Clinical outcomes in a murine model after envenoming by the Amazonian scorpions Tityus strandi and Tityus dinizi.

The Brazilian Amazon is home to a rich fauna of scorpion species of medical importance, some of them still poorly characterized regarding their biological actions and range of clinical symptoms after envenoming. The Amazonian scorpion species Tityus strandi and Tityus dinizi constitute some of the scorpions in this group, with few studies in the literature regarding their systemic repercussions. In the present study, we characterized the clinical, inflammatory, and histopathological manifestations of T. strandi and T. dinizi envenoming in a murine model using Balb/c mice. The results show a robust clinical response based on clinical score, hyperglycemia, leukocytosis, increased cytokines, and histopathological changes in the kidneys and lungs. Tityus strandi envenomed mice presented more prominent clinical manifestations when compared to Tityus dinizi, pointing to the relevance of this species in the medical scenario, with both species inducing hyperglycemia, leukocytosis, increased cytokine production in the peritoneal lavage, increased inflammatory infiltrate in the lungs, and acute tubular necrosis after T. strandi envenoming. The results presented in this research can help to understand the systemic manifestations of scorpion accidents in humans caused by the target species of the study and point out therapeutic strategies in cases of scorpionism in remote regions of the Amazon.

Pioneering in vitro characterization of macrophage response induced by scorpion venoms from the Brazilian Amazon.

There are several scorpion species of medical relevance around the world. Some of them are well characterized by their toxins and clinical outcomes. Brazilian Amazon has a great amount of these arthropods that have an impact in the scorpionism events specifically in this region of Brazil. Recently, several studies pointed out the immune system activation during scorpion envenouming as an important facet of scorpionism, inducing a sepsis-like state that culminates in clinical severity and death. In this work, we characterized the macrophage response of three species of clinical relevance in Brazilian Amazon: Tityus silvestris, T. metuendus and T. obscurus and one specie with no toxic effects to humans, Brotheas amazonicus. All the four species analyzed were able to induce pro- and anti-inflammatory cytokine production in a J774.1 murine macrophage model. This activation was dependent on TLR2/TLR4/MyD88 activation and abolished by TLRs antagonists. These results suggest that the venoms of the four species analyzed were able to induce macrophage response in agreement to the well-established immune activation by T. serrulatus venom. Our findings provide new insights into the clinical repercussions of scorpionism of uncharacterized species and point to new biotechnological applications of these venoms and possible supportive therapies in scorpionism.

On the noxious black Amazonian scorpion, Tityus obscurus (Scorpiones, Buthidae): Taxonomic notes, biology, medical importance and envenoming treatment.

Tityus obscurus has caused mild, moderate and severe accidents of medical relevance in the eastern Brazilian Amazon and French Guiana. Tityus obscurus has sexual dimorphism although males and females have uniform black coloration. In the Amazon, one of the habitats of this scorpion is seasonally flooded forests (igapós and várzeas). However, most stings occur in terra firme forest areas (non-flooded region), where most rural communities are located. Adults and children stung by T. obscurus may experience an "electric shock" sensation for more than 30 h after the sting. Our data shows that people inhabiting remote forest areas, including rubber tappers, fishermen and indigenous people, with no access to anti-scorpion serum, use parts of native plants, such as seeds and leaves, against pain and vomiting caused by scorpion stings. Although there is a technical effort to produce and distribute antivenoms in the Amazon, many cases of scorpion stings are geographically unpredictable in this region, due to the lack of detailed knowledge of the natural distribution of these animals. In this manuscript, we compile information on the natural history of T. obscurus and the impact of its envenoming on human health. We identify the natural sites that host this scorpion in the Amazon, in order to warn about the risk of human envenoming. The use of specific antivenom serum is the recommended treatment for accidents involving venomous animals. However, atypical symptoms not neutralized by the available commercial antivenom are reported in the Amazon region. Facing this scenario, we present some challenges to the study of venomous animals in the Amazon rainforest and possible experimental bottlenecks and perspectives for establishing a method aimed at producing an efficient antivenom.

On the noxious black amazonian scorpion, Tityus obscurus (Scorpiones, Buthidae): taxonomic notes, biology, medical importance and envenoming treatment

Tityus obscurus has caused mild, moderate and severe accidents of medical relevance in the eastern Brazilian Amazon and French Guiana. Tityus obscurus has sexual dimorphism although males and females have uniform black coloration. In the Amazon, one of the habitats of this scorpion is seasonally flooded forests (igapós and várzeas). However, most stings occur in terra firme forest areas (non-flooded region), where most rural communities are located. Adults and children stung by T. obscurus may experience an “electric shock” sensation for more than 30 h after the sting. Our data shows that people inhabiting remote forest areas, including rubber tappers, fishermen and indigenous people, with no access to anti-scorpion serum, use parts of native plants, such as seeds and leaves, against pain and vomiting caused by scorpion stings. Although there is a technical effort to produce and distribute antivenoms in the Amazon, many cases of scorpion stings are geographically unpredictable in this region, due to the lack of detailed knowledge of the natural distribution of these animals. In this manuscript, we compile information on the natural history of T. obscurus and the impact of its envenoming on human health. We identify the natural sites that host this scorpion in the Amazon, in order to warn about the risk of human envenoming. The use of specific antivenom serum is the recommended treatment for accidents involving venomous animals. However, atypical symptoms not neutralized by the available commercial antivenom are reported in the Amazon region. Facing this scenario, we present some challenges to the study of venomous animals in the Amazon rainforest and possible experimental bottlenecks and perspectives for establishing a method aimed at producing an efficient antivenom.

Kinetic Activity of Chromosomes and Expression of Recombination Genes in Achiasmatic Meiosis of Tityus (Archaeotityus) Scorpions.

Several species of Tityus (Scorpiones, Buthidae) present multi-chromosomal meiotic associations and failures in the synaptic process, originated from reciprocal translocations. Holocentric chromosomes and achiasmatic meiosis in males are present in all members of this genus. In the present study, we investigated synapse dynamics, transcriptional silencing by γH2AX, and meiotic microtubule association in bivalents and a quadrivalent of the scorpion Tityus maranhensis. Additionally, we performed RT-PCR to verify the expression of mismatch repair enzymes involved in crossing-over formation in Tityus silvestris gonads. The quadrivalent association in T. maranhensis showed delay in the synaptic process and long asynaptic regions during pachytene. In this species, γH2AX was recorded only at the chromosome ends during early stages of prophase I; in metaphase I, bivalents and quadrivalents of T. maranhensis exhibited binding to microtubules along their entire length, while in metaphase II/anaphase II transition, spindle fibers interacted only with telomeric regions. Regarding T. silvestris, genes involved in the recombination process were transcribed in ovaries, testes and embryos, without significant difference between these tissues. The expression of these genes during T. silvestris achiasmatic meiosis is discussed in the present study. The absence of meiotic inactivation by γH2AX and holo/telokinetic behavior of the chromosomes are important factors for the maintenance of the quadrivalent in T. maranhensis and the normal continuation of the meiotic cycle in this species.

Scorpion species of medical importance in the Brazilian Amazon: a review to identify knowledge gaps.

Scorpionism is a relevant medical condition in Brazil. It is responsible for most accidents involving venomous animals in the country, which leads to severe symptoms that can evolve to death. In recent years, an increase of almost 50% in the incidence of scorpionism has been observed in the Northern Region, where the highest severity of envenoming has been notified since the beginning of the 21st century. This review aims to provide an in-depth assessment of public data and reports on symptoms and epidemiology of envenoming, ecological aspects of scorpions, and characterization of venoms and toxins to access the gaps that need to be filled in the knowledge of the scorpion species of medical importance from the Brazilian Amazon. A systematic search using the string words "Amazon" and "scorpion" was performed on 11 databases. No restriction on date, language or status of the publication was applied. Reports not related to the Brazilian Amazon were excluded. Therefore, 88 studies remained. It is shown that populations of scorpions of medical importance, even of the same species, may present significant toxic variations peculiar to some regions in the Brazilian Amazon, and commercial scorpion antivenoms were not able to shorten the intensity and duration of neurological manifestations in patients stung by T. silvestris, T. apiacas or T. obscurus. It is also highlighted that the toxins responsible for triggering these alterations have not been elucidated yet and this is a fruitful field for the development of more efficient antivenoms. Furthermore, the geographic distribution of scorpions of the genus Tityus in the Brazilian Amazon was revised and updated. The cumulative and detailed information provided in this review may help physicians and scientists interested in scorpionism in the Brazilian Amazon.

Scorpion species of medical importance in the Brazilian Amazon: a review to identify knowledge gaps

Scorpionism is a relevant medical condition in Brazil. It is responsible for most accidents involving venomous animals in the country, which leads to severe symptoms that can evolve to death. In recent years, an increase of almost 50% in the incidence of scorpionism has been observed in the Northern Region, where the highest severity of envenoming has been notified since the beginning of the 21st century. This review aims to provide an in-depth assessment of public data and reports on symptoms and epidemiology of envenoming, ecological aspects of scorpions, and characterization of venoms and toxins to access the gaps that need to be filled in the knowledge of the scorpion species of medical importance from the Brazilian Amazon. A systematic search using the string words "Amazon" and "scorpion" was performed on 11 databases. No restriction on date, language or status of the publication was applied. Reports not related to the Brazilian Amazon were excluded. Therefore, 88 studies remained. It is shown that populations of scorpions of medical importance, even of the same species, may present significant toxic variations peculiar to some regions in the Brazilian Amazon, and commercial scorpion antivenoms were not able to shorten the intensity and duration of neurological manifestations in patients stung by T. silvestris, T. apiacas or T. obscurus. It is also highlighted that the toxins responsible for triggering these alterations have not been elucidated yet and this is a fruitful field for the development of more efficient antivenoms. Furthermore, the geographic distribution of scorpions of the genus Tityus in the Brazilian Amazon was revised and updated. The cumulative and detailed information provided in this review may help physicians and scientists interested in scorpionism in the Brazilian Amazon.(AU)