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1.
Cureus ; 16(2): e54738, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38524004

RESUMO

INTRODUCTION: With the advent of the COVID-19 pandemic, numerous questions have arisen regarding the screening, diagnosis, treatment, and prognosis of infected patients. Among these, screening infected patients through body temperature measurement has proven ineffective. However, doubts persist regarding the role of fever as a prognostic factor in the disease. OBJECTIVE: To assess the prevalence of fever and its relevance as a marker of mortality in COVID-19. METHODOLOGY: This prospective and longitudinal cohort study was conducted between April 2020 and December 2021 and analyzed 1400 COVID-19 patients systematically admitted to the emergency department of a reference hospital during the period from April 2020 to December 2021, in the city of Curitiba, Brazil. [LG1] The study evaluated [LG2] the presence of fever (body temperature above 37,7ºC) upon admission and/or during hospitalization, patient profiles, and outcomes (in-hospital death, discharge, admission at the intensive care unit, need of mechanical ventilation). RESULTS: Fever was present in 128 participants (9.1%), with a higher prevalence in males (71%) and obese individuals (42.9%). Among the febrile patients, 39 required intubation (30.4%), with two intubated upon admission (1.5%), 104 were discharged (81.2%), and 24 deceased (18.7%). Fever was not associated with a higher mortality rate. CONCLUSION: Fever showed low prevalence, is more common in males and obese individuals, and is not related to worse clinical outcomes.

2.
J Photochem Photobiol B ; 251: 112847, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38241947

RESUMO

The bovine tick Rhipicephalus microplus, a primary ectoparasite of veterinary concern, contributes significantly to disease transmission and reduced cattle productivity, resulting in substantial economic losses. The overuse of chemical acaricides has led to the emergence of resistant strains, posing a considerable challenge to veterinary medicine. Consequently, the development of alternative parasite control methods is essential to ensure livestock quality and enhance food safety worldwide. Our study introduces an innovative approach to photodynamic inactivation (PDI) of the bovine tick, harnessing natural daylight for a potential field application. Reproductive parameters (female and egg mass, egg production index, and larval hatch) were evaluated in engorged female ticks under photodynamic action using the hematoporphyrin (HP) and tetra-cationic porphyrins free-base meso-tetra-ruthenated (4-pyridyl) (RuTPyP) and its zinc(II) complex (ZnRuTPyP) as photosensitizers (PS). The results showed that there was no significant difference between the groups treated with tetra­ruthenium porphyrins and the control group. However, HP exhibits a control percentage of 97.9% at a concentration of 2.5 µmol.L-1, aligning with the expected control rates achieved by conventional chemical acaricides. Photophysical and physicochemical parameters such as the number of singlet oxygen produced and lipophilicity were discussed for each PS and related to tick control percentages. Furthermore, the interaction between HP and chitin, an important macromolecule presents in the tick's cuticle, considered as the primary target tick structure during PDI was observed by the absorption and fluorescence emission spectroscopic techniques. Therefore, the results presented here extend the potential for controlling R. microplus through photodynamic inactivation while utilizing sunlight as a source of natural irradiation.


Assuntos
Acaricidas , Porfirinas , Rhipicephalus , Animais , Feminino , Bovinos , Acaricidas/farmacologia , Rhipicephalus/fisiologia , Porfirinas/farmacologia , Reprodução
3.
Nanomedicine (Lond) ; 18(18): 1175-1194, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37712604

RESUMO

Aim: To develop, characterize and evaluate an oil/water nanoemulsion with squalene (CTVad1) to be approved as an adjuvant for the SpiN COVID-19 vaccine clinical trials. Materials & methods: Critical process parameters (CPPs) of CTVad1 were standardized to meet the critical quality attributes (CQAs) of an adjuvant for human use. CTVad1 and the SpiN-CTVad1 vaccine were submitted to physicochemical, stability, in vitro and in vivo studies. Results & conclusion: All CQAs were met in the CTVad1 production process. SpiN- CTVad1 met CQAs and induced high levels of antibodies and specific cellular responses in in vivo studies. These results represented a critical step in the process developed to meet regulatory requirements for the SpiN COVID-19 vaccine clinical trial.


Assuntos
COVID-19 , Vacinas , Humanos , Vacinas contra COVID-19/uso terapêutico , Emulsões/química , COVID-19/prevenção & controle , Adjuvantes Imunológicos/uso terapêutico , Adjuvantes Imunológicos/química , Vacinas/química
4.
Trans R Soc Trop Med Hyg ; 117(11): 804-810, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37477502

RESUMO

BACKGROUND: Ocular toxoplasmosis (OT) is a frequent clinical manifestation due to infection by Toxoplasma gondii. It is characterized by an inflammatory process involving macrophages activated by pro-inflammatory cytokines. The expression of microRNAs takes place during the inflammatory process and, among them, miRNA 511 regulates the activation of macrophages. This study evaluated the expression of miRNA 511_5p in patients with OT and healthy controls. METHODS: A total of 361 patients from the Hospital de Base of Fundação Faculdade de Medicina de São José do Rio Preto were enrolled and divided into four groups: G1-patients with active ocular lesions and reagent serology for T. gondii; G2-patients with scars and reagent serology for T. gondii; G3-patients without ocular lesions or scars and reagent serology for T. gondii; G4-patients without ocular lesions or scars and non-reagent serology for T. gondii. All patients underwent clinical and laboratory evaluation to confirm the diagnosis of OT. Serology tests, RNA extraction and cDNA synthesis were performed. RESULTS: The miRNA 511_5p levels were compared among the groups. The G1 group showed a high blood plasma concentration of miRNA 511_5p (mean 22.34) compared with the G2 (4.65), G3 (8.91) and G4 (3.52) groups (p<0.0001). CONCLUSION: These data suggest that miRNA 511_5p has significant potential as a biomarker for OT.


Assuntos
MicroRNAs , Toxoplasma , Toxoplasmose Ocular , Humanos , Toxoplasmose Ocular/genética , MicroRNAs/genética , Cicatriz , Toxoplasma/genética , Biomarcadores
5.
Sci Rep ; 13(1): 3463, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36859446

RESUMO

The majority of early prediction scores and methods to predict COVID-19 mortality are bound by methodological flaws and technological limitations (e.g., the use of a single prediction model). Our aim is to provide a thorough comparative study that tackles those methodological issues, considering multiple techniques to build mortality prediction models, including modern machine learning (neural) algorithms and traditional statistical techniques, as well as meta-learning (ensemble) approaches. This study used a dataset from a multicenter cohort of 10,897 adult Brazilian COVID-19 patients, admitted from March/2020 to November/2021, including patients [median age 60 (interquartile range 48-71), 46% women]. We also proposed new original population-based meta-features that have not been devised in the literature. Stacking has shown to achieve the best results reported in the literature for the death prediction task, improving over previous state-of-the-art by more than 46% in Recall for predicting death, with AUROC 0.826 and MacroF1 of 65.4%. The newly proposed meta-features were highly discriminative of death, but fell short in producing large improvements in final prediction performance, demonstrating that we are possibly on the limits of the prediction capabilities that can be achieved with the current set of ML techniques and (meta-)features. Finally, we investigated how the trained models perform on different hospitals, showing that there are indeed large differences in classifier performance between different hospitals, further making the case that errors are produced by factors that cannot be modeled with the current predictors.


Assuntos
COVID-19 , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Brasil , Hospitais , Hospitalização , Aprendizado de Máquina
6.
Antiviral Res ; 212: 105578, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36934985

RESUMO

The Zika virus (ZIKV) is an arbovirus and belongs to the Flaviviridae family and Flavivirus genus, with dissemination in the Americas. In Brazil, the predominant strain is the Asian, promoting outbreaks that started in 2015 and are directly related to microcephaly in newborns and Guillain-Barré syndrome in adults. Recently, researchers identified a new African strain circulating in Brazil at the mid-end of 2018 and the beginning of 2019, with the potential to originate a new epidemic. To date, there is no approved vaccine or drug for the treatment of Zika syndrome, and the development of therapeutic alternatives to treat it is of relevance. A critical approach is to use natural products when searching for new chemical agents to treat Zika syndrome. The present investigation describes the preparation of a series of 1,2,3-triazoles derived from the natural product vanillin and the evaluation of their virucide activity. A series of fourteen derivatives were prepared via alkylation of vanillin followed by CuAAC (the copper(I)-catalyzed azide-alkyne cycloaddition) reaction. The compounds were fully characterized by infrared (I.R.), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS) techniques. The cytotoxicity of Vero cells and the effect on the Zika Virus of the vanillin derivatives were evaluated. It was found that the most effective compound corresponded to 4-((1-(4-isopropylbenzyl)-1H-1,2,3-triazol-4-yl)methoxy)-3-methoxybenzaldehyde (8) (EC50 = 27.14 µM, IC50 = 334.9 µM). Subsequent assessments, namely pre and post-treatment assays, internalization and adsorption inhibition assays, kinetic, electronic microscopy analyses, and zeta potential determination, revealed that compound 8 blocks the Zika virus infection in vitro by acting on the viral particle. A molecular docking study was performed, and the results are also discussed.


Assuntos
Infecção por Zika virus , Zika virus , Animais , Chlorocebus aethiops , Adulto , Recém-Nascido , Humanos , Infecção por Zika virus/prevenção & controle , Células Vero , Simulação de Acoplamento Molecular , Replicação Viral
7.
Mol Nutr Food Res ; 67(12): e2200308, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36938670

RESUMO

SCOPE: Human milk (HM) has a wide range of proteins with biological and nutritional functions, essential for newborns. The roles of proteins and their proteoforms in HM are not fully understood. This study aims to assess, by 2-DE proteomics, the differential proteoforms in HM, present in colostrum (COL), transition (TRA), and mature milk (MAT), aiming to contribute to understanding neonates' protein needs. METHODS AND RESULTS: HM samples are collected from 39 healthy lactating women. COL presents the higher concentration of essential amino acids. After MALDI-MS/MS and bioinformatics analysis, proteoforms are differentially detected. Abundances of ß-casein (CSN2), α-s1 casein, and α-lactalbumin (LALBA) are higher in MAT; CSN2s are found in 11 spots and the isoforms increase in size as the pI becomes more acidic; regarding LALBA, two variant forms are found with different abundances in TRA and MAT; CSN2, LALBA, lactotransferrin (LTF), and serum albumin forms are present in all lactation phases. CONCLUSION: This study reveals differential proteoforms in COL involved in tissue growth and body development, besides essential amino acids, and, in MAT, involved in muscle mass gain, strengthening of the immune system, and energy production. The results provide new insight about proteoforms involved in maturation of the newborn's organs and systems.


Assuntos
Caseínas , Leite Humano , Recém-Nascido , Feminino , Humanos , Animais , Leite Humano/química , Caseínas/análise , Lactação , Lactalbumina , Lactoferrina , Albumina Sérica/análise , Proteômica , Espectrometria de Massas em Tandem , Leite/química , Fatores de Transcrição , Aminoácidos Essenciais , Proteínas do Leite/química
8.
Pharmaceutics ; 15(2)2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36839905

RESUMO

Cisplatin (CDDP) is a potent antitumor drug used in first-line chemotherapy against several solid tumors, including breast cancer. However, toxicities and drug resistance limit its clinical application. Thermosensitive liposome (TSL) functionalized with hyaluronic acid (HA) containing cisplatin (TSL-CDDP-HA) was developed by our research group aiming to promote the release of CDDP in the tumor region under hyperthermia conditions, as well as to decrease toxicity. Thus, this study aimed to evaluate this new formulation (HA-coated TSL-CDDP) concerning in vitro behavior and in vivo toxicity compared to non-coated TSL-CDDP and free CDDP. Cytotoxicity assays and nuclear morphology were carried out against triple-negative breast cancer cells (MDA-MB-231), while an in vivo toxicity study was performed using healthy Swiss mice. The results showed an increase (around 3-fold) in cytotoxicity of the cationic formulation (non-coated TSL-CDDP) compared to free CDDP. On the other hand, TSL-CDDP treatment induced the appearance of 2.5-fold more senescent cells with alteration of nuclear morphology than the free drug after hyperthermia condition. Furthermore, the association of liposomal formulations treatment with hyperthermia increased the percentage of apoptotic cells compared to those without heating. The percentage of apoptotic cells was 1.7-fold higher for TSL-CDDP-HA than for TSL-CDDP. For the in vivo toxicity data, the TSL-CDDP treatment was also toxic to healthy cells, inducing nephrotoxicity with a significant increase in urea levels compared to the saline control group (73.1 ± 2.4 vs. 49.2 ± 2.8 mg/mL). On the other hand, the HA-coated TSL-CDDP eliminated the damages related to the use of CDDP since the animals did not show changes in hematological and biochemical examinations and histological analyses. Thus, data suggest that this new formulation is a potential candidate for the intravenous therapy of solid tumors.

9.
Comput Biol Med ; 147: 105695, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35785665

RESUMO

Proteins play a crucial role in organisms in nature. They are able to perform structural, catalytic, transport and defense functions in cells, among others. We understand that a variety of resources do exist to work with protein structural bioinformatics, which perform tasks such as protein modeling, protein docking, protein molecular dynamics, protein interaction, active and binding site prediction and mutation analysis. Nonetheless, they are generally spread all over different online repositories. For the students or professionals interested in working with protein structural bioinformatics, it may not be trivial to know what resources he/she should learn/use or where these could be accessed. Here, the main subareas in the field of protein structural bioinformatics are introduced with a brief description, and we point to and discuss several online resources, such as methods, databases and tools, in order to give an overview of this research field. Furthermore, we developed Protein Structural bioinformatics Overview (PreStO), a web tool available at http://bioinfo.dcc.ufmg.br/presto/, to organize and make it possible to retrieve these online resources based on a search term. We believe that this paper can be a starting point for potential bioinformaticians to trace a path that can be followed to build competencies and achieve knowledge milestones in the context of protein structural bioinformatics.


Assuntos
Biologia Computacional , Proteínas , Sítios de Ligação , Biologia Computacional/métodos , Bases de Dados Factuais , Humanos , Proteínas/química
10.
PLoS One ; 17(4): e0267471, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35452494

RESUMO

The development of new drugs is a very complex and time-consuming process, and for this reason, researchers have been resorting heavily to drug repurposing techniques as an alternative for the treatment of various diseases. This approach is especially interesting when it comes to emerging diseases with high rates of infection, because the lack of a quickly cure brings many human losses until the mitigation of the epidemic, as is the case of COVID-19. In this work, we combine an in-house developed machine learning strategy with docking, MM-PBSA calculations, and metadynamics to detect potential inhibitors for SARS-COV-2 main protease among FDA approved compounds. To assess the ability of our machine learning strategy to retrieve potential compounds we calculated the Enrichment Factor of compound datasets for three well known protein targets: HIV-1 reverse transcriptase (PDB 4B3P), 5-HT2A serotonin receptor (PDB 6A94), and H1 histamine receptor (PDB 3RZE). The Enrichment Factor for each target was, respectively, 102.5, 12.4, 10.6, which are considered significant values. Regarding the identification of molecules that can potentially inhibit the main protease of SARS-COV-2, compounds output by the machine learning step went through a docking experiment against SARS-COV-2 Mpro. The best scored poses were the input for MM-PBSA calculations and metadynamics using CHARMM and AMBER force fields to predict the binding energy for each complex. Our work points out six molecules, highlighting the strong interaction obtained for Mpro-mirabegron complex. Among these six, to the best of our knowledge, ambenonium has not yet been described in the literature as a candidate inhibitor for the SARS-COV-2 main protease in its active pocket.


Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Humanos , Antivirais/química , Antivirais/farmacologia , Proteases 3C de Coronavírus , Aprendizado de Máquina , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases/química
11.
Rev. Bras. Cancerol. (Online) ; 68(2)Abr.-Jun. 2022.
Artigo em Português | LILACS | ID: biblio-1379087

RESUMO

Introdução: O linfoma primário de mama (LPM) representa cerca de 0,5% das neoplasias mamárias, sendo considerado um tipo raro de tumor. Alguns dos tipos de LPM, por sua vez, possuem ligação intensa com o período gravídico e pós-parto em virtude do estímulo hormonal. O objetivo deste estudo é relatar um caso de LPM com apresentação rara de linfoma de Burkitt, considerando propostas terapêuticas eficazes para o seguimento. Relato do caso: Paciente do sexo feminino, 23 anos, portadora de tumoração periareolar em mama direita com aspecto de casca de laranja e crescimento rápido há um mês, queixas flogísticas no local da lesão, bom estado geral e sem outros sintomas associados. O quadro relatado iniciou-se sete meses após a expulsão fetal com feto morto. A paciente foi submetida à biópsia da lesão e encaminhada para seguimento ambulatorial sem sucesso, necessitando de retorno ao ambiente hospitalar por piora das condições clínicas e extensão da tumoração. Houve diagnóstico de linfoma de Burkitt, com tratamento multidisciplinar, sendo submetida a protocolo CODOX-M de quimioterapia, com óbito após 22 dias de acompanhamento hospitalar. Conclusão: Este relato demonstra uma situação rara em uma paciente jovem, ressaltando a importância de investigar as alterações mamárias, de maneira eficaz, para um diagnóstico precoce correto e um tratamento adequado, em todas as faixas etárias


Introduction: Primary breast lymphoma (PML) represents about 0.5% of breast cancers, being considered a rare type of tumor. Some of the types of PML, in turn, have an intense connection with the pregnancy and postpartum period due to hormonal stimulation. The aim of this study is to report a case of PML with a rare presentation of Burkitt's lymphoma, considering effective therapeutic proposals for follow-up. Case report: A 23-year-old female patient with a peri-areolar tumor in the right breast with orange peel aspect and rapid growth for one month, phlogistic complaints at the lesion site, good general condition and no other associated symptoms. The reported condition started seven months after fetal expulsion with a dead fetus. The patient underwent lesion biopsy and was referred to an outpatient follow-up with unsuccessful outcome, requiring return to the hospital due to worsening of clinical conditions and extension of the tumor. There was a diagnosis of Burkitt's lymphoma, with multidisciplinary treatment. She underwent the CODOX-M chemotherapy protocol, and died after 22 days of hospital follow-up. Conclusion: This report demonstrates a rare situation in a young patient, emphasizing the importance of effective investigation of breast changes so that correct early diagnosis and appropriate treatment can be made for all age groups


Introducción: El linfoma primario de mama (LMP) representa aproximadamente el 0,5% de los cánceres de mama, siendo considerado un tipo de tumor poco común. Algunos de los tipos de LPM, a su vez, tienen una conexión intensa con el embarazo y el posparto debido a la estimulación hormonal. El objetivo de este estudio es reportar un caso de LMP con rara presentación de linfoma de Burkitt, considerando propuestas terapéuticas efectivas para el seguimiento. Relato del caso: Paciente, 23 años, con un tumor periareolar en la mama derecha con aspecto de piel de naranja y rápido crecimiento durante un mes, quejas flogísticas en el sitio de la lesión, buen estado general y ningún otro. síntomas asociados. La condición reportada comenzó siete meses después de la expulsión fetal con un feto muerto. El paciente fue sometido a biopsia de la lesión y fue derivado sin éxito a seguimiento ambulatorio, requiriendo el retorno al entorno hospitalario por empeoramiento de la clínica y extensión del tumor. Hubo un diagnóstico de linfoma de Burkitt, con tratamiento multidisciplinario. Se sometió al protocolo de quimioterapia CODOX-M y murió a los 22 días de seguimiento hospitalario. Conclusión: Este informe demuestra una situación poco común en una paciente joven, enfatizando la importancia de investigar de manera efectiva los cambios en los senos para un diagnóstico temprano correcto y un tratamiento adecuado en todos los grupos de edad


Assuntos
Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Relatos de Casos , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/radioterapia
12.
Mol Biol Rep ; 48(11): 7165-7170, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34554386

RESUMO

BACKGROUND: Until a few years ago, keratoconus was defined as a noninflammatory degenerative disease. However, recent studies have shown that the altered balance between inflammatory cytokines, proteases, and protease inhibitors, as well as free radicals and oxidants, have a crucial role in the pathogenesis of this disease. The aim of this study is to investigate whether interleukin 17 A G197A (rs2275913) and interleukin 17 F T7488C (rs763780) polymorphisms are associated with keratoconus in patients from a population of the northwestern region of the State of São Paulo, Brazil. METHODS AND RESULTS: 35 patients and 61 controls were enrolled. Genotyping of interleukin 17 A G197A and interleukin 17 F T7488C polymorphisms was carried out using the polymerase chain reaction-restriction fragment length polymorphism technique. Statistical analyses were conducted using the chi-square test, and an odds ratio with a 95% confidence interval was also calculated to evaluate the association between polymorphisms and disease. Evaluating interleukin 17 F T7488C, we found that the TT genotype is associated as a risk factor for keratoconus (P = 0.04; OR = 3.01; CI 1.11-8.14). As for evaluating interleukin 17 A G197A, the allele and genotype frequencies between patients and controls were compared and no statistically significant differences were found. CONCLUSIONS: Our data showed that the interleukin 17 F T7488C polymorphisms may exert an influence in keratoconus.


Assuntos
Genótipo , Interleucina-17/genética , Ceratocone/genética , Polimorfismo de Fragmento de Restrição , Adolescente , Adulto , Feminino , Humanos , Masculino , Fatores de Risco
13.
BMC Bioinformatics ; 22(1): 1, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33388027

RESUMO

BACKGROUND: Protein-peptide interactions play a fundamental role in a wide variety of biological processes, such as cell signaling, regulatory networks, immune responses, and enzyme inhibition. Peptides are characterized by low toxicity and small interface areas; therefore, they are good targets for therapeutic strategies, rational drug planning and protein inhibition. Approximately 10% of the ethical pharmaceutical market is protein/peptide-based. Furthermore, it is estimated that 40% of protein interactions are mediated by peptides. Despite the fast increase in the volume of biological data, particularly on sequences and structures, there remains a lack of broad and comprehensive protein-peptide databases and tools that allow the retrieval, characterization and understanding of protein-peptide recognition and consequently support peptide design. RESULTS: We introduce Propedia, a comprehensive and up-to-date database with a web interface that permits clustering, searching and visualizing of protein-peptide complexes according to varied criteria. Propedia comprises over 19,000 high-resolution structures from the Protein Data Bank including structural and sequence information from protein-peptide complexes. The main advantage of Propedia over other peptide databases is that it allows a more comprehensive analysis of similarity and redundancy. It was constructed based on a hybrid clustering algorithm that compares and groups peptides by sequences, interface structures and binding sites. Propedia is available through a graphical, user-friendly and functional interface where users can retrieve, and analyze complexes and download each search data set. We performed case studies and verified that the utility of Propedia scores to rank promissing interacting peptides. In a study involving predicting peptides to inhibit SARS-CoV-2 main protease, we showed that Propedia scores related to similarity between different peptide complexes with SARS-CoV-2 main protease are in agreement with molecular dynamics free energy calculation. CONCLUSIONS: Propedia is a database and tool to support structure-based rational design of peptides for special purposes. Protein-peptide interactions can be useful to predict, classifying and scoring complexes or for designing new molecules as well. Propedia is up-to-date as a ready-to-use webserver with a friendly and resourceful interface and is available at: https://bioinfo.dcc.ufmg.br/propedia.


Assuntos
Sistemas de Gerenciamento de Base de Dados , Bases de Dados de Proteínas , Peptídeos/química , Proteínas/química , Algoritmos , Humanos
14.
Biochim Biophys Acta Biomembr ; 1863(1): 183449, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32828849

RESUMO

Studies have suggested that antimicrobial peptides act by different mechanisms, such as micellisation, self-assembly of nanostructures and pore formation on the membrane surface. This work presents an extensive investigation of the membrane interactions of the 14 amino-acid antimicrobial peptide hylaseptin P1-NH2 (HSP1-NH2), derived from the tree-frog Hyla punctata, which has stronger antifungal than antibacterial potential. Biophysical and structural analyses were performed and the correlated results were used to describe in detail the interactions of HSP1-NH2 with zwitterionic and anionic detergent micelles and phospholipid vesicles. HSP1-NH2 presents similar well-defined helical conformations in both zwitterionic and anionic micelles, although NMR spectroscopy revealed important structural differences in the peptide N-terminus. 2H exchange experiments of HSP1-NH2 indicated the insertion of the most N-terminal residues (1-3) in the DPC-d38 micelles. A higher enthalpic contribution was verified for the interaction of the peptide with anionic vesicles in comparison with zwitterionic vesicles. The pore formation ability of HSP1-NH2 (examined by dye release assays) and its effect on the size and surface charge as well as on the lipid acyl chain ordering (evaluated by Fourier-transform infrared spectroscopy) of anionic phospholipid vesicles showed membrane disruption even at low peptide-to-phospholipid ratios, and the effect increases proportionately to the peptide concentration. On the other hand, these biophysical investigations showed that a critical peptide-to-phospholipid ratio around 0.6 is essential for promoting disruption of zwitterionic membranes. In conclusion, this study demonstrates that the binding process of the antimicrobial HSP1-NH2 peptide depends on the membrane composition and peptide concentration.


Assuntos
Proteínas de Anfíbios/química , Membranas Artificiais , Proteínas Citotóxicas Formadoras de Poros/química , Animais , Anuros , Conformação Proteica em alfa-Hélice
15.
Pharmaceuticals (Basel) ; 12(4)2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31775273

RESUMO

Conventional chemotherapy regimens have limitations due to serious adverse effects. Targeted drug delivery systems to reduce systemic toxicity are a powerful drug development platform. Encapsulation of antitumor drug(s) in thermosensitive nanocarriers is an emerging approach with a promise to improve uptake and increase therapeutic efficacy, as they can be activated by hyperthermia selectively at the tumor site. In this review, we focus on thermosensitive nanosystems associated with hyperthermia for the treatment of cancer, in preclinical and clinical use.

16.
J Bras Pneumol ; 42(3): 196-202, 2016.
Artigo em Inglês, Português | MEDLINE | ID: mdl-27383933

RESUMO

OBJECTIVE: The gait speed test (GST) is a physical test that can predict falls and aid in the diagnosis of sarcopenia in the elderly. However, to our knowledge, there have been no studies evaluating its reproducibility in hospitalized elderly patients. The objective of this study was to evaluate the safety and reproducibility of the six-meter GST (6GST) in hospitalized elderly patients. METHODS: This repeated measures study involved hospitalized elderly patients (≥ 60 years of age) who underwent the 6GST by the fifth day of hospitalization, were able to walk without assistance, and presented no signs of dyspnea or pain that would prevent them from performing the test. The 6GST was performed three times in sequence, with a rest period between each test, in a level corridor. Gait speed was measured in meters/second. Reproducibility was assessed by comparing the means, intraclass correlation coefficients (ICCs) and Bland-Altman plots. RESULTS: We evaluated 110 elderly patients in a total of 330 tests. All participants completed all of the tests. The comparisons between the speeds obtained during the three tests showed high ICCs and a low mean bias (Bland-Altman plots). The correlation and accuracy were greatest when the mean maximum speed was compared with that obtained in the third test (1.26 ± 0.44 m/s vs. 1.22 ± 0.44 m/s; ICC = 0.99; p = 0.001; mean bias = 0.04; and limits of agreement = -0.27 to 0.15). CONCLUSIONS: The 6GST was proven to be safe and to have good reproducibility in this sample of hospitalized elderly patients. The third measurement seems to correspond to the maximum speed, since the first two measurements underestimated the actual performance. OBJETIVO: O teste de velocidade de marcha (TVM) é um teste físico que pode predizer quedas e auxiliar no diagnóstico de sarcopenia em idosos da comunidade. Entretanto, pelo que sabemos, não há estudos que avaliaram sua reprodutibilidade em idosos hospitalizados. O objetivo deste estudo foi avaliar a segurança e a reprodutibilidade do TVM de seis metros (TVM6) em idosos hospitalizados. MÉTODOS: Estudo com medidas repetidas envolvendo idosos hospitalizados (idade ≥ 60 anos) que realizaram o TVM6 até o quinto dia de hospitalização, sendo capazes de andar sem auxílio e não apresentando dispneia ou dor que os incapacitasse para a realização dos testes. O TVM6 foi realizado sequencialmente três vezes, com período de descanso, em um corredor plano, e a velocidade de marcha foi calculada em metros/segundo. A reprodutibilidade foi avaliada pela comparação das médias, coeficientes de correlação intraclasse (CCI) e disposições gráficas de Bland-Altman. RESULTADOS: Foram avaliados 110 idosos avaliados com um total de 330 testes. Todos os participantes completaram todos os testes. As comparações entre as velocidades obtidas nos três testes realizados indicaram CCIs elevados e viés médio baixo pela disposição gráfica de Bland-Altman. Em relação à maior velocidade aferida, a correlação e a precisão foram maiores quando comparadas à obtida no terceiro teste (1,26 ± 0,44 m/s vs. 1,22 ± 0,44 m/s; CCI = 0,99; p = 0,001; viés médio = 0,04; e limites de concordância = -0,27 a 0,15). CONCLUSÕES: O TVM6 mostrou-se seguro e teve boa reprodutibilidade nessa amostra de idosos hospitalizados. A terceira aferição parece corresponder à velocidade máxima, já que duas primeiras subestimaram o desempenho real.


Assuntos
Pacientes Internados , Velocidade de Caminhada/fisiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Brasil , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Desempenho Psicomotor/fisiologia , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Risco , Sarcopenia/diagnóstico , Sarcopenia/fisiopatologia , Fatores de Tempo
17.
J. bras. pneumol ; 42(3): 196-202, tab, graf
Artigo em Inglês | LILACS | ID: lil-787487

RESUMO

ABSTRACT Objective: The gait speed test (GST) is a physical test that can predict falls and aid in the diagnosis of sarcopenia in the elderly. However, to our knowledge, there have been no studies evaluating its reproducibility in hospitalized elderly patients. The objective of this study was to evaluate the safety and reproducibility of the six-meter GST (6GST) in hospitalized elderly patients. Methods: This repeated measures study involved hospitalized elderly patients (≥ 60 years of age) who underwent the 6GST by the fifth day of hospitalization, were able to walk without assistance, and presented no signs of dyspnea or pain that would prevent them from performing the test. The 6GST was performed three times in sequence, with a rest period between each test, in a level corridor. Gait speed was measured in meters/second. Reproducibility was assessed by comparing the means, intraclass correlation coefficients (ICCs) and Bland-Altman plots. Results: We evaluated 110 elderly patients in a total of 330 tests. All participants completed all of the tests. The comparisons between the speeds obtained during the three tests showed high ICCs and a low mean bias (Bland-Altman plots). The correlation and accuracy were greatest when the mean maximum speed was compared with that obtained in the third test (1.26 ± 0.44 m/s vs. 1.22 ± 0.44 m/s; ICC = 0.99; p = 0.001; mean bias = 0.04; and limits of agreement = −0.27 to 0.15). Conclusions: The 6GST was proven to be safe and to have good reproducibility in this sample of hospitalized elderly patients. The third measurement seems to correspond to the maximum speed, since the first two measurements underestimated the actual performance.


RESUMO Objetivo: O teste de velocidade de marcha (TVM) é um teste físico que pode predizer quedas e auxiliar no diagnóstico de sarcopenia em idosos da comunidade. Entretanto, pelo que sabemos, não há estudos que avaliaram sua reprodutibilidade em idosos hospitalizados. O objetivo deste estudo foi avaliar a segurança e a reprodutibilidade do TVM de seis metros (TVM6) em idosos hospitalizados. Métodos: Estudo com medidas repetidas envolvendo idosos hospitalizados (idade ≥ 60 anos) que realizaram o TVM6 até o quinto dia de hospitalização, sendo capazes de andar sem auxílio e não apresentando dispneia ou dor que os incapacitasse para a realização dos testes. O TVM6 foi realizado sequencialmente três vezes, com período de descanso, em um corredor plano, e a velocidade de marcha foi calculada em metros/segundo. A reprodutibilidade foi avaliada pela comparação das médias, coeficientes de correlação intraclasse (CCI) e disposições gráficas de Bland-Altman. Resultados: Foram avaliados 110 idosos avaliados com um total de 330 testes. Todos os participantes completaram todos os testes. As comparações entre as velocidades obtidas nos três testes realizados indicaram CCIs elevados e viés médio baixo pela disposição gráfica de Bland-Altman. Em relação à maior velocidade aferida, a correlação e a precisão foram maiores quando comparadas à obtida no terceiro teste (1,26 ± 0,44 m/s vs. 1,22 ± 0,44 m/s; CCI = 0,99; p = 0,001; viés médio = 0,04; e limites de concordância = −0,27 a 0,15). Conclusões: O TVM6 mostrou-se seguro e teve boa reprodutibilidade nessa amostra de idosos hospitalizados. A terceira aferição parece corresponder à velocidade máxima, já que duas primeiras subestimaram o desempenho real.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pacientes Internados , Velocidade de Caminhada/fisiologia , Fatores Etários , Brasil , Hospitalização , Unidades de Terapia Intensiva , Desempenho Psicomotor/fisiologia , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Risco , Sarcopenia/diagnóstico , Sarcopenia/fisiopatologia , Fatores de Tempo
18.
Clinics (Sao Paulo) ; 70(5): 369-72, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26039955

RESUMO

OBJECTIVES: The ability of the Timed Up and Go test to predict sarcopenia has not been evaluated previously. The objective of this study was to evaluate the accuracy of the Timed Up and Go test for predicting sarcopenia in elderly hospitalized patients. METHODS: This cross-sectional study analyzed 68 elderly patients (≥60 years of age) in a private hospital in the city of Salvador-BA, Brazil, between the 1st and 5th day of hospitalization. The predictive variable was the Timed Up and Go test score, and the outcome of interest was the presence of sarcopenia (reduced muscle mass associated with a reduction in handgrip strength and/or weak physical performance in a 6-m gait-speed test). After the descriptive data analyses, the sensitivity, specificity and accuracy of a test using the predictive variable to predict the presence of sarcopenia were calculated. RESULTS: In total, 68 elderly individuals, with a mean age 70.4±7.7 years, were evaluated. The subjects had a Charlson Comorbidity Index score of 5.35±1.97. Most (64.7%) of the subjects had a clinical admission profile; the main reasons for hospitalization were cardiovascular disorders (22.1%), pneumonia (19.1%) and abdominal disorders (10.2%). The frequency of sarcopenia in the sample was 22.1%, and the mean length of time spent performing the Timed Up and Go test was 10.02±5.38 s. A time longer than or equal to a cutoff of 10.85 s on the Timed Up and Go test predicted sarcopenia with a sensitivity of 67% and a specificity of 88.7%. The accuracy of this cutoff for the Timed Up and Go test was good (0.80; IC=0.66-0.94; p=0.002). CONCLUSION: The Timed Up and Go test was shown to be a predictor of sarcopenia in elderly hospitalized patients.


Assuntos
Precisão da Medição Dimensional , Avaliação Geriátrica/métodos , Sarcopenia/diagnóstico , Estudos de Tempo e Movimento , Acidentes por Quedas , Idoso , Transtornos Cognitivos/diagnóstico , Estudos Transversais , Avaliação da Deficiência , Feminino , Marcha/fisiologia , Hospitalização , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Valor Preditivo dos Testes
19.
BMC Musculoskelet Disord ; 16: 108, 2015 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-25943762

RESUMO

BACKGROUND: Sarcopenia is an important public health problem that affects mainly elders, and has negative consequences, such as disability and even death. Due to the lack of studies evaluating sarcopenia in elderly persons hospitalized in Brazil, the aim of the present study was to describe the frequency of sarcopenia and associated factors among elders in a hospital in the city of Salvador-Brazil. METHODS: This cross-sectional study included 110 hospitalized elderly patients in a multi-specialty hospital in Salvador-BA, Brazil. Inclusion criteria: were elders aged ≥60 years between the first and fifth day of hospitalization; who were able to walk without external assistance; with medical permission to walk, and who did not take vasoactive and inotropic drugs. The diagnosis of sarcopenia was determined by combining the reduction in skeletal muscle mass with muscle weakness (women, <20 kg; men, <30 kg) and/or poor physical performance (gait speed ≤0.8 m/s). To obtain reduced skeletal muscle mass, the skeletal muscle mass index ≤6.37 kg/m(2) for women and ≤8.90 kg/m(2) for men was used. Cognitive function, Charlson index, admission profile (clinical and surgical), smoking, falls suffered in the last year and physical inactivity prior to admission were also evaluated. The frequency of sarcopenia was described in percentages with their respective confidence intervals and logistic regression was performed for multivariate analysis of factors associated with sarcopenia. RESULTS: Among the 110 patients included, the frequency of sarcopenia was 21.8%, with 10.0% being of the severe type. There was a predominance of clinical profile (59.1%), such as heart disease (20.0%), pneumonia (13.6%) and skin infections (9.1%), with a Charlson index of 5.4 ± 1.8. The factors associated with sarcopenia were age (OR = 1.14; 95% CI = 1.06 to 1.23), clinical profile on admission (OR = 5.15; 95% CI = 1.16-22.9) and smoking (OR = 7.8; 95% CI = 1.53-39.9). CONCLUSIONS: The frequency of sarcopenia in elderly hospitalized patients was high (1 in 5 elderly) and anthropometric equation can be a viable and inexpensive alternative to screening and programming intervention in this population.


Assuntos
Hospitalização , Sarcopenia/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Brasil , Estudos Transversais , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Músculo Esquelético/patologia , Sarcopenia/complicações , Sarcopenia/patologia
20.
Clinics ; 70(5): 369-372, 05/2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-748271

RESUMO

OBJECTIVES: The ability of the Timed Up and Go test to predict sarcopenia has not been evaluated previously. The objective of this study was to evaluate the accuracy of the Timed Up and Go test for predicting sarcopenia in elderly hospitalized patients. METHODS: This cross-sectional study analyzed 68 elderly patients (≥60 years of age) in a private hospital in the city of Salvador-BA, Brazil, between the 1st and 5th day of hospitalization. The predictive variable was the Timed Up and Go test score, and the outcome of interest was the presence of sarcopenia (reduced muscle mass associated with a reduction in handgrip strength and/or weak physical performance in a 6-m gait-speed test). After the descriptive data analyses, the sensitivity, specificity and accuracy of a test using the predictive variable to predict the presence of sarcopenia were calculated. RESULTS: In total, 68 elderly individuals, with a mean age 70.4±7.7 years, were evaluated. The subjects had a Charlson Comorbidity Index score of 5.35±1.97. Most (64.7%) of the subjects had a clinical admission profile; the main reasons for hospitalization were cardiovascular disorders (22.1%), pneumonia (19.1%) and abdominal disorders (10.2%). The frequency of sarcopenia in the sample was 22.1%, and the mean length of time spent performing the Timed Up and Go test was 10.02±5.38 s. A time longer than or equal to a cutoff of 10.85 s on the Timed Up and Go test predicted sarcopenia with a sensitivity of 67% and a specificity of 88.7%. The accuracy of this cutoff for the Timed Up and Go test was good (0.80; IC=0.66-0.94; p=0.002). CONCLUSION: The Timed Up and Go test was shown to be a predictor of sarcopenia in elderly hospitalized patients. .


Assuntos
Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/mortalidade , Íleo/microbiologia , Intestino Delgado/transplante , Intestinos/microbiologia , Complicações Pós-Operatórias , /genética , Seguimentos , Rejeição de Enxerto/diagnóstico , Intestino Delgado/patologia , Intestino Delgado/cirurgia , Metagenoma/genética , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida
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