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1.
Clinics (Sao Paulo) ; 79: 100422, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38972247

RESUMO

OBJECTIVE: Cancer genomics and transcriptomics studies have provided a large volume of data that enables to test of hypotheses based on real data from cancer patients. Ezrin (encoded by the EZR gene) is a highly expressed protein in cancer that contributes to linking the actin cytoskeleton to the cell membrane and signal transduction pathways involved in oncogenesis and disease progression. NSC305787 is a pharmacological ezrin inhibitor with potential antineoplastic effects. In the present study, the authors prospected EZR mRNA levels in a pan-cancer analysis and identified potential cancers that could benefit from anti-EZR therapies. METHODS: This study analyzed TCGA data for 32 cancer types, emphasizing cervical squamous cell carcinoma and stomach adenocarcinoma. It investigated the impact of EZR transcript levels on clinical outcomes and identified differentially expressed genes. Cell lines were treated with NSC305787, and its effects were assessed through various cellular and molecular assays. RESULTS: EZR mRNA levels are highly expressed, and their expression is associated with biologically relevant molecular processes in cervical squamous carcinoma and stomach adenocarcinoma. In cellular models of cervical and gastric cancer, NSC305787 reduces cell viability and clonal growth (p < 0.05). Molecular analyses indicate that the pharmacological inhibition of EZR induces molecular markers of cell death and DNA damage, in addition, to promoting the expression of genes associated with apoptosis and inhibiting the expression of genes related to survival and proliferation. CONCLUSION: The present findings provide promising evidence that ezrin may be a molecular target in the treatment of cervical and gastric carcinoma.


Assuntos
Adenocarcinoma , Proteínas do Citoesqueleto , Perfilação da Expressão Gênica , Neoplasias Gástricas , Neoplasias do Colo do Útero , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Proteínas do Citoesqueleto/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/metabolismo , Linhagem Celular Tumoral , Feminino , Adenocarcinoma/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , RNA Mensageiro , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/genética
2.
Eur J Pharmacol ; 977: 176723, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38851560

RESUMO

Acute lymphoblastic leukemia (ALL), a complex malignancy, displays varying expression profiles of PIP4K2-related genes in adult patients. While PIP4K2A expression is elevated in ALL bone marrow cells compared to healthy bone marrow cells, PIP4K2B is downregulated, and PIP4K2C remains relatively unchanged. Despite the correlation between increased PIP4K2A expression and increased percentage of peripheral blood blasts, clinical outcomes do not strongly correlate with the expression of these genes. Here we investigated the therapeutic potential of three PIP4K2 inhibitors (THZ-P1-2, a131, and CC260) in ALL cell models. THZ-P1-2 emerges as the most effective inhibitor, inducing cell death and mitochondrial damage while reducing cell viability and metabolism significantly. Comparative analyses highlight the superior efficacy of THZ-P1-2 over a131 and CC260. Notably, THZ-P1-2 uniquely disrupts autophagic flux and inhibits the PI3K/AKT/mTOR pathway, indicating a distinct molecular mechanism. In summary, our findings elucidate the differential expression of PIP4K2-related genes in ALL and underscore the potential role of PIP4K2A in disease pathogenesis. The therapeutic promise of THZ-P1-2 in ALL treatment, along with its distinct effects on cell death mechanisms and signaling pathways, enriches our understanding of PIP4K2's involvement in ALL development and offers targeted therapy prospects.


Assuntos
Fosfotransferases (Aceptor do Grupo Álcool) , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Autofagia/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Apoptose/efeitos dos fármacos
3.
Hematol Transfus Cell Ther ; 46(3): 273-282, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38326180

RESUMO

Myeloid neoplasms result from molecular alterations in hematopoietic stem cells, with acute myeloid leukemia (AML) being one of the most aggressive and with a poor prognosis. Hematopoietic cell kinase (HCK) is a proto-oncogene that encodes a protein-tyrosine kinase of the Scr family, and it is highly expressed in AML. The present study investigated HCK expression in normal hematopoietic cells across myeloid differentiation stages and myeloid neoplasm patients. Within the AML cohort, we explored the impact of HCK expression on clinical outcomes and its correlation with clinical, genetic, and laboratory characteristics. Furthermore, we evaluated the association between HCK expression and the response to antineoplastic agents using ex vivo assay data from AML patients. HCK expression is higher in differentiated subpopulations of myeloid cells. High HCK expression was observed in patients with chronic myelomonocytic leukemia, chronic myeloid leukemia, and AML. In patients with AML, high levels of HCK negatively impacted overall and disease-free survival. High HCK expression was also associated with worse molecular risk groups and white blood cell count; however, it was not an independent prognostic factor. In functional genomic analyses, high HCK expression was associated with several biological and molecular processes relevant to leukemogenesis. HCK expression was also associated with sensitivity and resistance to several drugs currently used in the clinic. In conclusion, our analysis confirmed the differential expression of HCK in myeloid neoplasms and its potential association with unfavorable molecular risks in AML. We also provide new insights into HCK biological functions, prognosis, and response to antineoplastic agents.

4.
Int J Mol Sci ; 24(23)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38069220

RESUMO

Phosphatidylinositol-5-phosphate 4-kinase type 2 (PIP4K2) protein family members (PIP4K2A, PIP4K2B, and PIP4K2C) participate in the generation of PIP4,5P2, which acts as a secondary messenger in signal transduction, a substrate for metabolic processes, and has structural functions. In patients with acute myeloid leukemia (AML), high PIP4K2A and PIP4K2C levels are independent markers of a worse prognosis. Recently, our research group reported that THZ-P1-2 (PIP4K2 pan-inhibitor) exhibits anti-leukemic activity by disrupting mitochondrial homeostasis and autophagy in AML models. In the present study, we characterized the expression of PIP4K2 in the myeloid compartment of hematopoietic cells, as well as in AML cell lines and clinical samples with different genetic abnormalities. In ex vivo assays, PIP4K2 expression levels were related to sensitivity and resistance to several antileukemia drugs and highlighted the association between high PIP4K2A levels and resistance to venetoclax. The combination of THZ-P1-2 and venetoclax showed potentiating effects in reducing viability and inducing apoptosis in AML cells. A combined treatment differentially modulated multiple genes, including TAp73, BCL2, MCL1, and BCL2A1. In summary, our study identified the correlation between the expression of PIP4K2 and the response to antineoplastic agents in ex vivo assays in AML and exposed vulnerabilities that may be exploited in combined therapies, which could result in better therapeutic responses.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Fosfotransferases (Aceptor do Grupo Álcool)/farmacologia
5.
Antibiotics (Basel) ; 12(11)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37998766

RESUMO

Microorganisms are abundant and necessary [...].

6.
Eur J Pediatr ; 182(8): 3631-3637, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37233777

RESUMO

The objective of this study was to reveal the signs and symptoms for the classification of pediatric patients at risk of CKD using decision trees and extreme gradient boost models for predicting outcomes. A case-control study was carried out involving children with 376 chronic kidney disease (cases) and a control group of healthy children (n = 376). A family member responsible for the children answered a questionnaire with variables potentially associated with the disease. Decision tree and extreme gradient boost models were developed to test signs and symptoms for the classification of children. As a result, the decision tree model revealed 6 variables associated with CKD, whereas twelve variables that distinguish CKD from healthy children were found in the "XGBoost". The accuracy of the "XGBoost" model (ROC AUC = 0.939, 95%CI: 0.911 to 0.977) was the highest, while the decision tree model was a little lower (ROC AUC = 0.896, 95%CI: 0.850 to 0.942). The cross-validation of results showed that the accuracy of the evaluation database model was like that of the training. CONCLUSION: In conclusion, a dozen symptoms that are easy to be clinically verified emerged as risk indicators for chronic kidney disease. This information can contribute to increasing awareness of the diagnosis, mainly in primary care settings. Therefore, healthcare professionals can select patients for more detailed investigation, which will reduce the chance of wasting time and improve early disease detection. WHAT IS KNOWN: • Late diagnosis of chronic kidney disease in children is common, increasing morbidity. • Mass screening of the whole population is not cost-effective. WHAT IS NEW: • With two machine-learning methods, this study revealed 12 symptoms to aid early CKD diagnosis. • These symptoms are easily obtainable and can be useful mainly in primary care settings.


Assuntos
Insuficiência Renal Crônica , Humanos , Criança , Estudos de Casos e Controles , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Diagnóstico Precoce , Aprendizado de Máquina
7.
Int J Infect Dis ; 123: 1-8, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35878801

RESUMO

OBJECTIVES: The performance of a new point-of-care CE-IVD-marked isothermal lab-on-phone COVID-19 assay was assessed in comparison to a gold standard real-time reverse transcriptase-PCR method. METHODS: The study was conducted following a nonprobability sampling of ≥16-year-old volunteers from three different laboratories, using direct mouthwash (N = 24) or nasopharyngeal (N = 191) clinical samples. RESULTS: The assay demonstrated 95.19% sensitivity and 100% specificity for detection of SARS-CoV-2 in direct nasopharyngeal crude samples and 78.95% sensitivity and 100% specificity in direct mouthwash crude samples. It also successfully detected currently predominant SARS-CoV-2 variants of concern (Beta B.1.351, Delta B.1.617.2, and Omicron B.1.1.529) and demonstrated to be inert against potential cross-reactions of other common respiratory pathogens that cause infections that present similar symptoms to COVID-19. CONCLUSION: This lab-on-phone pocket-sized assay relies on an isothermal amplification of SARS-CoV-2's N and E genes, taking just 50 minutes from sample to result, with only 2 minutes of hands-on time. It presents good performance when using direct nasopharyngeal crude samples, enabling a low-cost, real-time, rapid, and accurate identification of SARS-CoV-2 infections at the point of care, which is important for both clinical management and population screening, as a tool to break the chain of transmission of COVID-19 pandemic, especially in low-resources environments.


Assuntos
COVID-19 , SARS-CoV-2 , Adolescente , COVID-19/diagnóstico , Teste para COVID-19 , Humanos , Laboratórios , Técnicas de Diagnóstico Molecular/métodos , Antissépticos Bucais , Técnicas de Amplificação de Ácido Nucleico/métodos , Pandemias , RNA Viral/análise , RNA Viral/genética , DNA Polimerase Dirigida por RNA/genética , SARS-CoV-2/genética , Sensibilidade e Especificidade
8.
Invest New Drugs ; 40(4): 728-737, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35477813

RESUMO

Pancreatic cancer is one of the most lethal human neoplasms, and despite advances in the understanding of the molecular complexity involved in the development and progression of this disease, little of this new information has been translated into improvements in therapy and prognosis. Ezrin (EZR) is a protein that regulates multiple cellular functions, including cell proliferation, survival, morphogenesis, adhesion, and motility. In pancreatic cancer, EZR is highly expressed and reflects an unfavorable prognosis, whereas EZR silencing ameliorates the malignant phenotype of pancreatic cancer cells. NSC305787 was identified as a pharmacological EZR inhibitor with favorable pharmacokinetics and antineoplastic activity. Here, we endeavored to investigate the impact of EZR expression on survival outcomes and its associations with molecular and biological characteristics in The Cancer Genome Atlas pancreatic adenocarcinoma cohort. We also assessed the potential antineoplastic effects of NSC305787 in pancreatic cancer cell lines. High EZR expression was an independent predictor of worse survival outcomes. Functional genomics analysis indicated that EZR contributes to multiple cancer-related pathways, including PI3K/AKT/mTOR signaling, NOTCH signaling, estrogen-mediated signaling, and apoptosis. In pancreatic cells, NSC305787 reduced cell viability, clonal growth, and migration. Our exploratory molecular studies identified that NSC305787 modulates the expression and activation of key regulators of the cell cycle, proliferation, DNA damage, and apoptosis, favoring a tumor-suppressive molecular network. In conclusion, EZR expression is an independent prognosis marker in pancreatic cancer. Our study identifies a novel molecular axis underlying the antineoplastic activity of NSC305787 and provides insights into the development of therapeutic strategies for pancreatic cancer.


Assuntos
Adenocarcinoma , Antineoplásicos , Neoplasias Pancreáticas , Adamantano/análogos & derivados , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Proteínas do Citoesqueleto , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Fosfatidilinositol 3-Quinases , Quinolinas , Neoplasias Pancreáticas
9.
Semin Dial ; 35(1): 66-70, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34405466

RESUMO

INTRODUCTION: The limited data on survival rates of small children undergoing hemodialysis preclude comparison with other countries. The goal of this study was to determine the mortality rate and its risk factors in children starting hemodialysis during their first year of life. METHODS: We performed a retrospective cohort study, based on data from a reference dialysis center in São Paulo city. Data from 47 (8 females) children who underwent chronic hemodialysis before the first year of age were analyzed. Survival was characterized using Kaplan-Meier methods and log-rank tests, followed by a multivariable Cox regression model. RESULTS: The survival rates were 93%, 75%, and 64% at 1, 2, and 3 years, respectively. Only cardiovascular comorbidity was significantly associated with the mortality outcome (HR = 5.7, 95% CI = 1.7-19.6, p = 0.006). CONCLUSION: The survival rate among children who started hemodialysis in their first year of life was reasonable, similar to international standards.


Assuntos
Falência Renal Crônica , Diálise Renal , Brasil/epidemiologia , Criança , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Modelos de Riscos Proporcionais , Diálise Renal/métodos , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
10.
J Funct Biomater ; 12(2)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200191

RESUMO

BACKGROUND: Several studies proved that anodic oxidation improves osseointegration. This study aimed to optimize osseointegration through anodization in dental implants, obtaining anatase phase and controlled nanotopography. METHODS: The division of the groups with 60 titanium implants was: control (CG); sandblasted (SG); anodized (AG): anodized pulsed current (duty cycle 30%, 30 V, 0.2 A and 1000 Hz). Before surgery, surface characterization was performed using Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM), X-ray Dispersive Energy Spectroscopy (EDS) and Raman Spectroscopy. For in vivo tests, 10 New Zealand white rabbits received an implant from each group. The sacrifice period was 2 and 6 weeks (n = 5) and the specimens were subjected to computed microtomography (µCT) and reverse torque test. RESULTS: AFM and SEM demonstrated a particular nanotopography on the surface in AG; the anatase phase was proved by Raman spectroscopy. In the µCT and in the reverse torque test, the AG group presented better results than the other groups. CONCLUSION: The chemical composition and structure of the TiO2 film were positively affected by the anodizing technique, intensifying the biological characteristics in osseointegration.

11.
Transplantation ; 104(8): e236-e242, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732842

RESUMO

BACKGROUND: Proper care of young children in need of kidney transplant (KT) requires many skilled professionals and an expensive hospital structure. Small children have lesser access to KT. METHODS: We describe a strategy performed in Brazil to enable and accelerate KT in children ≤15 kg based on the establishment of one specialized transplant center, focused on small children, and cooperating with distant centers throughout the country. Actions on 3 fronts were implemented: (a) providing excellent medical assistance, (b) coordinating educational activities to disseminate expertise and establish a professional network, and (c) fostering research to promote scientific knowledge. We presented the number and outcomes of small children KT as a result of this strategy. RESULTS: Three hundred forty-six pediatric KTs were performed in the specialized center from 2009 to 2017, being 130 in children ≤15 kg (38%, being 41 children ≤10 kg) and 216 in >15 kg (62%). Patient survival after 1 and 5 years of the transplant was 97% and 95% in the "small children" group, whereas, in the "heavier children" group, it was 99% and 96% (P = 0.923). Regarding graft survival, we observed in the "small children" group, 91% and 87%, whereas in the "heavier children" group, 94% and 87% (P = 0.873). These results are comparable to the literature data. Groups were similar in the incidence of reoperation, vascular thrombosis, posttransplant lymphoproliferative disease, and estimated glomerular filtration rate. CONCLUSIONS: The strategy allowed an improvement in the number of KT in small children with excellent results. We believe this experience may be useful in other locations.


Assuntos
Rejeição de Enxerto/epidemiologia , Hospitais Pediátricos/organização & administração , Falência Renal Crônica/cirurgia , Transplante de Rim/estatística & dados numéricos , Tempo para o Tratamento/organização & administração , Adolescente , Peso Corporal/fisiologia , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/fisiopatologia , Sobrevivência de Enxerto/fisiologia , Implementação de Plano de Saúde , Acessibilidade aos Serviços de Saúde/organização & administração , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Incidência , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Transplante de Rim/efeitos adversos , Masculino , Avaliação de Programas e Projetos de Saúde , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
12.
J Fungi (Basel) ; 6(1)2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32050673

RESUMO

Fungal infections and, in particular, those caused by species of the Candida genus, are growing at an alarming rate and have high associated rates of mortality and morbidity. These infections, generally referred as candidiasis, range from common superficial rushes caused by an overgrowth of the yeasts in mucosal surfaces to life-threatening disseminated mycoses. The success of currently used antifungal drugs to treat candidiasis is being endangered by the continuous emergence of resistant strains, specially among non-albicans Candida species. In this review article, the mechanisms of action of currently used antifungals, with emphasis on the mechanisms of resistance reported in clinical isolates, are reviewed. Novel approaches being taken to successfully inhibit growth of pathogenic Candida species, in particular those based on the exploration of natural or synthetic chemicals or on the activity of live probiotics, are also reviewed. It is expected that these novel approaches, either used alone or in combination with traditional antifungals, may contribute to foster the identification of novel anti-Candida therapies.

13.
Sci Rep ; 9(1): 18137, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792433

RESUMO

Oral lichen planus (OLP) is a chronic Th1-mediated inflammatory mucocutaneous disease of the skin and oral mucosa that can have various clinical presentations. Lesions are usually bilateral and often painful. While cutaneous Lichen Planus (LP) lesions are self-limiting, the oral lesions are chronic and rarely remissive. The diagnosis of oral lichen planus (OLP) is often challenging, and confirmation by histopathological criterion is generally advised. The aim of our study was to identify the cytokines present in OLP-suggestive lesions and in non-specific inflammatory lesions (NSIL) used as controls. Moreover, assess cytokines protein levels and oral microbiota composition in whole saliva samples. Histopathological analysis, immunohistochemistry and gene expression were used as techniques to analyze the oral mucosal tissue samples. ELISA was conducted to analyze salivary cytokine levels and 16S rRNA sequencing was used to determine the salivary microbiome. As a result we observed larger number of infiltrated lymphocytes (p = 0.025), as well, more T CD4 lymphocytes in the epithelial tissue (p = 0.006) in OLP samples compared to NSIL. In addition, the OLP samples displayed more apoptotic cells compared to NSIL (p = 0.047). Regarding the cytokine analysis, IFN-γ and IL-33 were more expressed in OLP lesions than in NSIL samples (p < 0.001; p = 0.026). Furthermore, our results demonstrated higher levels of IFN-γ protein expression in the saliva of OLP group compared to controls (p = 0.0156). We also observed noted differences in the oral microbiota composition between OLP and NSIL saliva samples. In conclusion, OLP lesions presented larger numbers of apoptotic and inflammatory cells, higher levels of IFN-γ and IL-33 compared to NSIL, and these lesions also differ regarding oral microbiota composition. These results are consistent with the Th-1-mediated chronic inflammation nature of oral lichen planus investigated lesions and displayed unique features that could be used as a diagnostic tool.


Assuntos
Citocinas/genética , Líquen Plano Bucal/diagnóstico , Saliva/metabolismo , Saliva/microbiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Citocinas/metabolismo , Feminino , Expressão Gênica , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-17/genética , Interleucina-33/genética , Líquen Plano Bucal/microbiologia , Líquen Plano Bucal/patologia , Masculino , Microbiota , Pessoa de Meia-Idade , Mucosa Bucal/microbiologia , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo
14.
PLoS One ; 14(4): e0215100, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002677

RESUMO

OBJECTIVE: To develop a clinical score for the early identification of chronic kidney disease (CKD) in children and adolescents. The early diagnosis of CKD in childhood allows the adoption of measures to slow the progression of the disease, thereby reducing morbidity and mortality. Nevertheless, the diagnosis is often made too late for proper patient management. STUDY DESIGN: We preformed a case-control study of a multicenter Brazilian sample of 752 pediatric patients; the study cases (n = 376) were CKD patients with a median estimated GFR of 37 (IQR = 22 to 57) ml/min/1.73 m2. The control group (n = 376) comprised age-, gender- and center-matched children who were followed for nonrenal diseases. Potential risk factors were investigated through a standard questionnaire that included symptoms, medical history, and a clinical examination. Two multivariable models (A and B) were fitted to assess predictors of the diagnosis of CKD. RESULTS: In model A, 9 variables were associated with CKD diagnosis: antenatal ultrasound with urinary malformation, recurrent urinary tract infection, polyuria, abnormal urine stream, nocturia, growth curve flattening, history of hypertension, foamy urine and edema (c-statistic = 0.938). Model B had the same variables as model A, except for the addition of the history of admission during the neonatal period and the exclusion of antenatal ultrasound variables (c-statistic = 0.927). CONCLUSIONS: The present scores may serve as a warning sign for CKD diagnosis in children among professionals working in the primary care setting where the symptoms associated with a risk of CKD may be overlooked.


Assuntos
Taxa de Filtração Glomerular , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Medição de Risco/métodos , Adolescente , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Progressão da Doença , Diagnóstico Precoce , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Adulto Jovem
15.
Antibiotics (Basel) ; 7(3)2018 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-30049958

RESUMO

The emergence of bacterial resistance to available antimicrobials has prompted the search for novel antibacterial compounds to overcome this public health problem. Metal-based complexes have been much less explored than organic compounds as antimicrobials, leading to investigations of the antimicrobial properties of selected complexes in which silver may occupy the frontline due to its use as medicine since ancient times. Like silver, camphor has also long been used for medicinal purposes. However, in both cases, limited information exists concerning the mechanisms of their antimicrobial action. This work reviews the present knowledge of the antimicrobial properties of camphor-derived silver complexes, focusing on recent research on the synthesis and antimicrobial properties of complexes based on silver and camphor imines. Selected examples of the structure and antimicrobial activity relationships of ligands studied so far are presented, showing the potential of silver camphorimine complexes as novel antimicrobials.

16.
PLoS One ; 13(5): e0196169, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29771925

RESUMO

Titanium (Ti) and Ti-6 Aluminium-4 Vanadium alloys are the most common materials in implants composition but ß type alloys are promising biomaterials because they present better mechanical properties. Besides the composition of biomaterial, many factors influence the performance of the biomaterial. For example, porous surface may modify the functional cellular response and accelerate osseointegration. This paper presents in vitro and in vivo evaluations of powder metallurgy-processed porous samples composed by different titanium alloys and pure Ti, aiming to show their potential for biomedical applications. The porous surfaces samples were produced with different designs to in vitro and in vivo tests. Samples were characterized with scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and elastic modulus analyses. Osteogenic cells from newborn rat calvaria were plated on discs of different materials: G1-commercially pure Ti group (CpTi); G2-Ti-6Al-4V alloy; G3-Ti-13 Niobium-13 Zirconium alloy; G4-Ti-35 Niobium alloy; G5-Ti-35 Niobium-7 Zirconium-5 Tantalum alloy. Cell adhesion and viability, total protein content, alkaline phosphatase activity, mineralization nodules and gene expression (alkaline phosphatase, Runx-2, osteocalcin and osteopontin) were assessed. After 2 and 4 weeks of implantation in rabbit tibia, bone ingrowth was analyzed using micro-computed tomography (µCT). EDS analysis confirmed the material production of each group. Metallographic and SEM analysis revealed interconnected pores, with mean pore size of 99,5µm and mean porosity of 42%, without significant difference among the groups (p>0.05). The elastic modulus values did not exhibit difference among the groups (p>0.05). Experimental alloys demonstrated better results than CpTi and Ti-6Al-4V, in gene expression and cytokines analysis, especially in early experimental periods. In conclusion, our data suggests that the experimental alloys can be used for biomedical application since they contributed to excellent cellular behavior and osseointegration besides presenting lower elastic modulus.


Assuntos
Ligas/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Titânio/química , Titânio/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Calcificação Fisiológica/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Osseointegração/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Porosidade , Pós , Coelhos
17.
Braz. dent. sci ; 20(1): 56-63, 2017. tab, ilus
Artigo em Inglês | LILACS, BBO - Odontologia | ID: biblio-836731

RESUMO

Objetivo: O objetivo deste estudo foi avaliar o potencial de radiografias panorâmicas (RP) e seus índices radiomorfométricos como método auxiliar para o diagnóstico da osteoporose. Material e Método: Foram selecionadas vinte e cinco mulheres, que tinham sido encaminhadas para PR com fins diferentes. As PR foram analisadas de acordo com o MCI, que avalia o córtex mandibular abaixo do forame mentual, e, em seguida, divididos em dois grupos: normal, e perda mineral de osso. Scans de densitometria óssea foram obtidos (DXA) da coluna lombar e colo do fémur / fêmur inteiro, que foram utilizados como padrão-ouro para comparação com o MCI. Teste de Kappa (p < 0,05) foi utilizado para determinar a associação entre a MCI e leituras de densitometria óssea. Resultados: Em relação à DXA, 7 pacientes eram normais na coluna lombar ou fêmur, 24 pacientes apresentaram osteopenia na coluna lombar ou fémur e 9 indivíduos tinham osteoporose na coluna lombar ou fêmur. Em relação à associação entre a DXA e MCI, 18 pacientes apresentaram algum grau de perda óssea na coluna detectado por ambos DXA e o índice Klemetti. Conclusões: PR não deve ser utilizada para confirmar o diagnóstico de osteoporose ou osteopenia, mas pode ser útil para avaliar o risco de tais doenças estar presente.(AU)


Objective: The aim of this study was to evaluate the potential of panoramic radiographs (PR) and their radiomorphometric indices as an auxiliary method for the diagnosis of osteoporosis. Material and Methods: Twenty five women were selected, who had been prescribed PR for different purposes. The PR were analysed according to the MCI, which evaluates the mandibular cortex below the mental foramen, and then divided into two groups: normal and bone mineral loss. Bone densitometry scans were obtained (DXA) from the lumbar spine and neck of the femur/whole femur, which were used as the gold standard for comparison against the MCI. Kappa test (p< 0.05) was used to determine the association between the MCI and bone densitometry readings. Results: Regarding the DXA, 7 patients were normal at the lumbar spine or femur, 24 subjects showed osteopenia at the lumbar spine or femur and 9 subjects had osteoporosis at the lumbar spine or femur. Regarding the association between DXA and MCI, 18 subjects showed some degree of bone loss at the spine detected by both DXA and the Klemetti index. Conclusions: PR should not be used to confirm the diagnosis of osteoporosis or osteopenia, but may be useful to assess the risk of such diseases being present.(AU)


Assuntos
Humanos , Feminino , Menopausa , Osteoporose , Radiografia Panorâmica
18.
Forensic Sci Int ; 266: 578.e1-578.e10, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27426840

RESUMO

This study aimed to evaluate the accuracy of dental age (DA) and skeletal age (SA) methods in order to estimate chronological age (CA) in individuals with Down syndrome (DS), contributing to the Forensic Dentistry and making the identification of these individuals age possible. For this, 278 images of individuals were selected and divided in 2 groups: 216 non-DS patients and 62 with DS. At first, DA was evaluated by Nolla method, on panoramic radiographs, followed by SA, evaluated by Greulich and Pyle method. The linear correlation coefficient of Pearson was used for the analysis of concordance between the methods. Paired t-test with confidence interval was used to evaluate the accuracy and Bland and Altman method was applied to estimate limits of concordance. Complementary to this first analysis, descriptive statistics and ANOVA test were applied for comparison among chronological age (CA), dental age (DA) and skeletal age (SA), with a significance level of 95% (p≥0.05), ordering to observe the differences among them. DA, estimated by Nolla, is underestimated in both, DS and non-DS individuals, and it is more notable in DS individuals. SA estimated by Greulich and Pyle method is overestimated, except for non-DS males. The range of variance is greater in SA and DS than DA and non-DS individuals, respectively. A greater accordance was found for DA×CA if compared to SA×CA, indicating that DA, estimated by Nolla method, is more accurate than SA, evaluated by Greulich and Pyle method, for estimating CA of both, DS and non-DS individuals. However, neither method seems to be precise and more caution is required for age estimation in DS individuals.


Assuntos
Determinação da Idade pelo Esqueleto , Determinação da Idade pelos Dentes , Síndrome de Down/diagnóstico por imagem , Dente Molar/diagnóstico por imagem , Adolescente , Desenvolvimento Ósseo , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Reprodutibilidade dos Testes
19.
Oral Maxillofac Surg ; 20(3): 289-94, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27417545

RESUMO

PURPOSE: The aim of this study was to evaluate the prevalence of bifid mandibular canals (BMC) by cone beam computed tomography (CBCT). MATERIALS AND METHODS: We examined CT scans from 300 patients both male and female, aged 25 to 87 years. The subjects were divided into groups according to gender, male group (MG) and female group (FG) as well as subgroups according to the side, right (R) and left (L). Tomographic acquisitions were performed on the device I-Cat ® Classic. Image analysis was performed on the XoranCat ® software of the equipment itself, aided by image filters associated with transverse, oblique, and panoramic reconstruction cuts for analysis of the BMC. The results were displayed as descriptive analysis of the values and comparisons between factors were performed using ANOVA at a significance level of 95 %. RESULTS: BMC was observed in 80 cases (26.67 %), of which, 39 (48.75 %) were in males and 41 (51.25 %) in females; no difference was seen between genders, neither by affected side, although the right side was more frequently affected (66.67 %) when both genders were combined. CONCLUSION: The prevalence of BMC is significant and should not be overlooked.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Interpretação de Imagem Assistida por Computador , Mandíbula/anormalidades , Mandíbula/diagnóstico por imagem , Radiografia Panorâmica , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
20.
Braz Oral Res ; 30(1): e49, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27119586

RESUMO

The aim of this study was to assess the presence, location and, multiplanar distance of the canalis sinuosus (CS) between the incisive foramen and the anterior maxillary alveolar ridge using cone beam computed tomography (CBCT). Therefore, 500 CBCT maxillary images obtained from male and female patients aged 20 to 80 years were selected to assist in the dental treatment. Low-quality tomographic images were discarded. All images were captured with the i-CATTM Classic tomograph and assessed using the XoranCatTM software. The axial sections were analyzed at the incisive foramen in order to verify the CS presence in laterality and location. Furthermore, linear measurements of the nasal cavity floor, buccal cortical bone, and alveolar ridge crest were made. All the collected data were statistically analyzed. Results show a variation of the CS in relation to the classification and distance of anatomical structures, but no significant difference between the right and left sides. It should be highlighted that CBCT is necessary before invasive procedures in order to preserve important anatomical structures. In conclusion, the location of the CS varies in relation to the alveolar ridge crest and buccal cortical bone, assuming that it is going to be located by the upper lateral incisor palatine.


Assuntos
Processo Alveolar/anatomia & histologia , Processo Alveolar/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/métodos , Maxila/anatomia & histologia , Maxila/diagnóstico por imagem , Nervo Maxilar/anatomia & histologia , Nervo Maxilar/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Variação Anatômica , Osso Cortical/anatomia & histologia , Osso Cortical/diagnóstico por imagem , Erros de Diagnóstico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Incisivo/anatomia & histologia , Incisivo/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Odontometria/métodos , Palato Duro/anatomia & histologia , Palato Duro/diagnóstico por imagem , Valores de Referência , Estudos Retrospectivos , Fatores Sexuais , Adulto Jovem
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