RESUMEN
OBJECTIVE: To correlate substance P content of synovial fluid with prostaglandin E2 content, radiographic evidence of joint abnormality, and anatomic location of the joint for normal and osteoarthritic joints of horses. SAMPLE POPULATION: Synovial fluid from 46 normal joints in 21 horses and 16 osteoarthritic joints in 10 horses. PROCEDURE: Normal and osteoarthritic joints were identified by clinical and radiographic examination, by response to nerve blocks, during scintigraphy or surgery, or by clinicopathologic evaluation. Substance P and prostaglandin E2 contents of synovial fluid were determined by radioimmunoassay. Radio-graphs of joints were assigned a numeric score reflecting severity of lesions. Joints were assigned a numeric score reflecting anatomic location. RESULTS: Median concentrations of substance P and prostaglandin E2 were significantly increased in osteoarthritic joints, compared with normal joints. A significant correlation was found between concentrations of substance P and prostaglandin E2 in synovial fluid, but a correlation was not detected between substance P concentration in synovial fluid and anatomic location of the joint or between radiographic scores of osteoarthritic joints and concentrations of substance P or prostaglandin E2. CONCLUSIONS AND CLINICAL RELEVANCE: A correlation existed between concentrations of substance P and prostaglandin E2 in synovial fluid obtained from normal and osteoarthritic joints. However, content of substance P in synovial fluid cannot be predicted by the radiographic appearance of the joint or its anatomic location. Substance P and prostaglandin E2 may share an important and related role in the etiopathogenesis of osteoarthritis, lending credence to the importance of neurogenic inflammation in horses.
Asunto(s)
Dinoprostona/análisis , Enfermedades de los Caballos/patología , Artropatías/veterinaria , Osteoartritis/veterinaria , Sustancia P/análisis , Líquido Sinovial/química , Animales , Dinoprostona/biosíntesis , Femenino , Enfermedades de los Caballos/etiología , Caballos , Artropatías/diagnóstico por imagen , Artropatías/etiología , Masculino , Osteoartritis/etiología , Osteoartritis/patología , Radiografía , Radioinmunoensayo/veterinaria , Estadísticas no Paramétricas , Sustancia P/biosíntesis , Líquido Sinovial/metabolismoRESUMEN
Rats were exposed to either oxygen (controls), 1.5% halothane in oxygen, or methoxyflurane (0.5%) in oxygen over a period of 2 h, then sacrificed at the end of exposure (2-h group), 4 h after removal from environmental chamber (4-h group), or at 24 h following anesthetic exposure (24-h group). Pituitary (excluding the neural lobe, Pit), brain, and spinal cord areas were isolated and processed with Met-enkephalin tissue concentrations determined. In halothane-exposed animals, Met-enkephalin concentrations in pit and across CNS areas studied were significantly lower at 2 h following anesthetic exposure than in control animals. Concentrations of Met-enkephalin in many areas of CNS and Pit of 4-h group approached control levels. Concentrations of Met-enkephalin in all areas studied except spinal cord returned to basal levels by 24 h following halothane exposure. Exposure to methoxyflurane resulted in less dramatic changes in Met-enkephalin concentrations across CNS regions examined. Exposure to methoxyflurane resulted in significant decreases in Met-enkephalin levels in olfactory bulb, thalamus, and hippocampus only. Met-Enkephalin levels did not change significantly in other areas of the central nervous system following methoxyflurane exposure. These results indicate that halothane and methoxyflurane may have differential effects on the endogenous opioid system.
Asunto(s)
Encéfalo/efectos de los fármacos , Encefalina Metionina/metabolismo , Halotano/farmacología , Metoxiflurano/farmacología , Médula Espinal/efectos de los fármacos , Animales , Masculino , Ratas , Ratas Sprague-DawleyAsunto(s)
Criptococosis/veterinaria , Dermatomicosis/veterinaria , Granuloma/veterinaria , Enfermedades de los Caballos , Animales , Biopsia/veterinaria , Criptococosis/tratamiento farmacológico , Criptococosis/patología , Criptococosis/cirugía , Desbridamiento/veterinaria , Dermatomicosis/tratamiento farmacológico , Dermatomicosis/patología , Dermatomicosis/cirugía , Granuloma/tratamiento farmacológico , Granuloma/patología , Granuloma/cirugía , Enfermedades de los Caballos/tratamiento farmacológico , Enfermedades de los Caballos/patología , Enfermedades de los Caballos/cirugía , Caballos , Masculino , PronósticoRESUMEN
Previous studies indicate that anoxia results in vascular smooth muscle contraction, and this phenomenon is mediated in part by a decrease in release of endothelium-derived relaxing factor (EDRF). The role of platelets that relax blood vessels by eliciting EDRF release on anoxic contraction is not known. To examine anoxic contraction in the presence of platelets, we exposed norepinephrine (NE)-precontracted rat aortic rings to washed platelets and then induced anoxia (switch from 95% O2 to 95% N2). Platelets transiently relaxed the precontracted aortic rings (decrease in tension 49 +/- 4%, n = 18). The subsequent anoxia-induced contraction was augmented, however (magnitude of contraction 71 +/- 12 vs. 49 +/- 6% in parallel buffer-treated rings, n = 18, p < 0.01). To determine the mechanism of platelet-mediated augmentation of anoxic contraction, vascular rings were treated with indomethacin, the thromboxane A2 (TxA2)/endoperoxide receptor antagonist SQ29,548, lipoxygenase inhibitor U60,257B, free oxygen radical scavengers superoxide dismutase (SOD) plus catalase, serotonin (S2) receptor blocker LY53,857, or the ADP scavenger apyrase. Although apyrase, U60,257B, SQ29,548, LY53,857, and SOD plus catalase had no effect on augmentation of anoxic contraction in the presence of platelets, treatment with indomethacin markedly decreased (p < 0.02) the augmented anoxic vasoconstriction. Because indomethacin decreases the activity of platelet-activating factor (PAF), vascular rings were treated with two different specific PAF receptor antagonists: L-659,989 and WEB 2170 BS. Both these agents blocked the platelet-augmented anoxic vasoconstriction. In addition, synthetic PAF (10(-7) and 10(-6) M) in itself potentiated anoxic contraction, mimicking the activity of platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Plaquetas/fisiología , Hipoxia/fisiopatología , Músculo Liso Vascular/fisiopatología , Factor de Activación Plaquetaria/fisiología , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/fisiopatología , Tampones (Química) , Endotelio Vascular/fisiología , Depuradores de Radicales Libres , Humanos , Técnicas In Vitro , Indicadores y Reactivos , Indometacina/farmacología , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Norepinefrina/farmacología , Factor de Activación Plaquetaria/antagonistas & inhibidores , Ratas , Ratas Sprague-DawleyRESUMEN
The objective of this study was to document, through comprehensive means, normal distribution and concentration of catecholamines in various regions of the CNS of pigs, an increasingly popular animal model used for transgenic manipulation of neural genes. The effects of gonadal steroidal status on this distribution were also assessed by comparing CNS catecholamine concentrations among mature male pigs (boars), immature (gilts) and mature female pigs (sows), and adult male pigs castrated prepuberally (barrows). Dissected tissue samples from the CNS were extracted in 2 N acetic acid, filtered through a 0.2 micron filter, then quantitated by reverse-phase high performance liquid chromatography using a C-18 reverse phase column with electrochemical detection. In both boars and sows the highest concentrations of norepinephrine (NE) were found in the diencephalic areas and brain stem. Gilts exhibited elevated concentrations of NE in the olfactory bulbs (OB), hypothalamus, pons, and corpus trapezoideum-locus ceruleus (LC) compared to lower concentrations in corresponding areas of sows. Prepuberal castration of the male was associated with significantly lower NE concentrations in the striatum, periaqueductal area (PAG), pons, LC, and spinal cord. The sow exhibited significantly lower NE concentrations in the mammillary area (Mam), PAG, pons, and spinal cord than those in corresponding areas of the boar. Dopamine concentrations appeared to be similar in all areas of the brain and spinal cord studied in the sow and boar. Results demonstrated that prepuberal castration of the male appears to significantly alter the DA content of the Mam and dorsal spinal cord, in contrast to gilts who possess significantly higher concentrations of DA. It is concluded from our studies that in general, catecholamine concentrations in various regions of the brain and spinal cord of sexually mature pigs parallel distributions of neuropeptides, substance P, and methionine enkephalin, as previously reported. In addition, significant association was found between gonadal activity and catecholamine concentrations in discrete areas of the pig brain.
Asunto(s)
Química Encefálica , Dopamina/análisis , Epinefrina/análisis , Norepinefrina/análisis , Médula Espinal/química , Animales , Cromatografía Líquida de Alta Presión , Femenino , Masculino , Orquiectomía , Especificidad de Órganos , Factores Sexuales , Maduración Sexual , PorcinosRESUMEN
Release of superoxide radicals during the early phase of coronary reperfusion may result in degradation of endothelium-derived relaxing factor (EDRF), extension of myocardial injury, precipitation of arrhythmias, and stimulation of platelet aggregation. These factors may relate to the occurrence of ventricular fibrillation during reperfusion and coronary reocclusion following initial thrombolysis. This study was designed to examine the effects of concomitant administration of superoxide radical scavenger superoxide dismutase (SOD) with tissue plasminogen activator (tPA) compared to tPA alone (without SOD) in acute coronary thrombosis in anesthetized dogs. Dogs with a stable electrically induced coronary thrombus were randomly given intravenously tPA (0.75 mg/kg) alone or SOD bolus (2 mg/kg) followed by SOD (4 mg/kg) + tPA (0.75 mg/kg) over 20 min. tPA alone restored coronary blood flow in six of nine dogs (reperfusion rate of 67%) with time to reflow of 18.5 +/- 6.7 (mean +/- SD) min. Coronary reocclusion occurred spontaneously in four of six dogs with initial reperfusion (reocclusion rate of 67%). In contrast, SOD + tPA restored coronary blood flow in 9 of 12 dogs (reperfusion rate of 75%, not significant vs. tPA alone) with time to reflow of 11.3 +/- 4.8 min and coronary reocclusion occurred in only 3 of 9 dogs with reperfusion (reocclusion rate of 33%, not significant vs. tPA alone). Reperfusion arrhythmias were more frequent in dogs who received tPA alone compared to those who received SOD in addition to tPA (mean Holter-monitored PVC count of 730 vs. 12 beats/h, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Arritmias Cardíacas/prevención & control , Enfermedad Coronaria/tratamiento farmacológico , Trombosis Coronaria/tratamiento farmacológico , Corazón/efectos de los fármacos , Superóxido Dismutasa/uso terapéutico , Terapia Trombolítica , Activador de Tejido Plasminógeno/uso terapéutico , Acetilcolina/farmacología , Animales , Arritmias Cardíacas/etiología , Arritmias Cardíacas/fisiopatología , Trombosis Coronaria/complicaciones , Trombosis Coronaria/fisiopatología , Vasos Coronarios/efectos de los fármacos , Perros , Femenino , Hemodinámica/efectos de los fármacos , Reperfusión Miocárdica , Agregación Plaquetaria/efectos de los fármacos , Proteínas Recombinantes/uso terapéutico , Activador de Tejido Plasminógeno/farmacologíaRESUMEN
To determine the contribution of thromboxane (Tx) A2 release in reperfusion injury, 17 dogs were subjected to total coronary occlusion for 1 h and reperfusion for 1 h. Eleven dogs were treated with saline, and six were treated with selective TxA2 synthetase inhibitor U63,557A (5 mg/kg iv) 30 min before coronary artery occlusion. In all saline-treated dogs, peak reactive hyperemia after 10-s total coronary artery occlusion was diminished (P less than 0.01) after reperfusion. Myocardial segmental shortening was also reduced (9.8 +/- 1.9 to -6.7 +/- 2.0%, P less than 0.01) in the reperfused region. Reperfusion was associated with 737 +/- 343 premature ventricular contractions (PVCs) per hour. Histology revealed extensive myocardial infiltration and capillary plugging by leukocytes in the reperfused region. Myeloperoxidase, an index of leukocyte infiltration, was also increased (P less than 0.02) in the reperfused region. In the U63,557A-treated animals, serum and plasma TxB2 levels were markedly (P less than 0.02) reduced. Decrease in myocardial shortening fraction was less in U63,557A- than in saline-treated animals (P less than 0.05). The frequency of reperfusion PVCs was also significantly reduced (10 +/- 5 PVCs/h, P less than 0.02 compared with saline-treated dogs). However, peak reactive hyperemia was reduced similar to that in saline-treated dogs. Myocardial infiltration and capillary plugging by leukocytes in the reperfused regions was also similar in the U63,557A- and saline-treated dogs. These results indicate that treatment with U63,557A decreases reperfusion arrhythmias and preserves myocardial function. However, coronary reperfusion-induced deterioration in reactive hyperemia is not affected.(ABSTRACT TRUNCATED AT 250 WORDS)