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1.
Artigo em Inglês | MEDLINE | ID: mdl-37997585

RESUMO

Multifilamentary MgB2 strands (filament numbers 36 to 114) prepared by the in-situ power-in-tube (PIT) route with carbon doping contents of 0, 2, and 3.2% were wound on barrels for transport Jc and n-value measurement at 4.2 K in fields of up to 12 T. The strand and gauge lengths were 1 m and 0.5 m. Heat treatments at 675 °C and 650 °C centered around the melting point of Mg (650 °C) and both utilized the liquid-solid reaction. A pair of strands, with and without 2% C doping exhibited the Jc (B) crossover effect. Studied were the dependencies of Jc on field strength, dopant concentration, and cabling and the dependence of n-value on field strength.

2.
Bone Rep ; 12: 100257, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32551335

RESUMO

Currently, the Spinal Instability Neoplastic Score system is used in clinics to evaluate the risk of fracture in patients with spinal metastases. This method, however, does not always provide a clear guideline due to the complexity in accounting for the effect of metastatic lesions on vertebral stability. The aim of this study was to use a validated micro Finite Element (microFE) modelling approach to analyse the effect of the size and location of lytic metastases on the mechanical properties of human vertebral bodies. Micro Computed Tomography based microFE models were generated with and without lytic lesions simulated as holes within a human vertebral body. Single and multiple lytic lesions were simulated with four different sizes and in five different locations. Bone was assumed homogenous, isotropic and linear elastic, and each vertebra was loaded in axial compression. It was observed that the size of lytic lesions was linearly related with the reduction in structural properties of the vertebral body (reduction of stiffness between 3% and 30% for lesion volume between 4% and 35%). The location of lytic lesions did not show a clear effect on predicted structural properties. Single or multiple lesions with the same volume provided similar results. Locally, there was a homogeneous distribution of axial principal strains among the models with and without lytic lesions. This study highlights the potential of microFE models to study the effect of lesions on the mechanical properties of the human vertebral body.

3.
Sci Rep ; 10(1): 5538, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32218496

RESUMO

Osteoarthritis affects the morphological properties of the femoral head. The goal of this study was to develop a method to elucidate whether these changes are localised to discrete regions, or if the reported trends in microstructural changes may be identified throughout the subchondral bone of the human femoral head. Whole femoral heads extracted from osteoarthritic (n = 5) and healthy controls (n = 5) underwent microCT imaging 39 µm voxel size. The subchondral bone plate was virtually isolated to evaluate the plate thickness and plate porosity. The trabecular bone region was divided into 37 volumes of interest spatially distributed in the femoral head, and bone morphometric properties were determined in each region. The study showed how the developed approach can be used to study the heterogeneous properties of the human femoral head affected by a disease such as osteoarthritis. As example, in the superior femoral head osteoarthritic specimens exhibited a more heterogeneous micro-architecture, with trends towards thicker cortical bone plate, higher trabecular connectivity density, higher trabecular bone density and thicker structures, something that could only be observed with the newly developed approach. Bone cysts were mostly confined to the postero-lateral quadrants extending from the subchondral region into the mid trabecular region. Nevertheless, in order to generalise these findings, a larger sample size should be analysed in the future. This novel method allowed a comprehensive evaluation of the heterogeneous micro-architectural properties of the human femoral head, highlighting effects of OA in the superior subchondral cortical and trabecular bone. Further investigations on different stages of OA would be needed to identify early changes in the bone.


Assuntos
Cistos Ósseos/diagnóstico por imagem , Cabeça do Fêmur/patologia , Osteoartrite do Quadril/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Cistos Ósseos/patologia , Estudos de Casos e Controles , Feminino , Cabeça do Fêmur/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/patologia , Microtomografia por Raio-X
4.
Biomech Model Mechanobiol ; 17(6): 1715-1730, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29987700

RESUMO

The calcaneus bone is formed of extensive trabecular bone and is therefore well suited to be used as an example of loaded bone to establish the ability of combining microfinite element (microFE) technique with high-resolution peripheral quantitative computed tomography (HR-pQCT) in determining its mechanical properties. HR-pQCT is increasingly used as a tool for in vivo bone clinical research, but its use has been limited to the distal radius and tibia. The goal of this study was to determine the applicability of HR-pQCT-derived microFE models of the calcaneus trabecular bone with 82 µm voxel size with reference to higher-resolution microCT-based models taken as gold standard. By comparing the outputs of microFE models generated from both HR-pQCT and microCT images of the trabecular bone of five calcaneus cadaveric specimens, it was found that the HR-pQCT-based models predicted mechanical properties for fracture load, total reaction force and von Mises stress are considerably different from microCT-based counterparts by 33, 64 and 70%, respectively. Also, the morphological analysis showed a comprehensive geometrical difference between HR-pQCT-based microFE models and their microCT-based equivalents. The results of the HR-pQCT-based models were found to have strong dependency on the threshold value chosen to binarise the images prior to finite element modelling. In addition, it was found that the voxel size has a strong impact on accuracy of imaged-based microFE models compared to other factors such as the presence of soft tissue and image scanning integration time. Therefore, although HR-pQCT has shown to be useful to predict overall structural and biomechanical changes, it is limited in providing local accurate biomechanical properties of trabecular bone and therefore should be used with caution when assessing bone remodelling through local changes of trabecular bone apposition and resorption in disease treatment monitoring.


Assuntos
Calcâneo/diagnóstico por imagem , Osso Esponjoso/anatomia & histologia , Análise de Elementos Finitos , Modelos Anatômicos , Tomografia Computadorizada por Raios X , Microtomografia por Raio-X , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Calcâneo/anatomia & histologia , Osso Esponjoso/diagnóstico por imagem , Feminino , Humanos , Tamanho do Órgão , Estresse Mecânico
5.
Foot Ankle Surg ; 17(3): 186-92, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21783082

RESUMO

BACKGROUND: The Achillon jig permits the placement of sutures deep to the fascia cruris and the paratenon through the substance of the ruptured tendon, permitting a safe minimally invasive repair. Our experience has suggested that these two layers may not be as clearly delineated as first thought or may merge at an, as yet, undefined level. METHODS: We performed an anatomical and radiological (US and MRI) study of the layers of tissue superficial to the Achilles tendon in cadaveric specimens. RESULTS: The mean distance for the confluence of the fascia cruris and paratenon from the postero-superior calcaneal tubercle (PSCT) was found to be 37.3mm (range 17-58mm). Ultrasound examination was found to be less distinct than MRI scanning. CONCLUSIONS: We recommend careful identification of the fascia cruris and paratenon and insertion of the central branches of the jig adjacent to the tendon substance when using this method for repair.


Assuntos
Tendão do Calcâneo/anatomia & histologia , Tendão do Calcâneo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Cadáver , Fáscia , Humanos , Ultrassonografia
6.
Colorectal Dis ; 8(8): 717-20, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16970585

RESUMO

BACKGROUND: Use of Nicorandil in the treatment of ischaemic heart disease has been associated with oral, ileal and more recently anal ulceration. We report a series of six cases of peri-anal ulceration in patients on nicorandil therapy, their response to withdrawal of the drug and review the literature. METHODOLOGY: Systematic case note review of all patients with anal ulceration presenting to a single colorectal unit. Including detailed medical and drug history, morphological and histological appearances of the peri-anal ulcer after biopsy. Nicorandil therapy stopped in conjunction with physician and the progress of the ulcer monitored. Photographs taken before and after cessation of Nicorandil after informed consent. A literature search on Nicorandil combined with the key words: anal, peri-anal, ulceration and adverse drug effects was performed using the Cochrane Library Medline (January 1966 to June 2005) and Embase (January 1974 to June, 2005). RESULTS: Six patients were identified from our hospital records. Histological examination of all ulcers revealed nonspecific chronic inflammation. Five patients demonstrated healing of ulceration within six weeks of withdrawal of Nicorandil, the remaining patient had circumferential involvement of the anal canal and has not improved at 3-month review. One patient was recommenced on Nicorandil after healing due to refractory angina and ulceration recurred. CONCLUSIONS: We believe ulceration due to Nicorandil remains widely under diagnosed and the mechanism of ulceration is unclear. Despite diversion colostomy one of our patients continued with peri-anal ulceration, which may suggest a systemic mechanism rather than local irritation. Biopsy of these lesions is essential to exclude neoplastic process and inflammatory bowel disease.


Assuntos
Fissura Anal/induzido quimicamente , Fissura Anal/patologia , Isquemia Miocárdica/tratamento farmacológico , Nicorandil/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nicorandil/uso terapêutico
7.
J Am Board Fam Pract ; 12(2): 137-42, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10220237

RESUMO

BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy), a compound chemically related to stimulant and hallucinogenic drugs, has been found to induce a state of euphoria and increased self-awareness. MDMA has been increasingly used for recreational purposes, especially among college students and other young adults, and has been associated with multiple toxic effects. METHODS: Using MEDLINE, the medical literature was searched from 1986 using the key words "ecstasy," "MDMA," and "designer drugs." Articles dating before 1986 were accessed from cross-reference of the more recent articles. A case report is described. RESULTS: MDMA was developed in 1912 as an appetite suppressant but never became commercially successful. It resurfaced in the 1950s as a psychotherapeutic agent. In 1985 MDMA was classified as a schedule 1 drug by the Food and Drug Administration after reports of neurotoxicity in laboratory animals. It again resurfaced in the mid 1980s as a recreational drug used primarily among college students and other young adults. There are a number of case reports describing toxic effects from MDMA, including hyperthermia, rhabdomyolysis, coagulopathy, and acute renal failure. Little information is available regarding acute management or treatment of toxic ingestions. CONCLUSIONS: MDMA ingestion has been associated with severe toxic effects. Although the literature describes numerous cases of toxic ingestion, there are no published recommendations or suggestions to guide physicians in the evaluation and treatment of such cases. By reviewing the history, neurochemistry, and toxicology of MDMA, as well as providing some guidance regarding management of toxic ingestion, we can arm the provider with valuable information for use in the acute setting. In addition, this information will assist providers in counseling young adults regarding the possible consequences of using this substance.


Assuntos
Alucinógenos , N-Metil-3,4-Metilenodioxianfetamina , Adulto , Animais , Encéfalo/efeitos dos fármacos , Overdose de Drogas/terapia , Alucinógenos/história , Alucinógenos/farmacologia , História do Século XX , Humanos , Masculino , N-Metil-3,4-Metilenodioxianfetamina/história , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/diagnóstico
8.
Eur J Vasc Endovasc Surg ; 14(5): 399-402, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9413382

RESUMO

OBJECTIVES: To investigate the in vivo haemodynamic performance and neurological outcome of two types of carotid shunt. DESIGN: Randomised single surgeon study of consecutive symptomatic patients. SETTING: 163 consecutive patients undergoing carotid endarterectomy for symptomatic carotid disease were randomised to the Javid or Pruitt shunt. CHIEF OUTCOME MEASURES: Middle cerebral artery velocity (MCAV), preoperatively, during clamping, during shunting and post-restoration of flow, embolic episodes, neurological outcome. MAIN RESULTS: The MCAV preoperatively, at carotid clamping, and postoperatively was the same for both groups (p > 0.15). During shunting the MCAV was significantly lower in the Pruitt group, p < 0.005, 59% of the Javid and 34% of the Pruitt shunts maintained MCAV at preoperative levels p < 0.005, chi 2 = 8.92. The Javid shunt produced significantly more emboli (73% of cases) at declamping than the Pruitt (41%), p < 0.0002, chi 2 = 14.7. Four Javid patients and one Pruitt had disabling thromboembolic strokes; overall thromboembolic stroke rate 3.7%. The difference in stroke rates was not statistically significant (p = 0.14). CONCLUSIONS: The Pruitt shunt was unable to maintain preoperative MCAV in 66% of cases, the Javid shunt had a higher incidence of emboli on declamping. These factors may lead to an increased risk of stroke; however, the numbers required for statistical confirmation would be large.


Assuntos
Velocidade do Fluxo Sanguíneo , Artérias Cerebrais/fisiologia , Endarterectomia das Carótidas/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ecoencefalografia , Endarterectomia das Carótidas/efeitos adversos , Feminino , Humanos , Embolia e Trombose Intracraniana/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Am Fam Physician ; 56(6): 1631-6, 1638, 1997 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-9351431

RESUMO

Family physicians who provide obstetric care may periodically encounter a patient with a history of epilepsy, which may manifest before or after pregnancy. In either case, several issues need to be addressed. Pregnant women with epilepsy may have an increased frequency of seizures, with the potential for resultant maternal and fetal morbidity and mortality. Teratogenic effects of antiepileptic drugs include craniofacial abnormalities and neural tube defects. Management strategies include the prenatal use of folic acid and vitamin K, monotherapy with a single antiepileptic drug, and obtaining at least monthly free serum drug levels. Fortunately, with close monitoring and proper management, more than 90 percent of pregnancies in women with epilepsy will be uncomplicated.


Assuntos
Epilepsia , Complicações na Gravidez , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Feminino , Humanos , Educação de Pacientes como Assunto , Guias de Prática Clínica como Assunto , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/tratamento farmacológico
10.
Eur J Vasc Endovasc Surg ; 11(1): 90-7, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8564494

RESUMO

OBJECTIVES: The effect of a plain 48-wire self-expanding flexible stent (Wallstent-Schneider (Europe) AG) on abdominal aortic aneurysms has been studied in a new animal model. METHODS: Aneurysms were created by interposing fusiform segments of glutaraldehyde-tanned bovine internal jugular vein into the infrarenal aortas of 12 Large White pigs. The first six pigs were assessed after 6 weeks by ultrasonography and arteriography; they were then sacrificed for pathological examination. Endovascular placement of the stents, 2 weeks after aneurysm creation, was performed under arteriographic control in the next six pigs. These pigs were assessed by ultrasonography and arteriography 6 weeks after stenting; they were then sacrificed for pathological examination. RESULTS: At 6 weeks the aneurysms in the first group were pulsatile with partial endothelialisation and no mural thrombus. Placement of the stent in the second group was accomplished easily. Stenting resulted in an immediate reduction in wall pulsatility of all aneurysms and thrombosis of the excluded aneurysm sac occurred in three cases. In the other three cases the pulse pressure in the sac was reduced. In all cases there was a significant reduction in maximum aneurysm diameter when measured 6 weeks after stenting. CONCLUSIONS: A pulsatile, non-thrombogenic aortic aneurysm model approaching human dimensions has been successfully developed for the study of endoprostheses prior to their clinical use. Endovascular placement of a plain, multiple-wire Wallstent was associated with reductions in aneurysm pulsatility, pulse pressure within the sac and maximum aneurysm diameter over the study period. Stenting was associated with thrombosis of the excluded aneurysm sac in 50% of cases.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Modelos Animais de Doenças , Stents , Suínos , Animais , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/patologia , Aortografia , Endotélio Vascular/patologia , Feminino , Ultrassonografia
12.
Physiol Behav ; 55(4): 723-6, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8190801

RESUMO

A number of problems are associated with investigation of the pathophysiology of peripheral vascular disease (PVD) in humans and unilateral ligation of the common iliac artery in the rat has been extensively used as an experimental model of PVD. However, techniques so far applied to monitor the effects of PVD on muscular function are invasive and difficult to relate to natural locomotion. The present study aimed to investigate gait during spontaneous, unforced locomotion in the animal model. No differences were observed between control and experimental rats in velocity or stride lengths. Although stride time was unchanged, its internal balance was disturbed with reduced stance, prolonged swing, for the ligated limb (LL) relative to the nonligated limb (NLL). Gait symmetry was also affected with NLL strike occurring earlier during LL stance. Analysis of footfall patterns showed a reduction of stance area and pressures exerted via LL relative to NLL. It is concluded that gait and footfall analysis could be useful for assessing limb function under natural exercise conditions.


Assuntos
Arteriopatias Oclusivas/fisiopatologia , Modelos Animais de Doenças , Marcha/fisiologia , Animais , Lateralidade Funcional/fisiologia , Membro Posterior/irrigação sanguínea , Claudicação Intermitente/fisiopatologia , Isquemia/fisiopatologia , Locomoção/fisiologia , Masculino , Ratos , Ratos Wistar , Tempo de Reação/fisiologia , Suporte de Carga/fisiologia
13.
Int J Microcirc Clin Exp ; 14(1-2): 27-33, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7960440

RESUMO

Reperfusion injury is responsible for the failure of up to 15% of otherwise successful lower limb bypass procedures for critical limb ischaemia. It is also responsible for complications in myocardial revascularisation, organ transplantation and free flap transfers. The majority of experimental work investigating reperfusion injury has studied acute ischaemia in normal tissues which may reflect the situation in organ transplantation and free flap transfers, but in vascular reconstructive surgery the distal limb circulation is severely compromised prior to surgery. In the present study a model of chronic ischaemia in the rat hind limb has been produced by ligation of the left common iliac artery. Femoral artery blood pressure and flow measurements showed a mean reduction to 53% and 41% respectively when compared to the contralateral limb. These changes were maintained for up to nine weeks following ligation of the common iliac artery. Contrast arteriography was used to establish the anatomy of the collaterals and demonstrated that the femoral artery is an end artery. This technique provides a model of experimental chronic ischaemia which is stable for up to nine weeks and may be used to investigate the mechanisms involved in the reperfusion injury.


Assuntos
Hemodinâmica/fisiologia , Membro Posterior/irrigação sanguínea , Isquemia/fisiopatologia , Traumatismo por Reperfusão/fisiopatologia , Anestésicos , Angiografia , Animais , Pressão Sanguínea/fisiologia , Capilares/fisiologia , Doença Crônica , Modelos Animais de Doenças , Masculino , Microscopia de Fluorescência , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional/fisiologia
14.
Eur J Vasc Surg ; 7(4): 470-4, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7689490
15.
Injury ; 24(6): 377-9, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8406741

RESUMO

Five cases of combined brachial plexus root avulsion and subclavian artery trauma are presented. A policy of preoperative myelography and minimal vascular reconstruction in the presence of root disruption is discussed.


Assuntos
Plexo Braquial/lesões , Traumatismo Múltiplo/cirurgia , Artéria Subclávia/lesões , Ferimentos não Penetrantes/cirurgia , Acidentes de Trânsito , Adolescente , Adulto , Idoso , Plexo Braquial/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motocicletas , Mielografia , Artéria Subclávia/cirurgia , Ferimentos não Penetrantes/diagnóstico por imagem
16.
Circ Shock ; 36(2): 154-61, 1992 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1582007

RESUMO

Splanchnic artery occlusion (SAO) with reperfusion results in a severe form of circulatory shock. To study the possible involvement of adenosine in this shock state, we have examined the effects of adenosine, an adenosine A1-receptor antagonist, and their combination in a rat model of SAO shock. Pentobarbital-anesthetized rats were subjected to a 90-min occlusion of both the celiac and superior mesenteric arteries followed by reperfusion. Rats given only the vehicle for adenosine (i.e., 0.9% NaCl) developed severe hypotension following reperfusion, and the survival rate was less than 30% 2 hr after reperfusion. Final plasma free amino-nitrogen concentrations, cathepsin D and myocardial depressant factor (MDF) activities were significantly elevated in rats receiving only the vehicle. Infusion of adenosine (i.e., 30 micrograms/kg/min, i.v.), starting 45 min postocclusion, did not significantly improve the survival rate but did attenuate the accumulation of MDF. Eighty percent (i.e., 4 of 5) rats given KF15372, an adenosine A1-antagonist, 45 min postocclusion (500 micrograms/kg), survived 2 hr. KF15372 also attenuated the increased plasma free amino-nitrogen and MDF. Seventy-five percent (i.e., 6 of 8) rats treated with KF15372 and adenosine survived 2 hr. This combined treatment significantly attenuated the increased plasma levels of free amino-nitrogen, cathepsin D, and MDF. These results suggest that endogenous adenosine plays a significant role in the pathogenesis of shock following SAO and reperfusion, and that blockade of the adenosine A1-receptor could be beneficial in shock states.


Assuntos
Adenosina/farmacologia , Isquemia/tratamento farmacológico , Antagonistas Purinérgicos , Xantinas/farmacologia , Adenosina/antagonistas & inibidores , Animais , Catepsina D/sangue , Catepsina D/efeitos dos fármacos , Modelos Animais de Doenças , Interações Medicamentosas , Hemodinâmica/efeitos dos fármacos , Masculino , Fator Depressor Miocárdico/sangue , Fator Depressor Miocárdico/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Reperfusão , Circulação Esplâncnica
17.
Circ Shock ; 33(3): 135-41, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2044207

RESUMO

Splanchnic artery occlusion (SAO) with subsequent reperfusion elicits a severe form of circulatory shock. To study the possible involvement of Ca2+ overload in this shock state, we have examined the effects of benidipine, a novel long-acting calcium antagonist, in a rat model of SAO shock, focusing on endothelial damage. Pentobarbital-anesthetized rats were subjected to 90-min occlusion of both the celiac and superior mesenteric arteries, followed by reperfusion. Rats given only the vehicle for benidipine developed hypotension following reperfusion, and only 7 of 16 rats (44%) survived 2 hr of reperfusion. In isolated superior mesenteric rings from SAO-shock rats, the EDRF-dependent dilator response to acetylcholine (ACh) (100 mM) was severely depressed (9% vs. 97% in control artery rings, P less than 0.001), whereas the EDRF-independent dilator response to acidified NaNO2 (100 microM) was unchanged. By contrast, 90% (9 of 10, P less than 0.05) rats treated with benidipine 45 min postocclusion (3 micrograms/kg, i.v.) survived 2 hr, and the dilator response to ACh was markedly improved (49% of initial, P less than 0.001). SAO-shock rats treated with benidipine also exhibited significantly attenuated accumulation of free amino-nitrogenous compounds (5.5 vs. 7.9 U/ml, P less than 0.05) and myocardial depressant factor (34 vs. 62 U/ml, P less than 0.001). These results suggest that endothelial damage plays a role in the pathogenesis of shock following bowel ischemia and reperfusion and that Ca(2+)-entry blockade improves endothelial function, which is involved in the amelioration of the shock state.


Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Endotélio Vascular/fisiopatologia , Isquemia/complicações , Artérias Mesentéricas , Choque/prevenção & controle , Acetilcolina/farmacologia , Animais , Pressão Sanguínea , Artéria Celíaca , Constrição , Cinética , Masculino , Fator Depressor Miocárdico/sangue , Ratos , Ratos Endogâmicos , Choque/etiologia , Choque/fisiopatologia , Vasodilatação/efeitos dos fármacos
18.
Methods Find Exp Clin Pharmacol ; 12(4): 231-7, 1990 May.
Artigo em Inglês | MEDLINE | ID: mdl-2165204

RESUMO

We studied the effects of BN 50739, a novel PAF antagonist, in a rat model of traumatic shock. Pentobarbital anesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by marked hypotension, significant increases in plasma cathepsin D (4.2-fold), free amino-nitrogen (2.8-fold) and myocardial depressant factor (4.7-fold) activities and a survival time of 1.62 +/- 0.16 h. Treatment with BN 50739 (10 mg/kg, i.v.) 10 min post-trauma prolonged survival time to 3.14 +/- 0.44 h (p less than 0.01) and attenuated the accumulations of cathepsin D (5.8 vs. 12.5 U/ml, p less than 0.01), free amino-nitrogen (4.6 vs. 12.5 U/ml, p less than 0.001) and myocardial depressant factor (19.4 vs. 65.1 U/ml, p less than 0.001). Moreover, in washed rabbit platelets, BN 50739 inhibited PAF (1.85 nM)-induced aggregation (IC50: 50 nM) without affecting ADP (5 microM)-induced aggregation. In anesthetized rats, BN 50739 (10 mg/kg, i.v.) attenuated PAF (10-30 ng/kg, i.v.)-induced hypotension for longer than 5 h, without influencing acetylcholine (10 micrograms/kg, i.v.)-induced hypotension. These findings indicate that BN 50739 is a specific PAF receptor antagonist with a long duration of action in vivo. The beneficial effects of PAF antagonism on traumatic shock are significant in the present study, and are consistent with the concept that PAF is involved in the pathogenesis of traumatic shock.


Assuntos
Azepinas/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Glicoproteínas da Membrana de Plaquetas , Receptores de Superfície Celular/metabolismo , Receptores Acoplados a Proteínas G , Choque Traumático/tratamento farmacológico , Triazóis/uso terapêutico , Animais , Azepinas/sangue , Pressão Sanguínea/efeitos dos fármacos , Catepsina D/sangue , Técnicas In Vitro , Masculino , Fator Depressor Miocárdico/sangue , Nitrogênio/sangue , Inibidores da Agregação Plaquetária/sangue , Coelhos , Ratos , Ratos Endogâmicos , Choque Traumático/fisiopatologia , Tromboxano B2/sangue , Triazóis/sangue
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