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1.
Int J Mol Sci ; 23(24)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36555465

RESUMO

Antimicrobial resistance (AMR) is a serious public health problem that results in high morbidity and mortality rates. In particular, multidrug-resistant (MDR) strains circulating in hospital settings pose a major threat as they are associated with serious nosocomial infections. Therefore, regular cleaning and disinfection procedures, usually using chemical disinfectants, must be implemented in these facilities. Hydrogen peroxide (HP)-based disinfectants have proven high microbicidal activity and several comparative advantages over conventional disinfectants. We assessed the in vitro biocidal activity of an 8% HP solution combined with 30 mg/L silver ions (HP + Ag) against MDR clinical isolates of Klebsiella pneumoniae (MDRKp) and Pseudomonas aeruginosa (MDRPa), and methicillin-resistant Staphylococcus aureus (MRSA). Accordingly, the in vitro antibacterial activity was determined using the macrodilution method, and the efficacy was determined for 30 min in terms of (1) activity on bacteria in suspension and (2) activity on surfaces using vaporized HP + Ag on a 20 cm2 stainless steel surface. A strong bactericidal effect of HP + Ag was observed against MDRKp, MDRPa, and MRSA strains, with minimum inhibitory concentrations and minimum bactericidal concentrations between 362.5 and 5800 mg/L. A strong effect was observed during the 30 min of HP + Ag exposure to the resistant clinical isolates, with over 4-Log10 reduction in CFUs. Regarding the efficacy of the disinfectant on surfaces, bacterial load reductions of >99% were observed. These results suggest that HP + Ag is potentially useful as an effective disinfectant for decontaminating surfaces in hospital settings suspected of contamination with MDR bacteria.


Assuntos
Desinfetantes , Staphylococcus aureus Resistente à Meticilina , Peróxido de Hidrogênio/farmacologia , Prata/farmacologia , Desinfetantes/farmacologia , Desinfecção/métodos , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana
2.
Pharmaceutics ; 14(6)2022 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-35745820

RESUMO

Bacterial antibiotic resistance is a serious global public health concern. Infections caused by colistin-resistant Pseudomonas aeruginosa (CRPa) strains represent a serious threat due to their considerable morbidity and mortality rates, since most of the current empirical antibiotic therapies are ineffective against these strains. Accordingly, cationic antimicrobial peptides (CAMPs) have emerged as promising alternatives to control resistant bacteria. In this study, the interaction of a CAMP derived from cecropin D-like (∆M2) with model membranes mimicking bacterial biomembranes of wild-type (WTPa) strains of P. aeruginosa and CRPa was evaluated through in vitro and in silico approaches. In vitro interaction was determined by infrared spectroscopy, whereas in silico molecular dynamics was performed to predict specific interactions between amino acids of ∆M2 and lipids of model membrane systems. Experimental analysis showed this peptide interacted with the lipids of bacterial-like model membranes of WTPa and CRPa. In both cases, an increase in the concentration of peptides induced an increase in the phase transition temperature of the lipid systems. On the other hand, the peptides in solution underwent a transition from a random to a helical secondary structure after interacting with the membranes mostly favored in the CRPa system. The α-helix structure percentage for ΔM2 interacting with WTPa and CRPa lipid systems was 6.4 and 33.2%, respectively. Finally, molecular dynamics showed ∆M2 to have the most affinities toward the phospholipids palmitoyl-oleyl-phosphatidylglycerol (POPG) and palmitoyl-oleoyl-phosphatidylethanolamine (POPE) that mimic membranes of WTPa and CRPa, respectively. This work provides clues for elucidating the membrane-associated mechanism of action of ∆M2 against colistin-susceptible and -resistant strains of Pseudomonas aeruginosa.

3.
Arq Bras Cardiol ; 118(2): 448-460, 2022 02.
Artigo em Inglês, Português | MEDLINE | ID: mdl-35262580

RESUMO

BACKGROUND: A methodology to identify patients with ascending aortic aneurysm (AsAA) under high risk for aortic growth is not completely defined. OBJETIVE: This research seeks to numerically characterize the aortic blood flow by relating the resulting mechanical stress distribution with AsAA growth. METHODS: Analytical, observational, single-center study in which a computational fluid dynamics (CFD) protocol was applied to aortic computed tomography angiogram (CTA) images of patients with AsAA. Two CTA exams taken at a minimum interval of one year were obtained. From the CTA-gathered images, three-dimensional models were built, and clinical data were registered. Study of velocity field and coherent structures (vortices) was performed aiming to relate them to the presence or absence of aneurysm growth, as well as comparing them to the patients' clinical data. The Kolmogorov-Smirnov test was used to evaluate the normality of the distribution, and the non-parametric Wilcoxon signed-rank test, for non-normal distribution, was used to compare the paired data of the aortic angles. Statistical significance was set at 5%. RESULTS: The incident jet in the aortic wall generated recirculation areas in the posterior region of the jet, inducing complex vortices formation in the group with aneurysm growth, leading to an average pressure increase in the ascending aortic wall between exams. In the group without aneurysm growth, the average pressure decreased. CONCLUSION: This pilot study showed that CFD based on CTA may in the near future be a tool to help identify flow patterns associated with AsAA remodeling process.


FUNDAMENTOS: Uma metodologia para identificação de pacientes portadores de aneurisma de aorta ascendente (AAAs) sob alto risco de remodelamento aórtico não está completamente definida. OBJETIVO: Esta pesquisa objetiva caracterizar numericamente o fluxo sanguíneo aórtico, relacionando a distribuição do estresse mecânico resultante com o crescimento de AAAs. MÉTODOS: Estudo analítico, observacional, unicêntrico, em que um protocolo de fluidodinâmica computacional (CFD - Computacional Fluid Dynamics) foi aplicado a imagens de angiotomografia computadorizada (ATC) de aorta de pacientes portadores de AAAs. Duas ATC de aorta com pelo menos um ano de intervalo foram obtidas. Dados clínicos dos pacientes foram registrados e, a partir das imagens de ATC, foram gerados modelos tridimensionais. Foram realizados estudos do campo de velocidade e estruturas coerentes (vórtices) com o objetivo de relacioná-los ao crescimento ou não do aneurisma e, posteriormente, compará-los com os dados clínicos dos pacientes. O teste de Kolmogorov-Smirnov foi utilizado para avaliar a normalidade da amostra e o teste não-paramétrico Wilcoxon signed-rank foi aplicado para comparações de dados pareados entre os ângulos aórticos. A significância estatística foi fixada em 5%. RESULTADOS: Para o grupo que apresentou crescimento do aneurisma, a incidência do jato na parede aórtica gerou áreas de recirculação posterior ao jato, induzindo à formação de vórtices complexos, ocasionando um incremento na pressão média no endotélio aórtico. O grupo sem crescimento do aneurisma apresentou diminuição na pressão média. CONCLUSÃO: Este estudo piloto mostrou que a CFD baseada em ATC pode, em um futuro próximo, ser uma ferramenta auxiliar na identificação dos padrões de fluxo associados ao processo de remodelamento de AAAs.


Assuntos
Aneurisma Aórtico , Hidrodinâmica , Aorta/diagnóstico por imagem , Aneurisma Aórtico/diagnóstico por imagem , Hemodinâmica/fisiologia , Humanos , Projetos Piloto
4.
Arq. bras. cardiol ; Arq. bras. cardiol;118(2): 448-460, 2022. tab, graf
Artigo em Inglês, Português | LILACS | ID: biblio-1364325

RESUMO

Resumo Fundamentos Uma metodologia para identificação de pacientes portadores de aneurisma de aorta ascendente (AAAs) sob alto risco de remodelamento aórtico não está completamente definida. Objetivo Esta pesquisa objetiva caracterizar numericamente o fluxo sanguíneo aórtico, relacionando a distribuição do estresse mecânico resultante com o crescimento de AAAs. Métodos Estudo analítico, observacional, unicêntrico, em que um protocolo de fluidodinâmica computacional (CFD - Computacional Fluid Dynamics) foi aplicado a imagens de angiotomografia computadorizada (ATC) de aorta de pacientes portadores de AAAs. Duas ATC de aorta com pelo menos um ano de intervalo foram obtidas. Dados clínicos dos pacientes foram registrados e, a partir das imagens de ATC, foram gerados modelos tridimensionais. Foram realizados estudos do campo de velocidade e estruturas coerentes (vórtices) com o objetivo de relacioná-los ao crescimento ou não do aneurisma e, posteriormente, compará-los com os dados clínicos dos pacientes. O teste de Kolmogorov-Smirnov foi utilizado para avaliar a normalidade da amostra e o teste não-paramétrico Wilcoxon signed-rank foi aplicado para comparações de dados pareados entre os ângulos aórticos. A significância estatística foi fixada em 5%. Resultados Para o grupo que apresentou crescimento do aneurisma, a incidência do jato na parede aórtica gerou áreas de recirculação posterior ao jato, induzindo à formação de vórtices complexos, ocasionando um incremento na pressão média no endotélio aórtico. O grupo sem crescimento do aneurisma apresentou diminuição na pressão média. Conclusão Este estudo piloto mostrou que a CFD baseada em ATC pode, em um futuro próximo, ser uma ferramenta auxiliar na identificação dos padrões de fluxo associados ao processo de remodelamento de AAAs.


Abstract Background A methodology to identify patients with ascending aortic aneurysm (AsAA) under high risk for aortic growth is not completely defined Objetive This research seeks to numerically characterize the aortic blood flow by relating the resulting mechanical stress distribution with AsAA growth. Methods Analytical, observational, single-center study in which a computational fluid dynamics (CFD) protocol was applied to aortic computed tomography angiogram (CTA) images of patients with AsAA. Two CTA exams taken at a minimum interval of one year were obtained. From the CTA-gathered images, three-dimensional models were built, and clinical data were registered. Study of velocity field and coherent structures (vortices) was performed aiming to relate them to the presence or absence of aneurysm growth, as well as comparing them to the patients' clinical data. The Kolmogorov-Smirnov test was used to evaluate the normality of the distribution, and the non-parametric Wilcoxon signed-rank test, for non-normal distribution, was used to compare the paired data of the aortic angles. Statistical significance was set at 5%. Results The incident jet in the aortic wall generated recirculation areas in the posterior region of the jet, inducing complex vortices formation in the group with aneurysm growth, leading to an average pressure increase in the ascending aortic wall between exams. In the group without aneurysm growth, the average pressure decreased. Conclusion This pilot study showed that CFD based on CTA may in the near future be a tool to help identify flow patterns associated with AsAA remodeling process.


Assuntos
Humanos , Aneurisma Aórtico/diagnóstico por imagem , Hidrodinâmica , Aorta/diagnóstico por imagem , Projetos Piloto , Hemodinâmica/fisiologia
5.
Pathogens ; 10(10)2021 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-34684290

RESUMO

Listeriosis is a foodborne disease caused by Listeria monocytogenes. Because outbreaks of listeriosis are associated with the ingestion of contaminated dairy products, surveillance of artisanal cheeses to detect the presence of this microorganism is necessary. We collected three types of artisanal non-acid fresh cheese (Campesino, Costeño, and Cuajada) from 12 municipalities of the Department of Quindío, Colombia. L. monocytogenes was identified using VIDAS® and confirmed with API® Listeria Rapid Kit. L. monocytogenes was detected in 104 (53.6%) of the 194 artisanal fresh-cheese samples analyzed. The highest percentages of contamination were detected in Salento (90.9%), Calracá (65.5%), Armenia (64.9%), and Filandia (50%). A significant association between municipality and contamination with L. monocytogenes was identified. However, no association could be established between the type of cheese and the occurrence of the bacterium. This is the first study on the presence of L. monocytogenes in artisanal fresh cheeses sold in the municipalities of the Department of Quindío, and the findings revealed very high percentages of contaminated samples. The presence of L. monocytogenes in artisanal cheeses remains a public health threat in developing countries, especially Colombia, where existing legislation does not require the surveillance of L. monocytogenes in food.

6.
Int J Mol Sci ; 22(15)2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34360692

RESUMO

The emergence of bacteria resistant to conventional antibiotics is of great concern in modern medicine because it renders ineffectiveness of the current empirical antibiotic therapies. Infections caused by vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-intermediate S. aureus (VISA) strains represent a serious threat to global health due to their considerable morbidity and mortality rates. Therefore, there is an urgent need of research and development of new antimicrobial alternatives against these bacteria. In this context, the use of antimicrobial peptides (AMPs) is considered a promising alternative therapeutic strategy to control resistant strains. Therefore, a wide number of natural, artificial, and synthetic AMPs have been evaluated against VRSA and VISA strains, with great potential for clinical application. In this regard, we aimed to present a comprehensive and systematic review of research findings on AMPs that have shown antibacterial activity against vancomycin-resistant and vancomycin-intermediate resistant strains and clinical isolates of S. aureus, discussing their classification and origin, physicochemical and structural characteristics, and possible action mechanisms. This is the first review that includes all peptides that have shown antibacterial activity against VRSA and VISA strains exclusively.


Assuntos
Proteínas Citotóxicas Formadoras de Poros/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus Resistente à Vancomicina/efeitos dos fármacos , Humanos , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/classificação , Proteínas Citotóxicas Formadoras de Poros/farmacologia
7.
Artif Organs ; 45(7): O195-O206, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33326639

RESUMO

Transcatheter aortic valve implantation (TAVI) is an increasingly widespread procedure. Although this intervention is indicated for high and low surgical risk patients, some issues still remain, such as prosthesis positioning optimization in the aortic annulus. Coaxial positioning of the percutaneous prosthesis influences directly on the aortic wall stress map. The determination of the mechanical stress that acts on the vascular endothelium resulting from blood flow can be considered an important task, since TAVI positioning can lead to unfavorable hemodynamic patterns, resulting in changes in parietal stress, such as those found in post-stenotic dilatation region. This research aims to investigate the influence of the prosthetic valve inclination angle in the mechanical stresses acting in the ascending aortic wall. Aortic compliance and blood flow during cardiac cycle were numerically obtained using fluid structure interaction. The aortic model was developed through segmentation of a computed tomography image of a specific patient submitted to TAVI. When compared to standard position (coaxiality match between the prosthesis and the aortic annulus), the inclination of 4° directed to the left main coronary artery decreased the aortic wall area with high values of wall shear stress and pressure. Coaxial positioning optimization of percutaneous aortic prosthesis may decrease the high mechanical stress area. These changes may be important to reduce the aortic remodeling process, vascular calcification or even the prosthesis half-life. Computational fluid dynamics makes room for personalized medicine, with manufactured prosthesis tailored to each patient.


Assuntos
Aorta/diagnóstico por imagem , Aorta/fisiologia , Valva Aórtica/cirurgia , Hemodinâmica , Estresse Mecânico , Substituição da Valva Aórtica Transcateter/métodos , Valva Aórtica/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo/fisiologia , Simulação por Computador , Humanos , Modelos Cardiovasculares , Tomografia Computadorizada por Raios X
8.
Molecules ; 25(23)2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33255849

RESUMO

A serious pandemic has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The interaction between spike surface viral protein (Sgp) and the angiotensin-converting enzyme 2 (ACE2) cellular receptor is essential to understand the SARS-CoV-2 infectivity and pathogenicity. Currently, no drugs are available to treat the infection caused by this coronavirus and the use of antimicrobial peptides (AMPs) may be a promising alternative therapeutic strategy to control SARS-CoV-2. In this study, we investigated the in silico interaction of AMPs with viral structural proteins and host cell receptors. We screened the antimicrobial peptide database (APD3) and selected 15 peptides based on their physicochemical and antiviral properties. The interactions of AMPs with Sgp and ACE2 were performed by docking analysis. The results revealed that two amphibian AMPs, caerin 1.6 and caerin 1.10, had the highest affinity for Sgp proteins while interaction with the ACE2 receptor was reduced. The effective AMPs interacted particularly with Arg995 located in the S2 subunits of Sgp, which is key subunit that plays an essential role in viral fusion and entry into the host cell through ACE2. Given these computational findings, new potentially effective AMPs with antiviral properties for SARS-CoV-2 were identified, but they need experimental validation for their therapeutic effectiveness.


Assuntos
Enzima de Conversão de Angiotensina 2/química , Tratamento Farmacológico da COVID-19 , SARS-CoV-2/química , Glicoproteína da Espícula de Coronavírus/química , Proteínas de Anfíbios/química , Proteínas de Anfíbios/uso terapêutico , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Antivirais/química , Antivirais/uso terapêutico , Sítios de Ligação/genética , COVID-19/genética , COVID-19/virologia , Simulação por Computador , Humanos , Pandemias , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/uso terapêutico , Ligação Proteica/genética , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/uso terapêutico , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/genética , Proteínas Estruturais Virais/uso terapêutico
9.
Molecules ; 25(21)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33142969

RESUMO

Antimicrobial resistance reduces the efficacy of antibiotics. Infections caused by multidrug-resistant (MDR), Gram-negative bacterial strains, such as Klebsiella pneumoniae (MDRKp) and Pseudomonas aeruginosa (MDRPa), are a serious threat to global health. However, cationic antimicrobial peptides (CAMPs) are promising as an alternative therapeutic strategy against MDR strains. In this study, the inhibitory activity of a cationic peptide, derived from cecropin D-like (ΔM2), against MDRKp and MDRPa clinical isolates, and its interaction with membrane models and bacterial genomic DNA were evaluated. In vitro antibacterial activity was determined using the broth microdilution test, whereas interactions with lipids and DNA were studied by differential scanning calorimetry and electronic absorption, respectively. A strong bactericidal effect of ΔM2 against MDR strains, with minimal inhibitory concentration (MIC) and minimal bactericidal concentrations (MBC) between 4 and 16 µg/mL, was observed. The peptide had a pronounced effect on the thermotropic behavior of the 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) membrane models that mimic bacterial membranes. Finally, the interaction between the peptide and genomic DNA (gDNA) showed a hyperchromic effect, which indicates that ΔM2 can denature bacterial DNA strands via the grooves.


Assuntos
Antibacterianos , Peptídeos Catiônicos Antimicrobianos , Klebsiella pneumoniae/crescimento & desenvolvimento , Pseudomonas aeruginosa/crescimento & desenvolvimento , Antibacterianos/química , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Humanos , Proteínas de Insetos/química , Klebsiella pneumoniae/isolamento & purificação , Precursores de Proteínas/química , Pseudomonas aeruginosa/isolamento & purificação
10.
Arq. bras. cardiol ; Arq. bras. cardiol;115(4): 680-687, out. 2020. graf
Artigo em Português | Sec. Est. Saúde SP, LILACS | ID: biblio-1131356

RESUMO

Resumo Fundamento O implante valvar aórtico percutâneo (TAVR, do inglês Transcatheter Aortic Valve Replacement) reduz a mortalidade de pacientes portadores de estenose aórtica grave. O conhecimento da distribuição da pressão e tensão de cisalhamento na parede aórtica pode ajudar na identificação de regiões críticas, onde o processo de remodelamento aórtico pode ocorrer. Neste trabalho é apresentado um estudo de simulação computacional da influência do posicionamento do orifício valvar protético na hemodinâmica na raiz de aorta e segmento ascendente. Objetivos A presente análise apresenta um estudo da variação do padrão de fluxo devido a alterações no ângulo do orifício valvar. Métodos Um modelo tridimensional foi gerado a partir do exame de angiotomografia computadorizada da aorta de um paciente que foi submetido ao procedimento de TAVR. Diferentes vazões de fluxo foram impostas através do orifício valvar. Resultados Pequenas variações no ângulo de inclinação causaram mudanças no padrão de fluxo, com deslocamento na posição dos vórtices, na distribuição de pressão e no local de alta tensão cisalhante na parede aórtica. Conclusão Essas características hemodinâmicas podem ser importantes no processo de remodelamento aórtico e distribuição de tensão, além de auxiliar, em um futuro próximo, a otimização do posicionamento da prótese valvar percutânea. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)


Abstract Backgroud Transcatheter aortic valve replacement (TAVR) can reduce mortality among patients with aortic stenosis. Knowledge of pressure distribution and shear stress at the aortic wall may help identify critical regions, where aortic remodeling process may occur. Here a numerical simulation study of the influence of positioning of the prosthetic valve orifice on the flow field is presented. Objective The present analysis provides a perspective of great variance on flow behavior due only to angle changes. Methods A 3D model was generated from computed tomography angiography of a patient who had undergone a TAVR. Different mass flow rates were imposed at the inlet valve. Results Small variations of the tilt angle could modify the nature of the flow, displacing the position of the vortices, and altering the prerssure distribution and the location of high wall shear stress. Conclusion These hemodynamic features may be relevant in the aortic remodeling process and distribution of the stress mapping and could help, in the near future, the optimization of the percutaneous prosthesis implantation. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)


Assuntos
Humanos , Estenose da Valva Aórtica/diagnóstico por imagem , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca , Substituição da Valva Aórtica Transcateter/efeitos adversos , Aorta , Valva Aórtica/cirurgia , Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Desenho de Prótese , Resultado do Tratamento , Angiografia por Tomografia Computadorizada , Hemodinâmica
11.
Sci Rep ; 10(1): 11198, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641782

RESUMO

Halving the proportion of the people without sustainable access to safe drinking water and basic sanitation is among the Sustainable Development Goals (SDG). Lack of access to safe drinking water has been associated with the prevalence of waterborne diseases. Due to this reported association, the development of household water treatment devices has been an alternative to improve the quality supply of domestic water. In this study, we aimed to evaluate the performance of a ceramic silver-impregnated pot filter (CSF) system coupled with an adsorption process, composed of silver-impregnated granular activated carbon and zeolite (CSF + GAC-Z), to remove waterborne bacteria Escherichia coli and Salmonella spp. from spiked water. The performance of this system was compared with the conventional CSF system. In this respect, we evaluated six CSF and six CSF + GAC-Z using spiked water with 103 and 102 CFU/mL of E. coli and Salmonella spp. The mean percentage of removals ranged between 98% and 99.98%. The highest bacterial removal efficiency was recorded by the CSF + GAC-Z (99%) and CSF (99.98%) for E. coli and Salmonella spp., respectively, but no significant statistical differences were found between filtration systems. Our findings suggest that the CSF + GAC-Z system was effective in the removal of waterborne bacteria from spiked water.


Assuntos
Cerâmica/química , Água Potável/microbiologia , Filtração/instrumentação , Prata/química , Purificação da Água/instrumentação , Adsorção , Carvão Vegetal/química , Escherichia coli , Salmonella , Poluição da Água , Zeolitas/química
12.
Evol Bioinform Online ; 16: 1176934320936266, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636607

RESUMO

Infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa and Klebsiella pneumoniae are a serious worldwide public health concern due to the ineffectiveness of empirical antibiotic therapy. Therefore, research and the development of new antibiotic alternatives are urgently needed to control these bacteria. The use of cationic antimicrobial peptides (CAMPs) is a promising candidate alternative therapeutic strategy to antibiotics because they exhibit antibacterial activity against both antibiotic susceptible and MDR strains. In this study, we aimed to investigate the in vitro antibacterial effect of a short synthetic CAMP derived from the ΔM2 analog of Cec D-like (CAMP-CecD) against clinical isolates of K pneumoniae (n = 30) and P aeruginosa (n = 30), as well as its hemolytic activity. Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of CAMP-CecD against wild-type and MDR strains were determined by the broth microdilution test. In addition, an in silico molecular dynamic simulation was performed to predict the interaction between CAMP-CecD and membrane models of K pneumoniae and P aeruginosa. The results revealed a bactericidal effect of CAMP-CecD against both wild-type and resistant strains, but MDR P aeruginosa showed higher susceptibility to this peptide with MIC values between 32 and >256 µg/mL. CAMP-CecD showed higher stability in the P aeruginosa membrane model compared with the K pneumoniae model due to the greater number of noncovalent interactions with phospholipid 1-Palmitoyl-2-oleyl-sn-glycero-3-(phospho-rac-(1-glycerol)) (POPG). This may be related to the boosted effectiveness of the peptide against P aeruginosa clinical isolates. Given the antibacterial activity of CAMP-CecD against wild-type and MDR clinical isolates of P aeruginosa and K pneumoniae and its nonhemolytic effects on human erythrocytes, CAMP-CecD may be a promising alternative to conventional antibiotics.

13.
Arq Bras Cardiol ; 115(4): 680-687, 2020 10.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32491131

RESUMO

BACKGROUD: Transcatheter aortic valve replacement (TAVR) can reduce mortality among patients with aortic stenosis. Knowledge of pressure distribution and shear stress at the aortic wall may help identify critical regions, where aortic remodeling process may occur. Here a numerical simulation study of the influence of positioning of the prosthetic valve orifice on the flow field is presented. OBJECTIVE: The present analysis provides a perspective of great variance on flow behavior due only to angle changes. METHODS: A 3D model was generated from computed tomography angiography of a patient who had undergone a TAVR. Different mass flow rates were imposed at the inlet valve. RESULTS: Small variations of the tilt angle could modify the nature of the flow, displacing the position of the vortices, and altering the prerssure distribution and the location of high wall shear stress. CONCLUSION: These hemodynamic features may be relevant in the aortic remodeling process and distribution of the stress mapping and could help, in the near future, the optimization of the percutaneous prosthesis implantation. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).


FUNDAMENTO: O implante valvar aórtico percutâneo (TAVR, do inglês Transcatheter Aortic Valve Replacement) reduz a mortalidade de pacientes portadores de estenose aórtica grave. O conhecimento da distribuição da pressão e tensão de cisalhamento na parede aórtica pode ajudar na identificação de regiões críticas, onde o processo de remodelamento aórtico pode ocorrer. Neste trabalho é apresentado um estudo de simulação computacional da influência do posicionamento do orifício valvar protético na hemodinâmica na raiz de aorta e segmento ascendente. OBJETIVOS: A presente análise apresenta um estudo da variação do padrão de fluxo devido a alterações no ângulo do orifício valvar. MÉTODOS: Um modelo tridimensional foi gerado a partir do exame de angiotomografia computadorizada da aorta de um paciente que foi submetido ao procedimento de TAVR. Diferentes vazões de fluxo foram impostas através do orifício valvar. RESULTADOS: Pequenas variações no ângulo de inclinação causaram mudanças no padrão de fluxo, com deslocamento na posição dos vórtices, na distribuição de pressão e no local de alta tensão cisalhante na parede aórtica. CONCLUSÃO: Essas características hemodinâmicas podem ser importantes no processo de remodelamento aórtico e distribuição de tensão, além de auxiliar, em um futuro próximo, a otimização do posicionamento da prótese valvar percutânea. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).


Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Aorta , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Angiografia por Tomografia Computadorizada , Hemodinâmica , Humanos , Desenho de Prótese , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
14.
Pharmaceutics ; 13(1)2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33396760

RESUMO

Colistin is a re-emergent antibiotic peptide used as a last resort in clinical practice to overcome multi-drug resistant (MDR) Gram-negative bacterial infections. Unfortunately, the dissemination of colistin-resistant strains has increased in recent years and is considered a public health problem worldwide. Strategies to reduce resistance to antibiotics such as nanotechnology have been applied successfully. In this work, colistin was characterized physicochemically by surface tension measurements. Subsequently, nanoliposomes coated with highly deacetylated chitosan were prepared with and without colistin. The nanoliposomes were characterized using dynamic light scattering and zeta potential measurements. Both physicochemical parameters fluctuated relatively to the addition of colistin and/or polymer. The antimicrobial activity of formulations increased by four-fold against clinical isolates of susceptible Pseudomona aeruginosa but did not have antimicrobial activity against multidrug-resistant (MDR) bacteria. Interestingly, the free coated nanoliposomes exhibited the same antibacterial activity in both sensitive and MDR strains. Finally, the interaction of colistin with phospholipids was characterized using molecular dynamics (MD) simulations and determined that colistin is weakly associated with micelles constituted by zwitterionic phospholipids.

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