RESUMO
The effects of quercetin on substance P-induced plasma protein extravasation (PE) in the rat dura mater, cerebellum, olfactory bulb and cortex and also its modulation by endopeptidases, angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) were studied. PE was assessed by photometric measurement of extravasated Evans blue. Substance P (SP) and NEP or ACE inhibitors increased the PE in dura mater. Pretreatment with captopril or phosphoramidon potentiated PE induced by SP in the dura mater and cerebellum, respectively. Quercetin increased the PE in the dura mater, cerebellum and cortex. Further results suggested that the PE induced by SP in the dura mater was enhanced by pretreatment with quercetin, similar to that observed with selective peptidase inhibitors. Quercetin-stimulated extravasation in all tissues was abolished by NK-1 receptor blockade. These results suggest that quercetin increases PE in the dura mater and CNS tissues by inhibiting NEP and/or ACE, showing that the effect induced in the dura mater, cerebellum and cortex occurs through endogenous SP accumulation.
Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Dura-Máter/efeitos dos fármacos , Neprilisina/antagonistas & inibidores , Peptidil Dipeptidase A/efeitos dos fármacos , Quercetina/farmacologia , Animais , Permeabilidade Capilar/efeitos dos fármacos , Captopril/farmacologia , Sistema Nervoso Central/irrigação sanguínea , Sistema Nervoso Central/metabolismo , Cerebelo/irrigação sanguínea , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Dura-Máter/irrigação sanguínea , Dura-Máter/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Azul Evans/metabolismo , Extravasamento de Materiais Terapêuticos e Diagnósticos/prevenção & controle , Glicopeptídeos/farmacologia , Veias Jugulares/efeitos dos fármacos , Masculino , Antagonistas dos Receptores de Neurocinina-1 , Bulbo Olfatório/irrigação sanguínea , Bulbo Olfatório/efeitos dos fármacos , Bulbo Olfatório/metabolismo , Peptidil Dipeptidase A/metabolismo , Quercetina/sangue , Ratos , Ratos Wistar , Substância P/metabolismoRESUMO
The venom of Lonomia obliqua caterpillar may induce a hemorrhagic syndrome in humans, and blood incoagulability by afibrinogenemia when intravenously injected in laboratory animals. The possible antithrombotic and thrombolytic activities of L. obliqua caterpillar bristle extract (LOCBE) were evaluated in this study. The minimal intravenous dose of the extract necessary to induce afibrinogenemia and anticoagulation was 3.0 and 10.0 microg protein/kg body weight for rabbits and rats, respectively. In rabbits, this dose induced total blood incoagulability for at least 10 h and did not reduce the weight of preformed venous thrombi, in contrast to streptokinase (30,000 IU/kg). In rats, pretreatment with 5.0 and 10.0 microg/kg LOCBE prevented the formation of thrombi induced by venous stasis or by injury to the venous endothelium. The dose of 5.0 microg/kg LOCBE did not modify blood coagulation assay parameters but increased bleeding time and decreased plasma factor XIII concentration. When the extract was administered to rats at the dose of 10.0 microg/kg, the blood was totally incoagulable for 6 h. These data show that LOCBE was effective in preventing experimental venous thrombosis in rats, justifying further studies using purified fractions of the extract to clarify the mechanisms of this effect.
Assuntos
Anticoagulantes/farmacologia , Venenos de Artrópodes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Fibrinolíticos/farmacologia , Trombose Venosa/prevenção & controle , Animais , Anticoagulantes/uso terapêutico , Venenos de Artrópodes/uso terapêutico , Tempo de Sangramento , Fator XIII/análise , Fibrinolíticos/uso terapêutico , Veias Jugulares/efeitos dos fármacos , Masculino , Coelhos , Ratos , Ratos Wistar , Veias Cavas/efeitos dos fármacosRESUMO
El proposito de este capítulo es revisar la neuromonitorización en quirófano coincidiendo con los metodos actuales y trasmitir nuestra experiencia en la práctica de ellos en nuestro hospital. En quirófano la monitorización de las variables más frecuentes (frecuencia cardiaca, presión arterial, SaO2, temperatura, hemoglobina), son visualizados en forma continua como un monitoreo básico. Estos son de valor para mostrar en todo momento lo referente al flujo sanguíneo cerebral en su componente arterial, de la presión de perfusión cerebral (PPC). El componente venoso es la presión en las venas en el espacio subaracnoideo, esto es bien medido por la presión intracraneana (PIC). La actividad eléctricacerebral (EEG), potenciales evocados (PE), saturación venosa yugularde oxigeno (SVjO2); son monitoreos avanzados empleados en forma opcional, dependiendo de las necesidades quirúrgicas y de la capacidad económica del hospital
Assuntos
Humanos , Pressão Intracraniana/efeitos dos fármacos , Pressão Intracraniana/fisiologia , Monitorização Intraoperatória , Monitorização Intraoperatória/instrumentação , Monitoramento de Medicamentos , Cuidados Intraoperatórios , Veias Jugulares/efeitos dos fármacos , Anestésicos , Circulação Cerebrovascular , Eletroencefalografia , Monitorização Fisiológica/métodos , OxigenaçãoRESUMO
1. Using the classical pharmacological criteria recommended by Schild, namely the order of potency of selective agonists (e.g., bradykinin, desArg9-bradykinin, [Hyp3]BK and [Aib7]BK) and the apparent affinity of competitive antagonists (e.g., DArg[Hyp3,DPhe7,Leu8]BK and WIN 64338), we have attempted to characterize B2 receptor subtypes. It has been shown that vascular tissues (e.g., dog carotid and renal arteries, rabbit jugular vein and rabbit aorta) are very sensitive to kinin agonists and antagonists (pD2 and pA2 values for BK and HOE 140 on B2 receptors are 8.5-10.1 and 9.2-9.4, respectively, and for desArg9BK and desArg9[Leu8]BK on B1 receptors they are 7.3-8.6 and 7.3-7.8, respectively). Mechanisms of action of kinins differ between pharmacological preparations. Kinin may act directly on the smooth muscle (e.g., rabbit jugular vein and rabbit aorta) as well as indirectly through other endogenous mediators such as nitric oxide (EDRF) (e.g., dog carotid and renal arteries) and prostaglandins (e.g., dog renal artery). 2. Pharmacological analysis of rabbit jugular vein (RJV) and guinea pig ileum (GPI) has revealed different sensitivities to certain synthetic analogs of BK and to competitive B2 receptor antagonists between the two tissues. 3. Agonist order of potency ([Hyp3]BK > BK > [Aib7]BK) obtained for RJV differed from that obtained for GPI (BK > or = [Aib7]BK > [Hyp3]BK). Competitive antagonists such as DArg[Hyp3, DPhe7, Leu8]BK and WIN 64338 discriminate in favor of B2A (RJV) and B2B (GPI) receptor subtypes, respectively. These data demonstrate the existence of B2 receptor subtypes. Correlation between data obtained in the present study and those reported for binding to the human B2 receptor support the view that the human receptor is similar to that of the rabbit.