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1.
Rev. enferm. UERJ ; 32: e79100, jan. -dez. 2024.
Article in English, Spanish, Portuguese | LILACS-Express | LILACS | ID: biblio-1556445

ABSTRACT

Objetivo: conhecer as representações sociais sobre o planejamento reprodutivo entre mulheres em gravidez não planejada na Estratégia Saúde da Família. Método: estudo qualitativo, orientado pela Teoria das Representações Sociais, realizado com 15 gestantes, entre abril e maio de 2019. Utilizou-se a entrevista semiestruturada. Os dados foram organizados por meio do Discurso do Sujeito Coletivo, com auxílio do software DSCsoft©. Protocolo de pesquisa aprovado pelo Comitê de Ética em Pesquisa. Resultados: as representações sociais das mulheres em gravidez não planejada evidenciadas pelo Discurso do Sujeito Coletivo foram representadas por oito ideias centrais, a saber: "eu não me preveni, nem ele", "nós nos prevenimos", "eu comprava", "pegava no posto", "construir uma família", "ter esse acesso", "estou por fora" e "eu sei que é disponível". Conclusão: as representações sociais nos discursos das mulheres em gravidez não planejada estavam pautadas no desconhecimento acerca do planejamento reprodutivo, dos anticoncepcionais disponíveis e seu uso correto.


Objective: to understand the social representations of reproductive planning among women with unplanned pregnancies in the Family Health Strategy. Method: qualitative study, guided by the Theory of Social Representations, carried out with 15 pregnant women between April and May 2019. Semi-structured interviews were used. The data was organized using the Discourse of the Collective Subject, with the aid of DSCsoft© software. Research protocol approved by the Research Ethics Committee. Results: the social representations of women with unplanned pregnancies as evidenced by the Collective Subject Discourse were represented by eight central ideas, namely: "I didn't prevent myself, nor did he", "we prevented ourselves", "I would buy it", "I would get it at the health center", "build a family", "have this access", "I am not aware" and "I know it is available". Conclusion: the social representations in the women's speeches about unplanned pregnancies were based on a lack of knowledge about reproductive planning, the contraceptives available and their correct use.


Objetivo: conocer las representaciones sociales sobre la planificación reproductiva de las mujeres con embarazo no planificado en la Estrategia Salud de la Familia. Método: estudio cualitativo, basado en la Teoría de las Representaciones Sociales, realizado con 15 mujeres embarazadas, entre abril y mayo de 2019. Se utilizaron entrevistas semiestructuradas. Los datos fueron organizados mediante el Discurso del Sujeto Colectivo, con ayuda del software DSCsoft©. El protocolo de investigación fue aprobado por el Comité de Ética en Investigación. Resultados: las representaciones sociales de las mujeres con embarazo no planificado reveladas por el Discurso del Sujeto Colectivo fueron representadas por ocho ideas centrales, a saber: "yo no me cuidé y él tampoco", "nos cuidamos", "yo los compraba", "los buscaba en el centro de salud", "construir una familia", "tener acceso", "no participo" y "sé que está disponible". Conclusión: las representaciones sociales en los discursos de las mujeres con embarazo no planificado se basaron en la falta de conocimiento sobre la planificación reproductiva, en los anticonceptivos disponibles y su uso correcto.

2.
Biochim Biophys Acta Proteins Proteom ; 1872(5): 141033, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39019246

ABSTRACT

Malonyl-CoA reductase utilizes two equivalents of NADPH to catalyze the reduction of malonyl-CoA to 3-hydroxypropionic acid (3HP). This reaction is part of the carbon fixation pathway in the phototrophic bacterium Chloroflexus aurantiacus. The enzyme is composed of two domains. The C-terminal domain catalyzes the reduction of malonyl-CoA to malonic semialdehyde, while the N-terminal domain catalyzes the reduction of the aldehyde to 3HP. The two domains can be produced independently and retain their enzymatic activity. This report focuses on the kinetic characterization of the C-terminal domain. Initial velocity patterns and inhibition studies showed the kinetic mechanism is ordered with NADPH binding first followed by malonyl-CoA. Malonic semialdehyde is released first, while CoA and NADP+ are released randomly. Analogs of malonyl-CoA showed that the thioester carbon is reduced, while the carboxyl group is needed for proper positioning. The enzyme transfers the pro-S hydrogen of NADPH to malonyl-CoA and pH rate profiles revealed that a residue with a pKa value of about 8.8 must be protonated for activity. Kinetic isotope effects indicated that NADPH is not sticky (that is, NADPH dissociates from the enzyme faster than the rate of product formation) and product release is partially rate-limiting. Moreover, the mechanism is stepwise with the pH dependent step occurring before or after hydride transfer. The findings from this study will aid in the development of an eco-friendly biosynthesis of 3HP which is an industrial chemical used in the production of plastics and adhesives.


Subject(s)
Chloroflexus , Malonyl Coenzyme A , NADP , Kinetics , NADP/metabolism , NADP/chemistry , Malonyl Coenzyme A/metabolism , Chloroflexus/metabolism , Chloroflexus/enzymology , Protein Domains , Alcohol Oxidoreductases/metabolism , Alcohol Oxidoreductases/chemistry , Alcohol Oxidoreductases/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Hydrogen-Ion Concentration , Oxidoreductases , Lactic Acid/analogs & derivatives
3.
bioRxiv ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38854064

ABSTRACT

The Escherichia coli heteromeric acetyl-CoA carboxylase (ACC) has four subunits assumed to form an elusive catalytic complex and are involved in allosteric and transcriptional regulation. The E. coli ACC represents almost all ACCs from pathogenic bacteria making it a key antibiotic development target to fight growing antibiotic resistance. Furthermore, it is a model for cyanobacterial and plant plastid ACCs as biofuel engineering targets. Here we report the catalytic E. coli ACC complex surprisingly forms tubes rather than dispersed particles. The cryo-EM structure reveals key protein-protein interactions underpinning efficient catalysis and how transcriptional regulatory roles are masked during catalysis. Discovering the protein-protein interaction interfaces that facilitate catalysis, allosteric and transcriptional regulation provides new routes to engineering catalytic activity and new targets for drug discovery.

4.
Plants (Basel) ; 13(10)2024 May 08.
Article in English | MEDLINE | ID: mdl-38794370

ABSTRACT

Bananas are a staple food that considerably contributes to both food security and income generation, especially in countries of Africa, Asia, and Central and South America. The banana plant (Musa spp.) is affected by various pathogens, of main concern being the plant-parasitic nematodes associated with the rhizosphere, the most important of which are Radopholus similis (burrowing nematode), Helicotylenchus sp. (spiral nematode), Pratylenchus sp. (root lesion nematode), and Meloidogyne sp. (gall nematode). Infected plants reduce their ability to absorb water and nutrients, which can lead to delayed flowering, fewer bunches, and lower fruit mass. Obtaining nematode-resistant banana cultivars through genetic improvement is an effective and sustainable option compared with chemical control with nematicides. Here, we provide the first systematic review of existing banana sources of resistance to nematodes to aid the management and control of nematodes in banana and plantain crops. Articles selected from different databases were evaluated, and searches were conducted using pre-established inclusion and exclusion criteria. We found 69 studies dealing with genetic improvement for nematode resistance in banana cultivation. Our findings revealed that sources of resistance are currently under investigation to combat the diseases caused by different nematode species in banana plants.

5.
J Nephrol ; 37(4): 1085-1092, 2024 May.
Article in English | MEDLINE | ID: mdl-38530601

ABSTRACT

BACKGROUND: This study aimed to compare the diagnostic yield of the FRAIL scale with respect to the physical frailty phenotype measure and their association with mortality in non-dialysis-dependent patients. METHODS: In this prospective cohort study, non-dialysis dependent patients with chronic kidney disease (CKD) stages 3b-5 seen in the nephrology outpatient clinics of two university hospitals were included. The presence of frailty was evaluated by physical frailty phenotype measure and the FRAIL scale. Patients were evaluated for six months, and mortality was recorded. The Kappa test was used to evaluate the diagnostic properties between the methods, and logistic regression to test the association between frailty and mortality. RESULTS: One hundred fifty-three patients were evaluated; average age was 65 (56-70) years, 50.9% were women, and the all-cause mortality rate was 2.6%. Forty-six patients were classified as living with frailty according to the physical frailty phenotype while 36 patients were rated frail by the FRAIL scale. In adults < 60 years of age, the FRAIL scale showed good accuracy (84.9%) and specificity (93.2%) but had low sensitivity (41.3%) and moderate agreement (Kappa = 0.41; p < 0.001) compared to the definition of the physical frailty phenotype. The adjusted logistic regression model showed that the patients with frailty assessed by the FRAIL scale had a greater chance of mortality than the non-frail patients (OR: 6.8; CI95%:1.477-31.513; p = 0.014). CONCLUSION: Physical frailty phenotype identifies more patients as having pre-frailty and frailty in non-dialysis dependent patients as compared to the FRAIL scale. However, the FRAIL scale is a simple bedside tool that can be useful for screening for frailty and whose results were associated with mortality.


Subject(s)
Frailty , Renal Insufficiency, Chronic , Humans , Female , Male , Aged , Frailty/diagnosis , Frailty/mortality , Middle Aged , Prospective Studies , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/complications , Predictive Value of Tests , Geriatric Assessment/methods , Logistic Models , Frail Elderly , Risk Factors , Phenotype , Prognosis
6.
Data Brief ; 52: 110043, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38299099

ABSTRACT

Vibration signals extracted from structures across diverse health conditions have become indispensable for monitoring structural integrity. These datasets represent a resource for real-time condition monitoring, enabling the precise detection and diagnosis of system anomalies. This paper aims to enrich the scientific community's database on structural dynamics and experimental methodologies pertinent to system modelling. Leveraging experimental measurements obtained from mass-reinforced beams, these datasets validate numerical models, refine identification techniques, quantify uncertainties, and continuously foster machine learning algorithms' evolution to monitor structural integrity. Furthermore, the beam dataset is data-driven and can be used to develop and test innovative structural health monitoring strategies, specifically identifying damages and anomalies within intricate structural frameworks. Supplemental datasets like Mass-position and damage index introduce parametric uncertainty into experimental and damage identification metrics. Thereby offering valuable insights to elevate the efficacy of monitoring and control techniques. These comprehensive tests also encapsulate paramedic uncertainty, providing robust support for applications in uncertainty quantification, stochastic modelling, and supervised and unsupervised machine learning methodologies.

7.
J. invasive cardiol ; 35(12)dez.2023. ilus
Article in English | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1524290

ABSTRACT

OBJECTIVES. Markers of myocardial injury, such as creatine kinase-myocardial band (CK-MB) mass, are elevated in up to 30% of patients undergoing percutaneous coronary intervention (PCI) with stent deployment. This elevation represents myocardial injury that can impact the patient in the long term, including the risk of death. Sevoflurane, an inhaled anesthetic, may have cardioprotective properties that benefit patients undergoing PCI. The primary objective was to compare serum CK-MB mass raise in patients who received sevoflurane to those who received a placebo prior to PCI. METHODS. We enrolled patients with coronary artery disease who were eligible for PCI in a randomized (1:1), double-blind, placebo-controlled trial; patients having experienced acute myocardial infarction within 72 hours and those with saphenous vein graft stenting were excluded. Patients (n = 1254) were randomized to receive sevoflurane (2% inspired fraction) or placebo (oxygen alone) for 30 minutes prior to PCI. Additionally, we compared substantial elevations in CK-MB mass (defined as >5x the upper limit of normal), length of stay in the intensive care unit and in-hospital, and 1-year mortality. RESULTS. Sevoflurane was unable to promote cardioprotection, as determined by CK-MB mass levels (sevoflurane group: 2.52 ± 9.64; control group: 1.84 ± 8.58; P=.32). No effect was noticed on the reduction among patients who (AQ: with?) increase (AQ: increased?) marker levels (prevalence of increase in CK-MB mass greater than the upper limit of normality was 30.8% in the sevoflurane group and 28.9% in the control group; P=.33; 4.6% vs 3.1%, respectively, for increases 5x above the upper limit of normality [P=.21]). CONCLUSIONS. Sevoflurane failed to reduce myocardial injury after PCI. Therefore, its usage should not be routinely recommended.


Subject(s)
Angioplasty , Stents , Sevoflurane
8.
J Invasive Cardiol ; 35(12)2023 Dec.
Article in English | MEDLINE | ID: mdl-38108873

ABSTRACT

OBJECTIVES: Markers of myocardial injury, such as creatine kinase-myocardial band (CK-MB) mass, are elevated in up to 30% of patients undergoing percutaneous coronary intervention (PCI) with stent deployment. This elevation represents myocardial injury that can impact the patient in the long term, including the risk of death. Sevoflurane, an inhaled anesthetic, may have cardioprotective properties that benefit patients undergoing PCI. The primary objective was to compare serum CK-MB mass raise in patients who received sevoflurane to those who received a placebo prior to PCI. METHODS: We enrolled patients with coronary artery disease who were eligible for PCI in a randomized (1:1), double-blind, placebo-controlled trial; patients having experienced acute myocardial infarction within 72 hours and those with saphenous vein graft stenting were excluded. Patients (n = 1254) were randomized to receive sevoflurane (2% inspired fraction) or placebo (oxygen alone) for 30 minutes prior to PCI. Additionally, we compared substantial elevations in CK-MB mass (defined as >5x the upper limit of normal), length of stay in the intensive care unit and in-hospital, and 1-year mortality. RESULTS: Sevoflurane was unable to promote cardioprotection, as determined by CK-MB mass levels (sevoflurane group: 2.52 ± 9.64; control group: 1.84 ± 8.58; P=.32). No effect was noticed on the reduction among patients who (AQ: with?) increase (AQ: increased?) marker levels (prevalence of increase in CK-MB mass greater than the upper limit of normality was 30.8% in the sevoflurane group and 28.9% in the control group; P=.33; 4.6% vs 3.1%, respectively, for increases 5x above the upper limit of normality [P=.21]). CONCLUSIONS: Sevoflurane failed to reduce myocardial injury after PCI. Therefore, its usage should not be routinely recommended.


Subject(s)
Heart Injuries , Percutaneous Coronary Intervention , Humans , Sevoflurane , Percutaneous Coronary Intervention/adverse effects , Prospective Studies , Heart , Myocardium
9.
REC: CardioClinics ; 58(4): 303-313, jul.2023. ilus, Tab
Article in English | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1509834

ABSTRACT

INTRODUCTION AND OBJECTIVES: Antiplatelet agents such as acetylsalicylic acid (ASA) play a prominent role in preventing atherothrombosis. However, low-responsive patients who will not benefit from an increased dosage of this drug, which can cause bleeding and gastrointestinal irritation, need to be identified. Drugs such as omega-3 fatty acids, which enhance the vasodilating condition and diminish platelet aggregation, can potentiate the anti-aggregating effects of ASA, avoiding its side effects. Thus, we assessed the alternative use of 200mg/day of ASA and 100mg/day of this drug combined with 1g of omega-3 in 152 patients with chronic coronary artery disease. METHODS: Our analysis included platelet function (ASPItest), TBX2 concentrations (ELISA), and SNPs polymorphisms in the rs3842787 and rs3842798 regions of the PTGS1 gene of the COX-1 enzyme and the rs5918 region of the ITGB3 gene of the fibrinogen's receptor subunit glycoprotein IIIa. RESULTS: ASPItest detected 38 non-responders. The reduction of ASPItest values was more significant in this group than in responders and fell to levels of responders in non-responders of the 200mg/day treatment. A rare allele of rs3842787 is associated with a worse ASPItest response, and the rare allele of the rs5918 polymorphism with a worse response related to TBX2 concentration. Both treatments showed no statistically significant difference in hematuria or bleeding, constituting safe treatment alternatives, and omega-3 treatment reduced monocyte levels. CONCLUSIONS: Our results underscore the usefulness of pharmacogenetics for personalized treatments, avoiding gastrointestinal effects and undesirable bleeding.

10.
J Invasive Cardiol ; 35(6): E281-E290, 2023 06.
Article in English | MEDLINE | ID: mdl-37220640

ABSTRACT

BACKGROUND: Despite the potential benefits of percutaneous procedures for the assessment and treatment of coronary artery disease, these interventions require the use of iodine contrast, which might lead to contrast-induced nephropathy (CIN) and increased risk of dialysis and major adverse cardiac events (MACE). AIMS: We sought to compare two different iodine contrasts (low vs. iso-osmolar) for the prevention of CIN among high-risk patients. METHODS: This is a single-center, randomized (1:1) trial comparing consecutive patients at high risk for CIN referred to percutaneous coronary diagnostic and/or therapeutic procedures with low (ioxaglate) vs. iso-osmolarity (iodixanol) iodine contrast. High risk was defined by the presence of at least one of the following conditions: age >70 years, diabetes mellitus, non-dialytic chronic kidney disease, chronic heart failure, cardiogenic shock, and acute coronary syndrome (ACS). The primary endpoint was the occurrence of CIN, defined as a >25% relative increase and/or >0.5 mg/dL absolute increase in creatinine (Cr) levels compared with baseline between the 2nd and 5th day after contrast media administration. RESULTS: A total of 2,268 patients were enrolled. Mean age was 67 years. Diabetes mellitus (53%), non-dialytic chronic kidney disease (31%), and ACS (39%) were highly prevalent. The mean volume of contrast media was 89 ml ± 48.6. CIN occurred in 15% of all patients, with no significant difference regarding the type of contrast used (iso = 15.2% vs. low = 15.1%, P>.99). Differences were not observed in specific subgroups such as diabetics, elderly, and ACS patients. At 30-day follow-up, 13 patients in the iso-osmolarity group and 11 in low-osmolarity group required dialysis (P =.8). There were 37 (3.3%) deaths in the iso-osmolarity cohort vs. 29 (2.6%) in the low-osmolarity group (P =.4). CONCLUSION: Among patients at high risk for CIN, the incidence of this complication was 15%, and independent of the use of low- or iso-osmolar contrast.


Subject(s)
Ioxaglic Acid , Kidney Diseases , Aged , Humans , Contrast Media/adverse effects , Coronary Angiography/adverse effects , Coronary Angiography/methods , Creatinine , Ioxaglic Acid/adverse effects , Kidney Diseases/chemically induced , Risk Factors , Triiodobenzoic Acids/adverse effects
11.
J. invasive cardiol ; 35(6): e281 e290, May 2023. graf, ilus, tab
Article in English | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1437590

ABSTRACT

BACKGROUND. Despite the potential benefits of percutaneous procedures for the assessment and treatment of coronary artery disease, these interventions require the use of iodine contrast, which might lead to contrast-induced nephropathy (CIN) and increased risk of dialysis and major adverse cardiac events (MACE). Aims. We sought to compare two different iodine contrasts (low vs. iso-osmolar) for the prevention of CIN among high-risk patients. METHODS. This is a single-center, randomized (1:1) trial comparing consecutive patients at high risk for CIN referred to percutaneous coronary diagnostic and/or therapeutic procedures with low (ioxaglate) vs iso-osmolarity (iodixanol) iodine contrast. High risk was defined by the presence of at least one of the following conditions: age >70 years, diabetes mellitus, non-dialytic chronic kidney disease, chronic heart failure, cardiogenic shock, and acute coronary syndrome (ACS). The primary endpoint was the occurrence of CIN, defined as a >25% relative increase and/or >0.5 mg/dL absolute increase in creatinine (Cr) levels compared with baseline between the 2nd and 5th day after contrast media administration. RESULTS. A total of 2268 patients were enrolled. Mean age was 67 years. Diabetes mellitus (53%), non-dialytic chronic kidney disease (31%), and ACS (39%) were highly prevalent. The mean volume of contrast media was 89 ml ± 48.6. CIN occurred in 15% of all patients, with no significant difference regarding the type of contrast used (iso = 15.2% vs low = 15.1%, P>.99). Differences were not observed in specific subgroups such as diabetics, elderly, and ACS patients. At 30-day follow-up, 13 patients in the iso-osmolarity group and 11 in low-osmolarity group required dialysis (P=.8). There were 37 (3.3%) deaths in the iso-osmolarity cohort vs 29 (2.6%) in the low-osmolarity group (P=.4). CONCLUSION. Among patients at high risk for CIN, the incidence of this complication was 15%, and independent of the use of low- or iso-osmolar contrast.

12.
J Invasive Cardiol ; 35(3): E113-E121, 2023 03.
Article in English | MEDLINE | ID: mdl-36884359

ABSTRACT

OBJECTIVE: To enlighten preprocedural risk factors of mitral valve restenosis in a large, single-center cohort of patients submitted to percutaneous mitral balloon commissurotomy (PMBC) for the treatment of mitral stenosis (MS) secondary to rheumatic heart disease. METHODS: This is a database analysis of a single-center, high-volume tertiary institution involving all consecutive PMBC procedures performed in the mitral valve (MV). Restenosis was diagnosed when MV area was <1.5 cm² and/or loss of 50% or more of the immediate procedural result aligned with the return/worsened symptoms of heart failure. The primary endpoint was to determine the preprocedural independent predictors of restenosis after PMBC. RESULTS: Among a total of 1921 PMBC procedures, 1794 consecutive patients without previous intervention were treated between 1987 and 2010. Throughout 24 years of follow-up, MV restenosis was observed in 483 cases (26%). Mean age was 36 years and most (87%) were female. Median follow-up duration was 9.03 years (interquartile range, 0.33-23.38). Restenosis population, however, presented a significantly lower age at the procedure time as well as a higher Wilkins-Block score. At multivariate analysis, independent preprocedure predictors of restenosis were left atrium diameter (hazard risk [HR], 1.03; 95% confidence interval [CI], 1.02-1.05; P<.04), preprocedure maximum gradient (HR, 1.02; 95% CI, 1.00-1.03; P=.04), and higher Wilkins-Block score (>8) (HR, 1.38; 95% CI, 1.14-1.67; P<.01). CONCLUSIONS: At long-term follow-up, MV restenosis was observed in a quarter of the population undergoing PMBC. Preprocedure echocardiographic findings, including left atrial diameter, maximum MV gradient, and Wilkins-Block score were found to be the only independent predictors.


Subject(s)
Catheterization , Mitral Valve Stenosis , Humans , Female , Adult , Male , Catheterization/adverse effects , Follow-Up Studies , Echocardiography , Mitral Valve Stenosis/diagnosis , Mitral Valve Stenosis/surgery , Mitral Valve Stenosis/etiology , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Constriction, Pathologic , Recurrence , Treatment Outcome
13.
J Invasive Cardiol ; 35(5): E225-E233, 2023 05.
Article in English | MEDLINE | ID: mdl-36920890

ABSTRACT

BACKGROUND: Although first-generation drug-eluting stent (DES) devices have effectively achieved their main goal of reducing restenosis, their safety has been limited by suboptimal polymer biocompatibility, delayed stent endothelialization, and local drug toxicity, which ultimately prompted the development of new-generation DES options carrying biocompatible or even biodegradable polymers. AIMS: We sought to assess the vessel-healing pattern of the novel sirolimus-eluting Inspiron DES (Scitech Medical) using serial optical coherence tomography (OCT) and assuming the hypothesis that this thin-strut (75-µm), biodegradable-polymer DES promotes a faster healing, with very early strut coverage. METHODS: This is a prospective, multicenter, open-label, single-arm study enrolling 68 patients who underwent percutaneous coronary intervention guided by OCT. These patients were consecutively assigned into 3 groups. The first group had its OCT imaging follow-up performed at 3 months, the second group at 2 months, and the third group at 1 month. RESULTS: Mean age was 59.5 years, 70.6% were male, 41.2% had type 2 diabetes, and 29.4% presented with acute coronary syndrome. A total of 72 lesions were treated and 1.06 stents were implanted per patient. OCT assessment of the stents at 1, 2, and 3 months showed a strut coverage of 90.41%, 93.96%, and 97.21%, respectively (P=.04). CONCLUSION: The Inspiron DES showed an early strut healing pattern, with >90% of the struts covered by neointima within the first month and with almost all struts covered by the third month.


Subject(s)
Coronary Artery Disease , Diabetes Mellitus, Type 2 , Drug-Eluting Stents , Humans , Male , Middle Aged , Female , Coronary Artery Disease/therapy , Tomography, Optical Coherence/methods , Prospective Studies , Treatment Outcome , Prosthesis Design , Stents , Polymers
14.
Microb Pathog ; 177: 106058, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36878333

ABSTRACT

The increase in antibiotic resistance rates has attracted the interest of researchers for antibacterial compounds capable of potentiating the activity of conventional antibiotics. Coumarin derivatives have been reported to develop effective antibacterials with possible new mechanisms of action for treating infectious diseases caused by bacteria with a profile of drug resistance. In this context, the aim of the present study we have now prepared one variety of new synthetic coumarins evaluating the pharmacokinetic and chemical similarity in silico, their antimicrobial activity against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922), and potential for the modulation of antibiotic resistance against Staphylococcus aureus (SA10) and Escherichia coli (EC06) clinical isolate bacteria by in vitro assay. The antibacterial activity and antibiotic-enhancing properties were evaluated by the broth microdilution method and pharmacokinetically characterized according to the Lipinsk rule of 5 and had their similarity analyzed in databases such as ChemBL and CAS SciFinder. The results demonstrated that only compound C13 showed significant antibacterial activity (MIC ≤256 µg/mL), and all other coumarins did not display relevant antibacterial activity (MIC ≥1024 µg/mL). However, they did modulate the antibiotics activities to norfloxacin and gentamicin, except, compound C11 to norfloxacin against Staphylococcus aureus (SA10). The in silico properties prediction and drug-likeness results demonstrated that all coumarins presented a good drug-likeness score with no violations and promising in silico pharmacokinetic profiles showing that they have the potential to be developed into an oral drug. The results indicate that the coumarin derivatives showed good in vitro antibacterial activity. These new coumarin derivatives also demonstrated the capacity to modulate antibiotic resistance with potential synergy action for current antimicrobials assayed, as antibiotic adjuvants, to reduce the emergence of antimicrobial resistance.


Subject(s)
Staphylococcal Infections , Staphylococcus aureus , Humans , Norfloxacin/pharmacology , Escherichia coli , Coumarins/pharmacology , Coumarins/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Staphylococcal Infections/drug therapy , Bacteria , Microbial Sensitivity Tests
15.
J. invasive cardiol ; 35(5)May. 2023. ilus, graf, tab
Article in English | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1426378

ABSTRACT

BACKGROUND: Although first-generation drug-eluting stent (DES) devices have effectively achieved their main goal of reducing restenosis, their safety has been limited by suboptimal polymer biocompatibility, delayed stent endothelialization, and local drug toxicity, which ultimately prompted the development of new-generation DES options carrying biocompatible or even biodegradable polymers. Aims. We sought to assess the vessel-healing pattern of the novel sirolimus-eluting Inspiron DES (Scitech Medical) using serial optical coherence tomography (OCT) and assuming the hypothesis that this thin-strut (75-µm), biodegradable-polymer DES promotes a faster healing, with very early strut coverage. METHODS. This is a prospective, multicenter, open-label, single-arm study enrolling 68 patients who underwent percutaneous coronary intervention guided by OCT. These patients were consecutively assigned into 3 groups. The first group had its OCT imaging follow-up performed at 3 months, the second group at 2 months, and the third group at 1 month. RESULTS: Mean age was 59.5 years, 70.6% were male, 41.2% had type 2 diabetes, and 29.4% presented with acute coronary syndrome. A total of 72 lesions were treated and 1.06 stents were implanted per patient. OCT assessment of the stents at 1, 2, and 3 months showed a strut coverage of 90.41%, 93.96%, and 97.21%, respectively (P=.04). CONCLUSION: The Inspiron DES showed an early strut healing pattern, with >90% of the struts covered by neointima within the first month and with almost all struts covered by the third month.


Subject(s)
Tomography, Optical Coherence , Acute Coronary Syndrome , Drug-Eluting Stents , Percutaneous Coronary Intervention
16.
J. invasive cardiol ; 35(3): 113-121, Mar. 2023. graf, tab
Article in English | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1427686

ABSTRACT

OBJECTIVES: to enlighten preprocedural risk factors of mitral valve restenosis in a large, single-center cohort of patients submitted to percutaneous mitral balloon commissurotomy (PMBC) for the treatment of mitral stenosis (MS) secondary to rheumatic heart disease. METHODS: this is a database analysis of a single-center, high-volume tertiary institution involving all consecutive PMBC procedures performed in the mitral valve (MV). Restenosis was diagnosed when MV area was <1.5 cm2 and/or loss of 50% or more of the immediate procedural result aligned with the return/worsened symptoms of heart failure. The primary endpoint was to determine the preprocedural independent predictors of restenosis after PMBC. Results: among a total of 1921 PMBC procedures, 1794 consecutive patients without previous intervention were treated between 1987 and 2010. Throughout 24 years of follow-up, MV restenosis was observed in 483 cases (26%). Mean age was 36 years and most (87%) were female. Median follow-up duration was 9.03 years (interquartile range, 0.33-23.38). Restenosis population, however, presented a significantly lower age at the procedure time as well as a higher Wilkins-Block score. At multivariate analysis, independent preprocedure predictors of restenosis were left atrium diameter (hazard risk [HR], 1.03; 95% confidence interval [CI], 1.02-1.05; P<.04), preprocedure maximum gradient (HR, 1.02; 95% CI, 1.00-1.03; P=.04), and higher Wilkins-Block score (>8) (HR, 1.38; 95% CI, 1.14-1.67; P<.01). CONCLUSIONS: at long-term follow-up, MV restenosis was observed in a quarter of the population undergoing PMBC. Preprocedure echocardiographic findings, including left atrial diameter, maximum MV gradient, and Wilkins-Block score were found to be the only independent predictors.


Subject(s)
Humans , Male , Female , Adult , Catheterization/adverse effects , Treatment Outcome , Mitral Valve/surgery , Mitral Valve Stenosis/diagnosis , Recurrence , Echocardiography , Follow-Up Studies , Constriction
17.
Catheter. cardiovasc. interv ; 101(3): 579-586, Feb. 2023.
Article in English | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1418152

ABSTRACT

One limitation to transradial access (TRA) is the occurrence of spasms (RAS), for which the use of prophylactic medications is recommended. Improvement in TRA material combined with the increase in operators' expertise, might mitigate this benefit. We assess the effect of preventive nitroglycerin on RAS during TRA, evaluating the role of the operator's experience. Patients received 500 µg nitroglycerin or placebo. The operator's expertise was classified as: inexperienced (I), intermediate (M), and experienced (E). 2040 patients were included. Prophylactic use of nitroglycerin did not reduce RAS (10.8% vs. 13.4% (placebo), p = 0.07). RAS incidence was 14.5% in I, 12.5% in M, and 9.7% in E (p = 0.01). In group I, nitroglycerin reduced RAS (17.4% vs. 11.1%, p = 0.04), which was not observed in other groups. Overall, nitroglycerin does not prevent RAS, which is more common among inexperienced operators. More experienced operators could abolish preventive nitroglycerin use.


Subject(s)
Humans , Vasodilator Agents , Nitroglycerin , Spasm/epidemiology , Cardiac Catheterization/adverse effects , Treatment Outcome , Radial Artery
18.
ACS Chem Biol ; 18(1): 49-58, 2023 01 20.
Article in English | MEDLINE | ID: mdl-36626717

ABSTRACT

Fatty acid and polyketide biosynthetic enzymes exploit the reactivity of acyl- and malonyl-thioesters for catalysis. A prime example is FabH, which initiates fatty acid biosynthesis in many bacteria and plants. FabH performs an acyltransferase reaction with acetyl-CoA to generate an acetyl-S-FabH acyl-enzyme intermediate and subsequent decarboxylative Claisen-condensation with a malonyl-thioester carried by an acyl carrier protein (ACP). We envision that crystal structures of FabH with substrate analogues can provide insight into the conformational changes and enzyme/substrate interactions underpinning the distinct reactions. Here, we synthesize acetyl/malonyl-CoA analogues with esters or amides in place of the thioester and characterize their stability and behavior as Escherichia coli FabH substrates or inhibitors to inform structural studies. We also characterize the analogues with mutant FabH C112Q that mimics the acyl-enzyme intermediate allowing dissection of the decarboxylation reaction. The acetyl- and malonyl-oxa(dethia)CoA analogues undergo extremely slow hydrolysis in the presence of FabH or the C112Q mutant. Decarboxylation of malonyl-oxa(dethia)CoA by FabH or C112Q mutant was not detected. The amide analogues were completely stable to enzyme activity. In enzyme assays with acetyl-CoA and malonyl-CoA (rather than malonyl-ACP) as substrates, acetyl-oxa(dethia)CoA is surprisingly slightly activating, while acetyl-aza(dethia)CoA is a moderate inhibitor. The malonyl-oxa/aza(dethia)CoAs are inhibitors with Ki's near the Km of malonyl-CoA. For comparison, we determine the FabH catalyzed decomposition rates for acetyl/malonyl-CoA, revealing some fundamental catalytic traits of FabH, including hysteresis for malonyl-CoA decarboxylation. The stability and inhibitory properties of the substrate analogues make them promising for structure-function studies to reveal fatty acid and polyketide enzyme/substrate interactions.


Subject(s)
3-Oxoacyl-(Acyl-Carrier-Protein) Synthase , Polyketides , Acetyl Coenzyme A/metabolism , Acyltransferases/genetics , Acyltransferases/metabolism , Acyl Carrier Protein/chemistry , Malonyl Coenzyme A/metabolism , Fatty Acids
19.
Catheter Cardiovasc Interv ; 101(3): 579-586, 2023 02.
Article in English | MEDLINE | ID: mdl-36640416

ABSTRACT

One limitation to transradial access (TRA) is the occurrence of spasms (RAS), for which the use of prophylactic medications is recommended. Improvement in TRA material combined with the increase in operators' expertise, might mitigate this benefit. We assess the effect of preventive nitroglycerin on RAS during TRA, evaluating the role of the operator's experience. Patients received 500 µg nitroglycerin or placebo. The operator's expertise was classified as: inexperienced (I), intermediate (M), and experienced (E). 2040 patients were included. Prophylactic use of nitroglycerin did not reduce RAS (10.8% vs. 13.4% (placebo), p = 0.07). RAS incidence was 14.5% in I, 12.5% in M, and 9.7% in E (p = 0.01). In group I, nitroglycerin reduced RAS (17.4% vs. 11.1%, p = 0.04), which was not observed in other groups. Overall, nitroglycerin does not prevent RAS, which is more common among inexperienced operators. More experienced operators could abolish preventive nitroglycerin use.


Subject(s)
Nitroglycerin , Vasodilator Agents , Humans , Radial Artery , Treatment Outcome , Cardiac Catheterization/adverse effects , Spasm/diagnosis , Spasm/etiology , Spasm/prevention & control
20.
Fundam Clin Pharmacol ; 37(2): 316-323, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36205463

ABSTRACT

The problem of antibiotic resistance by bacteria threatens human health. Therefore, studies in this area seek alternatives to circumvent it. The study with coumarins and eugenol has already proven that these classes of compounds act against bacteria. In this same aspect, exposure to LED also shows a bactericidal effect. Seeking a possible enhancement of this effect, the present work studied coumarins derived from eugenol in association with LED to investigate the bactericidal effect. Four compounds were tested. For this, minimum inhibitory concentrations (MICs) and modulation with three antibiotics against Escherichia coli and Staphylococcus aureus bacteria were determined. To test the behavior of the activity against exposure to LED, the plates were exposed for 20 min to blue light, 415 nm and then incubated at 37°C for 24 h. For control, duplicates were made, and one of them did not undergo this exposure. C1 exhibited better activity against S. aureus, as synergism prevailed under the conditions tested. C3 and C4 were promising against E. coli as they showed synergism in association with the three antibiotics both with and without LED exposure. Thus, the compounds showed bactericidal activity, and LED was shown to enhance synergism.


Subject(s)
Eugenol , Staphylococcus aureus , Humans , Eugenol/pharmacology , Escherichia coli , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Coumarins/pharmacology
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