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1.
J Clin Nurs ; 33(9): 3615-3623, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38499992

RESUMO

AIMS: It is extremely important to determine the relationship between COPD and self-management (SM) in the disease process. However, the impact of symptom management (SpM) on this relationship is still unclear. The study aimed to examine the mediating role of SpM in the effect of the COPD stage on SM. DESIGN: A predictive correlational study was reported following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. METHODS: This study was conducted between 15 February 2023 and 15 June 15 2023, with 306 patients. Data were collected using the Symptom Management Scale for Self-Efficacy and the Chronic Disease Self-Management Scale. Descriptive statistics and Process Macro Model 4 in the SPSS program were used for data analysis. RESULTS: Most of the patients were in the moderate stage of COPD; their SM scores were at low levels; SpM scores were at moderate levels. The model was significant, and the variables explained 65% of the model. The COPD stage was significantly positively correlated with SpM and negatively correlated with SM. There was a significant positive impact between SpM and SM. The positive and significant standardised indirect effect of SpM on SM evidenced a full mediating effect. CONCLUSIONS: Symptom management has a full mediating role in the effect of the COPD stage on SM. It was revealed that the level of SM can be increased by achieving SpM. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Symptoms are vital in COPD. Progression of COPD increases symptom severity. Being successful in SpM greatly contributes to the achievement of self-management. Therefore, nurses should definitely consider symptom control in strengthening self-management in the care of patients with COPD. PATIENT OR PUBLIC CONTRIBUTION: Patients' COPD stage was determined by a pulmonologist involved in the study. Voluntary patients with COPD hospitalised in the pulmonology clinic were included in the study.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Autogestão , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/psicologia , Doença Pulmonar Obstrutiva Crônica/enfermagem , Masculino , Feminino , Autogestão/métodos , Autogestão/psicologia , Pessoa de Meia-Idade , Idoso , Autoeficácia , Autocuidado , Inquéritos e Questionários , Adulto
2.
Kardiologiia ; 64(2): 67-72, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38462806

RESUMO

AIM: The MAPH score is a new score that combines mean platelet volume (MPV), hematocrit, and total protein, which are markers of whole blood viscosity (WBV). We aimed to investigate the relationship between the MAPH score and the coronary slow flow phenomenon (CSF). MATERIAL AND METHODS: A total of 201 patients were included in the study. 105 had CSF and 96 had normal coronary flow (NCF). Coronary flow was measured by the Thrombolysis in Myocardial Infarction frame count (TFC) method. The patients' MPV, age, hematocrit, and total protein were recorded. High (HSR) and low shear rates (LSR) were calculated, based on total protein and hematocrit values. Cut-off values for CSF were determined using the Youden's index, and the score was determined as 0 or 1 according to the cut-off values. The sum of these scores was the MAPH score. RESULTS: The mean age of the patients included in the study was 51.1±7.9 (n=201, 54.2 % male). Hyperlipidemia, DM, and HT rates of both groups were similar, but the mean age of the CSF group was higher (p=0.773; p=0.549; p=0.848; p <0.001, respectively). Total protein, MPV, hematocrit, HSR and LSR were higher in the CSF group (p< 0.001, for all values). Comparative receiver operating characteristic (ROC) curve analysis showed that the performance of the MAPH score in predicting CSF is better than the performance of these parameters separately. CONCLUSION: A new score, the MAPH score, may be used to identify the presence of CSF.


Assuntos
Circulação Coronária , Infarto do Miocárdio , Humanos , Masculino , Feminino , Estudos Retrospectivos , Estudos de Casos e Controles , Curva ROC , Angiografia Coronária
3.
Sleep Breath ; 27(5): 1865-1874, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36877355

RESUMO

PURPOSE: Metrnl, a newly discovered adipokine with significant expression in white adipose tissue, promotes energy expenditure and contributes to the development of cardiovascular disorders. Endocan is a surrogate marker for endothelial dysfunction and is linked to cardiovascular risk factors. Higher cardiovascular morbidity and mortality have been linked to obstructive sleep apnea (OSA). In this study, we investigated the potential of serum Metrnl and endocan as biomarkers to identify patients with OSA who are at increased cardiovascular risk and differentiate them from healthy controls. METHODS: The study included the evaluation of serum levels of endocan and Metrnl in individuals with OSA and healthy controls. All participants underwent full polysomnography to evaluate their sleep, and carotid intima-media thickness (CIMT) was measured in each of them. RESULTS: Patients with OSA (n = 117) had considerably lower levels of Metrnl and significantly higher levels of endocan than controls (n = 59). Once confounding factors were taken into account, both Metrnl and endocan were effective predictors of OSA. Additionally, the severity of OSA, as determined by the apnea-hypopnea index (AHI), was linked to Metrnl and endocan levels. The study also found a significant and independent inverse association between CIMT and Metrnl, along with a positive association with endocan after making multiple adjustments. Furthermore, there was a significant and independent connection between CIMT and AHI. CONCLUSION: Based on these findings, Metrnl and endocan have the potential to be valuable markers for identifying patients with OSA who are at increased risk of early vascular damage.


Assuntos
Doenças Cardiovasculares , Apneia Obstrutiva do Sono , Humanos , Biomarcadores , Espessura Intima-Media Carotídea , Sono , Apneia Obstrutiva do Sono/complicações
4.
Vascular ; : 17085381231192731, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37495213

RESUMO

AIM: To evaluate the results of revascularization of stenotic iliac stents using drug-eluting balloons (DEBs). MATERIAL AND METHODS: Seventy-four patients with various levels of iliac stent restenosis were enrolled to study. All restenotic stents were treated using paclitaxel-coated balloons. RESULTS: Through a follow-up median period of 24 months (4-24 months), there were no in-stent re-restenosis in 55 patients (74.3%) and there was one in class 1 (1.4%), four in class 2 (5.4%), and fourteen in class 3 (18.9%). CONCLUSION: We conclude that; DEBs can be used for restenotic iliac artery stents for some Type C and D lesions, in addition to Types A and B with satisfacting results.

5.
Kardiologiia ; 63(5): 40-46, 2023 May 31.
Artigo em Russo | MEDLINE | ID: mdl-37307207

RESUMO

Background    Very short-lasting episodes of AF-like activity (micro-AF) may be precursors of undiagnosed silent episodes of atrial fibrillation. In this study, we examined the relationship between increased left atrial sphericity index (LASI) and stroke in patients with micro-AF.Material and Methods    A total of 100 consecutive patients with micro-AF enrolled in this study. The histories, cranial magnetic resonance, and computed tomography images of these patients were scanned from the hospital database. The patients were divided into two groups according to whether or not they had a stroke. LASI was calculated as a fraction of the left atrial maximum volume to the left atrial volume of the sphere in a 4­chamber view. Atrial electromechanical delay (AEMD) intervals were calculated from the atrial wall and atrioventricular valve annulus levels by using tissue Doppler imaging (TDI). These two groups were compared in terms of stroke predictors.Results    A history of stroke was present in 25 (25 %) patients diagnosed with micro-AF (Group 1). 75 patients did not have stroke (Group 2). There was a significant difference between the two groups in terms of left atrial lateral wall electromechanical delay (LA lateral AEMD) times, left atrial volume index (LAVI), and left atrial sphericity index (LASI). Findings: LAVI, 40.9±3.72 vs. 29.9±3.84, p<0.001; LASI, 0.84±0.07 vs. 0.66±0.07, p<0.001; LA lateral AEMD, 77.2±4.85 vs. 66.5±3.66, p<0.001.Conclusions    Stroke precautions should be taken in patients with micro-AF. New predictive indexes should be given importance. Changes in LASI, LAVI and LA lateral AEMD values may be a predictor of stroke in patients with micro AF.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Átrios do Coração , Hospitais
6.
Kardiologiia ; 63(2): 46-51, 2023 Feb 28.
Artigo em Russo | MEDLINE | ID: mdl-36880143

RESUMO

Aim    The primary objective of this study was to comparatively assess the effects of levosimendan and dobutamine on RVEF, right ventricular diastolic function, and hormonal balance in patients with biventricular heart failure. The secondary objective was to investigate the relationship between the RVEF and the peak systolic velocity (Sa), an indicator of right ventricular systolic function, as measured by tissue Doppler echocardiography from the tricuspid annulus, and by the tricuspid annular plane systolic excursion (TAPSE).Material and Methods    The population of this cross-sectional, single-center, prospective study was comprised of 81 patients, who between December 2019 and January 2022, applied to the study health institution with diagnosis of ADHF. The study sample included 67 biventricular heart failure patients with left ventricular ejection fraction (LVEF) <35 % and RVEF <50 %, as measured by the ellipsoidal shell model, and who met the other study inclusion criteria. Of these 67 patients, 34 were treated with levosimendan, and 33 were treated with dobutamine. RVEF, LVEF, Sa, peak early (Ea) and peak late (Aa) annular velocities, Ea / Aa ratio, TAPSE, systolic pulmonary artery pressure (SPAP), n-terminal pro-brain natriuretic peptide (NT-pro BNP), and functional capacity (FC) were measured before treatment and at 48 hrs of treatment. The within group pre- and post-treatment differences (Δs) of these variables were compared.Results    RVEF, SPAP, and BNP, and FC significantly improved in both treatment groups (p<0.05 for all). Sa (p<0.01), TAPSE (p<0.01), LVEF (p<0.01), and Ea / Aa (p<0.05) improved only in the levosimendan group. The pre- and post-treatment Δs for RVEF, LVEF, SPAP, Sa, TAPSE, FC, and Ea / Aa were higher in the levosimendan group than in the dobutamine group (p<0.05 for all).Conclusion    Compared to dobutamine, levosimendan produced greater improvement in right ventricular systolic and diastolic function in patients with biventricular heart failure and in need of inotropic therapy support.


Assuntos
Fármacos Cardiovasculares , Insuficiência Cardíaca , Humanos , Estudos Transversais , Dobutamina/farmacologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Estudos Prospectivos , Simendana , Volume Sistólico , Função Ventricular Esquerda , Função Ventricular Direita
7.
Kardiologiia ; 63(7): 62-67, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37522829

RESUMO

BACKGROUND: Although scoring systems showing liver fibrosis using non-invasive methods have been accepted as effective tools for predicting cardiovascular risk, their role in predicting coronary ectasia (CAE) has not been evaluated. This study investigated whether aprison (APRI) and fibrosis-4 indices (FIB-4), which are indicators of fibrosis in nonalcoholic fatty liver disease (NAFLD), are associated with CAE. MATERIAL AND METHODS: A retrospective, cross-sectional study consisted of 215 patients, 108 with CAE and 107 without CAE, as diagnosed by angiography. The mean age of all patients was 61.8±9.9 yrs, and 171 (78.8 %) were males. The relationships between APRI, FIB-4, NAFLD, and Bard scores and CAE were evaluated. RESULTS: APRI, FIB-4, NAFLD, and Bard scores were independent predictors of CAE. Fib 4, APRI, NAFLD, and Bard scores were higher in the CAE patients. There were a moderate, positive correlations for FIB-4, APRI, and NAFLD scores with coronary ectasia (r=0.55, p<0.001; r=0.52, p<0.001; r=0.51, p<0.001, respectively). A weak-moderate positive correlation was observed between the Bard score and CAE (r=0.34, p<0.001). Univariate and multivariate regression analysis showed that APRI score, low HDL, and Bard score were independent risk factors for CAE ectasia (p<0.001). Cut-off values to predict CAE as determined by ROC curve analysis were: FIB-4 index ≥1.43 (AUC=0.817, 95 % confidence interval (CI): 0.762 to 0.873, p<0.001), APRI index ≥0.25 (AUC=0.804, 95 % CI: 0.745 to 0.862, p<0.001), NAFLD score ≥-0.92 (AUC=0.798, 95 % CI: 0.738 to 0.857.p<0.001), Bard score ≥2 (AUC=0.691, 95 % CI: 0.621 to 0.761, p<0.001). CONCLUSION: APRI, FIB-4, NAFLD, and Bard scores are associated with CAE.

8.
Omega (Westport) ; : 302228231224572, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38135283

RESUMO

The study was conducted to examine the moderating effect of dyspnea (according to Modified Medical Research Council-mMRC scale) on the relationship between death anxiety (DA) and self-management (SM) levels in patients suffering from chronic obstructive pulmonary disease (COPD) (n = 313). Model fit indices are within appropriate limits (χ2/DF = 2.284, GFI = .855, CFI = .796, RMSEA = .064). In mMRC 2, females had 33 times more DA than males. In mMRC 3, DA increased 36 times with increasing age and 14 times with comorbidity. It decreased 15-fold in those with past exacerbation experience. The second model explained DA by 18% while the moderating effect of severe dyspnea contributed 28% to this association. In this group of patients, a one unit increase in DA led to a 53-fold increase in SM. Age, gender, comorbidity and previous exacerbation history affect DA in patients with COPD. Increased DA decreases self-management. Severe dyspnea has a moderating effect between DA and SM.

9.
J Biol Chem ; 295(50): 17187-17199, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33028638

RESUMO

Mammalian circadian clocks are driven by transcription/translation feedback loops composed of positive transcriptional activators (BMAL1 and CLOCK) and negative repressors (CRYPTOCHROMEs (CRYs) and PERIODs (PERs)). CRYs, in complex with PERs, bind to the BMAL1/CLOCK complex and repress E-box-driven transcription of clock-associated genes. There are two individual CRYs, with CRY1 exhibiting higher affinity to the BMAL1/CLOCK complex than CRY2. It is known that this differential binding is regulated by a dynamic serine-rich loop adjacent to the secondary pocket of both CRYs, but the underlying features controlling loop dynamics are not known. Here we report that allosteric regulation of the serine-rich loop is mediated by Arg-293 of CRY1, identified as a rare CRY1 SNP in the Ensembl and 1000 Genomes databases. The p.Arg293His CRY1 variant caused a shortened circadian period in a Cry1-/-Cry2-/- double knockout mouse embryonic fibroblast cell line. Moreover, the variant displayed reduced repressor activity on BMAL1/CLOCK driven transcription, which is explained by reduced affinity to BMAL1/CLOCK in the absence of PER2 compared with CRY1. Molecular dynamics simulations revealed that the p.Arg293His CRY1 variant altered a communication pathway between Arg-293 and the serine loop by reducing its dynamicity. Collectively, this study provides direct evidence that allosterism in CRY1 is critical for the regulation of circadian rhythm.


Assuntos
Proteínas CLOCK , Ritmo Circadiano , Criptocromos , Simulação de Dinâmica Molecular , Fatores de Transcrição ARNTL/química , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Regulação Alostérica , Substituição de Aminoácidos , Animais , Arginina/química , Arginina/genética , Arginina/metabolismo , Proteínas CLOCK/química , Proteínas CLOCK/genética , Proteínas CLOCK/metabolismo , Criptocromos/química , Criptocromos/genética , Criptocromos/metabolismo , Células HEK293 , Humanos , Camundongos , Camundongos Knockout , Mutação de Sentido Incorreto , Proteínas Circadianas Period/química , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Polimorfismo de Nucleotídeo Único , Ligação Proteica , Estrutura Secundária de Proteína , Transcrição Gênica
10.
Gene Ther ; 28(6): 290-305, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33318646

RESUMO

The novel coronavirus pneumonia (COVID-19) is a highly infectious acute respiratory disease caused by Severe Acute Respiratory Syndrome-Related Coronavirus (SARS-CoV-2) (Prec Clin Med 2020;3:9-13, Lancet 2020;395:497-506, N. Engl J Med 2020a;382:1199-207, Nature 2020;579:270-3). SARS-CoV-2 surveillance is essential to controlling widespread transmission. However, there are several challenges associated with the diagnostic of the COVID-19 during the current outbreak (Liu and Li (2019), Nature 2020;579:265-9, N. Engl J Med 2020;382:727-33). Firstly, the high number of cases overwhelms diagnostic test capacity and proposes the need for a rapid solution for sample processing (Science 2018;360:444-8). Secondly, SARS-CoV-2 is closely related to other important coronavirus species and subspecies, so detection assays can give false-positive results if they are not efficiently specific to SARS-CoV-2. Thirdly, patients with suspected SARS-CoV-2 infection sometimes have a different respiratory viral infection or co-infections with SARS-CoV-2 and other respiratory viruses (MedRxiv 2020a;1-18). Confirmation of the COVID-19 is performed mainly by virus isolation followed by RT-PCR and sequencing (N. Engl J Med 2020;382:727-33, MedRxiv 2020a, Turkish J Biol 2020;44:192-202). The emergence and outbreak of the novel coronavirus highlighted the urgent need for new therapeutic technologies that are fast, precise, stable, easy to manufacture, and target-specific for surveillance and treatment. Molecular biology tools that include gene-editing approaches such as CRISPR-Cas12/13-based SHERLOCK, DETECTR, CARVER and PAC-MAN, antisense oligonucleotides, antisense peptide nucleic acids, ribozymes, aptamers, and RNAi silencing approaches produced with cutting-edge scientific advances compared to conventional diagnostic or treatment methods could be vital in COVID-19 and other future outbreaks. Thus, in this review, we will discuss potent the molecular biology approaches that can revolutionize diagnostic of viral infections and therapies to fight COVID-19 in a highly specific, stable, and efficient way.


Assuntos
COVID-19 , Edição de Genes , Interferência de RNA , COVID-19/diagnóstico , COVID-19/terapia , Sistemas CRISPR-Cas , Humanos , Oligonucleotídeos Antissenso
11.
Med Princ Pract ; 30(1): 45-51, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32422635

RESUMO

OBJECTIVE: Postoperative atrial fibrillation (PoAF) is the most frequently encountered rhythm problem after coronary artery bypass graft (CABG) surgery. This situation decreases the capacity of the patients with respect to functional exercise and creates a risk for stroke. In this study, we aimed to determine the effect of coronary artery disease extensiveness and HATCH score on PoAF in patients undergoing CABG surgery with cardiopulmonary bypass. SUBJECTS AND METHODS: Patients who underwent CABG between December 2014 and December 2018 were included retrospectively. Preoperative demographic characteristics, laboratory parameters, and operative parameters of the patients were recorded retrospectively. RESULTS: Of the 352 patients, 274 had HATCH scores ≤2 (71.1% male, mean age: 61.7 ± 12.4 years), and 78 had HATCH scores >2 (69.2% male, mean age: 65.9 ± 11.7 years). Significant differences were found between the 2 groups in terms of the age (p = 0.014), presence of hypertension (p = 0.012), PoAF (p < 0.001), and SYNTAX (synergy between percutaneous coronary intervention with taxus and cardiac surgery) score I (p = 0.001). A HATCH score >2 and SYNTAX score I were identified as independent predictors of PoAF (OR: 1.022, 95% CI: 1.004-1.128, p = 0.032, and OR 1.098, 95% CI 1.035-1.164, p = 0.002, respectively). For predicting PoAF, the cutoff level in the ROC curve analysis was 19.7 for SYNTAX score (AUC 0.647, 95% CI 0.581-0.714, p < 0.001, 72.2% sensitivity and 66.4% specificity), and the cutoff level for HATCH score was 2 (AUC 0.656, 95% CI 0.595-0.722, p < 0.001, 69.4% sensitivity and 56.8% specificity) Conclusions: HATCH and SYNTAX scores are predictors of PoAF.


Assuntos
Fibrilação Atrial/etiologia , Fibrilação Atrial/patologia , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Complicações Pós-Operatórias/patologia , Fatores Etários , Idoso , Índice de Massa Corporal , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença
12.
Kardiologiia ; 61(9): 61-65, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34713787

RESUMO

Background    High serum uric acid (UA) levels and low high-density lipoprotein cholesterol (HDL-C) levels are accepted as risk factors for cardiovascular mortality. Hyperuricemia and low HDL-C levels were associated with an increased risk of cardiovascular mortality and the development of diabetes and hypertension. However, the association of UA with cardiovascular (CV) mortality,collateral index are undetermined in patients with chronic total occlusion (CTO).Material and methods    124 patients who underwent coronary angiography with the diagnosis of stable or unstable angina pectoris and had chronic total occlusion were included in our study. Blood samples were collected from all patients before the angiography procedure. Coronary collateral circulation (CCC) was graded according to the Rentrop grading system of 0-3. Rentrop grades of 0 and 1 indicated low-grade CCC group, whereas grades 2 and 3 indicated high-grade CCC group. We divided our patients into two groups as low-grade CCC and high-grade CCC and examined these two groups in terms of uric acid / HDL ratios. Group 1: Rentrop classification grade 0-1 (mean age, 63,9±9,9), Group 2: Rentrop classification grade 2-3 (mean age, 62,1±9,4).Results    The baseline characteristics were similar in both groups. Uric acid / High density lipoprotein-cholesterol ratios and uric acid levels were higher in group 1 with poor collateral circulation [group 1; 0,21 (0,07-0,39) vs. group 2; 0,16 (0,08-0,31), group 1; 8,2 (3,4-10,4) vs. group 2; 5,85 (3,5-7,7), p<0,001, p<0,001 respectively].Conclusions    We found that high Uric acid / High-density lipoprotein-cholesterol ratios and high uric acid levels are associated with poor collateral circulation.


Assuntos
HDL-Colesterol/sangue , Circulação Colateral , Oclusão Coronária/sangue , Ácido Úrico , Idoso , Angiografia Coronária , Circulação Coronária , Humanos , Pessoa de Meia-Idade , Ácido Úrico/sangue
13.
Echocardiography ; 36(11): 2108-2109, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31628761

RESUMO

Cardiac blood cysts are confirmed by autopsies in stillbirths but rarely detected in adults. Although cardiac blood cysts are common in newborns, they disappear within a few months after birth. These cysts are blood-filled diverticula surrounded by endothelium. Their possible etiology is invaginations of atrial endothelium into the stroma of atrioventricular valves. Most blood cysts originate from the left side of the heart and are located on the atrioventricular valves. Complication is followed in very little cases, such as embolic stroke, valvular dysfunction, and ventricular outflow system obstruction. The blood cysts leading to complications should be removed surgically.


Assuntos
Cistos/complicações , Átrios do Coração/diagnóstico por imagem , Cardiopatias Congênitas/complicações , Insuficiência da Valva Tricúspide/etiologia , Valva Tricúspide/diagnóstico por imagem , Idoso , Cistos/congênito , Cistos/diagnóstico , Ecocardiografia , Endotélio Vascular/diagnóstico por imagem , Feminino , Cardiopatias Congênitas/diagnóstico , Humanos , Insuficiência da Valva Tricúspide/diagnóstico
14.
PLoS Pathog ; 8(7): e1002832, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22910833

RESUMO

Hepatitis C virus (HCV) infects over 170 million people worldwide and is the leading cause of chronic liver diseases, including cirrhosis, liver failure, and liver cancer. Available antiviral therapies cause severe side effects and are effective only for a subset of patients, though treatment outcomes have recently been improved by the combination therapy now including boceprevir and telaprevir, which inhibit the viral NS3/4A protease. Despite extensive efforts to develop more potent next-generation protease inhibitors, however, the long-term efficacy of this drug class is challenged by the rapid emergence of resistance. Single-site mutations at protease residues R155, A156 and D168 confer resistance to nearly all inhibitors in clinical development. Thus, developing the next-generation of drugs that retain activity against a broader spectrum of resistant viral variants requires a comprehensive understanding of the molecular basis of drug resistance. In this study, 16 high-resolution crystal structures of four representative protease inhibitors--telaprevir, danoprevir, vaniprevir and MK-5172--in complex with the wild-type protease and three major drug-resistant variants R155K, A156T and D168A, reveal unique molecular underpinnings of resistance to each drug. The drugs exhibit differential susceptibilities to these protease variants in both enzymatic and antiviral assays. Telaprevir, danoprevir and vaniprevir interact directly with sites that confer resistance upon mutation, while MK-5172 interacts in a unique conformation with the catalytic triad. This novel mode of MK-5172 binding explains its retained potency against two multi-drug-resistant variants, R155K and D168A. These findings define the molecular basis of HCV N3/4A protease inhibitor resistance and provide potential strategies for designing robust therapies against this rapidly evolving virus.


Assuntos
Antivirais/farmacologia , Farmacorresistência Viral/genética , Hepacivirus/efeitos dos fármacos , Inibidores de Proteases/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/química , Antivirais/metabolismo , Ciclopropanos , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Humanos , Indóis/química , Indóis/metabolismo , Indóis/farmacologia , Isoindóis , Lactamas/química , Lactamas/metabolismo , Lactamas/farmacologia , Lactamas Macrocíclicas , Leucina/análogos & derivados , Modelos Moleculares , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Oligopeptídeos/farmacologia , Prolina/análogos & derivados , Prolina/química , Prolina/metabolismo , Prolina/farmacologia , Inibidores de Proteases/química , Inibidores de Proteases/metabolismo , Inibidores de Proteases/uso terapêutico , Estrutura Terciária de Proteína , Relação Estrutura-Atividade , Sulfonamidas/química , Sulfonamidas/metabolismo , Sulfonamidas/farmacologia , Proteínas não Estruturais Virais/química
15.
Acta Cardiol ; 69(6): 619-27, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25643432

RESUMO

AIM: This study tried to determine the efficacy and safety of low-dose intracoronary unfractionated heparin (UFH) in elective percutaneous coronary intervention (PCI). METHODS: Two-hundred patients who underwent elective PCI of an uncomplicated lesion were included into the study. The patients were assigned to either a control group (70-100 IU/kg intravenous UFH) or a low-dose intracoronary UFH (1,000 IU intracoronary UFH) group. RESULTS: At 30 days, the primary end point (composite of death, myocardial infarction, or urgent target vessel revascularization) was similar in both groups [intracoronary UFH group, 1.0%; control group, 2.0%; odds ratio; 0.49 (95% CI: 0.04 - 5.54), P = 0.56]. Post-procedural myocardial injury (according to CK-MB, P = 0.91; according to Tn I, P = 0.81) and bleeding events (based on TIMI criteria, P = 0.33; based on STEEPLE criteria, P = 0.20) were similar in the control and intracoronary groups. The primary end point at 6 months was also similar between the two groups (P = 0.33). Moreover, the health care cost at 30 days of follow-up was lower in the intracoronary group than in the control group (1,016 ± 54 $/patient vs 1,110 ± 102 $/patient, P < 0.001). CONCLUSION: This pilot study suggests that elective PCI could be safely performed with low-dose intracoronary UFH in the treatment of uncomplicated lesions and at a lower cost as compared to standard systemic anticoagulation.These results should be confirmed by further studies.


Assuntos
Fibrinolíticos/administração & dosagem , Heparina/administração & dosagem , Intervenção Coronária Percutânea , Angiografia Coronária , Método Duplo-Cego , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento
16.
Rev Assoc Med Bras (1992) ; 70(8): e20240647, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39230152

RESUMO

OBJECTIVE: Sudden cardiac death or arrest describes an unexpected cardiac cause-related death or arrest that occurs rapidly out of the hospital or in the emergency room. This study aimed to reveal the relationship between coronary angiographic findings and cardiac death secondary to acute ST-elevation myocardial infarction. MATERIALS AND METHODS: Patients presenting with acute ST-elevation myocardial infarction complicated with cardiac arrest were included in the study. The severity of coronary artery disease, coronary chronic total occlusion, coronary collateral circulation, and blood flow in the infarct-related artery were recorded. Patients were divided into two groups, namely, deaths secondary to cardiac arrest and survivors of cardiac arrest. RESULTS: A total of 161 cardiac deaths and 42 survivors of cardiac arrest were included. The most frequent (46.3%) location of the culprit lesion was on the proximal left anterior descending artery. The left-dominant coronary circulation was 59.1%. There was a difference in the SYNTAX score (16.3±3.8 vs. 13.6±1.9; p=0.03) and the presence of chronic total occlusion (19.2 vs. 0%; p=0.02) between survivors and cardiac deaths. A high SYNTAX score (OR: 0.38, 95%CI: 0.27-0.53, p<0.01) was determined as an independent predictor of death secondary to cardiac arrest. CONCLUSION: The chronic total occlusion presence and SYNTAX score may predict death after cardiac arrest secondary to ST-elevation myocardial infarction.


Assuntos
Angiografia Coronária , Parada Cardíaca , Infarto do Miocárdio com Supradesnível do Segmento ST , Índice de Gravidade de Doença , Humanos , Feminino , Masculino , Parada Cardíaca/mortalidade , Pessoa de Meia-Idade , Idoso , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Fatores de Risco , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Oclusão Coronária/mortalidade , Oclusão Coronária/complicações , Oclusão Coronária/diagnóstico por imagem , Valor Preditivo dos Testes , Medição de Risco , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/epidemiologia
17.
Rev Assoc Med Bras (1992) ; 70(3): e20231299, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38656008

RESUMO

OBJECTIVE: The Glasgow prognosis score is a simple parameter calculated using serum levels of albumin and C-reactive protein. The aim of this study was to examine whether this parameter may predict ischemic stroke in patients with infective endocarditis. METHODS: A total of 80 patients who were diagnosed with definitive infective endocarditis according to Duke criteria between 2016 and 2023 were included in the study. Glasgow prognosis score was based on serum levels of albumin and C-reactive protein. In imaging methods, patients were divided into two groups according to whether they had a stroke or not. These two groups were compared in terms of biochemical parameters, and infective endocarditis findings on echocardiography and Glasgow prognosis score. RESULTS: We found that the results were statistically similar except for serum C-reactive protein (Group 1: 54.9±71.1 and Group 2: 39±70.7; p=0.03), neutrophil (Group 1: 19.8±10.8*109/L and Group 2: 13.3±7.3*109/L; p=0.014), albumin (Group 1: 2.3±0.6 and Group 2: 2.8±0.5; p=0.03), and Glasgow prognosis score (Group 1: median 2, min.-max. (1-2) and Group 2: median 1, min.-max. (0-1); p=0.004). In the receiver operating characteristics analysis, Glasgow prognosis score had 82.4% sensitivity and 58.3% specificity in predicting ischemic stroke if the Glasgow prognosis score cutoff was ≥1. In multivariate logistic regression analysis, chronic renal failure [odds ratio (OR): 1.098; 95% confidence interval: 1.054-1.964; p=0.044], age (OR: 1.050; 95%CI 1.006-1.096; p=0.024), and Glasgow prognosis score (OR: 0.695; 95%CI 0.411-0.949; p=0.035) were independent variables in predicting ischemic stroke. CONCLUSION: High Glasgow prognosis score is an independent predictor of ischemic stroke in patients with infective endocarditis. Glasgow prognosis score, determined using albumin and C-reactive protein levels, is a simple and practical index for predicting the prognosis of patients hospitalized with infective endocarditis.


Assuntos
Proteína C-Reativa , AVC Isquêmico , Albumina Sérica , Humanos , Feminino , Masculino , Proteína C-Reativa/análise , Prognóstico , Pessoa de Meia-Idade , AVC Isquêmico/sangue , AVC Isquêmico/complicações , Albumina Sérica/análise , Idoso , Endocardite/sangue , Endocardite/complicações , Adulto , Ecocardiografia , Biomarcadores/sangue , Fatores de Risco , Valor Preditivo dos Testes
18.
Rev Assoc Med Bras (1992) ; 70(8): e20240515, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39230149

RESUMO

OBJECTIVE: Coronary artery disease (CAD) is frequent, but coronary slow flow (CSF) is a less common cardiovascular disease with a significant risk of mortality and morbidity. Endocan is a proinflammatory glycopeptide that has been investigated in cardiovascular diseases as well as some inflammatory diseases in recent years. We planned to compare the levels of endocan in both CAD and CSF in a similar population and examine the relationship of endocan with additional clinical variables. MATERIALS AND METHODS: In the trial, we included 169 consecutive subjects having a coronary angiography indication. According to the results of coronary angiography, 58 people were included in the CAD group, 52 were in the CSF group, and 59 people were in the control group. The control group includes those who did not have any lesions in their epicardial coronary arteries. Thrombolysis in myocardial infarction (TIMI)-frame counts (TFC) were calculated for all patients. RESULTS: Notably, 2.6% of the population in our study had CSF. Both the CAD (555±223 pg/mL) and CSF (559±234 pg/mL) groups had higher endocan levels than the control group (331±252 pg/mL) (p<0.001). There were similar endocan levels between the CAD and CSF groups. Endocan levels were shown to be favorably associated with mean TFC (r=0.267; p0.001). Serum endocan levels (particularly those above 450 pg/mL) and the presence of hyperlipidemia were the most important predictors of both CAD and CSF. CONCLUSION: Endocan levels are higher in CAD and CSF patients than in those with normal coronary arteries.


Assuntos
Biomarcadores , Angiografia Coronária , Doença da Artéria Coronariana , Proteínas de Neoplasias , Proteoglicanas , Humanos , Proteoglicanas/sangue , Proteoglicanas/líquido cefalorraquidiano , Masculino , Feminino , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/líquido cefalorraquidiano , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/líquido cefalorraquidiano , Proteínas de Neoplasias/análise , Estudos de Casos e Controles , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Idoso , Circulação Coronária/fisiologia , Valor Preditivo dos Testes , Fatores de Risco
19.
Echocardiography ; 30(10): 1180-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23742118

RESUMO

Diastolic dysfunction leads to atrial fibrillation (AF) by increasing left atrial pressure and also increases recurrence rate after cardioversion. So, L-wave, which is associated with severe diastolic dysfunction, could predict recurrent AF after cardioversion. The aim of this study was to investigate predictive value of L-wave for AF recurrence at first month after electrical cardioversion. A total of 127 patients with persistent AF were evaluated for this study and finally 73 patients were included according to the study criteria. Echocardiographic examinations were performed for all patients before and at 24th hour after electrical cardioversion. Heart rates and rhythms were followed with electrocardiography monitor and 12-lead ECG at first week and first month. Seventy patients achieved sinus rhythm (SR) after cardioversion and 3 patients who did not go into SR excluded from the study. Patients were divided into 2 groups according to having (group 1) or not having (group 2) L-wave on echocardiography. Twenty-two patients (6 men, 16 women) had L-wave and 48 patients (19 men, 29 women) did not have L-wave. Duration of AF was longer in group 1 as compared to group 2 (P = 0.03). Mean heart rate was lower in group 1 than in group 2 (P < 0.001). Duration of AF and presence of L-wave were significant parameters for AF recurrence in univariate analysis, however, presence of L-wave was the only significant parameter for AF recurrence in multivariate analysis. Ten patients in group 1 (45.5%) and 7 patients (14.6%) in group 2 (P = 0.005) had AF recurrence at the end of first month after cardioversion. L-wave did predict AF recurrence with 59% sensitivity, 77% specificity, 45% positive predictive value, and 85% negative predictive value at 1 month. Echocardiographic L-wave could predict the AF recurrence.


Assuntos
Fibrilação Atrial/diagnóstico por imagem , Idoso , Fibrilação Atrial/terapia , Ecocardiografia , Ecocardiografia Doppler em Cores , Ecocardiografia Transesofagiana , Cardioversão Elétrica , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Prevenção Secundária
20.
Turk Kardiyol Dern Ars ; 51(2): 112-118, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36916806

RESUMO

OBJECTIVE: We designed a retrospective study to evaluate the performance and outcomes of a novel iopromide-based paclitaxel-coated balloon for the treatment of chronic total occlusion of femoropopliteal arteries. METHODS: Patients with femoropopliteal chronic total occlusion (<100 mm) on angiogram were screened from hospital management system and were included in the study. The width and length of the drug-eluting peripheral balloon was chosen to ensure a vessel/balloon ratio of 1: 1 and exceed the lesion by 10 mm on both ends (based on visual estimation). RESULTS: The proportion of patients with ankle-brachial index improvement was 89.8% (106 of 118). The mean ankle-brachial index was 0.5 (0.4-0.7) at baseline and 0.8 (0.7-0.9) at 12 months (P < 0.001). Changes in the Rutherford category between baseline and 12 months were statistically significant (P < 0.001), with the majority of patients (77.9%, 92/118) having ≥1 level improvement. The rate of clinically driven target lesion revasculariza-tion at 12 months was 13.5%(16/118). Overall, the 1-year primary patency rate was 86.4% (102 of 118). The major adverse limb event rate was 9.8% (16/162). Acute limb ischemia was detected in 14 patients, and amputation was performed in 2 patients. CONCLUSION: Our study is a non-randomized clinical study focusing on the use of drug-eluting balloon as a single treatment strategy. There was significant clinical benefit to patients, as clearly demonstrated by the improvement in ankle-brachial index and the reduction in Rutherford class in the short term, and these results may offer clear insights on the revascularization strategy outlook of interventionalists.


Assuntos
Angioplastia com Balão , Fármacos Cardiovasculares , Doença Arterial Periférica , Humanos , Artéria Poplítea , Paclitaxel/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Doença Arterial Periférica/terapia , Angioplastia com Balão/métodos , Artéria Femoral , Fármacos Cardiovasculares/efeitos adversos
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