Pulmonary function,airway cytology and bronchoalveolar lavage fluid drug concentration after aerosol administration of cefquinome to horses

The administration of antibiotics by aerosol to horses suffering from respiratory infections may partially circumvent the limitations of antimicrobial therapy, e.g. large injection volumes, low bioavailability and risk of diarrhoea. Only injectable formulations are available currently and usually contain other substances that could irritate the mucosa and induce coughing and bronchospasm. In addition, the quality of the aerosol, particularly in terms of the delivery of antibiotics to the deep parts of the lung, is unknown. Although used under field conditions, cefquinome delivered by aerosol has never been studied in horses. This study examined the safety of cefquinome injectable solution, administered by aerosol at a dose of 225 mg/inhalation to 7 healthy horses, by assessing (1) pulmonary function before and 15 min after a single inhalation, at the first day (Day 1) and the fifth day (Day 5) of a 5 day period treatment; and (2) the inflammatory status of the lung, i.e. percentage neutrophils and myeloperoxidase concentration, based on bronchoalveolar lavage (BAL) at D1 and D5. In addition, cefquinome concentrations were measured in bronchoalveolar lavage fluid after aerosol, intravenous (i.v.) and intramuscular (i.m.) administrations. A single aerosol of cefquinome injectable solution did not induce any immediate nor delayed pulmonary side effects in healthy horses and produced cefquinome concentrations in bronchoalveolar lavage (BAL) within 30 min that were higher than the minimal inhibitory concentration of the main equine respiratory pathogens. These results should stimulate further studies, especially in horses suffering from bronchial hyper‐reactivity. Aerosol delivery of antibiotics may well have a role in equine therapeutics.     

英国兽药理事会批准的可用于马匹的兽药产品分析

为了探究英国兽药理事会(VMD)批准上市的马匹兽药产品情况,从VMD 2016年3月提供的产品信息数据库统计分析。结果显示,上市的可用于马匹的兽药产品占兽药总数的12%,而马匹专属产品占6%;1990年-2015年年均批准马匹用兽药产品约12个;持有上市总兽药以及马匹兽药数量最多的前3个企业依次为Norbrook laboratories Ltd,Zoetis UK Ltd和Intervet UK Ltd;批准产品中抗炎药、中枢神经系统药和抗寄生虫药比例最高;优势兽药活性成分中非甾体抗炎药美洛昔康、抗寄生虫药伊维菌素及其同吡喹酮复方和镇静剂甲苯噻嗪获批产品数名列前3位;从给药途径来看,注射给药产品占62%,而口服产品占27%,外用和吸入给药产品比例较低。以上统计结果说明国际兽药企业注重马匹用药在英国的审批和上市,从马匹用兽药优势品种和主要活性成分可以提示马匹用药热点,该统计结果为管理和制定同国际接轨的我国马匹用药标准提供参考。     

Critical Evaluation of Whole-Body Cryostimulation Protocol in Race Horses

Cold therapy is commonly used to relieve pain and inflammation and to aid in muscle recovery after exercise in human medicine. A number of applications have also been observed in veterinary practice. In this article, a critical evaluation of equine protocol applied with a new commercial concept of equine whole-body cryostimulation (WBC) was made. With this new concept of WBC, the protocol usually utilized for relieving pain and discomfort in humans has been extended to horses. The investigations described herein focus on the reduction of horse skin temperature when applying human WBC protocols. Based on infrared thermography measurements, results show that exposing a horse for 3 minutes to a temperature of −140°C, which are conventional parameters used for humans, does not induce sufficient skin thermal gradients in horses. Consequently, beneficial cold reflexes such as vasomotor, neuroconduction, and biochemical reactions cannot be triggered. Further investigations should therefore be carried out to design an adequate protocol specifically aimed at horses.     

Thromboelastography in equine medicine: Technique and use in clinical research

Thromboelastography (TEG) is a viscoelastic, whole blood‐based assay that integrates information from both the cellular and soluble components of coagulation, providing a global evaluation of the haemostatic system. This contrasts with the conventional coagulation assays (i.e. platelet count, prothrombin time [PT], activated partial thromboplastin time [aPTT] and fibrinogen concentration [FIB]), which only provide information about one component (e.g. clotting factors in the case of PT and aPTT) of the haemostatic process, requiring the combination of several assays for a complete evaluation of haemostasis. Thromboelastography is an old technology that has been used in human medicine for over 50 years. However, it is relatively new in veterinary medicine and has only been applied to horses in the last 5 years. Clinical applications in human medicine include diagnosis and monitoring of coagulopathies. Currently, extensive research is being carried out to expand the use of TEG in dogs and cats. Therefore, it is expected that the use of this technique will also further expand in horses in the near future. To date, the available studies in the equine species have evaluated TEG in healthy horses, horses with gastrointestinal disease, septic foals, horses with exercise‐induced pulmonary haemorrhage (EIPH) and a filly with Glanzmann's thrombasthenia. The main objective of this review is to introduce the TEG technique to equine clinicians, providing information on how the TEG functions, blood sample collection and processing, variables measured and their interpretations, normal reference values and areas of potential clinical application.     

Overview of the use of antimicrobial drugs for the treatment of bacterial infections in horses

The use of antimicrobials in veterinary medicine is under great scrutiny with the emergence of antimicrobial resistance in the human population. Equine veterinarians rely on antimicrobials as an essential tool for the treatment of infections in horses, but there is much criticism of some use, particularly prophylaxis. While the appropriate use of antimicrobials can be justified in equine medicine, the misuse cannot. The definition of appropriate use is complex and involves the indication for therapy, antimicrobial selection, dosing regimen and timing and route of administration, duration of therapy and modification of therapy based on microbial susceptibility and clinical response. The aim of this article is to provide guidance on these factors to assist equine veterinarians in determining what constitutes appropriate antimicrobial use in horses.     

The rapid and effective administration of a beta 2-agonist to horses with heaves using a compact inhalation device and metered-dose inhalers.

The purpose of the study was to administer therapeutic aerosol generated by metered-dose inhalers to horses exhibiting clinical signs of heaves using a compact inhalation device developed for human medicine. It was fitted to a custom face mask in order to study the effect of an inhaled beta 2-agonist, fenoterol. Pulmonary function testing was performed on six horses following an acute exacerbation of heaves, characterized by tachypnea, wheezes, crackles, and spasmodic cough. Horses inhaled fenoterol in 1 mg increments administered as one 200 microgram puff every 5-10 s with the recording of data 5 min after the cessation of drug inhalation. A significant effect of fenoterol was shown for maximum change in transpulmonary pressure, dynamic compliance, lung resistance, and work of breathing, and the wheezes and crackles disappeared when auscultation was performed at the end of the test. This study demonstrates a novel, highly effective method for the rapid administration of inhaled medication in horses.     

Use of antiviral medications against equine herpes virus associated disorders

Numerous types of equine herpesviruses (EHV) continue to afflict horses resulting in a variety of clinical manifestations. While many of the clinical manifestations of EHV are self‐limiting or require only supportive care, some clinical expressions of EHV infections cause severe risk to the horse's overall health and can result in abortion, long‐term deficits or death. Antiviral medications are infrequently utilised therapeutics in equine medicine and their exact efficacy is largely unknown. However, the use of antiviral medications may potentially decrease convalescent time and improve outcome in horses with EHV‐related diseases. Thus, equine practitioners should consider the potential use of antiviral medications in the future. The purpose of this article is to familiarise the equine practitioner with current information in regard to antiviral medications and their potential uses in equine medicine.     

Antioxidant activity of hyaluronic acid investigated by means of chemiluminescence of equine neutrophil bursts and electron paramagnetic resonance spectroscopy

Activated neutrophils (PMNs), the ROS/RNS released by PMNs and the derived inflammatory processes are involved in the pathogenesis and progression of human inflammatory airway diseases. Similar diseases are also present in horses which suffer from recurrent airway obstruction (RAO), exercise‐induced pulmonary haemorrhage (EIPH) and inflammatory airway diseases (IAD). Hyaluronic acid (HA) plays numerous roles in modulating inflammatory processes. The aim of this study was to examine whether a preparation of HA (MW 900 000 Da) interferes with ROS/RNS during the course of equine PMN respiratory bursts, and to establish the lowest concentration at which it still has antioxidant activity by means of luminol‐amplified chemiluminescence (LACL). Electron paramagnetic resonance (EPR) spectroscopy was also used to investigate the direct antiradical activity of HA. The hydroxyl radical was significantly scavenged in a concentration‐dependent manner at HA concentrations ranging from 2.5 to 0.16 mg/mL. Superoxide anion, Tempol radical and the ABTS^{? +} were significantly inhibited at concentrations ranging from 2.5 to 0.62 mg/mL. The LACL of stimulated equine neutrophils showed that HA induced a statistically significant concentration–effect reduction from 5 mg/mL to 1.25 mg/mL. These findings were confirmed also when l ‐Arg was added to investigate the inhibition of the resulting peroxynitrite anion. Our findings indicate that, in addition to the human use, HA can also be used to antagonize the oxidative stress generated by free radicals in horses peripheral blood mononuclear cells (PBMCs). In order to achieve therapeutic concentrations, a direct aerosol administration to horses with horse respiratory diseases can be considered, as this route of application is also recommended in human medicine.     

A cross-sectional study of geriatric horses in the United Kingdom. Part 1: Demographics and management practices

Reasons for performing study: With growing numbers of aged horses, geriatric medicine is becoming increasingly important in equine veterinary practice; however, there is a paucity of information on the UK equine geriatric population. Objectives: To describe the demographic characteristics of the equine geriatric population and to assess management practices undertaken by owners of geriatric horses (aged ≥15 years). Methods: A cross‐sectional study was conducted, surveying a randomly selected sample of veterinary registered owners with horses aged ≥15 years, using a self‐administered postal questionnaire. Results: Horses aged ≥15 years represented 29% of the equine population in the study area. The response rate to the questionnaire survey was 80.2%. Management practices were similar to those previously described for the general equine population. However, the level of exercise and feeding practices changed significantly with increasing age. A summary of the demographic characteristics, feeding and management of horses in a sample of the geriatric equine population is presented. Conclusions and potential relevance: The management of geriatric horses has a direct effect on their health and welfare and this study has provided valuable information on the demographics and management of geriatric horses and ponies in the UK. The information can be used to form targeted owner education programmes for geriatric health and should aid in the investigation and prevention of disease.     

Methicillin-resistant Staphylococcus aureus in horses and horse personnel.

Fortunately, MRSA infection and colonization are currently uncommon in veterinary medicine. Nevertheless, the increasing reports of the occurrence of MRSA infection in horses, veterinarians, and equine personnel dictate that serious consideration be given to the control of this pathogen in veterinary hospitals as well as in the equine community. It is unclear whether extrapolation from human hospitals and people in the community is appropriate; however, given the rapid increase in nosocomial MRSA in human hospitals and the recent shift of certain clones of MRSA into the community, it would be unwise to ignore this potential pathogen. If equine MRSA did, indeed, originate in the human population, complete eradication in the equine population is unlikely, regardless of the prevalence of infection in horses and the intensity of infection control measures, without concurrent eradication of MRSA in the human population, which is surely an impossible feat. Early institution of appropriate surveillance and other infection control measures should be used to attempt to limit the impact of MRSA in veterinary medicine, however. It has been stated, "The time to act is now, before the prevalence of MRSA in the community begins to rise and we end up with 50% of the community strains becoming methicillin-resistant". This statement was directed at control of MRSA in people; however, it is equally relevant in the veterinary context and should receive strong consideration.     

Development of Immunologic Assays to Measure Response in Horses Vaccinated with Xenogeneic Plasmid DNA Encoding Human Tyrosinase

Xenogeneic plasmid DNA constructs have been developed and optimized for immunotherapies targeting cancer in both humans and dogs. Specifically, plasmid vectors containing the tumor antigen tyrosinase have demonstrated immunoreactivity and clinical benefit in the treatment of melanocytic tumors in these species. Overexpression of tyrosinase has also been noted in equine melanocytic tumors, supporting its role as a valid tumor antigen in the horse. Vaccination with plasmid constructs containing tyrosinase may thus have translational immunoreactivity in the treatment of equine melanomas. Here, we describe a methodology that is highly sensitive and specific for the detection of both humoral and cell-mediated immunoreactivity against tyrosinase in equine patients. These antigen-specific immunoassays are used to measure the humoral and cell-mediated responses in a cohort of horses vaccinated with xenogeneic plasmid DNA encoding human tyrosinase. Serum humoral responses were measured using standard enzyme-linked immunosorbent assay technique against the full-length recombinant human tyrosinase protein. Peripheral blood mononuclear cells were collected from vaccinated horses and stimulated with tyrosinase-specific peptides. Cell-mediated responses were then measured using a novel quantitative real-time-polymerase chain reaction technique to determine resultant interferon-γ expression. All horses developed significantly positive humoral and cell-mediated immune responses compared with their individual prevaccination values. No adverse reactions or signs of autoimmunity were detected. Vaccination with xenogeneic plasmid DNA expressing tyrosinase appears to elicit tumor antigen-specific reactivity and should be evaluated in a larger cohort of horses with melanocytic tumors.     

Deciphering the Role of Bronchial Hyper-Responsiveness in Equine Pasture Asthma

Bronchial hyper-responsiveness (BHR) describes a lung abnormality in which airways are easily triggered to constrict in response to normally harmless inhaled stimuli, and is a key element of human asthma pathophysiology. BHR contributes to equine respiratory diseases including inflammatory airway disease and recurrent airway obstruction. Collectively these diseases account for over 80% of poor performance in equine athletes, and at least 10% of veterinary admissions. BHR is also a contributing factor in ‘exercise induced pulmonary hemorrhage’. Increased sensitivity to airway constriction that characterizes BHR is a documented sequel to viral respiratory infections in several species, including horses and humans. Five respiratory viruses known to circulate extensively in equine populations place the horse at risk for BHR. Despite adverse effects of BHR on equine health, there remains a gap in our fundamental understanding of how gene products coordinate in the lung to cause BHR. Leveraging the equine genome sequence, we employ systems biology including proteomics and RNA sequencing to model the complex biology of BHR in the lungs of horses with pasture asthma. Using a self controlled experimental design, gene products that segregate with seasonal asthma exacerbation in diseased horses are being identified and their relevant physiology identified to address the need for better recognition and management of BHR in equine disease.     

Equine chronic diarrhea: Traditional Chinese veterinary medicine review

Chronic diarrhea is a common problem in equine practice. Herbal medicine has been used for the treatment of gastrointestinal disease in horses for at least one thousand years. In present-day equine practice in China, the most common approach to treat chronic diarrhea is herbal medicine, or a combination of herbal medicine and acupuncture. Three types of chronic diarrhea in horses will be described in detail in term of symptoms, diagnosis and herbal treatments in this paper. Nineteen herbal formulas for treatment of different types of diarrhea will be introduced. Clinical results of each herbal formula will be evaluated. Acupuncture treatment of this problem will also be included.     

Methods, applications and limitations of gait analysis in horses

Over the last 30 years, the increase in interest in horses for racing and riding activities has stimulated scientific research in equine locomotion. This paper presents a review of the measurement methods and their applications used to assess equine locomotion. After describing gaits and velocity-related changes in stride variables, the current applications of gait analysis are presented. The economic consequences of lameness justifies the great effort now being put into lameness quantification and prevention. To improve breeding and reduce the costs of training, early performance evaluation tests for each discipline are proposed. After extensive fundamental and methodological research on the various aspects of equine locomotion, the horse industry should benefit from the applications of gait analysis by improving the profitability of racing and riding activities.     

Non-steroidal anti-inflammatory drugs in equine orthopaedics

Orthopaedic disorders are commonly encountered in equine veterinary medicine, and non-steroidal anti-inflammatory drugs (NSAIDs) play an important role in the management of many equine orthopaedic disorders. There are multiple NSAIDs available for use in horses, including both non-selective and selective NSAIDS, and the body of literature evaluating the efficacy of these medications, their effects on normal and inflamed musculoskeletal tissues, and their side effects is broad. This review aims to summarise the current literature on the use of NSAIDs for equine orthopaedic disorders and examines new and future avenues for the management of inflammation in equine orthopaedics.     

Concepts for the clinical use of stem cells in equine medicine

Stem cells from various tissues hold great promise for their therapeutic use in horses, but so far efficacy or proof-of-principle has not been established. The basic characteristics and properties of various equine stem cells remain largely unknown, despite their increasingly widespread experimental and empirical commercial use. A better understanding of equine stem cell biology and concepts is needed in order to develop and evaluate rational clinical applications in the horse. Controlled, well-designed studies of the basic biologic characteristics and properties of these cells are needed to move this new equine research field forward. Stem cell research in the horse has exciting equine specific and comparative perspectives that will most likely benefit the health of horses and, potentially, humans.     

Equine Articular Chondrocytes on MACT Scaffolds for Cartilage Defect Treatment

Treatment of cartilage defects poses challenging problems in human and veterinary medicine, especially in horses. This study examines the suitability of applying scaffold materials similar to those used for human cartilage regeneration on equine chondrocytes. Chondrocytes gained from biopsies of the talocrural joint of three horses were propagated in 2D culture and grown on two different scaffold materials, hyaluronan (HYAFF^®) and collagen (BioGide^®), and evaluated by light and electron microscopy. The equine chondrocytes developed well in both types of materials. They were vital and physiologically highly active. On the surface of the scaffolds, they formed cell multilayers. Inside the hyaluronan web, the chondrocytes were regularly distributed and spanned the large scaffold fibre distances by producing their own matrix sheath. Half‐circle‐like depressions occasionally found in the cell membrane were probably related to movement on the flexible matrix sheath. Inside the dense collagen scaffold, only single cells were found. They passed through the scaffold strands by cell shape adaptation. This study showed that the examined scaffold materials can be used for equine chondrocyte cultivation. Chondrocytes tend to form multilayers on the surface of both, very dense and very porous scaffolds, and have strategies to span between and move in large gaps.     

Probiotic Use in Horses – What is the Evidence for Their Clinical Efficacy?

The gastrointestinal microbiota is extremely important for human and animal health. Investigations into the composition of the microbiota and its therapeutic modification have received increasing interest in human and veterinary medicine. Probiotics are a way of modifying the microbiota and have been tested to prevent and treat diseases. Probiotics are proposed to exert their beneficial effects through various pathways. Production of antimicrobial compounds targeting intestinal pathogens, general immune stimulation, and colonization resistance are among these mechanisms. Despite widespread availability and use, scientific, peer‐reviewed evidence behind commercial probiotic formulations in horses is limited. Additionally, quality control of commercial over‐the‐counter products is not tightly regulated. Although promising in vitro results have been achieved, in vivo health benefits have been more difficult to prove. Whether the ambiguous results are caused by strain selection, dosage selection or true lack of efficacy remains to be answered. Although these limitations exist, probiotics are increasingly used because of their lack of severe adverse effects, ease of administration, and low cost. This review summarizes the current evidence for probiotic use in equine medicine. It aims to provide veterinarians with evidence‐based information on when and why probiotics are indicated for prevention or treatment of gastrointestinal disease in horses. The review also outlines the current state of knowledge on the equine microbiota and the potential of fecal microbial transplantation, as they relate to the topic of probiotics.     

Isolation and characterization of bone marrow-derived equine mesenchymal stem cells

OBJECTIVE: To isolate and characterize bone marrow-derived equine mesenchymal stem cells (MSCs) for possible future therapeutic applications in horses. SAMPLE POPULATION: Equine MSCs were isolated from bone marrow aspirates obtained from the sternum of 30 donor horses. PROCEDURES: Cells were cultured in medium (alpha-minimum essential medium) with a fetal calf serum content of 20%. Equine MSC features were analyzed to determine selfrenewing and differentiation capacity. For potential therapeutic applications, the migratory potential of equine MSCs was determined. An adenoviral vector was used to determine the transduction rate of equine MSCs. RESULTS: Equine MSCs can be culture-expanded. Equine MSCs undergo cryopreservation in liquid nitrogen without altering morphologic characteristics. Furthermore, equine MSCs maintain their ability to proliferate and differentiate after thawing. Immunocytochemically, the expression of the stem cell marker CD90 can be detected on equine MSCs. The multilineage differentiation potential of equine MSCs was revealed by their ability to undergo adipogenic, osteogenic, and chondrogenic differentiation. CONCLUSIONS AND CLINICAL RELEVANCE: Our data indicate that bone marrow-derived stromal cells of horses can be characterized as MSCs. Equine MSCs have a high transduction rate and migratory potential and adapt to scaffold material in culture. As an autologous cell population, equine MSCs can be regarded as a promising cell population for tissue engineering in lesions of the musculoskeletal system in horses.