Preventing Pediatric Opioid Poisoning: Unusual Sources and Scenarios.

This retrospective study analyzed 230 pediatric opioid exposures from a statewide poison control center over a 5-year period. Most exposures involved pharmaceutical opioids and children below 2-years-old. Narrative details were reviewed to identify uncommon sources of opioids involved in poisoning and highlight the need for tailored prevention strategies and guidance.

Self-medication cases reported to a poison information center in Brazil from 2014 to 2020.

INTRODUCTION: Self-medication is the use of drugs to treat self-diagnosed illnesses or symptoms, on one's own initiative, without the guidance of a healthcare professional. Poison centers play an important role in understanding the relationship between self-medication and poisoning. The objective of this study is to evaluate the clinical and epidemiological profile of patients exposed to and/or poisoned by different drugs through self-medication. METHODS: This retrospective, cross-sectional, and descriptive study analyzed data from 2014 to 2020, provided by the Toxicological Information and Assistance Center of Santa Catarina, Brazil. Data were selected, tabulated, and analyzed by using descriptive statistics and group comparison with the chi-square test or Fisher's exact test. A P value <0.05 was considered statistically significant. RESULTS: There were 683 cases of self-medication identified. Most patients were female (62.8 percent) and between 20 and 29 years old (26.1 percent). A toxic dose of a substance was administered in only 22.8 percent of the cases, and five deaths were recorded. The most commonly used medications were anxiolytics (18 percent), followed by analgesics and antipyretics (15.4 percent). Paracetamol was the drug used in three of the five cases that resulted in deaths. DISCUSSION: This study demonstrates the prevalence of self-medication among women aged between 20 and 29 years old. Statistical analysis failed to show a relationship between a toxic dose and clinical manifestations. Anxiolytics, analgesics, and antipyretics are the most reported medications probably because healthcare professionals are mostly the ones who contact the center. Analgesics and antipyretics account for more than fifty percent of the deaths caused by self-medication in the present report. Some limitations such as secondary sources are related. CONCLUSION: We highlight the importance of health professionals in promoting the rational use of medicines, as well as poison centers in assisting the population and raising their awareness regarding the issue.

Bioactive alkaloids from the venom of Dendrobatoidea Cope, 1865: a scoping review.

Bioactive compounds derived from secondary metabolism in animals have refined selectivity and potency for certain biological targets. The superfamily Dendrobatoidea is adapted to the dietary sequestration and secretion of toxic alkaloids, which play a role in several biological activities, and thus serve as a potential source for pharmacological and biotechnological applications. This article constitutes a scoping review to understand the trends in experimental research involving bioactive alkaloids derived from Dendrobatoidea based upon scientometric approaches. Forty-eight (48) publications were found in 30 journals in the period of 60 years, between 1962 and 2022. More than 23 structural classes of alkaloids were cited, with 27.63% for batrachotoxins, 13.64% for pyridinics, with an emphasis on epibatidine, 16.36% for pumiliotoxins, and 11.82% for histrionicotoxins. These tests included in vivo (54.9%), in vitro (39.4%), and in silico simulations (5.6%). Most compounds (54.8%) were isolated from skin extracts, whereas the remainder were obtained through molecular synthesis. Thirteen main biological activities were identified, including acetylcholinesterase inhibitors (27.59%), sodium channel inhibitors (12.07%), cardiac (12.07%), analgesic (8.62%), and neuromuscular effects (8.62%). The substances were cited as being of natural origin in the "Dendrobatidae" family, genus "Phyllobates," "Dendrobates," and seven species: Epipedobates tricolor, Phyllobates aurotaenia, Oophaga histrionica, Oophaga pumilio, Phyllobates terribilis, Epipedobates anthonyi, and Ameerega flavopicta. To date, only a few biological activities have been experimentally tested; hence, further studies on the bioprospecting of animal compounds and ecological approaches are needed.

Hellebrigenin triggers death of promyelocytic leukemia cells by non-genotoxic ways.

Bufadienolides are digitalis-like aglycones mainly found in skin secretions of toads. Among their biological properties, the mechanisms of antiproliferative action on tumor cells remain unclear for many compounds, including against leukemia cells. Herein, it was evaluated the mechanisms involved in the antiproliferative and genotoxic actions of hellebrigenin on tumor cell lines and in silico capacity to inhibit the human topoisomerase IIa enzyme. Firstly, its cytotoxic action was investigated by colorimetric assays in human tumor and peripheral blood mononuclear cells (PBMC). Next, biochemical and morphological studies were detailed by light microscopy (trypan blue dye exclusion), immunocytochemistry (BrdU uptake), flow cytometry and DNA/chromosomal damages (Cometa and aberrations). Finally, computational modelling was used to search for topoisomerase inhibition. Hellebrigenin reduced proliferation, BrdU incorporation, viability, and membrane integrity of HL-60 leukemia cells. Additionally, it increased G2/M arrest, internucleosomal DNA fragmentation, mitochondrial depolarization, and phosphatidylserine externalization in a concentration-dependent manner. In contrast to doxorubicin, hellebrigenin did not cause DNA strand breaks in HL-60 cell line and lymphocytes, and it interacts with ATPase domain residues of human topoisomerase IIa, generating a complex of hydrophobic and van der Waals interactions and hydrogen bonds. So, hellebrigenin presented potent anti-leukemic activity at concentrations as low as 0.06 µM, a value comparable to the clinical anticancer agent doxorubicin, and caused biochemical changes suggestive of apoptosis without genotoxic/clastogenic-related action, but it probably triggers catalytic inhibition of topoisomerase II. These findings also emphasize toad steroid toxins as promising lead antineoplasic compounds with relatively low cytotoxic action on human normal cells.

Investigation of crude methanolic extract from poison secreted by the Rhaebo gutattus on status redox antioxidant in mice

The study evaluated the antioxidant properties of a crude methanolic extract (CME) from Rhaebo guttatus poison in mice over a period of 7 and 30 days. The mice were divided into groups and treated with different concentrations of the extract (0; 8 µg mL-1; 16 µg mL-1 and 32 µg mL-1 or vehicle; 100 µL/animal/day; via gavage). The liver samples were analyzed for status redox parameters as catalase (CAT), glutathione-S-transferase (GST), reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). The results showed that the CME caused changes in the levels of various antioxidants and oxidative stress markers. At 7 days, there was an increase in TBARS levels (8 µg mL-1 dose) and GST activity (16 µg mL-1 dose), and a reduction in GSH levels (32 µg mL-1 dose) compared to the control group. At 30 days, TBARS and GSH levels returned to control values in the same period, but GSH increased (32 µg mL-1 dose) compared at 7 days; GST activity remained high after 30 days for 32 µg mL-1 dose compared other groups and time of treatment (7 days). Overall, the study suggests that the extract modulates antioxidant properties per se that can affect various markers of status redox in the liver of mice, mainly 16 µg mL-1 dose demonstrated to act under antioxidant enzymes in different times (7 or 30 days).

Positive Outcome in Catastrophic Momordica charantia-Associated Herb-Induced Liver Injury: A Tale of Two Cities - From Gonaives, Haiti to New York City.

Herb-induced liver injury (HILI) is a global concern due to the uptrend in Complementary and Alternative Medicine (CAM). The authors add to the current literature by reporting a case of a 61-year-old man with recent travel to Haiti. His past medical history include hepatitis C virus treated in 2021 with a sustained virologic response (SVR). He presented with profound weakness and abnormal liver transaminases in the thousands. It was initially unclear what the etiology of the patient's hepatocellular necrosis was, however, the level of abnormality was most consistent with either toxic metabolic injury or vascular ischemic injury. We initiated N-acetylcysteine and vitamin K and had a positive outcome. Upon further questioning, he admitted to consuming an herbal product cleansing tea called "asowosi" in large quantities. We searched the botanical name of the extract and found the active ingredient was Momordica charantia. The team utilized the updated Roussel Uclaf Causality Assessment Method (RUCAM), and the results demonstrated a highly probable relationship with M. charantia.

Outcomes of multifarious selection on the evolution of visual signals.

Multifarious sources of selection shape visual signals and can produce phenotypic divergence. Theory predicts that variance in warning signals should be minimal due to purifying selection, yet polymorphism is abundant. While in some instances divergent signals can evolve into discrete morphs, continuously variable phenotypes are also encountered in natural populations. Notwithstanding, we currently have an incomplete understanding of how combinations of selection shape fitness landscapes, particularly those which produce polymorphism. We modelled how combinations of natural and sexual selection act on aposematic traits within a single population to gain insights into what combinations of selection favours the evolution and maintenance of phenotypic variation. With a rich foundation of studies on selection and phenotypic divergence, we reference the poison frog genus Oophaga to model signal evolution. Multifarious selection on aposematic traits created the topology of our model's fitness landscape by approximating different scenarios found in natural populations. Combined, the model produced all types of phenotypic variation found in frog populations, namely monomorphism, continuous variation and discrete polymorphism. Our results afford advances into how multifarious selection shapes phenotypic divergence, which, along with additional modelling enhancements, will allow us to further our understanding of visual signal evolution.

Perfil clínico e epidemiológico dos acidentes por Lepidópteros, do gênero Lonomia, atendidos no CIATox/PR, 2015-2019 / Clinical and epidemiological profile of accidents caused by Lepidoptera, of the Lonomia genus, assisted at CIATox/PR

Introdução: Os acidentes por lepidópteros são agravos de interesse à saúde pública e a avaliação de suas características pode contribuir para melhorar sua assistência e prevenção. Este estudo analisou o perfil epidemiológico dos acidentes por lagartas do gênero Lonomia no Paraná. Métodos: Trata-se de estudo retrospectivo de base secundária realizado no Centro de Informação e Assistência Toxicológica do Paraná (CIATox/PR), em Curitiba, no período de 2015 a 2019. A análise foi realizada por estatística descritiva e Teste do qui-quadrado (p<0,05). Resultados: A amostra foi composta de 84 acidentes por Lonomia sp. com predomínio em adultos (45,2%), do sexo masculino (59,5%), e de lesões em membros superiores (84,5%). O contato com as lagartas ocorreram na área peridomiciliar da residência habitual do paciente (72,6%), na zona rural (64,27%) da macrorregião oeste paranaense (38,1%). O verão concentrou 71,4% dos casos, seguido por primavera e outono com 14,3% dos casos, respectivamente, sem registros no inverno. As manifestações clínicas mais frequentes foram dor local (62,4%), equimose (34,1%), eritema (34,1%), edema e queimação (17,6% cada). A classificação leve mostrou uma redução entre a fase inicial e a final do processo, ao contrário da moderada e grave, que tiveram aumento significativo de casos (p=0,006). O RNI (Relação Normatizada Internacional) foi incoagulável em 16,7% dos pacientes. Dois casos apresentaram piora do quadro clínico, sendo uma evolução para acidente vascular cerebral hemorrágico e um óbito. Discussão: Maior número de casos registrados na zona rural, tanto na residência habitual ou ambiente laboral, se dá pelo maior contato com o habitat das lagartas como árvores frutíferas e grandes monoculturas, o que também explica o fato de a macrorregião oeste ter o maior número de casos registrados. O aumento do desmatamento, incentivos à construção de parques públicos e plantio de árvores frutíferas na zona urbana são hipóteses para o aumento de casos nessa área. Percebeu-se que manifestações clínicas discretas podem ter uma evolução desfavorável, quando comparado estadiamento inicial e final. A realização do RNI se mostrou de grande importância na mudança de estadiamento, conduta terapêutica e diagnóstico. Conclusão: O perfil encontrado foi de acidentes por Lonomia sp. com sazonalidade no verão, em homens adultos da zona rural com gravidade moderada. Esses achados revelam a importância do diagnóstico e tratamento precoce frente às diferentes possibilidades de evolução clínica desses acidentes. É fundamental estimular estratégias para identificação da lagarta, notificação dos casos e medidas preventivas permanentes para reduzir riscos e agravos (AU).

Introduction: Lonomic accidents are of public health interest and the evaluation of their characteristics can contribute to the improvement of their attention and prevention. This study analyzed the epidemiological profile of Lonomic accidents in Paraná. Methods: This study is a retrospective secondary-based study carried out at the Center of Toxicologic Information and Assistance of Paraná (CIATox/PR), in Curitiba, from 2015 to 2019. Descriptive statistical analyses were performed using the Chi-square test (p<0.05). Results: The sample consisted of 84 accidents with Lonomia sp., showing greater occurrences among adults (45.2%) of the male gender (59.5%) and injuries on the upper limbs (84.5%). Contact with the worm occurred mainly in the patient's usual residence (72.6%), in the rural area (64.27%), and in Paraná's West macro-region (38.1%). Most cases were registered in the summer (71.4%), followed by spring and autumn (14.3%), and no accidents were registered in winter. The most frequent clinical manifestations were local pain (62.3%), ecchymosis (34.1%), erythema (34.1%), swelling and burning (17.6% each). The mild classification showed a reduction between the initial and the final phase of the process, as opposed to moderate and severe classifications, which showed a significant increase in the percentage (p=0,006). The INR was incoagulable in 16.7% of patients. Two cases showed progressive worsening, one of them evolved into a hemorrhagic stroke and one death. Discussion: The greater number of incidents registered in the rural area, both in the patients' usual residence and work environment, can be due to the greater contact with the caterpillar's natural habits, such as fruit trees and large monocultures. This also explains the larger number of registered incidents in the western macro-region. The increased deforestation, the construction of public parks, and the planting of fruit trees in the urban area are hypotheses for the increase of reported cases in this area. When comparing initial and final staging, it was noticed that discrete clinical manifestations could have an unfavorable evolution. The INR request proved to be of great importance in the management, diagnosis and change of staging of the patient. Conclusion:The epidemiological profile was of Lonomia sp. accidents happening in summer in adult males in the rural area with moderate severity. These findings reveal the importance of early diagnosis and treatment in view of these accidents' different possibilities of clinical evolution. It is essential to encourage strategies for identifying the caterpillar, reporting cases, and implementing permanent preventive measures to reduce risks and complications (AU).

Selection and Admixture in a Polytypic Aposematic Frog.

AbstractPhenotypic differentiation within polytypic species is often attributed to selection, particularly when selection might be acting on a trait that serves as a signal for predator avoidance and mate choice. We evaluated this hypothesis by examining phenotypic and genotypic clines between populations of the strawberry poison frog Oophaga pumilio, a polytypic species that exhibits aposematic color pattern variation that is thought to be subject to both natural and sexual selection. Our aim was to assess the extent of admixture and to estimate the strength of selection acting on coloration across a region of Panama where monomorphic populations of distinctly colored frogs are separated by polymorphic populations containing both color variants alongside intermediately colored individuals. We detected sharp clinal transitions across the study region, which is an expected outcome of strong selection, but we also detected evidence of widespread admixture, even at sites far from the phenotypic transition zone. Additionally, genotypic and phenotypic clines were neither concordant nor coincident, and with one exception, selection coefficients estimated from cline attributes were small. These results suggest that strong selection is not required for the maintenance of phenotypic divergence within polytypic species, challenging the long-standing notion that strong selection is implicit in the evolution of warning signals.

Pesticide exposure and poisoning in Brazil: Outcome severity, clinical manifestations and management of cases reported to a poison control center.

This work aimed to identify variables associated with increased risk of outcome severity as well as to describe clinical manifestations/symptoms and management of pesticide-related cases reported to a poison center in Brazil. An increased risk of more severe outcomes was observed when exposures occurred in rural areas, involved suicide attempts and moderately to extremely hazardous pesticides. Clinical manifestations with higher frequencies included vomiting, nausea, sialorrhea, headache, miosis and sweating. From the treatment initially applied to the patient, 51.91% encompassed gastric lavage, but this procedure was only recommended in 20.01% of cases by the CIATox. Identifying risk factors associated with poor outcome, describing clinical manifestations, and contrasting initial treatment measures adopted against those recommended by the Poison Center can help determine diagnosis, prognosis and ensure appropriate clinical interventions are used in cases of pesticide poisoning.

Evaluation of Paralytic Shellfish Toxins in Marine Oyster Farming and Microalgae in the Atlantic Amazon Evidences Safety but Highlights Potential Risks of Shellfish Poisoning.

Marine phycotoxins are organic compounds synthesized by some species of microalgae, which accumulate in the tissues of filter-feeder organisms such as bivalve mollusks. These toxins can cause acute intoxication episodes in humans, a severe threat to aquaculture and fisheries. In the State of Pará, Brazil, oyster farming has community, artisanal and sustainable bases, using mangroves as cultivation environment and seed banks. In small-scale production, there are often no established methods of safeguarding the health of consumers elevating the potential risks of shellfish poisoning outbreaks. Our study evaluated the presence of phycotoxins in oysters cultivated in five municipalities in the region of the Atlantic Amazon (Pará, Brazil) assessing the quality of the final product. We further evaluated the microalgae, water quality, and the spatio-temporal variation of physicochemical factors in the same area. Diatoms dominated the microalgae composition, followed by dinoflagellates, some of which are reported to be potentially toxic and producers of paralytic shellfish toxins. For the first time, we describe the occurrence of the potentially toxic dinoflagellate Ostreopsis sp. in the Amazon region. Furthermore, for the first time, toxins were detected in oyster farming in the northeast of the State of Pará, namely GTX2,3, STX, and dc-STX nevertheless, with nontoxic values. The identified toxins represent a potential threat to shellfish consumers.

Loxoscelismo: revisión de la literatura a propósito de un caso / Loxoscelism: Literary review about a case

La mordedura de la araña de rincón es un motivo de consulta frecuente en los servicios de urgencia de Chile, que puede producir un cua-dro severo con manifestaciones cutáneas y sistémicas. En Chile, Loxocelles laeta se ubica principalmente desde la I a la VIII región, aunque se han reportado casos de loxocelismo en todo el país. El veneno de esta araña tiene efecto cutáneo-necrosante, hemolítico, vasculítico y coagulante. Podemos identificar 3 tipos de loxocelismo: cutáneo necrótico (80% de los casos), cutáneo edematoso (5%) y cutáneo visceral (10-15%). Este último tiene una letalidad entre 1 y 3% del total de casos de loxocelismo, la cual depende en gran parte de la precocidad de su diagnóstico y manejo oportuno. Se debe controlar cualquier tipo de loxocelismo durante las primeras 24 a 48 horas y vigilar la aparición de síntomas y signos sugerentes del cuadro visceral. No existe ningún examen de laboratorio que confirme el diagnóstico, los cuales sólo se alteran de modo marcado en los casos viscerales. El manejo de las lesiones cutáneas es con hielo local, antiinflamatorios, antihistamínicos y curaciones seriadas. En caso del loxocelismo visceral, el tratamiento principal es de soporte. La dapsona fue una indicación frecuente en el pasado y se asocia a efectos adversos graves, siendo el principal la exacerbación de la hemólisis, por lo que actualmente su uso no está recomendado. El suero anti-loxoceles no tiene evidencia que avale menor severidad ni mortalidad del cuadro.

The bite of the corner spider is a frequent reason for consultation in the emergency services of Chile, which can produce a severe reaction with cutaneous and systemic manifestations. In Chile, Loxocelles laeta is located mainly in the first to the eighth region, but cases of loxoscelism are reported throughout the country. The venom of this spider has cutaneous-necrotizing, hemolytic, vasculitic, and coagulant effects. Three types of loxoscelism can be identified, necrotic cutaneous (80% of cases), edematous cutaneous (5%), and visceral cutaneous (10-15%). The latter has a lethality between 1 and 3% of all cases of loxoscelism, which largely depends on the early diagnosis and timely management. Any loxoscelism should be controlled during the first 24 to 48 hours, and be alert to the appearance of symptoms and signs suggestive of visceral manifestations. There isn ́t any laboratory test to confirm the diagnosis. Laboratory tests are only markedly altered in visceral cases. The management of skin lesions is with local ice, NSAIDs, antihistamine and serial dressings. In the case of visceral loxoscelism, treatment begins with suspicion and early diagnosis. For these patients, the principal treatment is supportive care. Although it was recommended in the past, Dapsone is associated with severe adverse effects, like exacerbation of he-molysis, so its use is not currently recommended. The anti-loxocelles serum has no evidence to support less severity or mortality reduction.

A biologia, morfologia craniana e as glândulas de veneno das pererecas-de-capacete: uma integração bem sucedida

With the great biodiversity existing on our planet, different organisms have developed defensive strategies based on the use of toxins. Among tetrapods, the Amphibia class are highlighted in this sense, since all its representatives have poison glands in their skin. A very interesting group from the toxinological point of view are the frogs, especially the casque-headed tree frogs. They form a group belonging to the Lophiohylini tribe, in which many species have a skull with high bone coverage, bone projections in the form of spines, dermal coossification and phragmotic behavior, using the head to seal the entrance of their shelters. Aspects of the natural history of representative species of Lophiohylini (Nyctimantis spp, Trachycephalus spp, Corythomantis greeningi and Itapotihyla langsdorffii) were elucidated through fieldwork. These data were associated with cranial anatomical and histological analyzes of the head of each species. The present work verified a correlation between the increase of the cranial bone coverage and its spinous projections related to venom glands with the execution of the phragmosis. It was also evidenced in the skin secretions of these species, significant differences in chemical composition, with the presence of molecules with enzymatic activities widely found in animal venoms, such as hyaluronidases. Furthermore, except for N. galeata and I. langsdorffii, the other species showed evident cytotoxic potential. Through the information gathered, it was possible to list different species of casque-headed tree frogs endowed with a “Toxin Inoculating System” (SIT), defined by the presence of spines related to cutaneous glands containing toxic secretions, which can, therefore, be considered venomous (instead of poisonous) species.

Com a grande biodiversidade existente em nosso planeta, diferentes organismos desenvolveram estratégias defensivas baseadas na utilização toxinas. Entre os tetrápodes, a classe Amphibia merece destaque nesse sentido, visto que todos seus representantes possuem glândulas de veneno em sua pele. Um grupo bastante interessante do ponto de vista toxinológico, são os anuros, em especial as “pererecasde-capacete”. São espécies pertencentes a tribo Lophiohylini, na qual muitas possuem o crânio com alta abrangência óssea, projeções ósseas em formato de espinhos, coossificação dérmica e comportamento fragmótico, utilizando a cabeça para tapar a entrada dos abrigos que ocupam. Através de trabalhos de campo foram elucidados aspectos da história natural de espécies representativas de Lophiohylini (Nyctimantis spp, Trachycephalus spp, Corythomantis greeningi e Itapotihyla langsdorffii). Esses dados foram associados a análises cranianas anatômicas e histológicas da cabeça de cada espécie. O presente trabalho verificou uma correlação entre o aumento da abrangência óssea craniana e suas projeções espinhosas, essas relacionadas a glândulas de veneno com a execução da fragmose. Foi também evidenciado nas secreções cutâneas dessas espécies, diferenças significativas de composição química e a presença de moléculas com atividades enzimáticas amplamente encontradas em peçonhas animais, como hialuronidases. Além disso, com exceção de N. galeata e I. langsdorffii, as demais espécies apresentaram evidente potencial citotóxico. Assim, por meio das informações levantadas, foi possível elencar diferentes espécies de pererecas-de-capacete dotadas de um “Sistema Inoculador de Toxinas” (SIT), definido pela presença de espinhos relacionados a glândulas cutâneas contendo secreções tóxicas, e que podem, por isso, ser consideradas como espécies peçonhentas ao invés de venenosas.

Total Synthesis of Decahydroquinoline Poison Frog Alkaloids ent-cis-195A and cis-211A.

The total synthesis of two decahydroquinoline poison frog alkaloids ent-cis-195A and cis-211A were achieved in 16 steps (38% overall yield) and 19 steps (31% overall yield), respectively, starting from known compound 1. Both alkaloids were synthesized from the common key intermediate 11 in a divergent fashion, and the absolute stereochemistry of natural cis-211A was determined to be 2R, 4aR, 5R, 6S, and 8aS. Interestingly, the absolute configuration of the parent decahydroquinoline nuclei of cis-211A was the mirror image of that of cis-195A, although both alkaloids were isolated from the same poison frog species, Oophaga (Dendrobates) pumilio, from Panama.

Morphology of the Cutaneous Poison and Mucous Glands in Amphibians with Particular Emphasis on Caecilians (Siphonops annulatus).

Caecilians (order Gymnophiona) are apodan, snake-like amphibians, usually with fossorial habits, constituting one of the most unknown groups of terrestrial vertebrates. As in orders Anura (frogs, tree frogs and toads) and Caudata (salamanders and newts), the caecilian skin is rich in mucous glands, responsible for body lubrication, and poison glands, producing varied toxins used in defence against predators and microorganisms. Whereas in anurans and caudatans skin gland morphology has been well studied, caecilian poison glands remain poorly elucidated. Here we characterised the skin gland morphology of the caecilian Siphonops annulatus, emphasising the poison glands in comparison to those of anurans and salamanders. We showed that S. annulatus glands are similar to those of salamanders, consisting of several syncytial compartments full of granules composed of protein material but showing some differentiated apical compartments containing mucus. An unusual structure resembling a mucous gland is frequently observed in lateral/apical position, apparently connected to the main duct. We conclude that the morphology of skin poison glands in caecilians is more similar to salamander glands when compared to anuran glands that show a much-simplified structure.

First characterization of toxic alkaloids and volatile organic compounds (VOCs) in the cryptic dendrobatid Silverstoneia punctiventris.

BACKGROUND: Poison frogs are known for the outstanding diversity of alkaloid-based chemical defences with promising therapeutic applications. However, current knowledge about chemical defences in Dendrobatoidea superfamily has two sources of bias. First, cryptic, brown-colored species have been neglected in comparison to those conspicuously colored, and second, there has been little interest in characterizing metabolites other than alkaloids mediating defensive functions. In an effort to contribute to fill the gap of knowledge about cryptic species and broadening the spectrum of compounds analyzed we have applied head-space solid phase microextraction coupled to gas chromatography and mass spectrometry (HS-SPME/GC-MS) for extracting amphibian alkaloids and volatile organic compounds (VOCs) from Silverstoneia punctiventris. RESULTS: Using the skin from 8 specimens in 4 biological replicates we have found 33 different compounds. Twenty of them were classified as VOCs into 15 chemical classes including alkanes, alcohols, carbonyl compounds, methylpyridines, benzothiazoles, N-alkylpyrrolidines, pyrazines, and sesquiterpenoids, some of which were previously reported as repellents, defence compounds or defence pheromones in other organisms, and as sex pheromones in a treefrog. Interestingly, six of the remaining compounds were identified as alkaloids previously reported in other toxic/unpalatable dendrobatid frogs. CONCLUSIONS: This is the first report of alkaloids and VOCs found in the Silverstoneia genus, which has been assumed for decades as non-chemically defended. This study establishes HS-SPME/GC-MS as a new application for a simultaneous approach to amphibian alkaloids and VOCs in poison frogs while opens up new research questions to assess the co-occurrence of both type of compounds and to investigate the evolutionary significance of a defence gradient that includes olfactory avoidance, unpalatability, and toxicity in dendrobatids. In addition, our results show that amphibian alkaloids could have a dual function (olfactory at distance, taste by contact) never explored before neither in Silverstonaeia nor in any other dendrobatid species.

Action of heparin and acetylcholine modulators on the neurotoxicity of the toad Rhinella schneideri (Anura: Bufonidae) in Brazil / Acción de la heparina y moduladores de acetilcolina en la neurotoxicidad del sapo Rhinella schneideri (Anura: Bufonidae) en Brasil

Abstract Introduction: Rhinella schneideri is a toad widely distributed in South America and its poison is characterized by inducing cardiotoxicity and neurotoxicity. Objective: In this work, we investigated pharmacological strategies to attenuate the peripheral neurotoxicity induced by R. schneideri poison in avian neuromuscular preparation. Methods: The experiments were carried out using isolated chick biventer cervicis preparation subjected to field stimulation for muscle twitches recordings or exposed to acetylcholine and potassium chloride for contracture responses. Results: Poison (10 μg/ml) produced complete neuromuscular blockade in chick biventer cervicis preparation within approximately 70 min incubation (times for 50 and 90 % blockade: 15 ± 3 min and 40 ± 2 min, respectively; P < 0.05, N= 5); contracture responses to exogenous acetylcholine and KCl were unaffected by poison indicating no specificity with postsynaptic receptors or myotoxicity, respectively. Poison (10 μg/ml)-induced neuromuscular blockade was not prevented by heparin (5 and 150 IU/ml) under pre- or post-treatment conditions. Incubation at low temperature (23-25 °C) abolished the neuromuscular blockade; after raising the temperature to 37 °C, the complete neuromuscular blockade was slightly slower than that seen in preparations directly incubated at 37 °C (times for 50 and 90 % blockade: 23 ± 2 min and 60 ± 2.5 min, respectively; P < 0.05, N= 4). Neostigmine (3.3 μM) did not reverse the neuromuscular blockade in BC preparation whereas 3,4-diaminopyridine (91.6 μM) produced a partial and sustained reversal of the twitch responses (29 ± 7.8 % of maximal reversal reached in approximately 40 min incubation; P < 0.05, N= 4). Conclusions: R. schneideri poison induces potent peripheral neurotoxicity in vitro which can be partially reversible by 3,4-diaminopyridine.

Resumen Introducción: Rhinella schneideri está ampliamente distribuida en Suramérica y su veneno es caracterizado por inducir cardiotoxicidad y neurotoxicidad. Objetivo: En este trabajo, investigamos estrategias farmacológicas para atenuar la neurotoxicidad periférica inducida por el veneno de R. schneideri en preparaciones neuromusculares de aves. Métodos: Los experimentos fueron realizados usando preparaciones de biventer cervicis de pollos sometidas a estimulación de campo para el registro de las contracciones musculares o expuestas a la acetilcolina y al cloruro de potasio para la respuesta contractural. Resultados: El veneno (10 µg/ml) provocó un bloqueo neuromuscular completo en las preparaciones después de aproximadamente 70 min de incubación (tiempos para 50 y 90 % de bloqueo: 15 ± 3 min y 40 ± 2 min, respectivamente; P < 0.05, N = 5); las contracturas en respuesta a la acetilcolina y el KCl exógenos no fueron afectadas por el veneno, indicando que no hay una interacción especifica con receptores postsinápticos o miotoxicidad respectivamente. El bloqueo neuromuscular causado por el veneno (10 µg/ml) no fue prevenido por la heparina (5 y 150 UI/ml) bajo condiciones pre y post-tratamiento. La incubación a bajas temperaturas (23-25 ºC) abolió el bloqueo neuromuscular; después de aumentar la temperatura a 37 ºC, el bloqueo neuromuscular total fue levemente más lento que el visto en preparaciones directamente incubadas a 37 ºC (tiempos para 50 y 90 % de bloqueo: 23 ± 2 min y 60 ± 2.5 min, respectivamente; P < 0.05, N= 4). Neostigmina (3.3 µM) no revirtió el bloqueo neuromuscular, mientras que 3.4-diaminopiridina (91.6 µM) produjo una reversión parcial y sostenida de las respuestas neuromusculares (29 ± 7.8 % de la reversión máxima alcanzada en aproximadamente 40 min de incubación; P < 0.05, N = 4). Conclusiones: El veneno de R. schneideri indujo neurotoxicidad periférica potente in vitro, el cual puede ser revertido por 3.4-diaminopiridina.

Sociodemographic characteristics and exposure patterns of pesticide-related cases reported to a poison service center in Brazil between 2012 and 2016.

Pesticide poisoning is a significant public health problem responsible for an estimated three million poisoning cases per year and more than 250,000 deaths, most of which occur in underdeveloped countries. We evaluated pesticide exposure cases reported to a toxicological service center in Brazil, between 2012 and 2016. There were 3211 cases of pesticide exposure, with a high prevalence in adults aged 20-39 years (41.2%). Attempted suicide was the leading cause of pesticide cases (48%). Occupational exposure to pesticides of agricultural use was more frequently observed among men. Accidental exposure and attempted suicide were more frequently observed in urban areas while occupational exposure was more prevalent in rural areas. A higher exposure rate was observed among men in counties with higher agricultural activities. Establishing prevalence and cause of pesticide exposure is important to provide subsidy for evidence-based interventions in the field.

Severe acute toxic exposures in children and adolescents: case series / Exposições tóxicas agudas graves em crianças e adolescentes: série de casos

ABSTRACT Objective: To describe a case series of severe acute toxic exposures (SATE) in individuals <20 years old followed-up by a regional Poison Control Center (PCC). Methods: Descriptive cross-sectional study. All patients who were <20yo and classified as score 3 (severe) and 4 (fatal) following Poisoning Severity Score were included for analysis. According to the outcome, patients were classified as PSS 3 when they developed intense clinical manifestations with risk of death or important sequelae; and as PSS 4 when death had resulted from direct cause or complication of the initial exposure. The data of patients were obtained from the Brazilian electronic database system (DATATOX). Results: During the biennium 2014-2015, Campinas PCC followed up 5,095 patients <20yo, with 30 being classified as SATE (PSS=3, n=24; PSS=4, n=6). The exposures circumstances were unintentional (15); intentional (14; suicide attempt = 11; street drugs consumption = 3); and not explained (1). The exposures were significantly more frequent in adolescents >14yo (n=17; p<0.01). The involved agents were venomous animals (8; scorpions=5); medicines (8; miscellaneous=6); chemicals (6); illegal rodenticides containing acetylcholinesterase inhibitors (chumbinho, 4); drugs of abuse (3); button battery (1). Three patients evolved with sequels (esophageal stricture post-corrosive ingestion). The median length of hospital stay was 6 days (IQR: 5-12 days); 26 patients were treated in intensive care units, and 22 of them needed mechanical ventilation; 12, inotropic/vasopressors; and 3, renal replacement therapy. Conclusions: Scorpion stings and poisonings caused by medicines and chemicals were the main causes of SATE. The SATE were significantly more frequent in adolescents, due to deliberate self-poisoning.

RESUMO Objetivo: Descrever uma série de casos de exposições tóxicas agudas graves (ETAG) em pacientes <20 anos seguidos por um Centro de Informação e Assistência Toxicológica (CIATox) regional. Métodos: Estudo descritivo de corte transversal. Incluídos no estudo todos os casos classificados como escore 3 (graves) e 4 (fatais) de acordo com o escore de gravidade de intoxicações (poisoning severity score - PSS). Segundo o PSS, os casos são classificados em relação ao desfecho como escore 3 quando os pacientes desenvolveram manifestações clínicas intensas, com risco de morte ou que resultaram em sequelas importantes; e escore 4 quando a morte foi resultado de causa direta ou por complicação da exposição. Os dados analisados foram obtidos da base eletrônica brasileira do Sistema Nacional de Informações Tóxico-Farmacológicas DATATOX. Resultados: No biênio 2014-2015 o CIATox de Campinas atendeu 5.095 casos de pacientes <20 anos, dos quais 30 foram classificados como ETAG (PSS=3, n=24; PSS=4, n=6). Quanto à circunstância, 15 foram acidentais, 14 intencionais (11 por tentativas de suicídio e três por abuso de drogas) e um de causa não esclarecida, sendo significativamente mais frequentes nos adolescentes >14 anos (n=17; p<0,01). Os grupos de agentes envolvidos foram: animais peçonhentos (8; escorpiões=5); medicamentos (8; associações=6); produtos químicos de uso domiciliar/industrial (6); rodenticidas inibidores da colinesterase de uso ilegal (chumbinho=4); drogas de abuso (3); e bateria no formato de disco (1). Três pacientes evoluíram com sequelas (estenose esofágica pós-ingestão de corrosivos). O tempo mediano de internação foi de seis dias (mediana, quartis e intervalo interquartil=5-12 dias), sendo 26 pacientes admitidos em unidades de cuidados intensivos, dos quais 22 necessitaram de ventilação mecânica, 12 de inotrópicos/vasopressores e três de terapia de substituição renal. Conclusões: Escorpionismo e intoxicações por medicamentos e por produtos químicos de uso domiciliar/industrial foram as principais causas de ETAG, sendo elas significativamente mais frequentes em adolescentes, principalmente por tentativas de suicídio.

Clinical and epidemiological analysis of suicide attempts in children assisted by a poison control center / Análise clínica e epidemiológica das tentativas de suicídio em crianças atendidas em um centro de informação e assistência toxicológica

ABSTRACT Objective: To assess suicide attempts in children seeking care at a Poison Control Center. Methods: Cross-sectional study with children (<12 years old) that attempted suicide and were cared at the Poison Control Center in Londrina, Paraná, Southern Brazil, from April 1985 to December 2018. Results: We identified 59 children, most of them females (74.6%), who used only one product (77.9%). Among the products involved, medications were the most important ones (88.1%). Neurological/psychiatric/muscular manifestations (61.0%) were the main symptoms presented. The main reason identified for the suicide attempt was conflicts with family and/or friends (27.1%). Suicide attempts were more frequent in 2001-2003 and 2016-2018. Conclusions: Suicide attempts occurred mainly in female children with a single agent (mainly medications), and the main reason was family conflicts..

RESUMO Objetivo: Analisar as tentativas de suicídio em crianças atendidas em um Centro de Informação e Assistência Toxicológica (CIATox-Londrina). Métodos: Estudo transversal com crianças (<12 anos) atendidas no CIATox-Londrina, Paraná, de abril/1985 a dezembro/2018, com tentativa de suicídio. Resultados: Identificaram-se 59 crianças, com predomínio do sexo feminino (74,6%) e com o uso de apenas um produto (77,9%). Entre os produtos envolvidos, destacaram-se os medicamentos (88,1%). As manifestações neurológicas/psíquicas/musculares (61,0%) foram os principais sintomas apresentados. O principal motivo identificado da tentativa de suicídio foram os conflitos com familiares e/ou amigos (27,1%). Houve maior frequência de tentativas de suicídio nos triênios 2001-2003 e 2016-2018. Conclusões: As tentativas de suicídio ocorreram predominantemente nas crianças do sexo feminino, com um único agente (em geral, medicamentos), em que o principal motivo foram os conflitos familiares, observando-se um aumento ao longo dos anos.