Data mining and analysis of oxaliplatin-related adverse events of nervous system / 中国药房

OBJECTIVE To provide reference for clinically safe drug use by mining oxaliplatin-related adverse drug events （ADE） of the nervous system. METHODS Oxaliplatin-related neurologic ADE data reported by the FDA adverse event reporting system （FAERS） between January 1st， 2004 and December 31st， 2022 were collected. The reporting odds ratio and proportional reporting ratio were used for data mining. The data were classified statistically by using systematic organ classification， high-level group term （HLGT） and preferred term （PT） in the MedDRA （version 26.0）. RESULTS A total of 7 266 cases of oxaliplatin- related ADE， which were classified as various neurological， were retrieved， and 100 PT were identified. Of these， fifty-seven PT were unspecified adverse reaction signals in the manual. Among these reports， males （46.85%） were more than females （42.98%）， the age of patients was 45-＜75 years （65.22%）， the number of reports was highest in Italy （16.32%）， and the severe type was hospitalization or prolonged hospitalization （38.16%）. The top 5 PT reports in the list of case number were peripheral neuropathy， paresthesia， neurotoxicity， loss of consciousness and dysarthria. The top 5 PT reports in the list of signal intensities were cold- induced paresthesia， neuromuscular rigidity， acute polyneuropathy， neuronal neuropathy， axonal and demyelinating polyneuropathy. A total of 13 HLGT were involved， with neurological diseases （not classified separately） having the highest number of signals （29）. CONCLUSIONS When using oxaliplatin in clinical practice， it is not only necessary to monitor the high incidence of acute and chronic peripheral neuropathy， but also to pay attention to the patient’s consciousness state and neurological symptoms. We should pay attention to the rare types of adverse reactions， such as guillain-barre syndrome， Lhermitte sign， posterior reversible encephalopathy syndrome， and hyperammoniacal encephalopathy， so as to ensure the safety of medication.

Neurotoxidad inducida por ifosfamida / Ifosfamide-induced neurotoxicity

Introducción: La ifosfamida es un agente alquilante utilizado para el tratamiento de enfermedades oncohematológicas. Entre sus eventos adversos agudos se encuentra la neurotoxicidad. Esta puede presentarse desde el inicio de la infusión hasta tres días después. El tratamiento consiste en suspender la administración y asegurar una adecuada hidratación. Objetivo: Describir eventos neurológicos asociados al uso de ifosfamida en pacientes pediátricos con enfermedades oncohematológicas. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo y transversal. Los datos se obtuvieron de historias clínicas de pacientes internados en el Hospital Garrahan que infundieron ifosfamida y desarrollaron síntomas neurológicos. Se analizaron edad, diagnóstico de base, dosis de ifosfamida, síntomas neurológicos y su relación con la infusión, tratamiento instaurado, exámenes complementarios y posibles factores de riesgo asociados. Resultados: Se registraron un total de catorce eventos neurológicos en doce pacientes, sin diferencia de sexo, con una mediana de edad de 9,5 años. La enfermedad de base más prevalente fue osteosarcoma. Las convulsiones fueron el síntoma más frecuente (50%), seguido de somnolencia y paresias. La combinación de ifosfamida y etopósido con/sin carboplatino se asoció en un 36% cada uno. El 64% desarrolló neurotoxicidad dentro de las primeras cuatro horas. Ningún paciente presentó alteraciones en los exámenes complementarios. Todos presentaron recuperación ad integrum. Conclusión: Este estudio brinda información acerca del tiempo de aparición de esta complicación, lo cual facilitará su detección precoz y tratamiento oportuno (AU)

Introduction: Ifosfamide is an alkylating agent used for the treatment of cancer. Among its acute adverse events is neurotoxicity. This can occur from the beginning of the infusion up to three days afterwards. Treatment consists of discontinuing administration and ensuring adequate hydration. Objective: To describe neurological events associated with the use of ifosfamide in children with cancer. Materials and methods: Observational, descriptive, retrospective, and cross-sectional study. Data were obtained from clinical records of patients admitted to the Garrahan Hospital who received ifosfamide infusion and developed neurological symptoms. Age, baseline diagnosis, ifosfamide dose, neurological symptoms and their relationship with the infusion, treatment, complementary tests, and possible associated risk factors were analyzed. Results: A total of fourteen neurological events were recorded in twelve patients, without difference in sex and with a median age of 9.5 years. The most prevalent underlying disease was osteosarcoma. Seizures were the most frequent symptom (50%), followed by drowsiness and paresis. The combination of ifosfamide and etoposide with/without carboplatin was associated in 36% each. Sixty-four percent developed neurotoxicity within the first four hours. None of the patients presented with abnormalities in the complementary examinations. All recovered ad integrum. Conclusion: This study provides information about the time of onset of this complication, which will facilitate its early detection and timely treatment (AU)

Encefalitis por inhibidores del punto de control inmunitario / Encephalitis associated to immune checkpoint inhibitors

Resumen Los inhibidores del punto de control inmunitario han demostrado mejorar el pronóstico de múltiples enfer medades oncológicas. Recientemente se han reportado eventos adversos relacionados a la inmunoterapia. La to xicidad neurológica es poco frecuente. Se presenta el caso de un paciente con encefalitis relacionada con inhibido res del punto de control inmunitario.

Abstract Immune checkpoint inhibitors have been shown to improve the prognosis of multiple oncological diseases. Recently, adverse events related to immunotherapy have been reported. Neurologic toxicity is infrequent. We pre sent the case of a patient with encephalitis associated to immune checkpoint inhibitors.

Lead Toxicity in Children: Health Effects, Policies and Recommendations

Lead is a dangerous element that exists naturally in the Earth's crust. Any kind of lead causes a detrimental response in the human body. It is discharged into the environment during the manufacturing of batteries, foundries, ammunition, lead paint, water pipes, and other manufactured goods. It can enter the body through a variety of pathways, including those in the air, water, soil, food, and dust. Concern is raised since there is no amount of lead that is safe for the human body. The problem persists despite several prevention measures that the state and the federal governments have put in place. This review assesses the effects of lead exposure on children as well as suggested solutions to the issue.

Successful stem cell transplantation after nelarabine, pegylated asparaginase, vincristine, doxorubicin, and prednisone in refractory early T-cell precursor acute lymphoblastic leukemia: A case report

Early T-cell precursor Acute Lymphoblastic Leukemia (ALL) has a dismal prognosis. Nelarabine is a purine nucleoside analog that increases the apoptosis rate in T-cell lymphoblasts. We present a 30-year-old patient diagnosed with T-cell ALL. He was a high-risk patient because of an early precursor phenotype and a complex karyotype that had been refractory to three previous lines of treatment. He started a course of nelarabine (1500 mg/m for three days), pegylated-asparaginase, doxorubicin, vincristine, and prednisone (Nelarabine Peg-Asp AdmVP). He reached complete remission and received an allogeneic sibling hematopoietic stem cell transplant with fludarabine, total body irradiation, and cyclophosphamide as the conditioning regimen. He developed a pulmonary mycosis, which resolved, and grade-2 neurotoxicity in his upper and lower limbs. He was discharged after 40 days and to date remains with 23 months of complete remission. The Nelarabine Peg-Asp AdmVP regimen seems to be effective and safe. Further research is needed to establish it as an induction treatment in refractory early T-cell precursor acute lymphoblastic leucemia.

Neurotoxicidad subaguda por metotrexato en pacientes con enfermedad oncohematológica. Reporte de tres casos / Subacute methotrexate neurotoxicity in patients with oncohematological disease. A report of 3 cases

El metotrexato es un fármaco análogo del ácido fólico ampliamente utilizado en el tratamiento de enfermedades autoinmunes, leucemias y linfomas. Su uso puede ocasionar la aparición de múltiples efectos adversos entre los que se encuentran aquellos relacionados con la presencia de toxicidad neurológica, que puede presentarse de forma aguda, subaguda o crónica. La neurotoxicidad subaguda es aquella que ocurre típicamente entre los 2 y los 14 días posteriores a la administración y puede manifestarse con una amplia gama de síntomas neurológicos. En la mayoría de los casos, no recurre con futuras exposiciones al medicamento. Presentamos tres casos de neurotoxicidad subaguda por metotrexato con manifestaciones clínicas diferentes en pacientes oncohematológicos que se internaron entre los años 2018 y 2020. Dos de ellos presentaron recurrencia frente a la nueva administración del fármaco y todos evidenciaron lesiones en resonancia magnética nuclear.

Methotrexate is a folic acid analogue widely used in the treatment of autoimmune diseases, leukemias, and lymphomas. Methotrexate use may cause multiple adverse effects, including those related to the presence of neurological toxicity, which may be acute, subacute, or chronic. Subacute neurotoxicity typically occurs between 2 and 14 days after administration and may present as a wide range of neurological symptoms. In most cases, it does not recur with future exposures to the drug. Here we describe 3 cases of subacute methotrexate neurotoxicity with different clinical manifestations in patients with oncohematological disease who were hospitalized between 2018 and 2020. Two of them showed recurrence with a new drug administration. Lesions were observed in the magnetic resonance imaging tests of all of them.

Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry / 药物分析学报

Aconitine,a common and main toxic component of Aconitum,is toxic to the central nervous system.However,the mechanism of aconitine neurotoxicity is not yet clear.In this work,we had the hypothesis that excitatory amino acids can trigger excitotoxicity as a pointcut to explore the mechanism of neurotoxicity induced by aconitine.HT22 cells were simulated by aconitine and the changes of target cell metabolites were real-time online investigated based on a microfluidic chip-mass spectrometry system.Meanwhile,to confirm the metabolic mechanism of aconitine toxicity on HT22 cells,the levels of lactate dehydrogenase,intracellular Ca2+,reactive oxygen species,glutathione and superoxide dismutase,and ratio of Bax/Bcl-2 protein were detected by molecular biotechnology.Integration of the detected results revealed that neurotoxicity induced by aconitine was associated with the process of excitotoxicity caused by glutamic acid and aspartic acid,which was followed by the accumulation of lactic acid and reduction of glucose.The surge of extracellular glutamic acid could further lead to a series of cascade reactions including intracellular Ca2+overload and oxidative stress,and eventually result in cell apoptosis.In general,we illustrated a new mechanism of aconitine neurotoxicity and presented a novel analysis strategy that real-time online monitoring of cell metabolites can provide a new approach to mechanism analysis.

Research progress on material basis for neurotoxicity of traditional Chinese medicine and its mechanism / 中国药房

In recent years， neurotoxicity caused by traditional Chinese medicine （TCM） has frequently occurred and has become one of the important factors restricting the development and application of TCM. TCM contains active components and its dosage-effect relationship is the key to determine its pharmacological activity and toxic effects. Among them， the endogenous toxic components include alkaloids， glycosides， diterpenoids， animal and plant toxic proteins and heavy metals， and so on； exogenous toxic components mainly refer to some harmful elements and pesticide residues during the cultivation， processing， transportation and storage of medicinal materials that are not synthesized by themselves. Effect on the processes such as oxidative stress， inflammation， ion exchange， and energy metabolism may be important mechanisms of TCM-induced neurotoxicity. Neural cells， myelin cells， axons and neurotransmitter systems are common targets of TCM-induced neurotoxicity. In the future， we can use modern research methods and big data mining means to establish a safety evaluation mode of “toxic symptoms-poisoning dose-toxic original agent-detoxification scheme” with the basic component group of toxic substances as the core， so as to provide support for development and clinical intervention of neurotoxic traditional Chinese medicine.

Advances on mechanisms of regulated cell death in neurotoxicity of aluminum / 环境与职业医学

Aluminum is a light metal which is rich in the earth's crust and widely used. Recently, the adverse health effects of environmental and occupational aluminum exposure on human have attracted more and more attention. Aluminum exposure has toxic effects on the central nervous system and is believed to be closely related to the development and progression of Alzheimer's disease. The neurotoxic mechanism of aluminum is complex, especially the role of regulated cell death (RCD) in aluminum-induced neuronal death remains to be further studied. RCD refers to all modes of cell death regulated by multiple intracellular signal transduction pathways under physiological and pathological conditions, including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis. This review summarized the morphological characteristics and mechanisms of each RCD mode in the process of aluminum-induced neuronal death, and discussed the relationship and transformation between different RCD modes, providing a new scientific basis for future studies on the treatment and intervention of neurotoxicity induced by aluminum exposure.

Relationship of cytokines to adverse reaction of chimeric antigen receptor T cell immunotherapy and targeted drug intervention / 中国生物制品学杂志

@#Chimeric antigen receptor T cell(CAR-T)immunotherapy is the most potential adoptive immunotherapy for malignant tumors,which needs no antigen presenting cells(APC)and is not limited by major histocompatibiliy complex(MHC). CAR-T immunotherapy not only recognizes and kills tumor cells directly,but also forms memory T cells and establishs long-term anti-tumor mechanism,of which the effect in leukemia,multiple myeloma and other non-solid tumors as well as the great potential in solid tumors have been widely verified. However,a variety of adverse reactions such as cytokine release syndrome(CRS),neurotoxicity(NT)and miss target effect are produced during CAR-T immunotherapy,of which the occurrence of CRS and NT may be related to the abnormal level of cytokines. Remarkable increase of cytokine level is a major characteristics of CRS. However,the increase of cytokines is neither the root cause nor the only result of CAR-T adverse reaction. CAR-T immunotherapy has a high incidence of adverse reaction which may even endanger the life of patients. Cytokine targeted drugs such as Anakinra and Tocilizumab may decrease the incidence of adverse reaction and improve the prognosis of patients. This paper reviews the correlation of cytokines with CRS and NT in CAR-T immunotherapy and the effect of cytokine targeting drugs,so as to provide a reference for the basic research,quality control and clinical application of CAR-T immunotherapy.

Methamphetamine: Mechanism of Action and Chinese Herbal Medicine Treatment for Its Addiction / 中国结合医学杂志

With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.

Caracterización del uso de emulsiones lipídicas como terapia antidotal en intoxicaciones diferentes a anestésicos locales en un centro de alta complejidad en Medellín / Characterization of the use of lipid emulsions as antidotal therapy in intoxications other than local anesthetics in a high complexity center in Medellin

Introducción. Las emulsiones lipídicas intravenosas (ELI) son unas emulsiones grasas no tóxicas con fosfolípidos, actualmente aprobadas para su uso en el tratamiento de intoxicaciones, específicamente en las producidas por anestésicos locales. El propósito de este estudio es la caracterización del uso de ELI en pacientes mayores de 18 años, que presentaron intoxicación por sustancias y medicamentos diferentes a anestésicos locales, en un hospital de alta complejidad de la ciudad de Medellín, durante el periodo comprendido entre 2015 y 2020. Metodología. Se realizó un estudio descriptivo, retrospectivo, de casos que recibieron ELI como tratamiento para su intoxicación. Se hizo revisión de las historias clínicas de la población objeto de estudio. Se recolectó información acerca de variables sociodemográficas, clínicas y paraclínicas, y de atención. Se hizo análisis univariado de las variables de interés. Resultados. Del total de 1.966 intoxicaciones, se incluyeron 51 (2,6 %) casos de intoxicación por sustancias y medicamentos diferentes a anestésicos locales, que recibieron la terapia con ELI entre 2015 y 2020. La mediana de edad de los participantes fue de 27 años. Un 74,5 % de los participantes presentó intoxicación por medicamentos. El promedio de la dosis de ELI recibida fue de 1.036 mL en 24 horas, dosis inferior a la calculada por kilo de peso que debían recibir, de 1.149 mL en promedio. Un 86,3 % (n=44) de los casos presentaron neurotoxicidad, y 76,5 % (n=39) presentaron cardiotoxicidad. La neurotoxicidad mejoró en el 34,7 % y la cardiotoxicidad en el 59,1 % de los individuos que recibieron terapia con ELI. Conclusión. La aplicación de las ELI se hizo en personas en su mayoría intoxicadas por antipsicóticos, hombres, jóvenes; menos de la mitad tenía compromiso de la ventilación, y hubo mejoría en la cardiotoxicidad y neurotoxicidad. Hubo una diferencia entre la dosis recibida y la que debían recibir ajustada por el peso

Introduction. Intravenous lipid emulsions (IVLE) are non-toxic fatty emulsions with phospholipids, currently approved for use in the treatment of poisoning, specifically those produced by local anesthetics. The purpose of this study is to characterize the use of IVLE in patients over 18 years of age, who presented intoxication by substances and medications other than local anesthetics, in a high complexity hospital in the city of Medellín, during the period between 2015 and 2020. Methodology. A retrospective descriptive study was carried out on cases that received IVLE as a treatment for their poisoning. The clinical records of the study population were reviewed. Information was collected about sociodemographic, clinical and paraclinical variables, and care. Univariate analysis of the variables of interest was performed. Results. Of the total of 1,966 poisonings, 51 (2.6%) cases caused by substances and medications other than local anesthetics, received ELI therapy between 2015 and 2020 and were included in the study. The median age of the participants was 27 years. 74.5% of the participants presented drug poisoning. The average IVLE dose received was 1,036 mL in 24 hours, a lower dose than the one calculated per kilo of weight, which had been on average 1,149 mL. 86.3% (n=44) of the cases presented neurotoxicity, and 76.5% (n=39) presented cardiotoxicity. Neurotoxicity improved in 34.7% and cardiotoxicity in 59.1% of individuals receiving ELI therapy. Conclusion. The application of IVLE was made in people mostly poisoned by antipsychotics, men, young people, less than half had compromised ventilation, and there was improvement in cardiotoxicity and neurotoxicity. There was a difference between the dose received and the one they should have received adjusted for weight

Study of the potential toxicity of adrenaline to neurons, using the SH-SY5Y human cellular model

Abstract Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline (ADR)-induced neurotoxicity, as a model to predict the toxicity of this catecholamine to peripheral nerves. Cells were exposed to several concentrations of ADR (0.1, 0.25, 0.5 and 1mM) and two cytotoxicity assays [lactate dehydrogenase (LDH) release and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction] were performed at several time-points (24, 48, and 96h). The cytotoxicity of ADR was concentration- and time-dependent in both assays, since the lowest concentration tested (0.1mM) also caused significant cytotoxicity at 96h. N-acetyl-cysteine (1mM), a precursor of glutathione synthesis, prevented ADR-induced toxicity elicited by 0.5mM and 0.25mM ADR following a 96-h exposure, while the antioxidant Tiron (100µM) was non-protective. In conclusion, ADR led to mitochondrial distress and ultimately cell death in non-differentiated SH-SY5Y cells, possibly because of ADR oxidation products. The involvement of such processes in the catecholamine-induced peripheral neuropathy requires further analysis.

Research progress on oxaliplatin-induced neurotoxicity in traditional Chinese medicine (TCM) and western medical cognition and prevention and treatment by TCM / 中国中药杂志

Chemotherapy is one of the main options in clinical tumor treatment. Although chemotherapy drugs have a good therapeutic effect, they can also cause a series of adverse reactions, such as neurotoxicity. Chemotherapy-induced neurotoxicity is a dose-limi-ting adverse reaction that significantly affects patients' long-term treatment and quality of life. This article reviewed literature from 2000 to the present on chemotherapy-induced neurotoxicity and found that oxaliplatin was the most frequently used chemotherapy drug. Based on the clinical characteristics of oxaliplatin-induced neurotoxicity, this article summarized the understanding of its pathogenesis from both traditional Chinese medicine(TCM) and western medicine perspectives, discussed the role and mechanism of TCM compounds and monomeric components, and explored the research direction of using cutting-edge biotechnology to reveal the mechanism of oxaliplatin-induced neurotoxicity from a temporal-spatial perspective of intercellular communication and the application prospects of an interdisciplinary model combining TCM pathogenesis, western medicine manifestations, and artificial intelligence in precise intervention decision-making for TCM, aiming to provide research ideas for the prevention and treatment of oxaliplatin-induced neurotoxicity and the development of new drugs.

Stress-another possible mechanism of neurotoxicity in neurodegenerative diseases

Theliteratureassociatesoxidativestresswiththeproductionoffreeradicals,whichleadtoneurodegeneration.Theypresentinnumerablehypotheses,amongwhichareabnormalitiesinthefunctioningofthehypothalamic-pituitary-adrenalaxis,neurotoxiceffectsandneuronaloxidativedamage.ClinicalobservationhasshownthatinneurodegenerativediseasessuchasMultipleSclerosis(MS)andAmyotrophicLateralSclerosis(ALS)thereisareportofprolonged or violent emotionalstressprecedingthesymptoms.Aims:UsingtheCarilloComplexSystemsModel,presentsomepossibilitiesonhowstresscancontributetoneurodegeneration.Methodology:NinecasesofALSandsixcasesofMSwereevaluated,pathologiesalreadyclassifiedasbelongingtosyphilinism.Literaturereviewonstressandneurotoxicitycarriedout.Resultsanddiscussion:Syphilinism is instability with a predominantly intrinsicorigin to the system with a chronic caracter.This diathesis is characterized by a dissipative deficiency, predominantly hepatic, to the processing of certain elements or potentially toxic substances with exogenous origin or endogenous Such non-processed substances are unstable factors in the system, with greater affinity for certain tissues,like the nervous system. Among the toxins, we find alcohol, esters, formaldehyde, aloe, ketones, aldehydes, etc. The final hepatic metabolism of cortisol results in cortic acids and cortol, which use the same enzymatic system as alcohol, and can be considered syphilinic toxins. Ethanol can act directly at the circadian rhythm, disrupting it and generating stressful substances such as cortisol, regardless of an external event, increasing the toxin level. The inflammatory process generated by the production of free radicals and metabolic abnormalities, including the reduction of neuropeptide Y that modulates inflammatory activity in the nervous system, leads to changes that can result in neurodegeneration. Conclusion: Inflammation caused by toxins from prolonged/violent emotional stress can lead to several changes in syphilinic individuals, due to failure in the dissipative process, including neurodegeneration.

Efectos patogénicos de la acrilamida para la salud. Una revisión

RESUMEN En abril de 2002, un grupo de investigadores suecos dio a conocer que algunos alimentos ricos en almidón y pobres en proteínas, sometidos a procesos con temperaturas mayores a 120 °C (fritura, horneado, asado y tostado) contenían el procancerígeno conocido como acrilamida, un "probable carcinógeno para los humanos" -mutágeno de categoría 2 y tóxico para la reproducción de categoría 3 según la Unión Europea-, comportándose como neurotóxico tras exposiciones agudas. La revisión tiene como objetivo mostrar una actualización de los avances en investigaciones sobre la toxicidad de la acrilamida como un aspecto preocupante en el tema alimentario, y exponer los mecanismos de la formación de este compuesto en los alimentos, sus efectos tóxicos, los métodos analíticos usados en su determinación, los niveles detectados en distintos alimentos y estudios recientes sobre su ingesta. Para ello se realizaron búsquedas en las bases de datos PubMed, SciELO, LILACS y ClinicalKey. Los estudios epidemiológicos llevan poco tiempo, y en su mayoría son inconsistentes respecto al cáncer en humanos, no obstante, se complementan con el empleo de biomarcadores, donde se obtienen resultados en cuanto a la toxicidad cancerígena y no cancerígena más fiables, con menor margen de error. Por el momento, la única recomendación para mitigar su exposición es la divulgación sobre los riesgos del consumo excesivo de alimentos fritos, demasiado tostados o procesados, y seguir una dieta equilibrada y saludable.

ABSTRACT In April 2002, a group of Swedish researchers revealed that some foods rich in starch and poor in protein, subjected to processes with temperatures above 120 °C (frying, baking, roasting and toasting) contained the procancerogen known as acrylamide, a "probable carcinogen for human"-mutagen of category 2 and toxic to category 3 reproduction according to European Union-behaving as neurotoxic after acute exposures. The review aims to show an update of the advances in research on the toxicity of acrylamide as a worrying aspect in the food issue, and to expose the mechanisms of formation of this compound in food, its toxic effects, the analytical methods used in its determination, the levels detected in different foods, and recent studies on its intake. For that, searches were conducted in PubMed, SciELO, LILACS and ClinicalKey. Epidemiological studies take a short time, and are mostly inconsistent with respect to cancer in human. However, they are complemented using biomarkers where results are obtained in terms of the most reliable carcinogenic and non-carcinogenic toxicity, with less margins of error. For now, the only recommendation to mitigate exposition is to divulge the risk of excessive consumption of fried, very roasted or processed foods, and to follow an equilibrated and healthy diet.

Compositional and toxicological investigation of pooled venom from farm-raised Naja atra

Background: Naja atra is a venomous snake species medically relevant in China. In the current study, we evaluated the composition and toxicological profile of venom collected from farm-raised N. atra. Methods: Venom was collected from third-generation captive bred N. atra on a snake farm in Hunan Province, China. The venom was analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis and nano-liquid chromatography with electrospray ionization tandem mass spectrometry. In addition, hemolytic activity, median lethal dose, serum biochemical and histopathological parameters were accessed. Results: N. atra venom proteome was dominated by phospholipase A2 (46.5%) and three-finger toxins (41.4 %), and a set of common low relative abundance proteins, including cysteine-rich secretory proteins (4.7%), NGF-beta (2.4%), snake venom metalloproteinase (1.5%), glutathione peroxidase (0.6%), vespryn (0.3%), and 5ʹ-nucleotidases (0.2%) were also found. Furthermore, the venom exhibited direct hemolytic activity, neurotoxicity, myotoxicity, and high lethal potency in mice, with a subcutaneous median lethal dose of 1.02 mg/kg. Histopathological analysis and serum biochemical tests revealed that venom caused acute hepatic, pulmonary and renal injury in mice. Conclusion: This study revealed the composition and toxicity of venom collected from farm-raised N. atra, thereby providing a reference for the analysis of venom samples collected from captive-born venomous snakes in the future.(AU)

Progress on radiotherapy of primary central nervous system lymphoma / 中华放射肿瘤学杂志

Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin′s lymphoma that occurs in the brain, spinal cord, meninges or eyes. Diffuse large B-cell lymphoma accounts for the vast majority, of which non-GCB subtype is more common. The median survival time of untreated patients is only 3 months. Surgical removal of the tumor alone has no obvious survival benefit. Early single use of whole brain radiation therapy (WBRT) yields a high remission rate, but the duration is short, and delayed neurotoxicity is an important complication, especially for elderly patients. Subsequent studies found that high-dose methotrexate-based chemotherapy combined with WBRT significantly improved the prognosis of this disease. However, combination therapy increases the risk of neurotoxicity, and this strategy has been questioned. In recent years, reduced-dose WBRT and autologous hematopoietic stem cell transplantation have gradually replaced the previous standard-dose WBRT. This article reviews the progress on the radiotherapy for PCNSL.

Clinical characteristics of 17 critically ill children with severe adverse reactions after chimeric antigen receptor T cells therapy / 中国小儿急救医学

Objective:To investigate the clinical characteristics, treatment process and prognosis of children with severe side effects after chimeric antigen receptor T cell immunotherapy(CAR-T), so as to provide evidence for timely intervention after CAR-T treatment.Methods:From June 1, 2015 to May 31, 2020, children with cytokine release syndrome(CRS)or immune cell related neurotoxicity syndrome(ICANS)who were treated with CAR-T therapy in our hospital and revealed severe effects transferred to PICU were included in the study, and their clinical course and multiple laboratory examination data were systematically analyzed.Results:Seventeen children showed CRS reaction and entered PICU after CAR-T therapy.The most common clinical symptoms were respiratory distress(13 cases) and circulatory disorder(10 cases), of which 7 cases were complicated with severe ICANS.Serum interferon -γ(IFN-γ)and interleukin-6(IL-6)levels significantly increased after CAR-T cell infusion, reaching the peak at (5.1±1.6)days.The serum levels of IFN-γ and IL-6 in children with severe CRS were significantly higher than those in children with mild CRS(all P<0.05). The level of serum IL-6 in children with high tumor load was significantly higher than that in children with low tumor load( P<0.05). The mortality rate of children with elevated level of serum TNF-α was higher(5/5 vs.3/11, P<0.05). Children with severe CRS were more likely to develop grade 4 ICANS(4/4 vs.0/3, P<0.05). The mortality rate of children with oxygenation index(P/F value)<200 mmHg(1 mmHg=0.133 kPa) was higher(5/5 vs.2/12, P<0.05). The vasoactive inotropic score[ M( Min, Max)] in the death group was significantly higher than that in survival group[29.5(14.0, 50.0) vs.1.5(0, 25.0), Z=8.000, P=0.027]. Conclusion:Serum IL-6 and IFN-γ are crucial causes of CRS.High tumor load is one of the factors causing high level of serum inflammatory factors.Respiration and circulation systems are the most frequently involved systems.Therefore, the evaluation indexes of these two systems can help us judge the prognosis of children.

Advance of general anesthetics-induced developing brain injury / 中国临床药理学与治疗学

The effect of general anesthetics (GA) on the developing brain has been a research hotspot in the last two decades. Numerous studies have shown that GA could damage the developing brain and cause long-term cognitive impairment in the preclinical setting, while it remains controversial in the clinical context regarding this topic. In light of the limitations of directly translating the preclinical findings into clinical context, drawbacks of retrospective studies, lack of standard behavioral and mental assessing tools in clinical studies, and other confounding factors, it is difficult to gain an agreement on the issue. To improve the repeatability and persuasion of data in the field of GA-induced developing brain, we tried to integrally analyze the current status and progress of the topic and make it as reference for the related studies in the future.