993 resultados para Toxins.


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Pós-graduação em Microbiologia Agropecuária - FCAV

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Envenomation via snakebites is an important public health problem in many tropical and subtropical countries that, in addition to mortality, can result in permanent sequelae as a consequence of local tissue damage, which represents a major challenge to antivenom therapy. Venom phospholipases A(2) (PLA(2)s) and PLA(2)-like proteins play a leading role in the complex pathogenesis of skeletal muscle necrosis, nevertheless their precise mechanism of action is only partially understood. Recently, detailed structural information has been obtained for more than twenty different members of the PLA(2)-like myotoxin subfamily. In this review, we integrate the available structural, biochemical and functional data on these toxins and present a comprehensive hypothesis for their myotoxic mechanism. This process involves an allosteric transition and the participation of two independent interaction sites for docking and disruption of the target membrane, respectively, leading to a five-step mechanism of action. Furthermore, recent functional and structural studies of these toxins complexed with ligands reveal diverse neutralization mechanisms that can be classified into at least three different groups. Therefore, the data summarized here for the PLA(2)-like myotoxins could provide a useful molecular basis for the search for novel neutralizing strategies to improve the treatment of envenomation by viperid snakes. (C) 2014 Elsevier B.V. All rights reserved.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Leprosy is a chronic infectious disease caused by Mycobacterium leprae, a microorganism that usually affects skin and nerves. Although it is usually well-controlled by multidrug therapy (MDT), the disease may be aggravated by acute inflammatory reaction episodes that cause permanent tissue damage particularly to peripheral nerves. Tuberculosis is predominantly a disease of the lungs; however, it may spread to other organs and cause an extrapulmonary infection. Both mycobacterial infections are endemic in developing countries including Brazil, and cases of coinfection have been reported in the last decade. Nevertheless, simultaneous occurrence of perianal cutaneous tuberculosis and erythema nodosum leprosum is very rare, even in countries where both mycobacterial infections are endemic.

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Several species of octopus are considered venomous due to toxins present in the glands connected to their "beak", which may be associated with hunt and kill of prey. Herein, we report an accident involving a common octopus (Octopus vulgaris) that injured an instructor during a practical biology lesson and provoked an inflamed infiltrated plaque on the hand of the victim. The lesion was present for about three weeks and was treated with cold compresses and anti-inflammatory drugs. It was healed ten days after leaving a hyperchromic macule at the bite site. The probable cause of the severe inflammation was the digestive enzymes of the glands and not the neurotoxins of the venom.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Snakes from Bothrops genus are responsible for more than 90% of the ophidian accidents in Brazil. One of the main complications from this kind of accident is muscular necrosis, which is related to the action of phospholipases A2 and metalloproteases, two groups of enzymes found in the venom of these animals. Although this complication cannot be solved by serum therapy administration, a great number of studies have been performed with the attempt to know the pharmacological sites of these toxins aiming, in the future, the development of complementary treatments to serum therapy. This work proposes structural studies of bothropic phospholipases A2 (PLA2s) in the presence of ions relevant to their activity, using the X-ray crystallography technique. Recently, it was demonstrated ions, as manganese, calcium and others, interfere in the biological activity of the PLA2s. Particularly, Lys49-PLA2s in the presence of manganese ions have miotoxicity reduced. Asp49-PLA2s show catalytic activity dependent of calcium, although structural studies with a miotoxic Asp49-PLA2, BthTX-II, suggest a possible catalytic mechanism independent of calcium. Therefore, co-crystallization of BthTX-II in the presence of calcium ions and of PrTX-I in the presence of manganese ions were performed. Comparative structural studies among obtained results and others already published in the literature were performed aiming a better understanding of the structure-function relationship of these toxins. The BthTX-II with the presence of calcium do not show this ion in the loop of coordination of calcium, presence necessary to develop the catalyses. After comparison of this model with the native one, only one distortion was found, but no apparent relationship with the residues responsible for its activity. In the PrTX-I structure, regions candidates of manganese ions were also found... (Complete abstract click electronic access below)

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Scorpions are among the oldest living groups of animals, and are present in almost every continent. Although many studies are made about the toxins present in their venom, little is known about their behavior. The aim of this paper is to investigate the expression of agressiveness in the brazilian yellow scorpion Tityus serrulatus, specifically the relation between agressiveness, motor activity and feeding condition. The study was divided in two parts. First, we used 16 adult individuals, placed in two terrarium, to establish an ethogram. Each group was observed for 36h, and the behaviors displayed were described and categorized as agonistic or non-agonistic. In the second part of the experiment, we used 32 adult animals in three different nutritional states: Feeding (still ingesting food), Sated (1 to 4 days since last meal) and Deprived (14 to 25 days since last meal). The individuals were paired, each pair placed in a terrarium and observed for 30min. Behaviors displayed were timed in seconds. Our results show that only Feeding individuals displayed agonism towards others, and no relation was observed between motor activity and feeding conditions

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This research presents a study of structural complexes formed between the bothropstoxin BthTX-I and PrTX-I and phospholipase A2 (PLA2s) inhibitor 12- methoxy-4-methyl-voachalotine (MMV) of Tabernamontana catharinensis and rosmarinic acid (Cv-RA) of Rosmarinus officinalis. For both were used cocrystallization experiments with the toxins and inhibitors. In the future, the experimental three-dimensional structures of these complexes will be obtained through the technique of crystallography. Simultaneously, construction occurred in silico of inhibitors Cv-RA and MMV and attempts of docking between these binders and protein structures. These theoretical data provide important information regarding the nature of interactions between inhibitors, toxins and structural changes induced by the protein molecule inhibitors. Therefore, the acquisition of this information has great value to identification, characterization and development (drug design) of compounds with great potential for biotechnology and drug use. Considering further and more relevant aplications, these compounds could be used to control symptoms in many cases of ophidic poisoning and also in combating of pathological processes (degenerative inflammatory diseases and auto-immune diseases, Alzheimer's disease, schizophrenia, among others) whose causes are related to molecules belonging to the same groups of proteins which are classified bothropstoxin that were studied in this project

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This study aimed to conduct a review in most articles relating mastitis and reproduction. Mastitis affects the reproduction according to its time of occurrence and agent. Mastitis affects the interval interestrus and also increases the number of days open, the number of services per conception, the abortion rate and decreases the conception rate. The inflammatory reaction generated by mastitis and all the toxins produced by bacteria alter the entire endocrine profile of cows that experienced episodes of mastitis and thus affect their reproduction