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1.
Comput Methods Biomech Biomed Engin ; 25(5): 543-553, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34427119

RESUMO

Computational models are increasingly used to assess spine biomechanics and support surgical planning. However, varying levels of model verification and validation, along with characterization of uncertainty effects limit the level of confidence in their predictive potential. The objective was to assess the credibility of an adult spine deformity instrumentation model for proximal junction failure (PJF) analysis using the ASME V&V40:2018 framework. To assess model applicability, the surgery, erected posture, and flexion movement of actual clinical cases were simulated. The loads corresponding to PJF indicators for a group of asymptomatic patients and a group of PJF patients were compared. Model consistency was demonstrated by finding PJF indicators significantly higher for the simulated PJF vs. asymptomatic patients. A detailed sensitivity analysis and uncertainty quantification were performed to further establish the model credibility.


Assuntos
Cifose , Fusão Vertebral , Adulto , Fenômenos Biomecânicos , Humanos , Amplitude de Movimento Articular , Estudos Retrospectivos , Coluna Vertebral/cirurgia
2.
Stud Health Technol Inform ; 140: 128-32, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18810013

RESUMO

Many new spine instrumentation concepts were introduced in recent years, like the incremental direct vertebral translation. The objective was to develop a biomechanical model in order to analyze the biomechanics of this instrumentation system. The patient-specific spine model was built using the 3D reconstruction based on bi-planar radiographs of a scoliotic patient (thoraco-lumbar Cobb: 49 degrees ). The mechanical properties were derived from literature, experiments on cadaver spines and patient's side bending radiographs. Each screw construct was modelled by four rigid bodies connected each other by kinematic joints. The screw-vertebra flexible joint was represented by 3 experimentally derived non-linear springs, and the rods by non-linear flexible elements. The correction manoeuvres were simulated by lowering the rod, tightening the crimps (incremental segmental translation) and applying secondary correction manoeuvres (direct vertebra derotation, compression, distraction and construct tightening). The simulations showed that the system allows a good force distribution among implants. The long post pushing and pulling contributed, to a great extent, to a global correction in the coronal plane, while the crimp tightening had more important effect in the sagittal plane. The preliminary results illustrated the effectiveness of local correction by a direct vertebra translation technique. Our next step is to validate the model and compare the performance of this strategy with other spinal instrumentation systems.


Assuntos
Imageamento Tridimensional/instrumentação , Vértebras Lombares/patologia , Intensificação de Imagem Radiográfica/instrumentação , Escoliose/patologia , Coluna Vertebral/patologia , Vértebras Torácicas/patologia , Fenômenos Biomecânicos/instrumentação , Estudos de Viabilidade , Humanos , Modelos Biológicos , Fatores de Tempo
3.
Br J Pharmacol ; 151(4): 450-6, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17420776

RESUMO

BACKGROUND AND PURPOSE: Liver X receptors (LXRs) activate genes that regulate lipid and cholesterol metabolism. LXR agonists were shown recently to also increase murine renin gene expression in vivo. To further examine a link between lipid metabolism, the renin-angiotensin-aldosterone-system and blood pressure regulation, we investigated the effect of a LXR agonist (GW3965) on angiotensin II (Ang II)-mediated vasoreactivity and vascular angiotensin II receptor (ATR) gene expression. EXPERIMENTAL APPROACH: Arterial blood pressure (BP) was measured during Ang II infusions (1.5 min duration; 0.001-3 microg kg(-1)) in pentobarbital-anesthetized male Sprague-Dawley rats (n = 6-9) after oral administration of GW3965 (10 mg kg(-1), q.d.) or vehicle for 7 - 15 days. Mesenteric arteries and plasma were collected to analyze ATR gene expression and to measure plasma renin activity (PRA) and lipid profile, respectively. KEY RESULTS: Basal mean arterial pressure (MAP) was similar between groups. GW3965 dosing blunted the vasopressor effect of Ang II, which was significantly different with the 0.3 and 3 microg kg(-1) doses. No difference in heart rate, PRA or lipid profile was observed between groups. A time-course indicated that ATR type 1 and 2 gene expression of GW3965-treated vs. vehicle-treated rats decreased by 50%, reaching significance for ATR type 2, but not for ATR type 1, at time-points coinciding with BP measurements. CONCLUSIONS AND IMPLICATIONS: GW3965 decreased Ang II-mediated vasopressor responses coincident with a trend toward reduced ATR gene expression, suggesting that LXR agonists could affect vascular reactivity.


Assuntos
Angiotensina II/farmacologia , Benzoatos/farmacologia , Benzilaminas/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Proteínas de Ligação a DNA/agonistas , Receptores Citoplasmáticos e Nucleares/agonistas , Animais , Proteínas de Ligação a DNA/fisiologia , Relação Dose-Resposta a Droga , Lipídeos/sangue , Receptores X do Fígado , Masculino , Receptores Nucleares Órfãos , Ratos , Ratos Sprague-Dawley , Receptores de Angiotensina/genética , Receptores Citoplasmáticos e Nucleares/fisiologia , Renina/sangue , Renina/genética
4.
J Thromb Haemost ; 4(12): 2710-5, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17010152

RESUMO

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is integrally involved in tumorigenesis by impacting on both proteolytic activity and cell migration during angiogenesis. OBJECTIVES: We hypothesized that an orally active small molecule inhibitor of PAI-1 (PAI-039; tiplaxtinin) could affect smooth muscle cell (SMC) attachment and migration in vitro on a vitronectin matrix, and exhibit antiangiogenic activity in vivo. METHODS: In vitro assays were used to assess the mechanism of inhibition of PAI-1 by PAI-039 using wild-type PAI-1 in the presence or absence of vitronectin and wild-type PAI-1 and specific PAI-1 mutants in SMC adhesion and migration assays. An in vivo tumor angiogenesis model was used to assess the effect of PAI-039 administration on neovascularization in a Matrigel implant. RESULTS: PAI-039 dose-dependently inhibited soluble, but not vitronectin-bound, PAI-1. Cell adhesion assays using PAI-1 mutants unable to bind vitronectin (PAI-1K) or inactivate proteases (PAI-1R) further suggested that PAI-039 inactivated PAI-1 by binding near its vitronectin domain. In a tumor angiogenesis model, PAI-039 treatment of wild-type mice dose-dependently decreased hemoglobin concentration and endothelial cell staining within the Matrigel implant, indicating reduced angiogenesis, but exhibited no in vivo efficacy in PAI-1 null mice. CONCLUSIONS: Administration of an orally active PAI-1 inhibitor prevented angiogenesis in a Matrigel implant. The lack of activity of PAI-039 against wild-type PAI-1 bound to vitronectin and PAI-1K suggests PAI-039 binding near the vitronectin-binding site. Our studies further substantiate a role for PAI-1 in cellular motility and tumor angiogenesis, and suggest for the first time that these effects can be modulated pharmacologically.


Assuntos
Inibidores da Angiogênese/farmacologia , Movimento Celular/efeitos dos fármacos , Ácidos Indolacéticos/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Neovascularização Patológica/prevenção & controle , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Inibidores da Angiogênese/uso terapêutico , Animais , Aorta , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Colágeno , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Ácidos Indolacéticos/uso terapêutico , Laminina , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Mutação , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Neovascularização Patológica/metabolismo , Inibidor 1 de Ativador de Plasminogênio/genética , Ligação Proteica , Proteoglicanas , Vitronectina/metabolismo
5.
Biochim Biophys Acta ; 1098(1): 79-89, 1991 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-1661160

RESUMO

We have tested the efficacy of fluorescent probes for the measurement of intracellular pH in Saccharomyces cerevisiae. Of the compounds tested (fluorescein, carboxyseminaphthorhodafluor-1 (C.SNARF-1) and 2',7'bis(carboxyethyl)-5(6')-carboxyfluorescein), C.SNARF-1 was found to be the most useful indicator of internal pH. Fluorescence microscopy showed that in Saccharomyces cerevisiae strain DAUL1, C.SNARF-1 and fluorescein had a heterogeneous distribution, with dye throughout the cytoplasm and concentration of the dye to an area close to the cell membrane. This region was also labeled by quinacrine, which is known to accumulate in acidic regions of the cell. Saccharomyces cerevisiae BJ4932, which carries a defect in vacuolar acidification, did not show the same degree of dye concentration, suggesting that the site of C.SNARF-1 and fluorescein localisation in DAUL1 is the acidic vacuole. Changes in intracellular pH could be monitored by measuring changes in the fluorescence intensity of C.SNARF-1. The addition of glucose caused an initial, rapid decrease in fluorescence intensity, indicating a rise in cellular pH. This was followed by slow acidification. Fluorescence intensity changes were similar in all strains studied, suggesting that the localisation of dye to acidic regions does not affect the measurement of intracellular pH in DAUL1. The changes in intracellular pH on the addition of glucose correlated well with glucose-induced changes in external pH. Preincubation of cells in the presence of the plasma membrane H(+)-ATPase inhibitor diethylstilbestrol reduced extracellular acidification and intracellular alkalinisation on the addition of glucose. Both amiloride and 5-(N-ethyl-N-isopropyl)amiloride also inhibited glucose-induced proton fluxes. Phorbol 12-myristate 13-acetate had no effect on the activity of the plasma membrane ATPase.


Assuntos
Saccharomyces cerevisiae/metabolismo , Benzopiranos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Sistema Livre de Células , Dietilestilbestrol/farmacologia , Fluoresceínas , Corantes Fluorescentes , Glucose/farmacologia , Concentração de Íons de Hidrogênio , Cinética , Microscopia de Fluorescência , Cloreto de Potássio/farmacologia , Prótons , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/efeitos dos fármacos
6.
Endocrinology ; 140(1): 154-8, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9886820

RESUMO

The role of angiotensin II (AII) in human preadipocyte physiology has been investigated in primary cultures from human adipose tissue. Receptor binding studies indicated that human preadipocytes express a high affinity AII binding site of the AT1 subtype, as binding of 125I-labeled [Sar1,Ile8]AII was rapid, saturable, and specific. As AII has previously been demonstrated to affect the cell cycle in adrenal and cardiac cells, the effect of AII on regulation of cycle progression was examined in human preadipocytes. Stimulation of preadipocytes with AII resulted in G1 phase progression of the cell cycle, as determined by flow cytometric analysis. AII treatment was associated with induction of expression of the messenger RNA for the cell cycle regulatory protein cyclin D1 in a dose-dependent manner. Pretreatment of cells with subtype-selective AT receptor ligands before AII stimulation indicated that the cyclin response was mediated via the AT1 receptor. The identity of the cells as preadipocyte was verified by culture in a defined differentiation medium, observing both leptin message expression and triglyceride accumulation by flow cytometry. These findings indicate that AII has early, receptor-mediated effects on cell cycle progression in human preadipocytes that may contribute to differentiation to the adipocyte phenotype.


Assuntos
Adipócitos/fisiologia , Tecido Adiposo/citologia , Ciclo Celular/fisiologia , Receptores de Angiotensina/fisiologia , 1-Sarcosina-8-Isoleucina Angiotensina II/metabolismo , Adipócitos/citologia , Adulto , Sítios de Ligação , Diferenciação Celular , Separação Celular , Células Cultivadas , Ciclina D1/biossíntese , Ciclina D1/genética , Feminino , Citometria de Fluxo , Humanos , Masculino , RNA Mensageiro/metabolismo , Receptores de Angiotensina/metabolismo
7.
J Clin Endocrinol Metab ; 85(7): 2609-14, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10902815

RESUMO

One of the initial stages of adipogenesis is migration of preadipocytes of mesenchymal origin into cell clusters to form primitive fat organs. The serine protease inhibitor plasminogen activator inhibitor-1 (PAI-1) is synthesized and released from human adipose tissue ex vivo and regulates smooth muscle and endothelial cell migration in vitro, but its role in adipose tissue is not known. We investigated the role of PAI-1 in cultures of human preadipocytes from men and women of various ages and body mass indexes. Human preadipocytes expressed the messenger ribonucleic acid for PAI-1 and released significant quantities of PAI-1 protein into the medium. As PAI-1 regulates motility through the interaction of vitronectin with its receptor, the integrin alphaVbeta3, we identified this receptor in human preadipocytes. Flow cytometric analysis indicated that human preadipocytes express the vitronectin receptor alphaVbeta3 in a similar pattern as human umbilical vein endothelial cells. Functional studies indicated that active, but not latent, PAI-1 inhibited preadipocyte attachment to vitronectin with an IC(50) of 13.3 nmol/L, and preincubation of vitronectin-coated Transwells with active PAI-1 prevented preadipocyte migration. Vitronectin was identified in homogenates of the stromal-vascular fraction of human adipose tissue, but was absent from human adipocytes and cultured preadipocytes. These data indicate that human preadipocyte migration is regulated through the endogenous expression of PAI-1 and alphaVbeta3 integrin, a novel autocrine mechanism for potentially regulating cell cluster formation in adipogenesis.


Assuntos
Adipócitos/fisiologia , Comunicação Autócrina/fisiologia , Inibidor 1 de Ativador de Plasminogênio/farmacologia , Inibidores de Serina Proteinase/farmacologia , Adipócitos/efeitos dos fármacos , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Adulto , Comunicação Autócrina/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
8.
J Clin Endocrinol Metab ; 84(9): 3222-7, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10487691

RESUMO

To further investigate the role of plasminogen activator inhibitor-1 (PAI-1) in adipose tissue physiology, the production and regulation of PAI-1 was determined in primary cultures of human preadipocytes. When expressed as production per cell and cultured under identical conditions, human preadipocytes from both visceral (omental) and sc depots of lean and obese individuals released significant, yet similar, amounts of PAI-1 protein into the conditioned medium. High steady-state PAI-1 messenger RNA (mRNA) concentrations were observed in visceral and sc preadipocytes, with the relative level of expression equivalent to beta-actin mRNA. Tumor necrosis factor alpha significantly decreased PAI-1 production in a concentration-dependent manner in both visceral and sc cultures, whereas transforming growth factor beta significantly elevated PAI-1 production, but only in sc preadipocytes from obese individuals. Addition of insulin had no effect on antigen levels in conditioned medium of preadipocyte cultures. Stimulation of the preadipocyte cultures with a defined medium resulted in differentiation to the adipocyte phenotype, as determined by flow cytometric analysis, verifying the cultures as human preadipocyte. These studies are the first to observe significant PAI-1 mRNA expression and protein production in primary cultures of a human adipose tissue cellular component, and they suggest that nascent adipocytes contribute significantly to the elevated plasma PAI-1 observed in obesity.


Assuntos
Adipócitos/metabolismo , Inibidor 1 de Ativador de Plasminogênio/biossíntese , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Células-Tronco/metabolismo , Actinas/genética , Adipócitos/efeitos dos fármacos , Contagem de Células , Diferenciação Celular , Células Cultivadas , Meios de Cultivo Condicionados , Expressão Gênica , Humanos , Insulina/farmacologia , Inibidor 1 de Ativador de Plasminogênio/genética , RNA Mensageiro/análise , Células-Tronco/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Fator de Necrose Tumoral alfa/farmacologia
9.
Am J Clin Nutr ; 34(5): 841-7, 1981 May.
Artigo em Inglês | MEDLINE | ID: mdl-7234711

RESUMO

To determine the relative effect of body weight and physical inactivity on susceptibility to drug-induced myocardial infarction, randomly selected groups of 100-day-old male Sprague-Dawley rats were subjected to a 10-wk program of exercise training and (or) to caloric restriction followed by two subcutaneous injections of L-isoproterenol. Two groups of rats were fed a restricted diet consisting of minimum calories to maintain body weight and were either exercised (R-Ex) or remained sedentary (R-C), one group was fed ad libitum and subjected to exercise (Ex), and one group remained sedentary (C), but was provided only enough food to maintain body weight in a range similar to Ex rats. Initially, there was no difference between group body weights, but Ex and C rats exhibited a significantly greater final body weight. All Ex, R-Ex, and R-C rats survived the isoproterenol injections, but 50% of C rats died. Group C rats exhibited significantly greater activity of total plasma lactate dehydrogenase (LDH), whereas R-Ex rats had the lowest total LDH activity (p less than 0.05). R-Ex and R-C rats had a significantly lower activity of plasma LDH-1, the heart isozyme, than did the heavier Ex and C rats. More specifically, R-C rats exhibited a significantly decreased amount of plasma LDH-1 activity when compared with Ex rats, indicating that smaller, untrained rats had less myocardial damage than the heavier, exercise-trained rats. These data suggest that either exercise or maintenance of body weight is beneficial toward prevention of the drug-induced myocardial infarction, but when weight maintenance is combined with exercise additional protection is provided.


Assuntos
Dieta Redutora , Infarto do Miocárdio/prevenção & controle , Esforço Físico , Animais , Aspartato Aminotransferases/sangue , Peso Corporal , Creatina Quinase/sangue , Isoproterenol , L-Lactato Desidrogenase/sangue , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/mortalidade , Ratos
10.
J Thromb Haemost ; 2(8): 1422-8, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15304050

RESUMO

Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of both tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Elevated levels of PAI-1 are associated with thrombosis and vascular disease, suggesting that high plasma PAI-1 may promote a hypercoagulable state by disrupting the natural balance between fibrinolysis and coagulation. In this study, we identify WAY-140312 as a structurally novel small molecule inactivator of PAI-1, compare its inhibitory activity with other previously identified small molecule inhibitors, and investigate the mechanism of inactivation of PAI-1 in the presence of both tPA and uPA. In an immunofunctional assay, WAY-140312 inhibited PAI-1 with an estimated inhibitory concentration (IC(50)) of 11.7 micro m, which was the lowest value obtained of the four different PAI-1 inactivators tested. Surface activity profiling indicated that the critical micelle concentration for WAY-140312 was 95.8 micro m, and that each inhibitor exhibited unique physical chemical properties. Using a sensitive direct activity assay, the IC(50) for WAY-140312 was similar when either tPA or uPA was used as the target protease. Immunoblot analysis demonstrated that WAY-140312 near the IC(50) inhibited the complex formation between either tPA or uPA and PAI-1. After oral administration, WAY-140312 exhibited 29% bioavailability with a plasma half-life of approximately 1 h. In an in-vivo model of vascular injury, a 10 mg kg(-1) oral dose of WAY-140312 was associated with improvement in arterial blood flow and reduction in venous thrombosis. Thus, WAY-140312 represents a structurally novel small molecule inhibitor of PAI-1, and is the first such molecule to exhibit efficacy in animal models of vascular disease following oral administration.


Assuntos
Benzofuranos/química , Benzofuranos/farmacologia , Análise Química do Sangue/métodos , Inibidor 1 de Ativador de Plasminogênio/química , Inativadores de Plasminogênio/farmacologia , Tetrazóis/química , Tetrazóis/farmacologia , Administração Oral , Animais , Artérias/patologia , Coagulação Sanguínea , Artérias Carótidas/patologia , Relação Dose-Resposta a Droga , Fibrinólise , Imunoensaio , Immunoblotting , Concentração Inibidora 50 , Micelas , Modelos Químicos , Inativadores de Plasminogênio/sangue , Ratos , Trombose , Fatores de Tempo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
11.
J Hypertens ; 7(8): 683-7, 1989 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2809192

RESUMO

The development of a novel model of human alcoholism has involved the presentation of a 30% alcohol solution to Sprague-Dawley rats via a syringe-feeding needle apparatus. With twice daily intermittent drinking, rats consumed an equivalent of 7-8 g/kg body weight of alcohol, which represented 25% of total daily caloric intake. Alcohol was absorbed rapidly, as significant circulating concentrations were observed within 15 min of gavage, eventually peaking at approximately 200 mg% 1 h later. Hemodynamic recordings in the conscious state after a 10-week drinking program indicated a normotensive blood pressure at peak blood alcohol levels, yet a hypertensive response 24 h after the final drink at a time when blood alcohol was not detected. Alcoholic rats continued to gain weight in parallel with controls fed ad libitum throughout the study, and changes in cardiac size and indices of contractility were not affected by 10 weeks of intermittent drinking. Additionally, no histological evidence of cardiac muscle damage was observed in alcoholic animals. Our animal model closely resembles the clinical situation in terms of the pattern of alcohol consumption, circulating concentrations of alcohol and the percentage of caloric intake in the form of alcohol. The hemodynamic changes observed support the hypothesis that alcoholic hypertension may be a manifestation of withdrawal, as opposed to any direct pressor effect of alcohol itself.


Assuntos
Consumo de Bebidas Alcoólicas , Alcoolismo/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Hipertensão/etiologia , Hipertensão/fisiopatologia , Masculino , Ratos , Ratos Endogâmicos , Síndrome de Abstinência a Substâncias/fisiopatologia
12.
Metabolism ; 34(5): 405-7, 1985 May.
Artigo em Inglês | MEDLINE | ID: mdl-3990558

RESUMO

Alterations in myocardial composition associated with obesity and weight reduction have been examined in the spontaneously obese rat. When compared to values obtained from obese animals, body weight reduction was associated with a significant decrease in body fat, heart weight, and absolute left ventricular mass. Compositional analysis indicated that protein, lipid, and water together accounted for approximately 98% of total heart weight, and that while each component decreased with weight reduction, decreased myocardial water content represented the largest contribution to the reduced total heart weight. These data therefore suggest that the cardiomegaly of obesity is contributed to by specific changes in myocardial composition which can be altered through body weight reduction.


Assuntos
Peso Corporal , Miocárdio/análise , Obesidade/metabolismo , Animais , Composição Corporal , Água Corporal/análise , Modelos Animais de Doenças , Lipídeos/análise , Tamanho do Órgão , Proteínas/análise , Ratos
13.
Metabolism ; 42(4): 511-5, 1993 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8387626

RESUMO

To better understand the role of the mitogenic vasoactive peptide angiotensin II (AII) in growth and differentiation, we have investigated the existence of membrane receptors for this peptide in rat adipocytes. Following isolation of epididymal fat cells, membrane protein was removed and incubated with varying concentrations of 125I-AII with or without submicromolar concentrations of unlabeled AII. Binding of AII was highly specific, rapid, and reversible. Scatchard analysis indicated that adipocyte membranes contain a high-affinity AII receptor with a Kd of 0.90 nmol/L and a binding site concentration (Bmax) of 53.7 fmol/mg protein. Additional pharmacologic analyses resulted in a rank order potency for peptide agonists and antagonists similar to that reported for the vascular receptor. Determination of subtype specificity with selective organic compounds indicated that the epididymal adipocyte receptor was displaced at low concentrations of DuP753, a selective AT1 subtype antagonist. These studies have successfully identified and characterized a high-affinity membrane receptor for AII in fat cells, further establishing adipose tissue as a peripheral site containing regulatory components of the local renin-angiotensin system.


Assuntos
Tecido Adiposo/metabolismo , Receptores de Angiotensina/metabolismo , 1-Sarcosina-8-Isoleucina Angiotensina II/metabolismo , Angiotensina II/metabolismo , Angiotensina III/metabolismo , Antagonistas de Receptores de Angiotensina , Animais , Ligação Competitiva , Compostos de Bifenilo/farmacologia , Membrana Celular/metabolismo , Epididimo , Imidazóis/farmacologia , Losartan , Masculino , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Sprague-Dawley , Saralasina/metabolismo , Temperatura , Tetrazóis/farmacologia
14.
J Appl Physiol (1985) ; 64(3): 1094-7, 1988 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2966792

RESUMO

An experimental model for investigating the disparate effects of obesity and hypertension on the heart was developed by ligation of the aorta of male Sprague-Dawley rats made obese through ad libitum feeding. Experimental obesity was associated with an increased body fat and cardiac muscle mass, yet a normotensive systemic arterial pressure. Aortic ligation produced an elevated mean arterial pressure and resting heart rate, whereas body weight was similar to that of normotensive lean control rats. Obesity and hypertension together were associated with a significantly increased percent body fat, mean arterial pressure, and left ventricular mass compared with lean controls, whereas pressure and left ventricular weight were greater than those observed in rats with only obesity or hypertension. Cardiac adaptations corrected for body weight indicated that left ventricular weight increased as a function of body weight and body fat, but hypertension produced left ventricular adaptations independent of these variables. These initial studies indicate an additional contribution of hypertension to the left ventricular adaptations of obesity, and this model could therefore be used in future investigations concerning the cardiovascular effects of the simultaneous occurrence of these separate diseases.


Assuntos
Cardiomegalia/etiologia , Modelos Animais de Doenças , Hipertensão/fisiopatologia , Obesidade/fisiopatologia , Ratos Endogâmicos , Tecido Adiposo/patologia , Animais , Pressão Sanguínea , Peso Corporal , Coração/fisiopatologia , Frequência Cardíaca , Hipertensão/complicações , Masculino , Miocárdio/patologia , Obesidade/complicações , Tamanho do Órgão , Ratos
15.
Artigo em Inglês | MEDLINE | ID: mdl-2845438

RESUMO

The effect of increased intake of linoleic acid on the alpha-adrenergic system was assessed by safflower oil supplementation to spontaneously hypertensive rats. Linoleic acid-enriched intake at 5%, 15% and 30% by weight of total food intake for 12 wk was associated with a reduction in resting arterial blood pressure, while heart rate and heart to body weight ratios were similar to control group values. A dose-response analysis to norepinephrine bitartrate administered intravenously indicated a significant reduction in the vascular reactivity to this alpha-adrenergic agonist in all groups given linoleic acid. Direct assessment of alpha-adrenoceptor number (Bmax) and affinity (KD) in cardiac sarcolemma with [3H]-prazosin indicated that receptor binding properties were not affected by linoleic acid intake. Our results suggest that short-term linoleic acid supplementation in the established hypertensive state may lower blood pressure through effects upon alpha-adrenergic reactivity in vascular tissue, without associated effects in cardiac tissue.


Assuntos
Hipertensão/metabolismo , Ácidos Linoleicos/farmacologia , Receptores Adrenérgicos alfa/metabolismo , Animais , Ácidos Graxos Insaturados/farmacologia , Hemodinâmica/efeitos dos fármacos , Ácido Linoleico , Masculino , Ratos , Ratos Endogâmicos SHR
16.
Ann Thorac Surg ; 57(6): 1436-9, 1994 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8010785

RESUMO

Spinal operation via an anterior thoracic approach is becoming increasingly common, and the thoracic surgeon is now being called upon to provide exposure for orthopedic and neurosurgical colleagues. We report experience with 126 such patients from 1982 through 1993. There were 61 male and 65 female patients (mean age, 39.0 years; range, 14 to 77 years). Indications were trauma in 45 patients (36%), spinal deformity in 42 (33%), cancer in 15 (12%), disc disease in 12 (10%), and infection in 12 (10%). Operative incisions included 22 (17%) right and 14 (11%) left thoracotomies, 33 (26%) right and 56 (44%) left thoracolumbar approaches, and one (1%) sternotomy. A prior spinal operation had been performed on 31 patients (25%), and 56 (44%) had a subsequent posterior spinal operation. Instrumentation was used in 38 (30%) and bone grafts in all but 6 patients. A neurologic deficit was present in 69 patients (55%) preoperatively and was improved in 67 patients postoperatively. Operative mortality was 3.2% (4 patients) due to myocardial infarction, stroke with pneumonia, adult respiratory distress syndrome, and malignant biliary obstruction. Univariate and multivariate risk analysis were performed. Only the diagnosis of osteomyelitis proved to be a significant (p = 0.0002) indicator of operative mortality, with 3 of 12 such patients dying (25%). These results suggest that anterior spinal exposure via thoracic approach is a major operation with considerable perioperative risk. Patients with osteomyelitis appear to be at increased risk for operative mortality.


Assuntos
Vértebras Torácicas/cirurgia , Adolescente , Adulto , Idoso , Perda Sanguínea Cirúrgica , Transfusão de Sangue , Transplante Ósseo , Causas de Morte , Feminino , Humanos , Disco Intervertebral/cirurgia , Masculino , Pessoa de Meia-Idade , Dispositivos de Fixação Ortopédica , Osteomielite/microbiologia , Osteomielite/cirurgia , Complicações Pós-Operatórias , Costelas/cirurgia , Doenças da Coluna Vertebral/complicações , Doenças da Coluna Vertebral/cirurgia , Fusão Vertebral/métodos , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/cirurgia , Taxa de Sobrevida , Vértebras Torácicas/anormalidades , Vértebras Torácicas/lesões , Toracotomia/métodos , Fatores de Tempo
17.
Life Sci ; 35(13): 1373-8, 1984 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-6482659

RESUMO

A dose-dependent decrease in mean arterial blood pressure was produced in spontaneously hypertensive rats by intravenous PAF infusion. Heart rate was monitored, while cardiac index and regional blood flow were quantitated during maintenance of the PAF-induced hypotension using the radioactive microsphere method. Our results suggest that PAF administration is associated with specific changes in vascular resistance, since estimated blood flow was decreased to certain organs or tissues, but remained unchanged in others. Therefore, the hypotension observed during PAF infusion is dose-dependent, and is contributed to by decreases in vascular resistance in specific organs.


Assuntos
Hipertensão/fisiopatologia , Fator de Ativação de Plaquetas/farmacologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Superfície Corporal , Débito Cardíaco/efeitos dos fármacos , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos SHR , Resistência Vascular/efeitos dos fármacos
18.
J Bone Joint Surg Am ; 76(11): 1629-35, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7962022

RESUMO

Thirteen patients who had a burst fracture of the thoracolumbar spine (the twelfth thoracic to the fifth lumbar vertebra) were managed with the use of long rods and a short arthrodesis (the so-called rod-long, fuse-short technique). The patients were followed for an average of seventy-four months (range, thirty-four to 118 months). Six months after the operation, the rods were removed and the fusion mass was explored. At that time, twelve patients had a solid fusion at all levels of the arthrodesis. Of the eighty-eight facet joints that had been spanned by the rods but had not been included in the arthrodesis, two had nevertheless progressed to fusion, as determined radiographically. Physiological motion was present in forty-three of the forty-four segments for which a fusion had not been intended. Before the operation, the average anterior height of the fractured vertebrae was 61 per cent of the estimated height before the injury; this improved after the operation to an average of 83 per cent (median, 87 per cent) of the height before the injury. At the latest follow-up examination, the anterior height was an average of 78 per cent of the estimated height before the injury (median, 82 per cent; range, 51 to 93 per cent), a slight decrease compared with the value immediately after the operation. Kyphosis of the injured segment before the operation, measured for twelve of the thirteen patients, averaged 15 degrees (median, 12 degrees; range, 0 to 33 degrees); as a result of the operation, this improved an average of 15 degrees, to 0 degrees of kyphosis.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Fixadores Internos , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Fusão Vertebral/métodos , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Adolescente , Adulto , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Masculino , Pessoa de Meia-Idade , Radiografia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/patologia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/patologia , Resultado do Tratamento
19.
Psychiatry Res ; 106(1): 15-24, 2001 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-11231096

RESUMO

Diffuse white matter pallor is the most frequent neuropathological feature of HIV-1 infection and has been found to be particularly prominent in the advanced stages of the disease. The purpose of this study was to determine whether subtle white matter abnormalities can be detected in medically stable, ambulatory HIV-1 patients, in vivo, using diffusion tensor imaging (DTI). DTI is a magnetic resonance imaging (MRI) technique that is uniquely suited for the study of subtle white matter abnormalities. DTI was performed in six HIV-1 patients and nine controls. The two groups were similar in age. Abnormal fractional anisotropy was found in the white matter of the frontal lobes and internal capsules of the HIV-1 patients, in the absence of group differences in mean diffusivity, computed proton density, and computed T2. DTI may be more sensitive than conventional MRI methods for detecting subtle white matter disruptions in HIV-1 disease.


Assuntos
Síndrome da Imunodeficiência Adquirida/virologia , Encéfalo/patologia , Encéfalo/virologia , HIV-1 , Imageamento por Ressonância Magnética , Adulto , Anisotropia , Humanos , Masculino
20.
Plast Reconstr Surg ; 104(6): 1732-8, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10541176

RESUMO

Because of the need for methods for successful transplantation of autologous fat, the differentiation of human preadipocytes on surgical mesh coated with various extracellular matrix components was investigated. Biopsy specimens of human adipose tissue were collected from seven different patients and were subjected to collagenase digestion and selective filtration, resulting in primary cultures of human preadipocytes. Fluortex monofilament-expanded polytetrafluoroethylene (52-/xm pore size) was as a template for coating with either human collagen, albumin, or fibronectin, followed by sodding with established cultures of human preadipocytes. Sodding efficiency on the different matrices was determined by trypsinization of attached cells at different time periods. Preadipocytes did not attach to uncoated polytetrafluoroethylene, but did attach to protein-coated mesh, and in a variable manner. Fibronectin-coating resulted in the highest efficiency of sodding, with differentiation of preadipocytes to adipocytes as assessed by scanning electron -microscopy and conventional Oil Red O staining. Similar results were achieved by using rat (n = 6) perirenal adipose tissue. This new method of adipocyte scaffolding may be used for improving soft-tissue augmentation and serving as a delivery system for growth factors important in wound healing.


Assuntos
Adipócitos , Tecido Adiposo/transplante , Politetrafluoretileno , Telas Cirúrgicas , Adipócitos/ultraestrutura , Células Cultivadas , Sistemas de Liberação de Medicamentos , Humanos , Microscopia Eletrônica de Varredura
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