donkey

The P-glycoprotein inhibitor ketoconazole causes a reversion to ivermectin sensitivity in cyathostomins in vitro

Citation

Laura Peachey, Jacqui. B. Matthews, Gina L. Pinchbeck, Faith A. Burden, Nikki Stradling, Jane Hodgkinson. The P-glycoprotein inhibitor ketoconazole causes a reversion to ivermectin sensitivity in cyathostomins in vitro. Presented at British Society for Parasitology Spring Meeting.

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Date presented: 
Monday 7 April 2014
Abstract

Anthelmintic resistance is a major veterinary and public health issue globally, of most concern is the level of resistance to the macrocyclic lactones. Recent studies have identified a role in resistance for the ATP binding cassette (ABC) drug transporters, P-glycoproteins (P-gps). This study demonstrates the effect of the P-gp inhibitor ketoconazole on the efficacy of ivermectin (IVM) against equid cyathostomin larvae using the larval migration inhibition test (LMIT). Third stage cyathostomin larvae (L3) were cultured from two populations; 1) with recent history of IVM resistance in vivo and 2) naive to anthelmintic exposure. The sensitivity to IVM in each group (n=8) was characterised using the LMIT. The IVM LMIT was repeated for each sample with and without the addition of 10µM ketoconazole. Probit analysis was performed on grouped data from each population to give LC-50 values. The LC-50 value for IVM in Populations 1 and 2 was 4.9 and 2.4µg/ml respectively indicating that Population 1 has a resistant phenotype in comparison to Population 2. Addition of 10µM ketoconazole to IVM in Population 1 caused a drop in LC-50 value from 5.8 to 1.6µg/ml. In Population 2 the effect of the addition of ketoconazole was negligible (1.1 to 0.9µg/ml). This study demonstrates that the P-gp inhibitor ketoconazole causes reversion to a sensitive phenotype in IVM-resistant cyathostomins, inferring that P-gps play a role in their resistance to IVM. This work will be corroborated by investigation into P-gp genes and their expression in cyathostomins.

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Chronic pleuropulmonary fibrosis and elastosis of aged donkeys - similarities to human pleuroparenchymal fibroelastosis (PPFE)

Citation

Amy Miele, K Dhaliwal, Nicole du Toit, J Murchison, C Dhaliwal, Harriet Brooks, Sionagh H. Smith, N Hirani, T Schwarz, C Haslett, W Wallace, Bruce McGorum. March 2014. Chronic pleuropulmonary fibrosis and elastosis of aged donkeys - similarities to human pleuroparenchymal fibroelastosis (PPFE). Chest.

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Publication details
Publication date: 
6 March 2014
Journal: 
Chest
DOI number: 
10.1378/chest.13-1306
Abstract

BACKGROUND:
Donkey Pulmonary Fibrosis (DPF) is a spontaneous syndrome of aged donkeys with high prevalence (35%). No previous detailed characterisation of DPF has been performed. We sought to determine the similarities of DPF to recognised patterns of human pulmonary fibrosis.

METHODS:
Whole lungs were collected from 32 aged donkeys at routine necropsy. Gross examination revealed pulmonary fibrosis in 19 donkeys (DPF cases), while 13 (controls) had grossly normal lungs. Eighteen whole inflated ex vivo lungs (11 DPF, 7 controls) were imaged with high resolution computed tomography (HRCT), while the remainder were sectioned and photographed. Tissue samples were collected from all lungs for histopathological evaluation using a standardised protocol. HRCT images and histology sections were reviewed independently and blindly. Lung tissue was analysed for herpes virus, fungal hyphae, mycobacteria and dust content.

RESULTS:
Ten of 19 DPF lungs were categorised as being 'consistent with' pleuroparenchymal fibroelastosis (PPFE) according to previously defined histological and imaging criteria. All 10 PPFE-like lungs had marked pleural and subpleural fibrosis, predominantly within the upper lung zone, with accompanying intra-alveolar fibrosis and elastosis. Asinine herpesvirus (AsHV) was ubiquitously expressed within control and DPF lung tissue. No other aetiological agents were identified.

CONCLUSIONS:
Many cases of DPF share key pathological and imaging features with human PPFE, a rare interstitial pneumonia. Consequently, further study of DPF may help elucidate the aetiopathogenesis of human PPFE.

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Review: Pharmacology and therapeutics in donkeys

Disclaimer

Non-DS research

This publication may be of interest, however, The Donkey Sanctuary has had no direct involvement with this publication, and claims no credit for published results.

To our best knowledge donkey welfare has not been compromised, and the following published research is furthering the understanding and respect of donkeys worldwide.

Citation

D. A. Grosenbaugh, C. R. Reinemeyer, D. Figueiredo. October 2011. Review: Pharmacology and therapeutics in donkeys. Equine Veterinary Education. 23:10. 523-530.

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Publication details
Publication date: 
1 October 2011
Volume: 
23
Issue: 
10
Page numbers: 
523-530
DOI number: 
10.1111/j.2042-3292.2011.00291.x
Abstract

Therapeutics are often administered to donkeys based on dosage and intervals recommended for horses because very few drugs have donkey-specific label indications. Yet differences between donkeys and horses in drug distribution, metabolism and elimination have been noted for most therapeutic agents studied. These differences can be partially explained by the donkey's unique physiology. Since their ancestors evolved in a desert environment, the modern donkey exhibits qualities that allow them to tolerate dehydration better than the horse and recover more quickly from its effects. Fluid balance and body water compartment partitioning differ from the horse and may have implications regarding drug distribution. Since donkeys are preferential browsers, differences in diet may have influenced evolutionary differences in metabolic disposition of drugs. It is important to acknowledge these differences when designing dose regimes for donkeys based on horse protocols in order to avoid either lack of efficacy or toxicity.

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Review: Anaesthesia and analgesia of the donkey and the mule

Disclaimer

Non-DS research

This publication may be of interest, however, The Donkey Sanctuary has had no direct involvement with this publication, and claims no credit for published results.

To our best knowledge donkey welfare has not been compromised, and the following published research is furthering the understanding and respect of donkeys worldwide.

Citation

Nora Matthews, J. P. A. M. van Loon. January 2013. Review: Anaesthesia and analgesia of the donkey and the mule. Equine Veterinary Education. 25:1. 47-51.

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Publication details
Publication date: 
1 January 2013
Volume: 
25
Issue: 
1
Page numbers: 
47-51
DOI number: 
10.1111/j.2042-3292.2011.00312.x
Abstract

The number of donkeys and mules throughout the world is stable, and awareness of their use and concern for welfare, pain recognition and treatment are receiving increasing veterinary interest. Therefore, accurate information about anaesthesia and analgesia in donkeys and mules is important to ever more equine practitioners. Since donkeys are physiologically and pharmacologically different from horses, knowledge on species specific aspects of anaesthesia and analgesia are very important. Mules combine elements from both donkey and horse backgrounds, leading to great diversity in size, temperament and body type. Physiologically, they seem to resemble horses more than donkeys. This review highlights the current knowledge on various anaesthetic and analgesic approaches in donkeys and mules. There is still much information that is not available about donkeys; in many circumstances, the clinician must use available equine information to treat the patient, while monitoring carefully to observe for differences in response to therapy compared to the horse.

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Comparative pharmacokinetics of meloxicam in clinically normal horses and donkeys

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Disclaimer

Non-DS research

This publication may be of interest, however, The Donkey Sanctuary has had no direct involvement with this publication, and claims no credit for published results.

To our best knowledge donkey welfare has not been compromised, and the following published research is furthering the understanding and respect of donkeys worldwide.

Citation

Melissa D. Sinclair, Katrina L. Mealey, Nora Matthews, Ken E. Peck, Tex S. Taylor, Brad S. Bennett. July 2006. Comparative pharmacokinetics of meloxicam in clinically normal horses and donkeys. American Journal of Veterinary Research. 67:6. 1082-1085.

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Publication details
Publication date: 
1 July 2006
Volume: 
67
Issue: 
6
Page numbers: 
1082-1085
DOI number: 
10.2460/ajvr.67.6.1082
Abstract

Objective: To determine the disposition of a bolus of meloxicam (administered IV) in horses and donkeys (Equus asinus) and compare the relative pharmacokinetic variables between the species.

Animals: 5 clinically normal horses and 5 clinically normal donkeys.

Procedures: Blood samples were collected before and after IV administration of a bolus of meloxicam (0.6 mg/kg). Serum meloxicam concentrations were determined in triplicate via high-performance liquid chromatography. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate standard noncompartmental pharmacokinetic variables.

Results: In horses and donkeys, mean +/- SD area under the curve was 18.8 +/- 7.31 microg/mL/h and 4.6 +/- 2.55 microg/mL/h, respectively; mean residence time (MRT) was 9.6 +/- 9.24 hours and 0.6 +/- 0.36 hours, respectively. Total body clearance (CL(T)) was 34.7 +/- 9.21 mL/kg/h in horses and 187.9 +/- 147.26 mL/kg/h in donkeys. Volume of distribution at steady state (VD(SS)) was 270 +/- 160.5 mL/kg in horses and 93.2 +/- 33.74 mL/kg in donkeys. All values, except VD(SS), were significantly different between donkeys and horses.

Conclusions and clinical relevance: The small VD(SS) of meloxicam in horses and donkeys (attributed to high protein binding) was similar to values determined for other nonsteroidal anti-inflammatory drugs. Compared with other species, horses had a much shorter MRT and greater CL(T) for meloxicam, indicating a rapid elimination of the drug from plasma; the even shorter MRT and greater CL(T) of meloxicam in donkeys, compared with horses, may make the use of the drug in this species impractical.

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Expression of PGP 9.5 by Enteric Neurons in Horses and Donkeys with and without Intestinal Disease

Citation

Neil Hudson, G.T. Pearson, I.G. Mayhew, Christopher Proudman, Faith A. Burden, Constance Fintl. November 2013. Expression of PGP 9.5 by Enteric Neurons in Horses and Donkeys with and without Intestinal Disease. Journal of Comparative Pathology.

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Publication details
Publication date: 
26 November 2013
DOI number: 
doi.org/10.1016/j.jcpa.2013.11.203
Abstract

Intestinal motility disorders are an important problem in horses and donkeys and this study was carried out in order to evaluate the enteric neurons in animals with and without intestinal disease. Surplus intestinal tissue samples were collected from 28 horses undergoing exploratory laparotomy for colic. In addition, surplus intestinal samples from 17 control horses were collected immediately following humane destruction for clinical conditions not relating to the intestinal tract. Similar samples were also collected during routine post-mortem examinations from 12 aged donkeys; six animals were humanely destroyed for conditions related to the intestinal tract, while the remaining six were humanely destroyed for other reasons including dental and orthopaedic diseases. Tissue samples were fixed in formalin and immunohistochemical labelling was performed targeting the enteric neurons using a polyclonal antibody specific for the neuronal marker PGP 9.5. The distribution and density of neuronal networks were assessed qualitatively and semiquantitatively. There was strong PGP 9.5 expression in both the horse and donkey samples and labelling was detected throughout the tissue sections. In both species, PGP 9.5-immunoreactive nerve fibres were detected in all layers of the intestinal tract, both in large and small intestinal samples. Networks of enteric neurons were present in the donkey with a similar distribution to that seen in the horse. There was no demonstrable difference in enteric neuronal density and distribution in the groups of animals with intestinal disease compared with those without, apart from two (out of 28) horses with intestinal disease that showed a marked reduction in PGP 9.5 immunoreactivity. Apart from these two animals, this total cohort analysis differs from some previously observed findings in horses with intestinal disease and may therefore reflect the different pathophysiological processes occurring in varying intestinal conditions resulting in colic both in the donkey and the horse.

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Participatory study of medicinal plants used in the control of gastrointestinal parasites in donkeys in Eastern Shewa and Arsi zones of Oromia region, Ethiopia

Citation

Claire Scantlebury, Laura Peachey, Jane Hodgkinson, Jacqui. B. Matthews, Andrew F. Trawford, Mulugeta Getachew, Gebre Tefera, Gina L. Pinchbeck. September 2013. Participatory study of medicinal plants used in the control of gastrointestinal parasites in donkeys in Eastern Shewa and Arsi zones of Oromia region, Ethiopia. BMC Veterinary Research. 9:179. 1-12.

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Publication details
Publication date: 
1 September 2013
Volume: 
9
Issue: 
179
Page numbers: 
1-12
DOI number: 
doi:10.1186/1746-6148-9-179
Abstract

Background

Gastrointestinal nematode infections constitute a threat to the health and welfare of donkeys worldwide. Their primary means of control is via anthelmintic treatments; however, use of these drugs has constraints in developing countries, including cost, limited availability, access to cheaper generic forms of variable quality and potential anthelmintic resistance. As an alternative, bioactive plants have been proposed as an option to treat and control gastrointestinal helminths in donkeys. This study aimed to use participatory methodology to explore donkey owner knowledge, attitudes and beliefs relating to the use of plant-based treatments for gastrointestinal parasites of donkeys in Ethiopia.

Results

In focus groups, 22/29 groups stated they knew of plants used for the treatment of gastrointestinal parasites in donkeys. All groups volunteered plants that were used in cattle and/or small ruminants. In total, 21 plants were named by participants. ‘Koso’ (Hagenia abyssinica) ‘Grawa’ (Vernonia amygdalina) and a mixed roots and leaves preparation were the most frequently named plant preparations. ‘Enkoko’ (Embelia shimperi) and ‘a mixture of roots and leaves’ were ranked highly for effectiveness in donkeys. However, ‘Grawa’ and ‘Koso’ were the highest ranked when taking into account both the rank position and the number of groups ranking the plant.

Thematic analysis of participants’ current attitudes and beliefs surrounding traditional plant-based remedies for gastrointestinal parasites revealed that anthelmintics obtained from clinics were generally favoured due to their ease of administration and perceived higher effectiveness. There was doubt surrounding the effectiveness of some plant-based treatments, but there were also perceived advantages including their low cost, ease of cultivation and availability. However, plant-based treatments were considered a “past trend” and people favoured “modern” medicine, particularly among the younger generation.

Conclusions

There was extensive knowledge of plant-based treatments for gastrointestinal parasites in livestock in Ethiopia. In donkeys, Koso (Hagenia abyssinica), Grawa (Vernonia amygdalina), Enkoko (Embelia shimperi) and ‘mixed roots and leaves’ were the most frequently named and/or highest ranked plants with reported efficacy against gastrointestinal parasites. Further in vitro and in vivo investigation of these plants is now required to determine viable alternatives for the treatment and control of gastrointestinal parasites in Ethiopia.

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Donkey assisted therapy

Citation

David Cook, Stephen Blakeway. Donkey assisted therapy. Presented at Donkey Welfare Symposium. (1 November 2013). California, USA.

Authors
Presentation details
Date presented: 
Saturday 3 November 2012
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