We investigated hematopoiesis in untreated and ionizing radiation-exposed cyclooxygenase-2-deficient (COX-2 KO) mice. We performed a complex hematological analysis of 16 parameters in untreated COX-2 KO male mice or COX-2 KO male mice irradiated with the dose of 4 Gy of γ-rays and their wildtype littermates. At baseline, hematopoiesis was increased in COX-2-deficient mice, but attenuated by irradation in COX-2- deficient mice compared to wildtype. To conclude, the antiinflammatory action of the COX-2 genetic disruption plays a positive role in hematopoiesis under basal conditions but is detrimental following radiation exposure., M. Hofer, Z. Hoferová L. Dušek, K. Souček, A. Gruzdev., and Obsahuje bibliografii
In this work, design and synthesis of high-molecular-weight N-(2- hydroxypropyl)methacrylamide-based polymer drug delivery systems tailored for cancer therapy is summarized. Moreover, the influence of their architecture on tumor accumulation and in vivo anti-cancer efficacy is discussed. Mainly, the high-molecularweight delivery systems, such as branched, grafted, multi-block, star-like or micellar systems, with molecular weights greater than the renal threshold are discussed and reviewed in detail., L. Kostka, T. Etrych., and Obsahuje bibliografii
A high VO2max in middle-age is related to high metabolic flexibility and lowered risk of metabolic diseases. However, the influence of a high VO2max induced by years of regular training in middle-age on protein expression related to muscle metabolism is not well studied. This study measures key proteins involved in mitochondrial oxidation, glucose and lipid metabolism in skeletal muscle of trained and untrained middle-aged men. 16 middle-aged men, matched for lean body mass, were recruited into an endurance trained (TR, n=8) or an untrained (CON, n=8) group based on their VO2max. A muscle biopsy was obtained from m. vastus lateralis and protein levels were analyzed by Western blotting. The TR had higher protein levels of mitochondrial complex III-V, endothelial lipase (EL) and perilipin 5 compared to the CON. Glycogen synthase (P=0.05), perilipin 3 (P=0.09) and ATGL (P=0.09) tended to be higher in TR than CON, but there was no difference in AKT I/II, HKII, GLUT4 and LPL protein expression. Lastly, there was a positive correlation between plasma HDL and EL (R2=0.53, P<0.01). In conclusion, a high VO2max in middle-aged men was as expected is reflected in higher muscle oxidative capacity, but also in higher endothelial lipase and perilipin 5 expression and a borderline higher glycogen synthase protein expression, which may contribute to a higher metabolic flexibility., A. Vigelsø, C. Prats, T. Ploug, F. Dela, J. W. Helge., and Obsahuje bibliografii
Here we analyzed associations between muscles mass, total bone mineral content (BMC), lumbar spine bone density (BMD L1-L4) and serum or urine hormones in healthy peripubertal girls. Total BMC and areal BMD L1-L4, muscle mass and fat were measured by dual-energy X-ray absorptiometry (DXA). Muscle force (N) was estimated by a dynamometer. Circulating estradiol, folliclestimulating hormone (FSH), luteinizing hormone (LH), 25-hydroxy vitamin D, parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), leptin, osteocalcin, bone isoenzyme of alkaline phosphatase (bALP) and total calcium and phosphorus were quantified as the nocturnal melatonin and serotonin urinary excretion. Partial correlations adjusted for height, Tanner score and physical activity confirmed positive relationships between BMC or BMD L1-L4 (Z-score) and lean mass or fat. Furthermore, positive relationship was observed between BMC or BMD L1-L4 (Z-score) and serum leptin. After adjustment for Tanner score and physical activity, positive associations were observed between lean mass and IGF-1, leptin levels or muscle force. We proved positive relationships between bone mass and serum leptin in peripubertal girls., V. Cirmanova, I. Zofkova, P. Kasalicky, V. Lanska, M. Bayer, L. Starka, R. Kanceva., and Obsahuje bibliografii
Testosterone has been widely investigated in associations with many aspects of social interactions, emotions and behavior. No research has been conducted on its contribution to the variability of love styles in human. The aim of this paper was to uncover the possible relationship between not only the actual plasma testosterone levels, but also the prenatal testosterone level (expressed as 2D:4D ratio) and the sensitivity of androgen receptor and love typology in young healthy men. There are six love styles which are primary including Eros (passionate romantic love), Ludus (playful) and Storge (friendly) and secondary love consisting of Mania (obsessive), Pragma (practical realistic) and Agape (altruistic). Our results pointed out that low testosterone concentrations are associated with higher score for Eros, Ludus, Pragma, Mania love style. No significant association was proved for other tested parameters of androgenicity (2D:4D, sensitivity of androgen receptor) and love style after correction was applied. Different attitudes and behavior in relationships do have a biological foundation related to endogenous testosterone levels in plasma. Future studies should address questions about the family and social background of participants to differentiate here between moral rules or/and social-conventional rules., J. Babková Durdiaková, P. Celec, I. Koborová, T. Sedláčková, G. Minárik, D. Ostatníková., and Obsahuje bibliografii
Hormones exert many actions in the brain. Their access and effects in the brain are regulated by the blood-brain barrier (BBB). Hormones as other substances may enter the brain and vice versa either by paracellular way requiring breaching tight junctions stitching the endothelial cells composing the BBB, or by passage through the cells (transcellular way). Hormones influence both ways through their receptors, both membrane and intracellular, present on/in the BBB. In the review the main examples are outlined how hormones influence the expression and function of proteins forming the tight junctions, as well as how they regulate expression and function of major protein transporters mediating transport of various substances including hormone themselves., R. Hampl, M. Bičíková, L. Sosvorová., and Obsahuje bibliografii
In this paper, we describe the synthesis, physicochemical characterization, drug release kinetics and preliminary biological evaluation of several N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer-retinoid conjugates designed for solid tumor immunotherapy. The conjugates are supposed to inhibit the immunosuppressive activity of myeloid-derived suppressor cells (MDSC) accumulated in the solid tumor microenvironment. All-trans retinoic acid (ATRA) was derivatized to hydrazide (AtrHy) and then attached to the polymer backbone via a spacer that is stable at the normal pH of blood (7.4) and hydrolytically degradable in mildly acidic environments (e.g. in endosomes or lysosomes, pH~5.0-6.5). Polymer-AtrHy conjugates were designed to achieve prolonged blood circulation and release of the immunomodulator intracellularly or extracellularly in solid tumor tissue. Three types of polymer precursors, differing in the structure of the keto acid-containing side chains, were synthesized. A linkage susceptible to hydrolytic cleavage was formed by the conjugation reaction of the carbonyl groupterminated side chains of the polymer precursors with the hydrazide group of a drug derivative. In vitro incubation of the conjugates in buffers resulted in much faster release of the drugs or their derivatives from the polymer at pH 5.0 than at pH 7.4, with the rate depending on the detailed structure of the spacer. Both the AtrHy derivative and its polymer conjugates showed the ability to induce the differentiation of retinoid-responsive HL-60 cells, thus demonstrating the required biological activity., O. Lidický, M. Šírová, T. Etrych., and Obsahuje bibliografii
There is evidence that a higher serum level of bilirubin (BIL) may be a protective factor for autoimmune diseases. We examined the effect of BIL supplementation in adjuvant-induced arthritis (AIA) where oxidative stress, inflammation and inadequate immune response are present. Male Lewis rats were randomized into groups: CO - control, AIA - untreated adjuvant-induced arthritis, AIA-BIL - adjuvant-induced arthritis administrated BIL (200 mg/kg b.w. daily i.p. during 14 days). Change of hind paw volume in the AIA-BIL group in comparison to the AIA group was significantly decreased after BIL administration. In CO and AIA groups we found almost untraceable levels of BIL. In the AIA-BIL group hyperbilirubinemia was observed. BIL administration significantly decreased plasma levels of C-reactive protein and ceruloplasmin in the AIA-BIL group in comparison to the AIA group. The values of white and red blood cells, hemoglobin and hematocrit were significantly decreased in AIA-BIL after BIL supplementation. Organs like spleen and thymus had a lower weight in AIA-BIL than in AIA. Histological findings showed decreased or even absent damage in hind paw joint of AIA-BIL animals. We observed an immunomodulatory effect of BIL on AIA development, which may also have a novel pharmacological impact., K. Bauerova, F. Drafi, V. Kuncirova, S. Ponist, D. Mihalova, P. Babal, T. Sykora., and Obsahuje bibliografii
The metabolic pathways that contribute to maintain serum calcium concentration in narrow physiological range include the bone remodeling process, intestinal absorption and renal tubule resorption. Dysbalance in t hese regulations may lead to hyper - or hypocalcemia. Hypercalcemia is a potentionally life -threatening and relatively common clinical problem, which is mostly associated with hyperparathyroidism and/or malignant diseases (90 %). Scarce causes of hypercalce mia involve renal failure, kidney transplantation, endocrinopathies, granulomatous diseases, and the long -term treatment with some pharmaceuticals (vitamin D, retinoic acid, lithium). Genetic causes of hypercalcemia involve familial hypocalciuric hypercalc emia associated with an inactivation mutation in the calcium sensing receptor gene and/or a mutation in the CYP24A1 gene. Furthermore, hypercalcemia accompanying primary hyperparathyroidism, which develops as part of multiple endocrine neoplasia (MEN1 and MEN2), is also genetically determined. In this review mechanisms of hypercalcemia are discussed. The objective of this article is a review of hypercalcemia obtained from a Medline bibliographic search., I. Žofková., and Obsahuje bibliografii
With the increasing prevalence of obesity and especially abdominal obesity, a simple clinical tool is needed that identifies the cardiometabolic risk for cardiovascular disease and type 2 diabetes. The aim of our study was to evaluate a broad spectrum of metabolic variables and IMT in subjects with and without hypertriglyceridemic waist (HTGW) and compare it with the harmonized definition of metabolic syndrome (MS) with both a higher (MS- I) and lower waist circumference (MS -II) for Europids. We enrolled 607 asymptomatic dyslipidemic subjects (295 men and 312 women) into our cross -sectional study. The subjects with HTGW had an atherogenic lipid profile (significantly higher triglycerides, AIP, non -HDL -C, lower HDL -C and ApoA -1, and the women also higher TC and ApoB), increased markers of insulin resistance (insulin, HOMA, C -peptide, proinsulin), inflammation (hsCRP), thrombosis (fibrinogen, PAI -1), SBP and DBP, and lower adiponectin (p<0.05 -0.001 for all). These risk factors were entirely similar in HTGW, MS- I and MS -II. Age -adjusted IMT was significantly higher only in the women with HTGW but this significance disappeared after further adjustment for TC, SBP, and smoking. Our results support the routine use of HTGW as a simple and inexpensive screening tool to detect subjects at increased cardiometabolic risk in clinical practice., H. Vaverková, D. Karásek, D. Novotný, M. Halenka, J. Orság, L. Slavík., and Obsahuje bibliografii