RESUMO
BACKGROUND AND AIMS: Thromboxane (TX) A2, released by activated platelets, plays an important role in atherothrombosis. Urinary 11-dehydro-TXB2 (U-TXM), a stable metabolite reflecting the whole-body TXA2 biosynthesis, is reduced by â¼70% by daily low-dose aspirin. The U-TXM represents a non-invasive biomarker of in vivo platelet activation and is enhanced in patients with diabetes. This study assessed whether U-TXM is associated with the risk of future serious vascular events or revascularizations (SVE-R), major bleeding, or cancer in patients with diabetes. METHODS: The U-TXM was measured pre-randomization to aspirin or placebo in 5948 people with type 1 or 2 diabetes and no cardiovascular disease, in the ASCEND trial. Associations between log U-TXM and SVE-R (n = 618), major bleed (n = 206), and cancer (n = 700) during 6.6 years of follow-up were investigated by Cox regression; comparisons of these associations with the effects of randomization to aspirin were made. RESULTS: Higher U-TXM was associated with older age, female sex, current smoking, type 2 diabetes, higher body size, urinary albumin/creatinine ratio of ≥3 mg/mmol, and higher estimated glomerular filtration rate. After adjustment for these, U-TXM was marginally statistically significantly associated with SVE-R and major bleed but not cancer [hazard ratios per 1 SD higher log U-TXM (95% confidence interval): 1.09 (1.00-1.18), 1.16 (1.01-1.34), and 1.06 (0.98-1.14)]. The hazard ratio was similar to that implied by the clinical effects of randomization to aspirin for SVE-R but not for major bleed. CONCLUSIONS: The U-TXM was log-linearly independently associated with SVE-R in diabetes. This is consistent with the involvement of platelet TXA2 in diabetic atherothrombosis.
Assuntos
Diabetes Mellitus Tipo 2 , Neoplasias , Trombose , Humanos , Feminino , Tromboxanos/metabolismo , Tromboxanos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Aspirina/uso terapêutico , Tromboxano B2/uso terapêutico , Tromboxano B2/urina , Tromboxano A2/uso terapêutico , Tromboxano A2/urina , Trombose/tratamento farmacológico , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: Systemic thromboxane A2 generation, assessed by quantifying the concentration of stable thromboxane B2 metabolites (TXB2-M) in the urine adjusted for urinary creatinine, is strongly associated with mortality risk. We sought to define optimal TXB2-M cutpoints for aspirin users and nonusers and determine if adjusting TXB2-M for estimated glomerular filtration rate (eGFR) in addition to urinary creatinine improved mortality risk assessment. METHODS: Urinary TXB2-M were measured by competitive ELISA in 1363 aspirin users and 1681 nonusers participating in the Framingham Heart Study. Cutpoints were determined for TXB2-M and TXB2-M/eGFR using log-rank statistics and used to assess mortality risk by Cox proportional hazard modeling and restricted mean survival time. Multivariable models were compared using the Akaike Information Criterion (AIC). A cohort of 105 aspirin users with heart failure was used for external validation. RESULTS: Optimized cutpoints of TXB2-M were 1291 and 5609â pg/mg creatinine and of TXB2-M/eGFR were 16.6 and 62.1 filtered prostanoid units (defined as pg·min/creatinine·mL·1.73â m2), for aspirin users and nonusers, respectively. TXB2-M/eGFR cutpoints provided more robust all-cause mortality risk discrimination than TXB2-M cutpoints, with a larger unadjusted hazard ratio (2.88 vs 2.16, AIC P < 0.0001) and greater differences in restricted mean survival time between exposure groups (1.46 vs 1.10 years), findings that were confirmed in the external validation cohort of aspirin users. TXB2-M/eGFR cutpoints also provided better cardiovascular/stroke mortality risk discrimination than TXB2-M cutpoints (unadjusted hazard ratio 3.31 vs 2.13, AIC P < 0.0001). CONCLUSION: Adjustment for eGFR strengthens the association of urinary TXB2-M with long-term mortality risk irrespective of aspirin use.
Assuntos
Aspirina , Tromboxanos , Humanos , Prognóstico , Creatinina/urina , Aspirina/uso terapêutico , Tromboxano B2/metabolismo , Rim/metabolismoRESUMO
BACKGROUND: Thromboxane metabolites could indirectly reflect platelet activation, among which 11-dehydro-thromboxane B2 (11dhTxB2) and 11-dehydro-2, 3-dinor thromboxane B2 (11dh23dinorTxB2) are two stable metabolites that are abundant in urine, and both are closely related to disease progression and drug use. However, most clinical application studies have focused on the single indicator of 11dhTxB2. We propose an LC-MS/MS method suitable for routine clinical screening with simultaneous determination of both metabolites and conduct preliminary studies in different populations. METHODS AND RESULTS: The thromboxane metabolites were extracted by liquid-liquid extraction and determined by LC-MS/MS. Reference intervals (RI) were established in 333 healthy adults and validated in 25 patients with coronary atherosclerosis (CA). This LC-MS/MS method was over a wide quantitative range (0.1-10 µmol/L), the imprecision and accuracy were 5.2 %-11 % and 89.3 %-106.5 %, and was suitable for clinical routine quantitative screening. The 95th percentile RI of unire 11dhTxB2 was 1220 (95 % CI: 1048, 1376) pg mg Cr -1, for 11dh23dinorTxB2, RI was 908 (95 % CI: 821, 1102) pg mg Cr -1. For the first time, we found a significant correlation between 11dhTxB2 and 11dh23dinorTxB2 in both healthy adults (r = 0.67, P < 0.001) and CA patients (r = 0.77, P < 0.001). CONCLUSION: The establishment of RI provides a reference for diseases related to platelet activation and the use of drugs, and the first discovery of the correlation between 11dhTxB2 and 11dh23dinorTxB2 in urine provides a new possibilitie for the diagnostic and prognostic of cardiovascular diseases.
Assuntos
Ativação Plaquetária , Espectrometria de Massas em Tandem , Tromboxano B2/análogos & derivados , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Valores de Referência , Tromboxanos/urina , Tromboxanos/metabolismo , Tromboxanos/sangue , Cromatografia Líquida , Idoso , Adulto Jovem , Doença da Artéria Coronariana/urina , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnósticoRESUMO
Biological samples are often frozen and stored for years and/or thawed multiple times, thus assessing their stability on long-term storage and repeated freeze-thaw cycles is crucial. The study aims were to assess:-the long-term stability of two major enzymatic and non-enzymatic metabolites of arachidonic acid, i.e. urinary 11-dehydro-thromboxane-(Tx) B2, 8-iso-prostaglandin (PG)F2α, and creatinine in frozen urine samples;-the effect of multiple freeze-thaw cycles. Seven-hundred and three urine samples measured in previously-published studies, stored at -40 °C, and measured for a second time for 11-dehydro-TxB2 (n = 677) and/or 8-iso-PGF2α (n = 114) and/or creatinine (n = 610) were stable over 10 years and the 2 measurements were highly correlated (all rho = 0.99, P < 0.0001). Urine samples underwent 10 sequential freeze-thaw cycles, with and without the antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (10 mM); urinary 11-dehydro-TxB2 and creatinine were stable across all cycles (11-dehydro-TxB2: 100.4 ± 21%; creatinine: 101 ± 7% of baseline at cycle ten; n = 17), while 8-iso-PGF2α significantly increased by cycle 6 (151 ± 22% of baseline at cycle ten, n = 17, P < 0.05) together with hydrogen peroxide only in the absence of antioxidant. Arachidonic acid metabolites and creatinine appear stable in human urines stored at -40 °C over 10 years. Multiple freeze-thaw cycles increase urinary 8-iso-PGF2α in urine samples without antioxidants. These data are relevant for studies using urine samples stored over long-term and/or undergoing multiple freezing-thawing.
Assuntos
Antioxidantes , Prostaglandinas F , Humanos , Ácido Araquidônico , Creatinina , Congelamento , Técnicas Imunoenzimáticas , TromboxanosRESUMO
The present study aimed to investigate the effect of a H2S donor, GYY 4137, on human pulmonary arteries and whether low-frequency ultrasound (20 kHz, 4 W/cm2) inhibits GYY 4137 contractions. Functional studies were conducted on human and rat pulmonary arteries mounted on microvascular myographs. We placed an ultrasonic gadget in the tissue organ bath to insonate the arteries with low-frequency ultrasound. To measure the effect of the low-frequency ultrasound on the entrance of extracellular Ca2+, the preparations were placed in a Ca2+-free solution, and the thromboxane agonist, U46619, and extracellular calcium were added in the presence of insonation. In isolated human pulmonary arteries, GYY 4137 induced contractions, which were most pronounced in the arteries contracted with the thromboxane analogue, U46619. The transient GYY4137 contractions were reversed by low-frequency ultrasound, a blocker of KV7 channels, XE-991 (10 µM), and glibenclamide (1 µM), a blocker of ATP-sensitive channels. Low-frequency ultrasound also inhibited the contractions induced by the smooth muscle entrance of increasing extracellular calcium concentrations. The present findings show that GYY 4137 can cause a transient contraction of pulmonary arteries in human arteries. GYY 4137 alone does not cause significant vascular contraction in rat lung arteries, but it contracts rat lung arteries precontracted with U46619. The transient contractions induced by GYY 4137 can be inhibited by low-frequency ultrasound, probably by counteracting the influx of external Ca2+. The effect of low-frequency ultrasound counteracts contraction in pulmonary arteries; therefore, a possibility could be to develop a larger device allowing treatment of patients with pulmonary hypertension.
Assuntos
Morfolinas , Músculo Liso Vascular , Compostos Organotiofosforados , Artéria Pulmonar , Humanos , Ratos , Animais , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Cálcio/farmacologia , Tromboxanos/farmacologiaRESUMO
ABSTRACT: Mechanisms of proteostasis in anucleate circulating platelets are unknown and may regulate platelet function. We investigated the hypothesis that plasma-borne growth factors/hormones (GFHs) maintain constitutive translation in circulating platelets to facilitate reactivity. Bio-orthogonal noncanonical amino acid tagging (BONCAT) coupled with liquid chromatography-tandem mass spectrometry analysis revealed constitutive translation of a broad-spectrum translatome in human platelets dependent upon plasma or GFH exposure, and in murine circulation. Freshly isolated platelets from plasma showed homeostatic activation of translation-initiation signaling pathways: phosphorylation of p38/ERK upstream kinases, essential intermediate MNK1/2, and effectors eIF4E/4E-BP1. Plasma starvation led to loss of pathway phosphorylation, but it was fully restored with 5-minute stimulation by plasma or GFHs. Cycloheximide or puromycin infusion suppressed ex vivo platelet GpIIb/IIIa activation and P-selectin exposure with low thrombin concentrations and low-to-saturating concentrations of adenosine 5'-diphosphate (ADP) or thromboxane analog but not convulxin. ADP-induced thromboxane generation was blunted by translation inhibition, and secondary-wave aggregation was inhibited in a thromboxane-dependent manner. Intravenously administered puromycin reduced injury-induced clot size in cremaster muscle arterioles, and delayed primary hemostasis after tail tip amputation but did not delay neither final hemostasis after subsequent rebleeds, nor final hemostasis after jugular vein puncture. In contrast, these mice were protected from injury-induced arterial thrombosis and thrombin-induced pulmonary thromboembolism (PE), and adoptive transfer of translation-inhibited platelets into untreated mice inhibited arterial thrombosis and PE. Thus, constitutive plasma GFH-driven translation regulates platelet G protein-coupled receptor reactivity to balance hemostasis and thrombotic potential.
Assuntos
Agregação Plaquetária , Trombose , Camundongos , Humanos , Animais , Trombina/metabolismo , Tromboxanos , Puromicina/efeitos adversosRESUMO
Unfractionated heparin (UFH) is an effective antithrombotic during surgery but has known adverse effects, in particular on platelets. A marked increase in platelet responsiveness has previously been observed in patients within minutes of receiving UFH, despite adequate inhibition by aspirin prior to heparin. We studied this phenomenon in patients undergoing cardiac artery bypass grafting (n = 17) to determine whether the effects of heparin were systemic or platelet-specific. All patients' platelets were fully inhibited by aspirin prior to surgery, but within 3 min of receiving heparin spontaneous aggregation and responses to arachidonic acid (AA) and ADP increased significantly (p ≥ 0.0002), and activated platelets were found in the circulation. While there was no rise in thromboxane in the plasma following heparin, levels of the major platelet 12-lipoxygenase product, 12-HETE, rose significantly. Mixing experiments demonstrated that the changes caused by heparin resided primarily in the platelets, while addition of AA pathway inhibitors, and analysis of oxylipins provided evidence that, following heparin, aggregating platelets regained their ability to synthesise thromboxane. These findings highlight potentially unrecognised pro-thrombotic and pro-inflammatory changes during CABG surgery, and provide further evidence of adverse effects associated with UFH.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Heparina , Humanos , Heparina/farmacologia , Ácido Araquidônico , Aspirina/farmacologia , Ponte de Artéria Coronária , TromboxanosRESUMO
In this study, we reported that novel single-chain fusion proteins linking thromboxane A2 (TXA2) receptor (TP) to a selected G-protein α-subunit q (SC-TP-Gαq) or to α-subunit s (SC-TP-Gαs) could be stably expressed in megakaryocytes (MKs). We tested the MK-released platelet-linked particles (PLPs) to be used as a vehicle to deliver the overexpressed SC-TP-Gαq or the SC-TP-Gαs to regulate human platelet function. To understand how the single-chain TP-Gα fusion proteins could regulate opposite platelet activities by an identical ligand TXA2, we tested their dual functions-binding to ligands and directly linking to different signaling pathways within a single polypeptide chain-using a 3D structural model. The immature MKs were cultured and transfected with cDNAs constructed from structural models of the individual SC-TP-Gαq and SC-TP-Gαs, respectively. After transient expression was identified, the immature MKs stably expressing SC-TP-Gαq or SC-TP-Gαs (stable cell lines) were selected. The stable cell lines were induced into mature MKs which released PLPs. Western blot analysis confirmed that the released PLPs were carrying the recombinant SC-TP-Gαq or SC-TP-Gαs. Flow cytometry analysis showed that the PLPs carrying SC-TP-Gαq were able to perform the activity by promoting platelet aggregation. In contrast, PLPs carrying SC-TP-Gαs reversed Gq to Gs signaling to inhibit platelet aggregation. This is the first time demonstrating that SC-TP-Gαq and SC-TP-Gαs were successfully overexpressed in MK cells and released as PLPs with proper folding and programmed biological activities. This bio-engineering led to the formation of two sets of biologically active PLP forms mediating calcium and cAMP signaling, respectively. As a result, these PLPs are able to bind to identical endogenous TXA2 with opposite activities, inhibiting and promoting platelet aggregation as reprogrammed for therapeutic process. Results also demonstrated that the nucleus-free PLPs could be used to deliver recombinant membrane-bound GPCRs to regulate cellular activity in general.
Assuntos
Megacariócitos , Tromboxanos , Humanos , Megacariócitos/metabolismo , Preparações de Ação Retardada , Plaquetas/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Tromboxano A2/metabolismoRESUMO
Resumen El síndrome de Kounis es la asociación de síndrome coronario agudo secundario a una reacción de anafilaxis, la cual es producida por mediadores inflamatorios y vasoactivos liberados principalmente por activación y degranulación de mastocitos que actúan en el sistema cardiovascular. Es una patología subdiagnosticada por cuanto no es considerada en los servicios de urgencias y cuidado coronario pues son pocos los registros en la literatura médica. El síndrome de Kounis es producido por diferentes mediadores como medicamentos, medios de contraste, enfermedades alérgicas, mastocitosis, venenos de insectos, etc.; en sí todo lo que conlleve a la activación de mastocitos puede producir el síndrome. Se puede presentar en cualquier grupo etáreo dado que ha sido descrito en niños y adultos. Debido a la falta de estudios clínicos, hasta el momento no hay un consenso acerca del tratamiento de esta patología.
Abstract Kounis syndrome is the concurrence of acute coronary syndromes with conditions associated to an anaphylaxis reaction, which is produced by vasoactive and inflammatory mediators, released mostly by activation and degranulation of mast cells that act in the cardiovascular system. It is an underdiagnosed condition, not included in the emergency room services or coronary care, as there are only few registers in medical literature. Kounis syndrome is produced by different mediators, such as drugs, contrast agents, allergic diseases, mastocytosis, insect stings, etc.; anything that could activate mast cells may trigger the syndrome. It can appear in any age group, in fact it has been described in children and adults. Due to the lack of clinical studies, until today there is no consensus on the treatment for this condition.
Assuntos
Humanos , Masculino , Feminino , Arteriosclerose , Síndrome de Kounis , Tromboxanos , Inflamação , IsquemiaRESUMO
La adaptación al medio extrauterino incluye un aumento considerable de la PaO2, que induce especialmente cambios estructurales y vasoactivos en la circulación pulmonar, que llevarán a una circulación previamente pobremente irrigada, a recibir ∼100% del gasto cardíaco del recién nacido, permitiendo el normal intercambio gaseoso. La regulación local de la circulación arterial pulmonar neonatal basal, es mantenida por un delicado equilibrio entre agentes vasoconstrictores y vasodilatadores. Este equilibrio, permite mantener la circulación pulmonar como un territorio de gran flujo sanguíneo y baja resistencia. La acción de los vasoconstrictores permite la formación de las interacciones entre actina y la cadena liviana de la miosina, esta es inducida en la célula muscular lisa principalmente por dos vías: a) dependiente de calcio, que consiste en aumentar el calcio intracelular, facilitando finalmente la unión de actina y miosina, y b) independiente de calcio, la cual a través de consecutivas fosforilaciones logra sensibilizar a las proteínas involucradas promoviendo la unión de actina y miosina. Estas acciones son mediadas por agonistas generados principalmente en el endotelio pulmonar, como endotelina-1 y tromboxano, o por agonistas provenientes de otros tipos celulares como la serotonina. Los agentes vasodilatadores regulan la respuesta vasoconstrictora, principalmente inhibiendo la señalización que induce la vasocontricción independiente de calcio, a través de la activación de proteínas quinasas que inhibirán la función de la ROCK quinasa, uno de los últimos efectores de la vasocontricción antes de la formación de la unión de actina y miosina. Esta revisión describe estos mecanismos de primordial importancia en las primeras horas de nuestra vida como individuos independientes.
The extrauterine-milieu adaptation includes a considerable increase in PaO2, that specifically induces structural and vasoactive changes at pulmonary circulation. Such changes transform a poor irrigated circulation into a circulation that receive ∼100% of neonatal cardiac output, supporting the normal alveolar-capillary gas exchange. Local regulation of basal neonatal pulmonary circulation is maintaining by a delicate equilibrium between vasoconstrictor and vasodilator agents. This equilibrium, allows to maintain the pulmonary circulation as an hemodynamic system with a high blood flow and a low vascular resistance. Vasocontrictors action allows actin and light-chain myosin interaction. Two main pathways induced this effect in smooth muscle cell: a) a calcium dependent pathway, that increases intracellular calcium, facilitating actin - myosin binding, and b) the independent calcium pathway, which achieves through consecutive phosphorylation reactions sensitize the proteins involved, promoting the binding of actin and light-chain myosin. These actions are mediated by agonists produced mainly in the pulmonary endothelium, such as endothelin-1 and thromboxane, or by agonists from other cell types such as serotonin. Vasodilator agents regulate the vasoconstrictor response, mainly by inhibiting signals that induce calcium-independent vasoconstriction, through activation of protein kinases, which in turn will inhibit the function of ROCK kinase, one of the last effectors of vasoconstriction before formation of the actin and light-chain myosin binding. This review will focus on describing these mechanisms of primal importance in the first hours of our lives as independent individuals.
Assuntos
Humanos , Recém-Nascido/fisiologia , Circulação Pulmonar/fisiologia , Pulmão/irrigação sanguínea , Resistência Vascular , Vasoconstrição/fisiologia , Vasoconstritores/antagonistas & inibidores , Vasodilatação/fisiologia , Vasodilatadores/antagonistas & inibidores , Adaptação Fisiológica , Serotonina/fisiologia , Tromboxanos/fisiologia , Cálcio , Endotelina-1/fisiologiaRESUMO
Acorus calamus L. is used as anti-inflammatory remedy in traditional system of medicine in Pakistan and India. This study was designed to explore the anti-inflammatory mechanism of Acorus calamus L. and its underlying signaling pathways. Aqueous, butanolic and n-hexane fractions of Acorus calamus were tested against cyclooxygenase (COX) and lipoxygenase (LOX) mediated eicosanoids production by arachidonic acid (AA). Butanolic fraction of Acorus calamus, but not the aqueous and n-hexane fractions, inhibited the COX mediated production of thromboxane B2 (TXB2) and liopxygenase product 1 (LP1) -a metabolite of LOX pathway. 12-(hydroxyeicosatetraenoic acid) HETE- another product of the LOX pathway was unaffected by all three fractions. Butanolic fraction of Acorus calamus showed strong inhibition against AA-induced platelet aggregation. Investigation of the underlying signaling pathways revealed that butanolic fraction inhibited phospholipase C (PLC) pathway in platelets, most probably acting on protein kinase C (PKC). Aqueous and n-hexane fractions of Acorus calamus were not effective against any platelet agonist. This study shows that butanolic fraction of Acorus calamus possesses components that inhibit AA metabolism and platelet aggregation through multiple pathways.
Acorus calamus L. se utiliza como remedio anti-inflamatorio en el sistema tradicional de la medicina en Pakistán y la India. Este estudio fue diseñado para explorar el mecanismo anti-inflamatorio de Acorus calamus L. y sus vías de señalización subyacentes. Fracciones acuosa, butanólica y de n-hexano de Acorus calamus se ensayaron frente a la ciclooxigenasa (COX) y de la lipoxigenasa (LOX) mediada por la producción de eicosanoides por el ácido araquidónico (AA). La fracción butanólica de Acorus calamus, pero no las fracciones acuosas y de n-hexano, inhibieron la producción de COX mediada por tromboxano B2 (TXB2) y el producto lipoxigenasa 1 (LP1) - un metabolito de la vía de LOX, 12 - (ácido hidroxieicosatetraenoico) HETE - otro producto de la ruta de LOX no fue afectado por las tres fracciones. La fracción butanólica de Acorus calamus mostró una fuerte inhibición contra la agregación plaquetaria inducida por AA. La investigación de las vías de señalización subyacentes reveló que la fracción butanólica inhibió la fosfolipasa C (PLC) y la vía en las plaquetas, probablemente actuando sobre la proteína quinasa C (PKC). Fracciones acuosas y de n - hexano de Acorus calamus no fueron eficaces contra ningún agonista de plaquetas. Este estudio muestra que la fracción butanólica de Acorus calamus posee componentes que inhiben el metabolismo del AA y la agregación plaquetaria a través de múltiples vías.
Assuntos
Anti-Inflamatórios , Acorus/química , Calamus aromaticus , Extratos Vegetais/farmacologia , Ácido Araquidônico , Agregação Plaquetária , Inflamação , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores de Lipoxigenase/farmacologia , Tromboxanos , Transdução de SinaisRESUMO
Este estudo avalia a resposta hemodinâmica sistêmica e cerebral à reposição volêmica com Solução de Ringer Lactato (RL) ou Salina Hipertônica a 3 por cento (SSH 3 por cento) e o comportamento da liberação de prostanóides encefálicos durante a fase aguda do choque hemorrágico (CH) associado ao traumatismo craniencefálico (TCE). Quinze cães foram distribuidos em três grupos (RL, SSH3 por cento, controle) e após CH eTCE simulamos o tratamento durante a fase pré-hospitalar e hospitalar precoce. No evento de um trauma de crânio grave e choque hemorrágico, o uso de SSH 3 por cento ou o dobro do volume de RL promoveram benefícios hemodinâmicos sistêmicos e cerebrais semelhantes. Os valores mais baixos de PIC foram observados após SSH 3 por cento. Não houve diferença nos valores da concentração venosa cerebral de prostaglandina e tromboxane.
This study evaluates the systemic and cerebral hemodynamic responses to volume replacement with 3 per cent hypertonic saline (HSS) or lactated Ringers solution (LR), during the acute phase of hemorrhagic shock (HS) associated with traumatic brain injury (TBI). Fifteen mongrel dogs were assigned to one of three groups (LR, HSS, control) and after HS+TBI we simulated treatment during prehospital and early hospital admission. In the event of severe head trauma and hemorrhagic shock, the use of HSS and larger volumes of LR promote similar systemic and cerebral hemodynamic benefits. A lower ICP was observed after HSS 3 per cent than after LR. There were no differences between groups in cerebral venous concentration of tromboxane and prostaglandin.
Assuntos
Animais , Cães , Solução Salina Hipertônica , Choque Hemorrágico , Lesões Encefálicas Traumáticas , Experimentação Animal , Soluções Isotônicas , Tromboxanos/administração & dosagemRESUMO
Efetua-se uma revisäo do conhecimento atual referente às prostaglandinas e toxemia baseados em diversos estudos realizados, revelando que os metabólitos do ácido aracdônicos, tais como a prostaciclina e o tromboxane, podem desempenhar papéis importantes na fisiologia da gravidez e na fisiopatologia da toxemia
Assuntos
Gravidez , Humanos , Feminino , Prostaglandinas/metabolismo , Pré-Eclâmpsia/fisiopatologia , Ácidos Araquidônicos/metabolismo , Tromboxanos/metabolismoRESUMO
The effects of an aqueous extract of guaraná (Paullinia cupana) on rabbit platelet aggregation and thromboxane synthesis were examined. The guaraná extract (100 mg/ml) and fractions separated by TLC (origin and xanthines) decreased platelet aggregation (37.27 and 31% of control values, respectively) and platelet thromboxane formation from [14C]-arachidonic acid (78, 70 and 50% of control values respectively). The decreased thromboxane synthesis could be responsible, at least in part, for the antiaggregatory action of guaraná
Assuntos
Animais , Coelhos , Extratos Vegetais/farmacologia , Plantas Medicinais , Inibidores da Agregação Plaquetária , Tromboxanos/biossíntese , Agregação PlaquetáriaRESUMO
Diversos estudios han asignado al consumo de alcohol un efecto protector cadiovascular que se manifiesta por una incidencia menor de enfermedad coronaria y desarrollo de aterosclerosis. Los mecanisos a través de los cuales el alcohol ejerce estos efectos no han sido aún dilucidados, habiéndose relacionado con una posible acción sobre los lípidos sanguíneos. Sin embargo, estudios recientes sugieren la participación de algunos eicosanoides en este efecto, particularmente la prostaciclina, un intenso antiagregante y vasodilatador, y el tromboxano, un potente agregante plaquetario y vasoconstrictor. En este estudio investigamos en ratas e individuos abstémicos y alcohólicos,el efecto del alcohol y sus metabolitos en la producción de prostaciclina, tromboxano y agregación plaquetaria, medidos por radioinmunoensayo. Los resultados obtenidos muestran que el etanol y su metabolito activo acetaldehido estimulan significativamente la producción vascular de prostaciclina. Además, el consumo de alcohol disminuyó en forma marcada la síntesis de tromboxano en las plaquetas y la agregación plaquetaria inducida por colágeno y trombina. Este último efecto se tradujo en un alargamiento del tiempo de sangría en los individuos alcohólicos. Estos resultados sugieren que los mecanismos responsables del efecto protector del alcohol son complejos y se relacionan no sólo con cambios en los lípidos sanguíneos, sino que también en la producción de prostaciclina, troboxano, agregación plaquetaria y reactividad vascular. Este conjunto de acciones explicaría el efecto protector cardiovascular asignado al consumo crónico de alcohol que se manifiesta por una incidencia disminuida de enfermedad coronaria y desarrollo de aterosclerosis
Assuntos
Humanos , Masculino , Animais , Adulto , Pessoa de Meia-Idade , Ratos , Doenças Cardiovasculares/prevenção & controle , Eicosanoides/farmacocinética , Agregação Plaquetária , Aterosclerose/prevenção & controle , Bebidas Alcoólicas , Estudos de Casos e Controles , Doença das Coronárias/prevenção & controle , Epoprostenol/isolamento & purificação , Tromboxanos/metabolismoRESUMO
Los conocimientos actuales sobre las funciones biológicas que cumplen los derivados del ácido araquidónico justifican esta revisión, la cual incluye aspectos de denominación, biosíntesis, mecanismo de acción y degradación. La participación de las prostaglandinas, tromboxanos y leucotrioenos en fenómenos de regulación funcional de endotelios vasculares, plaquetas, músculo liso, secreción glandular y leucocitos han sido estudiados en forma tal que ha sido posible la interpretación de la fisiología a diferentes niveles. Derivado de este conocimiento también ha sido posible establecer el papel de estos compuestos en situaciones patológicas. El proceso inflamatorio se analiza con detención con el conocer la participación de los derivados del ácido araquidónico y establecer su rol en enfermedades caracterizadas por inflamación
Assuntos
Ácidos Araquidônicos/análogos & derivados , Inflamação/tratamento farmacológico , Músculo Liso/metabolismo , Ácidos Araquidônicos/fisiologia , Plaquetas/metabolismo , Química , Leucotrieno B4/fisiologia , Fosfolipases A/fisiologia , Prostaglandinas/fisiologia , Tromboxanos/fisiologiaRESUMO
Se estudiaron siete pacientes con tromboastenia de Glanzmann. Se realizó agregación plaquetaria con reacción de liberación en un agregómetro Lumi. No se observó agregación con ADP, adrenalina o colágeno. El ácido araquidónico indujo una agregación de sólo 14,9%. Con ristocetina y con factor VIII bovino la aglutinación fue marcadamente disminuida. La liberación de ATP estuvo ausente con todos los agentes agregantes excepto con ácido araquidónico que provocó una liberación normal. Se realizó curva dosis respuesta con análogo de PGH2. Con dosis de 1 micronM a 100 micronM sólo se obtuvo una mínima agregación mientras que la liberación de ATP fue normal. Los resultados confirmarían la independencia de los mecanismos de agregación y liberación. La liberación de ATP inducida por ácido araquidónico o análogo de endoperóxido no parece requerir la exposición y fijación del fibrinógeno a su receptor
Assuntos
Pré-Escolar , Criança , Adulto , Humanos , Masculino , Feminino , Retração do Coágulo , Agregação Plaquetária , Trombastenia/sangue , Ácidos Araquidônicos/metabolismo , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Trombastenia/fisiopatologia , Tromboxanos/metabolismoRESUMO
Los eicosanoides son derivados de ácidos grasos esenciales poliinsaturados de 20 átomos de carbono que afectan prácticamente todas las funciones biológicas. Se ha propuesto un rol modulador a nivel del sistema nervioso central para ellos. La presente revisión se refiere al posible rol central de los eicosanoides, productos de dos vías biosintéticas: la ciclooxigenasas y las lipooxigenasas, así como el rol de agentes terapéuticos que actúan sobre ellos. Se analiza su efecto sobre la circulación cerebrovascular y su acción neuromoduladora, que afecta la función hipotalámica, el umbral convulsivante y la nocicepción, entre ellos. Claramente durante los últimos años el descubrimiento del tromboxano, prostaciclina y leucotrienos ha desviado el interés de las prostaglandinas primarias (PGE y PGF) en busca de acciones fisiológicas mas específicas