Nitric oxide (NO) is an important endogenous neurotransmitter and mediator. It participates in regulation of physiological processes in different organ systems including airways. Therefore, it is important to clarify its role in the regulation of both airway and vascular smooth muscle, neurotransmission and neurotoxicity, mucus transport, lung development and in the surfactant production. The bioactivity of NO is highly variable and depends on many factors: the presence and activity of NO-producing enzymes, activity of competitive enzymes (e.g. arginase), the amount of substrate for the NO production, the presence of reactive oxygen species and others. All of these can change NO primary physiological role into potentially harmful. The borderline between them is very fragile and in many cases not entirely clear. For this reason, the research focuses on a comprehensive understanding of NO synthesis and its metabolic pathways, genetic polymorphisms of NO synthesizing enzymes and related effects. Research is also motivated by frequent use of exhaled NO monitoring in the clinical manifestations of respiratory diseases. The review focuses on the latest knowledge about the production and function of this mediator and understanding the basic physiological processes in the airways., M. Antosova, D. Mokra, L. Pepucha, J. Plevkova, T. Buday, M. Sterusky, A. Bencova., and Obsahuje bibliografii
Clusterin is a heterodimeric glycoprotein with wide range of functions. To further explore its possible regulatory role in energy homeostasis and in adipose tissue, we measured plasma clusterin and its mRNA expression in subcutaneous adipose tissue (SCAT) of 15 healthy lean women, 15 obese women (OB) and 15 obese women with type 2 diabetes mellitus (T2DM) who underwent a 2-week very low-calorie diet (VLCD), 10 obese women without T2DM who underwent laparoscopic sleeve gastrectomy (LSG) and 8 patients with T2DM, 8 patients with impaired glucose tolerance (IGT) and 8 normoglycemic patients who underwent hyperinsulinemic euglycemic clamp (HEC). VLCD decreased plasma clusterin in OB but not in T2DM patients while LSG and HEC had no effect. Clusterin mRNA expression in SCAT at baseline was increased in OB and T2DM patients compared with controls. Clusterin mRNA expression decreased 6 months after LSG and remained decreased 12 months after LSG. mRNA expression of clusterin was elevated at the end of HE C compared with baseline only in normoglycemic but not in IGT or T2DM patients. In summary, our data suggest a possible local regulatory role for clusterin in the adipose tissue rather than its systemic involvement in the regulation of energy homeostasis., J. Kloučková, Z. Lacinová, P. Kaválková, P. Trachta, M. Kasalický, D. Haluzíková, M. Mráz, M. Haluzík., and Obsahuje bibliografii
Serum adipocyte fatty acid-binding protein (FABP-4) concentrations are linked to human obesity and other features of metabolic syndrome. Patients with Cushing's syndrome (CS) develop numerous features of metabolic syndrome due to chronic cortisol excess. Here we tested the hypothesis that chronically increased cortisol levels in CS patients may alter circulating levels of FABP-4. Fourteen patients with CS, 19 patients with simple obesity (OB) and 36 healthy control subjects (C) were included in the study. Serum FABP-4 concentrations were significantly higher in both CS and OB patients relati ve to C group, but they did not differ between CS and OB groups. In a combined population of all groups, serum FABP-4 levels correlated positively with BMI, body fat content, serum glucose, triglycerides, HbA1c and HOMA index and were inversely relate d to HDL-cholesterol, resting energy expenditure and freeT3 levels. We conclude that FABP-4 levels are significantly increased in both patients with simple obesity and obese patients with Cushing's syndrome. We suggest that increased FABP-4 concentrations in CS patients are rather due to their excessive fat accumulation and related metabolic abnormalities than due to a direct effect of cortisol on FABP-4 production., V. Ďurovcová, J. Marek, V. Hána, M. Matoulek, V. Zikán, D. Haluzíková, P. Kaválková, Z. Lacinová, M. Kršek, M. Haluzík., and Obsahuje bibliografii
The impact of anesthetic agen ts on endocrine and metabolic factors is an important issue. The present study has compared the effects of a short-term exposure to diethyl ether, isoflurane, or CO2 on plasma corticosterone, insulin and glucose concentrations since the duration of anesthetic exposure may have an effect on those factors. Male rats were divided into fed and fasted groups. The experimental rats were briefly exposed to diethyl ether, isoflurane, or CO2 (the degree of anesthesia was identical), while a control group was not exposed to the anesthetics. In the fed rats, diethyl ether exposure increased the levels of plasma glucose. CO2 exposure decreased plasma corticosterone and increased plasma glucose levels. Isoflurane exposure caused no changes in plasma corticosterone, glucose, or insulin levels. In the fasted rats, diethyl ether exposure increased plasma corticosterone and reduced plasma insulin levels. The plasma corticosterone and insulin levels were significantly increased by CO2 exposure. Isoflurane exposure decreased plasma insulin levels. A brief exposure to either diethyl ether or CO2 changed the plasma corticosterone, glucose, and insulin levels in fed and/or fasted rats. However, isoflurane exposure had the least effect on the concentration of these factors in both the fed and fasted states., H. Zardooz, F. Rostamkhani, J. Zaringhalam, F. Faraji Shahrivar., and Obsahuje bibliografii
Tissue betaine is an intracellular osmolyte that also provides a store of labile methyl groups. Despite these important biological roles, there are few data regarding tissue betaine content. We measured the betaine concentration of plasma and various tissues (brain, heart, lungs, liv er, kidney, spleen, intestine, reproductive tissues, skeletal muscle and skin) in male and female rats and assessed whether there were any gender-specific differences in betaine content or distribution and whether there was any relationship between tissue accumulation and plasma levels. Betaine was highest in the liver and kidney with values ranging from 1.6 to 9.5 mmol/l and 2.0 to 5.4 mmol/l, respectively. Plasma betaine concentrations were significantly lower than tissue levels except in the brain ( ≈ 25 % of plasma) and skeletal muscle (similar to pl asma). Regression analysis of the combined male and female data revealed a significant plasma-related accumulation of betaine in the heart, skin and skeletal muscle, while the lung, liver, kidney, spleen, and intestine showed significant plasma-related and plasma- independent accumulations of be taine. The betaine content of the skin, liver and kidney was no t significantly different between males and females, but in plasma and all tissues analyzed it was significantly higher in males (P<0.01)., S. Slow, M. Lever, S. T. Chambers, P. M. George., and Obsahuje bibliografii
Antidepressants, particularly tricyclic (TCA) antidepressants, may have cardiotoxic effects, such as cardiac arrhythmias, especially in patients with cardiovascular diseases. For most of TCA, no exact correlation between dosage, plasma levels and changes of ECG parameters of standard ECG has been found. So far, no relationship between dosulepine plasma levels and heart electric field parameters has been studied. We selected 18 female outpatient subjects diagnosed with recurrent depressive disorders, currently in the remission phase (HAMD < 10), without any cardiovascular disease. Patients were treated with daily dosulepine doses of 25-125 mg for 4-8 weeks. 30 heart electric field parameters were analyzed by Cardiag 128.1 diagnostic system as part of BSPM (Body Surface Potential Mapping). Acquired data were correlated with dosulepine plasma levels by means of Spearmanís rank order correlation test. Four ECG parameters showed a significant correlation with dosulepine plasma levels: QRS axis deviation in frontal plane (p=0.01), DIAM 40 max (p < 0.05), QRS-STT angle in transversal and left sagittal plane (p < 0.05). The demonstrated changes confirmed dosulepine influence on the early myocardium depolarization phase and the correlation of this effect with dosulepine dose (its plasma concentration). The higher the dosulepine level, the more marked are the changes of the QRS-STT angle in transversal and sagittal planes and the changes in the QRS axis deviation in frontal plane. Repeatedly recorded changes in the heart electric field were dosulepine-specific and dependent on its plasma levels., E. Kitzlerová, I. Paclt, J. Slavíček, K. Pišvejcová, M. Anders, A. Dohnalová, M. Balíková., and Obsahuje bibliografii
Microparticles are small fragments of the plasma membrane released by activated and/or apoptotic cells. In theory, all type of cells can shed microparticles representing a physiological process in the cell life. Mainly, microparticles generation has been studied in different cardiovascular pathologies due to the facility to obtain blood samples from individuals. Although microparticles have been considered as simply markers of several diseases, in the last decade, several studies support the hypothesis that they participate in the regulation of the cardiovascular system function by carrying biological messages between cells. Among the effects of microparticles, recent data show that they can be implicated in the modulation of neovascularization, an essential function of cells from cardiovascular system during either ischemic diseases or cancer development. Whereas during pathologies associated with ischemia an increase of neovascularization may have beneficial effects, anti-angiogenic strategies represent new approaches for manipulation of tumor development. Here, we give an overview of the mechanisms and factors involved in neovascularization, and finally, we look at the role and the consequences of the modulation of this process by microparticles in pathological situations., H. A. Mostefai, R. Andriantsitohaina, M. C. Martínez., and Obsahuje bibliografii a bibliografické odkazy
Obestatin is a recently discovered peptide produced in the stomach, which was originally described to suppress food intake and decrease body weight in experimental animals. We investigated fasting plasma obestatin levels in normal weight, obese and anorectic women and associations of plasma obestatin levels with anthropometric and hormonal parameters. Hormonal (obestatin, ghrelin, leptin, insulin) and anthropometric parameters and body composition were examined in 15 normal weight, 21 obese and 15 anorectic women. Fasting obestatin levels were significantly lower in obese than in normal weight and anorectic women, whereas ghrelin to obestatin ratio was increased in anorectic women. Compared to leptin, only minor differences in plasma obestatin levels were observed in women who greatly differed in the amount of fat stores. However, a negative correlation of fasting obestatin level with body fat indexes might suggest a certain role of obestatin in the regulation of energy homeostasis. A significant relationship between plasma obestatin and ghrelin levels, independent of anthropometric parameters, supports simultaneous secretion of both hormones from the common precursor. Lower plasma obestatin levels in obese women compared to normal weight and anorectic women as well as increased ghrelin to obestatin ratio in anorectic women might play a role in body weight regulation in these pathologies., H. Zamrazilová, V. Hainer, D. Sedláčková, H. Papežová, M. Kunešová, F. Bellisle, M. Hill, J. Nedvídková., and Obsahuje bibliografii a bibliografické odkazy
Plasma procalcitonin (PCT) is a highly specific marker for the diagnosis of bacterial infections and sepsis. PCT levels are usually low in viral infections, chronic inflammation or postsurgical states. The purpose of this study was to characterize PCT plasma levels in patients with various types of ileus at preoperative stage, where the other inducing factors suchas a surgical stress are excluded. The prospective study was performed on 54 patients admitted to in-patient surgical department with a proven diagnosis of ileus. Patients were divided to three groups – obstructive, vascular and paralytic ileus. Plasma levels of PCT (Kryptor analysis), TNFα, IL-1β, IL-6, cortisol (ELISA) and CRP (Kryptor ultrasensitive analysis) were estimated before any invasive procedure was realized. We demonstrated significant elevation of PCT in both obstructive ileus in adhesions and vascular ileus compared with healthy subjects (p<0.01). PCT levels were not elevated in paralytic ileus. The regression coefficient was the highest for PCT and CRP (r=0.78, p<0.01), for TNFα and IL-8 (r=0.76, p<0.01) in vascular ileus. There was no significant correlation between PCT and other inflammatory parameters. The different types of ileus induce an elevation of plasma PCT levels and PCT shows itself as an acute phase reactant. The highest PCT concentrations were presented in patients with vascular ileus, whereas paralytic ileus revealed similar cytokine and PCT pattern as in healthy subjects. Plasma PCT estimation extended to a measurement of CRP and IL-6 may become a useful complementary examination for diagnostics of acute abdomen in patients., P. Maruna, R. Fraško, R. Gürlich., and Obsahuje bibliografii a bibliografické odkazy
Tissue factor is a cell surface protein that is expressed constitutively by monocytes, macrophages and fibroblasts, but also by some other cells in response to a variety of stimuli. The main function of the tissue factor is to form a complex with factor VII/VIIa that converts factors IX and X to their active forms. Tissue factor is also involved in the pathophysiology of systemic inflammatory disorders, coagulopathies, atherosclerotic disease, tumor angiogenesis and metastasis. Increased tissue factor expression either locally in the coronary plaques or systematically on circulating blood elements of patients with acute coronary syndromes may be responsible for increased thrombin generation, thus leading to platelet activation and fibrin formation. Tissue factor therefore plays a pivotal role in the initiation of thrombotic complications in patients with coronary artery disease., J. Vojáček, J. Dušek, J. Bis, J. Šťásek, M. Blažek., and Obsahuje bibliografii a bibliografické odkazy