Regular Disciplines

TOX001 - INTRODUCTION TO TOXINOLOGY
Coordination: Denise Vilarinho Tambourgi, Ana Maria Moura da Silva and Sandra Coccuzzo Sampaio Vessoni
Level: PhD and Masters degree
Hours: 78
Credits: 5.0
Concentration Area (s): Toxinology
Content:
This discipline presents fundamental concepts of toxinology, addressing the origin of toxins, mechanisms of action and effects on victims of accidents with venomous animals. Basic notions for deepening in optional disciplines: poisons and toxins, venomous animals and poisonings.
Program Content:
1- Natural history of the main groups of venomous animals: Evolution, Ecology, Classification; 2- Poisoning by venomous animals, Clinical symptoms of poisoning by animals of medical importance, Therapeutic approaches; 3- Toxins and biological systems: Neurotoxins, Toxins affecting hemostasis, Toxins and inflammatory response, Cytotoxins; 4 - Seminars.
Bibliography:
1- - Animais peçonhentos no Brasil: Biologia, clínica e terapêutica dos acidentes. Cardoso et al., São Paulo, Sarvier, 2003, 1ª. Ed. 2- Handbook of Clinical Toxicology of Animal Venoms and Poisons. Jurg Meier, Julian White. 3- Handbook of animal toxins. R. Stocklin, 2003. 4- Journal articles specialized in Toxinology and basic areas of knowledge such as biochemistry, pharmacology, immunology and cell biology, all bringing recent advances in the area.

TOX002 - SEMINARS OF INTEGRATION AND SCIENTIFIC DISCUSSION
Coordination: Norma Yamanouye, Luís Roberto de Camargo Gonçalves and Roxane Maria Fontes Piazza
Hours: 15 hours
Number of credits: 01
The analytical capacity is summed to the quality of the research object exposure. To stimulate scientific exchange and the collective production of knowledge, the Discipline constructs the environment of interaction:
1. It enables students to present and discuss their results and fosters the integration of students from various research lines, stimulating multidisciplinarity.
2. It encourages Doctorate students to present their project and results in English.
These seminars would be an opportunity to train and improve students and to stimulate knowledge of the various areas within Toxinology. Thus, it is intended that the student present his results and scientific articles related to themes, in a clear and didactic way in the context of an updated literature. This will allow discussion of results, learning of updated methodologies, adequacy of experimental approaches and development of the critical analysis of their research project. In addition, since the Program is encouraging the internationalization of its activities, it is imperative that students, at least as a doctorate candidate, be able to present and discuss their results in English.
Program content:
Presentation of the projects and / or results obtained in the dissertations or thesis by the Graduate Program students, and the students of Doctorate will present in English; Discussion of the work presented.
Bibliography: Not applicable.

TOX005 – BUTANTAN INSTITUTE SEMINARS (Compulsory)
Coordination: Ana Marisa Chudzinski Tavassi
Level: PhD and Master of Science
Hours: 15
Credits: 1.0
Content:
To offer postgraduates lectures and mini workshops with themes relevant to the program and to Butantan Institute with invited researchers from both the Institution and from other Institutions in Brazil and abroad. Through lectures and mini workshops it is intended to broaden the knowledge of the student on various topics as well as provide an environment conducive to contact with new themes, professionals in the field, as well as stimulate the student to discuss the aspects of interest presented.
Program Content: There is no specific content. The programming of the seminars and lectures is carried out by a Commission designated for this purpose that will define the line of the lectures to be realized in a certain period.
Bibliography: Not applicable. Eventually the invited researchers provide elements of their scientific production related to the topic to be presented as a way to provide elements to deepen the discussions to be carried out in the lecture.

TOX006 - EDUCATIONAL PRACTICES IN NON-FORMAL ENVIRONMENTS I (Compulsory)
Coordination: Roxane Maria Fontes Piazza and Norma Yamanouye
Level: PhD and Master of Science
Required: Yes
Working Hours: 15
Credits: 1.0
Content:
To permit the student elaborate and execute a didactic activity in health and biological sciences next to high school students and teachers of basic education. It is of great importance to introduce the graduate student in didactic activities aimed at scientific diffusion. This process is based on the idea that scientific knowledge undergoes a transformation process by becoming a knowledge that can be taught or propagated.
Program Content: Formal and non-formal education; Construction of a guide of educational activity: objectives, target audience, methodology, contents and evaluation. Who is the average high school student in a public school: day to day school and content; teaching strategies in science: problematization.
Bibliography:
1. Falk, J. and Dierking, L. Creating Museum Experiences for organized groups. In Falk, J. and Dierking, L. The Museum  experience, 2011 (original 1992), ch. 11, p. 151-160.
2. Johnson, A. Building effective tours: taming wild docents. In Johnson, A .; Huber, K .; Cutler, N.; Bingman, N .; Grove, T. The Museum Educator's Manual, American Association for State nd Local History / Altamira Press, cp.4. P. 47-51.
3. Mott, M. L. et al. A defesa contra o ofidismo de Vital Brazil e a sua contribuição à Saúde Pública brasileira. Cadernos de História da Ciência, vol. 7, n2, Julho/dezembro 2011, p. 89-110
4. Santos, F. M. T. & Gói, M.E.J. Resolução de problemas e atividades práticas de laboratório: uma articulação possível. In: Atas de V Encontro Nacional de Pesquisa em Educação em Ciências, 2005. Available http://www.nutes.ufrj.br/abrapec/venpec/conteudo/oralarea1.htm.

TOX007 - EDUCATIONAL PRACTICES IN NON-FORMAL ENVIRONMENTS II
Coordination: Roxane Maria Fontes Piazza and Norma Yamanouye
Level: PhD and Master of Science
Working Hours: 30
Credits: 2.0
Content
The students should also propose, structure and execute a set of educational actions aimed at teachers and students totalizing 40 hours each during the period of “Projeto Novos Talentos”. A practical discipline, in which the postgraduate is expected to contact formal education, in view of partner schools of “Projeto Novos Talentos”, and non-formal, in view of the partner schools of “Projeto Novos Talentos”, and non-formal, through the use of different practices in the museums and laboratories of the Butantan Institute. Thus, it proposes to the postgraduate student an analysis about its set of knowledge, so that it can choose what is fundamental to the public to which this activity is destined. In addition, the student should know and choose different strategies of Science teaching to develop the selected contents and to elaborate evaluations of these contents.
Program content:
Elaboration and application of educational activities: objectives, target audience, methodology,
Contents and evaluation.
Bibliography:
1. Johnson, A. Building effective tours: taming wild docents. In Johnson, A .; Huber, K .; Cutler, N.; Bingman, N .; Grove, T. The Museum Educator's Manual, American Association for State and Local History / Altamira Press, cp.4. P. 47-51.
2. Hein, G. Learning in the Museum, London: Rutledge, 1998.
3. Hein, G. O dilemma da educação científica: O dilema da educação científica: como ensinar quando os visisntantes apenas querem aprender. InMarandino, M.; Almeida, A.M.; Valente, M. E. A. Museu Lugar do Público, Rio de Janeiro: Ed. Fiocruz, 2009, p- 63-75.

TOX010 - BIOPROSPECTION IN ANIMAL TOXINS
Coordination: Lanfranco Ranieri Paolo Troncone
Level: PhD and Master of Science
Hours: 60
Credits: 4.0
Content
The aim of the course is to present the bioprospecting subject to the student in general and to deepen the subject focusing on the characteristics of the study of poisons. The biological origin of the poisons represents a nature strategy for the production of active compounds. Most animal poisons are peptidic toxins and thus represent inherited traits selected for their efficiency in assigning selective advantages to their bearer. Non-peptidic toxins are mostly derived from metabolic adaptations that introduced active compounds into animal secretions from food or symbiotic sources. In both cases, Nature delegated the production in its immense chemical laboratory a great diversity of active compounds and gathered them in the form of poisons. The pharmaceutical industry has great interest in active molecules and can generate new drugs from toxins of animal origin, justifying the specific development of this theme.
Program Content: 1- Introduction to the course; 2- Basic concepts of bioprospecting - the stages; 3- The study of diseases and the validation of pharmacological targets; Pharmacological screening - general concepts; 5- Alternative strategies - screening in vivo - in vitro - in silico; 6- Bioprospecting in practice - case studies in the large industry; 7- Animal poisons - characteristics and peculiarities; 8- Strategies: recommendations; 9- Errors and hits; 10- Conclusion.
Bibliography
1- Schroeder, F.C .; Taggi, A.E .; Gronquist, M .; Malik, R.U .; Grant, J.B .; Eisner, T .; Meinwald, J. NMR spectroscopic screening of spider venom reveals sulfated nucleosides as major components for the brown recluse and related species. Proc Natl Acad Sci U S A. 105 (38): 14283-7.2008. 2- Han, T.S .; Teichert, R.W .; Olivera, B.M .; Bulaj, G. Conus venoms - the rich source of peptide-based therapeutics. Curr Pharm Des. 14 (24): 2462-79, 2008, Review. 3- Menin, L .; Perchu, A .; Favreau, P .; Perret, F .; Michalet, S .; Schöni, R .; Wilmer, M .; Stöcklin, R . High throughput screening of bradykinin-potentiating peptides in Bothrops moojeni snake venom using precursor ion mass spectrometry. Toxicon 51 (7): 1288-302, 2008. 4- Butler, M. S. Natural products to drugs: natural product-derived compounds in clinical trials. Nat.Prod. Rep. 25 (3): 475-516, 2008. 5- Leeson, P.D .; Springthorpe, B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat Rev Drug Discov. 6 (11): 881-90, 2007. Review. 6- Taggi, A.E .; Meinwald, J .; Schroeder, F.C. A new approach to natural products discovery exemplified by the identification of sulfated nucleosides in spider venom. J. Am. Chem. Soc. 126 (33): 10364-9, 2004. 7- Deng, X.Q .; Wang, H. Y .; Zhao, Y.L .; Xiang, M.L .; Jiang, P.D .; Cao, Z.X .; Zheng, Y.Z .; Luo, S. D .; Yu, L.T .; Wei, Y.Q .; Yang, S.Y. Pharmacophore modeling and virtual screening for identification of new Aurora-A kinase inhibitors. Chem Biol Drug Des. 71 (6): 533-9, 2008. 8- Vogt, M .; Bajorath, J. Bayesian screening for active compounds in high-dimensional chemical spaces combining property descriptors and molecular fingerprints. Chem. Biol. Drug. Des. 71 (1): 8-14, 2008. 9- Nisbet, L.J .; Moore, M. Will natural products remain an important source of drug research for the future? Curr. Opin. Biotechnol. 8 (6): 708-12, 1997, Review. 10- Guidebook to protein toxins and their use in cell biology. R. Rappouli and C. Montecucco eds. Oxford U. Press. (1997).

TOX012 - NATURAL HISTORY AND EVOLUTION OF VENOMOUS VERTEBRATES
Coordination: Carlos Alberto Gonçalves Silva Jared and Marta Maria Antoniazzi
Level: PhD and Master of Science
Hours: 60
Credits: 4.0
Content
The course aims to introduce the student to the fundamentals of vertebrate evolution and biology in general, with particular emphasis on amphibians and reptiles. From this, the origin and the adaptive role of the chemical defense systems, through toxins, are discussed in each group. It is intended, therefore, to provide the zoological and natural history theory so that the student can have conceptual tools to form a multidisciplinary view of Toxinology. Currently, within the study of toxins, it is common that the student work in the experimental areas, compartmentalizing their knowledge. In this context, we intend to develop a course in which Toxinology is conceived within a wider universe of study, including concepts of general biology and zoology, involved with Evolution and Natural History.
Program content:
1- General concepts and History of Evolution; 2- Adaptation and Natural Selection; 3- The Evolution of Vertebrates; 4- The Amphibians; 5- The Reptiles; 6- Evolution of Defense Systems; 7- Passive and Active Defense; 8- The biology and poison of fish, amphibians and reptiles; 9- Other groups of venomous vertebrates; 10- Myths and folklore related to vertebrate venom.
Bibliography:
1-Ménez A. The subtle beast. Snakes, from Myth to Medicine. Taylor & Francis Group, London, 2003. 2-Pough F.H., Andrews R.M., Cadle J.E., Crump M.L., Savitzky A.H. & Wells K.D. Herpetology. (3rd Edition). Benjamin Cummings Publisher, USA, 2003. 3- Pough F.H., Janis C.M. & Heiser J.B. A Vida dos Vertebrados (4a Edição). Atheneu Ed. São Paulo Ltda., São Paulo, 2008. 4- Clarke B.T. The natural history of amphibian skin secretions, their normal functioning and potential medical applications. Biol. Rev. 72: 365-379, 1997.

TOX013 - NEUROTOXINS AS PHARMACOLOGICAL TOOLS
Coordination: Ana Leonor Abrahão Nencioni and Solange Castro Afeche
Level: PhD and Master of Science
Hours: 90
Credits: 6.0
Content
To show the neurotoxins present in poisons or other natural sources as a tool for the study of nervous structures, physiological or pathological processes as well as possible therapeutic uses. Discuss the mechanisms of action of these toxins by relating them to their applicability. Venomous, poisons and products of bacterial origin are rich sources of substances selected by nature in the course of evolution which, in addition to having their function in the life cycle of those who produce them, may have multiple applicability as a tool for studies of several biological processes. In this panorama, we highlight the neurotoxins that have been used to elucidate the structure and the functioning of the localities where they bind. In addition, several possibilities exist as therapeutic or biological control products already used and that can still be developed from the study of its mechanisms of action.
Program content:
Theoretical classes: 1- Toxins as a tool for the study of sodium channels; 2- Toxins as a tool for the study of potassium channels; 3 - Toxins as a tool for the study of calcium channels; 4- Therapeutic aspects of conotoxins; 5. Neurotoxins of microbial origin (botulinum and tetanum toxins) and their applications; 6- Therapeutic aspects of conotoxins; 7- Neurotoxins of microbial origin (botulinum and tetanic toxins) and their applications; 8- Convulsive neurotoxins; Anticonvulsive neurotoxins; 10- Antimicrobial and cytolytic peptides; 11- Phospholipases A2; 12- Alpha-elapidic neurotoxins and their applications; 13- Dendrotoxins; 14- Neurotoxins and the treatment of neoplasias. Seminars: 1 - Scorpion neurotoxins; 2- Spiders neurotoxins; 3- Snake neurotoxins; Conus neurotoxins; 5- Neurotoxins of microbial origin; 6- Neurotoxins and development.
Bibliography:
Arias, H. R. and Blanton, M.P., Alpha-conotoxins. Int.J.Biochem.Cell Biol. 32: 1017-1028, 2000. 2- Catterall, W.A .; Cestele, S .; Yarov-Yarovoy, V .; Yu, F. H .; Konoki, K. and Scheuer, T. Voltage-gated ion channels and gating modifier toxins. Toxicon 49: 124-141, 2007. 3- Cestele, S. and Catterall, W.A. Molecular mechanisms of neurotoxin action on voltage-gated sodium channels. Biochimie 82: 883-892, 2000. 4- Davletov, B .; Basshrs, M. and Binz, T .. Beyond BOTOX: advantages and limitations of individual botulinum neurotoxins. Trends Neurosci. 28: 446-452, 2005. 5- Gurevitz, M .; Karbat, I .; Cohen, L .; Ilan, N .; Kahn, R .; Turkov, M .; Stankiewicz, M .; Stuhmer, W .; Dong, K. and Gordon, D .. The insecticidal potential of scorpion beta-toxins. Toxicon 49: 473-489, 2007. 6- Harvey, A. L .; Bradley, K. N .; Cochran, S.A .; Rowan, E. G .; Pratt, J.A .; Quillfeldt, J. A. and Jerusalinsky, D. A .. What can toxins tell us for drug discovery? Toxicon 36: 1635-1640, 1998. 7- Harvey, A. L .. Twenty years of dendrotoxins. Toxicon, 39: 15-26, 2001.

TOX015 - ANTIVENOMS AND IMMUNODIAGNOSIS
Coordination: Kátia Cristina Bárbaro Nogueira and Eliana Faquim de Lima Mauro
Level: PhD and Master of Science
Hours: 60
Credits: 4.0
Content
To provide students with theoretical and practical knowledge of the antivenoms antibodies and their role, both in the study of the mechanism of action of animal poisons as well as in the treatment of poisoning and immunodiagnostic of accidents caused by venomous animals. In Brazil, more than 90,000 accidents are reported annually for venomous animals, with lethality that may be higher than 1.0% depending on the animal that caused the poisoning. These data give the dimension and importance of these poisons to health. This course aims to give postgraduate students a theoretical and practical basis on production of antibodies, antigen neutralization mechanisms and the role of antibodies, both in clinical and epidemiological studies of patients stung by venomous animals, as well as in understanding and characterization of the antibodies. 
Program content: Theoretical classes: 1- Introductory class; 2 - General aspects of the immune system; 3- Structure of antibodies; 4. Antigen-antibody interaction; 5. Monoclonal antibodies; 6- Recombinant antibodies; 7- Preparation of antivenoms sera. Practical classes: 1- Isolation of antibodies by chromatography; 2- Detection, quantification and kinetics and specificity of antibodies; 3- Antivenoms and immunodiagnostic by the ELISA technique; 4. Cross-reactive antigen recognition and reactivity in animals revealed by Western blotting with antivenoms sera; 5- Analysis and discussion of the results obtained; 6- Seminars.
Bibliography
1- Cardoso, J.L.C.; França, F.O.S.; Wen, F.H.; Málaque, C.M.S.; Haddad Jr, V. Eds. Animais Peçonhentos no Brasil: Biologia, Clínica e Terapêutica dos Acidentes. Savier, São Paulo, Brasil, 2003. 2- Abbas, A.K. And Lichtman, A.H. Cellular and Molecular Immunology. 6th Edition. Editora Elsevier, São Paulo, 2008. 3- Nelson, D.L. and Cox, M.M. Lehninger - Principles of Biochemistry. 4th Edition, São Paulo, Savier, 2006.

TOX016 - "OMIC" TOOLS FOR THE STUDY OF VENON
Coordination: Inácio de Loiola Meirelles Junqueira de Azevedo and Solange Maria de Toledo Serrano
Level: PhD and Master of Science
Hours: 60
Credits: 4.0
Content
To learn the molecular techniques currently employed in the study of toxins that are based on the investigation of cDNAs and genomes. Provide extensive knowledge about the proteomic / peptidomeric complexity of animal toxic secretions, the classes of toxins that constitute each type of toxic secretion, and the methodological approaches for its analysis. Review the main literature in the area and discuss their contributions.
After decades of biochemical studies aimed at characterization of specific toxins, the spread of omic sciences (genomic, transcriptomic and proteomics) has brought new perspectives to a global understanding of venoms. The speed of information and the possibility of gene manipulation are attractive for omic sciences. Through this path, various venoms have been characterized and new toxins discovered. The transcriptomic and proteomic analyzes also allow the discovery of new toxins and / or biological or therapeutic tools. This course aims to develop a critical view of the benefits and limitations of the various experimental approaches used in the study of toxins, where the students are able to understand and use such methodologies when necessary.
Program content:
- Relations between Genome, Transcriptome and Proteome;
- Classical methods for the analysis of transcripts and genomes;
- New Generation Sequencing Platforms (NGS);
- RNAseq as a tool for the discovery of toxins;
- Basic bioinformatics for analysis of gene expression;
- Classical methods for the isolation of proteins and peptides;
- Sequencing of peptides and proteins by Edman degradation;
- Basic concepts on the analysis of peptides and proteins by mass spectrometry;
- Two-dimensional protein electrophoresis;
- Identification of proteins by in vitro digestion with trypsin and mass spectrometry analysis;
- Analysis of complex protein mixtures by trypsin digestion, two-dimensional chromatography analysis and mass spectrometry analysis;
- Articles seminars on the above themes throughout the course.
Bibliography:
1- Available at the beginning of the course. 2- Bases Moleculares da Biotecnologia. H. Ulrich (Ed.). Editora Roca, São Paulo, 2008, 218p. 3- Bioquímica. D. Voet e J. G. Voet. 3ª. Edição, Artmed, 1596p. 4- Lehninger Princípios de Bioquímica. D. L. Nelson e M. M. Cox, 4ª. Edição, Sarvier, 1232p. 5- Protein Sequencing and Identification Using Tandem Mass Spectrometry. M. Kinter and N.E. Sherman (Wiley Interscience, 2000), 301p. 6- Other Molecular and Genomic Biology Books. 7- Review Articles. 8- Websites of NGS Platforms and Bioinformatics.

TOX017 - MOLECULAR MECHANISMS OF HEMOSTATIC DISORDERS INDUCTION BY ANIMAL TOXINS
Coordination: Ana Marisa Chudzinski-Tavassi
Level: PhD and Master of Science
Hours: 60
Credits: 4.0
Content
This discipline aims to deepen students' knowledge about the mechanisms of hemostatic disorders induced by animal toxins, using a molecular approach linked to the pathophysiological systems of mammals. Animal poisons and secretions, derived from snakes, arthropods, hematophagous, induce significant changes in control of hemostasis. It is of fundamental importance to understand the mechanisms and the therapeutic action of poisonings and to identify molecules that may have therapeutic application, or to use as a biological tool for human pathologies linked to hemostasis disorders.
Programmatic Content: 1- Biochemical characterization and mechanism of action of toxins or active molecules with the following action: in the coagulation system, fibrinolysis, platelet aggregation, endothelial cells, basement membrane and components of the extracellular matrix; 2- Seminars; 3- Evaluation.
Bibliography
1- Haemostasis and Thrombosis Basic Principles and Clinical Practice. Colman,R.W. et al, Philadelphia, J.B. Lippincott Company, 2006, 5a Ed. 2- Animais peçonhentos no Brasil: Biologia, clínica e terapêutica dos acidentes. Cardoso et al., São Paulo, Sarvier, 2003, 1ª. Ed. 3- Handbook of Clinical Toxicology of Animal Venoms and Poisons: Jurg Meier, Julian White. 4- Handbook of animal toxins: R. Stocklin, 2003. 5- Selistre-de-Araujo, H. S. (Org.); Souza, D. H. F. (Org.) . Métodos em Toxinologia: Toxinas de serpentes. 1. ed. São Carlos: EDUFSCar, 2007. 1. 258p. 6- Journal articles specialized in Toxinology and basic areas of knowledge such as biochemistry, pharmacology, immunology and cell biology with recent advances of the area.

TOX020 - TOXINS IN INFLAMMATION, PAIN AND PRODUCT DEVELOPMENT
Coordination: Catarina de Fátima Pereira Teixeira and Gisele Picolo
Level: PhD and Master of Science
Hours: 75
Credits: 5.0
Content
The aim of the course is to provide the student with up-to-date knowledge in the area of toxins, with emphasis on inflammatory, anti-inflammatory, nociceptive and analgesic effects, and to enhance the students’ critical capacity for using toxins as scientific tools for studies on inflammation and pain and for development of new drugs with anti-inflammatory and analgesic activity. In the last two decades, the area of toxinology has enhanced the discovery of animal toxins with important pharmacological activities, useful as scientific tools and / or as models for the development of new drugs. On the other hand, the search for new compounds with more effective anti-inflammatory and analgesic activity and with fewer adverse effects, became intense. In this context, animal toxins represent an important source of information and are important models for the design of new therapeutic agents. The Brazilian biodiversity, still under-explored, and the formation of human resources in science, trained to investigate natural active products in the area of inflammation and pain, is of paramount importance.
Program content:
Theoretical lectures will be devoted to general concepts of the pathophysiology of inflammation and pain and its control, as well as the mechanisms involved in the inflammatory, nociceptive, anti-inflammatory and analgesic effects of different groups of toxins and other substances obtained from animal poisons. Theoretical classes will consist of the following topics: i) general aspects of inflammation - acute, chronic and resolution; Vascular phenomena; Cellular components and functions; Adhesion molecules and inflammatory mediators; Ii) molecular aspects of inflammation-receptors and signal transduction; Iii) general concepts about peripheral and central sensitization, nociception, hypernociception, hyperalgesia and allodynia; Iv) activation of nociceptors, chemical mediators and ion channels responsible for the transduction and transmission of nociceptive information; V) peripheral and central pain transmission channels; Vi) endogenous mechanisms of pain modulation; Vii) mode of action of analgesic and anti-inflammatory drugs; Viii) animal toxins with inflammatory activity and mechanisms of action; Ix) animal toxins with anti-inflammatory activity and mechanisms of action; X) cellular and molecular, peripheral and central mechanisms involved in pain caused by poisons / animal toxins; Xi) animal toxins with analgesic activity: mechanisms of action. Theoretical concepts will be consolidated and discussed in seminars. In addition, practical classes will be taught to show experimental models in vivo and ex vivo, for studies of inflammation and for pain studies in vivo. The models for the study of inflammation will be: peritonitis, paw edema, induction of plasma extravasation (vascular permeability) and alterations of microcirculatory network and phagocytosis. For the study of pain, the experimental models will be: hyperalgesia, by the methods of Randall & Sellito and von Frey electronic; Phasic pain, through hot plate model; incapacitance test for manifested pain. From the application of these models, the effects of toxins with activities already described will be studied.
Bibliography:
1- Cells, Tissues and Disease. Eds. Majno, G.; Joris, I.. Blackwell Sci, USA, 1996. 2- Robbins Pathologic basis of disease. Eds: Cotran, R.S.; Kumar, V.; Collins, T. 6a ed., W.B. Saunders Com., Philadelphia, USA, 1999. 3- Medzitov, R. Origin and physiological roles of inflammation. Nature 454, 428-435, 2008. 4- Serhan, C.N., Savill, J.. Resolution of inflammation: the beginning programs the end. Nature Immunol. 6, 1191-1197, 2005. 5- Henson, P. M. Dampening inflammation. Nature Immunology, 6: 1179-1205, 2005. 6- Wool, C.J. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann. Intern. Med. 140: 441-451, 2004. 7- Giordano, J. The neurobiology of nociceptive and anti-nociceptive systems. Pain Physician. 8: 277-90, 2005. 8- Lee, Y.; Lee, C. H. Oh. U. Painful channels in sensory neurons. Mol. Cells 20: 315-324, 2005. 9- Millan, M. J. Descending control of pain. Progress in Neurobiology, 66: 355-474, 2002. 10- Schaible, H. G.; Richter, F. Pathophysiology of pain. Langenbecks Arch. Surg., 389: 237-243, 2004. 11- Cury, Y., Oliveira-Filho, R.M., DeLucia R. Opióides In: Farmacologia Integrada.3 ed.Rio de Janeiro : Livraria e Editora Revinter Ltda, v.31, p. 267- 281, 2007. 

TOX021 - ANIMAL VENOMS: LOCAL ACTIONS AND HEMOSTASIA
Coordination: Ida Sigueko Sano-Martins and Luís Roberto de Camargo Gonçalves
Level: PhD and Master of Science
Hours: 90
Credits: 6.0
Content
To present and discuss the pathophysiology of poisonings by opossums, arachnids and Lepidoptera, in which the symptomatology results in changes in hemostasis and / or lesions at the site of the bite. Most of venomous animals of medical importance in Brazil have poisons that induce haemostatic alterations and / or alterations at the location of the bite. Many have toxins that act on various components of the hemostatic system (coagulation, platelets, fibrinolysis, vessels, etc.) causing bleeding coagulopathies. In addition to hemostatic disorders, lesions at the site of the bite can cause serious sequelae. Serotherapy, which is efficient in reversing hemostatic disorders, does not have the same efficiency in local lesions observed in these poisonings. Thus, it is essential that specialists in toxinology have basic knowledge of the pathophysiology of experimental and / or accidental human poisoning and the efficacy of the treatment.
Program content:
1- Epidemiology of accidents by venomous animals; 2 - Clinical aspects of poisoning by opossums, arachnids and lepidópteros; 3 - Normal hemostasis and actions of animal poisons in hemostasis; 4- Haemostatic alterations in accidents by venomous animals; 5- Pathophysiology of local actions induced by animal poisons; 6- Serotherapy: limitations and perspectives.
Bibliography
1- Cardoso, J.L.C.; França, F.O.S.; Wen, F.H.; Málaque, C.M.S.; Haddad Jr., V.. Acidentes por animais peçonhentos: Biologia, clínica e terapêutica dos acidentes. São Paulo, Sarvier, 2003. 2. Scientific articles provided during the course.

TOX022 - DEVELOPMENT OF MOLECULES WITH THERAPEUTIC POTENTIAL
Level: PhD and Master of Science 
Hours: 60
Credits: 4.0
Content
This course aims to develop students' interest in innovative processes and indication of intellectual protection, as well as the steps for developing innovations from elements of biodiversity. Secretions and biological fluids like poisons have in their composition molecules with highly specialized functions that can be studied after well defined proofs of concept to become new agents that can be used in areas such as biotechnology, pharmaceutical, veterinary, cosmetology, etc. Although we have a critical mass in the country with scientific conditions for the discovery of new substances with potential for patenting and development of new products, there is a shortage of specialized human resources in the area or even the infrastructure necessary to carry out proofs of concept, according to required criteria by regulatory bodies, as well as for pre-clinical testing. This is still very insipient in Brazil, with a necessity for personnel trained for this activity. For this reason, it is necessary to train postgraduate students at various points in the innovation chain, from the design of a document for intellectual protection to the development of technologies, passing through the preparation of quality system concepts. This course aims to raise awareness and enthusiasm for students for innovations that can integrate productive processes.
Program content:
1- Definition of patentability and patents; 2- Quality system concepts; 3- Proofs of concept and stages of development; 4- Seminars; 5- Evaluation.
Bibliography:
1- www.uspto.gov; www.anvisa.gov.br; www.inpi.gov.br; Www.ich.org. 2- Expert articles with examples of potential pharmaceutical development, using animal secretions: a- Bailey, P., Wilce, J . Venom as a source of useful biologically active molecules. Emerg. Med. (Fremantle), 13: 28-36, 2006. b- Brazil,  V. Do emprego da peçonha em terapeutica. Anais Paulistas de Medicina e Cirurgia, 60 (5): 389-408, 1950. c- De Lima, D. C.; Alvarez Abreu, P.; de Freitas, C. C.; Santos, D. O.; Borges, R. O.; Dos Santos, T. C.; Mendes Cabral, L., Rodrigues, C. R.; Castro, H. C.. Snake venom: Any Clue for Antibiotics and Cam? Evid Based Complement Alternt. Med. 2 (1): 39-47, 2005. d- Hogg, R. C. Novel approaches to pain relief using venom-derived peptides. Curr. Med. Chem. 13: 3191-3201, 2006. e- Newman, D.J .; Cragg, G.M. Marine natural products and related compounds in clinical and advanced preclinical trials. J Nat Prod, 67: 1216-38, 2004. Drug Discov. 2: 790-802, 2003.

TOX023 – PEPTIDE - ISOLATION AND BIOLOGICAL CHARACTERIZATION
Coordination: Ivo Lebrun and Daniel Carvalho Pimenta
Level: PhD and Master of Science 
Hours: 75
Credits: 5.0
Content
The study of peptides and their mechanisms of action have gained increasing importance due to structural advantages (synthesis and generation of analogues) and pharmacological (specificity and bioavailability) and the importance in the modulation of pathophysiological processes. Recently the possibility, non-existent before, for the large-scale production and development of new compounds for drug delivery has created the possibility of real use of these compounds as pharmaceutical prototypes and even as drugs. Therefore, the study and the understanding of the role played by these compounds as well as the understanding of the strategies for the isolation and elucidation of the structure is fundamental for the student who wishes to expand the knowledge in this area.
Objectives of the course 1 - to give an overview of the importance of peptides in physiological processes and a systematic view of the different approaches in this area. 2- Study of the main families of bioactive peptides already characterized (kinins, enkephalins, endorphins, etc.) and their mechanism of action. 3 - Strategies for the isolation of peptides and definition of their structure (HPLC, FPLC, mass spectrometry and Edman degradation sequencing). 4- Types of strategies for the definition of three-dimensional structure (X-ray diffraction, circular dichroism, nuclear magnetic resonance) and peptide synthesis (solid phase solution) or molecular biology. 5- Importance of peptides in the enzymatic processes (kinetics and inhibition) and as effectors in ion channels. 6- Biological activity of peptides and definition of effects through experimental models in biological preparations. 7- Perspectives in the use of peptides as drugs.
The course will be taught through lectures, seminars and eventually practical demonstrations.
Program content:
1- Presentation of the course; 2 - General Aspects of the Theme; 3- Methods of purification and isolation of peptides; 4- Determination of the structure of peptides; 5- Synthesis of peptides; 6- Biological methods for the characterization of peptides; 7- Peptides as substrates or inhibitors of enzymes; 8- Main "families" of bioactive peptides and their importance in pathophysiological processes; 9- Perspectives for the use of peptides as biopharmaceuticals.
Bibliography:
1- The Pharmacological Basis of Therapeutics. Tenth Edition Goodmann & Gillman, McGraw-Hill, Biochemistry Stryer; 4th Edition; Freeman & Co. 2-Structural and mechanism in protein science -Alan Fersht; Freeman & Co. 3-Mass Spectrometry of proteins and peptides. John R. Chapman; Human Press. 4- Practical HPLC method development. Second Edition; Snyder, Kirkland, & Glajch; John Wiley & Sons, Inc. 5- Will be selected, In addition to these basic references, recent articles on the topics covered for presentation and discussion.

TOX024 - TOXINS AND IMMUNITY
Coordination: Denise Vilarinho Tambourgi and Osvaldo Augusto Brazil Esteves Sant'anna
Level: PhD and Master of Science
Hours: 60
Credits: 4.0
Content
There is a growing fragmentation of knowledge as a result of mechanistic approaches to the structure and function of toxins and the protagonists of immunity. This discipline suggests an innovative approach as an attempt to motivate students to develop a critical view of the concepts coming from studies on the central theme proposed, contributing to their creative formation. This discipline aims to transmit the knowledge about resistance and toxin sensitivity following an integrated approach between the actions of toxins and the immune system.
Program content:
1) Adventures of Knowledge on Poisons; 2) - Evolutionary Aspects of Toxins and Immunity; 3) - Models of Studies on Immune Characteristics of Toxin Resistance and Sensitivity; 4) - Genetic and Environmental Factors in Immune Response; 5) - Quantitative and Qualitative Expressions of Toxins and Immunities; 6) - Cellular Aspects and Signs of Recognition; 7) - Receptors and Presentation of Antigens; 8) - Molecular Aspects: Immunity Effectors q`; 9) - Local Aspects of Poisons: Innate and Acquired Response; 10) - Systemic Aspects of Poisons: Inborn and Acquired Response
Bibliography
Janeway's Immunobiology - 7th edition - 2008, Garland Science, Taylor & Francis Group Handbook of Clinical Toxicology of Animal Venoms and Poisons. Jurg Meir, Julian White. Articles from periodicals specialized in Toxinology and Immunology.

TOX26 - TOXINS IN INTRACELLULAR SIGNALING
Coordination: Norma Yamanouye and Roxane Maria Fontes Piazza
Level: PhD and Master of Science
Hours: 60
Credits: 4.0
Content
To review and update the molecular mechanisms of cell signaling, to study toxins that interfere with signaling, as well as to highlight the most used techniques in the area of intracellular signaling. The increasing number of intracellular systems involved in signaling shows the importance and complexity of the cellular response, such as contraction, secretion, growth, differentiation, etc. The understanding of these systems is of fundamental importance for the development of researches in the area of toxinology, to study of the mechanism of action of toxins. This study may favor the discovery of pharmacological tools important for the study of signaling as well as therapeutic agents.
Program content:
Understanding Receptors, Understanding Molecular Mechanisms of Intracellular Signaling, Bacterial Toxins Definition and Classification; Mechanisms and target of action; Group I toxins (superantigens and thermostable toxin); Group II toxins (cell membrane damaging toxins); Group II toxins (A / B toxins type). Toxins interfering in signaling, Techniques applied to the study of signaling; Techniques applied to detect the bacterial toxins production.
Bibliography:
1-Signal Transduction, Ed. By Heldin, CH & Purton, M, 1st edition, Published by Chapman & Hall, London, 1996. 2-Molecular Biology of the Cell, Ed. By Alberts, B. et al., 3rd edition, Garland Publishing, Inc., New York & London, 1994. 3- Cell Biology, A Laboratory Handbook, Ed. By Celis, J.E., 2nd edition, Academic Press, San Diego, 1998. 4- Signal transduction protocols, Ed. By Kendall, DA & Hill, SJ, Human Press, Totowa, 1995. 5- Handbook of Cell Signaling, Ed. By Bradshaw, RA & Dennis, EA, Academic Press, 2004, 3 volumes. 6-Guidebook to protein toxin and their use in cell biology, Ed. By Rappuoli, R & Montecucco, C, Sambrook & Tooze Publication, 1997.

TOX027 - CLONING AND EXPRESSION OF RECOMBINANT PROTEINS
Coordination: Ronaldo Z. Mendonça, Geraldo S. Magalhães and Patrícia Bianca Clissa
Level: PhD and Master of Science
Working Hours: 60
Credits: 4.0
Content
Provide to students the necessary concepts to develop projects involving the expression, production and study of recombinant proteins. In order to find new molecules with potential pharmacological use, a large number of toxins of different animal species have been studied. However, a limitation in these studies is precisely the difficulty of obtaining the toxins of interest isolated and available in large quantities for tests of biological action. At present, to solve these problems, several genetic engineering techniques are used to isolate genes from different toxins and then express them in different organisms such as bacteria, yeast, insect or mammalian cells. This procedure not only guarantees a large amount of the toxin of interest, but also allows manipulation of the DNA sequence of the cloned toxin. The choice for different cell types to express recombinant toxins takes into account, among other factors, the ease of manipulation of the organism, the complexity of the molecule to be expressed and the operational cost of producing the recombinant protein. In this way, the present course aims to study the biology of the different cellular expression systems, to explore the choice of each of these systems to perform these expressions and to present methodologies of cloning and gene analysis through bioinformatics.
Program Content: 1) Cells as bioreactors in the production of toxins: - prokaryotic and eukaryotic cells, - cell cultures; 2) Protein and gene expression in prokaryotic and eukaryotic cells: - structure of DNA and genetic code, - transcription and control of gene transcription, - protein translation and targeting; 3) Use of bioinformatics as a tool for gene analysis and cloning: - using databases with nucleotide and protein sequences, - searching for similarity in databases, - designing primers for PCR, - construction of multiple sequence alignment, - some useful bioinformatics resources; 4) Cloning and expression of toxins in heterologous organisms: - bacteria, - yeast, - baculovirus, - mammalian cells; 5) Analysis of recombinant expression of proteins: - analysis of mRNA expression by real-time PCR, - analysis by immunochemical methods (SDS-PAGE / Western Blot, ELISA, immunofluorescence), - biological activity analysis; 6) Structural analysis of recombinant proteins: - secondary structure (circular dichroism), - working with 3D structures of proteins, - structure and function: comparative examples between native and recombinant proteins.
Bibliography:
1- Molecular Biology of the Cell, 5th edition. Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts and Peter Walter (New York: Garland Science, 2007) - ISBN-10: 0815341059 / ISBN-13: 978-0815341055. 2- Real-Time PCR Current Technology and Applications. Julies Logan, Kirstin Edwards and Nick Saunders (Caister Academic Press- Norfolk, UK). ISBN: 978-1-904455-39-4. Gene Cloning and DNA Analysis: An Introduction 5th edition (March 3, 2006) - ISBN: 1405111216. 4- Protein Expression: a practical approach (Practical Approach Series) [Paperback]. S. J. Higgins (Editor), B. D. Hames (Editor). 5- From Genes to Cells. Stephen R. Bolsover, Jeremy S. Hyams, Steve Jones, Elizabeth A. Shephard and Hugh A. White (Wiley-Liss, 1997) - ISBN 0-47459792-9.

TOX28 - PHARMACOLOGY APPLIED TO THE STUDY OF TOXINS
Coordination: Paulo Flávio Silveira and Fernando Maurício Francis Abdalla
Level: PhD and Master of Science
Hours: 75
Credits: 5.0
Content
The course includes the revision and updating of fundamental concepts in pharmacology and a deepening in specific themes of the area of toxins, especially the study of actions of toxins on cholinergic receptors and neuroendocrine targets. The objective is to develop the knowledge and critical capacity in application-oriented pharmacology in this area. Updates on the concepts underlying pharmacology and emphasis on specific topics in the area of toxins will allow the acquisition of knowledge about the main variables involved in this area and strategies for the search of pharmacologically active principles in toxins of diverse origins, identifying new tools for the Pharmacological study or therapeutic potential for several diseases. This knowledge will also allow the identification of pathophysiological mechanisms and the evaluation of new possibilities for therapeutic intervention in toxin poisoning.
Program content:
1.Introduction to Pharmacology: fundamental concepts exemplified by the study of toxins with activity in cholinergic receptors and neuroendocrine targets; 2. Usual tests in Pharmacology: a- in vivo, ex vivo and in vitro assays - Determination of pharmacological parameters and the importance of interpretations; - Mechanisms of action of pharmacologically active substances - Strategies usually employed in pharmacology for characterization of compounds: isolated organ, transmitter release assays: enzymatic assays; Drug-receptor interaction through radioligand studies (saturation curve, competition curves and Scatchard plot, interpretation of dissociation constant parameters, inhibition constant and ecological receptor density); B- Complementary tests: - Immunohistochemistry; QPCR, Western blot. 3 - Toxins of plants, animals and microorganisms as part of the defensive strategy and / or capture of prey; 4- Xenobiotics: general concepts; 5. Toxins of plants, animals, microorganisms and xenobiotics: carcinogenic, estrogenic effects on glycemia and the renin-angiotensin-aldosterone system; 6- Seminars.

TOX30 - USE OF STEM CELLS IN TOXICOLOGY OF MEDICINES AND DEVELOPMENT OF NEW DRUGS
Coordination: Irina Kerkis
Level: PhD and Master of Science
Working Hours: 45
Credits: 3.0
Content
The objectives of the discipline are to promote modern knowledge about: a) toxins as therapeutic agents and their action in cell cultures; b) use of stem cells in drug toxinology; c) possible use of stem cells in the study of cellular and anticancer drugs from toxins; d) to use  stem cells as therapeutic agents. The pharmaceutical industry has great interest in stem cell research, since these tools have become biotools for the development and testing of new drugs. Toxins from animals, on the other hand, encompass large families of biologically active polypeptides, which differ considerably from one another in terms of primary sequences, structural architecture and specifically the cellular target toxicity. Toxins constitute a very attractive source of natural molecules of great interest for the development of new biopharmaceuticals, considering nature molecular diversity. Research into the composition of a particular venom and the study of mechanism of action of a toxic individual component in its target receptor (group of cells, tissues and whole organism) contributes to the deepening and understanding of the pharmacological action of biopharmaceuticals derived from toxins. In addition, the development of new drugs from stem cells should become a reality uniting studies of pharmacology and cell biology, because the range of substances produced by stem cells in culture could open new frontiers for pharmacology.
Program content:
1. Introduction. Current knowledge about stem cells. 2. Stem cells as a model for studying the toxicity of drugs. 3. Toxins: primary sequences, structural architecture and target cell toxicity 4. Toxins and stem cells as a platform for the development of new drug. 5. Stem cells as medicinal signaling agents and their therapeutic use. 6. Seminars, presentation of papers on the topics covered.
Bibliography:
1.Ulrich H et al.; 2008. Bases moleculares de biotecnologia. Ed.: ROCA, São Paulo, 1 edição, p. 217. 2. Estevan et al., 2011. Embryonic stem cells in toxicological studies. P.213-231. In: Embryonic stem cells-basic biology to bioengineering Ed .: by Michael S. Kallos, 478 pages. Publisher: InTech.http // www.intechopen.com / books / embryonic-stem-cells-basic-biology-to bioengineering / embryonic-stem-cells-in-toxicological-studies. 3. Kang KS, Trosko JE. 2011. Stem cells in toxicology: fundamental biology and practical considerations. Toxicol Sci .; 120Suppl 1: S269-89. 4. Stummann, TC and Bremer, S. 2008. The potential impact of human embryonic stem cells on safety pharmacological and toxicological assessments in drug discovery and drug development. Current Stem Cell Research & Therapy, 3 (2): 117-130 (Annex 1). 5. Caplan AI. 2009. Why are MSCs therapeutic? New data: new insight. J. Pathol., 217 (2): 318-324. 6. Kerkis I, Silva Fde S, Pereira A, Kerkis A, Rádis-Baptista G. 2010. Biological versatility of crotamine-a cationic peptide from the venom of a South American rattlesnake. Expert Opin Investig Drugs, 19 (12) 1515-25. 7. Rádis-Baptista G. Kerkis, I. 2011. Crotamine, a small basic polypeptide myotoxin from rattlesnake venom with cell-penetrating properties. Curr Pharm Des. 17 (38): 4351-61.


TOX032 - THEORETICAL BASES OF THE EVOLUTION OF SERPENT TOXINS
Coordination: Nancy Oguiura
Level: PhD and Master of Science
Hours: 48
Credits: 3.0
Content
Objectives
Discuss topics such as genome and gene evolution, focusing on the gene families of snake toxins.
Justification
Serpent toxins are, for the most part, proteins that are encoded in the animal genome by gene families. Thus, the basis of its evolution is gene and genomic evolution. This course will discuss general topics such as evolution of the genome in animals; duplications; Models of gene evolution; Gene families, mutations and recombination. These themes are directly or indirectly involved in the increase of genetic variability, in the appearance of pseudogenes, in the creation of gene families, in gene expression, etc.
Program content
Genome: C-value, chromosomes, sequence Gene: structure, genetic code, expression control Mechanisms of gene variation: duplication, recombination, mutation, Evolution: in concert, birth-and-death, accelerated Gene families and toxins.
Bibliography
Gregory, T.R 2005. The Evolution of the genome. Elsevier Academic Press, 740p. Lewin, B. 2008. Genes IX. Jones and Bartlett Publishers. Sudbury, MA. Li W-H. 1997. Molecular evolution. Sinauer Associates, Inc., Publishers. Lynch, M. 2007. The origins of genome architecture. Sinauer Associates, Inc. Publishers. Sunderland. BAD. Ohno, S. 1970. Evolution by gene duplication. Springer-Verlag, New York. Scientific articles