Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 86
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Thromb Haemost ; 6(6): 944-50, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18384651

RESUMO

BACKGROUND: Hemodialysis (HD) grafts often fail because of stenosis at the venous anastomosis and thrombotic occlusion. Percutaneous management relies on thrombolysis with plasminogen activators, mechanical removal of thrombus, and angioplasty of the stenotic lesion. OBJECTIVES: This report describes a phase I trial using Plasmin (Human) TAL 05-00018, a direct-acting fibrinolytic agent, to evaluate safety and, secondarily, to establish effective thrombolytic dosing. PATIENTS/METHODS: Six cohorts of five patients with acute HD graft occlusion documented by angiography were treated with escalating dosages of plasmin (1, 2, 4, 8, 12, and 24 mg) infused over 30 min via criss-crossed pulse-spray catheters within the graft. The primary efficacy endpoint was > or =50% thrombolysis, as determined by comparison of pre-plasmin and 30-min post-plasmin fistulograms. RESULTS: Of 31 subjects who received study drug (safety population), one withdrew and 30 completed the trial (evaluable for efficacy). There was no significant change in plasma alpha-2 antiplasmin or fibrinogen concentration, major bleeding did not occur, and there were no deaths. Serious adverse events in four patients were not related to the study drug. There was a dose-response relationship for the primary efficacy endpoint, all five subjects receiving 24 mg achieving >75% lysis. CONCLUSIONS: This first phase I study of Plasmin (Human) TAL 05-00018, infused into thrombosed HD grafts, documents safety at dosages of 1-24 mg and an effective thrombolytic dosage of 24 mg. The results establish a foundation for further clinical study of catheter-based plasmin administration in thrombotic disorders.


Assuntos
Fibrinolisina/administração & dosagem , Fibrinolisina/farmacologia , Diálise Renal/métodos , Terapia Trombolítica/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Fibrinolisina/química , Fibrinolisina/metabolismo , Fibrinolíticos/farmacologia , Humanos , Isquemia/patologia , Masculino , Pessoa de Meia-Idade , Terapia Trombolítica/métodos , Trombose/patologia
2.
J Thromb Haemost ; 1(12): 2621-5, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14675099

RESUMO

Plasmin is a direct thrombolytic which has been shown to have a strikingly favorable benefit to risk profile in comparison with plasminogen activators, notably tissue plasminogen activator (t-PA). As heparin is known to increase the risk of hemorrhage when co-administered with a plasminogen activator, we asked whether adjunct antithrombotic agents such as aspirin and heparin would affect the safety of plasmin. Three groups of rabbits were administered plasmin at a dose (4 mg kg-1) designed to induce significant decreases in antiplasmin, fibrinogen and factor (F)VIII, to about 25, 40 and 40%, respectively, of baseline values, but not cause prolongation of the ear puncture bleeding time. In a blinded and randomized trial, the results show that an intravenous aspirin bolus plus heparin administered as a bolus followed by a maintenance continuous infusion did not significantly prolong the bleeding time during plasmin infusion. These data indicate that in the rabbit, concomitant use of aspirin plus heparin does not affect the safety of a therapeutic dose of plasmin.


Assuntos
Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Animais , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Tempo de Sangramento , Interações Medicamentosas , Quimioterapia Combinada , Fibrinolisina/administração & dosagem , Fibrinolisina/efeitos adversos , Heparina/administração & dosagem , Heparina/efeitos adversos , Modelos Animais , Coelhos , Terapia Trombolítica/efeitos adversos
3.
Domest Anim Endocrinol ; 24(4): 323-39, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12742550

RESUMO

The objectives of this study were to develop an assay for the direct measure of porcine corticosteroid-binding globulin (pCBG) and to confirm age-related changes in plasma pCBG concentration. Isolation and purification of pCBG from plasma was performed by affinity chromatography and HPLC-DEAE anion exchange techniques. Analysis by SDS-PAGE revealed two polypeptides (54 and 59 kDa) having similar amino acid homology (>50%) to previously reported sequences of seven mammalian species for the first 33 amino acids. Porcine CBG (20 ng/well) was immobilized to microtiter plates and standards or samples added along with rabbit antiserum developed against the purified pCBG. Goat anti-rabbit IgG-alkaline phosphatase conjugate was added followed by p-NPP substrate. The resultant color development was read at 405 nm. Intra- and interassay coefficients of variation (n=26) of a pooled sample were 10 and 15%, respectively. Age-related changes (P<0.001) in plasma pCBG concentration (n=203) from day 3 through 168 of age confirmed that, in the pig, changes seen in the percent distribution of cortisol among protein bound and free forms around day 28 of age are associated with an increase in CBG concentration.


Assuntos
Envelhecimento , Ensaio de Imunoadsorção Enzimática , Suínos/sangue , Transcortina/análise , Sequência de Aminoácidos , Animais , Cromatografia de Afinidade , Cromatografia Líquida de Alta Pressão , Cromatografia por Troca Iônica , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Homologia de Sequência , Transcortina/química
4.
Hypertension ; 37(6): 1388-93, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11408382

RESUMO

We examined the effects of the angiotensin-converting enzyme inhibitor perindopril and the beta-blocker propranolol on dilator responses of cerebral arterioles in chronic hypertension. Dilator responses to acute hypotension were examined in untreated Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) that were untreated or treated for 3 months with a low (0.3 mg. kg(-1). day(-1)) or a high (2 mg. kg(-1). day(-1)) dose of perindopril or a dose of propranolol (250 mg. kg(-1). day(-1)) alone or in combination with the low dose of perindopril. Pressure (servo-null) and diameter were measured in cerebral arterioles during acute reductions in arterial pressure both before and during maximal dilatation (EDTA). The high dose of perindopril or the combination of propranolol and perindopril normalized cerebral arteriolar pressure (52+/-2 [mean+/-SEM], 49+/-2 mm Hg versus 50+/-2 mm Hg in WKY and 96+/-3 mm Hg in untreated SHRSP; P<0.05). In contrast, the low dose of perindopril or propranolol alone did not normalize arteriolar pressure (74+/-2 mm Hg and 58+/-3 mm Hg). Both the low and high doses of perindopril improved autoregulatory dilatation, maximal dilatation, and dilator reserve of cerebral arterioles in SHRSP, with the low dose of perindopril being almost as effective as the high dose of perindopril. Propranolol alone did not significantly improve dilator function of cerebral arterioles. Furthermore, dilator function of cerebral arterioles was not further improved by the addition of propranolol to the low dose of perindopril. These findings suggest that angiotensin-converting enzyme inhibitors, such as perindopril, may be more effective than propranolol in attenuating the impairment of cerebral autoregulatory vasodilatation, maximal dilatation, and dilator reserve during treatment of chronic hypertension.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Artérias Cerebrais/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Perindopril/uso terapêutico , Propranolol/uso terapêutico , Animais , Pressão Sanguínea/efeitos dos fármacos , Artérias Cerebrais/patologia , Doença Crônica , Dilatação Patológica/tratamento farmacológico , Hipertensão/patologia , Hipertensão/fisiopatologia , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
5.
J Hypertens Suppl ; 18(1): S7-11, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10939784

RESUMO

Chronic hypertension profoundly alters the function and structure of cerebral blood vessels. Cerebral arterioles undergo remodelling, with a reduction in external diameter and hypertrophy of the vessel wall and a paradoxical increase in distensibility. The primary aim of this review is to consider recent findings in relation to determinants of remodelling, hypertrophy, and altered distensibility and composition of cerebral blood vessels during chronic hypertension, with an emphasis on the renin-angiotensin system. In particular, we highlight studies designed to examine the hypothesis that the effects of angiotensin-converting enzyme (ACE) inhibitors on cerebral vascular structure in stroke-prone spontaneously hypertensive rats (spSHR) may be independent of their effects on reductions in arterial pressure. For example, treatment of spSHR with the ACE inhibitor perindopril attenuates remodelling of cerebral arterioles, even when given in a low dose that only partially normalizes systemic arterial pressure and does not prevent hypertrophy. In contrast, treatment of spSHR with propranolol does not prevent cerebral arteriolar remodelling, even when given in a dose that produces a larger decrease in blood pressure than is achieved with the low dose of perindopril. Results such as these suggest that remodelling of cerebral arterioles during chronic hypertension may be independent of increases in arterial pressure, and instead may depend primarily on increased activity of the renin-angiotensin system. Evidence is also reviewed that suggests that the renin-angiotensin system may not contribute significantly to hypertrophy of cerebral arterioles during chronic hypertension. Rather, hypertrophy appears to depend in large part on increases in arterial pressure and, in particular, its pulsatile component.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Circulação Cerebrovascular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/patologia , Arteríolas/fisiopatologia , Circulação Cerebrovascular/fisiologia , Humanos , Hipertensão/patologia , Hipertensão/fisiopatologia , Hipertrofia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/prevenção & controle
6.
Chemosphere ; 40(2): 225-32, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10665436

RESUMO

This report presents results of emission measurements of polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF) in the flue gas of seven oil, nine gas, and two wood firing systems under laboratory conditions. The burn rate of the combustion was in the range of the rated useful heat output. Two additional test series varied the amount of combustion air and thus the heat output. The PCDD/PCDF emissions for oil- and gas-fired boilers are in the range of 0.0020-0.0142 ng I-TEQ/m3 (referring to 3% O2 in the dry flue gas). No correlation between the combustion technique and the PCDD/PCDF emissions could be established. In the tests with the wood-fired furnaces PCDD/PCDF concentrations in the flue gas ranging from 0.014 to 0.076 ng I-TEQ/m3 (referring to 13% O2 in the dry flue gas) were found. A significant correlation between the firing rate of the heating insert and the measured PCDD/PCDF concentrations was found. On examination of three typical 2,3,7,8-CDD/CDF congener profiles, a comparable pattern could be observed with natural gas and light fuel oil. The congener distribution for wood combustion is considerably different.


Assuntos
Benzofuranos/análise , Calefação , Dibenzodioxinas Policloradas/análogos & derivados , Dibenzofuranos Policlorados , Combustíveis Fósseis , Óleos Combustíveis , Temperatura Alta , Habitação , Dibenzodioxinas Policloradas/análise , Madeira
7.
Hypertension ; 33(3): 856-61, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10082499

RESUMO

We examined the effects of an angiotensin-converting enzyme inhibitor, perindopril, and a beta-blocker, propranolol, on cerebral arterioles in stroke-prone spontaneously hypertensive rats (SHRSP). The structure and mechanics of cerebral arterioles were examined in untreated Wistar-Kyoto rats (WKY) and SHRSP that were untreated or treated for 3 months with a high (2 mg/kg per day) or a low (0.3 mg/kg per day) dose of perindopril or propranolol (250 mg/kg per day) alone or in combination with the low dose of perindopril. We measured pressure, external diameter, and cross-sectional area of the vessel wall (CSA) in maximally dilated (with EDTA) cerebral arterioles. Treatment of SHRSP with the high dose of perindopril or the combination of propranolol and the low dose of perindopril normalized cerebral arteriolar mean pressure (50+/-1 [mean+/-SEM] and 43+/-2 mm Hg vs 50+/-1 mm Hg in WKY and 94+/-3 mm Hg in untreated SHRSP; P<0.05), pulse pressure (15+/-1 and 16+/-1 mm Hg vs 13+/-1 mm Hg in WKY and 35+/-1 mm Hg in untreated SHRSP; P<0.05), and CSA (1103+/-53 and 1099+/-51 microm2, respectively, vs 1057+/-49 microm2 in WKY and 1281+/-62 microm2 in untreated SHRSP; P<0.05). In contrast, treatment of SHRSP with the low dose of perindopril or propranolol alone did not normalize arteriolar pulse pressure (24+/-1 and 21+/-1 mm Hg) and failed to prevent increases in CSA (1282+/-77 and 1267+/-94 microm2). Treatment with either dose of perindopril or the combination of propranolol and perindopril significantly increased external diameter in cerebral arterioles of SHRSP (99+/-3, 103+/-2, and 98+/-3 microm vs 87+/-2 microm in untreated SHRSP; P<0.05), whereas propranolol alone did not (94+/-3 microm; P>0.05). These findings suggest that effects of angiotensin-converting enzyme inhibitors on cerebral arteriolar hypertrophy in SHRSP may depend primarily on their effects on arterial pressure, particularly pulse pressure, whereas their effects on cerebral arteriolar remodeling (defined as a reduction in external diameter) may be pressure independent.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Arteríolas/efeitos dos fármacos , Encéfalo/irrigação sanguínea , Hipertensão/tratamento farmacológico , Indóis/farmacologia , Propranolol/farmacologia , Animais , Arteríolas/patologia , Pressão Sanguínea/efeitos dos fármacos , Ácido Edético , Hipertensão/patologia , Hipertrofia/prevenção & controle , Masculino , Perindopril , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Estresse Fisiológico/tratamento farmacológico
8.
Pediatr Neurosurg ; 29(2): 86-91, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9792962

RESUMO

Schilder's diffuse myelinoclastic sclerosis is a rare demyelinating disease which often mimics intracranial neoplasm or abscess. We have treated 3 patients with this disorder in the past 5 years and followed their postoperative course. Certain distinct features of this disease will allow neurosurgeons to preoperatively entertain this diagnosis. We discuss postoperative treatment and propose a new hypothesis regarding the variable prognoses of this disorder. Schilder's disease constitutes an important diagnosis for any neurosurgeon to be aware of (especially those treating the pediatric age group) which has not received adequate coverage in the neurosurgical literature.


Assuntos
Esclerose Cerebral Difusa de Schilder , Adolescente , Criança , Esclerose Cerebral Difusa de Schilder/diagnóstico , Esclerose Cerebral Difusa de Schilder/terapia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética
9.
Hypertension ; 30(5): 1097-104, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9369262

RESUMO

We examined the effects of nitric oxide (NO) synthase inhibition on the structure and mechanics of cerebral arterioles. We measured pressure, diameter, and cross-sectional area of the vessel wall (histologically) in maximally dilated cerebral arterioles in Sprague-Dawley rats that were untreated or treated for 3 months with the NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg per day). Treatment with L-NAME increased cerebral arteriolar mean (87+/-6 versus 42+/-2 mm Hg, P<.05) and pulse (25+/-2 versus 13+/-2 mm Hg, P<.05) pressures, as well as cross-sectional area of the vessel wall (1839+/-70 versus 1019+/-58 microm2, P<.05) and external diameter (101+/-4 versus 87+/-2 microm, P<.05). These findings suggest that hypertension induced by NO synthase inhibition is accompanied by hypertrophy of the vessel wall and enlargement of cerebral arterioles in rats. To determine the role of cerebral arteriolar pulse pressure in hypertrophy of cerebral arterioles during inhibition of NO synthase, we measured the cross-sectional area of the vessel wall in rats treated with L-NAME that underwent unilateral carotid clipping. Unilateral carotid clipping failed to prevent increases in cross-sectional area of the vessel wall (1507+/-173 and 1613+/-148 microm2 in the clip and sham sides, respectively) in rats treated with L-NAME, even though increases in pulse pressure were prevented (16+/-1 and 27+/-1 mm Hg in the clip and sham sides, respectively, P<.05). These findings suggest that inhibition of NO synthase may promote hypertrophy of cerebral arterioles independently of increases in arteriolar pulse pressure.


Assuntos
Circulação Cerebrovascular/fisiologia , Óxido Nítrico Sintase/antagonistas & inibidores , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/patologia , Arteríolas/fisiologia , Circulação Cerebrovascular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Sprague-Dawley
10.
Biol Neonate ; 72(3): 192-200, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9303219

RESUMO

Thirty-five time-dated pregnant gilts were used to document plasma levels of total and free cortisol, corticosteroid-binding globulin (CBG) binding capacity, and percent distribution of cortisol among protein-bound (CBG and albumin) and free forms in the fetal pig during the last 24 days of gestation. Plasma from fetal pigs on days 110-114 of gestation (gestation length 114 days) had significantly higher levels of total cortisol (p < 0.01), percent albumin-bound and free cortisol (p < 0.10), and free cortisol concentration (p < 0.05) compared to samples on days 90, 100 and 105. Fetal plasma CBG binding capacity increased (p < 0.05) linearly from day 100 to 114. Fetal pigs located in the cervical region of the uterus had lower (p < 0.05) total and free cortisol and higher (p < 0.05) albumin and total protein concentrations compared to fetuses in the middle and oviductal regions. Total, percent free and free cortisol concentrations in maternal plasma on days 105-114 were greater (p < 0.10) than that measured on days 12-100 of gestation. These results suggest that the developmental patterns of plasma cortisol and CBG in the prenatal pig are directly related and highly similar to those of another precocious species, the sheep.


Assuntos
Sangue Fetal/química , Hidrocortisona/sangue , Prenhez/sangue , Albumina Sérica/metabolismo , Transcortina/metabolismo , Animais , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/metabolismo , Feminino , Sangue Fetal/metabolismo , Idade Gestacional , Hidrocortisona/classificação , Hidrocortisona/metabolismo , Masculino , Troca Materno-Fetal , Gravidez , Ligação Proteica , Albumina Sérica/análise , Suínos
12.
Bioorg Med Chem ; 4(5): 699-708, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8804536

RESUMO

The chromatographic purification of vWF (von Willebrand Factor) from human plasma represents a challenge because it consists of multimers with molecular weights ranging from 0.5 to 10 million Daltons. Phage peptide library screening yielded a lead peptide (RLRSFY) that interacts with vWF. Conservative substitutions of terminal residues of the lead peptide led to a second peptide, RVRSFY, which was more efficient in the affinity chromatographic purification of vWF from protein mixtures. Adsorption isotherm measurements indicated multiple interactions between vWF and the immobilized peptide RVRSFY. Increases in peptide density on the chromatographic supports resulted in stronger association constants and higher maximum protein binding capacities. When the peptide density was lower than 32 mg/mL, there was no measurable interaction between vWF and immobilized peptide RVRSFY in HEPES buffer containing 0.5 M NaCl at pH 7. An increase in peptide density from 32 to 60 mg/mL increased the association constants from 0.9 x 10(6) to 2 x 10(6) (M-1). Divalent salts (calcium and magnesium chloride) were used to elute the retained vWF with 82.5% of the activity recovered. The interactions between vWF and the immobilized peptide RVRSFY are dominated by ionic attractions and also involve hydrophobic interactions at close contact. Finally, the purification of vWF from crude material PEG filtrate of a cryoprecipitate of human plasma is demonstrated using affinity chromatography with immobilized N-acetyl-RVRSFYK.


Assuntos
Oligopeptídeos/química , Oligopeptídeos/metabolismo , Fator de von Willebrand/isolamento & purificação , Adsorção , Sequência de Aminoácidos , Animais , Soluções Tampão , Cátions Bivalentes/química , Cromatografia de Afinidade/métodos , Cromatografia Líquida de Alta Pressão , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Humanos , Concentração de Íons de Hidrogênio , Ligantes , Dados de Sequência Molecular , Concentração Osmolar , Coelhos , Propriedades de Superfície , Temperatura , Fator de von Willebrand/metabolismo
13.
Hypertension ; 27(3 Pt 2): 794-8, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8613242

RESUMO

The purpose of this study was to examine the effects of endothelin receptor inhibition on cerebral arterioles in stroke-prone spontaneously hypertensive rats (SHRSP). Structure and mechanics of cerebral arterioles were examined in untreated Wistar-Kyoto rats (WKY) and SHRSP that were either untreated or treated for 3 months with bosentan, an inhibitor of endothelin receptors (100 mg/kg per day). We measured pressure, external diameter, and cross-sectional area of the vessel wall (histologically) in maximally dilated (EDTA) arterioles on the cerebrum. Bosentan reduced but did not normalize arteriolar mean pressure (103 +/- 3 and 81 +/- 5 mm Hg in untreated and treated SHRSP versus 51 +/- 4 mm Hg in WKY, P < .05; mean +/- SEM) and pulse pressure (40 +/- 2 and 33 +/- 2 mm Hg in untreated and treated SHRSP versus 25 +/- 3 mm Hg in WKY, P < .05) in SHRSP. Cross-sectional area of the vessel wall (CSA) was increased in untreated SHRSP (1627 +/- 173 microm2), and CSA in treated SHRSP (1287 +/- 78 microm2) was similar to that in WKY (1299 +/- 65 microm2). Bosentan had no effect on reductions in external diameter (remodeling) of cerebral arterioles (104 +/- 7 and 96 +/- 4 microm in untreated and treated SHRSP compared with 126 +/- 7 microm in WKY, P < .05). Stress-strain curves indicate that bosentan had no significant effect on distensibility of arterioles on the cerebrum in SHRSP. The results suggest that endothelin-1 may contribute to the development of hypertrophy, but not remodeling or changes in distensibility, of cerebral arterioles in SHRSP.


Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Antagonistas dos Receptores de Endotelina , Hipertensão/fisiopatologia , Sulfonamidas/farmacologia , Animais , Arteríolas/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Bosentana , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptores de Endotelina/fisiologia , Vasodilatação/efeitos dos fármacos
14.
Hypertension ; 27(2): 159-67, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8567036

RESUMO

The goal of this study was to examine the hypothesis that increases in pulse pressure produce hypertrophy of cerebral arterioles, even in the absence of increases in mean pressure. Sprague-Dawley rats underwent creation of an arteriovenous fistula and clipping of one carotid artery at 1 month of age. Rats that underwent exposure of the abdominal aorta without fistula production and unilateral carotid clipping served as controls. At about 6 months of age, the mechanics of sham and clipped pial arterioles were examined in vivo in anesthetized rats. Stress-strain relations were calculated from measurements of pial arteriolar pressure (servo null) and diameter and cross-sectional area of the arteriolar wall. Point counting stereology was used to quantify individual components in the arteriolar wall. Before deactivation of smooth muscle with EDTA, cross-sectional areas of the vessel wall and pulse pressures in sham pial arterioles were significantly greater (P < .05) in arteriovenous fistula rats than in control rats (cross-sectional area, 1468 +/- 100 versus 1129 +/- 104 microns 2; pulse pressure, 26 +/- 1 versus 14 +/- 1 mm Hg). In contrast, systolic and mean pressures in sham arterioles were not significantly different and diastolic pressure was significantly less in arteriovenous fistula rats (systolic pressure, 69 +/- 1 versus 67 +/- 4 mm Hg; mean pressure, 52 +/- 2 versus 57 +/- 3 mm Hg; diastolic pressure, 43 +/- 2 versus 53 +/- 3 mm Hg). Carotid clipping normalized cross-sectional area of the vessel wall (1083 +/- 86 microns 2) and pulse pressure (12 +/- 1 mm Hg) in pial arterioles of arteriovenous fistula rats. During maximal dilatation, the stress-strain curve in sham arterioles of arteriovenous fistula rats was shifted to the right of the curve in control rats, which indicates that arteriovenous fistulae increase passive distensibility of cerebral arterioles. The proportion of distensible components in the vessel wall (smooth muscle, elastin, and endothelium) was increased in sham arterioles of arteriovenous fistula rats. These findings (1) suggest that increases in pulse pressure, even in the absence of increases in mean pressure, are sufficient to produce hypertrophy of cerebral arterioles and (2) provide support for the concept that increases in distensibility of cerebral arterioles in association with hypertrophy of the vessel wall may be related to alterations in wall composition.


Assuntos
Arteríolas/fisiologia , Derivação Arteriovenosa Cirúrgica , Pressão Sanguínea , Circulação Cerebrovascular , Pia-Máter/irrigação sanguínea , Análise de Variância , Animais , Aorta Abdominal/cirurgia , Arteríolas/anatomia & histologia , Arteríolas/patologia , Dióxido de Carbono/sangue , Artérias Carótidas/cirurgia , Fístula , Concentração de Íons de Hidrogênio , Hipertrofia , Músculo Liso Vascular/anatomia & histologia , Músculo Liso Vascular/patologia , Músculo Liso Vascular/fisiologia , Oxigênio/sangue , Pressão Parcial , Ratos , Ratos Sprague-Dawley
15.
Int J Pept Protein Res ; 47(1-2): 70-83, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8907502

RESUMO

We have developed a new resin for peptide synthesis that can be used to synthesize and evaluate directly combinatorial peptide libraries for binding target proteins. Fidelity of the peptide synthesis using this hydrophilic resin is comparable to polystyrene-based resins. Peptide libraries synthesized on this resin were probed by a two color PEptide Library Immunostaining Chromatographic ANalysis (PELICAN) technique for sequences binding the serine protease Factor IX zymogen. This PELICAN technique readily distinguishes between beads interacting with the reagents for target detection (blue beads) from those beads specific for the target protein itself (red beads). Validation of the PELICAN technique, as well as purification of Factor IX from plasma, is demonstrated utilizing this resin.


Assuntos
Cromatografia de Afinidade/métodos , Biblioteca Gênica , Peptídeos/genética , Cromatografia Líquida de Alta Pressão , Cor , Fator X/química , Imunoensaio , Peptídeos/química , Reprodutibilidade dos Testes , Resinas Vegetais
16.
Hypertension ; 26(3): 509-13, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7649590

RESUMO

This review describes vascular changes in atherosclerotic and hypertensive vessels as well as effects of treatment. Changes in vascular structure in both atherosclerosis and hypertension are characterized by thickening of the vessel wall and vascular "remodeling." Remodeling tends to preserve the size of the lumen in atherosclerotic vessels and results in a smaller lumen in hypertensive vessels. Changes in vascular function are characterized by preservation of smooth muscle relaxation, with the exception of activity of ATP-sensitive potassium channels, and dysfunction of endothelium. Regression of atherosclerosis, by treatment of hyperlipidemia, results in quite rapid removal of lipid from the vessel wall but with inconsistent improvement in maximal vasodilator capacity. In contrast, endothelial function improves during regression of atherosclerosis, and hyperresponsiveness to serotonin subsides rapidly. Effective treatment of hypertension produces regression of vascular hypertrophy, and some approaches (especially angiotensin-converting enzyme inhibitors) are effective in correcting vascular remodeling. Endothelium-dependent relaxation generally improves during antihypertensive treatment. Reduction in pulse pressure may be more important than reduction in mean arterial pressure in reversing the structural and functional abnormalities of hypertensive vessels.


Assuntos
Arteriosclerose/fisiopatologia , Vasos Sanguíneos/fisiopatologia , Hipertensão/fisiopatologia , Arteriosclerose/tratamento farmacológico , Arteriosclerose/patologia , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/patologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Músculo Liso Vascular/fisiopatologia
17.
J Hum Hypertens ; 9(6): 449-53, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7473526

RESUMO

Hypertension and atherosclerosis are associated with structural and functional changes that may be collectively described as a 'sick vessel syndrome'. Structural changes in blood vessels (remodelling and hypertrophy) may be protective and adaptive. Functional changes in blood vessels include impairment of endothelium-dependent relaxation and impaired relaxation in response to activation of ATP-sensitive potassium channels. In general, vasorelaxation in response to direct activation of adenylate and guanylate cyclase is preserved in chronic hypertension and atherosclerosis. Vasoconstrictor responses to selected stimuli, such as serotonin, may be greatly potentiated. Impairment of endothelial function in combination with exaggeration of vasoconstrictor responses may predispose to vasospasm particularly during atherosclerosis.


Assuntos
Arteriosclerose/patologia , Arteriosclerose/fisiopatologia , Vasos Sanguíneos/patologia , Vasos Sanguíneos/fisiopatologia , Hipertensão/patologia , Hipertensão/fisiopatologia , Doenças Vasculares/fisiopatologia , Adaptação Fisiológica , Animais , Endotélio Vascular/fisiopatologia , Humanos , Músculo Liso Vascular/fisiopatologia , Síndrome , Vasodilatação/fisiologia
18.
Am J Physiol ; 267(6 Pt 2): H2132-7, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7528989

RESUMO

Volume overload-induced cardiac hypertrophy is characterized by normal coronary reserve and maximal flow. Accordingly, we tested the hypothesis that both arteriolar and capillary growth are proportional to the magnitude of hypertrophy in this model. Five months after performing an aortocaval fistula [arteriovenous (A-V) shunt] in young rats, right and left ventricles were 61 and 55%, respectively, heavier than their sham controls. Using morphometric methods and image analysis, we found that increases in cardiac myocyte cross-sectional area accounted for approximately 50% of the hypertrophy and that arteriolar length density (LV) (7.5 +/- 0.9 and 7.0 +/- 0.4 mm/mm3) and the frequency distribution of arteriolar diameters were similar in the hearts from A-V shunt and control rats. Capillary LV in the right ventricle was similar in the two groups; in the left ventricle a significantly lower LV for the A-V shunt rats was noted only in the endomyocardium. Capillary volume density was not attenuated in the A-V shunt rats, since slightly larger luminal diameters compensated for any decrements in LV in the left ventricle. These findings provide an anatomic basis for the observation that maximal myocardial perfusion is not necessarily compromised in ventricular enlargement due to aortocaval fistula. Because diastolic volume is increased in this model and thereby provides a stretch on the microvasculature, our findings are consistent with those from other models of cardiac hypertrophy in which enhancement of mechanical factors is associated with angiogenesis.


Assuntos
Arteríolas/patologia , Cardiomegalia/patologia , Animais , Arteríolas/fisiopatologia , Derivação Arteriovenosa Cirúrgica , Volume Sanguíneo , Capilares/patologia , Cardiomegalia/etiologia , Cardiomegalia/fisiopatologia , Ventrículos do Coração/patologia , Masculino , Neovascularização Patológica , Tamanho do Órgão , Ratos , Ratos Sprague-Dawley
19.
Stroke ; 25(7): 1456-61; discussion 1461-2, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8023363

RESUMO

BACKGROUND AND PURPOSE: The goal of this study was to examine effects of local reductions in intravascular pressure and dP/dt on endothelium-dependent responses of cerebral arterioles in normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). METHODS: WKY and SHRSP underwent clipping of one carotid artery at 1 month of age. At 6 months of age, responses of pial arterioles were examined in vivo in anesthetized rats. Bilateral craniotomies were performed to expose pial arterioles in the sham-operated and clipped cerebral hemispheres. Pressure (servo-null) was measured in sham-operated and clipped pial arterioles, and arteriolar diameter was measured before and during suffusion with bradykinin, A23187, and nitroprusside. RESULTS: Carotid clipping normalized pial arteriolar pulse pressure but not mean pressure in SHRSP. Responses of sham-operated pial arterioles to bradykinin and A23187 were less in SHRSP than in WKY. Responses of sham-operated pial arterioles to nitroprusside were greater in SHRSP than in WKY. Carotid clipping in SHRSP normalized responses of pial arterioles to bradykinin but not A23187 and had no effect on responses to nitroprusside. CONCLUSIONS: These findings suggest that elevated intravascular pressure per se may contribute to impairment of endothelium-dependent relaxation to at least some agonists in cerebral arterioles during chronic hypertension. Furthermore, the findings lead us to speculate that arteriolar pulse pressure may play a more important role than mean pressure in development of impaired endothelium dilatation during chronic hypertension.


Assuntos
Arteríolas/fisiologia , Pressão Sanguínea , Encéfalo/irrigação sanguínea , Endotélio Vascular/fisiologia , Vasodilatação/efeitos dos fármacos , Animais , Bradicinina/farmacologia , Encéfalo/efeitos dos fármacos , Calcimicina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Hipertensão/fisiopatologia , Óxido Nítrico/metabolismo , Nitroprussiato/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Wistar
20.
Am J Physiol ; 266(3 Pt 2): H1027-33, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8160806

RESUMO

The goal of this study was to investigate factors that contribute to reductions in internal diameter of large and small cerebral arteries during chronic hypertension. We measured diameter of second- and third-order branches of the posterior cerebral artery in vitro during maximal dilation with EDTA in 6-mo-old stroke-prone spontaneously hypertensive rats (SHRSP, n = 7) and Wistar-Kyoto rats (WKY, n = 7). Cross-sectional area of the vessel wall, measured histologically, was not significantly different at 70 mmHg in SHRSP and WKY in large or small branches of posterior cerebral artery. In large branches of posterior cerebral artery, external and internal diameters were significantly less at 70 mmHg in SHRSP than in WKY, whereas external and internal diameters converged at 0 mmHg in the two groups of rats. In small branches, on the other hand, external and internal diameters were significantly less at all levels of intravascular pressure in SHRSP than in WKY. The stress-strain relation in posterior cerebral artery of SHRSP was shifted to the left in large branches and to the right in small branches, which indicates that distensibility was reduced in large cerebral arteries of SHRSP and increased in small cerebral arteries. These findings suggest that different mechanisms are responsible for impairment of maximal dilator capacity in large and small cerebral arteries of SHRSP: reduced distensibility in large arteries and remodeling with reduced external diameter in small arteries. Furthermore the findings provide additional support for the concept that hypertrophy may not be a primary factor in impaired maximal dilation.


Assuntos
Artérias Cerebrais/fisiopatologia , Hipertensão/fisiopatologia , Animais , Doença Crônica , Elasticidade , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Estresse Mecânico , Vasodilatação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...