Unveiling the Antiviral Capabilities of Targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2.

The urgent need for effective treatments against emerging viral diseases, driven by drug-resistant strains and new viral variants, remains critical. We focus on inhibiting the human dihydroorotate dehydrogenase (HsDHODH), one of the main enzymes responsible for pyrimidine nucleotide synthesis. This strategy could impede viral replication without provoking resistance. We evaluated naphthoquinone fragments, discovering potent HsDHODH inhibition with IC50 ranging from 48 to 684 nM, and promising in vitro anti-SARS-CoV-2 activity with EC50 ranging from 1.2 to 2.3 µM. These compounds exhibited low toxicity, indicating potential for further development. Additionally, we employed computational tools such as molecular docking and quantitative structure-activity relationship (QSAR) models to analyze protein-ligand interactions, revealing that these naphthoquinones exhibit a protein binding pattern similar to brequinar, a potent HsDHODH inhibitor. These findings represent a significant step forward in the search for effective antiviral treatments and have great potential to impact the development of new broad-spectrum antiviral drugs.

Study of the Antioxidant, Antimicrobial, and Wound Healing Properties of Raw Hydrolyzed Extract from Nile Tilapia Skin (Oreochromis niloticus).

Oreochromis niloticus (Nile tilapia) skin is a by-product of Brazilian fish farming, rich in collagen. The present study aims to evaluate the wound healing, antioxidant, and antimicrobial potential of the raw hydrolyzed extract of Nile tilapia skin, as well as the identification of the main compounds. The in vitro activity was performed using antioxidant, antimicrobial and scratch wound healing assays. An in vivo experiment was performed to evaluate the wound healing potential. On days 1, 7, 14 and 21, the lesions were photographed to assess wound retraction and on the 7th , 14th and 21st  days the skins were removed for histological evaluation and the blood of the animals was collected for glutamic oxaloacetic transaminase and glutamic pyruvic transaminase determination. The chemical study was carried out through liquid chromatography-tandem mass spectrometry and de novo sequencing of peptides. The in vitro assays showed a reduction of the gap area in 24 h, dose-dependent antimicrobial activity for both bacteria, and antioxidant activity. The chemical analysis highlighted the presence of active biopeptides. The histological evaluation showed that the raw hydrolyzed extract of Nile tilapia skin has a healing potential, and does not present toxicological effects; therefore, is promising for the treatment of wounds.

Development of an immunogen containing CD4+/CD8+ T-cell epitopes for the prophylaxis of tegumentary leishmaniasis.

Tegumentary leishmaniasis (TL) is a disease of high severity and incidence in Brazil, and Leishmania braziliensis is its main etiological agent. The inefficiency of control measures, such as high toxicity and costs of current treatments and the lack of effective immunoprophylactic strategies, makes the development of vaccines indispensable and imminent. In this light, the present work developed a gene encoding multiple T-cell (CD4+/CD8+) epitope, derived from conserved proteins found in Leishmania species and associated with TL, to generate a chimeric protein (rMEP/TL) and compose a vaccine formulation. For this, six T-cell epitopes were selected by immunoinformatics approaches from proteins present in the amastigote stage and associated with host-parasite interactions. The following formulations were then tested in an L. braziliensis murine infection model: rMEP/TL in saline or associated with MPLA-PHAD®. Our data revealed that, after immunization (three doses; 14-day intervals) and subsequent challenging, rMEP/TL and rMEP/TL + MPLA-vaccinated mice showed an increased production of key immunological biomarkers of protection, such as IgG2a, IgG2a/IgG1, NO, CD4+, and CD8+ T-cells with IFN-γ and TNF-α production, associated with a reduction in CD4+IL-10+ and CD8+IL-10+ T-cells. Vaccines also induced the development of central (CD44highCD62Lhigh) and effector (CD44highCD62Llow) memory of CD4+ and CD8+ T-cells. These findings, associated with the observation of lower rates of parasite burdens in the vaccinated groups, when compared to the control groups, suggest that immunization with rMEP/TL and, preferably, associated with an adjuvant, may be considered an effective tool to prevent TL. KEY POINTS: • Rational design approaches for vaccine development. • Central and effector memory of CD4+ and CD8+ T-cells. • Vaccine comprised of rMEP/TL plus MPLA as an effective tool to prevent TL.

Mapping linear B-cell epitopes of the Tryparedoxin Peroxidase and its implications in the serological diagnosis of tegumentary leishmaniasis.

Diagnosis of tegumentary leishmaniasis (TL) is essential to avoid permanent damage and severe functional sequelae and there is an urgent need to discover new antigens. The present study aimed to comprehensively evaluate the potential use of the Tryparedoxin Peroxidase (TryP) as an antigen for serological tests. The proposal integrates data from immunoproteomics with immunoinformatics, in addition to a precise analysis of protein levels in the evolutionary stages of the parasite by flow cytometry. To evaluate the performance in the diagnosis of TL, Enzyme-Linked Immunosorbent Assay (ELISA) assays were performed using the recombinant protein and the respective B-cell epitope, followed by an analysis of the contribution of this peptide in the recognition of the protein by patients, evaluated by serum depletion assays. We showed that the TryP has a linear B-cell epitope with high divergence compared to orthologs from Trypanosoma cruzi and Homo sapiens. The results also show high expression and positive cells for TryP (TryP+) in the infective metacyclic promastigotes (MET) and intracellular (24 and 48 hours) stages. From the depletion assays, it was possible to confirm the contribution of the peptide in the specific recognition of the TryP protein by patients with TL (13.7-15.9%). ELISA using the peptide showed high performance in the diagnosis compared to the recombinant TryP (rTryP), Soluble Leishmania braziliensis Antigen (sLba) and Immunofluorescence Assay (IFA) with accuracy of 94.29, 89.29, 65.00 and 37.14%, respectively). We can conclude that the MNEPAPP peptide is a potential antigen for the diagnosis of TL.

Chemical composition and biological activity of Baccharis erioclada DC. essential oil

Abstract The chemically complex essential oils of Baccharis species are associated with several biological activities, such as antimicrobial and antiulcerous properties. However, few studies have investigated Baccharis erioclada DC. Therefore, in this study, we aimed to characterize the essential oil of B. erioclada and evaluate its antioxidant, antimicrobial, and hemolytic potential. The essential oil was extracted by hydrodistillation using a Clevenger apparatus and analyzed via gas chromatography-mass spectrometry (GC-MS). Phosphomolybdenum complex formation, reducing antioxidant power, and thiobarbituric acid reactive substances (TBARS) methods were used to determine antioxidant potential. To evaluate the essential oil's antimicrobial activity, minimum inhibitory concentrations (MIC) in Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were calculated. Hemolytic activity was determined in sheep red blood cells. Thirty-one compounds were identified via GC-MS analysis, representing 81.60% of the total essential oil. These compounds included: turmerone (27.97%), fokienol (13.47%), ledol (9.78%), and santalol (5.35%). The class of compounds identified was the oxygenated sesquiterpenes (62.52%). Antioxidant activity was confirmed via phosphomolybdenum complex formation and TBARS methods. Moderate antimicrobial activity and low hemolysis rates were displayed at concentrations of 250 and 500 µg/mL

Avaliação da simulação em parada cardiorrespiratória durante o debriefing entre estudantes de enfermagem na pandemia / Assessment of a simulation in cardiopulmonary arrest during the debriefing among nursing students in the pandemic / Evaluación de la simulación de paro cardiorrespiratorio durante el debriefing entre los estudiantes de enfermería en la pandemia

Objetivo: avaliar a simulação em parada cardiorrespiratória durante o debriefing entre estudantes de enfermagem na pandemia da COVID-19. Método: estudo descritivo de abordagem qualitativa realizado entre 22 estudantes de enfermagem em duas etapas: simulação clínica em parada cardiorrespiratória e debriefing associado à simulação. O corpus textual decorrente dos diálogos foi submetido à análise lexicográfica, com auxílio do software "IRAMUTEQ". Resultados: a maioria dos estudantes nunca havia participado de cenários de simulação clínica no decorrer da graduação. Mediante o debriefing, identificaram-se aspectos facilitadores como a voz do manequim e o realismo da simulação. Como dificultadores, os estudantes atribuíram o nervosismo e a falta de conhecimento no atendimento em parada cardiorrespiratória. Conclusão: na avaliação da simulação durante o debriefing verificou-se a importância desta estratégia de ensino prático para formação acadêmica, impactando positivamente no processo de ensino-aprendizagem do estudante de enfermagem, sobretudo na pandemia da COVID-19.

Objective: to evaluate the simulation in cardiopulmonary arrest during the debriefing among nursing students in the COVID-19 pandemic. Method: a descriptive study with a qualitative approach carried out among 22 nursing students in two stages: clinical simulation in cardiopulmonary arrest and debriefing associated with the simulation. The textual corpus resulting from the dialogues was submitted to lexicographical analysis, with the aid of the "IRAMUTEQ" software. Results: most students had never participated in clinical simulation scenarios during graduation. Through the debriefing, facilitating aspects such as the manikin's voice and the realism of the simulation were identified. As difficulties, the students attributed nervousness and lack of knowledge in cardiopulmonary arrest care. Conclusion: in the evaluation of the simulation during the debriefing, the importance of this practical teaching strategy for academic training was verified, positively impacting the teaching-learning process of the nursing student, especially in the COVID-19 pandemic.

Objetivo: evaluar la simulación en paro cardiorrespiratorio durante el debriefing entre los estudiantes de enfermería en la pandemia de COVID-19. Método: estudio descriptivo con enfoque cualitativo realizado entre 22 estudiantes de enfermería en dos etapas: simulación clínica en paro cardiorrespiratorio y debriefing asociado a la simulación. El corpus textual resultante de los diálogos fue sometido a un análisis lexicográfico, con la ayuda del programa "IRAMUTEQ". Resultados: la mayoría de los estudiantes nunca han participado en escenarios de simulación clínica en el transcurso del pregrado. Mediante el debriefing, se identificaron aspectos facilitadores como la voz del maniquí y el realismo de la simulación. Como dificultadores, los estudiantes atribuyeron el nerviosismo y la falta de conocimiento a la atención en paro cardiorrespiratorio. Conclusión: en la evaluación de la simulación durante el debriefing, se notó la importancia de esta estrategia de enseñanza práctica para la formación académica, impactando positivamente en el proceso de enseñanza-aprendizaje del estudiante de enfermería, sobre todo en la pandemia de COVID-19.

Chagas Disease Drug Discovery in Latin America-A Mini Review of Antiparasitic Agents Explored Between 2010 and 2021.

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi that endangers almost 70 million people worldwide. The only two drugs that are currently approved for its treatment, benznidazole and nifurtimox, have controversial efficacy in adults and restricting safety issues, leaving thousands of patients without a suitable treatment. The neglect of Chagas disease is further illustrated by the lack of a robust and diverse drug discovery and development portfolio of new chemical entities, and it is of paramount importance to build a strong research and development network for antichagasic drugs. Focusing on drug discovery programs led by scientists based in Latin America, the main endemic region for this disease, we discuss herein what has been published in the last decade in terms of identification of new antiparasitic drugs to treat Chagas disease, shining a spotlight on the origin, chemical diversity, level of characterization of hits, and strategies used for optimization of lead compounds. Finally, we identify strengths and weaknesses in these drug discovery campaigns and highlight the importance of multidisciplinary collaboration and knowledge sharing.

Immunomodulatory and cytotoxic activities of euphol.

AIMS: This study evaluated the effect of euphol isolated from Euphorbia umbellata (Pax) Bruyns latex on the activation of complement pathways (classical (CP), alternative (AP) and lectin (LP)), neutrophil chemotaxis, cytotoxic activity, cell morphology and death in HRT-18 and 3T3 cells lines. MAIN METHODS: CP and AP were assessed using hemolytic assays and ELISA for LP; neutrophil chemotaxis was performed using Boyden's chamber; cytotoxicity was evaluated by neutral red methodology and characteristics of cell death were assessed by cell morphology with hematological staining. KEY FINDINGS: Although euphol increased CP activation (38% at a concentration of 976.1 µM), an inhibitory effect on AP, LP (31% and 32% reduction in the concentration of 976.1 µM) and neutrophil chemotaxis (inhibit 84% of neutrophil migration at a concentration 292.9 µM) was observed. In addiction euphol was able to induce significant cell death in a time-dependent manner, presenting an IC50 of 70.8 µM and 39.2 µM for HRT-18 and 3T3 cell lines respectively and it was also observed apoptotic characteristics as cellular rounding, chromatin condensation and blebs formation for both cell lines. SIGNIFICANCE: Euphol has a potential use for the treatment of complement-related inflammatory diseases due to its ability to downregulate inflammation. On the other hand, the controlled activation of CP can contribute to complement-dependent cytotoxicity in the context of monoclonal antibody-based cancer treatment.

Effects of Euphorbia umbellata extracts on complement activation and chemotaxis of neutrophils.

ETHNOPHARMACOLOGICAL RELEVANCE: The species Euphorbia umbellata (leitosinha) has been traditionally used for the treatment of inflammatory diseases and cancer. AIM OF THE STUDY: Evaluation the effect of E. umbellata latex extracts obtained with hexane, chloroform, ethyl acetate and methanol on the activation of the complement pathways and neutrophil chemotaxis. MATERIALS AND METHODS: The latex was partitioned using Soxhlet apparatus and hexane, chloroform, ethyl acetate and methanol as solvents. The classical and alternative pathway activity were performed by hemolytic assays with sensitized sheep or rabbit erythrocytes, respectively; the lectin pathway activity was quantified by ELISA, through the measurement of C4 molecules and the chemotaxis of human neutrophils was performed using 1% casein as the chemotactic inducer and Boyden's chamber. GC-Q-ToF and NMR analyses were applied to evaluate the chemical composition of E. umbellata latex extracts. RESULTS: All E. umbellata latex extracts exhibited an inhibitory effect on the activation of the alternative pathway. Methanol and ethyl acetate extracts inhibited the classical pathway while chloroform extract activated this pathway. Ethyl acetate and hexane extracts inhibited lectin activation. All E. umbellata extracts inhibited casein-induced neutrophil chemotaxis. Terpenes and phenolic compounds have been suggested to be present in the E. umbellta latex extracts. CONCLUSION: The E. umbellata latex was able to modulate the functions of the immune system. Thus, it is possible to infer that the terpenes and phenolic compounds of the phytocomplex of E. umbellata latex can contribute for the activity on the complement pathways.

The Sigma-2 receptor / transmembrane protein 97 (σ2R/TMEM97) modulator JVW-1034 reduces heavy alcohol drinking and associated pain states in male mice.

Alcohol Use Disorder (AUD) is a chronic relapsing disorder characterized by compulsive alcohol intake, loss of control over alcohol intake, and a negative emotional state when access to alcohol is prevented. AUD is also closely tied to pain, as repeated alcohol drinking leads to increased pain sensitivity during withdrawal. The sigma-2 receptor, recently identified as transmembrane protein 97 (σ2R/TMEM97), is an integral membrane protein involved in cholesterol homeostasis and lipid metabolism. Selective σ2R/Tmem97 modulators have been recently shown to relieve mechanical hypersensitivity in animal models of neuropathic pain as well as to attenuate alcohol withdrawal signs in C. elegans and to reduce alcohol drinking in rats, suggesting a potential key role for this protein in alcohol-related behaviors. In this study, we tested the effects of a potent and selective σ2R/TMEM97 ligand, JVW-1034, on heavy alcohol drinking and alcohol-induced heightened pain states in mice using an intermittent access model. Administration of JVW-1034 decreased both ethanol intake and preference for ethanol, without affecting water intake, total fluid intake, or food intake. Notably, this effect was specific for alcohol, as JVW-1034 had no effect on sucrose intake. Furthermore, JVW-1034 reduced both thermal hyperalgesia and mechanical hypersensitivity in ethanol withdrawn mice. Our data provide important evidence that modulation of σ2R/TMEM97 with small molecules can mediate heavy alcohol drinking as well as chronic alcohol-induced heightened pain sensitivity, thereby identifying a promising novel pharmacological target for AUD and associated pain states.

Enriched Terpenes Fractions of the Latex of Euphorbia umbellata Promote Apoptosis in Leukemic Cells.

The current study was carried out by a bioguided fractionation of a hexane extract of the latex of Euphorbia umbellata against leukemic cells. Samples were analyzed by NMR, GC/MS, triterpenes quantification, and MTT reduction assay. Morphological, cell cycle, mitochondrial membrane potential and caspases 3/7 analyses were performed for the dichloromethane and ethanol fractions, and selectivity index for the dichloromethane fraction. NMR analysis presented characteristic signals of terpenes and steroids, data were confirmed by the quantification of triterpenes and GC/MS analysis. MTT reduction assay demonstrated that HL-60 was the most sensitive cell lineage against dichloromethane and ethanol fractions. Compounds of these matrices caused morphological changes compatible with apoptosis induction, altered cell cycle, increment of depolarized population cells and activation of caspases 3/7. Selectivity indices were higher than 22.44. Bioguided-fractionation study showed that samples of the latex of E. umbellata raised the activity of the phytocomplex against leukemic cells, and the cytotoxicity can be associated with an apoptosis pathway.

Toxicological Evaluation and Quantification of Ingested Metal-Core Nanoplastic by Daphnia magna Through Fluorescence and Inductively Coupled Plasma-Mass Spectrometric Methods.

There are few studies on nanoplastic that propose quantification of the amount ingested combined with evaluation of the toxic effects on aquatic organisms. We propose 2 methods to quantify the amount of polystyrene nanoplastic (PSNP) ingested by Daphnia magna: fluorescence intensity, where a fluorescent monomer (F) is added to the PSNP and quantified through fluorescence light microscopy, and total aluminum quantification, where PSNP is synthesized with Al2 O3 metal-core nanoparticles and used for quantification of the nanoplastic ingested by the organism Daphnia magna using inductively coupled plasma-mass spectrometry. In addition, the PSNP was functionalized with palmitic acid to simulate the environmental conditions leading to biological and chemical transformations. Acute and chronic toxicity tests were performed with fluorescent PSNP (PSNP/F) and palmitic acid-functionalized PSNP/F (PSNP/F-PA). The ingestion quantified was higher by factors of 2.8 and 3.0 for PSNP/F-PA and 1.9 and 1.7 for PSNP/F applying the fluorescence intensity and total Al quantifying methods, respectively, when compared to PSNP. These results are consistent with the data obtained in the toxicity tests, which showed an approximately 3 times increase in the adverse effect of PSNP/F-PA on the mobility and reproduction of the organisms. Thus, the strong inhibition of D. magna reproduction caused by PSNP/F-PA in the chronic toxicity tests could be associated with a greater amount of this nanoplastic being ingested by the organisms. Environ Toxicol Chem 2019;38:2101-2110. © 2019 SETAC.

Pharmacokinetics and cytotoxic study of euphol from Euphorbia umbellata (Bruyns) Pax latex.

BACKGROUND: Medicinal plants are an important source to identify new active pharmaceutical compounds. Traditionally, the sap of Euphorbia umbellata is widely used to treat cancer and inflammatory conditions. These effects have been attributed to the presence of terpenes and phenolic compounds in the extracts of this plant. Euphol, a tetracyclic triterpene alcohol, is one of the major compounds present in Euphorbia species, and some biological activities have been attributed to this compound. PURPOSE: This study aimed to evaluate the in vitro cytotoxicity of euphol against Jurkat, HL-60, K-562, B16F10, and HRT-18 cells lines, as well as the biological stability, distribution, metabolism properties in vitro, and the determination of the concentration of euphol in the plasma and liver of rats. METHODS: The MTT reduction assay was used to evaluate the cytotoxicity of euphol against cancer cell lines, and the selectivity index, the morphology and cell cycle assays to evaluate the death mechanisms in K-562 and B16F10 lineages. UHPLC-MS was applied for the in vivo evaluation of the concentration of euphol in plasma and liver, and in vitro metabolic stability in human liver microsomes and S9 fraction, plasma protein binding, and stability in simulated gastric and intestinal fluids assays. CONCLUSIONS: This study demonstrated that euphol exhibited cytotoxic effects against a variety of cancer cells lines, selectivity against leukemia and possibly, the mechanism involved is apoptosis. The evaluation of stability, distribution, and metabolism properties showed that euphol was unstable in gastric and intestinal fluids, presenting moderate plasma protein binding with two hours elimination half-life and possible phase II liver metabolism. All the results suggested that further studies could be developed to prove the viability of euphol as an anticancer agent.

Dentine Tubule Occlusion by Novel Bioactive Glass-Based Toothpastes.

There are numerous over-the-counter (OTC) and professionally applied (in-office) products and techniques currently available for the treatment of dentine hypersensitivity (DH), but more recently, the use of bioactive glasses in toothpaste formulations have been advocated as a possible solution to managing DH. Aim. The aim of the present study, therefore, was to compare several bioactive glass formulations to investigate their effectiveness in an established in vitro model. Materials and Methods. A 45S5 glass was synthesized in the laboratory together with several other glass formulations: (1) a mixed glass (fluoride and chloride), (2) BioMinF, (3) a chloride glass, and (4) an amorphous chloride glass. The glass powders were formulated into five different toothpaste formulations. Dentine discs were sectioned from extracted human teeth and prepared for the investigation by removing the cutting debris (smear layer) following sectioning using a 6% citric acid solution for 2 minutes. Each disc was halved to provide test and control halves for comparison following the brushing of the five toothpaste formulations onto the test halves for each toothpaste group. Following the toothpaste application, the test discs were immersed in either artificial saliva or exposed to an acid challenge. Results. The dentine samples were analyzed using scanning electron microscopy (SEM), and observation of the SEM images indicated that there was good surface coverage following artificial saliva immersion. Furthermore, although the acid challenge removed the hydroxyapatite layer on the dentine surface for most of the samples, except for the amorphous chloride glass, there was evidence of tubular occlusion in the dentine tubules. Conclusions. The conclusions from the study would suggest that the inclusion of bioactive glass into a toothpaste formulation may be an effective approach to treat DH.

O fazer coletivo nas políticas de saúde da FÓ/Brasilândia (SP): fóruns, redes, grupalidades / The collective practices in health policies in FÓ/Brasilândia (SP): foruns, networks, groupalities / El hacer colectivo en las políticas de salud de FÓ/Brasilândia (SP): foros, redes, grupalidades

Relata-se neste trabalho experiências de fazeres-coletivos de profissionais e serviços da rede de saúde do território Freguesia do Ó/Brasilândia, em São Paulo. Trata-se de um resgate histórico importante para o fortalecimento da integração ensino-serviço, que tem sido potencializada pelos projetos do Pró e Pet-Saúde desenvolvidos pela Pontifícia Universidade Católica de São Paulo em parceria com a Supervisão Técnica de Saúde da Freguesia do Ó/Brasilândia. O texto foi construído com base em pesquisa participativa que envolveu profissionais que atuaram e atuam nesse território. Narrativas orais construídas em oficinas foram ponto de partida para a escrita conjunta entre tutores e profissionais que manifestaram interesse por relatar as experiências de fazeres coletivos desse território. Um breve histórico de alguns espaços coletivos de articulação de redes no período "pós-Plano de Atendimento à Saúde" foi traçado, firmando o Fórum de Saúde Mental como precursor da afirmação de práticas compartilhadas de saúde, para além das paredes dos diferentes saberes e serviços. Outros espaços, como o Fórum da Infância e Adolescência, o Grupo de Trabalho Interdisciplinar e o Fórum de Reabilitação foram trazidos como importantes espaços que articulam o cuidado nas suas singularidades. A Política Nacional de Humanização foi apresentada como uma articuladora e potencializadora destes espaços. As narrativas dessas práticas e saberes evidenciam a potência deste fazer coletivo que fortalece a cogestão da saúde e amplia a integralidade do cuidado.

This narrative brings the experience work of the collective way of producing health of professionals, networks and services from the territory Freguesia do Ó/Brasilândia, in Sao Paulo. This is an important historical recovery to strengthen the integration between university and health policies, which have been enhanced by Pro projects and Pet- health developed by Pontifícia Universidade Católica de São Paulo in partnership with Supervisão Técnica de Saúde da Freguesia do Ó/Brasilândia. The text was constructed based on participatory research involving professionals who acted and act in that territory. Initially from oral narratives, the text was produced together by tutors and professionals who have expressed interest in reporting the 2 experiences of collective practices on that territory. A brief history of some collective network spaces of the period "post-Plano de Atendimento à Saúde-PAS" was produced. The Mental Health Forum was described as a precursor of shared health practices, beyond the walls of different knowledges and services. Other spaces, such as the Child and Adolescent Forum, the Group of Interdisciplinary Work and the Rehabilitation Forum were brought as important spaces that articulate care in their singularities. The National Policy of Humanization was brought as an articulator and potentiating these spaces. The narratives of these practices and knowledges show the power of these collective practices, in order to strengthen the collective management of health and extend the comprehensive care.

En este trabajo se relatan experiencias de haceres-colectivos de profesionales y servicios ofrecidos por la red de salud del territorio Freguesia do Ó/Brasilândia, en São Paulo. Se trata de un rescate histórico importante para el fortalecimiento de la integración enseñanza-servicio, que ha sido potenciada por los proyectos del Pro y Pet-Salud desarrollados por la Pontifícia Universidade Católica de São Paulo en asociación con la Supervisión Técnica de Salud de la Freguesia do Ó/Brasilândia. El texto fue construido em base a la investigación participativa realizada por profesionales que actuaron y actúan en este territorio. Las narrativas orales surgidas en los talleres realizados en este territorio fueron el punto de partida para la escritura conjunta entre los tutores y profesionales que manifestaron interés por relatar las experiencias de hacer colectivo.Fue delineado um resumen cronológico de algunos espacios colectivos de articulación de redes en el periodo del "Pos-Plan de Atención para la Salud", identificando el Foro de Salud Mental como el precursor de la afirmación de prácticas compartidas en salud, más allá de las paredes de los diferentes saberes y servicios. Otros espacios, como el Foro de Infancia y Adolescencia, el Grupo de Trabajo Interdisciplinar y el Foro de Rehabilitación también fueron reconocidos como ámbitos relevantes que promueven el cuidado em sus singularidades. La Política Nacional de Humanización des SUS fue presentada como articuladora y potencializadora de estos espacios. El relato de estas prácticas y saberes evidencia la pontencia de este hacer colectivo que fortalece la cogestión de la salud y amplía la integralidad del cuidado.

O trabalho em rede nos casos de alta complexidade e de alta vulnerabilidade: a experiência de uma UBS / Health care networking in cases of high complexity and high vulnerability: the experience of an Health Center / El trabajo en redes en los casos de alta complejidad y alta vulnerabilidad: la experiencia de una Unidad Básica de Salud

Este estudo tem como objetivo apresentar e analisar os processos de formação de redes de atenção à saúde em torno de casos complexos e em contextos de alta vulnerabilidade, atendidos pela Estratégia Saúde da Família na UBS XXX, na região da Brasilândia, São Paulo. Tais processos foram desenvolvidos a partir de oficinas de escrita realizadas pelo Pró-Saúde-PUCSP em parceria com a Supervisão Técnica de Saúde da Freguesia do Ó/Brasilândia da Secretaria Municipal de Saúde de São Paulo. As oficinas se constituíram como forma de mobilizar o relato de experiências e a reflexão sobre a prática profissional. Partiu-se de três casos índices atendidos na Unidade Básica de Saúde que demandaram uma configuração de redes ampliadas de cuidado que se estenderam para além do atendimento multiprofissional da Unidade e do apoio do Núcleo de Apoio à Saúde da Família (NASF). Foram tecidas reflexões em torno dos diferentes modelos de assistência em saúde, da resolubilidade de tais casos e a da corresponsabilidade dos atores envolvidos no cuidado. Concluiu-se que a formação de rede aproxima os profissionais do território, explora a potencialidade de assistência e possibilita uma abordagem mais integrada, proporcionando um atendimento mais humanizado.

This study aims to present and analyze the health care network formation processes around cases of high complexity and high vulnerability served by the Family Health Strategy at UBS XXXX, in the region of Brasilândia, in São Paulo, Brazil. Such processes have been developed from writing workshops conducted by PUC-SP Pro-Health in partnership with Health Supervision Technical FÓ/Brasilândia SMS/ SP. The workshops were formed as a way to mobilize the narrative of experiences and reflection about the professional practices. The work was started from three index cases treated at UBS, which required a configuration of extended care networks that extended beyond the multidisciplinary care of the Unit and the support of NASF. Reflections were woven around the different health care models, of the possibility of resolving such cases and the responsibility of the actors involved in the care. It was concluded that the network formation approximates professionals of the territory, explores the assistance capability and makes it possible a more integrated approach, providing a more humanized care.

Este estudio tiene como objetivo presentar y analizar los procesos de formación de la red de atención de salud en torno de casos complejos y en contextos de alta vulnerabilidad, atendidos por la Estrategia Salud de la Familiar en la Unidad Básica de Salud (UBS) XXXX, en la región de Brasilândia, en Sao Paulo, Brasil. Tales procesos se han desarrollado a partir de talleres de escritura realizadas por ProSalud-PUC-SP en colaboración con la Supervisión Técnica de Salud de la "Freguesia do Ó"/ Brasilândia Secretaria Municipal de São Paulo. Los talleres se formaron como una forma de movilizar la narración de experiencias y la reflexión sobre las prácticas profesionales. El trabajo se inició a partir de tres casos índice tratados en la UBS, que requerían una configuración de redes ampliadas de atención que se extendieron más allá de la atención multidisciplinaria de la Unidad y del apoyo del Núcleo de Apoyo a la Salud (NASF). Reflexiones fueron tejidas en torno a los diferentes modelos de atención de la salud, a la posibilidad de resolver este tipo de casos y a la corresponsabilidad de los actores implicados en la atención. Se concluyó que la formación de la red aproxima a los profesionales del territorio, explora la capacidad de asistencia y hace posible un enfoque más integrado, proporcionando una atención más humanizada.

Euphorbia umbellata bark extracts – an in vitro cytotoxic study

ABSTRACT Euphorbia umbellata (Pax) Bruyns, Euphorbiaceae, is commonly used in folk medicine of southern Brazil to treat several kinds of cancer. The latex (part of the plant used for this purpose) is mixed with water and taken as treatment; but this matrix contains toxic potential related to the presence of some phorbol type diterpenes. So the aim of this study was to evaluate the cytotoxicity of the crude extract of the bark of E. umbellata and its fractions (Hex, CHCl3, EtOAc and MeOH) using in vitro assay (applying Jurkat cells line). A preliminary cytotoxic study (MTT reduction, trypan blue exclusion and DNA quantification assays) was executed to identify the most active material. The CHCl3 fraction displayed the highest activity and was selected for further investigation of any cytotoxic mechanism and evaluation of chemical composition; flow cytometry, Acridine orange and Hoechst 33342 staining experiments and Gas chromatography–mass spectrometry analysis were applied to achieve these results. This fraction demonstrated the best cytotoxic results against Jurkat cells line with IC50 of 29.00 ± 1.49, 10.06 ± 1.48 and 4.83 ± 2.25 µg/ml for 24, 48 and 72 h of experiment, respectively (trypan blue exclusion). The mechanism responsible for this action can be associated with the promotion of cell cycle arrest and apoptosis. The two main classes of compounds present in the CHCl3 fraction are steroids and triterpenes. Further, phytochemical studies with this fraction need to be evaluated, to try isolating these substances and establishing a more detailed cytotoxic study against Jurkat cells.

Chemical and pharmacological investigation of the stem bark of Synadenium grantii.

Based on the fact that Synadenium grantii is used in folk medicine for the treatment of peptic ulcers and inflammatory diseases, this work describes its chemical and pharmacological properties. Pharmacological investigation of the crude bark extract showed a high antioxidant activity over several scavenger systems, such as 2,2'-azino-bis (3-ethylenebenzothiazoline-6-sulfonic acid)• +, 1-diphenyl-2-picrylhydrazyl•, O2 • - , and HOCl, as well as an enzymatic system with human myeloperoxidase and an ex vivo hemolysis system. Furthermore, the oral administration of the crude bark extract was able to reduce carrageenan-induced rat paw edema as effectively as ibuprofen. These biological activities may be associated with the presence of flavonoids and terpenes, as revealed by HPLC and NMR analyses of the crude stem bark extract. The phytochemical investigations in this study resulted in the isolation of friedelin and 3ß-friedelinol for the first time, while euphol and lanosterol were also isolated.