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1.
Eur J Radiol ; 175: 111426, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38493558

RESUMO

PURPOSE: We aimed to identify the optimal reconstruction settings based on qualitative and quantitative image quality parameters on standard and ultra-high resolution (UHR) images using photon-counting CT (PCCT). METHOD: We analysed 45 patients, 29 with standard and 16 with UHR acquisition, applying both smoother and sharper kernel settings. Coronary CT angiography images were performed on a dual-source PCCT system using standard (0.4/0.6 mm slice thickness, Bv40/Bv44 kernels, QIR levels 0-4) or UHR acquisition (0.2/0.4 mm slice thickness, Bv44/Bv56 kernels, QIR levels 0-4). Qualitative image quality was assessed using a 4-point Likert scale. Image noise (SD), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated in both the proximal and distal segments. RESULTS: On standard resolution, larger slice thickness resulted in an average increase of 12.5 % in CNR, whereas sharper kernel led to an average 8.7 % decrease in CNR. Highest CNR was measured on 0.6 mm, Bv40, QIR4 images and lowest on 0.4 mm, Bv44, QIR0 images: 25.8 ± 4.1vs.8.3 ± 1.6 (p < 0.001). On UHR images, highest CNR was observed on 0.4 mm, Bv40, QIR4 and lowest on 0.2 mm, Bv56 and QIR0 images: 21.5 ± 3.9vs.3.6 ± 0.8 (p < 0.001). Highest qualitative image quality was found on images with Bv44 kernel and QIR level 3/4 with both slice thicknesses on standard reconstruction. Additionally, Bv56 with QIR4 on 0.2 mm slice thickness images showed highest subjective image quality. Preserved distal vessel visualization was detected using QIR 2-4, Bv56 and 0.2 mm slice thickness. CONCLUSIONS: Photon-counting CT demonstrated high qualitative and quantitative image quality for the assessment of coronaries and stents.


Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Fótons , Humanos , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Razão Sinal-Ruído , Doença da Artéria Coronariana/diagnóstico por imagem , Reprodutibilidade dos Testes , Adulto
2.
Heliyon ; 10(1): e23201, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38163124

RESUMO

Chitosan nanocoatings (thickness range of 120-540 nm) were produced on glass, zinc and silicon substrates with dip-coating and spin coating techniques to study their pH-dependent wetting and swelling behaviour. The coatings were N-acetylated with the methanolic solution of acetic anhydride to increase the degree of acetylation from 36 % to 100 % (according to ATR-FTIR studies). The measured contact angles of Britton-Robinson (BR) buffer solutions (pH 6.0, 7.4 and 9.0) were lower on the acetylated surfaces (ca. 50°), than that of their native counterparts (ca. 70°) and does not depend on the pH. Contrary, contact angles on the native coating deteriorated 10°-15° with increasing the pH. In addition, for native coatings, the decrease of the contact angles over time also showed a pH dependence: at pH 9.0 the contact angle decreased by 7° in 10 min, while at pH 6.0 it decreased by 13° and at a much faster rate. The constraint swelling of the coatings in BR puffer solutions was studied in situ by scanning angle reflectometry. The swelling degree of the native coatings increased significantly with decreasing pH (from 250 % to 500 %) due to the increased number of protonated amino groups, while the swelling degree of acetylated coatings was ca. 160 % regardless of the pH. The barrier properties of the coatings were studied by electrochemical tests on zinc substrates. The analysis of polarization curves showed the more permeable character of the acetylated coatings despite the non-polar character of the bulk coating matrix. It can be concluded that in the case of native coatings, 49 % of the absorbed water is in bound form, which does not assist ion transport, while in the case of acetylated coatings, this value is only 33 %.

3.
J Cardiovasc Comput Tomogr ; 18(1): 69-74, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38097408

RESUMO

BACKGROUND: We sought to compare the degree of maximal stenosis and the rate of invasive coronary angiography (ICA) recommendations in patients who underwent coronary CT angiography (CCTA) with photon-counting detector CT (PCD-CT) versus those who underwent CCTA with whole heart coverage energy-integrating detector CT (EID-CT). METHODS: In our retrospective single-center study, we included consecutive patients with suspected CAD who underwent CCTA performed with either PCD-CT or a 280-slice EID-CT. The degree of coronary stenosis was classified as no CAD, minimal (1-24 â€‹%), mild (25-49 â€‹%), moderate (50-69 â€‹%), severe stenosis (70-99 â€‹%), or occlusion. RESULTS: A total of 812 consecutive patients were included in the analysis, 401 patients scanned with EID-CT and 411 patients with PCD-CT (mean age: 58.4 â€‹± â€‹12.4 years, 45.4 â€‹% female). Despite the higher total coronary artery calcium score (CACS) in the PCD-CT group (10 [interquartile range (IQR) â€‹= â€‹0-152.8] vs 1 [IQR â€‹= â€‹0-94], p â€‹< â€‹0.001), obstructive CAD was more frequently reported in the EID-CT vs PCD-CT group (no CAD: 28.7 â€‹% vs 26.0 â€‹%, minimal: 23.2 â€‹% vs 30.9 â€‹%, mild: 19.7 â€‹% vs 23.4 â€‹%, moderate: 14.5 â€‹% vs 9.7 â€‹%, severe: 11.5 â€‹% vs 8.5 â€‹% and occlusion: 2.5 â€‹% vs 1.5 â€‹%, respectively, p â€‹= â€‹0.025). EID-CT was independently associated with downstream ICA (OR â€‹= â€‹2.76 [95%CI â€‹= â€‹1.58-4.97] p â€‹< â€‹0.001) in the overall patient population, in patients with CACS<400 (OR â€‹= â€‹2.18 [95%CI â€‹= â€‹1.13-4.39] p â€‹= â€‹0.024) and in patients with CACS≥400 (OR â€‹= â€‹3.83 [95%CI â€‹= â€‹1.42-11.05] p â€‹= â€‹0.010). CONCLUSION: In patients who underwent CCTA with PCD-CT the number of subsequent ICAs was lower as compared to patients who were scanned with EID-CT. This difference was greater in patients with extensive coronary calcification.


Assuntos
Angiografia por Tomografia Computadorizada , Tomografia Computadorizada por Raios X , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Angiografia Coronária , Estudos Retrospectivos , Constrição Patológica , Estudos Prospectivos , Valor Preditivo dos Testes , Encaminhamento e Consulta , Imagens de Fantasmas
4.
Pharmaceuticals (Basel) ; 16(7)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37513923

RESUMO

The exact incidence of cancer-associated venous thromboembolism (CA-VTE) in patients with oral and facial cancer (OFC) is not exactly known, and this risk is empirically considered to be low. However, this suggestion may result in disease underdiagnosis, prolong the initiation of adequate therapy, and consecutively increase CA-VTE-related morbidity and mortality. In addition, there might be specific clinical problems in the treatment of CA-VTE in patients with oral and facial cancer, such as swallowing difficulties, that might limit the possibilities of oral anticoagulation. Finally, there are limited data regarding the optimal treatment of CA-VTE in patients with oral and facial cancer, and this includes data on novel therapeutic strategies, including the use of direct oral anticoagulants. This article reviews current data on the optimal treatment strategy for CA-VTE in patients with OFC.

5.
Heliyon ; 9(3): e14440, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36967904

RESUMO

The action potential forms the basis of cardiac pacemaking, conduction, and contraction. Action potentials can be recorded from numerous preparation types, including ventricular or atrial trabecules, Purkinje fibers, isolated cardiac myocytes. Numerous techniques are also available as well, such as the conventional microelectrode and the single-cell current clamp techniques, optical mapping, or in silico modeling. With such a vast array of electrophysiological methods comes an array of available hardware and software solutions. In this work, we present a software with an intuitive graphical user interface, ActionPytential, that enables the analysis of any type of cardiac action potential, regardless of acquisition method or tissue type. In most available software tools, the analysis of continuous (gap-free) recordings often requires manual user interaction to segment the individual action potentials. We provide an automated solution for this, both for slow-response and for externally paced action potentials. As of now, ActionPytential calculates 34 parameters from each action potential. The most often utilized ones, including amplitude, maximal rate of depolarization, and action potential duration values, were validated on 1200 action potentials from human, dog, rabbit, guinea pig, and rat cardiac preparations. We also provide new parameters that were previously only measurable manually, including the position and the depth of the notch in potentials showing a spike-and-dome morphology. Further notable features include a Butterworth-type low-pass filter, the averaging of multiple potentials, automated corrections for baseline drifting, aided manual analysis, high-quality plots, and batch processing for any number of potentials. ActionPytential is available for all major platforms (Windows, MacOS, GNU + Linux, BSD).

6.
Elife ; 122023 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-36815557

RESUMO

The health benefits of regular physical exercise are well known. Even so, there is increasing evidence that the exercise regimes of elite athletes can evoke cardiac arrhythmias including ventricular fibrillation and even sudden cardiac death (SCD). The mechanism of exercise-induced arrhythmia and SCD is poorly understood. Here, we show that chronic training in a canine model (12 sedentary and 12 trained dogs) that mimics the regime of elite athletes induces electrophysiological remodeling (measured by ECG, patch-clamp, and immunocytochemical techniques) resulting in increases of both the trigger and the substrate for ventricular arrhythmias. Thus, 4 months sustained training lengthened ventricular repolarization (QTc: 237.1±3.4 ms vs. 213.6±2.8 ms, n=12; APD90: 472.8±29.6 ms vs. 370.1±32.7 ms, n=29 vs. 25), decreased transient outward potassium current (6.4±0.5 pA/pF vs. 8.8±0.9 pA/pF at 50 mV, n=54 vs. 42), and increased the short-term variability of repolarization (29.5±3.8 ms vs. 17.5±4.0 ms, n=27 vs. 18). Left ventricular fibrosis and HCN4 protein expression were also enhanced. These changes were associated with enhanced ectopic activity (number of escape beats from 0/hr to 29.7±20.3/hr) in vivo and arrhythmia susceptibility (elicited ventricular fibrillation: 3 of 10 sedentary dogs vs. 6 of 10 trained dogs). Our findings provide in vivo, cellular electrophysiological and molecular biological evidence for the enhanced susceptibility to ventricular arrhythmia in an experimental large animal model of endurance training.


Assuntos
Arritmias Cardíacas , Fibrilação Ventricular , Cães , Animais , Morte Súbita Cardíaca , Ventrículos do Coração , Modelos Animais
7.
Int J Biol Macromol ; 232: 123336, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-36708905

RESUMO

Chitosan coatings of 353 ± 12 nm thickness were prepared on glass and zinc substrates by dip-coating method to study their barrier-behaviour. The coatings were chemically modified to increase their degree of acetylation (DA) from ca. 44 % up to ca. 98 % resulting a quasi-chitin coating. The effect of the acetylation reaction was studied by infrared spectroscopy, and the structural changes of the native and acetylated coatings were investigated by UV-Vis spectrophotometry and X-ray diffraction. The surface properties of the coated samples were characterized by wettability measurements - advancing water contact angle decreased from ca. 80° (native) to ca. 43° (fully acetylated) - and microscopic (SEM, AFM) studies. The barrier behaviour of the chitosan layer depending on the DA was evaluated by electrochemical impedance spectroscopy studies and with a special mesoporous silica - chitosan bilayer system by measuring the amount of dye (Rhodamine 6G) accumulated in the silica through the chitosan coating during an impregnation step. These methods showed significant decrease in the barrier-effect of the coatings with increasing DA (accumulation of approximately six times more dye and a reduction of charge transfer resistance by an order of magnitude), due to the structural and ionization changes in the coatings.


Assuntos
Quitosana , Quitosana/química , Quitina/química , Água , Propriedades de Superfície , Dióxido de Silício , Materiais Revestidos Biocompatíveis/química
8.
Sci Rep ; 12(1): 21830, 2022 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-36528651

RESUMO

Sinus node (SN) pacemaking is based on a coupling between surface membrane ion-channels and intracellular Ca2+-handling. The fundamental role of the inward Na+/Ca2+ exchanger (NCX) is firmly established. However, little is known about the reverse mode exchange. A simulation study attributed important role to reverse NCX activity, however experimental evidence is still missing. Whole-cell and perforated patch-clamp experiments were performed on rabbit SN cells supplemented with fluorescent Ca2+-tracking. We established 2 and 8 mM pipette NaCl groups to suppress and enable reverse NCX. NCX was assessed by specific block with 1 µM ORM-10962. Mechanistic simulations were performed by Maltsev-Lakatta minimal computational SN model. Active reverse NCX resulted in larger Ca2+-transient amplitude with larger SR Ca2+-content. Spontaneous action potential (AP) frequency increased with 8 mM NaCl. When reverse NCX was facilitated by 1 µM strophantin the Ca2+i and spontaneous rate increased. ORM-10962 applied prior to strophantin prevented Ca2+i and AP cycle change. Computational simulations indicated gradually increasing reverse NCX current, Ca2+i and heart rate with increasing Na+i. Our results provide further evidence for the role of reverse NCX in SN pacemaking. The reverse NCX activity may provide additional Ca2+-influx that could increase SR Ca2+-content, which consequently leads to enhanced pacemaking activity.


Assuntos
Nó Sinoatrial , Trocador de Sódio e Cálcio , Animais , Coelhos , Nó Sinoatrial/metabolismo , Cloreto de Sódio , Miócitos Cardíacos/metabolismo , Cálcio/metabolismo
9.
Int J Mol Sci ; 23(23)2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36498977

RESUMO

Life-long stable heart function requires a critical balance of intracellular Ca2+. Several ion channels and pumps cooperate in a complex machinery that controls the influx, release, and efflux of Ca2+. Probably one of the most interesting and most complex players of this crosstalk is the Na+/Ca2+ exchanger, which represents the main Ca2+ efflux mechanism; however, under some circumstances, it can also bring Ca2+ into the cell. Therefore, the inhibition of the Na+/Ca2+ exchanger has emerged as one of the most promising possible pharmacological targets to increase Ca2+ levels, to decrease arrhythmogenic depolarizations, and to reduce excessive Ca2+ influx. In line with this, as a response to increasing demand, several more or less selective Na+/Ca2+ exchanger inhibitor compounds have been developed. In the past 20 years, several results have been published regarding the effect of Na+/Ca2+ exchanger inhibition under various circumstances, e.g., species, inhibitor compounds, and experimental conditions; however, the results are often controversial. Does selective Na+/Ca2+ exchanger inhibition have any future in clinical pharmacological practice? In this review, the experimental results of Na+/Ca2+ exchanger inhibition are summarized focusing on the data obtained by novel highly selective inhibitors.


Assuntos
Antiarrítmicos , Trocador de Sódio e Cálcio , Humanos , Trocador de Sódio e Cálcio/metabolismo , Antiarrítmicos/farmacologia , Canais Iônicos/metabolismo , Arritmias Cardíacas/tratamento farmacológico , Transporte Biológico/fisiologia , Cálcio/metabolismo
10.
BJR Open ; 4(1): 20220016, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36452055

RESUMO

Objective: We aimed to assess the differences in the severity and chest-CT radiomorphological signs of SARS-CoV-2 B.1.1.7 and non-B.1.1.7 variants. Methods: We collected clinical data of consecutive patients with laboratory-confirmed COVID-19 and chest-CT imaging who were admitted to the Emergency Department between September 1- November 13, 2020 (non-B.1.1.7 cases) and March 1-March 18, 2021 (B.1.1.7 cases). We also examined the differences in the severity and radiomorphological features associated with COVID-19 pneumonia. Total pneumonia burden (%), mean attenuation of ground-glass opacities and consolidation were quantified using deep-learning research software. Results: The final population comprised 500 B.1.1.7 and 500 non-B.1.1.7 cases. Patients with B.1.1.7 infection were younger (58.5 ± 15.6 vs 64.8 ± 17.3; p < .001) and had less comorbidities. Total pneumonia burden was higher in the B.1.1.7 patient group (16.1% [interquartile range (IQR):6.0-34.2%] vs 6.6% [IQR:1.2-18.3%]; p < .001). In the age-specific analysis, in patients <60 years B.1.1.7 pneumonia had increased consolidation burden (0.1% [IQR:0.0-0.7%] vs 0.1% [IQR:0.0-0.2%]; p < .001), and severe COVID-19 was more prevalent (11.5% vs 4.9%; p = .032). Mortality rate was similar in all age groups. Conclusion: Despite B.1.1.7 patients were younger and had fewer comorbidities, they experienced more severe disease than non-B.1.1.7 patients, however, the risk of death was the same between the two groups. Advances in knowledge: Our study provides data on deep-learning based quantitative lung lesion burden and clinical outcomes of patients infected by B.1.1.7 VOC. Our findings might serve as a model for later investigations, as new variants are emerging across the globe.

11.
Geroscience ; 44(5): 2361-2369, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35864376

RESUMO

It is well accepted that COVID-19-related mortality shows a strong age dependency. However, temporal changes in the age distribution of excess relative mortality between waves of the pandemic are less frequently investigated. We aimed to assess excess absolute mortality and the age-distribution of all-cause mortality during the second and third waves of the COVID-19 pandemic in Hungary compared to the same periods of non-pandemic years. Rate ratios for excess all-cause mortality with 95% confidence intervals and the number of excess deaths for the second (week 41 of 2020 through week 4 of 2021) and third waves (weeks 7-21 of 2021) of the COVID pandemic for the whole of Hungary compared to the same periods of the pre-pandemic years were estimated for 10-year age strata using Poisson regression. Altogether, 9771 (95% CI: 9554-9988) excess deaths were recorded during the second wave of the pandemic, while it was lower, 8143 (95% CI: 7953-8333) during the third wave. During the second wave, relative mortality peaked for ages 65-74 and 75-84 (RR 1.37, 95%CI 1.33-1.41, RR 1.38, 95%CI 1.34-1.42). Conversely, during the third wave, relative mortality peaked for ages 35-44 (RR 1.43, 95%CI 1.33-1.55), while those ≥65 had substantially lower relative risks compared to the second wave. The reduced relative mortality among the elderly during the third wave is likely a consequence of the rapidly increasing vaccination coverage of the elderly coinciding with the third wave. The hugely increased relative mortality of those 35-44 could point to non-biological causes, such as less stringent adherence to non-pharmaceutical measures in this population.


Assuntos
COVID-19 , Humanos , Idoso , SARS-CoV-2 , Pandemias , Hungria/epidemiologia , Risco
12.
Langmuir ; 38(19): 6201-6208, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35523001

RESUMO

The capillary bridge probe method was introduced previously as a high-accuracy contact angle determination method relying on capillary bridges on hydrophilic and superhydrophilic surfaces [Nagy, N. Langmuir 2019, 35 (15), 5202-5212]. In this work, the behavior of r-ϑ type liquid bridges was studied and the contact angles were determined on hydrophobic surfaces. The equilibrium shape of these liquid bridges often does not contain the neck or haunch region. The unknown neck/haunch radius prevents analytical evaluation of the capillary bridge shape. In this work, the possible incomplete liquid bridge shapes were classified and a novel procedure was developed for the Delaunay's analytical solution-based evaluation of these states. The parameter space of the capillary bridges was visualized and described without using dimensionless variables. As a demonstration, Cyclo Olefin Polymer and PTFE surfaces were investigated, with advancing and receding contact angles determined and compared to the results of sessile drop measurements.

13.
Can J Physiol Pharmacol ; 100(9): 880-889, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35442802

RESUMO

Even though rodents are accessible model animals, their electrophysiological properties are deeply different from those of humans, making the translation of rat studies to humans rather difficult. We compared the mechanisms of ventricular repolarization in various animal models to those of humans by measuring cardiac ventricular action potentials from ventricular papillary muscle preparations using conventional microelectrodes and applying selective inhibitors of various potassium transmembrane ion currents. Inhibition of the IK1 current (10 µmol/L barium chloride) significantly prolonged rat ventricular repolarization, but only slightly prolonged it in dogs, and did not affect it in humans. On the contrary, IKr inhibition (50 nmol/L dofetilide) significantly prolonged repolarization in humans, rabbits, and dogs, but not in rats. Inhibition of the IKur current (1 µmol/L XEN-D0101) only prolonged rat ventricular repolarization and had no effect in humans or dogs. Inhibition of the IKs (500 nmol/L HMR-1556) and Ito currents (100 µmol/L chromanol-293B) elicited similar effects in all investigated species. We conclude that dog ventricular preparations have the strongest translational value and rat ventricular preparations have the weakest translational value in cardiac electrophysiological experiments.


Assuntos
Canais de Potássio , Potássio , Potenciais de Ação , Animais , Cães , Coração/fisiologia , Ventrículos do Coração , Humanos , Miocárdio/metabolismo , Potássio/metabolismo , Coelhos , Ratos
14.
Pharmaceuticals (Basel) ; 15(3)2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35337111

RESUMO

Sinus pacemaking is based on tight cooperation of intracellular Ca2+ handling and surface membrane ion channels. An important player of this synergistic crosstalk could be the small-conductance Ca2+-activated K+-channel (ISK) that could contribute to the sinoatrial node (SAN) pacemaking driven by the intracellular Ca2+ changes under normal conditions and beta-adrenergic activation, however, the exact role is not fully clarified. SK2 channel expression was verified by immunoblot technique in rabbit SAN cells. Ionic currents and action potentials were measured by patch-clamp technique. The ECG R-R intervals were obtained by Langendorff-perfusion method on a rabbit heart. Apamin, a selective inhibitor of SK channels, was used during the experiments. Patch-clamp experiments revealed an apamin-sensitive current. When 100 nM apamin was applied, we found no change in the action potential nor in the ECG R-R interval. In experiments where isoproterenol was employed, apamin increased the cycle length of the SAN action potentials and enhanced the ECG R-R interval. Apamin did not amplify the cycle length variability or ECG R-R interval variability. Our data indicate that ISK has no role under normal condition, however, it moderately contributes to the SAN automaticity under beta-adrenergic activation.

15.
Biomedicines ; 10(2)2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35203454

RESUMO

Vagal nerve stimulation (VNS) has a meaningful basis as a potentially effective treatment for heart failure with reduced ejection fraction. There is an ongoing VNS randomized study, and four studies are completed. However, relatively little is known about the effect of acetylcholine (ACh) on repolarization in human ventricular cardiomyocytes, as well as the effect of ACh on the rapid component of the delayed rectifier K+ current (IKr). Here, we investigated the effect of ACh on the action potential parameters in human ventricular preparations and on IKr in human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). Using standard microelectrode technique, we demonstrated that ACh (5 µM) significantly increased the action potential duration in human left ventricular myocardial slices. ACh (5 µM) also prolonged repolarization in a human Purkinje fiber and a papillary muscle. Optical mapping revealed that ACh increased the action potential duration in human left ventricular myocardial slices and that the effect was dose-dependent. Perforated patch clamp experiments demonstrated action potential prolongation and a significant decrease in IKr by ACh (5 µM) in hiPSC-CMs. Computer simulations of the electrical activity of a human ventricular cardiomyocyte showed an increase in action potential duration upon implementation of the experimentally observed ACh-induced changes in the fully activated conductance and steady-state activation of IKr. Our findings support the hypothesis that ACh can influence the repolarization in human ventricular cardiomyocytes by at least changes in IKr.

16.
Br J Pharmacol ; 179(13): 3382-3402, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35106755

RESUMO

BACKGROUND AND PURPOSE: The aim of the present study was to study the antiarrhythmic effects and cellular mechanisms of desethylamiodarone (DEA), the main metabolite of amiodarone (AMIO), following acute and chronic 4-week oral treatments (25-50 mg·kg-1 ·day-1 ). EXPERIMENTAL APPROACH: The antiarrhythmic effects of acute iv. (10 mg·kg-1 ) and chronic oral (4 weeks, 25 mg·kg-1 ·day-1 ) administration of DEA were assessed in carbachol and tachypacing-induced dog atrial fibrillation models. Action potentials were recorded from atrial and right ventricular tissue following acute (10 µM) and chronic (p.o. 4 weeks, 50 mg·kg-1 ·day-1 ) DEA application using the conventional microelectrode technique. Ionic currents were measured by the whole cell configuration of the patch clamp technique in isolated left ventricular myocytes. Pharmacokinetic studies were performed following a single intravenous dose (25 mg·kg-1 ) of AMIO and DEA intravenously and orally. In chronic (91-day) toxicological investigations, DEA and AMIO were administered in the oral dose of 25 mg·kg-1 ·day-1 ). KEY RESULTS: DEA exerted marked antiarrhythmic effects in both canine atrial fibrillation models. Both acute and chronic DEA administration prolonged action potential duration in atrial and ventricular muscle without any changes detected in Purkinje fibres. DEA decreased the amplitude of several outward potassium currents such as IKr , IKs , IK1 , Ito , and IKACh , while the ICaL and late INa inward currents were also significantly depressed. Better drug bioavailability and higher volume of distribution for DEA were observed compared to AMIO. No neutropenia and less severe pulmonary fibrosis was found following DEA compared to that of AMIO administration. CONCLUSION AND IMPLICATIONS: Chronic DEA treatment in animal experiments has marked antiarrhythmic and electrophysiological effects with better pharmacokinetics and lower toxicity than its parent compound. These results suggest that the active metabolite, DEA, should be considered for clinical trials as a possible new, more favourable option for the treatment of cardiac arrhythmias including atrial fibrillation.


Assuntos
Amiodarona , Fibrilação Atrial , Potenciais de Ação , Amiodarona/análogos & derivados , Amiodarona/farmacologia , Animais , Antiarrítmicos/farmacologia , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/metabolismo , Cães , Átrios do Coração , Miócitos Cardíacos
17.
Br J Radiol ; 95(1129): 20210759, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34889645

RESUMO

OBJECTIVE: To determine the diagnostic accuracy of a deep-learning (DL)-based algorithm using chest computed tomography (CT) scans for the rapid diagnosis of coronavirus disease 2019 (COVID-19), as compared to the reference standard reverse-transcription polymerase chain reaction (RT-PCR) test. METHODS: In this retrospective analysis, data of COVID-19 suspected patients who underwent RT-PCR and chest CT examination for the diagnosis of COVID-19 were assessed. By quantifying the affected area of the lung parenchyma, severity score was evaluated for each lobe of the lung with the DL-based algorithm. The diagnosis was based on the total lung severity score ranging from 0 to 25. The data were randomly split into a 40% training set and a 60% test set. Optimal cut-off value was determined using Youden-index method on the training cohort. RESULTS: A total of 1259 patients were enrolled in this study. The prevalence of RT-PCR positivity in the overall investigated period was 51.5%. As compared to RT-PCR, sensitivity, specificity, positive predictive value, negative predictive value and accuracy on the test cohort were 39.0%, 80.2%, 68.0%, 55.0% and 58.9%, respectively. Regarding the whole data set, when adding those with positive RT-PCR test at any time during hospital stay or "COVID-19 without virus detection", as final diagnosis to the true positive cases, specificity increased from 80.3% to 88.1% and the positive predictive value increased from 68.4% to 81.7%. CONCLUSION: DL-based CT severity score was found to have a good specificity and positive predictive value, as compared to RT-PCR. This standardized scoring system can aid rapid diagnosis and clinical decision making. ADVANCES IN KNOWLEDGE: DL-based CT severity score can detect COVID-19-related lung alterations even at early stages, when RT-PCR is not yet positive.


Assuntos
COVID-19/diagnóstico por imagem , Aprendizado Profundo , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/patologia , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Radiografia Torácica , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
18.
Tomography ; 7(4): 697-710, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34842822

RESUMO

We sought to analyze the prognostic value of laboratory and clinical data, and an artificial intelligence (AI)-based algorithm for Coronavirus disease 2019 (COVID-19) severity scoring, on CT-scans of patients hospitalized with COVID-19. Moreover, we aimed to determine personalized probabilities of clinical deterioration. Data of symptomatic patients with COVID-19 who underwent chest-CT-examination at the time of hospital admission between April and November 2020 were analyzed. COVID-19 severity score was automatically quantified for each pulmonary lobe as the percentage of affected lung parenchyma with the AI-based algorithm. Clinical deterioration was defined as a composite of admission to the intensive care unit, need for invasive mechanical ventilation, use of vasopressors or in-hospital mortality. In total 326 consecutive patients were included in the analysis (mean age 66.7 ± 15.3 years, 52.1% male) of whom 85 (26.1%) experienced clinical deterioration. In the multivariable regression analysis prior myocardial infarction (OR = 2.81, 95% CI = 1.12-7.04, p = 0.027), immunodeficiency (OR = 2.08, 95% CI = 1.02-4.25, p = 0.043), C-reactive protein (OR = 1.73, 95% CI = 1.32-2.33, p < 0.001) and AI-based COVID-19 severity score (OR = 1.08; 95% CI = 1.02-1.15, p = 0.013) appeared to be independent predictors of clinical deterioration. Personalized probability values were determined. AI-based COVID-19 severity score assessed at hospital admission can provide additional information about the prognosis of COVID-19, possibly serving as a useful tool for individualized risk-stratification.


Assuntos
COVID-19 , Pneumonia , Idoso , Idoso de 80 Anos ou mais , Inteligência Artificial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico por imagem , SARS-CoV-2 , Tomografia Computadorizada por Raios X
19.
Can J Physiol Pharmacol ; 99(11): 1159-1174, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34636643

RESUMO

In clinical trials of heart failure reduced ejection fraction (HFrEF), ivabradine seemed to be an effective heart rate lowering agent associated with lower risk of cardiovascular death. In contrast, ivabradine failed to improve cardiovascular outcomes in heart failure preserved ejection fraction (HFpEF) despite the significant effect on heart rate. This meta-analysis is the first to compare the effects of ivabradine on heart rate and mortality parameters in HFpEF versus HFrEF. We screened three databases: PubMed, Embase, and Cochrane Library. The outcomes of these studies were mortality, reduction in heart rate, and left ventricular function improvement. We compared the efficacy of ivabradine treatment in HFpEF versus HFrEF. Heart rate analysis of pooled data showed decrease in both HFrEF (-17.646 beats/min) and HFpEF (-11.434 beats/min), and a tendency to have stronger bradycardic effect in HFrEF (p = 0.094) in randomized clinical trials. Left ventricular ejection fraction analysis revealed significant improvement in HFrEF (5.936, 95% CI: [4.199-7.672], p < 0.001) when compared with placebo (p < 0.001). We found that ivabradine significantly improves left ventricular performance in HFrEF, at the same time it exerts a tendency to have improved bradycardic effect in HFrEF. These disparate effects of ivabradine and the higher prevalence of non-cardiac comorbidities in HFpEF may explain the observed beneficial effects in HFrEF and the unchanged outcomes in HFpEF patients after ivabradine treatment.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Ivabradina/farmacologia , Ivabradina/uso terapêutico , Volume Sistólico , Função Ventricular Esquerda , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/mortalidade , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
20.
Nanomaterials (Basel) ; 11(9)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34578555

RESUMO

Nanostructured photoactive systems are promising for applications such as air and water purification, including self-cleaning coatings. In this study, mesoporous TiO2 sol-gel coatings with different pore structures were prepared and modified with silver by two methods: the "mixing" method by adding AgNO3 to the precursor sol, and the "impregnation" method by immersing the samples in AgNO3 solution (0.03 and 1 M) followed by heat treatment. Our aim was to investigate the effects that silver modification has on the functional properties (e.g., those that are important for self-cleaning coatings). Transmittance, band gap energy, refractive index, porosity and thickness values were determined from UV-Vis spectroscopy measurements. Silver content and structure of the silver modified samples were characterized by X-ray photoelectron spectroscopy, Rutherford backscattering spectrometry, High-resolution transmission electron microscopy and Energy Dispersive X-ray Spectrometry elemental mapping measurements. Wettability properties, including photoinduced wettability conversion behavior were investigated by water contact angle measurements. Photoactivity was studied under both UV and visible light with rhodamine 6G and methylene blue dye molecules, at the liquid-solid and air-solid interfaces modeling the operating conditions of self-cleaning coatings. Samples made with "impregnation" method showed better functional properties, in spite of their significantly lower silver content. The pore structure influenced the Ag content achieved by the "impregnation" method, and consequently affected their photoactivity.

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