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1.
J Pregnancy ; 2023: 6669700, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026545

RESUMO

Aim: To suggest cut-off points for body mass index (BMI) using gestational hypertension, preeclampsia, and gestational diabetes mellitus (GDM) as cardiometabolic conditions in pregnancy. Methods: In this prospective study, singleton pregnant women from the fetal medicine service of the Brazilian Unified Health System were included. The pregnancy, perinatal, and newborn data were obtained from the clinical medical records. Maternal anthropometry included an assessment of weight and height and the prepregnancy BMI evaluation categorized according to the World Health Organization cut-off points. The area under the curve and confidence interval values from receiver operator curves were generated to identify the optimal cut-off points using prepregnancy BMI with better sensitivity and specificity. Results: Data on 218 pregnancies were analyzed, with 57.9% (n = 124) being classified as overweight/obese, 11% (n = 24) with GDM, 6.9% (n = 15) with preeclampsia, and 11.0% (n = 24) with gestational hypertension. The BMI cut-off points for predicting cardiometabolic conditions were 27.52 kg/m2 (S: 66.7%; E: 63.8%) for women with GDM; 27.40 kg/m2 (S: 73.3%; E: 62.4%; S: 79.2%; E: 64.9%; S: 70.3%; E: 66.3%) for women with preeclampsia, gestational hypertension, and gestational hypertension plus preeclampsia, respectively; and 27.96 kg/m2 (S: 69.6%; E: 65.6%) for women with preeclampsia plus GDM. Conclusion: The findings suggest that the optimal prepregnancy BMI cut-off point is around 27 kg/m2 for pregnant women with maternal cardiometabolic conditions.


Assuntos
Diabetes Gestacional , Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Recém-Nascido , Gravidez , Feminino , Humanos , Hipertensão Induzida pela Gravidez/diagnóstico , Pré-Eclâmpsia/diagnóstico , Índice de Massa Corporal , Estudos Prospectivos , Obesidade , Diabetes Gestacional/diagnóstico , Fatores de Risco
2.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-511203

RESUMO

With the coexistence of multiple lineages and increased international travel, recombination and gene flow are likely to become increasingly important in the adaptive evolution of SARS-CoV-2. This could result in the incipient parallel evolution of multiple recombinant lineages. However, identifying recombinant lineages is challenging, and the true extent of recombinant evolution in SARS-CoV-2 may be underestimated. This study describes the first SARS-CoV-2 Deltacron recombinant case identified in Brazil. We demonstrate that the recombination breakpoint is at the beginning of Spike gene (S). The 5' genome portion (circa 22 kb) resembles the AY.101 lineage (VOC Delta), and the 3' genome portion (circa 8 kb nucleotides) is most similar to the BA.1.1 lineage (VOC Omicron). Furthermore, evolutionary genomic analyses indicate that the new strain emerged after a single recombination event between lineages of diverse geographical locations in December 2021 in South Brazil. This Deltacron, named AYBA-RS, is one out of almost 30 recombinants described this year. The submission of only four sequences in the GISAID database suggests that this Brazilian lineage had a minor epidemiological impact. On the other hand, the recent emergence of this and various other Deltacron recombinant lineages (i.e., XD, XF, and XS) suggests that gene flow and recombination may play an increasingly important role in the COVID-19 pandemic. We explain the evolutionary and population genetic theory that support this assertion, and we conclude that this stresses the need for continued genomic and epidemiological surveillance. This is particularly important for countries where multiple variants are present, as well as for countries that receive significant inbound international travel.

3.
Av. psicol. latinoam ; 40(3): 1-20, sep.-dic. 2022.
Artigo em Português | LILACS, COLNAL | ID: biblio-1428015

RESUMO

O processamento da leitura é resultado da interação de distintos processos cognitivos, como reconhecimento de palavras, compreensão oral e fluência. Há evidências sobre a importância da fluência para predizer a com-preensão de leitura, mas ainda não é claro seu papel ao longo do desenvolvimento. Essa revisão sistemática analisou estudos nacionais e internacionais sobre a re-lação das habilidades de reconhecimento de palavras e fluência de leitura com a compreensão de leitura em alunos do 4º ao 9º ano. A revisão foi conduzida de acordo com a metodologia prisma e utilizou a base de dados PubMed, de 2000 a setembro de 2019. Foram incluídos artigos que respondiam à pergunta norteadora e atendiam à temática estabelecida pelos descritores e palavras-chave. Foram encontrados 992 artigos, dos quais 904 foram excluídos pelo título e resumo e 56 pela leitura do texto completo. Isto possibilitou a análise de 32 artigos. Os resultados sugerem que, diferentemente do reconhecimento de palavras, a habilidade de fluência de leitura tende a manter relação significativa com a compreensão de leitura no decorrer do segundo ciclo do Ensino Fundamental.


El procesamiento de la lectura es el resultado de la interacción de diferentes procesos cognitivos, como el reconocimiento de palabras, la comprensión oral y la fluidez. Existe evidencia sobre la importancia de la fluidez en la predicción de la comprensión lectora, pero a lo largo del desarrollo su papel no está claro. Esta revisión sistemática analizó estudios nacionales e internacionales sobre la relación entre las habilidades de reconocimiento de palabras y fluidez lectora con la comprensión lectora en estudiantes de 4° a 9° grado. La revisión se realizó de acuerdo con la metodología prisma y utilizó la base de datos PubMed, desde el 2000 hasta septiembre de 2019. Fueron incluidos artículos que respondieron a la pregunta guía y cumplieron con la temática establecida por los descriptores y palabras clave. Se encontraron 992 artículos, de los cuales 904 fueron excluidos por título y resumen, y 56 por lectura de texto completo. Esto permitió el análisis de 32 artículos. Los resultados sugieren que, a diferencia del reconocimiento de palabras, la habilidad de fluidez lectora tiende a mantener una relación significativa con la comprensión lectora durante el segundo ciclo de la escuela primaria.


Text processing results from the interaction of different cognitive processes, such as word recognition, listening comprehension, and fluency. There is evi-dence relating to the importance of fluency in pre-dicting reading comprehension, but its role during the course of development is still uncertain. The present systematic review has analyzed national and inter-national research on the relationship between word recognition skills and reading fluency with reading comprehension in students from the 4th to 9th grade. The review was conducted according to theprismamethodology and employed the PubMed database from 2000 to September 2019. The chosen papers answered the orienting question and corresponded to the topic established by the descriptors and keywords. We found 992 articles, of which 904 were excluded by reading the titles and abstracts and 56 by reading the full texts. It was possible to analyze 32 papers. The results suggest that, unlike word recognition, the ability to read fluently tends to uphold a significant relationship with reading comprehension during the second cycle of Elementary School.


Assuntos
Humanos , Aptidão , Leitura , Instituições Acadêmicas , Estudantes , Ensino Fundamental e Médio , Compreensão
4.
Cell Biol Int ; 46(9): 1433-1446, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35842770

RESUMO

Ankyrin repeat and KH domain-containing protein 1, ANKHD1, has been identified as a regulator of signaling pathways and cellular processes of relevance in carcinogenesis. However, the role of ANKHD1 in breast cancer remains unclear. The aim of the present study was to characterize the expression pattern and involvement of ANKHD1 in the malignant phenotype of breast cancer cell lines and to investigate the clinical relevance of ANKHD1 in a breast cancer context. Gene and protein expressions were assessed in the cell lines by quantitative reverse transcription PCR and Western blot analysis, respectively, and ANKHD1 silencing through siRNA transfection was conducted for further in vitro functional assays. The expression of ANKHD1 was identified in non-tumorigenic breast epithelium and breast cancer cell lines, but differences in cellular localization were found among the neoplasia subtypes. ANKHD1 silencing reduced the viability, clonogenicity, and migration of triple-negative breast cancer (TNBC) cells. Bioinformatics analyses demonstrated that patients with triple-negative basal-like 2 and mesenchymal breast cancer subtypes had high ANKHD1 expression associated with poor recurrence-free survival. Therefore, these data indicate that ANKHD1 relevance in breast cancer varies among its subtypes, indicating the importance of ANKHD1 in TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Fenótipo , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
5.
Syst Rev ; 10(1): 205, 2021 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-34274019

RESUMO

BACKGROUND: Biologic drugs such as adalimumab, etanercept, and infliximab represent major first-line and second-line treatments for rheumatoid arthritis (RA) patients. However, their high cost poses a massive burden on healthcare systems worldwide. The expiration of patents for these biologics has driven the production of biosimilar drugs, which are potentially less costly and remarkably similar, albeit not identical to the reference molecules. This paper aims to outline the protocol of a systematic review that will investigate the efficacy and safety profile of biosimilars compared to biologics (objective 1) and the impact of switching between biosimilar drugs and reference biologics on the management of RA patients (objective 2). METHODS: We will investigate the effects of any biosimilars of adalimumab, etanercept, and infliximab on RA patients. We will include randomized controlled trials (RCTs) or quasi-RCTs to assess efficacy and safety outcomes and RCTs with two- or multiple-part designs to evaluate the consequences of switching from reference biologics to biosimilar drugs (and vice-versa). Electronic searches will be performed through MEDLINE (via PubMed), EMBASE, LILACS, and CENTRAL (from inception to April 2021). Two independent reviewers will screen studies, extract data, and evaluate the risk of bias. The latter will be carried out considering specific domains from equivalence trials and switching studies. Random-effects models will be fitted to obtain summary estimates using either relative risk or standardized mean difference as a metric. The primary outcome will be the rate of treatment success according to the American College of Rheumatology 20 (ACR20), and the co-primary outcome will be the Health Assessment Questionnaire-Disability Index (HAQ-DI). Conclusions will be based on equivalence hypothesis testing using predefined margins of equivalence elicited from a group of experienced rheumatologists and prior studies. The overall certainty of the evidence will be assessed based on the GRADE system. DISCUSSION: The present investigation proposes a comprehensive, clinician-oriented approach to assess the equivalence and the impact of switching between biosimilars and biologics on the management of patients with RA. Our results will elucidate the efficacy, safety, immunogenicity of biosimilars, and the clinical consequences of substituting biologics with biosimilars in the management of RA. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019137152 and CRD42019137155.


Assuntos
Antirreumáticos , Artrite Reumatoide , Medicamentos Biossimilares , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/uso terapêutico , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Resultado do Tratamento
6.
Biochim Biophys Acta Gen Subj ; 1865(9): 129937, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34052310

RESUMO

BACKGROUND: Antimicrobial peptides (AMPs) are molecules with potential application for the treatment of microorganism infections. We, herein, describe the structure, activity, and mechanism of action of RQ18, an α-helical AMP that displays antimicrobial activity against Gram-positive and Gram-negative bacteria, and yeasts from the Candida genus. METHODS: A physicochemical-guided design assisted by computer tools was used to obtain our lead peptide candidate, named RQ18. This peptide was assayed against Gram-positive and Gram-negative bacteria, yeasts, and mammalian cells to determine its selectivity index. The secondary structure and the mechanism of action of RQ18 were investigated using circular dichroism, large unilamellar vesicles, and molecular dynamic simulations. RESULTS: RQ18 was not cytotoxic to human lung fibroblasts, peripheral blood mononuclear cells, red blood cells, or Vero cells at MIC values, exhibiting a high selectivity index. Circular dichroism analysis and molecular dynamic simulations revealed that RQ18 presents varying structural profiles in aqueous solution, TFE/water mixtures, SDS micelles, and lipid bilayers. The peptide was virtually unable to release carboxyfluorescein from large unilamellar vesicles composed of POPC/cholesterol, model that mimics the eukaryotic membrane, indicating that vesicles' net charges and the presence of cholesterol may be related with RQ18 selectivity for bacterial and fungal cell surfaces. CONCLUSIONS: RQ18 was characterized as a membrane-active peptide with dual antibacterial and antifungal activities, without compromising mammalian cells viability, thus reinforcing its therapeutic application. GENERAL SIGNIFICANCE: These results provide further insight into the complex process of AMPs interaction with biological membranes, in special with systems that mimic prokaryotic and eukaryotic cell surfaces.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Colesterol/farmacologia , Fosfolipídeos/farmacologia , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Candida/efeitos dos fármacos , Colesterol/química , Escherichia coli/efeitos dos fármacos , Células Eucarióticas/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Simulação de Dinâmica Molecular , Fosfolipídeos/química , Proteínas Citotóxicas Formadoras de Poros/síntese química , Proteínas Citotóxicas Formadoras de Poros/química , Staphylococcus/efeitos dos fármacos
7.
Artigo em Inglês | MEDLINE | ID: mdl-33925277

RESUMO

Sedentary behaviors, those that involve sitting and low levels of energy expenditure, have been associated with several adverse cardiometabolic effects. This study evaluated the chronic effects of a combined circuit weight interval training (CWIT) on physical fitness, quality of life, and heart rate variability (HRV), and compared the effects of CWIT-induced autonomic adaptations on different postures in adult sedentary workers. Twenty-seven sedentary workers (age 36.9 ± 9.2 years old, 13 men and 14 women) were divided into two groups: control, who continued their sedentary behavior, and experimental, who were submitted to a CWIT for 12 weeks, completing two ~40 min sessions per week. Monitoring of 8th, 16th, and 24th sessions revealed a moderate training load during sessions. Participants exhibited an improved aerobic capacity (VO2max, 34.03 ± 5.36 vs. 36.45 ± 6.05 mL/kg/min, p < 0.05) and flexibility (22.6 ± 11.4 vs. 25.3 ± 10.1 cm, p < 0.05) after the training period. In addition, they showed greater quality of life scores. However, the CWIT did not change body composition. Interestingly, more HRV parameters were improved in the seated position. The CWIT used in the current study was associated with improvements in several fitness and quality of life parameters, as well as in cardiac autonomic control of HR in adult sedentary workers. Examination of different body positions when evaluating changes in HRV appears to be a relevant aspect to be considered in further studies. Future randomized controlled trials (RCTs) with larger samples of both sexes should confirm these promising results.


Assuntos
Aptidão Física , Qualidade de Vida , Adaptação Fisiológica , Adulto , Sistema Nervoso Autônomo , Exercício Físico , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade
8.
Curr Stem Cell Res Ther ; 16(6): 695-709, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33372881

RESUMO

The use of stem cells in cell therapies has shown promising results in the treatment of several diseases, including diabetes mellitus, in both humans and animals. Mesenchymal stem cells (MSCs) can be isolated from various locations, including bone marrow, adipose tissues, synovia, muscles, dental pulp, umbilical cords, and the placenta. In vitro, by manipulating the composition of the culture medium or transfection, MSCs can differentiate into several cell lineages, including insulin-producing cells (IPCs). Unlike osteogenic, chondrogenic, and adipogenic differentiation, for which the culture medium and time are similar between studies, studies involving the induction of MSC differentiation in IPCs differ greatly. This divergence is usually evident in relation to the differentiation technique used, the composition of the culture medium, the cultivation time, which can vary from a few hours to several months, and the number of steps to complete differentiation. However, although there is no "gold standard" differentiation medium composition, most prominent studies mention the use of nicotinamide, exedin-4, ß-mercaptoethanol, fibroblast growth factor b (FGFb), and glucose in the culture medium to promote the differentiation of MSCs into IPCs. Therefore, the purpose of this review is to investigate the stages of MSC differentiation into IPCs both in vivo and in vitro, as well as address differentiation techniques and molecular actions and mechanisms by which some substances, such as nicotinamide, exedin-4, ß-mercaptoethanol, FGFb, and glucose, participate in the differentiation process.


Assuntos
Diferenciação Celular , Células Secretoras de Insulina , Células-Tronco Mesenquimais , Animais , Técnicas de Cultura de Células , Células Cultivadas , Humanos , Insulina , Células Secretoras de Insulina/citologia , Células-Tronco Mesenquimais/citologia
9.
Front Immunol ; 12: 760291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35046936

RESUMO

Human vaccination against leptospirosis has been relatively unsuccessful in clinical applications despite an expressive amount of vaccine candidates has been tested over years of research. Pathogenic Leptospira encompass a great number of serovars, most of which do not cross-react, and there has been a lack of genetic tools for many years. These obstacles have hampered the understanding of the bacteria's biology and, consequently, the identification of an effective antigen. Thus far, many approaches have been used in an attempt to find a cost-effective and broad-spectrum protective antigen(s) against the disease. In this extensive review, we discuss several strategies that have been used to develop an effective vaccine against leptospirosis, starting with Leptospira-inactivated bacterin, proteins identified in the genome sequences of pathogenic Leptospira, including reverse vaccinology, plasmid DNA, live vaccines, chimeric multi-epitope, and toll- and nod-like receptors agonists. This overview should be able to guide scientists working in the field to select potential antigens and to choose the appropriate formulation to administer the candidates.


Assuntos
Vacinas Bacterianas/imunologia , Leptospira/imunologia , Leptospirose/prevenção & controle , Desenvolvimento de Vacinas , Vacinas Bacterianas/farmacologia , Humanos
10.
Curr Protein Pept Sci ; 21(10): 1011-1026, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32933457

RESUMO

Aminoglycosides and ß-lactams are the most commonly used antimicrobial agents in clinical practice. This occurs because they are capable of acting in the treatment of acute bacterial infections. However, the effectiveness of antibiotics has been constantly threatened due to bacterial pathogens producing resistance enzymes. Among them, the aminoglycoside-modifying enzymes (AMEs) and ß-lactamase enzymes are the most frequently reported resistance mechanisms. AMEs can inactivate aminoglycosides by adding specific chemical molecules in the compound, whereas ß-lactamases hydrolyze the ß-lactams ring, preventing drug-target interaction. Thus, these enzymes provide a scenario of multidrug-resistance and a significant threat to public health at a global level. In response to this challenge, in recent decades, several studies have focused on the development of inhibitors that can restore aminoglycosides and ß-lactams activity. In this context, peptides appear as a promising approach in the field of inhibitors for future antibacterial therapies, as multiresistant bacteria may be susceptible to these molecules. Therefore, this review focused on the most recent findings related to peptide-based inhibitors that act on AMEs and ß-lactamases, and how these molecules could be used for future treatment strategies.


Assuntos
Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Ácido Clavulânico/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sulbactam/uso terapêutico , Tazobactam/uso terapêutico , Aminoglicosídeos/metabolismo , Aminoglicosídeos/uso terapêutico , Antibacterianos/metabolismo , Antibacterianos/uso terapêutico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Desenho de Fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/enzimologia , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/enzimologia , Bactérias Gram-Positivas/crescimento & desenvolvimento , Humanos , Canamicina Quinase/antagonistas & inibidores , Canamicina Quinase/química , Canamicina Quinase/metabolismo , Nucleotidiltransferases/antagonistas & inibidores , Nucleotidiltransferases/química , Nucleotidiltransferases/metabolismo , beta-Lactamases/química , beta-Lactamases/metabolismo , beta-Lactamas/metabolismo , beta-Lactamas/uso terapêutico
11.
Int J Biol Macromol ; 164: 2497-2511, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32798540

RESUMO

The utilization of vegetable oils as biological oligomers for the synthesis of macromolecular materials has considerably evolved in the last decades, opening the way for the preparation of sophisticated materials based on synthetic processes for the design of polymers with very specific applications. Tung oil (TO), easily obtained from the seeds of the Asian tung tree (Vernicia fordii), is a relatively cheap commodity that has as its main constituent (~85%) a peculiar natural oligomeric triglyceride structure in which each chain bears three conjugated unsaturations corresponding to α-eleostearic acid. Following a previous study based on the association of TO with furans for the preparation of linear and cross-linked structures based on the Diels-Alder click reaction, the present study deals with the cationic (co) polymerization of xylan-derived furfuryl alcohol (FA) with TO, in order to combine the high intrinsic flexibility of the crosslinked TO polymers with the stiffness of the FA resin, which should lead to fully bio-based crosslinked materials with a tunable glass transition. Three approaches were investigated using trifluoroacetic acid (TFA) in chloroform, viz. (i) combining crude TO and furfuryl alcohol, (ii) combining methyl α-eleostearate and furfuryl alcohol, and (iii) polymerizing furfuryl α-eleostearate itself. The polymerization reactions with varying TFA concentrations were followed by 1H NMR spectroscopy, and it was possible to get valuable information on mechanistic aspects. Also, higher concentrations of TFA were used to synthesize and isolate polymer networks, in order to understand their molecular characteristic as well as access their main thermal properties.


Assuntos
Furanos/química , Óleos de Plantas/química , Polímeros , Xilanos/química , Polímeros/síntese química , Polímeros/química
12.
Am J Perinatol ; 37(9): 955-961, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31170750

RESUMO

OBJECTIVE: This study aimed to describe the experience with a protocol of therapeutic hypothermia (TH) in southern Brazil. STUDY DESIGN: Newborns with gestational age > 35 weeks with evidence of perinatal asphyxia plus moderate or severe encephalopathy were recruited between March 2011 and November 2017. Whole-body hypothermia for 72 hours, starting within the first 6 hours of life was used. Survivors underwent magnetic resonance imaging (MRI) and electroencephalogram (EEG). The primary outcome was death during hospitalization and neurodevelopment assessed using the Bayley Scales of Infant Development III (BSID III) at 12 months of age. RESULTS: A total of 72 newborns were treated (41 with moderate encephalopathy and 31 with severe encephalopathy), of whom 16 died. MRI was performed in 56 patients, and 24 presented some alterations. Fifty-three patients had an EEG: 11 normal, 20 mildly altered, 12 moderately altered, and 10 severely altered. Forty patients were evaluated through BSID III: 45% presented with some delay in neurodevelopment, 8 (20%) had motor retardation, 15 (37.5%) had language delay, and 13 (32.5%) had a delay in cognitive development. CONCLUSION: Mortality and adverse events were similar to those described in large randomized controlled trials. TH is a safe and an effective method of neurologic protection in asphyxiated newborns in a developing country when performed adequately.


Assuntos
Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/terapia , Imageamento por Ressonância Magnética/métodos , Adulto , Asfixia Neonatal/complicações , Brasil , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/etiologia , Eletroencefalografia , Estudos de Viabilidade , Feminino , Humanos , Hipotermia Induzida/mortalidade , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/mortalidade , Lactente , Recém-Nascido , Doenças do Recém-Nascido , Masculino , Gravidez , Índice de Gravidade de Doença , Adulto Jovem
13.
Int J Mol Sci ; 20(19)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581426

RESUMO

The advent of multidrug resistance among pathogenic bacteria has attracted great attention worldwide. As a response to this growing challenge, diverse studies have focused on the development of novel anti-infective therapies, including antimicrobial peptides (AMPs). The biological properties of this class of antimicrobials have been thoroughly investigated, and membranolytic activities are the most reported mechanisms by which AMPs kill bacteria. Nevertheless, an increasing number of works have pointed to a different direction, in which AMPs are seen to be capable of displaying non-lytic modes of action by internalizing bacterial cells. In this context, this review focused on the description of the in vitro and in vivo antibacterial and antibiofilm activities of non-lytic AMPs, including indolicidin, buforin II PR-39, bactenecins, apidaecin, and drosocin, also shedding light on how AMPs interact with and further translocate through bacterial membranes to act on intracellular targets, including DNA, RNA, cell wall and protein synthesis.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bactérias/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Bactérias/metabolismo , Glicopeptídeos/metabolismo , Insetos , Biossíntese de Proteínas
14.
Front Pharmacol ; 10: 686, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31258482

RESUMO

The rapid increase in the number of individuals with obesity, over the past four decades, is triggered by a number of complex interactions among factors. Despite the plethora of treatments available, side effects are commonly observed and, in this context, herbal medicines have been employed as an alternative form of therapy. Ginkgo biloba extract (GbE) has been described as a promising new pharmacological approach to treat obesity. In order to better comprehend the mechanisms involved with this potential effect, the present study evaluated the effects of GbE treatment on diet-induced obese rats, focusing on the proteome and the oxidative stress defense system of visceral adipose tissue. After 14 days treatment, GbE significantly modulated 25 proteins. Retroperitoneal adipose tissue of treated animals exhibited higher amounts of proteins associated with adipogenesis (decorin), carbon metabolism and mitochondrial function (citrate synthase), and a concomitant reduction in adipocyte hypertrophy. In parallel, GbE down-regulated proteins involved in oxidative stress (peroxiredoxin) and the inflammatory response (complement C3, mast cell protease 1, and Ig gamma-2B chain C region). Moreover, also related to oxidative stress defense, GbE stimulated catalase activity, reduced malondialdehyde levels (lipid peroxidation indicator), and increased lactoylglutathione lyase levels. It was concluded that GbE acts as an antioxidant agent, and improved the proteome profile and oxidative stress response in the adipose tissue of diet-induced obese rats.

15.
Microb Pathog ; 135: 103605, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31228542

RESUMO

Biofilm-related infections represent an enormous clinical challenge nowadays. In this context, diverse studies are underway to develop effective antimicrobial agents targeting bacterial biofilms. Here, we describe the antibacterial and anti-biofilm activities of a short, cationic peptide named R5F5, obtained from sliding-window analysis based on a peptide (PcDBS1R5) derived from Plasmodium chabaudi. Ten fragments were generated (R5F1 to F10) and submitted to initial antibacterial assays against Pseudomonas aeruginosa. As a result, R5F5 showed the highest antimicrobial activity. We therefore carried out further antibacterial and anti-biofilm assays against P. aeruginosa and Klebsiella pneumoniae carbapenemase-producing bacterial strains. R5F5 revealed selective anti-biofilm activity, as the peptide inhibited >60% biofilm formation in all cases from 8 to 64 µg·mL-1. Moreover, R5F5 was not hemolytic against mice erythrocytes at 640 µg mL-1. Cytotoxic effects on human lung fibroblast cells were not detected at 160 µg·mL-1. Structural studies revealed that R5F5 presents random coil conformations in water and 50% 2,2,2-trifluoroethanol (TFE)/water (v/v), whereas amphipathic, extended conformations were observed in contact with sodium dodecyl sulfate (SDS) micelles. Thus, here we report a novel peptide with selective anti-biofilm activity against susceptible and resistant bacterial strains, with no toxicity toward mammalian cells and that adopts a stable structure in anionic environment.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Biofilmes/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Proteínas de Bactérias , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Simulação de Dinâmica Molecular , Plasmodium chabaudi/química , beta-Lactamases
16.
Microorganisms ; 7(2)2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30791633

RESUMO

Pathogenic Leptospira spp. is the etiological agent of leptospirosis. The high diversity among Leptospira species provides an array to look for important mediators involved in pathogenesis. Toxin-antitoxin (TA) systems represent an important survival mechanism on stress conditions. vapBC modules have been found in nearly one thousand genomes corresponding to about 40% of known TAs. In the present study, we investigated TA profiles of some strains of Leptospira using a TA database and compared them through protein alignment of VapC toxin sequences among Leptospira spp. genomes. Our analysis identified significant differences in the number of putative vapBC modules distributed in pathogenic, saprophytic, and intermediate strains: four in L. interrogans, three in L. borgpetersenii, eight in L. biflexa, and 15 in L. licerasiae. The VapC toxins show low identity among amino acid sequences within the species. Some VapC toxins appear to be exclusively conserved in unique species, others appear to be conserved among pathogenic or saprophytic strains, and some appear to be distributed randomly. The data shown here indicate that these modules evolved in a very complex manner, which highlights the strong need to identify and characterize new TAs as well as to understand their regulation networks and the possible roles of TA systems in pathogenic bacteria.

17.
Nutrients ; 11(2)2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30795551

RESUMO

Many Clostridium species are found as commensal members of the intestinal microbiota. However, imbalances of the microbiota may lead to certain infections caused by these microorganisms, mainly Clostridium butyricum, Clostridium difficile, and Clostridium perfringens. In many cases, infection recurrence can occur after antibiotics, indicating the need for novel therapeutic options that act on the pathogens and also restore the microbiota. Herein, the in vitro antimicrobial activity and probiotic potential of clinical and reference strains of Bifidobacterium and Lactobacillus were investigated against Clostridium species. Antimicrobial activity was evaluated by the agar spot test and inhibition of gas production. Then, the probiotic potential of selected strains was assessed by analyzing their coaggregation ability, adhesive properties to host cells and mucin, tolerance to acidic pH and bile salts, and antimicrobial susceptibility profiles. Lactobacillus plantarum ATCC 8014 was the most promising strain based on its inhibitory activity against Clostridium spp. Also, this strain met criteria to be considered a probiotic based on its coaggregation ability, adhesive properties, and tolerance to harsh pH and bile acid salt conditions. The results indicate that among the studied strains, L. plantarum ATCC 8014 presents probiotic potential for controlling infections induced by the studied Clostridium species and should be further evaluated in in vivo animal models.


Assuntos
Bifidobacterium/crescimento & desenvolvimento , Infecções por Clostridium/microbiologia , Clostridium/crescimento & desenvolvimento , Microbioma Gastrointestinal , Lactobacillus/crescimento & desenvolvimento , Interações Microbianas , Probióticos , Anti-Infecciosos , Aderência Bacteriana , Ácidos e Sais Biliares , Infecções por Clostridium/tratamento farmacológico , Clostridium butyricum/crescimento & desenvolvimento , Clostridium perfringens/crescimento & desenvolvimento , Humanos , Concentração de Íons de Hidrogênio , Lactobacillus plantarum/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Probióticos/uso terapêutico
18.
Australas J Ageing ; 38(2): e58-e66, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30761707

RESUMO

OBJECTIVE: To describe the experience of a Brazilian medical school in implementing different active methods to teach Geriatric Medicine, reporting the students' opinions and satisfaction with the classes and comparing pre- and postcourse measurements of knowledge, attitudes and skills. METHODS: A total of 166 third-year medical students received different active theoretical-practical activities for teaching Geriatric Medicine and their knowledge, attitudes, clinical skills and satisfaction were investigated. RESULTS: All activities had good acceptance among students ranging from 8.54 in the activity "Walking aids" to 9.81 in the activity "Nursing Home visit" (ranging 0-10). After the course, students had better attitudes towards older persons (r = 0.55-0.81, P < 0.001), better knowledge (r = 0.84, P < 0.001), greater empathy (r = 0.51, P < 0.001) and better clinical skills (r = 0.86, P < 0.001). Finally, the course was evaluated positively by the students. CONCLUSION: New active Geriatric Medicine learning activities resulted in improvement in medical students knowledge, attitudes and skills.


Assuntos
Competência Clínica , Geriatria/educação , Conhecimentos, Atitudes e Prática em Saúde , Estudantes de Medicina , Ensino , Adulto , Feminino , Humanos , Masculino
19.
JBRA Assist Reprod ; 22(3): 244-252, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29932615

RESUMO

Breast cancer may affect young women who have not yet completed childbearing. Assisted reproductive technology (ART) provides alternatives for fertility preservation such as oocyte, embryo or ovarian tissue cryopreservation. We reviewed the published literature on fertility-preserving management in breast cancer, aiming at finding evidence to answer the following questions: (1) What are the fertility sparing options available?; (2) How do these women respond to IVF? and (3) Can pregnancy influence breast cancer recurrence? There is a paucity of publications describing clinical experience and outcome data which limits accessibility to fertility preservation in this setting. Presently, oocyte or embryo cryopreservation are the main options for fertility preservation. IVF success rates are comparable to the ones of non-oncological populations according to the woman's age but current published studies lack data on definitive success rates following embryo banking for cancer patients. The perception that IVF and pregnancy may worsen cancer prognosis remains, despite the lack of scientific evidence to support this notion. Published studies show reassuring results for pregnancies occurring >2 years after breast cancer diagnosis. The best published evidence suggests pregnancy after breast cancer does not increase the risk of disease recurrence, thus pregnancy should not be forbidden once treatment is completed. Decision making for women diagnosed with cancer requires up-to-date knowledge of the efficacy and safety of available options. Providing consultation with a reproductive specialist and appropriate information on fertility preservation for these women should be an essential aspect of their supportive care.


Assuntos
Neoplasias da Mama/terapia , Preservação da Fertilidade , Criopreservação , Feminino , Humanos , Gravidez , Técnicas de Reprodução Assistida
20.
BMC Geriatr ; 17(1): 279, 2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29207946

RESUMO

BACKGROUND: It remains unclear into which level the systolic blood pressure (SBP) should be lowered in order to provide the best cardiovascular protection among older people. Hypertension guidelines recommendation on attaining SBP levels <150 mmHg in this population is currently based on experts' opinion. To clarify this issue, we systematically reviewed and quantified available evidence on the impact of achieving different SBP levels <150 mmHg on various adverse outcomes in subjects aged ≥60 years old receiving antihypertensive drug treatment. METHODS: We searched 8 databases to identify randomized controlled trials (RCTs) and post-hoc analyses or subanalyses of RCTs reporting the effects of attaining different SBP levels <150 mmHg on the risk of stroke, acute myocardial infarction, heart failure, cardiovascular mortality and all-cause mortality in participants aged ≥60 years. We performed random-effects meta-analyses stratified by study design. RESULTS: Eleven studies (> 33,600 participants) were included. Compared with attaining SBP levels ≥140 mmHg, levels of 130 to <140 mmHg were not associated with lower risk of outcomes in the meta-analysis of RCTs, whereas there was an associated reduction of cardiovascular mortality (RR 0.72, 95% CI 0.59-0.88) and all-cause mortality (RR 0.86, 95% CI 0.75-0.99) in the meta-analysis of post-hoc analyses or subanalyses of RCTs. Limited and conflicting data were available for the SBP levels of <130 mmHg and 140 to <150 mmHg. CONCLUSIONS: Among older people, there is suggestive evidence that achieving SBP levels of 130 to <140 mmHg is associated with lower risks of cardiovascular and all-cause mortality. Future trials are required to confirm these findings and to provide additional evidence regarding the <130 and 140 to <150 mmHg SBP levels.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/fisiopatologia , Idoso , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Comportamento de Redução do Risco
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