Eficacia y seguridad de una alternativa a la terapia hormonal de la menopausia: extracto purificado de polen / Efficacy and safety of an alternative to menopausal hormone therapy: purified cytoplasm of pollen

Los síntomas vasomotores (SVM) se encuentran entre los síntomas más comunes de la transición a la menopausia. Más del 70% de las mujeres de mediana edad informan SVM en algún momento durante la transición a la menopausia, y para un tercio de las mujeres los SVM son muy frecuentes o graves. Muchas mujeres recurren a terapias naturales para tratar los SVM. Esta revisión se centra en una de esas opciones naturales: el extracto purificado de polen (Serelys®). Se realizó una búsqueda e identificación de artículos publicados hasta octubre de 2022 recopilados de sistemas de búsqueda electrónicos, como Google Scholar, MEDLINE, PubMed y Scopus. Las palabras de búsqueda fueron “Vasomotor symptoms”, “menopause” AND “pollen”. Los estudios preclínicos señalan un mecanismo de acción en su implicación sobre el sistema serotoninérgico, así como su unión a los receptores de dopamina. Los estudios clínicos demuestran la seguridad y el efecto positivo sobre los SVM.

Vasomotor symptoms (VMS) are among the most common symptoms of the menopausal transition. More than 70% of middle-aged women report VMS at some point during the menopausal transition, and for a third of women, VMS is very common or severe. Many women turn to natural therapies to treat VMS. This review focuses on one such natural option, purified pollen extract (Serelys®). The information available until October 2022 was collected via the library and electronic search systems such as Google Scholar, MEDLINE, PubMed, and Scopus. The search words were: “Vasomotor symptoms”, “menopause” AND “pollen”. Preclinical studies point to a mechanism of action in its involvement in the serotonergic system, as well as its binding to dopamine receptors. Clinical studies demonstrate the safety and positive effect on VMS.

Negative affect symptoms, anxiety sensitivity, and vasomotor symptoms during perimenopause

Objective: Vasomotor symptoms affect 60-80% of women during the menopausal transition. Anxiety, depression, and anxiety sensitivity can have an important role in the distressful experience of vasomotor symptoms. Our aim was to evaluate the prevalence and association of vasomotor and negative affect symptoms. Methods: A cross-sectional study was conducted with 89 perimenopausal women aged 45-55 years. Broad psychiatric and clinical evaluations were carried out. The primary outcome was the vasomotor symptom problem rating and the main study factor was anxiety sensitivity. Linear regression analyses were conducted to examine the associations between the study factors and the primary outcome, and a multiple regression model was created to assess which variables were independently associated with vasomotor symptom problem rating. Results: The prevalence of anxiety, depression, and vasomotor symptoms were 58, 62, and 73%, respectively. Negative affect symptoms were positively associated with vasomotor symptom problem rating. The association of anxiety sensitivity and vasomotor symptom problem rating remained significant after controlling for perimenopausal stage, thyrotropin, follicle-stimulating hormone levels, and psychotropic medication use (β = 0.314, p = 0.002). Conclusion: A better understanding of the experience of vasomotor symptoms is needed, especially the role of negative affect symptoms and anxiety sensitivity. New strategies focusing on related thoughts and behaviors could improve the quality of life of perimenopausal women.

Síndrome vasomotor: puente de unión entre la disfunción endotelial y la esclerosis arterial / Vasomotor syndrome: meeting point between endothelial dysfunction and atherosclerosis

Resumen Introducción: Los síntomas vasomotores y la disfunción endotelial probablemente resulten del déficit estrogénico postmenopausia; no obstante, la relación de ambos con la progresión de la aterosclerosis es un tema controversial. Objetivo: Identificar en mujeres de edad mediana con disfunción endotelial, la presencia de aterosclerosis subclinica y de cambios cardiometabólicos durante la transición a la menopausia. Método: Estudio observacional de corte transversal, en el que incluyeron 43 mujeres con edad entre 40-59 años, con disfunción endotelial previa y 14 mujeres con función endotelial normal. En cada mujer se identificaron: manifestaciones de rigidez arterial y del grosor de la grasa epicárdica y su relación con variables antropométricas, intensidad de los síntomas vasomotores, etapas del climaterio y niveles de estradiol. Análisis estadístico: Regresión lineal múltiple y regresión logística para identificar asociación entre intensidad de los síntomas vasomotores, parámetros de rigidez arterial y cardiometabólicos (p< 0,05) para significación estadística. Resultados: Los parámetros de rigidez arterial (VLPP, CA, AI), de aterosclerosis (GIMc) y el grosor de la grasa epicárdica no mostraron cambios compatibles con daño arterial. A mayor intensidad de los síntomas vasomotores se encontró mayor probabilidad de incremento de la VLPP. Evolutivamente un subgrupo de mujeres desarrolló cambios metabólicos y disfunción endotelial sin asociación con el hipoestrogenismo, la edad ni la etapa del climaterio. Conclusiones: Una mayor intensidad de los síntomas vasomotores podría constituir un marcador que identifique de manera temprana el riesgo de desarrollar aterosclerosis clínica.

Abstract Introduction: Vasomotor symptoms and endothelial dysfunction probably result in a post-menopausal oestrogen deficiency. However, the relationship of both with the progression of atherosclerosis is a controversial subject. Objective: To identify the presence of sub-clinical atherosclerosis in middle-aged women with endothelial dysfunction, as well as cardiometabolic changes during the transition to the menopause. Method: A cross-sectional, observation study was conducted on 43 women between 40 and 59 years of age, with previous endothelial dysfunction, and 14 women with normal endothelial function. The variables recorded in each woman were, signs of arterial stiffening epicardial fat thickness and their relationship with anthropometric variables, intensity of the vasomotor symptoms, stages of menopause, and oestradiol levels. Statistical analysis: Multiple linear regression and logistic regression was performed in order to identify an association between the intensity of the vasomotor symptoms, arterial stiffness, and cardiometabolic parameters. A P< .05 was significantly significant. Results: The arterial stiffness parameters (pulse wave propagation (PWP), Arterial distensibility, augmentation index), and that of atherosclerosis (carotid intima-media thickness, GIMc), and the thickness of the epicardial fat showed no changes compatible with arterial damage. At a higher intensity of vasomotor symptoms, a higher probability of an increase in PWP was found. Evolutionarily, a sub-group of women developed metabolic changes and endothelial dysfunction with no relationship with low oestrogens, age, or the stage of the menopause. Conclusions: A greater intensity of vasomotor symptoms could be a marker for the early identification of the risk for clinical atherosclerosis.

Updated treatment guideline for hormone therapy in postmenopausal women

Since menopause hormone therapy was first introduced, it has been widely used worldwide as the most effective treatment for vasomotor symptoms in menopausal women and for genitourinary syndrome of menopause. Menopause hormone therapy has been shown to prevent bone loss and fracture, but it may additionally offer various benefits for numerous other symptoms. The benefit-to-risk ratio of menopause hormone therapy is most favorable for women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications. Longer durations of therapy should be limited to patients with documented indications, such as persistent vasomotor symptoms or bone loss. For genitourinary syndrome of menopause, low-dose vaginal estrogen therapy or other therapies are recommended. Tibolone is a synthetic steroid that provides a therapeutic effect in the treatment of menopausal symptoms.

Thermographic analysis and autonomic response in the hands of patients with leprosy

Abstract: Background: Low temperatures and slow blood flow may result from peripheral neuropathy caused by leprosy, and the simple detection of cold fingers could already be a preliminary classification for these patients. Objective: To investigate whether infrared thermography would be able to measure this change in temperature in the hands of people with leprosy. Method: The study assessed 17 leprosy patients who were under treatment at the National Reference Center for Sanitary Dermatology and Leprosy, Uberlândia/MG, and 15 people without leprosy for the control group. The infrared camera FLIR A325 and Therma CAM Researcher Professional 2.9 software were used to measure the temperature. The room was air-conditioned, maintaining the temperature at 25°C; the distance between the camera and the limb was 70 cm. The vasomotor reflex of patients was tested by a cold stress on the palm. Results: The study showed a significant interaction between the clinical form of leprosy and temperature, where the control group and the borderline-borderline form revealed a higher initial temperature, while borderline-lepromatous and lepromatous leprosy showed a lower temperature. Regarding vasomotor reflex, lepromatous leprosy patients were unable to recover the initial temperature after cold stress, while those with the borderline-tuberculoid form not only recovered but exceeded the initial temperature. Conclusion: Thermography proved a potential tool to assist in the early detection of neuropathies, helping in the prevention of major nerve damage and the installation of deformities and disabilities that are characteristic of leprosy.

Cerebral vasomotor reactivity assessment using Transcranial Doppler and MRI with apnea test

Differently from previous studies that used Transcranial Doppler (TCD) and functional MRI (fMRI) for cerebral vasomotor reactivity (CVR) assessment in patients with carotid stenosis (CS), we assessed CVR using an identical stimulus, the Breath-Holding Test (BHT). We included 15 patients with CS and 7 age-matched controls to verify whether fMRI responded differently to BHT between groups and to calculate the agreement rate between tests. For TCD, impaired CVR was defined when the mean percentage increase on middle cerebral artery velocities was ≤31% on 3 consecutive 30-s apnea intercalated by 4-min normal breathing intervals. For fMRI, the percent variation on blood oxygen level-dependent (BOLD) signal intensity in the lentiform nucleus (LN) ipsilateral to the CS (or both LNs for controls) from baseline breathing to apnea was measured. The Euclidian differences between the series of each subject and the series of controls and patients classified it into normal or impaired CVR. We found different percent variations on BOLD-signal intensities between groups (P=0.032). The agreement was good in Controls (85.7%; κ=0.69) and overall (77.3%; κ=0.54). We conclude that BHT was feasible for CVR assessment on fMRI and elicited different BOLD responses in patients and controls, with a good overall agreement between the tests.

Regulation of Giα Protein Expression by Vasoactive Peptides in Hypertension: Molecular Mechanisms.

Guanine nucleotide regulatory proteins (G proteins) play a key role in the regulation of various signal transduction systems, including adenylyl cyclase/cAMP and phospholipase C (PLC)/phosphatidyl inositol (PI) turnover, which are implicated in the modulation of a variety of physiological functions, such as platelet functions, including platelet aggregation, secretion, and clot formation and cardiovascular functions, including arterial tone and reactivity. Several abnormalities in adenylyl cyclase activity, cAMP levels and G proteins have been shown to be responsible for the altered cardiac performance and vascular functions observed in cardiovascular disease states. The enhanced or unaltered levels of inhibitory G proteins (Giα) and mRNA have been reported in different models of hypertension, whereas Gsα levels are shown to be unaltered. The enhanced levels of Giα proteins precede the development of blood pressure and suggest that overexpression of Gi proteins may be one of the contributing factors for the pathogenesis of hypertension. The levels of vasoactive peptides including ET-1 and Ang II and growth factors are augmented in hypertension and contribute to the enhanced expression of Giα proteins in hypertension. In addition, oxidative stress due to enhanced levels of Ang II and ET-1 is enhanced in hypertension and may also be responsible for the enhanced expression of Giα proteins observed in hypertension. Furthermore, Ang II- and ET-1-induced transactivation of growth factor receptor through the activation of MAP kinase signaling is also shown to contribute to the augmented levels of Giα in hypertension. Thus, it appears that the enhanced levels of vasoactive peptides by increasing oxidative stress and transactivation growth factor receptors enhance MAP kinase activity that contribute to the enhanced expression of Giα proteins responsible for the pathogenesis of hypertension. In this review, we describe the role of vasoactive peptides and the signaling mechanisms responsible for the enhanced expression of Giα proteins in hypertension.

Beneficio del ejercicio aeróbico sobre síntomas vasomotores de pacientes postmenopáusicas / Benefit of aerobic exercise on vasomotor symptoms in postmenopausal patients

Objetivo: analizar el beneficio del ejercicio aeróbico sobre los síntomas vasomotores de las pacientes postmenopáusicas. Material y Métodos: estudio prospectivo, cuasi experimental, comparativo del antes y el después de ejercicio aeróbico en postmenopáusicas con síntomas vasomotores que acudieron para tratamiento no hormonal. Fueron ingresando desde el 2 de enero del 2012 y todas tuvieron seguimiento hasta el 30 de junio del 2012. Todas realizaron una rutina de ejercicio con evaluación basal, a los dos y cuatro meses, con el instrumento International Physical Activity Questionnaire Long Form (IPAQ) y la Escala de Puntuación Menopáusica (MRS), para valorar su sintomatología vasomotora. Los datos fueron procesados con el programa Excel 2010 y SPSS versión 19.0. Resultados: participaron 100 postmenopáusicas con promedio de edad de 52.6 años (DS 2.05). 78% estaban casadas y todas eran físicamente activas. Todas cumplieron con la rutina de ejercicios (IPAQ alto) y llenaron el MRS. Existió significancia estadística por la prueba de Mann-Whitney (p<0.001) en la disminución de s¡ntomas de los dominios som tico y psicológico: de 0.85 a 0.61 y de 0.43 a 0.32 respectivamente. Ninguna empeoró ni hubo complicaciones. Conclusiones: el ejercicio aeróbico tuvo un impacto positivo en la reducción de los s¡ntomas vasomotores en la postmenopausia.

Objective: analyze the benefits of aerobic exercise on vasomotor symptoms in postmenopausal patients. Material and Methods: Prospective, quasi-experimental, comparative trial, before and after postmenopausal women with vasomotor symptoms who presented for non-hormonal treatment since January 2, 2012 and who were followed through June 30, 2012. All had an aerobic exercise routine baseline, at 2 and 4 months, using the International Physical Activity Questionnaire instrument Long Form (IPAQ) and Menopausal Rating Scale (MRS) to assess their vasomotor symptoms. The data were processed with Excel 2010 and SPSS version 19.0. Results: Involved 100 postmenopausal women with a mean age of 52.6 years (SD 2.05). 78% were married and all were physically actives. All of them met exercise routine (IPAQ high) and filled the MRS. There was statistically significant by the Mann-Whitney test (p <0.001) in reducing symptoms of somatic and psychological domains. From 0.85 to 0.61 and from 0.43 to 0.32 respectively. No complications occurred or worsened. Conclusions: aerobic exercises were found to have a positive impact reduce vasomotor symptoms in postmenopausal women.

Impacto dos stents e do sirolimus por via oral na vasomotilidade coronariana dependente e independente do endotelio / Impact of stenting and oral sirolimus on endothelium-dependent and independent coronary vasomotion

FUNDAMENTO: Não há consenso sobre o impacto do implante de stent sobre a função endotelial no longo prazo. Há relatos de disfunção endotelial aumentada com stent com sirolimus quando comparado com o stent metálico convencional (BMS). OBJETIVO: Este estudo visa a avaliar o impacto do BMS e o efeito do sirolimus por via oral sobre a função endotelial. MÉTODOS: Quarenta e cinco pacientes foram randomizados em três grupos: BMS + altas doses de sirolimus oral (dose inicial de 15 mg, seguida de 6 mg/dia durante quatro semanas); BMS + baixa dose de sirolimus (6 mg, seguida de 2 mg por dia durante quatro semanas) e BMS sem sirolimus. Mudanças na vasoconstrição ou vasodilatação, em um segmento de 15 milímetros começando pelo extremo distal do stent em resposta a acetilcolina e nitroglicerina, foram avaliadas por angiografia quantitativa. RESULTADOS: Os grupos apresentaram características angiográficas semelhantes. A variação percentual de diâmetro em resposta a acetilcolina foi semelhante em todos os grupos, nos dois momentos (p = 0,469). Quatro horas após o implante de stent, o segmento alvo apresentou uma disfunção endotelial que se manteve após oito meses em todos os grupos. Em todos os grupos, a vasomotricidade independente de endotélio em resposta a nitroglicerina foi semelhante, às quatro horas e aos oito meses, com diâmetro do segmento alvo aumentado após a infusão de nitroglicerina (p = 0,001). CONCLUSÃO: A disfunção endotelial esteve igualmente presente no segmento distal de 15 milímetros do segmento tratado, às 4 horas e aos 8 meses após implante do stent. O sirolimus administrado por via oral durante quatro semanas para evitar a reestenose não afetou o estado de vasomotricidade endotélio dependente e independente.

BACKGROUND: There is no consensus regarding the impact of stenting on long-term endothelial function. There have been reports of increased endothelial dysfunction with sirolimus-eluting stents as compared to bare metal stenting (BMS). OBJECTIVE: This study aims to assess the impact of BMS and the effect of oral sirolimus on endothelial function. METHODS: Forty-five patients were randomized into three groups: BMS + high-dose oral sirolimus (initial dose of 15 mg, followed by 6 mg/day for four weeks); BMS + low-dose sirolimus (6 mg followed by 2 mg daily for four weeks); and BMS without sirolimus. Changes in vasoconstriction or vasodilation in a 15 mm segment starting at the distal stent end in response to acetylcholine and nitroglycerin were assessed by quantitative angiography. RESULTS: The groups had similar angiographic characteristics. The percent variation in diameter in response to acetylcholine was similar in all groups at the two time points (p = 0.469). Four hours after stenting, the target segment presented an endothelial dysfunction that was maintained after eight months in all groups. In all groups, endothelium-independent vasomotion in response to nitroglycerin was similar at four hours and eight months, with increased target segment diameter after nitroglycerin infusion (p = 0.001). CONCLUSION: The endothelial dysfunction was similarly present at the 15 mm segment distal to the treated segment, at 4 hours and 8 months after stenting. Sirolimus administered orally during 4 weeks to prevent restenosis did not affect the status of endothelium-dependent and independent vasomotion.

K(ATP) channel action in vascular tone regulation: from genetics to diseases / 生理学报

ATP-sensitive potassium (K(ATP)) channels are widely distributed in vasculatures, and play an important role in the vascular tone regulation. The K(ATP) channels consist of 4 pore-forming inward rectifier K(+) channel (Kir) subunits and 4 regulatory sulfonylurea receptors (SUR). The major vascular isoform of K(ATP) channels is composed of Kir6.1/SUR2B, although low levels of other subunits are also present in vascular beds. The observation from transgenic mice and humans carrying Kir6.1/SUR2B channel mutations strongly supports that normal activity of the Kir6.1/SUR2B channel is critical for cardiovascular function. The Kir6.1/SUR2B channel is regulated by intracellular ATP and ADP. The channel is a common target of several vasodilators and vasoconstrictors. Endogenous vasopressors such as arginine vasopressin and α-adrenoceptor agonists stimulate protein kinase C (PKC) and inhibit the K(ATP) channels, while vasodilators such as β-adrenoceptor agonists and vasoactive intestinal polypeptide increase K(ATP) channel activity by activating the adenylate cyclase-cAMP-protein kinase A (PKA) pathway. PKC phosphorylates a cluster of 4 serine residues at C-terminus of Kir6.1, whereas PKA acts on Ser1387 in the nucleotide binding domain 2 of SUR2B. The Kir6.1/SUR2B channel is also inhibited by oxidants including reactive oxygen species allowing vascular regulation in oxidative stress. The molecular basis underlying such a channel inhibition is likely to be mediated by S-glutathionylation at a few cysteine residues, especially Cys176, in Kir6.1. Furthermore, the channel activity is augmented in endotoxemia or septic shock, as a result of the upregulation of Kir6.1/SUR2B expression. Activation of the nuclear factor-κB dependent transcriptional mechanism contributes to the Kir6.1/SUR2B channel upregulation by lipopolysaccharides and perhaps other toll-like receptor ligands as well. In this review, we summarize the vascular K(ATP) channel regulation under physiological and pathophysiological conditions, and discuss the importance of K(ATP) channel as a potentially useful target in the treatment and prevention of cardiovascular diseases.

Síntomas vasomotores en la mujer climatérica / Vasomotor symptoms in climateric woman

Introducción: los síntomas más precoces y característicos del período climatérico son los síntomas vasomotores, los cuales se producen por la pérdida intermitente del control vasomotor por la falta de retroalimentación negativa del estradiol sobre el hipotálamo. Objetivo: aportar un conocimiento actualizado sobre la fisiopatología de la sintomatología vasomotora presentada en la mujer climatérica. Métodos: se realizó una revisión bibliográfica actualizada sobre la sintomatología vasomotora relacionada con el síndrome climatérico. Se revisaron textos, revistas y monografías. Resultados: se confeccionaron cuadros resúmenes y esquemas de la fisiopatología de los síntomas, así como una propuesta de algoritmo para el manejo de los síntomas vasomotores en la Atención Primaria de Salud. Conclusiones: las modificaciones perimenopáusicas suelen comenzar durante la quinta década de la vida. En este período, los síntomas más precoces son los sofocos y sudoraciones que afectan al 75 - 85 por ciento de las mujeres

Introduction: the more precocious and characteristic symptoms of climateric period are the vasomotor symptoms, which are produced due to the intermittent loss of vasomotor control by lack of a negative feedback of estradiol on the hypothalamus. Objective: to provide an updated knowledge on the physiopathologic features of vasomotor symptomatology in climateric woman. Methods: authors carried out an updated bibliographic review on above mentioned symptomatology related to climateric syndrome, as well as texts, journals and monographs. Results: summarized pictures and schemes of the physiopathologic features of symptoms, as well as a proposal of algorithm for management of vasomotor symptoms in the Health Primary Care. Conclusions: the perimenopause modifications may to begin during the fifth decade of life. In this period the earlier symptoms include: suffocations and sweatings involving the 75-85 percent of women

Efeito vasomotor após intoxicação aguda com bupivacaína e levobupivacaína via intraperitoneal em ratos, analisado por imagem infravermelha digital / Vasomotor effect after acute intoxication with bupivacaine and levobupivacaine in rats via intraperitoneal route analyzed via digital infrared imaging

JUSTIFICATIVA E OBJETIVOS: O estudo do efeito vasomotor dos anestésicos locais (AL) é de suma importância para a análise da ocorrência de efeitos cardiotóxicos, neurotóxicos e interações medicamentosas. Com a finalidade de encontrar um fármaco mais seguro do que a bupivacaína racêmica, o presente estudo teve por objetivo a análise por imagem infravermelha digital do efeito vasomotor da intoxicação aguda da bupivacaína e da levobupivacaína via intraperitoneal em ratos. MÉTODO: Utilizaram-se 30 ratos machos da linhagem Wistar, alocados em três grupos (n = 10) e submetidos a uma injeção intraperitoneal de AL. No Grupo C (Controle), foi realizada injeção intraperitoneal de soro fisiológico 0,9 por cento 1 mL. No Grupo B (bupivacaína), injeção intraperitoneal de bupivacaína racêmica a 0,5 por cento (R50-S50), dose de 20 mg.kg-1 de peso. No Grupo L (levobupivacaína), injeção intraperitoneal de levobupivacaína a 0,5 por cento, excesso enantiomérico (S75-R25) em dose de 20 mg.kg-1 de peso. Procedeu-se à filmagem termográfica contínua desde o momento da pré-injeção até 30 minutos após a injeção. Os resultados das filmagens foram analisados em forma gráfica, verificando-se a temperatura máxima de cada rato e a temperatura média do sistema que abrigava o animal. RESULTADOS: Os resultados da análise gráfica revelaram que não houve diferença entre o Grupo L e o Grupo C, e a temperatura média permaneceu estável durante todo o experimento em ambos os grupos. No Grupo B, houve um fenômeno de aumento de temperatura após a injeção intraperitoneal de bupivacaína. CONCLUSÕES: Os resultados demonstraram que o efeito vasomotor da toxicidade aguda da levobupivacaína foi semelhante ao Grupo C com soro fisiológico, por meio de estudos macroscópicos por filmagem digital infravermelha, e que houve alterações vasomotoras (vasoconstrição) com a intoxicação por bupivacaína em relação ao Grupo C e em relação ao Grupo L.

BACKGROUND AND OBJECTIVES: The study of the vasomotor effect of local anesthetics (LA) is of paramount importance for the analysis of the occurrence of cardiotoxic and neurotoxic effects, and drug interactions. In order to find a safer drug than racemic bupivacaine, this study aimed to analyze digital infrared imaging of acute vasomotor effect of bupivacaine and levobupivacaine in rats intraperitoneally. METHOD: We used 30 male Wistar rats distributed into three groups (n = 10) and subjected to an intraperitoneal injection of LA. In Group C (control) 1 mL 0.9 percent saline was injected intraperitoneally. In Group B (bupivacaine), intraperitoneal injection of 0.5 percent of racemic bupivacaine (S50-R50), dose of 20 mg.kg-1 of body weight. In Group L (levobupivacaine), intraperitoneal injection of levobupivacaine 0.5 percent enantiomeric excess (S75-R25) in dose of 20 mg.kg-1 of body weight. The procedure was thermographicly continuously filmed from the time of pre-injection until 30 minutes after injection. The results of the recordings were analyzed in graphical form, verifying the maximum temperature of each rat and the average temperature of the system that housed the animal. RESULTS: The results of graphic analysis showed no difference between Group L and Group C, and the average temperature remained stable through-out the experiment in both groups. In Group B, there was a phenomenon of temperature increase after intraperitoneal injection of bupivacaine. CONCLUSIONS: The results demonstrated that the vasomotor effect of the acute toxicity of levobupivacaine was similar to Group C with saline, through macroscopic studies by infrared digital filmmaking, and that there were vasomotor changes (vasoconstriction), with bupivacaine intoxication in relation to both Group C and Group L.

JUSTIFICATIVA Y OBJETIVOS: El estudio del efecto vasomotor de los anestésicos locales (AL), es de suma importancia para el análisis del aparecimiento de efectos cardiotóxicos, neurotóxicos e interacciones medicamentosas. Con el fin de encontrar un fármaco más seguro que la bupivacaína racémica, el presente estudio se propuso analizar por imagen infrarroja digital, el efecto vasomotor de la intoxicación aguda de la bupivacaína y de la levobupivacaína vía intraperitoneal en ratones. MÉTODO: Fueron usados 30 ratones machos de la raza Wistar, divididos en tres grupos (n = 10) y sometidos a una inyección intraperitoneal de AL. En el Grupo C (Control), fue realizada una inyección intraperitoneal de suero fisiológico al 0,9 por ciento 1 mL. En el Grupo B (bupivacaína), una inyección intraperitoneal de bupivacaína racémica al 0,5 por ciento (R50-S50), dosis de 20 mg.kg-1 de peso. En el Grupo L (levobupivacaína), una inyección intraperitoneal de levobupivacaína al 0,5 por ciento, con exceso enantiomérico (S75-R25) en dosis de 20 mg.kg-1 de peso. Después de procedió a la filmación termográfica continua desde el momento anterior a la inyección hasta 30 minutos después de ella. Los resultados de las filmaciones se analizaron de forma gráfica, verificando la temperatura máxima de cada ratón y la temperatura promedio del sistema que abrigaba al animal. RESULTADOS: Los resultados del análisis gráfico revelaron que no hubo diferencia entre el Grupo L y el Grupo C, y que la temperatu-ra promedio se mantuvo estable durante todo el experimento en los dos grupos. En el Grupo B, se produjo un fenómeno de aumento de temperatura después de la inyección intraperitoneal de bupivacaína. CONCLUSIONES: Los resultados demostraron que el efecto vasomotor de la toxicidad aguda de la levobupivacaína fue similar al Grupo C con suero fisiológico, por medio de estudios macroscópicos por filmación digital infrarroja, y que se produjeron alteraciones vasomotoras (vasoconstricción)...

Alterations in pulmonary arterial reactivity during pulmonary arterial hypertension at the early-stage of pulmonary fibrosis in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the alterations in pulmonary arterial reactivity during pulmonary arterial hypertension at the early-stage of pulmonary fibrosis in rats.</p><p><b>METHODS</b>Sixty-six male Sprague-Dawley rats were randomly divided into 2 groups: bleomycin (BLM) group and sham group. The rats in BLM group were received single intratracheal instillation of BLM (5 mg/kg), and the rats in sham group received equal volume of 0.9% normal saline (NS). The alterations in pulmonary arterial reactivity were measured by vascular tension detected technique, the pathomorphological changes in the wall of pulmonary arteries were displayed with Hematoxylin-Eosin (HE) staining, the degree of fibrosis in lung was revealed with Masson staining, and the mean pulmonary arterial pressure was detected via a catheter in the pulmonary artery.</p><p><b>RESULTS</b>(1) The contractile response to a- adrenoceptor agonist phenylephrine (PE), of pulmonary arteries both with remaining endothelium and with removing endothelium, from BLM-treated rats , was reduced significantly, compared with sham rats (P both < 0.05). (2) The relaxant response to the endothelially dependent vasodilator acetylcholine (Ach), of pulmonary arteries with remaining endothelium, from BLM-treated rats, was also reduced, compared with sham rats (P < 0.01). (3) In sham rats, the contractile response to (omega) -nitro-L-arginine methyl ester (L-NAME) plus PE, of pulmonary arteries with remaining endothelium, was enhanced, compared with that to PE alone (P < 0.01), while in BLM group, the contractile responses to L-NAME plus PE, of pulmonary arteries with remaining endothelium, was not different from that to PE alone (P > 0.05). (4) In BLM group, vascular endothelial cells lost. (5) In BLM group, the initial stage of fibrogenesis was observed in lungs, and the mean pulmonary arterial pressure increased, compared with that in sham group (P < 0.05).</p><p><b>CONCLUSION</b>The abnormal responsibility of pulmonary arteries occurred during pulmonary arterial hypertension at the early-stage of pulmonary fibrosis in rats.</p>

Effect of ischemia/hypoxia on mesenteric vasomotor function in spontaneously hypertensive rats and its possible mechanism / 生理学报

Hypertension is a common cardiovascular disease and can induce many complications, such as stroke and coronary heart disease. The purpose of the present study was to investigate the effect of ischemia/hypoxia on mesenteric artery vasomotor function in spontaneously hypertensive rats (SHR). Rat mesenteric arterial rings were cultured in modified ischemia-mimetic solution in a hypoxia incubator for a certain time period. Isometric tension changes of isolated mesenteric arterial rings were recorded continuously by a myograph system. The results obtained were as follows: In SHR group, the maximum contractions to KCl and phenylephrine (PE) were increased, and the maximum relaxation to acetylcholine (ACh) was decreased, compared to those in Wistar-Kyoto (WKY) rats group. Compared with SHR group and WKY with acute ischemia/hypoxia (WKY+H) group, SHR with acute ischemia/hypoxia (SHR+H) increased the maximum contractions induced by KCl and PE and inhibited the maximum relaxations by ACh. In SHR+H and SHR groups, the vasodilation induced by ACh was unaffected by N(G)-nitro-L-arginine methylester (L-NAME), whereas in WKY group, the relaxation to ACh was attenuated by L-NAME. CaCl2-induced contraction in depolarized rings in SHR+H group significantly shifted to the left compared with SHR group. In Ca(2+)-free K-H solution, the maximum contractions induced by PE and caffeine were increased in SHR+H group compared to those in WKY+H group; the PE- and caffeine-induced contractions were also enhanced in SHR group versus WKY group; the maximum contraction induced by PE was significantly increased in SHR+H group versus SHR group. These findings suggest that acute ischemia/hypoxia aggravates mesenteric artery dysfunction in SHR. The mechanism may be related to the decreased NO generation and increased sarcoplasmic reticulum Ca(2+) release.

Effect of reversible inactivation of the kolliker fuse nucleus on basal blood pressure and heart rate in anesthetized rat

Several supra spinal areas such as rostral ventrolateral medulla [RVLM] area are involved in basic cardiovascular regulation. The Kolliker- Fuse nucleus [KF] is located in pons and is heavily connected with RVLM. The cardiovascular effect of KF nucleus has been shown and it is suggested that KF is involved in sympathetic vasomotor tone and basic cardiovascular regulation. Therefore, in the present study, the effects of KF on basic cardiovascular values were evaluated. After induction of anesthesia, a polyethylene catheter [PE-50] filled with heparinized saline was inserted into the femoral artery of rats. Animals were then placed in a stereotaxic apparatus and KF nucleus was inactivated by microinjection of cobalt chloride [CoCl2]. Blood pressure and heart rate [HR] were continuously recorded pre and post inactivation. Our result showed that inactivation of KF slightly changed mean arterial blood pressure [MAP] [92.3 +/- 2.45 mmHg vs. 90.86 +/- 1.7 mmHg] and HR [343.8 +/- 4.6 beats/min vs. 350.7 +/- 8.32 beats /min]. However, these effects were not significant in comparison to the control group. We concluded that synapses in the KF nucleus have no effect on regulation of basal blood pressure and heart rate, because CoCl2 is a synaptic blocker

Terapia estrogênica no climatério: qual a melhor via? Uma resposta baseada nas melhores evidências / Estrogen therapy in climacteric: what is the best route? An answer based on the best evidences

Foi realizada uma pesquisa abrangente acerca de revisões sistemáticas, trabalhos randomizados e controlados, utilizando o banco de dados, Medline, Pubmed, Scielo e Biblioteca Cochrane com descritores apropriados para avaliar os efeitos das diferentes vias de administração dos estrogênios nas principais indicações da terapia estrogênica para o controle dos sintomas atribuídos à deficiência estrogênica do climatério (sintomas vasomotores e atrofia urogenital). Concluiu-se que, para os sintomas vasomotores, a administração de estrogênios pelas vias oral ou não-oral são eficientes. No caso da atrofia urogenital, a administração de estrogênios pela via vaginal parece ser mais eficaz do que a sistêmica

To evaluate the influence of different forms of estrogens delivery on the primary indication of estrogen therapy in postmenopausal women for the control of symptoms attributed to estrogen deficiency (vasomotor symptoms and urogenital atrophy) a comprehensive literature search was conducted using the database Medline, Pubmed, Scielo and Cochrane Library with appropriate key words for systematic reviews and controlled randomized trials on the subjects. It was concluded that, for vasomotor symptoms, oral or non-oral routes of estrogens administrations are safe and effective, and for urogenital atrophy, the vaginal route has showed to be better than systemic route

Effects of salvianolic acid B and diammonium glycyrrhizinate on portal pressure in rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the relaxant effects of glycyrrhizinate and salvianolic acid B on rat portal vein in vitro.</p><p><b>METHODS</b>Healthy female Wistar rats were canalized from hepatic artery, portal vein and hepatic vein in vitro. Remained blood in liver was eliminated with heparinized Krebs-Henseleit solution through hepatic artery, then the liver was isolated under infusing manner. Being constricted with phenylephrine and relaxed with acetylcholine, and infused with glycyrrhizinate or salvianolic acid B, the portal pressures of infused rat livers were consistently monitored by BL-420S physiological experiment system. The median effective concentration (EC50) of the two agents were analyzed with non-linear various slope regression using Prism-4 software.</p><p><b>RESULTS</b>EC50 of glycyrrhizinate in relaxing the phenylephrine-contracted portal was 1.5556 x 10(-9) mol/L, suggesting one of the mechanism of action of diammonium glycyrhizinate for the treatment of portal hypertension was direct relaxation. Salvianolic acid B showed constrictive action on the phenylephrine-retracted portal vein, the EC50 was 1.4639 x 10(-9) mol/L, indicating that its indirect control action was took part in the portal hypertension therapy synergistically.</p><p><b>CONCLUSION</b>Under the mode with both controlled-velocity and monitored pressure, glycyrrhizinate showed relaxation and salvianolic acid B showed constriction on portal pressure in vitro.</p>

Alterations in aortic vasomotor function in rats with chronic heart failure and its mechanism / 生理学报

The aim of the present study was to investigate the alterations in thoracic aortic vasomotor function in rats with chronic heart failure (CHF) post myocardial infarction (MI), and then explored the possible mechanism of pathological changes. Male Sprague-Dawley rats were divided into sham and CHF groups randomly. The CHF model group of rats was generated by ligating the left anterior descending artery. In sham-operated rats the ligation was placed but not tightened. A total of 20 rats underwent either sham-operated (n=8) or surgery for MI (n=12). All sham-operated rats survived the surgical procedure and the post-surgical period, whereas total mortality among MI-rats was 25% (3 out of 12). Only MI-rats with infarct-size >30% of the left ventricle (LV) were included for analysis (8 out of 9). Ten weeks after surgery, rats were anaesthetized for hemodynamic measurements, which contains systolic pressure, diastolic pressure, left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), LV+dp/dt(max) and LV-dp/dt(max). After that hearts were rapidly excised and weighed. Myocardial infarct size was determined by triphenyltetrazolium chloride (TTC) staining method. Isolated thoracic artery ring preparations were studied in a wire-myograph. The arterial constrictive responses to KCl, CaCl2, phenylephrine (PE), and caffeine and the arterial diastolic responses to acetylcholine (ACh) were recorded by the Multi Myograph System. To explore the possible mechanism, nitric oxide synthase (NOS) inhibitor N-nitrl-L-arginine methylester (L-NAME) and non-selective cyclooxygenase (COX) inhibitor indomethacin (Indo) were used. The results obtained were as follows: (1) CHF group showed an increased contraction response to KCl (5-100 mmol/L) and PE (1x10(-8)-3x10(-4) mol/L), and a reduced endothelium-dependent relaxation response to ACh (1x10(-12)-1x10(-4) mol/L) compared with those observed in sham group (P<0.01, P<0.05); (2) In the presence of L-NAME (1 mmol/L), the endothelium-dependent cumulative contractions to ACh (1x10(-7)-1x 10(-4) mol/L) was significantly enhanced in CHF group (P<0.05), and this effect was reversed by pretreatment with Indo (10 mumol/L); (3) In CHF group, the vessels incubated with Indo (10 mumol/L) showed an increased vasodilation induced by ACh (1x10(-12)-1x10(-4) mol/L) (P<0.05); (4) In the Ca(2+)-free K-H solution, calcium-dependent contraction curves induced by CaCl2 (1x10(-4)-3x10(-2) mol/L) in CHF group significantly shifted to the left compared with sham group (P<0.05); while the vascular contraction induced by caffeine (30 mmol/L) had no significant changes. These findings suggest that thoracic arteries of rats with CHF have endothelial dysfunction, and the contribution of endothelial dilation and contraction was significantly altered in CHF rats. The mechanism could be partly associated with the increased endothelium-dependent contracting factors by COX pathway, or the increased extracellular Ca(2+) influx through voltage-operated channels, thus leading to elevated vasoconstriction.

Role of the medulla oblongata in normal and high arterial blood pressure regulation: the contribution of Escola Paulista de Medicina - UNIFESP

Several forms of experimental evidence gathered in the last 37 years have unequivocally established that the medulla oblongata harbors the main neural circuits responsible for generating the vasomotor tone and regulating arterial blood pressure. Our current understanding of this circuitry derives mainly from the studies of Pedro Guertzenstein, a former student who became Professor of Physiology at UNIFESP later, and his colleagues. In this review, we have summarized the main findings as well as our collaboration to a further understanding of the ventrolateral medulla and the control of arterial blood pressure under normal and pathological conditions.

Numerosas formas de evidência experimental obtidas nos últimos 37 anos demonstraram inequivocamente que a medula oblongata contém os principais circuitos responsáveis pela geração e manutenção do tono vasomotor e a regulação da pressão arterial. A visão atual que possuímos destes circuitos deriva em grande parte dos estudos de Pedro Guertzenstein, um estudante e mais tarde Professor de Fisiologia da UNIFESP e seus colaboradores. Nesta revisão nós sumarizamos os seus principais resultados assim como a nossa colaboração para uma melhor compreensão da regulação da pressão arterial em condições normais e patológicas.