Basic principles and oncological applications of the PET-CT/18F-FDG

A Tomografia por Emissão de Pósitrons/Tomografia Computadorizada representa um grande salto tecnológico para a Medicina Nuclear e particularmente, para a Oncologia, visto que é capaz de distinguir alterações benignas e malignas com base em dados semiquantitativos da metabolização de radiofármacos pelos tecidos corporais. Este trabalho teve como objetivo realizar uma revisão narrativa dos principais levantamentos bibliográficos contemporâneos acerca dos princípios físicos da PET-CT/18F-FDG, suas aplicações na Oncologia e os avanços tecnológicos desta metodologia. Este trabalho foi elaborado com base em artigos obtidos de bancos de dados como PubMed, SciELO e Microsoft Academic Search, com descritores relacionados a PET-CT/18F-FDG e a Oncologia. A partir dos artigos analisados, observa-se que a PET-CT/18F-FDG é uma importante técnica para a obtenção de imagens morfofuncionais do corpo do paciente com sensibilidade e especificidade, muitas vezes, superiores aos métodos convencionais de diagnóstico por imagem. Dessa forma, a PET-CT/18F-FDG é recomendada nos casos de identificação e acompanhamento do estadiamento tumoral, monitoramento da taxa de resposta das terapias oncológicas e planejamento do alvo em tratamentos radioterápicos. Ainda, o desenvolvimento de algoritmos matemáticos e de sistemas de detecção de radiação mais eficientes na PET-CT/18F-FDG melhoram a qualidade da imagem e reduzem o tempo de exame.Positron Emission Tomography/Computed Tomography represents a technological leap for Nuclear Medicine and particularly for Oncology, as it is able to differentiate between benign and malignant changes based on semiquantitative data from the metabolism of radiopharmaceuticals by body tissues. The present work aimed to perform a narrative review of the main contemporary bibliographical surveys about the physical principles of PET-CT/18F-FDG, their applications in Oncology and the technological advances of this methodology. This work was elaborated based on articles obtained from databases PubMed, SciELO and Microsoft Academic Search, with descriptors related to PET-CT and Oncology. The reviewed articles show that PET-CT/18F-FDG is an important technique for obtaining morphofunctional images of the patient’s body with great applicability in Oncology. The PET-CT/18F-FDG is recommended in cases of identification and follow-up of tumor staging, monitoring therapeutic results against cancer and target planning in radiotherapy treatments. Furthermore, the development of more efficient mathematical algorithms and radiation detection systems in PET-CT/ 18F-FDG improves image quality and reduces examination time

Perfil epidemiológico dos acidentes ofí­dicos na cidade de Ituiutaba, Minas Gerais, Brasil (2007-2021)

As pesquisas epidemiológicas sobre os acidentes ofí­dicos são importantes para a Saúde Pública. Devido à carência de estudos sobre o ofidismo no municí­pio de Ituiutaba, Estado de Minas Gerais- Brasil, o presente trabalho descreve as caracterí­sticas epidemiológicas dos acidentes ofí­dicos notificados no municí­pio no perí­odo de 2007 a 2021. As informações foram obtidas do banco de dados do Sistema de Informação de Agravos de Notificação (SINAN). De acordo com nosso estudo, foram registrados 244 casos de acidentes por serpentes peçonhentas na cidade de Ituiutaba no perí­odo analisado, sendo 82% deles ocasionados pelo gênero Bothrops, seguido de Crotalus (16%) e Micrurus (2%). Quanto a gravidade, foram notificados 115 (47,1%) e 107 (44%) casos de acidentes ofí­dicos classificados como leves e moderados, respectivamente, com 232 (99%) casos evoluí­dos para cura e uma taxa de letalidade de 1,0%. Ainda, os dados sobre o intervalo de tempo entre o acidente e atendimento médico mostraram que 208 casos (85,5%) tiveram o atendimento médico nas primeiras três horas após a picada. O presente trabalho é um precursor na caracterização do perfil epidemiológico dos acidentes ofí­dicos no municí­pio de Ituiutaba-MG e apresenta dados importantes que podem fomentar ações de vigilância em saúde e de orientação dos profissionais de saúde da região, possibilitar ações educativas para a população em geral e contribuir para a distribuição racional dos soros antiofí­dicos no municí­pio

Fluorescent Markers: Proteins and Nanocrystals

This book chapter will comment on fluorescent reporter proteins and nanocrystals’ applicability as fluorescent markers. Fluorescent reporter proteins in the Drosophila model system offer a degree of specificity that allows monitoring cellular and biochemical phenomena in vivo, such as autophagy, mitophagy, and changes in the redox state of cells. Titanium dioxide (TiO2) nanocrystals (NCs) have several biological applications and emit in the ultraviolet, with doping of europium ions can be visualized in the red luminescence. Therefore, it is possible to monitor nanocrystals in biological systems using different emission channels. CdSe/CdS magic-sized quantum dots (MSQDs) show high luminescence stability in biological systems and can be bioconjugated with biological molecules. Therefore, this chapter will show exciting results of the group using fluorescent proteins and nanocrystals in biological systems

Peçonha de Bothrops alternatus: avaliação in vitro da atividade antiviral contra a infecção pelo vírus da dengue e a influência de uma toxina isolada na secreção de citocinas

The snake venom has a promising future for medicine because their components have various physiological and pharmacological effects when interacting with molecules of cells. These components can be used as therapeutic agents, diagnostic markers for various diseases and research tools for deciphering physiological and pathological processes in humans. Our study aimed to isolate a phospholipase A2 from the venom of Bothrops alternatus and characterize their influence on the release of pro and anti-inflammatory cytokines and analyze its action on the antiviral effect against dengue virus serotype 2. The toxin PLA2 Ba3dP7 had a molecular weight of approximately 17 kDa and has the ability to stimulate the production of IL-10, IL-12 and TNF-α, however, the expression of the latter two was statistically significant compared with the production of IL- 10, suggesting a proinflammatory profile of this toxin (p <0.05). The results also showed that the toxin stimulated nitric oxide production, which enhances the proinflammatory role of PLA2 Ba3dP7, thus this toxin may be an important protein related to inflammatory processes generated by poisoning by snakes of the species B. alternatus. It was observed that the crude venom decreased cytotoxicity generated by DENV 2 after pre-treatment of C6/36 cells with the same, possibly featuring its protective role against viral infection. Furthermore, the crude venom showed virucidal activity (p <0.05). Importantly, more studies are needed to determine which (es) component (s) present in the venom is (are) responsible (s) for the protection activity and for virucidal action.Fundação de Amparo a Pesquisa do Estado de Minas GeraisMestre em Biologia Celular e Estrutural AplicadasA peçonha de serpentes tem um futuro promissor para a medicina, pois seus componentes apresentam diversos efeitos fisiológicos e farmacológicos ao interagirem com moléculas das células. Esses componentes podem ser usados como agentes terapêuticos, marcadores para o diagnóstico de várias doenças e ferramentas de pesquisas para decifrar processos fisiológicos e patológicos em humanos. Nosso trabalho teve como objetivo isolar uma fosfolipase A2 da peçonha da serpente Bothrops alternatus e caracterizar sua influência na liberação de citocinas pró e anti-inflamatórias, bem como avaliar a sua ação sobre o efeito antiviral contra o vírus da dengue sorotipo 2. A toxina PLA2 Ba3dP7 apresentou um peso molecular de aproximadamente 17 kDa e teve a capacidade de estimular a produção das citocinas IL-10, IL-12 e TNF-α, porém, a expressão das duas últimas foi estatisticamente significativa, quando comparada com a produção de IL-10, o que sugere um perfil pró-inflamatório dessa toxina (p < 0,05). Os resultados obtidos mostraram ainda que a toxina estimulou a produção de óxido nítrico, o que reforça o papel pró-inflamatório da PLA2 Ba3dP7, dessa forma, essa toxina pode ser uma importante proteína relacionada aos processos inflamatórios gerados pelo envenenamentos por serpentes da espécie B. alternatus. Foi observado que a peçonha bruta diminuiu a citotoxicidade gerada pelo DENV 2 após o pré-tratamento das células C6/36 com a mesma, caracterizando possivelmente seu papel protetor contra a infecção viral. Além disso, a peçonha bruta apresentou atividade virucida (p < 0,05). É importante ressaltar que mais estudos são necessários para determinar qual (ais) componente (s) presente na peçonha é (são) responsável (is) pela a atividade de proteção e pela ação virucida

In vitro tracking of phospholipase A2 from Bothrops alternatus venom by magic-sized quantum dots

Phospholipases A2 represent a family of enzymes with important application in medicine. However, direct tracking in cells has been difficult due to the absence of a stable, effective and specific marker for these enzymes. Magic-sized quantum dots (MSQDs) are nanocrystals of extremely small size and with unique physical properties. In addition, they are excellent biocompatible luminescent markers and can be conjugated to various biomolecules. In this work, we labelled BaltPLA2, a PLA2 isolated from Bothrops alternatus snake venom, with Cadmium selenide (CdSe)/cadmium sulphate (CdS) MSQDs. Bioconjugation was confirmed using infrared spectra and fluorescence microscopy, which demonstrated that the CdSe/CdS MSQDs interact with BaltPLA2 without interfering with its catalytic activity. This probe allowed the tracking of BaltPLA2 since its entry through the plasma membrane to its incorporation into the myoblast nucleus. Complementary studies were carried out to evaluate the antiviral activity of BatPLA2 against the dengue virus. Our tests showed a decrease of approximately 72% 50%, 56% of the cytotoxicity caused by DENV2 infection in the virucidal, post-treatment and adsorption assays, respectively. Thus, the results demonstrated the antiviral activity of BaltPLA2 and that this protein could be an important tool for the development of therapeutic alternatives in the future.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFAPEMIG - Fundação de Amparo a Pesquisa do Estado de Minas GeraisINCT - Instituto Nacional de Ciência e Tecnologia de NanobiofarmacêuticaTese (Doutorado)As fosfolipases A2 representam uma classe de enzimas com importante aplicação na medicina. Entretanto, o rastreamento direto em células tem sido difícil devido à ausência de um marcador estável, efetivo e específico para essas enzimas. Os pontos quânticos de tamanhos mágicos (MSPQs) são nanocristais de tamanho extremamente pequeno e com propriedades físicas únicas. Além disso, são excelentes marcadores luminescentes biocompatíveis e podem ser conjugados com várias biomoléculas. Neste trabalho, nós etiquetamos a BaltPLA2, uma fosfolipase A2 isolada da peçonha de Bothrops alternatus, com MSPQs de seleneto de cádmio/sulfeto de cádmio (CdSe/CdS). A bioconjugação foi confirmada usando espectros de infravermelho e microscopia de fluorescência, os quais demonstraram que os CdSe/CdS MSQDs interagem com a BaltPLA2 sem interferir em sua atividade catalítica. Essa sonda permitiu o rastreamento da BaltPLA2 desde sua entrada através da membrana plasmática até sua incorporação no núcleo dos mioblastos. Estudos complementares foram realizados a fim de avaliar a atividade antiviral da BatPLA2 contra o vírus da dengue. Nossos testes mostraram a diminuição de aproximadamente 72% 50%, 56% da citotoxicidade causada pela infecção pelo DENV nos ensaios virucida, pós-tratamento e adsorção, respectivamente. Assim, os resultados demonstraram a atividade antiviral da BaltPLA2 e que esta proteína pode ser uma importante ferramenta para o desenvolvimento de alternativas terapêuticas no futuro

A New Platelet-Aggregation-Inhibiting Factor Isolated from Bothrops moojeni Snake Venom

This work reports the purification and functional characterization of BmooPAi, a platelet-aggregation-inhibiting factor from Bothrops moojeni snake venom. The toxin was purified by a combination of three chromatographic steps (ion-exchange on DEAE-Sephacel, molecular exclusion on Sephadex G-75, and affinity chromatography on HiTrap™ Heparin HP). BmooPAi was found to be a single-chain protein with an apparent molecular mass of 32 kDa on 14% SDS-PAGE, under reducing conditions. Sequencing of BmooPAi by Edman degradation revealed the amino acid sequence LGPDIVPPNELLEVM. The toxin was devoid of proteolytic, haemorrhagic, defibrinating, or coagulant activities and induced no significant oedema or hyperalgesia. BmooPAi showed a rather specific inhibitory effect on ristocetin-induced platelet aggregation in human platelet-rich plasma, whereas it had little or no effect on platelet aggregation induced by collagen and adenosine diphosphate. The results presented in this work suggest that BmooPAi is a toxin comprised of disintegrin-like and cysteine-rich domains, originating from autolysis/proteolysis of PIII SVMPs from B. moojeni snake venom. This toxin may be of medical interest because it is a platelet aggregation inhibitor, which could potentially be developed as a novel therapeutic agent to prevent and/or treat patients with thrombotic disorders

BaltDC: purification, characterization and infrared spectroscopy of an antiplatelet DC protein isolated from Bothrops alternatus snake venom

Abstract Background Snake venoms are a complex mixture of proteins, organic and inorganic compounds. Some of these proteins, enzymatic or non-enzymatic ones, are able to interact with platelet receptors, causing hemostatic disorders. The possible therapeutic potential of toxins with antiplatelet properties may arouse interest in the pharmacological areas. The present study aimed to purify and characterize an antiplatelet DC protein from Bothrops alternatus snake venom. Methods The protein, called BaltDC (DC protein from B. alternatus snake venom), was purified by a combination of ion-exchange chromatography on DEAE-Sephacel column and gel filtration on Sephadex G-75. The molecular mass was estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE). The amino acid sequence of the N-terminal region was carried out by Edman degradation method. Platelet aggregation assays were performed in human platelet-rich plasma (PRP). Infrared (IR) spectroscopy was used in order to elucidate the interactions between BaltDC and platelet membrane. Results BaltDC ran as a single protein band on SDS-PAGE and showed apparent molecular mass of 32 kDa under reducing or non-reducing conditions. The N-terminal region of the purified protein revealed the amino acid sequence IISPPVCGNELLEVGEECDCGTPENCQNECCDA, which showed identity with other snake venom metalloproteinases (SVMPs). BaltDC was devoid of proteolytic, hemorrhagic, defibrinating or coagulant activities, but it showed a specific inhibitory effect on platelet aggregation induced by ristocetin and epinephrine in PRP. IR analysis spectra strongly suggests that PO3 2− groups, present in BaltDC, form hydrogen bonds with the PO2 − groups present in the non-lipid portion of the membrane platelets. Conclusions BaltDC may be of medical interest since it was able to inhibit platelet aggregation

BaltDC: purification, characterization and infrared spectroscopy of an antiplatelet DC protein isolated from Bothrops alternatus snake venom

<div><p>Abstract Background: Snake venoms are a complex mixture of proteins, organic and inorganic compounds. Some of these proteins, enzymatic or non-enzymatic ones, are able to interact with platelet receptors, causing hemostatic disorders. The possible therapeutic potential of toxins with antiplatelet properties may arouse interest in the pharmacological areas. The present study aimed to purify and characterize an antiplatelet DC protein from Bothrops alternatus snake venom. Methods: The protein, called BaltDC (DC protein from B. alternatus snake venom), was purified by a combination of ion-exchange chromatography on DEAE-Sephacel column and gel filtration on Sephadex G-75. The molecular mass was estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE). The amino acid sequence of the N-terminal region was carried out by Edman degradation method. Platelet aggregation assays were performed in human platelet-rich plasma (PRP). Infrared (IR) spectroscopy was used in order to elucidate the interactions between BaltDC and platelet membrane. Results: BaltDC ran as a single protein band on SDS-PAGE and showed apparent molecular mass of 32 kDa under reducing or non-reducing conditions. The N-terminal region of the purified protein revealed the amino acid sequence IISPPVCGNELLEVGEECDCGTPENCQNECCDA, which showed identity with other snake venom metalloproteinases (SVMPs). BaltDC was devoid of proteolytic, hemorrhagic, defibrinating or coagulant activities, but it showed a specific inhibitory effect on platelet aggregation induced by ristocetin and epinephrine in PRP. IR analysis spectra strongly suggests that PO 3 2 − groups, present in BaltDC, form hydrogen bonds with the PO 2 − groups present in the non-lipid portion of the membrane platelets. Conclusions: BaltDC may be of medical interest since it was able to inhibit platelet aggregation.</p></div