The purpose of this study was to evaluate the effects of hyperglycemia on skeletal muscle recovery following disuseinduced muscle atrophy in rats. Wistar rats were grouped as streptozotocin-induced diabetic rats and non-diabetic rats. Both ankle joints of each rat were immobilized to induce atrophy of the gastrocnemius muscles. After two weeks of immobilization and an additional two weeks of recovery, tail blood and gastrocnemius muscles were isolated. Serial cross sections of muscles were stained for myosin ATPase (pH 4.5) and alkaline phosphatase activity. Serum insulin and muscle insulin-like growth factor-1 (IGF-1) levels were also measured. Serum insulin levels were significantly reduced in the diabetic rats compared to the non-diabetic controls. The diameters of type I, IIa, and IIb myofibers and capillary-to-myofiber ratio in the isolated muscle tissue were decreased after immobilization in both treatments. During the recovery period, these parameters were restored in the non-diabetic rats, but not in the diabetic rats. In addition, muscle IGF-1 levels after recovery increased significantly in the non-diabetic rats, but not in the diabetic rats. We conclude that decreased levels of insulin and IGF-1 and impairment of angiogenesis associated with diabetes might be partly responsible for the inhibition of regrowth in diabetic muscle., H. Kataoka, J. Nakano, Y. Morimoto, Y. Honda, J. Sakamoto, T. Origuchi, M. Okita, T. Yoshimura., and Obsahuje bibliografii
Hyperinflation is the consequence of a dysbalance of static forces (determining the relaxation volume) and/or of the dynamic components. The relaxation volume is determined by an equilibrium between the elastic recoil of the lungs and of the chest walls. The dynamic components include the pattern of breathing, upper airway resistance and postinspiratory activity of inspiratory muscles. The respiratory and laryngeal muscles are under control and thus both static and dynamic hyperinflation can be secured. Our knowledge of the mechanism of increased FRC is based on clinical observations and on experiments. The most frequent stimuli leading to a dynamic increase of functional residual lung capacity (FRC) include hypoxia and vagus afferentation. Regulation of FRC is still and undetermined concept. The controlled increase of FRC, hyperinflation, participates in a number of lung diseases., F. Paleček., and Obsahuje bibliografii
The aim of the study was to compare the effect of short-term hyperglycemia and short-term hyperinsulinemia on parameters of oxidative stress in Wistar rats. Twenty male rats (aged 3 months, average body weight 325 g) were tested by hyperinsulinemic clamp (100 IU/l) at two different glycemia levels (6 and 12 mmol/l). Further 20 rats were used as a control group infused with normal saline (instead of insulin) and 30 % glucose simultaneously. Measured parameters of oxidative stress were malondialdehyde (MDA), reduced glutathione (GSH) and total antioxidant capacity (AOC). AOC remained unchanged during hyperglycemia and hyperinsulinemia. Malondialdehyde (as a marker of lipid peroxidation) decreased significantly (p<0.05) during the euglycemic hyperinsulinemic clamp, and increased significantly during isolated hyperglycemia without hyperinsulinemia. Reduced glutathione decreased significantly (p<0.05) during hyperglycemia without hyperinsulinemia. These results suggest that the short-term exogenous hyperinsulinemia reduced the production of reactive oxygen species (ROS) during hyperglycemia in an animal model compared with the control group., P. Kyselová, M. Žourek, Z. Rušavý, L. Trefil, J. Racek., and Obsahuje bibliografii
a1_Chronic hypoxia causes pulmonary hypertension, the mechanism of which includes altered collagen metabolism in the pulmonary vascular wall. This chronic hypoxic pulmonary hypertension is gradually reversible upon reoxygenation. The return to air after the adjustment to chronic hypoxia resembles in some aspects a hyperoxic stimulus and we hypothesize that the changes of extracellular matrix proteins in peripheral pulmonary arteries may be similar. Therefore, we studied the exposure to moderate chronic hyperoxia (FiO2 = 0.35, 3 weeks) in rats and compared its effects on the rat pulmonary vasculature to the effects of recovery (3 weeks) from chronic hypoxia (FiO2 = 0.1, 3 weeks). Chronically hypoxic rats had pulmonary hypertension (Pap = 26±3 mm Hg, controls 16±1 mm Hg) and right ventricular hypertrophy. Pulmonary arterial blood pressure and right ventricle weight normalized after 3 weeks of recovery in air (Pap = 19±1 mm Hg). The rats exposed to moderate chronic hyperoxia also did not have pulmonary hypertension (Pap = 18±1 mm Hg, controls 17±1 mm Hg). Collagenous proteins isolated from the peripheral pulmonary arteries (100-300 mm) were studied using polyacrylamide gel electrophoresis. A dominant low molecular weight peptide (approx. 76 kD) was found in hypoxic rats. The proportion of this peptide decreases significantly in the course of recovery in air. In addition, another larger peptide doublet was found in rats recovering from chronic hypoxia. It was localized in polyacrylamide gels close to the zone of a2 chain of collagen type I. It was bound to anticollagen type I antibodies. An identically localized peptide was found in rats exposed to moderate chronic hyperoxia. The apparent molecular weight of this collagen fraction suggests that it is a product of collagen type I cleavage by a rodent-type interstitial collagenase (MMP-13)., a2_We conclude that chronic moderate hyperoxia and recovery from chronic hypoxia have a similar effect on collagenous proteins of the peripheral pulmonary arterial wall., J. Novotná, J. Bíbová, V. Hampl, Z. Deyl, J. Herget., and Obsahuje bibliografii
We investigated the influence of oxygenation of in vitro lung preparation on the pulmonary vascular reactivity. Small pulmonary vessels isolated from adult male Wistar rats exposed for 4 days to hypoxia (FiO2 = 0.1, group CH) were compared with those of normoxic controls (group N). The bath in the chamber of small vessel myograph was saturated with gas mixture containing either 21 % or 95 % of O2 with 5 % CO2 and we measured the reactions of vessels to acute hypoxic challenge with 0 % O2 or to PGF2α. We did not observe any difference of the contractile responses between both groups when the normoxic conditions were set in the bath. When the bath oxygenation was increased to 95 % O2, the contractions induced by hypoxic challenge and PGF2α decreased in chronically hypoxic rats and did not change in normoxic controls. We hypothesize that reduced reactivity of vessels from hypoxic rats in hyperoxia results from the effect of chronic hypoxia on Ca2+ signaling in the vascular smooth muscle, which is modulated by increased free radical production during the exposure to chronic hypoxia and further hyperoxia., M. Žaloudíková, M. Vízek, J. Herget., and Obsahuje seznam literatury
Experimental pneumonia induced by intratracheal application of carrageenan or paraquat increases the functional residual lung capacity (FRC) in rats. The mechanism of this increase is not clear, but a decrease in PO2 may be involved. To test this possibility, we attempted to eliminate the PO2 decrease in carrageenan-treated rats by exposing them to hyperoxia. Animals of the first group were exposed to 7 days of hyperoxia (FIO2 0.78-0.84, group Car+O2) after intratracheal application of carrageenan (0.5 ml of 0.7 % carageenan in saline), whereas animals of the second group were given the same dose of carrageenan but breathed air (group Car+A). The third group of rats was kept for seven days in hyperoxia (group O2) and the fourth group served as controls (C). The animals were then anesthetized and intubated and their ventilatory parameters and FRC were measured during air breathing. Carrageenan application induced a FRC increase (Car+A 2.0±0.2 ml, C 1.6±0.1 ml), which was not seen in carrageenan-treated rats exposed to hyperoxia (Car+O2 1.6±0.1 ml). Hyperoxia alone did not affect the value of FRC (O2 1.5±0.1 ml). These results support the hypothesis that a decrease in PO2 plays an important role in the carrageenan-induced increase of FRC in rats., B. Fišárková, M. Vízek., and Obsahuje bibliografii
Hyperhomocysteinemia has been suggested to induce hypertension due to its role in endothelial dysfunction. However, it remains controversial whether homocysteine and hypertension are truly causally related or merely loosely associated. To test the hypothesis that hyperhomocysteinemia occurs in spontaneously hypertensive rats (SHR) we measured plasma levels of homocysteine in 10 male adult SHR and in 10 normotensive controls using ion exchange chromatography. In addition, plasma concentrations of the 22 most common amino acids were measured to explore the relation of homocysteine with amino acid metabolism. Plasma levels of homocysteine were significantly lower in SHR (4.1±0.1 μmol/l) than in controls (7.2±0.3 μmol/l) (p<0.00001). The amounts of aminobutyric acid, alanine, citrulline and valine were also decreased, whereas we found increased levels of aspartate, glutamate, glutamine, histidine and ornithine. Thus, contrary to our hypothesis, hypertension in SHR occurs despite low plasma levels of homocysteine. We provide a new hypothesis whereby reduced conversion of arginine to citrulline is related to increased ornithine levels, but decreased bioavailability of nitric oxide, resulting in impaired blood vessel relaxation and hypertension. In conclusion, our findings do not necessarily exclude that homocysteine and hypertension might be pathophysiologically connected, but corroborate the notion that hypertension can arise due to mechanisms independent of high homocysteine levels., D. Kondziella, H. Zetterberg, E. Haugen, M. Fu., and Obsahuje bibliografii a bibliografické odkazy
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
Relatively frequent pituitary hormone deficiencies are observed after traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) and according to the published studies the neuroendocrine consequenses of traumatic brain injury are underdiagnosed. In a cohort of 59 patients (49 males, mean age 68.3 years, 36-88 years) after evacuation of subdural hematoma (SDH) were evaluated hypothalamo-pituitary functions one week after surgery, after three months and after one year. Hypogonadism was present in 26 % of patients in an acute phase, but in the majority had a transient character. Less than half of patients was GH deficient (GHD) according to the GHRH+arginine test. We did not find any serious case of hypocortisolism, hypothyroidism, diabetes insipidus centralis nor syndrome of inappropriate secretion of ADH (SIADH). Transient partial hypocortisolism was present in two cases, but resolved. We did not find relation between extension of SDH or clinical severity and development of hypopituitarism. In conclusion, in some patients with SDH growth hormone deficiency or hypogonadism was present. No serious hypocortisolism, hypothyroidism, diabetes insipidus nor SIADH was observed. The possibility of neuroendocrine dysfunction should be considered in patients with SDH, although the deficits are less frequent than in patients after TBI or SAH., V. Hána ... [et al.]., and Obsahuje seznam literatury
a1_Reactive oxygen species (ROS) are common products of the physiological metabolic reactions, which are associated with cell signaling and with the pathogenesis of various nervous disorders. The brain tissue has the high rate of oxidative metabolic activity, high concentration of polyunsaturated fatty acids in membrane lipids, presence of iron ions and low capacity of antioxidant enzymes, which makes the brain very susceptible to ROS action and lipid peroxidation formation. Membranes of brain cortex show a higher production of thiobarbituric acid-reactive substances (TBARS) in prooxidant system (ADP.Fe3+/NADPH) than membranes from the heart or kidney. Lipid peroxidation influences numerous cellular functions through membrane-bound receptors or enzymes. The rate of brain cortex Na+ ,K+ -ATPase inhibition correlates well with the increase of TBARS or conjugated dienes and with changes of membrane fluidity. The experimental model of short-term hypoxia (simulating an altitude of 9000 m for 30 min) shows remarkable increase in TBARS in four different parts of the rat brain (cortex, subcortical structures, cerebellum and medulla oblongata) during the postnatal development of Wistar rat of both sexes. Young rats and males are more sensitive to oxygen changes than adult rats and females, respectively. Under normoxia or hypobaric hypoxia both ontogenetic aspects and sex differences play a major role in establishing the activity of erythrocyte catalase, which is an important part of the antioxidant defense of the organism. Rats pretreated with L-carnitine (and its derivatives) have lower TBARS levels after the exposure to hypobaric hypoxia. The protective effect of L-carnitine is comparable with the effect of tocopherol, well-known reactive species scavenger. Moreover, the plasma lactate increases after a short-term hypobaric hypoxia and decreases in L-carnitine pretreated rats., a2_Acute hypobaric hypoxia and/or L-carnitine-pretreatment modify serum but not brain lactate dehydrogenase activity. The obtained data seem to be important because the variations in oxygen tension represent specific signals of regulating the activity of many specific systems in the organism., H. Rauchová, M. Vokurková, J. Koudelová., and Obsahuje seznam literatury