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1.
Vet J ; 296-297: 105995, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37207985

RESUMO

Plasma adrenocorticotropic hormone (ACTH) concentration is commonly measured to diagnose pituitary pars intermedia dysfunction (PPID). Several intrinsic and extrinsic factors affect ACTH concentrations, including breed. The objective of this study was to prospectively compare plasma ACTH concentrations among different breeds of mature horses and ponies. Three breed groups comprised Thoroughbred horses (n = 127), Shetland ponies (n = 131) and ponies of non-Shetland breeds (n = 141). Enrolled animals did not show any signs of illness, lameness or clinical signs consistent with PPID. Blood samples were collected 6 months apart, around the autumn equinox and spring equinox, and plasma concentrations of ACTH were measured by chemiluminescent immunoassay. Pairwise breed comparisons within each season were performed on log transformed data using the Tukey test. Estimated mean differences in ACTH concentrations were expressed as fold difference with 95 % confidence intervals (CI). Reference intervals for each breed group per season were calculated using non-parametric methods. In autumn, higher ACTH concentrations were found among non-Shetland pony breeds compared with Thoroughbreds (1.55 fold higher; 95 % CI, 1.35-1.77; P < 0.001), and in Shetland ponies compared with Thoroughbreds (2.67 fold higher; 95 % CI, 2.33-3.08; P < 0.001) and non-Shetland pony breeds (1.73 fold higher; 95 % CI, 1.51-1.98; P < 0.001). In spring, no differences were identified among breed groups (all P > 0.05). Reference intervals were similar among breed groups in spring, but upper limits for ACTH concentrations were markedly different between Thoroughbred horses and pony breeds in autumn. These findings emphasise that breed should be accounted for when determining and interpreting reference intervals for ACTH concentrations among healthy horses and ponies in autumn.


Assuntos
Doenças dos Cavalos , Doenças da Hipófise , Cavalos/genética , Animais , Doenças dos Cavalos/genética , Doenças da Hipófise/genética , Doenças da Hipófise/veterinária , Hormônio Adrenocorticotrópico , Estações do Ano , Marcha
2.
Domest Anim Endocrinol ; 74: 106530, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32818904

RESUMO

Although it is understood that equine endocrinopathic laminitis can be triggered by high concentrations of insulin, it is unclear whether this represents a direct action on lamellar tissue via insulin receptors (InsR), an interaction with IGF-1 receptors (IGF-1R), or some other, indirect action. This uncertainty is because of the reported scarcity of InsR in lamellar tissue and the low affinity of insulin for equine IGF-1R. In the present study, the effects of insulin and IGF-1 (as a positive control) were examined using lamellar explants isolated from the hooves of healthy horses and incubated in cell culture medium for between 2 min and 48 h. In this system, a low physiological concentration of IGF-1 (10 nM; 1.31 ng/mL) caused a marked increase in the appearance of phosphorylated IGF-1R after 5 min (P < 0.05), and this effect was blocked by a human anti-IGF-1R monoclonal antibody (mAb). However, a high concentration of insulin (10 nM; 1,430 µIU/mL) appeared to cause dephosphorylation of the IGF-1R after 5 min (P < 0.01), 15 min, and 30 min (P < 0.001). Using 3H-thymidine as a marker, it was also demonstrated that insulin and IGF-1-stimulated cell proliferation in lamellar explants over the same concentration range as each other (1-100 nM), implying that each peptide acts via its own receptor (P < 0.001). Conversely, the effect of both peptides could be blocked using a selective anti-IGF-1R mAb (P < 0.001), implying that insulin acts via IGF1-R (either directly or indirectly). Notwithstanding this conundrum, the results demonstrate that insulin acts directly on lamellar tissue and suggest that a therapeutic anti-IGF-1R mAb could be useful in treating or preventing endocrinopathic laminitis.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Casco e Garras/metabolismo , Cavalos/metabolismo , Insulina/farmacologia , Receptor IGF Tipo 1/metabolismo , Técnicas de Cultura de Tecidos/veterinária , Animais , Anticorpos Monoclonais , Western Blotting , Proliferação de Células , Receptor IGF Tipo 1/genética
3.
Aust Vet J ; 98(12): 616-621, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33001453

RESUMO

OBJECTIVE: To compare circannual plasma concentrations of adrenocorticotropic hormone (ACTH) and seasonal dexamethasone suppression test (DST) results between three different equine breed groups. METHODS: Six Standardbred horses, six Andalusian horses and six mixed-breed ponies were followed over a 1-year period, during which time groups were managed identically. Blood samples were collected monthly (around the autumn equinox) or in every second month (other times of the year) for the determination of plasma ACTH concentrations using a chemiluminescent immunoassay. Overnight DSTs were performed quarterly, with suppression of plasma cortisol to below 27 nmol/L at 19 h considered a normal result. RESULTS: Seasonal variation in plasma ACTH concentrations was present among all breed groups with, as expected, higher levels detected around the autumn equinox, from February to April (P < 0.001). Plasma ACTH concentrations were different between breed groups in March, with higher levels in Andalusians compared with Standardbreds (P = 0.048) and in ponies compared with Standardbreds (P = 0.010). Suppression of cortisol during the DST was normal for all animals in winter, spring and summer, but five Andalusians and three ponies returned abnormally high results in autumn, compared with zero Standardbreds. CONCLUSION: Higher plasma ACTH concentrations and more false-positive DST results were obtained during autumn in ponies and Andalusian horses when compared with Standardbred horses. Potential differences between breeds should be considered when interpreting test results for horses and ponies that are evaluated for pituitary pars intermedia dysfunction. Further work is recommended to establish population-based reference intervals and clinical cut-off values for ACTH in different equine breeds.


Assuntos
Doenças dos Cavalos , Doenças da Hipófise , Hormônio Adrenocorticotrópico , Animais , Cruzamento , Dexametasona , Cavalos , Hidrocortisona , Doenças da Hipófise/veterinária
4.
Aust Vet J ; 96(7): 233-242, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29862508

RESUMO

The purpose of this article is to provide a review of the current knowledge and opinions about the epidemiology, clinical findings (including sequelae), diagnosis, treatment and monitoring of equine pituitary pars intermedia dysfunction, particularly in the Australian context. This information and the recommendations provided will assist practitioners in making informed decisions regarding the diagnosis and management of this disorder.


Assuntos
Doenças dos Cavalos , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia , Hormônio Adrenocorticotrópico/sangue , Animais , Austrália/epidemiologia , Agonistas de Dopamina/uso terapêutico , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/fisiopatologia , Cavalos , Nova Zelândia/epidemiologia , Pergolida/uso terapêutico , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/epidemiologia , Adeno-Hipófise Parte Intermédia/fisiopatologia , Guias de Prática Clínica como Assunto , Fatores de Risco , Sociedades Científicas
5.
J Vet Pharmacol Ther ; 41(1): e35-e39, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28804940

RESUMO

Polymyxin-B is used to treat equine systemic inflammation. Bacterial toxins other than lipopolysaccharide (LPS) contribute to systemic inflammation but the effects of polymyxin-B on these are poorly defined. Whole blood aliquots from six healthy horses diluted 1:1 with RPMI were incubated for 21 hr with 1 µg/ml of LPS, lipoteichoic acid (LTA) or peptidoglycan (PGN) in the presence of increasing concentrations of polymyxin-B (10-3000 µg/ml). A murine L929 fibroblast bioassay was used to measure TNF-α activity. Polymyxin-B significantly inhibited the effects of all three bacterial toxins. Analysis of variance showed the IC50 value for polymyxin-B for TNF-α inhibition caused by LTA (11.19 ± 2.89 µg/ml polymyxin-B) was significantly lower (p = .009) than the values for LPS (46.48 ± 9.93 µg/ml) and PGN (54.44 ± 8.97 µg/ml). There was no significant difference in IC50 values between LPS and PGN (p > .05). Maximum inhibition of TNF-α was 77.4%, 73.0% and 82.7% for LPS, PGN and LTA, respectively and was not significantly different between toxins. At the two highest concentrations of polymyxin-B, TNF-α began to increase. These data suggest that polymyxin-B may inhibit the effects of bacterial toxins other than LPS and might be a more potent inhibitor of LTA than LPS or PGN.


Assuntos
Antibacterianos/farmacologia , Toxinas Bacterianas/farmacologia , Lipopolissacarídeos/farmacologia , Peptidoglicano/farmacologia , Polimixina B/farmacologia , Ácidos Teicoicos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Antibacterianos/administração & dosagem , Toxinas Bacterianas/antagonistas & inibidores , Relação Dose-Resposta a Droga , Cavalos/sangue , Lipopolissacarídeos/antagonistas & inibidores , Camundongos , Polimixina B/administração & dosagem , Ácidos Teicoicos/antagonistas & inibidores , Fator de Necrose Tumoral alfa/sangue
6.
BMC Pregnancy Childbirth ; 17(1): 439, 2017 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-29282072

RESUMO

BACKGROUND: Few data are available to guide biological sample collection around the time of birth for large-scale birth cohorts. We are designing a large UK birth cohort to investigate the role of infection and the developing immune system in determining future health and disease. We undertook a pilot to develop methodology for the main study, gain practical experience of collecting samples, and understand the acceptability of sample collection to women in late pregnancy. METHODS: Between February-July 2014, we piloted the feasibility and acceptability of collecting maternal stool, baby stool and cord blood samples from participants recruited at prolonged pregnancy and planned pre-labour caesarean section clinics at University College London Hospital. Participating women were asked to complete acceptability questionnaires. RESULTS: Overall, 265 women were approached and 171 (65%) participated, with ≥1 sample collected from 113 women or their baby (66%). Women had a mean age of 34 years, were primarily of white ethnicity (130/166, 78%), and half were nulliparous (86/169, 51%). Women undergoing planned pre-labour caesarean section were more likely than those who delivered vaginally to provide ≥1 sample (98% vs 54%), but less likely to provide maternal stool (10% vs 43%). Pre-sample questionnaires were completed by 110/171 women (64%). Most women reported feeling comfortable with samples being collected from their baby (<10% uncomfortable), but were less comfortable about their own stool (19% uncomfortable) or a vaginal swab (24% uncomfortable). CONCLUSIONS: It is possible to collect a range of biological samples from women around the time of delivery, and this was acceptable for most women. These data inform study design and protocol development for large-scale birth cohorts.


Assuntos
Fezes , Sangue Fetal , Testes para Triagem do Soro Materno/métodos , Aceitação pelo Paciente de Cuidados de Saúde , Gravidez Prolongada/diagnóstico , Cuidados Pré-Operatórios/métodos , Manejo de Espécimes/métodos , Adulto , Coleta de Amostras Sanguíneas/métodos , Coleta de Amostras Sanguíneas/psicologia , Cesárea , Estudos de Viabilidade , Feminino , Humanos , Estudos Longitudinais , Testes para Triagem do Soro Materno/psicologia , Projetos Piloto , Gravidez , Gravidez Prolongada/psicologia , Cuidados Pré-Operatórios/psicologia , Manejo de Espécimes/psicologia , Reino Unido
7.
Aust Vet J ; 95(10): 370-374, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28948628

RESUMO

OBJECTIVES: The aims of this study were to (1) report the incidence of laminitis among a population of horses and ponies attending Pony Clubs in Victoria, Australia, and (2) describe the dietary and management practices of the sample population. METHODS: Researchers visited 10 Pony Clubs over a 10-month period. Horse and pony owners completed a questionnaire to provide information on management relating to diet and exercise. Owners were also asked to report their animal's history of laminitis, if any. RESULTS: From a survey population of 233 horses and ponies, 15.0% of animals (35 individuals) were reported to have suffered from at least one episode of laminitis. Of the animals that had suffered from laminitis, more than half had experienced multiple episodes. The majority of previously laminitic horses and ponies (71.4%) had not experienced an episode of laminitis within the past 12 months; however, 14.2% had experienced an incident within the past month. The proportion of ponies affected by laminitis (31/142; 21.8%) was significantly higher (P < 0.001) than the proportion of horses affected by laminitis (4/91; 4.4%). The incidence of laminitis within the pony group sampled was 6.5 cases per 100 pony years, while the incidence in horses was 0.55 cases per 100 horse years. CONCLUSION: This study provided information on the incidence of laminitis in the general population of pleasure horses and ponies in south-eastern Australia. It also provided an overview of dietary and management practices. Given the high incidence of animals that had been affected by laminitis (and the associated welfare implications), this study highlights the importance of owner education regarding appropriate feeding and management strategies to reduce the risk of laminitis.


Assuntos
Criação de Animais Domésticos/métodos , Doenças do Pé/veterinária , Doenças dos Cavalos/epidemiologia , Animais , Feminino , Doenças do Pé/epidemiologia , Cavalos , Incidência , Masculino , Austrália do Sul/epidemiologia , Inquéritos e Questionários , Vitória
9.
Vaccine ; 35(32): 3917-3921, 2017 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-28645716

RESUMO

In 2013, the Council for International Organizations of Medical Sciences (CIOMS) created a Working Group on Vaccine Safety (WG) to address unmet needs in the area of vaccine pharmacovigilance. Generating reliable data about specific vaccine safety concerns is becoming a priority due to recent progress in the development and deployment of new vaccines of global importance, as well as novel vaccines targeting diseases specifically endemic to many resource-limited countries (RLCs), e.g. malaria, dengue. The WG created a Guide to Active Vaccine Safety Surveillance (AVSS) to assist national regulatory authorities and national immunization program officers in RLCs in determining the best course of action with regards to non-routine pharmacovigilance activities, when confronted with a launch of a new vaccine or a vaccine that is new to their country. Here we summarize the results of the WG, further detailed in the Guide, which for the first time provides a structured approach to identifying and analyzing specific vaccines safety knowledge gaps, while considering all available sources of information, in order to determine whether AVSS is an appropriate solution. If AVSS is confirmed as being the appropriate tool, the Guide provides additional essential information on AVSS, a detailed overview of common types of AVSS and practical implementation considerations. It also provides a framework for a well-constructed and informative AVSS when needed, thus aiming to ensure the best possible safety of immunization in this new landscape.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Farmacovigilância , Vacinas/administração & dosagem , Vacinas/efeitos adversos , Humanos
10.
Contemp Clin Trials ; 52: 35-38, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27836506

RESUMO

Primary care patient-centered medical homes (PCMHs) are an effective healthcare delivery model. Evidence regarding the most effective payment models for increased coordination efforts is sparse. This protocol paper describes the evaluation of an Alternative Payment Methodology (APM) implemented in a subset of Oregon community health centers (CHCs), using a prospective matched observational design. The APM is a primary care payment reform intervention that changed Oregon's Medicaid payment for several CHCs from fee-for-service reimbursement to a per-member-per-month capitated payment. We will implement a difference-in-difference analytic approach to evaluate pre-post APM changes between intervention and control groups, including: 1) clinic-level outcomes, 2) patient-level clinical outcomes, and 3) patient-level econometric outcomes. Findings from the project will be of national significance, as there is a need for evidence regarding how novel payment methods might enhance PCMH capabilities and support their capacity to produce better quality and outcomes. If this capitated payment method is proven effective, study findings will inform dissemination of similar APMs nationwide.


Assuntos
Capitação , Centros Comunitários de Saúde/organização & administração , Assistência Centrada no Paciente/organização & administração , Atenção Primária à Saúde/organização & administração , Centros Comunitários de Saúde/economia , Planos de Pagamento por Serviço Prestado , Humanos , Medicaid , Oregon , Assistência Centrada no Paciente/economia , Atenção Primária à Saúde/economia , Estudos Prospectivos , Mecanismo de Reembolso , Estados Unidos
11.
Aust Vet J ; 94(11): 427-432, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27785793

RESUMO

OBJECTIVE: To determine the prevalence of obesity within a population of pleasure horses and ponies in Victoria, Australia, and to compare owners' perceptions of their animals' body condition with researchers' assessments. DESIGN: An observational study plus owner questionnaire. METHODS: Ten Pony Club rallies in different regions of Victoria were attended. Information regarding 229 horses and ponies were obtained from owner questionnaires, and owners' perceptions of the current body condition of their animals were assessed using a visual analogue scale. Body condition score (BCS) was assessed by the researchers using the modified Henneke method. RESULTS: The prevalence of researcher-assessed obesity (BCS ≥7/9) in the total surveyed population was 23.1%. A higher prevalence of obesity was identified in Shetland ponies (71.5%) and other pony types (32.0%) compared with horse breeds (9.3%). Owners perceived their animals to be in significantly lower body condition compared with the researchers' assessments (P < 0.001). CONCLUSION: Although the overall prevalence of obesity within Australian pleasure horses and ponies was 24.5%, a considerably higher proportion of pony breeds fell into this category. Owners frequently underestimated their own animal's body condition. Knowing the prevalence of obesity in this population and understanding how owners perceive the body condition of their animals may help with targeting education around preventative health care, with the aim of reducing the risk of conditions such as insulin dysregulation and laminitis.


Assuntos
Composição Corporal , Doenças dos Cavalos/epidemiologia , Obesidade/veterinária , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Cavalos/classificação , Humanos , Masculino , Obesidade/epidemiologia , Prevalência , Inquéritos e Questionários , Vitória/epidemiologia
12.
Vet J ; 214: 14-20, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27387720

RESUMO

The relationships between diet, obesity and insulin dysregulation in equids require further investigation due to their association with laminitis. This study examined the effect of dietary glycaemic load and increased adiposity on insulin sensitivity and adipokine concentrations in different equine breeds. Equal numbers of Standardbred horses, mixed-breed ponies and Andalusian horses were provided with ad libitum hay plus either cereal-rich (CHO; n = 12), fat-rich (FAT; n = 12) or control (CON; n = 9) meals over 20 weeks. The isocaloric CHO and FAT diets were fed to induce obesity by gradually increasing the supplementary feeds to provide 200% of daily digestible energy requirements by Week 20. The CON group were fed a basal ration only and maintained moderate body condition. At Week 20, the CHO and FAT groups demonstrated significantly increased body condition score, bodyweight, total body fat mass and plasma leptin concentrations compared with the CON group (P <0.001). The CHO group had lower insulin sensitivity (SI; P <0.001) and higher acute insulin response to glucose (P = 0.002) than the CON group. In contrast, the FAT group was no different to the control group. Ponies and Andalusians had lower SI values compared with Standardbreds, regardless of diet group (P = 0.001). Adiponectin concentrations were similar between the FAT and CON groups, but were significantly lower in the CHO group (P = 0.010). The provision of cereal-rich meals appeared to be a more important determinant of insulin sensitivity than the induction of obesity per se. Whether hypoadiponectinaemia is a cause or consequence of insulin dysregulation warrants further investigation.


Assuntos
Adipocinas/metabolismo , Adiposidade , Gorduras na Dieta/análise , Grão Comestível , Carga Glicêmica , Doenças dos Cavalos/fisiopatologia , Resistência à Insulina/fisiologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Doenças dos Cavalos/genética , Cavalos , Masculino
13.
Equine Vet J ; 48(3): 368-73, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25726948

RESUMO

REASONS FOR PERFORMING STUDY: The relative influences of obesity and adaptation to high glycaemic diets on the development of insulin dysregulation in equids are unclear. OBJECTIVES: To determine whether increased adiposity per se is responsible for the decreased insulin sensitivity often observed in obese horses or whether a dietary glycaemic response is critically important. STUDY DESIGN: Randomised controlled trial. METHODS: Eighteen horses and ponies were studied over a 20-week period. They received ad libitum hay plus either a high fat (low glycaemic) diet (FAT; n = 6) or a similar (isocaloric) diet containing 1.5 g/kg bwt once daily glucose (GLU; n = 6) to induce obesity. A third group received a control ration (CON; n = 6). Adiposity was monitored using body condition score (BCS) and total body fat mass percentage (TBFM) determined using a deuterium oxide dilution technique. Insulin sensitivity was assessed using a frequently sampled i.v. glucose tolerance test. Plasma concentrations of glucose, insulin, leptin, adiponectin, tumour necrosis factor-α (TNF-α) and serum amyloid A (SAA) were measured. RESULTS: The FAT and GLU groups became obese (BCS ≥7) whereas the CON group maintained moderate condition (BCS ≤6). Total body fat mass and leptin concentrations were increased in the FAT and GLU groups than in the CON group (P<0.001 and P = 0.003, respectively). Values for both insulin-dependent (SI) and insulin-independent (Sg) glucose disposal were higher in the GLU group compared with the FAT and CON groups (P = 0.006 and P = 0.03, respectively). There were no differences in adiponectin, TNF-α or SAA between groups (all P≥0.4). CONCLUSIONS: Increased adiposity did not reduce insulin sensitivity in either the FAT or the GLU diet groups, suggesting that obesity per se might not be responsible for the lower SI values reported in previous studies. Contrary to expectations, once daily glucose appeared to increase insulin sensitivity. Further work is required into the dietary causes of insulin resistance in equids.


Assuntos
Adipocinas/metabolismo , Adiposidade/efeitos dos fármacos , Ração Animal/análise , Gorduras na Dieta/administração & dosagem , Cavalos/metabolismo , Resistência à Insulina/fisiologia , Adipocinas/genética , Adiposidade/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Glicemia , Dieta/veterinária , Gorduras na Dieta/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Índice Glicêmico
15.
J Vet Intern Med ; 30(1): 260-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26683003

RESUMO

BACKGROUND: Acute gastrointestinal disease occurs commonly in horses. Novel biomarkers might improve the understanding of SIRS and aid diagnosis and determination of prognosis. HYPOTHESES: Increased plasma concentrations of the biomarkers HMGB-1 and nucleosomes are associated with severity of gastrointestinal lesions in horses; concentrations of these biomarkers will be greater in horses with lesions more likely to cause SIRS; and will provide additional information compared with standard biomarkers fibrinogen and SAA. ANIMALS: Thirty horses with gastrointestinal disease, 22 healthy horses. METHODS: Prospective study. Plasma samples taken on admission were used for measurement of HMGB-1, nucleosomes, fibrinogen, and SAA. Values were compared between healthy horses and those with gastrointestinal disease, and between horses with gastrointestinal disease grouped by lesion type (inflammatory, strangulating, and nonstrangulating). Correlations between biomarkers were assessed. RESULTS: Plasma concentrations of all biomarkers were significantly higher in horses with gastrointestinal disease compared to healthy horses (P ≤ .001). HMGB-1 and nucleosomes were significantly higher in inflammatory and strangulating groups compared to healthy horses (3.5-fold and 5.4-fold increases, respectively, for HMGB-1 (P < .05) and 4.8-fold and 5.6-fold increases for nucleosomes (P < .05)), but concentrations in the group with nonstrangulating disease did not differ from healthy horses. There was significant correlation between HMGB-1 and nucleosomes (Spearman's r = 0.623; P < .001), and fibrinogen and SAA (Spearman's r = 0.801; P < .001) but not between other biomarkers. CONCLUSIONS AND CLINICAL IMPORTANCE: High mobility group box-1 and nucleosomes might have use as biomarkers for horses with gastrointestinal disease. Further studies are required to determine kinetics and prognostic value of serial measurements of these biomarkers in horses.


Assuntos
Cólica/veterinária , Proteína HMGB1/sangue , Doenças dos Cavalos/sangue , Nucleossomos/metabolismo , Animais , Biomarcadores , Cólica/sangue , Cólica/metabolismo , Feminino , Regulação da Expressão Gênica/fisiologia , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Doenças dos Cavalos/metabolismo , Cavalos , Masculino , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/veterinária
16.
J Anim Sci ; 93(7): 3377-83, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26440006

RESUMO

The enteroinsular axis is a complex system that includes the release of incretin hormones from the gut to promote the absorption and utilization of glucose after a meal. The insulinogenic effect of incretin hormones such as glucagon-like peptide-1 (GLP-1) remains poorly characterized in the horse. The aim of this study was to compare postprandial glucose, insulin, and GLP-1 responses of different equine breeds adapted to twice-daily meals containing micronized maize. Four Standardbred horses, 4 mixed-breed ponies, and 4 Andalusian cross horses in moderate BCS (5.5 ± 0.2 out of 9) were fed meals at 0800 and 1600 h each day. The meals contained micronized maize (mixed with soaked soybean hulls and lucerne chaff), with the amount of maize gradually increased over 12 wk to reach a final quantity of 1.7 g/kg BW (1.1 g/kg BW starch) in each meal. Animals had ad libitum access to the same hay throughout. After 12 wk of acclimation, serial blood samples were collected from all animals over a 14-h period to measure concentrations of glucose, insulin, and GLP-1, with meals fed immediately after the 0 and 8 h samples. Glucose area under the curve (AUC) values were similar between breed groups (P = 0.41); however, ponies and Andalusian horses exhibited significantly higher insulin AUC values after both meals compared with Standardbred horses (both P < 0.005). Postprandial GLP-1 AUC values were also significantly higher in ponies and Andalusian horses compared with Standardbred horses (breed × time interaction; P < 0.001). Correlation analysis demonstrated a strong positive association between concentrations of insulin and GLP-1 over time (rs = 0.752; P < 0.001). The increased insulin concentrations in ponies and Andalusian horses may partly reflect lower insulin sensitivity but could also be attributed to increased GLP-1 release. Given that hyperinsulinemia is a recognized risk factor for the development of laminitis in domestic equids, this study provides evidence that the enteroinsular axis warrants further investigation.


Assuntos
Ração Animal/análise , Manipulação de Alimentos , Peptídeo 1 Semelhante ao Glucagon/sangue , Cavalos/fisiologia , Insulina/sangue , Zea mays , Fenômenos Fisiológicos da Nutrição Animal , Animais , Glicemia/análise , Cruzamento , Dieta/veterinária , Polipeptídeo Inibidor Gástrico , Glucagon/metabolismo , Cavalos/genética , Resistência à Insulina , Período Pós-Prandial
17.
J Vet Pharmacol Ther ; 38(3): 290-6, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25407884

RESUMO

Despite the severity and common occurrence of equine endotoxaemia, the available anti-endotoxic treatments do not effectively target key inflammatory mechanisms such as leucocyte activation and cytokine production. In this study, four compounds with potential anti-endotoxic effects, namely rolipram, azithromycin, ethyl pyruvate and metformin, were investigated in vitro using equine whole blood stimulated with bacterial lipopolysaccharide. TNF-α and IL-1ß production were measured in plasma. Rolipram was the most potent inhibitor of cytokine production (IC50 0.84 and 4.68 µm for TNF-α and IL-1ß, respectively) with almost complete inhibition of TNF-α, but inhibited IL-1ß by only 39.46%. Azithromycin produced almost complete inhibition of both cytokines, but tended to be less potent than rolipram (IC50 10.66 and 17.4 µm for TNF-α and IL-1ß, respectively). Metformin inhibited TNF-α production with similar potency to rolipram and azithromycin (IC50 3.35 µm) but showed significantly lower efficacy (45.93%; P < 0.05), and had no inhibitory effect on IL-1ß. Ethyl pyruvate was the least potent (IC50 68.35 µm and >10 mm for TNF-α and IL-1ß production, respectively). Further work is required to investigate whether these or related compounds may have potential use in the treatment of equine endotoxaemia in vivo.


Assuntos
Anti-Inflamatórios/uso terapêutico , Azitromicina/uso terapêutico , Endotoxemia/tratamento farmacológico , Doenças dos Cavalos/tratamento farmacológico , Metformina/uso terapêutico , Piruvatos/uso terapêutico , Rolipram/uso terapêutico , Animais , Cavalos , Técnicas In Vitro , Interleucina-1beta/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores
18.
Vet Immunol Immunopathol ; 159(1-2): 83-90, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24703062

RESUMO

Collagen induced arthritis (CIA) is the most studied and used rheumatoid arthritis (RA) model in animals, as it shares many pathological and immunological features of the human disease. The aim of this study was to characterize clinical and immunological aspects of the ovine CIA model, and develop lameness and histopathological scoring systems, in order to validate this model for use in therapeutic trials. Sheep were sensitized to bovine type II collagen (BCII), arthritis was induced by injection of bovine collagen type II into the hock joint and the response was followed for two weeks. Clinical signs of lameness and swelling were evident in all sheep and gross thickening of the synovium surrounding the tibiotarsal joint and erosion on the cartilage surface in the arthritic joints. Leucocyte cell counts were increased in synovial fluid and there was synovial hyperplasia, thickening of the intimal layer, inflammation and marked angiogenesis in the synovial tissue. There was a large influx of monocytes and lymphocytes into the synovial tissue, and increased expression of TNF-α and IL-1ß in arthritic intima, angiogenesis and upregulation of VCAM-1. CIA in sheep appears to be an excellent large animal model of RA and has the potential for testing biological therapeutics for the treatment of rheumatoid arthritis.


Assuntos
Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Coxeadura Animal/imunologia , Animais , Artrite Experimental/patologia , Artrite Reumatoide/patologia , Colágeno Tipo II , Feminino , Imuno-Histoquímica , Interleucina-1beta/imunologia , Articulações/imunologia , Articulações/patologia , Coxeadura Animal/patologia , Contagem de Leucócitos , Ovinos , Estatísticas não Paramétricas , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Fator de Necrose Tumoral alfa/imunologia , Molécula 1 de Adesão de Célula Vascular/imunologia
19.
Inflamm Res ; 63(8): 637-47, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24764104

RESUMO

OBJECTIVE AND DESIGN: Insulin and inflammatory cytokines may be involved in equine laminitis, which might be associated with digital vascular dysfunction. This study determined the effects of TNF-α and insulin on the endothelial-dependent relaxant responses of equine digital blood vessels and on equine digital vein endothelial cell (EDVEC) cGMP production. MATERIAL: Isolated rings of equine digital arteries (EDAs) and veins (EDVs) were obtained and EDVECs were cultured from horses euthanized at an abattoir. METHODS: The effect of incubation with TNF-α (10 ng/ml) and/or insulin (1,000 µIU/ml) for 1.5 h or overnight under hyperoxic and hypoxic conditions on carbachol (endothelium-dependent) induced relaxation was assessed. The time course and concentration dependency of the effect of TNF-α and the effect of insulin (1,000 µIU/ml) on EDVEC cGMP production was determined. RESULTS: Incubation of EDAs overnight with TNF-α under hypoxic conditions resulted in endothelial-dependent vascular dysfunction. EDVs produced a more variable response. TNF-α increased EDVEC cGMP formation in a time- and concentration-dependent manner. Insulin had no significant effects. CONCLUSIONS: There is a mismatch between the results obtained from isolated vessel rings and cultured endothelial cells suggesting TNF-α may reduce the biological effect of NO by reducing its bioavailability rather than its formation, leading to endothelial cell dysregulation.


Assuntos
Artérias/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Insulina/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Veias/efeitos dos fármacos , Animais , Artérias/fisiologia , Carbacol , Células Cultivadas , GMP Cíclico/metabolismo , Células Endoteliais/metabolismo , Cavalos , Hiperóxia/fisiopatologia , Hipóxia/fisiopatologia , Técnicas In Vitro , Articulação Metatarsofalângica , Vasodilatação/efeitos dos fármacos , Veias/fisiologia
20.
Domest Anim Endocrinol ; 47: 101-7, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24308928

RESUMO

Breed-related differences may occur in the innate insulin sensitivity (SI) of horses and ponies, an important factor believed to be associated with the risk of laminitis. The aim of this study was to measure the glucose and insulin responses of different breeds of horses and ponies in moderate body condition to a glucose-containing meal and to compare these responses with the indices of SI as determined by a frequently sampled intravenous glucose tolerance test (FSIGT). Eight Standardbred horses, 8 mixed-breed ponies, and 7 Andalusian-cross horses with a mean ± SEM BCS 5.0 ± 0.3 of 9 were used in this study. Each animal underwent an oral glucose tolerance test (OGTT) in which they were fed a fiber-based ration (2.0 g/kg BW) containing 1.5 g/kg BW added glucose, as well as a standard FSIGT with minimal model analysis. The glucose response variables from the OGTT were similar between groups; however, the peak insulin concentration was higher in ponies (94.1 ± 29.1 µIU/mL; P = 0.003) and Andalusians (85.3 ± 18.6; P = 0.004) than in Standardbreds (21.2 ± 3.5). The insulin area under the curve was also higher in ponies (13.5 ± 3.6 IU · min · L(-1); P = 0.009) and Andalusians (15.0 ± 2.7; P = 0.004) than in Standardbreds (3.1 ± 0.6). Insulin sensitivity, as determined by the FSIGT, was lower in Andalusians (0.99 ± 0.18 × 10(-4)/[mIU · min]) than in Standardbreds (5.43 ± 0.94; P < 0.001) and in ponies (2.12 ± 0.44; P = 0.003) than in Standardbreds. Peak insulin concentrations from the OGTT were negatively correlated with SI (P < 0.001; rs = -0.75). These results indicate that there are clear breed-related differences in the insulin responses of horses and ponies to oral and intravenous glucose. All animals were in moderate body condition, indicating that breed-related differences in insulin dynamics occurred independent of obesity.


Assuntos
Composição Corporal/fisiologia , Cavalos/sangue , Cavalos/fisiologia , Resistência à Insulina/fisiologia , Insulina/fisiologia , Animais , Teste de Tolerância a Glucose/veterinária , Cavalos/genética
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