Toxinology in the proteomics era: a review on arachnid venom proteomics

The word venomics was coined to acknowledge the studies that use omics to investigate venom proteins and peptides. Venomics has evolved considerably over the last 20 years. The first works on scorpion or spider venomics were published in the early 2000's. Such studies relied on peptide mass fingerprinting (PMF) to characterize venom complexity. After the introduction of new mass spectrometers with higher resolution, sensitivity and mass accuracy, and the next-generation nucleotide sequencing, the complexity of data reported in research on scorpion and spider venomics increased exponentially, which allowed more comprehensive studies. In the present review article, we covered key publications on scorpion venomics and spider venomics, presenting historical grounds and implemented technologies over the last years. The literature presented in this review was selected after searching the PubMed database using the terms "(scorpion venom) AND (proteome)" for scorpion venomics, and "(spider venom) AND (proteome)" for publications on spider venomics. We presented the key aspects related to proteomics in the covered papers including, but not restricted to, the employed proteomic strategy (i.e., PMF, two-dimensional gel electrophoresis, shotgun/bottom-up and/or top-down/peptidome), and the type of mass spectrometer used. Some conclusions can be drawn from the present study. For example, the scorpion genus Tityus is the most studied concerning venomics, followed by Centruroides; whereas for spiders the studied genera were found more equally distributed. Another interesting conclusion is the lack of high throughput studies on post-translational modifications (PTMs) of scorpion and spider proteins. In our opinion, PTMs should be more studied as they can modulate the activity of scorpion and spider toxins.(AU)

Overview of protein posttranslational modifications in Arthropoda venoms

Accidents with venomous animals are a public health issue worldwide. Among the species involved in these accidents are scorpions, spiders, bees, wasps, and other members of the phylum Arthropoda. The knowledge of the function of proteins present in these venoms is important to guide diagnosis, therapeutics, besides being a source of a large variety of biotechnological active molecules. Although our understanding about the characteristics and function of arthropod venoms has been evolving in the last decades, a major aspect crucial for the function of these proteins remains poorly studied, the posttranslational modifications (PTMs). Comprehension of such modifications can contribute to better understanding the basis of envenomation, leading to improvements in the specificities of potential therapeutic toxins. Therefore, in this review, we bring to light protein/toxin PTMs in arthropod venoms by accessing the information present in the UniProtKB/Swiss-Prot database, including experimental and putative inferences. Then, we concentrate our discussion on the current knowledge on protein phosphorylation and glycosylation, highlighting the potential functionality of these modifications in arthropod venom. We also briefly describe general approaches to study "PTM-functional-venomics", herein referred to the integration of PTM-venomics with a functional investigation of PTM impact on venom biology. Furthermore, we discuss the bottlenecks in toxinology studies covering PTM investigation. In conclusion, through the mining of PTMs in arthropod venoms, we observed a large gap in this field that limits our understanding on the biology of these venoms, affecting the diagnosis and therapeutics development. Hence, we encourage community efforts to draw attention to a better understanding of PTM in arthropod venom toxins.(AU)

Anafilaxia no primeiro ano de vida: como diagnosticar / Anaphylaxis in the first year of life: how to diagnose

A anafilaxia é uma reação alérgica mais grave e potencialmente fatal. Apresenta-se quase sempre com manifestações cutâneas, acompanhadas por acometimento dos sistemas respiratório, gastrointestinal, nervoso e cardiovascular. Indivíduos de todas as faixas etárias podem manifestar anafilaxia, e seu diagnóstico no primeiro ano de vida é difícil por ser o lactente incapaz de expressar de modo claro as sensações vividas durante o episódio agudo. Nessa faixa etária os alimentos são os agentes desencadeantes mais envolvidos, embora medicamentos e veneno de himenópteros também o sejam. Em pacientes submetidos a várias cirurgias e procedimentos médicos a alergia ao látex pode ocorrer. A adrenalina intramuscular é a primeira linha de tratamento da anafilaxia na fase inicial, mas continua sendo subutilizada. Além disso, medidas de suporte, tais como decúbito supino, reposição de fluidos, vias aéreas pérvias e oxigenação, devem ser instituídas. Após a alta, o paciente deve ser encaminhado à avaliação e seguimento por especialista visando à identificação do agente desencadeante, assim como educar responsáveis/cuidadores destes pacientes sobre a prevenção de novos episódios. É importante que esse paciente tenha consigo algum tipo de identificação que o aponte como tendo tido episódio de anafilaxia, sobretudo se tiver sido recorrente. A oferta de um plano escrito de como proceder diante de um novo episódio é fundamental.

Anaphylaxis is a serious and potentially fatal allergic reaction. Most frequently, it features cutaneous manifestations accompanied by involvement of the respiratory, gastrointestinal, nervous, and/or cardiovascular systems. Individuals of all age groups may present with anaphylaxis, and its diagnosis in the first year of life is difficult because the infant is unable to clearly express the sensations experienced during the acute episode. In this age group, foods are the most common triggering agents, together with medications and Hymenoptera venom. In patients undergoing multiple surgeries and medical procedures, latex allergy may occur. Intramuscular epinephrine is the first line of treatment for early anaphylaxis, but it remains underutilized. In addition, supportive measures such as supine decubitus, fluid replacement, patent airways, and oxygenation should be instituted. After discharge, the patient should be referred for evaluation and follow-up by a specialist, with the purpose of identifying the triggering agent as well as educating the caregivers of these patients about the prevention of new episodes. This patient should always carry some type of identification that indicates that he/she has had any episode of anaphylaxis, especially if it has been recurrent. Providing a written plan of how to proceed in the face of a new episode is essential.

Anti-inflammatory activities of arthropod peptides: a systematic review

Peptides obtained from different animal species have gained importance recently due to research that aims to develop biopharmaceuticals with therapeutic potential. In this sense, arthropod venoms have drawn attention, not only because of their toxicity but mainly for the search for molecules with various bioactivities, including anti-inflammatory activity. The purpose of the present study is to gather data available in the literature on new peptides derived from arthropod species with anti-inflammatory potential. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies on peptides from arthropods that display anti-inflammatory activity were retrieved from PubMed, Scopus, Web of Science, and Google Scholar databases. The bibliographic research started in 2020 and searched papers without a limit on the publication date. The articles were analyzed using a search string containing the following terms: "Peptides" and "Anti-inflammatory", in combinations such as "Ant", "Bee", "Wasp", "Crab", "Shrimp", "Scorpion", "Spider", "Tick" and "Centipedes". Besides, a search was carried out in the databases with the terms: "Peptides", "Antitumor", or "Anticancer", and "Arthropods". Articles that met the inclusion and exclusion criteria totalized 171, and these served for data extraction. Additionally, the present review included anti-inflammatory peptides with anticancer properties. Peptides with confirmed anti-inflammatory activity were from insects (ants, bees, and wasps), crustaceans (shrimp and crabs), arachnids (scorpions, spiders, and ticks), and centipedes. These arthropod peptides act mainly by decreasing pro-inflammatory cytokines as analyzed in vitro and in vivo. Some showed significant antineoplastic activity, working in essential cellular pathways against malignant neoplasms.(AU)

Venom of the giant ant Dinoponera quadriceps attenuates inflammatory pain in mouse cutaneous wound healing model

Arthropod venoms are potential sources of bioactive substances, providing tools for the validation of popular use and new drugs design. Ants belonging to the genus Dinoponera are used in the folk medicine to treat inflammatory conditions. It was previously demonstrated that the venom of the giant ant Dinoponera quadriceps (DqV), containing a mixture of polypeptides, elicit antinociceptive effect in mice models of chemical, mechanical and thermal nociception. The aim of this study was to evaluate DqV antiinflammatory and antihypernociceptive effects in a mice model of traumatic cutaneous wound. Colonies of D. quadriceps were collected in the ‘‘Serra de Maranguape’’ (State of Ceará, northeastern Brazil), a small mountain range located on the coastal zone, and the venom secreted by the ant glands was extracted with capillary tubes, further lyophilized and maintained at -20 ± 1ºC until use. Wounds were performed in the dorsum of Swiss mice. Animals received intravenous (i.v.) injection of DqV (50 µg -1kg day-1) during 3 days for evaluation of inflammatory parameters present in the wounds: hypernociception, leukocyte infiltrate, myeloperoxidase activity, nitrite nitrate-1 content. Data was tested by two-way ANOVA and Bonferroni’s post-hoc test. DqV reduced (2.7 folds) hypernociception at 48 hours, leukocyte infiltration by 65% at 6 hours and myeloperoxidase activity by 60% at 0.5 hour after wound induction. In conclusion, the venom extracted from D. quadriceps glands attenuates inflammation and hypernociception in mice cutaneous wounds.

Hemostatic disorders induced by skin contact with Lonomia obliqua (Lepidoptera, Saturniidae) caterpillars

ABSTRACT Patients envenomed by Lonomia sp caterpillars initially experience a mild burning pain, headache, nausea, vomiting, and skin and mucosal hemorrhages. Some patients can rapidly progress to a severe coagulopathy that presents as visceral or intracerebral hemorrhaging. We studied the hemostatic alterations that occurred in 14 patients who were envenomed by Lonomia obliqua in Southern Brazil and presented at the Hospital São Vicente de Paulo (Passo Fundo, RS), Brazil during the summers of 1993 and 1994 when Lonomia antivenom was not yet available for treatment. The patients were classified into to 4 clinical groups: 0 (two patients), I (eight patients), II (two patients), and III (two patients). The patients were admitted to the hospital between 4 hours and five days after contact with the caterpillars. In this study, the coagulation parameters of the patients were followed up for up to 172 hours after the accidents. The patients received no treatment with the exceptions of two patients who received blood transfusions and antifibrinolytic treatment. The observed abnormalities related to blood coagulation and fibrinolytic factors were similar regardless of the severity of the bleeding symptoms. These findings suggest that alterations in hemostatic parameters without thrombocytopenia are not predictors of the seriousness of such accidents. Thus, consumptive disorder and reactive fibrinolysis are not proportional to mild coagulopathy. Furthermore, these patients recovered. The hemostatic parameters of most of the patients normalized between 96 and 120 h after the accident.

Niña con erucismo hemorrágico por Lonomia spp.: / Hemorrhagic erucism due to Lonomia spp. in a girl:

RESUMEN Los accidentes causados por las setas urticantes o venenosas de las orugas de lepidópteros, se conocen como erucismo. Estos accidentes se producen por el contacto accidental, especialmente por los niños, con las cerdas sobre el cuerpo del insecto, conectadas con glándulas venenosas. Los síntomas pueden ser locales o sistémicos, con presentaciones clínicas fatales. El accidente ocasionado por las orugas del género Lonomia spp. puede desencadenar síndromes hemorrágicos, constituyendo estos la forma más grave de erucismo. Se reporta el caso de una niña de 5 años, procedente del poblado de Villarondos, en la Amazonía del Perú, departamento de Huánuco, la cual incidentalmente se hinca con las cerdas de una oruga, cursando luego con anemia hemolítica, plaquetopenia y trastorno de la coagulación. El diagnóstico fue establecido por la anamnesis, cuadro clínico, exámenes de laboratorio y respuesta al suero antilonómico. Se discuten los aspectos clínicos, laboratoriales y terapéuticos de erucismo por Lonomia spp.

ABSTRACT Accidents caused by urticating or poisonous setae from lepidoptera caterpillars are known as erucism. These accidents are produced by accidental contact, especially in children, with bristles on the insect's body surface, connected to venom glands. Symptoms may be local or systemic, with deadly clinical presentations. The accident caused by Lonomia spp. caterpillars can trigger bleeding disorders, which is considered the most severe type of erucism. The case of a 5-year-old girl is reported. She was from the town of Villarondos, in the Peruvian Amazon, department of Huánuco, who accidentally knelt down on caterpillar bristles, and subsequently experienced hemolytic anemia, plateletopenia, and coagulation disorder. The diagnosis was made based on the medical history, clinical manifestation, laboratory examination results, and response to antilonomic serum. The clinical, laboratory, and therapeutic aspects of erucism due to Lonomia spp. are discussed.

Venomous and poisonous arthropods: identification, clinical manifestations of envenomation, and treatments used in human injuries

Abstract This review presents the main species of venomous and poisonous arthropods, with commentary on the clinical manifestations provoked by the toxins and therapeutic measures used to treat human envenomations. The groups of arthopods discussed include the class Arachnida (spiders and scorpions, which are responsible for many injuries reported worldwide, including Brazil); the subphylum Myriapoda, with the classes Chilopoda and Diplopoda (centipedes and millipedes); and the subphylum Hexapoda, with the class Insecta and the orders Coleoptera (beetles), Hemiptera (stink bugs, giant water bugs, and cicadas), Hymenoptera (ants, wasps, and bees), and Lepidoptera (butterflies and moths).

Accidentes causados por la oruga Lonomia obliqua (Walker, 1855): Un problema emergente / Accidents with caterpillar Lonomia obliqua (Walker, 1855). An emerging problem

Lonomia obliqua (Walker, 1855) es una mariposa nocturna de la familia Saturniidae, ampliamente distribuida en selvas tropicales de Sudamérica. Su larva (oruga) se caracteriza por poseer espículas ramificadas puntiagudas a lo largo de su cuerpo, que contienen una mezcla compleja de moléculas tóxicas en su interior. Cuando las espículas contactan con la piel de las personas, las toxinas ingresan pasivamente a través de la lesión, generando un envenenamiento caracterizado por manifestaciones no solo locales sino también sistémicas (fundamentalmente manifestaciones hemorrágicas). Debido al elevado número de casos que se produjeron en Brasil en las últimas décadas, el Instituto Butantan ha producido un antiveneno capaz de neutralizar los efectos deletéreos de los accidentes por contacto con L. obliqua. En Argentina, los accidentes por Lonomia son poco frecuentes y se limitan a la provincia de Misiones. Teniendo en cuenta que a la fecha no hay en la literatura descripciones de casos clínicos ocurridos en el país con tratamiento específico (antiveneno), el propósito del presente trabajo es comunicar seis casos de accidentes por contacto con orugas Lonomia que fueron atendidos en el Hospital SAMIC de Puerto Iguazú (Misiones, Argentina) durante el año 2014, y que fueron tratados con el suero antilonómico producido en Brasil. Se destaca la evolución rápida y favorable de todos los pacientes, por lo que se recomienda el uso de este antiveneno para tratar los casos de erucismo por Lonomia en la Argentina.

Lonomia obliqua (Walker, 1855) is a moth from the family Saturniidae, widely distributed in tropical rainforests of South America. In its larval stage (caterpillar) it is characterized by bristles that cover the animal’s body. These structures are hard and branched spiny evaginations of the cuticle, underneath which a complex mixture of toxic molecules is stored. When spicules are brought into contact with the skin of people, toxins enter passively through the injury, causing not only local but also systemic poisoning (primarily hemorrhagic manifestations). When the whole animal is accidentally crushed, the insect’s chitinous bristles are broken and the venomous secretions penetrate the human skin, reaching the blood circulation. Due to the numerous registered cases of erucism in Southern Brazil, the Butantan Institute has produced an antivenom able to neutralize the deleterious effects produced by contact with L. obliqua caterpillar bristles. In Argentina, these kinds of accidents are rare and restricted to the province of Misiones. Taking into account that to date there is no report in this country about clinical cases submitted to a specific treatment (antivenom), our aim is to communicate here six cases of Lonomia caterpillar-induced bleeding syndrome that were treated in the Hospital SAMIC of Puerto Iguazú (Misiones, Argentina) during 2014 with the antilonomic serum produced in Brazil. It is worthy to note that all patients evolved favorably within the first few hours, and for this reason, the use of this antivenom is recommended to treat the cases of Lonomia erucism in Argentina.

Lonomia obliqua Walker (Lepidoptera: Saturniidae): hemostasis implications / Lonomia obliqua Walker (Lepidoptera: Saturniidae): implicações em hemostasia.

Summary In southern Brazil, since 1989, several cases of accidents produced by unwilling contact with the body of poisonous caterpillars of the moth species Lonomia obliqua Walker, 1855 (Lepidoptera: Saturniidae), were described. L. obliqua caterpillars have gregarious behavior and feed on leaves of host trees during the night, staying grouped in the trunk during the day, which favors the occurrence of accidents with the species. This caterpillar has the body covered with bristles that on contact with the skin of individuals, breaks and release their contents, inoculating the venom into the victim. The basic constitution of the venom is protein and its components produce physiological changes in the victim, which include disturbances in hemostasis. Hemorrhagic syndrome associated with consumption coagulopathy, intravascular hemolysis and acute renal failure are some of the possible clinical manifestations related to poisoning by L. obliqua. Specific laboratory tests for diagnosis of poisoning have not been described previously. The diagnosis of poisoning is made based on the patient's medical history, clinical manifestations, erythrocyte levels, and, primarily, parameters that evaluate blood coagulation. Treatment is performed with the use of supportive care and the administration of specific hyperimmune antivenom. Poisoning can be serious and even fatal.

Na região Sul do Brasil, a partir de 1989, foram descritos inúmeros casos de contato acidental com o corpo de lagartas venenosas da mariposa da espécie Lonomia obliqua Walker, 1855 (Lepidoptera: Saturniidae). As lagartas de L. obliqua possuem comportamento gregário e alimentam- -se de folhas das árvores hospedeiras durante a noite, permanecendo agrupadas no tronco durante o dia, o que favorece a ocorrência de acidentes. Essa lagarta possui o corpo recoberto por cerdas urticantes, que, ao contato com a pele dos indivíduos, se rompem e liberam seu conteúdo, inoculando o veneno na vítima. A constituição básica do veneno é proteica e seus componentes produzem modificações fisiológicas no acidentado, que incluem distúrbios na hemostasia. Síndrome hemorrágica associada a coagulopatia de consumo, hemólise intravascular e insuficiência renal aguda são algumas das manifestações clínicas possíveis relacionadas ao envenenamento por L. obliqua. Ainda não foram descritas avaliações laboratoriais específicas para diagnóstico do envenenamento, que é feito com base na anamnese do paciente, nas manifestações clínicas, nos índices hematimétricos e, principalmente, nos parâmetros que avaliam a coagulação sanguínea. A terapêutica é feita com a utilização de medidas de suporte e com a administração de um soro heterólogo hiperimune específico. Os envenenamentos podem ser graves e até mesmo fatais.

Neuroactive compounds obtained from arthropod venoms as new therapeutic platforms for the treatment of neurological disorders

The impact of neurological disorders in society is growing with alarming estimations for an incidence increase in the next decades. These disorders are generally chronic and can affect individuals early during productive life, imposing real limitations on the performance of their social roles. Patients can have their independence, autonomy, freedom, self-image, and self-confidence affected. In spite of their availability, drugs for the treatment of these disorders are commonly associated with side effects, which can vary in frequency and severity. Currently, no effective cure is known. Nowadays, the biopharmaceutical research community widely recognizes arthropod venoms as a rich source of bioactive compounds, providing a plethora of possibilities for the discovery of new neuroactive compounds, opening up novel and attractive opportunities in this field. Several identified molecules with a neuropharmacological profile can act in the central nervous system on different neuronal targets, rendering them useful tools for the study of neurological disorders. In this context, this review aims to describe the current main compounds extracted from arthropod venoms for the treatment of five major existing neurological disorders: stroke, Alzheimer's disease, epilepsy, Parkinson's disease, and pathological anxiety.(AU)

Arthropod venom Hyaluronidases: biochemical properties and potential applications in medicine and biotechnology

Hyaluronidases are enzymes that mainly degrade hyaluronan, the major glycosaminoglycan of the interstitial matrix. They are involved in several pathological and physiological activities including fertilization, wound healing, embryogenesis, angiogenesis, diffusion of toxins and drugs, metastasis, pneumonia, sepsis, bacteremia, meningitis, inflammation and allergy, among others. Hyaluronidases are widely distributed in nature and the enzymes from mammalian spermatozoa, lysosomes and animal venoms belong to the subclass EC 3.2.1.35. To date, only five three-dimensional structures for arthropod venom hyaluronidases (Apis mellifera and Vespula vulgaris) were determined. Additionally, there are four molecular models for hyaluronidases fromMesobuthus martensii, Polybia paulista and Tityus serrulatus venoms. These enzymes are employed as adjuvants to increase the absorption and dispersion of other drugs and have been used in various off-label clinical conditions to reduce tissue edema. Moreover, a PEGylated form of a recombinant human hyaluronidase is currently under clinical trials for the treatment of metastatic pancreatic cancer. This review focuses on the arthropod venom hyaluronidases and provides an overview of their biochemical properties, role in the envenoming, structure/activity relationship, and potential medical and biotechnological applications.(AU)

Neuroactive compounds obtained from arthropod venoms as new therapeutic platforms for the treatment of neurological disorders

The impact of neurological disorders in society is growing with alarming estimations for an incidence increase in the next decades. These disorders are generally chronic and can affect individuals early during productive life, imposing real limitations on the performance of their social roles. Patients can have their independence, autonomy, freedom, self-image, and self-confidence affected. In spite of their availability, drugs for the treatment of these disorders are commonly associated with side effects, which can vary in frequency and severity. Currently, no effective cure is known. Nowadays, the biopharmaceutical research community widely recognizes arthropod venoms as a rich source of bioactive compounds, providing a plethora of possibilities for the discovery of new neuroactive compounds, opening up novel and attractive opportunities in this field. Several identified molecules with a neuropharmacological profile can act in the central nervous system on different neuronal targets, rendering them useful tools for the study of neurological disorders. In this context, this review aims to describe the current main compounds extracted from arthropod venoms for the treatment of five major existing neurological disorders: stroke, Alzheimers disease, epilepsy, Parkinsons disease, and pathological anxiety.

Arthropod venom Hyaluronidases: biochemical properties and potential applications in medicine and biotechnology

Hyaluronidases are enzymes that mainly degrade hyaluronan, the major glycosaminoglycan of the interstitial matrix. They are involved in several pathological and physiological activities including fertilization, wound healing, embryogenesis, angiogenesis, diffusion of toxins and drugs, metastasis, pneumonia, sepsis, bacteremia, meningitis, inflammation and allergy, among others. Hyaluronidases are widely distributed in nature and the enzymes from mammalian spermatozoa, lysosomes and animal venoms belong to the subclass EC 3.2.1.35. To date, only five three-dimensional structures for arthropod venom hyaluronidases (Apis mellifera and Vespula vulgaris) were determined. Additionally, there are four molecular models for hyaluronidases fromMesobuthus martensii, Polybia paulista and Tityus serrulatus venoms. These enzymes are employed as adjuvants to increase the absorption and dispersion of other drugs and have been used in various off-label clinical conditions to reduce tissue edema. Moreover, a PEGylated form of a recombinant human hyaluronidase is currently under clinical trials for the treatment of metastatic pancreatic cancer. This review focuses on the arthropod venom hyaluronidases and provides an overview of their biochemical properties, role in the envenoming, structure/activity relationship, and potential medical and biotechnological applications.

"Sign of the kiss" in dermatitis caused by vesicant beetles ("potós" or Paederus sp.)

The cosmopolitan beetles of the Paederus genus (potós) cause a severe dermatitis when the insect is crushed against the skin of exposed areas (the cervical region is the most affected). Toxins (pederin and others) from the hemolymph of the insect cause plaques and/or bizarre, linear lesions with erythema, edema, blisters, pustules, crusts and exulcerations. There may be a burning sensation and severe conjunctivitis. Lesions disappear after 10 days and may leave hyperchromic macules. Treatment is made with topical corticosteroids and intensive washing.

Aspectos clínicos, epidemiológicos y de tratamiento de 11 casos de envenenamiento por ciempiés en Adícora, Península de Paraguaná, estado Falcón, Venezuela / Clinical, epidemiological and treatment aspects of eleven cases of centipede envenomation in Adícora, Paraguaná peninsula, Falcón state, Venezuela

A pesar de que las picaduras por ciempiés o centípedos (Phylum Arthropoda, Clase Chilopoda) son frecuentes y pueden potencialmente ocasionar el deceso del individuo, en Venezuela son pocos los estudios acerca de su ocurrencia. Entre octubre de 2006 y mayo de 2007, se realizó un estudio descriptivo y prospectivo para determinar los perfiles clínicos, epidemiológicos y tratamiento de los envenenamientos ocasionados por centípedos en individuos que asistieron a la emergencia ambulatoria en Adícora, estado Falcón, Venezuela. Se hizo la evaluación clínica y la anamnesis para indagar la hora y el lugar del accidente. El centípedo se recolectó para identificación. El tratamiento consistió en aplicación tópica de solución antiséptica yodada (Povidona®); analgésico antiinflamatorio endovenoso y toxoide tetánico; en el caso de abscesos se administró antibiótico terapia per os. Se registraron 11 pacientes mordidos por Scolopendra sp., 6 (54,55%) femeninos y 5 (45,46%) varones. Los accidentes ocurrieron con mayor frecuencia en meses de la estación seca (diciembre-abril; >60%), en adultos (39-62 años; 81,82%), residentes locales (81,82%) dentro del domicilio (54,55%) en horas nocturnas (63,64%) y en los miembros inferiores (54,55%). Los pacientes asistieron a la emergencia ambulatoria entre 5 a 600 minutos después del accidente ( =169,9 ± 236,3). Las manifestaciones clínicas mayormente observadas fueron de tipo local: dolor intenso [Escala Analógica Visual (VAS) = : 8,5 ± 0,63)], y eritema en 100% de los casos. Se obtuvo una evolución postratamiento satisfactoria entre 4 y 5 días y VAS de dolor promedio significativamente menor ( = 0,09± 0,20; t= 42,0, P= 0,0001). Los accidentes por Scolopendra sp. en Adícora, estado Falcón, Venezuela son un problema de salud pública, que parecieran incrementarse por los hábitos sinantrópicos y nocturnos de los centípedos, y seguir un patrón estacional. Se presentaron manifestaciones locales que requirieron un tratamiento básicamente local.

Despite centipede (Phylum Arthropoda, Clase Chilopoda) bites in humans are frequent and may potentially result in fatal consequences, in Venezuela publications on its envenoming and related characteristics are really scarce. Between October 2006 and May 2007, a descriptive and prospective survey was conducted to investigate epidemiological, clinical and treatment profiles on injuries caused by centipedes in patients that were attended in ambulatory emergency service at Adicora, Falcón state, Venezuela. These were clinically examined, and by mean of anamnesis were recorded site and time of bite. The centipede was collected for identification. Treatment consisted on the application of a topical antiseptic solution (povidone-iodine), intravenous administration of an anti-inflammatory analgesic, antibiotic therapy per os and tetanus immunization. It was registered 11 cases bitten by Scolopendra sp., 6 (54.55%) females and 5 (45.46%) males. Most of accidents occurred in the dry season (December- April>60%), adults (39-62 years old; 81.82%) local residents (81.82%), inside the home (54.55%), during the night (63.64%) and on the lower limbs (54.55%). The time between ambulatory medical assistance and the accident varied from 5 to 600 minutes, with a mean time of 169.9 ± 236.3. Most clinical manifestations observed were local: intense pain [Visual Analog Scale (VAS) = : 8.5 ± 0.63)], and erythema 100% of the cases. Patients had a satisfactory post-treatment evolution after 4 and 5 days, and pain VAS mean values significantly lower ( = 0.09 ± 0.20; t= 42.0, P= 0.0001). Envenoming injuries caused by Scolopendra sp. are public health concern at Adicora, Falcon state, Venezuela, that appear to increase with sinanthropic and nocturnal habits of centipede, and follow a seasonal pattern, requiring local symptomatic therapeutical treatment.

Morphology: histology and histochemistry of the venom apparatus of the centipede, Scolopendra valida (Chilopoda, Scolopendridae) / Morfología, histología e histoquímica del aparato venenoso del ciempiés: Scolopendra valida (Chilopoda, Scolopendridae)

Morphological, histological and histochemical characterizations of the venom apparatus of the centapede, S. valida have been investigated. The venom apparatus of Scolopendra valida consists of a pair of maxillipedes and venom glands situated anteriorly in the prosoma on either side of the first segment of the body. Each venom gland is continuous with a hollow tubular claw possessing a sharp tip and subterminal pore located on the outer curvature. The glandular epithelium is folded and consists of a mass of secretory epithelium, covered by a sheath of striated muscles. The secretory epithelium consists of high columnar venom-producing cells having dense cytoplasmic venom granules. The glandular canal lacks musculature and is lined with chitinous internal layer and simple cuboidal epithelium. The histochemical results indicate that the venom-producing cells of both glands elaborate glycosaminoglycan, acid mucosubstances, certain amino acids and proteins, but are devoid of glycogen. The structure and secretions of centipede venom glands are discussed within the context of the present results.

Fueron investigadas las características morfológicas, histológicas e histoquímicas del aparato venenoso del ciempiés, S. valida. El aparato venenoso de Scolopendra valida consta de un par de maxilopodos y glándulas de veneno situadas anteriormente en el prosoma, a cada lado del primer segmento del cuerpo. Cada glándula de veneno se continúa en una garra con una cavidad tubular que posee una punta afilada y un poro subterminal situado sobre la curvatura externa. El epitelio glandular es plegado y se compone de una masa de epitelio secretor, cubierto por una vaina de los músculos estriados. El epitelio secretor consiste en células columnares altas productoras de veneno con gránulos citoplasmáticos de veneno densos. El conducto glandular carece de musculatura y está revestido por capa interna quitinosa y epitelio cuboidal simple. Los resultados histoquímicos indican que las células productoras de veneno de ambas glándulas elaboran glucosaminoglucanos mucosustancias ácidas, ciertos aminoácidos y proteínas, pero carecen de glucógeno. La estructura y las secreciones de las glándulas de veneno del ciempiés son examinadas en el contexto de los presentes resultados.

Specific immunotherapy using Hymenoptera venom: systematic review / Imunoterapia específica com venenos de Hymenoptera: revisão sistemática

CONTEXT AND OBJECTIVE: The only effective treatment for patients who have severe reactions after Hymenoptera stings is venom immunotherapy. The aim of this study was to review the literature to assess the effects of venom immunotherapy among patients presenting severe reactions after Hymenoptera stings. DESIGN AND SETTING: Randomized controlled trials in the worldwide literature were reviewed. The manuscript was produced in the Discipline of Allergy and Clinical Immunology, Universidade de São Paulo (USP). METHODS: Randomized controlled trials involving venom immunotherapy versus placebo or only patient follow-up were evaluated. The risk of systemic reactions after specific immunotherapy was evaluated by calculating odds ratios (OR) and their 95 percent confidence intervals. RESULTS: 2,273 abstracts were identified by the keywords search. Only four studies were included in this review. The chi-square test for heterogeneity showed that two studies were homogeneous and could be included in a meta-analysis. By combining the two studies, the odds ratio became significant: 0.29 (0.10-0.87). However, analysis on the severity of the reactions after immunotherapy showed that the benefits may not be so significant because the reactions were mostly similar to or milder than the original reaction. CONCLUSIONS: Specific immunotherapy should be recommended for adults and children with moderate to severe reactions, but there is no need to prescribe it for children with skin reactions alone, especially if the exposure is very sporadic. On the other hand, the risk-benefit relation should always be assessed in each case.

CONTEXTO E OBJETIVO: O único tratamento eficaz para pacientes que têm reações graves após ferroada de Hymenoptera é a imunoterapia com veneno. O objetivo deste estudo foi rever a literatura para avaliar os efeitos da imunoterapia com veneno em pacientes com reações graves após ferroada de Hymenoptera. TIPO DE ESTUDO E LOCAL: Foram revisados na literatura mundial ensaios clínicos controlados e aleatórios. O manuscrito foi realizado na Disciplina de Alergia e Imunologia Clínica, Universidade de São Paulo (USP). MÉTODOS: Ensaios clínicos controlados e aleatórios envolvendo imunoterapia com veneno de Hymenoptera versus placebo ou apenas acompanhamento dos pacientes foram avaliados. Realizada imunoterapia específica, o risco de reações sistêmicas foi avaliado através de cálculo do "odds ratio" e intervalo de confiança de 95 por cento. RESULTADOS: 2.273 resumos foram identificados na busca pelas palavras chave. Apenas quatro estudos foram incluídos nesta revisão. O teste qui-quadrado de heterogeneidade mostrou que dois estudos foram homogêneos e puderam ser incluídos na metanálise. Ao combinar os dois estudos, o "odds ratio" passou a ser significativo: 0.29 (0.10-0.87). Entretanto, ao analisar a gravidade das reações ocorridas após a imunoterapia, observou-se que os benefícios podem não ser tão relevantes, pois as reações foram, na grande maioria, ou mais leves ou semelhantes à reação original. CONCLUSÕES: A imunoterapia específica deve ser recomendada para adultos e crianças com reações moderadas a graves, porém não há necessidade de prescrevê-la para as crianças apenas com reações cutâneas, especialmente se a exposição é muito esporádica. No outro lado, a relação risco-benefício deve ser sempre avaliada em cada caso.

Evaluación de la toxicidad in vitro del veneno del alacrán Rophalurus junceus a través de un ensayo celular / In vitro toxicity assessment caused by Rophalurus junceus scorpion poison though a cellular assay

El veneno del alacrán azul, Rophalurus junceus es comercializado con el nombre de Escozul. Este producto natural se emplea en el tratamiento de diferentes patologías. Este trabajo evaluó el efecto citotóxico in vitro de este producto en las líneas tumorales P3-X63/AG8/653 y Dunning R3327-G provenientes de mieloma murino y próstata de rata, respectivamente. La citotoxicidad fue evaluada mediante la cinética de crecimiento celular y el daño metabólico. Se utilizaron dosis de 1, 10, 20, 50, 100 y 200 mg/mL. El veneno presentó un efecto citostático dependiente de la línea tumoral en cuestión. Las dosis efectivas variaron entre las líneas celulares ensayadas. Se estudió además la estabilidad del producto almacenado durante 30 días a temperaturas de -20 y 4ºC, se evidenció la pérdida de la actividad biológica. El trabajo demostró la citotoxicidad del veneno crudo del alacrán azul en cultivos celulares.

Poison of blue scorpion (Rophalurus junceus) is marketed as Escozul. This natural product is used in treatment of different pathologies. Present paper evaluated the in vitro cytotoxic effect of this product in P3-X63/AG8/653 and Dunning R3327-G tumor lines from murine myeloma and rat prostate, respectively. Cytotoxic effect was evaluated by means of cellular growing kinetics and the metabolic damage. Doses of 1,10, 20, 50, 100, and 200 ìg/mL. Poison had a cytostatic effect dependent of tumor line at issue. Doses effective varied among the cellular lines assessed. We studied also stability of product stored during 30 days at temperatures of -20° and 4° C, evidenced the loss of biological activity. We showed cytotoxic effect of crude poison of blue scorpion in cellular cultures.