Atendimento psicossocial nos serviços de proteção social especial do SUAS / Psychosocial care in the special social protection services of SUAS / Atención psicosocial en los servicios de protección social especial del Sistema Único de Asistencia Social (SUAS)

Documentos normativos determinam que serviços de Proteção Social Especial (PSE) do Sistema Único de Assistência Social (SUAS) devem oferecer atendimento psicossocial às(aos) usuárias(os). No entanto, não especificam que atendimento é esse, que tipo de atividades ele inclui, porque ele caracteriza principalmente serviços da PSE ou o que o diferencia das outras atividades desenvolvidas pelas equipes desses serviços. Diante disso, neste artigo, buscamos responder às seguintes questões: como profissionais que atuam nas equipes técnicas ou na gestão de serviços de proteção social especial do município de São Paulo compreendem a noção de "atendimento psicossocial"? E como essa noção é convertida em práticas concretas de intervenção? Para respondê-las, realizamos uma pesquisa bibliográfica e documental, bem como fizemos 10 entrevistas semiestruturadas com profissionais da PSE. As entrevistas e documentos analisados indicam a polissemia da expressão atendimento psicossocial. Ora ela refere-se a determinadas práticas ou ações que fazem parte do cotidiano dos serviços do SUAS; ora a um aspecto ou uma visão que norteia o trabalho. Indicam, ainda, que tal forma de atendimento é caracterizada, entre outras coisas, por sua interdisciplinaridade, pela importância que dá ao contexto e ao território e por não ser equivalente à clínica psicoterápica tradicional.(AU)

Regulatory documents determine that Special Social Protection (PSE) services of the Unified Social Assistance System (SUAS) must offer psychosocial support to its users. However, they do not specify which support, what type of activities it includes, why it mainly characterizes PSE services or what differentiates it from other activities developed by teams in these services. Given this, in this article, we seek to answer the following questions: how do professionals working in the technical teams or in the management of special social protection services in the municipality of São Paulo understand the notion of "psychosocial support"? And how is this notion converted into concrete intervention practices? To answer them, we conducted a bibliographic and documentary research, as well as 10 semi-structured interviews with professionals from PSE services. The interviews and documents analyzed indicate the polysemy of the expression psychosocial support. At times, it refers to certain practices or actions that are part of the daily routine of SUAS services; at other times, it refers to an aspect or vision that guides the work. They also indicate that this form of support is characterized, among other things, by its interdisciplinary nature, by the importance given to context and territory and by not being equivalent to the traditional psychotherapeutic clinic.(AU)

Los documentos normativos determinan que los servicios de Protección Social Especial (PSE) del Sistema Único de Asistencia Social (SUAS) deben ofrecer atención psicosocial a los usuarios. Sin embargo, no especifican en qué consiste esta atención, qué tipo de actividades incluye, por qué caracteriza principalmente a los servicios de PSE o qué lo diferencia de otras actividades desarrolladas por los equipos de estos servicios. Teniendo esto en cuenta, en este artículo buscamos responder a las siguientes preguntas: ¿Qué piensan sobre la noción de "atención psicosocial" los profesionales que trabajan en los equipos técnicos o en la gestión de los servicios de protección social especial en el municipio de São Paulo? ¿Y cómo convierten esta noción en prácticas concretas de intervención? Para responderlas, realizamos una investigación bibliográfica y documental, así como diez entrevistas semiestructuradas con profesionales de la PSE. Las entrevistas y los documentos analizados indican la polisemia de la expresión atención psicosocial. A veces, se refiere a ciertas prácticas o acciones que forman parte de la rutina diaria de los servicios del SUAS; otras veces, a un aspecto o visión que guía el trabajo. También esta forma de atención se caracteriza, entre otras cosas, por su interdisciplinariedad, por la importancia que se da al contexto y al territorio, y por no ser equivalente a la clínica psicoterapéutica tradicional.(AU)

2-Arylpropionic Acid Pyrazolamides as Cannabinoid CB2 Receptor Inverse Agonists Endowed with Anti-Inflammatory Properties.

Among the most recent proposals regarding the mechanism of action of dipyrone, the modulation of cannabinoid receptors CB1 and CB2 appears to be a promising hypothesis. In this context, the present work describes a series of five novel pyrazolamides (7-11) designed as molecular hybrids of dipyrone metabolites and NSAIDs, such as ibuprofen and flurbiprofen. Target compounds were obtained in good overall yields (50-80%) by classical amide coupling between 4-aminoantipyrine and arylacetic or arylpropionic acids, followed in some cases by N-methylation of the amide group. The compounds presented good physicochemical properties in addition to stability to chemical (pH 2 and 7.4) and enzymatic (plasma esterases) hydrolysis and showed medium to high gastrointestinal and BBB permeabilities in the PAMPA assay. When subjected to functional testing on CB1- or CB2-transfected cells, compounds demonstrated an inverse agonist profile on CB2 receptors and the further characterization of compound LASSBio-2265 (11) revealed moderate binding affinity to CB2 receptor (Ki = 16 µM) with an EC50 = 0.36 µM (Emax = 63%). LASSBio-2265 (11) (at 1, 3, and 10 mg/kg p.o.) was investigated in the formalin test in mice and a remarkable analgesic activity in the late inflammatory phase was observed, suggesting it could be promising for the treatment of pain syndromes associated with chronic inflammatory diseases.

Identification of LASSBio-1945 as an inhibitor of SARS-CoV-2 main protease (MPRO) through in silico screening supported by molecular docking and a fragment-based pharmacophore model.

In December 2019, an infectious disease was detected in Wuhan, China, caused by a new pathogenic coronavirus, named SARS-CoV-2. It spread very rapidly, and on March 11th of 2020, the outbreak was declared a pandemic by the World Health Organization. Currently, effective treatment options remain limited. SARS-CoV-2 enzyme main protease (MPRO) plays a pivotal role in the viral life cycle, making it a putative drug target. In order to identify suitable hits to develop inhibitors with adequate antiviral properties, we explored the LASSBio Chemical Library employing multiple strategies of virtual screening. A fragment-based pharmacophore model enabled the identification of key interactions involved in the molecular recognition at the catalytic site of MPRO, namely, with amino acid residues His41, His163 and Glu166. Docking-based virtual screening was performed, leading to the identification of LASSBio-1945 (9), a new hit of MPRO, presenting an IC50 = 15.97 µM. This compound, an 1,3-benzodioxolyl sulfonamide, represents an interesting starting point for subsequent hit-to-lead optimization steps and, to the best of our knowledge, a new distinct chemotype for MPRO inhibition.

Novel phosphatidylinositol 4-kinases III beta (PI4KIIIß) inhibitors discovered by virtual screening using free energy models.

Herein, the LASSBio Chemical Library is presented as a valuable source of compounds for screening to identify hits suitable for subsequent hit-to-lead optimization stages. A feature of the LASSBio Chemical Library worth highlighting is the fact that it is a smart library designed by medicinal chemists with pharmacological activity as the main priority. The great majority of the compounds part of this library have shown in vivo activity in animal models, which is an indication that they possess overall favorable bioavailability properties and, hence, adequate pharmacokinetic profiles. This, in turn, is supported by the fact that approximately 85% of the compounds are compliant with Lipinski's rule of five and ca. 95% are compliant with Veber's rules, two important guidelines for oral bioavailability. In this work it is presented a virtual screening methodology combining a pharmacophore-based model and an empirical Gibbs free energy-based model for the ligand-protein interaction to explore the LASSBio Chemical Library as a source of new hits for the inhibition of the phosphatidylinositol 4-kinase IIIß (PI4KIIIß) enzyme, which is related to the development of viral infections (including enteroviruses, SARS coronavirus, and hepatitis C virus), cancers and neurological diseases. The approach resulted in the identification of two hits, LASSBio-1799 (7) and LASSBio-1814 (10), which inhibited the target enzyme with IC50 values of 3.66 µM and IC50 and 6.09 µM, respectively. This study also enabled the determination of the structural requirements for interactions with the active site of PI4KIIIß, demonstrating the importance of both acceptor and donor hydrogen bonding groups for forming interactions with binding site residues Val598 and Lys549.

Projeto Bandeira Científica: uma Extensão Interdisciplinar com Impactos na Formação em Psicologia / Bandeira Científica Project: an Interdisciplinary Extension Course with Impacts on the Professional Training in Psychology / Proyecto Bandeira Científica: una Extensión Interdisciplinaria con Efectos en la Formación en Psicología

Trata-se de um relato de experiência cujo objetivo é apresentar e descrever o projeto de extensão acadêmica em saúde Bandeira Científica, com foco na importância de projetos dessa natureza para a formação em Psicologia, sobretudo no que se refere a sua dinâmica interdisciplinar. O projeto foi criado na década de 1950, na Faculdade de Medicina da Universidade de São Paulo, e hoje congrega estudantes de 12 cursos da USP. Apresentamos como se organiza o projeto e os espaços interdisciplinares criados, e em seguida elegemos quatro situações a fim de ilustrar e discutir como essas experiências ressoam na formação em Psicologia. O artigo evidencia o diferencial desse projeto para o estudante de Psicologia: nele ocorrem reflexões sobre temas e situações a que pouco se tem acesso no currículo básico, e são desenvolvidos saberes em diálogo com outras áreas do conhecimento, ressaltando o valor do caráter interdisciplinar e interprofissional para a construção das práticas do projeto e para a formação dos estudantes....(AU)

This article is an experience report that introduces and describes the project of health academic extension called Bandeira Científica, focusing on the importance of projects of this nature to the academic education and professional formation of psychologists following an interdisciplinary dynamic. This project was created in 1950 in the Faculty of Medicine of the University of São Paulo and currently includes 12 different graduation courses. We present how the project is organized and the interdisciplinary spaces that were created, in addition we elect four situations to illustrate and discuss how these experiences impact professional training in Psychology. This article reveals the differential aspects of a project like this to Psychology students: reflections and discussions related to themes and situations that students barely have access to during the basic curriculum and knowledge related to other professional fields is possible to be developed, highlighting the importance of interdisciplinary and interprofessional characters during the construction of the project and during the professional education of the participant students....(AU)

Se trata de un relato de experiencia cuyo objetivo es presentar y describir el proyecto de extensión académica en salud, Bandeira Científica, enfocándose en la importancia de proyectos de esa naturaleza para la formación en Psicología, sobre todo en lo que se refiere a su dinámica interdisciplinaria. El proyecto comenzó en la década de 1950, en la Facultad de Medicina de la Universidad de São Paulo (USP), y actualmente se compone por estudiantes de 12 cursos de la USP. Primero, presentamos cómo el proyecto se organiza y cuáles son los espacios interdisciplinarios creados, en seguida elegimos cuatro situaciones para ilustrar y discutir cómo esas experiencias resuenan en la formación en Psicología. El artículo evidencia los diferenciales de ese proyecto para el estudiante de Psicología: las reflexiones que se dan sobre temas y situaciones a las cuales se tienen poco acceso en el plan de estudios y el desarrollo de saberes con otras áreas del conocimiento, resaltando el valor del carácter interdisciplinario e interprofesional para la construcción de las prácticas del proyecto y la formación de los estudiantes....(AU)

The Use of Conformational Restriction in Medicinal Chemistry.

During the early preclinical phase, from hit identification and optimization to a lead compound, several medicinal chemistry strategies can be used to improve potency and/or selectivity. The conformational restriction is one of these approaches. It consists of introducing some specific structural constraints in a lead candidate to reduce the overall number of possible conformations in order to favor the adoption of a bioactive conformation and, as a consequence, molecular recognition by the target receptor. In this work, we focused on the application of the conformational restriction strategy in the last five years for the optimization of hits and/or leads of several important classes of therapeutic targets in the drug discovery field. Thus, we recognize the importance of several kinase inhibitors to the current landscape of drug development for cancer therapy and the use of G-protein Coupled Receptor (GPCR) modulators. Several other targets are also highlighted, such as the class of epigenetic drugs. Therefore, the possibility of exploiting conformational restriction as a tool to increase the potency and selectivity and promote changes in the intrinsic activity of some ligands intended to act on many different targets makes this strategy of structural modification valuable for the discovery of novel drug candidates.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors: a new antidiabetic drug class.

Diabetes mellitus is a chronic, complex and multifactorial disease associated characteristically with hyperglycemia. One of the most recently approved antidiabetic drug classes for clinical use are sodium-glucose cotransporter type 2 (SGLT-2) inhibitors. SGLT-2 is a protein expressed in the kidneys, responsible for glucose reabsorption from the glomerular filtrate to the plasma. It is known, nowadays, that diabetic patients show an increased glucose renal reabsorption capacity, caused by the overexpression of the SGLT-2 transporter, thus contributing to hyperglycemia. From establishing this correlation, the SGLT-2 transporter started to be considered as a therapeutic target of interest, culminating in the approval of the first antidiabetic SGLT-2 inhibitor, dapagliflozin (Forxiga® or Farxiga®, Bristol-Myers Squibb & AstraZeneca), in 2012 in Europe. On the other hand, canagliflozin (Invokana®, Janssen Pharmaceutical) was the first drug in this class to be approved by the FDA, the U.S. Food and Drug Administration, in 2013. This review concerns the discovery and development of the first representatives of this class of antidiabetic drugs, and the description of new optimized analogues that are currently in the clinical and preclinical stages of development.

Recent trends in neuropathic pain patents.

INTRODUCTION: Neuropathic pain (NP) is one of the most important health problems faced nowadays. NP is a chronic disease that cannot be treated like other pain conditions because it is developed from a nerve injury that evolves into a permanent dysfunction of the central and/or peripheral nervous system. Therefore, it involves the participation of several systems and should be viewed as a multi-factorial disease that needs a whole new pharmacological strategy in order to achieve the desired pain relief. Areas covered: The Espacenet site was used as the main source in order to perform the patent research for NP treatment. This review covers the patents with relevant approaches for NP treatment from 2014 until today. Expert opinion: Our patent research has shown that there is not a consensus approach to treat NP in any of its forms. In our opinion, the approach regarding NP needs to be like cancer's approach. As there are different types of cancer and different ways to treat them, the same needs to be done for NP. Currently, there are several promising targets, which corroborates that this is a wide-open research area. For these reasons, neuropathic pain is a therapeutic field full of potential for innovation.

Synthesis and Biological Evaluation of Pyrazolo[3,4-b]pyridin-4-ones as a New Class of Topoisomerase II Inhibitors.

A series of 1,3,6-triphenylpyrazolo[3,4-b]pyridin-4-one derivatives was designed, synthesized and evaluated for cytotoxic activity in A375 human melanoma and human erythroleukemia (HEL) cells. The new pyrazolopyridones displayed comparable activities to the antitumor compound etoposide. The inhibitory effect of compounds 17, 18, 27 and 32 against topoisomerase II-mediated cleavage activities was measured finding good correlation with the results obtained from MTS assay. Docking studies into bacterial topoisomerase II (DNA Gyrase), topoisomerase IIα and topoisomerase IIß binding sites in the DNA binding interface were performed.

Acylhydrazone derivatives: a patent review.

INTRODUCTION: The N-acylhydrazone (NAH) moiety has been characterized as a privileged structure, capable of providing ligands points for more than one type of bioreceptor. Modifications of the subunits bonded to its acyl and imine functions resulted in several derivatives, which modulate a great diversity of molecular targets. In this context, this patent review reflects the use of the NAH moiety in different compounds. AREAS COVERED: In this review, the authors perform an analysis of the therapeutic profile of NAH compounds together with their perspective of its usability. The Espacenet and Delphion databases were used as main sources of search, and 'N-acylhydrazone,', 'Acylhydrazone' and 'hydrazone' were used as keywords. From a total of 117 patents retrieved, 22 presented pharmacological activities described in the document, thus being chosen for this review. EXPERT OPINION: In the last century, only six patents disclosing NAH derivatives for therapeutic purposes were published, and only in 2010, this subunit started receiving some real attention regarding its therapeutic potential. In this review, the Brazilian and Chinese Universities were identified as the major patent applicants, especially for drug candidates for the treatment of chronic pain, inflammatory disorders and cancer. The NAH subunit is very versatile both from synthetic and medicinal chemistry point of view. This feature is a direct result from the conformational diversity that this framework presents, achievable by subtle and simple chemical changes. Therefore, our opinion is that this moiety suits a lot more drug discovery projects than it seems to at first glance. In conclusion, we strongly support and encourage a raise in the use of this unique subunit.

N-acylhydrazone improves exercise intolerance in rats submitted to myocardial infarction by the recovery of calcium homeostasis in skeletal muscle.

AIMS: This work investigated the effects of 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294) treatment on the contractile response of soleus (SOL) muscle from rats submitted to myocardial infarction (MI). MAIN METHODS: Following coronary artery ligation, LASSBio-294 (2mg/kg, i.p.) or vehicle was administrated once daily for 4 weeks. KEY FINDINGS: The run time to fatigue for sham rats was 17.9 ±2.6 min, and it was reduced to 3.3 ± 0.8 min (P<0.05) in MI rats. In MI rats treated with LASSBio-294, the time to fatigue was 15.1 ± 3.6 min. During the contractile test, SOL muscles from sham rats showed a response of 7.12 ± 0.54N/cm(2) at 60 Hz, which was decreased to 5.45 ± 0.49 N/cm(2) (P<0.05) in MI rats. The contractility of SOL muscles from the MI-LASSBio-294 group was increased to 9.01 ± 0.65N/cm(2). At 16 mM caffeine, the contractility was reduced from 2.31 ± 0.33 to 1.60 ± 0.21 N/cm(2) (P<0.05) in the MI group. In SOL muscles from MI-LASSBio-294 rats, the caffeine response was increased to 2.62 ± 0.33 N/cm(2). Moreover, SERCA2a expression in SOL muscles was decreased by 0.31-fold (31%) in the MI group compared to the Sham group (P<0.05). In the MI-LASSBio-294 group, it was increased by 1.53-fold (153%) compared to the MI group (P<0.05). Meanwhile, the nuclear density in SOL muscles was increased in the MI group compared to the Sham group. Treatment with LASSBio-294 prevented this enhancement of cellular infiltrate. SIGNIFICANCE: LASSBio-294 treatment prevented the development of muscular fatigue and improved exercise intolerance in rats submitted to MI.

Beneficial effects of a novel agonist of the adenosine A2A receptor on monocrotaline-induced pulmonary hypertension in rats.

BACKGROUND AND PURPOSE: Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance, right ventricular hypertrophy and increased right ventricular systolic pressure. Here, we investigated the effects of a N-acylhydrazone derivative, 3,4-dimethoxyphenyl-N-methyl-benzoylhydrazide (LASSBio-1359), on monocrotaline (MCT)-induced pulmonary hypertension in rats. EXPERIMENTAL APPROACH: PAH was induced in male Wistar rats by a single i.p. injection of MCT (60 mg·kg(-1)) and 2 weeks later, oral LASSBio-1359 (50 mg·kg(-1)) or vehicle was given once daily for 14 days. Echocardiography was used to measure cardiac function and pulmonary artery dimensions, with histological assay of vascular collagen. Studies of binding to human recombinant adenosine receptors (A1, A2A, A3) and of docking with A2A receptors were also performed. KEY RESULTS: MCT administration induced changes in vascular and ventricular structure and function, characteristic of PAH. These changes were reversed by treatment with LASSBio-1359. MCT also induced endothelial dysfunction in pulmonary artery, as measured by diminished relaxation of pre-contracted arterial rings, and this dysfunction was reversed by LASSBio-1359. In pulmonary artery rings from normal Wistar rats, LASSBio-1359 induced relaxation, which was decreased by the adenosine A2A receptor antagonist, ZM 241385. In adenosine receptor binding studies, LASSBio-1359 showed most affinity for the A2A receptor and in the docking analyses, binding modes of LASSBio-1359 and the A2A receptor agonist, CGS21680, were very similar. CONCLUSION AND IMPLICATIONS: In rats with MCT-induced PAH, structural and functional changes in heart and pulmonary artery were reversed by treatment with oral LASSBio-1359, most probably through the activation of adenosine A2A receptors.

Phenylpiperazine derivatives: a patent review (2006 - present).

INTRODUCTION: The N-phenylpiperazine subunit represents one of the most versatile scaffolds used in the medicinal chemistry field. Recently, some N-phenylpiperazine derivatives have reached late stage clinical trials for the treatment of CNS disorders, thus, this is clearly a molecular template that already has proven its "druglikeness," However, this scaffold is still strictly seen as a "CNS structure" by great part of the scientific community. The aim of this review is to draw a contemporary profile of the patents regarding N-phenylpiperazine derivatives and, them, suggest new research fields to be explored. AREAS COVERED: The site of the World Intellectual Property Organization (WIPO) was used as the main source in order to perform the research of the patents containing N-phenylpiperazine compounds with therapeutic uses. This review highlights some examples to show that this heterocyclic moiety can successfully yield new classes of hits and prototypes for many other therapeutic fields through appropriate substitution of the molecular skeleton. EXPERT OPINION: The patent research concerning N-phenylpiperazine derivatives indicated for therapeutic uses from 2006 to present date resulted in thirty three documents. It is a low number if one considers the several compounds bearing the N-phenylpiperazine nucleus that reached the market and/or clinical trials. Therefore, this subunit seems to be much underrated at the moment. The adequate use of the N-phenylpiperazine moiety, through modulation of its basicity and substitution pattern of the aromatic ring, can yield pharmacokinetic and pharmacodynamic improvements that are certainly useful in several therapeutic areas, thus, being able to diversify the application and utility of this scaffold. We expect and strongly suggest the growth of this diversification.

Novel furfurylidene N-acylhydrazones derived from natural safrole: discovery of LASSBio-1215, a new potent antiplatelet prototype.

We describe herein the discovery of (E)-N-methyl-N'-((5-nitrofuran-2-yl)methylene)benzo[d]( 1 , 3 ) dioxole-5-carbohydrazide (9e), named LASSBio-1215, as a novel antiplatelet agent belonging to the N-methyl-N-acylhydrazone class, which exert their antiaggregating actions on human and rabbit platelets induced by different agonists, through cyclooxygenase-1 (COX-1) or thromboxane synthase inhibition. This compound was elected after screening of a series of functionalized furyl N-acylhydrazone derivatives, synthesized from natural safrole 10. In vitro assays showed that compound 9e presents platelet-aggregating activity in rabbit platelet-rich plasma (PRP) induced by arachidonic acid (IC(50) = 0.7 µM) and collagen (IC(50) = 4.5 µM). Moreover, LASSBio-1215 also inhibited almost completely the second wave of adenosine diphosphate-induced platelet aggregation in human PRP, and this effect was correlated with their ability to block the production of pro-aggregating autacoid thromboxane A(2).

Synthesis and analgesic profile of conformationally constrained N-acylhydrazone analogues: discovery of novel N-arylideneamino quinazolin-4(3H)-one compounds derived from natural safrole.

In this work we reported the synthesis and evaluation of the analgesic, anti-inflammatory, and platelet anti-aggregating properties of new 3-(arylideneamino)-2-methyl-6,7-methylenedioxy-quinazolin-4(3H)-one derivatives (3a-j), designed as conformationally constrained analogues of analgesic 1,3-benzodioxolyl-N-acylhydrazones (1) previously developed at LASSBio. Target compounds were synthesized in very good yields exploiting abundant Brazilian natural product safrole (2) as starting material. The pharmacological assays lead us to identify compounds LASSBio-1240 (3b) and LASSBio-1272 (3d) as new analgesic prototypes, presenting an antinociceptive profile more potent and effective than dipyrone and indomethacin used, respectively, as standards in AcOH-induced abdominal constrictions assay and in the formalin test. These results confirmed the success in the exploitation of conformation restriction strategy for identification of novel cyclic N-acylhydrazone analogues with optimized analgesic profile.