Nickel is a ubiquitous environmental pollutant, which has various effects on reproductive endocrinology. In this study, human adrenocortical carcinoma (NCI-H295R) cell line was used as an in vitro biological model to study the effect of nickel chloride (NiCl2) on the viability and steroidogenesis. The cells were exposed to different concentrations (3.90; 7.80; 15.60; 31.20; 62.50; 125; 250 and 500 μM) of NiCl2 and compared with control group (culture medium without NiCl2). The cell viability was measured by the metabolic activity assay. Production of sexual steroid hormones was quantified by enzyme linked immunosorbent assay. Following 48 h culture of the cells in the presence of NiCl2 a dose-dependent depletion of progesterone release was observed even at the lower concentrations. In fact, lower levels of progesterone were detected in groups with higher doses (≥125 μM) of NiCl2 (P<0.01), which also elicited cytotoxic action. A more prominent decrease in testosterone production (P<0.01) was also noted in comparison to that of progesterone. On the other hand, the release of 17β-estradiol was substantially increased at low concentrations (3.90 to 62.50 μM) of NiCl2. The cell viability remained relatively unaltered up to 125 μM (P>0.05) and slightly decreased from 250 μM of NiCl2 (P<0.05). Our results indicate endocrine disruptive effect of NiCl2 on the release of progesterone and testosterone in the NCI-H295R cell line. Although no detrimental effect of NiCl2 (≤62.50 μM) could be found on 17β-estradiol production, its toxicity may reflect at other points of the steroidogenic pathway., Norbert Lukac, Zsolt Forgacs, Hana Duranova, Tomas Jambor, Jirina Zemanova, Peter Massanyi, Barbara Tombarkiewicz, Shubhadeep Roychoudhury, Zuzana Knazicka., and Obsahuje bibliografii
Chronic inflammation of adipose tissue is associated with the pathogenesis of cardiovascular diseases. Mast cells represent an important component of the innate defense system of the organism. In our work, we quantified mast cell number in epicardial adipose tissue (EAT), subcutaneous adipose tissue (SAT), and right atrial myocardium (RA) in patients undergoing open heart surgery (n=57). Bioptic samples of EAT (n=44), SAT (n=42) and RA (n=17) were fixed by 4 % paraformaldehyde and embedded into paraffin. An anti-mast cell tryptase antibody was used for immunohistochemical detection and quantification of mast cells. We also demonstrated immunohistochemically the expression of CD117 and chymase markers. In EAT of patients with coronary artery disease (CAD), higher incidence of mast cells has been found compared to patients without CAD (3.7±2.6 vs. 2.1±1.2 cells/mm2 ). In SAT and RA, there was no difference in the number of mast cells in CAD and non-CAD patients. Mast cells in SAT, EAT and RA expressed CD117 and chymase. An increased incidence of mast cells in EAT of CAD patients may indicate the specific role of these inflammatory cells in relation to EAT and coronary arteries affected by atherosclerosis., Karolína Rozsívalová, Aneta Pierzynová, Helena Kratochvílová, Jaroslav Lindner, Michal Lipš, Tomáš Kotulák, Peter Ivák, Ivan Netuka, Martin Haluzík, Tomáš Kučera., and Obsahuje bibliografii
Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is a technique used in patients with severe heart failure. The aim of this study was to evaluate its effects on left ventricular afterload and fluid accumulation in lungs with electrical impedance tomography (EIT). In eight swine, incremental increases of extracorporeal blood flow (EBF) were applied before and after the induction of ischemic heart failure. Hemodynamic parameters were continuously recorded and computational analysis of EIT was used to determine lung fluid accumulation. With an increase in EBF from 1 to 4 l/min in acute heart failure the associated increase of arterial pressure (raised by 44 %) was accompanied with significant decrease of electrical impedance of lung regions. Increasing EBF in healthy circulation did not cause lung impedance changes. Our findings indicate that in severe heart failure EIT may reflect fluid accumulation in lungs due to increasing EBF., Michaela Popková, Eduard Kuriščák, Pavel Hála, David Janák, Leoš Tejkl, Jan Bělohlávek, Petr Ošťádal, Petr Neužil, Otomar Kittnar, Mikuláš Mlček., and Obsahuje bibliografii
Histidine (HIS) is an essential amino acid investigated for therapy of various diseases, used for tissue protection in transplantation and cardiac surgery, and as a supplement to increase muscle performance. The data presented in the review show that HIS administration may increase ammonia and affect the level of several amino acids. The most common are increased levels of alanine, glutamine, and glutamate and decreased levels of glycine and branched-chain amino acids (BCAA, valine, leucine, and isoleucine). The suggested pathogenic mechanisms include increased flux of HIS through HIS degradation pathway (increases in ammonia and glutamate), increased ammonia detoxification to glutamine and exchange of the BCAA with glutamine via L-transporter system in muscles (increase in glutamine and decrease in BCAA), and tetrahydrofolate depletion (decrease in glycine). Increased alanine concentration is explained by enhanced synthesis in extrahepatic tissues and impaired transamination in the liver. Increased ammonia and glutamine and decreased BCAA levels in HIS-treated subjects indicate that HIS supplementation is inappropriate in patients with liver injury. The studies investigating the possibilities to elevate carnosine (β-alanyl-L-histidine) content in muscles show positive effects of β-alanine and inconsistent effects of HIS supplementation. Several studies demonstrate HIS depletion due to enhanced availability of methionine, glutamine, or β-alanine., Milan Holeček., and Obsahuje bibliografii
Current knowledge suggests a complex role of C-peptide in human physiology, but its mechanism of action is only partially understood. The effects of C-peptide appear to be variable depending on the target tissue, physiological environment, its combination with other bioactive molecules such as insulin, or depending on its concentration. It is apparent that C-peptide has therapeutic potential for the treatment of vascular and nervous damage caused by type 1 or late type 2 diabetes mellitus. The question remains whether the effect is mediated by the receptor, the existence of which is still uncertain, or whether an alternative non-receptor-mediated mechanism is responsible. The Institute of Endocrinology in Prague has been paying much attention to the issue of C-peptide and its metabolic effect since the 1980s. The RIA methodology of human C-peptide determination was introduced here and transferred to commercial production. By long-term monitoring of C-peptide oGTT-derived indices, the Institute has contributed to elucidating the pathophysiology of glucose tolerance disorders. This review summarizes the current knowledge of C-peptide physiology and highlights the contributions of the Institute of Endocrinology to this issue., Daniela Vejrazkova, Marketa Vankova, Petra Lukasova, Josef Vcelak, Bela Bendlova., and Obsahuje bibliografii
Cancer is a complex, multifactorial disease that modern medicine ultimately aims to overcome. Downstream of tyrosine kinase 2 (DOK2) is a well-known tumor suppressor gene, and a member of the downstream protein DOK family of tyrosine kinases. Through a search of original literature indexed in PubMed and other databases, the present review aims to extricate the mechanisms by which DOK2 acts on cancer, thereby identifying more reliable and effective therapeutic targets to promote enhanced methods of cancer prevention and treatment. The review focuses on the role of DOK2 in multiple tumor types in the lungs, intestines, liver, and breast. Additionally, we discuss the potential mechanisms of action of DOK2 and the downstream consequences via the Ras/MPAK/ERK or PI3K/AKT/mTOR signaling pathways., Pei Sun, Rumeng Li, Yingying Meng, Shijun Xi, Qinqi Wang, Xiulan Yang, Xiaochun Peng, Jun Cai., and Obsahuje bibliografii
Iodine is essential in the biosynthesis of thyroid hormones that affect metabolic processes in the organism from the prenatal state to the elderly. The immediate indicator of iodine intake is the concentration of iodine in urine, but the indicator of iodine intake in the longer term of several months is thyroglobulin (Tg). Tg negatively correlated with increasing intake of iodine in population that do not suffer from thyroid disease, while a more than adequate to excessive iodine intake leads to an increase in Tg. The dependence of Tg on iodine can be described by a U-shaped curve. Thyroglobulin in serum is elevated in thyroid disease mainly in hyperthyroidism (diagnosis E05 of WHO ICD-10 codes) and in goiter (diagnosis E04 of WHO ICD-10 codes). Tg values decrease below 20 µg/l after effective treatment of patients with thyroid disease. Thyroglobulin may thus be an indicator of thyroid stabilization and the success of the thyroid gland treatment., Radovan Bílek, Marcela Dvořáková, Tereza Grimmichová, Jan Jiskra., and Obsahuje bibliografii
Application of knowledge about ischemic tolerance to clinic requires the solid understanding of mechanism of creation of this phenomenon. This review summarizes research that has been carried out in many laboratories over a long period of time, but the main focus will be on own experimental research. The main emphasis is devoted to the possibility of preparing full tolerance in the donor's body and its transfer to the patient in the form of activated blood plasma. Such plasma could be administered as soon as the patient is transported to the hospital and would take effect immediately after administration to the patient's bloodstream. One chapter is also devoted to anticonditioning, i.e. the possibility of preventing the activation of tolerance. Anticonditioning could be used to treat oncologic patients. We expect that this method could increase effectiveness of cancer treatment. Cross-tolerance with a wide range of diverse stressors gives us the courage to assume that activated plasma can significantly help with a wide range of pathological events., Jozef Burda, Rastislav Burda., and Obsahuje bibliografii
Leptin-melanocortin pathway plays an essential role in the body weight regulation. Enhanced melanocortin signaling in the hypothalamus results in both decreased food intake and increased energy expenditure. The discovery of monogenic obesities with dysfunction of melanocortin-4 receptor (MC4R) greatly contributed to understanding of energy balance regulation. This review presents phenotypical characterization and prevalence of the MC4R gene mutations. Genome-wide association studies revealed that MC4R gene is significantly related not only to monogenic obesities but also to common obesity. An interaction of variants in the MC4R gene with fat mass and obesity associated (FTO) gene significantly increases the risk for obesity, particularly in adolescence. On the other hand, about 15 % of the MC4R gene variants result in a gain of function that protects against obesity and is associated with favorable metabolic profile. Long-term attempts to activate the MC4R have recently been finalized by a discovery of setmelanotide, a novel specific MC4R agonist that is devoid of untoward cardiovascular side-effects. The employment of specific MC4R agonists may open new horizons not only in the treatment of rare monogenic obesities but also in some common obesities where stimulation of MC4R could be achieved., Vojtěch Hainer, Irena Aldhoon Hainerová, Marie Kunešová, Radka Taxová Braunerová, Hana Zamrazilová, Běla Bendlová., and Obsahuje bibliografii
Midazolam is a short acting sedative with small number of adverse effects. Administered orally, it is currently the most common form of conscious sedation in children. The objective of this paper is to describe effect of midazolam administered to children during dental treatment on their vital signs, and to monitor changes in children’s behavior. We described values of vital signs and behavior in 418 sedations conducted in 272 children between 1-12 years of age. To achieve the following results, we used data from 272 all first-time sedations. After administration of midazolam arterial blood pressure and blood oxygen saturation decreased by values which were not clinically significant. The heart rate increased, with values staying within the limits of physiological range. The speed of onset of midazolam’s clinical effects depends on age and dose. The lower age and dose correlated with the higher behavior score. The effectiveness of midazolam treatment is 97.8 %. Unwillingness of child to receive midazolam is predictor for disruptive behavior during sedation. 1.8 % of all sedation cases showed paradoxical reactions. The administration of midazolam in dose of 0.5 mg per 1 kg of child’s body weight is safe and could be recommended for dental treatment in pediatric dentistry., Jana Vasakova, Jana Duskova, Jitka Lunackova, Klara Drapalova, Lucie Zuzankova, Luboslav Starka, Michaela Duskova, Zdenek Broukal., and Obsahuje bibliografii