Defining the Role of Trimetazidine in the Treatment of Cardiovascular Disorders: Some Insights on Its Role in Heart Failure and Peripheral Artery Disease

Trimetazidine is a cytoprotective drug whose cardiovascular effectiveness, especially in patients with stable ischemic heart disease, has been the source of much controversy in recent years; some have gone so far as to treat the medication as a ‘placebo drug’ whose new side effects, such as Parkinsonian symptoms, outweigh its benefits. This article is an attempt to present the recent key studies, including meta-analyses, on the use of trimetazidine in chronic heart failure, also in patients with diabetes mellitus and arrhythmia, as well as in peripheral artery disease. This paper also includes the most recent European Society of Cardiology guidelines, including those of 2013, on the use of trimetazidine in cardiovascular disease

Statyny — leki stosowane w Polsce wciąż za rzadko lub w zbyt małych dawkach

Hipercholesterolemia jest najczęstszym czynnikiem ryzyka chorób układu sercowo-naczyniowego w populacji polskiej. Większość chorych nie ma świadomości obecności tego czynnika ryzyka, kolejna duża grupa pacjentów, mimo świadomości choroby, nie stosuje ani niefarmakologicznych, ani farmakologicznych metod obniżania stężenia cholesterolu. W artykule przedstawiono niepokojące dane epidemiologicznie dotyczące hipercholesterolemii w populacji polskiej, wskazując jednocześnie sposoby poprawienia diagnostyki i leczenia tego zaburzenia

Fenofibrate — a place in contemporary pharmacotherapy

Farmakoterapia zaburzeń lipidowych w ostatnich latach ulega dynamicznej zmianie w związku z wprowadzaniem na rynek nowych leków o odmiennym mechanizmie działania od dotychczas stosowanych. Niemniej, w codziennej praktyce klinicznej wciąż najpopularniejszymi preparatami, obok statyn, pozostają fibraty, a zwłaszcza fenofibrat. W artykule autorzy omawiają najważniejsze duże, randomizowane badania kliniczne z zastosowaniem tego leku, analizują bezpieczeństwo farmakoterapii tym lekiem, również w skojarzeniu z innymi preparatami oraz wskazują aktualne miejsce fenofibratu w leczeniu zaburzeń lipidowych.Lipid disorder pharmacotherapy has been dynamically changing in recent years in connection with the introduction of new drugs with a different mechanism of action than those previously used. However, in everyday clinical practice still the most common drugs applied, next to statins, are fibrates, and in particular fenofibrate. In the article, the authors discuss the most important large randomized clinical trials using this drug, analyze the safety of pharmacotherapy with this drug also in combination with other drugs, and show the current position of fenofibrate in the treatment of lipid disorders

Atorvastatin in patients with overweight and obesity

Nadwaga i otyłość stanowią jeden z najpoważniejszych, i według danych WHO — narastających, problemów klinicznych w populacjach krajów uprzemysłowionych, przyczyniając się do rozwoju wielu powikłań zdrowotnych. Najczęstszymi konsekwencjami nadwagi i otyłości są choroby układu sercowo-naczyniowego, zespół metaboliczny i cukrzyca. W artykule autorzy omawiają możliwości zastosowania atorwastatyny jako leku zmniejszającego niebezpieczeństwo występowania tych powikłań, wskazując jednocześnie na bezpieczeństwo podawania go chorym z nadwagą lub otyłością. Opisano również powiązania otyłości z nadmiarem tłuszczowej tkanki nasierdziowej, której rola w rozwoju chorób układu sercowo-naczyniowego jest dotychczas niedostatecznie poznana, a może być istotna parametrem oceny ryzyka.Overweight and obesity is one of the most serious and according to WHO data growing clinical problems in populations of industrialized countries, contributing to the development of many health complications. The most common consequences of overweight and obesity are diseases of the cardiovascular system, metabolic syndrome and diabetes mellitus. In the article, the authors discuss the possibility of applying atorvastatin as a drug reducing the possibility of risk occurrence of these complications, pointing out the safety of this drug in patients who are overweight or obese. They also describe the relationship between obesity and excess epicardial adipose tissue, whose role in the development of cardiovascular diseases hasn’t been so far sufficiently known and might be significant risk predictor

Comparison of the predictive value of digital examination (Bishop’s score) and ultrasound evaluation for labor induction success

Abstract Aim: Cervical ripening is the main factor of success in the induction of labor. The aim of the study was to compare predictive value of digital examination (Bishop’s score) and ultrasound evaluation for labor induction success. Material and methods: The study was carried out in the Fetal Medicine Department of Medical University of Lodz between 2006-2009. 101 pregnant women comprised the study group. Results: Comparing the subgroups with successful and unsuccessful labor induction, the main differences were observed in the entire Bishop’s score (7.21 versus 5.4 points;

Divergence entropy-based evaluation of hydrophobic core in aggressive and resistant forms of transthyretin

The two forms of transthyretin differing slightly in the tertiary structure, despite the presence of five mutations, show radically different properties in terms of susceptibility to the amyloid transformation process. These two forms of transthyretin are the object of analysis. The search for the sources of these differences was carried out by means of a comparative analysis of the structure of these molecules in their native and early intermediate stage forms in the folding process. The criterion for assessing the degree of similarity and differences is the status of the hydrophobic core. The comparison of the level of arrangement of the hydrophobic core and its initial stages is possible thanks to the application of divergence entropy for the early intermediate stage and for the final forms. It was shown that the minimal differences observed in the structure of the hydrophobic core of the forms available in PDB, turned out to be significantly different in the early stage (ES) structure in folding process. The determined values of divergence entropy for both ES forms indicate the presence of the seed of hydrophobic core only in the form resistant to amyloid transformation. In the form of aggressively undergoing amyloid transformation, the structure lacking such a seed is revealed, being a stretched one with a high content of β-type structure. In the discussed case, the active presence of water in the structural transformation of proteins expressed in the fuzzy oil drop model (FOD) is of decisive importance for the generation of the final protein structure. It has been shown that the resistant form tends to generate a centric hydrophobic core with the possibility of creating a globular structure, i.e., a spherical micelle-like form. The aggressively transforming form reveals in the structure of its early intermediate, a tendency to form the ribbon-like micelle as observed in amyloid

Structure of the hydrophobic core determines the 3D protein structure-verification by single mutation proteins

Four de novo proteins differing in single mutation positions, with a chain length of 56 amino acids, represent diverse 3D structures: monomeric 3$\alpha$ and 4$\beta$ + $\alpha$ folds. The reason for this diversity is seen in the different structure of the hydrophobic core as a result of synergy leading to the generation of a system in which the polypeptide chain as a whole participates. On the basis of the fuzzy oil drop model, where the structure of the hydrophobic core is expressed by means of the hydrophobic distribution function in the form of a 3D Gaussian distribution, it has been shown that the composition of the hydrophobic core in these two structural forms is different. In addition, the use of a model to determine the structure of the early intermediate in the folding process allows to indicate differences in the polypeptide chain geometry, which, combined with the construction of a common hydrophobic nucleus as an effect of specific synergy, may indicate the reason for the diversity of the folding process of the polypeptide chain. The results indicate the need to take into account the presence of an external force field originating from the water environment and that its active impact on the formation of a hydrophobic core whose participation in the stabilization of the tertiary structure is fundamental

Karyometric evaluations of the seminal tubule cells in men with azoospermia

Objectives: The aim of the study is to confirm that karyometric evaluations of the seminal tubule cells in men with azoospermia indicate stimulating influence of the Leydig cell and testosterone on the functions of Sertoli cells, whereas serum LH concentration may in fact lead to regressive changes in the wall of the seminal tubule. Material and methods: Material consists of 75 patients with azoospermia and hypospermatogenesis. In all patients surgical biopsy of the testes was done, prior to an assessment of serum LH and testosterone levels. In histopathology, sperminal epithelium, basal membrane, myoid cells of the tubular wall and interstitial cells have been examined. Karyometry in Sertoli cells, spermatogonia and myoid cells was performed. Also, the thickness of the tubular wall was assessed quantitatively. Results: The size of Sertoli cells nuclei was significantly bigger in hypospermatogenesis associated with hyperplasia of Leydig cells than in hypospermatogenesis alone (p=0,01). Regression analysis revealed positive correlations between serum testosterone and the size of Sertoli cells nuclei (p=0,02), between the size of Sertoli cell nuclei and of spermatogonia and between nuclear size of myoid cells and spermatogonia (p=0,0001). Serum LH correlated positively with the thickness of tubular wall (p=0,01). Conclusions: Leydig cell hyperplasia and testosterone stimulate the functions of Sertoli cells whereas Sertoli cells activate spermatogonia. The Sertoli cell function is positively interrelated with the function of myoid cells. There is a close interrelationship between LH and the thickness of tubular wall, which may suggest that hippersecretion of LH causes the enlarged thickness of tubular wall, observed in hipergonadotropizm

The value of an initial drop in human Chorionic gonadotropin levels in predicting a response to methotrexate in women with low-risk gestational trophoblastic neoplasia

Objectives: The early identification of patients who are being treated for low-risk gestational trophoblastic neoplasia (LRGTN) with single-agent chemotherapy, who are at high risk of developing chemoresistance, is of crucial importance. The aim of our research was to evaluate the pretreatment beta subunit of human chorionic gonadotropin (βhCG) concentration and its decrease after the administration of the first course of methotrexate (MTX) in predicting later chemo-resistance to single-agent chemotherapy.  Material and methods: A total of 46 patients diagnosed with LRGTN treated with a 5-day methotrexate (MTX) regimen were retrospectively studied. 24 of the patients were successfully cured with only MTX therapy (MTX group). The disease was considered resistant in the remaining 22 patients who, after MTX therapy, required further chemotherapy with an EMA/CO regimen (EMA/CO group). To compare changes in the βhCG concentrations between the two courses of treatment (and the two groups), we calculated the percentage of decline. We determined the specificity and sensitivity of the initial βhCG level and its percentage decline, as a potential predictor of the need for a future EMA/CO regimen. For diagnostic purposes, βhCG levels were measured before the first and second administrations of MTX with a commercial ELISA kit.  Results: In the EMA/CO group, we found the initial βhCG level before the first MTX dose was higher (median = 6275 mIU/mL, range: 21.53–192.610.0 mIU/mL) than in the MTX group (median = 532 mIU/mL, range: 56.5 mIU/mL–360.397.0 mIU/mL) (p = 0.034, Mann-Whitney test). The percentage decreases in the βhCG values relative to the initial concentrations were higher in the MTX group (median decrease = 82.7%, range: from 13.3% to 99.9%) than in the EMA/CO group (median de- crease = 71.1%, range: from an increase of 56.1% to a decrease of 97.1%) (p = 0.0079, Mann-Whitney test). An analysis of the ROC curves implied optimal cutoff values for the initial βHCG (6054 IU, sensitivity = 55%, specificity = 86%) and the percentage change in βhCG levels (decrease by 76.5%, sensitivity = 72%, specificity = 71%).  Conclusions:  Women with initially higher βhCG levels have a greater risk of developing MTX chemo resistance. It would be advantageous to consider administering an EMA/CO regimen in women with LRGTN when their initial βhCG levels are greater than 6000.