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.

Mitochondrial swelling in cardiomyocytes: Insights from a murine model of Tityus serrulatus scorpion envenomation.

Immune system hyperactivation is involved with clinical severity and pathological alterations during scorpion envenomation. In a murine model, mice inoculated with a lethal dose of Tityus serrulatus scorpion venom presented mitochondrial swelling in cardiomyocytes, with other structures such as sarcomeres and intercalated disks preserved. Treatment with dexamethasone or knockout animals to the interleukin-1ß receptor do not undergo mitochondrial changes in cardiomyocytes during envenomation.

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.

Scorpion envenomation and inflammation: Beyond neurotoxic effects.

Scorpion envenomation results in a wide range of clinical manifestations that are mostly attributed to the activation of the autonomic nervous system by venom toxins. In fact, sympathetic and parasympathetic disturbances play important roles during poisoning. However, scorpion venom also induces a complex hyperinflammatory state that occurs parallel to systemic inflammatory response syndrome and acute sepsis. After a scorpion sting, innate immune cells are exposed to the venom molecules, which bind to pattern recognition receptors and activate pro-inflammatory pathways that contribute toward the promotion of severe symptoms, such as pulmonary edema, and eventually lead to death. In this review, we highlight studies that pointed out inflammation as a major pathological facet of scorpion envenomation, so as to provide novel targets to improve therapeutics for scorpionism.

Lipoxin A4 encapsulated in PLGA microparticles accelerates wound healing of skin ulcers.

Lipoxin A4 (LXA4) is involved in the resolution of inflammation and wound healing; however, it is extremely unstable. Thus, to preserve its biological activities and confer stability, we encapsulated LXA4 in poly-lactic-co-glycolic acid (PLGA) microparticles (LXA4-MS) and assessed its application in treating dorsal rat skin lesions. Ulcers were sealed with fibrin adhesive and treated with either LXA4-MS, unloaded microparticles (Un-MS), soluble LXA4, or PBS/glue (vehicle). All groups were compared at 0, 2, 7, and 14 days post-lesions. Our results revealed that LXA4-MS accelerated wound healing from day 7 and reduced initial ulcer diameters by 80%. Soluble LXA4, Un-MS, or PBS closed wounds by 60%, 45%, and 39%, respectively. LXA4-MS reduced IL-1ß and TNF-α, but increased TGF-ß, collagen deposition, and the number of blood vessels. Compared to other treatments, LXA4-MS reduced inflammatory cell numbers, myeloperoxidase (MPO) concentration, and metalloproteinase-8 (MMP8) mRNA in scar tissue, indicating decreased neutrophil chemotaxis. In addition, LXA4-MS treatment increased macrophages and IL-4, suggesting a positive impact on wound healing. Finally, we demonstrated that WRW4, a selective LXA4 receptor (ALX) antagonist, reversed healing by 50%, indicating that LXA4 must interact with ALX to induce wound healing. Our results show that LXA4-MS could be used as a pharmaceutical formulation for the treatment of skin ulcers.

Ocorrência de enteroparasitoses em manipuladores de alimentos de restaurantes em Parnaíba, Piauí-Brasil / Occurrence of intestinal parasites in food handlers working in restaurants of the city of Parnaíba, Piauí-Brazil

As enteroparasitoses têm se mostrado um sério problema de saúde pública no Brasil e no mundo.O processo de transmissão fecal-oral dessas doenças facilita sua disseminação por meio dealimentos. Este trabalho teve como objetivos avaliar a ocorrência de contaminação parasitária emmanipuladores de alimentos de restaurantes de médio e grande porte na cidade de Parnaíba, Piauí, ediscutir a influência destes na transmissão de parasitoses. Foram analisadas amostras fecais de 251indivíduos na faixa etária entre 20 e 59 anos, segundo os métodos de Hoffman, Pons e Janer e de Willis. Foram aplicados questionários estruturados sobre os aspectos socioeconômicos e sanitáriosdos indivíduos. A análise estatística dos resultados foi realizada pelos testes exato de Fischer equi-quadrado para identificar associações entre as variáveis com nível de significância de 5 por cento. Oíndice de positividade para parasitos nas amostras foi de 51 por cento (129 amostras), sendo identificadoscasos de poliparasitismo. Entre os protozoários foram encontrados: Entamoeba coli (38 por cento),Endolimax nana (26 por cento), Entamoeba histolytica/E. dispar (17 por cento), Iodamoeba bustchlii (8 por cento). Entre os helmintos: Ascaris lumbricoides (48 por cento), ancilostomídeos (19 por cento), Enterobius vermicularis (13 por cento),Strongyloides stercolaris (10 por cento), Hymenolepis nana (6 por cento) e Taenia spp (4 por cento). Verificou-se elevada prevalência (51 por cento) de enteroparasitoses em manipuladores de alimentos, com predominânciasignificativa (p<0,05) de protozooses (74 por cento) sobre helmintíases (26 por cento).

Introduction: Intestinal parasites are a serious public health problem in Brazil and worldwide, affectingindividuals from several social classes. The fecal-oral route of transmission of these infectionsfacilitates their spread by food. This study aimed to evaluate the occurrence of parasitic contaminationsamong restaurant food handlers in the city of Parnaíba, Piauí, also discussing their possible influenceson the transmission of enteroparasites. Methodology: Fecal samples from 251 individuals agedbetween 20 and 59 years were analyzed. Hoffman, Pons and Janer and Willis methods were performedon samples. Structured questionnaires about socio-economic and health aspects of individuals wereapplied. Fisher’s exact and chi-square tests with significance level of 5 percent were used to identifyassociations between categorical variables. Results: Positive samples for parasites were found in 51 percent (129 samples). Cases of polyparasitism were also found. Protozoa detected were Entamoeba coli(38 percent ), Endolimax nana (26 percent ), Entamoeba histolytica / E. dispar (17 percent ), Iodamoeba bustchlii (8 percent ).Helminths detected were Ascaris lumbricoides (48 percent ), ancylostomides (19 percent ), Enterobius vermicularis(13 percent ), Strongyloides stercoralis (10 percent ), Hymenolepis nana (6 percent ) and Taenia spp. (4 percent ). Conclusion:A high prevalence (51 percent ) of intestinal parasites was found in restaurant food handlers. Prevalence ofprotozoan infections (74 percent ) was significantly (p<0.05) higher than helminth infections (26 percent ).