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1.
Microb Pathog ; 192: 106704, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761893

RESUMO

The indiscriminate use of antimicrobials has led to the emergence of resistant bacteria, especially pathogenic strains of Escherichia coli, which are associated with diseases in animals and humans. The aim of the present study was to characterize E. coli isolates in calves with regards to the presence of virulence genes and investigate the resistance of the isolates to different antimicrobials. Between 2021 and 2023, 456 fecal samples were collected from calves in the Pantanal and Cerrado biomes of the state of Mato Grosso do Sul, Brazil. All samples were subjected to microbiological analysis and disc diffusion antibiogram testing. The polymerase chain reaction method was used to detect virulence genes. Bacterial growth was found in 451 of the 456 samples and biochemically identified as Escherichia coli. All 451 isolates (100 %) exhibited some phenotypic resistance to antimicrobials and 67.62 % exhibited multidrug resistance. The frequency of multidrug-resistant isolates in the Cerrado biome was significantly higher than that in the Pantanal biome (p = 0.0001). In the Cerrado, the most common pathotype was Shiga toxin-producing Escherichia coli (STEC) (28 %), followed by toxigenic Escherichia coli (ETEC) (11 %), enterohemorrhagic Escherichia coli (EHEC) (8 %) and enteropathogenic Escherichia coli (EPEC) (2 %). In most cases, the concomitant occurrence of pathotypes was more common, the most frequent of which were ETEC + STEC (33 %), ETEC + EHEC (15 %) and ETEC + EPEC (3 %). The STEC pathotype (30 %) was also found more frequently in the Pantanal, followed by EHEC (12 %), ETEC (9 %) and EPEC (6 %). The STEC pathotype had a significantly higher frequency of multidrug resistance (p = 0.0486) compared to the other pathotypes identified. The frequency of resistance was lower in strains from the Pantanal biome compared to those from the Cerrado biome. Although some factors are discussed in this paper, it is necessary to clarify the reasons for this difference and the possible impacts of these findings on both animal and human health in the region.


Assuntos
Antibacterianos , Doenças dos Bovinos , Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli , Escherichia coli , Fezes , Testes de Sensibilidade Microbiana , Fatores de Virulência , Animais , Bovinos , Brasil , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/epidemiologia , Fezes/microbiologia , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/epidemiologia , Fatores de Virulência/genética , Escherichia coli Shiga Toxigênica/isolamento & purificação , Escherichia coli Shiga Toxigênica/genética , Escherichia coli Shiga Toxigênica/efeitos dos fármacos , Escherichia coli Êntero-Hemorrágica/genética , Escherichia coli Êntero-Hemorrágica/isolamento & purificação , Escherichia coli Êntero-Hemorrágica/efeitos dos fármacos , Escherichia coli Enterotoxigênica/efeitos dos fármacos , Escherichia coli Enterotoxigênica/genética , Escherichia coli Enterotoxigênica/isolamento & purificação , Proteínas de Escherichia coli/genética
2.
Med Oral Patol Oral Cir Bucal ; 29(1): e78-e86, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37471301

RESUMO

BACKGROUND: Lymphomas affecting the submandibular glands are very uncommon and few reports are currently available in the literature. Therefore, the aim of the current study is to describe the clinical and microscopic features of an original series of lymphomas affecting the submandibular glands. MATERIAL AND METHODS: The pathology files of two institutions were searched for lymphoma cases affecting the submandibular glands. The original hematoxylin and eosin, and immunohistochemical slides were revised by a pathologist for diagnosis confirmation following the revised 4th edition of the World Health Organization classification of tumours of haematopoietic and lymphoid tissues. Clinical data regarding age, sex, clinical manifestation, treatment, follow-up and status at last appointment were retrieved from the patients' medical charts. RESULTS: During the period investigated, 16 cases were included in the study. Females predominated (10:6) with a mean age of 57.8 years-old. Tumors usually presented as asymptomatic swellings. MALT lymphoma represented the most common subtype, followed by diffuse large B cell lymphoma and follicular lymphoma. Three patients died, one of them affected by plasmablastic lymphoma, one by DLBCL and one by MALT lymphoma. CONCLUSIONS: Low-grade B cell lymphomas predominate in the submandibular glands, but DLBCL and other subtypes may also be rarely diagnosed in this salivary gland.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Linfoma Difuso de Grandes Células B , Feminino , Humanos , Pessoa de Meia-Idade , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/terapia , Glândula Submandibular/patologia , Glândulas Salivares , Linfoma Difuso de Grandes Células B/patologia
3.
Nanotechnology ; 34(20)2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36652705

RESUMO

Bismuth nanoparticles (NPs) colloids synthesized in deionized water by laser ablation of solids in liquids technique (LASL) were oxidized using NaClO solutions at different concentrations. Oxidized nanomaterials were characterized using several techniques. The crystalline phases of the bismuth compound were determined using Raman microspectroscopy, and the crystallographic structure was identified by x-ray diffraction (XRD). The size and morphology of the obtained nanomaterials were studied by transmission electron microscopy (TEM). The chemical states were determined using x-ray photoelectron spectroscopy (XPS), and the optical properties of the colloids were characterized by UV-vis spectroscopy. The absorption spectra were analyzed using the Tauc method to determine the band gaps of the obtained nanomaterials. Our results showed morphological changes, starting from small nanoparticles to nanosheets and a mixture of nanosheets with hollow nanoparticles. Two kinds of nanomaterials were found depending on the NaClO solution concentration: Bi2O2CO3single phase and a mixture ofδ-Bi2O3and Bi2O2CO3. Some samples were tested as photocatalysts and showed good performance in the degradation of methylene blue in solution. To the best of our knowledge, this is the first study on the oxidation process of bismuth colloidal nanoparticles at room temperature.

4.
J Endocrinol Invest ; 45(4): 887-897, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34791604

RESUMO

PURPOSE: To identify consensus aspects related to the diagnosis, monitoring, and treatment of short stature in children to promote excellence in clinical practice. METHODS: Delphi consensus organised in three rounds completed by 36 paediatric endocrinologists. The questionnaire consisted of 26 topics grouped into: (1) diagnosis; (2) monitoring of the small-for-gestational-age (SGA) patient; (3) growth hormone treatment; and (4) treatment adherence. For each topic, different questions or statements were proposed. RESULTS: After three rounds, consensus was reached on 16 of the 26 topics. The main agreements were: (1) diagnosis tests considered as a priority in Primary Care were complete blood count, biochemistry, thyroid profile, and coeliac disease screening. The genetic test with the greatest diagnostic value was karyotyping. The main criterion for initiating a diagnostic study was prediction of adult stature 2 standard deviations below the target height; (2) the main criterion for initiating treatment in SGA patients was the previous growth pattern and mean parental stature; (3) the main criterion for response to treatment was a significant increase in growth velocity and the most important parameter to monitor adverse events was carbohydrate metabolism; (4) the main attitude towards non-responding patients is to check their treatment adherence with recording devices. The most important criterion for choosing the delivery device was its technical characteristics. CONCLUSIONS: This study shows the different degrees of consensus among paediatric endocrinologists in Spain concerning the diagnosis and treatment of short stature, which enables the identification of research areas to optimise the management of such patients.


Assuntos
Nanismo/diagnóstico , Nanismo/terapia , Consenso , Técnica Delphi , Nanismo/epidemiologia , Retardo do Crescimento Fetal/genética , Humanos , Espanha/epidemiologia , Inquéritos e Questionários
5.
BMC Health Serv Res ; 22(1): 680, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35597936

RESUMO

BACKGROUND: The existing digital healthcare solutions demand a service development approach that assesses needs, experience, and outcomes, to develop high-value digital healthcare services. The objective of this study was to develop a digital transformation of the patients' follow-up service after cardiac surgery, based on a remote patient monitoring service that would respond to the real context challenges. METHODS: The study followed the Design Science Research methodology framework and incorporated concepts from the Lean startup method to start designing a minimal viable product (MVP) from the available resources. The service was implemented in a pilot study with 29 patients in 4 iterative develop-test-learn cycles, with the engagement of developers, researchers, clinical teams, and patients. RESULTS: Patients reported outcomes daily for 30 days after surgery through Internet-of-Things (IoT) devices and a mobile app. The service's evaluation considered experience, feasibility, and effectiveness. It generated high satisfaction and high adherence among users, fewer readmissions, with an average of 7 ± 4.5 clinical actions per patient, primarily due to abnormal systolic blood pressure or wound-related issues. CONCLUSIONS: We propose a 6-step methodology to design and validate a high-value digital health care service based on collaborative learning, real-time development, iterative testing, and value assessment.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Atenção à Saúde , Seguimentos , Humanos , Aprendizagem , Projetos Piloto
6.
Ann Oncol ; 32(1): 34-48, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33098993

RESUMO

Chimeric antigen receptor (CAR) T cells directed against the B-cell marker CD19 are currently changing the landscape for treatment of patients with refractory and/or relapsed B-cell malignancies. Due to the nature of CAR T cells as living drugs, they display a unique toxicity profile. As CAR T-cell therapy is extending towards other diseases and being more broadly employed in hematology and oncology, optimal management strategies of side-effects associated with CAR T-cell therapy are of high relevance. Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias constitute challenges in the treatment of patients with CAR T cells. This review summarizes the current understanding of CAR T-cell toxicity and its management.


Assuntos
Síndromes Neurotóxicas , Receptores de Antígenos Quiméricos , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Imunoterapia Adotiva , Recidiva Local de Neoplasia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética
7.
Osteoarthritis Cartilage ; 29(9): 1351-1361, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34052396

RESUMO

OBJECTIVE: Tissues have complex structures, comprised of solid and fluid phases. Improved understanding of interactions between joint fluid and extracellular matrix (ECM) is required in models of cartilage mechanics. X-ray photon correlation spectroscopy (XPCS) directly measures nanometer-scale dynamics and can provide insight into biofluid-biosolid interactions in cartilage. This study applies XPCS to evaluate dynamic interactions between intact cartilage and biofluids. DESIGN: Cartilage biopsies were collected from bovine femoral condyles. During XPCS measurements, cartilage samples were exposed to different fluids: deionized water, PBS, synovial fluid, or sonicated synovial fluid. ECM-biofluid interactions were also assessed at different length scales and different depths from the cartilage surface. RESULTS: Using XPCS, cartilage ECM mobility was detected at length scales from 50 to 207 nm. As length scale decreased, time scale for autocorrelation decay decreased, suggesting smaller ECM components are more mobile. ECM dynamics were slowed by dehydrating the sample, demonstrating XPCS assesses matrix mobility in hydrated environments. At all length scales, the matrix was more mobile in deionized water and slowest in synovial fluid. Using the 207 nm length scale assessment, ECM dynamics in synovial fluid were fastest at the cartilage surface and progressively slowed as depth into the sample increased, demonstrating XPCS can assess spatial distribution of ECM dynamics. Finally, ECM mobility increased for degraded synovial fluid. CONCLUSIONS: This study demonstrates the potential of XPCS to provide unique insights into nanometer-scale cartilage ECM mobility in a spatially resolved manner and illustrates the importance of biosolid-biofluid interactions in dictating ECM dynamics.


Assuntos
Cartilagem Articular/anatomia & histologia , Cartilagem Articular/fisiologia , Matriz Extracelular , Líquido Sinovial , Animais , Bovinos , Análise Espectral
8.
Eur J Neurol ; 27(12): 2396-2404, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32810879

RESUMO

BACKGROUND AND PURPOSE: Acquired hepatocerebral degeneration (AHD) and hepatic encephalopathy (HE) are neurological complications of chronic liver disease (CLD) with portosystemic shunt. While HE is common, AHD is a rare entity, and the clinical imaging relationships observed in small series lack validation in large patient cohorts. The aim of this study was to characterize a cohort of AHD patients and to explore possible associations with HE coexistence. METHODS: We performed a retrospective analysis of patients with a working AHD diagnosis, between 2008 and 2019. Clinical, laboratory, imaging and neuropsychological results at first neurological observation were reviewed and compared between the 'AHD' group and the 'AHD with HE' group. RESULTS: A total of 76 patients were recruited. The most frequent neurological manifestations were neuropsychiatric (93.4%) and extrapyramidal (84.2%). Only 38% of patients had hypermanganesemia. Compared with the AHD group, the AHD with HE group had more hyperkinetic movement disorders (71.4% vs. 38.5%; P = 0.05), a higher number of patients on the dementia spectrum (57.7% vs. 20%; P = 0.04), higher median ammonia levels (P = 0.014) and more widespread cortico-subcortical and pyramidal involvement on brain magnetic resonance imaging. Nineteen patients underwent liver transplantation, with significantly improved survival (P = 0.006). DISCUSSION: Hepatic encephalopathy and AHD often coexist in the same patient. Seventy-six patients with CLD and AHD were evaluated, making this one of the largest reported AHD cohorts. Blood manganese level was a weak diagnostic marker in AHD. Early liver function restoration through liver transplantation improved survival. Our report provides a detailed description of the phenotype and long-term outcome of AHD, with relevance for diagnosis and treatment.


Assuntos
Encefalopatia Hepática , Encefalopatia Hepática/epidemiologia , Encefalopatia Hepática/etiologia , Degeneração Hepatolenticular/complicações , Degeneração Hepatolenticular/epidemiologia , Humanos , Cirrose Hepática , Transplante de Fígado , Estudos Retrospectivos
9.
Mod Pathol ; 32(4): 490-498, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30401948

RESUMO

The purpose of this study is to examine hematopoietic neoplasms with 9p24/JAK2 rearrangement including neoplasms associated with t(8;9)(p22;p24)/PCM1-JAK2 fusion neoplasm as well as cases with translocations involving 9p24/JAK2 and other partner genes. From seven large medical centers, we identified ten patients with t(8;9)(p22;p24) /PCM1-JAK2 and 3 with t(9p24;v)/JAK2 at diagnosis. Majority of the cases showed myeloproliferative neoplasm (MPN) associated features (n = 7) characterized by variable degrees of eosinophilia, myelofibrosis, frequent proliferations of early erythroblasts in bone marrow and extramedullary sites, and infrequent/absent somatic mutations. Other less common presentations included myelodysplastic syndromes (MDS) or MDS/MPN (one each). Four patients presented with B-lymphoblastic leukemia (B-ALL), and of them, two patients with t(8;9)(p22;p24.1) were proven to be B-lymphoblastic crisis of MPN; and the other two cases with t(9p24;v) both were de novo B-ALL, BCR-ABL1-like (Ph-like). We show that the hematopoietic neoplasms with 9p24/JAK2 rearrangement are extremely rare, and most of them are associated with t(8;9)(p22;p24)/PCM1-JAK2, a recent provisional World Health Organization entity under "myeloid/lymphoid neoplasm with a specific gene rearrangement". Cases of t(8;9)(p22;p24)/PCM1-JAK2, though heterogeneous, do exhibit some common clinicopathological characteristic features. Cases with t(9p24;v)/JAK2 are extremely rare; while such cases with a MPN presentation may resemble t(8;9)(p22;p24.1)/PCM1-JAK2, B-ALL cases presenting de novo B-ALL might belong to Ph-like B-ALL.


Assuntos
Cromossomos Humanos Par 9/genética , Neoplasias Hematológicas/genética , Janus Quinase 2/genética , Proteínas de Fusão Oncogênica/genética , Adulto , Feminino , Rearranjo Gênico , Humanos , Masculino , Pessoa de Meia-Idade
10.
Opt Express ; 27(7): 9838-9847, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31045132

RESUMO

In this work we investigate the implementation of ultra-wideband polarization rotator in the mid-infrared spectral region. A new design method of the rotation section is proposed, yielding a polarization rotator with an extinction ratio of at least 15 dB in a wavelength range of 2 µm. For a spectral range wider than 3.8 µm, an extinction ratio of at least 10 dB is achieved for this design. The device is 1660 µm long and the associated insertion loss is below 1.2 dB on the full operational wavelength range. The influence of geometrical parameters with respect to the design method to obtain such a broadband behavior is discussed. Finally, to increase the tolerance to fabrication errors, a tapered rotator design is proposed. Such a device can support up to ± 100 nm fabrication errors and still guarantees remarkable broadband behavior. To the best of our knowledge, this is the first time an integrated polarization rotator is designed to operate for the wavelength range of 4 to 9 µm with a bandwidth exceeding 2 µm.

11.
J Biol Inorg Chem ; 24(4): 563-574, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31030324

RESUMO

Calcium is an element widely used in the development of biomaterials for bone tissue engineering as it plays important roles in bone metabolism and blood coagulation. The Ca ions can condition the microenvironment at the tissue-material interface, affecting the protein deposition process and cell responses. The aim of this study was to analyze the changes in the patterns of protein adsorption on the silica hybrid biomaterials supplemented with different amounts of CaCl2, which can function as release vehicles. This characterization was carried out by incubating the Ca-biomaterials with human serum. LC-MS/MS analysis was used to characterize the adsorbed protein layers and compile a list of proteins whose affinity for the surfaces might depend on the CaCl2 content. The attachment of pro- and anti-clotting proteins, such as THRB, ANT3, and PROC, increased significantly on the Ca-materials. Similarly, VTNC and APOE, proteins directly involved on osteogenic processes, attached preferentially to these surfaces. To assess correlations with the proteomic data, these formulations were tested in vitro regarding their osteogenic and inflammatory potential, employing MC3T3-E1 and RAW 264.7 cell lines, respectively. The results confirmed a Ca dose-dependent osteogenic and inflammatory behavior of the materials employed, in accordance with the protein attachment patterns.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Cálcio/química , Proteômica , Células 3T3 , Animais , Camundongos , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Células RAW 264.7 , RNA Mensageiro/genética , Transcriptoma/efeitos dos fármacos
12.
Arch Biochem Biophys ; 669: 71-79, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31141701

RESUMO

J-domain/Hsp40 proteins cooperate in aiding with folding in the cell by binding partially folded client proteins and delivering them to be folded by Hsp70. The delivery occurs concomitantly to the stimulation of the ATPase activity of Hsp70 via the N-terminally located J-domain. Although several lines of investigation have been used to study J-domain proteins, the presence of highly flexible domains (G/F- and G/M-rich) hold up obtaining a detailed full-length structure. In this work, we present the high-resolution structure of the J-domain and the N-terminal part of the G/F domain of Sis1, solved by NMR, and used chemical-shift perturbation approaches to further study the structure/function relationship of the Sis1/Hsp70 interaction. When the J-domain was compared to the full-length protein and to a G/M domain deletion mutant, an internal interaction patch formed by hydrophobic and positively charged residues (V2, D9, R27, T39, F52 and R73) was identified. Curiously, the same patch is protected by internal contacts in the full-length protein and, in combination with the loop containing the conserved HPD motif, participates in the interaction with Hsp70. Combined, these results suggest that the J-domain in the full-length Sis1 is in a transient intermediate conformation, in which its interacting patch is protected and, at the same time, also in a favorable condition to bind Hsp70, facilitating the interaction between the two proteins. Finally, 1D NMR experiments showed that the addition of ATP is followed by the disruption of the J-domain/Hsp70 complex, a necessary step for aiding the folding of the client protein.


Assuntos
Proteínas de Choque Térmico HSP40/química , Proteínas de Saccharomyces cerevisiae/química , Sítios de Ligação , Escherichia coli/genética , Proteínas de Choque Térmico HSP40/genética , Proteínas de Choque Térmico HSP40/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Mutação , Ligação Proteica , Domínios Proteicos , Estrutura Terciária de Proteína , Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
13.
Hum Reprod ; 33(5): 914-918, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29538680

RESUMO

Testotoxicosis is a rare cause of peripheral precocious puberty in boys caused by constitutively activating mutations of the LHCG receptor. Affected males usually have normal gonadotropin profiles and fertility in their adult life. Here, we described the long-term follow-up of a 24-year-old young man with severe testotoxicosis due to a de novo activating mutation in the third transmembrane helix of the LHCGR (p.Leu457Arg). This patient was treated with different medications, including medroxyprogesterone acetate, ketoconazole, cyproterone acetate and aromatase inhibitor from age 2.5 to 9.5 years. His basal and GnRH-stimulated gonadotropin levels were continually suppressed during and after medical treatment. At adulthood, extremely high serum testosterone levels (>35 nmol/L), undetectable gonadotropin levels (LH < 0.15 IU/L and FSH < 0.6 IU/L) and oligozoospermia were evidenced. Despite his suppressed FSH levels and an unfavorable spermogram, the patient fathered a healthy girl and biological paternity was confirmed through analysis of microsatellites. Spontaneous fertility in a young man with severe testotoxicosis and chronic suppression of FSH levels reinforces the key role of high intratesticular testosterone levels in human spermatogenesis.


Assuntos
Fertilidade/genética , Puberdade Precoce/genética , Receptores do LH/genética , Testosterona/sangue , Adulto , Humanos , Masculino , Mutação , Puberdade Precoce/sangue
14.
Br J Surg ; 105(2): e192-e203, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29341150

RESUMO

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is one of the preferred initial treatment strategies for locally advanced rectal cancer. Responses are variable, and most patients still require surgery. The aim of this study was to identify molecular mechanisms determining poor response to CRT. METHODS: Global gene expression and pathway enrichment were assessed in pretreatment biopsies from patients with non-metastatic cT2-4 N0-2 rectal cancer within 7 cm of the anal verge. Downstream Akt activation was assessed in an independent set of pretreatment biopsies and in colorectal cancer cell lines using immunohistochemistry and western blot respectively. The radiosensitizing effects of the Akt inhibitor MK2206 were assessed using clonogenic assays and xenografts in immunodeficient mice. RESULTS: A total of 350 differentially expressed genes were identified, of which 123 were upregulated and 199 downregulated in tumours from poor responders. Mitochondrial oxidative phosphorylation (P < 0·001) and phosphatidylinositol signalling pathways (P < 0·050) were identified as significantly enriched pathways among the set of differentially expressed genes. Deregulation of both pathways is known to result in Akt activation, and high immunoexpression of phosphorylated Akt S473 was observed among patients with a poor histological response (tumour regression grade 0-2) to CRT (75 per cent versus 48 per cent in those with a good or complete response; P = 0·016). Akt activation was also confirmed in the radioresistant cell line SW480, and a 50 per cent improvement in sensitivity to CRT was observed in vitro and in vivo when SW480 cells were exposed to the Akt inhibitor MK2206 in combination with radiation and 5-fluorouracil. CONCLUSION: Akt activation is a key event in the response to CRT. Pharmacological inhibition of Akt activation may enhance the effects of CRT. Surgical relevance Organ preservation is an attractive alternative in rectal cancer management following neoadjuvant chemoradiotherapy (CRT) to avoid the morbidity of radical surgery. Molecular steps associated with tumour response to CRT may provide a useful tool for the identification of patients who are candidates for no immediate surgery. In this study, tumours resistant to CRT were more likely to have activation of specific genetic pathways that result in phosphorylated Akt (pAkt) activation. Pretreatment biopsy tissues with high immunoexpression of pAkt were more likely to exhibit a poor histological response to CRT. In addition, the introduction of a pAkt inhibitor to cancer cell lines in vitro and in vivo led to a significant improvement in sensitivity to CRT. Identification of pAkt-activated tumours may thus allow the identification of poor responders to CRT. In addition, the concomitant use of pAkt inhibitors to increase sensitivity to CRT in patients with rectal cancer may constitute an interesting strategy for increasing the chance of a complete response to treatment and organ preservation.


Assuntos
Quimiorradioterapia/métodos , Terapia Neoadjuvante/métodos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Retais/metabolismo , Idoso , Animais , Western Blotting , Linhagem Celular Tumoral , Ensaio de Unidades Formadoras de Colônias , Feminino , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Neoplasias Retais/terapia , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
15.
J Biol Inorg Chem ; 23(3): 459-470, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29572572

RESUMO

The prime objectives in the development of biomaterials for dental applications are to improve the quality of osseointegration and to short the time needed to achieve it. Design of implants nowadays involves changes in the surface characteristics to obtain a good cellular response. Incorporating osteoinductive elements is one way to achieve the best regeneration possible post-implantation. This study examined the osteointegrative potential of two distinct biomaterials: sandblasted acid-etched titanium and a silica sol-gel hybrid coating, 70% MTMOS-30% TEOS. In vitro, in vivo, and proteomic characterisations of the two materials were conducted. Enhanced expression levels of ALP and IL-6 in the MC3T3-E1 cells cultured with coated discs, suggest that growing cells on such surfaces may increase mineralisation levels. 70M30T-coated implants showed improved bone growth in vivo compared to uncoated titanium. Complete osseointegration was achieved on both. However, coated implants displayed osteoinductive properties, while uncoated implants demonstrated osteoconductive characteristics. Coagulation-related proteins attached predominantly to SAE-Ti surface. Surface properties of the material might drive the regenerative process of the affected tissue. Analysis of the proteins on the coated dental implant showed that few proteins specifically attached to its surface, possibly indicating that its osteoinductive properties depend on the silicon delivery from the implant.


Assuntos
Materiais Revestidos Biocompatíveis , Osseointegração , Proteômica/métodos , Células 3T3 , Fosfatase Alcalina/metabolismo , Animais , Materiais Revestidos Biocompatíveis/efeitos adversos , Materiais Revestidos Biocompatíveis/química , Interleucina-6/metabolismo , Camundongos , Propriedades de Superfície
17.
Water Sci Technol ; 78(9): 1833-1842, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30566087

RESUMO

Anaerobic digestion allows efficient treatment of high loaded wastewater, and membrane technology allows obtaining high quality effluents with complete biomass retention. However, high biomass concentration interferes with membrane fouling. In the present work, a new bioreactor that integrates an attached biomass anaerobic culture on a fixed bed and a submerged membrane has been started up. The recirculation between the digestion and filtration chambers is coupled to the gas-lift effect of the bubbling employed for the scouring of the membranes, avoiding the use or electromechanical pumps that damage the suspended biomass. The support material retains the biomass in the digestion tank despite the downwards flow, avoiding the submerged membrane contacting with a high concentrated suspension. This novel system, called an anaerobic filter membrane bioreactor was immediately started up, achieving chemical oxygen demand (COD) removal efficiencies of 96% at an organic loading rate (OLR) of 7 kg COD/m3·d. In order to select filtration flux, specific gas demand and filtration cycle duration, the results of 15 short term assays, eight hours for each one, is presented for fluxes between 15.7 and 17.7 L/m2·h, cycle duration between 10 and 30 minutes, and three levels of scouring. It was checked that reversible and irreversible fouling were directly related when dTMP/dt > 2.5 mbar/min.


Assuntos
Reatores Biológicos , Filtração , Eliminação de Resíduos Líquidos/métodos , Anaerobiose , Análise da Demanda Biológica de Oxigênio , Membranas Artificiais , Águas Residuárias
18.
Cir Pediatr ; 31(2): 81-84, 2018 Apr 20.
Artigo em Espanhol | MEDLINE | ID: mdl-29978959

RESUMO

INTRODUCTION: Foreign body aspiration (FBA) is a potentially life-threatening event, and is the leading cause of death in children after road traffic injuries. If suspected, a prompt exploration of the airway should be performed. We present our experience in FBA treatment in the last 10 years. MATERIAL AND METHODS: A retrospective study of patients admitted in our center with suspected FBA between 2005 and 2015 was performed. Clinical history, physical findings, radiologic imaging, treatment and evolution were assessed. RESULTS: A total of 115 children (70 M/45 F) with a median age of 2 years old (8 months-13 years), presented with a clinical history of FBA. All of them suffered a choking event and the most frequent symptoms were persistent cough (88.3%) and respiratory distress (46.8%). Pathologic physical examination was registered in 75% and an abnormal chest X-ray was seen in 72%. Rigid bronchoscopy (RB) was performed in 100% based on compatible history, regardless of physical and radiologic exams. A foreign body was found during RB in 78 patients (68.1%) and the most frequent were seeds and nuts (63.4%), located mainly in the right bronchus (46.8%). If the criteria for RB had been based on a compatible history along with clinical findings and abnormal chest X-ray, 21 foreign bodies (26.9%) would have been missed, with the subsequent risk of sudden death. All the foreign bodies were removed with success, without any immediate complication during the procedure. CONCLUSION: FBA is a frequent accident among children. The history, clinical findings and imaging cannot always concur. In case of a positive history of FBA an examination of the tracheobronchial tree must be done.


OBJETIVOS: La aspiración de cuerpos extraños (ACE) es una urgencia pediátrica frecuente, descrita como segunda causa de muerte infantil tras los accidentes de tráfico. Presentamos nuestra experiencia en el tratamiento de la ACE en los últimos 10 años. MATERIAL Y METODOS: Estudio retrospectivo de pacientes atendidos por sospecha de ACE entre los años 2005-2015, describiendo historia clínica, sintomatología, pruebas de imagen, procedimiento y evolución. RESULTADOS: Un total de 115 pacientes (70 V/45 M), con una mediana de 2 años (8 meses-13 años), presentaron historia sugestiva de ACE. Los síntomas más frecuentes fueron: tos (88,3%) y dificultad respiratoria (46,8%). El 75% presentaban exploración física patológica y un 72% presentaban alteraciones en la radiografía de tórax. Se realizó broncoscopia rígida (BR) en el 100% de los pacientes con historia compatible, sin importar los resultados de la exploración física o las pruebas de imagen. En 78 pacientes (68,1%) se encontró un cuerpo extraño (CE) durante la BR, siendo los más frecuentes semillas y frutos secos (63,4%); localizándose sobre todo en el bronquio derecho (46,8%). Si el criterio para realizar una BR se hubiese basado en la historia compatible, junto con alteraciones en la exploración física y pruebas de imagen, 21 CE (26,9%) no habrían sido diagnosticados con el consiguiente riesgo de muerte. Todos los CE se extrajeron con éxito, sin ninguna complicación inmediata. CONCLUSIONES: La ACE es frecuente en la infancia. La historia y los hallazgos clínico-radiológicos pueden no concordar, por lo que ante historia sugestiva de ACE es recomendable una exploración de la vía aérea, dado el bajo riesgo que asocia.


Assuntos
Brônquios/diagnóstico por imagem , Broncoscopia/métodos , Corpos Estranhos/terapia , Aspiração Respiratória/terapia , Adolescente , Obstrução das Vias Respiratórias/etiologia , Criança , Pré-Escolar , Tosse/etiologia , Feminino , Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico por imagem , Humanos , Lactente , Masculino , Aspiração Respiratória/diagnóstico por imagem , Estudos Retrospectivos
19.
Int J Obes (Lond) ; 41(11): 1662-1668, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28669988

RESUMO

Backgrounds/Objectives:The activity of brown/beige adipose tissue (B/BAT) is inversely proportional to body adiposity. Studies have shown that obese subjects submitted to distinct approaches aimed at reducing body mass present an increase of B/BAT activation. However, it is unknown if this beneficial effect of body mass reduction applies to patients with type 2 diabetes mellitus. In this study, we evaluated the impact of massive body mass reduction obtained as a consequence of bariatric surgery in the cold-induced activation of B/BAT in obese non-diabetic (OND) and obese diabetic (OD) subjects. SUBJECTS/METHODS: This is an observational study. Fourteen OND, 14 OD and 11 subjects were included in the study. All obese subjects were submitted to Roux-in-Y gastric bypass and measurements were performed before and 8 months after surgery. B/BAT was evaluated by (18F)-FDG-PET/CT scan and determination of signature transcript expression in specimens obtained in biopsies. RESULTS: Before surgery, mean B/BAT activity and the expression of signature transcripts were similar between OND and OD groups. Eight months after surgery, body mass reduction was similar between the obese groups. Nevertheless, the activity of B/BAT was increased in OND and unchanged in OD subjects. This effect was correlated with a more pronounced improvement of insulin resistance, as evaluated by the hyperinsulinemic, euglycemic clamp, in OND subjects as compared with OD subjects. CONCLUSIONS: Body mass reduction has a more efficient effect to induce the activation of B/BAT in non-diabetic than in diabetic subjects. This effect is accompanied by more pronounced insulin sensitivity and serine 473 phosphorylation of Akt in B/BAT of non-diabetic than in diabetic subjects.


Assuntos
Tecido Adiposo Bege/fisiologia , Tecido Adiposo Marrom/fisiologia , Diabetes Mellitus Tipo 2/cirurgia , Derivação Gástrica , Resistência à Insulina/fisiologia , Obesidade Mórbida/cirurgia , Redução de Peso/fisiologia , Adaptação Fisiológica , Adulto , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Fluordesoxiglucose F18 , Humanos , Obesidade Mórbida/diagnóstico por imagem , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Resultado do Tratamento , Adulto Jovem
20.
Lupus ; 26(4): 417-425, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27872396

RESUMO

Objective We aimed to compare estimates of body fat content with respect to their ability to predict the percentage of body fat, confirmed by dual-energy X-ray absorptiometry scans in childhood-onset systemic lupus erythematosus. Methods We included 64 consecutive childhood-onset systemic lupus erythematosus patients and 64 healthy age and sex-matched controls in a cross-sectional study. Anthropometric data, body mass index and body adiposity index were calculated for all subjects. Childhood-onset systemic lupus erythematosus patients were further assessed for clinical and laboratory childhood-onset systemic lupus erythematosus manifestations and fat mass, lean mass and percentage of body fat evaluated by dual-energy X-ray absorptiometry. Results Elevated waist/hip ratio was observed in childhood-onset systemic lupus erythematosus patients when compared to controls ( p < 0.001). We did not find differences between body mass index and body adiposity index classification in childhood-onset systemic lupus erythematosus patients and controls. Using dual-energy X-ray absorptiometry as gold standard we observed that all indirect estimates of body fat were correlated with whole body fat mass. We observed a correlation between height and cumulative corticosteroid dose adjusted by weight ( r = 0.429, p = 0.005) in childhood-onset systemic lupus erythematosus. On whole body analysis we observed a correlation between lean mass and ACR Damage Index scores ( r = -0.395; p = 0.019); percentage of body fat and adjusted Systemic Lupus Erythematosus Disease Activity Index ( r = 0.402; p = 0.008), disease duration ( r = -0.370; p = 0.012). On trunk analysis we observed a correlation between lean mass and ACR Damage Index ( r = -0.319; p = 0.042); percentage of body fat with adjusted Systemic Lupus Erythematosus Disease Activity Index ( r = 0.402; p = 0.005), disease duration ( r = -0.408; p = 0.005). Conclusions This is the first study analyzing body adiposity index in childhood-onset systemic lupus erythematosus patients. We observed that all indirect estimates of body fat were correlated with whole body fat mass. This study shows that we should not replace body mass index by body adiposity index to evaluating fat levels in childhood-onset systemic lupus erythematosus. In consideration of the importance of overweight classification in cardiovascular diseases, any direct estimates of body fat can be used in an attempt to improve the prognosis of patients. Note We believe that we have presented evidence of body adiposity index accuracy in childhood-onset systemic lupus erythematosus patients but further research on the generalizability of body adiposity index to other patient groups needs to be done.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Absorciometria de Fóton/métodos , Adolescente , Corticosteroides/uso terapêutico , Idade de Início , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Adulto Jovem
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