New Biomarkers in Screening Anthracycline-Induced Cardiotoxicity Only with Peripheral Blood Sampling

Because oxidative stress after administration of doxorubicin was identified as playing a central role in cardiac dysfunction, we hypothesized that the expression (or overexpression) of TLR2 and TLR4 contributes to the pathogenesis of doxorubicin-induced cardiac dysfunction. Toll-like receptors (TLRs) are members of the interleukin-1 receptor family (IL1) and are involved in the ability to react to the molecular trigger associated with pathogenic microorganisms. Recent studies have shown that TLR receptors are activated by endogenous signals, such as heat shock proteins and oxidative stress, which can contribute to congestive heart failure. Until recently, the best detection method for cardiotoxicity induced by anthracyclines was myocardial biopsy. Other early screening and early diagnosis methods (biomarkers—cardiac troponins and natriuretic peptide) have not yet proven their efficacy. Our proposed method is a new, revolutionary one that does not imply any kind of physical (and psychic) aggression on the patient: the targeted genetic (TLR2/TLR4) analysis of the human peripheral blood (which is a minimally invasive procedure)

Preliminary study on a polymer carrier containing ginger extract with possible applications in cardiovascular disease

OBJECTIVES AND BACKGROUND The aim of the study was to synthesize and characterize a polyurethane drug delivery system used for a ginger extract with possible applications in cardiovascular disease. MATERIALS AND METHODS The obtained procedure is based on a poly-addition reaction between a diisocyanate and a mixture of polyols and a spontaneous emulsification in the presence of a surfactant. Only aliphatic compounds were used as raw materials and no other chemicals were added as reaction catalyst or promoters. RESULTS Nanostructures sized between 92 and 128 nm, with a medium tendency of agglomeration and very stable to thermal degradation between 30 and 300oC were obtained. We observed the fact that nanostructures’ diluted aqueous solution presents a pH around 6.7 and no evidence of any irritation potential was found after using different assays. CONCLUSIONS The obtained nanostructures can be used as a polymer carrier for ginger extract based on our results. Graphical abstract: Chemical structures of: (a) gingerol, (b) eucalyptol, (c) borneol. REFERENCES 1. Prasad EM, Mopuri R, Islam MS, Kodidhela LD. Cardioprotective effect of Vitex negundo on isoproterenol-induced myocardial necrosis in wistar rats: A dual approach study. Biomed Pharmacother. 2016 [epub ahead of print]. 2. Abdel-Naeem HH, Mohamed HM. Improving the physico-chemical and sensory characteristics of camel meat burger patties using ginger extract and papain. Meat Sci. 2016;118:52-60. 3. Shirpoor A, Rezaei F, Fard AA, Afshari AT, Gharalari FH, Rasmi Y. Ginger extract protects rat’s kidneys against oxidative damage after chronic ethanol administration. Biomed Pharmacother. 2016;84:698-704

Pharmaco-Toxicological Assessment of the Combined Cytotoxic Effects of Digoxin and Betulinic Acid in Melanoma Cells

Betulinic acid, a small molecule from pentacyclic triterpenes class, has been widely studied for its antitumor activity, revealing that it induces the apoptosis of tumor cells in a selective manner. In recent years, digoxin, a cardiac glycoside found particularly in the plant species Digitalis lanata, has drawn interest for its potential antitumor properties. The present study was designed to evaluate the antimelanoma potential of betulinic acid (BA), digoxin (DG), and their association (DG + BA). In vitro assessments were performed 24 h post-treatment on two human melanoma cell lines (SK-Mel-28 and RPMI-7951). In addition, the potential irritant effects of the test samples were evaluated using the chorioallantoic membrane of hen’s eggs. BA and DG exhibit a concentration-dependent cytotoxic activity, with the combination of the two having a more marked effect on the decrease in cell viability (~17% for SK-Mel-28 cells and ~23% for RPMI-7951 cells). Further, morphological changes (rounding of the cells and their separation from the plaque) and alterations in the nucleus and actin fibers (condensation of chromatin and actin fibers, formation of apoptotic bodies) were observed, indicating an apoptotic-like process. Moreover, no irritating effects were observed in ovo. As a result, DG + BA acid may have synergistic potential in the antitumor treatment of melanoma, but future studies are needed in order to clarify the biological mechanisms involved

Myocardial Work Evaluation—A Useful Non-Invasive Method to Predict Coronary Artery Sub-Occlusion in a Patient with Unstable Angina and Multiple Myocardial Revascularization Interventions

Background: While lifestyle changes, management of coronary artery disease (CAD) risk factors, myocardial revascularization procedures, and medication can improve a patient’s prognosis, de novo native coronary lesions and in-stent restenosis (ISR) remain significant clinical concerns. ISR is more frequent with a bare-metal stent than with a drug-eluting stent and has been documented in around 12% of DES patients. Acute coronary syndrome (ACS) manifests as unstable angina in about 30% to 60% of ISR patients. Myocardial work imaging is a modern, non-invasive technique able to identify individuals with critical coronary artery lesions with high sensitivity and specificity. Case report: We present the case of a 72-year-old Caucasian gentleman with multiple cardiovascular risk factors, admitted to the Cardiology Clinic of Timișoara Municipal Hospital with unstable angina. From 1999 to 2021, the patient experienced two myocardial infarctions, a double aortocoronary bypass graft, and multiple percutaneous coronary interventions with 11 stent implantations, including 6 for ISR. Using two-dimensional speckle-tracking echocardiography and myocardial work assessment, we detected that the lateral wall of the left ventricle had a severely impaired deformation pattern. Angio-coronarography was performed, and sub-occlusion of the posterolateral branch of the right coronary artery was found. Angioplasty was performed and a DES was inserted, with a good final angiographic result and complete release of symptoms. Conclusion: In patients with a history of multiple myocardial revascularization interventions and ISR, it is challenging to identify the critical ischemia region by non-invasive methods. Myocardial work imaging was beneficial in the detection of the altered deformation patterns indicating significant ischemia, its accuracy being superior to that of LV strain, as proven by coronary angiography. Urgent coronary angiography followed by angioplasty and stent implantation resolved the issue

Perindopril Induces TSP-1 Expression in Hypertensive Patients with Endothelial Dysfunction in Chronic Treatment

Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in drug development for treating cancer. Several studies performed in the cardiovascular field on TSP-1 are contradictory, the role of TSP-1 in the physiopathology of cardiovascular disorders (CVDs) being, for the moment, incompletely understood and may be due to the presence of several domains in its structure which can stimulate many cellular receptors. It has been reported to inhibit NO-mediated signaling and to act on the angiogenesis, tissue perfusion, endothelial cell proliferation, and homeostasis, so we aimed to quantify the effect Perindopril has on TSP-1 plasma levels in hypertensive patients with endothelial dysfunction in comparison with other antihypertensive drugs, such as beta blockers, calcium channel blockers, and diuretics, in a chronic treatment. As a conclusion, patients under treatment with Perindopril had increased plasma levels of TSP-1 compared with other hypertensive patients and with the control group. The results of this study confirms the pleiotropic properties of Perindopril: anti-proliferative, anti-inflammatory, with effects showed by quantifying a single biomarker: TSP-1

Significant Association between Subclinical Left Cardiac Dysfunction and Liver Stiffness in Metabolic Syndrome Patients with Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease

Background and Objectives: Diabetes mellitus (DM) is connected to both cardiovascular disease and non-alcoholic fatty liver disease (NAFLD), and is an important component of metabolic syndrome (MetS). NAFLD can be detected and quantified using the vibration controlled transient elastography (VCTE) and the controlled attenuation parameter (CAP), whereas traditional and two-dimensional speckle tracking echocardiography (2D-STE) can reveal subclinical abnormalities in heart function. We sought to see if there was a link between left cardiac dysfunction and different levels of hepatic fibrosis in MetS patients with DM and NAFLD. Patients and Methods: We recruited successive adult subjects with MetS and a normal left ventricular ejection fraction, who were divided into two groups according to the presence or absence of DM. The presence of NAFLD was established by CAP and VCTE, while conventional and 2D-STE were used to assess left heart’s systolic and diastolic function. The mean age of the MetS subjects was 62 ± 10 years, 82 (55%) were men. The distribution of liver steatosis severity was similar among diabetics and non-diabetics, while liver fibrosis grade 2 and 3 was significantly more frequent in diabetics (p = 0.02, respectively p = 0.001). LV diastolic dysfunction was found in 52% of diabetic and in 36% of non-diabetic MetS patients (p = 0.04). 2D-STE identified in the diabetic subjects increased LA stiffness (40% versus 24%, p = 0.03) and reduced global left ventricular longitudinal strain (47% versus 16%, p p Conclusions: The current investigation confirms the link between liver stiffness and subclinical cardiac dysfunction as detected by 2D-STE in MetS patients with DM. The novel parameters derived from LA and LV 2D-STE have demonstrated greater sensitivity compared to the older measurements, and a substantial connection with hepatic fibrosis

Left Ventricular Remodeling and Heart Failure Predictors in Acute Myocardial Infarction Patients with Preserved Left Ventricular Ejection Fraction after Successful Percutaneous Intervention in Western Romania

(1) Acute myocardial infarction (AMI) patients are at risk of left ventricular (LV) remodeling and heart failure (HF), even after successful revascularization by percutaneous coronary intervention (PCI). We wanted to assess the independent predictors of these outcomes in AMI patients. (2) Methods: The study enrolled patients with a LVEF ≥50% after a successful PCI for their first AMI. After 24 months, patients were separated into two groups based on whether their LVEF remained ≥50% (group I), or decreased to p 2, infarct-related longitudinal strain ≤−12.5%, and the presence of LV remodeling were identified as independent predictors of HF hospitalizations. (4) Conclusions: About 26% of AMI patients with normal LV function after a successful PCI developed HF. More sensitive techniques are required that allow for a more efficient risk-stratification and preventive therapy to reduce LV remodeling and HF in AMI patients with LVEF ≥50% after a successful PCI. The detection of abnormal ventricular deformation patterns after PCI by speckle-tracking echocardiography might be a valuable method in this approach

Thrombospondin-1 Serum Levels In Hypertensive Patients With Endothelial Dysfunction After One Year Of Treatment With Perindopril

BACKGROUND: Thrombospondin-1 (TSP-1) is a matricellular functional protein of the extracellular matrix. As it is not constitutively present extracellularly, its secretion is enhanced in several situations, namely injury, chronic pathology, tissue remodeling, angiogenesis, and aging. Over the last decade, TSP-1 has been reported to be involved in complex and opposing biological effects on vasculature in the context of NO signaling. Several studies have reported high patient TSP-1 plasma levels, indicating that the protein can potentially serve as a prognostic marker for pulmonary arterial hypertension. MATERIALS AND METHODS: Here, we aimed to quantify TSP-1 serum levels in hypertensive patients with endothelial dysfunction before and after one year of treatment with Perindopril (an antihypertensive drug with vasoprotective properties). RESULTS: After one year of treatment, TSP-1 levels increased in hypertensive patients compared to baseline (T0: 8061.9 ± 3684.80 vs T1: 15380±5887 ng/mL, p<0.001) and compared to non-hypertensive controls (9221.03 ± 6510.21 ng/mL). In contrast, pentraxin-3 plasma levels were decreased after one year of Perindopril treatment in both hypertensive (T0: 0.91 ± 0.51 vs T1: 0.50 ± 0.24 ng/mL, p<0.001) and control group (1.36 ±1.5 ng/mL) patients, although flow-mediated vasodilation and intima-media thickness assessment parameters were not significantly changed. Systolic and diastolic blood pressure values as well as levels of fibrinogen, high-sensitivity C-reactive protein, triglycerides, and alanine aminotransferase were found to be significantly lower after one year of treatment with Perindopril. High levels of TSP-1 strongly correlated with platelet count (positive), lymphocytes (positive), red cell distribution width-CV (positive), systolic blood pressure (negative), and mean corpuscular hemoglobin (negative) after one year of treatment. Blood urea nitrogen was found to be a protective factor for TSP-1, while glucose and heart rate were found to be risk factors prior to and after treatment