Manejo agudo de la intoxicación medicamentosa / Acute management of drug intoxication

Resumen Las intoxicaciones o las sobredosis de drogas constituyen una fuente importante de morbilidad, mortalidad y gasto en salud en todo el mundo. Especialmente en adultos menores de 35 años, las intoxicaciones vienen a ser la principal causa de paro cardíaco no traumático, siendofármacos más comunes involucrados, analgésicos, antidepresivos, opioides, sin embargo, esto puede variar. Es importante realizar un abordaje rápido, con base en interrogatorio, información de cualquier testigo y evidencia, además la clínica del paciente. El paro cardíaco debido a toxicidad se maneja de acuerdo conlos estándares actuales de reanimación cardiopulmonar básica y avanzada, siguiendo los principios del A, B, C, D, E. Las manifestaciones clínicas y abordaje clínico pueden variar bastante dependiendo de la sustancia involucrada. Las pruebas de laboratorio casi nunca están disponibles en un marco de tiempo que respalde las decisiones de reanimación tempranas, aún así, es recomendable realizarlas. En general los efectos tóxicos pueden reducirse si se limita la absorción del o los fármacos o se aumenta su eliminación. Además, se puede bloquear efectos farmacológicos no deseados con los llamados antídotos. El uso del carbón activado, algunos antídotos específicos, y tratamientos extracorpóreos también se contemplan en la presente revisión.

Abstract Poisoning or drug overdose is a major source of morbidity, mortality and health expenditure worldwide, especially in adults under 35, where it is the leading cause of non-traumatic cardiac arrest, being more common drugs involved, analgesics, antidepressants, opioids, however, this may vary. It is important to make a quick approach, based on questioning, information from any witness and evidence, and the patient's clinic. Cardiac arrest due to toxicity is managed according to current Basic and Advanced life support standards, following the principles of A, B, C, D, E. Clinical manifestations and clinical approach can vary considerably depending on the substance involved. Laboratory tests are almost never available in a time frame that supports early resuscitation decisions, yet it is advisable to perform them. In general, the toxic effects can be reduced if the absorption of the drugs is limited or their elimination increased. In addition, you can block unwanted pharmacological effects with so-called antidotes. The use of activated charcoal, specific antidotes, and extracorporeal treatments are also covered in this review.

Campo magnético de frecuencia extremadamente baja: Seguridad de su aplicación a nivel del sistema nervioso central / Magnetic field of extremely low frequency: Safety of its application at the level of the central nervous system

Introducción: La enfermedad cerebrovascular constituye un importante problema de salud a nivel mundial. En la actualidad se desarrollan investigaciones científicas dedicadas al estudio de los efectos del campo magnético de frecuencia extremadamente baja para su tratamiento. No es suficientemente clara la información acerca de su inocuidad en las dosis estudiadas. Objetivo: Estudiar la seguridad de la aplicación del campo magnético de frecuencia extremadamente baja a nivel del sistema nervioso central a través de un estudio toxicológico a dosis aguda, repetida y ensayo de micronúcleos en médula ósea. Métodos: Se conformaron tres grupos experimentales con ratas Sprague Dawley Cenp:SPRD jóvenes y sanas para los experimentos de toxicidad y ratones CENP: NMRI para la evaluación mutagénica. Se utilizaron controles negativos no tratados. En el ensayo de micronúcleos se incorporó un grupo control positivo al que se administró Ciclofosfamida por vía intraperitoneal. Se aplicó un campo magnético no homogéneo con niveles de inducción magnética de 6,5 y 15 mT, tomando como referencia el valor máximo sobre la superficie de la bobina. Para la aplicación del campo magnético la bobina estimuladora se colocó sobre la cabeza asegurando la exposición completa del encéfalo. Resultados: En ninguno de los ensayos se detectaron signos de toxicidad. Se comprobó así mismo que no se indujeron efectos genotóxicos ni citotóxicos sobre las células somáticas. Conclusiones: El tratamiento con campo magnético de frecuencia extremadamente baja a nivel del sistema nervioso central en las condiciones experimentales y dosis estudiadas es seguro(AU)

Introduction: Stroke is a major health problem all over the world. Nowadays are developed scientific researches devoted to the study of extremely low frequency magnetic field effects over this illness. The information about it safety is unclear yet. Objective: To study the safety of extremely low frequency magnetic field applied at central nervous system level wasby means ofa toxicological assay (Acute, repeated doses and micronucleus in bone marrow assay) Methods: Three experimental groups were made with Sprague Dawley Cenp: SPRD young and healthy rats for toxicity experiments and CENP: NMRI mice for mutagen evaluation. Untreated negative controls were used. In the micronucleus assay, an additional positive control group was included. This group received Cyclophosphamide by intraperitoneal administration. Was applied a non-homogenousmagnetic fieldof 6,5 and 15 mT, taken as reference the maximum value over the coil surface. The coil was positioned over the head, ensuring full exposure of brain to magnetic field. Results : In none of trials were detected any sign of toxicity. It was also found no genotoxic or cytotoxic effects induced on somatic cells. Conclusions : These results indicated the safety of treatmentwith extremely low frequency magnetic field at central nervous system level for experimental conditions and doses studied(AU)

Humidifier disinfectant-associated specific diseases should be called together as “humidifier disinfectant syndrome”

Humidifier disinfectant (HD) damage was terrible chemical damage caused by household goods that happened in only South Korea, but still very little is known in HD damage. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchioles and alveoli because it is a specific finding, compared with other diseases. To figure out whole effects from HDs, much epidemiologic and toxicologic research is underway. HDs were shown to give rise to typical toxicologic effects on various target organs, such as skin, conjunctiva, naval mucosa, bronchial mucosa, alveoli and so on, which shared common toxicological responses. On a specific target, specific toxicologic effects existed. Diverse diseases along exposure pathways can occur at the same time with a common toxicologic mechanism and cause of HDs, which can be called as HD syndrome. To gain stronger scientific evidence about it, further epidemiological and toxicological studies should be applied.

Influencing factor of diagnosis capacity in toxicologic pathology diagnostic laboratories / 中国职业医学

OBJECTIVE: To observe the diagnostic capacity and its influencing factors in the toxicologic pathology diagnostic laboratories in China. METHODS: Inter-laboratory comparison of toxicologic pathology diagnosis was cosponsored by Chinese Society of Toxicology-Toxicologic Pathology Specialty Section and Guangdong Province Hospital for Occupational Disease Prevention and Treatment. Nine digital slices of digestive system lesions were screened as comparison samples,and the reference institution with toxicologic pathology diagnostic laboratories completed the diagnosis within the prescribed time. According to the three grades of “excellent”,“satisfaction”and “dissatisfaction”,the evaluation was carried out.RESULTS: A total of 74 reference institution participated in this comparison,which distributed in 20 provinces and 4 municipalities and 156 pathologists. The reference institutions were mainly distributed in North China,Southern China and East China. There was an average of 2 pathologists per laboratory,and in the quantity of academic title,the junior,intermediate,and senior was 15,70 and 46 persons respectively. Parasitic hepatocyte cysts( 97. 3%),adenocarcinoma of small intestine( 95. 9%) and polyarteritis nodosa of the pancreas( 89. 2%) had the highest rate of “excellent”grade,while the duodenal gland inflammation( 67. 6%),foam cell aggregation in colonic propria( 40. 5%) and hepatoma adenoma( 32. 4%) had the highest rate of dissatisfaction grade in the evaluation of single case. In the overall evaluation,reference laboratories reached the “excellent”grade and the “satisfaction”grade were 78. 4% and 21. 6% respectively.The number of pathologists provided by each reference laboratory had impacts on the overall evaluation level and the single case evaluation( neoplastic lesions) in the evaluation of single case( P < 0. 05). The types of the reference laboratory,the regional distribution and the grade of the academic title had no effect on the diagnostic ability( P > 0. 05). CONCLUSION: The reference laboratory is superior in diagnosing the digestive system lesions in the inter-laboratory comparison activity.The number of pathologists in the reference laboratory is one of the influencing factors of its diagnostic ability.

Examination and assessment of target organ toxicity in toxicologic pathology of preclinical safety evaluation of drugs / 药物评价研究

Examination and assessment of target organ toxicity in toxicologic pathology of preclinical safety evaluation of drugs should combine the results of the gross pathology,histopathology and clinical pathology examination data in a well-considered,stepwise approach.In addition,the nomenclature and diagnostic criteria recommended by INHAND should be used to avoid subjective and inappropriate diagnosis.In this paper,we briefly introduced the basic principles for the examination of organ toxicity in toxicology studies,gross pathology,histopathology,diagnostic approach,procedures,and considerations,international harmonization of diagnostic term and criteria,clinical pathology parameters analysis,results of a well-concerted combination of anatomical and clinical pathology data so as to provide some reference for the examination and assessment of target organ toxicity in toxicologic pathology in the field ofpreclinical safety evaluation of drugs in China.

Principles of necropsy and gross pathology examination for toxicologic pathology assessment / 药物评价研究

Toxicologic pathology plays an important role in the safety evaluation of drugs.The results of toxicologic pathology can answer the basic problems of pathological lesions such as location,severity grading,nature and prognosis,etc.Necropsy and gross pathology examination are important aspects of toxicologic pathology assessment.Procedures typically include preparation for the necropsy,euthanasia procedures,identification and recording all gross lesions,collection of tissues listed in the study protocol,determination of organ weight,as well as tissue fixation so as to be ready for the subsequent tissue processing and histopathology examination.All the procedures must be done in a consistent manner and in accordance with standard operating procedures (SOPs).The present paper briefly introduced the principles of necropsy and gross pathology examination for toxicologic pathology in order to standardize the procedures and to lay foundation for the improvement of the histopathology examination in the field of preclinical safety evaluation of drugs of China.

Avaliação toxicológica aguda e screening hipocrático da epiisopilosina, alcalóide secundário de Pilocarpus microphyllus Stapf / Toxicological screening failure and the Hippocratic epiisopilosina, alkali secondary Pilocarpus microphyllus Stapf

A espécie Pilocarpus microphyllus Stapf. recebe a designação geral de jaborandi, fonte industrial de pilocarpina, utilizada no tratamento do glaucoma. O jaborandi contém vários alcalóides secundários. A epiisopilosina foi submetida a testes farmacológicos para determinação da DL50’ screening hipocrático e determinação do peso corporal dos animais sobreviventes da DL50. A análise dos resultados revelou que a epiisopilosina apresentou DL50 duas vezes maior que a pilocarpina. Os animais que sobreviveram à determinação da DL50 ganharam peso no período de 14 dias de observação. A eplisopilosina demonstrou ser um estimulante periférico do sistema nervoso parassimpático, semelhante à pilocarpina, somente em altas doses.

Pilocarpus microphyllus Stapf. (Rutaceae) is a source for industrial isolation of pilocarpine, alkaloid used in the treatment of glaucoma. It contains several secondary alkaloids; one of them being eplisopilosine. Pharmacological evaluation showed DL50 value of epiisopilosine two times higher than of pilocarpine. Epiisopilosine also showed to be a pilocarpine-like peripheric stimulant of parasympatic nervous system, although in higher dosis.