RESUMO
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/terapia , Paraganglioma/diagnóstico , Paraganglioma/terapia , Feocromocitoma/diagnóstico , Feocromocitoma/terapia , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/patologia , Assistência ao Convalescente , Algoritmos , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Catecolaminas/antagonistas & inibidores , Diagnóstico por Imagem/métodos , Aconselhamento Genético , Predisposição Genética para Doença , Testes Genéticos , Humanos , Estadiamento de Neoplasias , Paraganglioma/genética , Paraganglioma/patologia , Feocromocitoma/genética , Feocromocitoma/patologia , Sociedades Médicas , Espanha/epidemiologia , Avaliação de Sintomas/métodosRESUMO
The genus Passiflora is popularly used to treat anxiety. Recent studies showed antidepressant-like effects of two varieties of P. edulis (edulis and flavicarpa) in mice. However, the mechanisms of antidepressant actions are still unknown. Here, the effects of P. edulis fo. edulis aqueous extract (AE, 100-300mg/kg, po), and ethyl acetate (AcOEt, 25-50mg/kg, po), butanol (BuOH, 25-50mg/kg, po) and residual aqueous (25-100mg/kg, po) fractions were investigated in the mouse forced swimming test. In addition, the involvement of monoamines in the P. edulis fractions-induced antidepressant actions was approached. HPLC analyses showed that AcOEt and BuOH, but not residual, fractions shared with AE the main peaks between 25 and 70min (UV 340nm), which are suggestive of flavonoids. Nortriptyline and fluoxetine reduced the immobility time and similar results were observed for AE, AcOEt and BuOH but not residual fractions. PCPA (inhibitor of 5-HT synthesis), AMPT (inhibitor of catecholamine synthesis) and sulpiride (selective D2 receptor antagonist), but not DSP-4 (noradrenergic neurotoxin), blocked the antidepressant actions of AcOEt and BuOH. In conclusion, AcOEt and BuOH fractions shared with AE similar phytochemical composition and antidepressant actions. Preserved 5-HT and dopamine transmissions were required for the antidepressant effects of P. edulis fractions.
Assuntos
Antidepressivos/administração & dosagem , Monoaminas Biogênicas/metabolismo , Depressão/metabolismo , Passiflora/química , Extratos Vegetais/administração & dosagem , Transmissão Sináptica , Acetatos/administração & dosagem , Animais , Antidepressivos/isolamento & purificação , Antidepressivos de Segunda Geração/administração & dosagem , Antidepressivos Tricíclicos/administração & dosagem , Comportamento Animal , Benzilaminas/administração & dosagem , Butanóis/administração & dosagem , Catecolaminas/antagonistas & inibidores , Catecolaminas/metabolismo , Depressão/tratamento farmacológico , Antagonistas de Dopamina/administração & dosagem , Fluoxetina/administração & dosagem , Masculino , Camundongos , Nortriptilina/administração & dosagem , Extratos Vegetais/isolamento & purificação , Sulpirida/administração & dosagemRESUMO
Stress impairs cutaneous wound healing; however, it is unclear how beta-adrenoceptors participates in alterations induced by stress on skin wound repair. Therefore, the aim of this study was to investigate the effects of propranolol, a non-selective beta-blocker, administration on cutaneous wound healing of chronically stressed mice. Male mice were spun at 115 rpm for 15 min every hour from three days before wounding until euthanasia. Control animals were not submitted to stress. Stressed and control animals were treated with propranolol dissolved in water; controls received only water. Propranolol administration began one day before wounding and was continued daily until euthanasia. A full-thickness excisional lesion was performed. Seven and fourteen days later, animals were killed, and lesions were formalin-fixed and paraffin-embedded. Sections were stained with hematoxylin-eosin and immunostained against F4/80 to quantify macrophages, alpha-smooth muscle actin to quantify the myofibroblast density and proliferating cell nuclear antigen to quantify the cell proliferation. Furthermore, matrix metalloproteinases (MMP)-2 and MMP-9 activity, nitrite and hydroxyproline levels and tumor necrosis factor-alpha (TNF-alpha) expression were measured in wound. Stress and control + propranolol groups presented a delay in wound contraction, re-epithelialization, F4/80-positive macrophages, neutrophils and mast cells infiltration, cellular proliferation, angiogenesis, myofibroblastic differentiation, MMP-2 and MMP-9 activation and TNF-alpha expression, whereas an increase in the nitrite levels. Stress + propranolol group presented results similar to control group. In conclusion, stress impairs cutaneous wound healing in mice through beta1- adrenoceptors and beta2-adrenoceptors activation.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Propranolol/uso terapêutico , Estresse Fisiológico , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/tratamento farmacológico , Antagonistas Adrenérgicos beta/farmacologia , Animais , Catecolaminas/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Epiderme/efeitos dos fármacos , Tecido de Granulação/efeitos dos fármacos , Inflamação/tratamento farmacológico , Masculino , Metaloproteases/metabolismo , Camundongos , Propranolol/farmacologia , Ferimentos e Lesões/complicações , Ferimentos e Lesões/psicologiaRESUMO
The noradrenergic innervation of Bothrops jararaca venom gland is thought to be important in the production and secretion of venom. We investigated the characteristics of the alpha-adrenoceptor in the venom gland and its role in venom production. This receptor had relatively low sensitivity to noradrenaline (pD(2)=4.77+/-0.09, N=7) and to phenylephrine (pD(2)=3.77+/-0.06, N=11). The receptor became desensitized just after venom extraction (pD(2) to phenylephrine fell to 3.27+/-0.02, N=6) and the sensitivity remained low for at least 15 days, returning to normal 30 days after venom extraction, by which time the snake was ready for a new cycle of venom production. Incubation of secretory cells with noradrenaline (10(-4) mol l(-1) for 5 min) reduced alpha-adrenoceptor sensitivity to the level seen after venom extraction. Blockade of catecholamine production with reserpine abolished the enlargement of the rough endoplasmic reticulum and the activation of the Golgi apparatus that are normally seen after venom extraction, and the venom production was restored by a single subcutaneous (s.c.) injection of phenylephrine (100 mg kg(-1)) immediately after venom extraction. Our data suggest that stimulation of the alpha-adrenoceptor during or shortly after biting is essential for the onset of the venom production cycle.
Assuntos
Bothrops/fisiologia , Venenos de Crotalídeos/biossíntese , Venenos de Crotalídeos/metabolismo , Glândulas Exócrinas/fisiologia , Receptores Adrenérgicos alfa/metabolismo , Animais , Catecolaminas/antagonistas & inibidores , Relação Dose-Resposta a Droga , Glândulas Exócrinas/metabolismo , Técnicas Histológicas , Norepinefrina/metabolismo , Fenilefrina/metabolismo , Reserpina/farmacologiaRESUMO
Os efeitos produzidos pelas peçonhas escorpiônicas säo consequentes, em sua maioria, à liberaçäo de acetilcolina (ACh) e catecolaminas. A verificaçäo de que o magnésio (Mg2+) inibe a liberaçäo de ACh em razäo de bloquear o influxo de cálcio nas terminaçöes nervosas, levou-nos a investigar a açäo deste cátion sobre os distúrbios produzidos pelas peçonhas escorpiônicas. Relatamos na presente comunicaçäo a açäo do Mg2+ sobre os efeitos induzidos pelas peçonhas dos escorpiöes Tityus serrulatus, T. bahiensis e Centruroides sculpturatus nas preparaçöes isoladas nervo frênico-diafragma, íleo, canal deferente e átrios de rato e in vivo, em ratos anestesiados com registro da pressäo arterial e do eletrocardiograma. Os efeitos da peçonha dos escorpiöes nas preparaçöes isoladas foram abolidos ou muito atenuados pelo Mg2+. O Mg2+, no entanto, somente antagonizou os efeitos da peçonha de C. sculpturatus no íleo de rato. Em ratos anestesiados, a hipertensäo e arritmias provocadas pela peçonha de T. serrulatus foram revertidas com exclusäo de bradicardia pela injeçäo do Mg2+. A peçonha de C. sculpturatus na maioria das experiências causou hipotensäo e arritmias de pequena gravidade. O Mg2+ reverteu as arritmias, mas causou quedas acentuadas da pressäo arterial. Os resultados da pesquisa sugerem o emprego do Mg2+ em acidentes graves na ausência de hipotensäo e bradicardia, produzidos por T. serrulatus e T. bahiensis. Parece contra-indicado nos acidentes causados por C. sculpturatus em vista de seu efeito acima referido na pressäo arterial.
Assuntos
Animais , Ratos , Acetilcolina/antagonistas & inibidores , Catecolaminas/antagonistas & inibidores , Átrios do Coração/efeitos dos fármacos , Íleo , Magnésio/farmacologia , Magnésio/uso terapêutico , Nervo Frênico , Picada de Aranha/terapia , Ducto Deferente/efeitos dos fármacos , Venenos de Escorpião/antagonistas & inibidores , Venenos de Escorpião/farmacologia , Arritmias Cardíacas/terapia , Frequência Cardíaca , Pressão Arterial , Ratos Wistar , EscorpiõesRESUMO
The cardiovascular effects of catecholamines intrathecally (i.t.) injected at the T12-L1 level were analyzed in pentobarbital anesthetized rats. Volumes of injection were not greater than 3 microliters. Noradrenaline in doses ranging from 0.03 to 0.3 micrograms (i.t.) did not alter the mean blood pressure (MBP) while higher doses (1, 3 and 10 micrograms, i.t.) caused a dose-dependent increase in MBP. Adrenaline induced hypotensive effects at low doses (0.03-0.3 micrograms i.t.) and pressor effects at high doses (3 and 10 micrograms, i.t.). Neither adrenaline nor noradrenaline modified the heart rate. The pressor responses to both catecholamines were antagonized by the alpha 1-adrenoceptor blocker prazosin (0.05-1 microgram, i.t.) and by the selective alpha 1A-adrenoceptor antagonist 5-methyl urapidil (10 and 15 micrograms, i.t.). In contrast, these pressor effects were not modified by the alpha 1B-adrenoceptor antagonist chloroethylclonidine (90 micrograms i.t.). In animals pretreated with 1 microgram prazosin (i.t.), low doses of noradrenaline (0.03 and 0.1 microgram, i.t.) caused a hypotensive effect. Prazosin (1 microgram i.t.) failed to alter the hypotension caused by 0.1 microgram adrenaline. The hypotensive response induced by either 0.1 microgram noradrenaline (in the presence of prazosin) or 0.1 microgram adrenaline was blocked by the alpha 2-adrenoceptor antagonist yohimbine (1 mg/kg, i.v.), by the GABA-A antagonists bicuculline (3.2 micrograms, i.t.) and picrotoxin (2.7 micrograms, i.t.), and by the GABA-B antagonist 2-hydroxy saclofen (30 micrograms, i.t.). The glycine-receptor antagonist strychnine (25 micrograms, i.t.) did not modify the hypotension induced by either noradrenaline (in the presence of prazosin) or adrenaline. These findings suggest that in the low thoracolumbar spinal cord of pentobarbital-anesthetized rats, noradrenaline and adrenaline have excitatory as well as inhibitory effects on the control of the BP. The pressor responses of high doses of i.t. injected catecholamines could be mediated by the activation of spinal alpha 1A-adrenoceptors, although the participation of alpha 1B-adrenoceptors cannot be rule out entirely. The hypotensive responses induced by low doses of i.t. injected catecholamines seem to involve the activation of spinal alpha 2A-adrenoceptors and the stimulation of an inhibitory GABAergic neuron in the spinal cord.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Catecolaminas/farmacologia , Agonistas Adrenérgicos/administração & dosagem , Agonistas Adrenérgicos/farmacologia , Antagonistas Adrenérgicos/farmacologia , Anestesia , Animais , Catecolaminas/administração & dosagem , Catecolaminas/antagonistas & inibidores , Clonidina/farmacologia , Epinefrina/administração & dosagem , Epinefrina/antagonistas & inibidores , Epinefrina/farmacologia , Feminino , Glicinérgicos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Injeções Intravenosas , Injeções Espinhais , Masculino , Norepinefrina/administração & dosagem , Norepinefrina/antagonistas & inibidores , Norepinefrina/farmacologia , Ratos , Ácido gama-Aminobutírico/fisiologiaRESUMO
Sleep disturbances are frequently associated with the use of antihypertensive drugs. They are observed mainly during the administration of drugs that affect central adrenergic mechanisms. Beta-adrenoceptor antagonists which readily penetrate into the brain (propranolol, pindolol) increase wakefulness and/or decrease REM sleep. Alpha 2-adrenoceptor agonists (clonidine, guanfacine) markedly reduce the duration of REM sleep. The catecholamine depleting agent reserpine increases REM sleep during single or repeated-dose administration, while the MAOI phenelzine shows opposite effects. The 5-HT2 antagonist ritanserin, which is chemically related to the antihypertensive agent ketanserin, increases slow wave sleep while REM sleep is decreased. Sleep disturbances have not been reported during the administration of calcium entry antagonists. However, they seem to modify the effects of hypnotics and CNS stimulants. There are no formal studies on the effects of angiotensin converting enzyme inhibitors and vasodilators on sleep in man.
Assuntos
Anti-Hipertensivos/efeitos adversos , Transtornos do Sono-Vigília/induzido quimicamente , Vigília/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/efeitos adversos , Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/efeitos adversos , Antagonistas Adrenérgicos alfa/farmacologia , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/farmacologia , Anti-Hipertensivos/farmacologia , Cálcio/antagonistas & inibidores , Catecolaminas/antagonistas & inibidores , Humanos , Inibidores da Monoaminoxidase/efeitos adversos , Inibidores da Monoaminoxidase/farmacologia , Receptores de Serotonina/efeitos dos fármacos , Sono REM/efeitos dos fármacosRESUMO
Con el fin de estudiar la participación de las catecolaminas (CA) en el proceso del crecimiento folicular y la ovulación en el animal adulto, se analizaron los efectos de la depleción aguda de CA por la administración de reserpina (RSP) (1 mg/KG) sobre la respuesta ovulatoria de animales tratados con FSH y LH. Dado que previamente se mostró que la sección bilateral de los nervios vago provoca aumento en el número de ovocitos liberados por animal ovulante se analizaron los efectos de la vagotomía bilateral previa a la denervación aguda provocada por RSP. La inyección de RSP 3 horas antes de la administración de FSH provocó aumento del número de ovocitos liberados (21.49 ñ 2.87 vs 11.84 ñ 1.58, P < 0.01), del peso de los ovarios (66.20 ñ 4.41 vs. 49.79 ñ 3.99 mg/100 peso corporal, P < 0.01) y disminución del número de folículos preovulatorios. En los animales tratados con RSP 3 horas antes que recibieran LH (53 horas después que fueron tratados con FSH) no se observaron cambios significativos en el número de ovocitos, ni en el peso de los ovarios, en relación con los testigos tratados con FSH y LH. La sección previa (20 días de los nervios vago bloqueó los efectos de la administración de RSP antes de la FSH (ovocitos 5.21 ñ 1.51 vs. 21.49 ñ 2.87, P < 0.001; peso de los ovarios 36.51 ñ 2.38 vs. 66.20 ñ 4.41 mg/100 g, P < 0.001). La sección bilateral de los nervios vago no modificó los resultados obtenidos por la administración de RSP antes de LH. Los resultados del presente estudio sugieren que en condiciones normales las CA tendrían efectos inhibidores sobre el número de receptores foliculares a FSH, mientras que no parecen intervenir en los receptores a LH vinculados al proceso de ovulación. El hecho que la sección bilateral de los nervios vago revierta los efectos de la inyección de RSP antes de la FSH sugiere que en condiciones normales la información que llevan los nervios vago al ovario es agonista con las CA
Assuntos
Ratos , Animais , Feminino , Catecolaminas/antagonistas & inibidores , Ovário/efeitos dos fármacos , Ovulação , Reserpina/farmacologia , Vagotomia , Hormônio Luteinizante/metabolismoRESUMO
Noxious electric stimulation may release sympathetic mediators, since subcutaneously administered propranolol inhibited a peripheral analgesic effect by decreasing the vocalizing response of conscious guinea pigs to electric stimulation. Local injection of noradrenaline and isoprenaline induced increased vocalization to stimulation. Propranolol inhibited the effect of noradrenaline. The activation of beta-adrenergic receptors may participate in peripheral nociceptive information.
Assuntos
Nociceptores/efeitos dos fármacos , Dor/fisiopatologia , Propranolol/farmacologia , Animais , Catecolaminas/antagonistas & inibidores , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Cobaias , Injeções Subcutâneas , Propranolol/administração & dosagemRESUMO
Plasma kininogen levels were significantly reduced in normal human blood, but not in cell-free human plasma, following 10 min in vitro exposure to, in order of decreasing effectiveness, 6 microM adrenaline, noradrenaline or isopropyl-noradrenaline. Phenoxybenzamine (0.1 mM), an alpha-receptor blocking drug, and 0.5 mM aspirin, an inhibitor of prostaglandin (PG) synthesis, inhibited the action of adrenaline, whereas 0.1 mM propranolol, a beta-receptor blocker, and 0.5 mM indomethacin, another inhibitor of the formation of PG, failed to do so. The results suggest that catecholamines are able to activate cell-mediated activation of the kallikrein system in human blood and that this process can be inhibited by aspirin.
Assuntos
Catecolaminas/farmacologia , Cininogênios/sangue , Adolescente , Adulto , Animais , Aspirina/farmacologia , Catecolaminas/antagonistas & inibidores , Feminino , Cobaias , Humanos , Íleo/efeitos dos fármacos , Técnicas In Vitro , Indometacina/farmacologia , Masculino , Pessoa de Meia-Idade , Fenoxibenzamina/farmacologia , Propranolol/farmacologiaRESUMO
In slices of isolated rat hypothalamus, the dextrophenylalanine (d-Phe) 3x10(-3)M produced an inhibition of a 47% in the fractional release of 3H-NA to the preparations of Holtzman rats, and of 39% to the Wistar rats, when the concentration of d-Phe (in this last) was of 1x10(-2)M, pointing that the effectiveness of the d-Phe is variable with the employed rat root. The mentioned effect is calcium dependent, for it was antagonized when the Ca++ was incremented in the medium of 1,68mM (normal) to 2,6mM. Neither atropine, nor phenoxybenzamine interfer the effect to the d-Phe, showing that it will not be due to mechanisms of alpha-adrenergic or muscarinic cholinergic negative feedback. For the moment it cannot be interpretated that the d-Phe effect is performed through specific negative feed-back receivers, for the possible operability of other kind of receptors such as PGs angiotensin, morphinic, etc., has not been discarded yet.