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1.
Circulation ; 149(5): 379-390, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-37950738

RESUMO

BACKGROUND: Left bundle branch area pacing (LBBAP) may be associated with greater improvement in left ventricular ejection fraction and reduction in death or heart failure hospitalization compared with biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy. We sought to compare the occurrence of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and new-onset atrial fibrillation (AF) in patients undergoing BVP and LBBAP. METHODS: The I-CLAS study (International Collaborative LBBAP Study) included patients with left ventricular ejection fraction ≤35% who underwent BVP or LBBAP for cardiac resynchronization therapy between January 2018 and June 2022 at 15 centers. We performed propensity score-matched analysis of LBBAP and BVP in a 1:1 ratio. We assessed the incidence of VT/VF and new-onset AF among patients with no history of AF. Time to sustained VT/VF and time to new-onset AF was analyzed using the Cox proportional hazards survival model. RESULTS: Among 1778 patients undergoing cardiac resynchronization therapy (BVP, 981; LBBAP, 797), there were 1414 propensity score-matched patients (propensity score-matched BVP, 707; propensity score-matched LBBAP, 707). The occurrence of VT/VF was significantly lower with LBBAP compared with BVP (4.2% versus 9.3%; hazard ratio, 0.46 [95% CI, 0.29-0.74]; P<0.001). The incidence of VT storm (>3 episodes in 24 hours) was also significantly lower with LBBAP compared with BVP (0.8% versus 2.5%; P=0.013). Among 299 patients with cardiac resynchronization therapy pacemakers (BVP, 111; LBBAP, 188), VT/VF occurred in 8 patients in the BVP group versus none in the LBBAP group (7.2% versus 0%; P<0.001). In 1194 patients with no history of VT/VF or antiarrhythmic therapy (BVP, 591; LBBAP, 603), the occurrence of VT/VF was significantly lower with LBBAP than with BVP (3.2% versus 7.3%; hazard ratio, 0.46 [95% CI, 0.26-0.81]; P=0.007). Among patients with no history of AF (n=890), the occurrence of new-onset AF >30 s was significantly lower with LBBAP than with BVP (2.8% versus 6.6%; hazard ratio, 0.34 [95% CI, 0.16-0.73]; P=0.008). The incidence of AF lasting >24 hours was also significantly lower with LBBAP than with BVP (0.7% versus 2.9%; P=0.015). CONCLUSIONS: LBBAP was associated with a lower incidence of sustained VT/VF and new-onset AF compared with BVP. This difference remained significant after adjustment for differences in baseline characteristics between patients with BVP and LBBAP. Physiological resynchronization by LBBAP may be associated with lower risk of arrhythmias compared with BVP.


Assuntos
Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Taquicardia Ventricular , Humanos , Terapia de Ressincronização Cardíaca/efeitos adversos , Volume Sistólico , Função Ventricular Esquerda , Resultado do Tratamento , Taquicardia Ventricular/epidemiologia , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/terapia , Fibrilação Ventricular/epidemiologia , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/terapia , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Eletrocardiografia
2.
Molecules ; 28(23)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38067443

RESUMO

The rapid growth of the dye and textile industry has raised significant public concerns regarding the pollution caused by dye wastewater, which poses potential risks to human health. In this study, we successfully improved the adsorption efficiency of activated carbon derived from pomegranate peel waste (PPAC) through a single-step and surface modification approach using 5-sulfonate-salicylaldehyde sodium salt. This innovative and effective sulfonation approach to produce sulfonated activated carbon (S-PPAC) proved to be highly effective in removing crystal violet dye (CV) from polluted water. The prepared PPAC and S-PPAC were characterized via FESEM, EDS, FTIR and BET surface area. Characterization studies confirmed the highly porous structure of the PPAC and its successful surface modification, with surface areas reaching 1180.63 m2/g and 740.75 m2/g for the PPAC and S-PPAC, respectively. The maximum adsorption capacity was achieved at 785.53 mg/g with the S-PPAC, an increase of 22.76% compared to the PPAC at 45 °C. The isothermic adsorption and kinetic studies demonstrated that the adsorption process aligned well with the Freundlich isotherm model and followed the Elovich kinetic model, respectively. The thermodynamic study confirmed that the adsorption of CV dye was endothermic, spontaneous and thermodynamically favorable onto PPAC and S-PPAC.

3.
J Cardiovasc Electrophysiol ; 33(6): 1234-1243, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35488749

RESUMO

INTRODUCTION: His bundle pacing (HBP) is the most physiologic form of pacing and has been associated with reduced risk for heart failure hospitalization (HFH) and mortality compared to right ventricular pacing. Left bundle branch area pacing (LBBAP) is a safe and effective alternative option for patients needing ventricular pacing. The aim of this study was to compare the clinical outcomes between LBBAP and HBP among a large cohort of patients undergoing permanent pacemaker implantation. METHODS: This observational registry included consecutive patients with AV block/AV node ablation who underwent de novo permanent pacemaker implantations with successful LBBAP or HBP between April 2018 and October 2020. The primary outcome was the composite endpoint of time to death from any cause or HFH. Secondary outcomes included the composite endpoint among patients with prespecified ventricular pacing burden and individual outcomes. RESULTS: The study population included 359 patients who met the inclusion criteria (163 in the HBP and 196 in the LBBAP group). Paced QRSd during LBBAP was similar to HBP (125 ± 20.2 vs. 126 ± 23.5 ms, p = .643). There were no statistically significant differences in the primary composite outcome in LBBAP (17.3%) compared to HBP (24.5%) (hazard ratio [HR]: 1.15, 95% CI: 0.72-1.82, p = .552). Secondary outcomes of death (10% vs. 17%; HR: 1.3, 95% CI: 0.73-2.33, p = .38) and HFH (10% vs. 12%; HR: 1.02, 95% CI: 0.54-1.94, p = .94) were not different among both groups. CONCLUSIONS: There were no statistically significant differences in the clinical outcomes of death or HFH in LBBAP when compared to HBP.


Assuntos
Fascículo Atrioventricular , Estimulação Cardíaca Artificial , Estimulação Cardíaca Artificial/efeitos adversos , Eletrocardiografia , Sistema de Condução Cardíaco , Ventrículos do Coração , Humanos , Resultado do Tratamento
4.
Respir Res ; 23(1): 43, 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241091

RESUMO

BACKGROUND: The prevalence of age-associated diseases, such as chronic obstructive pulmonary disease (COPD), is increasing as the average life expectancy increases around the world. We previously identified a gene signature for ageing in the human lung which included genes involved in apical and tight junction assembly, suggesting a role for airway epithelial barrier dysfunction with ageing. AIM: To investigate the association between genes involved in epithelial barrier function and age both in silico and in vitro in the airway epithelium. METHODS: We curated a gene signature of 274 genes for epithelial barrier function and tested the association with age in two independent cohorts of bronchial brushings from healthy individuals with no respiratory disease, using linear regression analysis (FDR < 0.05). Protein-protein interactions were identified using STRING©. The barrier function of primary bronchial epithelial cells at air-liquid interface and CRISPR-Cas9-induced knock-down of target genes in human bronchial 16HBE14o-cells was assessed using Trans epithelial resistance (TER) measurement and Electric cell-surface impedance sensing (ECIS) respectively. RESULTS: In bronchial brushings, we found 55 genes involved in barrier function to be significantly associated with age (FDR < 0.05). EPCAM was most significantly associated with increasing age and TRPV4 with decreasing age. Protein interaction analysis identified CDH1, that was negatively associated with higher age, as potential key regulator of age-related epithelial barrier function changes. In vitro, barrier function was lower in bronchial epithelial cells from subjects > 45 years of age and significantly reduced in CDH1-deficient 16HBE14o-cells. CONCLUSION: The significant association between genes involved in epithelial barrier function and age, supported by functional studies in vitro, suggest a role for epithelial barrier dysfunction in age-related airway disease.


Assuntos
Envelhecimento/fisiologia , Brônquios/metabolismo , Células Epiteliais/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Adolescente , Adulto , Idoso , Brônquios/patologia , Células Cultivadas , Células Epiteliais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/patologia , Mucosa Respiratória/metabolismo , Adulto Jovem
5.
COPD ; 19(1): 81-87, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35118915

RESUMO

Current knowledge about the respiratory microbiome is mainly based on 16S ribosomal RNA gene sequencing. Newer sequencing approaches, such as metatranscriptomics, offer the technical ability to measure the viable microbiome response to environmental conditions such as smoking as well as to explore its functional role by investigating host-microbiome interactions. However, knowledge about its feasibility in respiratory microbiome research, especially in lung biopsies, is still very limited. RNA sequencing was performed in bronchial biopsies from clinically stable smokers (n = 5) and ex-smokers (n = 6) with COPD not using (inhaled) steroids. The Trinity assembler was used to assemble non-human reads in order to allow unbiased taxonomical and microbial transcriptional analyses. Subsequently, host-microbiome interactions were analyzed based on associations with host transcriptomic data. Ultra-low levels of microbial mass (0.009%) were identified in the RNA-seq data. Overall, no differences were identified in microbiome diversity or transcriptional profiles of microbial communities or individual microbes between COPD smokers and ex-smokers in the initial test dataset as well as a larger replication dataset. We identified an upregulated host gene set, related to the simultaneous presence of Bradyrhizobium, Roseomonas, Brevibacterium.spp., which were related to PERK-mediated unfolded protein response (UPR) and expression of the microRNA-155-5p. Our results show that metatranscriptomic profiling in bronchial biopsy samples from stable COPD patients yields ultra-low levels of microbial mass. Further, this study illustrates the potential of using transcriptional profiling of the host and microbiome to gain more insight into their interaction in the airways.


Assuntos
MicroRNAs , Microbiota , Doença Pulmonar Obstrutiva Crônica , Biópsia , Ex-Fumantes , Humanos , Microbiota/genética , Doença Pulmonar Obstrutiva Crônica/patologia , Fumantes
6.
J Cardiovasc Electrophysiol ; 32(3): 851-855, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33484212

RESUMO

Left bundle branch pacing (LBBP) has emerged as an alternative to His bundle pacing (HBP) to achieve physiologic ventricular stimulation. The extent of myocardial injury during permanent LBBP implantation is currently not known. The aim of the study was to prospectively assess the extent of myocardial injury during LBBP implantation. Cardiac troponin (cTn) levels were measured at baseline and 6-12 h following permanent LBBP. The number of attempts to achieve LBBP was documented. Troponin levels were measured in a control population undergoing other electrophysiology procedures including HBP, other devices involving right ventricular (RV) pacing, radiofrequency ablation for atrial fibrillation (AF) and supraventricular tachycardia (SVT). Significant elevation of troponin (SET) was defined as threefold increase above the upper reference limit (URL) for cTn. Between December 2019 and April 2020, 204 were prospectively enrolled: LBBP in 98 and Control group 106 (SVT, 55; AF, 20; HBP, 17; other devices, 14). SET (>3× URL) was seen in 49.4% of patients in the LBBP group compared to 58.4% in the control group (p = .23). Peak troponin levels were greater in the control group compared to the LBBP group (230.3 ± 320.1 vs. 87.4 ± 71.3 pg/ml; p = .0001). Compared to LBBP (49.4%), SET was observed less frequently following HBP (17.5%; p = .01), and other device implantation (29%; p = .15). Patients requiring >2 attempts (n = 33) had significantly higher incidence of SET compared to <2 attempts (n = 56; 66.7% vs. 39.3%; p = .01). LBBP implantation is associated with myocardial injury. Asymptomatic troponin release following LBBP is less than or comparable to other interventional electrophysiology procedures.


Assuntos
Fascículo Atrioventricular , Estimulação Cardíaca Artificial , Estimulação Cardíaca Artificial/efeitos adversos , Eletrocardiografia , Sistema de Condução Cardíaco , Humanos , Troponina
7.
Europace ; 23(5): 757-766, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33236070

RESUMO

AIMS: His bundle pacing (HBP) is the most physiologic form of pacing. Long-term HBP capture threshold stability and its relation to lead characteristics at the time of implantation have not been adequately described. The aim of this study was to characterize HB capture threshold in follow-up and to identify potential lead characteristics predictive of lead capture instability. METHODS AND RESULTS: Consecutive patients with successful HBP for bradycardia indications were identified from the Geisinger HBP registry. His bundle capture thresholds, baseline comorbidities, and radiographic lead slack characteristics were analysed. An increase in HB capture threshold ≥1 V above implant values at any time during follow-up was tracked. Forty-four of the 294 studied (15%) experienced HB capture threshold increase by ≥ 1 V. Threshold increase was seen early (41% by 8 weeks, 66% by 1 year). Eighteen (6%) patients required lead revision in follow-up. Abnormal slack shape was associated with a trend toward capture threshold increase [hazard ratio (HR) 2.07; 95% confidence interval (CI) 0.9-4.6; P = 0.08]. Non-perpendicular angle of lead insertion on radiography was associated with the capture threshold increase (HR 2.81, 95% CI 1.4-5.8; P < 0.01). CONCLUSION: His bundle capture threshold remains stable in the majority (85%) of patients. Implant characteristics may predict the threshold rise. Further evaluation of the aetiology of threshold increase and design changes in lead and delivery systems may lead to chronically stable capture thresholds.


Assuntos
Fascículo Atrioventricular , Estimulação Cardíaca Artificial , Bradicardia/terapia , Eletrocardiografia , Seguimentos , Humanos , Resultado do Tratamento
8.
Molecules ; 26(17)2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34500816

RESUMO

The pharmacological activities of thiazole and pyrazole moieties as antimicrobial and anticancer agents have been thoroughly described in many literature reviews. In this study, a convenient synthesis of novel pyrazolo[5,1-b]thiazole-based heterocycles was carried out. The synthesized compounds were characterized by IR, 1H and 13C NMR spectroscopy and mass spectrometry. Some selected examples were screened and evaluated for their antimicrobial and anticancer activities and showed promising results. These products could serve as leading compounds in the future design of new drug molecules.


Assuntos
Antibacterianos/síntese química , Antineoplásicos/síntese química , Antibacterianos/toxicidade , Antineoplásicos/toxicidade , Células HCT116 , Células Hep G2 , Humanos , Pirazóis/química , Tiazóis/química
9.
Med J Malaysia ; 75(3): 301-303, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32467550

RESUMO

Chest X-ray is valuable in the primary care setting in helping clinicians to confirm the underlying findings of the respiratory and cardiovascular systems. This view also includes the lower cervical vertebrae region which is helpful in elaborating the findings surrounding the neck. However, a single view of the film may sometimes cause confusion regarding the exact origin of the abnormal signs of the X-ray images. Thus, clinical correlation and application of 'rule of two' in X-ray imaging is definitely useful to clarify the findings and avoiding any misdiagnosis, medical errors and non-justifiable further investigations. Here we report a case of an 18-year-old female student with abnormal radiopaque neck mass seen from her chest the X-ray image. She was clinically well without any significant clinical findings. Surprisingly, the findings totally resolved after repeat the Xray at two different occasions within the same week. This strange abnormal finding was later confirmed to be her hair tier. She was saved from unnecessary investigations for tuberculosis and thyroid disorder by repeating the X-ray (rule of two occasions). Now you see, now you don't of X-ray findings is indeed illogical and technical error needs to be rule out.


Assuntos
Erros de Diagnóstico , Pescoço/diagnóstico por imagem , Radiografia , Adolescente , Feminino , Humanos
10.
J Cardiovasc Electrophysiol ; 30(9): 1594-1601, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31310410

RESUMO

INTRODUCTION: Several single-center short-term studies have demonstrated the feasibility, safety, and positive clinical outcomes of permanent His bundle pacing (HBP). We performed a retrospective study to evaluate long-term technical and safety performances of HBP in a large population of pacemaker patients from two different centers. METHODS AND RESULTS: The analysis includes 844 patients (345 female, mean age = 75 ± 9 years) who underwent successful permanent HBP for pacemaker indications from 2004 to 2016. The main endpoints were long term electrical performances including pacing threshold, sensing, impedance, and freedom from pacing related complications. The pacing indication was AV Block in 348 (41.2%) patients, sinus node disease in 147 (17.4%), any bradycardia indication in patients with atrial fibrillation in 335 (39.7%) patients and need for cardiac resynchronization therapy in 14 (1.7%) patients. Mean pacing capture thresholds and sensed R waves were 1.6 V and 5.8 mV, respectively at implant and 2.0 V and 6.1 mV at chronic follow-up. During the median follow up of 3 years (interquartile range = 1-6 years), HBP was free of any complication in 91.6% of patients. In the first 368 patients, HBP was achieved using a deflectable curve delivery system, while in 476 using the fixed curve sheath. A significant difference was found in the thresholds (2.4 ± 1.0 V and 1.7 ± 1.1 V, P < .001, respectively) and complications (11.9% and 4.2%, P < .001, respectively) between the two groups. CONCLUSIONS: Permanent HBP was safe and effective during long-term follow-up. The fixed curved delivery sheath offered significantly better electrical parameters and reliability over time. The results of this multicenter study are consistent with recent studies.


Assuntos
Bloqueio Atrioventricular/terapia , Bradicardia/terapia , Fascículo Atrioventricular/fisiopatologia , Estimulação Cardíaca Artificial , Marca-Passo Artificial , Síndrome do Nó Sinusal/terapia , Potenciais de Ação , Idoso , Idoso de 80 Anos ou mais , Bloqueio Atrioventricular/diagnóstico , Bloqueio Atrioventricular/fisiopatologia , Bradicardia/diagnóstico , Bradicardia/fisiopatologia , Estimulação Cardíaca Artificial/efeitos adversos , Falha de Equipamento , Feminino , Frequência Cardíaca , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Pennsylvania , Estudos Retrospectivos , Síndrome do Nó Sinusal/diagnóstico , Síndrome do Nó Sinusal/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
11.
Molecules ; 24(9)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31035531

RESUMO

A series of new thiazoline derivatives were synthesized. Structure analyses were accomplished employing 1H-NMR, 13C-NMR, X-ray and MS techniques. The in vitro antitumor activities were assessed against human hepatocellular carcinoma (HepG-2) and colorectal carcinoma (HCT-116) cell lines. The results revealed that the thiazolines 5b and 2c exhibited significant activity against the two cell lines. The in vitro antimicrobial screening showed that the thiazolines 2c, 5b and 5d showed promising inhibition activity against Salmonella sp. Additionally, the inhibition activity of thiazolines 2e and 5b against Escherichia coli was comparable to that of the reference compound gentamycin.


Assuntos
Técnicas de Química Sintética , Simulação de Acoplamento Molecular , Compostos Orgânicos/química , Compostos Orgânicos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Ligação de Hidrogênio , Estrutura Molecular , Compostos Orgânicos/síntese química , Análise Espectral , Relação Estrutura-Atividade
12.
Physiol Genomics ; 50(9): 705-713, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29932825

RESUMO

BACKGROUND: Understanding effects of acute smoke exposure (ASE) on airway epithelial gene expression and their relationship with the effects of chronic smoke exposure may provide biological insights into the development of smoking-related respiratory diseases. METHODS: Bronchial airway epithelial cell brushings were collected from 63 individuals without recent cigarette smoke exposure and before and 24 h after smoking three cigarettes. RNA from these samples was profiled on Affymetrix Human Gene 1.0 ST microarrays. RESULTS: We identified 91 genes differentially expressed 24 h after ASE (false discovery rate < 0.25). ASE induced genes involved in xenobiotic metabolism, oxidative stress, and inflammation and repressed genes related to cilium morphogenesis and cell cycle. While many genes altered by ASE are altered similarly in chronic smokers, metallothionein genes are induced by ASE and suppressed in chronic smokers. Metallothioneins are also suppressed in current and former smokers with lung cancer relative to those without lung cancer. CONCLUSIONS: Acute exposure to as little as three cigarettes and chronic smoking induce largely concordant changes in airway epithelial gene expression. Differences in short-term and long-term effects of smoking on metallothionein expression and their relationship to lung cancer requires further study given these enzymes' role in the oxidative stress response.


Assuntos
Brônquios/metabolismo , Brônquios/patologia , Regulação da Expressão Gênica , Fumar/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Metalotioneína/metabolismo , Pessoa de Meia-Idade , Abandono do Hábito de Fumar , Adulto Jovem
13.
Clin Exp Allergy ; 48(10): 1286-1296, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29786918

RESUMO

BACKGROUND: Asthma is a chronic respiratory disease without a cure, although there exists spontaneous remission. Genome-wide association (GWA) studies have pinpointed genes associated with asthma development, but did not investigate asthma remission. OBJECTIVE: We performed a GWA study to develop insights in asthma remission. METHODS: Clinical remission (ClinR) was defined by the absence of asthma treatment and wheezing in the last year and asthma attacks in the last 3 years and complete remission (ComR) similarly but additionally with normal lung function and absence of bronchial hyperresponsiveness (BHR). A GWA study on both ClinR and ComR was performed in 790 asthmatics with initial doctor diagnosis of asthma and BHR and long-term follow-up. We assessed replication of the 25 top single nucleotide polymorphisms (SNPs) in 2 independent cohorts (total n = 456), followed by expression quantitative loci (eQTL) analyses of the 4 replicated SNPs in lung tissue and epithelium. RESULTS: Of the 790 asthmatics, 178 (23%) had ClinR and 55 ComR (7%) after median follow-up of 15.5 (range 3.3-47.8) years. In ClinR, 1 of the 25 SNPs, rs2740102, replicated in a meta-analysis of the replication cohorts, which was an eQTL for POLI in lung tissue. In ComR, 3 SNPs replicated in a meta-analysis of the replication cohorts. The top-hit, rs6581895, almost reached genome-wide significance (P-value 4.68 × 10-7 ) and was an eQTL for FRS2 and CCT in lung tissue. Rs1420101 was a cis-eQTL in lung tissue for IL1RL1 and IL18R1 and a trans-eQTL for IL13. CONCLUSIONS AND CLINICAL RELEVANCE: By defining a strict remission phenotype, we identified 3 SNPs to be associated with complete asthma remission, where 2 SNPs have plausible biological relevance in FRS2, CCT, IL1RL1, IL18R1 and IL13.


Assuntos
Asma/genética , Asma/imunologia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Adulto , Alelos , Asma/diagnóstico , Hiper-Reatividade Brônquica/genética , Hiper-Reatividade Brônquica/imunologia , Biologia Computacional/métodos , Feminino , Regulação da Expressão Gênica , Estudos de Associação Genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Avaliação de Resultados da Assistência ao Paciente , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Testes de Função Respiratória , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo
14.
Curr Cardiol Rep ; 20(11): 109, 2018 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-30259196

RESUMO

PURPOSE OF REVIEW: Cardiac resynchronization therapy (CRT) using biventricular pacing (BVP) is the cornerstone of treatment for patients with heart failure and left bundle branch block. Up to a third of patients do not respond to BVP. This article reviews the utility of His-bundle pacing (HBP) and Left ventricular (LV) endocardial pacing as alternatives to BVP to provide ventricular synchrony. RECENT FINDINGS: HBP has shown promising results in observational studies. By significantly narrowing or normalizing QRS, HBP has improved clinical outcomes including ejection fractions both as a rescue option in patients who failed BVP or as a primary alternative. LV endocardial pacing has also shown promise with improved clinical outcomes. Using traditional pacing leads or novel technology, direct stimulation of the LV endocardium allows for better site selection as well as a more physiological activation of the LV compared to traditional epicardial LV stimulation. HBP and LV endocardial pacing are valuable alternatives to traditional BVP to achieve CRT. Randomized clinical trials in progress will allow for a deeper understanding of how they can benefit our patients.


Assuntos
Fascículo Atrioventricular/fisiopatologia , Bloqueio de Ramo/terapia , Eletrocardiografia , Ventrículos do Coração/fisiopatologia , Função Ventricular Esquerda , Bloqueio de Ramo/fisiopatologia , Terapia de Ressincronização Cardíaca , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
Molecules ; 23(1)2018 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-29329257

RESUMO

Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antipsychotic CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a H2-receptor agonist and the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Owing to this diversity in the biological field, this nucleus has attracted the attention of many researchers to study its skeleton chemically and biologically. This review highlights the different synthesis methods and the pharmacological properties of pyrazole derivatives. Studies on the synthesis and biological activity of pyrazole derivatives developed by many scientists around the globe are reported.


Assuntos
Pirazóis/síntese química , Pirazóis/farmacologia , Animais , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Antidepressivos/química , Antidepressivos/farmacologia , Antipsicóticos/química , Antipsicóticos/farmacologia , Química Farmacêutica/métodos , Desenho de Fármacos , Humanos
17.
Thorax ; 72(1): 74-82, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27325752

RESUMO

BACKGROUND: Asthma affects 300 million people worldwide. In asthma, the major cause of morbidity and mortality is acute airway narrowing, due to airway smooth muscle (ASM) hypercontraction, associated with airway remodelling. However, little is known about the transcriptional differences between healthy and asthmatic ASM cells. OBJECTIVES: To investigate the transcriptional differences between asthmatic and healthy airway smooth muscle cells (ASMC) in culture and investigate the identified targets using in vitro and ex vivo techniques. METHODS: Human asthmatic and healthy ASMC grown in culture were run on Affymetrix_Hugene_1.0_ST microarrays. Identified candidates were confirmed by PCR, and immunohistochemistry. Functional analysis was conducted using in vitro ASMC proliferation, attachment and contraction assays and ex vivo contraction of mouse airways. RESULTS: We suggest a novel role for latrophilin (LPHN) receptors, finding increased expression on ASMC from asthmatics, compared with non-asthmatics in vivo and in vitro, suggesting a role in mediating airway function. A single nucleotide polymorphism in LPHN1 was associated with asthma and with increased LPHN1 expression in lung tissue. When activated, LPHNs regulated ASMC adhesion and proliferation in vitro, and promoted contraction of mouse airways and ASMC. CONCLUSIONS: Given the need for novel inhibitors of airway remodelling and bronchodilators in asthma, the LPHN family may represent promising novel targets for future dual therapeutic intervention.


Assuntos
Asma/genética , Asma/metabolismo , Miócitos de Músculo Liso/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores de Peptídeos/genética , Acetilcolina/farmacologia , Animais , Estudos de Casos e Controles , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Masculino , Glicoproteínas de Membrana , Proteínas de Membrana/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Contração Muscular/efeitos dos fármacos , Miócitos de Músculo Liso/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Peptídeos/metabolismo , Sistema Respiratório/citologia , Venenos de Aranha/farmacologia , Transcrição Gênica
18.
Haemophilia ; 23(5): 736-742, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28181360

RESUMO

INTRODUCTION: Family members of Von Willebrand disease (VWD) patients may have low levels of VWF without major bleeding episodes and often remain undiagnosed. AIM: The purpose of this study was to assess the utility of a modified Screening Tool in identifying previously untested reproductive age female family members of VWD patients for haemostatic evaluation. METHODS: Ninety-four reproductive age women including 41 previously untested family members of VWD patients, 26 previously diagnosed VWD patients and 27 healthy controls were administered a modified Screening Tool and had blood drawn for CBC, ferritin, and VWF testing. Participants completed a pictorial blood assessment chart (PBAC) with menses. RESULTS: The modified Screening Tool was positive in 32% family members, 77% VWD patients, and 19% controls (P < 0.001). Combined with low ferritin, the modified Screening Tool was positive in 66% family members, 92% VWD patients, and 44% controls (P = 0.001). In family members, incorporating low ferritin with the modified Screening Tool resulted in a sensitivity of 86% (95% CI, 42-100) and negative predictive value of 93% (95% CI, 66-100). In the control group, NPV was between 92% and 95% for the modified Screening Tool and also for the modified Screening Tool combined with low ferritin or a positive PBAC. CONCLUSION: These data in a racially diverse population suggest the usefulness of a simple, easy to administer modified Screening Tool. In conjunction with ferritin it could be used in a primary care setting to stratify reproductive age women with a family history of VWD for haemostatic evaluation.


Assuntos
Família , Doenças de von Willebrand/epidemiologia , Adolescente , Adulto , Testes de Coagulação Sanguínea , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Vigilância da População , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores Sexuais , Adulto Jovem , Doenças de von Willebrand/diagnóstico , Fator de von Willebrand
19.
Europace ; 19(suppl_4): iv10-iv16, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29220422

RESUMO

AIMS: Atrioventricular node ablation (AVNA) and right ventricular pacing (RVP) are effective therapies for patients with atrial fibrillation (AF) and rapid ventricular rates. His bundle pacing (HBP) is a physiologic alternative to RVP. The aim of our study is to assess the feasibility and safety of HBP in patients undergoing AVNA and its effect on left ventricular (LV) function. METHODS AND RESULTS: Permanent HBP is the preferred form of ventricular pacing at our institute. Atrioventricular node ablation and HBP were performed in patients with AF and difficulty in rate control. His bundle pacing implant characteristics and thresholds were recorded. Fluoroscopic relationship of AVNA site to HBP lead electrodes was documented. Left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) functional class at baseline and during follow-up were assessed. Forty-two patients underwent HBP and AVNA: age 74 ± 11 years; men 45%; HTN 64%; DM 19%; CAD 36%; permanent AF 40%; cardiomyopathy 55%. His bundle pacing was successful in 40 of 42 patients (95%). Successful AVNA site was at or below the ring electrode in 22 (no acute change in HBP threshold); above the ring electrode in 13 and left side in 2 pts (acute increase in HBP threshold in 7 of 15 pts). Final HBP threshold at implant was 1 ± 0.8 V@1 ms and increased to 1.6 ± 1.2 V@1 ms during a mean follow-up of 19 ± 14 months. Left ventricular ejection fraction increased from 43 ± 13% to 50 ± 11% (P = 0.01). New York Heart Association functional status improved from 2.5 ± 0.5 to 1.9 ± 0.5 (P = 0.04). CONCLUSION: Atrioventricular node ablation and HBP were successful in 95% of patients. His bundle pacing lead characteristics remained relatively stable. Left ventricular ejection fraction improved significantly during follow-up. His bundle pacing is feasible, safe and effective in pts undergoing AVNA.


Assuntos
Fibrilação Atrial/terapia , Nó Atrioventricular/cirurgia , Fascículo Atrioventricular/fisiopatologia , Estimulação Cardíaca Artificial/métodos , Ablação por Cateter/métodos , Potenciais de Ação , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Nó Atrioventricular/fisiopatologia , Estimulação Cardíaca Artificial/efeitos adversos , Ablação por Cateter/efeitos adversos , Ecocardiografia , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Estudos de Viabilidade , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda
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