ArticleLiterature Review

Advances in Diagnostics and Treatments in Horses and Foals with Gastric and Duodenal Ulcers

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Abstract

Equine gastric ulcer syndrome (EGUS) primarily describes ulceration in the terminal esophagus, nonglandular squamous mucosa, glandular mucosa of the stomach, and proximal duodenum. EGUS is common in all breeds and ages of horses and foals. This article focuses on the current terminology for EGUS, etiologies and pathogenesis for lesions in the nonglandular and glandular stomach, diagnosis, and a comprehensive approach to the treatment and prevention of EGUS in adult horses and foals.

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... Strictures can form as a sequel to gastric ulceration, with tissue damage associated with ulceration leading to inflammation, scarring and the development of granulation tissue, and functional and mechanical obstruction (Zedler et al., 2009). In gastroduodenal ulcer disease (GDUD), which is mainly encountered in foals between 2 and 6 months of age, stricture formation at the pylorus and duodenum may occur, leading to gastric outflow obstruction (Camacho-Luna et al., 2018;McKenzie, 2018;Zedler et al., 2009). Affected foals are dull and may develop bruxism and ptyalism, and in some cases, they may present with gastric reflux (McKenzie, 2018). ...
... Currently, a diagnosis of gastric ulceration can only be made by gastroscopy (Camacho-Luna et al., 2018;McKenzie, 2018), while transcutaneous ultrasonography and barium-contrast radiography can be used to confirm delayed gastric emptying (Camacho-Luna et al., 2018;McKenzie, 2018). If a stricture is present, complete emptying of the stomach takes more than 2 h (McKenzie, 2018;Sprayberry, 2015). ...
... Currently, a diagnosis of gastric ulceration can only be made by gastroscopy (Camacho-Luna et al., 2018;McKenzie, 2018), while transcutaneous ultrasonography and barium-contrast radiography can be used to confirm delayed gastric emptying (Camacho-Luna et al., 2018;McKenzie, 2018). If a stricture is present, complete emptying of the stomach takes more than 2 h (McKenzie, 2018;Sprayberry, 2015). ...
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A 2‐month‐old Warmblood colt presented with recurrent colic and regurgitation. Gastroscopy, performed on several occasions, and barium‐contrast radiography revealed severe squamous gastric ulceration and stenosis at the level of the margo plicatus. Treatment with omeprazole reduced the extent and severity of the gastric ulcers but did not affect the stenosis. The foal was euthanised because of a poor prognosis, and post‐mortem examination confirmed the clinical diagnosis. Severe squamous gastric ulceration, granulation tissue formation and cicatrisation of deep gastric lesions were considered to have caused the stenosis. Gastroduodenal outflow obstruction is a recognised disorder in foals, but stenosis at the level of the margo plicatus has not been reported in foals or adult horses. To the authors' knowledge, this is the first case of severe squamous gastric ulceration, complicated by stenosis at the level of the margo plicatus, in a foal. Although rare, gastric stenosis should be considered in foals suffering recurrent colic and regurgitation.
... 13 Although mucosal ulcers may heal spontaneously, 15 this is uncommon in horses in training or racing, and medical treatment is therefore required: omeprazole, a proton pump inhibitor, is considered the drug of choice for prevention and treatment of squamous ulceration, acting by suppressing acid secretion. 1,5,11,[16][17][18][19][20][21][22] However, pharmacological treatment is expensive and may require prolonged administrations: therefore, interest in nutraceutical supplements with anti-ulcerogenic properties has increased and numerous studies have been carried out to evaluate their effectiveness in preventing and treating gastric ulceration. 13,15,[23][24][25][26][27][28][29] supplement designed to protect gastric mucosa, containing pectin, soy lecithin, zinc oxide and Castanea sativa Mill. ...
... The administration of the supplement was accompanied by changes in management, which could have contributed to the reduction of gastric mucosa lesions and hyperkeratosis; indeed, stall confinement, intermittent feeding, and high in carbohydrates diets are considered to be important risk factors for EGUS [40][41][42][43][44][45] ; therefore, increasing pasture turnout, providing ad libitum goodquality hay and reducing nonstructural carbohydrate intake may decrease the severity of EGUS. 1,21,40,41,46 However, the control group was also subjected to the same environmental and dietary modifications, without obtaining any improvement in ESGD grade: therefore, it is likely that the administration of Trophogast pellet had a decisive role in the healing of the squamous gastric mucosa. An improvement in the control group could also have been expected because of environmental and dietary changes. ...
... Gastric ulceration is commonly associated with a poor body condition 1,5,11,20,21,42 ; different studies have reported an increase in body weight after treatment, associated with an improvement in ulcer grades 13,16,23,41 . However, the results of the present study showed no significant difference in body weight before and after the treatment period, neither in the treatment group nor in the control group. ...
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Introduction: Equine squamous gastric disease (ESGD) may require prolonged treatments with acid suppressants; therefore, interest in nutraceutical supplements with anti-ulcerogenic properties has increased. This study aims to investigate the efficacy of Trophogast pellet for the treatment of ESGD in endurance horses. Material and methods: Fifteen endurance horses were included based on their gastroscopic examination and randomly assigned to a treatment group, receiving Trophogast pellet for 30 days together with management changes, or to a control group, only subjected to management modifications. At the end of treatment, gastroscopy was repeated. Scores were assigned according to the Equine Gastric Ulcer Council scoring system. All horses were weighed at the beginning and at the end of the study. ESGD grades and weight before and after treatment were compared. Results: At enrolment, median ESGD score in the treatment group was 2, while in the control group it was 1. After the treatment period, a significant decrease in ESGD grade was observed in the treatment group (median 1, p = 0.0078), while there was no change in the control group (median 2). No significant weight change was observed in either group. Conclusion: Trophogast pellet was effective at promoting healing of mild ESGD in endurance horses.
... 68 To prevent ESGD recurrence, nutritional and management changes are needed in addition to pharmacologic treatment. [69][70][71] Nutrition plays a clearer role in ESGD prevention and management but it is thought that these principles also may apply for EGGD. ...
... The recurrence rate of ESGD is high; thus, medical and nutritional management strategies should be applied together to achieve long-term beneficial effects. [69][70][71] The nutritional recommendations are summarized in Fig. 2. Pasture turnout is preferred, even if feeding grass hay ad libitum is possible. 71 Stressors (eg, competition for feed and bullying) and feeding feedstuff high in nonstructural carbohydrates (NSCs) should be avoided. ...
... 71 Stressors (eg, competition for feed and bullying) and feeding feedstuff high in nonstructural carbohydrates (NSCs) should be avoided. 69,70 When pasture grazing is not possible, forage (alfalfa hay and good quality grass hay) should be fed ad libitum, but if not possible, forage should be fed in an amount of at least 1.5% of the BW on a DM basis in 4 meals to 6 meals per day. [68][69][70] The small meals should be divided equally during daylight hours and the last meal late in the evening should provide enough forage to eat during night-time. ...
Article
Many horses are fed differently than their wild ancestors. They often have limited access to pasture and are fed conserved forage and concentrates rich in starch and sugars, in only 2 meals per day. Feeding practices in contrast to natural feeding behavior can lead to gastrointestinal issues. Standard nutritional evaluation is warranted because of its important role in prevention and in treatment and management of diseases. When medical and nutritional treatments are combined, success rates are higher. New techniques to characterize equine microbiota have been used, allowing for microbiota manipulation to prevent and treat intestinal diseases.
... Equine gastric ulcer syndrome (EGUS) is a broad term, commonly used to characterise erosive and ulcerative stomach diseases in horses. The nonglandular stomach (squamous mucosa), glandular stomach, terminal oesophagus, and proximal duodenum are relatively the most prevalent anatomical sites in which gastric disease may occur (Andrews et al. 1999;Andrews et al. 2005;Sykes et al. 2015;Camacho-Luna et al. 2018). ...
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Equine gastric ulcer syndrome (EGUS) is a multifactorial disorder and one of the most common diseases in horses. The objective of this research was to detect one of the potential risk factors of equine squamous gastric disease (ESGD), the Helicobacter pylori specific gene, and tracing the presence of the duodenal ulcer-promoting gene (dupA) as a possible virulence marker. Gastric fluid together with faecal samples were collected from twenty rural horses from around Tabriz, Iran. Throughout the endoscopic examinations, the type, numbers, severity, and the location of the lesions were documented. Nine of twenty horses exhibited macroscopic lesions in the squamous mucosa that were later classified into grades 1, 2, 3, and 4. Only three of these horses exhibited H. pylori in their gastric fluid samples, whereas all faecal samples were H. pylori-negative. All the H. pylori-positive cases manifested severe forms of ESGD (grades 3–4). The age and sex were both unrelated to the lesion severity and ESGD status in this study. Research is required to further discuss the virulence aspects of dupA regarding ESGD.
... However, many TB breeders are reluctant to do this, believing that the lower energy and protein digestibility of fiber feeds reduce growth rates and cause "fiber-belly" in comparison with conventional high-starch diets [16,17]. Despite the facts that Saastamoinen and S€ arkij€ arvi [18] have reported that weanlings are capable of digesting a high-quality fiber diet and that reduction of starch and increase in fiber intake aids in the recovery of gastric ulcers in horses [19], there is still much prejudice against feeding high-fiber diets to young growing TB. ...
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Traditions and the economic advantage when producing big athletic TB yearlings for sale, encourages owners to feed high levels of cereals. Such diets can predispose gastric ulceration and developmental orthopaedic diseases, impacting negatively on future careers. Study aims: 1. Determine if an all fibre creep feed (TMFR) would sustain equal growth rates in TB foals versus a cereal based stud cube (SC); 2. Compare pH and lactate produced by SC and TMFR in in vitro foregut and hind gut conditions. Eight TB foals in matched-pairs were fed SC or TMFR for 18 weeks. Weight gain (ADG), height at wither and hip, heart girth and body length were recorded weekly. Similar growth rates were recorded for all measurements. ADG of 1 and 1.1kg/head/d for TMFR and SC respectively. In vitro foregut incubation of SC and TMFR at 37oC in pepsin HCl solution for 6 hours, produced higher pH 5.84 (TMFR) compared with 5.33 (SC) (P<0.05). Gas production measured fermentation rate, acidity and lactate from TMFR and SC, incubated with faecal inoculum from the foals on the same diet. Fermentation rates and lag times were equal for both feeds; total gas produced, t 50 and Y50 were greater (P<0.05) for SC. Lactate and pH levels were lower and higher respectively for the TMFR. This study showed that similar growth in TB foals was achieved on the TMFR feed and that potentially better gut health, denoted by higher pH and lower lactate levels could be maintained by fibre compared with cereal feed.
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Over the last 10 years there has been increasing awareness and subsequently recorded cases of equine gastric ulcer syndrome and with this comes an increased interest in appropriate nutrition and feed management. This review presents a systematic approach to assessing the ration of a horse at risk or diagnosed with equine gastric ulcer syndrome and demonstrates the ample evidence upon which to base nutritional recommendations for horses with equine squamous gastric disease, and to a lesser extent, equine glandular gastric disease, with an emphasis on forage. Careful selection and management of the forage ration should be the first step in designing a suitable ration, followed by selection of an appropriately low starch and sugar (less than 2g per kg body weight per day and 1g per kg body weight per meal) complementary feed. There is still more to learn about the role of supplements in the prevention and treatment of equine gastric ulcer syndrome, thus these should currently be viewed as an adjunct to an appropriate base diet and not as an isolated solution.
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Many domesticated horses have gastric ulcers which can be diagnosed and graded during gastroscopy. A distinction should be made between equine squamous gastric disease (ESGD), which is caused by exposure of the mucosa to acid, and equine glandular gastric disease (EGGD), thought to occur when mucosal defence mechanisms are compromised. Horses with gastric ulcers may, but do not always, show clinical signs such as poor appetite, mild colic, discomfort during girthing, behavioural changes and reduced performance. The mainstay of treatment is blocking acid production using the proton pump inhibitor omeprazole. Treatment is usually successful in cases of ESGD, but less so for EGGD, where treatment duration is longer and for which sucralfate may be added or alternatives necessary, such as misoprostol, a prostaglandin analogue. To prevent recurrence of ulcers known risk factors, such as high concentrate diets, intense exercise and stress should be avoided or minimized.
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This study evaluated the incidence of gastritis in foals subjected to different weaning management methods. Sixteen crossbreed foals [230±35 kg], were enrolled in an experiment with a randomized block design. After weaning, foals were housed in either individual pens or a group pen. Gastritis in the foals was evaluated through gastroscopy. Data were submitted to analysis of variance by the non-parametric Friedman test at 0.05 significance level. Before weaning, gastritis was observed in 87.5% of the foals, and the scores for the number of gastric lesions were 2.10 and 1.56 for foals housed in group and individual pens, respectively. After weaning, the scores for the number of gastric lesions were 1.75 and 1.25 for foals housed in group and individual pens, respectively. For the intensity of gastric lesions, the average scores observed before weaning were 3.31 and 1.37 for foals housed in groups and individual pens, respectively. After weaning, the scores for the intensity of gastric lesions were 1.93 and 1.00 for foals housed in group and individual pens, respectively. The intensity of the gastric lesions decreased when comparing foals prior to weaning and after weaning, regardless of the management system (P<0.05). The number of lesions was not significantly different but tended to decrease after weaning. Differences in plasma cortisol concentrations were observed between samples collected on the weaning date and after weaning (P<0.05). No differences were detected in plasma gastrin concentration. In conclusion, gastritis in foals can be observed before weaning, which contributes to a decreased gastric lesion incidence.
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Equine gastric ulcer syndrome (EGUS) is characterized by ulceration in the terminal esophagus, proximal (squamous) stomach, distal (glandular) stomach, and proximal duodenum. It is a common disease in all breeds and ages of horses and foals. Risk factors for EGUS include stress, transport high-energy feed confinement in stalls, intermittent feed, and intense exercise and racing. Horses are very sensitive to any environmental change, which is cause of high prevalence of gastric ulcers especially in racing horses. Taking into consideration of high prevalence of EGUS, our research work was based on pathomorfological and gross evaluation of gastric mucosa in different breeds of horses. Assessment of the severity of lesions is most commonly achieved by assigning a grade that describes the mucosal appearance at different anatomic sites. A variety of different systems have been published for the horses. 10 stomachs were removed from a mixed population post mortem. In our study pathological classification of lesion type was evaluated by two different scoring system, with scales ranging from 0–4. Samples from areas with lesion were taken for histopathology evaluation. EGUS was confirmed on stomachs of six horses. Lesions with different score mostly localized on squamous region near margo plicatus. Changes on squamous mucosa was confirmed on stomach of four horses as well as glandular region two horses. According to score systems mentioned in publication changes on gastric mucosa was measured up 1, 2, 3 score and were characterized as hyperceratosis, erosions and deeper lesion involving the mucosa, extending to the submucosa layer and hyperemia of glandular mucosa. The results of pathomorphological examination of the condition of the wall of the gastric mucosa and histological changes, the effectiveness of the submitted classification systems was established.
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Gastroscopy is a routine technique performed in equine practice to evaluate the stomach and is the gold standard diagnostic test for equine gastric ulcer syndrome (EGUS). There are few publications on the safety of the technique and any associated complications, in particular colic. The objective of the study was to review all gastroscopic examinations performed at two equine clinics over a 5‐year period, and to describe any colic episodes in the 48 h post gastroscopy. In this clinical audit, hospital databases were searched for animals that had a gastroscopic examination in the 5‐year study period. Signalment, sedative drugs, stomach insufflation/deflation, gastroscopic findings, occurrence of colic in the 48 h post examination and any medication administered during that time were recorded. A total of 436 horses underwent 573 gastroscopic examinations during the study period. Post‐gastroscopy colic was recorded in 17/573 examinations (2.9%); 16 were mild, but one (0.2%) required exploratory laparotomy. Cases of gastric impaction were more commonly associated with colic post gastroscopy. When examinations of horses with gastric impaction were excluded, the prevalence of colic post gastroscopy was 5/561 (0.9%). A limitation of the study was that variability in technique was likely, due to multiple different clinicians performing gastroscopic examinations. A study with a larger sample size is required to confirm the findings of this audit. Gastroscopy is a relatively safe procedure but there is a small risk of colic afterwards.
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Gastric ulcers are common in horses and equine gastric ulcer syndrome describes ulcers in the distal oesophagus, nonglandular and glandular stomach as well as the proximal duodenum. Ulcers in the distal oesophagus and nonglandular region of the stomach are probably caused by hydrochloric acid, whereas ulcers in the glandular stomach and proximal duodenum are likely to be caused by a breakdown in the mucosal defence mechanisms. Regardless of the location of ulcers, initial treatment with pharmacological agents is necessary to suppress hydrochloric acid; however, nutrition and management changes are required to maintain ulcer healing and help prevent recurrence. In addition, many dietary supplements have been marketed to help maintain stomach health and some scientific data on their effects on gastric ulcer scores and gastric juice pH are presented.
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Reasons for performing the study: A previous study demonstrated that a dose effect between 1.6 and 4.0 mg/kg bwt of omeprazole per os s.i.d. is present in the treatment of equine gastric ulceration. In the same study, healing of glandular ulceration appeared inferior to healing of squamous ulceration. However, several limitations were recognised in that study and further investigation is warranted. Objectives: To further investigate the presence of a dose relationship in the treatment of gastric ulceration under conditions that may favour omeprazole efficacy such as administration prior to exercise and after a brief fast, and potential differences between the response of squamous and glandular ulceration to omeprazole therapy. Study design: A blinded, randomised, dose–response clinical trial. Methods: Sixty Thoroughbred racehorses with grade ≥2/4 squamous and/or glandular ulceration were identified by gastroscopy. Horses were randomly assigned to receive either 1.0, 2.0 or 4.0 mg/kg bwt of enteric coated omeprazole per os s.i.d. 1–4 h prior to exercise. Gastroscopy was repeated at approximately 28 days. Results: The lower doses studied (1.0 and 2.0 mg/kg bwt) were noninferior to the reference dose (4.0 mg/kg bwt) in the treatment of squamous ulceration. Healing was greater in squamous ulceration than glandular ulceration (86% vs. 14%; P<0.0001). Improvement in ulcer grade was more likely in squamous lesions than glandular lesions (96% vs. 34%; P<0.0001). Worsening of the glandular ulcer grade was observed in 36% of horses. Conclusions: The results of this study suggest that, under the conditions studied, where omeprazole is administered before exercise and following a brief fast, doses of omeprazole as low as 1 mg/kg bwt per os s.i.d. may be as effective as higher doses. The proportion of glandular ulceration that heals with 28 days of omeprazole therapy is less than that of squamous ulceration.
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Gastric ulcers are common in horses. The purpose of this study was to test the effect of a commercially available supplement, SmartGut® Ultra pellets (SmGU) on gastric ulcer scores and gastric juice pH after omeprazole treatment in stall-confined horses. Eight Thoroughbred horses were studied in a 2-period, 2-treatment crossover design, where the SmGU (40 g, twice daily) was mixed in grain feed. Horses were stall-confined and treated with the supplement or control for 6 weeks, consisting of 2 weeks (Days 1–14) omeprazole treatment, 2 weeks (Days 14–28) following discontinuation of omeprazole treatment, one week (Days 28–35) alternating feed deprivation to induce or worsen existing ulcers and a one week (Days 35–42) recovery period. Gastroscopy was performed and gastric juice pH measured on Days 0, 14, 28, 35 and 42. Gastric ulcer lesion number (NGN) and severity (NGS) scores were assigned to each horse by an investigator (F.M.A.) masked to treatment. On Day 0 before treatment, mean NGN and NGS scores and gastric juice pH were not different (P>0.05) between treatment groups. By Day 14, mean NGN and NGS scores decreased (P<0.05) in both treatment groups. By Days 28 and 35, mean NGN score significantly increased in the untreated control horses but not the SmGU-treated horses. By Day 42, mean NGN and NGS scores were not different in either group and were significantly lower than Day 0. Mean gastric juice pH was higher in both groups on Day 14 as a result of omeprazole treatment when compared with other days. SmartGut® Ultra supplement added to the feed prevented the worsening of gastric ulcer number 2 weeks after omeprazole treatment, without altering the gastric juice pH. Supplementation with SmGU might aid in protection of the nonglandular stomach from recurrence of ulcers after omeprazole treatment in stall-confined horses undergoing intermittent feeding.
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Interest in Equine Gastric Ulcer Syndrome (EGUS) has recently increased in part due to a growing awareness of the differences between squamous and glandular disease. The pathophysiology and epidemiology of squamous and glandular disease are different and recently it has been shown that the response of glandular gastric ulceration to monotherapy with omeprazole is poor. Given these differences it has been recommended that specific treatment guidelines be formulated for equine glandular disease and that adjunctive therapies be investigated. Along these lines it has been suggested that the addition of antimicrobials may enhance healing. The objective of this study was to investigate whether the addition of trimethoprim-sulphadimidine to omeprazole therapy would result in superior healing of naturally occurring equine glandular ulceration compared with omeprazole monotherapy. Combination therapy of omeprazole plus trimethoprim-sulphadimidine could not be demonstrated to be superior to omeprazole monotherapy. Healing of the glandular mucosa was observed in 7/15 (47%; 95% CI 24 to 71%) and 3/13 (23%; 95% CI 7% to 50%) of horses in the TMPS and OMEP groups, respectively (OR = 1.8; 95% CI 0.32 to 10.0; p = 0.67). Improvement of the glandular mucosa was observed in 12/15 (80%; 95% CI 56 to 94%) and 9/13 (69%; 95% CI 42 to 89%) of horses in the TMPS and OMEP groups, respectively (OR = 2.9; 95% CI 0.6 to 15.0; p = 0.25). The results of the present study do not support the addition of trimethoprim-sulphadimidine to therapeutic protocols for equine glandular ulceration. Several limitations were present in the study and the use of antimicrobials as an adjunctive treatment warrants further investigation. However, given the potential deleterious consequences associated with the indiscriminate use of antimicrobials, the inclusion of antimicrobials in treatment regimes for EGUS is not justified until their efficacy is further validated.
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Equine gastric ulcer syndrome (EGUS) is very common among performance horses, with a reported prevalence of approximately 90% in racehorses, and also > 50% in foals. Omeprazole, an acid pump inhibitor 5 times more potent than ranitidine, has been used with great success to treat EGUS. This multicentre study of Thoroughbred racehorses with endoscopically verified gastric ulcers was designed to demonstrate the efficacy of an equine oral paste formulation of omeprazole in the treatment and prevention of recurrence of EGUS. Of the 100 horses entered into the study, 25 were sham-dosed for the full 58 days of the study. The remaining 75 horses all received omeprazole paste, 4 mg/kg bwt/day once daily for 28 days. At Day 28, 25 of treated horses continued on this dosing regimen while 25 received a half dose (2 mg/kg bwt once daily) and 25 horses were sham-dosed. By Day 28, gastric ulcers were completely healed in 77% of omeprazole-treated horses, while 92% were significantly (P < 0.01) improved. In contrast, 96% of the sham-dosed horses still had gastric ulcers at Day 28. The improvement was maintained in horses that continued on either a full dose or half dose of omeprazole paste until Day 58. However, in those horses that were removed from omeprazole treatment at Day 28, the incidence and severity of the gastric ulcers at the end of the study were similar to those horses that did not receive the omeprazole paste. This study demonstrates that omeprazole paste, 4 mg/kg bwt per os, once daily, is highly effective in healing gastric ulcers in Thoroughbred racehorses and that either a full dose or half dose of omeprazole paste effectively prevents the recurrence of EGUS. The study also indicates that gastric ulcers in untreated horses did not demonstrate a significant rate of spontaneous healing.
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To measure pH, volatile fatty acid (VFA) concentrations, and lactate concentrations in stomach contents and determine number and severity of gastric lesions in horses fed bromegrass hay and alfalfa hay-grain diets. Six 7-year-old horses. A gastric cannula was inserted in each horse. Horses were fed each diet, using a randomized crossover design. Stomach contents were collected immediately after feeding and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours after feeding on day 14. The pH and VFA and lactate concentrations were measured in gastric juice Number and severity of gastric lesions were scored during endoscopic examinations. The alfalfa hay-grain diet caused significantly higher pH in gastric juice during the first 5 hours after feeding, compared with that for bromegrass hay. Concentrations of acetic, propionic, and isovaleric acid were significantly higher in gastric juice, and number and severity of nonglandular squamous gastric lesions were significantly lower in horses fed alfalfa hay-grain. Valeric acid, butyric acid, and propionic acid concentrations and pH were useful in predicting severity of nonglandular squamous gastric lesions in horses fed alfalfa hay-grain, whereas valeric acid concentrations and butyric acid were useful in predicting severity of those lesions in horses fed bromegrass hay. An alfalfa hay-grain diet induced significantly higher pH and VFA concentrations in gastric juice than did bromegrass hay. However, number and severity of nonglandular squamous gastric lesions were significantly lower in horses fed alfalfa hay-grain. An alfalfa hay-grain diet may buffer stomach acid in horses.
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EGUS is a common problem in horses and foals. Acids are the important causative factors and current therapy targets the suppression of gastric HCl and creation of a permissive environment for ulcer healing. Diagnosis is based on history, clinical signs, gastroscopy, and response to treatment. Of the products available, only GastroGard (FDA approved) and ranitidine have been shown to be efficacious in the treatment of EGUS. Ranitidine is often associated with treatment failure as a result of incorrect dosing and lack of owner compliance, because of the three times daily dosing required. Also, EGUS occurs in critically ill neonatal foals, but the pathogenesis may be different than in adult horses and acid-suppressive therapy may not be as effective.
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To compare the effects of hydrochloric acid (HCl) and various concentrations of volatile fatty acids (VFAs) on tissue bioelectric properties of equine stomach nonglandular (NG) mucosa. Gastric tissues obtained from 48 adult horses. NG gastric mucosa was studied by use of Ussing chambers. Short-circuit current (Isc) and potential difference (PD) were measured and electrical resistance (R) and conductance calculated for tissues after addition of HCl and VFAs (5, 10, 20, and 40 mM) in normal Ringer's solution (NRS). Mucosa exposed to HCl in NRS (pH of 1.5 and, to a lesser extent, 4.0) had a significant decrease in Isc, PD, and R, whereas tissues exposed to acetic acid at a pH of < 4.0, propionic and butyric acids at a pH of <or= 4.0, and valeric acid at a pH of <or= 7.0 induced a concentration-dependent effect on reduction in these same values. Values for Isc returned to baseline (recovery of sodium transport) after addition of calcium carbonate in tissues exposed to all concentrations of VFAs except the higher concentrations of valeric acid at a pH of <or= 4.0. Histologic examination revealed cell swelling in the mucosal layers below and adjacent to the stratum corneum in tissues exposed to HCl and VFAs at a pH of <or= 4.0. The VFAs, especially acetic acid, in the presence of HCl at a pH of <or= 4.0 appear to be important in the pathogenesis of NG mucosal ulcers in horses.
Article
The use of anti-ulcer medication in the neonatal intensive care unit (ICU) is common due to the concern for development of catastrophic gastric ulcer disease. In man, however, the use of acid-suppressive medication has been shown in some studies to be a substantial risk factor for the development of Clostridium difficile-associated diarrhoea (CDAD), bacteraemia and neonatal sepsis. The purpose of the study reported herein is to evaluate the influence of anti-ulcer medications on the development of diarrhoea in the neonatal foal. The use of anti-ulcer medication does not alter the incidence of diarrhoea in foals treated in an ICU. The records of 1710 foals from 6 different equine hospitals were examined and the use of anti-ulcer drugs was recorded. The presence of in-hospital acquired diarrhoea, CDAD, Clostridium perfringens-associated diarrhoea, neonatal sepsis and salmonellosis were documented. In addition, the presence of gastric ulceration, duration of hospital stay and short-term outcome were examined. The use of anti-ulcer medications increased the odds of in-hospital diarrhoea by 2.0 (95% CI 1.4-2.9; P < 0.0001), relative to the use of no anti-ulcer medication. There was no significant association of anti-ulcer medication with CDAD (P = 0.3189) (OR 2.0; 95% CI 0.4-9.5). Further, results indicated that decreased prevalence of gastric ulceration was not associated with use of anti-ulcer drugs among foals in the study for which these data were known (P = 0.5522). Use of anti-ulcer drugs increases the odds of developing diarrhoea, and may not reduce the incidence of gastric ulceration in hospitalised equine neonates. The use of anti-ulcer drugs in neonatal foals being treated in a hospital setting should be carefully evaluated on an individual basis to determine if such use is warranted.
Article
Although several studies have assessed the short-term effect of dietary supplements on the treatment and prevention of gastric ulceration in horses, few have assessed the response over a duration of more than 30 days. A blinded randomized noninferiority clinical trial was conducted using 42 Thoroughbred horses in race training with squamous ulceration of ≥ grade 2/4, randomly assigned to one of two treatment groups for a period of 90 days: omeprazole at the full label dose of 4 mg/kg or the Succeed digestive conditioning supplement. Noninferiority analyses and Wilcoxon sign rank tests were used to analyze the data. At day 90, Succeed was noninferior to 4 mg/kg omeprazole administered daily in terms of the proportion of horses with complete resolution of squamous ulceration. At day 30, Succeed was found to be inferior to omeprazole in terms of the proportion of horses with grade ≤1/4 squamous ulceration. The proportion of horses with reducing squamous ulcer score (compared with day 0) was statistically significant for both treatments at days 30 and 60. At day 90 of the 17 horses on Succeed, nine had a reducing squamous ulcer score (P value = .049), and of the 19 horses on omeprazole, 10 had a reducing squamous ulcer score at day 90 (P value = .091). The noninferiority of Succeed compared to omeprazole at 90 days for the complete resolution of squamous ulceration and the reduced efficacy of omeprazole following 90 days of treatment are likely to be of interest to practitioners managing gastric ulceration in performance horses.
Article
Equine gastric ulcer syndrome is common in domesticated horses, especially those performing in athletic endeavours. However, the prevalence of equine gastric ulcer syndrome in feral populations of horses is not documented. This study investigated the prevalence and severity of squamous and glandular gastric ulceration in an abattoir population of horses in the UK. Both squamous and glandular ulceration were more prevalent in domesticated horses when compared to the feral horses studied.
Article
Reasons for performing the studyA previous study demonstrated that a dose effect between 1.6 and 4.0 mg/kg bwt of omeprazole per os s.i.d. is present in the treatment of equine gastric ulceration. In the same study, healing of glandular ulceration appeared inferior to healing of squamous ulceration. However, several limitations were recognised in that study and further investigation is warranted.Objectives To further investigate the presence of a dose relationship in the treatment of gastric ulceration under conditions that may favour omeprazole efficacy such as administration prior to exercise and after a brief fast, and potential differences between the response of squamous and glandular ulceration to omeprazole therapy.Study designA blinded, randomised, dose-response clinical trial.Methods Sixty Thoroughbred racehorses with grade ≥2/4 squamous and/or glandular ulceration were identified by gastroscopy. Horses were randomly assigned to receive either 1.0, 2.0 or 4.0 mg/kg bwt of enteric coated omeprazole per os s.i.d. 1-4 h prior to exercise. Gastroscopy was repeated at approximately 28 days.ResultsThe lower doses studied (1.0 and 2.0 mg/kg bwt) were noninferior to the reference dose (4.0 mg/kg bwt) in the treatment of squamous ulceration. Healing was greater in squamous ulceration than glandular ulceration (86% vs. 14%; P<0.0001). Improvement in ulcer grade was more likely in squamous lesions than glandular lesions (96% vs. 34%; P<0.0001). Worsening of the glandular ulcer grade was observed in 36% of horses.Conclusions The results of this study suggest that, under the conditions studied, where omeprazole is administered before exercise and following a brief fast, doses of omeprazole as low as 1 mg/kg bwt per os s.i.d. may be as effective as higher doses. The proportion of glandular ulceration that heals with 28 days of omeprazole therapy is less than that of squamous ulceration.
Article
It has recently been highlighted that significant differences exist between ulceration of the squamous gastric mucosa and ulceration of the glandular gastric mucosa in the horse. The first article in this series discussed terminology, clinical signs and diagnosis and the second reviewed ulceration of the squamous gastric mucosa in detail. The purpose of this article, the third and last in the series, is to review the pathophysiology, risk factors, prevalence, treatment and prevention of ulceration of the glandular gastric mucosa.
Article
The objectives were to document the pharmacokinetics of intravenous, enteric-coated oral and plain oral omeprazole in fasted horses and to investigate the impact of feeding on the bioavailability of an enteric-coated omeprazole. Twelve horses received four treatments: intravenous omeprazole (0.5 mg/kg) in the fasted state (IV-Fasted), enteric-coated omeprazole (4 mg/kg) orally in the fasted state (ECO-Fasted), enteric-coated omeprazole (4 mg/kg) orally in the fed state (ECO-Fed) and plain omeprazole (4 mg/kg) orally in the fasted state (PL-Fasted). Plasma omeprazole concentrations were determined by UHPLC-MS. Bioavailability was higher (P = 0.038) in the ECO-Fasted group (21.5 [9.0–27.7]%) than the PL-Fasted group (10.1 [7.7–13.3]%). Similarly, AUC0-∞ was higher in the ECO-Fasted group than the PL-Fasted group (P = 0.027). No significant differences were present between the ECO-Fasted and ECO-Fed groups with regards to bioavailability, Cmax, Tmax or AUC0-∞. When the half-life data from the oral formulations was pooled, it was longer than that observed in the IV-Fasted group (100 [73–118] min) and 35 [34-39] min, respectively; P < 0.0001). Bioavailability of enteric-coated omeprazole was higher than previously reported and feeding had minimal impact. Bioavailability of plain omeprazole was approximately half that of enteric-coated omeprazole. The longer half-life observed following oral administration was consistent with the flip-flop effect and has not previously been described for omeprazole in the horse.
Article
It was hypothesized that horses exhibiting crib-biting (CB) have a greater degree of gastric mucosal damage and higher serum gastrin response to concentrate feeding than non-crib-biting (NCB) horses. Eighteen mature horses, 9 CB and 9 NCB, were used to determine prevalence and severity of gastric mucosal damage and effect of concentrate feeding on circulating gastrin. Horses were maintained on pasture with free access to hay and fed a pelleted concentrate diet twice daily. Number of crib-bites and duration of cribbing bouts were recorded in a 24-hour period. Endoscopic examinations (EE) of the squamous mucosa were performed and gastric fluid sampled after 24 to 28 hour feed removal. Following EE, horses were returned to pasture for 72 hours. Blood was collected following 12-hour feed removal (0 minutes), and at 60 and 120 minutes after consuming 1 kg of concentrate. Mean number of crib bites in 24 hours was 1,558 ± 303 with CB peaking prior to and during the afternoon feeding (3:30 PM, P < .05). There were no differences in the number or severity of ulcers, prevalence of hyperkeratosis, or baseline gastric pH between CB and NCB. Serum gastrin concentration at 60 and 120 minutes was greater (P < .05) and tended to be greater (P < .06), respectively, in CB than in NCB horses following feeding of concentrate. Crib-biting behavior in horses maintained on pasture was not associated with gastric mucosal damage; however, consumption of concentrate feed resulted in greater serum gastrin concentration in CB horses.
Article
A necropsy was performed on over 500 horses from a Texas abattoir for the presence of gastric and colonic ulceration. A first group of 365 horses from a variety of sources was examined, and 55% were found to have gastric ulcers, while 44% exhibited colonic ulcers. A second group of 180 performance horses was also examined, and 87% were shown to have gastric ulcers, while 63% exhibited colonic ulcers. The second study included a correlated guaiac-based fecal occult blood test (gFOBT), which was shown to have high specificity but a fairly low sensitivity resulting in several false negatives.
Article
The regulation of gastric secretion is of crucial impor-tance to the equilibrium of the gastroenteric system. Despite the large number of factors involved in the causes of peptic illnesses, pH ¼ 4 is considered the threshold between physiologic and deleterious effects of stomach acid secretion. With the aim of maintaining pH greater than 4, proton-pump inhibitors, such as eso-meprazole magnesium (NEXIUM), have shown excel-lent results in the control of acid secretion. Aimed at examining the action of this drug in the control of pH levels of gastric secretion in thoroughbreds, a single dose of 40 or 80 mg of esomeprazole magnesium was administered daily, and pH was determined serially for 5 consecutive days. The results obtained corroborated the efficacy of esomeprazole magnesium in the control of gastric pH at both doses tested, with 100% of the mean pH being greater than 5. Moreover, no statistical difference was noted between the two doses tested.
Article
The purposes of this study were to evaluate a technique for contrast gastrointestinal (GI) radiography and to define the normal radiographic anatomy of the foal GI tract as demonstrated by survey and contrast radiography. GI studies were performed in five normal foals. Right lateral standing, right and left lateral recumbent, and ventrodorsal (dorsal recumbent) radiographs were evaluated. The recumbent lateral and ventrodorsal positions were preferred, although the right lateral standing position demonstrated most structures. Radiographic positions that clearly identified a specific GI region were determined. The dosage of contrast medium used (5 ml/kg of a 30% wt/vol barium suspension) was adequate to outline the GI tract. Transit times allowed evaluation of the large colon within eight hours.
Article
†California Veterinary Diagnostic Laboratory Service, California 95616, California 91024, USA. Although gastric ulcers have been identified relatively frequently in racing Thoroughbreds, there have been no large scale studies to determine their effect on health and performance. Two hundred and two Thoroughbred horses in active race training were selected by the attending veterinarians for gastro-endoscopic examination. Images of the stomach mucosa were stored in a digitised format for subsequent evaluation. The number of ulcers and a score of severity were determined. Gastric ulceration of the squamous mucosa was identified in 82% of horses. Seventy-three (39%) horses displayed clinical signs consistent with gastric ulceration. Increasing Furr and Murray Score was associated with poor hair coat (P = 0.03), colic (P = 0.03), and increasing serum creatinine concentration (P = 0.029). There were no associations between haematology and serum biochemistry values (other than serum alkaline phosphatase concentration and serum creatinine concentration) and gastric ulceration. Our study confirmed the relatively high incidence of gastric ulceration in Thoroughbred horses involved in active race training. Gastric ulceration is a potential, but rare, cause of overt colic, but may produce more subtle detrimental effects on a horse's condition. It is concluded that the diagnosis of gastric ulceration should be based on an endoscopic examination of the stomach, although future studies are required to elucidate further the aetiology and clinical significance of gastric ulceration.
Article
Equine gastric ulceration syndrome (EGUS) is commonly recognised in Thoroughbred racehorses. Although EGUS has previously been associated with reduced athletic performance, no objective studies have been reported.This case report describes 4 racehorses referred for investigation of poor athletic performance where EGUS was the only abnormal finding during a thorough investigation of all body systems. All horses showed considerable improvement in performance following treatment with omeprazole. Therefore, this is the first report in which evidence is presented suggesting a direct link between EGUS and decreased performance, other causes of poor performance having been excluded.
Article
To determine whether expression of mRNA for sodium-potassium adenosine-triphosphatase (NAKA) and sodium-hydrogen exchanger (NHE) in samples of the nonglandular portion of the equine gastric mucosa was altered by exposure to volatile fatty acids (VFAs) in an acidic environment. 10 horses (5 < or = 5 years old and 5 > or = 12 years old). Samples of the nonglandular portion of the gastric mucosa were collected and exposed in Ussing chambers to Ringer's solution (control samples), Ringer's solution containing a mixture of VFAs (pH, 1.5 or 4.0), or Ringer's solution containing acetic acid (pH, 1.5 or 4.0). Expression of mRNA for the gene for the beta1 subunit of NAKA and the gene for the NHE-3 isoform was determined by means of real-time PCR assays. For horses < or = 5 years old, relative expression of mRNA for NAKA was significantly decreased and expression of mRNA for NHE was significantly increased following exposure to the mixture of VFAs or acetic acid, compared with expression in control samples. In contrast, for horses > or = 12 years old, relative expression of mRNA for both NAKA and NHE was significantly increased following exposure to the mixture of VFAs or acetic acid, compared with expression in control samples. Results suggested that relative expression of mRNA for NAKA, but not NHE, in samples of the nonglandular portion of the equine gastric mucosa in response to exposure to VFAs in an acidic environment was an age-dependent event.
Article
Peptic ulcer disease had a tremendous effect on morbidity and mortality until the last decades of the 20th century, when epidemiological trends started to point to an impressive fall in its incidence. Two important developments are associated with the decrease in rates of peptic ulcer disease: the discovery of effective and potent acid suppressants, and of Helicobacter pylori. With the discovery of H pylori infection, the causes, pathogenesis, and treatment of peptic ulcer disease have been rewritten. We focus on this revolution of understanding and management of peptic ulcer disease over the past 25 years. Despite substantial advances, this disease remains an important clinical problem, largely because of the increasingly widespread use of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin. We discuss the role of these agents in the causes of ulcer disease and therapeutic and preventive strategies for drug-induced ulcers. The rare but increasingly problematic H pylori-negative NSAID-negative ulcer is also examined.
Article
Objective: To develop a protocol to induce and maintain gastric ulceration in horses and to determine whether gastric ulceration affects physiologic indices of performance during high-speed treadmill exercise. 20 healthy Thoroughbreds. Each horse was acclimatized to treadmill exercise during a 2-week period. Subsequently, baseline data were collected (day 0) and each horse began an incrementally increasing exercise training program (days 1 through 56). Beginning on day 14, horses were administered omeprazole (4 mg/kg, PO, q 24 h until day 56) or no drug (10 horses/group) and underwent alternating 24-hour periods of feeding and feed withholding for 10 days to induce gastric ulceration. Extent of gastric ulceration was assessed weekly thereafter via gastroscopy. Physiologic indices of performance were measured at days 0 and 56. Gastric ulceration and exercise performance indices were compared within and between groups. In untreated horses, gastric ulcers were induced and maintained through day 56. Gastric ulcer formation was prevented in omeprazole-treated horses. There were significant interactions between time (pre- and post-training data) and treatment (nonulcer and ulcer groups) for mass-specific maximal O(2) consumption ([Formula: see text]O(2max)/M(b)) and mass-specific maximal CO(2) production ([Formula: see text]CO(2max)/M(b)). Post hoc analysis revealed a difference between groups for [Formula: see text]O(2max)/M(b) at day 56. Within-group differences for [Formula: see text]O(2max)/M(b) and [Formula: see text]CO(2max)/M(b) were detected for omeprazole-treated horses, but not for the horses with ulcers. In horses, gastric ulcers were induced and maintained by use of alternating periods of feeding and feed withholding in association with treadmill exercise (simulated racetrack training). Gastric ulcers adversely affected physiologic indices of performance in horses.
Article
Gastroendoscopic examinations were conducted on 75 Thoroughbred foals aged two to 85 days on seven breeding farms in England and Ireland. The foals showed no signs of gastric disease. There was no significant difference between lesion prevalence in foals in England (16 of 28 foals; 57 per cent) or Ireland (22 of 47 foals; 47 per cent). Neither was there any sex predilection (18 of 36 males; 20 of 39 females). Lesions were most prevalent in foals under 10 days old (8 of 9) and least prevalent in foals older than 70 days (3 of 10). Lesions occurred most frequently in the squamous mucosa immediately adjacent to the margo plicatus along the greater curvature (34 foals), whereas lesions in the squamous fundus, the glandular fundus, and the lesser curvature were observed in 11, six and three foals, respectively. Lesions were not observed in the squamous mucosa surrounding the cardia. Gastric lesions were more prevalent in foals with a previous disorder than in those without (68 vs 43 per cent) and particularly with a history of recent or concurrent diarrhoea (9 of 14).
Article
Twenty four hour intragastric acidity was measured in nine patients with duodenal ulcer before and after one week of treatment with oral omeprazole 30 mg daily, a drug that inhibits gastric secretion by inhibition of parietal cell H+K+ adenosinetriphosphatase (ATPase). Omeprazole virtually eliminated intragastric acidity in all patients: the median 24 hour intragastric pH rose from 1.4 to 5.3 and the mean hourly hydrogen ion activity fell from 38.50 to 1.95 mmol(mEq)/1 (p less than 0.001). This inhibition of 24 hour intragastric acidity is more profound than that previously reported with either cimetidine 1 g daily or ranitidine 300 mg daily.
Article
To identify the cause and mechanisms of injury in gastroesophageal ulcer disease in market weight swine. Comparison of mechanisms of injury caused by HCI with those caused by short chain fatty acids (SCFA) in gastric mucosa. Pigs weighing 30 to 40 kg. Gastric tissues were studied in Ussing chambers; short-circuit current (lsc) and electrical resistance (R) were recorded in response to treatment, and tissues were examined histologically. 60 mM mucosal acetate abruptly ( < or = 75 minutes) and irreversibly abolished lsc at pH < or = 4.5, whereas R decreased more slowly. These data were associated with cell swelling and vesicle formation in mid-zonal layers, followed by sloughing of the outer barrier, erosion into deeper zones, and finally, ulceration. Mucosal HCl at pH > 1.5 was ineffective; however, at pH 1.5, HCl induced an abrupt decrease in R, followed by a slow decrease in lsc, an effect opposite to that caused by SCFA. Serosal addition of HCl rapidly abolished lsc suggesting a barrier to free H+ diffusion from the mucosal solution. Undissociated SCFA rapidly penetrate the outer barrier and acidify underlying viable tissue. Cellular acidification inhibits Na pumping and osmoregulation, resulting in cell swelling and necrosis. In contrast, HCl induces and increase in outer barrier permeability before accessing the transporting cells, a much longer process ( > or = 5 hours) requiring a lower pH. These studies suggest that microbial production of SCFA may be important in the pathogenesis of porcine gastric ulcers.
Article
To investigate the prokinetic effect of bethanechol and erythromycin in the upper gastrointestinal tract of healthy horses by measuring the gastric emptying (GE) rate of a radioactive meal. 4 healthy adult horses. After food was withheld for 12 hours, horses were given 370 MBq of 99mTc-labeled sulfur colloid incorporated into egg albumen and 37 MBq of 111In-labeled diethyltriaminepentaacetic acid in 120 ml of water via nasogastric intubation. Intravenously administered treatments were 0.9% NaCl solution, erythromycin (0.1 or 1.0 mg/kg of body weight), or bethanechol (0.25 mg/kg). All drugs were given in 10 ml of 0.9% NaCl solution. Dual-phase scintigraphic images were obtained by use of a gamma camera. The best-fit function was determined for each study, and the resultant curves were then analyzed by use of least squares nonlinear regression. Two variables, time to 50% emptying of the stomach (T-50) and slope of the emptying curve, were derived from the calculated power exponential equation. Treatment had a significant (P < 0.05) overall effect on T-50 of solid-phase GE. The T-50 of bethanechol (30.09 +/- 10.01 minutes), erythromycin at 0.1 mg/kg (59.08 +/- 10.01 minutes), and erythromycin at 1 mg/kg (60.50 +/- 10.01 minutes) were significantly shorter than T-50 after saline administration (89.97 +/- 10.01 minutes). There was a trend (P = 0.09) for the slope of solid-phase GE of bethanechol and erythromycin (0.1 mg/ kg; P = 0.37) to be steeper than that of saline solution. For liquid-phase GE, the T-50 and the slope of bethanechol differed significantly (P < or = 0.05) from those for saline solution. Bethanechol and erythromycin significantly increased solid-phase GE in healthy horses and may have value for use as prokinetic agents in certain gastrointestinal tract diseases.
Article
Omeprazole has been shown to promote healing of spontaneously occurring gastric ulcers in horses when administered for 28 days at a dose of 4 mg/kg bwt/day and to prevent recurrence of ulcers in almost all horses when treatment is continued at a dose of at least 2 mg/kg bwt/day. The purpose of the 3 studies reported here was to 1) evaluate the evolution of potential effects of omeprazole paste (GastroGard), at a dose of 20 mg/kg bwt/day (5x the recommended dose) for 91 days in mature Thoroughbred horses; 2) evaluate the safety in young horses of omeprazole paste when dosed at 4 mg/kg bwt/day (1x), 12 mg/kg bwt/day (3x) or 20 mg/kg bwt/day (5x) for 91 days in Tennessee walking horse foals; and 3) evaluate the safety of omeprazole paste when dosed at 40 mg/kg bwt/day (10x) for 21 days in mature Thoroughbred horses. Within each study, horses were allocated randomly to the control or omeprazole paste treatment group. Clinical examinations, serum biochemistry and haematology were performed at regular intervals until necropsy at the end of the study. There were no treatment-related clinical signs in any treated horse and serum biochemistry and haematology were normal. In conclusion, omeprazole paste is safe for use in horses as demonstrated in studies with foals and mature horses.
Article
Unlabelled: Esomeprazole (S-isomer of omeprazole), the first single optical isomer proton pump inhibitor, generally provides better acid control than current racemic proton pump inhibitors and has a favourable pharmacokinetic profile relative to omeprazole. In a large well designed 8-week trial in patients (n >5000) with erosive oesophagitis, esomeprazole recipients achieved significantly higher rates of endoscopically confirmed healed oesophagitis than those receiving lansoprazole. Respective healed oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were 92.6 and 88.8%. Overall, esomeprazole was also better than omeprazole, although these differences were not always statistically significance. Ninety-two to 94% of esomeprazole recipients (40mg once daily) achieved healed oesophagitis versus 84 to 90% of omeprazole recipients (20mg once daily). Esomeprazole was effective across all baseline grades of oesophagitis; notably, relative to lansoprazole, as baseline severity of disease increased, the difference in rates of healed oesophagitis also increased in favour of esomeprazole. Resolution of heartburn was also significantly better with esomeprazole 40mg than with these racemic proton pump inhibitors. Long-term (up to 12 months) therapy with esomeprazole effectively maintained healing in these patients. Once-daily esomeprazole 20 or 40mg for 4 weeks resolved symptoms in patients with symptomatic gastro-oesophageal reflux disease (GORD) without oesophagitis. Symptoms were effectively managed in the long-term with symptom-driven on-demand esomeprazole (20 or 40mg once daily). Eradicating Helicobacter pylori infection is considered pivotal to successfully managing duodenal ulcer disease. Seven days' treatment (twice-daily esomeprazole 20mg plus amoxicillin 1g and clarithromycin 500mg) eradicated H. pylori in >/=86% of patients (intention-to-treat), a rate that was similar to equivalent omeprazole-based regimens. Esomeprazole is generally well tolerated, both as monotherapy and in combination with antimicrobial agents, with a tolerability profile similar to that of other proton pump inhibitors. Few patients discontinued therapy because of treatment-emergent adverse events (<3% of patients), with very few (<1%) drug-related serious adverse events reported. Conclusions: Esomeprazole is an effective, well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis and overall, provided better efficacy than omeprazole. Notably, in a large (n >5000 patients) double-blind trial, esomeprazole 40mg provided significantly better efficacy than lansoprazole in terms of healing rates and resolution of symptoms. Long-term therapy with esomeprazole maintained healed oesophagitis in these patients. Esomeprazole also proved beneficial in patients with symptomatic GORD without oesophagitis. Thus, esomeprazole has emerged as an option for first-line therapy in the management of acid-related disorders.
Article
Ulceration of the squamous gastric mucosa is commonly associated with intensive training programmes in horses, but only one compound ('Gastrogard') has been subjected to controlled scrutiny as to therapeutic efficacy. To compare the gastric acid inhibitory efficacy of one manufactured ('GastroGard') and 3 generic pharmacy-compounded preparations of the proton pump inhibitor omeprazole (OME) in the mature horse. All OME preparations tested would induce a clinically acceptable effect. Six healthy mature gastrically cannulated horses of various breeds, 3 mares and 3 geldings, were used. Each product was administered per os once daily (0730 h) at an equivalent dose of 4 mg OME/kg bwt, in a randomised complete repeated measures design for sequence of individual preparation treatment per horse. There was a minimum of 14 days between treatment regimens. A portable unit that recorded pH continuously was attached to a recording electrode fixed within the gastric lumen via the gastric cannula. Three 24 h recordings were made one day before and during Days 2 and 7 after commencement of a 7 day treatment with each of the 4 individual preparations. The horses were fed as usual throughout the study. Only the GastroGard and one other preparation induced a significant increase over baseline in mean percentage of time that the pH was > 4.0 and mean median intragastric pH, during the first 14 and 12 h post treatment respectively, for both Days 2 and 7 post treatment. Both these products had a vehicle pH > 8.0, in contrast to the 2 less effective products, where the vehicle pH was < 6.0. OME at 4 mg/kg per os s.i.d. can effectively maintain intragastric pH at an accepted anti-ulcerogenic level for at least 12 h post administration in mature horses. In contrast to GastroGard, it should not be expected that all compounded preparations of OME are equally effective in achieving this performance. It appears that vehicle pH might play an important part in determining preparation efficacy. Optimal timing for daily dosing of athletic horses with an effective OME preparation, in order to suppress gastric squamous ulceration, might be 4-8 h prior to a training session.
Article
Proton pump inhibitors (PPIs) are a mainstay of treatment for acid-related ulceration in man and horses. Currently, only an oral preparation of omeprazole is approved for use in horses in the USA. Intravenous administration of a PPI would provide a useful therapeutic alternative for those foals in which oral medication is not feasible. To investigate the pharmacokinetics and pharmacodynamics of pantoprazole following i.v. or intragastric administration in healthy neonatal foals. Seven healthy foals age 6-12 days at the start of the study were evaluated. Treatments included no drug administration, i.v. pantoprazole (1.5 mg/kg bwt) and intragastric pantoprazole (1.5 mg/kg bwt). Intragastric pH was recorded for 24 h after drug administration for pharmacodynamic evaluation. Plasma pantoprazole concentrations were measured using high-performance liquid chromatography. Plasma concentrations of pantoprazole were detectable at the 5 min sampling point following i.v. or intragastric administration. Bioavailability of intragastric-administered pantoprazole was 41%. Baseline mean hourly pH was 1.5-6.1. There was a statistically significant increase in mean hourly pH relative to untreated foals 2-24 h after i.v. or intragastric pantoprazole administration. Based on these data, i.v. or intragastric administration of pantoprazole results in a significant, prolonged increase in intragastric pH. The i.v. formulation of pantoprazole may provide a clinically useful alternative means of acid suppression in foals unable to tolerate enteral administration of a PPI, such as those with pyloric outflow obstruction.
Article
To compare the effects of oral administration of omeprazole and ranitidine on gastric squamous ulceration in Thoroughbreds in race training. Modified crossover study. 60 Thoroughbreds in race training with gastric squamous mucosal ulceration. Horses were randomly allocated into 3 groups. Group 1 received no treatment for 28 days followed by administration of omeprazole (4 mg/kg [1.8 mg/lb], PO, once daily) for 28 days; group 2 received omeprazole (4 mg/kg, PO, once daily) for 28 days followed by no treatment for 28 days; and group 3 received ranitidine (6.6 mg/kg [3.0 mg/lb], PO, q 8 h) for 28 days followed by administration of omeprazole (4 mg/kg, PO, once daily) for 28 days. Ulceration was assessed endoscopically at days 0, 28, 42, and 56. Lesions were scored from 0 (no ulceration) to 3 (severe ulceration). After the initial 28 days of treatment, the decrease in ulcer severity was significantly greater after omeprazole treatment than after ranitidine treatment. Ulcer severity decreased significantly in group 3 horses after 14 days of treatment with omeprazole. Discontinuation of omeprazole resulted in worsening of ulcer scores; however, ulcer scores at completion of the study were less than at day 0. Horses that received omeprazole after 28 days of ranitidine treatment had a further reduction in ulcer severity. Omeprazole was more effective than ranitidine in healing gastric squamous ulcers in Thoroughbreds in race training. Improvement was detected by 14 days and persisted in most of the group 2 horses for at least 28 days after omeprazole treatment was discontinued.
Article
To assess the presence of Helicobacter DNA in the gastric mucosa Thoroughbred horses. Squamous and glandular mucosa samples were collected from 20 Thoroughbreds. None of these horses had shown any clinical symptoms of gastrointestinal disease. Necropsy tissues were analysed using histopathological techniques and a Helicobacter genus-specific PCR assay followed by sequencing of the amplicons. Seven horses were diagnosed with gastric ulceration, five with gastritis and six with both pathologies. Only two horses had a healthy gastric mucosa. Helicobacter-like DNA was detected in two out of seven horses with gastric ulcers, three out of five horses with gastritis, five out of six horses with both pathologies and one horse with normal gastric mucosa. The sequences of 1195 and 1237 bp fragments of the 16S rRNA gene shared 99% identity with the Helicobacter pylori 16S rRNA gene. However, all the samples were negative when tested with H. pylori-specific PCR assays targeting the cagA and glmM genes. The Helicobacter genus might colonize the gastric mucosa of horses. This is the first report of Helicobacter-like DNA in the gastric mucosa of horses and the pathogenic potential of these organisms requires further investigation.
Gastric and duodenal ulcers in foals: a retrospective study
  • J H Wilson
Wilson JH. Gastric and duodenal ulcers in foals: a retrospective study. In: Proceedings of the Second Equine Colic Research Symposium. Athens (GA): Georgia Center for Continuing Education; Oct 1-3, 1986. p. 126-9.
Misoprostol is superior to combined omeprazole and sucralfate for healing glandular gastric lesions in horses with clinical disease
  • V Georgina
  • M Bowen
  • V Nicholls
Georgina V, Bowen M, Nicholls V, et al. Misoprostol is superior to combined omeprazole and sucralfate for healing glandular gastric lesions in horses with clinical disease. In Proceedings of the ACVIM Forum. Denver, CO, June 9-11, 2016, p. E25.
Brand of OrafateÔ) Prescribing Information FDA 510k 123904 -Cleared
  • Equine Mucosalfateô
Equine MucosalfateÔ (Brand of OrafateÔ) Prescribing Information FDA 510k 123904 -Cleared August 2013. Sterling Foster Animal Health (A Mueller Medical International, LLC Company).
Expedited management of ulcer, colic and diarrhea in 209 horses: an open-labeled observational study of a potency-enhanced sucralfate-like elm phyto-saccharide
  • R W Mccollough
McCollough RW. Expedited management of ulcer, colic and diarrhea in 209 horses: an open-labeled observational study of a potency-enhanced sucralfate-like elm phyto-saccharide. J Vet Med Anim Health Vol 2013;5:32-40.
Effects of collagen hydrolysates on equine gastric ulcer scores and gastric juice pH
  • M L Keowen
  • P Camacho-Luna
  • L Micheau
Keowen ML, Camacho-Luna P, Micheau L, et al. Effects of collagen hydrolysates on equine gastric ulcer scores and gastric juice pH. J Vet Int Med 2016;30(4): 1512.
Feeding alfalfa hay to exercising horses reduces the severity of gastric squamous mucosal ulceration
  • T Lybbert
  • P Gibbs
  • N Cohen
Lybbert T, Gibbs P, Cohen N, et al. Feeding alfalfa hay to exercising horses reduces the severity of gastric squamous mucosal ulceration. In: Proceedings of the 53rd Annual Convention of the American Association of Equine Practitioners. Orlando, Florida, December 1-5, 2007. p. 525-6.
Investigation of misoprostol as a novel anti-inflammatory in equine leukocytes
  • E Medlin
  • S Jones
Medlin E, Jones S. Investigation of misoprostol as a novel anti-inflammatory in equine leukocytes. ACVIM Forum, June 7-10 Denver, CO. J Vet Intern Med Forum 2016;30:1520.