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1.
Am J Vet Res ; 85(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38513345

RESUMO

OBJECTIVE: Polyacrylamide hydrogel (4% PAHG) is an inert viscoelastic supplement used to manage osteoarthritis in horses. Even with a prolonged clinical effect, horses may be administered multiple doses during their performance career. The effect of the serial 4% PAHG treatments is not known. The objectives of this study were to evaluate the clinical, histologic, and synovial fluid biomarker effects following serial administration of 4% PAHG in normal equine fetlock joints. ANIMALS: 8 healthy horses. METHODS: In a blinded, controlled in vivo study, horses received serial intra-articular injections of 4% PAHG (Noltrex Vet; Nucleus ProVets LLC) and contralateral 0.9% saline control on days 0, 45, 90, and 135. Treatment and control joints were randomly assigned. Synovial fluid was collected before administration of 4% PAHG or 0.9% saline on day 0 and at study completion for cellular and biomarker evaluation. Serial physical and lameness examinations were performed throughout the study. On day 240, gross examination and harvest of cartilage and synovial membrane for histology were completed. RESULTS: There were no histologic changes in articular cartilage or synovial fluid biomarkers. The 4% PAHG was seen on the surface of the synovium in 5 of 8 treated joints 105 days after the last treatment. There are minimal effects following serial injections of 4% PAHG on normal joints in horses following administration at 0, 45, 90, and 135 days, with final evaluation on day 240. CLINICAL RELEVANCE: Serial administration of intra-articular 4% PAHG in horses may provide long-term joint lubrication with no detrimental effects.


Assuntos
Resinas Acrílicas , Biomarcadores , Líquido Sinovial , Animais , Cavalos , Líquido Sinovial/efeitos dos fármacos , Líquido Sinovial/química , Resinas Acrílicas/administração & dosagem , Injeções Intra-Articulares/veterinária , Feminino , Masculino , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/induzido quimicamente , Doenças dos Cavalos/patologia , Coxeadura Animal/induzido quimicamente , Membrana Sinovial/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Osteoartrite/veterinária , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Articulações/efeitos dos fármacos , Articulações/patologia
2.
BMC Vet Res ; 18(1): 436, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36514067

RESUMO

BACKGROUND: Intra-articular corticosteroids, such as isoflupredone acetate, are commonly used in the treatment of joint inflammation, especially in performance horses. Following administration in a non-inflamed joints blood concentrations of isoflupredone were low and detectable for only a short period of time post-administration compared to synovial fluid concentrations. For some drugs, inflammation can affect pharmacokinetics, therefore, the goal of the current study was to describe the pharmacokinetics of isoflupredone acetate following intra-articular administration using a model of acute synovitis. Secondarily, pharmacodynamic effects, including effects on joint circumference, joint flexion, and lameness following intra-articular administration of isoflupredone acetate in the experimental model were described. METHODS: Sixteen horses received a single intra-articular dose of 8 mg of isoflupredone acetate or saline 12 h post-administration of lipopolysaccharide. Blood and urine samples were collected up to 72 h and synovial fluid for 28 days post-administration, drug concentrations determined by liquid chromatography- mass spectrometry and pharmacokinetic analysis performed. Joint circumference, maximum angle of pain free joint flexion and lameness were evaluated prior to and post-treatment. RESULTS: The maximum isoflupredone plasma concentration was 2.45 ± 0.61 ng/mL at 2.5 ± 0.75 h and concentrations were less than the limit of quantitation by 72 h. Isoflupredone was below detectable concentrations in urine by 72 h post-administration in all horses and no longer detectable in synovial fluid by 96 h post-administration. Joint circumference was significantly decreased in the isoflupredone treatment group compared to the saline group at 24 and 48 h post drug administration. Pain free joint flexion was significantly different between the saline and isoflupredone treatment groups on day 4 post-treatment. CONCLUSIONS: Synovial fluid concentrations and maximum plasma concentrations of isoflupredone differed slightly between the current study and a previous one describing administration into a non-inflamed joint, however, the detection time of isoflupredone in blood was comparable. Effects of isoflupredone on joint circumference and degree of pain free joint flexion suggest a short duration of effect with respect to alleviation of lipopolysaccharide induced synovitis, however, results of this study support future studies of the anti-inflammatory effects of intra-articular isoflupredone acetate.


Assuntos
Doenças dos Cavalos , Sinovite , Cavalos , Animais , Lipopolissacarídeos , Coxeadura Animal/induzido quimicamente , Coxeadura Animal/tratamento farmacológico , Injeções Intra-Articulares/veterinária , Sinovite/induzido quimicamente , Sinovite/tratamento farmacológico , Sinovite/veterinária , Líquido Sinovial , Inflamação/tratamento farmacológico , Inflamação/veterinária , Doenças dos Cavalos/induzido quimicamente , Doenças dos Cavalos/tratamento farmacológico
3.
Exp Neurol ; 350: 113963, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34968423

RESUMO

Neurobehavioral deficits emerge in nearly 50% of patients following a mild traumatic brain injury (TBI) and may persist for months. Ketamine is used frequently as an anesthetic/analgesic and for management of persistent psychiatric complications. Although ketamine may produce beneficial effects in patients with a history of TBI, differential sensitivity to its impairing effects could make the therapeutic use of ketamine in TBI patients unsafe. This series of studies examined male C57BL/6 J mice exposed to a mild single blast overpressure (mbTBI) for indications of altered sensitivity to ketamine at varying times after injury. Dystaxia (altered gait), diminished sensorimotor gating (reduced prepulse inhibition) and impaired working memory (step-down inhibitory avoidance) were examined in mbTBI and sham animals 15 min following intraperitoneal injections of saline or R,S-ketamine hydrochloride, from day 7-16 post injury and again from day 35-43 post injury. Behavioral performance in the forced swim test and sucrose preference test were evaluated on day 28 and day 74 post injury respectively, 24 h following drug administration. Dynamic gait stability was compromised in mbTBI mice on day 7 and 35 post injury and further exacerbated following ketamine administration. On day 14 and 42 post injury, prepulse inhibition was robustly decreased by mbTBI, which ketamine further reduced. Ketamine-associated memory impairment was apparent selectively in mbTBI animals 1 h, 24 h and day 28 post shock (tested on day 15/16/43 post injury). Ketamine selectively reduced immobility scores in the FST in mbTBI animals (day 28) and reversed mbTBI induced decreases in sucrose consumption (Day 74). These results demonstrate increased sensitivity to ketamine in mice when tested for extended periods after TBI. The results suggest that ketamine may be effective for treating neuropsychiatric complications that emerge after TBI but urge caution when used in clinical practice for enhanced sensitivity to its side effects in this patient population.


Assuntos
Anestésicos Dissociativos/farmacologia , Comportamento Animal/efeitos dos fármacos , Traumatismos por Explosões/psicologia , Lesões Encefálicas Traumáticas/psicologia , Ketamina/farmacologia , Anestésicos Dissociativos/efeitos adversos , Animais , Ataxia/etiologia , Ataxia/psicologia , Concussão Encefálica , Ketamina/efeitos adversos , Coxeadura Animal/induzido quimicamente , Coxeadura Animal/psicologia , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Inibição Pré-Pulso , Desempenho Psicomotor/efeitos dos fármacos , Filtro Sensorial/efeitos dos fármacos
4.
Sensors (Basel) ; 21(4)2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33670238

RESUMO

(1) Background: Postural sway is frequently used to quantify human postural control, balance, injury, and neurological deficits. However, there is considerably less research investigating the value of the metric in horses. Much of the existing equine postural sway research uses force or pressure plates to examine the centre of pressure, inferring change at the centre of mass (COM). This study looks at the inverse, using an inertial measurement unit (IMU) on the withers to investigate change at the COM, exploring the potential of postural sway evaluation in the applied domain. (2) Methods: The lipopolysaccharide model was used to induce transient bilateral lameness in seven equines. Horses were monitored intermittently by a withers fixed IMU over seven days. (3) Results: There was a significant effect of time on total protein, carpal circumference, and white blood cell count in the horses, indicating the presence of, and recovery from, inflammation. There was a greater amplitude of displacement in the craniocaudal (CC) versus the mediolateral (ML) direction. A significant difference was observed in the amplitude of displacement in the ML direction between 4-12 h and 168 h. (4) Conclusions: The significant reduction in ML displacement during the acute inflammation period alongside greater overall CC displacement may be a compensatory behaviour for bilateral lameness.


Assuntos
Cavalos , Coxeadura Animal/diagnóstico , Equilíbrio Postural , Animais , Estudos de Viabilidade , Coxeadura Animal/induzido quimicamente , Pressão , Tronco
5.
Comp Med ; 70(3): 248-257, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32331555

RESUMO

Knee osteoarthritis is one of the most common causes of chronic pain worldwide, and several animal models have been developed to investigate disease mechanisms and treatments to combat associated morbidities. Here we describe a novel method for assessment of locomotor pain behavior in Yucatan swine. We used monosodium iodoacetate (MIA) to induce osteoarthritis in the hindlimb knee, and then conducted live observation, quantitative gait analysis, and quantitative weight-bearing stance analysis. We used these methods to test the hypothesis that locomotor pain behaviors after osteoarthritis induction would be detected by multiparameter quantitation for at least 12 wk in a novel large animal model of osteoarthritis. MIA-induced knee osteoarthritis produced lameness quantifiable by all measurement techniques, with onset at 2 to 4 wk and persistence until the conclusion of the study at 12 wk. Both live observation and gait analysis of kinetic parameters identified mild and moderate osteoarthritis phenotypes corresponding to a binary dose relationship. Quantitative stance analysis demonstrated the greatest sensitivity, discriminating between mild osteoarthritis states induced by 1.2 and 4.0 mg MIA, with stability of expression for as long as 12 wk. The multiparameter quantitation used in our study allowed rejection of the null hypothesis. This large animal model of quantitative locomotor pain resulting from MIA-induced osteoarthritis may support the assessment of new analgesic strategies for human knee osteoarthritis.


Assuntos
Modelos Animais de Doenças , Osteoartrite do Joelho , Animais , Feminino , Membro Posterior , Humanos , Iodoacetatos/farmacologia , Coxeadura Animal/induzido quimicamente , Masculino , Medição da Dor , Suínos
6.
J Vet Pharmacol Ther ; 43(1): 38-49, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31660636

RESUMO

Intra-articular (IA) hyaluronic acid (HA) is commonly used to treat equine arthritis. Inflammatory response or "joint flare" is a recognized potential side effect. However, the incidence and severity of inflammation following IA HA injection in horses is not well documented. This study compared the effects of two IA HA formulations of different molecular weight (MW) and a saline control on clinical signs and synovial fluid markers of inflammation in normal equine joints. Eight adult horses each had three healthy fetlock joints randomly assigned to treatment with either 1.4 mega Dalton HA, 0.8 mega Dalton HA or saline control once weekly for three weeks. Clinical evaluation and synovial fluid analysis were performed by blinded assessors. Outcomes of interest were lameness score, joint effusion score and synovial fluid white cell count and differential, total protein, viscosity and serum amyloid A. Joints injected with HA developed significant mild-to-moderate inflammatory responses often associated with lameness and joint effusion compared with saline control joints. The higher MW HA formulation elicited a significantly greater inflammatory response than the lower MW HA after the first injection. In HA injected joints, viscosity remained poor for the entire study. Both IA HA formulations in this study induced an inflammatory response in healthy equine joints. This may have implications for the use of HA in equine joints. The findings in this study are limited to the two HA formulations used. Further investigation of different HA formulations and the use of HA in normal and arthritic equine joints is warranted.


Assuntos
Cavalos/metabolismo , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Animais , Composição de Medicamentos , Contagem de Eritrócitos , Feminino , Ácido Hialurônico/química , Inflamação , Injeções Intra-Articulares , Coxeadura Animal/induzido quimicamente , Masculino , Líquido Sinovial/química , Líquido Sinovial/citologia
7.
Am J Vet Res ; 80(11): 1001-1006, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31644340

RESUMO

OBJECTIVE: To investigate the ability of a proprietary antagonist of E-type prostanoid receptor (EP) 4, grapiprant, and carprofen to attenuate lameness attributable to urate-induced synovitis in dogs. ANIMALS: 5 purpose-bred hound-cross dogs. PROCEDURES: A blinded, 3-way crossover study was performed. Dogs received each of 3 treatments (L-766, a proprietary antagonist of EP4; 4.0 mg/kg), grapiprant (an antagonist of EP4; 2.0 mg/kg), and carprofen (4.4 mg/kg); dogs received 4 doses of each treatment (14 and 2 hours before and 22 and 46 hours after urate injection). Synovitis was induced by intra-articular injection of sodium urate. Measurements (vertical ground reaction forces and clinical lameness scores) were obtained immediately before (0 hours; baseline) and 6, 12, 24, 36, and 48 hours after sodium urate injection. All data were analyzed with repeated-measures ANOVA. RESULTS: Lameness scores at 6 hours were significantly higher than baseline lameness scores for all treatments. Lameness scores for the grapiprant treatment remained significantly higher at 12 and 24 hours, compared with baseline lameness scores. Lameness scores for the carprofen treatment were significantly lower than lameness scores for the grapiprant treatment at 6, 12, and 24 hours. Analysis of peak vertical force and vertical impulse data revealed a pattern similar to that for lameness scores. Treatment with L-766 resulted in a significantly higher vertical impulse at 48 hours than did treatment with carprofen or grapiprant. CONCLUSIONS AND CLINICAL RELEVANCE: In these dogs, carprofen was the most effective treatment for attenuating lameness induced by injection of sodium urate, and grapiprant was the least effective treatment.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Carbazóis/uso terapêutico , Doenças do Cão/tratamento farmacológico , Coxeadura Animal/tratamento farmacológico , Receptores de Prostaglandina E Subtipo EP4/antagonistas & inibidores , Compostos de Sulfonilureia/uso terapêutico , Sinovite/veterinária , Animais , Carbazóis/farmacologia , Estudos Cross-Over , Cães , Marcha , Injeções Intra-Articulares/veterinária , Coxeadura Animal/induzido quimicamente , Masculino , Método Simples-Cego , Sinovite/induzido quimicamente , Sinovite/tratamento farmacológico , Ácido Úrico
8.
PLoS One ; 13(5): e0197736, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29813093

RESUMO

OBJECTIVE: The aim of this study was to verify whether transient inflammatory reactions induced by intra-articular medicinal ozone administration affect joint components, by in vivo evaluation of inflammatory (prostaglandin E2, Substance P, Interleukin-6, Interleukine-1, Tumor Necrosis Factor), anti-inflammatory (Interleukin-10) and oxidative (superoxide dismutase activity and oxidative burst) biomarkers and extracellular matrix degradation products (chondroitin sulphate and hyaluronic acid) in synovial fluid. METHODS: The effects of medicinal ozone were analyzed at two ozone concentrations (groups A and B, 20 and 40 µg/ml, respectively), using oxygen-injected joints as controls (group C); each group received ten treatments (15 ml gas per treatment). Physical evaluation, evaluation of lameness, ultrasonography, and synovial fluid analysis were performed. RESULTS: All joints presented mild and transient effusion throughout the study. Group B exhibited the highest lameness score on day 14 (P<0.05), detected by the lameness measurement system, probably because of the higher ozone concentration. All groups exhibited increased ultrasonography scores on day 14 (P < 0.05). Groups A and B exhibited increased proteins concentrations on day 21 (P<0.05). There was no change in hyaluronic acid concentration or the percentage of high-molecular weight hyaluronic acid throughout the experiment. Chondroitin sulfate concentrations decreased in group B, and did not change in group A and C, indicating that neither treatment provoked extracellular matrix catabolism. Cytokine and eicosanoid concentrations were not significantly changed. CONCLUSIONS: The ozonetherapy did not cause significant inflammation process or cartilage degradation, therefore, ozonetherapy is safe at both evaluated doses.


Assuntos
Doenças dos Cavalos/diagnóstico por imagem , Articulações/efeitos dos fármacos , Coxeadura Animal/diagnóstico por imagem , Ozônio/administração & dosagem , Animais , Sulfatos de Condroitina/metabolismo , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Eicosanoides/metabolismo , Doenças dos Cavalos/induzido quimicamente , Doenças dos Cavalos/metabolismo , Cavalos , Ácido Hialurônico/metabolismo , Articulações/metabolismo , Coxeadura Animal/induzido quimicamente , Coxeadura Animal/metabolismo , Ozônio/farmacologia , Distribuição Aleatória , Líquido Sinovial/efeitos dos fármacos , Líquido Sinovial/metabolismo , Ultrassonografia/veterinária
9.
BMC Vet Res ; 13(1): 182, 2017 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-28629364

RESUMO

BACKGROUND: Septic arthritis is a common and potentially devastating disease characterized by severe intra-articular (IA) inflammation and fibrin deposition. Research into equine joint pathologies has focused on inflammation, but recent research in humans suggests that both haemostatic and inflammatory pathways are activated in the joint compartment in arthritic conditions. The aim of this study was to characterize the IA haemostatic and inflammatory responses in horses with experimental lipopolysaccharide (LPS)-induced joint inflammation. Inflammation was induced by IA injection of LPS into one antebrachiocarpal joint of six horses. Horses were evaluated clinically with subjective grading of lameness, and blood and synovial fluid (SF) samples were collected at post injection hours (PIH) -120, -96, -24, 0, 2, 4, 8, 16, 24, 36, 48, 72 and 144. Total protein (TP), white blood cell counts (WBC), serum amyloid A (SAA), haptoglobin, iron, fibrinogen, thrombin-antithrombin (TAT) and d-dimer concentrations were assessed in blood and SF. RESULTS: Intra-articular injection of LPS caused local and systemic signs of inflammation including increased rectal temperature, lameness and increased joint circumference and skin temperature. Most of the biomarkers (TP, WBC, haptoglobin, fibrinogen and TAT) measured in SF increased quickly after LPS injection (at PIH 2-4), whereas SAA and d-dimer levels increased more slowly (at PIH 16 and 144, respectively). SF iron concentrations did not change statistically significantly. Blood WBC, SAA, haptoglobin and fibrinogen increased and iron decreased significantly in response to the IA LPS injection, while TAT and d-dimer concentrations did not change. Repeated pre-injection arthrocenteses caused significant changes in SF concentrations of TP, WBC and haptoglobin. CONCLUSION: Similar to inflammatory joint disease in humans, joint inflammation in horses was accompanied by an IA haemostatic response with changes in fibrinogen, TAT and d-dimer concentrations. Inflammatory and haemostatic responses were induced simultaneously and may likely interact. Further studies of interactions between the two responses are needed for a better understanding of pathogenesis of joint disease in horses. Knowledge of effects of repeated arthrocenteses on levels of SF biomarkers may be of value when markers are used for diagnostic purposes.


Assuntos
Artrite Experimental/veterinária , Biomarcadores/metabolismo , Doenças dos Cavalos/metabolismo , Líquido Sinovial/metabolismo , Animais , Proteínas Antitrombina/metabolismo , Artrite Experimental/sangue , Artrite Experimental/metabolismo , Artrocentese/veterinária , Biomarcadores/sangue , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Hemostasia/efeitos dos fármacos , Doenças dos Cavalos/imunologia , Cavalos , Inflamação/metabolismo , Injeções Intra-Articulares , Coxeadura Animal/induzido quimicamente , Coxeadura Animal/metabolismo , Lipopolissacarídeos , Masculino , Trombina/metabolismo
10.
Aust Vet J ; 95(5): 167-173, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28444753

RESUMO

OBJECTIVE: Collagen cross-linking is an attractive therapeutic route aimed at supplementing natural collagen stabilisation. In this study the toxicity of the cross-linker genipin (GP) was examined in avascular (tendon) and vascular (dermis) tissue. METHODS: High doses of GP were injected intratendinously into three yearling horses and evaluated at various time points up to 30 days. A second group of three yearlings were injected into the dermis and evaluated at various time points up to 1 year. Metrics used included lameness, circumferential swelling, ultrasound evaluation, microscopic morphology, collagen production and systemic effect on blood parameters. RESULTS: The tendon injection sites exhibited mild lameness and swelling with no apparent systemic toxicity or stabilisation defects. Treated tendons exhibited increased linear collagen microscopically. Dermal injections showed similar results, with mild swelling at the injection site. Microscopic morphology resulted in a decrease in dermal collagen at 30 days post-injection. Dermis injected at the high dose of 355 mmol/L examined 1 year post-treatment appeared similar to the untreated biopsies; however, there was an increase in mature collagen. CONCLUSION: GP injection appeared to be well tolerated, with transient lameness and mild circumferential swelling when injected into the tendon and local tissue swelling when injected into the dermis. No systemic hypersensitivities or toxicities were observed. Microscopically, GP resulted in increased linear collagen in tendons at 30 days post-injection and overall increased collagen in dermal tissue when evaluated 1 year post-injection.


Assuntos
Colágeno/efeitos dos fármacos , Derme/efeitos dos fármacos , Iridoides/metabolismo , Iridoides/toxicidade , Tendões/efeitos dos fármacos , Animais , Derme/patologia , Cavalos/lesões , Injeções Intradérmicas/veterinária , Coxeadura Animal/induzido quimicamente , Masculino , Projetos Piloto , Traumatismos dos Tendões/tratamento farmacológico , Traumatismos dos Tendões/veterinária , Cicatrização
11.
J Anim Sci ; 95(12): 5407-5419, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29293794

RESUMO

The objectives of this study were to examine the clinical response, changes in ruminal bacterial microbiota, and inflammatory response in lamellar tissues during oligofructose-induced laminitis. Ten fistulated sheep were randomly assigned into a control group ( = 5) and a treatment group ( = 5). The treatment group was infused with oligofructose (21 g/kg BW) by rumen cannula, and the control group was sham-treated with saline. Results showed that all 5 sheep treated with oligofructose developed anorexia and diarrhea 8 to 12 h after the administration of oligofructose. By 12 to 24 h after treatment, the treatment group developed lameness and roach back. Compared with the control group, oligofructose administration decreased ( < 0.001) the rumen pH and concentrations of total VFA and increased ( < 0.001) the level of lactic acid in the rumen. Microbial data analysis revealed that oligofructose infusion increased the abundance of ( = 0.009) and ( = 0.008) and decreased the percentage of unclassified Christensenellaceae ( = 0.028), unclassified Ruminococcaceae ( = 0.009), ( = 0.016), unclassified Lachnospiraceae ( = 0.009), and ( = 0.009) compared with the control group. Oligofructose infusion decreased the ACE ( = 0.047) and Shannon ( = 0.009) indices compared with the control group. The histomorphology analysis revealed that oligofructose overload resulted in damage to the dermoepidermal junction in the lamellar tissue of sheep. Quantitative real-time PCR results showed that compared with the control group, the mRNA expression of membrane-type metalloproteinase-1 ( = 0.049) was downregulated whereas the expression of proinflammatory IL-6 ( = 0.004) and matrix metalloprotease-9 ( = 0.037) was upregulated in the lamellar tissues of the oligofructose treatment group. In general, the present study provides the foundation for a sheep model of oligofructose-overload-induced acute laminitis that could be used in later experiments. Our findings suggest that intraruminal infusion of oligofructose altered ruminal microbiota and resulted in acute laminitis and that the inflammatory damage to the lamellae tissue may be related to the upregulation of matrix metalloprotease-9. The information generated will provide more insight into the systemic effects of lameness caused by oligofructose overload in sheep.


Assuntos
Bactérias/isolamento & purificação , Diarreia/veterinária , Coxeadura Animal/induzido quimicamente , Microbiota/efeitos dos fármacos , Oligossacarídeos/administração & dosagem , Doenças dos Ovinos/induzido quimicamente , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Diarreia/induzido quimicamente , Dieta/veterinária , Fermentação , Inflamação/induzido quimicamente , Inflamação/veterinária , Interleucina-6/metabolismo , Masculino , Microbiota/genética , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Rúmen/microbiologia , Ovinos
12.
Prev Vet Med ; 136: 11-18, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28010903

RESUMO

Electronic medical records from first opinion equine veterinary practice may represent a unique resource for epidemiologic research. The appropriateness of this resource for risk factor analyses was explored as part of an investigation into clinical and pharmacologic risk factors for laminitis. Amalgamated medical records from seven UK practices were subjected to text mining to identify laminitis episodes, systemic or intra-synovial corticosteroid prescription, diseases known to affect laminitis risk and clinical signs or syndromes likely to lead to corticosteroid use. Cox proportional hazard models and Prentice, Williams, Peterson models for repeated events were used to estimate associations with time to first, or subsequent laminitis episodes, respectively. Over seventy percent of horses that were diagnosed with laminitis suffered at least one recurrence. Risk factors for first and subsequent laminitis episodes were found to vary. Corticosteroid use (prednisolone only) was only significantly associated with subsequent, and not initial laminitis episodes. Electronic medical record use for such analyses is plausible and offers important advantages over more traditional data sources. It does, however, pose challenges and limitations that must be taken into account, and requires a conceptual change to disease diagnosis which should be considered carefully.


Assuntos
Anti-Inflamatórios/efeitos adversos , Doenças do Pé/veterinária , Glucocorticoides/efeitos adversos , Doenças dos Cavalos/epidemiologia , Coxeadura Animal/epidemiologia , Animais , Estudos de Coortes , Registros Eletrônicos de Saúde , Doenças do Pé/induzido quimicamente , Doenças do Pé/epidemiologia , Doenças dos Cavalos/induzido quimicamente , Cavalos , Coxeadura Animal/induzido quimicamente , Fatores de Risco , Reino Unido/epidemiologia
13.
Am J Vet Res ; 76(10): 869-76, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26413824

RESUMO

OBJECTIVE: To develop a model of hip joint synovitis on the basis of intra-articular injection of a sodium urate suspension in dogs and to characterize associated gait changes. ANIMALS: 6 healthy adult dogs. PROCEDURES: Each dog was sedated, and synovitis was induced by injection of 1 mL of a sodium urate suspension (20 mg/mL) into the right hip joint under ultrasonographic guidance. Observational and instrumented gait analyses to determine temporospatial, kinetic, and kinematic variables were performed prior to and 4, 8, and 24 hours after sedation and synovitis induction. RESULTS: Injection of a sodium urate suspension into the hip joint of healthy dogs resulted in lameness of the ipsilateral pelvic limb as determined by observational and instrumented gait analyses. For all dogs, lameness was clinically detectable within 1.5 to 2 hours after injection, reached its maximum intensity at 4 hours after injection, and had subsided by 24 hours after injection. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that injection of a sodium urate suspension into the hip joint of healthy dogs reliably induced synovitis and signs of pain and lameness in the ipsilateral pelvic limb that lasted 24 hours. This model can be used in conjunction with instrumented gait analysis to provide information on gait changes associated with hip joint disease and might be useful for evaluating the efficacy of analgesics or other interventions for the treatment of hip joint disease in dogs.


Assuntos
Modelos Animais de Doenças , Doenças do Cão/induzido quimicamente , Marcha , Osteoartrite do Quadril/veterinária , Sinovite/veterinária , Animais , Fenômenos Biomecânicos , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/fisiopatologia , Cães , Feminino , Injeções Intra-Articulares/veterinária , Coxeadura Animal/induzido quimicamente , Masculino , Osteoartrite do Quadril/induzido quimicamente , Medição da Dor/veterinária , Sinovite/induzido quimicamente , Ultrassonografia , Ácido Úrico/administração & dosagem
14.
J Vet Sci ; 16(4): 405-11, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26243595

RESUMO

Lameness is one of the most painful conditions that affects dairy cattle. This study was conducted to evaluate clinical signs and plasma concentration of several pain and stress biomarkers after oligofructose-induced lameness in dairy heifers. Lameness was induced using an oligofructose overload model in 12 non-pregnant heifers. Clinical parameters and blood samples were obtained at 48 and 24 h and at 6, 12, 24, 36 and 48 h after induction of lameness. Clinical parameters included heart rate, respiratory rate, ruminal frequency and lameness score. Plasma biomarkers included cortisol, haptoglobin, norepinephrine, beta-endorphin and substance P. Differences were observed in all parameters between control and treated heifers. The plasma concentration of biomarkers increased significantly in treated animals starting 6 h after induction of lameness, reaching maximum levels at 24 h for cortisol, 48 h for haptoglobin, 6 h for norepinephrine, 12 h for substance P and at 24 h for beta-endorphin. Overall, our results confirm that lameness associated pain induced using the oligofructose model induced changes in clinical parameters and plasma biomarkers of pain and stress in dairy heifers.


Assuntos
Doenças dos Bovinos/fisiopatologia , Coxeadura Animal/fisiopatologia , Oligossacarídeos/administração & dosagem , Dor/veterinária , Animais , Biomarcadores/sangue , Bovinos , Doenças dos Bovinos/induzido quimicamente , Feminino , Coxeadura Animal/induzido quimicamente , Dor/sangue , Estresse Fisiológico
15.
Aust Vet J ; 93(8): 265-70, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26220318

RESUMO

OBJECTIVE: To determine the efficacy and bioavailability of non-steroidal anti-inflammatory drugs (NSAIDs) when administered orally to sheep. DESIGN: Randomised experimental design with four treatment groups: three NSAID groups and one control group (n = 10/group). The study animals were 40 18-month-old Merino ewes with an average weight of 31.4 ± 0.5 kg. METHODS: Treatment was given orally at 24 h intervals for 6 days at dose rates expected to achieve therapeutic levels in sheep: carprofen (8.0 mg/kg), ketoprofen (8.0 mg/kg) and flunixin (4.0 mg/kg). Oil of turpentine (0.1 mL) was injected into a forelimb of each sheep to induce inflammation and pain; responses (force plate pressure, skin temperature, limb circumference, haematology and plasma cortisol) were measured at 0, 3, 6, 9, 12, 24, 36, 48, 72 and 96 h post-injection. NSAID concentrations were determined by ultra-high-pressure liquid chromatography. RESULTS: The NSAIDs were detectable in ovine plasma 2 h after oral administration, with average concentrations of 4.5-8.4 µg/mL for ketoprofen, 2.6-4.1 µg/mL for flunixin and 30-80 µg/mL for carprofen. NSAID concentrations dropped 24 h after administration. Pain response to an oil of turpentine injection was assessed using the measures applied but no effect of the NSAIDs was observed. Although this pain model has been previously validated, the responses observed in this study differed from those in the previous study. CONCLUSIONS AND CLINICAL RELEVANCE: The three NSAIDs reached inferred therapeutic concentrations in blood at 2 h after oral administration. The oil of turpentine lameness model may need further validation.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacocinética , Coxeadura Animal/tratamento farmacológico , Dor/veterinária , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/sangue , Disponibilidade Biológica , Carbazóis/administração & dosagem , Carbazóis/sangue , Carbazóis/farmacocinética , Clonixina/administração & dosagem , Clonixina/análogos & derivados , Clonixina/sangue , Clonixina/farmacocinética , Estudos de Coortes , Modelos Animais de Doenças , Feminino , Membro Anterior , Hidrocortisona/sangue , Irritantes/efeitos adversos , Cetoprofeno/administração & dosagem , Cetoprofeno/sangue , Cetoprofeno/farmacocinética , Coxeadura Animal/induzido quimicamente , Coxeadura Animal/complicações , Dor/tratamento farmacológico , Ovinos , Terebintina/efeitos adversos
16.
J Anim Sci ; 93(5): 2100-10, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26020306

RESUMO

Pain associated with lameness on farm is a negative affective state and has a detrimental impact on individual farm animal welfare. Animal pain can be managed utilizing husbandry tools and through pharmacological approaches. Nonsteroidal anti-inflammatory drugs including meloxicam and flunixin meglumine are compounds used in many species for pain management because they are easy to administer, long lasting, and cost-effective. Assessing an animal's biomechanical parameters using such tools as the embedded microcomputer-based force plate system and GAITFour pressure mat gait analysis walkway system provides an objective, sensitive, and precise means to detect animals in lame states. The objectives of this study were to determine the efficacy of meloxicam and flunixin meglumine for pain mitigation in lame sows using the embedded microcomputer-based force plate system and GAITFour pressure mat gait analysis walkway system. Lameness was induced in 24 mature mixed-parity sows using a chemical synovitis model and compared 3 treatments: meloxicam (1.0 mg/kg per os), flunixin meglumine (2.2 mg/kg intramuscular) and sterile saline (intramuscular). Weight distribution (kg) for each foot was collected twice per second for a total of 5 min for each time point using the embedded microcomputer-based force plate system. Stride time, stride length, maximum pressure, activated sensors, and stance time were collected using 3 quality walks (readings) for each time point using the GAITFour pressure mat gait analysis walkway system. Sows administered flunixin meglumine or meloxicam tolerated more weight on their lame leg compared with saline sows (P < 0.005). Sows administered flunixin meglumine or meloxicam had smaller differences in stance time, maximum pressure, and activated sensors between the sound and lame legs compared with saline-treated sows between 37 and 60 h after lameness induction (P < 0.03). In conclusion, flunixin meglumine and meloxicam administration mitigated pain sensitivity in sows after lameness induction when pain sensitivity was evaluated with the embedded microcomputer-based force plate system and GAITFour pressure mat gait analysis walkway system. Analgesic drugs may be a key tool to manage negative pain affective states associated with lameness.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Clonixina/análogos & derivados , Coxeadura Animal/complicações , Dor/veterinária , Doenças dos Suínos/tratamento farmacológico , Tiazinas/farmacologia , Tiazóis/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Fenômenos Biomecânicos , Clonixina/farmacologia , Feminino , Pé/patologia , Marcha , Coxeadura Animal/induzido quimicamente , Coxeadura Animal/tratamento farmacológico , Meloxicam , Microcomputadores , Dor/tratamento farmacológico , Dor/etiologia , Gravidez , Pressão , Suínos , Doenças dos Suínos/induzido quimicamente , Suporte de Carga/fisiologia
17.
J Neuropathol Exp Neurol ; 73(6): 568-79, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24806304

RESUMO

In rodents exposed to 3,3'-iminodipropionitrile (IDPN), neurofilaments (NFs) accumulate in swollen proximal axon segments; this also occurs in motor neurons of patients with amyotrophic lateral sclerosis. We hypothesized that early loss of NFs in neuromuscular junctions (NMJs) in IDPN proximal neuropathy would result in neuromuscular dysfunction and lead to neuromuscular detachment. Adult male rats were given 0 or 15 mmol/L IDPN in drinking water for up to 1 year. The IDPN-exposed rats dragged their tails and had impaired endurance in a grip test. Neuromuscular junctions and distal axons were examined in the levator auris longus muscle after 3, 6, 9, and 12 months. Neuromuscular junctions showed a progressive reduction in NF immunolabeling, which became undetectable in up to 70% of the NMJs after 12 months. Neurofilament labeling was also reduced in preterminal axons and in a more proximal axon level within the muscle. Triple-label analysis with antisyntaxin demonstrated that the terminals remained in place and usually contained a few minute NF bundles. Electron microscopy revealed the disappearance of terminal NFs, reduced content in synaptic vesicles, and accumulation of multilamellar bodies, but scant degeneration. Thus, IDPN proximal neurofilamentous axonopathy is associated with NF depletion in motor terminals; motor weakness and structural changes in the NMJs suggest impaired synaptic function despite long-term preservation of the NMJs.


Assuntos
Axônios/metabolismo , Axônios/patologia , Coxeadura Animal/patologia , Proteínas de Neurofilamentos/deficiência , Doenças da Junção Neuromuscular/patologia , Doenças Vestibulares/patologia , Animais , Axônios/ultraestrutura , Modelos Animais de Doenças , Membro Anterior/fisiopatologia , Coxeadura Animal/induzido quimicamente , Masculino , Microscopia Eletrônica de Transmissão , Junção Neuromuscular/metabolismo , Junção Neuromuscular/patologia , Junção Neuromuscular/ultraestrutura , Doenças da Junção Neuromuscular/induzido quimicamente , Doenças da Junção Neuromuscular/fisiopatologia , Nitrilas/toxicidade , Proteínas Qa-SNARE/metabolismo , Ratos , Ratos Long-Evans , Fatores de Tempo , Doenças Vestibulares/induzido quimicamente
18.
Iran Biomed J ; 18(2): 101-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24518551

RESUMO

BACKGROUND: Acrylamide (ACR) is a well-known industrial toxic chemical that produces neurotoxicity, which is characterized by progressive central and peripheral neuronal degeneration. Chrysin is a natural, biologically active flavonoid compound, which is commonly found in many plants. The antioxidant and neuroprotective properties of chrysin have been demonstrated. METHODS: In this study, the possible effect of chrysin on ACR-induced toxicity was evaluated in both in vitro and in vivo experiments. PC12 cells were used as a suitable in vitro model. Cells were exposed to chrysin (0.5-5 µM) for 12 and 24 h, and then ACR in IC50 concentration was added to the cells. Finally, cell viability was determined using (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium assay. For in vivo assay, Wistar rats were treated with ACR (50 mg/kg i.p. for 11 days) alone or in combination with chrysin (12.5, 25, and 50 mg/kg). At the end of treatment, behavioral index was evaluated. RESULTS: ACR decreased cell viability and pre-treatment with chrysin (0.5-5 µM) significantly decreased ACR-induced cytotoxicity in the time- and dose-dependent manner. In Wistar rats, exposure to ACR significantly induced severe gait abnormalities, but treatment with chrysin (50 mg/kg) reduced ACR-induced neurotoxicity in animals. CONCLUSION: In the current study, chrysin exhibited neuroprotective effect on PC12 cells as an in vitro model and also on Wistar rats.


Assuntos
Acrilamida/toxicidade , Flavonoides/farmacologia , Coxeadura Animal/induzido quimicamente , Coxeadura Animal/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Acrilamida/antagonistas & inibidores , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Flavonoides/uso terapêutico , Masculino , Fármacos Neuroprotetores/uso terapêutico , Células PC12 , Ratos , Ratos Wistar
19.
Neuromolecular Med ; 16(1): 106-18, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24008671

RESUMO

Till date, an exact causative pathway responsible for neurodegeneration in Huntington's disease (HD) remains elusive; however, mitochondrial dysfunction appears to play an important role in HD pathogenesis. Therefore, strategies to attenuate mitochondrial impairments could provide a potential therapeutic intervention. In the present study, we used curcumin encapsulated solid lipid nanoparticles (C-SLNs) to ameliorate 3-nitropropionic acid (3-NP)-induced HD in rats. Results of MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and succinate dehydrogenase (SDH) staining of striatum revealed a marked decrease in Complex II activity. However, C-SLN-treated animals showed significant increase in the activity of mitochondrial complexes and cytochrome levels. C-SLNs also restored the glutathione levels and superoxide dismutase activity. Moreover, significant reduction in mitochondrial swelling, lipid peroxidation, protein carbonyls and reactive oxygen species was observed in rats treated with C-SLNs. Quantitative PCR and Western blot results revealed the activation of nuclear factor-erythroid 2 antioxidant pathway after C-SLNs administration in 3-NP-treated animals. In addition, C-SLN-treated rats showed significant improvement in neuromotor coordination when compared with 3-NP-treated rats. Thus, the results of this study suggest that C-SLNs administration might be a promising therapeutic intervention to ameliorate mitochondrial dysfunctions in HD.


Assuntos
Curcumina/uso terapêutico , Doença de Huntington/tratamento farmacológico , Animais , Ataxia/tratamento farmacológico , Ataxia/etiologia , Corpo Estriado/patologia , Curcumina/administração & dosagem , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Glutationa/metabolismo , Humanos , Doença de Huntington/induzido quimicamente , Doença de Huntington/metabolismo , Doença de Huntington/psicologia , Coxeadura Animal/induzido quimicamente , Coxeadura Animal/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Atividade Motora/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/biossíntese , Fator 2 Relacionado a NF-E2/genética , Nanopartículas , Nitrocompostos/toxicidade , Estresse Oxidativo , Fitoterapia , Propionatos/toxicidade , Distribuição Aleatória , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
20.
Am J Vet Res ; 75(1): 19-25, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24370241

RESUMO

OBJECTIVE: To evaluate the effects of sequential anesthesia of the individual compartments of the equine stifle joint on lameness induced by intra-articular deposition of interleukin (IL)-1ß. ANIMALS: 6 horses. PROCEDURES: For each horse, baseline hind limb lameness was first evaluated. A randomly selected compartment of 1 stifle joint was then injected with IL-1ß to induce synovitis and lameness; subsequently, the same compartment was anesthetized with 2% mepivacaine hydrochloride, and lameness was reevaluated. Two weeks later, baseline lameness was evaluated, and lameness was similarly induced; thereafter, the 2 synovial compartments of the stifle joint not injected with IL-1ß were anesthetized sequentially in random order (ie, first and second blocks); lameness was evaluated after each block. Finally, the IL-1ß-treated compartment was anesthetized (third block); lameness was again evaluated. This second experiment was repeated for the contralateral stifle joint 2 weeks later. Throughout the study, lameness was quantified objectively by assessing vertical pelvic movement asymmetry with a wireless, inertial sensor-based system. RESULTS: Intra-articular deposition of IL-1ß induced lameness in all injected limbs. In the first experiment, anesthesia of the compartment injected with IL-1ß resulted in a significant decrease in lameness, with vertical pelvic movement asymmetry approaching baseline. In the second experiment, lameness improved significantly after the second and third blocks and was almost completely abolished after all 3 synovial compartments were anesthetized. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, lameness caused by a lesion in 1 compartment of a stifle joint can be improved more by instillation of local anesthetic solution into that compartment than by anesthesia of the other compartments.


Assuntos
Anestésicos Locais/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Cápsula Articular/efeitos dos fármacos , Coxeadura Animal/tratamento farmacológico , Mepivacaína/uso terapêutico , Joelho de Quadrúpedes/efeitos dos fármacos , Sinovite/veterinária , Anestesia Local/veterinária , Anestésicos Locais/administração & dosagem , Animais , Feminino , Doenças dos Cavalos/induzido quimicamente , Cavalos , Injeções Intra-Articulares/veterinária , Interleucina-1beta/efeitos adversos , Cápsula Articular/fisiopatologia , Coxeadura Animal/induzido quimicamente , Mepivacaína/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Joelho de Quadrúpedes/fisiopatologia , Sinovite/induzido quimicamente , Sinovite/tratamento farmacológico
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