RESUMO
Twelve consecutively selected patients with multiple sclerosis and incontinence had electrophysiologic studies performed of the pudendal and perineal innervations of the anal and urinary sphincter. Single-fiber electromyogram density measurements were obtained in the external anal sphincter. Fecal incontinence was found to be unexpectedly frequent. The results suggest that incontinence in patients with multiple sclerosis is often due to the interaction of several factors, including central lesions, lesions of the conus medullaris and, also, coincidental pelvic nerve lesions associated with childbirth. Thus, incontinence is especially a problem in women with this disease.
Assuntos
Incontinência Fecal/fisiopatologia , Esclerose Múltipla/fisiopatologia , Paridade , Incontinência Urinária/fisiopatologia , Potenciais de Ação , Adulto , Idoso , Canal Anal/fisiopatologia , Eletromiografia , Incontinência Fecal/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios Motores/fisiologia , Esclerose Múltipla/complicações , Músculos/fisiopatologia , Pelve/inervação , Nervos Periféricos/fisiopatologia , Tempo de Reação , Incontinência Urinária/etiologiaRESUMO
1. The affinities of a number of alpha 1-adrenoceptor antagonists were determined by displacement of [3H]-prazosin binding from cloned human alpha 1A-adrenoceptors (previously designated cloned alpha 1c subtype), alpha 1B alpha 1D and rat alpha 1D-adrenoceptors, stably expressed in rat-1 fibroblasts. Functional affinity estimates for these compounds were also determined from noradrenaline-mediated contractions of rat aorta. 2. BMY 7378 displayed high affinity for cloned human alpha 1D-adrenoceptors (pKi = 8.2 +/- 0.10) and was selective over alpha 1A (pKi = 6.2 +/- 0.10) and alpha 1B subtypes (6.7 +/- 0.11). WB 4101, benoxathian and phentolamine displayed high affinity for alpha 1A and alpha 1D adrenoceptors compared to the alpha 1B subtype. Spiperone displayed high affinity and selectivity for alpha 1B adrenoceptors (pKi 8.8 +/- 0.16). 5-Methyl-urapidil was selective for cloned alpha 1A adrenoceptors. 3. Comparative binding affinities (pKi) for compounds at cloned human and rat1D adrenoceptors were almost identical (r = 0.99, slope = 1.08). 4. Prazosin, doxazosin and 5-methyl-urapidil were potent, competitive antagonists of noradrenaline-mediated contractions of rat aorta (pA2 values of 9.8, 8.8 and 7.8 respectively). The selective alpha 1D antagonist BMY 7378 was also a potent antagonist on rat aorta (pKB = 8.3 +/- 0.1) but the interaction of this compound was not consistent with competitive antagonism at a single population of receptors. 5. Functional affinities for compounds determined against noradrenaline-mediated contractions of rat aorta correlated well with binding affinities at cloned alpha 1D-adrenoceptors (r = 0.96), but not with alpha 1A (r = 0.61) or alpha 1B (r = 0.46) subtypes. 6. Noradrenaline-mediated contractions of rat aorta were sensitive to the alkylating effects of chlorethylclonidine (CEC). CEC (10 microM) caused a small rightward shift in the noradrenaline concentration-response curve. CEC at 100 microM caused a further shift and suppression of the maximum response to noradrenaline.7. The results of this study suggest that noradrenaline predominantly, but not exclusively, mediates contraction of rat aorta through the activation of an alphalD-adrenoceptor.
Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1 , Aorta/efeitos dos fármacos , Norepinefrina/farmacologia , Receptores Adrenérgicos alfa 1/efeitos dos fármacos , Animais , Ligação Competitiva , Relação Dose-Resposta a Droga , Doxazossina/farmacologia , Masculino , Piperazinas/farmacologia , Prazosina/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos alfa 1/fisiologia , VasodilataçãoRESUMO
1. The profile of a range of alpha 1 adrenoceptor antagonists was determined in vitro against cloned human alpha 1A, alpha 1B and alpha 1D adrenoceptors and against noradrenaline-mediated contractions of rat aorta and human prostate. The in vivo profile of compounds was determined in an anaesthetized dog model which allowed the simultaneous assessment of antagonist potency against phenylephrine-mediated increases in blood pressure and prostatic pressure. 2. The quinazoline antagonists, prazosin, doxazosin and alfuzosin displayed high affinity but were non selective for the three cloned human alpha 1 adrenoceptors. Indoramin and SNAP 1069 showed selectivity for alpha 1A and alpha 1B adrenoceptors relative to the alpha 1D subtype. Rec 15/2739, WB 4101, SL 89,0591, (+)- and (-)- tamsulosin showed selectivity for alpha 1A and alpha 1D adrenoceptors relative to the alpha 1B subtype. RS 17053 showed high affinity and selectivity for alpha 1A adrenoceptors (pKi 8.6) relative to alpha 1B (pKi = 7.3) and alpha 1D (pKi = 7.1) subtypes. 3. (+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, SNAP 1069 and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned human alpha 1D adrenoceptors. The following rank order was obtained: prazosin = (-)-tamsulosin > doxazosin > SL 89,0591 = (+)-tamsulosin > Rec 15/2739 > RS 17053 = SNAP 1069. 4. (-)-Tamsulosin was a very potent, insurmountable antagonist of noradrenaline-mediated contractions of human prostate, yielding an approximate pA2 estimate of 9.8 at 1 nM. The corresponding (+)-enantiomer was 30 fold weaker. SL 89,0591, SNAP 1069 and Rec 15/2739 yielded pA2 estimates which compared well with their alpha 1A binding affinities. The affinity estimate for prazosin on human prostate was lower than the corresponding binding affinity determined at alpha 1A adrenoceptors and RS 17053 was a very weak antagonist on human prostate (pA2 = 6.0) relative to the high affinity (pKi = 8.6) determined at cloned human alpha 1A adrenoceptors. 5. In the anaesthetized dog, in vivo pseudo "pA2' values showed that doxazosin, (+)- and (-)-tamsulosin inhibited phenylephrine-induced increases in prostatic and blood pressure with similar affinity, implying that these agents show little or no selectivity for prostatic responses in this model. SL 89,0591 and SNAP 1069 were moderately selective (3 and 6 fold respectively) for prostatic pressure relative to blood pressure. Rec 15/2739 was a more potent antagonist of phenylephrine-mediated increases in prostatic pressure ("pA2' = 8.74) compared to blood pressure ("pA2' = 7.51). 6. Data in this study suggest that the alpha 1 adrenoceptor mediating noradrenaline-induced contractions of human prostate, whilst having some of the characteristics of an alpha 1A adrenoceptor, cannot be satisfactorily aligned with cloned alpha 1A, alpha 1B or alpha 1D adrenoceptors. In addition, studies in the anaesthetized dog have shown that agents having high affinity and selectivity for prostatic alpha 1 adrenoceptors, particularly over the alpha 1D subtype, appear to inhibit phenylephrine-induced increases in prostatic pressure selectively compared to blood pressure.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Aorta Torácica/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Norepinefrina/farmacologia , Próstata/efeitos dos fármacos , Receptores Adrenérgicos alfa 1/metabolismo , Antagonistas Adrenérgicos alfa/metabolismo , Animais , Cães , Relação Dose-Resposta a Droga , Doxazossina/metabolismo , Doxazossina/farmacologia , Humanos , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Norepinefrina/antagonistas & inibidores , Fenilefrina/farmacologia , Prazosina/metabolismo , Prazosina/farmacologia , Pressão , Próstata/citologia , Próstata/metabolismo , Próstata/fisiologia , Quinazolinas/metabolismo , Quinazolinas/farmacologia , Ratos , Ratos Sprague-Dawley , Sulfonamidas/antagonistas & inibidores , Sulfonamidas/farmacologia , TansulosinaRESUMO
In this study 12 patients with drug-resistant hypertension after renal transplantation had their own kidneys ablated by therapeutic embolisation. The technical aspects of the procedure are described in detail. An improvement in blood-pressure control was achieved in eight of the 12 patients. These results are similar to those which have been reported after bilateral nephrectomy. It is concluded that embolisation of the host kidneys is a simple, effective and less hazardous alternative to surgery in the treatment of severe hypertension after renal transplantation.
Assuntos
Embolização Terapêutica , Hipertensão Renal/prevenção & controle , Transplante de Rim , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Radiografia , Artéria Renal/diagnóstico por imagemAssuntos
Morte Súbita/etiologia , Metilprednisolona/efeitos adversos , Adulto , Anafilaxia/induzido quimicamente , Anafilaxia/patologia , Feminino , Rejeição de Enxerto/efeitos dos fármacos , Humanos , Injeções Intravenosas , Rim/efeitos dos fármacos , Transplante de Rim , Metilprednisolona/administração & dosagemAssuntos
Ciclosporinas/efeitos adversos , Nefropatias/induzido quimicamente , Transplante de Rim , Sulfametoxazol/efeitos adversos , Trimetoprima/efeitos adversos , Creatinina/sangue , Combinação de Medicamentos/efeitos adversos , Interações Medicamentosas , Humanos , Masculino , Combinação Trimetoprima e SulfametoxazolRESUMO
A percutaneous embolisation technique was used for host kidney ablation in 13 patients with renal allografts and hypertension. Markedly improved blood pressure control was achieved in 9 of them, and morbidity was minimal. All patients have been followed from 12 to 25 months. Embolisation of the host kidneys appears to be a simple, effective, and less hazardous alternative to surgery in the treatment of drug-resistant hypertension after renal transplantation in some patients.