Perfil de las víctimas mortales por intoxicaciones agudas en Costa Rica del 2012 al 2021 asociadas al consumo de sustancias psicoactivas y drogas de abuso: etanol, metanol, benzodiacepinas, anfetaminas, heroína, cocaína y mixto / Profile of fatalities due to acute intoxications in Costa Rica from 2012 to 2021 associated with the consumption of psychoactive substances and drugs of abuse: ethanol, methanol, benzodiazepines, amphetamines, heroin, cocaine and mixed

Resumen Introducción: La mortalidad por intoxicaciones agudas de sustancias psicoactivas representa un problema de salud pública, especialmente en personas jóvenes. El objetivo del estudio fue crear un perfil de las víctimas mortales por intoxicación aguda en Costa Rica entre los años 2012 y 2021 asociado al consumo de sustancias psicoactivas y drogas de abuso. Materiales y métodos: Se recopilaron datos de Sección de Patología Forense del Departamento de Medicina Legal en Costa Rica, con los cuales se realizó una revisión de las víctimas mortales por intoxicaciones agudas a partir del 1 de enero de 2012 hasta el 31 de diciembre de 2021. La revisión incluyó las siguientes variables: variables epidemiológicas: sexo, edad, nacionalidad, ocupación, estado civil, provincia, consumo frecuente asociado, manera de muerte, tipo de sustancia y lugar de intoxicación. Resultados: De los 456 casos de muertes asociados a intoxicaciones agudas por etanol, metanol, benzodiacepinas, anfetaminas, heroína, cocaína y mixtas; reportados entre el 1 de enero de 2012 y el 31 de diciembre de 2021: el año que más casos reportó fue 2020; 82% de las víctimas fueron hombres y 18% mujeres; las principales edades de las personas reportadas abarcan entre 41 y 60 años. 80% de las personas eran costarricenses; San José fue la provincia con mayor número de casos de intoxicación letal, siendo el domicilio el sitio más frecuente. 14% de las víctimas eran desempleadas; 77% de las personas presentaban algún trastorno de la adicción o consumo frecuente de alguna de las sustancias estudiadas. La mayoría de muertes fueron de manera accidental. Conclusiones: El perfil predominante de las víctimas fue: masculino, entre 41 y 60 años, costarricense, de estado civil indeterminado o soltero, desempleado, que muere de manera accidental, en su domicilio, por intoxicación aguda con alcohol o mixta (alcohol y cocaína).

Abstract Introduction. Mortality from acute poisoning of psychoactive substances represents a public health problem, especially in young adults. The purpose of the study was to create a profile of fatalities due to acute poisoning in Costa Rica between 2012 and 2021 associated with the consumption of psychoactive substances and drugs of abuse. Materials and methods. Data were collected from the Forensic Pathology Section of the Legal Medicine Department in Costa Rica, then a review of fatalities due to acute poisoning was carried out from January 1, 2012 to December 31, 2021. The review included the following epidemiological variables: sex, age, nationality, occupation, marital status, province, consumption associated, manner of death, type of substance, and place of intoxication. Results. Out of the 456 reported cases of deaths associated with acute intoxication with ethanol, methanol, benzodiazepines, amphetamines, heroin, cocaine, and mixed substances between January 1, 2012, and December 31, 2021: the year with the highest number of cases reported was 2020; 82% of the victims were male, and 18% were female; the main age group of reported victims ranged from 41 to 60 years old. 80% of the victims were Costa Rican, and San Jose was the province with the highest number of lethal intoxication cases, with the home being the most frequent site. 14% of the victims were unemployed, and 77% of the individuals had some addiction disorder or frequent consumption of one of the studied substances. The majority of deaths were accidental. Conclusion. The main profile of the victims was male, between 41 and 60 years old, Costa Rican, of indeterminate or single marital status, unemployed, who died accidentally, at home, due to acute intoxication with alcohol or a mixture of substances (alcohol and cocaine).

Stability of dentin matrix treated with caffeic acid phenethyl ester at different concentrations

Aim: The aim of this study was to investigate the impact of pretreatment with ethanolic solutions of caffeic acid phenethyl ester (CAPE) at varying concentrations on the dentin collagen matrix, specifically focusing on its biomodification potential. This was assessed through evaluations of the modulus of elasticity and changes in mass. Methods: Seventy dentin collagen matrices (demineralized sticks) were prepared to receive treatments with ethanolic solutions of CAPE at concentrations of 0.05%, 0.1%, 0.5%, or 2.5%, or with control treatment solutions (distilled water or ethanol) for one hour. The dentin matrices were evaluated for modulus of elasticity and mass before (baseline), immediately after treatment (immediately), and after storage in Simulated Body Fluid (SBF) for time intervals of 1 and 3 months. Results: Generalized linear models for repeated measures over time indicated no significant differences between groups (p=0.7530) or between different time points (p=0.4780) in terms of the modulus of elasticity. Regarding mass variation, no differences were observed in the time interval between 1 month and the immediate time (p=0.0935). However, at the 3-month mark compared to the immediate time, the 0.1% CAPE group exhibited less mass loss compared to the water group (p=0.0134). Conclusion: This study concludes that various concentrations of CAPE in an ethanolic solution did not affect the modulus of elasticity of dentin, suggesting that CAPE lacks biomodifying potential in this context. However, it was observed that 0.1% CAPE positively influenced the variation in mass over different evaluation time intervals

Antiulcerogenic and antioxidant activities of Plantago ovata ethanolic extract in rats

Abstract This study aimed to determine the antiulcerogenic and antioxidant activities of Psyllium (Plantago ovata Forssk) seed ethanolic extract in rats. We assessed the antioxidant potential using free radical scavenging on DPPH, -carotene bleaching activity, ferric reducing power, and hydroxyl radical scavenging activity. In the antiulcerogenic study, pre-treatment with Plantago ovata seeds ethanolic extract (POE) (400 mg/kg b.wt) significantly protected against ethanol-induced gastric ulcer in rats by decreasing the ulcer index value and preserving the integrity of the gastric mucosa. The oxidative stress status in the stomach tissues showed a significant increase in the antioxidant enzyme levels of superoxide dismutase, catalase, and glutathione peroxidase with a significant decrease in lipid peroxidation during pre-treatment with POE. In conclusion, the POE protects against gastric ulcer due to its antioxidant potential and presence of bioactive molecules.

Resumo O presente estudo teve como objetivo determinar as atividades antiulcerogênica e antioxidante das sementes de Psyllium (Plantago ovata Forssk) em ratos. O potencial antioxidante foi avaliado utilizando o método do sequestro do radical livre DPPH, autooxidação do -caroteno, poder redutor de ferro e atividade de sequestro do radical hidroxila. No estudo antiulcerogênico, o pré-tratamento com o extrato etanólico das sementes de Plantago ovata (POE) (400 mg/Kg b.wt) reduziu a úlcera gástrica induzida pelo etanol em ratos, diminuindo o valor do índice de úlcera e preservando a integridade da mucosa gástrica. O estudo do estresse oxidativo nos tecidos estomacais mostrou um aumento significativo dos níveis das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase, com uma diminuição significativa da peroxidação lipídica enquanto pré-tratamento com POE. Em conclusão, o POE protege contra úlcera gástrica devido aos seus potenciais antioxidantes e à presença de moléculas bioativas.

Optimization of ethanol extraction process for Yihuang powder by orthogonal experiment combined with AHP and GA-BP neural network / 中国药房

OBJECTIVE To optimize ethanol extraction process of Yihuang powder. METHODS An orthogonal experiment was designed by reflux extraction with ethanol volume fraction， liquid-to-material ratio， and extraction time as investigation factors. The parameters used were the contents of hesperidin， nobiletin， tangeretin， gallic acid， chebulagic acid， chebulinic acid， liquiritin， glycyrrhizin， eugenol， and the paste-forming rate. The analytic hierarchy process （AHP） was used to calculate the comprehensive score. The optimal ethanol extraction process parameters of Yihuang powder were determined by verifying the results predicted by orthogonal experiment and genetic algorithm （GA）-back propagation neural network （BP neural network）. RESULTS The optimal ethanol extraction process parameters， as optimized by orthogonal experiment， were as follows: ethanol volume fraction of 60%， liquid-solid ratio of 14∶1 （mL/g)， extraction time of 90 min， and extraction for 2 times. The comprehensive score obtained by verification was 79.19. Meanwhile， the optimal ethanol extraction process parameters， optimized by GA-BP neural network， were ethanol volume fraction of 65%， liquid-solid ratio of 14∶1 （mL/g )， extraction time of 60 min， and extraction for 2 times. The comprehensive score obtained by verification was 85.30， higher than the results obtained from orthogonal experiment. CONCLUSIONS The optimization method of orthogonal experiment combined with GA-BP neural network is superior to the traditional orthogonal experiment optimization method. The optimized ethanol extraction process of Yihuang powder is stable and reliable.

Correlation between the severity and blood alcohol level of traffic accidents victims / Correlação entre gravidade e alcoolemia de vítimas de acidentes de trânsito

ABSTRACT Objective: To evaluate the correlation between blood alcohol levels and the severity of injuries assessed by the Injury Severity Score (ISS) in patients who were victims of traffic accidents admitted to the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo (HCFMUSP). Methods: Cross-sectional study carried out between July 2018 and June 2019, at the Central Emergency Room of the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo (PSC-HCFMUSP). A total of 172 hospitalized patients victims of traffic accidents were included in this study. Blood samples were analyzed by the FMUSP Toxicology Laboratory. Results: 36 patients (20.9%) had positive BAC (≥ 0.2 g/L) with a mean of 1.21 g/L. Overall, patients had a mean age of 37.2 years old, and 136 (79.1%) were men. The ISS of the total casuistry was 15.6; regarding the external cause, the motorcycle was ranked first with 100 cases (58.1%), and drivers were the majority with 57.4% of the sample. Conclusion: There was no correlation between the severity of the injuries and the blood alcohol levels of traffic accident victims admitted to a reference hospital. Level of Evidence II, Cross-Sectional Study.

RESUMO Objetivo: Avaliar a correlação entre a alcoolemia e a gravidade das lesões avaliadas pelo Índice de Gravidade da Lesão ( Injury Severity Score* - ISS) em vítimas de acidentes de trânsito internadas no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP).* Método: Estudo transversal realizado entre julho de 2018 e junho de 2019, no Pronto Socorro Central do HC-FMUSP. Foram incluídas 172 vítimas de acidentes de trânsito. Amostras de sangue foram analisadas pelo Laboratório de Toxicologia da FMUSP. Resultados: 36 pacientes (20,9%) apresentaram alcoolemia positiva (≥ 0,2 g/L), com valor médio de 1,21 g/L. No geral, os pacientes tinham uma idade média de 37,2 anos, e 136 (79,1%) eram homens. O ISS da casuística total foi 15,6; quanto à causa externa, a motocicleta ficou em primeiro lugar com 100 casos (58,1%); e os condutores foram prevalentes entre as vítimas (57,4%). Conclusão: Não houve correlação entre a gravidade das lesões e a alcoolemia das vítimas de acidente de trânsito internadas em um hospital de referência. Nível de Evidência II, Estudo de Corte Transversal.

Antiulcerogenic and antioxidant activities of Plantago ovata ethanolic extract in rats / Atividade antiulcerogênica e antioxidante do extrato etanólico de Plantago ovata em ratos

This study aimed to determine the antiulcerogenic and antioxidant activities of Psyllium (Plantago ovata Forssk) seed ethanolic extract in rats. We assessed the antioxidant potential using free radical scavenging on DPPH, ß-carotene bleaching activity, ferric reducing power, and hydroxyl radical scavenging activity. In the antiulcerogenic study, pre-treatment with Plantago ovata seeds ethanolic extract (POE) (400 mg/kg b.wt) significantly protected against ethanol-induced gastric ulcer in rats by decreasing the ulcer index value and preserving the integrity of the gastric mucosa. The oxidative stress status in the stomach tissues showed a significant increase in the antioxidant enzyme levels of superoxide dismutase, catalase, and glutathione peroxidase with a significant decrease in lipid peroxidation during pre-treatment with POE. In conclusion, the POE protects against gastric ulcer due to its antioxidant potential and presence of bioactive molecules.

O presente estudo teve como objetivo determinar as atividades antiulcerogênica e antioxidante das sementes de Psyllium (Plantago ovata Forssk) em ratos. O potencial antioxidante foi avaliado utilizando o método do sequestro do radical livre DPPH, autooxidação do ß-caroteno, poder redutor de ferro e atividade de sequestro do radical hidroxila. No estudo antiulcerogênico, o pré-tratamento com o extrato etanólico das sementes de Plantago ovata (POE) (400 mg/Kg b.wt) reduziu a úlcera gástrica induzida pelo etanol em ratos, diminuindo o valor do índice de úlcera e preservando a integridade da mucosa gástrica. O estudo do estresse oxidativo nos tecidos estomacais mostrou um aumento significativo dos níveis das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase, com uma diminuição significativa da peroxidação lipídica enquanto pré-tratamento com POE. Em conclusão, o POE protege contra úlcera gástrica devido aos seus potenciais antioxidantes e à presença de moléculas bioativas.

Factores pronósticos del deterioro cognitivo en pacientes adictos a sustancias psicoactivas

Introducción: Es importante considerar los daños que el consumo de sustancias psicoactivas produce al cerebro, para entender el pronóstico y la evolución del paciente, ya que puede causar deterioro cognitivo y llegar a la demencia. Objetivo: Determinar los factores pronósticos del deterioro cognitivo en pacientes adictos a sustancias psicoactivas. Método: Se desarrolló un estudio observacional, analítico y transversal. Se trabajó con los pacientes atendidos por consumos de sustancias, en un servicio de psicología, del año 2016 al 2019. Las variables estudiadas fueron: función ejecutiva, edad, ideación suicida, sexo, características clínicas del consumo, sustancia consumida, coeficiente intelectual, deterioro cognitivo, ansiedad, depresión y tiempo de consumo. Se utilizaron técnicas tanto de la estadística descriptiva, como de la estadística inferencial. Resultados: Se estudiaron 257 pacientes, con consumo fundamentalmente de alcohol y marihuana, edad promedio de 34 años, predominó el sexo masculino (89 %) y una media de 17 años de consumo. El 47 % de los pacientes presentó deterioro cognitivo leve y 9,34 % deterioro cognitivo moderado. El deterioro cognitivo se asoció con tener tolerancia invertida (odd ratio - OR= 6,4), disfunción ejecutiva (OR= 4,2), depresión (OR= 4,1), ansiedad (OR= 2,4), consumir otras sustancias diferentes al alcohol (OR= 2,6), tener necesidad subjetiva de consumo (OR= 2,5), alterada capacidad de abstención (OR= 2,3) e ideación suicida (OR= 2,0). Conclusiones: Los factores pronósticos del deterioro cognitivo en los pacientes adictos son: tolerancia invertida, alteraciones ejecutivas, depresión, ansiedad, consumir otras drogas diferentes al alcohol, tener alterada la capacidad de abstención y presentar ideas suicidas.

Introduction: It is important to consider the damage that the consumption of psychoactive substances produces to the brain, in order to understand the prognosis and evolution of the patient, since it can cause cognitive impairment and reach dementia. Objective: To determine the prognostic factors of cognitive impairment in patients addicted to psychoactive substances. Methods: An observational, analytical and cross-sectional study was developed. We worked with patients treated for substance use, in a psychology service, from 2016 to 2019. The variables studied were: executive function, age, suicidal ideation, sex, clinical characteristics of consumption, substance consumed, intelligence quotient, cognitive impairment, anxiety, depression and time of consumption. Both descriptive and inferential statistical techniques were used. Results: 257 patients were studied, with consumption mainly of alcohol and marijuana, average age of 34 years, predominantly male (89%) and an average of 17 years of consumption. 47% of the patients had mild cognitive impairment and 9.34% had moderate cognitive impairment. Cognitive impairment was associated with having inverted tolerance (odd ratio OR= 6.4), executive dysfunction (OR= 4.2), depression (OR= 4.1), anxiety (OR= 2.4), consuming substances other than alcohol (OR= 2.6), having subjective need for consumption (OR= 2.5), altered abstinence capacity (OR= 2.3) and suicidal ideation (OR= 2.0). Conclusions: The prognostic factors of cognitive impairment in addicted patients are: inverted tolerance, executive alterations, depression, anxiety, consuming drugs other than alcohol, having altered abstinence capacity and presenting suicidal ideation.

Ethanol Ablation for Odontogenic myxoma: New alternative of conservative treatment

Odontogenic myxoma is a maxillofacial tumor that is benign in nature. It is characterized by a slow-growing, painless, and site-aggressive behavior. A main feature is that it is not encapsulated so it has high potential of invasiveness and penetration into peripheral tissues. Large lesions may cause extensive compromise of the region. Treatment strategy for Odontogenic Myxoma is still controversial. Radical resection with an appropriate surgical margin is recommended, but emerging evidence has suggested that a more conservative approach will result in less morbidity and adequate results. This report shows a remarkable result on a 16-year-old patient who had a Mandibular Odontogenic Myxoma treated with a conservative approach. Intra-lesional absolute alcohol irrigation was performed during a 5-month period. Considerable volume reduction of the lesion happened which allowed a minimal overall resection. No recurrence was found after a 3 year follow-up.

Efecto del alcohol sobre el corazón y el sistema cardiovascular: hipertrofia, remodelamiento y disminución del strain. Información actual / Alcohol Impact on the Heart and Cardiovascular System - Hypertrophy, Remodeling and Strain Impairment - Contemporary State-of-the-Art

RESUMEN Datos recientes muestran que el abuso crónico de alcohol puede conducir a disfunción cardiovascular, a partir de dosis de etanol tradicionalmente consideradas bajas, y que la aparición de arritmias, incluyendo la fibrilación auricular, aumenta aún en consumidores de alcohol moderados. Los otros mecanismos comunes del impacto negativo del etanol están relacionados con el desarrollo de hipertensión y su consecuencia directa, la hipertrofia, fibrosis y disfunción diastólica. Debido a que la probabilidad de reversibilidad del remodelamiento cardíaco depende de un diagnóstico temprano de disfunción cardíaca, se debería recomendar la aplicación más amplia de métodos nuevos y más sensibles de evaluación de la función miocárdica, incluyendo el strain longitudinal ventricular izquierdo y derecho, así como de los protocolos adaptados a la ecocardiografía de estrés.

ABSTRACT The recent data show that chronic overuse of alcohol may lead to cardiovascular dysfunction, starting from traditionally judged as low ethanol doses, and that the burden of arrhythmias, including atrial fibrillation, increases even in moderate alcohol consumers. The other common mechanisms of the disadvantageous impact of ethanol are related to the development of hypertension and its direct aftermath, hypertrophy, fibrosis, and diastolic dysfunction. Since the chance of the reversibility of cardiac remodeling depends on the early diagnosis of cardiac dysfunction, the wider application of novel and sensitive methods of myocardial function assessment, including longitudinal strain of the left and right ventricles, as well as the adapted protocols for stress echocardiography, should be recommended.

Muerte accidental por consumo combinado de cocaína y etanol Revisión bibliográfica / Accidental death from combined cocaine and ethanol use. Literature review

La autopsia médico legal en Costa Rica, en casos sospechosos de intoxicación por cocaetileno se debe realizar bajo las normas establecidas en la Guía de estándares de trabajo para la Sección de Patología Forense del Departamento de Medicina Legal. El análisis del mecanismo fisiopatológico de cómo estas sustancias provocan alteraciones en el organismo que pueden conllevar a un eventual fallecimiento corresponde a parte del análisis requerido en la investigación ante la sospecha de esta causa de muerte. Por lo anterior, el objetivo de este artículo es describir los mecanismos fisiopatológicos que ocurren durante el consumo combinado de cocaína y etanol, los mecanismos que conllevan a la muerte de personas consumidoras de estas sustancias y las consideraciones médico legales a tomar en cuenta para el diagnóstico de esta causa de muerte. Se realizó revisión de artículos científicos, sobre los efectos del uso combinado de la cocaína y el etanol. La literatura describe que el uso combinado de cocaína y etanol potencia los efectos farmacocinéticos y bioquímicos de cada una de estas sustancias, que su derivado, el cocaetileno, es capaz de generar por sí mismo los mecanismos causantes de la muerte. Que los principales mecanismos fisiopatológicos que conllevan la muerte ante el uso combinado de estas sustancias son de origen cardiovascular y hepático. Como consideraciones médico legales a tomar en cuenta para el diagnóstico de esta manera de muerte accidental, en la Sección de Toxicología del Departamento de Ciencias Forenses de Costa Rica, la cuantificación del cocaetileno y las sustancias relacionadas no se realiza, aunque se encuentra actualmente en el desarrollo de un proyecto para la determinación de la estabilidad de las drogas en sangre bajo las condiciones de almacenamiento, con el fin de ofrecer la posibilidad de cuantificar ciertas drogas (en donde se podría incluir el cocaetileno) en un futuro próximo.

Medical-legal autopsy in Costa Rica, in suspected cases of cocaethylene poisoning must be performed under the regulations established in the Work Standards Guide for the Forensic Pathology Section of the Department of Legal Medicine. The analysis of the pathophysiological mechanism of how these substances cause alterations in the organism that can lead to eventual death corresponds to part of the analysis required in the investigation when this cause of death is suspected. Therefore, the objective of this article is to describe the pathophysiological mechanisms that occur during the combined consumption of cocaine and ethanol, the mechanisms that lead to the death of people who consume these substances, and the medico-legal considerations to be considered for the diagnosis. of this cause of death. A review of scientific articles was carried out on the effects of the combined use of cocaine and ethanol. The literature describes that the combined use of cocaine and ethanol enhances the pharmacokinetic and biochemical effects of each one of these substances, that its derivative, cocaethylene, can generate the mechanisms that cause death by itself. That the main pathophysiological mechanisms that lead to death in the combined use of these substances are of cardiovascular and hepatic origin. As legal medical considerations to take into account for the diagnosis of this type of accidental death, in the Toxicology Section of the Department of Forensic Sciences of Costa Rica, the quantification of cocaethylene and related substances is not carried out, although it is currently in the development of a project for the determination of the stability of drugs in blood under storage conditions, in order to offer the possibility of quantifying certain drugs (which could include cocaethylene) in the near future.

Manejo conservador del endometrioma ovárico con escleroterapia usando etanol previo a fecundación in vitro

El endometrioma ovárico es un quiste con tejido endometrial ectópico que se asocia a disminución de la reserva ovárica, siendo su manejo en infertilidad controversial. Presentamos el caso de una mujer de 32 años con reserva ovárica disminuida y endometrioma mayor de 100 mm. Fue sometida a aspiración transvaginal ecoguiada y a escleroterapia con etanol, lográndose reducción del tamaño en 65% a los tres meses. Posteriormente se realizó fecundación in vitro (FIV), consiguiéndose embarazo. La exéresis del endometrioma es controversial, debido a que reduce la reserva ovárica. La escleroterapia demuestra conservarla, se asocia a una tasa baja de recurrencia y facilita la accesibilidad ovárica. La escleroterapia con etanol del endometrioma es una técnica ambulatoria, segura y eficaz que permite el embarazo en mujeres con infertilidad.

Ovarian endometrioma is a cyst with ectopic endometrial tissue associated with decreased ovarian reserve. Its management in infertility is controversial. We present the case of a 32-year-old woman with decreased ovarian reserve and endometrioma larger than 100 mm. She underwent ultrasound-guided transvaginal aspiration and subsequent sclerotherapy with ethanol, achieving a 65% reduction in size after three months. Subsequently, in vitro fertilization (IVF) was performed, and pregnancy was achieved. The excision of the endometrioma is controversial because it reduces the ovarian reserve. Sclerotherapy has been shown to preserve ovarian reserve, is associated with a low recurrence rate and facilitates ovarian accessibility. Ethanol sclerotherapy of endometrioma is a safe and effective outpatient technique that allows pregnancy in women with infertility.

Gastroprotective potential and mechanisms of action of Hedera nepalensis

Abstract Hedera nepalensis (H. nepalensis) , belonging to the family Araliaceae, is a medicinal plant traditionally used to treat stomach problems. The current study investigated the gastroprotective potential and the mechanism of action of H. nepalensis in diclofenac-and ethanol-induced ulcer models. Anti-oxidant and lipid peroxidation inhibitory prospects of H. nepalensis were checked out by free radical scavenging assay and UV spectrophotometer respectively. Effect of H. nepalensis on the pH, gastric total acidity of gastric juice and protective effects of H. nepalensis against ulcer models have been examined. Histopathological studies have been carried out. The aqueous methanol extract of H. nepalensis (100 µg/mL) showed anti-oxidant (83.55%) and lipid peroxidation inhibitory (70.88%) potential at 1000 µg/mL; the extract had no buffer potential. The extract (400 mg/kg) significantly (81.12% and 63.46%) showed gastroprotective effect in diclofenac and ethanol-induced rat ulcer models respectively. Histopathological studies confirmed the biochemical findings. FTIR analysis showed the presence of carboxylic acid, alkanes, conjugated alkanes, aldehydes and alkyl-aryl ethers. Gallic acid, M-coumaric acid and quercetin were found by HPLC analysis. H. nepalensis exhibited significant protection against diclofenac and ethanol induced gastric damage by anti-oxidant and lipid peroxidation suppression effects suggesting potential broad utility in treatment of diseases characterized with gastric damage.

Lock terapia na prevenção e tratamento da infecção da corrente sanguínea associada ao cateter vascular: revisão integrativa / Terapia de bloqueo en la prevención y tratamiento de infecciones del torrente sanguíneo asociadas al catéter vascular: revisión integradora / Lock therapy in prevention and treatment of catheter-associated bloodstream infection: integrative review

Resumo Objetivo Sintetizar o conhecimento sobre o uso da lock terapia na prevenção e no tratamento da infecção da corrente sanguínea associada ao dispositivo de acesso vascular central de longa permanência em pacientes adultos e idosos hospitalizados. Métodos Revisão integrativa com busca nas bases de dados CINAHL, Cochrane Central, Embase, LILACS, PubMed, Scopus e Web of Science, no período de 1º janeiro de 2010 a 28 de setembro de 2021 sem restrições de idioma. Os dados foram analisados de forma descritiva. Resultados Foram identificados 16 estudos sendo seis (37,5%) sobre o uso da lock terapia como prevenção de infecção associada ao dispositivo de acesso vascular central e dez (62,5%) sobre tratamento. Os artigos sobre prevenção relataram o uso de soluções não antibióticas. Nove dos dez estudos que abordaram a lock terapia como tratamento, utilizaram soluções antibióticas. Dois estudos avaliaram a eficácia da lock terapia em curta duração (de três a quatro dias), sete em maior duração (entre 10 e 14 dias) e um não especificou a duração. Cada estudo descreveu uma técnica de intervenção e o tempo de permanência da solução intraluminal. Em relação ao risco de viés, foram avaliados como baixo risco: cinco ensaios clínicos randomizados, dois ensaios clínicos sem randomização e oito estudos observacionais. Apenas um estudo observacional foi classificado como risco moderado. Conclusão Na prevenção, identificou-se o uso de soluções não antibióticas como o etanol. Para o tratamento, foi utilizada a daptomicina endovenosa. Enquanto os estudos incluídos nessa revisão sobre prevenção não demonstraram evidência estatística, os dez estudos sobre tratamento demonstraram que a lock terapia é um complemento eficaz ao tratamento sistêmico, apresentando boas taxas de salvamento do cateter.

Resumen Objetivo Sintetizar el conocimiento sobre el uso de la terapia de bloqueo en la prevención y tratamiento de infecciones del torrente sanguíneo asociadas al dispositivo de acceso vascular central de larga permanencia en pacientes adultos y adultos mayores hospitalizados. Métodos Revisión integradora con búsqueda en las bases de datos CINAHL, Cochrane Central, Embase, LILACS, PubMed, Scopus y Web of Science, en el período del 1 de enero de 2010 al 28 de septiembre de 2021 sin restricción de idioma. Los datos fueron analizados de forma descriptiva. Resultados Se identificaron 16 estudios, de los cuales seis (37,5 %) trataban sobre el uso de la terapia de bloqueo como prevención de infecciones asociadas al dispositivo de acceso vascular central y diez (62,5 %) sobre tratamiento. En los artículos sobre prevención se relató el uso de soluciones no antibióticas. En nueve de los diez estudios que abordaban la terapia de bloqueo como tratamiento, se utilizaron soluciones antibióticas. En dos estudios se evaluó la eficacia de la terapia de bloqueo de corta duración (de tres a cuatro días), siete de mayor duración (entre 10 y 14 días) y uno sin especificar la duración. En cada estudio se describió una técnica de intervención y el tiempo de permanencia de la solución intraluminal. Con relación al riesgo de sesgo, fueron evaluados con riesgo bajo: cinco ensayos clínicos aleatorizados, dos ensayos clínicos no aleatorizados y ocho estudios observacionales. Solo un estudio observacional fue clasificado con riesgo moderado. Conclusión Para la prevención, se identificó el uso de soluciones no antibióticas como el etanol. Para el tratamiento, se utilizó la daptomicina intravenosa. Aunque los estudios incluidos en esta revisión sobre prevención no hayan demostrado evidencia estadística, los diez estudios sobre tratamiento demostraron que la terapia de bloqueo es un complemento eficaz para el tratamiento sistémico y presentó buenos índices de salvamento del catéter.

Abstract Objective To synthesize knowledge on the use of lock therapy for prevention and treatment of long-term central vascular access devices-associated bloodstream infection in hospitalized adult and elderly patients. Methods Integrative review conducted in CINAHL, Cochrane Central, Embase, LILACS, PubMed, Scopus, and Web of Science databases, from January 1st, 2010 to September 28th, 2021, without language restrictions. Data were analyzed descriptively. Results Sixteen studies were identified, six (37.5%) on the use of lock therapy for prevention of bloodstream infection associated with central vascular access devices, and ten (62.5%) on treatment. The articles on prevention reported the use of non-antibiotic solutions. Nine of the ten studies that addressed lock therapy as treatment used antibiotic solutions. Two studies assessed the effectiveness of lock therapy in a short duration (three to four days), seven in a longer duration (between 10 and 14 days), and one did not specify the length of time. Each study described an intervention technique and the length of stay of the intraluminal solution. Regarding the risk of bias, five randomized clinical trials, two non-randomized clinical trials, and eight observational studies were rated as low risk. Only one observational study was classified as moderate risk. Conclusion The use of non-antibiotic solutions such as ethanol was identified for prevention of bloodstream infection. For treatment, intravenous daptomycin was used. While the studies included in this review on prevention did not show statistical evidence, the ten studies on treatment demonstrated that lock therapy is an effective complement to systemic treatment, showing good catheter salvage rates.

Antibacterial activity: a comparism of ripe and unripe extracts of two varieties (red and yellow) of cashew apple (anacardium occidentale) on some clinical bacterial isolates

The emergence of pathogenic bacteria that are resistant to several antibiotics has recently presented a significant challenge to the healthcare system. Therefore, an alternative source of antimicrobial agents is needed. The study aimed to compare the antibacterial activities of aqueous and ethanol extracts of ripe and unripe fruits of red and yellow varieties of Anacardium occidentale against Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa and Staphylococcus aureus. Cold maceration method of extraction was used using water and ethanol. Antibacterial activities of the extracts against the isolates were evaluated by agar diffusion method while minimum inhibitory concentration (MIC) was determined using broth dilution method. In the determination of the antibacterial activities of all the extracts, the highest zones of inhibition were shown by ethanolic extracts of both ripe red cashew (25 mm) and yellow cashew (26 mm) against Escherichia coli. Both the aqueous and ethanolic extracts of unripe red and yellow cashew had no antibacterial effect against Klebsiella pneumoniae and Pseudomonas aeruginosa. As well, both aqueous and ethanol extracts of ripe red and yellow cashew and ethanolic extract of ripe yellow cashew inhibited all the test organisms. Minimum inhibitory concentration ranged from 50 to 150 mg/ml. At 100 mg/ml, both ethanolic extracts of ripe red and yellow cashew were bactericidal to Escherichia coli while aqueous extract of ripe red cashew was bactericidal to Escherichia coli at 150 mg/ml. The antibacterial activities of A. occidentale apple (fruit) extracts underscore the credence to the efficacy of their use as traditional remedy against some human ailments.

Research on the mechanisms of ethanol extract of Scutellaria baicalensis Georgi in improving CFA-induced inflammatory pain rats based on 1H NMR metabolomics / 药学学报

The purpose of this study was to investigate the effects of ethanol extract of Scutellaria baicalensis Georgi (SGE) on endogenous metabolites in toes of rats with inflammatory pain induced by complete Freund's adjuvant (CFA) based on 1H NMR metabolomics, which would provide foundation for revealing the effects and mechanisms of SGE in improving inflammatory pain. This animal experiment was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2022062). The rats model of inflammatory pain was induced by subcutaneous injection of CFA (0.1 mL), and the effect of low, medium and high doses of SGE (1.5, 3, 6 g·kg-1) on inflammatory pain were explored. The effects of SGE on relieving inflammatory pain was evaluated by mechanical nociceptive thresholds (MNTs) test. Western blot was used to detect the effects of SGE on protein expression of cyclooxygenase-2 (COX-2), nuclear factor kappa-B (NF-κB) and phospho-NF-κB (p-NF-κB). 1H NMR metabolomics was used to analyze the regulatory effects of SGE on endogenous metabolites in the toes of rats with inflammatory pain. The results showed that SGE (6 g·kg-1) could significantly relieve CFA-induced inflammatory pain, and also notably inhibit the protein expression of COX-2, NF-κB and p-NF-κB. SGE could markedly reverse the changes of 8 differential metabolites, such as glycine, glutamine, succinate, phosphorylcholine, etc. The metabolites were involved in eight metabolic pathways, such as glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism, glutathione metabolism, glycerophospholipid metabolism. These results suggest that SGE may relieve inflammatory pain by regulating NF-κB signaling pathway and metabolic abnormality.

Study on chemical compositions and hepatotoxicity of water extract and ethanol precipitate of processed products of Psoralea corylifolia / 中国药房

OBJECTIVE To study the content changes of 5 chemical compositions in water extract and ethanol precipitate of different processed products of Psoralea corylifolia， and to preliminarily evaluate its hepatotoxicity. METHODS The water extracts from crude product of P. corylifolia and processed products by Leigong method， running water rinsing method， and salt stir-frying method were prepared， as well as the ethanol precipitates of processed products by Leigong method and salt stir-frying method were prepared. The contents of psoralenoside， isopsoralenoside， psoralen， isopsoralen and bakuchiol were determined by high- performance liquid chromatography and compared. The median lethal concentration （LC50） and maximum non-lethal concentration （MNLC） of each sample to wild-type zebrafish juveniles were calculated after 72 h of treatment with different concentrations of water extracts from raw product and processed products by running water rinsing method， Leigong method and salt stir-frying method， different concentrations of ethanol precipitates from processed products by Leigong method and salt stir-frying method， and the acetaminophen was used as the positive control. The basic morphology of wild-type zebrafish juveniles and the liver phenotype of transgenic zebrafish juveniles were observed after 72 h of treatment with the above samples （MNLC）. Pearson correlation analysis was used to evaluate the correlation between component content and hepatotoxicity. RESULTS Compared with the water extract of raw products， the contents of psoralenoside and isopsoralenoside in the water extract of different processed products were generally decreased （P＜0.05）， while the contents of psoralen， isopsoralen and bakuchiol in the ethanol precipitate of Leigong method and salt stir-frying products were significantly increased （P＜0.05）. The LC50 of water extracts of crude product and processed products by running water rinsing method， Leigong method， salt stir-frying method， and ethanol precipitates of processed products by Leigong method and salt stir- frying method were 2.45， 5.00， 5.38， 1.55， 2.36， 0.64 g/L （calculated by crude drug）， and MNLC were 2.21， 4.53， 5.02， 1.37， 2.13， 0.53 g/L （calculated by crude drug）. Compared with the blank control group， the zebrafish juveniles in each sample treatment group showed different degrees of deformity， the liver relative fluorescence intensity was significantly weakened （P＜0.05 or P＜ 0.01）. Fat-soluble components such as bakuchiol， isopsoralen and psoralen were highly correlated with liver fluorescence intensity （R 2＞0.7）. CONCLUSIONS The processed products of P. corylifolia mainly compose of psoralenoside and isopsoralenoside after water extraction， the contents of psoralen， isopsoralen and bakuchiol increase after alcohol precipitation， and the hepatotoxicity is positively correlated with the contents of liposoluble compositions in P. corylifolia.

Screening of active fractions of Jiegu ointment for promoting fracture healing in New Zealand rabbits / 中国药房

OBJECTIVE To screen the active site of Jiegu ointment in promoting fracture healing in New Zealand rabbits. METHODS The ethanol extract of Jiegu ointment， as well as the ethyl acetate and n-butanol parts， were prepared and mixed with honey to form a plaster with appropriate viscosity. The radial fracture model of left forelimb in New Zealand rabbit was established and divided into model control group， ethanol extract group， ethyl acetate fraction group and n-butanol fraction group， with 6 rabbits in each group. Except for model control group， rabbits of all other groups were treated with corresponding polar part of Jiegu ointment for external application， for 4 weeks. The radial fracture healing of rabbits was studied by X-ray examination. Enzyme-linked immunosorbent assay was used to detect the serum levels of interleukin-6 （IL-6）， tumor necrosis factor α （TNF-α）， osteocalcin （OC）， vascular endothelial growth factor A （VEGFA）， basic fibroblast growth factor 2 （bFGF2） and alkaline phosphatase （ALP）. HE staining was adopted to observe the changes of pathological morphology of rabbit fracture site， and immunohistochemical method was used to detect the protein expression of bFGF2 in fracture site of rabbits. RESULTS The healing speed of the fracture site in the n-butanol fraction group was the fastest， followed by ethanol extract group， and the ethyl acetate fraction group was the slowest； the serum levels of TNF-α and IL-6 in n-butanol fraction group decreased the fastest， while the levels of ALP， bFGF2， OC and VEGFA increased the fastest [significant increase compared with ethanol extract group （P＜0.01）]； the chondrocytes at the fracture fraction completely disappeared， forming a large number of bone marrow cavities， and the bone trabeculae in the bone marrow cavity were officially formed. The expression level of bFGF2 was also higher than ethanol extract group. CONCLUSIONS The effect of n-butanol fraction on promoting fracture healing is more significant than ethyl acetate fraction and ethanol extract， and n-butanol fraction is the active fraction of Jiegu ointment to promote fracture healing.

Notch signaling pathway inhibitor DAPT improves alcohol-induced neuronal differentiation impairment in zebrafish / 南方医科大学学报

OBJECTIVE@#To explore the role of the Notch signaling pathway in regulating neuronal differentiation and sensorimotor ability in a zebrafish model of fetal alcohol spectrum disorder.@*METHODS@#Zebrafish embryos treated with DMSO or 50 μmol/L DAPT (a Notch signaling pathway inhibitor) were examined for mortality rate, hatching rate, malformation rate, and body length at 15 days post fertilization (dpf). The mRNA expression levels of sox2, neurogenin1 and huc in the treated zebrafish embryos were detected using in situ hybridization and qRT-PCR, and their behavioral responses to strong light and vibration stimulation were observed. The zebrafish embryos were then exposed to DMSO, 1.5% ethanol, DAPT, or both ethanol and DAPT, and the changes in mRNA expression levels of sox2, neurogenin1, huc, and the Notch signaling pathway genes as well as behavioral responses were evaluated.@*RESULTS@#Exposure to 50 μmol/L DAPT significantly increased the mortality rate of 1 dpf zebrafish embryos (P < 0.01), decreased the hatching rate of 2 dpf embryos (P < 0.01), increased the malformation rate of 3 dpf embryos (P < 0.001), and reduced the body length of 15 dpf embryos (P < 0.05). DAPT treatment significantly downregulated sox2 mRNA expression (P < 0.01) and increased neurogenin1 (P < 0.05) and huc (P < 0.01) mRNA expressions in zebrafish embryos. The zebrafish with DAPT treatment exhibited significantly shortened movement distance (P < 0.001) and lowered movement speed (P < 0.05) in response to all the stimulation conditions. Compared with treatment with 1.5% ethanol alone, which obviously upregulated notch1a, her8a and NICD mRNA expressions in zebrafish embryos (P < 0.05), the combined treatment with ethanol and DAPT significantly increased neurogenin1 and huc mRNA expression, decreased sox2 mRNA expression (P < 0.01), and increased the moving distance and moving speed of zebrafish embryos in response to strong light stimulation (P < 0.05).@*CONCLUSION@#Ethanol exposure causes upregulation of the Notch signaling pathway and impairs neuronal differentiation and sensorimotor ability of zebrafish embryos, and these detrimental effects can be lessened by inhibiting the Notch signaling pathway.

Study on the promotion effect mechanism of ethanol extract from Atractylodes macrocephala on microglia phagocytosis and degradation of Aβ based on regulating PPAR-γ signaling pathway / 中国药房

OBJECTIVE To explore the effect mechanism of ethanol extract from Atractylodes macrocephala （EEAM） on microglial phagocytosis and degradation of amyloid β （Aβ） based on peroxisome proliferator-activated receptor γ （PPAR- γ） signaling pathway. METHODS Taking neuromicroglial cell BV2 as subjects， confocal microscopy was used to observe the effects of EEAM （0.3， 0.4， 0.5 mg/mL， similarly hereinafter） on phagocytosis and degradation of Aβ in microglia. Human embryonic kidney cell HEK293 was used to investigate the effects of EEAM on luciferase transcriptional activity of PPAR-γ. The effect of EEAM on nuclear translocation of PPAR-γ was investigated by immunofluorescence. Alzheimer’s disease BV2 cell model was induced by Aβ1-42， and quantitative polymerase chain reaction was used to investigate the effects of EEAM on mRNA expressions of PPAR-γ downstream target genes （Lxra， Lxrb， Abca1， Abcg1， Cd36， Sra and Apoe）. RESULTS The results of Aβ uptake experiment showed that after the intervention of medium and high doses of EEAM， fluorescence intensity of Aβ in BV2 cells increased significantly （P＜0.05）. The degradation experiment of Aβ showed that after the intervention of medium and high doses of EEAM， fluorescence intensity of Aβ in BV2 cells decreased significantly （P＜0.05）. After the intervention of different doses of EEAM， luciferase transcriptional activity of PPAR-γ in HEK293 cells increased significantly （P＜0.05）； fluorescence intensity of PPAR-γ in BV2 cells and nuclei （except for low-dose group） increased significantly （P＜0.05）. mRNA expressions of Lxra， Lxrb， Abca1， Abcg1， Cd36， Sra and Apoe in BV2 cells were increased significantly （P＜0.05）. CONCLUSIONS EEAM can promote the uptake and degradation of Aβ in microglia by activating PPAR-γ signaling pathway， thus improving Alzheimer’s disease.

Optimization of ethanol precipitation process of Nauclea officinalis extract based on concept of quality by design(QbD) / 中国中药杂志

The ethanol precipitation process of Nauclea officinalis extract was optimized based on the concept of quality by design(QbD). Single factor tests were carried out to determine the levels of test factors. The ethanol volume fraction, pre-ethanol precipitation drug concentration, and ethanol precipitation time were taken as critical process parameters(CPPs). With the comprehensive scores of strictosamide transfer rate and solid removal rate as the critical quality attributes(CQAs), Box-Behnken design was employed to establish the mathematical models and space design between CPPs and CQAs, and the obtained optimal operating space was validated. The optimal operating space included ethanol volume fraction of 65%-70%, pre-ethanol precipitation drug concentration of 22-27 mg·mL~(-1), and ethanol precipitation time of 12 h. Based on the concept of QbD, this study adopted the design space to optimize the ethanol precipitation process of N. officinalis extract, which provided a reliable theoretical basis for the quality control in the production process of N. officinalis preparations. Moroever, this study provided a reference value for guiding the research and industrial production of traditional Chinese medicines.