Mecanismos regulatorios del tono vascular pulmonar neonatal: una perspectiva molecular / Regulatory mechanisms of neonatal pulmonary vascular tone: a molecular perspective

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.

Síndrome de Kounis o angina alérgica / Kounis syndrome or allergic angina

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.

Pharmacological basis of the use of Acortus calamus L. in inflammatory diseases and underlying signal transduction pathways / Bases farmacológicas del uso de Acorus calamus L. en enfermedades inflamatorias y las vías de transducción de señales subyacentes

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.

Effects of thrombolytic drugs and a selective endothelin-1 receptor antagonist on acute pulmonary thromboembolism in dogs / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been shown that neurohumoral factors other than mechanical obstruction are involved in the pathophysiology of acute pulmonary thromboembolism (APTE). The aim of this study was to investigate the effects of thrombolytic drugs, a selective endothelin-1 receptor (ET-1R) antagonist alone or their combination on APTE in a canine model.</p><p><b>METHODS</b>Twenty dogs were randomly assigned to five groups: sham, model, urokinase (UK), BQ123, and combination (UK plus BQ123). The dogs in the sham group underwent sham surgery. APTE was induced in the other four groups by intravenous injection of autologous blood clots. Dogs in the UK, BQ123 and combination groups received UK, BQ123 (a selective ET-1R antagonist), or UK plus BQ123, respectively. The dogs in the model group were given saline. Mean pulmonary artery pressure (mPAP), serum concentrations of ET-1, thromboxane (TXB2), and tumor necrosis factor (TNF)-alpha were determined at different time points following the induction of APTE.</p><p><b>RESULTS</b>UK and BQ123 alone markedly decreased mPAP in APTE. By comparison, the reduction was more significant in the combination group. Compared with the sham group ((-0.90 +/- 0.61) mmHg), mPAP increased by (7.44 +/- 1.04), (3.42 +/- 1.12) and (1.14 +/- 0.55) mmHg in the model group, UK alone and BQ123 alone groups, respectively, and decreased by (2.24 +/- 0.67) mmHg in the combination group (P < 0.01). Serum ET-1 concentrations in the BQ123 and combination groups were (52.95 +/- 8.53) and (74.42 +/- 10.27) pg/ml, respectively, and were significantly lower than those in the model and UK groups ((84.56 +/- 7.44) and (97.66 +/- 8.31) pg/ml respectively; P < 0.01). Serum TNF-alpha concentrations were significantly lower in the BQ123 group than in the model, UK and combination groups (P < 0.05).</p><p><b>CONCLUSIONS</b>Our results indicate that the selective ET-1R antagonist BQ123 not only reduces the increase of mPAP and serum ET-1 level, but also inhibits the production of TNF-alpha, and attenuates the local inflammatory response induced by APTE. Selective ET-1R antagonists may be beneficial to the treatment of APTE, particularly when used in combination with a thrombolytic agent.</p>

Effects and mechanisms of Herba dendrobii on rats with stomach-heat syndrome / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effects of Herba dendrobii on rats with stomach-heat syndrome and to explore the mechanisms.</p><p><b>METHOD</b>Rats were fed with decoction of Rhizoma Zingiberis for 15 continuous days to induce the model of stomach-heat syndrome. After modeling, Herba Dendrobii (HD) decoction were given (in the doses of 1.5, 0.75 g x kg(-1) respectively) for 10 days. After treatment, amount of the daily diet, volume and absorbance of urine, pellet number and moistness of excrement, color and coating degree of tongue were recorded; the body thermal effects were detected with thermal texture maps (TTM) system; the biochemical indexes of blood reflecting the physiological function of stomach, including thromboxaneB2 (TXB2), 6-keto-prostaglandin F1alpha(6-keto-PGF1alpha), motilin (MTL), gastrin (Gas), somatostation (SS), interleukin-4 (IL-4) and interleukin-8 (IL-8) were measured by radio immunoassay; and the histological changes of gastric mucosa were observed by hematoxylin-eosin (HE) stain.</p><p><b>RESULT</b>The model rat had yellow coating and red tongues (P < 0.05). The amount of daily diet were increased (over 10%), urine volume and excrement pellet number were decreased (over 10%). The their urine color became deep (P < 0.01) and their excrement became dry. The temperatures in head, neck, left fore-armpit, chest, up-abdomen, mid-abdomen of the model rats were raised up (difference > 0.5 degrees C or difference > 1.0 degree C ). The content of 6-keto-PGF1alpha in blood of model rats decreased evidently (P < 0.01), and the contents of MTL, Gas and IL-8 increased conspicuously (P < 0.01). The histological changes of gastric mucosa in the model rats were as follows: diffuse congestion, infiltration of neutrophil, less secretion, decrease of the number of chief and parietal cells, etc (P < 0. 05 or P < 0.01). After treatment with HD, except the daily food weight, the temperatures in head, neck and chest, the content of MTL and the number of chief cells, the other indexes observed above were improved noticeably (difference > 0.5 RC or difference > 1.0 degree C, P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>The reason why HD relieves the general symptom and sign the gastric mucosa of rats with stomach-heat syndrome is that HD can increase 6-keto-PGF1alpha and decrease IL-8, Gas, TXB2 in their blood.</p>

Estudo da reposição volêmica inicial em modelo experimental de choque hemorrágico associado ao traumatismo craniencefálico: comparação entre as soluções de ringer lactato e salina hipertônica 3 por cento / Volume replacement with lactated ringer's or 3 per cent hypertonic saline solution during combined experimental hemorrhagic shok and traumatic brain injury

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 Ringer’s 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.

[Biochemical mechanism of inflammation in colorectal cancer]

Biological and chemical stimulators cause tissue injury. Many epidemiological studies imply that chronic stimulation of tissues leads to cancer. One of the most important type of chronic tissue stimulation criteria is increased activity of the metabolic pathway of arachidonic acid and production of biochemical intermediates. Cyclooxygenase pathway [COX] of arachidonic acid leads to production of a variety of prostaglandins and thromboxanes. These inflammatory agents exert their biological effects on different organs and initiate human cancers. Lately, a variety of synthetic and natural drugs have been discovered that suppress the production of these inflammatory agents and inhibit cancer promotion. One of the most popular drugs, are nonsteroidal anti-inflammatory drugs, [NSAIDs]. In this review, we discuss the role of these inflammatory agents in colorectal carcinogenesis and also their mechanism of inhibition

patient of low dose aspirin: a concern for the anesthesiologist?

Low dose aspirin administration has been generally accepted as prophylactic therapy for myocardial infarction and cerebrovascular disease. It is also used generally to prevent embolic phenomenon, as for example in pregnant patients. Thus, anesthesiologists are often confronted with patients receiving aspirin for whom neuraxial anesthesia may be the preferred technique. Much controversy has arisen in the literature as to whether the possible complications of anticoagulation outweigh the benefits of regional techniques. The anesthesiologist must be able to provide patients with a rational and current approach to the selection of an appropriate anesthetic technique

Participación de los eicosanoides en el efecto protector cardiovascular del consumo de alcohol / Role of eicosanoids in the cardiovascular protective effect of alcohol consumption

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

Value of doppler waveform velocities, the biophysical profile scoring, maternal thromboxane and prostacyclin levels as indicators of severity of preeclampsia and perinatal outcome

This study included forty cases who were divided into two groups: Group I included twenty cases [control group] and group II included twenty cases [preeclamptic group]. For all cases, the maternal plasma levels of thromboxane B2, 6 keto-prostaglandin F1 alpha, Doppler study of both uterine and umbilical arteries, modified biophysical scoring value, Apgar score and neonatal birth weight were all done to know the relative importance of these investigations in determining both the severity of preeclampsia and the perinatal outcome. Both thromboxane B2 and umbilical artery Doppler A/B ratio were increased significantly only in cases with severe preeclampsia. So, both could be used as indicators of severity of preeclampsia. They could reflect also the fetal condition. Uterine artery Doppler A/B ratio was increased significantly in both mild and severe cases of preeclampsia. So, it has a limited value in reflecting the fetal condition or severity of preeclampsia. The biophysical profiles scoring showed significant reduction in preeclamptic cases having an umbilical artery Doppler A/B ratio more than 3 if compared with those with ratios less than 3. This indicated that biophysical profile is a valuable tool for evaluation of the fetal condition in utero with easy detection of fetal hypoxia. This could be added to the other advantages as being simple, noninvasive, rapid and inexpensive test. The umbilical artery Doppler study could be used as confirmatory, not a substituting, test to the biophysical profile for evaluation of the fetal condition

Síndrome de Hellp como manifestación de descompensación de la preeclampsia durante el puerperio: presentación de dos casos / Hellp syndrome as a decompensation of pre-eclampsia during puerperium. two cases presentation

Se presentan dos casos clínicos extremos de enfermedad hipertensiva inducida por el embarazo y síndrome de Hellp puerperal, así como la revisión de la literatura. Hellp es un acrónimo en inglés, utilizado para describir a la paciente con preclampsia severa o eclampsia, quien también presenta hemólisis, enzimas hepáticas elevadas y plaquetas disminuidas. No ha sido dilucida por completo su etiología pero se ha aceptado la teoría de un desequilibrio en el metabolismo prostanoide. Su incidencia oscila de 5 a 15 por ciento entre las pacientes con enfermedad hipertensiva inducida por el embarazo. La mortalidad materna entre 10 y 28 por ciento y la neonatal al rededor de 40 por ciento. Debido a las complicaciones fatales que puede presentar, la base del tratamiento es la interrupción del embarazo. Se señala la importancia de la detección temprana de esta entidad clínica, lo cual mejora el pronóstico materno-fetal

Influence of low dose enteric-coated aspirin on platelet function.

Little is known about the effect of low dose, enteric-coated aspirin on human blood platelet function. This study was conducted to evaluate the acute effects of a single daily dose of commercially available enteric-coated aspirin on platelet biochemistry, physiology and function. Blood for these studies was obtained from drug-free volunteer donors prior to ingestion of aspirin or following ingestion, either before breakfast or following lunch. Response of platelets to the action of weak agonists was evaluated. In addition, ability of platelets to convert radiolabeled arachidonic acid to thromboxane was monitored. Results of our studies show that a single daily dose of 50 mg of aspirin taken either before breakfast or after lunch effectively prevented the secondary wave aggregation response, as well as secretion of dense body contents when stimulated by agonists such as epinephrine and ADP. Aspirin ingestion caused a dose-dependent inhibition of platelet cyclooxygenase activity as evidenced by the extent of arachidonic acid converted to thromboxane by platelets exposed to aspirin for different time periods. Based on these observations, it is suggested that low dose aspirin may be very useful and desirable to restrain platelet activity in clinical situations in which increased thromboxane formation may initiate vascular hypertension and platelet hyperactivity.

La inflamación en los procesos infecciosos / Inflammation in Infectious processes

La inflamación es un fenómeno fisiopatológico frecuente, cuya importancia radica en su función como mecanismo de protección contra el daño tisular producido por diferentes agentes. En el artículo se discuten los mecanismos del proceso inflamatorio, la función e importancia de los mediadores químicos de la inflamación, y las relaciones existentes entre la inflamación y la respuesta inmune. Las infecciones son de las causas más frecuentes que desencadenan una respuesta inflamatoria, además de activar los mecanismos de inmunidad; ambos fenómenos tienen un efecto sinérgico entre sí: a) a través de los mediadores químicos producidos durante la inflamación, se favorece la activación de células fagocíticas y linfocitos T, y b) la respuesta inmunológica amplifica la reacción inflamatoria, incrementando su eficiencia para limitar el daño tisular producido por los microorganismos invasores.

An aqueous extract of guaraná (Paullinia cupana) decreases platelet thromboxane synthesis

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

Involvement of eicosanoids and PAF in immune-coplex alveolitis

An immune-complex-mediated hypersensitivity reaction induced in the rat lung was followed by release of the eicosanoids thromboxane, prostaglandin E2 and leukotriene B4 into bronchoalveolar space. Concomitantly, there was a decrease in the number of circulating platelets. The thrombocytopenia was inhibited by a cyclo-oxygenase inhibitor (indomethacin), a platelet activating factor (PAF) antagonist (BN-52021) and an inhibitor of thromboxane (econazozle), but was not affected by a lipoxygenase inhibitor (NDGA). These results suggest the involvement of eicosanoids and PAF in the immune complex hypersensitivity reaction in the rat lung and indicate the ocurrence of interactions between PAF and thromboxane

Eicosanoides en el sistema nervioso central / Eicosanoids in the central nervous system

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