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.

Application of brain organoids in environmental toxicology / 环境与职业医学

Since the 19th century, the emergence of model systems has helped researchers further understand cellular signaling pathways, identify potential drug targets, and conduct environmental toxicological studies. Exogenous chemicals, such as pollutants, drugs, and industrial chemicals, may affect brain biological processes and functions and eventually lead to neurological diseases. However, the brain is a complex and well-organized human organ, which is fundamentally different from any existing model system. Animal models may not be able to completely simulate the human brain in testing the neurotoxicity of environmental pollutants due to species differences. Human brain organoids, generated from human pluripotent stem cells, are emerging model systems for neurotoxicological research in line with the real situation of human body at the level of genome, transcriptome, and metabolome, and provide an effective platform for testing neurotoxicity of environmental toxins. We reviewed the latest development of brain organoids technology and its application in the evaluation of environmental neurotoxins, and provided new insights into the application of brain organoids in environmental neurotoxicology.

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.

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.

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.

Mechanism of Sophorae tonkinensis radix et rhizome-induced nephrotoxicity in rats based on network toxicology and experimental validation / 中国药理学通报

Aim To investigate the mechanism of Sophorae tonkinensis radix et rhizome (ST) induced nephrotoxicity based on network toxicology and experimental verification. Methods Through network toxicology the target of toxic components of ST was predicted, nephrotoxicity-related target genes were located, the intersection of targets was taken, the STRING platform was imported to map the target protein interactions, MetaScape database was used for GO and KEGG analysis, BioGPS database for screening the key expressed genes in rat nephrotoxicity and the component-target-pathway network was constructed. The mechanism of ST induced nephrotoxicity was verified through animal experiments, and qRT-PCR was applied to detect mRNA expression level of key genes in kidney tissue. Results Twenty toxic components of ST were screened from network toxicology, mainly including matrine, sophoridine, maackiain. A total of 135 targets were involved, and HSP90AA1, SRC, MAPK1, MAPK3, AKT1 were the main targets. A total of 169 related signaling pathways were yielded by KEGG analysis, and the mechanism of nephrotoxicity might be related to cancer pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, MAPK signaling pathway. PPARA, RAF1, MAP2K1, SRC, AKT1 and MAPK3 were screened from BioGPS database. The results of animal experiments showed that BUN and SCr level increased (P <0. 01) in rats with high-dose group, and the kidney tissue was significantly damaged. qRT-PCR results indicated that the expression of PPARA, RAF1, MAP2K1, MAPK3 mRNA increased, the expression of AKT1 mRNA decreased in the high-dose group of ST (P <0. 05). Conclusions The mechanism of Sophorae tonkinensis radix et rhizome induced nephrotoxicity is found to be related to the combined action of multiple components, multiple targets and multiple pathways, which also provides a theoretical basis for the in-depth exploration of the toxicology.

The neuroprotective effect of traditional Chinese medicinal plants-A critical review

Neurodegenerative and neuropsychiatric diseases are increasingly affecting individuals' quality of life, thus increasing their cost to social and health systems. These diseases have overlapping mechanisms, such as oxidative stress, protein aggregation, neuroinflammation, neurotransmission impairment, mitochondrial dysfunction, and excitotoxicity. Currently, there is no cure for neurodegenerative diseases, and the available therapies have adverse effects and low efficacy. For neuropsychiatric disorders, such as depression, the current therapies are not adequate to one-third of the patients, the so-called treatment-resistant patients. So, searching for new treatments is fundamental. Medicinal plants appear as a strong alternative and complement towards new treatment protocols, as they have been used for health purposes for thousands of years. Thus, the main goal of this review is to revisit the neuroprotective potential of some of the most predominant medicinal plants (and one fungus) used in traditional Chinese medicine (TCM), focusing on their proven mechanisms of action and their chemical compositions, to give clues on how they can be useful against neurodegeneration progression.

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.

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.

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.

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.

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.

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.

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.

Qualitative and Quantitative Analysis of Five Indoles or Indazole Amide Synthetic Cannabinoids in Suspected E-Cigarette Oil by GC-MS / 法医学杂志

OBJECTIVES@#To establish the GC-MS qualitative and quantitative analysis methods for the synthetic cannabinoids, its main matrix and additives in suspicious electronic cigarette (e-cigarette) oil samples.@*METHODS@#The e-cigarette oil samples were analyzed by GC-MS after diluted with methanol. Synthetic cannabinoids, its main matrix and additives in e-cigarette oil samples were qualitatively analyzed by the characteristic fragment ions and retention time. The synthetic cannabinoids were quantitatively analyzed by using the selective ion monitoring mode.@*RESULTS@#The linear range of each compound in GC-MS quantitative method was 0.025-1 mg/mL, the matrix recovery rate was 94%-103%, the intra-day precision relative standard deviations (RSD) was less than 2.5%, and inter-day precision RSD was less than 4.0%. Five indoles or indazole amide synthetic cannabinoids were detected in 25 e-cigarette samples. The main matrixes of e-cigarette samples were propylene glycol and glycerol. Additives such as N,2,3-trimethyl-2-isopropyl butanamide (WS-23), glycerol triacetate and nicotine were detected in some samples. The content range of synthetic cannabinoids in 25 e-cigarette samples was 0.05%-2.74%.@*CONCLUSIONS@#The GC-MS method for synthesizing cannabinoid, matrix and additive in e-cigarette oil samples has good selectivity, high resolution, low detection limit, and can be used for simultaneous qualitative and quantitative analysis of multiple components; The explored fragment ion fragmentation mechanism of the electron bombardment ion source of indole or indoxamide compounds helps to identify such substances or other compounds with similar structures in cases.

Detection and Analysis of Blood Dexmedetomidine in Drug-Facilitated Cases / 法医学杂志

OBJECTIVES@#To establish a simple and rapid qualitative and quantitative detection method of dexmedetomidine in blood.@*METHODS@#Blood was separated on the Allure PFP Propyl liquid chromatography column with isocratic elution after it was precipitated by acetonitrile and filtered. Qualitative and quantitative analysis of dexmedetomidine was performed using positive ion scan mode and multi-reaction monitoring mode.@*RESULTS@#The limit of detection of dexmedetomidine in blood was 0.2 ng/mL and the limit of quantification was 0.5 ng/mL. The linearity of the method was good in the range of 0.5-1 000 ng/mL, and the correlation coefficient was greater than 0.99. The accuracy of the method was 90.34%-112.67% and the extraction recovery was 50.05%-91.08%, with no significant matrix effect.@*CONCLUSIONS@#This method is simple, selective and suitable for the qualitative and quantitative analysis of dexmedetomidine in blood, which can provide a reference for drug-facilitated cases involving dexmedetomidine.

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.