Should the use of omeprazole be allowed during equestrian competition?

BACKGROUND: Prioritising equine welfare, making evidenced-based policy, and consistent decision-making across sports are crucial to maintaining the social licence for equestrian sport. Regulations on the use of omeprazole during competition differ; all regulators argue that their rules prioritise welfare. This discrepancy is a matter of concern to the public and equestrian stakeholders. OBJECTIVES: To apply Campbell's Ethical Framework for the use of Horses in Sport to the question: 'Should the use of omeprazole be allowed during equestrian competition?' STUDY DESIGN: A desk-based ethico-legal study. METHODS: Campbell's Ethical Framework for the Use of Horses in Sport was applied in a stepwise fashion: definition of the ethical question; analysis of the evidence base; consideration of stakeholders' interests; harm:benefit analysis; application of the three central tenets of the framework, and formulation of conclusions and recommendations. RESULTS: Stakeholders in equine sports have a variety of (frequently conflicting) interests; all of them share an interest in optimising equine welfare. The incidence of EGUS in competition horses is high. Omeprazole is a cornerstone treatment. There are currently discrepancies in regulation about the use of omeprazole during competitions. Recent evidence suggests that withholding omeprazole treatment for two clear days before competition allows the recurrence of squamous EGUS, whereas withholding treatment on the day of competition only does not have that effect. MAIN LIMITATIONS: The current state of scientific knowledge about the use of omeprazole in horses. The analysis did not consider possible health and thus welfare effects of the out-of-competition treatment with omeprazole. CONCLUSIONS: Based on recent scientific evidence, if horses are being treated with omeprazole outside of competition then treatment on the day of competition should be permitted on welfare grounds. Revision of regulations around the use of omeprazole during competition by governing bodies is necessary to safeguard the ethical use of horses in sport.

CONTEXTO: Priorizar o bem­estar equino, elaborar políticas baseadas em evidências e tomar decisões consistentes em todos os esportes são cruciais para manter a licença social para o esporte equestre. As regulamentações sobre o uso de omeprazol durante a competição diferem; todos os reguladores argumentam que suas regras priorizam o bem­estar. Essa discrepância é motivo de preocupação para o público. OBJETIVOS: Aplicar o Modelo Ético de Campbell para o Uso de Cavalos em Esportes1 à pergunta: 'Deve o uso de omeprazol ser permitido durante a competição equestre?' DESENHO DO ESTUDO: Um estudo ético­legal baseado em pesquisa documental. METODOLOGIA: O Modelo Ético de Campbell para o Uso de Cavalos em Esportes1 foi aplicado de forma gradual: definição da questão ética; análise da base de evidências; consideração dos interesses do público alvo; uma análise de dano:benefício; aplicação dos três princípios centrais do modelo; e formulação de conclusões e recomendações. RESULTADOS: O público de esporte equino têm uma variedade de interesses (frequentemente conflitantes), enquanto todos compartilham o interesse em otimizar o bem­estar equino. A incidência de EGUS (Síndrome da Úlcera Gástrica Equina) em cavalos de competição é alta, a qual o omeprazol é um tratamento fundamental. Atualmente, há discrepâncias na regulamentação sobre o uso de omeprazol durante competições. Evidências recentes sugerem que a suspensão do tratamento com omeprazol por 2 dias antes da competição permite a recorrência da EGUS da porção escamosa, enquanto a suspensão do tratamento apenas no dia da competição não tem esse efeito. PRINCIPAIS LIMITAÇÕES: O estado atual do conhecimento científico sobre o uso de omeprazol em cavalos. A análise não considerou possíveis efeitos sobre a saúde e, portanto, sobre o bem­estar do tratamento com omeprazol fora da competição. CONCLUSÕES: Com base em evidências científicas recentes, se os cavalos estão sendo tratados com omeprazol fora da competição, o tratamento no dia da competição deve ser permitido por razões de bem­estar. A revisão das regulamentações sobre o uso de omeprazol durante a competição pelos órgãos reguladores é necessária para salvaguardar o uso ético dos cavalos no esporte.

Trimethoprim-sulfonamide: a valid antimicrobial treatment in foals?

Trimethoprim-sulfonamide (TMPS) combinations are widely used to treat a range of infectious diseases in horses, but some equine practitioners are reluctant to use them for treatment of both neonatal and older foals. Considering the emergence of increased antimicrobial resistance, the use of protected antimicrobials commonly prescribed to foals should be avoided and alternative first-line therapy considered, where appropriate. This review examines the characteristics and pharmacokinetics of TMPS and its suitability for treatment of foals. Data regarding dosage and route of administration are reported on the basis of recent publications in foals. The review intends to share significant information about the common infections that are most likely responsive to TMPS treatment in foals and, as such, where TMPS might be considered a suitable first-line therapeutic option.

Survival of formalin intoxication in a 13-year-old Thoroughbred gelding.

BACKGROUND: Formalin intoxication via the gastrointestinal route has not been previously reported in the horse. Whereas ingestion of formalin in humans, although rare, is well documented. Majority of human cases are either accidental, suicidal or homicidal and often lead to fatality, with a reported lethal formaldehyde dose equating to 0.12 - 0.16 g/kg bwt. OBJECTIVES: To describe a single case report of the clinical management of an adult horse referred to a veterinary teaching hospital following accidental administration of 10% formalin via nasogastric tube. METHODS: A 13-year-old Thoroughbred gelding originally presented to the referring veterinarian for colic where 1.8 L of 10% formalin was accidentally administered instead of mineral oil via nasogastric intubation, a potentially lethal dose of formaldehyde (0.12 g/kg bwt). Approximately 20-hours following 10% formalin administration the horse was admitted to the referral hospital with moderate tachycardia, occasional ectopic beats, tacky and hyperaemic mucous membranes, delayed capillary refill time, reduced borborygmi, and pronounced digital pulses. Diagnostic investigations included laboratory blood analysis, urinalysis, electrocardiogram, abdominal ultrasound, palpation per rectum and gastroscopy. RESULTS: Patient assessment found evidence of toxicity to the gastrointestinal tract, hypovolaemia and risk for laminitis. Intensive care included fluid and electrolyte therapy, anti-inflammatories and analgesia, continuous digital cryotherapy, gastro-protectants and other methods of gastrointestinal support. The horse was discharged from hospital on day 14 with no long-term complications and the client-veterinarian relationship was preserved. DISCUSSION: In human cases of ingestion, gastrointestinal injury is typically accompanied by severe metabolic acidosis and multiple organ dysfunction syndrome due to toxicity of other body systems that can contribute to non-survival. Formaldehyde toxicity in the present case predominantly affected the gastrointestinal tract, most likely a direct result of the route of administration. Aside from gastrointestinal injury, primary toxicity of other body systems was not confirmed. To prevent this medical error recurring, the referring veterinary clinic revised their labelling and storage of 10% formalin. CONCLUSION: This is the first report of systemic formalin intoxication in the horse. Following a high dose of 10% formalin (0.12 g/kg bwt formaldehyde) enterally, the horse survived having received intensive supportive care based on human guidelines for ingested formalin.

Understanding and treating equine behavioural problems.

Behaviour-related issues are common in horses. Many 'undesirable behaviours' pose important safety concerns for the human handlers / riders / carers, as well as welfare concerns for the horse. Undesirable behaviours can also devalue a horse, or result in the horse being re-homed, relinquished, or euthanased. Undesirable behaviours occur for a range of reasons. These include physiological causes, poor management, and the use of inappropriate or poorly applied handling and training techniques. The potential contribution of each of these aspects must be considered when attempting to reduce or eliminate undesirable behaviours. Effectively modifying the existing behaviour includes investigation and treatment of potential physiological causes, assessing and adjusting existing handling, husbandry and management, and undertaking behaviour modifying training. Unlike in the treatment of dogs and cats, the use of psychotropic agents is uncommon in equine behaviour medicine but the benefits of using these agents in appropriate cases is gaining recognition. This review discusses potential causes for the development and maintenance of undesirable behaviours in horses and highlights the various considerations involved in determining the most appropriate course for reducing or eliminating these behaviours. There is also a brief discussion about the potential role of psychotropic agents as an additional component of an overall behaviour modification plan to reduce or eliminate undesirable behaviours in horses.

Horse Grimace Scale Does Not Detect Pain in Horses with Equine Gastric Ulcer Syndrome.

Equine gastric ulcer syndrome (EGUS) is a highly prevalent and presumptively painful condition, although the amount of pain horses might experience is currently unknown. The aims of this study were to determine if the Horse Grimace Scale (HGS) could identify pain behaviours in horses with and without EGUS and if severity would be positively associated with the HGS score. Horse grimace scale scores were assessed blindly using facial photographs by seven observers and involved evaluation of 6 facial action units as 0 (not present), 1 (moderately present) and 2 (obviously present). Lameness examination, serum amyloid A (SAA) measurement and gastroscopy evaluation were performed on all horses. Horses (n = 61) were divided into two and three groups based on the presence (yes, no) and severity (none, mild, moderate-severe) of EGUS, respectively. Presence of lameness and elevated SAA (≥50 µg/mL) were used as exclusion criteria. Inter-observer reliability was analyzed by intra-class correlation coefficients (ICC). HGS scores between groups were compared using Welch's and Brown Forsythe tests (p < 0.05). Overall, HGS ICC was "excellent" (0.75). No significant differences (p = 0.566) were observed in HGS scores between horses with and without gastric lesions (mean, 95% CI; 3.36, 2.76-3.95 and 3, 1.79-4.20, respectively). HGS was not influenced by the presence or severity of EGUS in this current study. Further studies investigating the use of different pain scales in horses with EGUS are needed.

Equine Gastric Ulcer Syndrome: An Update on Current Knowledge.

Equine Gastric Ulcer Syndrome (EGUS) is a term that has been used since 1999, initially being used to describe all gastric mucosal disease in horses. Since this time, the identification of two distinct main disease entities of the equine gastric mucosa have been described under the umbrella of EGUS; these are Equine Squamous Gastric Disease (ESGD) and Equine Glandular Gastric Disease (EGGD). In 2015 the European College of Equine Internal Medicine (ECEIM) released a consensus statement defining these disease entities. This document highlighted the lack of evidence surrounding EGGD compared to ESGD, and identified knowledge gaps for further research to be directed. Subsequently, many studies on EGGD have been published, especially on pathophysiology, diagnosis, and treatment. This article updates current knowledge on both ESGD and EGGD as understanding has evolved since the last large-scale review.

Factors that influence owner consent for exploratory laparotomy in horses with colic in Australia and New Zealand.

BACKGROUND: Horse owners' motivators and barriers for consent to exploratory laparotomy are poorly understood. OBJECTIVES: To (1) determine the proportion of Australian and New Zealand horse owners who would consent to exploratory laparotomy and (2) identify motivators and barriers for consent. STUDY DESIGN: Cross-sectional survey. METHODS: A questionnaire was developed and distributed online. Descriptive statistics were calculated by tabulating respondents by their answers to whether they would consent to exploratory laparotomy. Univariate and multivariate analyses were used to identify variables associated with consenting to exploratory laparotomy. RESULTS: Two thousand two hundred horse owners participated with a 68.3% survey completion rate. Most were female (95.6%), and 18.7% stated they would consent to exploratory laparotomy, 55.2% would consider exploratory laparotomy and 26.1% would not consent to exploratory laparotomy being performed on their horse. Geographical location, intended use of the horse and perceptions regarding the cost and prognosis of exploratory laparotomy, as well as the previous experience of respondents significantly impacted the decision. Self-reported level of financial comfort, gender of respondents, number of horses owned and pre-existing relationship with nearest equine referral clinic did not impact the decision. Top motivators for exploratory laparotomy were high probability of survival, trust in hospital, emotional value of horse and the alternative being euthanasia. Top barriers for exploratory laparotomy were financial cost, uncertain outcome, welfare concern and age of the horse. MAIN LIMITATIONS: Self-selection bias and acquiescence in responses. CONCLUSIONS: Most respondents indicated that they would consider or consent to exploratory laparotomy. Several factors for owners to decide for exploratory laparotomy could be identified. Improved owner education regarding the positively reported survival rates for exploratory laparotomy would be beneficial.

INTRODUCTION/CONTEXTE: Les motivateurs et les obstacles derrières la décision des propriétaires d'autoriser ou pas une laparotomie exploratrice (LE) sur leurs chevaux demeurent mal compris. OBJECTIFS: (1) Déterminer la proportion des propriétaires de chevaux en Australie et Nouvelle-Zélande qui consentiraient à une LE et (2) identifier les motivateurs et obstacles contribuant à leur consentement. TYPE D'ÉTUDE: Étude transversale. MÉTHODES: Un questionnaire a été développé et distribué en ligne. Des statistiques descriptives ont été calculées en classifiant les répondants selon s'ils consentiraient ou non à une LE. Des analyses uni et multivariées ont été utilisées pour identifier les variables associées au consentement à la LE. RÉSULTATS: Deux milles deux cents propriétaires de chevaux ont participé et le taux de remplissage du sondage était de 68.3%. La majorité étaient des femmes (95.6%) et 18.7% donneraient leur consentement pour une LE, 55.2% considéraient une LE et 26.1% ne consentiraient pas à une LE pour leur cheval. La localisation géographique, la discipline du cheval et les perceptions relativement aux coûts et au pronostic pour une LE, de même que leurs expériences précédentes influenceraient la décision des participants de façon significative. La situation monétaire des participants (rapportés de leur plein gré), leur genre, le nombre de chevaux dont ils sont propriétaires et une relation pré-existante avec une clinique de référence à proximité n'influenceraient pas leur décision. Les motivateurs les plus importants pour le consentement à la LE étaient une chance de survie élevée, leur confiance envers le centre de référence, la valeur émotionnelle du cheval et les alternatives possibles à l'euthanasie. Les obstacles les plus flagrants étaient les coûts, une chance de survie incertaine, des préoccupations par rapport au bien-être du cheval et son âge. LIMITES PRINCIPALES: Biais de sélection et degré d'accord des réponses. CONCLUSIONS: La plupart des répondants consentiraient ou au moins considéraient une LE. Plusieurs facteurs influençant la décision des propriétaires ont pu être identifiés. Il est impératif pour les vétérinariares traitants d'éduquer les clients en ce qui concerne les taux de survie plus positifs suivant les laparotomies exploratrices.

Moving toward Fear-Free Husbandry and Veterinary Care for Horses.

Husbandry and veterinary procedures have the potential to generate fear and stress in animals. In horses, the associated responses can pose a significant safety risk to the human personnel involved in the procedure, as well as to the animal itself. Traditionally, physical restraint, punishment, and/or threat of an aversive, have been the most common strategies used to achieve compliance from the horse. However, from a welfare perspective, this is less than ideal. This approach also has the potential for creating a more dangerous response from the horse in future similar situations. When caring for companion animals, and captive animals within zoological facilities, there has been a steady transition away from this approach, and toward strategies aimed at reducing fear and stress during veterinary visits and when undertaking routine husbandry procedures. This review discusses the current approaches to horse care and training, the strategies being used in other animal sectors, and potential strategies for improving human safety, as well as the horse's experience, during husbandry and veterinary procedures.

Prophylactic effects of Glycyrrhiza glabra root extract on phenylbutazone-induced Equine Glandular Gastric Disease (EGGD).

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), like phenylbutazone (PBZ), are prescribed to treat pain and inflammation in the equine. However, experimentally their use has been associated with the development of Equine Glandular Gastric Disease (EGGD). To evaluate the prophylactic effects of Glycyrrhiza glabra root extracts (GGRE) on EGGD induction following oral administration of PBZ, 12 donkeys were used. Animals were divided into three equal groups (A, B and C) in a randomized block design. A: placebo, B: PBZ (4.4 mg/kg PO q 12 h) and C: PBZ plus GGRE (17.6 mg/kg PO q 24h). Gastroscopy and blood sampling for CBC, biochemical tests and antioxidant status were performed days 0 and 7. All but 1 animal had no EGGD lesions on day 0, but on day 7, severe EGGD lesions were seen in group B animals (grade 1/4 (× 1), grade 2/4 (× 2), and grade 3/4 (× 1)). Only mild changes were seen in group C animals, the most severe lesions being grade 1/4 lesions in 2 animals. No change was observed in Group A. Hematology and serum antioxidant status did not change significantly in any group. In group B glucose decreased and ALT and ALP increased, while in group C only ALP increased. In conclusion, GGRE reduced the severity of EGGD caused by PBZ. Further, GGRE prevented PBZ induced hypoglycemia and might reduce the possible hepatic injury of PBZ.

Thromboelastography in obese horses with insulin dysregulation compared to healthy controls.

BACKGROUND: Both obesity and metabolic syndrome are associated with hypercoagulability in people, increasing the risk of cardiovascular disease and thromboembolic events. Whether hypercoagulability exists in obese, insulin-dysregulated horses is unknown. HYPOTHESIS/OBJECTIVES: To determine if coagulation profiles differ between healthy horses and those with obesity and insulin dysregulation. ANIMALS: Fifteen healthy horses (CON) and 15 obese, insulin-dysregulated horses (OBID). Individuals were university or client owned. METHODS: Case-control study. Obesity was defined as a body condition score (BCS) ≥7.5/9 (modified Henneke scale). Insulin dysregulation status was assessed by an oral sugar test (OST). Kaolin-thromboelastography and traditional coagulation variables were compared between groups. The direction and strength of the association between coagulation variables and BCS and OST results were determined using Spearman's correlation. RESULTS: Thromboelastography variables MA (OBID: 69.5 ± 4.5 mm; CON: 64.8 ± 4.3 mm; P = .007) and G-value (OBID: 11749 ± 2536 dyn/m2 ; CON: 9319 ± 1650 dyn/m2 ; P = .004) were higher in OBID compared to CON. Positive correlations between MA and BCS (R = 0.45, P = .01) and serum insulin (T0 : R = 0.45, P = .01; T60 : R = 0.39, P = .03), and G-value and BCS (R = 0.46, P = .01), and serum insulin (T0 : R = 0.48, P = .007; T60 : R = 0.43, P = .02; T90 : R = 0.38, P = .04) were present. CONCLUSIONS AND CLINICAL IMPORTANCE: Obese, insulin-dysregulated horses are hypercoagulable compared to healthy controls.

Management factors and clinical implications of glandular and squamous gastric disease in horses.

BACKGROUND: To date, risk factors for equine glandular gastric disease (EGGD) have not been described in Thoroughbred racehorses. OBJECTIVES: To determine management factors associated with EGGD, identify clinical signs in affected horses, and compare these to equine squamous gastric disease (ESGD). ANIMALS: The study was carried out on 109 Thoroughbred racehorses from 8 training yards (3 in the United Kingdom and 5 in Australia). METHODS: Gastroscopic examination alongside a questionnaire regarding management, feeding, exercise, and health. RESULTS: Management factors and clinical signs were different for EGGD versus ESGD. Exercising ≥5 days per week was associated with a 10.4 times (95% CI [confidence interval]: 1.34-26.9) increased risk of EGGD. Horses racing below expectation were 3.7 times (95% CI: 1.1-16.7) more likely to have EGGD. Trainer was also identified as a risk factor for EGGD. Time in work ≤6 weeks was associated with a decreased risk of ESGD (odds ratio [OR] 0.3; 95% CI: 0.1-0.99). Horses aggressive to humans were less likely to have ESGD (OR 0.12; 95% CI: 0.03-0.54). Horses with stereotypies were more likely to have ESGD (OR 5.0; 95% CI: 1.6-15.9). CONCLUSIONS AND CLINICAL IMPORTANCE: The findings of our study further support the notion that EGGD should be considered as a distinct disease entity to ESGD. Exercising ≤4 days per week could reduce the risk of EGGD. Horses with EGGD are more likely to perform below expectation and, as such, EGGD might be performance limiting in some affected individuals. Stress minimization could reduce the risk of EGGD.

The Relationship between Estrogen and Nitric Oxide in the Prevention of Cardiac and Vascular Anomalies in the Developing Zebrafish (Danio Rerio).

It has been known that both estrogen (E2) and nitric oxide (NO) are critical for proper cardiovascular system (CVS) function. It has also been demonstrated that E2 acts as an upstream effector in the nitric oxide (NO) pathway. Results from this study indicate that the use of a nitric oxide synthase (NOS) inhibitor (NOSI) which targets specifically neuronal NOS (nNOS or NOS1), proadifen hydrochloride, caused a significant depression of fish heart rates (HR) accompanied by increased arrhythmic behavior. However, none of these phenotypes were evident with either the inhibition of endothelial NOS (eNOS) or inducible NOS (iNOS) isoforms. These cardiac arrhythmias could also be mimicked by inhibition of E2 synthesis with the aromatase inhibitor (AI), 4-OH-A, in a manner similar to that of nNOSI. In both scenarios, by using an NO donor (DETA-NO) in either NO + nNOSI or E2 + AI co-treatments, fish could be significantly rescued from decreased HR and increased arrhythmias. However, the addition of an NOS inhibitor (L-NAME) to the E2 + AI co-treatment fish prevented the rescue of low heart rates and arrhythmias, which strongly implicates the NO pathway as a downstream E2 targeted molecule for the maintenance of healthy cardiomyocyte contractile conditions in the developing zebrafish. Cardiac arrhythmias could be mimicked by the S-nitrosylation pathway inhibitor DTT (1,4-dithiothreitol) but not by ODQ (1H-[1-3]oxadiazolo[4,3-a]quinoxalin-1-one), the inhibitor of the NO receptor molecule sGC in the cGMP-dependent pathway. In both the nNOSI and AI-induced arrhythmic conditions, 100% of the fish expressed the phenotype, but could be rapidly rescued with maximum survival by a washout with dantrolene, a ryanodine Ca2+ channel receptor blocker, compared to the time it took for rescue using a control salt solution. In addition, of the three NOS isoforms, eNOS was the one most implicated in the maintenance of an intact developing fish vascular system. In conclusion, results from this study have shown that nNOS is the prominent isoform that is responsible, in part, for maintaining normal heart rates and prevention of arrhythmias in the developing zebrafish heart failure model. These phenomena are related to the upstream stimulatory regulation by E2. On the other hand, eNOS has a minimal effect and iNOS has little to no influence on this phenomenon. Data also suggests that nNOS acts on the zebrafish cardiomyocytes through the S-nitrosylation pathway to influence the SR ryanidine Ca2+ channels in the excitation-coupling phenomena. In contrast, eNOS is the prominent isoform that influences blood vessel development in this model.

Diagnostic evaluation and short-term outcome as indicators of long-term prognosis in horses with findings suggestive of inflammatory bowel disease treated with corticosteroids and anthelmintics.

BACKGROUND: Recurrent colic and unexplained weight loss despite good appetite and adequate feeding and management practices are common conditions in the horse. However, little information has been published on the systematic diagnostic evaluation, response to treatment, prognostic factors or outcome of either presentation. The aims of this study were to 1) identify possible prognostic indicators and 2) report the short- and long-term response to treatment with corticosteroid therapy of a variety of horses with a presumptive diagnosis of inflammatory bowel disease (IBD). Thirty-six horses with a history of recurrent colic and/or unexplained weight loss were screened with a detailed clinical, clinicopathological and diagnostic imaging examination. Twenty horses were subsequently selected that had findings consistent with inflammatory bowel disease based on the fulfilment of one or more of the following additional inclusion criteria: hypoproteinaemia, hypoalbuminaemia, malabsorption, an increased intestinal wall thickness on ultrasonographic examination or histopathological changes in rectal biopsy. These 20 horses were treated with a standardized larvicidal anthelmintic regime and a minimum of three weeks of corticosteroid therapy. RESULTS: The initial response to treatment was good in 75% (15/20) of horses, with a 3-year survival rate of 65% (13/20). The overall 3-year survival in horses that responded to initial treatment (12/15) was significantly higher (P = 0.031) than in those that did not respond to initial treatment (1/5). The peak xylose concentration was significantly (P = 0.048) higher in survivors (1.36 ± 0.44 mmol/L) than non-survivors (0.94 ± 0.36 mmol/L). CONCLUSIONS: The overall prognosis for long-term survival in horses with a presumptive diagnosis of IBD appears to be fair to moderate, and the initial response to anthelmintic and corticosteroid therapy could be a useful prognostic indicator. The findings of the present study suggest that a low peak xylose concentration in absorption testing is associated with a less favourable prognosis, supporting the use of this test.

Estrogen prevents cardiac and vascular failure in the 'listless' zebrafish (Danio rerio) developmental model.

The presence of a robust estrogen (E2) response system throughout heart and blood vessel tissues of vertebrates, including humans, has led to the speculation that this ubiquitous hormone may play a prominent role in the health and maintenance of the adult cardiovascular system (CVS). We previously established an embryonic zebrafish model called 'listless', which results from the inhibition of E2 synthesis by treatment with aromatase enzyme inhibitors (AI). These fish have outward symptoms similar to the human condition of congestive heart failure and tamponade. E2 replacement therapy (1) reduced the severity of cardiac sac abnormalities, (2) protected heart function, (3) prevented reduction in heart size, and (4) reduced blood vessel deterioration. Nitric oxide may be a critical downstream mediator of these events. We also demonstrate that removal of fluid around the heart increases survival of AI-treated fish. These results strongly indicate the importance of E2 in the developing CVS of the zebrafish and offer a potential model for the study of its role in CVS development, maintenance, and disease conditions.

In vivo pretreatment with PGG-glucan fails to alter cytokine mRNA expression of equine peripheral blood mononuclear cells exposed to endotoxin ex vivo.

Twelve healthy horses were assigned to treatment or control groups. Treated horses received PGG-Glucan[ED-1] (1 mg/kg, IV) 24 hours prior to peripheral blood mononuclear cell (PBMC) isolation. PBMCs were isolated and incubated in the presence of lipopolysachharide (LPS). At 0, 6, 12, 24 and 48 hours messenger RNA (mRNA) was extracted. Reverse transcription polymerase chain reaction (PCR) was performed and cytokine mRNA expression for tumor necrosis factor alpha (TNFalpha), interleukin 1beta (IL-1beta), interleukin 10 (IL-10) and interferon gamma (IFN-gamma) determined using real time PCR. A significant effect of LPS stimulation over time was seen on TNFalpha, IL-1beta, IL-10 and IFN-gamma production. No significant difference was observed between the PGG-Glucan treatment group and control cells at any time point.