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1.
Arch Endocrinol Metab ; 67(6): e230123, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38048417

RESUMO

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up,14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusion: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.


Assuntos
Gastroenterologia , Doenças Metabólicas , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Brasil , Seguimentos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/complicações , Obesidade/terapia , Sobrepeso/complicações , Sobrepeso/diagnóstico , Sobrepeso/terapia
2.
Arch Endocrinol Metab ; 67(4): e230174, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37585688

RESUMO

Obesity is largely undertreated, in part because of the stigma surrounding the disease and its treatment. The use of the term "weight loss drugs" to refer to medications for the treatment of obesity may contribute to this stigma, leading to the idea that anyone who wants to lose weight could use them and that short-term use, only in the active weight loss phase would be enough. On the contrary, the use of terms such as "medications to treat obesity" or "anti-obesity medications" conveys the idea that the treatment is directed at the disease rather than the symptom. This joint statement by the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO) and the Brazilian Society of Endocrinology and Metabolism (SBEM) intends to alert the press, healthcare professionals and scientific community about the importance of the appropriate use of language, with the aim of improving obesity care.


Assuntos
Fármacos Antiobesidade , Síndrome Metabólica , Humanos , Fármacos Antiobesidade/uso terapêutico , Brasil , Obesidade/terapia , Redução de Peso
3.
Diabetol Metab Syndr ; 15(1): 160, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37468901

RESUMO

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

4.
Langmuir ; 39(25): 8603-8611, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37320858

RESUMO

Physical membrane models permit to study and quantify the interactions of many external molecules with monitored and simplified systems. In this work, we have constructed artificial Langmuir single-lipid monolayers with dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylethanolamine (DPPE), dipalmitoylphosphatidylserine (DPPS), or sphingomyelin to resemble the main lipid components of the mammalian cell membranes. We determined the collapse pressure, minimum area per molecule, and maximum compression modulus (Cs-1) from surface pressure measurements in a Langmuir trough. Also, from compression/expansion isotherms, we estimated the viscoelastic properties of the monolayers. With this model, we explored the membrane molecular mechanism of toxicity of the well-known anticancer drug doxorubicin, with particular emphasis in cardiotoxicity. The results showed that doxorubicin intercalates mainly between DPPS and sphingomyelin, and less between DPPE, inducing a change in the Cs-1 of up to 34% for DPPS. The isotherm experiments suggested that doxorubicin had little effect on DPPC, partially solubilized DPPS lipids toward the bulk of the subphase, and caused a slight or large expansion in the DPPE and sphingomyelin monolayers, respectively. Furthermore, the dynamic viscoelasticity of the DPPE and DPPS membranes was greatly reduced (by 43 and 23%, respectively), while the reduction amounted only to 12% for sphingomyelin and DPPC models. In conclusion, doxorubicin intercalates into the DPPS, DPPE, and sphingomyelin, but not into the DPPC, membrane lipids, inducing a structural distortion that leads to decreased membrane stiffness and reduced compressibility modulus. These alterations may constitute a novel, early step in explaining the doxorubicin mechanism of action in mammalian cancer cells or its toxicity in non-cancer cells, with relevance to explain its cardiotoxicity.


Assuntos
Cardiotoxicidade , Esfingomielinas , Animais , Humanos , 1,2-Dipalmitoilfosfatidilcolina/química , Doxorrubicina/farmacologia , Membrana Celular/química , Propriedades de Superfície , Mamíferos
5.
Chemistry ; 29(20): e202203731, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36693212

RESUMO

Sixteen geosterane derivatives were synthesized in up to 57 % overall yields in four steps harnessing the olefin cross-metathesis (OCM) and Metal hydride H atom transfer (MHAT) or homogeneous hydrogenation reactions as key steps. Drawing on this strategy, the diastereomeric ratio (d. r.) reached up to 24 : 1 for the thermodynamic isomer and 7 : 1 for the other isomer in the hydrogenation step. In a geological sample from northeast Brazil, we confirmed the putative structures previously assumed as methyl 2-(3α-5αH-cholestan) acetate, methyl 2-(3ß-5αH-cholestan)acetate, and methyl 6-(3ß-5αH-cholestan)hexanoate, as well three new molecular fossils of approximately 120 million years old. We also proved the migration marking ability of those carboxylic acids derived from forerunner geosteranes during an oil migration event, which suggests their aptitudes as molecular odometers. Our approach demonstrated swiftness and effectiveness in preparing a molecular library of geological biomarkers would also be appropriate to generate stereochemical diversity in molecular libraries for medicinal chemistry and natural product anticipation.

6.
Arch. endocrinol. metab. (Online) ; 67(4): e230174, Mar.-Apr. 2023. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1520071

RESUMO

ABSTRACT Obesity is largely undertreated, in part because of the stigma surrounding the disease and its treatment. The use of the term "weight loss drugs" to refer to medications for the treatment of obesity may contribute to this stigma, leading to the idea that anyone who wants to lose weight could use them and that short-term use, only in the active weight loss phase would be enough. On the contrary, the use of terms such as "medications to treat obesity" or "anti-obesity medications" conveys the idea that the treatment is directed at the disease rather than the symptom. This joint statement by the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO) and the Brazilian Society of Endocrinology and Metabolism (SBEM) intends to alert the press, healthcare professionals and scientific community about the importance of the appropriate use of language, with the aim of improving obesity care.

7.
Arch. endocrinol. metab. (Online) ; 67(6): e230123, Mar.-Apr. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1527754

RESUMO

ABSTRACT Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up, 14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusions: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

8.
J Org Chem ; 87(12): 7610-7617, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35171607

RESUMO

Ellipticine was synthesized in six steps and 20% global yield starting from the readily available 2,5-dimethoxy isoquinoline. Unprecedented regioselective control of the nucleophilic attack on the isoquinoline-5,8-dione is first described. Investigation of the possible pathways of this transformation through density functional theory calculations reveals unexpected N-oxide assistance in cascade tautomerizations, which was crucial for directing the nucleophilic attack and hastening the overall process. Using this strategy, we prepared the aniline-isoquinolinedione adduct and submitted it to an intramolecular double C-H cross-coupling activation to furnish ellipticinequinone, which gave ellipticine after a MeLi addition/BH3 reduction sequence.


Assuntos
Elipticinas , Isoquinolinas
9.
Growth Horm IGF Res ; 62: 101442, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34952478

RESUMO

OBJECTIVE: Cardiovascular (CV) disease is still a major cause of excessive morbidity and mortality in patients with active acromegaly, which may be attributed to a high prevalence of associated pro-atherosclerotic risk factors. However, a direct effect of GH/IGF-1 excess on the vasculature has been previously suggested, warranting further investigation. The present study was designed to investigate whether chronic GH/IGF-1 excess is associated with an increased prevalence of subclinical atherosclerosis in patients with acromegaly. DESIGN: We measured carotid intima-media thickness (cIMT) and assessed carotid plaques by ultrasonography along with classical CV risk factors in 54 acromegaly patients (34 females, 50 ± 12 years and compared those with 62 (42 females, 53 ± 13 years) age-, sex- and CV risk factors- matched controls. In order to compare cIMT measurements between patients and controls we analyzed common carotid artery far wall data as well as a combined measurement result, which consisted of the mean value of the six different measurements, three at each side. RESULTS: mean ± SD serum GH and IGF-1 levels were 2.76 ± 4.65 ng/mL and 1.7 ± 1.25 x ULN, respectively, in all acromegaly patients. Age, body mass index, blood pressure, lipid levels, fasting glucose and Framingham's global cardiovascular risk score classification were similar comparing patients and controls. Combined median [IQR] cIMT measurements were similar in acromegaly patients and matched controls (0.59 [0.52-0.66] mm vs. 0.59 [0.52-0.69] mm; P = 0.872) as well as in acromegaly patients with active and controlled disease (0.59 [0.51-0.68] mm vs. 0.60 [0.54-0.68] mm; P = 0.385). No significant correlations were observed between cIMT measurements and GH (Spearman r = 0.1, P = 0.49) or IGF-1 (Spearman r = 0.13, P = 0.37) levels in patients with acromegaly. Carotid atherosclerotic plaques prevalence was similar in patients and controls (26% vs. 32%; P = 0.54) as well as in patients with active and controlled acromegaly (22% vs. 30%; P = 0.537). CONCLUSIONS: Our data suggest that GH/IGF-1 excess itself is not one of the main drivers of subclinical morphological atherosclerosis changes in patients with acromegaly and that optimal control of acromegaly-associated CV risk factors may preserve vasculature structure even when strict biochemical control is not achieved.


Assuntos
Acromegalia , Aterosclerose , Doenças Cardiovasculares , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Espessura Intima-Media Carotídea , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Fator de Crescimento Insulin-Like I , Masculino , Fatores de Risco
10.
Int J Mol Sci ; 22(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34576044

RESUMO

α,ß-amyrenone (ABAME) is a triterpene derivative with many biological activities; however, its potential pharmacological use is hindered by its low solubility in water. In this context, the present work aimed to develop inclusion complexes (ICs) of ABAME with γ- and ß-cyclodextrins (CD), which were systematically characterized through molecular modeling studies as well as FTIR, XRD, DSC, TGA, and SEM analyses. In vitro analyses of lipase activity were performed to evaluate possible anti-obesity properties. Molecular modeling studies indicated that the CD:ABAME ICs prepared at a 2:1 molar ratio would be more stable to the complexation process than those prepared at a 1:1 molar ratio. The physicochemical characterization showed strong evidence that corroborates with the in silico results, and the formation of ICs with CD was capable of inducing changes in ABAME physicochemical properties. ICs was shown to be a stronger inhibitor of lipase activity than Orlistat and to potentiate the inhibitory effects of ABAME on porcine pancreatic enzymes. In conclusion, a new pharmaceutical preparation with potentially improved physicochemical characteristics and inhibitory activity toward lipases was developed in this study, which could prove to be a promising ingredient for future formulations.


Assuntos
Inibidores Enzimáticos/farmacologia , Lipase/antagonistas & inibidores , Triterpenos/farmacologia , beta-Ciclodextrinas/farmacologia , Animais , Varredura Diferencial de Calorimetria , Simulação por Computador , Inibidores Enzimáticos/química , Lipase/química , Orlistate/farmacologia , Solubilidade/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Suínos , Triterpenos/síntese química , Triterpenos/química , Difração de Raios X , beta-Ciclodextrinas/química
11.
Diagn. tratamento ; 26(3): 101-4, jul-set. 2021. ilus, tab
Artigo em Português | LILACS | ID: biblio-1291194

RESUMO

Contexto: O fibrohistiocitoma maligno é um sarcoma de tecidos moles muito agressivo, com rara apresentação limitada à pele e tecido subcutâneo em face. O diagnóstico é anatomopatológico com auxílio da imuno-histoquímica. Descrição do caso: Este artigo relata o caso de um paciente com diagnóstico de fibrohistiocitoma maligno restrito à face com boa resposta terapêutica após exérese cirúrgica. Discussão: Tendo em vista a raridade dessa afecção, dificuldade diagnóstica devido ao quadro inespecífico e com rápida evolução, é importante lembrar desse possível diagnóstico e atuar precocemente. Conclusões: O diagnóstico precoce interfere de forma significativa na evolução do quadro, sendo necessária a manutenção do acompanhamento oncológico e dermatológico com o intuito de detectar precocemente recidivas locais e metástases a distância.


Assuntos
Humanos , Masculino , Idoso , Neoplasias Cutâneas/patologia , Histiocitoma Fibroso Maligno/patologia , Face , Neoplasias Cutâneas/cirurgia , Imuno-Histoquímica , Histiocitoma Fibroso Maligno/cirurgia
12.
Rev. polis psique ; 11(2): 225-244, maio-ago. 2021. ilus
Artigo em Português | LILACS, Index Psicologia - Periódicos | ID: biblio-1352148

RESUMO

O presente relato de experiência visa problematizar a prática com grupos de adolescentes em situação de vulnerabilidade social. Realizou-se cinco grupos entre agosto e dezembro de 2019. Os grupos eram fechados e com duração de 1 hora e 40 minutos cada. Como método e forma de manejo grupal utilizou-se a estratégia de coordenação cartográfica. Os resultados e discussão apontam rizomaticamente para diferentes direções: a alta disponibilidade dos adolescentes em participar dos grupos; a importância do delineamento e da sensibilização ao setting grupal; o modo como os vetores macropolíticos e institucionais incidem nos processos grupais; os efeitos da sub-apropriação da língua formal na dinâmica dos grupos e na circulação social; a importância de dar lugar ao que não tem lugar; e, o mapeamento de expressões com camadas de sentido. Por fim, aponta-se o grupo como dispositivo potente para a instauração de novas formas de vida.(AU)


The present experience report aims to problematize the practice with groups of adolescents in situations of social vulnerability. Five groups were held between August and December 2019. The groups were closed and lasting 1 hour and 40 minutes each. As a method and as a form of group management was used the strategy of cartographic coordination. The results and discussion indicate rhizomatically to different directions: the high availability of adolescents to participate in groups; the importance of design and sensation by the participants of the group setting; the macro-political and institutional vectors converging on group processes; the effects of the sub-appropriation of formal language in the groups dynamics and social mobilities; the importance of step up a place for what has no place; and, the mapping of expressions with layers of meaning. Finally, the group is pointed out as a powerful device for the creation of new forms of life.(AU)


El presente informe de experiencia tiene como objetivo problematizar la práctica con grupos de adolescentes en situaciones de vulnerabilidad social. Se realizaron cinco grupos entre agosto y diciembre de 2019. Los grupos fueron cerrados y ocurrieron durante 1 hora y 40 minutos cada uno. Como método y forma de seguimiento grupal se utilizó la estrategia de coordinación cartográfica. Los resultados y la discusión apuntan rizomaticamente a diferentes direcciones: la alta disponibilidad de adolescentes para participar de los grupos; la importancia del diseño y de la sensibilización del espacio grupal; los vectores macropolíticos y institucionales en los procesos grupales; los efectos de la sub-apropiación de la lengua formal sobre la dinámica grupal y la circulación social; la importancia de producir lugar para lo que no tiene lugar; y, el mapeo de expresiones con capas de sentido. Finalmente, se señala el grupo como un fuerte dispositivo para la producción de nuevas formas de vida.(AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Vulnerabilidade Social , Processos Grupais , Psicologia , Intervenção Psicossocial
13.
Arch Endocrinol Metab ; 65(2): 212-230, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33905631

RESUMO

Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.


Assuntos
Endocrinologia , Hipopituitarismo , Brasil , Terapia de Reposição Hormonal , Humanos , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/etiologia , Hormônios Hipofisários
14.
Arch. endocrinol. metab. (Online) ; 65(2): 212-230, Mar.-Apr. 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1248814

RESUMO

ABSTRACT Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.


Assuntos
Humanos , Endocrinologia , Hipopituitarismo/etiologia , Hipopituitarismo/tratamento farmacológico , Hormônios Hipofisários , Brasil , Terapia de Reposição Hormonal
15.
Diagn. tratamento ; 26(1): 16-20, jan.-mar. 2021.
Artigo em Português | LILACS | ID: biblio-1247975

RESUMO

Contexto: Alopecia frontal fibrosante (AFF) é uma alopecia cicatricial que acomete a região frontotemporal, e predomina em mulheres pós-menopausadas. Objetivo: Descrever o perfil clínico, histopatológico e tricoscópico de pacientes com diagnóstico de AFF. Desenho e local: Estudo de coorte retrospectivo observacional que foi desenvolvido no ambulatório de tricologia do departamento de dermatologia do Hospital Santa Casa de Misericórdia de Vitória, Vitória (ES), Brasil. Métodos: O estudo foi realizado por meio da análise de prontuários e de revisão histopatológica de pacientes com diagnóstico de AFF atendidos entre 1 de março de 2019 a 29 de fevereiro de 2020. Resultados: No período, 17 pacientes do sexo feminino foram diagnosticadas com AFF, 76,5% delas na pós-menopausa. Todas apresentavam alopecia frontotemporal e madarose. À tricoscopia, ausência de pelos velus, aberturas foliculares reduzidas, hiperceratose folicular e eritema perifolicular foram encontrados na maioria dos casos. Todas as biópsias mostraram aspectos microscópicos compatíveis com AFF. O tratamento mais utilizado foi tacrolimo 0,1%. Discussão: A patogênese da AFF ainda não é compreendida. A associação com doenças autoimunes sugere a influência da imunidade no quadro. A tricoscopia é uma ferramenta de fácil acesso e não invasiva que pode auxiliar no diagnóstico. Histopatologicamente a AFF é indistinguível do líquen plano pilar. O tratamento objetiva reduzir a inflamação e retardar a progressão da doença. Conclusões: Embora apresentações clínicas e tricoscópicas tenham sido descritas ao longo dos anos, a patogênese, a histologia e os tratamentos eficazes para AFF ainda são debatidos. O reconhecimento e o tratamento precoce da doença permitiriam a redução da progressão da doença.


Assuntos
Estudos Epidemiológicos , Dermoscopia , Alopecia , Doenças do Cabelo , Líquen Plano
16.
Mol Divers ; 25(1): 1-12, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31820222

RESUMO

Tuberculosis, caused by Mycobacterium tuberculosis (M. tuberculosis), is still responsible for a large number of fatal cases, especially in developing countries with alarming rates of incidence and prevalence worldwide. Mycobacterium tuberculosis has a remarkable ability to develop new resistance mechanisms to the conventional antimicrobials treatment. Because of this, there is an urgent need for novel bioactive compounds for its treatment. The dehydroquinate dehydratase II (DHQase II) is considered a key enzyme of shikimate pathway, and it can be used as a promising target for the design of new bioactive compounds with antibacterial action. The aim of this work was the construction of QSAR models to aid the design of new potential DHQase II inhibitors. For that purpose, various molecular modeling approaches, such as activity cliff, QSAR models and computer-aided ligand design were utilized. A predictive in silico 4D-QSAR model was built using a database comprising 86 inhibitors of DHQase II, and the model was used to predict the activity of the designed ligands. The obtained model proved to predict well the DHQase II inhibition for an external validation dataset ([Formula: see text] = 0.72). Also, the Activity Cliff analysis shed light on important structural features applied to the ligand design.


Assuntos
Antituberculosos/farmacologia , Inibidores Enzimáticos/farmacologia , Hidroliases/antagonistas & inibidores , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/metabolismo , Sítios de Ligação/efeitos dos fármacos , Desenho de Fármacos , Ligantes , Modelos Moleculares , Mycobacterium tuberculosis/enzimologia , Relação Quantitativa Estrutura-Atividade
17.
Mol Divers ; 25(4): 2219-2235, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32557280

RESUMO

Chagas disease kills over 10,000 people per year, and approximately 8 million people are infected by Trypanosoma cruzi. The reference drug for treatment of the disease, benznidazole, is the same since the 70s. In recent years, many CYP51 inhibitors were tested against this parasite's target. One of them, posaconazole, was even tested in clinical trials that unfortunately were not successful. Nevertheless, there are still many evidences that CYP51 is a great potential target to treat T. cruzi infection. The research for new effective molecules that can cure the chronic phase of the disease is essential. 2D and 3D-quantitative structure activity relationship (QSAR) studies were conducted in this work to create three QSAR models using the chemical structures of 197 published compounds that already went through either in vivo or in vitro tests. After the analysis of the models, new analogues not yet synthesized were suggested here and had their biological activity and synthetic availability assessed.


Assuntos
Relação Quantitativa Estrutura-Atividade , Inibidores de 14-alfa Desmetilase
18.
Psicol. soc. (Online) ; 33: e232754, 2021.
Artigo em Português | LILACS, Index Psicologia - Periódicos | ID: biblio-1346844

RESUMO

Resumo O presente trabalho busca analisar os modos como se organizam os Centros de Referência em Assistência Social (CRAS), a partir de experiências coletivas e práticas comunitárias realizadas pelas equipes-território, destacando os processos de dissensos e consensos nas relações de trabalho. Metodologicamente, com base na análise de discurso, foram realizadas coletivamente 14 entrevistas semiestruturadas com cada equipe dos CRAS de dois estados da macrorregião sul do Brasil. Os resultados apontam que trabalhar as divergências internas sem tentar homogeneizá-las, compondo práticas transdisciplinares e horizontalizantes, se mostrou um modo potente de organização das equipes de trabalho. Ademais, foi relatado também a potência na produção dos fazeres de territorialização, com e a partir do território, por meio de seus significantes e possibilidades singulares. Finalmente, apontam-se as práticas comunitárias com grupos e coletivos nos CRAS como um dos vetores potentes no enfrentamento ao sofrimento ético-político produzido pelas desigualdades sociais.


Resumen El presente trabajo busca analizar las formas en que se organizan los Centros de Referencia de Asistencia Social (CRAS), a partir de experiencias colectivas y prácticas comunitarias realizadas por los equipos del territorio, destacando los procesos de desacuerdos y consensos en las relaciones laborales. Metodológicamente, con base en el análisis del discurso, se realizaron colectivamente 14 entrevistas semiestructuradas con cada equipo de los CRAS de dos estados del macrorregión sur del Brasil. Los resultados muestran que trabajar las diferencias internas sin tratar de homogeneizarlas, componiendo prácticas transdisciplinarias y horizontales, resultó ser una forma poderosa de organizar equipos de trabajo. Además, también se informó del poder en la producción de actividades de territorialización, con y desde el territorio, a través de sus significantes y posibilidades singulares. Finalmente, las prácticas comunitarias con grupos y colectivos en los CRAS se señalan como uno de los vectores poderosos para enfrentar el sufrimiento ético-político que producen las desigualdades sociales.


Abstract This paper analyzes the ways through which the Social Assistance Reference Centers (CRAS) is organized, based on collective experiences and community practices carried out by the territory-teams, highlighting the processes of dissent and consensus in working relations. Methodologically, based on discourse analysis, 14 semi-structured interviews were conducted collectively with each CRAS team from two states of the Brazilian southern region. The results indicate that working internal differences without trying to homogenize them, composing transdisciplinary and horizontal practices, proved to be a powerful way of organizing the work teams. Besides, the power in the production of territorialization actions, with and from the territory, was also reported through its significant and singular possibilities. Finally, the community practices with groups and collectives in CRAS are pointed as one of the potent vectors in facing the ethical-political suffering produced by social inequalities.


Assuntos
Psicologia , Serviço Social , Democracia , Política Pública , Territorialidade , Redes Comunitárias
19.
Rev. enferm. UFSM ; 11: e6, 2021.
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1177503

RESUMO

Objetivo: descrever a percepção de pessoas com hipertensão arterial sobre aspectos que facilitam e dificultam a adesão ao tratamento. Método: estudo qualitativo descritivo desenvolvido com 16 pessoas atendidas em consultas de enfermagem. Realizaram-se entrevistas com roteiro semiestruturado e utilizou-se a técnica de análise de conteúdo. Os dados foram coletados entre os meses de janeiro e agosto de 2017. Resultados: observou-se que ter força de vontade, apoio familiar e multiprofissional, conhecimento sobre a patologia e formas de prevenção e medo da morte facilitou a adesão; por outro lado, pouco conhecimento, preguiça, falta de infraestrutura urbana e condições climáticas, hábito de consumir alimentos não saudáveis, bebidas alcoólicas e tabaco, custo do tratamento e esquecimento de tomar a medicação dificultaram a adesão. Conclusão: o tratamento da hipertensão acarreta mudanças na dinâmica da vida para as quais é fundamental ter força de vontade, apoio familiar e profissional, além de superar hábitos não saudáveis.


Objective: to describe the perception of people with arterial hypertension of the aspects that facilitate and hinder treatment adherence. Method: descriptive qualitative study developed with 16 people met in Nursing consultations. Interviews were conducted with a semi-structured guide and the content analysis technique was used. Data were collected between January and August 2017. Results: having willpower, family and multidisciplinary support, knowledge about the pathology and forms of prevention and fear of death facilitated adherence; on the other hand, little knowledge, laziness, lack of urban infrastructure and climatic conditions, habit of consuming unhealthy foods, alcoholic beverages and tobacco, cost of treatment and forgetfulness of taking the medication hindered adherence. Conclusion: the treatment of hypertension causes changes in the dynamics of life, being essential to have willpower, family and professional support, in addition to overcoming unhealthy habits.


Objetivo: describir la percepción de las personas con hipertensión arterial sobre los aspectos que facilitan y dificultan la adherencia al tratamiento. Método: estudio cualitativo descriptivo desarrollado con 16 personas atendidas en consultas de enfermería. Se realizaron entrevistas con un guion semiestructurado y se utilizó la técnica de análisis de contenido. Los datos se recopilaron entre enero y agosto de 2017. Resultados: se observó que tener fuerza de voluntad, apoyo familiar y multidisciplinario, conocimiento sobre la patología y las formas de prevención y miedo a la muerte facilitaba la adherencia; por otro lado, poco conocimiento, pereza, falta de infraestructura urbana y condiciones climáticas, hábito de consumir alimentos no saludables, bebidas alcohólicas y tabaco, costo de tratamiento y olvido de tomar el medicamento obstaculizaba la adherencia. Conclusión: el tratamiento de la hipertensión provoca cambios en la dinámica de la vida para los que es esencial contar con fuerza de voluntad, apoyo familiar y profesional, además de superar hábitos poco saludables.


Assuntos
Humanos , Enfermagem , Cooperação do Paciente , Adesão à Medicação , Cooperação e Adesão ao Tratamento , Hipertensão
20.
J Med Virol ; 92(12): 3799-3806, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32989777

RESUMO

Cervical carcinoma is the fourth leading cause of death among women worldwide. Epidemiological studies claim that human papillomavirus (HPV) infection is a necessary condition for cervical cancer development. Knowledge of the geographic distribution of HPV is important in guiding the introduction of prophylactic vaccines. This study analyzed the prevalence of HPV infection in cervical samples obtained from women with abnormal cervical histopathological diagnosis in Northeast Brazil. The study included an analysis of 211 women whose diagnosis was confirmed for cervical intraepithelial neoplasia type 1 (CIN-1), cervical intraepithelial neoplasia type 2 (CIN-2), cervical intraepithelial neoplasia type 3 (CIN-3), and cancer. The identification of the HPV genotypes was based on the polymerase chain reaction-restriction fragment length polymorphism technique. A total of 42.7% of the samples showed a single HPV infection, while 57.3% showed multiple infections. The most common genotypes detected were HPV-16, HPV-18, and HPV-31. HPV-16, HPV-31, HPV-35, and HPV-18 were the most common types in CIN-1 with a single infection. HPV-16 and HPV-18 were the most often found in CIN-2 with a single infection. HPV-16, HPV-18, and HPV-31 were the most detected in CIN-3 with a single infection. HPV-16 and HPV-31 were the most frequent in cancer with a single infection. Multiple infection with HPV-16 shows a 2.7 times greater risk of CIN-3 (P = .04). Multiple infections for HPV with HPV-16 and excluding the HPV18/31 types, were associated with CIN-3 (P = .01). The results allowed the detection and genotyping of HPV types circulating in the population studied. These findings must be taken into account when devising vaccination strategies against HPV.

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