Dry eye disease in head and neck cancer patients undergoing radiotherapy

Purpose: To study the incidence of dry eye disease (DED) in head and neck cancer (HNC) patients undergoing external beam radiotherapy (EBRT), to find a correlation between tumor location and total radiation dose with DED, and to report various radiotherapy (RT) induced acute toxic effects on ocular and adnexal structures. Methods: A prospective cohort study was conducted at a tertiary eye?care center on 90 patients of HNC undergoing EBRT from March 2021 to May 2022. All underwent a thorough clinical history and complete ophthalmological examination including an ocular surface disease index (OSDI) questionnaire, visual acuity, anterior segment, angle and posterior segment examination, dry eye workup including the Schirmer test, tear meniscus height, tear break?up time, corneal fluorescein staining and grading, and meibography by auto?refractometer and its scoring at each visit. Patients were evaluated before the start of RT and then at 1 week, 4 weeks, and 12 weeks post?RT. Radiation records of all patients were noted. Data were analyzed using percentage and Microsoft Excel. Results: Of the 90 patients, 66 were male and 24 female (M: F ratio of 2.75) with a median age of 52.5 years (range 24 to 80 years). The most common HNC was the carcinoma oral cavity and lip. Most patients received a total radiation dose between 46 to 55 Gy. DED developed in 48 (53.3%) patients. The incidence of DED increased with the increase in total radiation dose (r = 0.987). DED was also found to be correlated with tumor location (r = 0.983). Conclusion: The incidence of DED positively correlated with the total radiation dose and tumor location.

Phytochemical Screening and Acute oral Toxicity Study of Root Extracts of Combretum hereroense Schinz and Balanites aegyptiaca Del. Traditionally Used to Treat Female Infertility in Baringo County, Kenya

Aims: To carry out phytochemical screening and acute oral toxicity test to validate their safety and efficacy. Study Design: Standard phytochemical screening tests were used to highlight phytochemical compounds of roots of the plants. The evaluation of acute toxicity of the root extracts of the plants followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. Place and Duration of the Study: The study was undertaken at the Department of Chemistry & Biochemistry for the extraction for samples extraction and phytochemical screening. Acute oral toxicity studies were done at the Department of Biological Sciences for acute toxicity study, University of Eldoret, Between June and September 2022. Methodology: Phytochemical screening for presence of Tannins, saponins, flavonoids, glycosides, alkaloids, anthocyanin, terpenoids, steroids, coumarins, lipids, proteins and carbohydrates were carried out. Acute oral toxicity studies were done using the fixed dose method at a dose of 2000mg/kg body weights of rats. Three groups were used: control and test groups for each of the respective plant root extracts. Signs of toxicity and/or mortality were monitored daily for 14 days. Weekly fasting body weights were also recorded. Results: The phytochemical screening results showed the presence of tannins, saponins, flavonoids, glycosides, alkaloids, anthocyanin, terpenoids, steroids, lipids, proteins and carbohydrates present in the root extract of Combretum hereroense. Tannins, saponins, flavonoids, glycosides, terpenoids, steroids, and carbohydrates were present in root extracts of Balanites aegyptiaca. Following the acute oral toxicity study, there were no abnormalities observed in physiological parameters. In addition, no deaths were recorded during the study period. The LD50 was therefore greater than 2000 mg/kg. The fasting body weights of extract treated rats increased stably compared to the control [p = .05]. Conclusion: The results showed C. hereroense and B. aegyptiaca methanol root extracts were considered safe in acute oral exposure. Long-term toxicity studies are needed for further toxicological profile elicitation of the plant, and a possible reinforcement of clinical relevance of the results of laboratory studies.

Avaliação toxicológica e determinação da dl 50 do extrato bruto de luffa operculata cogn. (cucurbitaceae) / Toxicological evaluation and determination of ld 50 of the crude extract of luffa operculata cogn. (cucurbitaceae) / Evaluación toxicológica y determinación de la dl 50 del extracto crudo de luffa operculata cogn. (cucurbitáceas)

As plantas medicinais têm sido bastante utilizadas para o tratamento de várias enfermidades pelo homem. Numerosos compostos bioativos obtidos de plantas medicinais apresentam atividades antimicrobianas, antivirais, anticancerígenas, anti- inflamatórias, antioxidantes e neuromoduladoras. Entretanto, existe um número crescente de estudos científicos que comprovam a toxicidade de plantas medicinais. O fruto da Luffa operculata Cogn. é utilizado popularmente como purgante, emenogogo, expectorante e rinossinusite. Este trabalho teve como objetivo avaliar a toxicidade aguda e determinar a dose letal 50% (LD50) do extrato bruto etanólico de Luffa operculata Cogn., por via intraperitoneal em camundongos. No experimento foi utilizado camundongos albinos fêmeas Swiss (Mus Muscullus). Os animais foram divididos em grupos (n=6/grupo), e a toxicidade foi avaliada em duas etapas: preliminar e definitiva. As reações comportamentais relacionadas às doses administradas do extrato de Luffa operculata Cogn. foram taquicardia, taquipneia, movimentos estereotipados e circulares e piloereção. Após essa fase, os animais apresentaram reações depressoras envolvendo apneia e prostração. Além disso, os animais apresentaram outros comportamentos como: contorções abdominais, tônus da musculatura abdominal, espasmos e irritação da conjuntiva. O extrato de Luffa operculata Cogn. apresentou uma DL50 de 3,3 mg/Kg de peso corpóreo, sendo considerada muito tóxica. Como essa planta é largamente usada pela população para fins terapêuticos, alertamos quanto a utilização indiscriminada devido ao alto potencial tóxico.

Medicinal plants have been sed for the treatment of various diseases by man. Numerous bioactive compounds obtained from medicinal plants exhibit antimicrobial, antiviral, anticancer, anti-inflammatory, antioxidant, and neuromodulatory activities. However, the number of scientific studies proving the toxicity of medicinal plants is increasing. The fruit of Luffa operculata Cogn. it is popularly used as a purgative, emmenagogue, expectorant, and rhinosinusitis. This work aimed to evaluate the acute toxicity and determine the lethal dose of 50% (LD50) of the crude ethanolic extract of Luffa operculata Cogn., intraperitoneally. In the experiment, Swiss female albino mice (Mus Muscullus) were used. The animals were divided into groups (n=6/group), and toxicity was evaluated in two steps: preliminary and definitive. Behavioral reactions related to administered doses of Luffa operculata Cogn. were tachycardia, tachypnea, stereotyped, and circular movements and piloerection. After this phase, the animals presented depressive reactions involving apnea and prostration. In addition, the animals showed other behaviors such as abdominal contortions, abdominal muscle tone, spasms, and irritation of the conjunctiva. The extract of Luffa operculata Cogn. presented an LD50 of 3.3 mg/Kg of body weight, being considered very toxic. As this plant is widely used by the population for therapeutic purposes, we warn about its use due to its high toxic potential.

Las plantas medicinales han sido ampliamente utilizadas para el tratamiento de diversas enfermedades por parte del hombre. Numerosos compuestos bioactivos obte- nidos de plantas medicinales exhiben actividades antimicrobianas, antivirales, anticance- rígenas, antiinflamatorias, antioxidantes y neuromoduladoras. Sin embargo, hay un nú- mero creciente de estudios científicos que prueban la toxicidad de las plantas medicinales. El fruto de Luffa operculata Cogn. se utiliza popularmente como purgante, emenogogo, expectorante y rinosinusitis. Este trabajo tuvo como objetivo evaluar la toxicidad aguda y determinar la dosis letal al 50% (DL50) del extracto etanólico crudo de Luffa operculata Cogn., por vía intraperitoneal. En el experimento se utilizaron ratones albinos hembra suizos (Mus Muscullus). Los animales se dividieron en grupos (n=6/grupo) y la toxicidad se evaluó en dos etapas: preliminar y definitiva. Reacciones conductuales relacionadas con las dosis administradas de Luffa operculata Cogn. fueron taquicardia, taquipnea, mo- vimientos estereotipados y circulares y piloerección. Después de esta fase, los animales presentaron reacciones depresivas involucrando apnea y postración. Además, los anima- les mostraron otros comportamientos como: contorsiones abdominales, tono muscular abdominal, espasmos e irritación de la conjuntiva. El extracto de Luffa operculata Cogn. presentó una DL50 de 3,3 mg/Kg de peso corporal, considerándose muy tóxico. Como esta planta es muy utilizada por la población con fines terapéuticos, advertimos contra su uso indiscriminado por su alto potencial tóxico.

Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine / 中西医结合学报

OBJECTIVE@#The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.@*METHODS@#The diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.@*RESULTS@#Two new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity.@*CONCLUSION@#Compared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines. Please cite this article as: Wang YJ, Wang Y, Tao P. Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine. J Integr Med. 2023; 21(3): 302-314.

El mejillón Semimytilus patagonicus (Mytilida: Mytilidae) y el gusano Pseudonereis gallapagensis (Phyllodocida: Nereididae) como herramientas ecotoxicológica para la contaminación por detergentes en ambientes marinos / The mussel Semimytilus patagonicus (Mytilida: Mytilidae) and the worm Pseudonereis gallapagensis (Phyllodocida: Nereididae) as ecotoxicological tools for detergent pollution in marine environments

Introduction: The bivalve Semimytilus patagonicus is a potentially useful bioindicator because of its feeding mechanism, and the worm Pseudonereis gallapagensis is also interesting as a bioindicator because it is benthonic, abundant, and a food source for the squid Doryteuthis gahi. However, their sensitivity to contaminants has not been sufficiently studied. Objective: To test the usefulness of the mussel Semimytilus patagonicus and the polychaete Pseudonereis gallapagensis as ecotoxicological tools for detergents in the marine environment. Methods: We used 120 individuals of S. patagonicus from Miraflores and 120 of P. gallapagensis from Barranco (both near the city of Lima, Peru). For the bioassays, we used two anionic detergents (active ingredient, ai, Sodium Dodecylbenzene Sulfonate). For S. patagonicus, with an average valve length of 32.3 ± 6.4 mm, we tested "Double power Ariel®" (90 %) at concentrations of 17.5, 35, 70 and 140 mg ai l-1, evaluated after 48 and 72 h of exposure; and for P. gallapagensis, with a total body length of 20.4 ± 8.8 mm, we tested "Caricia®" at 62.5, 125, 250, 500 and 1 000 mg of ai l-1 at 24, 48 and 72 h of exposure. Results: The LC50 values (Mean Lethal Concentration) were 34.95 mg ia l-1 for S. patagonicus and 102.48 mg ia l-1 for P. gallapagensis at 72 h of exposure. The detergents were toxic for S. patagonicus and slightly toxic for P. gallapagensis. The risk classification for S. patagonicus is "harmful" and for P. gallapagensis "not classifiable". Conclusions: These two bioindicators allow evaluating the acute toxicity of SDBS-based commercial detergents in the marine aquatic environment.

Introducción: El bivalvo Semimytilus patagonicus es un bioindicador potencialmente útil por su mecanismo de alimentación, y el gusano Pseudonereis gallapagensis también es interesante como bioindicador por ser bentónico, abundante y fuente de alimento para el calamar Doryteuthis gahi. Sin embargo, su sensibilidad a los contaminantes no ha sido suficientemente estudiada. Objetivo: Probar la utilidad del mejillón S. patagonicus y el poliqueto P. gallapagensis como herramientas ecotoxicológicas para detergentes en el medio marino. Métodos: Se utilizaron 120 individuos de S. patagonicus de Miraflores y 120 de P. gallapagensis de Barranco (ambos cerca de la ciudad de Lima, Perú). Para los bioensayos se utilizaron dos detergentes aniónicos (ingrediente activo, ia, dodecilbenceno sulfonato de sodio). Para S. patagonicus, con una longitud valver promedio de 32.3 ± 6.4 mm, probamos Ariel Doble Poder® (90 %) a concentraciones de 17.5, 35, 70 y 140 mg·ia·l-1, evaluadas a las 48 y 72 h de exposición; y para P. gallapagensis, con una longitud corporal total de 20.4 ± 8.8 mm, probamos Caricia® a 62.5, 125, 250, 500 y 1 000 mg·ia·l-1 a las 24, 48 y 72 h de exposición. Resultados: Los valores de CL50 (Concentración Letal Media) fueron de 34.95 mg·ia·l-1 para S. patagonicus y 102.48 mg·ia·l-1 para P. gallapagensis a las 72 h de exposición. Los detergentes fueron tóxicos para S. patagonicus y levemente tóxicos para P. gallapagensis. La clasificación de riesgo para S. patagonicus es "nocivo" y para P. gallapagensis "no clasificable". Conclusiones: Estos dos bioindicadores permiten evaluar la toxicidad aguda del detergente comercial a base de SDBS en el ambiente acuático marino.

“EFFECT OF COPPER ACETATE ON ACUTE TOXICITY OF FISH CHANNA PUNCTATUS AT 48 HR BY DRAGSTEDT AND BEHREN'S METHOD ”

This study was carried out on ?sh channa punctatus to investigate the lethal concentration of copper acetate on ?sh channa punctatus at 48 hr. Experiment procedure was repeated ?ve times at the selected copper acetate concentrations, noting the number of ?sh killed. The mean values was taken. These values was taken to determine LC50 value for 48 hr. By Dragstedt and Behrens Method

EFFECT OF CADMIUM NITRATE ON ACUTE TOXICITY OF FISH CHANNA PUNCTATUS AT 48 HR. BY STATISTICAL METHOD

This study was carried out on ?sh channa punctatus to investigate the lethal concentration of cadmium nitrate on ?sh channa punctatus at 48 hr. Experiment procedure was repeated ?ve times at the selected cadmium nitrate concentrations, noting the number of ?sh killed. The mean value was taken. These values were taken to determine LC50 value for 48 hr.

Acute toxicity study and phytochemical screening of Pterocarpus marsupium heartwood

Background: Conventionally, Ayurvedic herbs are being used to treat various diseases. These medicinal compounds have to be evaluated for their safety and presence of therapeutic compounds for the clinical application. Aims and Objectives: The present study was designed to obtain the scientific knowledge on the safety profile as well as to assess the presence of pharmacologically active principles in the Pterocarpus marsupium heartwood. Materials and methods: The aqueous extract of P. marsupium heartwood was subjected to an acute toxicity in albino rats. The animals were divided into four groups (n = 6) and fed with graded doses (1000, 2000, and 5000 mg/kg p.o.) of plant extract, respectively, whereas control group had received 2 ml distilled water orally. Animals were continuously observed for the toxicological symptoms for 2 h and intermittently for 48 h and latter once in a day for 14 days. The body weight of the animals was recorded. In addition, the qualitative phytochemical investigations were conducted to identify the presence of active principles. Results: The animals fed with aqueous extract of P. marsupium heartwood did not exhibit any toxic symptoms and the mortality. However, there was a significant (P < 0.05) dose-dependent change in the weight gain observed in comparison to the control group. The median lethal dose (LD50) of the plant extract was considered as >5000 mg/kg. Furthermore, the phytochemical investigations of the plant extract showed the presence of carbohydrates, flavonoids, triterpenoids, saponins, tannins and phenols. Conclusion: The aqueous extract of P. marsupium heartwood was found to be safe and well tolerated even at a large dose of 5000 mg/kg. Furthermore, the plant extract found to possess pharmacologically active principles having wide pharmacological spectrum. Hence, it can be preferred in various therapeutic conditions.

Acute and Subchronic Toxicities of the Aqueous Extract of the Hymenocardia acida (Euphorbiaceae) Roots in Rodents

The roots of Hymenocardia acida are used in traditional African medicine to treat mainly erectile dysfunction. This study aims to evaluate the lethal and sub-lethal toxicities of the aqueous extract of Hymenocardia acida roots in in two rodents species, namely Mus musculus and Rattus norvegicus. The acute intraperitoneal and oral toxicities of the extract were determined by the method of Miller and Tainter. Subchronic oral toxicity with doses of 500 and 1000 mg/kg body weight was assessed according to the slightly modified OECD 408 method. The results showed that the 50% intraperitoneal lethal dose was 223.87 mg/kg body weight in mice. In addition, the 50% oral lethal dose in mice was greater than 12,000 mg/kg body weight. In the subchronic study, the extract induced a significant (P < .001) increase in white blood cell count at 1000 mg/kg body weight after 60 days of treatment. From the thirtieth day of treatment onwards, the extract induced a significant (P < .05) reduction in blood glucose levels at the 500 mg/kg body weight dose and a significant (P < .05) increase in blood glucose levels at the 1000 mg/kg body weight dose. Aqueous extract of Hymenocardia acida roots is toxic by the intraperitoneal route and exerts a non-specific immunity action at high doses. It was harmless to rats at doses of 500 and 1000 mg/Kg of body weight.

Activity of aromatic pyrrole-based compounds against of Schistosoma japonicum cercariae and acute toxicity to fish / 中国血吸虫病防治杂志

Objective To test the activity of aromatic pyrrole-based compounds against cercariae of Schistosoma japonicum and test their acute toxicity to fish. Methods A series of aromatic pyrrole-based compounds were synthesized using 4-benzyl-5-(trifluoromethyl)-1H-pyrrole-3-nitrile as the lead compound. The synthesized compounds were prepared into solutions at concentrations of 10.00, 1.00, 0.10, 0.01 mg/L, and the activity of these solutions against S. japonicum cercariae was tested in 30 min, while 0.10 mg/L and 0.01 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% dimethyl sulfoxide (DMSO) was used as a negative control, with 10 to 30 cercariae of S. japonicum in each group. In addition, the compounds were prepared into solutions at concentrations of 0.50, 0.25, 0.12, 0.06, 0.03 mg/L, and their toxicity to zebrafish was tested in 72 h, while 0.15 mg/L and 0.30 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% DMSO was used as a negative control, with 10 zebrafishes in each group. Results A total of 7 aromatic pyrrole-based compounds were successfully synthesized. Treatment with compounds 102, 104 and 106 at a concentration of 0.01 mg/L for 30 min killed all S. japonicum cercariae, and compounds 105 and 107 showed no activity against cercariae. No death of cercariae was found in the blank control group, while treatment with 0.10 mg/L niclosamide for 10 min caused a 100% mortality rate of S. japonicum cercariae and 0.01 mg/L niclosamide failed to kill S. japonicum cercariae. No zebrafish death was found 72 h post-treatment with compounds 101, 104 and 105 at a concentration of 0.03 mg/L, and exposure to compounds 102, 103 and 106 at a concentration of 0.03 mg/L for 12 h resulted in a 100% mortality rate of zebrafish. No zebrafish death occurred 72 h post-treatment with 0.50 mg/L Compound 104, and no zebrafish death was found in the blank control group, while treatment with 0.30 mg/L niclosamide for 24 h resulted in a 100% mortality rate of zebrafish. Conclusions Compound 104 achieves a 100% mortality rate against S. japonicum cercariae at a concentration of 0.01 mg/L for 30 min, and causes no death of zebrafish at a concentration of 0.50 mg/L for 72 h, which may serve as a cercaricide candidate.

Assessment of carbamazepine acute toxicity in the cockle Cerastoderma edule through chemical, physiological and biochemical tools / Avaliação da toxicidade aguda da carbamazepina no berbigão Cerastoderma edule por meio de ferramentas químicas, fisiológicas e bioquímicas

The cockle Cerastoderma edule was exposed to four concentrations (5, 10, 20 and 70 µg L-1) of carbamazepine (CBZ). This anticonvulsant was found to alter the mussel behavior of by reducing its clearance rate (CR). Analysis of CBZ accumulation in tissues of C. edule was carried out using HPLC-UV after 48 or 96 hours of exposure. In addition, an overproduction of H2O2 by the bivalves was detected following exposure to CBZ but nitrite levels remained unchanged. Moreover, superoxide dismutase and catalase activities showed a significant increase in relation to their contact with CBZ. The activity of the biotransformation enzyme gluthatione-S-transferase did not change during exposure. Malondialdehyde (MDA) levels indicating cellular damage, increased when bivalves were exposed to 20 and 70 µg l-1 of carbamazepine for 96 h CBZ. The results also indicate that acetylcholinesterase activity (AChE) was inhibited in all CBZ concentrations during the 48 h exposure period. However, during the 96 h exposure period, AChE was only inhibited at the highest concentration. Further studies are needed now for more exploration of the toxicity of CBZ since it could be bioaccumulable throughout the food web and may affect non-target organisms.

O berbigão Cerastoderma edule foi exposto a quatro concentrações (5, 10, 20 e 70 µg L-1) de carbamazepina (CBZ). Este anticonvulsivante alterou o comportamento do mexilhão, reduzindo sua taxa de depuração (CR). A análise do acúmulo de CBZ nos tecidos de C. edule foi realizada por HPLC-UV após 48 ou 96 horas de exposição. Além disso, uma superprodução de H2O2 pelos bivalves foi detectada após a exposição à CBZ, mas os níveis de nitrito permaneceram inalterados. Além disso, as atividades de superóxido dismutase e catalase apresentaram aumento significativo em relação ao contato com CBZ. A atividade da enzima de biotransformação glutationa-S-transferase não se alterou durante a exposição. Os níveis de malondialdeído (MDA), indicando dano celular, aumentaram quando os bivalves foram expostos a 20 e 70 µg l-1 de carbamazepina por 96 h CBZ. Os resultados também indicam que a atividade da acetilcolinesterase (AChE) foi inibida em todas as concentrações de CBZ durante o período de exposição de 48 horas. No entanto, durante o período de exposição de 96 horas, a AChE foi inibida apenas na concentração mais alta. Mais estudos são necessários agora para uma maior exploração da toxicidade da CBZ, uma vez que pode ser bioacumulável em toda a cadeia alimentar e pode afetar organismos não alvo.

Assessment of carbamazepine acute toxicity in the cockle Cerastoderma edule through chemical, physiological and biochemical tools / Avaliação da toxicidade aguda da carbamazepina no berbigão Cerastoderma edule por meio de ferramentas químicas, fisiológicas e bioquímicas

The cockle Cerastoderma edule was exposed to four concentrations (5, 10, 20 and 70 μg L-¹) of carbamazepine (CBZ). This anticonvulsant was found to alter the mussel behavior of by reducing its clearance rate (CR). Analysis of CBZ accumulation in tissues of C. edule was carried out using HPLC-UV after 48 or 96 hours of exposure. In addition, an overproduction of H2O2 by the bivalves was detected following exposure to CBZ but nitrite levels remained unchanged. Moreover, superoxide dismutase and catalase activities showed a significant increase in relation to their contact with CBZ. The activity of the biotransformation enzyme gluthatione-S-transferase did not change during exposure. Malondialdehyde (MDA) levels indicating cellular damage, increased when bivalves were exposed to 20 and 70 μg l-¹ of carbamazepine for 96 h CBZ. The results also indicate that acetylcholinesterase activity (AChE) was inhibited in all CBZ concentrations during the 48 h exposure period. However, during the 96 h exposure period, AChE was only inhibited at the highest concentration. Further studies are needed now for more exploration of the toxicity of CBZ since it could be bioaccumulable throughout the food web and may affect non-target organisms.

O berbigão Cerastoderma edule foi exposto a quatro concentrações (5, 10, 20 e 70 μg L-¹) de carbamazepina (CBZ). Este anticonvulsivante alterou o comportamento do mexilhão, reduzindo sua taxa de depuração (CR). A análise do acúmulo de CBZ nos tecidos de C. edule foi realizada por HPLC-UV após 48 ou 96 horas de exposição. Além disso, uma superprodução de H2O2 pelos bivalves foi detectada após a exposição à CBZ, mas os níveis de nitrito permaneceram inalterados. Além disso, as atividades de superóxido dismutase e catalase apresentaram aumento significativo em relação ao contato com CBZ. A atividade da enzima de biotransformação glutationa-S-transferase não se alterou durante a exposição. Os níveis de malondialdeído (MDA), indicando dano celular, aumentaram quando os bivalves foram expostos a 20 e 70 μg l-1 de carbamazepina por 96 h CBZ. Os resultados também indicam que a atividade da acetilcolinesterase (AChE) foi inibida em todas as concentrações de CBZ durante o período de exposição de 48 horas. No entanto, durante o período de exposição de 96 horas, a AChE foi inibida apenas na concentração mais alta. Mais estudos são necessários agora para uma maior exploração da toxicidade da CBZ, uma vez que pode ser bioacumulável em toda a cadeia alimentar e pode afetar organismos não alvo.

Assessment of carbamazepine acute toxicity in the cockle Cerastoderma edule through chemical, physiological and biochemical tools

Abstract The cockle Cerastoderma edule was exposed to four concentrations (5, 10, 20 and 70 g L-1) of carbamazepine (CBZ). This anticonvulsant was found to alter the mussel behavior of by reducing its clearance rate (CR). Analysis of CBZ accumulation in tissues of C. edule was carried out using HPLC-UV after 48 or 96 hours of exposure. In addition, an overproduction of H2O2 by the bivalves was detected following exposure to CBZ but nitrite levels remained unchanged. Moreover, superoxide dismutase and catalase activities showed a significant increase in relation to their contact with CBZ. The activity of the biotransformation enzyme gluthatione-S-transferase did not change during exposure. Malondialdehyde (MDA) levels indicating cellular damage, increased when bivalves were exposed to 20 and 70 g l-1 of carbamazepine for 96 h CBZ. The results also indicate that acetylcholinesterase activity (AChE) was inhibited in all CBZ concentrations during the 48 h exposure period. However, during the 96 h exposure period, AChE was only inhibited at the highest concentration. Further studies are needed now for more exploration of the toxicity of CBZ since it could be bioaccumulable throughout the food web and may affect non-target organisms.

Resumo O berbigão Cerastoderma edule foi exposto a quatro concentrações (5, 10, 20 e 70 g L-1) de carbamazepina (CBZ). Este anticonvulsivante alterou o comportamento do mexilhão, reduzindo sua taxa de depuração (CR). A análise do acúmulo de CBZ nos tecidos de C. edule foi realizada por HPLC-UV após 48 ou 96 horas de exposição. Além disso, uma superprodução de H2O2 pelos bivalves foi detectada após a exposição à CBZ, mas os níveis de nitrito permaneceram inalterados. Além disso, as atividades de superóxido dismutase e catalase apresentaram aumento significativo em relação ao contato com CBZ. A atividade da enzima de biotransformação glutationa-S-transferase não se alterou durante a exposição. Os níveis de malondialdeído (MDA), indicando dano celular, aumentaram quando os bivalves foram expostos a 20 e 70 g l-1 de carbamazepina por 96 h CBZ. Os resultados também indicam que a atividade da acetilcolinesterase (AChE) foi inibida em todas as concentrações de CBZ durante o período de exposição de 48 horas. No entanto, durante o período de exposição de 96 horas, a AChE foi inibida apenas na concentração mais alta. Mais estudos são necessários agora para uma maior exploração da toxicidade da CBZ, uma vez que pode ser bioacumulável em toda a cadeia alimentar e pode afetar organismos não alvo.

A Report on the Distribution of "Lethal Dose/Pharmaceutical Product Strength” in High-Risk Drugs / 医薬品情報学

Objective: This study assessed the distribution of "lethal dose/pharmaceutical product strength" in high-risk drugs.Methods: In 707 pharmaceutical products (312 ingredients) that had been defined as high-risk drugs in Japan, we collected acute toxicity information from these products on single dose toxicity studies conducted in mice, including median lethal dose (LD50) and approximate lethal dose (aLD). The LD50 and aLD were then divided by the strength (quantity of active ingredients) of the pharmaceutical product, after which the LD50or aLD values having an inequality sign was excluded.Results: We collected data on the acute lethal dose of 707 products (312 ingredients) from high-risk drugs. Data with an inequality sign, which was 143 of 495 products (28.9%) in tablets and capsules, then 43 of 212 items (20.3%) in injections, were excluded from the analysis. As observed, median (Q1, Q3) of "LD50/pharmaceutical product strength" and "aLD/pharmaceutical product strength" for tablets or capsules was 36.8 tablet/kg (11.5 tablet/kg, 144 tablet/kg) and 16.7 tablet/kg (6.9 tablet/kg, 65 tablet/kg), respectively. However, median (Q1, Q3) of "LD50/pharmaceutical product strength" and "aLD/pharmaceutical product strength" for injections were 1.3 bottle/kg (0.6 bottle/kg, 4.7 bottle/kg) and 0.8 bottle/kg (0.4 bottle/kg, 15 bottle/kg), respectively. In both cases, injections were distributed at a lower value than oral products.Conclusion: From this study, the distribution of "lethal dose/pharmaceutical product strength" in high-risk drugs was clarified. This information will therefore help pharmacists assess risks associated with individual pharmaceutical products.

Lesiones dermatológicas ocasionadas por la exposición a los componentes del jagüey blanco

RESUMEN Introducción: Muchas plantas poseen efectos perjudiciales para la salud, no siempre del dominio público; dentro de estas se encuentra el jagüey blanco, que posee compuestos capaces de producir dermatitis de contacto. Objetivos: Presentar un caso clínico ocasionado por la exposición a los componentes del jagüey blanco. Caso clínico: Niño de 8 años, saludable, que acudió al médico con dolor intenso, quemante, en las manos, asociado a prurito. Al examen físico de la piel de ambas manos, en las palmas, presentaba eritema, en sus dorsos y espacios interdigitales el eritema era más intenso con incremento de la temperatura; se le adicionaron ampollas, la mayor alcanzó prácticamente todo el dorso de la mano derecha, las demás entre uno y tres centímetros de diámetro. Al interrogatorio, se conoció que se había expuesto a la savia que desprendían los frutos del árbol jagüey blanco. Se le aplicó limpieza del área afectada, cura local, vendaje, nitrofurazona en crema, analgésico y antihistamínico. Presentó una evolución satisfactoria; a los 10 días de iniciado el cuadro, ya estaba en fase de recuperación. Conclusiones: Este paciente presentó una dermatitis de contacto de tipo irritativa, como quemadura, al ponerse en contacto con componentes del jagüey blanco, que requirió de tratamiento médico, con el cual se logró una evolución satisfactoria.

ABSTRACT Introduction: Many plants have harmful effects on health, not always in the public domain, within these is the shortleaf fig, which has compounds capable of producing contact dermatitis. Objectives: Present a clinical case caused by exposure to the components of Shortleaf fig. Clinical case: 8-year-old boy, healthy, who came to the doctor with intense, burning pain in the hands, associated with itching. On physical examination of the skin of both hands, on the palms, he presented erythema, and on his backs and interdigital spaces the erythema was more intense with an increase in temperature, where blisters were added, the largest reached practically the entire back of the right hand, and others between one and three centimeters. Upon interrogation, it was discovered that he had been exposed to the sap that the fruits of the shortleaf fig tree. Cleaning of the affected area, local cure, bandage, nitrofurazone cream, analgesic and antihistamine were applied; presented a satisfactory evolution, 10 days after the beginning of the picture he was already in recovery phase. Conclusions: This patient presented irritative contact dermatitis, as a burn, when coming into contact with components present in the shortleaf fig, which required medical treatment with which a satisfactory evolution was achieved.

Ecotoxicidade de nanocatalisadores de óxidos de ferro, produzidos a partir da drenagem ácida de mina, quando submetidos à ação de ozônio em meio aquoso / Ecotoxicity of iron oxide nanocatalysts, produced from acid mine drainage, when submitted to the action of ozone in aqueous medium

RESUMO Óxidos de ferro recuperados da drenagem ácida de minas representam uma matéria-prima potencial para a produção de baixo custo de nanogoetita ou nanohematita, com grau de pureza adequado para o seu uso como catalisador em processos de tratamento de efluentes líquidos com ozônio. Assim, a toxicidade das nanopartículas de ferro precisa ser determinada para prever seu impacto no meio ambiente, antes e depois de terem sido utilizadas nesses processos. Nesse contexto, o objetivo deste estudo foi avaliar a toxicidade de nanogoetita e nanohematita produzidas a partir da drenagem ácida de minas bem como comparar os resultados com hematita sintética de alta pureza. A nanogoetita foi obtida da drenagem ácida de minas e, após seu tratamento térmico a 450°C, produziu nanopartículas de hematita. Os materiais foram caracterizados por difração de raios X, microscopia eletrônica de transmissão e determinação da área superficial específica e porosidade com base nas isotermas de adsorção/dessorção de N2. Foram realizados os ensaios de ecotoxicidade usando os protocolos padronizados para bioluminescência com Vibrio fischeri, letalidade da Artemia sp., germinação de sementes de Lactuca sativa L. (alface) e crescimento das raízes de Allium cepa L. (cebola). Os resultados de toxicidade indicaram estabilidade das nanopartículas, que não são alteradas significativamente pela ação do ozônio em meio aquoso. Para todas as amostras, os valores indicaram baixa ou nenhuma toxicidade nas condições dos experimentos, para os bioindicadores utilizados. Esses resultados fornecem indicação de que as nanopartículas de ferro recuperadas da indústria de resíduos podem ser usadas como catalisadores sem efeitos adversos ao meio ambiente.

ABSTRACT Iron oxides recovered from acid mine drainage represent a potential raw material for the low-cost production of nanogoethite or nanohematite, with a degree of purity suitable for its use as a catalyst in processes for treating liquid effluents with ozone. Thus, the toxicity of iron nanoparticles needs to be determined to predict their impact on the environment, before and after they have been used in these processes. In this context, the objective of this study was to evaluate the toxicity of nanogoethite and nanohematite produced from acid mine drainage as well as to compare the results with high-purity synthetic hematite. Nanogoethite was obtained from acid mine drainage and, after its heat treatment at 450°C, produced nanoparticles of hematite. The materials were characterized by X-ray diffraction, transmission electron microscopy, and determination of the specific surface area and porosity based on N2 adsorption/desorption isotherms. Ecotoxicity tests were carried out using standardized protocols for bioluminescence with Vibrio fischeri, lethality of Artemia sp, germination of Lactuca sativa L (lettuce) seeds, and growth of Allium cepa L (onion) roots. The toxicity results indicated stability of the nanoparticles, which are not significantly altered by the action of ozone in aqueous medium. For all samples, the values indicated low or no toxicity under the conditions of the experiments. These results provide an indication that the iron nanoparticles recovered from the waste industry can be used as catalysts without adverse effects on the environment.

Toxicological diagnosis in the critical patient: The challenge

Abstract Introduction: A high percentage of patients who survived poisoning will be transferred to the Intensive Care Unit (ICU) to continue their management in relation to the severity of the poisoning, and possible complications that arise in this scenario. The clinical results will depend on several factors, such as the ingested dose, the characteristics of the substance, the time of medical attention, and the pre-existing state of health of the patient. Objective: To review the clinical behavior of poisonings in the critically ill patient. Recent findings: The data bases that yielded relevant bibliographical results were Web of Sciences, Scopus, PubMed, SciELO, and bibliographic references published between 2012 and 2020 were chosen. Conclusions: The clinical behavior of poisonings in the critically ill patient is atypical. The intensivist must have an in-depth knowledge of the behavior and pathophysiology of the toxins since making a medical diagnosis on the stage of the critically ill patient is challenging. The integration of all possible medical tools is required to achieve this in the absence of clinical history, and the implementation of early management strategies is necessary to reach physiological restoration by using a continuous evaluation approach. The severity of poisoning in the critically ill patient demands interdisciplinary management that includes assessment by Clinical Toxicology.

Arsenotoxicidad aguda experimental en ratones Balb/c: marcadores orgánicos y compromiso esplénico / Experimental acute arsenic toxicity in Balb/c mice: organic markers and splenic involvement

Resumen | Introducción. El arsénico es un tóxico ambiental ampliamente diseminado en todo el mundo. En hombres y animales, diversos órganos y tejidos son blancos de sus efectos deletéreos, entre ellos, el los del sistema inmunológico. Objetivo. Determinar la intoxicación aguda por arsénico en tejidos y células diana de ratones Balb/c in vivo. Materiales y métodos. Se aplicó una inyección intraperitoneal de 9,5 o 19 mg/kg de arsenito de sodio (NaAsO2) o un volumen equivalente de solución fisiológica como control, en ratones Balb/c con 3 por cada grupo experimental. Tras media hora, los animales fueron sacrificados y se extrajeron bazos, timos, hígados, riñones y sangre. En cada muestra, se determinó la concentración de arsénico, polifenoles y hierro, y también, se evaluaron marcadores oxidativos, como peróxidos, productos avanzados de oxidación proteica y grupos sulfhidrilos libres. En los esplenocitos obtenidos del bazo, se determinaron la viabilidad celular y el potencial mitocondrial. Resultados. La dosis aguda inyectada de NaAsO2 redujo la función mitocondrial de los esplenocitos, lo que derivó en muerte celular. La presencia confirmada de arsénico en las muestras de bazo y la citotoxicidad resultante, produjeron disminución de los polifenoles y de los grupos sulfhidrilos libres, y alteraron el contenido y la distribución del hierro, pero no se aumentó la producción de peróxidos. Conclusión. Estos hallazgos aportan evidencia científica sobre los cambios en biomarcadores involucrados en la inmunotoxicidad del arsénico y ofrecen, además, una metodología para ensayar potenciales tratamientos frente a la acción deletérea de este compuesto en el sistema inmunológico.

Abstract | Introduction: Arsenic is an environmental toxic present worldwide. In men and animals, various organs and tissues are targets of its deleterious effects including those of the immune system. Objective: To determine acute arsenic toxicity in tissues and target cells of Balb/c mice using an in vivo methodology. Materials and methods: We injected Balb/c mice intraperitoneally with 9.5 or 19 mg/ kg of sodium arsenite (NaAsO2), or an equivalent volume of physiological solution as a control (with 3 per experimental group). After 30 minutes, the animals were sacrificed to obtain spleen, thymus, liver, kidneys, and blood. We determined arsenic, polyphenols, and iron concentrations in each sample and we evaluated the oxidative markers (peroxides, advanced products of protein oxidation, and free sulfhydryl groups). In splenocytes from the spleen, cell viability and mitochondrial potential were also determined. Results: The exposure to an acute dose of NaAsO2 reduced the mitochondrial function of splenocytes, which resulted in cell death. Simultaneously, the confirmed presence of arsenic in spleen samples and the resulting cytotoxicity occurred with a decrease in polyphenols, free sulfhydryl groups, and an alteration in the content and distribution of iron, but did not increase the production of peroxides. Conclusion: These findings provide scientific evidence about changes occurring in biomarkers involved in the immunotoxicity of arsenic and offer a methodology for testing possible treatments against the deleterious action of this compound on the immune system.

Acute Toxicity and Hepatotoxicity of Aqueous Extracts of Taxilli Herba from Different Hosts in Zebrafish Model / 中国实验方剂学杂志

Objective:To explore the acute toxicities and hepatotoxicities of aqueous extracts of Taxilli Herba from <italic>Morus alba</italic>， <italic>Toxicodendron</italic> <italic>trichocarpum</italic>， <italic>Camellia oleifera</italic>， <italic>Salix babylonica</italic>， <italic>Melia azedarach</italic>， and <italic>Nerium indicum</italic> against zebrafish model and the effect of different hosts on the toxicity of Taxilli Herba， hoping to provide a theoretical basis for the safe use of Taxilli Herba. Method:The normally developed AB zebrafish at 3-day post fertilization was selected for acute toxicity study. According to the results of preliminary toxicity experiments， the zebrafishes were treated with aqueous extracts of Taxilli Herba from different hosts at six doses， and their mortality was calculated 72 h later. GraphPad Prism 6.0 was used for plotting the dose-toxicity curve， followed by the calculation of their median lethal concentration （LC₅₀） and 10% lethal concentration （LC₁₀）. The gz15Tg/+（AB） liver fluorescent protein transgenic zebrafish with normal development at 4-day post fertilization was applied for the hepatotoxicity study. The zebrafishes were divided into the low-， medium-， and high-dose groups of aqueous extracts of Taxilli Herba from six hosts， the positive control （acetaminophen） group， and the blank （embryo amniotic fluid） group， and then treated with the corresponding drugs. Seventy-two hours later， the liver morphology and fluorescent area changes in zebrafish were observed. And the activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were detected. Result:The results of acute toxicity test demonstrated that the LC₅₀ values of water extracts of Taxilli Herba from <italic>M. alba</italic>， <italic>T.</italic> <italic>trichocarpum</italic>， <italic>C. oleifera</italic>， <italic>S. babylonica</italic>， <italic>M. azedarach</italic>， and <italic>N. indicum</italic> were 1.24， 0.94， 0.51， 0.38， 0.11， 0.09 g·L^-1， respectively， and the LC₁₀ values were 0.70， 0.60， 0.35， 0.28， 0.08， 0.07 g·L^-1， respectively. As revealed by hepatotoxicity test， compared with the blank group， the positive control group exhibited liver morphological changes， decreased fluorescent area （<italic>P</italic><0.01）， and elevated ALT and AST activities （<italic>P</italic>< 0.01）， suggesting that acetaminophen was hepatotoxic to zebrafish. However， there was no change in the liver morphology or fluorescent area of zebrafish in the low-， medium-， and high-dose groups of water extracts of Taxilli Herba from <italic>M. alba</italic>， and the ALT and AST activities were decreased. By contrast， the liver morphology and fluorescent areas in the medium- and high-dose groups of water extracts of Taxilli Herba from <italic>T.</italic> <italic>trichocarpum</italic>， <italic>C. oleifera</italic>， <italic>S. babylonica</italic>， <italic>M. azedarach</italic>， and <italic>N. indicum</italic> changed to varying degrees （<italic>P</italic><0.05， <italic>P</italic><0.01）. Besides， the activities of both ALT and AST were also enhanced. These indicated that Taxilli Herba from <italic>M. alba</italic> had no hepatotoxicity to zebrafish， while that from <italic>T.</italic> <italic>trichocarpum</italic>， <italic>C. oleifera</italic>， <italic>S. babylonica</italic>， <italic>M. azedarach</italic>， and <italic>N. indicum</italic> showed varying degrees of hepatotoxicity to zebrafish. Conclusion:The toxicity of Taxilli Herba is host-dependent. Taxilli Herba from <italic>M. alba</italic> has no hepatotoxicity， but that from the other five hosts shows varying degrees of hepatotoxicity. Standardizing the host source may be an important measure to realize the medication safety of Taxilli Herba.

Toxicology study of Hippolytii birch (B. Hippolytii. Sukacz) leaves and flat leaved birch (B.Platyphylla. Sukacz) / Монголын эм зүй, эм судлал

Abstract@#Numerous researches conducted in Russia, Bulgaria, Japan, and China on <i>B.pubescens, B. pendula, B.rezniczenkoana (Litv) </i> Schischk, <i>B.humilis</i> Schrank, <i>B.mandshurica</i> Rgl Nakai found that birch barks and leaves contain antioxidants and they have anti-cancer, anti-fungi, antibac- terial and anti-inflammatory properties, protect liver and promote bile secretion. Flat leaved birch (<i>B.platyphylla</i> Sukacz) cortex contains betulin and lupeol of triterpenoids and it’s leaves contain flavonoid and polyphenol compounds. The amounts of compounds found in the cortex are smaller than leaves. Specifically, the amount of flavonoid in leaves is more contained than the that of cortex and leaf buds. In any pharmacology study of new medicines, determination and evaluation of toxicity is the first priority. According to scientific evidences that birch leaves are considered to have less toxins. Not many studies have been conducted on determining toxicity of birch leaves in Mongolia. Therefore, the purpose of this research is to study the species of birches, hippolytii birch (<i>B.hippolytii. </i> Sukacz) and flat leaved birch (<i>B.platyphylla. </i> Sukacz), that were noted to have medical properties in traditional medications and identify their acute toxicity using dry extract and determine mortality dosage (LD₅₀) on animals.@*Research materials and methods@#Evaluation of the acute toxicity of birch leaves was conducted in Pharmacology laboratory of Monos group’s Drug Research Institute between June 19, 2020 and August 10. In this research, 150-204 g of WISTAR breed non-linear 44 white rats were used and 20 g of <i>B.Hippolytii’</i>s dry extract and 20 g of B. <i>Platyphylla</i> ‘s dry extract were injected.</br> The experiments to determine the toxicity of dry extracts of <i>B. hippolytii</i> and <i>B. platyphylla</i> (LD₅₀) were conducted according to Litchfield and Wilcoxon’s method and subcutaneous injects were per formed in the pelvic area of the rats. @*Results of determining acute toxicity level@#The experiments to determine the acute toxicity level of the birch’s dry extracts followed Litchfield and Wilcoxon’s method with 2-stage. LD₅₀ level was determined from the first stage of the research using G.N.Pirshen’s method and the toxicity level was identified using K.K.Sidorov’s toxicity categorization.</br> From the acute toxicity research, no-observed-adverse-effect level (NOAEL), animal daily dosage and human daily dosage (experimental) were determined. LD₅₀ 2950 mg/kg was determined as a result of acute toxicity research of B.hippolytii and B.platyphilla leaves’ dry extract.