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1.
Clin Transplant Res ; 38(3): 241-245, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39344700

RESUMO

Progressive familial intrahepatic cholestasis type 2 (PFIC2) is an autosomal recessive disorder typically presenting in infancy with cholestasis and rapidly progressing to cirrhosis. PFIC has been associated with an elevated risk of hepatocellular carcinoma (HCC), a neoplasm that is uncommon in children. PFIC type 4 has the strongest link to this type of cancer, although a few cases have also been connected to PFIC2. Herein, we report the case of a 2-year-old boy who underwent liver transplantation due to PFIC2. Histological examination showed cirrhosis and four small HCCs. Over a 20-year period following the transplantation, there was no recurrence of the disease or HCC. Although rare, HCC development can occur in PFIC and may complicate the prognosis. Liver transplantation offers a potential cure for both the metabolic disease and the neoplasm.

2.
Am J Case Rep ; 25: e942951, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38561939

RESUMO

BACKGROUND Primary central nervous system diffuse large B-cell lymphoma (DLBCL) is an extremely aggressive brain disease that rarely affects immunocompetent non-elderly patients, particularly with hemorrhagic presentation. Brain magnetic resonance imaging (MRI) plays an important role in the diagnosis of this entity, which typically demonstrates restricted diffusion and a T2 hypointense appearance, suggesting hypercellularity. CASE REPORT A 44-year-old man came to the emergency department with a persistent and treatment-resistant bilateral frontal headache that had been bothering him for the past 3 weeks. Upon conducting a neurological assessment, the patient displayed temporal disorientation and incoherent speech, but without any observable motor deficits. A non-contrast enhanced brain computed tomography scan was carried out, revealing a hyperattenuating, space-occupying lesion and hemorrhage in the left hemisphere of the brain. Subsequently, brain MRI demonstrated hypointense signal on T2-weighted images, restricted diffusion, and homogeneous lesional contrast enhancement, suggesting a very cellular expansive lesion with hemorrhage. To establish a definitive diagnosis, a brain biopsy was undertaken, confirming the presence of DLBCL of the primary central nervous system (germinal center phenotype). CONCLUSIONS Hemorrhagic presentation of primary central nervous system DLBCL occurs very rarely, particularly in non-elderly immunocompetent patients. Brain MRI plays an important role in the diagnosis of this entity, which allows differentiation from high-grade glial or other lesions that present more frequently with hemorrhage. Therefore, it is crucial to suspect lymphoma before surgical intervention for appropriate patient management.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma Difuso de Grandes Células B , Adulto , Humanos , Masculino , Encéfalo/patologia , Neoplasias do Sistema Nervoso Central/complicações , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Hemorragia , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/patologia , Imageamento por Ressonância Magnética/métodos
3.
Med Sci Sports Exerc ; 56(5): 796-804, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38480490

RESUMO

INTRODUCTION: Platelet-rich plasma (PRP) has been used for arthroscopic rotator cuff repairs (aRCR), but no studies have addressed the impact of platelet concentration. The primary aim was to evaluate whether the PRP cell concentration has an effect on tendon healing after aRCR compared with surgery alone. The secondary aim was to assess the functional and pain outcomes. MATERIALS AND METHODS: A systematic review was performed with searches in the MEDLINE (PubMed), Scopus, Web of Science, and Cochrane (Central) databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Metanalytic procedures were performed for randomized controlled trials (RCTs), and a subgroup analysis was used for studies with target (approximately 10 6 cells·µL -1 ) or below-target PRP cellular concentrations (app. 5 × 10 5 cells·µL -1 ) regarding the primary outcome of tendon healing. RESULTS: This review included 10 studies (8 RCTs) with 342 patients in the aRCR + PRP group and 344 patients with isolated aRCR. The risk of bias was low to intermediate (6/4, respectively). Meta-analysis of the RCT revealed that the aRCR + high-concentration PRP group had an approximately 3.9-fold higher chance of healing than the non-PRP group (odds ratio, 3.89; 95% confidence interval, 1.78-8.44; P = 0.0007). No significant difference in healing was found between the aRCR + low-concentration PRP and non-PRP groups (odds ratio, 2.21; 95% confidence interval, 0.66-7.45; P = 0.2). The Constant-Murley score and University of California Los Angeles scores were significantly improved in the aRCR + PRP groups with more than 12 months of follow-up, and no significant differences were found consistently for the American Shoulder and Elbow Society and visual analog scale scores. CONCLUSIONS: This study highlights that a PRP cell concentration close to the target (10 6 cells·µL -1 ) of patients with aRCR may improve their healing and functional outcomes and that dosing may be potentially useful in therapy.


Assuntos
Plasma Rico em Plaquetas , Lesões do Manguito Rotador , Humanos , Lesões do Manguito Rotador/cirurgia , Manguito Rotador/cirurgia , Resultado do Tratamento , Cicatrização , Artroscopia/métodos
4.
J Clin Endocrinol Metab ; 109(2): 361-369, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-37700637

RESUMO

CONTEXT: Antidrug antibodies (ADA) can potentially affect drug pharmacokinetics, safety, and efficacy. OBJECTIVE: This work aimed to evaluate treatment-emergent (TE) ADA in tirzepatide (TZP)-treated participants across 7 phase 3 trials and their potential effect on pharmacokinetics, efficacy, and safety. METHODS: ADA were assessed at baseline and throughout the study until end point, defined as week 40 (SURPASS-1, -2, and -5) or week 52 (SURPASS-3, -4, Japan-Mono, and Japan-Combo). Samples for ADA characterization were collected at SURPASS trial sites. Participants included ADA-evaluable TZP-treated patients with type 2 diabetes (N = 5025). Interventions included TZP 5, 10, or 15 mg. ADA were detected and characterized for their ability to cross-react with native glucose-dependent insulinotropic polypeptide (nGIP) and glucagon-like peptide-1 (nGLP-1), neutralize tirzepatide activity on GIP and GLP-1 receptors, and neutralize nGIP and nGLP-1. RESULTS: TE ADA developed in 51.1% of tirzepatide-treated patients. Proportions were similar across dose groups. Maximum ADA titers ranged from 1:20 to 1: 81 920 among TE ADA+ patients. Neutralizing antibodies (NAb) against TZP activity on GIP and GLP-1 receptors were observed in 1.9% and 2.1% of patients, respectively. Less than 1.0% of patients had cross-reactive NAb against nGIP or nGLP-1. TE ADA status, ADA titer, and NAb status had no effect on the pharmacokinetics or efficacy of TZP. More TE ADA+ patients experienced hypersensitivity reactions or injection site reactions than TE ADA- patients. The majority of hypersensitivity and injection site reactions were nonserious and nonsevere, and most events occurred and/or resolved irrespective of TE ADA status or titer. CONCLUSION: Immunogenicity did not affect TZP pharmacokinetics or efficacy. The majority of hypersensitivity or injection site reactions experienced by TE ADA+ patients were mild to moderate in severity.


Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Reação no Local da Injeção , Polipeptídeo Inibidor Gástrico/uso terapêutico , Anticorpos Neutralizantes , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Hipoglicemiantes/efeitos adversos , Receptor do Peptídeo Semelhante ao Glucagon 1
6.
Rev. adm. pública (Online) ; 57(1): 0-0209, jan.-fev. 2023. tab, graf
Artigo em Português | LILACS | ID: biblio-1431415

RESUMO

Resumo O capital social é uma lente teórica importante para explicar os relacionamentos interorganizacionais e a construção da resiliência nas redes de suprimentos. Para corroborar essa perspectiva, este estudo visa identificar quais atributos do capital social contribuem para explicar o desenvolvimento da resiliência nas redes de suprimentos da administração pública e de que forma eles se combinam nessa explicação. Para tanto, foi realizada uma pesquisa qualitativa e descritiva que utilizou entrevistas com a técnica da grade de repertório para a coleta de dados. Os dados foram analisados mediante a análise de conteúdo de Honey e a análise de coincidência (CNA). Os resultados da pesquisa indicam que o capital social se mostrou fundamental para desenvolver resiliência nas redes de suprimentos na administração pública, por meio dos atributos de compartilhamento de informações técnicas; precisão na comunicação; antecipação na comunicação de informações relevantes; reciprocidade; confiança; transparência e comprometimento. A originalidade do estudo reside na utilização da teoria do capital social em estudos sobre resiliência na administração pública e na adoção de um método de coleta e análise de dados robusto e ainda não explorado em pesquisas na administração pública brasileira. As principais contribuições do estudo foram: 1) destacar o capital social como constructo multinível que influencia o desenvolvimento da resiliência; 2) ampliar os estudos sobre resiliência na administração pública; 3) fornecer informações que podem ser utilizadas por gestores públicos, a fim de evitar ou minimizar a ocorrência de riscos que comprometam a prestação de serviços públicos e 4) adotar um método de pesquisa inédito na administração pública brasileira.


Resumen El capital social es una lente teórica importante para explicar las relaciones entre organizaciones y desarrollar la resiliencia en las redes de suministro. Corroborando esta perspectiva, este estudio tiene como objetivo identificar qué atributos del capital social contribuyen a explicar el desarrollo de la resiliencia en las redes de suministro de la administración pública y cómo se combinan en esta explicación. Se realizó una investigación cualitativa y descriptiva, utilizando entrevistas con la técnica de rejilla de repertorio para la recolección de datos. Los datos se analizaron utilizando el análisis de contenido de Honey y el análisis de coincidencia (CNA). Los resultados de la investigación indican que el capital social demostró ser fundamental para desarrollar resiliencia en las redes de abastecimiento de la administración pública, a través de los atributos de compartición de información técnica, precisión en la comunicación, anticipación en la comunicación de información relevante, reciprocidad, confianza, transparencia y compromiso. La originalidad del estudio radica en el uso de la teoría del capital social en estudios sobre resiliencia en la administración pública y en la adopción de un método robusto de recopilación y análisis de datos que aún no ha sido explorado en investigaciones en la administración pública brasileña. Las principales contribuciones del estudio fueron: (1) resaltar el capital social como un constructo multinivel que influye en el desarrollo de la resiliencia, (2) ampliar los estudios sobre resiliencia en la administración pública, (3) proporcionar información que pueda ser utilizada por los administradores para evitar o minimizar la ocurrencia de riesgos que comprometan la prestación de los servicios públicos y (4) adoptar un método de investigación inédito en la administración pública brasileña.


Abstract Social capital is an important theoretical lens for explaining interorganizational relationships and building resilience in supply networks. This study corroborates this perspective, aiming to identify which attributes of social capital contribute to explaining the development of resilience in public administration supply networks and how they combine in this explanation. A qualitative and descriptive research was carried out, using interviews with the repertoire grid technique for data collection. Data were analyzed using Honey's content analysis and coincidence analysis (CNA). The research results indicate that social capital proved to be fundamental to developing resilience in supply networks in public administration, through the attributes of sharing technical information, precision in communication, anticipation in communicating relevant information, reciprocity, trust, transparency, and commitment. The originality of the study lies in the use of social capital theory in studies on resilience in public administration and in the adoption of a robust data collection and analysis method that has not yet been explored in research in Brazilian public administration. The main contributions of the study were: (1) to highlight social capital as a multilevel construct that influences the development of resilience, (2) to expand studies on resilience in public administration, (3) to provide information that public managers can use to avoid or minimize the risks that jeopardize the provision of public services, and (4) to adopt an unprecedented research method in the Brazilian public administration.


Assuntos
Administração Pública , Brasil , Capital Social
7.
Ann Thorac Surg ; 115(2): e37-e39, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35314157

RESUMO

Angiomyolipomas are benign mesenchymal tumors classified as PEComas, consisting of blood vessels, smooth muscle, and fat, and generally found in renal tissue. Extrarenal cases are uncommon, and those of the mediastinum are rare, with only 23 reports in the literature. We present a successful surgically managed case of a symptomatic 44-year-old woman with a large heart-shaped mediastinal angiomyolipoma in the right hemithorax associated with chylopericardium.


Assuntos
Angiomiolipoma , Hamartoma , Neoplasias Renais , Derrame Pericárdico , Feminino , Humanos , Adulto , Angiomiolipoma/diagnóstico , Angiomiolipoma/diagnóstico por imagem , Mediastino/patologia , Derrame Pericárdico/diagnóstico por imagem , Derrame Pericárdico/etiologia , Hamartoma/complicações , Neoplasias Renais/patologia
8.
Commun Biol ; 5(1): 804, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948611

RESUMO

The interplay among neuropathological mechanisms underlying Alzheimer's disease (AD), as neuroinflammation and amyloid-beta (Aß), as well their impact on neuronal function remains elusive. A major gap in knowledge is the functional impact of neuroinflammation. The posterior cingulate cortex (PCC), as the most prominent site of amyloid pathology in AD, is a pivotal region to investigate the concomitant presence of pathophysiological mechanisms such as microglia activation, indexing neuroinflammation, and changes in task related activity. Here we used a dual PET approach to simultaneously study Aß load and neuroinflammation (TSPO uptake marker), using 11C-PiB and 11C-PK11195 radiotracers, respectively and fMRI to study task related neural activation in an AD sample (n = 19) and matched controls (n = 19). Here we show significantly increased Aß deposition, neuroinflammation and brain activity related to a visual object working memory task in this key region. Microglia activation was associated with increased brain activity specifically in patients, independently of amyloid binding, raising the possibility that abnormal brain activity might be restored in clinical trials aimed at reducing microglia activation.


Assuntos
Doença de Alzheimer , Amiloidose , Doença de Alzheimer/metabolismo , Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Amiloidose/metabolismo , Encéfalo/metabolismo , Humanos , Imageamento por Ressonância Magnética , Doenças Neuroinflamatórias , Tomografia por Emissão de Pósitrons , Receptores de GABA/metabolismo
9.
Rev. bras. ativ. fís. saúde ; 27: 1-7, fev. 2022. quad, fig
Artigo em Inglês | LILACS | ID: biblio-1418245

RESUMO

Recent systematic reviews point out the positive acute effects of physical activity on executive func-tions in children and adolescents, but the chronic effects in this age group are still uncertain. This study aims to describe a systematic review with meta-analysis protocol to elucidate the chronic effects of physical activity at school on the executive functions and attention of children and ad-olescents, considering the effect-moderators and examining different interventions in the school environment. A systematic search will be carried out for studies published in the PUBMED, Em-base, Scopus and Cochrane Library databases. Studies that meet the following predefined criteria (PICOS criteria) will be included: 1) studies conducted with healthy children and adolescents (6-18 years-old), 2) studies with physical activity interventions in school, 3) studies conducted with a control group, and 4) studies with cognitive flexibility, working memory, inhibitory control and attention outcomes. Target outcomes will be extracted as pre-and post-test values. Intervention time, frequencies, intensity, volume, session time, and intervention type will be extracted for meta-regres-sion analysis. For methodological quality will be using the tool for the assessment of study quality and reporting in exercise training studies. Pooled effect estimates will be calculated from the scores of changes between baseline and end of interventions. The effect size will be expressed as Cohens' and presented as standardized mean differences and calculations will be performed using random-effects models. Statistical heterogeneity will be evaluated by Cochran's Q statistic and the I² inconsistency test. The meta-analyses will be performed using OpenMeta[Analyst]


Revisões sistemáticas recentes apontam os efeitos agudos positivos da atividade física nas funções executivas em crianças e adolescentes, mas os efeitos crônicos nessa faixa etária ainda são incertos. Este artigo tem como objetivo descrever o protocolo de revisão sistemática e meta-análise que busca elucidar os efeitos crônicos da atividade física no ambiente escolar sobre as funções executivas e atenção de crianças e adolescentes, conside-rando os efeitos-moderadores e examinando diferentes tipos de intervenções no ambiente escolar. Será reali-zada uma busca sistemática de estudos publicados nas bases de dados PUBMED, Embase, Scopus e Cochrane Library. Serão incluídos estudos que atendam aos seguintes critérios pré-definidos (critérios PICOS): 1) estudos realizados com crianças e adolescentes saudáveis (6-18 anos), 2) estudos com intervenções de ativi-dade física na escola, 3) estudos de intervenção, randomizados ou não, realizados com grupo controle e 4) estudos com flexibilidade, memória de trabalho, controle inibitório e resultados de atenção. Os resultados alvo serão extraídos como valores pré e pós-teste. Tempo de intervenção, frequências, intensidade, volume, tempo de sessão e tipo de intervenção serão extraídos para análise de meta-regressão. Para a qualidade metodológica será utilizado o instrumento para avaliação da qualidade do estudo e relato em estudos de treinamento físico. As estimativas de efeito agrupadas serão calculadas a partir das pontuações das mudanças entre a linha de base e o final das intervenções. O tamanho do efeito será expresso em Cohens e apresentado como diferenças médias padronizadas e os cálculos serão realizados utilizando modelos de efeitos aleatórios. A heterogeneida-de estatística será avaliada pela estatística Q de Cochran e pelo teste de inconsistência I². As meta-análises serão realizadas usando OpenMeta[Analyst]


Assuntos
Política Pública , Criança , Adolescente , Promoção da Saúde
10.
J Clin Pathol ; 75(4): 274-278, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33649143

RESUMO

AIMS: Cholangiocarcinoma (CC) is a rare tumour arising from the biliary tract epithelium. The aim of this study was to perform a genomic characterisation of CC tumours and to implement a model to differentiate extrahepatic (ECC) and intrahepatic (ICC) cholangiocarcinoma. METHODS: DNA extracted from tumour samples of 23 patients with CC, namely 10 patients with ECC and 13 patients with ICC, was analysed by array comparative genomic hybridisation. A support vector machine algorithm for classification was applied to the genomic data to distinguish between ICC and ECC. A survival analysis comparing both groups of patients was also performed. RESULTS: With these whole genome results, we observed several common alterations between tumour samples of the same CC anatomical type, namely gain of Xp and loss of 3p, 11q11, 14q, 16q, Yp and Yq in ICC tumours, and gain of 16p25.3 and loss of 3q26.1, 6p25.3-22.3, 12p13.31, 17p, 18q and Yp in ECC tumours. Gain of 2q37.3 was observed in the samples of both tumour subtypes, ICC and ECC. The developed genomic model comprised four chromosomal regions that seem to enable the distinction between ICC and ECC, with an accuracy of 71.43% (95% CI 43% to 100%). Survival analysis revealed that in our cohort, patients with ECC survived on average 8 months less than patients with ICC. CONCLUSIONS: This genomic characterisation and the introduction of genomic models to clinical practice could be important for patient management and for the development of targeted therapies. The power of this genomic model should be evaluated in other CC populations.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/patologia , Variações do Número de Cópias de DNA , Genômica , Humanos
11.
J Gastrointest Surg ; 25(3): 698-707, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32410177

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the third cause of cancer-related death. Current clinical/pathological criteria contribute to risk stratification, but are far from the desired on individualized medicine. Recently, HCC classifications have been published based on immunohistochemical and morphological features. METHODS: A retrospective review of patients submitted to surgical treatment-partial hepatectomy (PH) or liver transplantation (LT), with pathological diagnosis of HCC, in a 9-year period (2007-2015) was performed. RESULTS: Applying the classification of Srivastava et al. (#1), based on the expression of CD31, p53, AFP and CD44, tumour size and presence of vascular invasion, HCC were categorized as low- and high-risk HCC. With the classification of Tsujikawa et al. (#2), HCC were classified into biliary/stem cell marker positive, Wnt signalling positive and the "all negative" HCC, according to the expression of CK19, SALL4, ß-catenin glutamine synthetase, EpCAM and p53. There were sixty-six patients (53 males; 13 females), with median age of 64.5 ± 9.46 years (range 38-86), with solitary HCC, comprehending 37 PH (56.1%) and 29 LT (43.9%). The mean overall survival (OS) was 75.4 ± 6.9 months. Biliary/stem cell type of HCC was a predictive factor of worse OS on the overall population (24.4 versus 78.3 months, p = 0.032) and in PH cohort (11.5 versus 64.01 months, p = 0.016), on uni- and multivariate analyses. CONCLUSION: These results support the relevance of a risk stratification classification of HCC. Classification #2 seems adequate to our reality demonstrating OS impact, allowing its application in future biopsies, prompting individualized medicine.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Seleção de Pacientes , Estudos Retrospectivos , Células-Tronco
12.
Cancer Manag Res ; 12: 11689-11699, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33244263

RESUMO

PURPOSE: Hepatectomy (Hp) is an alternative approach for the treatment of gastric carcinoma liver metastases (GCLM). However, prognostic factors that may assist patient selection are still controversial. Several pathologic features, such as the growth pattern (GP), associated with prognosis in colorectal cancer liver metastases, were never investigated in GCLM. Our principal aim was to assess if the GP has prognostic impact on GCLM. PATIENTS AND METHODS: Review of the clinical and pathological characteristics of 19 consecutive patients submitted to surgical resection of GCLM with curative intent at our department. Major potential prognostic factors considered were patients' gender, age, timing and extent of Hp, postoperative course, as well as histopathological characteristics of primary and secondary tumors. RESULTS: Major morbidity occurred in four patients, mortality in one. Median and 5-year overall survival were 17 months and 26.7%, respectively. Ten patients developed recurrent disease and two patients survived more than 10 years. Factors independently associated with overall survival were the absence of major morbidity, distal location of the primary tumor, and desmoplastic GP (p<0.05). CONCLUSION: The selection of patients is crucial for the improvement of survival rates of GCLM. Consequently, we demonstrate for the first time that the desmoplastic GP of GCLM is associated with improved outcomes, prompting further research on tumor-host interactions.

14.
Lipids ; 55(2): 185-191, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32045496

RESUMO

Hepatocellular carcinoma and cholangiocarcinoma are the most common primary malignant liver tumors. Since the liver plays a key role in lipid metabolism, the study of serum phospholipid (PL) profiles may provide a better understanding of alterations in hepatic lipid metabolism. In this study, we used a high-resolution HILIC-LC-MS lipidomic approach to establish the serum phospholipidome profile of patients with liver cancer before (T0) and after tumor resection (T1) and a control group (CT) of healthy individuals. After the analysis of PL profiles, we observed that the phospholipidome of patients with liver cancer was significantly modified after the tumor resection procedure. We observed an upregulation of some phosphatidylcholine (PtdCho) species, namely, PtdCho(36:6), PtdCho(42:6), PtdCho(38:5), PtdCho(36:5), PtdCho(38:6) and choline plasmalogens (PlsCho), and/or 1-O-alkyl-2-acyl-glycerophosphocholine (PakCho) in patients with liver cancer at T0 compared to the CT group, and a downregulation after tumor resection (T1) when compared to T0. These results show that LC-MS can detect different serum PL profiles in patients with liver cancer, before and after tumor resection, by defining a specific PL fingerprint that was used to determine the effect of tumor and tumor resection on lipid metabolism.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Lipidômica/métodos , Neoplasias Hepáticas/cirurgia , Fosfolipídeos/sangue , Idoso , Animais , Estudos de Casos e Controles , Cromatografia Líquida , Feminino , Humanos , Neoplasias Hepáticas/sangue , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Fosfatidilcolinas/sangue , Plasmalogênios/sangue
16.
Int J Oncol ; 56(3): 709-727, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31922240

RESUMO

Cholangiocarcinoma (CC) is an aggressive liver tumor with limited therapeutic options. Natrium­iodide symporter (NIS) mediates the uptake of iodine by the thyroid, representing a key component in metabolic radiotherapy using iodine­131 (131I) for the treatment of thyroid cancer. NIS expression is increased in CC, providing the opportunity for a novel therapeutic approach for this type of tumor. Thus, in this study, we aimed to evaluate therapeutic efficacy of 131I in two human CC cell lines. Uptake experiments analyzed the 131I uptake profiles of the tumor cell lines under study. The cells were irradiated with various doses of 131I to evaluate and characterize the effects of metabolic radiotherapy. NIS protein expression was assessed by immunofluorescence methods. Cell survival was evaluated by clonogenic assay and flow cytometry was used to assess cell viability, and the type of death and alterations in the cell cycle. The genomic and epigenetic characterization of both CC cells was performed before and after irradiation. NIS gene expression was evaluated in the CC cells by RT­qPCR. The results revealed that CC cells had a higher expression of NIS. 131I induced a decrease in cell survival in a dose­dependent manner. With the increasing irradiation dose, a decrease in cell viability was observed, with a consequent increase in cell death by initial apoptosis. Karyotype and array comparative genomic hybridization (aCGH) analyses revealed that both CC cell lines were near­triploid with several numerical and structural chromosomal rearrangements. NIS gene expression was increased in the TFK­1 and HuCCT1 cells in a time­dependent manner. On the whole, the findings of this study demonstrate that the presence of NIS in cholangiocarcinoma cell lines is crucial for the decreased cell viability and survival observed following the exposure of cholangiocarcinoma cells to 131I.


Assuntos
Neoplasias dos Ductos Biliares/radioterapia , Morte Celular/efeitos da radiação , Colangiocarcinoma/fisiopatologia , Variação Estrutural do Genoma/efeitos da radiação , Radioisótopos do Iodo/uso terapêutico , Simportadores/genética , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Colangiocarcinoma/radioterapia , Variações do Número de Cópias de DNA/efeitos da radiação , Metilação de DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Radioisótopos do Iodo/farmacocinética , Simportadores/metabolismo
17.
J Immunol ; 203(9): 2451-2458, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31562208

RESUMO

Granuloma formation is a hallmark of several infectious diseases, including those caused by Mycobacterium sp These structures are composed of accumulations of inflammatory cells, and it has been shown that cytokines such as IFN-γ and TNF-α are required for granuloma assembly during M. avium infections in mice. Macrophages (MΦs) insensitive to IFN-γ (MIIG) mice have MΦs, monocytes, and dendritic cells that are unresponsive to IFN-γ. We observed that although IFN-γ-/- mice present an exacerbated infection, the same is not true for MIIG animals, where the same levels of protection as the wild-type animals were observed in the liver and partial protection in the spleen. Unlike IFN-γ-/- mice, MIIG mice still develop well-defined granulomas, suggesting that IFN-γ-mediated MΦ activation is not required for granuloma assembly. This work also shows that MIIG animals exhibit increased cell recruitment with higher CD4+ T cells numbers as well as increased IFN-γ and TNF-α expression, suggesting that TNF-α may have a role in protection and may compensate the lack of MΦ response to IFN-γ in the MIIG model. TNF-α-deficient MIIG mice (MIIG.TNF-α-/-) exhibited increased bacterial burdens when compared with MIIG mice. These results suggest that in the absence of IFN-γ signaling in MΦs, TNF-α has a protective role against M. avium.


Assuntos
Interferon gama/fisiologia , Ativação de Macrófagos/imunologia , Mycobacterium avium/imunologia , Fator de Necrose Tumoral alfa/fisiologia , Animais , Linfócitos T CD4-Positivos/fisiologia , Granuloma/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais
18.
Cytometry B Clin Cytom ; 96(6): 490-495, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30828998

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent the most common primary liver malignancies whose outcome is influenced by the immune response. METHODS: In this study, we have functionally characterized, by flow cytometry, circulating myeloid dendritic cells (mDCs) and FcεRI+ monocytes in a group of healthy individuals (n = 10) and in a group of patients with HCC (n = 19) and CCA (n = 8), at the time point of the surgical resection (T0) and once the patient had recovered from surgery (T1). Moreover, we proceeded to a more in depth phenotypic characterization of the FcεRI+ monocyte subpopulation. RESULTS: A significant decrease in the frequency of TNFα producing FcεRI+ monocytes and mDCs in HCC and CCA patients when compared to the group of healthy individuals was observed, and a close association between FcεRI+ monocytes and mDCs dysfunction was identified. In addition, the phenotypic characteristics of FcεRI+ monocytes from healthy individuals strongly suggest that this population drives to mDCs, which matches with the fact that both populations are functionally affected. CONCLUSIONS: The frequency and the function of circulating mDCs and FcεRI+ monocytes are affected in both HCC and CCA patients, and FcεRI+ monocytes could represent those fated to become mDCs. © 2019 International Clinical Cytometry Society.


Assuntos
Carcinoma Hepatocelular/metabolismo , Colangiocarcinoma/metabolismo , Células Dendríticas/metabolismo , Neoplasias Hepáticas/metabolismo , Monócitos/metabolismo , Células Mieloides/metabolismo , Receptores de IgE/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Células Dendríticas/patologia , Feminino , Citometria de Fluxo , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Células Mieloides/patologia , Fenótipo , Receptores de IgE/sangue
19.
Rev. APS ; 22(1): 168-182, 20190101.
Artigo em Português | LILACS | ID: biblio-1102693

RESUMO

O estado do Amazonas abrange municípios ribeirinhos que, devido a suas peculiaridades, são um desafio para organização da Atenção Primária à Saúde (APS). Este estudo objetivou avaliar os atributos essenciais de integralidade e longitudinalidade da APS da mulher em idade reprodutiva em três municípios amazônicos, pois doenças preveníveis pela APS apresentam alta incidência nessa população. Esta é uma pesquisa transversal, de caráter exploratório e abordagem quantitativa, que utilizou o instrumento Avaliação da Atenção Primária (PCATool) Versão Adulto para entrevistar 857 mulheres. Os resultados foram insatisfatórios na avaliação dos dois atributos, longitudinalidade e integralidade, com diferenças significativas entre os municípios. Na avaliação da APS sobre questões de relevância epidemiológica para saúde da mulher amazônica os resultados demonstraram que os serviços de assistência pré-natal e a realização de exame preventivo para o câncer de colo de útero estavam disponíveis para cerca de 90% das mulheres. O aconselhamento para testagem de HIV foi relatado por mais de 60% das mulheres entrevistadas. Assim, este estudo identificou limites e desafios da Atenção Primária a Saúde da mulher nesses municípios, reforçando a importância de processos avaliativos como instrumentos de melhor gerenciamento das políticas públicas em saúde.


The State of Amazonas has riparian municipalities that, due to their peculiarities, are a challenge for the organization of Primary Health Care (PHC). This study aimed to evaluate the integral attributes and longitudinality of PHC to Women's Health in reproductive age in three municipalities of the state, because diseases preventable by PHC are present at high incidence in this population. This is a cross-sectional, exploratory and quantitative study that used the Primary Care Assessment Tool (PCATool) instrument - Adult version - to interview 857 women. The results were unsatisfactory in the evaluation of the two attributes, longitudinality and Integrality, with significant differences between the municipalities. In the PHC evaluation on issues of epidemiological relevance for the health of Amazonian women, the results showed that prenatal care and preventive examination for cervical cancer were available for about 90% of the women. Counseling for HIV testing was reported by more than 60% of the women interviewed. Therefore, this study identified the limits and challenges of Primary Health Care for Women in these municipalities, reinforcing the importance of evaluation processes as tools for better management of public health policies.


Assuntos
Atenção Primária à Saúde , Saúde da Mulher , Integralidade em Saúde , Avaliação em Saúde , Continuidade da Assistência ao Paciente , Gestão em Saúde
20.
Einstein (Säo Paulo) ; 17(1): eAO4410, 2019. graf
Artigo em Português | LILACS | ID: biblio-975111

RESUMO

RESUMO Objetivo: Reduzir a identificação errônea de colírios, por meio do uso de substâncias com cores diferentes. Métodos: Um grupo de 34 voluntários saudáveis foi apresentado a dois grupos de quatro colírios cada. Todos os colírios foram colocados em frascos idênticos sem rótulo. Em um grupo de quatro colírios, todos tinham conteúdos transparentes. No outro grupo, cada um dos quatro possuía uma substância de cor diferente. A cada um foi atribuído um número, e o voluntário foi solicitado a identificá-lo por meio da cor. Medimos o índice de acerto na identificação dos colírios dos dois grupos. Resultados: Os voluntários possuíam nível de formação desde Fundamental incompleto até Pós-Graduação completa, sendo 16 do sexo masculino (48%) e 18 do sexo feminino (52%), com idades variando de 21 até 87 anos. O índice de acerto no grupo de colírios coloridos foi de 88% e, no grupo de colírios transparentes, de 24%. Conclusão: O uso de colorações em colírios pode auxiliar na diferenciação entre os frascos e prevenir a identificação errônea.


ABSTRACT Objective: To reduce the inappropriate identification of eye drops, through the use of different colors. Methods: A group of 34 healthy volunteers was presented to two groups of four eye drops each. All eye drops were placed in identical, unlabelled vials. In one group, all four eye drops were transparent. In the other group, each had a different color. A number was assigned to each eye drop, and the volunteer was asked to identify it by color. We measured the correct index in the identification of the eye drops of the two groups. Results: The volunteers had a level of education from incomplete junior school to complete graduate course, with 16 males (48%) and 18 females (52%), age range of 21 to 87 years. The success rate in the group of colored eye drops was 88% and, in the group of transparent, 24%. Conclusion: The use of colorings in eye drops can help distinguishing the vials and preventing misidentification.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Soluções Oftálmicas , Cor , Escolaridade
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