Actividad citotóxica y antiproliferativa de un extracto rico en fucoidan de Lessonia trabeculata sobre células de adenocarcinoma mamario murino 4T1

Introducción. Los tumores neoplásicos se caracterizan por su invasividad y metástasis. Las células neoplásicas tienen heterogeneidad genética, por lo cual pueden desarrollar resistencia a los quimioterápicos. Por esta razón, las plantas continúan siendo una fuente importante de nuevos productos anticancerígenos. Objetivo. Evaluar la actividad citotóxica y antiproliferativa de un extracto rico en fucoidan de Lessonia trabeculata nativa (EFLt) sobre la línea celular de adenocarcinoma mamario murino, triple negativo 4T1. Métodos. La citotoxicidad y la IC50 se determinaron en monocapas de 4T1 empleando el reactivo MTT. Para demostrar la actividad antiproliferativa se aplicaron los métodos de cierre de herida y anticlonogénico utilizando las IC50 del EFLt y Dox (doxorubicina). El cierre de herida fue evaluado mediante barrido de tiempos discretos; el efecto anticlonogénico fue evaluado 7 días postratamiento mediante el conteo de colonias y se determinó la fracción de sobrevivencia. Adicionalmente, se evaluaron la citotoxicidad y actividad antiproliferativa combinando las IC50 de EFLt y Dox. El porcentaje de migración y conteo de colonias se realizó con el programa ImageJ. Resultados. La IC50 del EFLt (950 μg/mL) produjo 56% de citotoxicidad, 80,3% de inhibición de la migración celular, 68% de inhibición en la formación de colonias. La IC50 de Dox fue 0,5 μg/mL. Conclusiones. El EFLt ejerce citotoxicidad dependiente de la concentración y tiene efecto antiproliferativo sobre 4T1. Se requiere continuar los ensayos en modelos de mayor complejidad que permitan esclarecer el potencial antitumoral del EFLt.

Introduction. Neoplastic tumors are characterized by invasiveness and metastasis. Neoplastic cells are genetically heterogeneous and can develop resistance to chemotherapeutic agents. For this reason, plants continue to be an important source of new anticancer products. Objective. To determine the cytotoxic and antiproliferative activity of a fucoidan-rich extract of native Lessonia trabeculata (EFLt) on the tripe negative murine mammary adenocarcinoma cell line 4T1. Methods. Cytotoxicity and IC50 were determined in 4T1 monolayers using the MTT reagent. To demonstrate antiproliferative activity, "wound" closure and anticlonogenic methods were applied using the IC50 of EFLt and Doc (doxorubicin). "Wound" closure was evaluated by discrete times sweep to determine percentage inhibition of cell migration; the anticlonogenic effect was evaluated by colony counting 7 days after treatment and the survival fraction was determined. In addition, cytotoxicity and antiproliferative activity were evaluated by combining the IC50 of EFLt and Dox. Percent migration and colony counts were performed using ImageJ software. Results. The IC50 (950 μg/mL) of EFLt was 56% cytotoxicity, 80,3% inhibition of cell migration, 68% inhibition of colony formation.The ICof Dox was 0,5 μg/mL. Conclusions. EFLt exerts concentration-dependent cytotoxicity and antiproliferative effect on 4T1. Further studies in more complex models are needed to elucidate the anti-tumor potential of EFLt.

The Effect of Low Tidal Volume Ventilation on Inflammatory Cytokines During Cardiopulmonary Bypass

Abstract Introduction: Halting ventilation during cardiopulmonary bypass (CPB) is implemented to operate in a less bleeding setting. It sustains a better visualization of the operation area and helps to perform the operation much more comfortably. On the other hand, it may lead to a series of postoperative lung complications such as atelectasis and pleural effusion. In this study, we investigated the effects of low tidal volume ventilation on inflammatory cytokines during CPB. Methods: Twenty-eight patients undergoing cardiovascular surgery were included in the study. Operation standards and ventilation protocols were determined and patients were divided into two groups: patients ventilated with low tidal volume and non-ventilated patients. Plasma samples were taken from patients preoperatively, perioperatively from the coronary sinus and postoperatively after CPB. IL-6, IL-8, TNF-α and C5a levels in serum samples were studied with enzyme-linked immunosorbent assay (ELISA) kits. Results: C5a, IL-6, IL-8 and TNF-α were similar when compared to the low tidal volume ventilated and non-ventilated groups (P>0.05) Comparing the groups by variables, IL-6 levels were increased during CPB in both groups (P=0.021 and P=0.001), and IL-8 levels decreased in the ventilation group during CPB (P=0.018). Conclusion: Our findings suggest that low tidal volume ventilation may reduce the inflammatory response during CPB. Although the benefit of low tidal volume ventilation in CPB has been shown to decrease postoperative lung complications such as pleural effusion, atelectasis and pneumonia, we still lack more definitive and clear proofs of inflammatory cytokines encountered during CPB.

Tecido Adiposo Epicárdico nos Fenótipos de Insuficiência Cardíaca - Uma Metanálise / Epicardial Adipose Tissue in Heart Failure Phenotypes - A Meta-Analysis

Resumo Fundamento O tecido adiposo epicárdico (TAE) é aumentado em comorbidades comuns na insuficiência cardíaca (IC). Dessa forma, o TAE teria o potencial de mediar efeitos que levam à deterioração da função cardíaca. Objetivos Esta metanálise tem o objetivo de investigar se a quantidade de TAE em todos os tipos de IC e cada tipo de IC são significativamente diferentes dos pacientes de controle. Métodos Esta metanálise seguiu as diretrizes da Meta-analysis of Observational Studies in Epidemiology (Metanálise de estudos observacionais em epidemiologia). A pesquisa foi realizada nos bancos de dados MEDLINE, Embase e Lilacs até novembro de 2020. Dois autores realizaram a triagem, a extração de dados e a avaliação de qualidade. Um p-valor <0,05 foi definido como estatisticamente significativo. Resultados Foram incluídos oito estudos observacionais, compreendendo 1248 pacientes no total, dos quais 574 eram de controle, 415 tinham IC com fração de ejeção reduzida (ICFER) e 259 tinham IC com fração de ejeção de faixa média ou preservada (ICFEfm ou ICFEP). A quantidade de TAE não era diferente entre todos os tipos de IC e o grupo de controle (DMP = -0,66, IC 95%: -1,54 a 0,23, p =0,14) . Analisando cada fenótipo de IC separadamente, pacientes com ICFER tinham TAE reduzido em comparação aos pacientes de controle (DMP = 1,27, IC 95%: - 1,87 a -0,67, p <0,0001), enquanto os pacientes com ICFEfm ou ICFEP tiveram TAE aumentado em comparação aos pacientes de controle (DMP = 1,24, IC 95%: 0,99 a 1,50, p <0,0001). Conclusão A quantidade de TAE não era significativamente diferente entre todos os tipos de IC e o grupo de controle. Em pacientes com ICFER o volume de TAE era reduzido, enquanto em pacientes com ICFEP e ICFEfm, a quantidade de TAE era significativamente aumentada. Número de registro PROSPERO: CRD42019134441.

Abstract Background Epicardial adipose tissue (EAT) is increased in comorbidities common in heart failure (HF). In this sense, EAT could potentially mediate effects that lead to an impaired cardiac function. Objectives This meta-analysis aims to investigate if the amount of EAT in all-types of HF and each HF phenotype is significantly different from control patients. Methods This meta-analysis followed the Meta-analysis Of Observational Studies in Epidemiology guidelines. The search was performed in the MEDLINE, Embase, and Lilacs databases until November 2020. Two authors performed screening, data extraction, and quality assessment. A p-value <0.05 was defined as statistically significant. Results Eight observational studies were included, comprehending 1,248 patients in total, from which 574 were controls, 415 had HF with reduced ejection fraction (HFrEF) and 259 had HF with mid-range or preserved ejection fraction (HFmrEF or HFpEF). The amount of EAT was not different between all types of HF and the control group (SMD = -0.66, 95% CI: -1.54 to 0.23, p =0.14). Analyzing each HF phenotype separately, patients with HFrEF had a reduced EAT when compared to the controls (SMD= -1.27, 95% CI: - 1.87 to -0.67, p <0.0001), while patients with HFmrEF or HFpEF showed an increased EAT when compared to controls (SMD= 1.24, 95% CI: 0.99 to 1.50, p <0.0001). Conclusion The amount of EAT was not significantly different between all types of HF and the control group. In patients with HFrEF, the EAT volume was reduced, whereas in HFpEF and HFmrEF, the amount of EAT was significantly increased. PROSPERO registration number: CRD42019134441.

Application of antibody-drug conjugates in the treatment of non-small cell lung cancer / 国际肿瘤学杂志

Antibody-drug conjugates (ADCs) have overcome the limitations of traditional chemotherapy and targeted therapy with unique advantage of antibody targeting, and made breakthrough achievements in the treatment of lung cancer. At present, the researches of ADCs in non-small cell lung cancer mainly involve HER2, HER3, TROP2, MET, CEACAM5. Many ADCs have passed rigorous clinical trials, and have shown good safety and efficacy, which provides theoretical basis for individualized treatment of lung cancer.

Experimental resin-based dual-cured calcium aluminate and calcium titanate materials for vital pulp therapy

Abstract: This paper evaluates the physicochemical and biological properties of experimental resin-based dual-cured calcium aluminate (CA) and calcium titanate (CTi) materials for vital pulp therapy (VPT). The experimental dual-cured materials were obtained as two pastes: a) Bis-EMA 10, PEG 400, DHEPT, EDAB, camphorquinone, and butylated hydroxytoluene; and b) fluoride ytterbium, Bis-EMA 10, Bis-EMA 30, benzoyl peroxide, and butylated hydroxytoluene. The materials were divided into six groups based on the added calcium component: MTA (MTA®, Angelus); CLQ (Clinker-Fillapex®, Angelus); CA (calcined at ,1200°C in pastes a and b); CA800 (calcined at 800°C in paste a); CA1200 (calcined at 1,200°C in paste a); and CTi (paste a). The real-time degree of conversion and rate of polymerization (n = 3), diametral tensile strength (n = 10), hydrogen potential (n = 15), calcium ion release (n = 10), water sorption and solubility (n = 10), and cell viability (n = 6) were evaluated. One- and two-way ANOVA and Tukey's post hoc test were used in the analysis of the parametric data, and Kruskal-Wallis and Dunn's multiple tests were used to analyze the nonparametric data (α = 0.05). CLQ, CA800 and CA1200 had the highest diametral tensile strength. The water solubility of MTA was similar to that of CA800, CA1200 and CTi. CA800 and CA1200 resulted in cell viabilities similar to those of MTA and CLQ. The experimental dual-cured CA-based material that calcined at 800°C showed physicochemical and biological properties suitable for VPT, and similar to those of MTA.

Quality of life of patients with cancer undergoing chemotherapy in hospitals in Belo Horizonte, Minas Gerais State, Brazil: does individual characteristics matter? / Qualidade de vida de pacientes com câncer submetidos a quimioterapia em hospitais em Belo Horizonte, Minas Gerais, Brasil: as características individuais importam? / Calidad de vida de pacientes con cáncer sometidos a quimioterapia en hospitales de Belo Horizonte, Minas Gerais, Brasil: ¿importan las características individuales?

This study aims to evaluate changes in quality of life of cancer patients at the beginning of the first and the second cycle of chemotherapy (CT) in hospitals in Belo Horizonte, Minas Gerais State, Brazil. Longitudinal, prospective, descriptive study with a quantitative approach. We enrolled 230 patients, from a broader cohort, diagnosed with the five most frequent types of cancer (breast, colorectal, cervical, lung, and head and neck), aged 18 years or older, who were initiating CT for the first time. quality of life was assessed with the EORTC QLQ-C30 version 3, applied at the beginning of the first and second chemotherapy cycle. The paired Wilcoxon test was used to identify differences in quality of life between the two time points. A multivariate linear regression analysis was performed using the bootstrap method to investigate potential predictors of global health Status/quality of life. There was a significant increase in patients' emotional function scores (p < 0.001) as well as symptom scores for pain (p = 0.026), diarrhea (p = 0.018), and nausea/vomiting (p < 0.001) after initiation of CT. Widowhood was associated with improvements in the global health Status/quality of life (p = 0.028), whereas the presence of cervical cancer (p = 0.034) and being underweight (p = 0.033) were related to poorer global health status/quality of life scores. CT has detrimental effects on patients' physical health but, on the other hand, it leads to improvements in the emotional domain. Patients' individual characteristics at the beginning of CT are associated with changes in their quality of life. Our study could help identify these characteristics.

O estudo teve como objetivo avaliar as mudanças na qualidade de vida de pacientes oncológicos no início do primeiro e segundo ciclos de quimioterapia (QT) em hospitais em Belo Horizonte, Minas Gerais, Brasil. Foi realizado um estudo descritivo, prospectivo e longitudinal com uma abordagem quantitativa. Arrolamos 230 pacientes de uma coorte maior, diagnosticados com os cinco tipos de câncer mais frequentes (mama, colorretal, colo uterino, pulmão e cabeça e pescoço), com idade 18 anos ou mais e que estavam no início da QT. A qualidade de vida foi avaliada com o EORTC QLQ-C30, versão 3, aplicado no início do primeiro e segundo ciclos de QT. O teste pareado de Wilcoxon foi utilizado para identificar diferenças na qualidade de vida entre os dois momentos. Para investigar potenciais preditores de estado de saúde global/qualidade de vida, foi realizada uma análise de regressão linear multivariada com o método bootstrap. Houve um aumento significativo na pontuação da função emocional dos pacientes (p < 0,001) e de dor (p = 0,026), diarreia (p = 0,018) e náusea/vômito (p < 0,001) após o início da quimioterapia. Estado civil "viúvo/a" esteve associado a melhoras no estado de saúde global/qualidade de vida (p = 0,028), enquanto presença de câncer do colo uterino (p = 0,034) e baixo peso (p = 0,033) estiveram relacionados a piores resultados no estado de saúde global/qualidade de vida. A QT tem efeitos deletérios na saúde física dos pacientes, mas leva a melhorias no domínio emocional. As características individuais dos pacientes no início da QT estão associadas a mudanças na qualidade vida. Nosso estudo pode ajudar a identificar essas características.

El objetivo del presente estudio fue evaluar cambios en la calidad de vida de pacientes con cáncer, entre el principio del primero y segundo ciclo de quimioterapia (CT), en hospitales en Belo Horizonte, Brasil. Se llevó a cabo un estudio longitudinal, prospectivo, descriptivo con un enfoque cuantitativo. Participaron 230 pacientes, de una cohorte más amplia, diagnosticados con los cinco tipos de cáncer más frecuentes (pecho, colorrectal, cervical, pulmón, cabeza y cuello), con 18 años y más, que estaban comenzando CT por primera vez. La calidad de vida fue evaluada mediante EORTC QLQ-C30 versión 3, aplicada al comienzo del primer y segundo ciclo de quimioterapia. Se usó el test pareado de Wilcoxon para identificar las diferencias en calidad de vida entre dos puntos en el tiempo. Para investigar los predictores potenciales del estatus de salud global/calidad de vida, se realizó un análisis lineal multivariado, usando el método de Bootstrap. Hubo un aumento significativo en las puntuaciones de las funciones emocionales de los pacientes (p < 0,001), así como las puntuaciones para dolor (p = 0,026), diarrea (p = 0,018) y náusea/vómitos (p < 0,001) tras el comienzo de la quimioterapia. Ser viudo/a estuvo asociado con mejoras en el estatus de salud global/calidad de vida (p = 0,028), mientras que la presencia de cáncer cervical (p = 0,034) y estar por debajo del peso (p = 0,033) estuvieron relacionados con puntuaciones más bajas estatus de salud global/calidad de vida. La CT tiene efectos perjudiciales en la salud física de los pacientes, sin embargo, por otro lado, conduce a mejoras en el ámbito emocional. Las características individuales de pacientes al comienzo de la CT están asociadas con cambios en su calidad de vida. Nuestro estudio podría ayudar a identificar estas características.

Efecto citotóxico y genotóxico in vitro del extracto crudo y etanólico del rizoma de Curcuma longa L / In vitro cytotoxic and genotoxic effect of the crude and ethanolic extract from the rhizome of Curcuma longa L

RESUMEN Objetivos: Determinar el efecto citotóxico y genotóxico in vitro del extracto crudo y etanólico del rizoma de Curcuma longa L. Materiales y métodos: El efecto citotóxico fue evaluado utilizando líneas celulares DU-145, HT-29, 3T3 BALB/c. Se hallaron los porcentajes de crecimiento en 48 horas y se determinó la concentración inhibitoria 50 (CI50). El efecto genotóxico en el ADN genómico humano se determinó mediante el método Tomasevich. Resultados: El extracto crudo produjo una CI50 de 12,98 ± 0,21 μg/mL para la línea celular tumoral HT-29, que es inferior a DU-145 con una CI50 de 36,77 ± 9,12 μg/mL; el extracto etanólico presentó una CI50 de 13,24 ± 0,77 y 20,54 ± 2,58 µg/mL para ambas líneas celulares, respectivamente; el compuesto estándar curcumina presentó una CI50 de 3,96 ± 0,60 y 13,94 ± 2,79 μg/mL, respectivamente. El extracto crudo a concentraciones de 50 y 100 mg/mL fragmentó entre el 40% a 95% de ADN genómico humano; mientras que, a 200 mg/mL, la fragmentación fue mayor al 95%. El extracto etanólico a todas las concentraciones no fragmentó el ADN. La curcumina a 200 mg/mL fragmentó menos del 5% de ADN genómico humano. Conclusiones: Los extractos crudo y etanólico de Curcuma longa L. demuestran efecto citotóxico in vitro diferencial para la línea celular tumoral humana DU-145 y HT29 semejante al compuesto estándar curcumina. El extracto crudo de Curcuma longa L. presenta una potente actividad genotóxica in vitro frente al ADN genómico humano, esta actividad está ausente en el extracto etanólico.

ABSTRACT Objectives: To determine the in vitro cytotoxic and genotoxic effect of the crude and ethanolic extract from the Curcuma longa L. rhizome. Materials and methods: The cytotoxic effect was evaluated using DU-145, HT-29, 3T3 BALB/c cell lines. The growth percentages in 48 hours; and the half maximal inhibitory concentration (IC50) were determined. The genotoxic effect on human genomic DNA was determined using the Tomasevich method. Results: Crude extract produced an IC50 of 12.98 ± 0.21 μg/mL for the HT-29 tumor cell line, which is lower than the value obtained for DU-145, with an IC50 of 36.77 ± 9.12 μg/mL. The ethanolic extract presented an IC50 of 13.24 ± 0.77 and 20.54 ± 2.58 μg/mL for both cell lines, respectively; the curcumin standard compound presented an IC50 of 3.96 ± 0.60 and 13.94 ± 2.79 μg/mL, respectively. Crude extract concentrations of 50 and 100 mg/mL fragmented between 40% to 95% of human genomic DNA; while at 200 mg/mL, fragmentation was greater than 95%. The ethanolic extract at all concentrations did not fragment the DNA. Curcumin at 200 mg/mL fragmented less than 5% of human genomic DNA. Conclusions: The crude and ethanolic extracts of Curcuma longa L. demonstrate different in vitro cytotoxic effects for the human tumor cell lines DU-145 and HT-29; similar to the standard curcumin compound. The crude extract of Curcuma longa L. shows a potent genotoxic in vitro activity against human genomic DNA; this type of effect is not produced by the ethanolic extract.

Cytotoxicity and degree of conversion of methacrylate and silorane

Composites have been proven to have a cytotoxic effect on a variety of tissues and cells. Aim: The aim of this study was to analyse the degree of conversion of resins and its correlation with the cell viability in primary gingival fibroblasts. Methods: Resin-based silorane (Filtek P90) and conventional methacrylate resins (Filtek Z100, Filtek Z250 and Filtek Z350XT) were used to evaluate cell viability and the degree of conversion. The resins were light-cured by a LED for 20 and 40 seconds. The degree of conversion was analysed by Fourier transform infrared spectroscopy. Cellular metabolism was evaluated after 24 hours by the MTT assay (n = 6) using the storage solution of composite resin for either 24 hours or 12 days. Variance analysis (ANOVA) with a Bonferroni correction (p < 0.05) was performed to compare the groups. Results: The composite Filtek P90 showed a higher degree of conversion when polymerised for 40 or 20 seconds, while the composites Filtek Z100, Filtek Z250 and Filtek Z350XT showed similar degree of conversion. Only the Filtek Z100 resin was cytotoxic. Conclusion: We found no statistically significant correlation between cell viability and the degree of conversion

A Case of Autoimmune Sensorineural Hearing Loss Responding to Cytotoxic Agent / 대한이비인후과학회지

Autoimmune sensorineural hearing loss is a rare disease characterized by bilateral sensorineural hearing loss, some in a progressive pattern and others in idiopathic or fluctuating pattern, often accompanied by vestibular symptoms. This disease is also known as autoimmune inner ear disease (AIED), which primarily involves the vestibulo-cochlear system. However, in some cases, it occurs in the context of systemic autoimmune disorder such as wegner granulomatosis, or the Bechet disease. Response to steroids has been the requisite clinical criterion for diagnosis. Treatment usually includes corticosteroids and immunosuppressive drugs. However, after continuous steroid treatment development of corticosteroids, resistance is common in many AIED. To patients with AIED, response to steroids is not only a criterion for diagnosis but also a criterion to test steroid-sparing therapies such as methotrexate. A 10 year-old boy presenting a fluctuating pattern of bilateral sensorineural hearing loss was treated with a cytotoxic agent in suspicion of autoimmune sensorineural hearing loss. We reviewed this case with reference to relevant publications in the medical literature.

The Diterpene Sclareol Vascular Effect in Normotensive and Hypertensive Rats / Efeito Vascular do Diterpeno Esclareol em Aortas Torácicas de Ratos Normotensos e Hipertensos

Abstract Background: The diterpene Sclareol has antimicrobial action, cytotoxic and cytostatic effects and anti-tumor activities. However, researches on the cardiovascular system are scarce. Objective: This study was designed to investigate the mechanisms involved in the Sclareol cardiovascular effect in normotensive and hypertensive rats. Methods: The arterial hypertension was promoted using 2-kidneys 1-clip model in rats. The effect of sclareol on blood pressure was performed by using three dose (10, 20 and 40 mg/kg). Cumulative dose-response curves for Sclareol were determined for endothelium-intact and endothelium-denuded aortic rings in presence or absence of L-NAME and ODQ. The NOx levels were measure in the plasma sample. Results: The Sclareol administration in vivo caused a significant reduction in blood pressure in both groups. In vitro the sclareol promoted relaxation in aorta, with endothelium, pre-contracted to Phe. The inhibitors of the nitric oxide synthase and soluble guanylate cyclase were as efficient as the removal of endothelium, in inhibiting the Sclareol-induced relaxation. Otherwise, it was no change of NOx. Also, for unknown reasons, the Sclareol is not selective for hypertensive animals. Conclusion: The diterpene Sclareol showed in vivo hypotensive and in-vitro vasodilator effects; The chemiluminescence plasmatic NO analysis showed no significant difference between groups and The Sclareol exhibit better effect on normotensive than hypertensive animals to reduce blood pressure. It is concluded that the diterpenes metabolites would be a promising source prototype for the development of new agents in the cardiovascular therapy.

Resumo Fundamento: O diterpeno Esclareol tem ação antimicrobiana, efeitos citotóxicos e citostáticos e atividades antitumorais. No entanto, pesquisas sobre o sistema cardiovascular são escassas. Objetivo: Este estudo foi desenvolvido para investigar os mecanismos envolvidos no efeito cardiovascular de Esclareol em ratos normotensos e hipertensos. Métodos: A hipertensão arterial foi promovida utilizando modelo de 2 clones de 1-clipe em ratos. O efeito do esclareol sobre a pressão arterial foi realizado utilizando três doses (10, 20 e 40 mg/kg). As curvas dose-resposta cumulativas para Esclareol foram determinadas para anéis aórticos endotélio-intactos e desprovidos de endotélio na presença ou ausência de L-NAME e ODQ. Os níveis de NOx foram medidos na amostra de plasma. Resultados: A administração de Esclareol in vivo causou uma redução significativa na pressão sanguínea em ambos os grupos. In vitro o esclareol promoveu relaxamento na aorta, com endotélio, pré-contraído a Phe. Os inibidores da óxido nítrico sintase e da guanilato ciclase solúvel foram tão eficientes quanto a remoção do endotélio, na inibição do relaxamento induzido por Esclareol. Por outra parte, não houve mudança de NOx. Além disso, por razões desconhecidas, o Sclareol não é seletivo para animais hipertensos. Conclusão: O diterpeno Esclareol apresentou efeitos hipotensores in vivo e vasodilatadores in vitro; A análise de NO plasmático por quimioluminescência não mostrou diferença significativa entre os grupos e O Esclareol exibe melhor efeito sobre os animais normotensos do que hipertensos para reduzir a pressão arterial. Conclui-se que os metabólitos de diterpenos seriam um protótipo de fonte promissora para o desenvolvimento de novos agentes na terapia cardiovascular.

Actualización sobre manejo de araneismo en Perú / Update management on araneism in Peru

La mordedura de araña es un accidente muy común e importante problema de salud pública en lugares con clima tropical y se presenta como un problema muy frecuente en algunas regiones de Latinoamérica. En Perú las especies de araña que presentan más casos de esta problemática son Loxosceles laeta, Latrodectus mactans and Phoneutria spp. El presente trabajo pretende explicar, clarificar y categorizar estas mordeduras de arañas, con el fin de dar a conocerlas para ayudar a que los profesionales de la salud tengan un mayor conocimiento sobre las mismas para un mejor manejo de los casos que se les presenten. (AU)

Spider bites are a common and important public health issue in tropical climates, and become a frequent problem in certain Latin American regions. In Peru, the main species of spiders that represent this problematic are Loxosceles laeta, Latrodectus mactans and Phoneutria spp. The present article intends to explain, clarify and categorize these spider bites, in order to make them known by every health professional to its better management. (AU)

In vitro cytotoxicity of self-curing acrylic resins of different colors

OBJECTIVE: The aim of this study was to assess the in vitro cytotoxicity of acrylic resins of different colors over time. METHODS: Specimens were divided into 4 groups (n = 6) according to the color of the acrylic resin (Orto Class, Clássico, Campinas, São Paulo, Brazil): Group 1: clear acrylic resin; group 2: pink acrylic resin; group 3: blue acrylic resin and group 4: green acrylic resin. All specimens were fabricated according to the mass manipulation technique and submitted to mechanical polishing protocol. The control was performed with an amalgam specimen (C+), a glass specimen (C-) and cell control (CC). Specimens were immersed in Minimum Eagle's Medium (MEM) and incubated for 24 h at 37o C. The extracts from the experimental material were filtered and mixed with L929 fibroblast. Cytotoxicity was evaluated at 4 different times, 24, 48, 72 and 168 h. After contact, cells were incubated for 24 h and added to 100 µ of 0.01% neutral red dye. The cells were incubated for 3 h for pigment incorporation and fixed. Cells viability was determined by a spectroscopic (BioTek, Winooski, Vermont, USA) with a 492-nm wavelength λ=492 nm). RESULTS: There were no statistical differences between the experimental groups and the CC and C- groups. CONCLUSION: Clear, pink, blue and green self-curing acrylic resins fabricated by means of the mass manipulation technique and mechanically polished are not cytotoxic. Neither the pigment added to the self-curing acrylic resin nor the factor of time influenced the cytotoxicity of the material. .

OBJETIVO: avaliar, in vitro, a citotoxicidade de resinas acrílicas autopolimerizáveis, de diferentes cores, ao longo do tempo. MÉTODOS: os corpos de prova foram divididos em quatro grupos (n = 3), de acordo com a cor da resina acrílica utilizada (Orto Class, Clássico, São Paulo/SP), sendo: grupo 1, acrílica incolor; grupo 2, acrílica rosa; grupo 3, acrílica azul; e, grupo 4, acrílico verde. Todos os corpos de prova foram confeccionados pela técnica de massa e polidos mecanicamente. Um corpo de prova de amálgama, um de vidro e célula constituíram o controle positivo (C+), controle negativo (C-), e controle de célula (CC), respectivamente. Em seguida, esses foram imersos em meio mínimo essencial de Eagle (MEM) por 24h, quando se removeu o sobrenadante e colocou-os em contato com fibroblastos L929. Avaliou-se a citotoxicidade em quatro períodos: 24, 48, 72 e 168h. Após o contato com o meio, as células foram incubadas por 24h e adicionou-se 100µ do corante vermelho neutro a 0,01%. Posteriormente, as células foram incubadas por 3h, para incorporação do corante, e fixadas. A contagem das células viáveis foi realizada em espectrofotômetro (BioTek, Winooski, EUA), com um comprimento de onda de 492nm (λ = 492nm). RESULTADOS: não houve diferença estatística entre os grupos experimentais e os grupos CC e C-. CONCLUSÇÕES: as resinas acrílicas autopolimerizáveis incolor, rosa, azul e verde, manipuladas pela técnica de massa e polidas mecanicamente não são citotóxicas. O corante utilizado em resinas autopolimerizáveis e tempo não influenciam na citotoxocidade do material. .

Anticancer Activity of Cobra Venom Polypeptide, Cytotoxin-II, against Human Breast Adenocarcinoma Cell Line (MCF-7) via the Induction of Apoptosis / 한국유방암학회지

PURPOSE: Breast cancer is a significant health problem worldwide, accounting for a quarter of all cancer diagnoses in women. Current strategies for breast cancer treatment are not fully effective, and there is substantial interest in the identification of novel anticancer agents especially from natural products including toxins. Cytotoxins are polypeptides found in the venom of cobras and have various physiological effects. In the present study, the anticancer potential of cytotoxin-II against the human breast adenocarcinoma cell line (MCF-7) was investigated. METHODS: The cytotoxic effects of cytotoxin-II were determined by morphological analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The mode and mechanism of cell death were investigated via acridine orange/ethidium bromide (AO/EtBr) double staining, flow cytometric analysis of cell death, detection of mitochondrial membrane potential, measurement of intracellular reactive oxygen species (ROS), annexin V/propidium iodide staining, and caspase-9 activity assays. RESULTS: The half maximal inhibitory concentration (IC50) of cytotoxin-II in MCF-7 cells was 4.18+/-1.23 microg/mL, while the value for cisplatin was approximately 28.02+/-1.87 microg/mL. Morphological analysis and AO/EtBr double staining showed typical manifestations of apoptotic cell death (in doses lower than 8 microg/mL). Dose- and time-dependent ROS generation, loss of mitochondrial membrane potential, caspase-9 activation, and cell cycle arrest were observed in their respective tests. CONCLUSION: In conclusion, cytotoxin-II has potent anticancer effects in the MCF-7 cell line, which are induced via the intrinsic pathways of apoptosis. Based on these findings, cytotoxin-II is a suitable choice for breast cancer treatment.

Identification and bioactivities analysis of Halomonas sp. from seawater / 第二军医大学学报

Objective: To determine the 16S rDNA sequences of 36 strains of Halomonas sp. Isolated from the seawater of the East China Sea and to study their bioactivities. Methods: The 16S rDNA sequences of all isolated strains were amplified by PCR, and the obtained sequences were subjected to phylogenetic analyses using MEGA4.1 and multiple sequence alignment with Clustal X1. 8 software. MTT assay was applied to assess the cytotoxic activities of their fermentation broth; ABTS and DPPH antioxidant models were applied to test the antioxidation activities of their fermentation broth. The HLE inhibition activities of the fermentation broth were tested by a stable HLE in hibitor screening model. Results: Analysis of 16S rDNA sequence showed that the 36 strains had a high affinity (96%-99%) to the Halomonas sp. Fermentation broth of the 36 strains showed different degrees of cytotoxic activities, antioxidation activities, and HLE inhibition activities. Eleven strains inhibited the growth of HepG2 cells, with the inhibition rate ranging (4.40±1.2)%to(24.90±3.5) %; 20 strains inhibited the growth of HL-60 cells, with the inhibition rate ranging (1.70±1.1)% to (50.90±4.2) %; 7 strains showed ABTS radical scavenging capacity, with the scavenging rate ranging (4.49±2.1) % to (58.43±4.4) %; 3 strains showed DPPH radical scavenging capacity, with the scavenging rate ranging (5.68±3.7) % to (59.06±3.2) %, and 3 strains showed HLE inhibition activities, with the inhibition rate ranging (12.71±1.81)% to (71.19±5.62) %. Conclusion: All the 36 Halomonassp. Strains show different degrees of cytotoxic effects, antioxidation activities, and HLE inhibition capacities. Several strains with high activities possess the potential for medicinal application.

Continuous renal replacement therapy in multiple organ dysfunction syndrome / 中国医师进修杂志

Objective To observe the efficacy of continuous renal replacement therapy (CRRT) treatment in multiple organ dysfunction syndrome (MODS),and explore its application value.Methods Forty-six cases of MODS were treated with CRRT.Blood gas analysis,toxin removal,electrolyte and APACHE Ⅱ score was observed before and after treatment.Results The APACHE Ⅱ score in the beginning of treatment was (20.8 ±4.4) scores,31 cases had clinical cure,and APACHE Ⅱ score was (13.6 ±4.9)scores,15 cases died.In patients of survival,blood pressure,blood gas analysis,electrolytes,toxin removal improved gradually,and the difference had statistical significance before and after treatment.In 8 cases withshock before treatment who need drugs to maintain blood pressure,after treatment 6 cases withdrew drugs gradually.In the course of treatment,heart function was stable in patients who had heart failure.Four cases had pulmonary infection-induced MODS.In the process of the treatment internal environment was stable,and urine after treatment improved in different degrees.Two cases died of drug-resistant pathogens ultimately.Conclusions CRRT is an effective method in the treatment of MODS patients.CRRT can effectively clear the metabolites and inflammatory mediators,and rebuild the immune homeostasis of the body.

Induction of CTX-d from cobra venoms on NB4 apoptosis and its mechanism / 中草药

Objective To investigate the effects of CTX-d from venoms of cobra (Naja naja atra) on inducing NB4 apoptosis and its mechanism. Methods MTT was used to detect the antitumor effect of CTX-d in vitro; Electron microscope and flow cytometry were used to observe the apoptotic inducing effect of CTX-d in NB4 cells; Mitochondrial transmembrane potential change (??m) was analyzed by flow cytometry; The levels of caspase-9, caspase-3, and cytochrome C in the cytosol fraction were analyzed by Western blotting. Results The IC50 values of CTX-d affected on NB4 cell for 6 and 12 h were 1.8 and 1.35 ?g/mL, respectively. CTX-d could induce morphological changes, such as condensed chromatin and swelling mitochondria in NB4 cells. Analyzed by flow cytometry, CTX-d induced apoptosis in NB4 cells evidenced by increasing sub G1 cell population in a dose- and time-dependent manner. The mitochondrial membrane potential of NB4 cells had already decreased when incubated with CTX-d (1.0 ?g/mL) for 0.5 h, and cytochrome C in the cytosol was detected simultaneously, which indicated the release of cytochrome C from mitochondria to cytosol. The caspase-9 was activated initially at 1 h after 1.0 ?g/mL CTX-d treatment, whereas the cleavage of caspase-3 was detected at 0.5 h. This suggested that some other mechanism may be involved in caspase-3 activation. Conclusion The results suggest that the loss of mitochondrial membrane potential and the release of cytochrome C from the mitochondria into the cytosol are the early events of CTX-d on NB4 apoptosis. Once release into the cytosol, cytochrome C precedes the activation of caspase-9 and -3 to leading to the apoptosis and there are maybe some other mechanism involved in caspase-3 activation.

Bacterial Endotoxin Test for Huangy angning Injection / 中药新药与临床药理

Objective To study the interference of Huangyangning Injection in bacterial endotoxin test and to establish bacterial endotoxin test method for this specimen.Methods According to China Pharmacopoeia 2000,inhibition or en-hancement test for bacterial endoto xins test was carried out for Huangyangning Injection.Results l ∶150solution of Huangyangning Injection had no inte rference on the test.Conclusion Reliable data and result are obtained and bacterial endotoxin test method for Huangyangning Injection has been established.

EXPERIMENTAL STUDIES ON THE CYTOTOXICITY OF HAEMATOPORPHYRIN DERIVATIVE AND LIGHT IN DIFFERENT WAVE-BANDS ON HUMAN TUMOR CELL LINE / 第二军医大学学报

Department of Pathological Anatomy of Second Military Medical College Photosensitive reaction of HPD and its cytotoxic action were studied, focussing on the spectral effect of the irradiating light. A human hepatocarcinoma cell line(SMMC-7721)with HPD was used. Killing effects on tumor cells after irradiation of light in three different wave-bands were observed, both qualitatively and quantitatively.Results were compared with those of Kinsey and Matsushima.