215 research outputs found
The cellular uptake of meta-tetra(hydroxyphenyl) chlorin entrapped in organically modified silica nanoparticles is mediated by serum proteins.
Nanosized objects made of various materials are gaining increasing attention as promising vehicles for the delivery of therapeutic and diagnostic agents for cancer. Photodynamic therapy (PDT) appears to offer a very attractive opportunity to implement drug delivery systems since no release of the sensitizer is needed to obtain the therapeutic effect and the design of the nanovehicle should be much easier. The aim of our study was to investigate the use of organic-modified silica nanoparticles (NPs) for the delivery of the second-generation photosensitizer meta-tetra(hydroxyphenyl) chlorin (mTHPC) to cancer cells in vitro. mTHPC was entrapped in NPs (similar to 33 nm diameter) in a monomeric form which produced singlet oxygen with a high efficiency. In aqueous media with high salt concentrations, the NPs underwent aggregation and precipitation but their stability could be preserved in the presence of foetal bovine serum. The cellular uptake, localization and phototoxic activity of mTHPC was determined comparatively in human oesophageal cancer cells after its delivery by the NPs and the standard solvent ethanol/poly(ethylene glycol) 400/water (20: 30: 50, by vol). The NP formulation reduced the cellular uptake of mTHPC by about 50% in comparison to standard solvent while it did not affect the concentration-dependent photokilling activity of mTHPC and its intracellular localization. Fluorescence resonance energy transfer measurements, using NPs with mTHPC physically entrapped and a cyanine covalently linked, and ultracentrifugation experiments indicated that mTHPC is transferred from NPs to serum proteins when present in the medium. However, the coating of the NP surface with poly(ethylene glycol) largely prevented the transfer to proteins. In conclusion, mTHPC is rapidly transferred from the uncoated nanoparticles to the serum proteins and then internalized by the cells as a protein complex, irrespective of its modality of delivery
Procoagulant properties of bare and highly-PEGylated vinyl-modified silica nanoparticles
The dynamics of moderate ischaemic mitral regurgitation (IMR) and left ventricular (LV) remodeling after isolated coronary artery bypass grafting (CABG) versus CABG and concomitant mitral valve repair (MVR)
Author: Aistė Jasinskaitė Scientific supervisor: prof. habil. dr. J. J. Vaškelytė Title: The dynamics of moderate ischaemic mitral regurgitation (IMR) and left ventricular (LV) remodeling after isolated coronary artery bypass grafting (CABG) versus CABG and concomitant mitral valve repair (MVR) The aim: To evaluate and compare the dynamics of moderate IMR and LV remodeling after isolated CABG versus CABG and concomitant MVR in one year period The objectives: 1. to evaluate the dynamics of moderate IMR and LV remodeling after isolated CABG, 2. to evaluate the dynamics of moderate IMR and LV remodeling after CABG and concomitant MVR 3. to compare the efficiecies of isolated CABG and combined operation for the dynamics of moderate IMR and LV remodeling. Methods and participants: It was a restrospective analysis of 43 pacients with moderate (I-IIº, IIº) IMR who were operated during the period of 2011-2016 years. The patients were divided into two groups: for 22 pacients was performed isolated CABG and for 21 patient - CABG and concomitant MVP. The echocardiographic parameters of IMR mechanisms, grading and LV remodeling were analysed before and one year after the operations. Results: The statistically significant difference of IMR grade was observed between the groups before the operations (54.5% pacients of isolated CABG group had IMR of I-IIº, 90.5% patients of combined operation group had IMR of IIº). The echocardiographic parameters of LV were statistically significantly higher in combined operation group before the operations (the means of left ventricular end diastolic diameter (LVEDD) index in groups were: 30.3±5.4 mm/m2 and 25.7±3.1 mm/m2 respectively) (p<0.005). The means of effective regurgitant orifice (ERA) area before the operations were: 0.12±0.07 cm2 of isolated CABG and 0.24±0.12 cm2 of combined operation group (p=0.001). The statistically insignificant decrease in LV parameters one year after combined operation and no significant dynamics of LV remodeling one year after isolated CABG were observed (the means of LVEDD index were: 29.8±7.3 mm/m2 of combined operation group, 26.7±3.4 mm/m2 of isolated CABG group, p=0.094).The means of ERA after one year period were: 24±0.13 cm2 of isolated CABG group and 0.16±0.12 cm2 of combined operation group (p=0.548). 59.1% patients of isolated CABG group had IMR of IIº, while 90.5% patients of combined group had IMR of Iº one year after the operations. Conclusions: 1. No significant dynamic of LV remodeling was observed, the grade of IMR did not differ or became higher for the majority of patients of isolated CABG group, while the pulmonary artery acceleration time significantly decreased one year after isolated CABG. 2. The statistically insignificant decrease of LV parameters was observed, the grade of IMR significantly decreased to Iº for the majority of patients one year after CABG and concomitant MVR. 3. The combined operation was considered as more effective because it had a positive influence on LV remodeling, IMR grade, pulmonary hypertension comparing to isolated CABG
A doppler echocardiographic study of the myocardial inotropic response to peak semisupine exercise in healthy children: Development of a simplified index of myocardial reserve
Background
Stress echocardiography has been advocated for the detection of abnormal myocardial function and unmasking diminished myocardial reserve in pediatric patients. The aim of this study was to create a simplified index of myocardial reserve, derived from the myocardial inotropic response to peak semisupine exercise in healthy children, and illustrate its applicability in a sample of pediatric oncology patients.
Methods
In this prospective analysis, children (7–18 years of age) with normal cardiac structure and function performed semisupine stress echocardiography to volitional fatigue. The quotient of wall stress at peak systole and heart rate–corrected velocity of circumferential fiber shortening were calculated at baseline and at peak exercise, the difference of which was termed the index of myocardial reserve (IMR). The IMR was also calculated in a retrospective sample of pediatric oncology patients with normal resting left ventricular function who had received anthracycline treatment and had performed the same exercise protocol to illustrate utility.
Results
Fifty healthy subjects (mean age, 13.2 ± 2.6 years) and 33 oncology patients (mean age, 12.7 ± 4.0 years) were assessed. In the healthy children at peak exercise, heart rate–corrected velocity of circumferential fiber shortening significantly increased (from 1.17 ± 0.17 to 1.58 ± 0.24 circ · sec−1, P < .001), while the quotient of wall stress at peak systole significantly decreased (from 75.3 ± 17.1 to 55.3 ± 13.8 g · cm−2, P < .001), shifting the plot of the relationship between the two parameters upward and to the left. The mean IMR was −30.8 ± 17.8, and the normal distribution ranged from −4.7 (fifth percentile) to −67.3 (95th percentile). The IMR was abnormal in 10 oncology patients who were treated with anthracyclines.
Conclusions
The authors have developed a novel IMR. Relative to the normal distribution of this IMR in healthy subjects, it is possible to identify patients with abnormal myocardial reserve. Thus, this study demonstrates the application of the IMR to aid in clinical decision making in individual patients.Peer reviewedFinal article publishedStress echocardiographyMyocardial reserveHealthy childrenCardiac contractilityExercis
Biological databases and tools for neurological disorders
Publisher Copyright: © 2022 The Author(s). Published by IMR Press.Computational approaches to study of neuronal impairment is rapidly evolving, as experiments and intuition alone do not explain the complexity of the brain system. An overwhelming increase in the amount of new data from both theory and computational modeling necessitate the development of databases and tools for analysis, visualization and interpretation of neuroscience data. To ensure the sustainability of this development, consistent update and training of young professionals is imperative. For this purpose, relevant articles, chapters, and modules are essential to keep abreast of developments. This review seeks to outline the biological databases and analytical tools along with their applications. It is envisaged that such knowledge could provide a ''training recipe'' for young scientists and a guide for professionals and researchers in neuroscience.Peer reviewe
Coronary revascularization in patients with left ventricle systolic dysfunction, current challenges and clinical outcomes
Copyright: \ua9 2022 The Author(s). Published by IMR Press. This is an open access article under the CC BY 4.0 license. The effects of coronary revascularization in patients with left ventricle systolic dysfunction (LVSD) are not well studied. The decision about revascularization and its timing remain challenging, not only related to procedural risk, but also linked to other several limitations including assessment of ischemia, viability, and ability to predict LV recovery. The role of viability as a prognostic marker for patients with LVSD and its use as a therapeutic target remains debatable. In this article, we will review the role of LVSD in patients undergoing coronary revascularization alongside the role of ischemia and viability assessment. We will provide a review of the literature on the outcomes of coronary revascularization, both surgically and percutaneously, in patients with LVSD
LDL-C: An Important Independent Risk Factor for New-Onset Heart Block in Patients with Severe Aortic Stenosis and Heart Failure after TAVR
Transcatheter aortic valve replacement (TAVR) is an effective alternative treatment for patients with aortic stenosis (AS) who have intermediate to high surgical risk or who are inoperable. However, the incidence of conduction abnormalities is high after TAVR, which can reduce the effectiveness of the surgery. Our research objective is to explore the risk factors of new-onset conduction abnormalities after TAVR, providing reference value for clinical doctors to better prevent and treat conduction abnormalities. Patients who underwent TAVR were divided into those who developed heart block and those who did not. Baseline clinical characteristics, cardiac structural parameters, procedural characteristics, electrocardiogram (ECG) changes before and after TAVR ( = postoperative minus preoperative), and surgical complications were compared. Logistic regression was applied to identify significant risk factors for new-onset heart block. We studied 93 patients, of whom 34.4% developed heart blocks. Univariate logistic regression showed that prior history of malignancy, atrial fibrillation, preoperative high-level total cholesterol and low-density lipoprotein cholesterol (LDL-C), HR, QRS interval, QT interval, and QTc interval were risk factors of new-onset heart block after TAVR. Multivariate analysis showed that preoperative high-level LDL-C and QRS interval remained significant independent risk factors after adjusting for potential confounds. Heart block is the most common complication of TAVR, and its significant independent risk factors include high-level LDL-C and QRS interval. [Abstract copyright: Copyright: © 2023 The Author(s). Published by IMR Press.
LDL-C: An important independent risk factor for new-onset heart block in patients with severe aortic stenosis and heart failure after TAVR
Transcatheter aortic valve replacement (TAVR) is an effective alternative treatment for patients with aortic stenosis (AS) who have intermediate to high surgical risk or who are inoperable. However, the incidence of conduction abnormalities is high after TAVR, which can reduce the effectiveness of the surgery. Our research objective is to explore the risk factors of new-onset conduction abnormalities after TAVR, providing reference value for clinical doctors to better prevent and treat conduction abnormalities. Patients who underwent TAVR were divided into those who developed heart block and those who did not. Baseline clinical characteristics, cardiac structural parameters, procedural characteristics, electrocardiogram (ECG) changes before and after TAVR ( = postoperative minus preoperative), and surgical complications were compared. Logistic regression was applied to identify significant risk factors for new-onset heart block. We studied 93 patients, of whom 34.4% developed heart blocks. Univariate logistic regression showed that prior history of malignancy, atrial fibrillation, preoperative high-level total cholesterol and low-density lipoprotein cholesterol (LDL-C), HR, QRS interval, QT interval, and QTc interval were risk factors of new-onset heart block after TAVR. Multivariate analysis showed that preoperative high-level LDL-C and QRS interval remained significant independent risk factors after adjusting for potential confounds. Heart block is the most common complication of TAVR, and its significant independent risk factors include high-level LDL-C and QRS interval. [Abstract copyright: Copyright: © 2023 The Author(s). Published by IMR Press.
Endothelialcell dysfunction: onset, progression, and consequences
Endothelial cell dysfunction is a complex process involving various causes, early and late events, and subsequent consequences. This review provides an overview of each aspect and outlines therapeutic interventions targeting these stages. Causes of endothelial dysfunction encompass a spectrum of risk factors including hypertension, diabetes, smoking, obesity, inflammation, oxidative stress, and genetic predispositions. Early events such as endothelial activation, inflammatory response, and dysregulated vasomotor tone precede late events like oxidative stress, endothelial apoptosis, and microvascular rarefaction. The consequences include endothelial remodelling, neovascularization, organ dysfunction, and clinical manifestations, highlighting the diverse impacts across multiple systems. While depicted linearly, the progression of endothelial dysfunction is dynamic, influenced by various factors such as the underlying cause and affected vascular bed. Understanding these dynamics is crucial for tailoring therapeutic interventions, ranging from lifestyle modifications to targeted therapies, to address the underlying causes and effects effectively. Here we provide comprehensive understanding of endothelial cell dysfunction that is essential for developing strategies to mitigate the impact of this dysregulation on health and cardiovascular diseases progression. [Abstract copyright: © 2024 The Author(s). Published by IMR Press.
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