Solid organ transplantation is an established treatment modality in patients with end-stage organ damage in cases where other therapeutic options fail. The long-term outcomes of solid organ transplant recipients have improved considerably since the introduction of the first calcineurin inhibitor (CNI) - cyclosporine. In 1984, the potent immunosuppressive properties of another CNI, tacrolimus, were discovered. The immunosuppressive effects of CNIs result from the inhibition of interleukin-2 synthesis and reduced proliferation of T cells due to calcineurin blockade. The considerable side effects that are associated with CNIs therapy include arterial hypertension and nephrotoxicity. The focus of this article was to review the available literature on the pathophysiological mechanisms of CNIs that induce chronic nephrotoxicity and arterial hypertension. CNIs lead to activation of the major vasoconstriction systems, such as the reninangiotensin and endothelin systems, and increase sympathetic nerve activity. On the other hand, CNIs are known to inhibit NO synthesis and NO-mediated vasodilation and to increase free radical formation. Altogether, these processes cause endothelial dysfunction and contribute to the impairment of organ function. A better insight into the mechanisms underlying CNI nephrotoxicity could assist in developing more targeted therapies of arterial hypertension or preventing CNI nephrotoxicity in organ transplant recipients, including heart transplantation., L. Hošková, I. Málek, L. Kopkan, J. Kautzner., and Obsahuje bibliografii
Hypertrophy of the left heart ventricle as a consequence of a haemodynamic overload is a process of ambiguous biological value. Although hypertrophy allows to increase the performance of the ventricle without substantial elevation in wall tension, it represents a risk factor of cardiac morbidity and mortality. The regression of hypertrophy seems to be a rational outcome of this ambivalent situation. Mot every reversal of hypertrophied muscle mass, however, can be unambiguously considered therapeutic success. The biological value of hypertrophy regression depends on the type of hypertrophy, on the level of deterioration of the heart by a long- lasting haemodynamic overload, as well as on the way in which the reversal of hypertrophy is achieved. Even in the case when functional characteristics are preserved or even improved compared to the hypertrophied heart, hypertrophy regression need not automatically mean a decrease of the cardiovascular risk induced by ventricular hypertrophy. Regression of hypertrophy may be even disadvantageous in those situations when reduction of hypertrophy and reduction of the haemodynamic overload proceed in a disproportional manner. Spontaneously developing regression of the hypertrophied left ventricle as demonstrated on the model of aortal insufficiency, is an explicitly pathological state, resulting in heart failure. Regression of myocardial hypertrophy should not be considered the primary therapeutic aim but rather a part of the management of haemodynamic overload of the heart. The main aim is to achieve optimal perfusion of the periphery, yet at the same time to provide such conditions which would prevent the working load of the heart to become a limiting factor of survival.
Extreme or unaccustomed eccentric exercise can cause exerciseinduced muscle damage, characterized by structural changes involving sarcomere, cytoskeletal, and membrane damage, with an increased permeability of sarcolemma for proteins. From a functional point of view, disrupted force transmission, altered calcium homeostasis, disruption of excitation-contraction coupling, as well as metabolic changes bring about loss of strength. Importantly, the trauma also invokes an inflammatory response and clinically presents itself by swelling, decreased range of motion, increased passive tension, soreness, and a transient decrease in insulin sensitivity. While being damaging and influencing heavily the ability to perform repeated bouts of exercise, changes produced by exercise-induced muscle damage seem to play a crucial role in myofibrillar adaptation. Additionally, eccentric exercise yields greater hypertrophy than isometric or concentric contractions and requires less in terms of metabolic energy and cardiovascular stress, making it especially suitable for the elderly and people with chronic diseases. This review focuses on our current knowledge of the mechanisms underlying exerciseinduced muscle damage, their dependence on genetic background, as well as their consequences at the structural, functional, metabolic, and clinical level. A comprehensive understanding of these is a prerequisite for proper inclusion of eccentric training in health promotion, rehabilitation, and performance enhancement., Andraž Stožer, Peter Vodopivc, Lidija Križančić Bombek., and Obsahuje bibliografii
Hypoxic-ischemic encephalopathy (HIE) is one of the leading pediatric neurological conditions causing long-term disabilities and socio-economical burdens. Nearly 20-50 % of asphyxiated newborns with HIE die within the newborn period and another third will develop severe health consequences and permanent handicaps. HIE is the result of severe systemic oxygen deprivation and reduced cerebral blood flow, commonly occurring in full-term infants. Hypoxic-ischemic changes trigger several molecular and cellular processes leading to cell death and
inflammation. Generated reactive oxygen species attack surrounding cellular components resulting in functional deficits and mitochondrial dysfunction. The aim of the present paper is to review present knowledge about the pathophysiology of perinatal hypoxic-ischemic encephalopathy, especially with respect to novel treatment strategies and biomarkers that might enhance early detection of this disorder and thus improve the general outcome of patients.
In this paper it is proved that every $3$-connected planar graph contains a path on $3$ vertices each of which is of degree at most $15$ and a path on $4$ vertices each of which has degree at most $23$. Analogous results are stated for $3$-connected planar graphs of minimum degree $4$ and $5$. Moreover, for every pair of integers $n\ge 3$, $ k\ge 4$ there is a $2$-connected planar graph such that every path on $n$ vertices in it has a vertex of degree $k$.
Heart disease diagnosis is an important non-invasive technique. Therefore, there exists an effort to increase the accuracy of arrhythmia classification based on ECG signals. In this work, we present a novel approach of heart arrhythmia detection. The model consists of two parts. The first part extracts important features from raw ECG signal using Auto-Encoder Neural Network. Extracted features obtained by Auto-Encoder represent an input for the second part of the model, the Gradient Boosting and Feedforward Neural Network classifiers. For comparison purposes, we evaluated our approach by using MIT-BIH ECG database and also following recommendations of the Association for the Advancement of Medical Instrumentation (AAMI) for ECG class labeling. We divided our experiment into two scenarios. The first scenario represents the classification task for the patient-adapted paradigm and the second one was dedicated to the inter-patient paradigm. We compared the measured results to the state-of-the-art methods and it shows that our method outperforms the state-of-the art methods in the Ventricular Ectopic (VEB) class for both paradigms and Supraventricular Ectopic (SVEB) class in the inter-patient paradigm.