Camelid Single-Domain Antibodies As an Alternative to Overcome Challenges Related to the Prevention, Detection, and Control of Neglected Tropical Diseases

Submitted by EMERSON LEAL ([email protected]) on 2019-05-06T13:12:18Z No. of bitstreams: 1 Camelid Single-Domain Antibodies As an Alternative to Overcome Challenges Related to the Prevention, Detection, and Control of Neglected Tropical Diseases.pdf: 417589 bytes, checksum: 6c1a7934b342f6a6fa4946ca8fc76f12 (MD5)Approved for entry into archive by EMERSON LEAL ([email protected]) on 2019-05-06T13:33:05Z (GMT) No. of bitstreams: 1 Camelid Single-Domain Antibodies As an Alternative to Overcome Challenges Related to the Prevention, Detection, and Control of Neglected Tropical Diseases.pdf: 417589 bytes, checksum: 6c1a7934b342f6a6fa4946ca8fc76f12 (MD5)Made available in DSpace on 2019-05-06T13:33:05Z (GMT). No. of bitstreams: 1 Camelid Single-Domain Antibodies As an Alternative to Overcome Challenges Related to the Prevention, Detection, and Control of Neglected Tropical Diseases.pdf: 417589 bytes, checksum: 6c1a7934b342f6a6fa4946ca8fc76f12 (MD5) Previous issue date: 2017Fundação Oswaldo Cruz. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Departamento de Medicina. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Fiocruz Ceará. Fortaleza, CE, Brasil.Universidade Federal de Rondônia. Departamento de Medicina. Porto Velho, RO, Brasil. / Plataforma Bi-Institucional de Medicina Translacional (Fiocruz-USP). Ribeirão Preto, SP, Brasil.Due mainly to properties such as high affinity and antigen specificity, antibodies have become important tools for biomedical research, diagnosis, and treatment of several human diseases. When the objective is to administer them for therapy, strategies are used to reduce the heterologous protein immunogenicity and to improve pharmacokinetic and pharmacodynamic characteristics. Size minimization contributes to ameliorate these characteristics, while preserving the antigen–antibody interaction site. Since the discovery that camelids produce functional antibodies devoid of light chains, studies have proposed the use of single domains for biosensors, monitoring and treatment of tumors, therapies for inflammatory and neurodegenerative diseases, drug delivery, or passive immunotherapy. Despite an expected increase in antibody and related products in the pharmaceutical market over the next years, few research initiatives are related to the development of alternatives for helping to manage neglected tropical diseases (NTDs). In this review, we summarize developments of camelid single-domain antibodies (VHH) in the field of NTDs. Particular attention is given to VHH-derived products, i.e., VHHs fused to nanoparticles, constructed for the development of rapid diagnostic kits; fused to oligomeric matrix proteins for viral neutralization; and conjugated with proteins for the treatment of human parasites. Moreover, paratransgenesis technology using VHHs is an interesting approach to control parasite development in vectors. With enormous biotechnological versatility, facility and low cost for heterologous production, and greater ability to recognize different epitopes, VHHs have appeared as an opportunity to overcome challenges related to the prevention, detection, and control of human diseases, especially NTDs

Snake Venom L-Amino Acid Oxidases: Some Consideration About their Functional Characterization

Snake Venom L-amino acid oxidases (LAAOs E.C. 1.4.3.2) are flavoenzymes broadly found in various snake venom compositions. LAAOs have become an attractive subject for molecular biology, biochemistry, physiology and medicine due to their actions on various cells and biological effects on platelets, apoptosis, hemorrhage and others. In this review we try to summarize some of these reports, with special emphasis on apoptosis, anti-protozoa, bactericidal and anti-viral activities.CNPqFINEPFAPESP, Brazi

Biochemical characterization, action on macrophages, and superoxide anion production of four basic Phospholipases A2 from Panamanian Bothrops asper Snake Venom

Submitted by EMERSON LEAL ([email protected]) on 2016-06-20T13:23:11Z No. of bitstreams: 1 Biochemical Characterization, Action on.pdf: 2093810 bytes, checksum: 0b5ba2ff6883e6faada0f1d189a44b90 (MD5)Approved for entry into archive by EMERSON LEAL ([email protected]) on 2016-07-14T15:25:25Z (GMT) No. of bitstreams: 1 Biochemical Characterization, Action on.pdf: 2093810 bytes, checksum: 0b5ba2ff6883e6faada0f1d189a44b90 (MD5)Made available in DSpace on 2016-07-14T15:25:25Z (GMT). No. of bitstreams: 1 Biochemical Characterization, Action on.pdf: 2093810 bytes, checksum: 0b5ba2ff6883e6faada0f1d189a44b90 (MD5) Previous issue date: 2013Made available in DSpace on 2016-07-15T18:40:37Z (GMT). No. of bitstreams: 3 Biochemical Characterization, Action on.pdf.txt: 41466 bytes, checksum: c3be979a3b56d53538068e99960e1440 (MD5) Biochemical Characterization, Action on.pdf: 2093810 bytes, checksum: 0b5ba2ff6883e6faada0f1d189a44b90 (MD5) license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) Previous issue date: 2013Universidade de São Paulo. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Ribeirão Preto, SP, Brasil. / Universidad Autónoma de Chiriquí. Departamento de Química. Facultad de Ciencias Naturales y Exactas. UNACHI, Panama. / Complejo Hospitalario Metropolitano. Departamento de Laboratorio Clínico. Caja de Seguro Social. CHM-CSS, Panama.Universidade de São Paulo. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Ribeirão Preto, SP, Brasil.Universidade de São Paulo. Departamento de Física e Química. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Ribeirão Preto, SP, Brasil.Fundação Oswaldo Cruz. Centro de Estudos de Biomoléculas Aplicadas a Saúde-CEBio. Núcleo de Saúde. Universidade Federal de Rondônia. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Centro de Estudos de Biomoléculas Aplicadas a Saúde-CEBio. Núcleo de Saúde. Universidade Federal de Rondônia. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Centro de Estudos de Biomoléculas Aplicadas a Saúde-CEBio. Núcleo de Saúde. Universidade Federal de Rondônia. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Centro de Estudos de Biomoléculas Aplicadas a Saúde-CEBio. Núcleo de Saúde. Universidade Federal de Rondônia. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Centro de Estudos de Biomoléculas Aplicadas a Saúde-CEBio. Núcleo de Saúde. Universidade Federal de Rondônia. Porto Velho, RO, Brasil.Bothrops asper (Squamata: Viperidae) is the most important venomous snake in Central America, being responsible for the majority of snakebite accidents. Four basic PLA2s (pMTX-I to -IV) were purified from crude venom by a single-step chromatography using a CM-Sepharose ion-exchange column (1.5 × 15 cm). Analysis of the N-terminal sequence demonstrated that pMTX-I and III belong to the catalytically active Asp49 phospholipase A2 subclass, whereas pMTX-II and IV belong to the enzymatically inactive Lys49 PLA2s-like subclass. The PLA2s isolated from Panama Bothrops asper venom (pMTX-I, II, III, and IV) are able to induce myotoxic activity, inflammatory reaction mainly leukocyte migration to the muscle, and induce J774A.1 macrophages activation to start phagocytic activity and superoxide production

Armoede en doelmatigheid van de sociale zekerheid in Europa

Abstract Background Wasp venoms constitute a molecular reservoir of new pharmacological substances such as peptides and proteins, biological property holders, many of which are yet to be identified. Exploring these sources may lead to the discovery of molecules hitherto unknown. This study describes, for the first time in hymenopteran venoms, the identification of an enzymatically inactive phospholipase A2 (PLA2) from the venom of the social wasp Polybia occidentalis. Methods P. occidentalis venom was fractioned by molecular exclusion and reverse phase chromatography. For the biochemical characterization of the protein, 1D and 2D SDS-PAGE were performed, along with phospholipase activity assays on synthetic substrates, MALDI-TOF mass spectrometry and sequencing by Edman degradation. Results The protein, called PocTX, was isolated using two chromatographic steps. Based on the phospholipase activity assay, electrophoresis and mass spectrometry, the protein presented a high degree of purity, with a mass of 13,896.47 Da and a basic pI. After sequencing by the Edman degradation method, it was found that the protein showed a high identity with snake venom PLA2 homologues. Conclusion This is the first report of an enzymatically inactive PLA2 isolated from wasp venom, similar to snake PLA2 homologues

Activation of J77A.1 macrophages by three phospholipases A2 isolated from bothrops atrox snake venom

Submitted by Claudete Queiroz ([email protected]) on 2016-05-03T17:00:14Z No. of bitstreams: 1 Activation of J77A.1 Macrophages by Three Phospholipases A2 Isolated from Bothrops atrox Snake Venom.pdf: 2090853 bytes, checksum: 0669d064c65a39c61c661542c067ee9b (MD5)Approved for entry into archive by EMERSON LEAL ([email protected]) on 2016-05-10T14:32:57Z (GMT) No. of bitstreams: 1 Activation of J77A.1 Macrophages by Three Phospholipases A2 Isolated from Bothrops atrox Snake Venom.pdf: 2090853 bytes, checksum: 0669d064c65a39c61c661542c067ee9b (MD5)Made available in DSpace on 2016-05-10T14:32:57Z (GMT). No. of bitstreams: 1 Activation of J77A.1 Macrophages by Three Phospholipases A2 Isolated from Bothrops atrox Snake Venom.pdf: 2090853 bytes, checksum: 0669d064c65a39c61c661542c067ee9b (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Laboratório de Imunofarmacologia Aplicada à Saúde. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Centro de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Laboratório de Imunofarmacologia Aplicada à Saúde. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Laboratório de Imunofarmacologia Aplicada à Saúde. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Laboratório de Imunofarmacologia Aplicada à Saúde. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Laboratório de Imunofarmacologia Aplicada à Saúde. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Laboratório de Imunofarmacologia Aplicada à Saúde. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Centro de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Centro de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Centro de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Laboratório de Imunofarmacologia Aplicada à Saúde. Porto Velho, RO, Brazil. / Fundação Oswaldo Cruz. Centro de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Centro de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Laboratório de Imunofarmacologia Aplicada à Saúde. Porto Velho, RO, Brazil. / Fundação Oswaldo Cruz. Centro de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.In the present study, we investigated the in vitro effects of two basic myotoxic phospholipases A2 (PLA2), BaTX-I, a catalytically inactive Lys-49 variant, and BaTX-II, a catalytically active Asp-49, and of one acidic myotoxic PLA2, BaPLA2, a catalytically active Asp-49, isolated from Bothrops atrox snake venom, on the activation of J774A.1 macrophages. At noncytotoxic concentrations, the toxins did not affect the adhesion of the macrophages, nor their ability to detach. The data obtained showed that only BaTXI stimulated complement receptor-mediated phagocytosis. However, BaTX-I, BaTX-II, and BaPLA2 induced the release of the superoxide anion by J774A.1 macrophages. Additionally, only BaTX-I raised the lysosomal volume of macrophages after 15 min of incubation. After 30 min, all the phospholipases increased this parameter, which was not observed within 60 min. Moreover, BaTX-I, BaTX-II, and BaPLA2 increased the number of lipid bodies on macrophages submitted to phagocytosis and not submitted to phagocytosis. However, BaTX-II and BaPLA2 induced the release of TNF- by J774A.1 macrophages. Taken together, the data show that, despite differences in enzymatic activity, the three toxins induced inflammatory events and whether the enzyme is acidic or basic does not seem to contribute to these effects

Snake venom L-Amino acid oxidases: trends in pharmacology and biochemistry

Submitted by Claudete Queiroz ([email protected]) on 2016-05-03T18:02:40Z No. of bitstreams: 1 Snake Venom L-Amino Acid Oxidases Trends in - Pharmacology and Biochemistry.pdf: 3419937 bytes, checksum: 77270860cee91bddcc146303c805335c (MD5)Approved for entry into archive by EMERSON LEAL ([email protected]) on 2016-05-17T14:23:25Z (GMT) No. of bitstreams: 1 Snake Venom L-Amino Acid Oxidases Trends in - Pharmacology and Biochemistry.pdf: 3419937 bytes, checksum: 77270860cee91bddcc146303c805335c (MD5)Made available in DSpace on 2016-05-17T14:23:25Z (GMT). No. of bitstreams: 1 Snake Venom L-Amino Acid Oxidases Trends in - Pharmacology and Biochemistry.pdf: 3419937 bytes, checksum: 77270860cee91bddcc146303c805335c (MD5) Previous issue date: 2014Universidade Federal de Uberlândia. Faculdade de Ciências Integradas do Pontal. Departamento de Genética e Bioquímica. Uberlândia, MG, Brazil.Fundação Oswaldo Cruz. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Universidade Federal de Uberlândia. Faculdade de Ciências Integradas do Pontal. Departamento de Genética e Bioquímica. Uberlândia, MG, Brazil.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. Ribeirão Preto, SP, Brazil.Fundação Oswaldo Cruz. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Universidade Federal de Uberlândia. Faculdade de Ciências Integradas do Pontal. Departamento de Genética e Bioquímica. Uberlândia, MG, Brazil.Universidade Federal de São João del Rei. Departamento de Química, Biotecnologia e Engenharia de Bioprocessos. Ouro Branco, MG, Brazil.Fundação Oswaldo Cruz. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Departamento de Medicina. Universidade Federal de Rondônia. Porto Velho, RO, Brazil.L-amino acid oxidases are enzymes found in several organisms, including venoms of snakes, where they contribute to the toxicity of ophidian envenomation. Their toxicity is primarily due to enzymatic activity, but other mechanisms have been proposed recently which require further investigation. L-amino acid oxidases exert biological and pharmacological effects, including actions on platelet aggregation and the induction of apoptosis, hemorrhage, and cytotoxicity. These proteins present a high biotechnological potential for the development of antimicrobial, antitumor, and antiprotozoan agents. This review provides an overview of the biochemical properties and pharmacological effects of snake venom L-amino acid oxidases, their structure/activity relationship, and supposed mechanisms of action described so far