experimental models and human medicine to dogs

The cellular events leading to pancreatitis have been studied extensively in experimental models. Understanding the cellular events and inciting causes of the multisystem inflammatory cascades that are activated with this disease is of vital importance to advance diagnosis and treatment of this condition. Unfortunately, the pathophysiology of pancreatitis in dogs is not well understood, and extrapolation from experimental and human medicine is necessary. The interplay of the inflammatory cascades (kinin, complement, cytokine) is extremely complex in both initiating leukocyte migration and perpetuating disease. Recently, nitric oxide (NO) and altered microcirculation of the pancreas have been proposed as major initiators of inflammation. In addition, the role of the gut is becoming increasingly explored as a cause of oxidative stress and potentiation of systemic inflammation in pancreatitis.     

Extracellular matrix in epitheliochorial,endotheliochorial and haemochorial placentation and its potential application for regenerative medicine

A placenta is defined as structural approximation of maternal and foetal tissues to perform physiological exchange. Associated processes of differentiation and the establishment of its cells take place within the extracellular matrix (ECM) that provides a rich environment of collagens, fibronectins, cytokines and other components. Placental ECM is promising for tissue regeneration purposes, because it has immune tolerance capacities that may cause only minimal rejections of transplants with immunological differences between donor and recipient. However, specific characteristics of ECM during evolution of the structurally very diverse mammalian placenta are not yet revealed. We here address the major aspects of placental types, that is non‐invasive (epitheliochorial), medium (endotheliochorial)‐to‐high (haemochorial) invasive nature of the interhemal barrier between the foetal and maternal blood system as well as their main components of ECM with special reference to species that are commonly used as animal models for human placentation and in the potential applications for regenerative medicine.