Hypertension and left ventricular hypertrophy.

In the initial stage, left ventricular hypertrophy (LVH) is adaptive, but in time, it transforms to maladaptive LVH which is specific for the development of various phenotypes that cause heart failure, initially with preserved, but later with reduced left ventricular ejection fraction. Pathophysiological mechanisms, which are characteristic for remodeling procedure, are numerous and extremely complex, and should be subjected to further research with the aim of making a comprehensive overview of hypertensive heart disease (HHD) and discovering new options for preventing and treating HHD. The contemporary methods, such as cardiac magnetic resonance (CMR) and computed tomography (CT) provide very accurate morphological and functional information on HHD. The objective of this review article is to summarize the available scientific information in terms of prevalence, pathophysiology, diagnostics, prevention, contemporary therapeutic options, as well as to present potential therapeutic solutions based on the research of pathological mechanisms which are at the core of HHD.

Left ventricular mechanics in patients with hematological malignancies before initiation of chemo- and radiotherapy.

Objective We sought to investigate left ventricular (LV) structure, function and mechanics in the patients with leukemia and lymphoma before initiation of chemotherapy, as well as the relationship between hematological malignancies and reduced LV longitudinal strain. Methods This retrospective investigation included 71 patients with leukemia and lymphoma before chemotherapy and 36 healthy controls. All participants underwent echocardiographic examination before initiation of chemotherapy and radiotherapy. Results LV global longitudinal strain (- 20.2 ± 1.7% vs. - 17.9 ± 3.0%, p < 0.001) was significantly lower in the patients with hematological malignancies than in controls. There was no difference in LV circumferential and radial strains between two observed groups. Subendocardial and subepicardial longitudinal strains were significantly lower in the patients with hematological malignancies (- 20.5 ± 3.6% vs. - 22.5 ± 3.8%, p = 0.001 for subendocardial strain; - 18.0 ± 1.5% vs. - 15.8 ± 2.6%, p < 0.001 for subepicardial strain). Hematological malignancies were associated with reduced global LV longitudinal strain (OR 21.0; 95%CI 2.04-215.0, p = 0.010) independently of age, gender, heart rate, body mass index, left ventricular ejection fraction, left ventricular mass index, and glucose level. Conclusions LV longitudinal strain was impaired in the patients with leukemia and lymphoma even before initiation of chemotherapy. Endocardial and epicardial LV layers are equally affected in the patients with hematological malignancies. Newly diagnosed hematological malignancies were related with reduced LV global longitudinal strain independently of common clinical and echocardiographic parameters.

Variability of Myocardial Strain During Isometric Exercise in Subjects With and Without Heart Failure.

Background: Fast strain-encoded cardiac magnetic resonance imaging (cMRI, fast-SENC) is a novel technology potentially improving characterization of heart failure (HF) patients by quantifying cardiac strain. We sought to describe the impact of isometric handgrip exercise (HG) on cardiac strain assessed by fast-SENC in HF patients and controls. Methods: Patients with stable HF and controls were examined using cMRI at rest and during HG. Left ventricular (LV) global longitudinal strain (GLS) and global circumferential (GCS) were derived from image analysis software using fast-SENC. Strain change < -0.5 and > +0.5 was classified as increase and decrease, respectively. Results: The study population comprised 72 subjects, including HF with reduced, mid-range and preserved ejection fraction and controls (HFrEF n = 18 HFmrEF n = 18, HFpEF n = 17, controls: n = 19). In controls, LV GLS remained stable in 36.8%, increased in 36.8% and decreased in 26.3% of subjects during HG. In HF subgroups, similar patterns of LV GLS response were observed (HFpEF: stable 41.2%, increase 35.3%, decrease: 23.5%; HFmrEF: stable 50.0%, increase 16.7%, decrease: 33.3%; HFrEF: stable 33.3%, increase 22.2%, decrease: 44.4%, p = 0.668). Mean change between LV GLS at rest and during HG ranged close to zero with broad standard deviation in all subgroups and was not significantly different between subgroups (+1.2 ± 5.4%, -0.6 ± 8.3%, -1.7 ± 10.7%, and -3.1 ± 19.4%, p = 0.746 in controls, HFpEF, HFmrEF and HFrEF, respectively). However, the absolute value of LV GLS change-irrespective of increase or decrease-was significantly different between subgroups with 4.4 ± 3.2% in controls, 5.9 ± 5.7% in HFpEF, 6.8 ± 8.3% in HFmrEF and 14.1 ± 13.3% in HFrEF (p = 0.005). The absolute value of LV GLS change significantly correlated with resting LVEF, NTproBNP and Minnesota Living with Heart Failure questionnaire scores. Conclusion: The response to isometric exercise in LV GLS is heterogeneous in all HF subgroups and in controls. The absolute value of LV GLS change during HG exercise is elevated in HF patients and associated with measures of HF severity. The diagnostic utility of fast-SENC strain assessment in conjunction with HG appears to be limited. Trial Registration: URL: https://www.drks.de; Unique Identifier: DRKS00015615.

Multilayer myocardial strain improves the diagnosis of heart failure with preserved ejection fraction.

AIMS: The diagnostic and treatment of patients with heart failure with preserved ejection fraction (HFpEF) are both hampered by an incomplete understanding of the pathophysiology of the disease. Novel imaging tools to adequately identify these patients from individuals with a normal cardiac function and respectively patients with HF with reduced EF are warranted. Computing multilayer myocardial strain with feature tracking is a fast and accurate method to assess cardiac deformation. Our purpose was to assess the HFpEF diagnostic ability of multilayer strain parameters and compare their sensitivity and specificity with other established parameters. METHODS AND RESULTS: We included 20 patients with a diagnosis of HFpEF and, respectively, 20 matched controls. We assessed using feature-tracking cardiac magnetic resonance longitudinal and circumferential myocardial strain at three distinct layers of the myocardium: subendocardial (Endo-), mid-myocardial (Myo-), and subepicardial (Epi-). Comparatively, we additionally assessed various others clinical, imaging, and biochemical parameters with a putative role in HFpEF diagnostic: left ventricular end-diastolic volume (LVEDV), left ventricular mass (LVM), interventricular septum (IVS) wall thickness and free wall thickness, left atrial volume and strain, septal and lateral mitral annular early diastolic velocity (e`), E/e´ ratio, and plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Global longitudinal strain (GLS) is significantly impaired at Endo (-20.8 ± 4.0 vs. -23.2 ± 3.4, P = 0.046), Myo- (-18.0 ± 3.0 vs. -21.0 ± 2.5, P = 0.002), and Epi- (-12.2 ± 2.0 vs. -16.2 ± 2.5, P < 0.001) levels. Compared with any other imaging parameter, an Epi-GLS lower than 13% shows the highest ability to detect patients with HFpEF [area under the curve (AUC) = 0.90 (0.81-1), P < 0.001] and in tandem with NT-proBNP can diagnose with maximal sensibility (93%) and specificity (100%), patients with HFpEF from normal, composed variable [AUC = 0.98 (0.95-1), P < 0.001]. In a logistic regression model, a composite predictive variable taking into account both GLS Epi and NT-proBNP values in each individual subject reached a sensitivity of 89% and a specificity of 100% with an AUC of 0.98 (0.95-1), P < 0.001, to detect HFpEF. CONCLUSIONS: Epi-GLS is a promising new imaging parameter to be considered in the clinical assessment of HFpEF patients. Given its excellent specificity, in tandem with a highly sensitive parameter such as NT-proBNP, Epi-GLS holds the potential to greatly improve the current diagnostic algorithms.

ß1-Adrenoreceptor Autoantibodies in Heart Failure: Physiology and Therapeutic Implications.

Antibodies that activate the ß1-AR (ß1-adrenoreceptor) can induce heart failure in animal models. These antibodies are often found in patients with heart failure secondary to varying etiologies. Their binding to the ß1 receptor leads to prolonged receptor activation with subsequent induction of cellular dysfunction, apoptosis, and arrhythmias. ß-blocker therapy while highly effective for heart failure, may not be sufficient treatment for patients who have ß1 receptor autoantibodies. Removal of these autoantibodies by immunoadsorption has been shown to improve heart failure in small studies. However, immunoadsorption is costly, time consuming, and carries potential risks. An alternative to immunoadsorption is neutralization of autoantibodies through the intravenous application of small soluble molecules, such as peptides or aptamers, which specifically target and neutralize ß1-AR autoantibodies. Peptides may induce immunogenicity. Animal as well as early phase human studies with aptamers have not shown safety concerns to date and have demonstrated effectiveness in reducing autoantibody levels. Novel aptamers have the potential advantage of having a wide spectrum of action, neutralizing a variety of known circulating G-protein coupled receptor autoantibodies. These aptamers, therefore, have the potential to be novel therapeutic option for patients with heart failure who have positive for ß1-AR autoantibodies. However, clinical outcomes trials are needed to assess the clinical utility of this novel approach to treat heart failure.

CMR Tissue Characterization in Patients with HFmrEF.

The characteristics and optimal management of heart failure with a moderately reduced ejection fraction (HFmrEF, LV-EF 40-50%) are still unclear. Advanced cardiac MRI offers information about function, fibrosis and inflammation of the myocardium, and might help to characterize HFmrEF in terms of adverse cardiac remodeling. We, therefore, examined 17 patients with HFpEF, 18 with HFmrEF, 17 with HFrEF and 17 healthy, age-matched controls with cardiac MRI (Phillips 1.5 T). T1 and T2 relaxation time mapping was performed and the extracellular volume (ECV) was calculated. Global circumferential (GCS) and longitudinal strain (GLS) were derived from cine images. GLS (-15.7 ± 2.1) and GCS (-19.9 ± 4.1) were moderately reduced in HFmrEF, resembling systolic dysfunction. Native T1 relaxation times were elevated in HFmrEF (1027 ± 40 ms) and HFrEF (1033 ± 54 ms) compared to healthy controls (972 ± 31 ms) and HFpEF (985 ± 32 ms). T2 relaxation times were elevated in HFmrEF (55.4 ± 3.4 ms) and HFrEF (56.0 ± 6.0 ms) compared to healthy controls (50.6 ± 2.1 ms). Differences in ECV did not reach statistical significance. HFmrEF differs from healthy controls and shares similarities with HFrEF in cardiac MRI parameters of fibrosis and inflammation.

Biatrial Remodeling in Patients with Cystic Fibrosis Running Title: Atrial Function in Cystic Fibrosis.

BACKGROUND: Previous studies have focused on left and right ventricular remodeling in cystic fibrosis (CF), whereas atrial function has not been assessed in detail so far. We sought to investigate left and right atrial (LA and RA) function in patients with CF. METHODS: This retrospective investigation included 82 CF patients (64 survivors and 18 non-survivors) who were referred to CF department over the period of four years, as well as 32 control subjects matched by age and gender. All participants underwent an echocardiographic examination including a strain analysis, which was performed offline and blinded for groups. RESULTS: LA and RA volume indexes were significantly higher in CF patients than in controls and were particularly high in CF non-survivors. LA conduit and reservoir functions were significantly worse in CF survivors and non-survivors, compared with control subjects. RA phasic function was not different between controls, CF survivors and non-survivors. The parameters of lung function (forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1)) and the LA and RA volume indexes were predictors of mortality in CF patients. However, in a multivariate analysis, only FVC was an independent predictor of mortality in CF patients. CONCLUSIONS: Our results suggest that both atria are enlarged, but only LA function is impaired in CF patients. LA reservoir and conduit function is particularly deteriorated in CF patients. Though statistical significance was not reached due to our limited sample size, there was a trend of deterioration of LA and RA function from controls across CF survivors to CF non-survivors. LA and RA enlargement represented predictors of mortality in CF patients.

Phasic Left Atrial Function in Cancer Patients Before Initiation of Anti-Cancer Therapy.

: We aimed to explore left atrial (LA) remodeling in the patients with solid cancer before initiation of chemo- or radiotherapy. This retrospective investigation included 92 chemo- and radiotherapy-naive cancer patients and 40 age- and gender-matched controls with a similar cardiovascular risk profile as the cancer group. All participants underwent comprehensive echocardiographic examination before the start of chemo- or radiotherapy. LA phasic function was evaluated in volumetric and strain method. Indexed minimal and pre-A LA volumes were significantly higher in the cancer patients. Total and passive LA emptying fraction (EF) were significantly lower, whereas active LAEF was significantly higher in the cancer patients. LA total longitudinal strain was significantly lower in the cancer patients. Strain rate analysis of LA phasic function showed that LA function during systole and early diastole was reduced in the cancer group, while it was increased during late diastole. These findings indicated that LA reservoir and conduit functions, assessed with LA volumetric and strain analysis, were deteriorated in the cancer group. On the other hand, LA booster pump function was elevated in the cancer group in comparison with the controls. In the whole population, cancer was associated with reduced LA total longitudinal strain independently of age, gender, BMI, LV hypertrophy, E/e' ratio, diabetes, and hypertension. LA phasic function was impaired in the chemo- and radiotherapy-naive cancer patients in comparison with the control group. Cancer, LV hypertrophy, and hypertension were associated with reduced LA longitudinal strain independently of other important clinical parameters.

Selection of recycling centre locations by using the interval type-2 fuzzy sets and two-objective genetic algorithm.

In the sense of contemporary industrial challenges, it may be said that many issues in the field of recycling may be analysed. In this paper, the model for choosing locations for construction of recycling centres equipped with new technology is proposed. The considered problem may be stated as a two-objective optimization problem, if the optimization criteria are presented as total distance and the overall suitability index sum. The relative importance and values of possible locations' attributes are described by pre-defined linguistic expressions, and modelled by interval triangular type-2 fuzzy numbers. Type-2 fuzzy numbers provide a possibility to incorporate the uncertainty of membership functions into the fuzzy set theory. The procedure for determination of the overall suitability index is proposed. Selection of the most appropriate locations is achieved by a two-objective genetic algorithm, since it is very suitable for the routing issues. The proposed model application is illustrated with the real-life data that come from a few regions in Serbia.

Distribution of natural and artificial radionuclides in chernozem soil/crop system from stationary experiments.

The present paper focuses on the determination of radiological characteristics of cultivated chernozem soil and crops from long-term field experiments, taking into account the importance of distribution and transfer of radionuclides in the soil-plant system, especially in agricultural cropland. The investigation was performed on the experimental fields where maize, winter wheat, and rapeseed were cultivated. Analysis of radioactivity included determination of the gross alpha and beta activity as a screening method, as well as the activities of the following radionuclides: natural ((210)Pb, (235)U, (238)U, (226)Ra, (232)Th, (40)K, (7)Be) and artificial ((90)Sr and (137)Cs). The activities of natural and artificial ((137)Cs) radionuclides were determined by gamma spectrometry, while the artificial radionuclide (90)Sr was determined by a radiochemical analytical method. Based on the obtained results for the specific activity of (40)K, (137)Cs, and (90)Sr, accumulation factors for these radionuclides were calculated in order to estimate transfer of radionuclides from soil to crops. The results of performed analyses showed that there is no increase of radioactivity that could endanger the food production through the grown crops.

Depth distribution of (137)Cs in anthrosol from the experimental field "Radmilovac" near Belgrade, Serbia.

This is a preliminary study of the depth distribution of (137)Cs radionuclides in cultivated anthrosol soil of a 15-year old peach tree plantation at the experimental field "Radmilovac" near Belgrade. Before planting, the soil was ploughed at the depth of 1 m. The soil had not been annually ploughed, irrigated and treated with mineral fertilizers for three years before sampling. Activity concentration for (137)Cs ranged from 1.8 Bq kg(-1) to 35 Bq kg(-1). Along the soil depth it varied highly, reaching as high a total variation coefficient as 83 %. Radiocaesium distribution patterns depended on the extent of soil mixing in the plough layer, as it was mechanically transferred from the surface to the lower soil layers during cultivation. (137)Cs was associated with humus content and fixation to clay fractions in the soil. Our results single out soil's hygroscopic water as a valuable parameter for (137)Cs behaviour that could be used commonly if the measurement is standardised.

Near-infrared spectroscopy study for determination of adsorbed acetochlor in the organic and inorganic bentonites.

NIR spectroscopy is used to determine acetochlor herbicide adsorption on Na-montmorillonite (NaP) and organically modified montmorillonite (NaOM). Both montmorillonites NIR spectra shows bands at 7061 and 6791 cm(-1). Organo-montmorillonite is characterised by two emphasized bands at 5871 and 5667 cm(-1) that are attributed to the fundamental overtones of the mid-IR bands at 2916 and 2850 cm(-1). Bands at 6017 and 6013 cm(-1) are attributed to acetochlor adsorbed to organo-montmorillonite and Na-montmorillonite, which is confirmed by X-ray powder diffraction (XRPD). Greater quantity of acetochlor is adsorbed to organo-clays compared to non-modified montmorillonite. Acetochlor poses high risk to environmental contamination. Organo-clays are the most useful for removing acetochlor from water and soil.

Dedifferentiated chondrosarcoma: our clinico-pathological experience and dilemmas in 25 cases.

BACKGROUND: Dedifferentiated chondrosarcoma represents a special form of the chondrosarcoma characterized by the presence of well-differentiated cartilaginous component in juxtaposition with the malignant mesenchymal tumor of high-malignancy grade. METHODS: The study was performed on 25 tissue samples obtained by biopsy of the primary malignant bone tumors. RESULTS: Out of the total of 25 patients, 13 were males and 12 were females. Their average age was 59.9 years (39-75). Radiological examination verified the presence of the pathological fractures in 14 patients. The skeletal distribution clearly indicates that the femur is the most frequent site of affection (in 15 patients--60%). Morphological analysis verified the presence of "precursor cartilaginous lesion" or low-grade cartilaginous component in all cases. Classification of the high-grade components was based on the immunohistochemical analyses, which evidenced MFH in 18 cases, osteosarcoma in 4, while fibrosarcoma was evidenced in 2 and rhabdomyosarcoma in 1 case. In 20 patients, out of whom 14 had existing fractures, amputation was indicated. In five patients (fracture-free), resection limb-salvage surgical intervention was performed. CONCLUSION: The lethal outcome ensues within less than 2 years in all patients.

Tissue-protective effects of fullerenol C60(OH)24 and amifostine in irradiated rats.

Polyhydroxylated fullerenes, named fullerenols (C(60)(OH)(n); n=12-26) are excellent antioxidants. Harmful effects of ionizing radiation on living organism are mainly mediated by free radical species and fullerenols attract an attention as a potential radioprotectors. Our preliminary investigations on mice and rats subjected to radiation injury show that fullerenol C(60)(OH)(24) provides high survival rate of irradiated small rodents. Radioprotective effect was comparable to that of the standard radioprotector amifostine. The aim of this study was to compare the efficacy of fullerenol C(60)(OH)(24) (10 and 100mg/kg i.p.) and amifostine (300 mg/kg i.p.) in protection of rats against harmful effects of ionizing radiation. The animals were whole-body irradiated by X-rays (8 MV). Both compounds were given 30 min before irradiation. In order to evaluate the general radioprotective efficacy of fullerenol and amifostine rats were irradiated with an absolutely lethal dose of X-rays (8 Gy) and their survival and body mass gain were monitored during the period of 30 days after irradiation. The aim of the second part of the study is to investigate the tissue-protective effects of tested compounds (100 mg/kg i.p. of fullerenol and 300 mg/kg i.p. of amifostine, 30 min before irradiation). It was carried out on rats irradiated with a sublethal dose of X-rays (7 Gy). Influence of ionizing radiation on hematopoesis as well as the radioprotective efficiency of the compounds given were evaluated by determining blood cell count during 28 days after irradiation. For this purpose the blood was taken from tail vein before irradiation and on the 3rd, 7th, 14th, 21st and 28th day after irradiation. In order to estimate the radioprotective effects of fullerenol and amifostine on other rat tissue, the animals were sacrificed on the 7th and 28th day after irradiation and their main organs (lung, heart, liver, kidney, small intestine and spleen) were taken for histopathological analysis. In the experiment in which the general radioprotective efficacy of fullerenol and amifostine was examined, fullerenol given in a dose of 100mg/kg produced better protection than given in a dose of 10mg/kg. This effect was comparable to that of amifostine. The results of hematological investigations showed that fullerenol better than amifostine prevented radiation-induced reduction in the white cell count (granulocytes and lymphocytes), particularly in the first 7 days after irradiation. Pathohistology examinations revealed better radioprotective effects of fullerenol compared to those of amifostine on the spleen, small intestine and lung, while amifostine had better radioprotective effects than fullerenol in protection of the heart, liver and kidney. These results confirm satisfactory radioprotective efficacy of fullerenol and encourage further investigations as a potential radioprotector.

Modulating activity of fullerol C60(OH)22 on doxorubicin-induced cytotoxicity.

Paper presents the effects of the newly synthesized fullerol C60(OH)22 on the growth of tumor cells in vitro and its modulating activity on doxorubicin (DOX)-induced cytotoxicity in human breast cancer cell lines. Cell growth inhibition was evaluated by tetrazolium colorimetric WST1 assay. Electron spin resonance (ESR) "trapping" method was used to investigate OH-radical scavenger activity of fullerol during Fenton's reaction. At a range of nanomolar concentrations fullerol induced cell growth inhibition, which was cell line, dose and time dependent. Fullerol also strongly suppressed DOX-induced cytotoxicity at all concentrations regardless the time of fullerol addition. Proanthocyanidins added as single agent to MCF-7 cell culture for 48 h induced low growth inhibition but in combination with DOX strongly decreased DOX cytotoxicity. Fullerol was found to be a potent hydroxyl radical scavenger: the relative intensity of ESR signals of DMPO-hydroxyl radical (DMPO-OH) spin adduct decreased by 88% in the presence of 0.5 microg/ml of fullerol. The obtained results suggest that antiproliferative effect of the fullerol and its protective effect on DOX-induced cytotoxicity might be mediated through hydroxyl-radical scavenger activity of C60(OH)22.