Prolonged use of NSAIDs leads to equine colic: Difference between revisions

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==Section 1 Genetics==
==Section 1 Genetics==
Include some current research, with at least one image.<br><br>
NSAIDs use in equines is much more regulated than in humans. Human NSAIDs can be sold over the counter whereas in equines a full veterinary examination is required before the proper NSAID can be determined. Equine NSAIDs such as ketofen and bute are used to inhibit inflammatory response enzymes including one enzyme called cyclooxygenase (COX). The COX group has two different medically relevant enzymes: COX-1 and COX-2. Recent studies have investigated the effects of selective COX-2 NSAIDs versus non-selective COX NSAIDS. They have found that COX-1 is a vital enzyme that contributes to multiple physiological studies.Therefore, multiple studies have shown that selective COX-2 NSAIDs are a safer option to reduce the likelihood for ulcerations (3).
 
One study looked specifically at Bute, a non-selective NSAID, and found that the recommended dosage of 4.4 mg/kg led to significantly degenerative effects on the GI tract (4). This is caused by increased permeability of the GI mucosa. Majority of the horses developed glandular ulcerations. Ulcerations are a major and well-known limitation for all NSAIDs. These sores within the lining of the stomach can cause copious amounts of internal bleeding and can be fatal. Ulcer disease can be caused by a number of factors including NSAIDs' irritant effect on the epithelium, impair the mucosal barrier, reduction of mucosal blood flow, and more (2).
 
Improved technology has led to the ability to create more target-specific drugs. As shown in figure 1, the COX-2 specific NSAID mainly only targets pain and inflammation, whereas non-selective COX NSAIDS inhibit not only pain and inflammation but also coagulation, kidney, and GI function (5). Ulcers are a result of unnecessary damage to the GI tract, but ulcers can be formed by other factors including changes in the GI microbiota.
 


Sample citations: <ref>[http://www.plosbiology.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pbio.1000005&representation=PDF Hodgkin, J. and Partridge, F.A. "<i>Caenorhabditis elegans</i> meets microsporidia: the nematode killers from Paris." 2008. PLoS Biology 6:2634-2637.]</ref>
Sample citations: <ref>[http://www.plosbiology.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pbio.1000005&representation=PDF Hodgkin, J. and Partridge, F.A. "<i>Caenorhabditis elegans</i> meets microsporidia: the nematode killers from Paris." 2008. PLoS Biology 6:2634-2637.]</ref>

Revision as of 02:46, 8 December 2021

Introduction

Equine colic is a broad term used to describe any form of abdominal pain caused by a variety of factors. Colic is the leading cause of unexpected deaths in domesticated horses (1). On average 4-10% of horses will experience colic throughout their lifetimes. Of that 10% about 64,000 horses die of colic-related problems each year. Death occurs due to the loss of proper function in the digestive system. Factors that can induce colic include obstructions in the digestive tract caused by sand ingestion, parasite infestation, and dehydration. Obstructive colic almost always requires surgery.

Changes in the digestive systems microbiome can also lead to colic. Factors that cause this include moldy feed, high grain based diets, bacterial infection (entritis), or long term use of non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs are a very common class of medications that are used for short-term pain relief and to reduce inflammation. However, long term use of NSAIDs can alter the microbiome which can lead to effects on the gastrointestinal (GI) tract. Common NSAIDs prescribed by veterinarians include phenylbutazone (Bute), flunixin, and ketoprofen (Ketofen) (3). These medications can alter a horse's microbiome and lead to ulcerations.

Interestingly enough NSAIDs have been shown to improve pain in already colicing horses. NSAIDs are a healing agent in colic just as much a causing agent. Little is known about NSAID enteropathy, and therefore NSAID misuse is incredibly common. The equine GI tract microbiome is made up of predominantly bacteroidetes and firmicutes. Bacteroidetes are gram-negative rod-shaped bacteria that perform essential metabolic conversions of proteins and complex sugar polymers. Firmicutes are gram-positive which break down carbohydrates such as starch. NSAIDs usually negatively affect the GI tract by decreasing the firmicutes population, which in turn increases the bacteroides population. This leads to decreased starch digestion, a common carbohydrate in food. Since the GI tract has no alternative way to digest the starch, it can lead to colic symptoms such as diarrhea.



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Section 1 Genetics

NSAIDs use in equines is much more regulated than in humans. Human NSAIDs can be sold over the counter whereas in equines a full veterinary examination is required before the proper NSAID can be determined. Equine NSAIDs such as ketofen and bute are used to inhibit inflammatory response enzymes including one enzyme called cyclooxygenase (COX). The COX group has two different medically relevant enzymes: COX-1 and COX-2. Recent studies have investigated the effects of selective COX-2 NSAIDs versus non-selective COX NSAIDS. They have found that COX-1 is a vital enzyme that contributes to multiple physiological studies.Therefore, multiple studies have shown that selective COX-2 NSAIDs are a safer option to reduce the likelihood for ulcerations (3).

One study looked specifically at Bute, a non-selective NSAID, and found that the recommended dosage of 4.4 mg/kg led to significantly degenerative effects on the GI tract (4). This is caused by increased permeability of the GI mucosa. Majority of the horses developed glandular ulcerations. Ulcerations are a major and well-known limitation for all NSAIDs. These sores within the lining of the stomach can cause copious amounts of internal bleeding and can be fatal. Ulcer disease can be caused by a number of factors including NSAIDs' irritant effect on the epithelium, impair the mucosal barrier, reduction of mucosal blood flow, and more (2).

Improved technology has led to the ability to create more target-specific drugs. As shown in figure 1, the COX-2 specific NSAID mainly only targets pain and inflammation, whereas non-selective COX NSAIDS inhibit not only pain and inflammation but also coagulation, kidney, and GI function (5). Ulcers are a result of unnecessary damage to the GI tract, but ulcers can be formed by other factors including changes in the GI microbiota.


Sample citations: [1] [2]

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[3]

Section 2 Microbiome

Include some current research, with a second image.

Conclusion

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References

  1. Hodgkin, J. and Partridge, F.A. "Caenorhabditis elegans meets microsporidia: the nematode killers from Paris." 2008. PLoS Biology 6:2634-2637.
  2. Bartlett et al.: Oncolytic viruses as therapeutic cancer vaccines. Molecular Cancer 2013 12:103.
  3. Lee G, Low RI, Amsterdam EA, Demaria AN, Huber PW, Mason DT. Hemodynamic effects of morphine and nalbuphine in acute myocardial infarction. Clinical Pharmacology & Therapeutics. 1981 May;29(5):576-81.

Resources:

1: https://thehorse.com/116386/equine-postoperative-ileus-insights/

https://www.myhorseuniversity.com/single-post/2017/09/25/equine-colic-causes-symptoms-treatment-and-prevention

3: https://vet.osu.edu/vmc/sites/default/files/import/assets/pdf/hospital/equineFarmAnimals/equine/articles/2008/colic.pdf

Primary article- https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0202527



Edited by Lauren S. Childs, student of Joan Slonczewski for BIOL 116 Information in Living Systems, 2021, Kenyon College.