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).

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.

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.

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.

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.

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

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.

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.

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.

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.

Effects of Spirulina phycocyanin on antioxidant capacity of ethanol-induced oxidative stress mice / 中国生物制品学杂志

@#Objective To investigate the effect of Spirulina phycocyanin on antioxidant capacity of ethanol-induced oxidative stress mice.Methods Forty-eight female KM mice were selected and randomly divided into four groups:The blank group,model group,low-dose group and high-dose group,12 for each group. Mice in low-dose and high-dose group were given0. 15 g/kg and 0. 30 g/kg phycocyanin by intragastric administration,once a day,continuously for 42 d,and the body mass of mice were weighed. Fasting for 16 h(overnight)after the last intragastric administration,50% ethanol was given once at 12 mL/kg body mass. The mice in model group were only given 50% ethanol by intragastric administration,while the mice in blank group were not given intragastric administration. After 6 h,the blood samples were collected and the sera were separated and detected for the content of 8-isoprostane by corresponding kit. The liver tissues of mice in each group were taken aseptically. After grinding and centrifuging,the supernatant was taken and detected for the contents of protein carbonyl,glutathione peroxidase(GSH-Px)and reduced glutathione(GSH)with corresponding kits. The correlation between mouse body mass and GSH was analyzed.Results Compared with the blank group,the body mass of mice in the model group increased,while the difference was not significant(F = 1. 585,P > 0. 05);the contents of 8-isoprostane in serum,protein carbonyl and GSH in liver tissue significantly increased(F = 11. 697,13. 582 and 17. 213 respectively,each P < 0. 05);the content of GSH-Px in liver tissue decreased,while the difference was not significant(F = 5. 978,P > 0. 05). Compared with the model group,the body mass of mice in low-dose and high-dose groups decreased significantly(F = 4. 125 and 18. 842 respectively,each P < 0. 05);the contents of 8-isoprostane in serum and protein carbonyl in liver tissue decreased significantly(F = 10. 695～40. 512,each P < 0. 01);the contents of GSH-Px and GSH in liver tissue significantly increased(F = 42. 65～76. 379,each P < 0. 01). The content of GSH in liver tissue was negatively correlated with the body mass of mice(R2= 0. 013 49,P > 0. 05).Conclusion Phycocyanin reduced the oxidative damage,improved the antioxidant capacity,and reduced the body mass of ethanol-induced oxidative stress mice.

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.

Protective Effect of Flos Puerariae，Hoveniae Semen， and Their Compatibility on Acute Alcoholic Gastric Mucosal Injury in Mice and Mechanism / 中国实验方剂学杂志

ObjectiveTo explore the improvement effect of Flos Puerariae， Hoveniae Semen， and their compatibility on acute alcoholic gastric mucosal injury， and lay a foundation for further development of Flos Puerariae， Hoveniae Semen， and their compatibility in the prevention and treatment of alcohol-induced multiple organ injury. MethodThe acute alcohol-induced gastric mucosal injury model of mice was established by multiple intragastric administration of 56% Hongxing Erguotou liquor （15 mL·kg-1）. A total of 120 male ICR mice were randomly divided into 8 groups， namely， the blank group， model group， omeprazole group （0.026 g·kg-1）， Flos Puerariae-Hoveniae Semen （compatibility） high， medium， and low-dose groups （29.2，14.6， 7.3 g·kg-1）， Flos Puerariae group （19.5 g·kg-1）， and Hoveniae Semen group （19.5 g·kg-1）， with 15 mice in each group. After one week of adaptive feeding， the animals were pre-administrated with the corresponding drug at the rate of 10 mL·kg-1 for 3 d. From the 4th day， after 1 h of administration， Erguotou liquid was administrated at the rate of 15 mL·kg-1 and the blank group was administrated with the same volume of deionized water to record the drunkenness and sober up time. The administration was lasted for 3 d. One hour after the last administration， the eyeballs were removed and the mice were sacrificed. The concentration of ethanol in serum was determined by gas chromatograph， and the activity of ethanol dehydrogenase （ADH） in gastric mucosa was determined by ultraviolet-vis spectrophotometer. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in gastric mucosa. Serum inflammatory factors were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of nuclear transcription factor-κB （NF-κB） p65 and NF-κB inhibitory protein α （IκBα） were detected by real-time polymerase chain reaction （Real-time PCR）. ResultAs compared with the normal group， the content of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in serum of mice in the model group was increased （P<0.05）， the mRNA expression of NF-κB p65 in gastric mucosa tissues was increased （P<0.01）， and the mRNA expression of IκBα was decreased （P<0.01）. As compared with the model group， the drunkenness time of the omeprazole group， high and medium-dose compatibility groups， and Flos Puerariae group was prolonged （P<0.05）， the sober up time of the high and medium-dose compatibility groups was shortened （P<0.05）， the ethanol concentration in the serum of the high-dose compatibility group was decreased （P<0.05）， the ADH activity in the gastric mucosa of the omeprazole group and high and medium-dose compatibility groups was increased （P<0.05）， the macroscopic injury score of the high， medium， and low-dose compatibility groups and Flos Puerariae group was decreased （P<0.05）， the score of pathological injury in the omeprazole group， high， medium， and low-dose compatibility groups， and Flos Puerariae group was decreased （P<0.01）， the expression of IL-6 in serum of all drug groups was decreased （P<0.05）， the expression of IL-1β in serum of the omeprazole group， high， medium， and low-dose Flos Puerariae groups， and Hoveniae Semen group was decreased （P<0.05）， the expression of TNF-α in serum of high and medium-dose groups was decreased （P<0.05）， the mRNA expression of NF-κB p65 in gastric mucosa tissues of all drug groups was decreased （P<0.05）， and the mRNA expression of IκBα in gastric mucosa tissues of the omeprazole group and high， medium， and low-dose compatibility groups was increased （P<0.05）. As compared with the high-dose compatibility group， the drunkenness time in the low-dose compatibility group and Hoveniae Semen group was shortened （P<0.01）， the sober up time in the Flos Puerariae and Hoveniae Semen groups was prolonged （P<0.01）， the concentration of ethanol in the serum of the medium and low-dose compatibility groups， Flos Puerariae group， and Hoveniae Semen group increased （P<0.05）， the macroscopic injury score of the medium and low-dose compatibility groups and Hoveniae Semen group was increased （P<0.05）， the pathological injury score of the medium and low-dose compatibility groups， Flos Puerariae group， and Hoveniae Semen group was increased （P<0.01）， the content of IL-1β in serum of low-dose compatibility group， Flos Puerariae group， and Hoveniae Semen group was increased （P<0.01）， and the mRNA expression of IκBα in gastric mucosa of the Flos Puerariae group and Hoveniae Semen group was decreased （P<0.05）. As compared with the medium-dose compatibility group， the drunkenness time in the Hoveniae Semen group was shortened （P<0.05）， the sober up time in the Flos Puerariae group was prolonged （P<0.05）， the pathological injury score in the Flos Puerariae group and Hoveniae Semen group was increased （P<0.01）， and the content of IL-1β in serum of the low-dose compatibility group， the Flos Puerariae group， and Hoveniae Semen group was increased （P<0.05）. As compared with the low-dose compatibility group， the pathological injury score of the Hoveniae Semen group was increased （P<0.05）. ConclusionFlos Puerariae， Hoveniae Semen， and their compatibility play a role in preventing and treating acute alcoholic gastric mucosal injury in mice， which may be related to the inhibition of the expression of NF-κB signal pathway in gastric mucosa， and the high-dose compatibility group has the optimal effect.

Establishment of UPLC fingerprint and study on anti-respiratory syncytial virus spectrum-effective relationship of ethanol extract from Callicarpa nudiflora / 中国药房

OBJECTIVE To establish the fingerprint of the ethanol extract from Callicarpa nudiflora， analyze its anti- respiratory syncytial virus （RSV） activity in vitro， and study the relationship between spectrum and effect. METHODS Using 10%， 30%， 50%， 70% and 90% ethanol as solvent， 20 batches of ethanol extracts from 4 batches of C. nudiflora were prepared. The fingerprints for 20 batches of ethanol extracts from C. nudiflora were mapped by ultra-high-performance liquid chromatography （UPLC）， and the similarity evaluation was conducted by using the Similarity Evaluation System for Traditional Chinese Medicine Chromatographic Fingerprints （2012 edition）. The cytopathic effect method and MTT method were used to investigate the in vitro inhibitory activity of the ethanol extracts from C. nudiflora on RSV. Pearson correlation analysis， grey correlation degree and orthogonal partial least squares （OPLS） analysis were used to study the spectrum-effect relationship. RESULTS There were 25 common peaks in 20 batches of ethanol extracts from C. nudiflora， and the similarities ranged from 0.912 to 0.998， and the RSDs of common peak areas were 33.54%-162.28%. The average values of IC50 for RSV of 20 batches of ethanol extracts from C. nudiflora were 9.55-272.23 μg/mL. The results of Pearson correlation analysis， grey correlation analysis and OPLS analysis showed that the Pearson correlation coefficients （P＜0.05） of the common peaks 8， 10， 12， 16， 18-19， 22-24 with pharmacodynamic indicators and regression coefficients were all negative， the correlation coefficients were all greater than 0.6， and the values of variable importance in projection were all greater than 1. CONCLUSIONS Twenty batches of ethanol extracts from C. nudiflora have similar components but significant differences in content， and exhibit different degrees of anti-RSV activity in vitro. The corresponding components of common peaks 8， 10， 12， 16， 18-19， 22-24 may be the characteristic components of anti-RSV of C. nudiflora.

Expression and characterization of mesophilic GH1 β-glucosidase CdBglA from acidophilic Cuniculiplasma divulgatum / 生物工程学报

β-glucosidase has important applications in food, pharmaceutics, biomass conversion and other fields, exploring β-glucosidase with strong adaptability and excellent properties thus has received extensive interest. In this study, a novel glucosidase from the GH1 family derived from Cuniculiplasma divulgatum was cloned, expressed, and characterized, aiming to find a better β-glucosidase. The amino acid sequences of GH1 family glucosidase derived from C. divulgatum were obtained from the NCBI database, and a recombinant plasmid pET-30a(+)-CdBglA was constructed. The recombinant protein was induced to express in Escherichia coli BL21(DE3). The enzymatic properties of the purified CdBglA were studied. The molecular weight of the recombinant CdBglA was 56.0 kDa. The optimum pH and temperature were 5.5 and 55 ℃, respectively. The enzyme showed good pH stability, 92.33% of the initial activity could be retained when treated under pH 5.5-11.0 for 1 h. When pNPG was used as a substrate, the kinetic parameters Km, Vmax and Kcat/Km were 0.81 mmol, 291.99 μmol/(mg·min), and 387.50 s-1 mmol-1, respectively. 90.33% of the initial enzyme activity could be retained when CdBglA was placed with various heavy metal ions at a final concentration of 5 mmol/L. The enzyme activity was increased by 28.67% under 15% ethanol solution, remained unchanged under 20% ethanol, and 43.68% of the enzyme activity could still be retained under 30% ethanol. The enzyme has an obvious activation effect at 0-1.5 mol/L NaCl and can tolerate 0.8 mol/L glucose. In conclusion, CdBglA is an acidic and mesophilic enzyme with broad pH stability and strong tolerance to most metal ions, organic solvents, NaCl and glucose. These characteristics may facilitate future theoretical research and industrial production.

Effects of Weichang'an Pill on contraction of isolated ileum smooth muscles in rats / 中国药理学通报

Aim To investigate the impact and mechanism of Weichang'an Pill(WCA),its ethanol extract(EE),water extract(WE),and active ingredients on the contraction of isolated rat ileum smooth muscles induced by acetylcholine(ACh). Methods In vitro tissue bath experiment,WCA,EE,WE,or their active ingredients were added under the action of ACh,and then the contraction tension of isolated ileum smooth muscle from rats was recorded. The binding affinity ofthe active ingredients to the muscarinic acetylcholine M3 receptor was explored by molecular docking. Results WCA,EE,and WE were able to considerably inhibit the excitatory contraction of the ileal smooth muscles induced by ACh. Costunolide,dehydrocostus lactone,santalol,muscone,emodin,chrysophanol,physcion,crotonoside,magnolol,and honokiol were also significantly effective against ACh-induced ileal smooth muscle contraction. Conclusions WCA,EE,WE,and their active ingredients may help to promote intestinal smooth muscle relaxation by blocking the binding of the M3 receptor on the membrane of ileal smooth muscle with ACh.

Investigating the efficacy of ultrasound-guided ethanol retention technique for endometrioma sclerotherapy and its effect on pro-inflammatory cytokine levels: A single-arm clinical trial

Abstract Background Endometriosis is a chronic inflammatory disease affecting about 10% of women of reproductive age. Endometrioma is the most common presentation of endometriosis in ovaries. Objectives Herein, the authors study the effect of the ultrasound-guided ethanol retention technique for endometrioma sclerotherapy and its effect on the plasma levels of pro-inflammatory cytokines. Materials and methods Each endometrioma was aspirated and washed with 0.9% saline until clearance and then 2/3 of the cyst volume was filled with ethanol 98%. Patients were followed for 3 months. After that, changes in their cyst diameter, dyspareunia, dysmenorrhea, and antral follicular count were assessed. Also, the sera levels of Interleukin 1β (IL-β), IL-6, and IL-8 were assayed before and after the treatment. The primary sera levels were also compared with a control group. Results In the treatment and control groups, 23 and 25 individuals (respectively) with a matched mean age (p-value = 0.680) were enrolled in the study. Among the laboratory variables, IL-1β (p-value = 0.035), as well as AMH (p-value = 0.002), were lower, and IL-6 (p-value = 0.011) was higher in the endometriosis group compared to the controls. Following the treatment, dysmenorrhea, dyspareunia, and the mean diameter of all cysts were significantly (p-values < 0.001) decreased in the treatment group. Also, right (p-value = 0.022) and left (p-value = 0.002) ovaries' antral follicular counts were increased following the treatment. No significant change was found among any of the investigated laboratory levels (p-value > 0.05). Conclusion Ethanol retention method is proven to be safe and could improve the clinical status of patients with endometrioma. Although further studies are necessary.

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.