Parabens are a group of chemicals used as preservatives in the food, cosmetic and pharmaceutical industries. They are known to possess estrogenic effects, and therefore have been classified as endocrine disruptors. In addition to the classical endocrine organs, other tissues have endocrine activity, including adipose tissue. Several chemicals are known to cause obesogenic effects, and parabens are currently being studied in this context. The aim of this study was to investigate the possible connections of paraben exposure and obesity. Blood plasma from 27 healthy women was collected during their menstrual cycle. Basal anthropometric measures, levels of parabens (methylparaben, ethylparaben and propylparaben), adipokines (adiponectin, adipsin, leptin, resistin and visfatin) and hormones affecting energy balance and metabolic health (c-peptide, ghreline, GIP, GLP-1, glucagon, insulin, PAI-1) were measured. A Kolmogorov- Smirnov test showed higher methylparaben and propylparaben levels in women with BMI 25-34.9 compared to those with BMI 18.5-24.9. Plasma levels of methylparaben as well as the sum of parabens were positively associated with the plasma adipsin levels. Negative associations for methylparaben were found for glucagon, leptin and PAI-1. In accordance with other experimental studies we observed important associations of methylparaben and hormones affecting energy balance and metabolic health, indicating its obesogenic potential., L. Kolatorova, M. Sramkova, J. Vitku, J. Vcelak, O. Lischkova, L. Starka, M. Duskova., and Obsahuje bibliografii
18F-fluorocholine positron emission tomography/computed tomography (FCH) was performed after inconclusive neck ultrasound and 99Tc-sestaMIBI SPECT (MIBI) scintigraphy in patients with primary hyperparathyroidism (PHPT) to localize abnormal parathyroid glands before surgery. The results were retrospectively evaluated and compared to postoperative histopathological findings. 13 patients with PHPT were enrolled (mean age 64.3 years, preoperative calcium 2.74 mmol/l and parathyroid hormone 114.6 ng/l). FCH localized hyperfunctioning parathyroid glands in 12 patients of 13 (per patient sensitivity 92 % and positive predictive value (PPV) 100 %). Fourteen parathyroid lesions (11 adenomas, 3 hyperplastic glands) were resected with a mean size of 11.9 mm (per lesion sensitivity 93 % and PPV 81 %). Four adenomas and one hyperplastic gland were composed of only chief cells, whereas five lesions contained both chief and oxyphil cells. In three patients an exclusively oxyphil adenoma was found, surprisingly with negative MIBI scintigraphy in spite of a high mitochondria content in the oxyphil parathyroid cells. 12 of 13 patients had thyroid disease. In our limited study sample, FCH correctly identified parathyroid adenomas and/or hyperplastic glands in 92 % of patients with previously inconclusive conventional imaging. Unlike MIBI, FCH successfully localized small, hyperplastic and multiple hyperfunctioning parathyroid glands, irrespective of their histopathological composition., K. Zajíčková, D. Zogala, J. Kubinyi., and Obsahuje bibliografii
Acute streptozotocin diabetes mellitus (DM) as well as remote ischemic preconditioning (RPC) has shown a favorable effect on the postischemic-reperfusion function of the myocardium. Cardioprotective mechanisms offered by these experimental models involve the mitochondria with the changes in functional properties of membrane as the end-effector. The aim was to find out whether separate effects of RPC and DM would stimulate the mechanisms of cardioprotection to a maximal level or whether RPC and DM conditions would cooperate in stimulation of cardioprotection. Experiments were performed on male Wistar rats divided into groups: control, DM, RPC and DM treated by RPC (RPC+DM). RPC protocol of 3 cycles of 5-min hind limb ischemia followed by 5-min reperfusion was used. Ischemicreperfusion injury was induced by 30-min ischemia followed by 40-min reperfusion of the hearts in Langendorff mode. Mitochondria were isolated by differential centrifugation, infarct size assessed by staining with 1 % 2,3,5-triphenyltetrazolium chloride, mitochondrial membrane fluidity with a fluorescent probe DPH, CoQ9 and CoQ10 with HPLC. Results revealed that RPC as well as DM decreased the infarct size and preserved mitochondrial function by increasing the mitochondrial membrane fluidity. Both used models separately offered a sufficient protection against ischemic-reperfusion injury without an additive effect of their combination., M. Ferko, I. Kancirová, M. Jašová, I. Waczulíková, S. Čarnická, J. Kucharská, O. Uličná, O. Vančová, M. Muráriková, T. Ravingerová, A. Ziegelhöffer., and Obsahuje bibliografii
Spontaneously Diabetic Torii (SDT) fatty rats, a new obese diabetic model, reportedly presented with features of non-alcoholic steatohepatitis (NASH) after 32 weeks of age. We tried to accelerate the onset of NASH in SDT fatty rats using dietary cholesterol loading and noticed changes in the blood choline level which is expected to be a NASH biomarker. Body weight and biochemical parameters were measured from 8 to 24 weeks of age. At 16, 20, 24 weeks, pathophysiological analysis of the livers were performed. Hepatic lipids, lipid peroxides, and the expression of mRNA related to triglyceride (TG) synthesis, inflammation, and fibrosis were evaluated at 24 weeks. Hepatic fibrosis was observed in SDT fatty rats fed cholesterol-enriched diets (SDT fatty-Cho) from 16 weeks. Furthermore, hepatic lipids and lipid peroxide were significantly higher in SDT fatty-Cho than SDT fatty rats fed normal diets at 24 weeks. Hepatic mRNA expression related to TG secretion decreased in SDT fatty-Cho, and the mRNA expression related to inflammation and fibrosis increased in SDT fatty-Cho at 24 weeks. Furthermore, SDT fatty-Cho presented with increased plasma choline, similar to human NASH. There were no significant changes in the effects of feeding a cholesterol-enriched diet in Sprague-Dawley rats. SDT fatty-Cho has the potential to become a valuable animal model for NASH associated with type 2 diabetes and obesity., Y. Toriniwa, M. Muramatsu, Y. Ishii, E. Riya, K. Miyajima, S. Ohshida, K. Kitatani, S. Takekoshi, T. Matsui, S. Kume, T. Yamada, T. Ohta., and Obsahuje bibliografii
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
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
Glucocorticoid (GC) therapy is one of the methods of choices for treatment of autoimmune diseases (ADs). In addition, adrenal androgens are known as immunoprotective GC-antagonists. Adrenal steroids preferentially influence the Th1-components over the Th2 ones. We investigated steroid metabolome (using gas chromatography-mass spectrometry) in healthy controls (H), GC-untreated patients with ADs different from IgA nephropathy (U), GC-treated patients with ADs different from IgA nephropathy (T) and in patients with IgA nephropathy (IgAN), which were monitored on the beginning (N0), after one week (N1) and after one month (N2) of prednisolone therapy (60 mg of prednisolone/day/m2 of body surface). Between-group differences were assessed by one-way ANOVA, while the changes during the therapy were evaluated by repeated measures ANOVA. The ANOVA testing was followed by Duncan’s multiple comparisons. IgAN patients and patients with other ADs exhibited lack of adrenal androgens due to attenuated activity of adrenal zona reticularis (ZR). Androgen levels including their 7α-, 7β-, and 16α-hydroxy-metabolites were further restrained by GC-therapy. Based on these results and data from the literature, we addressed the question, whether a combination of GCs with Δ5-steroids or their more stable synthetic derivatives may be optimal for the treatment of antibodies-mediated ADs., I. Šterzl, M. Hill, L. Stárka, M. Velíková, R. Kančeva, J. Jemelková, L. Czerneková, P. Kosztyu, J. Zadražil, K. Matoušovic, K. Vondrák, M. Raška., and Obsahuje bibliografii
A tumor-targeting drug delivery system consists of a tumor recognition moiety and a directly linked cytotoxic agent or an agent attached to a water-soluble synthetic polymer carrier through a suitable linker. Conjugation of a drug with a polymer carrier can change its solubility, toxicity, biodistribution, blood clearance and therapeutic specificity. Increased therapeutic specificity of a polymer drug can be achieved by the attachment of a targeting moiety (e.g. a lectin, protein, antibody, or peptide) that specifically interacts with receptors on the target cells. A large number of tumor-specific peptides were described in recent years. After a short introduction, some important examples of peptide-targeted conjugates will be described and discussed., E. Böhmová, R. Pola., and Obsahuje bibliografii
The purpose of the present study was to define the indirect central effect of hydrogen sulfide (H2S) on baroreflex control of sympathetic outflow. Perfusing the isolated carotid sinus with sodium hydrosulfide (NaHS), a H2S donor, the effect of H2S was measured by recording changes of renal sympathetic nerve activity (RSNA) in anesthetized male rats. Perfusion of isolated carotid sinus with NaHS (25, 50, 100 μmol/l) dose and timedependently inhibited sympathetic outflow. Preconditioning of glibenclamide (20 μmol/l), a ATP-sensitive K+ channels (KATP) blocker, the above effect of NaHS was removed. With 1, 4-dihydro-2, 6-dimethyl-5-nitro-4-(2-[trifluoromethyl] phenyl) pyridine-3-carboxylic acid methyl ester (Bay K8644, 500 nmol/l) pretreatment, which is an agonist of L-calcium channels, the effect of NaHS was eliminated. Perfusion of cystathionine γ-lyase (CSE) inhibitor, DL-propargylglycine (PPG, 200 μmol/l), increased sympathetic outflow. The results show that exogenous H2S in the carotid sinus inhibits sympathetic outflow. The effect of H2S is attributed to opening KATP channels and closing the L-calcium channels., Qi Guo, Yuming Wu, Hongmei Xue, Lin Xiao, Shneg Jin, Ru Wang., and Obsahuje bibliografii