Liver Injury Caused by Psoraleae Fructus： A Review / 中国实验方剂学杂志

Psoraleae Fructus （PF） is a non-toxic Chinese herbal medicine， while the liver injury caused by PF has aroused wide concern in recent years. At present， animal experiments and in vitro studies have been carried out to explore the mechanism， targets， and toxic components of PF in inducing liver injury， which， however， have differences compared with the actual conditions in clinical practice， and there are still some potential hepatotoxic components and targets of PF that have not been discovered. With the continuous progress in systems biology， establishing the drug-induced liver injury model and the liver injury prediction model based on network toxicology can reduce the cost of animal experiments， improve the toxicity prediction efficiency， and provide new tools for predicting toxic components and targets. To systematically explain the characteristics of liver injury in the application of PF and explore the potential hepatotoxic components and targets of PF， we reviewed the related articles published by China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， and PubMed from 1962 to 2021 and analyzed the characteristics and influencing factors of liver injury caused by PF in the patients. Furthermore， we summarized the chemical components of PF and the components entering blood. By reviewing the mechanism， targets， and components of PF in inducing liver injury that were discovered by in vivo and in vitro experiments， we summarized the known compounds in PF that may cause liver injury. Finally， the current methods for building the prediction model of PF-induced liver injury were summarized， and the predicted toxic components and targets were introduced. The possible factors of PF in causing liver injury were explained from three aspects： clinical characteristics， preclinical studies， and computer-assisted network prediction， which provide a reference for predicting the risk of PF-induced liver injury.

Epidemiological study of bee stings in the state of Paraiba, Northeastern Brazil, from 2015 to 2019

INTRODUCTION: In Brazil, envenomation by bee sting is a public health problem due to its incidence in all regions of the country, as well as the severity of cases. Despite the medical and sanitary importance, the literature on this topic in Brazil is scarce, in the Northeast region. OBJECTIVE: To describe the epidemiological characteristics of bee stings in Paraíba, in the Northeast region of Brazil, from 2015 to 2019. METHODS: The current study is a descriptive and retrospective epidemiological investigation conducted through the recovery of secondary data made available by the database from the Ministry of Health Notification Information System. RESULTS: A total of 1,151 cases were analyzed, and they were reported during all the months of the period of the study and were more frequent in the regions Agreste and Sertão of the Paraíba. The victims were men aged 20 to 59 years. Most individuals received medical assistance within 3 hours of the incident. The cases were classified as mild and progressed to cure. CONCLUSION: In Paraíba, bee stings have increased in recent years, especially in regions with a semi-arid climate. In addition, this study provides data that may be used in the development of educational health actions to promote the prevention and control of bee stings in this region.

Spongiform leukoencephalopathy unveiled in an autopsy of a drug abuser

ABSTRACT Toxic leukoencephalopathy (TLE) is a rare neurological debilitating and fatal condition. It has been previously associated with exposure to leukotoxic offenders such as chemotherapy, cranial radiation, certain drugs, and environmental factors. Currently, it is a commoner white matter syndrome resulting from increased substance abuse, classically by inhaled heroin and other opioids. Herein, we report a case of fatal TLE unveiled in an autopsy of a drug abuser. A 24-year-old male was found dead on the roadside. A day before, he was located in a state of delirium. In this case, the autopsy findings and histopathology characteristics of cerebral cortex involvement particularly directed to speculate the heroine as the principal offender.

Regulamentação e criminalização das drogas no Brasil / Drug regulation and criminalization in Brazil

O presente estudo visa avaliar, através de uma revisão narrativa da literatura, como o controle do Estado exerceu ao longo da história do Brasil a regulamentação do uso de drogas. Método Foram consultados livros, artigos de periódicos acadêmicos indexados, trabalhos completos apresentados em congressos e documentos históricos disponíveis na internet relativos ao tema. Resultados A primeira legislação penal em relação ao uso de drogas surge apenas no Brasil império. Nesse período começam a surgir também os primeiros problemas devido ao uso de drogas. A criação de cursos superiores nas áreas de saúde e de ciências naturais veio a formar profissionais capacitados na manipulação e fiscalização de produtos químicos e farmacêuticos. Com o tempo, observando-se os efeitos, algumas substâncias passam a ser proscritas. Conclusão Por toda história do país, o uso e a regulação das drogas, permearam todas as épocas influenciando na cultura, educação e no modo de vida da população. Atualmente há um grande debate acerca das políticas sobre drogas no Brasil, principalmente sobre a maconha e seus usos terapêuticos, mostrando novamente a influência do Estado sobre a saúde e a segurança da população.

The present study aims to evaluate, through a narrative review of the literature, how State's control has exercised regulation of drug use throughout the history of Brazil. Method Books, articles from indexed academic journals, complete works presented at conferences and historical documents available on the internet relating to the topic were consulted. Results The first criminal legislation related to drug use only appeared in Imperial Brazil. During this period, the first problems due to drug use also begin to appear. The creation of higher education courses in the areas of health and natural sciences resulted in the training of professionals capable of handling and supervising chemical and pharmaceutical products. Over time, observing the effects, some substances become proscribed. Conclusion Throughout the country's history, the use and regulation of drugs has permeated all eras, influencing culture, education and the population's way of life. There is currently a great debate about drug policies in Brazil, mainly regarding marijuana and its therapeutic uses, once again showing the influence of the State on the health and safety of the population.

Pesquisa e desenvolvimento de nanomedicamentos: olhar bioético / Nanodrug research and development: a bioethical approach / Investigación y desarrollo de nanomedicinas: desde la mirada bioética

Resumo Nanotecnologia é a utilização de materiais na escala nanométrica, em que estes adquirem características próprias. A área de pesquisa e desenvolvimento de novos nanomedicamentos é uma das mais promissoras atualmente, todavia essas partículas necessitam de avaliação particular e ainda não há consenso referente às testagens específicas a serem seguidas, o que dificulta a formação de uma legislação que garanta a segurança e eficácia destes medicamentos, além de um processo de registro mais eficaz. Assim, é necessária uma abordagem bioética da nanotecnologia e sua utilização em medicamentos, visando garantir que o progresso científico não acarrete impactos irreversíveis. Diante dessa problemática, busca-se promover uma discussão nanoética referente ao processo de pesquisa e desenvolvimento de nanomedicamentos, por meio de estudo qualitativo, exploratório-descritivo e de caráter analítico, utilizando revisão bibliográfica, análise documental e dados quantitativos disponíveis como técnicas de pesquisa.

Abstract Nanotechnology consist of using materials at the nanoscale, in which they acquire specific characteristics. Nanodrug research and development is one of the most promising fields today; however, these particles require particular evaluation. Moreover, studies lack consensus on which specific tests to follow, thus hindering the elaboration of legislation that ensure their safety and efficacy, as well as a more effective registration process. Thus, a bioethical approach to nanotechnology and its use in drug development is necessary to ensure scientific progress without irreversible impacts. Given this scenario, this article proposes a nanoethics discussion regarding nanodrug research and development by means of a qualitative, exploratory and descriptive analysis, based on literature review, documental analysis and quantitative data available.

Resumen La nanotecnología utiliza materiales nanométricos, en que estos adquieren características propias. El área de investigación y desarrollo de nuevas nanomedicinas es una de las más prometedoras en la actualidad, sin embargo, estas partículas requieren de una evaluación particular y aún no existe consenso en cuanto a las pruebas específicas que seguir, lo que dificulta establecer una legislación que garantice la seguridad y eficacia de estos medicamentos, además de un proceso de registro más efectivo. Por lo tanto, se necesita un enfoque bioético de la nanotecnología y su uso en medicamentos para garantizar que el avance científico no tenga impactos irreversibles. Ante esta problemática, se pretende promover el debate sobre la nanoética en el proceso de investigación y desarrollo de nanomedicinas a partir de un estudio cualitativo, exploratorio-descriptivo y analítico, que utiliza como técnicas de investigación la revisión bibliográfica, el análisis de documentos y los datos cuantitativos disponibles.

Advances and challenges in using nirmatrelvir and its derivatives against SARS-CoV-2 infection / 药物分析学报

On December 22,2021,the United States Food and Drug Administration approved the first main protease inhibitor,i.e.,oral antiviral nirmatrelvir(PF-07321332)/ritonavir(Paxlovid),for the treatment of early severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Nirmatrelvir inhibits SARS-CoV-2 infection,but high doses or long-term treatment may cause embryonic developmental toxicity and changes in host gene expression.The chiral structure of nirmatrelvir plays a key role in its antiviral activity.Ritonavir boosts the efficacy of nirmatrelvir by inactivating cytochrome P450 3A4 expression and occupying the plasma protein binding sites.Multidrug resistance protein 1 inhibitors may increase the efficacy of nirmatrelvir.However,Paxlovid has many contraindications.Some patients treated with Paxlovid experience a second round of coronavirus disease 2019(COVID-19)symptoms soon after re-covery.Interestingly,the antiviral activity of nirmatrelvir metabolites,such as compounds 12-18,is similar to or higher than that of nirmatrelvir.Herein,we review the advances and challenges in using nirmatrelvir and its derivatives with the aim of providing knowledge for drug developers and physicians in the fight against COVID-19.

Application of Microfluidic Liver and Kidney Chips in Toxicology Research of Chinese Medicine / 中国实验方剂学杂志

Microfluidic liver and kidney chips have become preferred model carriers in recent years for new drug development， pharmacological and toxicological research， mechanism exploration， and disease model construction. In the context of the USA. Food and Drug Administration allowing the use of in vitro model data as a substitute for animal model data in new drug applications when animal disease models are difficult to construct， microfluidic chips have received widespread attention due to their high throughput， ability to highly mimic biological characteristics of living organisms， convenient evaluation of drug toxicity in normal or pathological states with repeated dosing， real-time induction and monitoring of culture processes， and real-time data acquisition and analysis. In toxicology research， liver and kidney chips can construct in vitro models suitable for the pharmacological and toxicological detection of different substances by combining 2D monocultures and co-cultures from different species sources， 3D cultures， spheroids/organoid cells， precision-cut liver and kidney slices， immortalized cell lines， or sandwich-cultured cell lines. This model maximally simulates or retains the organ function and in vivo microenvironment of the liver and kidney， including specific physiological tissue structures， multicellular interactions/crosstalk， and multi-organ coordination/feedback， to obtain results similar to or the same as in vivo experimental data， reducing interspecies differences. At the same time， it greatly reduces the use of experimental animals and lowers costs. Microfluidic technology provides necessary shear force microenvironments for the cultivation of contents and solves problems encountered in the cultivation process of liver and kidney chips， such as insufficient tissue oxygen supply， nutrient deficiencies， and accumulation of metabolites， leading to cell apoptosis and even tissue necrosis fibrosis， which make it difficult to maintain long-term structure and function. This article reviewed the application of microfluidic technology combined with liver and kidney chips in Chinese medicine toxicology research. By summarizing the development of microfluidic technology， liver chips， kidney chips， and providing application examples of microfluidic liver and kidney chips in Chinese medicine toxicology research， combined with the characteristics of Chinese medicine administration， the article explored the advantages and future development directions of their application in the field of Chinese medicine toxicology research.

Application progress of air-liquid interface exposure technology in respiratory system toxicity induced by diesel exhaust in vitro / 环境与职业医学

Diesel exhaust (DE) is an important pollution source widely existing in the living and production environment, which is closely related to the health of the public and occupational groups. The International Agency for Research on Cancer has classified DE as a Group 1 carcinogen. Considering the negative health impacts on the respiratory system due to DE exposure in vitro, it is crucial to apply reliable test systems allowing accurate assessment of the biological effects of DE. The exposure technology of respiratory system in vitro is considered as one of the feasible measures to implement the 3R (reduce, refine, and replace) principle in animal experiments. Compared with the traditional submerged culture in vitro models, the air-liquid interface (ALI) exposure technology has the advantages including fewer influencing factors, easier exposure condition control, and shorter exposure cycle. ALI has become an important tool to study molecular events associated with physiology and pathology of respiratory system, and action modes and interactions of different cell types. Also, ALI has been increasingly widely used because it can simulate the actual processes of human respiratory system cells and/or tissues to DE exposure. This review was intended to introduce the development and advantages of ALI exposure technology, and further summarized the application progress of ALI exposure technology in studying the respiratory toxicity induced by DE exposure in vitro, so as to provide new ideas and pathways for the use of ALI exposure technology in the study of biomarkers and mechanisms of respiratory toxicity associated with DE exposure, and provide basic data to screen and promote biomarkers for exposed populations.

Exploring the safe and rational use of Epimedii Folium based on the evolution of efficacy/toxicity records in ancient and modern literature / 药学学报

Epimedii Folium is a traditional non-toxic Chinese herbal medicine. However, liver injury caused by Chinese herb preparations, including Epimedii Folium, is frequently reported over the years. Based on ancient and modern literature, this paper systematically summarized and analyzed the safe application of Epimedii Folium from the perspectives of varieties, processing methods, clinical adverse reactions, pharmacological effects and toxic mechanism. Combined with our team work, we build the comprehensive prevention and control system "human-drug-application", for the safe and rational application of Epimedii Folium. This study is expected to provide support for scientific evaluation and precise prevention and control of the safety risk of Epimedii Folium.

Cytotoxicity of 4 Wild Mushrooms in a Case of Yunnan Sudden Unexplained Death / 法医学杂志

OBJECTIVES@#To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD.@*METHODS@#Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope.@*RESULTS@#Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts.@*CONCLUSIONS@#The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.

Análise de intoxicação por medicamentos / Analysis of drug intoxication / Análisis de intoxicaciones medicamentosas

Os Centros de Assistência Toxicológica possuem uma importância relevante na promoção, prevenção e controle de agravos à saúde em casos de intoxicação, pois fornece um serviço de orientação e atendimento especializado para lidar com essas situações e para minimizar os prejuízos causados pelos agentes tóxicos. Diante disso, o objetivo do estudo foi analisar o perfil epidemiológico de intoxicações por medicamento, no período de 2017 a 2021, no estado do Ceará. Este estudo está caracterizado como epidemiológico exploratório- descritivo, de abordagem quantitativa, em que serão analisados os dados secundários do registro de casos de intoxicações por medicamento, registrados no Sistema Nacional de Agravos de Notificação, entre os anos de 2017 e 2021. Os dados foram coletados no período de março a abril de 2022. As variáveis levantadas são faixa etária, sexo, circunstâncias das intoxicações, óbito. Nas análises epidemiológicas foi feito o cálculo dos registros de intoxicação por medicamentos coletados no SINAN-TABNET. Resultados: Os resultados desse estudo no período de 2017 a 2021 permitiram a identificação do perfil de intoxicações medicamentosas no Estado do Ceará. Observamos que dentre as variáveis estudadas houve uma prevalência do sexo feminino, faixa etária entre 20-39 anos, e dentre as circunstâncias demostradas, a tentativa de suicídio apresentou dados mais alarmantes. Conclusão: Verificamos a necessidade de medidas efetivas no combate ao uso incorreto dos medicamentos, com ações sociais para conscientizar a população para o uso racional dos medicamentos e orientação para os riscos apresentados por medicamentos devido seu abuso intencional ou não intencional, e uma reavaliação do perfil das pessoas com alta prevalência de intoxicações.

The Toxicological Assistance Centers are relevant in promoting, preven- tion, and control of health aggravations in cases of poisoning, as it provides a specialized guidance and assistance service to deal with such situations and to minimize the damage caused by toxic agents. Therefore, the aim of the study was to analyze the epidemiolog- ical profile of medication poisonings in the period from 2017 to 2021 in the state of Ceará. This study is characterized as an exploratory-descriptive epidemiological study, with a quantitative approach, in which secondary data from the record of drug poisoning cases, registered in the National System of Notifiable Diseases, registered in the years 2017 to 2021 will be analyzed. collected from March to April 2022. The variables are age group, sex, circumstances of poisoning, death. In the epidemiological analyses, the calculation of the records of intoxication by drugs collected in SINAN-TABNET was performed. Results: The results of this study in the period from 2017 to 2021 allowed the identification of the profile of drug poisoning in the State of Ceará. We observed that among the variables studied, there was a prevalence of females, the age group is 20-39 years, and among the circumstances, suicide attempt presented the most alarming data. Conclusion: We verified the need for effective measures to combat the misuse of medi- cine, with social actions to make the population aware about the rational use of medi- cines and guidance for the risks presented by medicines due to their intentional or unin- tentional abuse, and a reassessment of the profile of the people with a high prevalence of poisoning.

Los Centros de Asistencia Toxicológica son relevantes en la promoción, prevención y control de los agravamientos de la salud en casos de intoxicación, ya que proporciona un servicio especializado de orientación y asistencia para hacer frente a es- tas situaciones y minimizar los daños causados por los agentes tóxicos. Por lo tanto, el objetivo del estudio fue analizar el perfil epidemiológico de las intoxicaciones medica- mentosas en el período de 2017 a 2021 en el estado de Ceará. Este estudio se caracteriza por ser un estudio epidemiológico exploratorio-descriptivo, con enfoque cuantitativo, en el que se analizarán datos secundarios del registro de casos de intoxicación medicamentosa, inscritos en el Sistema Nacional de Enfermedades de Declaración Obli- gatoria, registrados en los años 2017 a 2021. recogidos de marzo a abril de 2022. Las variables son grupo de edad, sexo, circunstancias de la intoxicación, muerte. En los aná- lisis epidemiológicos se ha realizado el cálculo de los registros de intoxicaciones por drogas recogidos en SINAN-TABNET. Resultados: Los resultados de este estudio en el período de 2017 a 2021 permitieron identificar el perfil de las intoxicaciones por drogas en el Estado de Ceará. Observamos que entre las variables estudiadas, hubo una preva- lencia de fe- varones, el grupo de edad es de 20-39 años, y entre las circunstancias, el intento de suicidio pre-sentó los datos más alarmantes. Conclusiones: Verificamos la necesidad de medidas eficaces para combatir el uso indebido de medicamentos, con ac- ciones sociales de concienciación de la población sobre el uso racional de medicamentos y orientación sobre los riesgos que presentan los medicamentos por su abuso intencional o no intencional, y una reevaluación del perfil de las personas con alta prevalencia de intoxicaciones.

Genomic instability in long-term culture of human adipose-derived mesenchymal stromal cells

Mesenchymal stromal/stem cells stem (MSC) have been widely studied due to their great potential for application in tissue engineering and regenerative and translational medicine. In MSC-based therapy for human diseases, cell proliferation is required to obtain a large and adequate number of cells to ensure therapeutic efficacy. During in vitro culture, cells are under an artificial environment and manipulative stress that can affect genetic stability. Several regulatory agencies have established guidelines to ensure greater safety in cell-based regenerative and translational medicine, but there is no specific definition about the maximum number of passages that ensure the lowest possible risk in MSC-based regenerative medicine. In this context, the aim of this study was to analyze DNA damage and chromosome alterations in adipose-derived mesenchymal stromal cells (ADMSC) until the eleventh passage and to provide additional subsidies to regulatory agencies related to number of passages in these cells. Thus, two methods in genetic toxicology were adopted: comet assay and micronucleus test. The comet assay results showed an increase in DNA damage from the fifth passage onwards. The micronucleus test showed a statistically significant increase of micronucleus from the seventh passage onwards, indicating a possible mutagenic effect associated with the increase in the number of passages. Based on these results, it is important to emphasize the need to assess genetic toxicology and inclusion of new guidelines by regulatory agencies to guarantee the safety of MSC-based therapies for human diseases.

Disección coronaria espontánea posterior a envenenamiento por escorpión / Spontaneous coronary artery dissection following scorpion poisoning

Resumen Hombre de 44 años que acude al servicio de urgencias posterior a picadura de escorpión. Presentaba parestesias, dolor toracoabdominal y náuseas. Desde el momento del ingreso presentó dolor torácico atípico, dolor abdominal epigástrico de intensidad leve, asociado a náuseas. Se realizó electrocardiograma que no evidenció alteraciones. La troponina fue elevada, por lo que se llevó a cuidado intensivo y se inició manejo antiisquémico, corroborando posteriormente en la angiografía una disección coronaria tipo 1 en el ramus intermedio como causante de su evento coronario. El paciente recibió un vial de suero antiescorpiónico en primer nivel de atención y posteriormente se indicó manejo con betabloqueante, antiagregación con ácido acetilsalicílico y clopidogrel, con disminución progresiva de sus síntomas. Es egresado asintomático. Se reporta un caso de infarto agudo de miocardio tipo 2 por disección coronaria posterior a una picadura de escorpión, del cual no hay casos reportados previamente en el mundo.

Abstract A 44-year-old man was admitted to the emergency department after a scorpion sting. He presented paresthesia, thoracoabdominal pain and nausea. From the moment of admission, he presented atypical chest pain, epigastric abdominal pain of mild intensity, associated with nausea. An ECG was taken that did not show alterations, troponin was elevated, he was admitted to intensive care unit, management was initiated, subsequently corroborating in the angiography, a type 1 coronary artery dissection in the intermediate ramus as the cause of coronary event. The patient received a vial of antiscorpionic serum in the first level of care, later treatment with beta-blocker, antiaggregation with acetylsalicylic acid and clopidogrel was indicated, with progressive reduction of his symptoms. He is an asymptomatic graduate. A case of type 2 acute myocardial infarction due to coronary dissection after a scorpion sting is reported, there are no previously reported cases in the world.

Alteración de la función pulmonar en vendedores informales de gasolina expuestos a sus vapores en Maicao, Colombia

Objetivo: Determinar los efectos de la exposición a vapores de gasolina sobre la función pulmonar en vendedores informales. Material y métodos: Estudio descriptivo de corte transversal realizado en expendedores informales de gasolina expuestos a sus vapores en el municipio de Maicao, Colombia. Se registraron datos sociodemográficos, se evaluó la función pulmonar por medio de espirometría, oximetría de pulso y, evaluación de la exposición a biomasa. Resultados: Se evaluaron 74 pacientes. El 87,8% eran de sexo masculino, encontrándose principalmente entre los 18 - 40 años (71,6%). El 21,6% (n=16) de la población reportó tener afecciones respiratorias, el 59,4% obtuvo un VEF1 <80% predicho, el 68,9% un FVC <80% predicho y, el 32,4% un VEF1/FVC <70% predicho. De aquellos que tuvieron espirometría anormal (n=45), el 62,2% reportó tener un tiempo de labor ≥ 5 años. Los síntomas reportados con mayor frecuencia fueron disfonía (14,8%), conjuntivitis (14,8%), epigastralgia (10,8%) y cefalea (9,45%). No se encontraron diferencias estadísticamente significativas entre la alteración de la espirometría y antecedentes, saturación de oxígeno medida y presencia de afección respiratoria. Conclusión: Este estudio encontró que un porcentaje representativo de vendedores informales de gasolina expuestos a vapores de combustibles en la frontera colombo-venezolana, presentaron alteración en la función pulmonar comprobado por espirometría anormal y, algunos reportaron sintomatología y afección respiratoria. Estos, son principalmente hombres, adultos jóvenes, con nivel socioeconómico y educacional bajo y, expuestos a diario de forma prolongada y por varios años, a gases derivados del manejo de combustibles fósiles.

SUMMARY Objective: To determine the effects of fuel vapor exposure on pulmonary function among informal sellers. Methods: Cross-sectional study carried-out among informal fuel sellers in Maicao, Colombia. Sociodemographic data were gathered as well as pulmonary function by spirometry, pulse oximetry and evaluation of biomass exposure. Results: 74 patients were evaluated; 87.8% were males, 71.6% of them had between 18 to 40 years of age; 21.6% (n=16) reported pulmonary diseases; 59.4% had a predicted FEV1 <80%; 68.9% had a predicted FVC <80% and 32.4% had a predicted FEV1/FVC < 70%. Among those who had abnormal spirometry, (n=45) 62.2% reported to had worked ≥5 years. The most common reported symptoms were dysphonia (14.8%), conjunctivitis (14.8), epigastric pain (10.8) and headache (9.45%). No statistically significant differences were found between spirometry alterations and history of p pulmonary diseases, mean oxygen saturations and presence of a respiratory disease. Conclusions: This study demonstrates that a significant proportion of informal fuel sellers exposed to fuel vapors in the Colombian-Venezuelan border had derangement of the pulmonary function measured by spirometry and that some of them reported symptoms and respiratory disease. Young male adults of low socioeconomic and educational levels with prolonged exposure to fuel vapors are mostly affected.

Implementation of Competency-based Medical Education in Forensic Medicine and Toxicology in Indian Medical Education — A Viewpoint on Challenges and Way Forward

The changing disease burden, living conditions and anticipations of end-users in health care have resulted in the decision of regulatory bodies in the Indian medical education system to shift the MBBS curriculum from Traditional to Competency-Based Medical Education (CBME).The efforts taken by the National Medical Commission (NMC) erstwhile Medical Council of India (MCI) to successful implementation of the herculean task of shifting curriculum are praiseworthy. MCI initiated a National Faculty Development Programme (FDP) in 2009 in all medical colleges under its ambit.MCI started with five regional centres, which now expanded to 22 centres, out of which 12 are regional centres, and 10 are advanced nodal centres. Nearly 44932 faculties were trained till December 2018. Despite all the advantages of CBME & the efforts taken up by governing bodies, there are many challenges. Some are common for all subjects, but few are unique or specific to a subject. This article views the possible challenges and the way forward for the successful implementation of CBME in Forensic Medicine and Toxicology.

Estudio retrospectivo de pacientes intoxicados admitidos en la unidad de cuidados intensivos pediátricos de un hospital en Chile / Retrospective study of poisoned patients admitted to a hospital's pediatric intensive care unit in Chile

Introducción. Las intoxicaciones pediátricas son un problema de salud pública a nivel mundial. El objetivo de este estudio fue caracterizar las intoxicaciones pediátricas que fueron atendidas en la unidad de cuidados intensivos pediátricos (UCIP) de un hospital en Chile. Población y métodos. Se revisaron las fichas clínicas de pacientes diagnosticados con intoxicación e ingresados a la UCIP entre los años 2013 y 2017. Resultados. Un total de 105 casos fueron identificados, lo que representa un 3 % del total de ingresos registrados en el período estudiado. La mediana de edad de los pacientes resultó ser de 10 años. El 73,3 % de los casos correspondieron a pacientes de sexo femenino. El 51 % de los casos se asociaron a intoxicaciones intencionales y el 83 % fue causado por exposición a medicamentos. Los medicamentos identificados con mayor frecuencia fueron los antidepresivos (11,2 %), analgésicos no esteroides (10,7 %). La ingesta fue la vía de exposición más común (93 %). El promedio de estadía de los pacientes en UCIP fue de 1,3 días. Dos pacientes ingresaron en la UCI: uno requirió intubación y otro hemodiálisis. Se determinaron relaciones estadísticamente significativas entre el sexo del paciente y la circunstancia de exposición, y entre la condición psiquiátrica del paciente y el número de sustancias tóxicas ingeridas. Conclusión. La mayoría de las intoxicaciones atendidas en la UCIP fueron intencionales y correspondieron a pacientes de sexo femenino, a quienes se les asoció alguna patología psiquiátrica. Los grupos de medicamentos identificados con mayor frecuencia fueron los antidepresivos y los antiinflamatorios no esteroides.

Introduction. Pediatric poisoning is a public health problem worldwide. The objective of this study was to establish the characteristics of pediatric cases of poisoning seen at the pediatric intensive care unit (PICU) of a hospital in Chile. Population and methods. The medical records of patients diagnosed with poisoning and admitted to the PICU between 2013 and 2017 were reviewed. Results. A total of 105 cases were identified, who account for 3% of all admissions recorded in the study period. Patients' median age was 10 years. In total, 73.3% of cases were female patients; 51% of cases were associated with intentional poisoning; and 83% were caused by drug exposure. The most common drugs identified were antidepressants (11.2%) and non-steroidal anti-inflammatory drugs (10.7%). Intake was the most frequent route of exposure (93%). The average length of stay in the PICU was 1.3 days. One patient required intubation and another required hemodialysis in the PICU. Statistically significant relationships were established between patient sex and the circumstance of exposure and between the patient's psychiatric condition and the number of toxic substances ingested. Conclusion. Most poisoning cases seen at the PICU were intentional and occurred in female patients, who had a psychiatric condition. The most common drugs identified were antidepressants and non-steroidal antiinflammatory drugs.

Caracterización de las intoxicaciones agudas en edad pediátrica en Sancti Spíritus, 2014-2018

RESUMEN Fundamento: las intoxicaciones agudas en niños constituyen una emergencia médica grave y son consideradas un problema de salud pública creciente a nivel mundial. Objetivo: caracterizar las intoxicaciones agudas en pacientes con ingreso en hospital pediátrico de la provincia Sancti Spíritus en el período 2014-2018. Métodos: se realizó un estudio descriptivo de corte transversal en el período 2014-2018. La información se obtuvo a través de la revisión de todas las historias clínicas de los pacientes ingresados. Se analizaron las variables edad, sexo, tipo de intoxicación circunstancial ya sea intencional o no, lugar de ocurrencia, vías de exposición, estadía hospitalaria y agente responsable. Se calcularon frecuencias absolutas y relativas. Resultados: predominaron las intoxicaciones accidentales sobre las voluntarias, ambas con tendencia al aumento. Las niñas presentaron el mayor porcentaje, por causa intencional a partir de los 11 años; los varones prevalecieron en el rango de 1 a 5 años por causa accidental. Los medicamentos (66,7 %) fueron los agentes causales más involucrados en ambos tipos de intoxicaciones, la vía digestiva fue la más frecuentemente observada, representativa de un 95,6 %. El 80,6 % de los casos ocurrió en el hogar y presentaron una estadía hospitalaria corta, con tres días o menos en la mayoría de ellas. Conclusiones: las intoxicaciones exógenas en niños son causa de morbilidad en la provincia de Sancti Spíritus, por lo que es de vital importancia dar seguimiento a los resultados obtenidos en esta investigación, tales como el índice de intoxicación por psicofármacos.

ABSTRACT Background: acute poisoning in children is a serious medical emergency and is considered a growing public health problem worldwide. Objective: to characterize acute intoxications in patients admitted to a pediatric hospital in Sancti Spíritus province from 2014 to 2018. Methods: a descriptive cross-sectional study was carried out from 2014 to 2018. The information was obtained through the review of all the medical records of the admitted patients. The variables age, sex, type of circumstantial poisoning, whether intentional or not, place of occurrence; routes of exposure, hospital stay and responsible agent were analyzed. Absolute and relative frequencies were calculated. Results: accidental poisonings prevailed over voluntary poisonings, both with a tendency to increase. Girls presented the highest percentage, due to intentional causes from 11 years old; boys prevailed in the range of 1 to 5 years due to accidental causes. Medications (66.7%) were the causal agents most involved in both types of poisoning, the digestive tract was the most frequently observed, representing 95.6%. 80.6% of the cases occurred at home and presented a short hospital stay, with three days or less in most of them. Conclusions: exogenous intoxications in children are a cause of morbidity in the Sancti Spíritus province, so it is vitally important to follow up on the results obtained in this research, such as the rate of intoxication by psychotropic drugs.

Effects of subchronic inhalation exposure to an organophosphorus insecticide compound containing dichlorvos on wistar rats' otoacoustic emissions / Efeitos da exposição inalatória subcrônica a um inseticida organofosforado contendo diclorvos nas emissões otoacústicas de ratos Wistar

Abstract Introduction Considering that previous studies suggest that pesticides may cause hearing disorders in humans, as well as the lack of studies proving the specific mechanisms of injury and the difficulty of separating concomitant etiological factors of the hearing damage, such as noise and vibration, it is important to develop studies using animal models to elucidate the effects of exposure to those substances isolated from other hearing damage etiologies. Objective To evaluate if the exposure to a dichlorvos based organophosphorus insecticide may induce ototoxicity. Methods 36 male Wistar rats were assigned to 3 groups (12 rats/group): control (exposed to water), positive control (treated with cisplatin to induce hearing damage) and experimental (exposed to dichlorvos based organophosphorus insecticide). The amplitude of distortion product otoacoustic emissions in the frequencies of 4, 6, 8, 10 and 12 kHz was evaluated before and after exposure, as well as systemic toxicity signs, body mass gain and plasma cholinesterase. Open field and plus maze tests were performed in 24 rats: experimental (n = 8), control (n = 8) and positive control group (n = 8 introduced new rats to induce anxiolytic activity) to evaluate the locomotor activity and anxiety, respectively. Results There was no significant change in body mass gain and plasma cholinesterase in the dichlorvos based organophosphorus insecticide group, however, the animals showed transient piloerection, depression and dyspnea during exposure. The behavior was not affected in any group. The frequencies of 8 and 10 kHz were significantly affected bilaterally in the insecticide group, which also showed a significant difference of the control in 10 kHz on the right and 8 and 10 kHz on the left ear. Conclusion Subchronic inhalation exposure to dichlorvos based organophosphorus insecticide induced ototoxicity in the cochlear function of rats without relevant systemic toxicity.

Resumo Introdução Considerando que estudos anteriores sugerem que pesticidas podem causar distúrbios auditivos em humanos, além da falta de estudos que comprovem os mecanismos específicos de lesão e a dificuldade em separar fatores etiológicos concomitantes dos danos auditivos, como ruído e vibração, é importante desenvolver estudos que usem modelos animais para elucidar os efeitos da exposição a substâncias isoladas de outras etiologias de danos auditivos. Objetivo Avaliar se a exposição a um inseticida organofosforado baseado em diclorvos pode induzir ototoxicidade. Método Foram divididos em 3 grupos 36 ratos Wistar machos (12 ratos/grupo): controle (exposto à água), controle positivo (tratado com cisplatina para induzir dano auditivo) e experimental (exposto ao inseticida). A amplitude das emissões otoacústicas por produto de distorção nas frequências de 4, 6, 8, 10 e 12 kHz foi avaliada antes e após a exposição, bem como sinais de toxicidade sistêmica, ganho de massa corporal e colinesterase plasmática. Os testes Open Field e Plus Maze foram feitos em 24 ratos: experimental (n = 8), controle (n = 8) e grupo controle positivo (n = 8, introduziu novos ratos para induzir atividade ansiolítica) para avaliar a atividade locomotora e a ansiedade, respectivamente. Resultados Não houve alteração significativa no ganho de massa corporal e colinesterase plasmática no grupo experimental; entretanto, os animais apresentaram piloereção transitória, depressão e dispneia durante a exposição. O comportamento não foi afetado em qualquer grupo. As frequências de 8 e 10 kHz foram significativamente afetadas bilateralmente no grupo exposto ao inseticida, o qual também mostrou uma diferença significativa do controle em 10 kHz na orelha direita e 8 e 10 kHz na orelha esquerda. Conclusão A exposição subcrônica inalatória de inseticida organofosforado baseado em diclorvos induziu ototoxicidade na função coclear de ratos sem toxicidade sistêmica relevante.

Detection of Synthetic Cannabinoid CUMYL-PEGACLONE in E-Cigarette Oil and Hair / 法医学杂志

OBJECTIVES@#To establish a combined high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) method to detect the synthetic cannabinoid CUMYL-PEGACLONE in e-cigarette oil and hair.@*METHODS@#HPLC-MS/MS and GC-MS were used to establish the detection method of CUMYL-PEGACLONE, and the hair of drug-involved persons and the seized e-cigarette oil were detected.@*RESULTS@#The main mass spectrometry characteristic ions m/z of CUMYL-PEGACLONE measured by GC-MS were 91, 179, 197, 254 and 372. CUMYL-PEGACLONE had a good linear relationship in the mass concentration range of 2-50 ng/mL, and the linear correlation coefficient (r) was greater than 0.99. The limit of detection (LOD) of CUMYL-PEGACLONE in hair was 0.01 ng/mg, and the limit of quantitation (LOQ) was 0.02 ng/mg. The LOD of CUMYL-PEGACLONE in e-cigarette oil was 1 ng/mg, and the LOQ was 2 ng/mg. The average recoveries of CUMYL-PEGACLONE under the attempt at high, intermediate and low levels in blank human hair and e-cigarette oil matrix were 98.2%-132.4% and 93.5%-110.6%, and the intraday and intraday precision were 1.2%-12.9% and 0.7%-2.9%. CUMYL-PEGACLONE was detected in the hair of 15 drug-involved persons. Except for 1 person who was lower than LOQ, the concentration of CUMYL-PEGACLONE in the hair of other 14 persons was 0.035-0.563 ng/mg. The mass fraction of CUMYL-PEGACLONE in 2 e-cigarette oil were 0.17% and 0.21%, respectively.@*CONCLUSIONS@#The established HPLC-MS/MS and GC-MS methods are applied to the detection of HPLC-MS/MS in drug-related cases, which provides strong evidence support for the handling authority to quickly investigate these cases, and also provides a reference for the identification of such substances in future.

Strategies for Collection and Analysis of Samples in Simple Asphyxiant Gas Acute Poisoning Death Cases / 法医学杂志

At present, the death cases of simple asphyxiant gas acute poisoning are increasing sharply. Common asphyxiant gases in death cases include nitrogen, helium, carbon dioxide, methane, propane, laughing gas, etc. Simple asphyxiant gas has no affinity for biological matrices and escapes quickly, which puts forward new requirements for autopsy procedures, selection and collection of samples, laboratory analysis and identification. This paper reviews the research and development process of death cases caused by simple asphyxiant gas acute poisoning and put forwards the collection and analysis strategy of the samples in such cases. The most valuable biological samples in such cases should be lung tissues associated with the airways, followed by brain tissue and cardiac blood. Gaseous samples from the esophageal cavity, tracheal cavity, pulmonary bronchi, gastric and cardiac areas are also recommended as valuable samples. In the case of postmortem examination, the gas should be injected into gas sample bag directly. Biological materials such as tissue and blood should be directly sealed in head-space vials and analyzed by using the headspace gas chromatography-mass spectrometry.