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Topic:Dexamethasone
Dexamethasone is a synthetic glucocorticoid commonly used in equine medicine for its anti-inflammatory and immunosuppressive properties. It is employed in the management of various inflammatory and allergic conditions in horses, such as arthritis, respiratory diseases, and skin disorders. Dexamethasone works by inhibiting the release of inflammatory mediators and suppressing immune responses. Its administration can be through oral, intravenous, or intramuscular routes, depending on the specific clinical situation. This page compiles peer-reviewed research studies and scholarly articles that investigate the pharmacokinetics, therapeutic applications, and potential side effects of dexamethasone in equine health.
Constitutive apoptosis in equine peripheral blood neutrophils in vitro. The aim of this study was to characterise constitutive apoptosis in equine peripheral blood neutrophils, including assessment of factors that potentially modulate neutrophil survival through alteration of the rate of constitutive apoptosis. Cells underwent spontaneous time-dependent constitutive apoptosis when aged in culture for up to 36 h, developing the structural and functional features of apoptosis observed in many cell types, including human neutrophils. Neutrophils undergoing apoptosis also had diminished zymosan activated serum (ZAS)-stimulated chemiluminescence, but maintained respo...
Concomitant inhibition of primary equine bronchial fibroblast proliferation and differentiation by selective β2-adrenoceptor agonists and dexamethasone. Altered airway cell proliferation plays an important role in the pathogenesis of human bronchial asthma and chronic obstructive pulmonary disease (COPD) as well as the equine recurrent airway obstruction (RAO) with consistent changes, i.e. narrowing the airway wall, explained by proliferation and differentiation of fibroblasts. In permanent cell lines, it has been suggested that β2-adrenoceptor agonists and glucocorticoids regulate cell proliferation via the β2-adrenoceptor pathway; indeed, no study was carried out in fresh isolated primary equine bronchial fibroblasts (EBF). We characterize...
Dexamethasone acutely down-regulates genes involved in steroidogenesis in stallion testes. In rodents, livestock and primate species, a single dose of the synthetic glucocorticoid dexamethasone acutely lowers testosterone biosynthesis. To determine the mechanism of decreased testosterone biosynthesis, stallions were treated with 0.1mg/kg dexamethasone 12h prior to castration. Dexamethasone decreased serum concentrations of testosterone by 60% compared to saline-treated control stallions. Transcriptome analyses (microarrays, northern blots and quantitative PCR) of testes discovered that dexamethasone treatment decreased concentrations of glucocorticoid receptor alpha (NR3C1), alpha a...
The effect of treatment with immune modulators on endometrial cytokine expression in mares susceptible to persistent breeding-induced endometritis. Research has shown that 6 h after breeding is a critical time during the uterine innate immune response, and the failure to respond appropriately will result in persistent breeding-induced endometritis. This presents a potential opportunity to modulate the course of inflammation towards a timely resolution. Objective: To evaluate the effects of immune modulation on endometrial mRNA expression of inflammatory genes in susceptible mares 6 h after breeding. The hypothesis was that immune modulation alters endometrial cytokine expression in susceptible mares. Methods: A randomised controlled s...
Recovery of insulin sensitivity in mature horses after a 3 week course of dexamethasone therapy. Dexamethasone is an anti-inflammatory drug commonly used in equine medicine. Insulin sensitivity decreases with prolonged dexamethasone administration, but little information is available about the duration of this side effect after long-term treatment ends. Objective: To determine how long it takes for blood glucose, insulin and markers of insulin sensitivity to return to normal ranges after extended dexamethasone treatment has ceased. Methods: Experimental study. Methods: Eight healthy, mature, mixed-breed horses received 0.04 mg/kg bwt/day oral dexamethasone for 21 days. Blood samples wer...
Treatment of idiopathic headshaking in horses with pulsed high-dose dexamethasone. Treatment of idiopathic headshaking in horses is complicated by an incomplete understanding of underlying pathophysiology and partially effective treatments. If an inflammatory etiology exists, corticosteroids could be beneficial. Objective: An anti-inflammatory dose of dexamethasone reduces the signs of idiopathic headshaking in a field setting. Methods: Convenience sample of 20 adult horses with idiopathic headshaking syndrome. Cases were recruited from the general population and diagnosed by attending veterinarians. Methods: Prospective, blinded clinical trial. Pulsed dosing was with oral d...
Identification of sample donor by 24-plex short tandem repeat in a post-race equine plasma containing dexamethasone. Animal sport such as horseracing is tainted with drug abuse as are human sports. Treatment of racehorses on race day with therapeutic medications in most cases is banned, and thus, it is essential to monitor the illicit use of drugs in the racing horse to maintain integrity of racing, ensure fair competition and protect the health, safety and welfare of the horse, jockeys and drivers. In the event of a dispute over the identity of the sample donor, if the regulator can provide evidence that the DNA genotype profile of the post-race sample matched that of the alleged donor, then the potential d...
Short-term effect of ovariectomy on measures of insulin sensitivity and response to dexamethasone administration in horses. To evaluate the effect of ovariectomy on insulin sensitivity in horses and determine whether the effects of suppression of the hypothalamo-pituitary-adrenal axis differ before and after ovariectomy. Methods: 6 healthy mares. Methods: The horses underwent an IV glucose tolerance test (IVGTT), an insulin sensitivity test, and a dexamethasone suppression test before and 5 weeks after ovariectomy. Body weight, serum cortisol and plasma ACTH concentrations, serum insulin-to-blood glucose concentration ratios, and changes in blood glucose concentration with time after injection of glucose or insulin...
Culture conditions for equine bone marrow mesenchymal stem cells and expression of key transcription factors during their differentiation into osteoblasts. The use of equine bone marrow mesenchymal stem cells (BMSC) is a novel method to improve fracture healing in horses. However, additional research is needed to identify optimal culture conditions and to determine the mechanisms involved in regulating BMSC differentiation into osteoblasts. The objectives of the experiments were to determine: 1) if autologous or commercial serum is better for proliferation and differentiation of equine BMSC into osteoblasts, and 2) the expression of key transcription factors during the differentiation of equine BMSC into osteoblasts. Equine BMSC were isolated fro...
Stimulation of airway neutrophils following dexamethasone administration and equid herpesvirus-2 challenge in horses. The aim of this study was to investigate neutrophil stimulation following experimentally-induced airway inflammation in healthy horses. Six horses received dexamethasone and four were then inoculated with equid herpesvirus-2 (EHV-2). Significant neutrophilia was detected in tracheal wash and bronchoalveolar lavage fluid for up to 6 days. Concentrations of neutrophil elastase (NE) and myeloperoxidase (MPO) were significantly increased compared to baseline for up to 14 days in tracheal washes and both markers were significantly correlated with neutrophil counts. Serum levels of surfactant protei...
[Study on the reproducibility of ACTH concentrations in plasma of horses with and without equine Cushing syndrome]. The evaluation of plasma ACTH and the dexamethasone suppression test are considered the methods of choice to evaluate the course of therapy of pituitary pars intermedia dysfunction (PPID). Sampling protocols as well as vacutainers for analysis differ between the laboratories. To evaluate the reproducability of plasma ACTH measurement between four different laboratories (A, B, C, D) in Germany as well as within the laboratories themselves, ten horses with previously diagnosed PPID and four healthy horses were sampled and analyzed. Each laboratory received two differently labeled samples of each...
Induction of cytochrome P450 enzymes in primary equine hepatocyte culture. In this study, we established cell culture conditions for primary equine hepatocytes allowing cytochrome P450 enzyme (CYP) induction experiments. Hepatocytes were isolated after a modified method of Bakala et al. (2003) and cultivated on collagen I coated plates. Three different media were compared for their influence on morphology, viability and CYP activity of the hepatocytes. CYP activity was evaluated with the fluorescent substrate 7-benzyloxy-4-trifluoromethylcoumarin. Induction experiments were carried out with rifampicin, dexamethasone or phenobarbital. Concentration-response curves for...
Severe hypertriglyceridaemia in horses and ponies with endocrine disorders. Severe hypertriglyceridaemia in horses and ponies with endocrine disorders has been reported anecdotally but has not been documented in the literature. Objective: To describe historical and clinicopathological findings as well as progression and outcome in horses and ponies with severe hypertriglyceridaemia (serum triglyceride concentration >5.65 mmol/l) secondary to an endocrine disorder that were otherwise apparently healthy. Methods: Cases from 6 participating institutions were identified and case details extracted from the medical records. Results: Case details of 3 horses and 4 ponies ...
Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses. Metformin is a potential therapeutic agent for the treatment of insulin resistance (IR). In laboratory animals, orally administered metformin reduces intestinal glucose absorption and may therefore affect insulinaemic responses to oral carbohydrate ingestion. Objective: To determine whether pretreatment with metformin reduces plasma glucose concentration and insulin responses following consumption of dextrose in horses. Methods: Therapeutic cross-over study. Methods: Seven healthy Standardbred and Thoroughbred geldings were subjected to an oral dextrose challenge test on 4 occasions: with and ...
Endocrine evaluation after an intra-articular therapeutic dosage of dexamethasone in horses. This study investigated whether a single intra-articular administration (IA) of dexamethasone (DEX) in horses at therapeutic dosage could exert a systemic effect by influencing the hypothalamic-pituitary-adrenal axis activity as a consequence of (limited) absorption and systemic distribution. The results indicated that DEX was detectable in urine collected 12-48 h after IA administration and that injection was accompanied by a reduced urine excretion of cortisol, 6β-hydroxycortisol (6βOHF) and two other metabolites of cortisol lasting up to 48 h post-DEX administration. The systemic effect...
Seasonal and annual influence on insulin and cortisol results from overnight dexamethasone suppression tests in normal ponies and ponies predisposed to laminitis. A simple, accurate test for identifying individual animals at increased risk of laminitis would aid prevention. Laminitis-prone ponies have a greater serum insulin response to dexamethasone administration than normal ponies in the summer, but the response during different seasons is unknown. Objective: To test the hypothesis that previously laminitic ponies have a greater insulin response to dexamethasone than normal ponies, which is present during all seasons. Methods: Prospective longitudinal study. Methods: Overnight dexamethasone suppression tests were performed on 7 normal ponies and 5 pr...
Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites. Engagement of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) is a master trigger of the deleterious effects of septic shock. Horses and humans are considered the most sensitive species to septic shock, but the mechanisms explaining these phenomena remain elusive. Analysis of tlr4 promoters revealed high similarity among LPS-sensitive species (human, chimpanzee, and horse) and low similarity with LPS-resistant species (mouse and rat). Four conserved nuclear factor kappa B (NFκB) binding sites were found in the tlr4 promoter and two in the md2 promoter sequences that are likely to be t...
Comparison of hair follicle histology between horses with pituitary pars intermedia dysfunction and excessive hair growth and normal aged horses. Pituitary pars intermedia dysfunction (PPID) in older equids is commonly recognized by a long hair coat that fails to shed. Objective: The aim of this study was to compare hair follicle stages in PPID-affected horses with excessively long hair coats with the stages of normal aged horses (controls) and to compare hair follicle stages in PPID-affected horses after 6 months of treatment with pergolide mesylate with those of control horses. Methods: Eight PPID-affected horses and four normal, age-matched, control horses. Methods: Skin biopsies were collected from the neck and rump of PPID-affected...
An investigation of uterine nitric oxide production in mares susceptible and resistant to persistent breeding-induced endometritis and the effects of immunomodulation. The first objective of this study was to evaluate intrauterine nitric oxide (NO) and endometrial inducible NO synthase (iNOS) in mares susceptible or resistant to persistent breeding-induced endometritis (PBIE) within 24 h after breeding. Mares susceptible (n = 6) or resistant (n = 6) to PBIE were inseminated over five cycles, and uterine secretions and endometrial biopsies were collected before and 2, 6, 12 and 24 h after insemination. Uterine secretions were analysed for NO and biopsies were analyzed for iNOS expression. A second experiment evaluated the effect of treatment with dexame...
Neutrophils are not less sensitive than other blood leukocytes to the genomic effects of glucocorticoids. Neutrophils are generally considered less responsive to glucocorticoids compared to other inflammatory cells. The reported increase in human neutrophil survival mediated by these drugs partly supports this assertion. However, it was recently shown that dexamethasone exerts potent anti-inflammatory effects in equine peripheral blood neutrophils. Few comparative studies of glucocorticoid effects in neutrophils and other leukocytes have been reported and a relative insensitivity of neutrophils to these drugs could not be ruled out. Objective: We assessed glucocorticoid-responsiveness in equine an...
Effect of immunomodulatory therapy on the endometrial inflammatory response to induced infectious endometritis in susceptible mares. The objective of the present study was to evaluate the effect of immunomodulatory therapy (glucocorticoids (GC) and mycobacterium cell wall extract (MCWE)) on the endometrial gene expression of inflammatory cytokines in susceptible mares with induced infectious endometritis. Endometrial gene expression of pro- and anti-inflammatory cytokines; interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, IL-1 receptor antagonist (ra), acute phase protein (APP) serum amyloid A (SAA) and clinical parameters were evaluated. Five mares were classified as susceptible to persistent endomet...
Seasonal variation in results of diagnostic tests for pituitary pars intermedia dysfunction in older, clinically normal geldings. To determine whether seasonal variations exist in endogenous plasma ACTH, plasma α-melanocyte-stimulating hormone (α-MSH), serum cortisol, and serum insulin concentrations and in the results of a dexamethasone suppression test for older, clinically normal geldings in Alabama. Methods: Cohort study. Methods: 15 healthy mixed-breed geldings (median age, 14 years). Methods: Sample collection was repeated monthly for 12 months. Dexamethasone (0.04 mg/kg [0.02 mg/lb], IM) was administered and cortisol concentrations were determined at 15 and 19 hours. Radioimmunoassays were used to measure ACTH, ...
Presumed case of “stiff-horse syndrome” caused by decreased gamma-aminobutyric acid (GABA) production in an American Paint mare. Glutamic acid decarboxylase (GAD) converts glutamic acid into the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Increased serum GAD (auto) antibody concentrations were found in a mare with increased postural musculature tone resulting in stiffness and recumbence. The mare was treated with dexamethasone which resulted in resolution of clinical signs and decreased GAD antibody concentrations. La glutamate décarboxylase (GAD) convertit l’acide glutamique en acide gamma-aminobutyrique (GABA), un inhibiteur des neurotransmetteurs. Des concentrations sériques accrues d’anticorps (a...
Pharmacokinetics of dexamethasone following intra-articular, intravenous, intramuscular, and oral administration in horses and its effects on endogenous hydrocortisone. This study investigated and compared the pharmacokinetics of intra-articular (IA) administration of dexamethasone sodium phosphate (DSP) into three equine joints, femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the intramuscular (IM), oral (PO) and intravenous (IV) administrations. No significant differences in the pharmacokinetic estimates between the three joints were observed with the exception of maximum concentration (Cmax ) and time to maximum concentration (Tmax ). Median (range) Cmax for the IAC, IAF, and IAS were 16.9 (14.6-35.4), 23.4 (13.5-73.0), and 46.9...
Efficacy of human chorionic gonadotropin to induce ovulation in the mare, when associated with a single dose of dexamethasone administered at breeding time. Human chorionic gonadotropin (hCG) and dexamethasone have a role in the reproductive management protocols of mares susceptible to persistent mating-induced endometritis (PMIE). However, it is possible that there is interference between these 2 drugs. Objective: The objective of this retrospective study was to determine the efficacy of hCG to induce ovulation in mares treated with dexamethasone at breeding time. Methods: Medical records from 152 mares and 223 cycles were analysed. In 113 cycles, mares susceptible to PMIE were treated with 1500 iu hCG and a single dose of 50 mg dexamethasone, 11...
Modulation of equine neutrophil adherence and migration by the annexin-1 derived N-terminal peptide, Ac2-26. Neutrophil activation, whilst a key component of host defence, must be tightly regulated in order to avoid an inappropriate cellular response. Annexin-1, which is present in large amounts in neutrophils, and its N-terminal peptides, reduce neutrophil accumulation but annexin peptides have also been shown to exhibit neutrophil activating properties. We have recently shown annexin-1 to be present in equine neutrophils and demonstrated that the annexin-1-derived peptide, Ac2-26, can both reduce superoxide production by these cells in response to other stimuli and directly induce free radical prod...
Time-dependent changes of cytokines mRNA in bronchoalveolar lavage fluid from symptomatic recurrent airway obstruction-affected horses. During an 18 day test, we measured the cytokine mRNA expression (Interleukin-1beta [IL-1beta], Interleukin-8 [IL-8], Interferon-gamma [IFN-gamma], Tumor Necrosis Factor-alpha [TNF-alpha]) of cells from bronchoalveolar lavage fluid [BALF] in five horses previously diagnosed with RAO, before and during challenge exposure, and after the desensitization phase which involved dexamethasone treatment and environmental modification. Simultaneously, the same cytokine mRNA expression of cells from BALF in four asymptomatic RAO-affected horses maintained outdoors was analyzed. An evident respiratory dist...
Dexamethasone-induced cytokine changes associated with diminished disease severity in horses infected with Anaplasma phagocytophilum. Anaplasma phagocytophilum is the zoonotic cause of granulocytic anaplasmosis. We hypothesized that immune response, specifically gamma interferon (IFN-γ), plays a role in disease severity. To test this, horses were infected and IFNG expression was pharmacologically downregulated using corticosteroids. Eight horses were infected with A. phagocytophilum; 4 received dexamethasone on days 4 to 8 of infection. Clinical signs, hematologic parameters, and transcription of cytokine/chemokine genes were compared among treated and untreated horses. Infection was quantitated by msp2 real-time PCR and mi...
Multiple small-intestine intussusceptions: a complication of purpura haemorrhagica in a horse. A Belgian draft horse stallion presented with classical signs of purpura haemorrhagica: oedema of the distal limbs, ventral abdomen and head, ecchymotic haemorrhage of mucous membranes, epistaxis, fever, lethargy, reluctance to move, and anorexia. Serum chemistry revealed a highly elevated gamma-globulin fraction. Streptococcal lymphadenitis (strangles) had been present on a neighbouring farm in the past few months. After an initial positive response to therapy with benzylpenicillin, flunixin and dexamethasone, the horse's condition deteriorated suddenly on day 4 of hospitalization, with signs...
Maternal dexamethasone treatment in late gestation induces precocious fetal maturation and delivery in healthy Thoroughbred mares. The foal requires an active hypothalamo-pituitary-adrenal (HPA) axis for organ maturation and post natal survival. Prenatal administration of synthetic glucocorticoids may provide an effective method for inducing fetal maturation safely in the mare. Objective: To determine whether dexamethasone administered to late pregnant mares: 1) will induce fetal maturation and precocious delivery; 2) is safe to use and 3) to identify endocrine responses in the mare and foal. Methods: Pregnant Thoroughbred mares received either 100 mg dexamethasone i.m. (treated n = 5) or 50 ml saline i.m. (control n = 5)...
