Mecanismo de los AINES y antiinflamatorios derivados para el control del dolor y la inflamación. Uso de antiinflamatorios en odontología / Mechanism of NSAIDs and derived drugs for pain and inflammation control. Use of anti-inflammatories in odontology

Las urgencias odontológicas son, quizá, las razones principales de atención en el consultorio, muchas veces el significado de dolor se encuentra acompañado por inflamación; el uso de antiinflamatorios no esteroideos (AINES) es común en el ejercicio de la odontología por la excelente respuesta analgésica y antiinflamatoria que tiene, por lo que es importante conocer la fisiopatología de la inflamación y el dolor y cómo actúan los AINES, ya que algunos de estos fármacos tienen respuestas adversas y sitios de acción importantes. Los factores de riesgo por inflamación y dolor nos obligan a conocer la variedad de fármacos que no entran en la clasificación de AINES y que tenemos a disposición, hay más opciones para la elección ante la presencia de inflamación por un factor en particular, cada uno de éstos tienen indicaciones y contraindicaciones que conoceremos, lo cual nos ampliará el conocimiento para dar una prescripción ante la presencia de eventos inflamatorios. Se realizó un estudio detallado de artículos bibliográficos de cada tema, los fármacos más usados en odontología son los AINES, hay poco uso y conocimiento de antiinflamatorios que podemos usar en urgencias, el porcentaje de uso de los AINES derivados del ácido propiónico es alto por la excelente respuesta en pacientes y otras veces por el desconocimiento de más opciones (AU)

Dental emergencies are perhaps the main reasons for care in the office, many times the meaning of pain is accompanied by inflammation, the use of non-steroidal anti-inflammatory drugs is common in the practice of dentistry due to the excellent analgesic and anti-inflammatory response it has, important is knowing the pathophysiology of inflammation and pain, how NSAIDs act, some of these drugs have adverse responses and important sites of action, risk factors for inflammation and pain require us to know the variety of drugs that do not enter the classification of NSAIDs and we have at our disposal, there are more options for choosing in the presence of inflammation due to a particular factor, each of these have indications and contraindications that we will know, it expands our knowledge to give a prescription in the presence of inflammatory events. A detailed study of bibliographic articles on each topic was carried out, the drugs most used in dentistry are NSAIDs, there is little use and knowledge of anti-inflammatories that we can use in the emergency room, the percentage of use of NSAIDs derived from propionic acid is high, due to the excellent response in patients and others due to lack of knowledge of more options (AU)

El tratamiento postnatal con melatonina modula la expresión de agentes prostanoides en pulmón de neonatos de oveja con hipertensión pulmonar / Melatonin modulates the expression of pulmonary prostanoids

Background: Living above 2,500 meters in hypobaric conditions induces pulmonary arterial hypertension of the neonate (PAHN), a syndrome whose main features are: pathological remodeling of the pulmonary vessels, abnormal vascular reactivity and increased oxidative stress. Melatonin could have pulmonary antioxidant, anti-remodeling and vasodilating properties for this condition. Aim: To determine the effect of melatonin at the transcript level of prostanoid pathways in the lung of neonatal lambs gestated and born under hypobaric hypoxia. Material and Methods: Vehicle (1.4% of ethanol, n = 6) or melatonin (1 mg * kg1, n = 5) were administered from the postnatal day 4 to 21 to lambs gestated and born at 3,600 meters above sea level. After one week of treatment completion, lung tissue was obtained, the transcript and protein levels of prostanoid synthases and receptors were assessed by RT-PCR and Western Blot. Results: Melatonin induced the expression of prostacyclin synthase transcript and increased protein expression of the prostacyclin receptor. In addition, the treatment decreased the expression of transcript and protein of cyclooxygenase-2, without changes in the expression of the prostanoid vasoconstrictor (thromboxane) pathway. Conclusions: Postnatal treatment with melatonin increases the expression of the prostacyclin-vasodilator pathway without changing the vasoconstrictor thromboxane pathway. Further, the decreased COX-2 induced by melatonin could be an index of lesser oxidative stress and inflammation in the lung.

Uso do misoprostol em mulheres com gravidez de alto risco: uma análise retrospectiva / Use of misoprostol in high risk pregnant women: a retrospective analysis

Analisar o intervalo de tempo entre as doses do misoprostol e o número de doses necessárias em gestantes de alto risco para o desencadeamento do trabalho de parto. O trabalho foi retrospectivo baseado em consulta de prontuários médicos de pacientes no período de janeiro a maio de 2017. Foram inclusas, gestantes de alto risco classificadas como nulíparas com apresentação fetal, idade gestacional igual ou superior a 37 semanas e em uso de misoprostol. As variáveis foram analisadas pelo programa Prism versão 5.0, cujos testes quantitativos foram Qui-quadrados de Pearson e teste de Fischer, enquanto as variáveis qualitativas foram teste t student e teste não paramétrico de Mann Whitney. As gestantes com desencadeamento por parto cesariana receberam mais comprimidos que as nulíparas com desencadeamento vaginal (p= 0,04). 25,6% das nulíparas utilizaram ocitocina após a administração do misoprostol. As gestantes de parto cesáreo receberam mais comprimidos para o amadurecimento do colo uterino quando comparado com as nulíparas com desencadeamento por parto vaginal. A maioria das gestantes recebeu doses de misoprostol em intervalos acima das seis horas preconizadas. Outro dado é o alto número de casos absolutos de indicações para o uso de ocitocina, entretanto acreditamos que o motivo de interrupção na utilização do misoprostol seja relacionado à inefetividade do fármaco pela administração em intervalos inadequados. Dessa maneira, o conhecimento sobre o uso do misoprostol no hospital pode contribuir para o uso racional e, consequentemente, maior efetividade do medicamento.

Reconstrucción de pene luego de necrosis de glande por priapismo / Penile Reconstruction after Glans Necrosis by Priapism

Introducción El priapismo se define como una erección parcial o completa que dura más de 4 horas en ausencia de estímulo sexual. Se clasifica en isquémico, no isquémico e intermitente. El primero corresponde a la mayoría de casos y puede producirse por un estímulo sexual o por medicamentos. El manejo inicial consiste en la aspiración de los cuerpos cavernosos y la inyección de simpaticomiméticos. Cuando esas medidas fallan, el manejo quirúrgico está indicado. Entre las complicaciones más frecuentes está la disfunción eréctil, sin embargo, en la literatura, hay muy pocos reportes de necrosis de pene. Descripción del Caso Clínico Paciente de 60 años de edad que presentó priapismo isquémico luego de la inyección intracavernosa de prostaglandina E. Viene a consulta y le realizan lavado de cuerpos cavernosos con inyección de simpaticomiméticos que no fue exitoso; por lo que le realizan fístula espongio-cavernosa distal (Al-Ghorab) y rafia de uretra por lesión advertida. Consulta nuevamente por persistencia de edema, áreas necróticas y sangrado en glande. Se decidió iniciar manejo médico. Presentó evolución estacionaria y aumento en necrosis por lo que se derivó con cistostomía y se realizó desbridamiento de tejido necrótico inicialmente. Posteriormente se realizó Reconstrucción peneana + Uretroplastia peneana + Lavado desbridamiento de tejidos + Cistoscopia con buena evolución clínica. Conclusiones Existen diferentes factores de riesgo para presentar priapismo de origen isquémico como es la inyección de medicamentos intracavernosos. La principal complicación que se presenta es la disfunción eréctil. Sin embargo, hay pocos casos descritos de necrosis de glande. En el caso de nuestro paciente se plantean diferentes hipótesis como factores contribuyentes a la necrosis como son el uso de simpaticomiméticos y/o la desvascularización del glande posterior a la cirugía. Al enfocar ese tipo de paciente, es indispensable realizar un adecuado manejo inicial para prevenir ese tipo de complicación que, aunque es poco frecuente, puede resultar catastrófica.

Introduction Priapism is defined as a prolonged and persistent penile erection that is unrelated to sexual stimulation and lasts longer than 4 hours in duration. It is classified as ischemic (low flow), non-ischemic (high flow), and stuttering (recurrent). Ischemic priapism is the most frequent. Initial treatment consists of corpora cavernosa aspiration. When it fails, surgical treatment is indicated. Erectile dysfunction is a frequent complication, however glans necrosis has been reported too. Case Report A 60 year-old patient with ischemic priapism after prostaglandin E intracavernous injection consulted. Initial treatment was corpora cavernosa aspiration without detumecense and then a distal espongio-cavernous fistula was done. Some days later, he presented edema, bloods and necrotic areas in his glands. Conservative medical treatment was done without success and a surgical treatment was considered. Reconstructive procedure was done with good evolution. Conclusions Ischemic priapism could be presented after intracavernous injection with low frequency. However, an appropriate treatment has to be done to prevent complications as penile necrosis. In this patient, there are some risk factors that could be contribute to glans necrosis as simpatico-mimetics used, lost of vascularization with surgery. When focusing on this type of patient, it is essential to carry out an adequate initial management to prevent this type of complication that, although rare, can result catastrophic

Effect of electroacupunture on supplementary analgesia and the levels of serum β-endorphin and prostaglandin E in patients with total knee arthroplasty / 中国针灸

OBJECTIVE@#To observe the effect on supplementary analgesia after total knee arthroplasty (TKA) treated with electroacupunture, and explore it's mechanism.@*METHODS@#A total of 40 patients with severe knee osteoarthritis were randomized into an observation group and a control group, 20 cases in each one. During the operation, patients were given epidural anesthesia in the two groups, conventional patient controlled epidural analgesia and oral celecoxib were applied after the operation. In the observation group, electroacupunture was used at Liangqiu (ST 34), Xuehai (SP 10), Yinlingquan (SP 9), Zusanli (ST 36), Fenglong (ST 40) and Qiuxu (GB 40) on the operation side from the 1st to 7th day after the operation to support analgesia, 30 min for each time, once a day. The visual analogue scale (VAS) was used to record postoperative pain of resting state and active state. The levels of serum prostaglandin E and β-endorphin were measured on the 1st and 7th day after surgery in the two groups.@*RESULTS@#In the observation group, the VAS scores of resting state and active state were superior to the control group on the 3rd, 5th and 7th day after the operaton (all <0.05); after the treatment, the level of serum β-endorphin was increased and the level of serum prostaglandin E was reduced in the two groups (all <0.05), and the change of the observation group was larger than that of the control group (both <0.05).@*CONCLUSION@#Electroacupunture has the effect of supplementary analgesia for patients after TKA, the mechanism may be related to promote the synthesis of β-endorphin and inhibit the synthesis of prostaglandin E.

Complementary Participation of Genetics and Epigenetics in Development of NSAID-exacerbated Respiratory Disease

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) has attracted a great deal of attention because of its association with severe asthma. However, it remains widely underdiagnosed in asthmatics as well as the general population. Upon pharmacological inhibition of cyclooxygenase 1 by NSAIDs, production of anti-inflammatory prostaglandin E2 and lipoxins ceases, while release of proinflammatory cysteinyl leukotrienes increases. To determine the underlying mechanisms, many studies have attempted to elucidate the genetic variants, such as single nucleotide polymorphisms, responsible for alterations of prostaglandins and leukotrienes, but the results of these genetic studies could not explain the whole genetic pathogenesis of NERD. Accordingly, the field of epigenetics has been introduced as an additional contributor to genomic alteration underlying the development of NERD. Recently, changes in CpG methylation, as one of the epigenetic components, have been identified in target tissues of NERD. This review discusses in silico analyses of both genetic and epigenetic components to gain a better understanding of their complementary roles in the development of NERD. Although the molecular mechanisms underlying NERD pathogenesis remain poorly understood, genetic and epigenetic variations play significant roles. Our results enhance the understanding of the genetic and epigenetic mechanisms involved in the development of NERD and suggest new approaches toward better diagnosis and management.

Emerging Therapies in Chronic Spontaneous Urticaria

Chronic spontaneous urticaria (CSU) is characterized by typically short-lived and fleeting wheals, angioedema or both, which occur spontaneously and persist for longer than 6 weeks. This term is applied to the most common subtype of chronic urticaria. The underlying pathophysiology for CSU involves mast cell and basophil degranulation with release of histamine, leukotrienes, prostaglandins and other inflammatory mediators. Although a variety of treatments exist, many patients do not tolerate or benefit from the existing therapies and even require more effective treatments. Omalizumab is currently the only licensed biologic for antihistamine-refractory CSU, and novel drugs are under development. This article reviews its current status regarding pathogenesis and approach to treatment as well as therapeutic agents that are under development for the treatment of CSU.

Diverse characters of Brennan’s paw incision model regarding certain parameters in the rat / 대한통증학회지

BACKGROUND: Brennan’s rodent paw incision model has been extensively used for understanding mechanisms underlying postoperative pain in humans. However, alterations of physiological parameters like blood pressure and heart rate, or even feeding and drinking patterns after the incision have not been documented as yet. Moreover, though eicosanoids like prostaglandins and leukotrienes contribute to inflammation, tissue levels of these inflammatory mediators have never been studied. This work further investigates the antinociceptive effect of protein C after intra-wound administration. METHODS: Separate groups of Sprague–Dawley rats were used for quantitation of cyclooxygenase (COX) activity and leukotriene B4 level by enzyme-linked immunosorbent assay, as well as estimation of cardiovascular parameters and feeding and drinking behavior after paw incision. In the next part, rats were subjected to incision and 10 μg of protein C was locally administered by a micropipette. Both evoked and non-evoked pain parameters were then estimated. RESULTS: COX, particularly COX-2 activity and leukotriene B4 levels increased after incision. Hemodynamic parameters were normal. Feeding and drinking were affected on days 1 and 3, and on day 1, respectively. Protein C attenuated non-evoked pain behavior alone up to day 2. CONCLUSIONS: Based upon current observations, Brennan’s rodent paw incision model appears to exhibit a prolonged period of nociception similar to that after surgery, with minimal interference of physiological parameters. Protein C, which is likely converted to activated protein C in the wound, attenuated the guarding score, which probably represents pain at rest after surgery in humans.

Obstetric outcome of induction of labor using prostaglandin gel in patients with previous one cesarean section

OBJECTIVE: After globally acceptance of planned vaginal birth after cesarean section (VBAC), the mode of induction is still a matter of debate and requires further discussion. We aimed to study obstetric outcomes in post-cesarean patients undergoing induction of labor with prostaglandin gel compared with patients who developed spontaneous labor pains. METHODS: All patients at 34 weeks or more of gestation with previous one cesarean section eligible for trial of labor after cesarean section admitted in a labor room within one year were divided in 2 groups. Group one consisted of patients who experienced the spontaneous onset of labor pains and group 2 consisted of patients who underwent induction of labor with prostaglandin gel. They were analyzed for maternofetal outcomes. Descriptive statistics, independent sample t-test, and chi-square test were applied using SPSS 20 software for statistical analysis. RESULTS: Both groups were comparable in maternal age, parity, and fetal weight, but different in bishop score, mode of delivery, and neonatal outcome. Admisson bishop score was 6.61±2.51 in group 1 and 3.15±1.27 in group 2 (P<0.005). In the patients who experienced spontaneous labor, 86.82% had successful VBAC. In the patients with induced labor, 64.34% had successful VBAC with an average dose of gel of 1.65±0.75. Both groups had one case each of uterine rupture. The neonatal intensive care unit admission rate was 4.1% in group one and 10.4% in group 2. CONCLUSION: This study reflects that supervised labor induction with prostaglandin gel in previous one cesarean section patients is a safe and effective option.

Indução do estro em cutias (Dasyprocta leporina) utilizando-se protocolos à base de prostaglandina isolada ou em associação com análogo de GnRH / Estrus induction in agoutis (Dasyprocta leporina) using protocols based on prostaglandin isolated or in association to GnRH analogue

Comparou-se a eficiência de protocolos para indução de estro em cutias. Em cinco fêmeas, foram administradas duas doses de cloprostenol (5µg) com intervalo de nove dias, via intraperitoneal; em outras cinco, administraram-se 30µg de análogo do hormônio liberador de gonadotrofinas (GnRH), via intravulvar, seguidos de 5µg de cloprostenol, via intraperitoneal, após sete dias e, após mais dois dias, nova dose do análogo de GnRH. A cada três dias, a ciclicidade reprodutiva dos animais foi monitorada, por meio de coleta de sangue, para dosagem hormonal, ultrassonografia ovariana e citologia vaginal. Duas das fêmeas que receberam apenas prostaglandina, as quais estavam em fase luteal no início do tratamento, manifestaram o estro aos três e seis dias após a segunda administração da droga. Já nas fêmeas que receberam a prostaglandina associada ao análogo do GnRH, duas que originalmente estavam em fase luteal apresentaram estro aos quatro dias após o tratamento, e uma outra apenas após 10 dias. Não foram evidenciadas diferenças estatísticas quanto à eficiência dos tratamentos (P>0,05). Conclui-se que, de acordo com os protocolos utilizados, o uso da prostaglandina isolada ou em associação com análogo do GnRH para a indução do estro em cutias D. leporina apresenta eficiência limitada às fêmeas que estejam em fase luteal por ocasião do início do tratamento.(AU)

We compared the efficiency of protocols for estrus induction in agoutis. Five females received double intraperitoneal administration of cloprostenol (5µg) on a 2-days interval; other five females were treated with intravulvar administration of 30µg gonadotrophin release hormone analogue (GnRH associated to intraperitoneal administration of 5µg cloprostenol after seven days and a new administration of GnRH analogue after two days. Every 3 days, the agoutis' reproductive cycle was monitored by blood collection for hormonal analysis, ovarian ultrasound and vaginal cytology. Two females, originally in luteal phase, that received isolated prostaglandin presented estrous signs at 3 and 6 days after the second drug administration. From the females that received the association, two that were originally in luteal phase presented estrus at 4 days after treatment, and one other presented estrus only after 10 days. There was no significant statistical difference regarding the efficiency of treatments for estrus induction (P>0.05). We conclude that, according to the protocols tested in the study, the use of isolated prostaglandin or its association to GnRH analogue for estrus induction in D. leporine shows an efficiency limited to the females that were in luteal phase in the beginning of the treatment.(AU)

Eicosanoids and cancer

Eicosanoids are 20-carbon bioactive lipids derived from the metabolism of polyunsaturated fatty acids, which can modulate various biological processes including cell proliferation, adhesion and migration, angiogenesis, vascular permeability and inflammatory responses. In recent years, studies have shown the importance of eicosanoids in the control of physiological and pathological processes associated with several diseases, including cancer. The polyunsaturated fatty acid predominantly metabolized to generate 2-series eicosanoids is arachidonic acid, which is the major n-6 polyunsaturated fatty acid found in animal fat and in the occidental diet. The three main pathways responsible for metabolizing arachidonic acid and other polyunsaturated fatty acids to generate eicosanoids are the cyclooxygenase, lipoxygenase and P450 epoxygenase pathways. Inflammation plays a decisive role in various stages of tumor development including initiation, promotion, invasion and metastasis. This review will focus on studies that have investigated the role of prostanoids and lipoxygenase-derived eicosanoids in the development and progression of different tumors, highlighting the findings that may provide insights into how these eicosanoids can influence cell proliferation, cell migration and the inflammatory process. A better understanding of the complex role played by eicosanoids in both tumor cells and the tumor microenvironment may provide new markers for diagnostic and prognostic purposes and identify new therapeutic strategies in cancer treatment.

El Misofar® como prostaglandina facilitadora: una nueva opción en obstetricia / Misofar® as facilitator prostaglandin: a new option in obstetrics

La inducción del parto resulta un procedimiento elemental en la práctica obstétrica, que se aplica en un grupo importante de pacientes para interrumpir con éxito el embarazo debido a riesgos materno y perinatal. En este artículo se expone brevemente un nuevo método que permite abordar con efectividad la respuesta a la oxitocina, después del uso del Misofar® en función facilitadora para inducir el parto, acortando la latencia en la rotura prematura de membranas y condicionando las estructuras cervicales en gestantes con preeclampsia para obtener una mejor respuesta. Esta nueva herramienta se pone a disposición de la comunidad médica, en beneficio materno y perinatal.

Labor induction is an elementary procedure in obstetrics that is applied in an important group of patients to successfully interrupt pregnancy due to maternal and perinatal risks. In this work, a new method that allows to approach with effectiveness the oxytocin response is briefly exposed, after the use of Misofar® in facilitator function to induce labor, shortening the latency in early break of membranes and conditioning the cervical structures in pregnant women with pre-eclampsia to obtain a better response. This new tool is at medical community disposal for the maternal and perinatal benefit.

A Single Resistance Exercise Session Improves Aortic Endothelial Function in Hypertensive Rats / Uma Única Sessão de Exercício Resistido Melhora a Função Endotelial Aórtica em Ratos Hipertensos

Abstract Background: Physical exercise is an important tool for the improvement of endothelial function. Objective: To assess the effects of acute dynamic resistance exercise on the endothelial function of spontaneously hypertensive rats (SHR). Methods: Ten minutes after exercise, the aorta was removed to evaluate the expression of endothelial nitric oxide synthase (eNOS), phosphorylated endothelial nitric oxide synthase (p-eNOS1177) and inducible nitric oxide synthase (iNOS) and to generate concentration-response curves to acetylcholine (ACh) and to phenylephrine (PHE). The PHE protocol was also performed with damaged endothelium and before and after NG-nitro-L-arginine methyl ester (L-NAME) and indomethacin administration. The maximal response (Emax) and the sensitivity (EC50) to these drugs were evaluated. Results: ACh-induced relaxation increased in the aortic rings of exercised (Ex) rats (Emax= -80 ± 4.6%, p < 0.05) when compared to those of controls (Ct) (Emax = -50 ± 6.8%). The Emax to PHE was decreased following exercise conditions (95 ± 7.9%, p < 0.05) when compared to control conditions (120 ± 4.2%). This response was abolished after L-NAME administration or endothelial damage. In the presence of indomethacin, the aortic rings' reactivity to PHE was decreased in both groups (EC50= Ex -5.9 ± 0.14 vs. Ct -6.6 ± 0.33 log µM, p < 0.05 / Emax = Ex 9.5 ± 2.9 vs. Ct 17 ± 6.2%, p < 0.05). Exercise did not alter the expression of eNOS and iNOS, but increased the level of p-eNOS. Conclusion: A single resistance exercise session improves endothelial function in hypertensive rats. This response seems to be mediated by increased NO production through eNOS activation.

Resumo Fundamento: O exercício físico é uma importante ferramenta para o aprimoramento da função endotelial. Objetivo: Avaliar os efeitos do exercício dinâmico resistido agudo na função endotelial de ratos espontaneamente hipertensos (SHR). Métodos: Após 10 minutos de exercício, a aorta foi removida para avaliação da expressão de óxido nítrico sintase endotelial (eNOS), óxido nítrico sintase endotelial fosforilada (p-eNOS1177) e óxido nítrico sintase endotelial induzível (iNOS), e para a construção de curvas concentração-resposta de acetilcolina (ACT) e fenilefrina (FEN). O protocolo FEN foi também realizado com lesão endotelial e antes e depois da administração de N-nitro-L-arginina metil éster (L-NAME) e indometacina. A resposta máxima (Emax) e a sensibilidade (EC50) a esses fármacos foram avaliadas. Resultados: Houve aumento do relaxamento induzido por ACT nos anéis aórticos dos ratos exercitados (Ex) (Emax = -80 ± 4,6%; p < 0,05) quando comparado àquele dos controles (Ct) (Emax = -50 ± 6,8%). A Emax à FEN diminuiu após exercício (95 ± 7,9%; p < 0,05) quando comparada àquela dos controles (120 ± 4,2%). Tal resposta foi abolida após administração de L-NAME ou lesão endotelial. Na presença de indometacina, a reatividade dos anéis aórticos à FEN diminuiu nos dois grupos (EC50= Ex -5,9 ± 0,14 vs. Ct -6,6 ± 0,33 log µM; p < 0,05/ Emax = Ex 9,5 ± 2,9 vs. Ct 17 ± 6,2%; p < 0,05). O exercício não alterou a expressão de eNOS e de iNOS, mas aumentou o nível de p-eNOS. Conclusão: Uma única sessão de exercício resistido melhora a função endotelial em ratos hipertensos. Essa resposta parece ser mediada por elevação da produção de NO através de ativação de eNOS.

Efecto terapéutico del alprostadil en pacientes con isquemia crítica terminal de los miembros inferiores / Therapeutic effect of alprostadil in patients with critical lower limb ischemia

Resumen Objetivo: El manejo de la isquemia crítica de los miembros inferiores representa un reto para el cirujano vascular debido a la alta tasa de amputaciones y mortalidad. Las opciones de manejo actuales: puente femorodistal, angioplastia con o sin la colocación de Stents y la resección de la placa con láser o de manera mecánica, presentan a largo plazo una tasa de éxito muy baja y un número de amputaciones supracondíleas que continúa siendo elevado. Métodos: Para este estudio prospectivo se reclutaron 173 pacientes con diagnóstico de estadio avanzado, con isquemia crítica de miembro inferior quienes fueron tratados con alprostadil (60- 120 mcgr/día) por vía intravenosa sistémica por 28 días. La respuesta se midió clínicamente por mejoría del llenado capilar y con el uso de la escala análoga visual del dolor. Resultados: Al momento del alta hospitalaria el 94.3% de los pacientes mejoró el puntaje en la escala análoga visual del dolor (p < 0.0001). El seguimiento a más de un año del tratamiento con alprostadil mostró que el 97% de los pacientes mejoró significativamente su estadio de isquemia, evitándose así una amputación mayor. No se observó respuesta al tratamiento en pacientes previamente intervenidos por vía endovascular (5 pacientes). Conclusiones: El tratamiento de pacientes con isquemia crítica de miembro inferior con alpostadil por infusión intravenosa, con bolos diarios de entre 60 y 120 mcg durante 28 días, este medicamento es seguro y presenta mínimos efectos secundarios. Esta terapia mejora sustancialmente el estadio funcional de Rutherford en estos pacientes y evita amputaciones mayores.

Abstract Objetive: Management of critical lower limb ischemia represents a challenge for the vascular surgeon due to the high rate of amputations and mortality. Current management options include femorodistal bypass, angioplasty with or without stent and laser or mechanical resection of the plaque. They present a low success rate in the long run and a number of supracondylar amputations that still remains high. Methods: This prospective study included 173 patients diagnosed with advanced stage critical lower limb ischemia who were treated with systemic intravenous alprostadil (60 - 120 mcg/day) during 8 days. Response was measured clinically with improvement of capillary refill and using the visual analog scale for pain. Results: Upon discharge 94.3% of patients improved their visual analogue scale score for pain (p < 0.0001). Follow-up for more than a year of alprostadil treatment revealed that 97% of patients significantly improved their ischemia status, thus avoiding further amputation. No response to treatment was observed in patients who had previously undergone endovascular surgery (5 patients). Conclusions: Treating patients with critical lower limb ischemia with intravenous alprostadil, administering daily doses of between 60 and 120 mcg during 28 days shows that this drug is safe and causes minimal secondary effects. This therapy significantly improves Rutherford's function state in these patients and avoids further amputations.

Resultados perinatales de pacientes con trastornos hipertensivos del embarazo que son sometidas a inducción del trabajo de parto con prostaglandinas en el centro obstétrico del Hospital Nacional de la Mujer, en el periodo de enero a julio de 2015 / Perinatal results of patients with hypertensive disorders of pregnancy who undergo induction of labor with prostaglandins at the obstetric center of the National Women's Hospital, from January to July 2015

Se realizó esta investigación para demostrar los resultados perinatales, en pacientes con trastornos hipertensivos del embarazo en los que se realizó inducción del trabajo de parto con misoprostol. La importancia de esta investigación radica en lo frecuente que es la inducción del parto en este tipo de pacientes. Se identificaron dentro de los factores epidemiológicos que la mayoría de las pacientes son primigestas con edades de más 30 años y en cuanto a los resultados perinatales en las pacientes en las que se realizó inducción, no se evidenciaron complicaciones frecuentes, además se identificó que las vías de administración usadas son la oral y la vaginal así como la dosis inicial es de 50 mcg. Todo esto se logró mediante la revisión de los expedientes clínicos de manera retrospectiva de las pacientes en las que se realizó inducción del trabajo de parto en el primer semestre del año 2015 en el Centro Obstétrico del Hospital Nacional de la Mujer, las cuales fueron un total de 112

Participation of COX-1 and COX-2 in the contractile effect of phenylephrine in prepubescent and old rats

Vascular reactivity can be influenced by the vascular region, animal age, and pathologies present. Prostaglandins (produced by COX-1 and COX-2) play an important role in the contractile response to phenylephrine in the abdominal aorta of young rats. Although these COXs are found in many tissues, their distribution and role in vascular reactivity are not clear. At a vascular level, they take part in the homeostasis functions involved in many physiological and pathologic processes (e.g., arterial pressure and inflammatory processes). The aim of this study was to analyze changes in the contractile response to phenylephrine of thoracic/abdominal aorta and the coronary artery during aging in rats. Three groups of rats were formed and sacrificed at three distinct ages: prepubescent, young and old adult. The results suggest that there is a higher participation of prostanoids in the contractile effect of phenylephrine in pre-pubescent rats, and a lower participation of the same in old rats. Contrarily, there seems to be a higher participation of prostanoids in the contractile response of the coronary artery of older than pre-pubescent rats. Considering that the changes in the expression of COX-2 were similar for the three age groups and the two tissues tested, and that expression of COX-1 is apparently greater in older rats, COX-1 and COX-2 may lose functionality in relation to their corresponding receptors during aging in rats.

Effects of host modulation by nonsteroidal anti-inflammatory drugs on periodontal disease: a systematic review and meta-analysis

PURPOSE: Nonsteroidal anti-inflammatory drugs that prohibit biosynthesis of arachidonic acid metabolites have been considered potent host modulation agents. The aim of this review was to determine the effect of nonsteroidal anti-inflammatory drugs adjunctive with nonsurgical periodontal treatment in patients with periodontal disease. MATERIALS AND METHODS: Three electronic databases were searched to identify relevant studies. The methodological quality and mean differences of the change in clinical attachment level and probing depth were analyzed according to Cochrane review methods. RESULTS: Twelve studies were included in the methodological assessment and nine studies were suitable for inclusion in the meta-analysis. The mean difference in the clinical attachment level gain did not differ significantly between the nonsteroidal anti-inflammatory drugs and control groups at any observation time. The highest mean difference in clinical attachment level gain was 0.30 mm at 4 weeks (95% confidence interval = -0.37 to 0.97). There was a significant mean difference in the probing depth reduction, of 0.34 mm (95% confidence interval = 0.29 to 0.40) at 6 weeks. CONCLUSION: Therefore, nonsteroidal anti-inflammatory drugs have additional therapeutic effect when administrated with nonsurgical periodontal treatment.

Inhibition of prostaglandins synthesis in the inflamed site results in opioid-mediated hypoalgesia in rats / 生理学报

This study was designed to investigate the contribution of prostaglandins to the maintenance of inflammatory pain. Inflammation was induced by intraplantar (i.pl.) injection of carrageenan in right hindpaw in rats. Indomethacin (non-selective COX inhibitor) was administered i.pl. 1 h after the carrageenan injection, and paw withdrawal latency (PWL) responding to noxious heat was measured. β-endorphin (β-END) and μ-opioid receptor (MOR) expressed in the inflamed site were examined by using immunocytochemistry, ELISA and RT-PCR techniques. The results showed that indomethacin dose-dependently increased PWL to the levels that were above the baseline on the day 2 and 3, referred to as hypoalgesia. The hypoalgesia was abolished by a local injection of the non-selective opioid receptor inhibitor naloxone methiodide. The number of β-END-positive cells, the content of β-END and the expression of MOR mRNA in the inflammatory site of inflammation model rats were all significantly increased by indomethacin. These results reveal a novel mechanism of prostaglandins for the inhibition of inflammation-induced endogenous opioid activity. This study provides further evidence that inhibition of prostaglandins in inflamed site could be a promising therapy for inflammatory pain.

Effects of exercise training on stress-induced vascular reactivity alterations: role of nitric oxide and prostanoids

Background: Physical exercise may modify biologic stress responses. Objective: To investigate the impact of exercise training on vascular alterations induced by acute stress, focusing on nitric oxide and cyclooxygenase pathways. Method: Wistar rats were separated into: sedentary, trained (60-min swimming, 5 days/week during 8 weeks, carrying a 5% body-weight load), stressed (2 h-immobilization), and trained/stressed. Response curves for noradrenaline, in the absence and presence of L-NAME or indomethacin, were obtained in intact and denuded aortas (n=7-10). Results: None of the procedures altered the denuded aorta reactivity. Intact aortas from stressed, trained, and trained/stressed rats showed similar reduction in noradrenaline maximal responses (sedentary 3.54±0.15, stressed 2.80±0.10*, trained 2.82±0.11*, trained/stressed 2.97± 0.21*, *P<0.05 relate to sedentary). Endothelium removal and L-NAME abolished this hyporeactivity in all experimental groups, except in trained/stressed rats that showed a partial aorta reactivity recovery in L-NAME presence (L-NAME: sedentary 5.23±0,26#, stressed 5.55±0.38#, trained 5.28±0.30#, trained/stressed 4.42±0.41, #P<0.05 related to trained/stressed). Indomethacin determined a decrease in sensitivity (EC50) in intact aortas of trained rats without abolishing the aortal hyporeactivity in trained, stressed, and trained/stressed rats. Conclusions: Exercise-induced vascular adaptive response involved an increase in endothelial vasodilator prostaglandins and nitric oxide. Stress-induced vascular adaptive response involved an increase in endothelial nitric oxide. Beside the involvement of the endothelial nitric oxide pathway, the vascular response of trained/stressed rats involved an additional mechanism yet to be elucidated. These findings advance on the understanding of the vascular processes after exercise and stress alone and in combination. .