RESUMEN
Equine atypical myopathy (AM) is a severe rhabdomyolysis syndrome primarily caused by hypoglycin A (HGA) and methylenecyclopropylglycine protoxins. This study aimed to refine diagnostic and prognostic criteria for AM while exploring apparently healthy cograzers. Blood samples from 263 horses, including AM cases (n= 95), cograzers (n= 73), colic horses (n= 19), and controls (n= 76), were analyzed for HGA, its toxic metabolite, and acylcarnitines profile. Diseased horses exhibited alterations in acylcarnitines that strongly distinguished them from controls and colic horses. Regression analyses identified distinct acylcarnitines profiles among groups, with cograzers showing intermediate alterations. Age and gelding status emerged as protective factors against AM. Furthermore, serum acylcarnitines profiling was valuable in predicting AM survival, with isovaleryl-/2-methylbutyrylcarnitine (i.e., C5 acylcarnitine) showing promise as both a diagnostic and prognostic marker. Subclinical alterations in cograzers underscore a novel aspect: the presence of subclinical cases of AM.
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Acer pseudoplatanus is a worldwide-distributed tree which contains toxins, among them hypoglycin A (HGA). This toxin is known to be responsible for poisoning in various species, including humans, equids, Père David's deer and two-humped camels. We hypothesized that any herbivore pasturing with A. pseudoplatanus in their vicinity may be at risk for HGA poisoning. To test this hypothesis, we surveyed the HGA exposure from A. pseudoplatanus in species not yet described as being at risk. Animals in zoological parks were the major focus, as they are at high probability to be exposed to A. pseudoplatanus in enclosures. We also searched for a toxic metabolite of HGA (i.e., methylenecyclopropylacetyl-carnitine; MCPA-carnitine) in blood and an alteration of the acylcarnitines profile in HGA-positive animals to document the potential risk of declaring clinical signs. We describe for the first instance cases of HGA poisoning in Bovidae. Two gnus (Connochaetes taurinus taurinus) exposed to A. pseudoplatanus in their enclosure presented severe clinical signs, serum HGA and MCPA-carnitine and a marked modification of the acylcarnitines profile. In this study, even though all herbivores were exposed to A. pseudoplatanus, proximal fermenters species seemed less susceptible to HGA poisoning. Therefore, a ruminal transformation of HGA is hypothesized. Additionally, we suggest a gradual alteration of the fatty acid metabolism in case of HGA poisoning and thus the existence of subclinical cases.
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Ácido 2-Metil-4-clorofenoxiacético , Acer , Ciervos , Enfermedades de los Caballos , Enfermedades Musculares , Animales , Carnitina , Herbivoria , Caballos , HumanosRESUMEN
Equine atypical myopathy (AM) is seasonal intoxication resulting from the ingestion of seeds and seedlings of the sycamore maple (Acer pseudoplatanus) that contain toxins, among them, hypoglycin A (HGA). Literature mentions several cases of AM among gravid mares and in unweaned foals. The objective of this study was to determine whether HGA and/or its metabolite are present in milk from grazing mares exposed to sycamore maple trees as confirmed by detection of HGA and its metabolite in their blood. Four mare/foal couples were included in the study. Both HGA and its metabolite were detectable in all but one of the milk samples. To our knowledge, this is the first study describing transfer of HGA to the milk. This unprecedented observation could partially explain cases of unweaned foals suffering from AM. However, a transplacental transfer of the toxin cannot be excluded for newborn foals. Besides being a source of contamination for offspring, milk contamination by toxins from fruits of trees of the Sapindaceae family might constitute a potential risk for food safety regarding other species' raw milk or dairy products.
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In 2014, atypical myopathy (AM) was linked to Acer pseudoplatanus (sycamore maple) in Europe. The emergence of this seasonal intoxication caused by a native tree has raised many questions. This manuscript aims at answering the five most frequently asked questions (FAQs) regarding (1) identification of toxic trees; reduction of risk at the level of (2) pastures and (3) equids; (4) the risk associated with pastures with sycamores that have always been used without horses being poisoned and (5) the length of the risk periods. Answers were found in a literature review and data gathered by AM surveillance networks. A guide is offered to differentiate common maple trees (FAQ1). In order to reduce the risk of AM at pasture level: Avoid humid pastures; permanent pasturing; spreading of manure for pasture with sycamores in the vicinity and avoid sycamore maple trees around pasture (FAQ2). To reduce the risk of AM at horse level: Reduce pasturing time according to weather conditions and to less than six hours a day during risk periods for horses on risk pasture; provide supplementary feeds including toxin-free forage; water from the distribution network; vitamins and a salt block (FAQ3). All pastures with a sycamore tree in the vicinity are at risk (FAQ4). Ninety-four percent of cases occur over two 3-month periods, starting in October and in March, for cases resulting from seeds and seedlings ingestion, respectively (FAQ5).
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BACKGROUND: Gastrointestinal stasis is a common perianaesthetic complication in rabbits. The objective of this study was to assess the impact on gastrointestinal transit time of ketamine-midazolam (KMZ) versus ketamine-medetomidine (later antagonised by atipamezole) (KMT-A) in rabbits anaesthetised with isoflurane. METHODS: This was a cross-over, randomised, single-blinded, controlled, experimental trial. Seven healthy adult New Zealand White rabbits were used. Gastrointestinal transit time was assessed by contrast radiography in awake rabbits. Presence of contrast medium in the small intestine (gastric transit time), in the caecum (small intestinal transit time) and in faeces in the colon was assessed. One week later, 55 minutes isoflurane anaesthesia was induced with ketamine (15 mg/kg) and either midazolam (3 mg/kg) or medetomidine (0.25 mg/kg) by intramuscular injection. Thirty minutes after discontinuation of isoflurane, atipamezole (0.5 mg/kg) was administered only to rabbits in KMT-A treatment. Gastrointestinal transit time was then assessed in both treatment groups, beginning 30 minutes after cessation of isoflurane administration. Two weeks later, the treatment groups were interchanged. RESULTS: Gastric and small intestinal transit times were significantly longer with KMT-A (92±109 minutes and 214±119 minutes, respectively) than with KMZ (1±0 minutes and 103±6 minutes, respectively) and in the awake state (7±7 minutes and 94±32 minutes, respectively). CONCLUSION: Clinicians should therefore be aware of the potential gastrointestinal side effects of KMT-A, particularly in rabbits at risk for gastrointestinal stasis.
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Anestesia/veterinaria , Anestésicos Combinados/farmacología , Tránsito Gastrointestinal/efectos de los fármacos , Ketamina/farmacología , Medetomidina/farmacología , Midazolam/farmacología , Anestesia/métodos , Animales , Estudios Cruzados , Femenino , Isoflurano/administración & dosificación , Conejos , Método Simple CiegoRESUMEN
Equine atypical myopathy in Europe results from hypoglycin A (HGA) exposure through the ingestion of samaras or seedlings of the sycamore maple tree. This pilot study aimed at better defining sources of HGA intoxication in spring. Samaras fallen on the ground and then seedlings were collected at two-week intervals from sycamore, Norway, and field maple trees over the spring 2016. In early April, rainwater from wet seedlings collected after a rainy night was harvested to be analysed. Mid-May, samaras of the box elder, common ash, and inflorescences of sycamore maples were collected on the tree. Quantification of HGA in samples was performed using high performance thin layer chromatography. Hypoglycin A was detected in all samples from sycamore including rainwater but tested negative for Norway, field maples. The samaras of the box elder found in the present study area did not contain a seed within their husk and thus tested negative. From the maximum HGA concentrations found, it may be extrapolated that at some periods and locations, about 20 g of samaras, 50 seedlings, 150 g of inforescences or 2 liters of water that has been in contact with seedlings would contain the maximum tolerated dose per day for a horse.
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Enfermedades de los Caballos/etiología , Hipoglicinas/envenenamiento , Intoxicación por Plantas/veterinaria , Alimentación Animal , Animales , Europa (Continente) , Caballos , Proyectos Piloto , Intoxicación por Plantas/etiología , Estaciones del AñoRESUMEN
As a potent bronchodilator, the anti-inflammatory effects of tiotropium and its interaction with budesonide against cadmium-induced acute pulmonary inflammation were investigated. Compared to values obtained in rats exposed to cadmium, cytological analysis indicated a significant decrease of total cell and neutrophil counts and protein concentration in bronchoalveolar lavage fluid (BALF) in rats pretreated with tiotropium (70µg/15ml or 350µg/15ml). Zymographic tests showed a decrease of MMP-2 activity in BALF in rats pretreated only with high concentration of tiotropium. Histological examination revealed a significant decrease of the severity and extent of inflammatory lung injuries in rats pretreated with both tested concentrations of tiotropium. Though tiotropium (70µg/15ml) or budesonide (250µg/15ml) could not reduce cadmium-induced bronchial hyper-responsiveness, their combination significantly decreased bronchial contractile response to methacholine. These two drugs separately decreased the neutrophil number and protein concentration in BALF but no significant interaction was observed when both drugs were combined. Although no inhibitory effects on MMP-2 and MMP-9 was observed in rats pretreated with budesonide alone, the combination with the ineffective dose of tiotropium induced a significant reduction on these parameters. The inhibitory effect of tiotropium on lung injuries was not influenced by budesonide which alone induced a limited action on the severity and extent of inflammatory sites. Our findings show that tiotropium exerts anti-inflammatory effects on cadmium-induced acute neutrophilic pulmonary inflammation. The combination of tiotropium with budesonide inhibits cadmium-induced inflammatory injuries with a synergistic interaction on MMP-2 and MMP-9 activity and airway hyper-responsiveness.
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Budesonida/farmacología , Cadmio/farmacología , Inhalación , Neutrófilos/efectos de los fármacos , Neumonía/inducido químicamente , Neumonía/prevención & control , Bromuro de Tiotropio/farmacología , Enfermedad Aguda , Animales , Bronquios/efectos de los fármacos , Bronquios/fisiopatología , Pruebas de Provocación Bronquial , Líquido del Lavado Bronquioalveolar , Recuento de Células , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Cloruro de Metacolina/farmacología , Contracción Muscular/efectos de los fármacos , Neumonía/inmunología , Neumonía/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
A scenario analysis in regard to the risk of chronic exposure of consumers to residues through the consumption of contaminated honey and beeswax was conducted. Twenty-two plant protection products and veterinary substances of which residues have already been detected in beeswax in Europe were selected. The potential chronic exposure was assessed by applying a worst-case scenario based on the addition of a "maximum" daily intake through the consumption of honey and beeswax to the theoretical maximum daily intake through other foodstuffs. For each residue, the total exposure was finally compared to the acceptable daily intake. It is concluded that the food consumption of honey and beeswax contaminated with these residues considered separately does not compromise the consumer's health, provided proposed action limits are met. In regard to residues of flumethrin in honey and in beeswax, "zero tolerance" should be applied.
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Exposición a Riesgos Ambientales/análisis , Contaminación de Alimentos/análisis , Miel/análisis , Residuos de Plaguicidas/análisis , Ceras/análisis , Exposición a Riesgos Ambientales/efectos adversos , Humanos , Insecticidas/análisis , Residuos de Plaguicidas/toxicidad , Piretrinas/análisis , Medición de Riesgo , Pruebas de Toxicidad Crónica , Drogas Veterinarias/análisis , Ceras/químicaRESUMEN
OBJECTIVES: Recent data indicate that degeneration of intervertebral discs occurs naturally in sheep, with a higher prevalence at the level of the lumbo-sacral disc. The objective of this ex vivo study was to evaluate a computed tomography (CT) guided method of injection into the ovine lumbo-sacral disc. METHODS: Six euthanatized sheep were used for identification of the approach plane, the optimal direction of the needle and the mean distance from skin to disc. Dissection after injection of coloured ink was used to determine the anatomical structures that were penetrated. In seven other animals, all spines were assessed beforehand by CT and magnetic resonance imaging to determine whether disc pathology was present. The final position of the needle was assessed by CT to determine the accuracy of the technique. Contrast agent was injected to identify any problems associated with administration of liquid into the disc. RESULTS: The CT guided injection technique was easy to perform and enabled adequate positioning of the needle into all (n = 7) lumbo-sacral discs. Distance between the skin and the disc ranged between 12 and 17 cm. No organ, vascular or nervous structure was penetrated and the needle path remained intramuscular without penetration of the peritoneal cavity. Contrast medium leaked out through three degenerate discs. CLINICAL SIGNIFICANCE: The current study described a consistently safe and accurate CT guided injection technique to the lumbo-sacral disc for future in vivo experimental studies that will use sheep as animal model for human intervertebral disc disease disease.
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Inyecciones Espinales/veterinaria , Enfermedades de las Ovejas/terapia , Terapia Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/veterinaria , Animales , Inyecciones Espinales/métodos , Disco Intervertebral/patología , Degeneración del Disco Intervertebral/veterinaria , Desplazamiento del Disco Intervertebral/veterinaria , Región Lumbosacra , Evaluación de Procesos y Resultados en Atención de Salud , OvinosRESUMEN
Intra-articular (IA) corticosteroids (CS) have been used in the treatment of osteoarthritis for many years, although their effects on articular cartilage are not fully understood. To identify whether previous animal studies have provided enough evidence about the effects of CS, we undertook a systematic review that identified 35 relevant in vivo animal experimental studies between 1965 and 2014 assessing the effects of CS on either normal cartilage, or in either induced osteoarthritis (OA) or synovitis. The quality of the methodology was assessed. Deleterious effects, both structural and biochemical, have mainly been reported in rabbits and are associated with frequent administration of CS, sometimes at high dose and with systemic side effects. In dogs, four identified studies concluded that there were beneficial effects with methylprednisolone acetate (MPA) and triamcinolone hexacetonide therapy. In horses, MPA was mostly deleterious, while triamcinolone acetonide had positive effects in one study highly rated at quality assessment. However, many methodological weaknesses have been identified, such as the lack of pharmacokinetic and pharmocodynamics data and the large variation in doses between studies, the limited selection criteria at baseline, the absence of blinding, and the lack of statistics or appropriate controls for testing the effects of the vehicle of the drug. Those methodological weaknesses weaken the conclusions of numerous studies that assess beneficial or deleterious effects of CS on articular cartilage. Animal studies have not yet provided definitive data, and further research is required into the role of CS in articular pathobiology.
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Corticoesteroides/administración & dosificación , Cartílago Articular/efectos de los fármacos , Osteoartritis/tratamiento farmacológico , Corticoesteroides/efectos adversos , Corticoesteroides/farmacocinética , Animales , Cartílago Articular/metabolismo , Cartílago Articular/patología , Modelos Animales de Enfermedad , Perros , Caballos , Humanos , Inyecciones Intraarticulares , Osteoartritis/diagnóstico , Osteoartritis/metabolismo , Conejos , Medición de Riesgo , Resultado del TratamientoRESUMEN
The anti-inflammatory properties of glucocorticoids are well known but their protective effects exerted with a low potency against heavy metals-induced pulmonary inflammation remain unclear. In this study, a model of acute pulmonary inflammation induced by a single inhalation of cadmium in male Sprague-Dawley rats was used to investigate whether formoterol can improve the anti-inflammatory effects of budesonide. The cadmium-related inflammatory responses, including matrix metalloproteinase-9 (MMP-9) activity, were evaluated. Compared to the values obtained in rats exposed to cadmium, pretreatment of inhaled budesonide (0.5 mg/15 ml) elicited a significant decrease in total cell and neutrophil counts in bronchoalveolar lavage fluid (BALF) associated with a significant reduction of MMP-9 activity which was highly correlated with the number of inflammatory cells in BALF. Additionally, cadmium-induced lung injuries characterized by inflammatory cell infiltration within alveoli and the interstitium were attenuated by the pre-treatment of budesonide. Though the low concentration of budesonide (0.25 mg/15 ml) exerted a very limited inhibitory effects in the present rat model, its combination with an inefficient concentration of formoterol (0.5 mg/30 ml) showed an enhanced inhibitory effect on neutrophil and total cell counts as well as on the histological lung injuries associated with a potentiation of inhibition on the MMP-9 activity. In conclusion, high concentration of budesonide alone could partially protect the lungs against cadmium exposure induced-acute neutrophilic pulmonary inflammation via the inhibition of MMP-9 activity. The combination with formoterol could enhance the protective effects of both drugs, suggesting a new therapeutic strategy for the treatment of heavy metals-induced lung diseases.
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Budesonida/farmacología , Budesonida/uso terapéutico , Etanolaminas/farmacología , Etanolaminas/uso terapéutico , Metaloproteinasa 9 de la Matriz/metabolismo , Neumonía/tratamiento farmacológico , Regulación hacia Arriba/efectos de los fármacos , Enfermedad Aguda , Administración por Inhalación , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Líquido del Lavado Bronquioalveolar/citología , Cadmio/toxicidad , Quimiocinas/metabolismo , Citocinas/metabolismo , Fumarato de Formoterol , Recuento de Leucocitos , Pulmón/patología , Masculino , Metaloproteinasa 9 de la Matriz/química , Neutrófilos/citología , Ratas , Ratas Sprague-DawleyRESUMEN
In veterinary medical education, it is now necessary to design competency frameworks (CFs) that list expected competencies at graduation. Three different CFs with different formats and contents have been published in Europe, such as the Day One Skills (DOS), the recommendations of the World Organization for Animal Health(OIE), and the Veterinary Professional (VetPro). In the current study, on the basis of a survey among Belgian veterinarians, a fourth document was designed that lists the necessary knowledge, skills, and attitudes grouped into families according to professional situations. The objectives of this study were to assess the perception of CFs by various categories of stakeholders, identify the possible uses of CFs, and determine whether one format should be preferred to another. We used a qualitative approach based on semi-structured face-to-face interviews with different stakeholders after they had reviewed the four different documents (CFs). This study showed that an obligation to design CFs was clearly perceived by academic and professional authorities. Teachers and veterinarians may be either enthusiastic or apprehensive about CFs, while students perceive the usefulness of the documents to plan and assess their learning objectives. Three main roles of CFs were identified: they can be used as communication tools, regulatory tools, or educational tools. However, not one of the documents used in this study was perceived to fulfill all roles. It is therefore likely that no one ideal document yet exists and a combination of formats is necessary.
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Competencia Clínica/normas , Educación Basada en Competencias/normas , Educación en Veterinaria , Veterinarios , Europa (Continente)RESUMEN
Nutraceuticals, or nutritional supplements, have been promoted for the ancillary treatment of liver disease in dogs. However, minimal information is available in the scientific literature about commonly used nutraceuticals, such as S-adenosylmethionine, silymarin, and vitamin E. No strong clinical evidence exists regarding the efficacy of these compounds as hepatoprotectants in canine liver disease. Until this evidence exists, individual veterinarians must assume responsibility for their decision to use nutritional supplements in their canine patients with liver disease.
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Suplementos Dietéticos , Enfermedades de los Perros/terapia , Hepatopatías/veterinaria , Animales , Perros , Hepatopatías/tratamiento farmacológicoRESUMEN
Understanding how veterinary practitioners make clinical decisions, and how they use scientific information to inform their decisions, is important to optimize animal care, client satisfaction, and veterinary education. We aimed to develop an understanding of private practitioners' process of decision making. On the basis of a grounded-theory qualitative approach, we conducted a telephone survey and semi-structured face-to-face interviews. We identified a decision-making framework consisting of two possible processes to make decisions, five steps in the management of a clinical case, and three influencing factors. To inform their decision, veterinary surgeons rarely take the evidence-based medicine (EBM) approach. They consult first-opinion colleagues, specialists, laboratories, and the Internet rather than scientific databases and peer-reviewed literature, mainly because of limited time. Most interviewees suggested the development of educational interventions to better develop decision-making skills in veterinary schools. Adequate information and EBM tools are needed to optimize the time spent in query and assessment of scientific information, and practitioners need to be trained in their use.
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Competencia Clínica , Toma de Decisiones , Educación en Veterinaria , Veterinarios , Bélgica , Educación en Veterinaria/normas , Medicina Basada en la Evidencia , Encuestas y CuestionariosRESUMEN
We suggest a definition of evidence-based veterinary medicine that takes into account its objectives and practicality. We view it as an information tool that does not replace experience but helps to improve background knowledge and solve clinical foreground questions. It could be defined as the use of accurate, informative, and clear summarized information (abstracts) of high-level research studies that is obtained quickly via free-access databases available via the Internet and that is provided by a proactive veterinary scientific community in search of transparency, accountability, and evidence.
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Medicina Basada en la Evidencia , Internet/estadística & datos numéricos , Medicina Veterinaria/normas , Animales , Bovinos , Competencia Clínica , Conocimientos, Actitudes y Práctica en Salud , HumanosRESUMEN
This study compares the potency and efficacy of different relaxant drugs including anticholinergic, ß-adrenergic and methylxanthine agents on acetylcholine-contracted feline bronchi, and investigates the influence of the initial muscarinic-induced tone on bronchodilator response. Feline bronchi were removed from euthanased client-owned cats and were contracted with acetylcholine to cause either 40% or 80% of the acetylcholine maximal contraction. The efficacy and potency of bronchodilating drugs were obtained from cumulative dose-response curves with efficacy (E(max)) as the maximal relaxant response and potency (-logEC(50)) as the logarithm of the concentration of drug inducing 50% of maximal relaxation. Under low contractile tone (40%), all bronchodilators relaxed feline bronchi in a concentration-dependent manner with the following rank order of potency: formoterol>ipratropium bromide>fenoterol>isoprenaline>salbutamol≥salmeterol>theophylline. E(max) values ranged from 80% to 100% depending on the tested drug. Constriction of feline bronchi with high-dose acetylcholine (80%) caused a rightward and downward shift of the ß(2)-mimetic dose-response curves. Significant decreases in -logEC(50) and E(max) values were reported for salbutamol, formoterol and salmeterol. This study provides evidence that existing classes of bronchodilators produce effective relaxation of acetylcholine-contracted feline bronchi and that airway responsiveness to ß(2)-stimulants is dependent on the magnitude of the initial muscarinic-induced tone. The clinical relevance of these in vitro findings has yet to be explored in clinical trials.
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Agonistas Adrenérgicos beta/farmacología , Bronquios/efectos de los fármacos , Broncodilatadores/farmacología , Gatos/fisiología , Antagonistas Colinérgicos/farmacología , Contracción Muscular , Músculo Liso/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Femenino , Ipratropio/farmacología , Masculino , Teofilina/farmacologíaRESUMEN
Evidence-based medicine (EBM) refers to the conscientious, explicit and judicious use of current best evidence from research for the care of an individual patient. The concept of EBM was first described in human medicine in the early 1990s and was introduced to veterinary medicine 10 years later. However, it is not clear that the EBM approach promulgated in human medicine can be applied to the same extent to veterinary medicine. EBM has the potential to help veterinarians to make more informed decisions, but obstacles to the implementation of EBM include a lack of high quality patient-centred research, the need for basic understanding of clinical epidemiology by veterinarians, the absence of adequate searching techniques and accessibility to scientific data bases and the inadequacy of EBM tools that can be applied to the busy daily practise of veterinarians. This review describes the development of EBM in the veterinary profession, identifies its advantages and disadvantages and discusses whether and how veterinary surgeons should further adopt the EBM approach of human medicine.
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Medicina Basada en la Evidencia , Medicina Veterinaria , AnimalesRESUMEN
The objective of this study was to investigate whether high-dose inhaled fluticasone propionate (FP), alone or in combination with salmeterol (SAL), is as effective as oral prednisolone in reducing airway inflammation and obstruction in cats with experimentally-induced acute asthma. Six cats sensitised to Ascaris suum (AS) were enrolled in a prospective controlled therapeutic trial and underwent four aerosol challenges, at 1-month intervals with AS allergen. The allergen - stimulated animals received four consecutive days treatment with either oral prednisolone at 1mg/kg twice daily, 500 µg of FP inhaled twice daily, or a combination of FP/SAL at 500 µg/50 µg inhaled twice daily, respectively, according to a randomised cross-over design. Treatment-related changes in lung function, airway responsiveness (AR) and bronchoalveolar lavage fluid (BALF) cytology were assessed. Barometric whole-body plethysmography (BWBP) was used for the assessment of respiratory variables and AR. No significant differences in respiratory rate or Penh (an estimate of airflow limitation measured by BWBP) were detected among treatment groups. Allergen-induced airway hyper-responsiveness was significantly inhibited by all three steroid treatments (P<0.05). The mean BALF eosinophil percentage (±SEM) was lower after oral and inhaled corticosteroid treatment and these changes were significant for groups receiving prednisolone and the FP/SAL combination. Findings suggest high-dose FP, particularly in combination with SAL, is effective in ameliorating airway inflammation and hyper-responsiveness in this model of acute feline asthma, and highlight the potential use of these drugs in cats experiencing acute exacerbations of the naturally occurring disease.
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Albuterol/análogos & derivados , Androstadienos/administración & dosificación , Antiinflamatorios/administración & dosificación , Asma/veterinaria , Broncodilatadores/administración & dosificación , Enfermedades de los Gatos/tratamiento farmacológico , Prednisolona/administración & dosificación , Administración por Inhalación , Administración Oral , Albuterol/administración & dosificación , Alérgenos/efectos adversos , Animales , Antígenos Helmínticos/efectos adversos , Ascaris suum/inmunología , Asma/tratamiento farmacológico , Asma/inmunología , Enfermedades de los Gatos/inmunología , Gatos , Estudios Cruzados , Combinación de Medicamentos , Femenino , Fluticasona , Combinación Fluticasona-Salmeterol , Masculino , Estudios ProspectivosRESUMEN
Chronic obstructive pulmonary disease (COPD) has become a global epidemic disease with an increased morbidity and mortality in the world. Inflammatory process progresses and contributes to irreversible airflow limitation. However, there is no available therapy to better control the inflammatory progression and therefore to reduce the exacerbations and mortality. Thus, the development of efficient anti-inflammatory therapies is a priority for patients with COPD. ß(2) -Adrenoceptor agonists and anticholinergic agents are widely used as first line drugs in management of COPD because of their efficient bronchodilator properties. At present, many studies in vitro and some data obtained in laboratory animals reveal the potential anti-inflammatory effects of these bronchodilators but their protective role against chronic inflammation and the development of emphysema in patients with COPD remains to be investigated. The anti-inflammatory effects of theophylline at low doses have also been identified. Beneficial interactions between glucocorticoids and bronchodilators have been reported, and signaling pathways explaining these synergistic effects begin to be understood, especially for theophylline. Recent data demonstrating interactions between anticholinergics with ß(2) -adrenoceptor agonists aiming to better control the pulmonary inflammation and the development of emphysema in animal models of COPD justify the priority to investigate the interactive effects of a tritherapy associating corticoids with the two main categories of bronchodilators.
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Broncodilatadores/uso terapéutico , Inflamación/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Agonistas de Receptores Adrenérgicos beta 2/farmacología , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Animales , Broncodilatadores/administración & dosificación , Broncodilatadores/farmacología , Antagonistas Colinérgicos/administración & dosificación , Antagonistas Colinérgicos/farmacología , Antagonistas Colinérgicos/uso terapéutico , Progresión de la Enfermedad , Sinergismo Farmacológico , Enfisema/tratamiento farmacológico , Enfisema/etiología , Humanos , Inflamación/etiología , Inflamación/patología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Teofilina/administración & dosificación , Teofilina/farmacología , Teofilina/uso terapéuticoRESUMEN
The objective of this study was to determine if inhaled salmeterol, a long-acting ß(2)-adrenergic agonist, and oral doxycycline, a tetracycline antibiotic displaying matrix metalloproteinase (MMP) inhibitory activity, reduce airway inflammation and obstruction in cats with experimentally-induced asthma. Eight Ascaris suum (AS)-sensitised cats were enrolled in a prospective study in which they underwent four AS-challenges at 1 month intervals. The challenged animals were given no treatment or were treated on 4 consecutive days with either: (1) oral prednisolone (1mg/kg twice daily), (2) inhaled salmeterol (50 µg twice daily), or (3) oral doxycycline (5mg/kg twice daily), according to a randomised cross-over design. Inhibition of allergen-induced early (EAR) and late (LAR) asthmatic reactions were assessed by barometric whole-body plethysmography. Cytology and measurement of MMP-2 and -9 activities were carried out on bronchoalveolar lavage fluid (BALF). Although none of the treatments prevented the EAR, prednisolone treatment inhibited the LAR. Relative to untreated cats, the eosinophil percentage and MMP-2 activity in BALF were significantly reduced following prednisolone treatment (P<0.05). Short-term therapy with either salmeterol or doxycycline had no effect on the EAR or LAR or on airway inflammation. Given the chronic nature of this disease in cats, long-term therapy may be required to produce more favourable functional and clinical outcomes.