Diabetes mellitus type 2 ranks among the strongest predictors of cardiovascular diseases (CVD) while the association of type 1 diabetes with CVD is more complex. We studied differences between type 1 and 2 diabetic women regarding association of cardiovascular risk factors with preclinical atherosclerosis expressed as intima-media thickness of common carotid (IMT CCA) and femoral arteries (IMT CFA) measured by high resolution ultrasound. Women with type 1 (n=203) and type 2 diabetes (n=123) were examined with regard to the presence of cardiovascular risk factors. In type 1 diabetic women strong association between IMT CCA and body mass index, waist circumference, and total body fat was found in contrast to type 2 diabetic women. In type 2 diabetic women strong association between IMT CCA and fasting glucose, glycated hemoglobin, and atherogenic index of plasma (log TG/HDL cholesterol) was observed in contrast to type 1 diabetic women. In type 1 diabetic women, IMT CFA was associated with body fat in contrast to type 2 diabetic women. Preclinical atherosclerosis in type 1 diabetic women was strongly associated with factors reflecting body fat and its distribution, while in type 2 diabetic women preclinical atherosclerosis was associated with markers reflecting glucose and lipid metabolic disorders., P. Piťhová, K. Štechová, J. Piťha, V. Lánská, M. Kvapil., and Obsahuje bibliografii
The fads2 gene encoding Δ6-desaturase, the rate-limiting enzyme of the LCPUFA biosynthesis is expressed in astrocytes. Dietary fatty acids, which cross the blood-brain barrier, may regulate the transcription of lipogenic enzymes through activation of transcription factors such as peroxisome proliferator-activated receptors (PPARs). The PPARs form the transcription complex with retinoid X receptors (RXRs) that are activated by 9-cis retinoic acid, a metabolite of vitamin A (VA). The study examines whether challenge of astrocytes with VA, prior 24-h treatment with palmitic acid (PA), α-linolenic acid (ALA) or docosahexaenoic acid (DHA) has the effect on the FADS2 expression. RT-qPCR showed that in astrocytes not challenged with VA, PA increased fads2 gene expression and DHA decreased it. However, in VA-primed astrocytes, PA doubled the FADS2 mRNA levels, while DHA increased fads2 gene expression, oppositely to non-primed cells. Furthermore, similar changes were seen in VA-primed astrocytes with regard to Δ6-desaturase protein levels following PA and DHA treatment. ALA did not have any effect on the FADS2 mRNA and protein levels in either VA-primed or non-primed astrocytes. These findings indicate that in the presence of vitamin A, DHA upregulates fads2 gene expression in astrocytes., B. Dziedzic, D. Bewicz-Binkowska, E. Zgorzynska, D. Stulczewski, L. Wieteska, B. Kaza, A.Walczewska., and Obsahuje bibliografii
The aim of our work was to provide data from women of fertile age with type 1 diabetes mellitus about the endogenous androgens and on their relations to the parameters of diabetes control. Forty-two women were examined, they did not use contraceptives for at least three months prior to the examination. A multivariate regression analysis showed that the daily insulin dose, the fasting glycemia and the HbA1c values and patient´s age correlated negatively with dehydroepiandrosterone sulfate, dehydroepiandrosterone and prolactin levels. The testosterone/ dehydroepiandrosterone sulfate ratio correlated positively with daily insulin dose and patient´s age. In contrast to adrenal androgens the values of other hormones, including total and free testosterone, androstenedione, dihydrotestosterone, estradiol, LH, FSH, 17-OH-P, progesterone and cortisol revealed no significant correlation. To conclude, significant relations between the glucose control parameters and the adrenal androgens and prolactin were demonstrated. These relationships should be considered as an important factor influencing diabetes control so the additional cardiovascular risk in women with DM1., H. Kvasnickova, R. Hampl, K. Vondra., and Obsahuje bibliografii
Diabetic macular edema (DME) is a major factor contributing to visual disabilities in diabetic patients, and the number of patients is increasing. Animal models play a key role in the development of novel therapies. In this study, pathophysiological analyses of ocular lesions in Spontaneously Diabetic Torii (SDT) fatty rats were performed. First, vascular endothelial growth factor (VEGF) concentrations in vitreous humor, retinal vascular permeability and retinal thickness were measured in SDT fatty rats (Experiment 1). Furthermore, the pharmacological effects of two anti-diabetic drugs, phlorizin and pioglitazone, on retinal lesions were evaluated (Experiment 2). As results, the SDT fatty rats exhibited VEGF increase in vitreous humor at 8 and 16 weeks of age, and both retinal vascular hyperpermeability and retinal thickening at 16 weeks of age. In particular, the layers between the retinal internal limiting membrane and the outer nuclear layer were thickened. Phlorizin treatment from 4 to 16 weeks of age improved hyperglycemia and normalized retinal thickness; however, the effect of pioglitazone on retinal thickness was not strong despite the normalization of hyperglycemia. These data demonstrate that the male SDT fatty rat is a useful model for developing new therapeutic approaches in DME., Y. Motohashi, Y. Kemmochi, T. Maekawa, H. Tadaki, T. Sasase, Y. Tanaka, A. Kakehashi, T. Yamada, T. Ohta., and Obsahuje bibliografii
The general population is potentially exposed to many chemicals that can affect the endocrine system. These substances are called endocrine disruptors (EDs), and among them bisphenol A (BPA) is one of the most widely used and well studied. Nonetheless, there are still no data on simultaneous measurements of various EDs along with steroids directly in the seminal fluid, where deleterious effects of EDs on spermatogenesis and steroidogenesis are assumed. We determined levels of BPA and 3 estrogens using LC-MS/MS in the plasma and seminal plasma of 174 men with different degrees of infertility. These men were divided according their spermiogram values into 4 groups: (1) healthy men, and (2) slightly, (3) moderate, and (4) severely infertile men. Estradiol levels differed across the groups and body fluids. Slightly infertile men have significantly higher BPA plasma and seminal plasma levels in comparison with healthy men (p<0.05 and p<0.01, respectively). Furthermore, seminal BPA, but not plasma BPA, was negatively associated with sperm concentration and total sperm count (-0.27; p<0.001 and -0.24; p<0.01, respectively). These findings point to the importance of seminal plasma in BPA research. Overall, a disruption of estrogen metabolism was observed together with a weak but significant impact of BPA on sperm count and concentration., J. Vitku, L. Sosvorova, T. Chlupacova, R. Hampl, M. Hill, V. Sobotka, J. Heracek, M. Bicikova, L. Starka., and Obsahuje bibliografii
Type I diabetes mellitus (DM1) is a complex disease with adverse effects on organs and tissues despite compensation by insulin treatment. The goal of our study was to study how kidney diseases change 31P MR parameters of muscle metabolism in DM1 patients with respect to gender. 51 DM1 patients (19 m/14 f without and 13 m/5 f with nephropathy) and 26 (14 m/12 f) healthy volunteers were examined using 31P magnetic resonance spectroscopy at 3T tomograph at rest, and during and after a calf muscle exercise. The exercise consisted of a six-minute plantar flexion using a pedal ergometer followed by a six-minute recovery. It is reflected by reduced relative β-ATP and increased Pi and phosphodiester signals to phosphocreatine (PCr) at rest and prolongation of the PCr recovery time after the exercise. Measurement on healthy volunteers indicated differences between males and females in pH at the rest and after the exercise only. These differences between patients groups were not significant. We have proven that nephropathy affects the metabolism in diabetic patients and our results confirm significant difference between patients with and without nephropathy. Gender differences in pH were observed only between male and female healthy volunteers., P. Sedivy, M. Dezortova, M. Drobny, Z. Vlasakova, V. Herynek, M. Hajek., and Obsahuje bibliografii
Increased oxidative stress is indisputably an important mechanism of doxorubicin side effects, especially its cardiotoxicity. To prevent impairment of non-tumorous tissue and to improve the specificity in targeting the tumor tissue, new drug nanotransporters are developed. In many cases preclinical therapeutic advantage has been shown when compared with the administration of conventional drug solution. Three forms of doxorubicin - conventional (DOX), encapsulated in liposomes (lipoDOX) and in apoferritin (apoDOX) were applied to Wistar rats. After 24 h exposition, the plasma level of 4-hydroxy-2- nonenal (4-HNE) as a marker of lipoperoxidation and tissue gene expression of thioredoxin reductase 2 (TXNRD2) and aldehyde dehydrogenase 3A1 (ALDH3A1) as an important part of antioxidative system were determined. Only conventional DOX significantly increases the level of 4-HNE; encapsulated forms on the other hand show significant decrease in plasma levels of 4-HNE in comparison with DOX. They also cause significant decrease in gene expression of ALDH3A1 and TXNRD2 in liver as a main detoxification organ, and a mild influence on the expression of these enzymes in left heart ventricle as a potential target of toxicity. Thus, 4-HNE seems to be a good potential biomarker of oxidative stress induced by various forms of doxorubicin., M. Hlaváčová, J. Gumulec, T. Stračina, M. Fojtů, M. Raudenská, M. Masařík, M. Nováková, H. Paulová., and Obsahuje bibliografii
a1_With hypoxic stress, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) are elevated and their responses are altered in skeletal muscles of plateau animals [China Qinghai-Tibetan plateau pikas (Ochotona curzoniae )] as compared with control animals [normal lowland Sprague-Dawley (SD) rats]. The results indicate that HIF-1α and VEGF are engaged in physiological functions under hypoxic environment. The purpose of the current study was to examine the protein levels of VEGF receptor subtypes (VEGFRs: VEGFR-1, VEGFR-2 and VEGFR-3) in the end organs, namely skeletal muscle, heart and lung in response to hypoxic stress. ELISA and Western blot analysis were employed to determine HIF-1α and the protein expression of VEGFRs in control animals and plateau pikas. We further blocked HIF-1α signal to determine if HIF-1α regulates alternations in VEGFRs in those tissues. We hypothesized that responsiveness of VEGFRs in the major end organs of plateau animals is differential with insult of hypoxic stress and is modulated by low oxygen sensitive HIF-1α. Our results show that hypoxic stress induced by exposure of lower O2 for 6 h significantly increased the levels of VEGFR-2 in skeletal muscle, heart and lung and the increases were amplified in plateau pikas. Our results also demonstrate that hypoxic stress enhanced VEGFR-3 in lungs of plateau animals. Nonetheless, no significant alternations in VEGFR-1 were observed in those tissues with hypoxic stress. Moreover, we observed decreases of VEGFR-2 in skeletal muscle, heart and lung; and decreases of VEGFR-3 in lung following HIF-1α inhibition. Overall, our findings suggest that in plateau animals 1) responsiveness of VEGFRs is different under hypoxic environment; 2) amplified VEGFR-2 response appears in skeletal muscle, heart and lung, and enhanced VEGFR-3 response is mainly observed in lung; 3) HIF-1α plays a regulatory role in the levels of VEGFRs. Our results provide the underlying cellular and molecular mechanisms responsible for hypoxic environment in plateau animals, having an impact on research of physiological and ecological adaptive responses to acute or chronic hypoxic stress in humans who living at high attitude and who live at a normal sea level but suffer from hypoxic disorders., H.-C. Xie, J.-G. Li, J.-P. He., and Obsahuje bibliografii
We aimed to determine the impact of Ca2+-related disorders induced in intact animal hearts on ultrastructure of the cardiomyocytes prior to occurrence of severe arrhythmias. Three types of acute experiments were performed that are known to be accompanied by disturbances in Ca2+ handling. Langedorffperfused rat or guinea pig hearts subjected to K+-deficient perfusion to induce ventricular fibrillation (VF), burst atrial pacing to induce atrial fibrillation (AF) and open chest pig heart exposed to intramyocardial noradrenaline infusion to induce ventricular tachycardia (VT). Tissue samples for electron microscopic examination were taken during basal condition, prior and during occurrence of malignant arrhythmias. Cardiomyocyte alterations preceding occurrence of arrhythmias consisted of non-uniform sarcomere shortening, disruption of myofilaments and injury of mitochondria that most likely reflected cytosolic Ca2+ disturbances and Ca2+ overload. These disorders were linked with non-uniform pattern of neighboring cardiomyocytes and dissociation of adhesive junctions suggesting defects in cardiac cell-to-cell coupling. Our findings identified heterogeneously distributed high [Ca2+]i-induced subcellular injury of the cardiomyocytes and their junctions as a common feature prior occurrence of VT, VF or AF. In conclusion, there is a link between Ca2+-related disorders in contractility and coupling of the cardiomyocytes pointing out a novel paradigm implicated in development of severe arrhythmias., N. Tribulova, V. Knezl, B. Szeiffova Bacova, T. Egan Benova, C. Viczenczova, E. Gonçalvesova, J. Slezak., and Obsahuje bibliografii
Left atrial (LA) volume (LAV) is used for the selection of patients with atrial fibrillation (AF) to rhythm control strategies. Calculation of LAV from the LA diameters and areas by two-dimensional (2D) echocardiography may result in significant error. Accuracy of atrial volume assessment has never been studied in patients with long-standing persistent AF (LSPAF) and significant atrial remodeling. This study investigated correlation and agreement between 2D echocardiographic (Simpson method) and electroanatomic (CARTO, Biosense Webster) left and right atrial (RA) volumes (LAVECHO vs. LAVCARTO and RAVECHO vs. RAVCARTO) in patients undergoing catheter ablation for LSPAF. The study enrolled 173 consecutive subjects (females: 21 %, age: 59±9 years). There was only modest correlation between LAVECHO (92±31 ml) and LAVCARTO (178±37 ml) (R=0.57), and RAVECHO (71±29 ml) and RAVCARTO (173±34 ml) (R=0.42), respectively. LAVECHO and RAVECHO underestimated LAVCARTO and RAVCARTO with the absolute bias (±1.96 standard deviation) of -85 (-148; -22) ml and -102 (-169; -35) ml, respectively, and with the relative bias of -48 (-75; -21) % and -59 (-88; -30) %, respectively (all P<0.000001 for their mutual difference). Significant confounders of this difference were not identified. In patients with LSPAF, 2D echocardiography significantly underestimated both LA and RA volumes as compared with electroanatomic reference. This disagreement was independent of clinical, echocardiographic and mapping characteristics., L. Škňouřil, Š. Havránek, V. Bulková, M. Dorda, T. Paleček, J. Šimek, Z. Fingrová, A. Linhart, J. Januška, D. Wichterle, M. Fiala., and Obsahuje bibliografii