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1.
An Acad Bras Cienc ; 90(1): 185-194, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29641758

RESUMEN

The N-salicyloyltryptamine (NST) is an indole derivative compound analogue to the alkaloid N-benzoyltryptamine. In the present study, the antiedematogenic activity of NST was investigated in animal models. Firstly, the acute toxicity for NST was assessed according to the OECD Guideline no. 423. The potential NST-induced antiedematogenic activity was evaluated by carrageenan-induced paw edema in rats, as well as by dextran-, compound 48/80-, histamine-, serotonin-, capsaicine-, and prostaglandin E2-induced paw edema in mice. The effect of NST on compound 48/80-induced ex vivo mast cell degranulation on mice mesenteric bed was investigated. No death or alteration of behavioral parameters was observed after administration of NST (2000 mg/kg, i.p.) during the observation time of 14 days. The NST (100 and 200 mg/kg, i.p.) inhibited the carrageenan-induced edema from the 1st to the 5th hour (**p<0.01; ***p<0.001). The edematogenic activity induced by dextran, compound 48/80, histamine, serotonin, capsaicin, and prostaglandin E2 was inhibited by NST (100 mg/kg, i.p.) throughout the observation period (**p<0.01; ***p<0.001). The pretreatment with NST (50, 100 or 200 mg/kg, i.p) attenuates the compound 48/80-induced mast cell degranulation (**p<0.01; ***p<0.001). Thus, the inhibition of both mast cell degranulation and release of endogenous mediators are probably involved in the NST-induced antiedematogenic effect.


Asunto(s)
Antiinflamatorios/farmacología , Edema/tratamiento farmacológico , Salicilatos/farmacología , Triptaminas/farmacología , Animales , Antiinflamatorios/toxicidad , Carragenina , Modelos Animales de Enfermedad , Edema/inducido químicamente , Femenino , Miembro Posterior , Mediadores de Inflamación , Masculino , Ratones , Péptidos/efectos de los fármacos , Ratas Wistar , Salicilatos/toxicidad , Factores de Tiempo , Triptaminas/toxicidad
2.
An. acad. bras. ciênc ; 90(1): 185-194, Mar. 2018. tab, graf
Artículo en Inglés | LILACS | ID: biblio-886919

RESUMEN

ABSTRACT The N-salicyloyltryptamine (NST) is an indole derivative compound analogue to the alkaloid N-benzoyltryptamine. In the present study, the antiedematogenic activity of NST was investigated in animal models. Firstly, the acute toxicity for NST was assessed according to the OECD Guideline no. 423. The potential NST-induced antiedematogenic activity was evaluated by carrageenan-induced paw edema in rats, as well as by dextran-, compound 48/80-, histamine-, serotonin-, capsaicine-, and prostaglandin E2-induced paw edema in mice. The effect of NST on compound 48/80-induced ex vivo mast cell degranulation on mice mesenteric bed was investigated. No death or alteration of behavioral parameters was observed after administration of NST (2000 mg/kg, i.p.) during the observation time of 14 days. The NST (100 and 200 mg/kg, i.p.) inhibited the carrageenan-induced edema from the 1st to the 5th hour (**p<0.01; ***p<0.001). The edematogenic activity induced by dextran, compound 48/80, histamine, serotonin, capsaicin, and prostaglandin E2 was inhibited by NST (100 mg/kg, i.p.) throughout the observation period (**p<0.01; ***p<0.001). The pretreatment with NST (50, 100 or 200 mg/kg, i.p) attenuates the compound 48/80-induced mast cell degranulation (**p<0.01; ***p<0.001). Thus, the inhibition of both mast cell degranulation and release of endogenous mediators are probably involved in the NST-induced antiedematogenic effect.


Asunto(s)
Animales , Masculino , Femenino , Ratas , Triptaminas/farmacología , Salicilatos/farmacología , Edema/tratamiento farmacológico , Antiinflamatorios/farmacología , Péptidos/efectos de los fármacos , Factores de Tiempo , Carragenina , Triptaminas/toxicidad , Salicilatos/toxicidad , Ratas Wistar , Mediadores de Inflamación , Modelos Animales de Enfermedad , Edema/inducido químicamente , Miembro Posterior , Antiinflamatorios/toxicidad
3.
Toxicol In Vitro ; 50: 1-10, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29476885

RESUMEN

Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is one of the most important parasitic diseases in the world, affecting over 200 million people in developing countries. Riparins are natural alkamides found in Aniba riparia (Lauraceae) fruits that possess several pharmacological properties. In this study, we reported the synthesis, characterization and structural analysis of six riparin derivatives (A-F), as well as their schistosomicidal activity against S. mansoni worms together with a biological, pharmacokinetic and toxicological in silico evaluation. Firstly, these compounds were synthesized, purified and characterized by elemental analysis, FT-IR spectroscopy, X-ray diffraction and theoretical calculations to evaluate their stability and conformation. Next, the schistosomicidal activity of the riparins was tested against S. mansoni worms. Bioassays revealed that Riparins E and F were the most active compounds, showing half-maximum inhibitory concentration at low micromolar ranges (IC50 values ~10 µM). Also, confocal laser scanning microscopy studies revealed tegumental damage in parasites after exposition with Riparins B, E and F. Additionally, based on MTT assay, all tested riparins showed no cytotoxic potential toward mammalian cells. Finally, in silico analyses were used to predict the absorption, distribution, metabolism, elimination and toxicity (ADMET) of the compounds. Taken together, the results revealed a promising ADMET profile and suggested that riparins could be starting points for lead optimization programs for natural products with antischistosomal properties.


Asunto(s)
Benzamidas , Fenetilaminas , Esquistosomicidas , Animales , Benzamidas/química , Benzamidas/farmacocinética , Benzamidas/farmacología , Benzamidas/toxicidad , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Simulación por Computador , Humanos , Absorción Intestinal , Modelos Biológicos , Estructura Molecular , Fenetilaminas/química , Fenetilaminas/farmacocinética , Fenetilaminas/farmacología , Fenetilaminas/toxicidad , Difracción de Polvo , Schistosoma mansoni/efectos de los fármacos , Esquistosomicidas/química , Esquistosomicidas/farmacocinética , Esquistosomicidas/farmacología , Esquistosomicidas/toxicidad , Absorción Cutánea , Espectroscopía Infrarroja por Transformada de Fourier , Células Vero , Difracción de Rayos X
4.
Vascul Pharmacol ; 82: 60-5, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27173831

RESUMEN

The development of new calcium channel blockers is still relevant for the understanding of their physiological role and pharmacological and therapeutic purposes. For this task, natural products represent a relevant source of new drugs. The present work investigated the mechanism and the structural relationship of the vasodilator effect of riparins I, II and III in mouse small mesenteric artery. Riparins I, II and III induced an endothelium-independent and concentration-dependent vasodilator effect in mesenteric arteries. Riparins II and III were more potent than riparin I, suggesting a structural relationship of the effect of these drugs. All riparins inhibited the contractile effect of KCl, similarly to nifedipine. However, the inhibitory profile was different for the contractile responses to phenylephrine and caffeine, passing from similar to nifedipine with riparin I, for similar to SKF-96365 with riparin III. A comparable effect was observed for the increase in the intracellular calcium concentration induced by caffeine and phenylephrine. These results suggest that the higher hydroxylation provides the alkamides the ability to inhibit non-selective cation channels in addition to the inhibition of L-type calcium channels in mouse mesenteric arteries. These observations may give support to the development of new selective inhibitors of non-selective cation channels using alkamides as leading compounds.


Asunto(s)
Benzamidas/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo L/efectos de los fármacos , Señalización del Calcio/efectos de los fármacos , Arterias Mesentéricas/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Benzamidas/química , Bloqueadores de los Canales de Calcio/química , Canales de Calcio Tipo L/metabolismo , Relación Dosis-Respuesta a Droga , Hidroxilación , Técnicas In Vitro , Masculino , Arterias Mesentéricas/metabolismo , Ratones , Estructura Molecular , Relación Estructura-Actividad , Tiramina/análogos & derivados , Tiramina/farmacología , Vasodilatadores/química
5.
Fundam Clin Pharmacol ; 29(4): 394-403, 2015 08.
Artículo en Inglés | MEDLINE | ID: mdl-25846646

RESUMEN

Riparin III (Rip III) is an alcamide isolated from Aniba riparia that has presented effects of antidepressant and anxiolytic activities in acute stress behavioral models. The trial's goal was to investigate the activity of Rip III in mice exposed to corticosterone-induced chronic depression model. Swiss female mice, 22-25 g, were distributed in following experimental groups: control group (vehicle1: saline containing 0.1% dimethyl sulfoxide and 0.1% Tween-80, SC+ vehicle 2: distilled water emulsified with 2% Tween-80, PO); stressed group (corticosterone, 20 mg/kg, SC, + vehicle 2, orally); Rip III group (50 mg/kg, orally); and fluvoxamine (Flu) group (50 mg/kg, orally). The mice were exposed to the behavioral tests, and posteriorly, Brain-derived neurotrophic factor protein levels were assessed in hippocampal samples. Statistical analysis of the data was performed by one-way anova, followed by Newman-Keuls test. Both administrations of Rip III and Flu significantly reduced the immobility time in tail suspension and forced swimming tests after 21 days without affecting locomotor function. There was also an increase in BDNF protein levels in the mice hippocampus. These findings further support the hypothesis that Rip III could be a new pharmacological target for the treatment of mood disorders.


Asunto(s)
Antidepresivos/farmacología , Benzamidas/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/tratamiento farmacológico , Hipocampo/metabolismo , Tiramina/análogos & derivados , Anhedonia/efectos de los fármacos , Animales , Ansiedad/tratamiento farmacológico , Ansiedad/psicología , Conducta Animal/efectos de los fármacos , Corticosterona/farmacología , Depresión/inducido químicamente , Depresión/psicología , Femenino , Fluvoxamina/farmacología , Suspensión Trasera/psicología , Hipocampo/efectos de los fármacos , Relaciones Interpersonales , Ratones , Actividad Motora/efectos de los fármacos , Natación/psicología , Tiramina/farmacología
6.
Chem Biol Interact ; 229: 55-63, 2015 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-25656915

RESUMEN

Inflammation is a local tissue response to attacks characterized by vascular and cellular events, including intense oxidative stress. Riparin A, a compound obtained from Aniba riparia, has been shown to have antioxidant activity and cytotoxicity in vitro. This study was aimed at evaluating the anti-inflammatory effect of riparin A against acute inflammation. The results of our evaluations in various experimental models indicated that riparin A reduced paw edema induced by carrageenan, compound 48/80, histamine, and serotonin. Furthermore, it decreased leukocyte and neutrophil counts, myeloperoxidase activity, thiobarbituric acid reactive substance (TBARS) levels, and cytokine (tumor necrosis factor-α and interleukin-1ß) levels increased by carrageenan-induced peritonitis, and reversed glutathione levels. Riparin A also reduced carrageenan-induced adhesion and rolling of leukocytes on epithelial cells and did not produce gastric-damage as compared with indomethacin. In conclusion, the data show that riparin A reduces inflammatory response by inhibiting vascular and cellular events, modulating neutrophil migration, inhibiting proinflammatory cytokine production, and reducing oxidative stress.


Asunto(s)
Antiinflamatorios/uso terapéutico , Benzamidas/uso terapéutico , Carragenina/efectos adversos , Edema/tratamiento farmacológico , Enfermedades del Sistema Inmune/tratamiento farmacológico , Trastornos Leucocíticos/tratamiento farmacológico , Neutrófilos/efectos de los fármacos , Peritonitis/tratamiento farmacológico , Fenetilaminas/uso terapéutico , Animales , Antiinflamatorios/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Antioxidantes/uso terapéutico , Benzamidas/aislamiento & purificación , Carragenina/inmunología , Adhesión Celular/efectos de los fármacos , Citocinas/inmunología , Edema/inducido químicamente , Edema/inmunología , Edema/patología , Extremidades/patología , Enfermedades del Sistema Inmune/inducido químicamente , Enfermedades del Sistema Inmune/inmunología , Enfermedades del Sistema Inmune/patología , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Inflamación/patología , Lauraceae/química , Trastornos Leucocíticos/inducido químicamente , Trastornos Leucocíticos/inmunología , Trastornos Leucocíticos/patología , Rodamiento de Leucocito/efectos de los fármacos , Masculino , Ratones , Neutrófilos/inmunología , Neutrófilos/patología , Estrés Oxidativo/efectos de los fármacos , Peritonitis/inducido químicamente , Peritonitis/inmunología , Peritonitis/patología , Peroxidasa/inmunología , Fenetilaminas/aislamiento & purificación
7.
J Biomed Biotechnol ; 2010: 230745, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20976310

RESUMEN

We investigated the antinociceptive and nerve excitability effects of the N-salicyloyltryptamine (NST) NST-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg (i.p.) were administered (i.p.). This effect was not antagonized by naloxone (1.5 mg/kg, i.p.). NST inhibited the licking response of the injected paw when 100 and 200 mg/kg were administered (i.p.) to mice in the first and second phases of the formalin test. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and showed that NST (3.57 mM) significantly reduced (29.2%) amplitude of the compound action potential (CAP) suggesting a sodium channel effect induced by NST. Our results demonstrated an antinociceptive activity of the NST that could be, at least in part, associated to the reduction of the action potential amplitude. NST might represent an important tool for pain management.


Asunto(s)
Analgésicos/farmacología , Conducta Animal/efectos de los fármacos , Bioensayo/métodos , Fenómenos Electrofisiológicos/efectos de los fármacos , Salicilatos/farmacología , Triptaminas/farmacología , Ácido Acético , Potenciales de Acción/efectos de los fármacos , Analgésicos/uso terapéutico , Animales , Diazepam/uso terapéutico , Formaldehído , Indometacina/farmacología , Masculino , Ratones , Dolor/tratamiento farmacológico , Prueba de Desempeño de Rotación con Aceleración Constante , Salicilatos/química , Salicilatos/uso terapéutico , Factores de Tiempo , Triptaminas/química , Triptaminas/uso terapéutico
8.
J. epilepsy clin. neurophysiol ; 15(4): 165-168, dez. 2009. tab
Artículo en Inglés | LILACS | ID: lil-545418

RESUMEN

AIM: In the present study we verified the anticonvulsant properties of the new tryptamine analogue, N-salicyloyltryptamine (NST), in rodents. METHODS AND RESULTS: In the evaluation of the anticonvulsant activity, NST protected the animals from the incidence of seizures induced by pentylenetetrazole (PTZ) and picrotoxin (PIC), in doses of 100 and 200 mg/kg. NST (100 and 200 mg/kg, i.p.) significantly eliminated the extensor reflex of maximal electric-induced seizure tests in 40 percent of the experimental animals. However, in the PTZ model FLU (10 mg/kg, i.p.), an antagonist of the benzodiazepine (BZD) site in the GABA A-BZD receptor complex, inhibited the prolongation of seizure latency induced by NST. CONCLUSION: Our results demonstrated an anticonvulsant activity of the new analogue that could be, at least in part, associated to the involvement of the GABAergic mechanism.


OBJETIVO: O presente estudo buscou avaliar o possível efeito anticonvulsivante do novo análogo da triptamina, N-saliciloiltriptamina (NST), em roedores. MÉTODOS E RESULTADOS: Na avaliação do efeito anticonvulsivante, os animais tratados com NST (100 e 200 mg/kg, i.p.) foram protegidos de maneira estatisticamente significativa (p<0,05) quanto a latência e incidência do aparecimento das convulsões induzidas pela administração do pentilenotetrazol (PTZ) e da picrotoxina (PIC). O efeito protetor do NST nas convulsões induzidas pelo PTZ foi revertido pela administração do flumazenil (10 mg/kg, i.p.), um antagonista dos receptores GABA-benzodiazepínicos (GABA A-BZD). A administração de NST (100 e 200 mg/kg, i.p.) protegeu de forma estatisticamente significativa (p < 0,05) os animais no teste das convulsões induzidas pelo eletrochoque-auricular em camundongos. CONCLUSÃO: Os resultados do presente estudo sugerem que o efeito anticonvulsivante de NST está associado, pelo menos em parte, ao sistema GABAérgico.


Asunto(s)
Humanos , Triptaminas , Flumazenil , Epilepsia , Anticonvulsivantes
9.
Minerva Chir ; 58(3): 305-11, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12955048

RESUMEN

Renal artery aneurysms are an uncommon vascular entity and are more likely to affect younger patients without significant atherosclerotic risk factors as compared to patients with renal artery occlusive disease. Hypertension is a commonly associated disease and the renal artery aneurysm may be causal, exclusive of renal artery occlusive disease. Diagnosis is often made incidentally but arteriography is essential for good operative planning. The main complication of RAA is rupture, which is increased in peripartum females. Operative therapy is primarily in situ aneurysmectomy and angioplastic closure or exclusion and bypass, usually with autologous conduit. It is currently recommended that in good operative risk patients, repair is recommended for RAA >1.0 cm when hypertension present and RAA >1.5 to 2.0 cm when no hypertension present. Given the anatomic complexity of these lesions, little role for endovascular therapy is forecast.


Asunto(s)
Aneurisma , Arteria Renal , Algoritmos , Aneurisma/diagnóstico , Aneurisma/terapia , Humanos , Resultado del Tratamiento
10.
J Vasc Surg ; 34(5): 798-804, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11700478

RESUMEN

PURPOSE: Duplex ultrasound scanning (US) is the accepted standard means of diagnosis for lower-extremity suprageniculate deep venous thrombosis (LE-DVT). Computed tomographic venography (CTV) has been proposed as an alternative modality for diagnosis of LE-DVT in patients with suspected pulmonary embolism (PE). This study compared CTV with US as a means of diagnosing acute LE-DVT. METHODS: A retrospective review of US and CTV scans from 136 patients with suspected PE who underwent both studies to exclude acute LE-DVT at a single institution was performed. Studies were reviewed and coded in a blinded manner. US was considered to be the reference test. Direct costs of each study were determined by using commercial software. RESULTS: The sensitivity and specificity rates of CTV were 71% and 93%, respectively. The positive predictive value, negative predictive value, and accuracy rates of CTV were 53%, 97%, and 90%, respectively. DVT localization was the same in eight of 10 cases in which the results of both US and CTV were positive. CTV costs and charges per study were greater than those of US by $46.88 and $602.00, respectively. CONCLUSION: CTV is specific, but has a lower sensitivity rate and positive predictive value for the diagnosis of acute LE-DVT compared with US. Additionally, CTV is more costly than US scanning. Because of the lower sensitivity rate and positive predictive value and the increased cost of CTV, US remains the screening study of choice in cases of suspected acute LE-DVT.


Asunto(s)
Embolia Pulmonar , Tomografía Computarizada por Rayos X , Trombosis de la Vena/diagnóstico por imagen , Costos y Análisis de Costo , Femenino , Humanos , Pierna/irrigación sanguínea , Masculino , Persona de Mediana Edad , Flebografía , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/economía , Ultrasonografía Doppler Dúplex/economía , Trombosis de la Vena/epidemiología
11.
Acad Radiol ; 8(9): 879-87, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11724043

RESUMEN

RATIONALE AND OBJECTIVES: The purpose of this study was to assess interobserver variability in the interpretation of gadolinium-enhanced magnetic resonance (MR) angiograms of splanchnic vessels in patients suspected of having chronic mesenteric ischemia (CMI). MATERIALS AND METHODS: Two readers blinded to the initial interpretation retrospectively reviewed gadolinium-enhanced MR angiograms obtained for suspected CMI in 26 patients (20 women and six men; age range, 23-77 years; mean age, 61 years) who also underwent conventional angiography. Each reader graded the degree of stenosis based on the percentage diameter reduction of the celiac artery (CA), superior mesenteric artery (SMA), and inferior mesenteric artery (IMA) by using a five-point ordinal scale: 0, no stenosis: 1, mild stenosis (<50%); 2, moderate stenosis (50%-75%); 3, severe stenosis (>75%); 4, occluded artery. Using the conventional angiogram as a reference standard, authors determined sensitivity and specificity for each observer, assigning two thresholds (grades 2 and 3) as significant stenoses. A kappa statistic (kappa) measured interobserver agreement. RESULTS: With grade 2 stenosis used as a threshold, cumulative accuracies for detecting significant stenosis were 0.95 (95% confidence interval, 0.86-0.99) for reader A and 0.97 (0.88-1.0) for reader B. Interobserver agreement for grading proximal splanchnic stenosis was 0.90 for CA, 0.92 for SMA, and 0.48 for IMA. CONCLUSION: Gadolinium-enhanced MR angiography is reproducibly accurate for detection of proximal splanchnic artery stenosis, with good to excellent interobserver agreement.


Asunto(s)
Isquemia/diagnóstico , Angiografía por Resonancia Magnética , Oclusión Vascular Mesentérica/diagnóstico , Adulto , Anciano , Arteria Celíaca/patología , Enfermedad Crónica , Femenino , Gadolinio , Humanos , Angiografía por Resonancia Magnética/métodos , Masculino , Arteria Mesentérica Inferior/patología , Arteria Mesentérica Superior/patología , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estudios Retrospectivos , Sensibilidad y Especificidad , Circulación Esplácnica
12.
Ann Surg ; 234(4): 454-62; discussion 462-3, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11573039

RESUMEN

OBJECTIVE: To define the relevance of treating renal artery aneurysms (RAAs) surgically. SUMMARY BACKGROUND DATA: Most prior definitions of the clinical, pathologic, and management features of RAAs have evolved from anecdotal reports. Controversy surrounding this clinical entity continues. METHODS: A retrospective review was undertaken of 168 patients (107 women, 61 men) with 252 RAAs encountered over 35 years at the University of Michigan Hospital. Aneurysms were solitary in 115 patients and multiple in 53 patients. Bilateral RAAs occurred in 32 patients. Associated diseases included hypertension (73%), renal artery fibrodysplasia (34%), systemic atherosclerosis (25%), and extrarenal aneurysms (6.5%). Most RAAs were saccular (79%) and noncalcified (63%). The main renal artery bifurcation was the most common site of aneurysms (60%). RAAs were often asymptomatic (55%), with a diagnosis made most often during arteriographic study for suspected renovascular hypertension (42%). RESULTS: Surgery was performed in 121 patients (average RAA size 1.5 cm), including 14 patients undergoing unilateral repair with contralateral RAA observation. The remaining 47 patients (average RAA size 1.3 cm) were not treated surgically. Operations included aneurysmectomy and angioplastic renal artery closure or segmental renal artery reimplantation, aneurysmectomy and renal artery bypass, and planned nephrectomy for unreconstructable renal arteries or advanced parenchymal disease. Eight patients underwent unplanned nephrectomy, being considered a technical failure of surgical therapy. Dialysis-dependent renal failure occurred in one patient. There were no perioperative deaths. Late follow-up (average 91 months) was available in 145 patients (86%). All but two arterial reconstructions remained clinically patent. Secondary renal artery procedures included percutaneous angioplasty, branch embolization, graft thrombectomy, and repeat bypass for late aneurysmal change of a vein conduit. Among 40 patients with clearly documented preoperative and postoperative blood pressure measurements, 60% had a significant decline in blood pressure after surgery while taking fewer antihypertensive medications. Late RAA rupture did not occur in the nonoperative patients, but no lessening of this group's hypertension was noted. CONCLUSION: Surgical therapy of RAAs in properly selected patients provides excellent long-term clinical outcomes and is often associated with decreased blood pressure.


Asunto(s)
Aneurisma/cirugía , Arteria Renal , Procedimientos Quirúrgicos Vasculares/métodos , Adolescente , Adulto , Anciano , Aneurisma/diagnóstico por imagen , Aneurisma/mortalidad , Angiografía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Nefrectomía/métodos , Complicaciones Posoperatorias/mortalidad , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/mortalidad
13.
Am J Physiol Cell Physiol ; 281(3): C801-9, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11502557

RESUMEN

ANG II type 1 (AT(1)) receptors respond to sustained exposure to ANG II by undergoing downregulation of absolute receptor numbers. It has been assumed previously that downregulation involves endocytosis. The present study hypothesized that AT(1) receptor downregulation occurs independently of receptor endocytosis or G protein coupling. Mutant AT(1) receptors with carboxy-terminal deletions internalized <5% of radioligand compared with 65% for wild-type AT(1) receptors. The truncated AT(1) receptors retained the ability to undergo downregulation. These data suggest the existence of an alternative pathway to AT(1) receptor degradation that does not require endocytosis, per se. Point mutations in either the second transmembrane region or second intracellular loop impaired G protein (G(q)) coupling. These receptors exhibited a biphasic pattern of downregulation. The earliest phase of downregulation (0-2 h) was independent of coupling to G(q), but no additional downregulation was observed after 2 h of ANG II exposure in the receptors with impaired coupling to G(q). These data suggest that coupling to G(q) is required for the later phase (2-24 h) of AT(1) receptor downregulation.


Asunto(s)
Regulación hacia Abajo/fisiología , Proteínas de Unión al GTP/fisiología , Receptores de Angiotensina/fisiología , Sustitución de Aminoácidos , Angiotensina II/metabolismo , Animales , Sitios de Unión , Células COS , Calcio/metabolismo , Chlorocebus aethiops , Clonación Molecular , Endocitosis , Radioisótopos de Yodo , Cinética , Mutagénesis Sitio-Dirigida , Fosfatidilinositoles/metabolismo , Ensayo de Unión Radioligante , Ratas , Receptor de Angiotensina Tipo 1 , Receptor de Angiotensina Tipo 2 , Receptores de Angiotensina/química , Receptores de Angiotensina/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Eliminación de Secuencia , Transfección
14.
J Vasc Surg ; 34(1): 34-40, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11436072

RESUMEN

OBJECTIVE: Limb length discrepancies (LLDs) in growing children may accompany extremity arterial occlusions. Revascularization with vein grafts has been questioned because of degenerative graft changes observed at other sites. This study was undertaken to define vein graft durability and efficacy in lower extremity revascularizations in preadolescent children. STUDY DESIGN: Fourteen children (10 boys, 4 girls) with a mean age of 7.3 years (range, 2-11 years) who underwent 16 lower extremity revascularizations with greater saphenous vein grafts were subjected to follow-up with graft ultrasonography, ankle/brachial indices (ABIs) with and without exercise, and limb length determinations. A mean of 5.7 years elapsed between the onset of ischemia and operation. Arterial occlusions resulted from cardiac catheterizations (11), arteritis (1), dialysis cannulation (1), and penetrating trauma (1). Indications for operation included LLD (6), claudication (4), both LLD and claudication (3), markedly diminished ABIs with a potential for LLD (2), and a traumatic transection with hemorrhage (1). The reconstructions with 15 reversed and one in situ vein grafts included iliofemoral (11), femorofemoral (1), aortofemoral (1), femoropopliteal (1), popliteal-popliteal (1), and popliteal-posterior tibial (1) arterial bypass grafts. RESULTS: Among patent grafts available for follow-up, 36% (5 of 14) remained unchanged, 50% (7 of 14) developed nonaneurysmal dilatation, and 14% (2 of 14) exhibited nonprogressive aneurysmal expansion. One graft became occluded, and one graft was lost to follow-up. Collectively, the grafts manifest an 11.2% expansion at an average of 10.7 years postoperatively. ABIs increased from 0.75 preoperatively to 0.97, at an average of 11.0 years postoperatively. LLDs were reduced from 1.66 to 1.24 cm, at an average of 11.4 years postoperatively. CONCLUSION: Vein graft reconstructions of lower extremity arteries in preadolescent children are durable. They provide an efficacious means of restoring normal blood flow, and in 70% of children their preexisting LLDs were reduced.


Asunto(s)
Implantación de Prótesis Vascular , Pierna/irrigación sanguínea , Vena Safena/trasplante , Angiografía de Substracción Digital , Niño , Preescolar , Femenino , Humanos , Masculino , Resultado del Tratamiento , Enfermedades Vasculares/cirugía
15.
J Vasc Surg ; 34(1): 76-83, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11436078

RESUMEN

OBJECTIVE: The hypothesis to be tested was that diminished bioavailable nitric oxide (NO) affects matrix metalloproteinase (MMP) expression and activation in vascular smooth muscle cells (SMCs). METHODS: Cultivated rat aortic SMCs (RA-SMCs) were exposed to increasing concentrations of L-N-monomethyl arginine (L-NMMA), a nonselective inhibitor of NO synthase, in the presence of proinflammatory cytokines (50 ng/mL interleukin [IL]-1beta, 50 ng/mL interferon-gamma, and 30 microg/mL lipopolysaccharide). Nitrite and nitrate, two of the final end products of NO metabolism, were measured in media collected at 48 hours with the use of the Saville assay (n = 4). MMP activity was measured with 1% gelatin zymography (n = 4). In separate experiments in which 2 ng/mL of IL-1beta and L-NMMA was used, MMP protein and messenger RNA (mRNA) levels were determined with Western blot analysis (n = 3) and semiquantitative reverse transcriptase-polymerase chain reaction (n = 3), respectively. Data were analyzed with nonparametric analysis of variance. RESULTS: Increasing concentrations of the NO synthase inhibitor L-NMMA caused a dose-dependent decrease (P <.05) in nitrite and nitrate production by RA-SMCs after cytokine exposure. Zymography documented an early dosedependent increase (P <.05 compared with cytokines alone) in 92-kd MMP activity, with no significant changes in 72-kd MMP activity after treatment with L-NMMA (P >.05 compared with cytokines alone). Reverse transcriptase-polymerase chain reaction and Western blot analysis revealed that the addition of L-NMMA to IL-1beta-stimulated RA-SMCs led to significant increases in MMP-9 mRNA (n = 3, P <.01 for 1.0 mmol/L L-NMMA) and MMP-9 protein levels (n = 3, P <.05), respectively. No differences in MMP-2 mRNA or protein levels were demonstrated. CONCLUSIONS: Inhibition of cytokine-induced NO expression in RA-SMCs is associated with a selective, dose-dependent increase in MMP-9 expression and synthesis. These findings suggest that alterations in local NO synthesis may influence MMP-9-dependent vessel wall damage.


Asunto(s)
Metaloproteinasa 9 de la Matriz/metabolismo , Músculo Liso Vascular/citología , Óxido Nítrico/fisiología , Animales , Aorta/citología , Western Blotting , Células Cultivadas , Electroforesis en Gel de Poliacrilamida , Inhibidores Enzimáticos/farmacología , Masculino , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , omega-N-Metilarginina/farmacología
17.
J Vasc Surg ; 33(1): 72-6, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11137926

RESUMEN

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is associated with abdominal aortic aneurysm (AAA) expansion and is considered by some to be a relative contraindication to conventional aortic surgery. This study was undertaken to determine if COPD increases operative death, morbidity, intensive care unit (ICU) length of stay (LOS), and hospital LOS, after AAA repair. METHODS: Data from national administrative records supplemented with laboratory data previously obtained for a system-wide study were analyzed in a retrospective review of 1053 consecutive patients (264 with and 789 without COPD) undergoing operation for intact or ruptured AAAs in Veterans Administration Hospitals from 1997 to 1998. Bivariate comparisons and multivariate regression were used to evaluate the impact of COPD on the number of days of ventilation, ICU LOS, total hospital LOS, and death, while controlling for other known risk factors, including acute myocardial infarction, renal failure, and age. RESULTS: The mortality rate in elective aneurysm patients did not differ (P =.99) between patients with (3.7%) or without COPD (3.7%). However, elective AAA repair was associated with longer hospital LOS (14.4 vs 12.3 days, P =.01), longer ICU LOS (6.5 vs 5.4 days, P =.01), and a higher incidence of requiring 96 hours or more ventilation (6.9% vs 3.6%, P =.02) in patients with COPD. Ruptured AAA affected 4.9% of patients and was strongly associated with COPD (P =.02); however, COPD did not result in a statistically significant increase in death (P =.25). CONCLUSIONS: Although COPD does not appear to increase operative death, it is associated with an increased risk of rupture. Elective repair of AAA should not be deferred in patients with COPD despite their higher LOSs and need for postoperative ventilation.


Asunto(s)
Aneurisma Roto/cirugía , Aneurisma de la Aorta Abdominal/cirugía , Urgencias Médicas , Tiempo de Internación/estadística & datos numéricos , Enfermedades Pulmonares Obstructivas/mortalidad , Complicaciones Posoperatorias/mortalidad , Anciano , Aneurisma Roto/complicaciones , Aneurisma Roto/mortalidad , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Enfermedades Pulmonares Obstructivas/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Riesgo , Tasa de Supervivencia
18.
J Nutr Biochem ; 11(10): 491-5, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11120446

RESUMEN

A small-scale preliminary cross-over study was conducted to investigate the effects of supercritical CO(2)-extracted sea buckthorn berry oil (SBO) on some risk factors of cardiovascular disease. Special features of the oil are high proportions of palmitic (16:0), oleic (18:1n-9), palmitoleic (16:1n-7), linoleic (18:2n-6), and alpha-linolenic (18:3n-3) acids as well as vitamin E, carotenoids, and sterols. Twelve healthy normolipidemic men were recruited and each volunteer consumed SBO and fractionated coconut oil (control) 5 g per day for a period of 4 weeks in a random order (wash-out 4-8 weeks). Phospholipid fatty acids, plasma lipids, and glucose were unaffected by SBO supplementation. Instead, a clear decrease in the rate of adenosine-5'-diphosphate-induced platelet aggregation and maximum aggregation were found. This suggested the beneficial effects of SBO on blood clotting, but further studies on the dose-response effects are needed to assess the practical use of SBO supplements.

19.
Anesthesiology ; 93(4): 964-70, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11020747

RESUMEN

BACKGROUND: Stroke is an important contributor to perioperative morbidity and mortality associated with carotid endarterectomy (CEA). This investigation was designed to compare the performance of the INVOS-3100 cerebral oximeter to neurologic function, as a means of detecting cerebral ischemia induced by carotid cross-clamping, in patients undergoing carotid endarterectomy with cervical plexus block. METHODS: Ninety-nine patients undergoing 100 CEAs with regional anesthesia (deep or superficial cervical plexus block) were studied. Bilateral regional cerebrovascular oxygen saturation (rSO2) was monitored using the INVOS-3100 cerebral oximeter. Patients were retrospectively assigned to one of two groups: those in whom a change in mental status or contralateral motor deficit was noted after internal carotid clamping (neurologic symptoms; n = 10) and those who did not show any neurologic change (no neurologic symptoms; n = 90). Data from 94 operations (neurologic symptoms = 10 and no neurologic symptoms = 84) were adequate for statistical analyses for group comparisons. A relative decrease in ipsilateral rSO2 after carotid occlusion (calculated as a percentage of preocclusion value) during all operations (n = 100) was also calculated to determine the critical level of rSO2 decrease associated with a change in neurologic function. RESULTS: The mean (+/- SD) decrease in rSO2 after carotid occlusion in the neurologic symptoms group (from 63.2 +/- 8.4% to 51.0 +/- 11.6%) was significantly greater (P = 0.0002) than in the no neurologic symptoms group (from 65.8 +/- 8.5% to 61.0 +/- 9.3%). Logistic regression analysis used to determine if a change in rSO2, calculated as a percentage of preclamp value, could be used to predict change in neurologic function was highly significant (likelihood ratio chi-square = 13.7; P = 0.0002). A 20% decrease in rSO2 reading from the preclamp baseline, as a predictor of neurologic compromise, resulted in a sensitivity of 80% and specificity of 82.2%. The false-positive rate using this cutoff point was 66.7%, and the false-negative rate was 2.6%, providing a positive predictive value of 33.3% and a negative predictive value of 97.4%. CONCLUSION: Monitoring rSO2 with INVOS-3100 to detect cerebral ischemia during CEA has a high negative predictive value, but the positive predictive value is low.


Asunto(s)
Isquemia Encefálica/diagnóstico , Endarterectomía Carotidea/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/irrigación sanguínea , Encéfalo/fisiología , Isquemia Encefálica/sangre , Isquemia Encefálica/etiología , Circulación Cerebrovascular , Plexo Cervical , Endarterectomía Carotidea/métodos , Femenino , Humanos , Complicaciones Intraoperatorias/sangre , Complicaciones Intraoperatorias/diagnóstico , Complicaciones Intraoperatorias/etiología , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Bloqueo Nervioso , Oximetría/instrumentación , Oximetría/métodos , Oxígeno/sangre , Estudios Retrospectivos , Espectroscopía Infrarroja Corta/métodos
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