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1.
N Engl J Med ; 386(13): 1244-1253, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35353962

RESUMO

BACKGROUND: In most of the Americas, the recommended treatment to prevent relapse of Plasmodium vivax malaria is primaquine at a total dose of 3.5 mg per kilogram of body weight, despite evidence of only moderate efficacy. METHODS: In this trial conducted in Brazil, we evaluated three primaquine regimens to prevent relapse of P. vivax malaria in children at least 5 years of age and in adults with microscopy-confirmed P. vivax monoinfection. All the patients received directly observed chloroquine for 3 days (total dose, 25 mg per kilogram). Group 1 received a total primaquine dose of 3.5 mg per kilogram (0.5 mg per kilogram per day) over 7 days with unobserved administration; group 2 received the same regimen as group 1 but with observed administration; and group 3 received a total primaquine dose of 7.0 mg per kilogram over 14 days (also 0.5 mg per kilogram per day) with observed administration. We monitored the patients for 168 days. RESULTS: We enrolled 63 patients in group 1, 96 in group 2, and 95 in group 3. The median age of the patients was 22.4 years (range, 5.4 to 79.8). By day 28, three P. vivax recurrences were observed: 2 in group 1 and 1 in group 2. By day 168, a total of 70 recurrences had occurred: 24 in group 1, 34 in group 2, and 12 in group 3. No serious adverse events were noted. On day 168, the percentage of patients without recurrence was 58% (95% confidence interval [CI], 44 to 70) in group 1, 59% (95% CI, 47 to 69) in group 2, and 86% (95% CI, 76 to 92) in group 3. Survival analysis showed a difference in the day 168 recurrence-free percentage of 27 percentage points (97.5% CI, 10 to 44; P<0.001) between group 1 and group 3 and a difference of 27 percentage points (97.5% CI, 12 to 42; P<0.001) between group 2 and group 3. CONCLUSIONS: The administration of primaquine at a total dose of 7.0 mg per kilogram had higher efficacy in preventing relapse of P. vivax malaria than a total dose of 3.5 mg per kilogram through day 168. (Supported by the U.S. Agency for International Development; ClinicalTrials.gov number, NCT03610399.).


Assuntos
Antimaláricos , Cloroquina , Malária Vivax , Primaquina , Adolescente , Adulto , Idoso , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Brasil , Criança , Pré-Escolar , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Terapia Diretamente Observada , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Malária Vivax/tratamento farmacológico , Malária Vivax/prevenção & controle , Pessoa de Meia-Idade , Primaquina/administração & dosagem , Primaquina/efeitos adversos , Primaquina/uso terapêutico , Recidiva , Prevenção Secundária , Adulto Jovem
2.
Inflammopharmacology ; 32(2): 1239-1252, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38472616

RESUMO

BACKGROUND: Osteoarthritis (OA) is a chronic disease that may lead to joint structure degeneration, cartilage destruction, osteophyte formation, subchondral bone disruption, and pain. In this scenario, a higher proportion of the proinflammatory macrophage type 1 (M1) than the anti-inflammatory macrophage type 2 (M2) could be highlighted as a hallmark of OA progression. The balance between these two macrophage types emerges as a new therapeutic target in OA. This study aimed to evaluate the analgesia and macrophage profile in the treatment of experimental osteoarthritis (EOA) with systemic dimethyl fumarate (DMF) or local intra-articular monomethyl fumarate (MMF). RESULTS: DMF via gavage or MMF via intra-articular in the right knee of EOA rats showed improvements in gait parameters and the nociceptive recovery of the mechanical threshold assessment by adapted electronic von Frey treatment on the twenty-first day (long-lasting phase). DMF treatment decreased proinflammatory TNF-α while increasing anti-inflammatory IL-10 cytokines from the macerated capsule on the fifth day (inflammatory phase). MMF treatment showed joint capsule mRNA extraction downregulating iNOS and TNF-α gene expression while upregulating IL-10 and MCP-1. However, CD206 was not significant but higher than untreated EOA rats' joints on the seventh day (inflammatory phase). CONCLUSIONS: Our studies with EOA model induced by MIA suggest a new perspective for human treatment committed with OA based on macrophage polarization as a therapeutic target, switching the proinflammatory profile M1 to the anti-inflammatory profile M2 with DMF systematic or by MMF locally treatment according to the OA severity.


Assuntos
Fumaratos , Interleucina-10 , Osteoartrite , Humanos , Ratos , Animais , Fator de Necrose Tumoral alfa , Osteoartrite/metabolismo , Dor/tratamento farmacológico , Fumarato de Dimetilo , Macrófagos/metabolismo , Anti-Inflamatórios/uso terapêutico
3.
Mol Cell Neurosci ; 118: 103694, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34954382

RESUMO

Rupture and stretching of spinal roots are common incidents that take place in high-energy accidents. The proximal axotomy of motoneurons by crushing of ventral roots is directly related to the degeneration of half of the lesioned population within the first two weeks. Moreover, only a small percentage of surviving motoneurons can successfully achieve regeneration after such a proximal lesion, and new treatments are necessary to improve this scenario. In this sense, mesenchymal stem cells (MSC) are of great interest once they secrete a broad spectrum of bioactive molecules that are immunomodulatory and can restore the environment after a lesion. The present work aimed at studying the effects of human mesenchymal stem cells (hMSC) therapy after ventral root crush (VRC) in mice. We evaluated motoneuron survival, glial reaction, and synapse preservation at the ventral horn. For this purpose, C57BL/6 J were submitted to a crush procedure of L4 to L6 ventral roots and treated with a single intravenous injection of adipose-derived hMSC. Evaluation of the results was carried out at 7, 14, and 28 days after injury. Analysis of motoneuron survival and astrogliosis showed that hMSC treatment resulted in higher motoneuron preservation (motoneuron survival ipsi/contralateral ratio: VRC group = 53%, VRC + hMSC group = 66%; p < 0.01), combined with reduction of astrogliosis (ipsi/contralateral GFAP immunolabeling: VRC group = 470%, VRC + hMSC group = 250%; p < 0.001). The morphological classification and Sholl analysis of microglial activation revealed that hMSC treatment reduced type V and increased type II profiles, indicating an enhancement of surveying over activated microglial cells. The glial reactivity modulation directly influenced synaptic inputs in apposition to axotomized motoneurons. In the hMSC-treated group, synaptic maintenance was increased (ipsi/contralateral synaptophysin immunolabeling: VRC group = 53%, VRC + hMSC group = 64%; p < 0.05). Overall, the present data show that intravenous injection of hMSC has neuroprotective and anti-inflammatory effects, decreasing reactive astrogliosis, and microglial reaction. Also, such cell therapy results in motoneuron preservation, combined with significant maintenance of spinal cord circuits, in particular those related to the ventral horn.


Assuntos
Gliose , Células-Tronco Mesenquimais , Animais , Gliose/terapia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Neuroproteção , Medula Espinal , Raízes Nervosas Espinhais/lesões , Raízes Nervosas Espinhais/patologia
4.
J Aging Phys Act ; 31(2): 311-318, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35940583

RESUMO

It is widely known that the aging process induces relevant impairments on both muscle morphology and function. In this sense, resistance training alongside proper protein intake are important strategies to mitigate the sarcopenia process in older individuals. However, adding protein supplementation (PS) to resistance training interventions for enhancing muscle strength and functional performance has shown mixed results in this population. Therefore, the present study aimed to review the most recent evidence regarding PS and its effects on muscle strength and functional parameters of older adults. In addition, the effect size of each individual study (post-pre intervention) was also calculated to provide further clinical relevance on the topic. The results of the studies included do not seem to support PS for healthy older adults with proper protein intake. However, further studies with other sample characteristics (very old, frail, obese, and inadequate protein consumption) must be carried out to better understand the effects of PS in an older population.


Assuntos
Treinamento Resistido , Sarcopenia , Idoso , Humanos , Suplementos Nutricionais , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Obesidade , Desempenho Físico Funcional , Sarcopenia/prevenção & controle
5.
World J Microbiol Biotechnol ; 39(3): 86, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36720739

RESUMO

The spread of polymyxin-resistant Klebsiella pneumoniae strains represents an emerging health challenge, limiting treatment options for the patients. Thus, the development of new antimicrobials is an urgent requirement. Antimicrobial peptides (AMPs) are a large class of compounds that are part of innate immune response; these peptides are promising compounds in the field of antimicrobial resistance and are present in all organisms. The present review evaluated patents on antimicrobial peptides tested against polymyxin-resistant K. pneumoniae, available on Espacenet as of September 2022. A total of 1313 patents were examined and 1197 excluded as they were out of focus for this review; 104 patents of peptides tested against K. pneumoniae were included; of which only 14 were tested against polymyxin-resistant K. pneumoniae strains. The results indicated that all AMPs evaluated were in the experimental or pre-clinical phase; the clinical phase is pending. Furthermore, a few peptides were tested effectively against polymyxin-resistant K. pneumoniae. Although, the research and patent filing alone are not enough to develop a suitable antimicrobial therapy, they can represent good starting point upon which to develop new antimicrobials. More investment is required to push these pharmaceuticals through the stages of development to introduce them into the market.


Assuntos
Peptídeos Antimicrobianos , Polimixinas , Humanos , Klebsiella pneumoniae , Polimixinas/farmacologia , Farmacorresistência Bacteriana
6.
Ann Neurol ; 90(2): 239-252, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34048612

RESUMO

OBJECTIVE: Protein misfolding plays a central role not only in amyotrophic lateral sclerosis (ALS), but also in other conditions, such as frontotemporal dementia (FTD), inclusion body myopathy (hIBM) or Paget's disease of bone. The concept of multisystem proteinopathies (MSP) was created to account for those rare families that segregate at least 2 out of these 4 conditions in the same pedigree. The calcium-dependent phospholipid-binding protein annexin A11 was recently associated to ALS in European pedigrees. Herein, we describe in detail 3 Brazilian families presenting hIBM (isolated or in combination with ALS/FTD) caused by the novel p.D40Y change in the gene encoding annexin A11 (ANXA11). METHODS: We collected clinical, genetic, pathological and skeletal muscle imaging from 11 affected subjects. Neuroimaging was also obtained from 8 patients and 8 matched controls. RESULTS: Clinico-radiological phenotype of this novel hIBM reveals a slowly progressive predominant limb-girdle syndrome, but with frequent axial (ptosis/dropped head) and distal (medial gastrocnemius) involvement as well. Muscle pathology identified numerous rimmed vacuoles with positive annexin A11, TDP-43 and p62 inclusions, but no inflammation. Central nervous system was also involved: two patients had FTD, but diffusion tensor imaging uncovered multiple areas of cerebral white matter damage in the whole group (including the corticospinal tracts and frontal subcortical regions). INTERPRETATION: These findings expand the phenotypic spectrum related to ANXA11. This gene should be considered the cause of a novel multisystem proteinopathy (MSP type 6), rather than just ALS. ANN NEUROL 2021;90:239-252.


Assuntos
Anexinas/genética , Variação Genética/genética , Mutação de Sentido Incorreto/genética , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/genética , Idoso , Sequência de Aminoácidos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Linhagem , Sequenciamento do Exoma/métodos
7.
Malar J ; 21(1): 306, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36307852

RESUMO

BACKGROUND: Resistance to anti-malarial drugs is associated with polymorphisms in target genes and surveillance for these molecular markers is important to detect the emergence of mutations associated with drug resistance and signal recovering sensitivity to anti-malarials previously used. METHODS: The presence of polymorphisms in genes associated with Plasmodium falciparum resistance to chloroquine and sulfadoxine-pyrimethamine was evaluated by Sanger sequencing, in 85 P. falciparum day of enrollment samples from a therapeutic efficacy study of artemether-lumefantrine conducted in 2018-2019 in Quibdo, Colombia. Samples were genotyped to assess mutations in pfcrt (codons 72-76), pfdhfr (codons 51, 59, 108, and 164), and pfdhps genes (codons 436, 437, 540, and 581). Further, the genetic diversity of infections using seven neutral microsatellites (NMSs) (C2M34, C3M69, Poly α, TA1, TA109, 2490, and PfPK2) was assessed. RESULTS: All isolates carried mutant alleles for pfcrt (K76T and N75E), and for pfdhfr (N51I and S108N), while for pfdhps, mutations were observed only for codon A437G (32/73, 43.8%). Fifty samples (58.8%) showed a complete neutral microsatellites (NMS) profile. The low mean number of alleles (2 ± 0.57) per locus and mean expected heterozygosity (0.17 ± 0.03) showed a reduced genetic diversity. NMS multilocus genotypes (MMG) were built and nine MMG were identified. CONCLUSIONS: Overall, these findings confirm the fixation of chloroquine and pyrimethamine-resistant alleles already described in the literature, implying that these drugs are not currently appropriate for use in Colombia. In contrast, mutations in the pfdhps gene were only observed at codon 437, an indication that full resistance to sulfadoxine has not been achieved in Choco. MMGs found matched the clonal lineage E variant 1 previously reported in northwestern Colombia.


Assuntos
Antimaláricos , Malária Falciparum , Humanos , Sulfadoxina/farmacologia , Sulfadoxina/uso terapêutico , Pirimetamina/farmacologia , Pirimetamina/uso terapêutico , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Plasmodium falciparum , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Colômbia , Malária Falciparum/epidemiologia , Artemeter/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Combinação de Medicamentos , Resistência a Medicamentos/genética , Polimorfismo Genético , Códon
8.
Nature ; 530(7589): 211-4, 2016 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-26840632

RESUMO

Land-use change occurs nowhere more rapidly than in the tropics, where the imbalance between deforestation and forest regrowth has large consequences for the global carbon cycle. However, considerable uncertainty remains about the rate of biomass recovery in secondary forests, and how these rates are influenced by climate, landscape, and prior land use. Here we analyse aboveground biomass recovery during secondary succession in 45 forest sites and about 1,500 forest plots covering the major environmental gradients in the Neotropics. The studied secondary forests are highly productive and resilient. Aboveground biomass recovery after 20 years was on average 122 megagrams per hectare (Mg ha(-1)), corresponding to a net carbon uptake of 3.05 Mg C ha(-1) yr(-1), 11 times the uptake rate of old-growth forests. Aboveground biomass stocks took a median time of 66 years to recover to 90% of old-growth values. Aboveground biomass recovery after 20 years varied 11.3-fold (from 20 to 225 Mg ha(-1)) across sites, and this recovery increased with water availability (higher local rainfall and lower climatic water deficit). We present a biomass recovery map of Latin America, which illustrates geographical and climatic variation in carbon sequestration potential during forest regrowth. The map will support policies to minimize forest loss in areas where biomass resilience is naturally low (such as seasonally dry forest regions) and promote forest regeneration and restoration in humid tropical lowland areas with high biomass resilience.


Assuntos
Biomassa , Florestas , Árvores/crescimento & desenvolvimento , Clima Tropical , Carbono/metabolismo , Ciclo do Carbono , Sequestro de Carbono , Ecologia , Umidade , América Latina , Chuva , Fatores de Tempo , Árvores/metabolismo
9.
Sensors (Basel) ; 22(21)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36366002

RESUMO

Simultaneous localization and mapping (SLAM) refers to techniques for autonomously constructing a map of an unknown environment while, at the same time, locating the robot in this map. RatSLAM, a prevalent method, is based on the navigation system found in rodent brains. It has served as a base algorithm for other bioinspired approaches, and its implementation has been extended to incorporate new features. This work proposes xRatSLAM: an extensible, parallel, open-source framework applicable for developing and testing new RatSLAM variations. Tests were carried out to evaluate and validate the proposed framework, allowing the comparison of xRatSLAM with OpenRatSLAM and assessing the impact of replacing framework components. The results provide evidence that the maps produced by xRatSLAM are similar to those produced by OpenRatSLAM when they are fed with the same input parameters, which is a positive result, and that implemented modules can be easily changed without impacting other parts of the framework.


Assuntos
Robótica , Robótica/métodos , Algoritmos , Encéfalo
10.
Malar J ; 20(1): 106, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608024

RESUMO

BACKGROUND: Vector control for malaria prevention relies most often on the use of insecticide-treated bed net (ITNs) and indoor residual spraying. Little is known about the longevity of long-lasting insecticidal nets (LLINs) in the Americas. The physical integrity and insecticide retention of LLINs over time were monitored after a bed net distribution campaign to assess community practices around LLIN care and use in Waspam, northeastern Nicaragua. METHODS: At least 30 nets were collected at 6, 12, 24, and 36 months post distribution. Physical integrity was measured by counting holes and classifying nets into categories (good, damaged, and too torn) depending on a proportionate hole index (pHI). Insecticide bioefficacy was assessed using cone bioassays, and insecticide content measured using a cyanopyrethroid field test (CFT). RESULTS: At 6 months, 87.3 % of LLINs were in good physical condition, while by 36 months this decreased to 20.6 %, with 38.2 % considered 'too torn.' The median pHI increased from 7 at the 6-month time point to 480.5 by 36 months. After 36 months of use, median mortality in cone bioassays was 2 % (range: 0-6 %) compared to 16 % (range: 2-70 %) at 6 months. There was a decrease in the level of deltamethrin detected on the surface of the LLINs with 100 % of tested LLINs tested at 12 months and 24 months crossing the threshold for being considered a failed net by CFT. CONCLUSIONS: This first comprehensive analysis of LLIN durability in Central America revealed rapid loss of chemical bioefficacy and progressive physical damage over a 36-month period. Use of these findings to guide future LLIN interventions in malaria elimination settings in Nicaragua, and potentially elsewhere in the Americas, could help optimize the successful implementation of vector control strategies.


Assuntos
Anopheles/efeitos dos fármacos , Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Inseticidas/farmacologia , Malária/prevenção & controle , Controle de Mosquitos/estatística & dados numéricos , Mosquitos Vetores/efeitos dos fármacos , Permetrina/farmacologia , Animais , Bioensaio , Feminino , Nicarágua , Estações do Ano
11.
Mol Biol Rep ; 48(2): 1233-1241, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33475929

RESUMO

The literature has shown the beneficial effects of microcurrent (MC) therapy on tissue repair. We investigated if the application of MC at 10 µA/90 s could modulate the expression of remodeling genes transforming growth factor beta (Tgfb), connective tissue growth factor (Ctgf), insulin-like growth factor 1 (Igf1), tenascin C (Tnc), Fibronectin (Fn1), Scleraxis (Scx), Fibromodulin (Fmod) and tenomodulin in NIH/3T3 fibroblasts in a wound healing assay. The cell migration was analyzed between days 0 and 4 in both fibroblasts (F) and fibroblasts + MC (F+MC) groups. On the 4th day, cell viability and gene expression were also analyzed after daily MC application. Higher expression of Ctgf and lower expression of Tnc and Fmod, respectively, were observed in the F+MC group in relation to F group (p < 0.05), and no difference was observed between the groups for the genes Tgfb, Fn1 and Scx. In cell migration, a higher number of cells in the scratch region was observed in group F+MC (p < 0.05) compared to group F on the 4th day, and the cell viability assay showed no difference between the groups. In conclusion, MC therapy at an intensity/time of 10 µA/90 s with 4 daily applications did not affect cell viability, stimulated fibroblasts migration with the involvement of Ctgf, and reduced the Tnc and Fmod expression.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/genética , Terapia por Estimulação Elétrica , Fibromodulina/genética , Tenascina/genética , Cicatrização/efeitos da radiação , Animais , Movimento Celular/efeitos da radiação , Fibronectinas/genética , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Fator de Crescimento Insulin-Like I/genética , Camundongos , Células NIH 3T3 , Fator de Crescimento Transformador beta1/genética , Cicatrização/genética
12.
Biomed Chromatogr ; 35(9): e5147, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33885176

RESUMO

Rivaroxaban is an anticoagulant (orally active direct Xa inhibitor) considered to reduce the risk of stroke and systemic embolism and treat deep vein thrombosis, pulmonary embolism, and other cardiovascular complications. Bioanalytical methods for rivaroxaban quantification in plasma are necessary for application in pharmacokinetic studies, as well as in drug therapeutic monitoring. In this work, we developed and validated a sensitive bioanalytical method using LC-MS/MS for rivaroxaban quantification in human plasma using an one-step liquid-liquid extraction. The linear concentration range was 1-600 ng/mL. The bioanalytical method was also applied to pharmacokinetic studies in healthy volunteers under fasting and fed conditions. The results demonstrated that the method is rapid, sensitive, and adequate for application in pharmacokinetic studies.


Assuntos
Cromatografia Líquida/métodos , Rivaroxabana/sangue , Rivaroxabana/farmacocinética , Espectrometria de Massas em Tandem/métodos , Adolescente , Adulto , Humanos , Limite de Detecção , Modelos Lineares , Extração Líquido-Líquido , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Rivaroxabana/química , Rivaroxabana/isolamento & purificação , Adulto Jovem
13.
Sensors (Basel) ; 21(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34577350

RESUMO

We investigated the magnetization dynamics through the magnetoimpedance effect in an integrated YIG/Pt-stripline system in the frequency range of 0.5 up to 2.0 GHz. Specifically, we explore the dependence of the dynamic magnetic behavior on the field orientation by analyzing beyond the traditional longitudinal magnetoimpedance effect of the transverse and perpendicular setups. We disclose here the strong dependence of the effective damping parameter on the field orientation, as well as verification of the very-low damping parameter values for the longitudinal and transverse configurations. We find considerable sensitivity results, bringing to light the facilities to integrate ferrimagnetic insulators in current and future technological applications.

15.
J Surg Oncol ; 121(5): 707-717, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31970764

RESUMO

The Brazilian Society of Surgical Oncology was established over 30 years ago. Despite that, surgical oncology was finally recognized as a Board-Certified medical specialty in 2017 and has strengthened its role in the standardization of surgical and multimodal approaches in our country. This article aims to describe the process and the main challenges of the specialists training who are qualified for job opportunities and who meet the expectations of the recently created competence matrix for surgical oncologists in Brazil. Thus, we hope to expose the challenges of teaching surgical oncology, describe its history and experiences in important country services, and outline the minimum requirements for creating a more humanistic surgical oncologist who is updated and fully committed with multidisciplinary treatment for cancer patients. We conclude that the main characteristic that the surgical oncologist must have is the ability to offer holistic treatments to the patient, based on the highest level of evidence, love, and compassion, to direct the treatment and understand all of the afflictions that arise with a cancer diagnosis. Moreover, the surgical oncologist in training and in the field must be continuously updating himself to offer the best options of treatment to patients.


Assuntos
Currículo , Educação de Pós-Graduação em Medicina/organização & administração , Oncologia Cirúrgica/educação , Brasil , Certificação , Competência Clínica/normas , Humanos , Internato e Residência/organização & administração , Sociedades Médicas , Especialização , Conselhos de Especialidade Profissional
16.
J Surg Oncol ; 121(5): 743-758, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31970785

RESUMO

INTRODUCTION: Soft tissue sarcomas (STSs) are rare tumors and constitute only 1% of all tumors in adults. Indeed, due to their rarity, most cases in Brazil are not treated according to primary international guidelines. METHODS: This consensus addresses the treatment of STSs in the extremities. It was made by workgroups from Brazilian Societies of Surgical Oncology, Orthopaedics, Clinical Oncology, Pathology, Radiology and Diagnostic Imaging, and Radiation Oncology. The workgroups based their arguments on the best level of evidence in the literature and recommendations were made according to diagnosis, staging, and treatment of STSs. A meeting was held with all the invited experts and the topics were presented individually with the definition of the degree of recommendation, based on the levels of evidence in the literature. RESULTS: Risk factors and epidemiology were described as well as the pathological aspects and imaging. All recommendations are described with the degree of recommendation and levels of evidence. CONCLUSION: Recommendations based on the best literature regional aspects were made to guide professionals who treat STS. Separate consensus on specific treatments for retroperitoneal, visceral, trunk, head and neck sarcomas, and gastrointestinal stromal tumor, are not contemplated into this consensus.


Assuntos
Extremidades/patologia , Sarcoma/terapia , Neoplasias de Tecidos Moles/terapia , Biópsia , Brasil , Quimioterapia Adjuvante , Extremidades/cirurgia , Humanos , Linfonodos/patologia , Metástase Neoplásica/diagnóstico , Metástase Neoplásica/terapia , Estadiamento de Neoplasias , Cuidados Paliativos , Complicações Pós-Operatórias/terapia , Radioterapia Adjuvante , Fatores de Risco , Sarcoma/diagnóstico por imagem , Sarcoma/patologia , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologia
17.
Chem Biodivers ; 17(9): e2000369, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32644295

RESUMO

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.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Euphorbia/química , Látex/química , Terpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Terpenos/química , Terpenos/isolamento & purificação , Células Tumorais Cultivadas
18.
Ecol Lett ; 22(2): 245-255, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30548766

RESUMO

Climate is widely recognised as an important determinant of the latitudinal diversity gradient. However, most existing studies make no distinction between direct and indirect effects of climate, which substantially hinders our understanding of how climate constrains biodiversity globally. Using data from 35 large forest plots, we test hypothesised relationships amongst climate, topography, forest structural attributes (stem abundance, tree size variation and stand basal area) and tree species richness to better understand drivers of latitudinal tree diversity patterns. Climate influences tree richness both directly, with more species in warm, moist, aseasonal climates and indirectly, with more species at higher stem abundance. These results imply direct limitation of species diversity by climatic stress and more rapid (co-)evolution and narrower niche partitioning in warm climates. They also support the idea that increased numbers of individuals associated with high primary productivity are partitioned to support a greater number of species.


Assuntos
Biodiversidade , Árvores , Clima
19.
J Neuroinflammation ; 16(1): 218, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727149

RESUMO

BACKGROUND: The development of new therapeutic strategies to treat amyotrophic lateral sclerosis (ALS) is of utmost importance. The use of cyclic nitroxides such as tempol may provide neuroprotection and improve lifespan. We investigated whether tempol (50 mg/kg) presents therapeutic potential in SOD1G93A transgenic mice. METHODS: Tempol treatment began at the asymptomatic phase of the disease (10th week) and was administered every other day until week 14, after which it was administered twice a week until the final stage of the disease. The animals were sacrificed at week 14 (initial stage of symptoms-ISS) and at the end stage (ES) of the disease. The lumbar spinal cord of the animals was dissected and processed for use in the following techniques: Nissl staining to evaluate neuronal survival; immunohistochemistry to evaluate astrogliosis and microgliosis (ISS and ES); qRT-PCR to evaluate the expression of neurotrophic factors and pro-inflammatory cytokines (ISS); and transmission electron microscopy to evaluate the alpha-motoneurons (ES). Behavioral analyses considering the survival of animals, bodyweight loss, and Rotarod motor performance test started on week 10 and were performed every 3 days until the end-stage of the disease. RESULTS: The results revealed that treatment with tempol promoted greater neuronal survival (23%) at ISS compared to untreated animals, which was maintained until ES. The intense reactivity of astrocytes and microglia observed in vehicle animals was reduced in the lumbar spinal cords of the animals treated with tempol. In addition, the groups treated with tempol showed reduced expression of proinflammatory cytokines (IL1ß and TNFα) and a three-fold decrease in the expression of TGFß1 at ISS compared with the group treated with vehicle. CONCLUSIONS: Altogether, our results indicate that treatment with tempol has beneficial effects, delaying the onset of the disease by enhancing neuronal survival and decreasing glial cell reactivity during ALS progression in SOD1G93A mice.


Assuntos
Esclerose Lateral Amiotrófica/fisiopatologia , Óxidos N-Cíclicos/uso terapêutico , Inflamação/tratamento farmacológico , Destreza Motora/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Medula Espinal/efeitos dos fármacos , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Óxidos N-Cíclicos/farmacologia , Modelos Animais de Doenças , Feminino , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/metabolismo , Masculino , Camundongos , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Destreza Motora/fisiologia , Fármacos Neuroprotetores/farmacologia , Teste de Desempenho do Rota-Rod , Marcadores de Spin , Medula Espinal/metabolismo , Medula Espinal/patologia , Superóxido Dismutase-1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
Proc Natl Acad Sci U S A ; 113(5): 1174-9, 2016 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-26768844

RESUMO

Probing the surface morphology of microthin fibers such as naturally occurring biofibers is essential for understanding their structural properties, biological function, and mechanical performance. The state-of-the-art methods for studying the surfaces of biofibers are atomic force microscopy imaging and scanning electron microscopy, which well characterize surface geometry of the fibers but provide little information on the local interaction potential of the fibers with the surrounding material. In contrast, complex nematic fluids respond very well to external fields and change their optical properties upon such stimuli. Here we demonstrate that liquid crystal droplets deposited on microthin biofibers--including spider silk and cellulosic fibers--reveal characteristics of the fibers' surface, performing as simple but sensitive surface sensors. By combining experiments and numerical modeling, different types of fibers are identified through the fiber-to-nematic droplet interactions, including perpendicular and axial or helicoidal planar molecular alignment. Spider silks align nematic molecules parallel to fibers or perpendicular to them, whereas cellulose aligns the molecules unidirectionally or helicoidally along the fibers, indicating notably different surface interactions. The nematic droplets as sensors thus directly reveal chirality of cellulosic fibers. Different fiber entanglements can be identified by depositing droplets exactly at the fiber crossings. More generally, the presented method can be used as a simple but powerful approach for probing the surface properties of small-size bioobjects, opening a route to their precise characterization.


Assuntos
Celulose/química , Seda/química , Aranhas , Animais , Sondas Moleculares , Propriedades de Superfície
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