Od dob, kdy Galileo Galilei položil základy matematického popisu přirozených procesů, musela fyzika projít ještě složitou cestu, než zacílila se vší vážností a energií tento popis na živé organismy. Neobyčejně smělý rozvrh Reného Descarta, jehož matematicky chápaná rozprostraněnost zahrnovala i živé organismy jakožto mechanismy podléhající stejným zákonům jako cokoli neživého, ovšem nenabízel žádnou cestu, jak fyziku systematicky provozovat. Tuto cestu vytyčil až Isaac Newton. Jeho program průzkumu fyzikální reality je však založen na zkoumání pohybů a hledání sil, které tyto pohyby odchylují od pohybu rovnoměrného a přímočarého. V tomto pojetí se tak živé organismy jeví jako prakticky nepřístupné nějakému fyzikálnímu průzkumu. Pojem pohybu chápaného jako geometrická trajektorie zde ztrácí svůj zásadní význam (je řada jiných podstatných "pohybů", jako růst či rozmanité změny vnitřní struktury) a pojem síly se stává problematickým (jaké "síly" zastaví pohybující se myš?). Až ve dvacátém století se fyzika začala vážně a systematicky zabývat i živými strukturami. Bylo to zejména díky rozvoji termodynamiky, molekulární fyziky, počítačových simulací a vysoce sofistikovaných experimentálních a zobrazovacích metod., The paper deals with living matter (living tissues and individual cells) from the point of view of physics. It passes through several upůto-date approaches that are clearly physical. Starting with thermodynamics that brings us to study the free-energy dependence on microscopic parameters of living tissues, we continue with special mechanical properties of living cells and the important role of pre-stress in their "skeleton". We mention the "tensegrity approach" and review briefly the approach in which a cell is understood as a soft glassy material. Then we discuss problems of description and experimental identification of properties of living tissues and present an example outlining a pure mechanical explanation how smooth muscle cells may efficiently control mechanical behaviour of the whole tissue. The concluding discussion tries to elucidate the role of physics in understanding the secret of life., Miroslav Holeček, Petra Kochová, Zbyněk Tonar., and Obsahuje bibliografii
Lipoprotein lipase (LPL) is a key factor determining the clearance of triglycerides from the circulation. The enzyme activity is tissue-specifically regulated by insulin, but it is not clear yet how insulin regulates the total LPL activity in the circulation. To answer such question, we measured LPL activity using the intravenous fat tolerance test (IVFTT) that was carried out 1 h before as well as 2 h and 4 h after oral administration of glucose (75 g) in eleven healthy male volunteers. In control experiments, no glucose was given to the subjects. Glucose administration resulted in an expected increase in plasma glucose and insulin and in a suppression of non-esterified fatty acid concentration. The LPL activity assessed in IVFTT as a k2 rate constant did not change in control experiments and decreased to 78 % and 73 % of baseline values 2 h and 4 h after glucose administration, respectively (p=0.01). Similarly, LPL activity measured in the plasma after intravenous injection of heparin at the end of the experiments was 16 % lower (p<0.05) after glucose administration. In conclusion, LPL activity is already downregulated in vivo 2 h after glucose administration. The results of our study indicate that repeated IVFTT is a promising approach for studying acute changes in LPL activity., E. Jindřichová, S. Kratochvílová, J. Kovář., and Obsahuje bibliografii a bibliografické odkazy
Nowadays Gregor Johann Mendel is among the most renowned Czech scientists. Although his ideas about cross-pollination of plants were ahead of their time, Mendel did not suffer from his lack of success. He was a valued abbot, popular teacher, successful breeder, beekeeper and meteorologist. and Hana Laudátová, Ondřej Dostál.
Huntingtonova choroba (Huntington´s disease, HD) je smrtelné dědičné neurodegenerativní onemocnění s nástupem projevů až v dospělosti. Onemocnění je způsobeno expanzí cytozin-adenin-guanin (CAG) repetic v genu pro protein huntingtin (Htt), který je exprimován ve většině tkání. HD je charakteristická především rozsáhlou degenerací buněk centrální nervové soustavy, ale mutace má velký dopad i na další orgány a tkáně. Mechanismy těchto změn nejsou stále dostatečně popsány. Jednou z nezbytných součástí výzkumu HD jsou zvířecí modely., Huntington's disease (HD) is a fatal inherited neurodegenerative disease with onset of symptoms in adulthood. The disease is caused by the expansion of CAG repeats in the gene for the huntingtin protein, which is expressed in most tissues. HD is characterized by extensive degeneration of the cells of the central nervous system, but the mutation has a large impact on other organs and tissues too. The mechanisms of these changes have not yet been adequately described. Animal models are one of the fundamental approaches in HD research., and Daniela Pallová ... [et al.].
Previous studies revealed altered levels of the circulating insulin-like growth factor-I (IGF-I) and of its binding protein-3 (IGFBP-3) in subjects with coronary atherosclerosis, metabolic syndrome and premature atherosclerosis. Hyperlipidemia is a powerful risk factor of atherosclerosis. We expected IGF-I and IGFBP-3 alterations in subjects with moderate/severe hyperlipidemia but without any clinical manifestation of atherosclerosis. Total IGF-I and IGFBP-3 were assessed in 56 patients with mixed hyperlipidemia (MHL; cholesterol>6.0 mmol/l, triglycerides>2.0 mmol/l), in 33 patients with isolated hypercholesterolemia (IHC; cholesterol>6.0 mmol/l, triglycerides<2.0 mmol/l), and in 29 healthy controls (cholesterol<6.0 mmol/l, triglycerides<2.0 mmol/l). The molar ratio of IGF-I/IGFBP-3 was used as a measure of free IGF-I. IHC subjects differed from controls by lower total IGF-I (164±60 vs. 209±73 ng/ml, p=0.01) and IGF-I/IGFBP-3 ratio (0.14±0.05 vs. 0.17±0.04, p=0.04). Compared to controls, MHL subjects had lower total IGF-I (153±54 ng/ml, p=0.0002) and IGFBP-3 (2.8±0.6 mg/ml, p<0.0001), but higher IGF-I/IGFBP-3 ratio (0.25±0.06, p<0.0001). Differences remained significant after the adjustment for clinical and biochemical covariates, except for triglycerides. Patients with both IHC and MHL have lower total IGF-I compared to controls. The mechanism is presumably different in IHC and MHL. Because of prominent reduction of IGFBP-3 in patients with MHL, they have reduced total IGF-I despite the actual elevation IGF-I/IGFBP-3 ratio as a surrogate of free IGF-I., J. Malík, T. Štulc, D. Wichterle, V. Melenovský, E. Chytilová, Z. Lacinová, J. Marek, R. Češka., and Obsahuje bibliografii a bibliografické odkazy
Chronic hypoxia results in hypoxic pulmonary hypertension characterized by fibrotization and muscularization of the walls of peripheral pulmonary arteries. This vessel remodeling is accompanied by an increase in the amount of lung mast cells (LMC) and the presence of small collagen cleavage products in the vessel walls. We hypothesize that hypoxia activates LMC, which release matrix metalloproteinases (MMPs) cleaving collagen and starting increased turnover of connective tissue proteins. This study was designed to determine whether in vitro hypoxia stimulates production of MMPs in rat LMC and increases their collagenolytic activity. The LMC were separated on the Percoll gradient and then were divided into two groups and cultivated for 24 h in 21 % O2 + 5 % CO2 or in 10 % O2 + 5 % CO2. Presence of the rat interstitial tissue collagenase (MMP-13) in LMC was visualized by immunohistological staining and confirmed by Western blot analysis. Total MMPs activity and tryptase activity were measured in both cultivation media and cellular extracts. Exposure to hypoxia in vitro increased the amount of cells positively labeled by anti-MMP-13 antibody as well as activities of all measured enzymes. The results therefore support the concept that LMC are an important source of increased collagenolytic activity in chronic hypoxia., H. Maxová, J. Novotná, L. Vajner, H. Tomášová, R. Vytášek, M. Vízek, L. Bačáková, V. Valoušková, T. Eliášová, J. Herget., and Obsahuje bibliografii a bibliografické odkazy
The total content of rat liver microsomal cytochrome P450 (CYP) significantly decreased after repeated i.p. administration of the antiviral agent tenofovir ((R)-9-[2-(phosphonomethoxy)propyl] adenine) and tenofovir disoproxil at a daily dose 25 mg/kg, although the content of liver microsomal protein did not change. The decrease of the CYP content was accompanied by concomitant increase of the amount of inactive CYP form, cytochrome P420. This effect was confirmed by a parallel study of the activities of selected CYP forms, CYP2E1 (p-nitrophenol hydroxylation) and CYP1A2 (7-ethoxyresorufin deethylation). The activity (expressed relatively to the protein content) of both CYP forms decreased significantly following the decrease of the total CYP. On the other hand, the CYP2E1 activity expressed relatively to the decreasing total CYP content remained unchanged. However, CYP1A2 activity also decreased when calculated relatively to the total native CYP content indicating lower stability of this form. Semiquantitative RT-PCR showed no significant changes in expression of major rat liver microsomal CYP forms after tenofovir treatment. In conclusion, repeated administration of tenofovir in higher doses led to significant decrease of the relative proportion of active liver microsomal CYPs accompanied by a conversion of these enzymes to the inactive form (CYP420) maintaining the sum of CYP proteins unchanged., E. Anzenbacherová, P. Anzenbacher, Z. Zídek, E. Buchar, E. Kmoníčková, P. Potměšil, J. Nekvindová, A. Veinlichová, A. Holý., and Obsahuje bibliografii a bibliografické odkazy
Galanin (GAL) is suggested to be a neuropeptide involved in pain transmission. In this study we tried to determine, whether the increase of GAL concentration in brain cells affects impulse transmission between the motor centers localized in the vicinity of the third and fourth cerebral ventricles. The experiments were carried out on rats under chloralose anesthesia. The study objectives were realized using the method allowing to record the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation during the perfusion of the cerebral ventricles with solutions containing tested compounds. Perfusion of the cerebral ventricles with GAL concentration-dependently inhibited the ETJ amplitude. The antinociceptive effect of GAL was blocked by a galanin receptor antagonist, galantide (GLT) and by opioid antagonists: non-selective naloxone (Nal) and μ-selective β-funaltrexamine (β-FNA). In contrast, a δ-opioid receptor antagonist, naltrindole (NTI) or the κ-opioid receptor antagonist, nor-binaltrophimine (nor-BNI) did not inhibit the effect of GAL. The antinociceptive effect of GAL was more pronounced when GAL was perfused in combination with other neuropeptides/neurohormones, such as endomorphin-2 (EM-2), vasopressin (AVP) and oxytocin (OT). The present results demonstrate that in the orofacial area analgesic activity is modulated by GAL, OT and AVP and that EM-2-induced antinociception involves GAL., M. Zubrzycka, A. Janecka., and Obsahuje bibliografii a bibliografické odkazy
Leptin is a hormone primarily secreted by adipocytes and participating in the regulation of food intake and energy expenditure. Its blood levels usually correlate with adiposity. The secretion of this hormone is affected, among others, by food consumption, insulin, fasting and cold exposure. Regulation of leptin secretion depends on many intracellular events. It is known that the activation of mTOR (the mamma lian target of rapamycin) as well as increase in ATP and malonyl-CoA content in adipocytes enhance secretion of leptin. The rise in intracellular cAMP and fatty acids is thought to evoke the opposite effect. Moreover, the undisturbed action of endogenous adenosine in adipocytes and the proper intracellular Ca2+ concentration in these cells were also found to have an important function in leptin release. The role of mTOR, ATP, cAMP, fatty acids, malonyl-CoA, adenosine and Ca2+ in the regulation of leptin secretion from adipocytes is discussed., T. Szkudelski., and Obsahuje bibliografii a bibliografické odkazy
The effect of exogenous noradrenaline (NA) (1.6 mg.kg-1 i.p., 35 min prior sacrifice) on the activity of antioxidant enzymes (AOE) copper zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD) and catalase (CAT), as well as lipid peroxides (LP) concentration were studied in the rat interscapular brown adipose tissue (IBAT) and heart of saline (controls) and Nω-nitro-L-arginine methyl ester (L-NAME) treated rats (10 mg.kg-1, i.p., during 3 days and 20 min before NA). NA differently affects both AOE activities and LP production in the IBAT and heart. Thus, NA inhibited the activity of all IBAT AOE and LP production while in the heart it markedly increased CAT activity only, but had no effect on any of SODs activities and LP concentration. L-NAME, a nitric oxide synthase blocker, completely abolished the NA-induced inhibition of the IBAT AOE and LP production, whereas in the heart it was without effect. In conclusion, these results indicate that both NA and L-NAME effects on AOE activity and LP production are tissue specific and also suggest that nitric oxide mediates the NA-induced inhibition of AOE activity and LP production in the IBAT only., A. Perovic, T. Vuckovic, G. Cvijic, J. Djordjevic, V. Davidovic., and Obsahuje bibliografii a bibliografické odkazy