RESUMEN
In this study we surveyed a rat skeletal muscle RNA-Seq for genes that are induced by hindlimb immobilization and, in turn, become attenuated by leucine supplementation. This approach, in search of leucine-atrophy protection mediating genes, identified histone deacetylase 4 (HDAC4) as highly responsive to both hindlimb immobilization and leucine supplementation. We then examined the impact of leucine on HDAC4 expression, tissue localization, and target genes. A total of 76 male Wistar rats (~280 g) were submitted to hindlimb immobilization and/or leucine supplementation for 3, 7 and 12 days. These animals were euthanized, and soleus muscle was removed for further analysis. RNA-Seq analysis of hindlimb immobilized rats indicated a sharp induction (log2 = 3.4) of HDAC4 expression which was attenuated by leucine supplementation (~50%). Real-time PCR and protein expression analysis by Western blot confirmed increased HDAC4 mRNA after 7 days of hindlimb immobilization and mitigation of induction by leucine supplementation. Regarding the HDAC4 localization, the proportion of positive nuclei was higher in the immobilized group and decreased after leucine supplementation. Also, we found a marked decrease of myogenin and MAFbx-atrogin-1 mRNA levels upon leucine supplementation, while CAMKII and DACH2 mRNA levels were increased by leucine supplementation. Our data suggest that HDAC4 inhibition might be involved in the anti-atrophic effects of leucine.
Asunto(s)
Suplementos Dietéticos , Miembro Posterior/patología , Histona Desacetilasas/metabolismo , Leucina/uso terapéutico , Músculo Esquelético/metabolismo , Animales , Peso Corporal , Miembro Posterior/metabolismo , Suspensión Trasera , Masculino , Microscopía Fluorescente , Atrofia Muscular/patología , RNA-Seq , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de SeñalRESUMEN
Cryotherapy is a non-pharmacological treatment commonly used to control inflammation and improve function after acute traumas. However, there are no definitive findings about its effects on chronic joint diseases such as knee osteoarthritis (KOA). The aim of this study was to investigate the effects of clinical-like cryotherapy on functional impairment and synovial inflammation in a rat model of KOA generated by anterior cruciate ligament transection (ACLT). Thirty-two male Wistar rats were randomly divided into four groups (n = 8/group): Control, KOA, KOA + Cryotherapy and KOA + Placebo. The last two groups were submitted to the relevant interventions twice a day for five days (61 to 65), with each session lasting 20 min. Gait test, skin temperature, thermal response threshold and joint swelling were assessed in all groups before ACLT surgery, and pre (60th day) and post (66th day) intervention protocols. On day 66, the animals were euthanized and exsanguinated to remove the synovial membrane for histopathological examination and synovial fluid to determine the leukocyte count and cytokine concentration. After the intervention period (66th day), footprint area only increased in the KOA + Cryotherapy group (P = 0.004; 14%) when compared to KOA and KOA + Placebo, but did not differ from controls. Cryotherapy lowered the synovial fluid leukocyte count (P < 0.0001; ≥95.0%) and cytokine concentration (P < 0.0001; ≥55%) when compared to the KOA and Placebo groups. Synovial score and synovial fibrosis did not differ in the KOA groups. In conclusion, footprint patterns improved in rats with ACLT-induced KOA as a result of clinical-like cryotherapy, which also lowered the synovial fluid leukocyte count and inflammatory cytokine concentration in these rats.
Asunto(s)
Crioterapia , Inflamación/patología , Osteoartritis de la Rodilla/terapia , Membrana Sinovial/patología , Heridas y Lesiones/terapia , Animales , Cartílago/metabolismo , Movimiento Celular , Modelos Animales de Enfermedad , Marcha , Miembro Posterior/patología , Interleucinas/metabolismo , Leucocitos , Masculino , Ratas , Ratas Wistar , Temperatura Cutánea , Líquido SinovialRESUMEN
Feline leishmaniasis (FeL) is an emerging infectious disease of cats caused by Leishmania infantum with global distribution. This study investigated the cause of chronic progressive cutaneous lesions in two cats from Central-west Brazil by using cytological, histopathologic, and immunohistochemical (IHC) analyses. Clinically, both cats had ulcerative cutaneous lesions at the nasal planum and ear resulting in a tentative diagnosis of squamous cell carcinoma (SCC). Moreover, both cats had varying degrees of onychogryphosis. However, cytology revealed chronic inflammatory reactions associated with intralesional amastigotes; histopathology confirmed chronic ulcerative dermatitis associated with intralesional and intracytoplasmic parasitic organisms consistent with amastigotes of Leishmania spp. within histiocytes. The IHC assay demonstrated that the intralesional parasitic structures identified by cytology and histopathology were immunoreactive to antigens of Leishmania spp., confirming the participation of this infectious disease agent in the development of the cutaneous lesions of these cats. The observation of onychogryphosis must be highlighted, since this lesion is frequently observed in dogs with visceral leishmaniasis but is underreported in FeL. Collectively, the pathologic and IHC findings of the chronic cutaneous disease confirmed active infections due to Leishmania spp. in these cats. Additionally, FeL with associated lesions to the ear and nasal planum must be considered as differential diagnosis for SCC in cats.
Asunto(s)
Enfermedades de los Gatos/parasitología , Leishmania infantum/aislamiento & purificación , Leishmaniasis Cutánea/veterinaria , Animales , Biopsia con Aguja Fina/veterinaria , Brasil/epidemiología , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/veterinaria , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/epidemiología , Gatos , Ciudades , Diagnóstico Diferencial , Oído Externo/patología , Femenino , Miembro Anterior/patología , Miembro Posterior/patología , Inmunohistoquímica/veterinaria , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/epidemiología , Leishmaniasis Cutánea/parasitología , Nariz/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/veterinariaRESUMEN
During chronic limb ischemia, oxidative damage and inflammation are described. Besides oxidative damage, the decrease of tissue oxygen levels is followed by several adaptive responses. The purpose of this study was to determine whether supplementation with N-acetylcysteine (NAC) is effective in an animal model of chronic limb ischemia. Chronic limb ischemia was induced and animals were treated once a day for 30 consecutive days with NAC (30mg/kg). After this time clinical scores were recorded and soleus muscle was isolated and lactate levels, oxidative damage and inflammatory parameters were determined. In addition, several mechanisms associated with hypoxia adaptation were measured (vascular endothelial growth factor - VEGF and hypoxia inducible factor - HIF levels, ex vivo oxygen consumption, markers of autophagy/mitophagy, and mitochondrial biogenesis). The adaptation to chronic ischemia in this model included an increase in muscle VEGF and HIF levels, and NAC was able to decrease VEGF, but not HIF levels. In addition, ex vivo oxygen consumption under hypoxia was increased in muscle from ischemic animals, and NAC was able to decrease this parameter. This effect was not mediated by a direct effect of NAC on oxygen consumption. Ischemia was followed by a significant increase in muscle myeloperoxidase activity, as well as interleukin-6 and thiobarbituric acid reactive substances species levels. Supplementation with NAC was able to attenuate inflammatory and oxidative damage parameters, and improve clinical scores. In conclusion, NAC treatment decreases oxidative damage and inflammation, and modulates oxygen consumption under hypoxic conditions in a model of chronic limb ischemia.
Asunto(s)
Acetilcisteína/farmacología , Miembro Posterior/patología , Isquemia/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Hipoxia/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Inflamación , Interleucina-6/metabolismo , Isquemia/metabolismo , Ácido Láctico/metabolismo , Masculino , Músculo Esquelético/metabolismo , Nitratos/metabolismo , Nitritos/metabolismo , Estrés Oxidativo , Oxígeno/química , Oxígeno/metabolismo , Consumo de Oxígeno , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Canine breed conformation may interfere with locomotion and may predispose to orthopedic disease. Bulldogs have a high incidence of orthopedic diseases such as hip dysplasia. Kinetic gait analysis provides an objective way to assess and analyze locomotion. The aim of this study was to study the vertical forces of English Bulldogs during walk using a pressure sensitive walkway. We hypothesize that Bulldogs affected by orthopedic diseases have decreased weight bearing and asymmetric locomotion in the limbs despite having mild to no sings during clinical examination. Thirty English Bulldogs were tested. Peak vertical force, vertical impulse, rate of loading, stance phase duration, symmetry index, goniometry and incidence of orthopedic diseases were recorded. RESULTS: Although none of the dogs showed signs of pain or discomfort upon manipulation of the hip joints, all dogs had radiographic evidences of hip dysplasia and lack of significant peak vertical force, vertical impulse and stance time differences. The dogs had a mean hind limb symmetry index of 19.8 ± 19.5% and rates of loading ranged from 1.0 to 3.1. CONCLUSIONS: Despite the lack of evident decrease in weight bearing, subclinical lameness can be inferred. The examined dogs had a mean hind limb symmetry index of 19.8 ± 19.5%. Symmetry indices reported in dogs free from orthopedic diseases range from 0.3 to 9.6%. Given non-lame dogs are expected to have a symmetry index close to 0%, data from this study suggests that Bulldogs have gait dysfunctions, which translates into hind limb asymmetries and rate of loading was consistent with severe hip dysplasia despite no visible signs of gait dysfunction. Future studies comparing lame and non-lame Bulldogs are warranted.
Asunto(s)
Enfermedades de los Perros/patología , Marcha/fisiología , Miembro Posterior/patología , Cojera Animal/patología , Animales , Fenómenos Biomecánicos , Enfermedades de los Perros/diagnóstico , Perros , Cojera Animal/diagnóstico , PresiónRESUMEN
Na osteocondrite dissecante (OCD), a articulação do ombro é mais comumente afetada, mas o joelho é ocasionalmente lesionado, o que, muitas vezes, passa desapercebido. O tratamento cirúrgico precoce é indicado para remover cartilagem solta, aliviar a dor e minimizar a artrose. Benefícios putativos da transferência de autoenxerto osteocondral em relação às técnicas convencionais incluem a reconstrução exata do contorno subcondral e articular, recobrimento da superfície com cartilagem hialina e criação de uma barreira imediata entre o líquido sinovial e o osso subcondral. O objetivo deste trabalho é relatar a técnica de transferência de autoenxerto osteocondral para o tratamento da osteocondrite do côndilo femoral. Um cão da raça Bull Terrier foi tratado cirurgicamente por meio da técnica de transferência de autoenxerto osteocondral, após ter sido diagnosticado com OCD do côndilo femoral, apresentando melhora clínica significativa e completa recuperação aos 30 dias de pós-operatório.(AU)
In osteochondritis dissecans (OCD), the shoulder joint is most commonly involved, but the stifle is occasionally involved and often goes unnoticed. Early surgical treatment is indicated to remove loose cartilage and minimize osteoartrosis. Putative benefits of Osteochondral Autograft Transfer (OAT) over conventional techniques include accurate reconstruction of subchondral and articular contour, resurfacing with hyaline or hyaline-like cartilage, and creation of an immediate barrier between synovial fluid and subchondral bone. The purpose of this work is to report the technique of OATs for the treatment of osteochondritis of the femoral condyle. A canine attended the Laboratory of Comparative Orthopedics and Traumatology USP-FMVZ underwent surgery after being diagnosed with OCD of the femoral condyle, with significant clinical improvement at 30 days postoperatively.(AU)
Asunto(s)
Animales , Perros , Trasplante Autólogo/veterinaria , Osteocondritis Disecante/veterinaria , Fémur/trasplante , Miembro Posterior/patología , AutoinjertosRESUMEN
Na osteocondrite dissecante (OCD), a articulação do ombro é mais comumente afetada, mas o joelho é ocasionalmente lesionado, o que, muitas vezes, passa desapercebido. O tratamento cirúrgico precoce é indicado para remover cartilagem solta, aliviar a dor e minimizar a artrose. Benefícios putativos da transferência de autoenxerto osteocondral em relação às técnicas convencionais incluem a reconstrução exata do contorno subcondral e articular, recobrimento da superfície com cartilagem hialina e criação de uma barreira imediata entre o líquido sinovial e o osso subcondral. O objetivo deste trabalho é relatar a técnica de transferência de autoenxerto osteocondral para o tratamento da osteocondrite do côndilo femoral. Um cão da raça Bull Terrier foi tratado cirurgicamente por meio da técnica de transferência de autoenxerto osteocondral, após ter sido diagnosticado com OCD do côndilo femoral, apresentando melhora clínica significativa e completa recuperação aos 30 dias de pós-operatório.(AU)
In osteochondritis dissecans (OCD), the shoulder joint is most commonly involved, but the stifle is occasionally involved and often goes unnoticed. Early surgical treatment is indicated to remove loose cartilage and minimize osteoartrosis. Putative benefits of Osteochondral Autograft Transfer (OAT) over conventional techniques include accurate reconstruction of subchondral and articular contour, resurfacing with hyaline or hyaline-like cartilage, and creation of an immediate barrier between synovial fluid and subchondral bone. The purpose of this work is to report the technique of OATs for the treatment of osteochondritis of the femoral condyle. A canine attended the Laboratory of Comparative Orthopedics and Traumatology USP-FMVZ underwent surgery after being diagnosed with OCD of the femoral condyle, with significant clinical improvement at 30 days postoperatively.(AU)
Asunto(s)
Animales , Perros , Fémur/trasplante , Miembro Posterior/patología , Osteocondritis Disecante/veterinaria , Trasplante Autólogo/veterinaria , AutoinjertosRESUMEN
Fibropapillomatosis (FP) is characterized by multiple fibroepithelial tumors in all parts of the skin and has been reported in sea turtles worldwide. Clinically infected individuals are often emaciated and anemic. In Mexico, however, there are few records of this disease. In this study of green turtles Chelonia mydas in Laguna San Ignacio in Baja California Sur (BCS), we noted one juvenile with multifocal fibropapilloma lesions on the external upper surface of its eyes and hind flippers. Light microscopy revealed hyperkeratosis, epidermal hyperplasia, dermal papillary projections, and fibroblast proliferation. Electron microscopy revealed viral particles. Biopsies of normal skin were done to determine the origin of the turtle through genetic analysis. Its mitochondrial DNA matched that of a haplotype (CMP2) from a Hawaiian green turtle population. Finding FP in a turtle captured in BCS elucidates the need for further monitoring along the west coast of Mexico. Further investigation should include testing tumors to detect and characterize any chelonid herpesviruses and explore any association with FP and other diseases that pose a health risk to other sea turtle species. Received March 26, 2016; accepted August 3, 2016.
Asunto(s)
Oftalmopatías/veterinaria , Miembro Posterior/patología , Papiloma/veterinaria , Tortugas , Virión/aislamiento & purificación , Migración Animal , Animales , Oftalmopatías/patología , Oftalmopatías/virología , Miembro Posterior/ultraestructura , Miembro Posterior/virología , México , Microscopía Electrónica de Transmisión , Papiloma/patología , Papiloma/virologíaRESUMEN
We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 µg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.
Asunto(s)
Adalimumab/farmacología , Antirreumáticos/farmacología , Huesos/efectos de los fármacos , Cartílago Articular/efectos de los fármacos , Osteoartritis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Ligamento Cruzado Anterior/cirugía , Artritis Experimental/tratamiento farmacológico , Artroplastia Subcondral , Huesos/metabolismo , Cartílago Articular/metabolismo , Matriz Extracelular/efectos de los fármacos , Femenino , Miembro Posterior/patología , Miembro Posterior/cirugía , Inmunohistoquímica , Puntaje de Gravedad del Traumatismo , Metaloproteinasa 13 de la Matriz/efectos de los fármacos , Metaloproteinasa 13 de la Matriz/metabolismo , Osteoartritis/cirugía , Factores Protectores , Distribución Aleatoria , Ratas Sprague-DawleyRESUMEN
We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 μg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.
Asunto(s)
Animales , Femenino , Adalimumab/farmacología , Antirreumáticos/farmacología , Huesos/efectos de los fármacos , Cartílago Articular/efectos de los fármacos , Osteoartritis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Artroplastia Subcondral , Ligamento Cruzado Anterior/cirugía , Artritis Experimental/tratamiento farmacológico , Huesos/metabolismo , Cartílago Articular/metabolismo , Matriz Extracelular/efectos de los fármacos , Miembro Posterior/patología , Miembro Posterior/cirugía , Inmunohistoquímica , Puntaje de Gravedad del Traumatismo , /efectos de los fármacos , /metabolismo , Osteoartritis/cirugía , Factores Protectores , Distribución Aleatoria , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Treatment for horses with pythiosis of a limb is challenging. This study aims to evaluate the effects of administering amphotericin B in a 10 % solution of dimethylsulfoxide by intravenous regional limb perfusion (IRLP) to treat horses for cutaneous pythiosis of a limb. RESULTS: All 15 of the horses treated had complete resolutions of their lesion between 6 to 9 weeks after a single IRLP treatment. No complications were observed at the site of venipuncture for IRLP. Before initiation of treatment, there was anemia and marked leucocytosis which resolved following treatment. Serum biochemistry showed no significant changes. CONCLUSIONS: IRLP administration of amphotericin B in a 10 % DMSO solution was easily performed, relatively inexpensive and an effective treatment for treating horses for pythiosis of a limb and resolved the infection with no complications.
Asunto(s)
Anfotericina B/uso terapéutico , Dimetilsulfóxido/uso terapéutico , Enfermedades de los Caballos/tratamiento farmacológico , Pitiosis/tratamiento farmacológico , Pythium/aislamiento & purificación , Anfotericina B/administración & dosificación , Animales , Antiinfecciosos/administración & dosificación , Antiinfecciosos/uso terapéutico , Dimetilsulfóxido/administración & dosificación , Quimioterapia Combinada , Femenino , Miembro Anterior/microbiología , Miembro Anterior/patología , Miembro Posterior/microbiología , Miembro Posterior/patología , Caballos , Inyecciones Intravenosas , MasculinoRESUMEN
The increase in PGE2 production by microsomal PGE synthase-1 (mPGES-1) in CNS contributes to the severity of the inflammatory and pain responses in the model of edema formation and hyperalgesia induced by carrageenan. PGI2, alike to PGE2, plays an important role in the inflammation. Low-level laser therapy (LLLT) has been used in the treatment of inflammatory pathologies, reducing both pain and the acute inflammatory process. In this work, we studied the effect of LLLT on the expression of both mPGES-1 and IP messenger RNA (mRNA), in either subplantar or total brain tissues obtained from rats submitted to model of edema formation and hyperalgesia induced by carrageenan administration. The test sample consisted of 30 rats divided into five groups: A1 (control-saline), A2 (carrageenan-0.5 mg/paw), A3 (carrageenan-0.5 mg/paw + LLLT), A4 (carrageenan-1.0 mg/paw), and A5 (carrageenan-1.0 mg/paw + LLLT). The animals from groups A3 and A5 were irradiated 1 h after induction of inflammation by carrageenan injection. Continuous-wave red laser with wavelengths of 660 nm and dose of 7.5 J/cm(2) was used. Six hours after carrageenan-induced inflammation, mPGES-1 and prostacyclin receptor (IP) mRNA expression were significantly increased both in subplantar and brain tissues. LLLT was able to reduce both mPGES-1 and IP mRNA expression in subplantar and brain tissues. We suggest that LLLT is able to reduce both inflammation and hyperalgesia observed in the model of edema formation and hyperalgesia induced by carrageenan, by a mechanism involving the decrease in the expression of both mPGES-1 and IP.
Asunto(s)
Encéfalo/metabolismo , Edema/radioterapia , Miembro Posterior/metabolismo , Oxidorreductasas Intramoleculares/genética , Láseres de Semiconductores/uso terapéutico , Terapia por Luz de Baja Intensidad , Receptores de Prostaglandina/metabolismo , Animales , Encéfalo/inmunología , Encéfalo/efectos de la radiación , Carragenina , Regulación hacia Abajo , Edema/inducido químicamente , Edema/metabolismo , Pie/patología , Pie/efectos de la radiación , Expresión Génica/efectos de la radiación , Miembro Posterior/patología , Miembro Posterior/efectos de la radiación , Hiperalgesia/metabolismo , Hiperalgesia/radioterapia , Oxidorreductasas Intramoleculares/metabolismo , Masculino , Prostaglandina-E Sintasas , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptores de Prostaglandina/genéticaRESUMEN
OBJECTIVE: To evaluate the effects of intravenous regional limb perfusion (IRLP) administration of amphotericin B in horses to treat pythiosis after surgical excision and thermocautery. STUDY DESIGN: Case series. ANIMALS: Horses (n = 12) with Pythium insidiosum infection of the distal aspect of the thoracic or pelvic limbs. METHODS: After surgical excision of granulation tissue and thermocautery, 50 mg amphotericin B was administered by IRLP through a catheter placed in a superficial vein of the affected limb next to the lesion after placing a tourniquet above the injection site. The lesions and locomotor system were evaluated before treatment and at 7, 14, 21, 28, 35, and 60 days. RESULTS: Ninety-two percent of horses treated with amphotericin B had complete lesion resolution 35 or 60 days after 1 or 2 IRLP treatments, respectively. IRLP induced limb edema and pain during regional palpation in 42%, and inflammation of the injection site in 33% of horses; however these signs resolved after 14 days. CONCLUSIONS: IRLP administration of amphotericin B was effective for treating pythiosis in equine limbs, resolving infection with manageable side effects.
Asunto(s)
Anfotericina B/uso terapéutico , Antiinfecciosos/uso terapéutico , Enfermedades de los Caballos/tratamiento farmacológico , Pitiosis/veterinaria , Pythium/aislamiento & purificación , Anfotericina B/administración & dosificación , Animales , Antiinfecciosos/administración & dosificación , Femenino , Miembro Anterior/microbiología , Miembro Anterior/patología , Miembro Posterior/microbiología , Miembro Posterior/patología , Caballos , Inyecciones Intravenosas , Masculino , Pitiosis/tratamiento farmacológicoRESUMEN
Constitutive vascular endothelial growth factor (VEGF) gene expression systems have been extensively used to treat peripheral arterial diseases, but most of the results have not been satisfactory. In this study, we designed a plasmid vector with a hypoxia-responsive element sequence incorporated into it with the phiC31 integrative system (pVHAVI) to allow long-term VEGF gene expression and to be activated under hypoxia. Repeated activations of VEGF gene expression under hypoxia were confirmed in HEK293 and C2C12 cells transfected with pVHAVI. In limb ischemic mice, the local administration of pVHAVI promoted gastrocnemius mass and force recovery and ameliorated limb necrosis much better than the group treated with hypoxia-insensitive vector, even this last group had produced more VEGF in muscle. Histological analyses carried out after four weeks of gene therapy showed increased capillary density and matured vessels, and reduced number of necrotic cells and fibrosis in pVHAVI treated group. By our study, we demonstrate that the presence of high concentration of VEGF in ischemic tissue is not beneficial or is less beneficial than maintaining a lower but sufficient and long-term concentration of VEGF locally.
Asunto(s)
Hipoxia , Isquemia/terapia , Factor A de Crecimiento Endotelial Vascular/genética , Animales , Línea Celular , Modelos Animales de Enfermedad , Terapia Genética , Vectores Genéticos/genética , Vectores Genéticos/uso terapéutico , Células HEK293 , Miembro Posterior/irrigación sanguínea , Miembro Posterior/patología , Humanos , Isquemia/patología , Ratones , Transfección , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVES: The effects of short-term 5-day and long-term 30-day hyperprolactinemia induced by domperidone (1.7 mg/kg/day, s.c.) or ectopic pituitary graft on the acute inflammatory response induced by carrageenan were evaluated in male rats. Both models of hyperprolactinemia effectively increased serum prolactin (PRL) levels. METHODS: The volume in milliliters of inflammatory edema was measured by plethysmography 1, 2, 3, 4, 6, 8 and 24 h after carrageenan injection. The areas under the inflammatory time-response curves were compared. Additionally, the effects of hyperprolactinemia on body weight and serum corticosterone levels were evaluated. RESULTS: In both domperidone-treated and pituitary graft-implanted animals, short-term 5-day hyperprolactinemia increased the inflammatory response, while long-term 30-day hyperprolactinemia had anti-inflammatory effects. Body weight was not affected by either short- or long-term hyperprolactinemia. CONCLUSION: These results show that PRL has biphasic effects on the carrageenan-induced inflammatory response.
Asunto(s)
Edema/inmunología , Hiperprolactinemia/inmunología , Inflamación/inmunología , Neuroinmunomodulación/fisiología , Animales , Peso Corporal , Carragenina/toxicidad , Corticosterona/sangre , Edema/inducido químicamente , Edema/metabolismo , Miembro Posterior/patología , Hiperprolactinemia/metabolismo , Inflamación/inducido químicamente , Inflamación/metabolismo , Irritantes/toxicidad , Masculino , Pletismografía , Prolactina/sangre , Radioinmunoensayo , Ratas , Ratas WistarRESUMEN
Mast cells are involved in immune disorders so that many of the proinflammatory and tissue destructive mediators produced by these cells have been implicated in the pathogenesis of rheumatoid arthritis. This scenario prompted us to investigate the correlation between mast cell degranulation and neutrophil influx within the digits and knees joints of arthritic mice assessing what could be the functional role(s) of joint mast cells in the response to collagen immunization. DBA/1J mice were submitted to collagen-induced arthritis and disease was assessed on day 21, 32 and 42 post-immunization. Pharmacological treatment with the glucocorticoid prednisolone, commonly used in the clinic, and nedocromil, a mast cell stabilizer, was performed from day 21 to 30. Arthritis develop after immunization, gradually increased up to day 42. Neutrophil infiltration peaked on day 32 and 21, in the digits and knees, respectively, showing an unequal pattern of recruitment between these tissues. This difference emerged for mast cells: they peaked in the digits on day 21, but a higher degree of degranulation could be measured in the knee joints. Uneven modulation of arthritis occurred after treatment of mice with prednisolone or nedocromil. Neutrophils migration to the tissue was reduced after both therapies, but only prednisolone augmented mast cell migration to the joints. Nedocromil exerted inhibitory properties both on mast cell proliferation and migration, more effectively on the digit joints. Thus, collagen induced an inflammatory process characterized by tissue mast cells activation and degranulation, suggesting a potential driving force in propagating inflammatory circuits yielding recruitment of neutrophils. However, the different degree of affected joint involvement suggests a time-related implication of digits and knees during collagen-induced arthritis development. These results provide evidence for local alterations whereby mast cells contribute to the initiation of inflammatory arthritis and may be targeted in intervention strategies.
Asunto(s)
Artritis Experimental/inmunología , Mastocitos/inmunología , Infiltración Neutrófila/inmunología , Neutrófilos/inmunología , Animales , Antiinflamatorios/farmacología , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Miembro Anterior/efectos de los fármacos , Miembro Anterior/patología , Glucocorticoides/farmacología , Miembro Posterior/efectos de los fármacos , Miembro Posterior/patología , Articulación de la Rodilla/efectos de los fármacos , Articulación de la Rodilla/inmunología , Articulación de la Rodilla/patología , Recuento de Leucocitos , Mastocitos/efectos de los fármacos , Mastocitos/patología , Ratones , Ratones Endogámicos DBA , Nedocromil/farmacología , Infiltración Neutrófila/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Neutrófilos/patología , Prednisolona/farmacología , Membrana Sinovial/efectos de los fármacos , Membrana Sinovial/inmunología , Membrana Sinovial/patología , Factores de TiempoRESUMEN
In transplantation, parasite diseases are transmitted from the donor, or appear as de novo infections, or activate from a dormant insource as a consequence of immunosuppression. Clinical findings have shown that an intact immune system is crucial to prevent recurrence of Leishmania infection. We used BALB/c and C57BL/6 mice to evaluate the role of FTY720 in leishmaniasis. Mice inoculated with Leishmania (Leishmania) amazonensis were followed over 7 weeks for foot thickness measurements after initiation of FTY720 treatment. After 10 days of treatment, spleen, blood, and the foot were harvested for evaluation. BALB/c showed greater evident foot thickness than C57BL/6 mice. Oral treatment with FTY720 (1 mg/kg/d) over 10 days produced the same outcome. Increases in CD4(+) and CD8(+) T cells were observed after infection; FTY720 treatment was associated with a decrease in CD4(+) T cells only in BALB/c mice, whereas CD8(+) T cells were decreased in both mice strains. CD11b(+) expression decreased after infection with a discrete increase after FTY720 treatment. Lymphopenia was observed among all FTY720-treated mice. In conclusion, we observed that FTY720 produced no worse an outcome as monotherapy in established infections with L (L) amazonensis.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Inmunosupresores/farmacología , Leishmania mexicana , Leishmaniasis Cutánea/inmunología , Glicoles de Propileno/farmacología , Esfingosina/análogos & derivados , Animales , Linfocitos T CD4-Positivos/efectos de los fármacos , Clorhidrato de Fingolimod , Citometría de Flujo , Miembro Posterior/efectos de los fármacos , Miembro Posterior/patología , Leishmaniasis Cutánea/patología , Recuento de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Esfingosina/farmacología , Bazo/efectos de los fármacos , Bazo/patologíaRESUMEN
Five cats were experimentally inoculated with Trypanosoma evansi in order to evaluate the pathological changes induced by this protozoan infection. Clinical signs observed included vomiting, diarrhoea, hyperthermia, weight loss, facial oedema, corneal opacity, lymphadenopathy and hindlimb instability. Reduction in hematocrit was observed from 7 days post-infection (dpi) (P<0.05). One cat died at 40 dpi and the other four cats were humanely destroyed. Necropsy examination was performed in two cats at 56 dpi and two cats at 120 dpi. Gross findings in all cats included generalized muscle atrophy, pale mucosae, icterus of the subcutaneous and serosal tissue and the intima of arteries, lymphadenopathy and splenomegaly. Other findings included corneal opacity, subcutaneous oedema (mainly of the head) and hydropericardium. Trypomastigotes of T. evansi were observed in impression smears prepared from the aqueous humor. Microscopically, there was lymphoid hyperplasia of the spleen and lymph nodes. The animals with corneal opacity had mild corneal oedema and accumulation of fibrin and inflammatory cells (neutrophils and plasma cells) in the anterior chamber. Similar inflammatory cells infiltrated the iris, ciliary body, corneoscleral limbus and conjunctiva.
Asunto(s)
Enfermedades Linfáticas/patología , Tripanosomiasis/patología , Animales , Gatos , Recuento de Células , Córnea/parasitología , Córnea/patología , Diarrea/parasitología , Diarrea/patología , Femenino , Miembro Posterior/parasitología , Miembro Posterior/patología , Enfermedades Linfáticas/parasitología , Actividad Motora , Bazo/parasitología , Bazo/patología , Esplenomegalia/parasitología , Esplenomegalia/patología , Trypanosoma , Vómitos/parasitología , Vómitos/patologíaRESUMEN
As afecções gastrintestinais dos cavalos são agravadas por complicações como a laminite, cuja etiopatogenia está relacionada à degradação da membrana basal do tecido laminar por metaloproteinases (MMPs). A ativação das MMPs pode ocorrer devido à liberação local de citocinas inflamatórias ou enzimas provenientes de leucócitos infiltrados no tecido laminar. O objetivo deste trabalho foi avaliar as alterações morfológicas do tecido laminar de equinos com síndrome cólica letal e sua provável associação com parâmetros clínicos e laboratoriais. Observou-se intensa destruição da arquitetura laminar, principalmente nos animais com alterações físicas e laboratoriais mais acentuadas, como tempo de preenchimento capilar prolongado (TPC), membranas mucosas congestas, taquicardia, hemoconcentração e redução nas contagens de plaquetas e leucócitos. Os resultados sinalizam o provável momento do desenvolvimento de lesões do tecido laminar em equinos com síndrome cólica, no qual é possível adotar medidas preventivas contra a laminite.
The gastrointestinal diseases of horses are aggravated by complications such as laminitis. The laminitis etiopathogeny are connected with lamellar basement membrane degradation by matrix metalloproteinases (MMPs). Inflammatory cytokines and leukocytes enzymes can active MMPs. The object of this study was to evaluate morphological changes on lamellar tissue of horses with colic syndrome and its association with clinical and laboratorial parameters. It was observed intensive destruction of lamellar architecture, mainly on animals with severe physical and laboratorial alterations, such as delayed capillary refill time, congested mucous membrane, tachycardia, hemoconcentration and low count of platelet and leukocytes. The results sign to the most likely moment of development of lamellar tissue injuries in horses with colic syndrome, which can be adopted preventive measures against laminitis.
Asunto(s)
Animales , Caballos/lesiones , Cólico/complicaciones , Miembro Anterior/patología , Miembro Posterior/patología , Tracto Gastrointestinal/lesiones , Tracto Gastrointestinal/patología , Endotoxemia/epidemiología , Endotoxemia/veterinariaRESUMEN
As afecções gastrintestinais dos cavalos são agravadas por complicações como a laminite, cuja etiopatogenia está relacionada à degradação da membrana basal do tecido laminar por metaloproteinases (MMPs). A ativação das MMPs pode ocorrer devido à liberação local de citocinas inflamatórias ou enzimas provenientes de leucócitos infiltrados no tecido laminar. O objetivo deste trabalho foi avaliar as alterações morfológicas do tecido laminar de equinos com síndrome cólica letal e sua provável associação com parâmetros clínicos e laboratoriais. Observou-se intensa destruição da arquitetura laminar, principalmente nos animais com alterações físicas e laboratoriais mais acentuadas, como tempo de preenchimento capilar prolongado (TPC), membranas mucosas congestas, taquicardia, hemoconcentração e redução nas contagens de plaquetas e leucócitos. Os resultados sinalizam o provável momento do desenvolvimento de lesões do tecido laminar em equinos com síndrome cólica, no qual é possível adotar medidas preventivas contra a laminite.(AU)
The gastrointestinal diseases of horses are aggravated by complications such as laminitis. The laminitis etiopathogeny are connected with lamellar basement membrane degradation by matrix metalloproteinases (MMPs). Inflammatory cytokines and leukocytes enzymes can active MMPs. The object of this study was to evaluate morphological changes on lamellar tissue of horses with colic syndrome and its association with clinical and laboratorial parameters. It was observed intensive destruction of lamellar architecture, mainly on animals with severe physical and laboratorial alterations, such as delayed capillary refill time, congested mucous membrane, tachycardia, hemoconcentration and low count of platelet and leukocytes. The results sign to the most likely moment of development of lamellar tissue injuries in horses with colic syndrome, which can be adopted preventive measures against laminitis.(AU)