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1.
Ann Anat ; : 152261, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38521363

ABSTRACT

INTRODUCTION: The appearance of artificial intelligence language models (AI LMs) in the form of chatbots has gained a lot of popularity worldwide, potentially interfering with different aspects of education, including medical education as well. The present study aims to assess the accuracy and consistency of different AI LMs regarding the histology and embryology knowledge obtained during the 1st year of medical studies. METHODS: Five different chatbots (ChatGPT, Bing AI, Bard AI, Perplexity AI, and ChatSonic) were given two sets of multiple-choice questions (MCQs). AI LMs test results were compared to the same test results obtained from 1st year medical students. Chatbots were instructed to use revised Bloom's taxonomy when classifying questions depending on hierarchical cognitive domains. Simultaneously, two histology teachers independently rated the questions applying the same criteria, followed by the comparison between chatbots' and teachers' question classification. The consistency of chatbots' answers was explored by giving the chatbots the same tests two months apart. RESULTS: AI LMs successfully and correctly solved MCQs regarding histology and embryology material. All five chatbots showed better results than the 1st year medical students on both histology and embryology tests. Chatbots showed poor results when asked to classify the questions according to revised Bloom's cognitive taxonomy compared to teachers. There was an inverse correlation between the difficulty of questions and their correct classification by the chatbots. Retesting the chatbots after two months showed a lack of consistency concerning both MCQs answers and question classification according to revised Bloom's taxonomy learning stage. CONCLUSION: Despite the ability of certain chatbots to provide correct answers to the majority of diverse and heterogeneous questions, a lack of consistency in answers over time warrants their careful use as a medical education tool.

2.
Front Cardiovasc Med ; 10: 1181803, 2023.
Article in English | MEDLINE | ID: mdl-37346287

ABSTRACT

Assessment of the functional significance of coronary artery stenosis using invasive measurement of fractional flow reserve (FFR) or non-hyperemic indices has been shown to be safe and effective in making clinical decisions on whether to perform percutaneous coronary intervention (PCI). Despite strong evidence from clinical trials, utilization of these techniques is still relatively low worldwide. This may be to some extent attributed to factors that are inherent to invasive measurements like prolongation of the procedure, side effects of drugs that induce hyperemia, additional steps that the operator should perform, the possibility to damage the vessel with the wire, and additional costs. During the last few years, there was a growing interest in the non-invasive assessment of coronary artery lesions, which may provide interventionalist with important physiological information regarding lesion severity and overcome some of the limitations. Several dedicated software solutions are available on the market that could provide an estimation of FFR using 3D reconstruction of the interrogated vessel derived from two separated angiographic projections taken during diagnostic coronary angiography. Furthermore, some of them use data about aortic pressure and frame count to more accurately calculate pressure drop (and FFR). The ideal non-invasive system should be integrated into the workflow of the cath lab and performed online (during the diagnostic procedure), thereby not prolonging procedural time significantly, and giving the operator additional information like vessel size, lesion length, and possible post-PCI FFR value. Following the development of these technologies, they were all evaluated in clinical trials where good correlation and agreement with invasive FFR (considered the gold standard) were demonstrated. Currently, only one trial (FAVOR III China) with clinical outcomes was completed and demonstrated that QFR-guided PCI may provide better results at 1-year follow-up as compared to the angiography-guided approach. We are awaiting the results of a few other trials with clinical outcomes that test the performance of these indices in guiding PCI against either FFR or angiography-based approach, in various clinical settings. Herein we will present an overview of the currently available data, a critical review of the major clinical trials, and further directions of development for the five most widely available non-invasive indices: QFR, vFFR, FFRangio, caFFR, and AccuFFRangio.

3.
Int J Mol Sci ; 24(6)2023 Mar 22.
Article in English | MEDLINE | ID: mdl-36983086

ABSTRACT

The PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) enzyme interferes with the metabolism of low-density lipoprotein (LDL) cholesterol. Inhibition of PCSK9 results in lower LDL cholesterol levels, which can be achieved by different molecular pathways. Monoclonal antibodies targeting circulating PCSK9 have shown strong and persistent effects on lowering the LDL cholesterol level, while reducing the risk of future cardiovascular events. However, this therapy requires once- or twice-monthly administration in the form of subcutaneous injection. This dosing regimen might impact the therapy adherence in cardiovascular patients who often require multiple drugs with different dosing intervals. Small interfering ribonucleic acid (siRNA) represents a promising therapy approach for patients with elevated LDL cholesterol level despite optimized background statin therapy. Inclisiran is a synthesized siRNA which inhibits PCSK9 synthesis in the liver and provides sustained and durable lowering of LDL cholesterol with twice-yearly application and a good tolerability profile. Herein, we present an overview of the current available data and critical review of the major clinical trials which assessed safety and efficacy of inclisiran in different groups of patients with elevated LDL cholesterol level.


Subject(s)
Anticholesteremic Agents , Proprotein Convertase 9 , Humans , Proprotein Convertase 9/genetics , Proprotein Convertase 9/metabolism , Cholesterol, LDL , RNA, Small Interfering/therapeutic use , Anticholesteremic Agents/adverse effects
4.
Sci Total Environ ; 804: 150160, 2022 Jan 15.
Article in English | MEDLINE | ID: mdl-34798729

ABSTRACT

Along six transects in each of six lakes across the Western Balkans, we collected data for three groups of littoral biological water quality indicators: epilithic diatoms, macrophytes, and benthic invertebrates. We assessed the relationships between them and three environmental pressures: nutrient load (eutrophication), hydro-morphological alteration of the shoreline, and water level variation, separating the effect of individual lakes and continuous explanatory variables. Lake water total phosphorus concentration (TP) showed substantial variation but was not related to any of the tested biological indicators, nor to any of the tested pressures. We suggest that this may be due to feedback processes such as P removal in the lake littoral zone. Instead, we found that a gradient in surrounding land-use towards increasing urbanization, and a land-use-based estimate of P run-off, served as a better descriptor of eutrophication. Overall, eutrophication and water level fluctuation were most important for explaining variation in the assessed indicators, whereas shoreline hydro-morphological alteration was less important. Diatom indicators were most responsive to all three pressures, whereas macrophyte biomass and species number responded only to water level fluctuation. The Trophic Diatom Index for Lakes (TDIL) was negatively related to urbanization and wave exposure. This indicates that it is a suitable indicator for pressures related to urbanization, although a confounding effect of wave exposure is possible. Invertebrate abundance responded strongly to eutrophication, but the indicator based on taxonomic composition (Average Score Per Taxon) did not. Our results suggest that our metrics can be applied in Western Balkan lakes, despite the high number of endemic species present in some of these lakes. We argue that local water management should focus on abating the causes of eutrophication and water level fluctuation, whilst preserving sufficient lengths of undeveloped shoreline to ensure good water quality in the long run.


Subject(s)
Lakes , Water Quality , Balkan Peninsula , Environmental Biomarkers , Environmental Monitoring , Eutrophication , Phosphorus/analysis , Quality Indicators, Health Care
5.
Sci Total Environ ; 748: 141193, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-32810803

ABSTRACT

Biological assessment metrics and water chemistry measurements are used to quantify the link between stressors and their effects on lake ecosystems, for the Water Framework Directive. However, correlations between metrics and water chemistry are often poor. This is seen as major weaknesses of Water Framework Directive-related monitoring and assessment. We analyzed macrophytes, benthic algae, benthic macroinvertebrates, water chemistry and sediment total phosphorus content in the littoral of six lakes in the Western Balkans and used CORINE land use data to estimate nutrient enrichment via runoff from the adjacent land. Lakes with a higher estimated phosphorus runoff from the adjacent land did not have higher littoral water nutrient concentrations, but littoral diatom assemblages indicated more eutrophic conditions. These lakes also had higher abundances of littoral benthic primary producers, which in turn were associated with low concentrations of dissolved nutrients, but only in autumn, not in spring. This is consistent with primary producers taking up nutrients during the summer growth season. In lakes with high abundances of benthic primary producers, it is likely that the littoral vegetation plays a large role in the transfer of nutrients from the water to the benthos. This process impairs correlations between biological metrics and water nutrient concentrations. Our results suggest that CORINE land cover may be more useful to characterize littoral nutrient enrichment than lake water chemistry. Increased benthic primary producer biomasses and "eutrophic" diatom indices may indicate littoral nutrient enrichment even if water nutrient concentrations are low.


Subject(s)
Ecosystem , Water , Balkan Peninsula , Eutrophication , Lakes , Nutrients , Phosphorus/analysis
6.
Cardiovasc Ultrasound ; 18(1): 29, 2020 Jul 21.
Article in English | MEDLINE | ID: mdl-32693812

ABSTRACT

BACKGROUND: Coronary chronic total occlusion (CTO) is characterized by the presence of collateral blood vessels which can provide additional blood supply to CTO-artery dependent myocardium. Successful CTO recanalization is followed by significant decrease in collateral donor artery blood flow and collateral derecruitment, but data on coronary hemodynamic changes in relation to myocardial function are limited. We assessed changes in coronary flow velocity reserve (CFVR) by echocardiography in collateral donor and recanalized artery following successful opening of coronary CTO. METHODS: Our study enrolled 31 patients (60 ± 9 years; 22 male) with CTO and viable myocardium by SPECT scheduled for percutaneous coronary intervention (PCI). Non-invasive CFVR was measured in collateral donor artery before PCI, 24 h and 6 months post-PCI, and 24 h and 6 months in recanalized artery following successful PCI of CTO. RESULTS: Collateral donor artery showed significant increase in CFVR 24 h after CTO recanalization compared to pre-PCI values (2.30 ± 0.49 vs. 2.71 ± 0.45, p = 0.005), which remained unchanged after 6-months (2.68 ± 0.24). Baseline blood flow velocity of the collateral donor artery significantly decreased 24 h post-PCI compared to pre-PCI (0.28 ± 0.06 vs. 0.24 ± 0.04 m/s), and remained similar after 6 months, with no significant difference in maximum hyperemic blood flow velocity pre-PCI, 24 h and 6 months post-PCI. CFVR of the recanalized coronary artery 24 h post-PCI was 2.55 ± 0.35, and remained similar 6 months later (2.62 ± 0.26, p = NS). CONCLUSIONS: In patients with viable myocardium, prompt and significant CFVR increase in both recanalized and collateral donor artery, was observed within 24 h after successful recanalization of CTO artery, which maintained constant during the 6 months. TRIAL REGISTRATION: ClinicalTrials.gov (Number NCT04060615 ).


Subject(s)
Coronary Occlusion/surgery , Coronary Vessels/physiopathology , Fractional Flow Reserve, Myocardial/physiology , Myocardial Contraction/physiology , Percutaneous Coronary Intervention , Chronic Disease , Coronary Occlusion/diagnosis , Coronary Occlusion/physiopathology , Coronary Vessels/diagnostic imaging , Coronary Vessels/surgery , Echocardiography , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Time Factors
7.
Eur J Pharmacol ; 882: 173281, 2020 Sep 05.
Article in English | MEDLINE | ID: mdl-32562800

ABSTRACT

Voltage-gated potassium (Kv) channels are the largest superfamily of potassium (K) channels. A variety of Kv channels are expressed in the vascular smooth muscle cells (SMC). Studies have shown that gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) cause various changes in the human umbilical vein (HUV). Recently, we have shown that 4-AP, a nonspecific Kv1-4 channel inhibitor, significantly decreases vasorelaxation induced by K channel opener pinacidil in vascular SMCs of the HUVs from normal pregnancies, but not in GDM and PIH. The goal of this study was to provide more detailed insight in the Kv channel subtypes involved in pinacidil-induced vasodilation of HUVs, as well as to investigate potential alterations of their function and expression during GDM and PIH. Margatoxin, a specific blocker of Kv1.2 and Kv1.3 channels, significantly antagonized pinacidil-induced vasorelaxation in normal pregnancy, while in HUVs from GDM and PIH that was not the case, indicating damage of Kv1.2 and Kv1.3 channel function. Immunohistochemistry and Western blot revealed similar expression of Kv1.2 channels in all groups. The expression of Kv1.3 subunit was significantly decreased in PIH, while it remained unchanged in GDM compared to normal pregnancy. Phrixotoxin, specific blocker of Kv4.2 and Kv4.3 channels, did not antagonize response to pinacidil in any of the groups. The major novel findings show that margatoxin antagonized pinacidil-induced relaxation in normal pregnancy, but not in GDM and PIH. Decreased expression of Kv1.3 channels in HUV during PIH may be important pathophysiological mechanism contributing to an increased risk of adverse pregnancy outcomes.


Subject(s)
Hypertension, Pregnancy-Induced/metabolism , Kv1.3 Potassium Channel/metabolism , Muscle, Smooth, Vascular/metabolism , Umbilical Veins/metabolism , Adult , Antihypertensive Agents/pharmacology , Diabetes, Gestational/metabolism , Female , Humans , Kv1.2 Potassium Channel/metabolism , Pinacidil/pharmacology , Pregnancy , Young Adult
8.
Can J Physiol Pharmacol ; 98(10): 708-716, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32353247

ABSTRACT

Heart failure (HF) is one of the major cardiovascular causes of death worldwide. In this study, we explored the effects of folic acid (FA) on cardiometabolic, oxidative stress biomarker changes, and the activity of proliferation marker Ki67 in monocrotaline-induced HF. The research was conducted during a 4 week period using five experimental groups (eight animals per group): blank solution exposed controls (C1: 1 mL/kg physiological saline, 1 day; C2: 1 mL/kg physiological saline, 28 days), monocrotaline (MCT) induced HF (50 mg/kg MCT), FA (5 mg·kg-1·day-1 FA), and MCT+FA (50 mg/kg MCT, 5 mg·kg-1·day-1 FA). Superoxide dismutase and glutathione peroxidase activities together with total glutathione and parameters of oxidative damage of proteins were determined in cardiac tissue as well as cardiometabolic parameters in plasma or serum. The total glutathionylation was determined by Western blot and proliferation marker Ki67 was assessed by immunohistochemistry. The right ventricular (RV) wall hypertrophy and Ki67 positivity, accompanied by a significant increase of troponin T, has been shown in MCT-induced HF. The antioxidant effect of FA was reflected through superoxide dismutase activity, reduced Ki67 positivity in the RV wall, and a slightly decreased total glutathionylation level.


Subject(s)
Antioxidants/pharmacology , Energy Metabolism/drug effects , Folic Acid/pharmacology , Heart Failure/drug therapy , Myocytes, Cardiac/drug effects , Oxidative Stress/drug effects , Animals , Biomarkers/metabolism , Cell Proliferation/drug effects , Disease Models, Animal , Glutathione/metabolism , Heart Failure/chemically induced , Heart Failure/metabolism , Heart Failure/pathology , Immunohistochemistry , Ki-67 Antigen/metabolism , Male , Monocrotaline , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Rats, Wistar , Ventricular Remodeling/drug effects
9.
Can J Physiol Pharmacol ; 98(2): 93-102, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31505124

ABSTRACT

The aim of this study was to test the hypothesis that subchronic co-application of vitamins B6 and folic acid (FA) could affect heart failure (HF) induced by monocrotaline (MCT), with the modulation of oxidative stress parameters and cardiometabolic biomarkers. Biochemical and histomorphometric analyses were assessed in blank solution-exposed controls (C1 physiological saline 1 mL/kg, 1 day, n = 8; C2 physiological saline 1 mL/kg, 28 days, n = 8), MCT-induced HF (MCT 50 mg/kg, n = 8), B6+FA (vitamin B6 7 mg·kg-1·day-1, FA 5 mg·kg-1·day-1; n = 8), and MCT+B6+FA (MCT 50 mg/kg, vitamin B6 7 mg·kg-1·day-1, FA 5 mg·kg-1·day-1; n = 8) in male Wistar albino rats (body mass 160 g at the start). Superoxide dismutase and glutathione peroxidase activities, thiol-, carbonyl groups, and nitrotyrosine were determined in cardiac tissue. Echocardiography was performed to confirm MCT-induced HF. The right ventricular wall hypertrophy, accompanied with significant increase of troponin T and preserved renal and liver function, has been shown in MCT-induced HF. However, these effects were not related to antioxidant effects of vitamin B6 and FA, since several parameters of oxidative stress were more pronounced after treatment. In this study, co-application of vitamins B6 and FA did not attenuate hypertrophy of the right ventricle wall but aggravated oxidative stress, which is involved in HF pathogenesis.


Subject(s)
Folic Acid/administration & dosage , Folic Acid/pharmacology , Heart Failure/metabolism , Myocardium/metabolism , Oxidative Stress/drug effects , Vitamin B 6/administration & dosage , Vitamin B 6/pharmacology , Animals , Biomarkers/metabolism , Electrocardiography/drug effects , Heart/drug effects , Heart/physiopathology , Heart Failure/chemically induced , Heart Failure/physiopathology , Male , Monocrotaline/adverse effects , Rats , Rats, Wistar , Time Factors
10.
Int Orthop ; 44(1): 155-160, 2020 01.
Article in English | MEDLINE | ID: mdl-31740994

ABSTRACT

INTRODUCTION: Split tendon transfer of tibialis posterior (SPOTT) is a treatment option for the hindfoot varus deformity in patients with cerebral palsy (CP). The purpose of this study was to present the long-term results of the newly modified SPOTT procedure developed by our senior author and compare it with the standard SPOTT technique in equinovarus foot deformity due to CP. METHOD: Our retrospective cohort study included patients with spastic foot deformity due to CP treated with the standard or modified SPOTT technique. Patients' age at the time of the surgery was ≥ five years with follow-up period of at least four years. Surgical outcomes were evaluated using Kling's criteria during the patient's last follow-up visit. RESULTS: The analysis included 124 patients (146 feet), where 105 feet were treated by the standard SPOTT technique and 41 feet by the modified SPOTT technique. Patients' median age at the time of the surgery was 11 years. Patients were followed-up for a median period of eight years during which the modified SPOTT technique showed significantly better surgical outcomes compared with the standard group (excellent/good results in 38 feet, 92.7%, vs. 79 feet, 75.2%, p = 0.02). Two groups of patients did not significantly differ in GMFCS level, age at the time of the surgery, or patient gender. There was similar distribution in CP patterns in the standard and modified groups; spastic hemiplegia was the most prevalent form, followed by spastic diplegia and spastic paraplegia. Overall, better surgical success was achieved in patients with GMFCS levels I-III (100%, 94.8%, and 69.8%, respectively). SPOTT procedure failure was frequently noticed in patients with GMFCS level IV (90.9%). CONCLUSION: The modified SPOTT procedure demonstrated efficiency and safety in patients with equinovarus foot deformity due to CP during the long-term follow-up. Compared with the standard procedure, the newly modified SPOTT technique showed significantly better surgical outcome, irrespective of the patients' gender, age, initial GMFCS level, and CP type.


Subject(s)
Cerebral Palsy/complications , Clubfoot/surgery , Tendon Transfer/methods , Adolescent , Child , Clubfoot/etiology , Female , Follow-Up Studies , Hemiplegia/etiology , Humans , Male , Muscle Spasticity/surgery , Paralysis/etiology , Retrospective Studies
11.
Exp Mol Pathol ; 111: 104323, 2019 12.
Article in English | MEDLINE | ID: mdl-31669131

ABSTRACT

Gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) can jeopardize mother and/or fetus. Vascular ATP-sensitive potassium (KATP) channels most likely participate in the processes of diabetes and hypertension. The aim of this research was to examine whether GDM and PIH cause changes in the expression and function of KATP channels in vascular smooth muscle of human umbilical vein (HUV). Western blot and immunohistochemistry detected significantly decreased expression of Kir6.1 subunit of KATP channels in GDM and PIH, while the expression of SUR2B was unchanged. In GDM, a K+ channel opener, pinacidil caused reduced relaxation of the endothelium-denuded HUVs compared to normal pregnancy. However, its effects in HUVs from PIH subjects were similar to normal pregnancy. In all groups KATP channel blocker glibenclamide antagonized the relaxation of HUV induced by pinacidil without change in the maximal relaxations indicating additional KATP channel-independent mechanisms of pinacidil action. Iberiotoxin, a selective antagonist of large-conductance calcium-activated potassium channels, inhibited the relaxant effect of pinacidil in PIH, but not in normal pregnancy and GDM. Experiments performed in K+-rich solution confirmed the existence of K+-independent effects of pinacidil, which also appear to be impaired in GDM and PIH. Thus, the expression of KATP channels is decreased in GDM and PIH. In GDM, vasorelaxant response of HUV to pinacidil is reduced, while in PIH it remains unchanged. It is very likely that KATP channels modulation and more detailed insight in KATP channel-independent actions of pinacidil may be precious in the therapy of pathological pregnancies.


Subject(s)
Adenosine Triphosphate/metabolism , Diabetes, Gestational/physiopathology , Hypertension, Pregnancy-Induced/physiopathology , KATP Channels/metabolism , Muscle, Smooth, Vascular/metabolism , Umbilical Veins/metabolism , Adult , Female , Humans , Muscle, Smooth, Vascular/pathology , Pregnancy , Umbilical Veins/pathology
12.
J Cardiothorac Surg ; 13(1): 12, 2018 Jan 18.
Article in English | MEDLINE | ID: mdl-29347958

ABSTRACT

BACKGROUND: Histopathological changes in the ascending aorta wall in patients with severe tricuspid aortic valve (TAV) stenosis were graded and correlated to echocardiographic parameters. Objective was to associate threshold echocardiographic values with structural defects in the ascending aorta providing a tool to improve decision-making process in cases when simultaneous aortic valve replacement (AVR) and ascending aorta replacement is considered. METHODS: Biopsies from 108 TAV stenosis patients subjected to AVR were graded into three grades according to severity of aortic wall changes. Echocardiographic parameters obtained preoperatively and correlated to grade, age, gender and risk factors, were diameters of ventriculo-aortic junction (AA), sinus Valsalva (SV), sinotubular junction (STJ), the largest diameter of the visualized ascending aorta (AscA) as well as indexes: sinus Valsalva (SVI), sinotubular junction (STJI), AscA/AA and STJ/AA. RESULTS: Two echocardiographic parameters portrayed grades with statistical significance: STJ (F = 5.417; p = 0.006 (p < 0.05)) and AscA (F = 3.924; p = 0.023 (p < 0.05)). By using multiple predictors in the setting of Regression analysis, statistically significant differences among grades were reached for AA, SV, STJ, AscA and SVI. With further ROC curves analysis, threshold values for different grades were recognized. Grade 2 is identified in patients with AscA > 3.3 cm, while Grade 3 is identified in patients with values of AscA > 3.5 cm, STJ > 2.9 cm and STJI > 1. CONCLUSIONS: Hemodynamic stress induced by TAV stenosis leads to elastic lamellae disruption in the aortic wall. Those changes could be graded and correlated with echocardiographic parameters of the aortic root and ascending aorta, providing a tool for decision to replace ascending aorta concomitantly with AVR.


Subject(s)
Aorta/diagnostic imaging , Aorta/pathology , Aortic Valve Stenosis/diagnostic imaging , Sinus of Valsalva/pathology , Aged , Aorta/surgery , Aortic Valve , Aortic Valve Stenosis/surgery , Clinical Decision-Making , Echocardiography , Female , Heart Valve Prosthesis Implantation , Humans , Male , Middle Aged , Organ Size , ROC Curve , Risk Factors , Sinus of Valsalva/diagnostic imaging
13.
Microsc Microanal ; 24(2): 132-138, 2018 04.
Article in English | MEDLINE | ID: mdl-29350612

ABSTRACT

The effects of betaine on hepatocytes chromatin architecture changes were examined by using fractal and gray-level co-occurrence matrix (GLCM) analysis in methionine/choline-deficient (MCD) diet-induced, nonalcoholic fatty liver disease (NAFLD). Male C57BL/6 mice were divided into groups: (1) Control: standard diet; (2) BET: standard diet and betaine supplementation through drinking water (solution 1.5%); (3) MCD group: MCD diet for 6 weeks; (4) MCD+BET: fed with MCD diet + betaine for 6 weeks. Liver tissue was collected for histopathology, immunohistochemistry, and determination of fractal dimension and GLCM parameters. MCD diet induced diffuse micro- and macrovesicular steatosis accompanied with increased Ki67-positive hepatocyte nuclei. Steatosis and Ki67 immunopositivity were less prominent in the MCD+BET group compared with the MCD group. Angular second moment (ASM) and inverse difference moment (IDM) (textural homogeneity markers) were significantly increased in the MCD+BET group versus the MCD group (p<0.001), even though no difference between the MCD and the control group was evident. Heterogeneity parameters, contrast, and correlation were significantly increased in the MCD group versus the control (p<0.001). On the other hand, betaine treatment significantly reduced correlation, contrast, and entropy compared with the MCD group (p<0.001). Betaine attenuated MCD diet-induced NAFLD by reducing fat accumulation and inhibiting hepatocyte proliferation. Betaine supplementation increased nuclear homogeneity and chromatin complexity with reduction of entropy, contrast, and correlation.


Subject(s)
Betaine/administration & dosage , Cell Nucleus/drug effects , Cell Proliferation/drug effects , Chromatin/drug effects , Gastrointestinal Agents/administration & dosage , Hepatocytes/drug effects , Non-alcoholic Fatty Liver Disease/drug therapy , Animals , Disease Models, Animal , Hepatocytes/physiology , Histocytochemistry , Immunohistochemistry , Ki-67 Antigen/analysis , Liver/pathology , Male , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/pathology
14.
Exp Mol Pathol ; 102(2): 303-313, 2017 04.
Article in English | MEDLINE | ID: mdl-28192087

ABSTRACT

Endothelial cell markers are membrane-bound or cytoplasmic molecules expressed by endothelial cells, which help their easier identification and discrimination from other cell types. During vasculogenesis, endothelial cells differentiate from hemangioblasts to form new blood vessels. With the discovery of endothelial progenitor cells (EPC) and their ability to form new blood vessels, the term vasculogenesis is not only reserved for the embryonic development. Possibility of de novo blood vessel formation from EPC is now widely explored in different ischemic conditions, especially in cardiovascular medicine. Numerous clinical trials have tested enhancing tissue vascularization by delivering hematopoietic cells that expressed endothelial markers. This therapeutic approach proved to be challenging and promising, particularly for patients who have exhausted all conventional therapeutic modalities. Angiogenesis, which refers to the formation of new blood vessels from existing vasculature, is indispensable process during tumor progression and metastasis. Blockage of tumor angiogenesis by targeting and inhibiting endothelial cell has emerged as novel safe and efficacious method to control many advanced malignant diseases. Numerous clinical studies are currently testing new antiangiogenic drugs which target and inhibit endothelial cell markers, receptors or molecules which transmit receptor-mediated signals, therefore inhibiting endothelial cell proliferation, migration and vascular tube formation. Many of these drugs are now widely used in clinical settings as first- or second-line chemotherapy in advanced malignant conditions. So far, these therapeutic approaches gave modest, yet encouraging clinical improvements, prolonging survival and improving functional capacity and quality of life for many terminally ill patients. Here we present the most commonly used endothelial cell markers along with their applicability in contemporary clinical practice.


Subject(s)
Biomarkers , Cardiovascular Diseases/genetics , Endothelial Cells/metabolism , Antigens, CD34/genetics , Antigens, CD34/metabolism , Cardiovascular Diseases/diagnosis , Endoglin/genetics , Endoglin/metabolism , Humans , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Platelet Endothelial Cell Adhesion Molecule-1/genetics , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Randomized Controlled Trials as Topic , Receptors, Vascular Endothelial Growth Factor/genetics , Receptors, Vascular Endothelial Growth Factor/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-3/genetics , Vascular Endothelial Growth Factor Receptor-3/metabolism , von Willebrand Factor/genetics , von Willebrand Factor/metabolism
15.
Ann Anat ; 208: 217-221, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27496251

ABSTRACT

Histology and embryology are prerequisite for understanding the complexity of cell and tissue organization, function and development. The aim of this study was to examine the attitudes of medical students toward relevance of histology and embryology in their pre-clinical and clinical medical practice. The study sample consisted of 900 undergraduate students of 1st and 6th study year at the School of Medicine in Belgrade, Serbia. Data were collected using an anonymous questionnaire. Senior students reported the relevance of histology and embryology knowledge for learning pathology, dermatology, physiology, gynecology and obstetrics, pathophysiology and pediatrics. Examination of students' attitudes revealed that 1st year participants more often acknowledged histology and embryology as being of great importance for their professional career. Analysis according to gender indicated that female students consider embryology as of greater importance for further medical education and future clinical practice than male students. Overall, study results suggest that medical students have a positive attitude toward histology and embryology undergraduate course. This evidence could be used as an additional motive for the development of histology and embryology courses, with special emphasis on practical application of knowledge in clinically-oriented setting.


Subject(s)
Attitude , Embryology/education , Histology/education , Students, Medical/psychology , Students, Medical/statistics & numerical data , Adult , Curriculum , Female , Humans , Male , Serbia , Young Adult
16.
Exp Mol Pathol ; 100(1): 31-8, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26657000

ABSTRACT

INTRODUCTION: Angiogenesis is the growth of both new vascular and lymphatic blood vessels from the existing vasculature. During this process, blood endothelial cells (BECs) and lymphatic endothelial cells (LECs) express specific markers, which help their discrimination and easier identification. Since the coronary thrombi material aspirated from patients with ST-elevation myocardial infarction (STEMI) proved as good angiogenesis model, we investigated the expression of CD34 and CD31 as BECs markers, and D2-40, LYVE-1 and VEGFR3 as LEC markers in this material. MATERIALS AND METHODS: Aspirated thrombi were stained immunohistochemically for CD34, CD31, D2-40, LYVE-1 and VEGFR3. Organizational patterns of immunopositive cells were graded as single cells, clusters or microvessels. Double immunofluorescence for CD31, D2-40, LYVE-1 and VEGRF3 was done. Thrombi were also graded as fresh (<1day old), lytic (1-5days old) and organized (>5days old). RESULTS: Serial sections of aspirated thrombi showed concordant BEC and LEC markers immunopositivity. Double immunoflorescence proved co-expression of CD31 and LEC markers on the same cells. Cells expressing LEC markers organized in clusters and microvessels were mainly present in lytic and organized thrombi. CONCLUSION: Co-expression of BEC and LEC markers on the same non-tumorous cell during thrombus neovascularization indicates existing in vivo plasticity of endothelial cells under non-tumorous pathological conditions. It also points that CD34 and CD31 on one hand, and D2-40, LYVE-1 and VEGFR3 immunostaining on the other hand, cannot solely be a reliable indicators whether vessel is lymphatic or not.


Subject(s)
Antigens, CD34/metabolism , Endothelial Cells/metabolism , Myocardial Infarction/metabolism , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Vascular Endothelial Growth Factor Receptor-3/metabolism , Vesicular Transport Proteins/metabolism , Biomarkers/analysis , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/blood , Myocardial Infarction/pathology , Neovascularization, Pathologic/metabolism , Thrombosis/metabolism
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