Case Report: Fatal Scorpion Envenomation in a Shuar Child by Tityus cisandinus from Amazonian Ecuador: A Call for Specific Antivenom Availability in the Amazon Basin.

Envenomation by scorpions belonging to the genus Tityus can be life threatening in the Americas, particularly in the Amazon Basin. We report a 4-month-old Ecuadorean boy of Shuar origin stung by a scorpion identified as Tityus cisandinus in the Amazonian province of Morona Santiago, presenting with pulmonary edema and systemic inflammation. We administered immunotherapy using the scorpion antivenom available in Ecuador, of Mexican origin (anti-Centruroides). Catecholamine discharge-related events such as hyperglycemia and thrombocytosis were resolved after treatment but leukocytosis did not, suggesting that factors associated with the sting-admission delay and specificity of antivenom played a role in the envenomation outcome. Cardiorespiratory arrest determined a fatal outcome, despite specific maneuvers. The case severity and the limited supply of nonspecific scorpion antivenoms in problematic areas of Amazonian Ecuador and elsewhere in northwestern Amazonia are discussed in regard to the need for specific therapeutic immunoglobulins in the area and in the Amazon Basin as a whole.

Venenos animais como possíveis ferramentas terapéuticas contra o estresse oxidativo em diversas doengas: Revisao da Literatura / Animal venoms as possible therapeutic tools against oxidative stress in several diseases: Literature Review

Resumo Venenos sao uma substancia tóxica (composta por uma ou mais toxinas) que podem causando lesao fisiológica dependente da dose. As toxinas sao moléculas bioativas formadas principalmente por compostos enzimáticos e nao enzimático que porque provocam consequéncias indesejáveis nas presas, além disso, exibem atividades biológicas únicas, diversas e específicas que perturbam os processos fisiológicos normais. Entretanto, muitas toxinas, de diferentes animais, tém sido isoladas e muitas delas sao consideradas ótimas ferramentas para pesquisa básica e alvos terapéuticos. Foi relatado que o estresse oxidativo desempenha um papel fundamental na patogénese de várias doengas, como distúrbios neurodegenerativos, distúrbios cardiovasculares e cáncer. O mecanismo pelo qual as toxinas animais atuam nos parametros de estresse oxidativo em várias doengas, ainda nao está estabelecido. O foco principal desta revisao é destacar os principais estudos com toxinas animais como ferramenta terapéutica em diversas doengas, atuando no balango redox do organismo.

Abstract Venoms are a toxic substance (comprised of one or more toxins) that can cause dose-dependent physiological injury. Toxins are bioactive molecules formed primarily by enzymatic and non-enzymatic compounds that cause undesirable conse-quences in prey, in addition, exhibit unique, diverse and specific biological activities that disrupt normal physiological processes. However, many toxins, from different animals, have been isolated and many of them are considered great tools for basic research and therapeutic targets. Oxidative stress has been reported to play a key role in the pathogenesis of various diseases such as neurodegenerative disorders, cardiovascular disorders and cancer. How animal toxins act on oxidative stress parameters in several diseases is not yet established. The main focus of this review is to highlight the main studies with animal toxins as a therapeutic tool in several diseases, acting on the organism's redox balance.

Resumen Los venenos son sustancias tóxicas (compuestas por una o más toxinas) que pueden causar daño fisiológico dependiente de la dosis. Las toxinas son moléculas bioactivas formadas principalmente por compuestos enzimáticos y no enzimáticos que debido a que causan consecuencias indeseables en las presas, además, exhiben actividades biológicas únicas, diversas y específicas que alteran los procesos fisiológicos normales. Sin embargo, se han aislado muchas toxinas de diferentes animales, y muchos de ellos se consideran grandes herramientas para la investigación básica y dianas terapéuticas. Se ha informado que el estrés oxidativo juega un papel clave en la patogenia de diversas enfermedades, como los trastornos neurodegenerativos, enfermedades cardiovasculares y cáncer. El mecanismo por el cual las toxinas animales actúan sobre los parámetros de estrés oxidativo en vários enfermedades, aún no está establecido. El enfoque principal de esta revisión es resaltar los principales estudios con toxinas animales como herramienta terapéutica en diversas enfermedades, actuando en el equilibrio redox del organismo.

Ischemic Stroke in a Child after a Probable Scorpion Sting.

Scorpion stings are common emergencies in the tropics. Species-specific antivenom therapies are available. However, fatalities resulting from scorpion stings remain a public health concern in many settings. Children residing in rural towns and peri-urban areas represent the most vulnerable populations. Delays in the diagnosis of scorpion stings often occur as a result of the non-specific clinical presentations, which then lead to life-threatening complications. We report a 2-year-old Venezuelan boy presenting with acute pancreatitis and pulmonary edema without an identifiable cause 48 hours after his initial symptoms. We administered antivenom therapy when an undetected scorpion sting was suspected. Despite some initial clinical improvement with respect to his acute pancreatitis, pulmonary edema, and coagulation abnormalities, our patient experienced an ischemic stroke. Fortunately, our patient did demonstrate some neurological improvement. Although acute pancreatitis and pulmonary edema are known end-organ damage manifestations of the sting of Tityus in the Americas, our particular case illustrates the risk of ischemic stroke.

Tityus serrulatus (Scorpion): From the Crude Venom to the Construction of Synthetic Peptides and Their Possible Therapeutic Application Against Toxoplasma gondii Infection.

Toxoplasmosis, caused by Toxoplasma gondii, is a major public concern owing to its neurotropic nature and high morbidity and mortality rates in immunocompromised patients and newborns. Current treatment for this disease is inefficient and produces side effects. Inflammatory mediators produced during T. gondii infection (e.g., cytokines and nitric oxide) are crucial in controlling parasite replication. In this context, Tityus serrulatus venom (TsV) induces the production of inflammatory mediators by immune cells. Thus, this study aimed to isolate and identify the components of TsV with potential anti-T. gondii activity. TsV was extracted from scorpions and lyophilized or loaded onto a column to obtain its fractions. TsV subfractions were obtained using chromatography, and its amino acid sequence was identified and applied to peptide design using bioinformatics tools. The C57BL/6 mice and their harvested macrophages were used to test the anti-Toxoplasma activity of TsV components and peptides. TsV and its fraction F6 attenuated the replication of tachyzoites in macrophages and induced nitric oxide and cytokine (IL-12, TNF, and IL-6) production by infected cells, without host cell toxicity. Moreover, Su6-B toxin, a subfraction of F6, demonstrated anti-T. gondii activity. The partially elucidated and characterized amino acid sequence of Sub6-B demonstrated 93% similarity with T. serrulatus 2 toxin (Ts2). Ts2 mimetic peptides ("Pep1," "Pep2a," and "Pep2b") were designed and synthesized. Pep1 and Pep2a, but not Pep2b, reduced the replication of tachyzoites in macrophages. In vivo, treatment of T. gondii-infected mice with Pep1, Pep2a, or Pep2b decreased the number of cerebral cysts and did not induce hepatotoxicity in the animals. Taken together, our data show promising immunomodulatory and antiparasitic activity of TsV that could be explored and applied in future therapies for treating infectious parasitic diseases such as toxoplasmosis.

Scorpion venoms and associated toxins as anticancer agents: update on their application and mechanism of action.

Cancer remains one of the deadliest non-infectious diseases of the 21st century, causing millions of mortalities per year worldwide. Analyses of conventional treatments, such as radiotherapy and chemotherapy, have shown not only a lower therapeutic efficiency rate but also plethora of side-effects. Considering the desperate need to identify promising anticancer agents, researchers are in quest to design and develop new tumoricidal drugs from natural sources. Over the past few years, scorpion venoms have shown exemplary roles as pivotal anticancer agents. Scorpion venoms associated metabolites, particularly toxins demonstrated in vitro anticancer attributes against diversified cell lines by inhibiting the growth and progression of the cell cycle, inhibiting metastasis by blocking ion channels such as K+ and Cl- , and/or inducing apoptosis by intrinsic and extrinsic pathways. This review sheds light not only on in vitro anticancer properties of distinct scorpion venoms and their toxins, but also on their mechanism of action for designing and developing new therapeutic drugs in future.

Pharmacokinetics and Biodistribution of Rhopalurus junceus Scorpion Venom in Tumor-Bearing Mice after Intravenous and Oral Administration

Background: Rhopalurus junceus scorpion venom has shown potential for anticancer treatment. However, there are no scientific evidence about venom pharmacokinetic (PK) and biodistribution (BD) in tumor-bearing mice. Methods: 131I-labeled venom was administrated by intravenous (IV) and oral (PO) routes at the single dose of 12.5 mg/kg. Mice were sacrificed and blood samples, major organs, and tumor were taken at 10, 20, 40, 90, 180, 300, 480, and 1440 min. Results: For IV route, maximum peak concentration (Cmax), elimination half-lives, total body clearance (CL), distribution volume (Vd), mean residence time (MRT), and area under curve (AUC) were 21.77 ± 2.45 %Dosis•h/mL, 12.65 ± 2.1 h, 4.59 ± 0.23 mL/h, 83.80 ± 12 mL, 12.49 ± 2.71 h, and 21.77 ± 2.45 %Dosis•h/mL, respectively. For PO route, they were 0.60 ± 0.07 %Dosis•h/mL, 9.33 ± 1.35 h, 36.94 ± 4.01 mL/h, 497.33 ± 30 mL, 12.40 ± 1.87 h, and 6.89 ± 1.18 %Dosis•h/mL, respectively. PK parameters (Cmax, CL, Vd, and AUC) showed significant differences between IV and PO routes. Bioavailability was 31.6 ± 4% for PO dose. Kidney, stomach, liver, and lung for IV and stomach, kidney, spleen, and lung for PO routes showed the major uptakes for 131I-labeled venom. In tumor tissue, after the maximum uptake for both routes, there was a consistent behavior of radioactivity respect to the major organs during the first 480 min. Conclusion: The PK and BD of R. junceus venom in mice depend on the administration route. These data represent a starting point for future experiments with this scorpion venom in experimental models of cancer.

Tityus serrulatus scorpion venom improves survival and lung inflammation in lethal sepsis induced by CLP in mice.

Tityus serrulatus venom (Tsv) modifies the behavior of immune cells and induces the production of inflammatory and anti-inflammatory cytokines; such action may interfere with physiological or pathological states. Because sepsis is characterized as an inflammatory disorder, the aim of present study was to investigate the effect of a non-lethal dose of Tsv in mice submitted to a polymicrobial infection by cecal ligation and puncture (CLP) model. The parameters evaluated were survival index, cellularity on lymphoid organs, peritoneal cavity and brochoalveolar space, production of IL-10, IL-12, IL-6, TNF-α, IFN-γ and MCP-1, pulmonary inflammation and oxidative burst. The results demonstrated that in sharp contrast to CLP group in which sepsis was lethal in a 24 h period all mice pretreated with Tsv survived even 60 h after CLP. Lung inflammation, another hallmark of CLP group, was also dramatically down regulated in Tsv/CLP group. Despite pretreatment with Tsv did not reduce the inflammatory serum cytokines when compared to CLP group; there was an increase in IL-10. In conclusion, subcutaneous Tsv administration 6 h before CLP was able to control the harmful effects of sepsis (lethality and lung inflammation). We suggest that both systemic IL-10 and oxidative burst are involved in this effect.

Preparation and in vitro characterization of chitosan nanoparticles containing Mesobuthus eupeus scorpion venom as an antigen delivery system

Hydrophilic nanoparticles have been widely investigated in recent years as delivery systems for therapeutic macromolecules such as antigens. In the present study Mesobuthus eupeus venom-loaded chitosan nanoparticles were prepared via ionic gelation of tripolyphosphate (TPP) and chitosan. The optimum encapsulation efficiency (91.1 percent) and loading capacity (76.3 percent) were obtained by a chitosan concentration of 2 mg/mL, chitosan-to-TPP mass ratio of 2 and M. eupeus venom concentration of 500 µg/mL. The average nanoparticle size at optimum conditions was determined by Zetasizer (Malvern Instruments, UK). The nanoparticle size was about 370 nm (polydispersity index: 0.429) while the zeta potential was positive. Transmission electron microscope (TEM) imaging showed a spherical, smooth and almost homogenous structure for nanoparticles. Fourier transform infrared (FTIR) spectroscopy confirmed tripolyphosphoric groups of TPP linked with ammonium groups of chitosan in the nanoparticles. The in vitro release of nanoparticles showed an initial burst release of approximately 60 percent in the first ten hours, followed by a slow and much reduced additional release for about 60 hours. It is suggested that the chitosan nanoparticles fabricated in our study may provide a suitable alternative to traditional adjuvant systems.(AU)

Diazepam and pentobarbital protect against scorpion venom toxin-induced epilepsy

We have characterized earlier the long-term behavioural, electroencephalographic and histopatologicfeatures after a single TsTx microinjection, consisting of a neuropeptide isolated from the Tityus serrulatusscorpion venom, into the hippocampus of rats. TsTx was able to induce status epilepticus (SE)and developed later epilepsy. The present study was designed to investigate the outcomes of diazepamplus pentobarbital administered at 30 min, 1, 2 or 6 h after the beginning of TsTx-induced SE, on thedevelopment of spontaneous recurrent motor seizures (SRMSs), mossy fibre sprouting and hippocampalneurodegeneration in rats. The administration of diazepam (DZ) + pentobarbital (PB) 30 min after thebeginning of the TsTx-induced SE was able to markedly reduce the frequency of the SRMSs and preventthe development of mossy fibres sprouting and hippocampal lesion. In the other groups the augmentof the extent of hipocampal neurodegeneration, the frequency of SRMSs and degree of aberrant mossyfibre sproutingwas directly proportional to the time that the animalswere subjected to TsTx-induced SE.In conclusion, our results point out that the early blockade of the TsTx-induced SE with diazepam pluspentobarbital,was effective treatment against later epilepsy development. The effectiveness of this treatmentdepends on the time that the animals were subjected to the SE. Furthermore, the TsTx model couldbe a useful tool to study antiepileptogenic drugs in chronic epileptic animals, neuronal degeneration, aswell as for the mechanisms underlying epilepsy.

Ocurrencia de escorpionismo en los distritos sanitarios del estado Mérida Venezuela / Ocurrence of scorpionism in sanitary districs of Mérida state Venezuela

Los accidentes escorpiónicos que involucran al género Tityus son la causa más común de los envenenamientos ocurridos en el Estado Mérida. Para estudiar la ocurrencia de estos accidentes de acuerdo a los distritos sanitarios del Estado, se evaluaron el registro de morbilidad mensual EP115 y mortalidad EP113, y la memoria y cuenta de la Coordinación de Epidemiología del Estado Mérida; los años revisados comprenden desde 1994 hasta 2003. En los reportes, se detectó que la mayoría de los accidentes ocurrieron en los distritos sanitarios de Mérida, Tovar y El Vigía. Sin embargo, las muertes registradas (11) ocurrieron en niños con edades iguales o menores a los 9 años y en los distritos sanitarios de Tovar y El Vigía, lo que hace suponer que pudieron ser ocasionadas por la especie Tityus zulianus, que es la más abundante en la zona.

Maintenance of scorpions of the genus Tityus koch (Scorpiones, Buthidae) for venom obtention at Instituto Butantan, São Paulo, Brazil

This work presents the experience of the Laboratory of Arthropods at Instituto Butantan, wich maintains scorpions in captivity in order to obtain the venom used in the production of anti-arachnid serum. Between 1993 and 2000, the laboratory received 24.781 specimens of Tityus serrulatus in order to obtain poison for the production of anti-scorpion serum. In the first extraction, performed by electrical stimulation, the animals gave an average quantity of 0.4 mg venom per specimen. Animal acquisition and involved professional safety are considered. In addition, the captivity, handling and feeding techniques are described, as well as the method and equipment used for venom extraction. It shows the importance of regular campaigns, offering information to the general population in order to motivate these to catch and send alive scorpions to the Institute to assuring a regular entrance of scorpions.

Envenenamento por Tityus stigmurus (Scorpiones; Buthidae) no Estado da Bahia, Brasil / Envenomation by Tityus stigmurus (Scorpiones; Buthidae) in Bahia, Brazil

A presente investigaçäo é um estudo descritivo dos aspectos clínicos dos acidentes causados pelo escorpiäo Tityus stigmurus no Estado da Bahia, Brasil. Foram analisados 237 casos confirmados, tratados pelo Centro de Informaçöes Antiveneno da Bahia (CIAVE), no período de 1982-1995. O envenenamento por T. stigmurus caracterizou-se por manifestaçöes locais: dor (94,4 por cento), dormência (30 por cento), edema (17,8 por cento), eritema (17,8 por cento) e parestesia (15,6 por cento)e gerais: cefaléia (14 por cento), vômitos (4,4 por cento) e sudorese (3,3 por cento). A maioria dos envenenamentos (94 por cento) foi leve e todos evoluíram para cura. A ausência de letalidade, com o restabelecimento dos pacientes, inclusive casos graves, sugere a eficácia do tratamento com o antiveneno específico, apesar do veneno desta espécie nao estar presente no pool de produçäo nacional do soro. Há necessidade de revisäo dos critérios regionais nos esquemas atuais de soroterapia. Os dados apontam para a semelhança da gravidade do envenenamento por T. serrulatus, com exceçäo da ocorrência de óbitos e complicaçöes sistêmicas