Anemia frequently complicates chronic kidney disease (CKD). We investigated here the effect of adenine-induced CKD in rats on erythrocyte count (EC), hematocrit (PCV) and hemoglobin (Hb) concentration, as well as on the activity of L-γ-glutamyl transferase (GGT) and the concentrations of iron (Fe), transferrin (Tf), ferritin (F), total iron binding capacity (TIBC) / unsaturated iron binding capacity (UIBC) and hepcidin (Hp) in serum and erythropoietin (Epo) in renal tissue. Renal damage was assessed histopathologically, and also by measuring the serum concentrations of the uremic toxin indoxyl sulfate (IS), creatinine, and urea, and by creatinine clearance. We also assessed the influence of concomitant treatment with gum acacia (GA) on the above analytes. Adenine feeding induced CKD, accompanied by significant decreases (P<0.05) in EC, PCV, and Hb, and in the serum concentrations of Fe, Tf, TIBC, UIBC and Epo. It also increased Hp and F levels. GA significantly ameliorated these changes in rats with CKD. A general improvement in the renal status of rats with CKD after GA is shown due to its antiinflammatory and anti-oxidant actions, and reduction of the uremic toxin IS, which is known to suppress Epo production, and this may be a reason for its ameliorative actions on the indices of anemia studied., B. H. Ali, M. Al Za'Abi, A. Ramkumar, J. Yasin, A. Nemmar., and Obsahuje bibliografii
Hemolytic uremic syndrome (HUS) is a type of thrombotic microangiopathy, in the course of which some patients may develop chronic kidney disease (CKD). It is clinically important to investigate the markers of a poor prognosis. The levels of angiotensinogen (AGT) and interleukin-18 (IL-18) in serum and urine were evaluated. Study was conducted in 29 children with a history of HUS. Serum and urine AGT concentration was significantly higher in children after HUS as compared to the control group. No differences depending on the type of HUS and gender were noted. The serum concentration of IL-18 in children after HUS was significantly lower, whereas in urine did not differ significantly between the sick and healthy children. A negative correlation between the concentration of AGT in serum and albuminuria in patients after HUS was detected. The results indicate that the concentration of AGT in serum and urine in children after HUS increases, which may indicate the activation of the intrarenal renin-angiotensin-aldosterone system. The statement, that AGT may be a good biomarker of CKD after acute kidney injury due to HUS requires prospective studies with follow-up from the acute phase of the disease on a larger group of patients. Reduced IL-18 serum concentration in children after HUS with no difference in its urine concentration may indicate a loss of the protective effects of this cytokine on renal function due to previously occurred HUS., K. Lipiec, P. Adamczyk, E. Świętochowska, K. Ziora, M. Szczepańska., and Obsahuje bibliografii
Exercise training-induced cardiac hypertrophy occurs following a program of aerobic endurance exercise training and it is considered as a physiologically beneficial adaptation. To investigate the underlying biology of physiological hypertrophy, we rely on robust experimental models of exercise training in laboratory animals that mimic the training response in humans. A number of experimental strategies have been established, such as treadmill and voluntary wheel running and swim training models that all associate with cardiac growth. These approaches have been applied to numerous animal models with various backgrounds. However, important differences exist between these experimental approaches, which may affect the interpretation of the results. Here, we review the various approaches that have been used to experimentally study exercise training-induced cardiac hypertrophy; including the advantages and disadvantages of the various models., Y. Wang, U. Wisloff, O. J. Kemi., and Obsahuje bibliografii a bibliografické odkazy
In our previous studies, a decreased blood pressure was reported in children treated by anthracycline (AC). The aim of this study was to assess the long-term effects of AC anticancer therapy in 45 subjects aged 13-22 years by repeated 24-hour Holter monitoring of blood pressure. Sixty four aged-matched subjects served as controls. The differences between mean values of systolic (SBP) and diastolic blood pressure (DBP) in each hour of both groups were evaluated by Mann-Whitney test. Also the parameters of the least-squares fit of the sinusoidal curve in each subject were estimated (M - mesor, midline-estimating, a mean value of sinusoidal curve corresponds to 24-hours mean pressure; A - amplitude, double amplitude corresponds to nightday difference; Acr - acrophase is a time of maximal value of a sinusoidal curve). SBP and DBP was significantly lower only during night hours in anthracycline patients 19-22 years old. Also M was lower in this age subgroup of patients comparing to age matched controls (SBP: 112±6 mm Hg versus 117±7 mm Hg, p<0.05; DBP: 67±3 mm Hg versus 69±6 mm Hg, p<0.05), A was not different, Acr in patients was shifted one hour earlier (SBP: 2.4 p.m. versus 3.6 p.m., p<0.05; DBP: 2.1 p.m. versus 3.3 p.m., p<0.01). This corresponds to the shift of the morning blood-pressure increase seen on 24-hours blood pressure profiles. M correlated with age in controls (SBP: r=0.374, p<0.01; regression coefficient b=1.34 mm Hg/1 year; DBP: r=0.365, p<0.01; b=0.95 mm Hg/1 year), but not in patients (SBP: r=0.182, DBP: r=0.064). A and Acr were age-independent in all subjects. It is concluded that blood pressure in 19-22 years old AC patients is lower during night hours, the age-dependent increase of blood pressure seen in healthy controls between 13 and 22 years of age does not occur in patients. This finding is consistent with the long-lasting impairment of the sympathetic nervous system caused by anthracyclines., Z. Nováková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Autoimmune thyropathies are frequently linked to many infections, such as Helicobacter pylori, which are also supposed to play a role in their pathogenesis. The aim of this study was to evaluate the relationships between thyroid and gastric autoimmunity and H. pylori infection on a large sample of Czech population (n=1621) by monitoring the autoantibodies against thyroglobulin (anti-Tg) and thyroid peroxidase (anti-TPO) and gastric parietal cell (anti-GPC, representing thyrogastric syndrome) in correlation with antibodies against Helicobacter pylori (anti-H. pylori) of classes IgG and IgA. The interrelation between autoantibodies and H. pylori antibodies was assessed by H. pylori seropositivity. In H. pylori seropositive persons as compared to seronegative irrespective of age and sex, a higher occurrence of anti-TPO (10.4 % vs. 5.8 %, p=0.001) and anti-GPC (6.1 % vs. 1.7 %, p<0.001) was found. Differences in anti-TPO occurrence were significant in both men (7.0 % vs. 3.3 %, p=0.03) and women (12.7 % vs. 8.0 %, p=0.02), differences in anti-GPC occurrence were significant only in women (7.2 % vs. 1.7 %, p<0.001). Results of this study support the idea of a connection between infection of H. pylori and the occurrence of anti-TPO autoantibodies representing thyroid autoimmunity and gastric parietal cells autoantibodies representing the thyrogastric syndrome., I. Šterzl, P. Hrdá, P. Matucha, J. Čeřovská, V. Zamrazil., and Obsahuje bibliografii a bibliografické odkazy
Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) exert beneficial effects on health and they could help to prevent development of obesity and associated metabolic disorders. In our previous studies in mice fed high-fat (cHF; ~60 % calories as fat) diet and maintained at 20 °C, dietary LC n-3 PUFA could counteract accretion of body fat, without inducing mitochondrial uncoupling protein 1 (UCP1) in adipose tissue, suggesting that the anti-obesity effect was not linked to adaptive (UCP1- mediated) thermogenesis. To exclude a possible dependence of the anti-obesity effect on any mechanism inducible by cold, experiments were repeated in mice maintained at thermoneutrality (30 °C). Male C57BL/6J mice were fed either cHF diet, or cHF diet supplemented with LC n-3 PUFA, or standard diet for 7 months. Similarly as at 20 °C, the LC n-3 PUFA supplementation reduced accumulation of body fat, preserved lipid and glucose homeostasis, and induced fatty acid re-esterification in epididymal white adipose tissue. Food consumption was not affected by LC n-3 PUFA intake. Our results demonstrated anti-obesity metabolic effect of LC n-3 PUFA, independent of cold-induced thermogenesis and they suggested that induction of fatty acid re-esterification creating a substrate cycle in white fat, which results in energy expenditure, could contribute to the anti-obesity effect., P. Janovská, ... [et al.]., and Obsahuje seznam literatury
The changes of the composition of blood lipoproteins caused by menopause could also change the effect of hypolipidemic therapy. Using an experimental model we studied the changes of serum lipids and the effect of immediate or delayed treatment with simvastatin on atherosclerosis after surgical menopause. Female golden Syrian hamster aged 6 months were fed hypercholesterolemic diet during the whole study. Atherosclerotic changes in thoracic and abdominal aortas were assessed by stereomicroscopic method after 12 weeks. Four experimental groups were studied: sham-operated animals (n=5), ovariectomized animals (n=9), ovariectomized animals treated for 12 weeks (n=10), and ovariectomized animals treated 4 weeks after ovariectomy for 8 weeks (n=9). The dose of simvastatin was 10 mg/kg of body weight. After 12 weeks, ovariectomized animals had tenfold higher concentration of triglycerides in LDL fraction and significantly higher prevalence of atherosclerosis than animals without ovariectomy. Treatment with simvastatin substantially decreased the prevalence of atherosclerotic changes, but otherwise did not change individual serum lipids including LDL cholesterol. However, it improved proportions of pro- and antiatherogenic serum lipids mainly by the increase of HDL cholesterol. The timing of simvastatin treatment had no significant effect on atherosclerotic changes or lipid parameters. Simvastatin treatment partly prevented atherosclerotic changes induced by ovariectomy. This effect was not mediated by decrease of LDL cholesterol, but by increase in HDL cholesterol., J. Pitha ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
a1_Modification of low density lipoprotein (LDL) particles due to oxidation, glycation and binding of advanced glycation end-products (AGEs) or malondialdehyde (MDA, a final product of lipid peroxidation) is considered most important in the process of atherogenesis. Oxidatively modified LDL are distinguished by another receptor type, which was discovered on the surface of macrophages and was called the scavenger receptor. Uncontrolled intake of LDL converts macrophages to foam cells; their accumulation under the vascular endothelium is considered as the first stage of atherosclerosis. Oxidation of LDL is a complex process taking place in both the extra- and intracellular space. At the end of this oxidative process, modified LDL particles show chemotactic, cytotoxic and immunogenic properties. Oxidized LDL express a large number of epitopes and cause production of polyclonal autoantibodies against these products, especially against apoB100 modified by MDA and 4-hydroxynonenal. IgoxLDL (antibodies against oxidized LDL) can be demonstrated either directly in intimal lesions or as a component of circulating immune complexes. IgoxLDL do not form a homogeneous group but a varied mixture of antibodies-isoantibodies caused by HDL and LDL polymorphism, antibodies against the lipid phase of LDL and antibodies against modified apoB100 of the immunoglobulin class IgA or IgG. Antibodies against oxLDL were found in many diseases other than atherosclerosis such as diabetes mellitus, renovascular syndrome, uremia, rheumatic fever, morbus Bechtjerev or lupus erythematodes. Newborns have practically the same levels of IgoxLDL as their mothers; however, these values did not differ from those in the healthy population of non-pregnant women of the same age., a2_The decrease in IgoxLDL titer was very slow and lasted many months; that is why this parameter cannot be considered suitable for describing the rapid changes during oxidative stress of the organism. Positive correlation of IgoxLDL with antiphospholipids and other antibodies was repeatedly demonstrated; their determination can thus be used as a marker for the description of total production of autoantibodies in various diseases. The changes and correlations of IgoxLDL, anti-b-2-glycoprotein I IgG and antiphospholipid antibodies support the immunological link between thrombotic and atherosclerotic processes in the human body., A. Steinerová, J. Racek, F. Stožický, T. Zima, L. Fialová, A. Lapin., and Obsahuje bibliografii
Neuroactive steroids represent potential antiepileptic drugs. We tested a newly synthesized analogue of allopregnanolone 3α- hydroxy-21ξ,22-oxido-21-homo-5α-pregnan-20-on (HOHP) against two types of pentylenetetrazol-induced seizures (100 mg/kg s.c.) in 12- and 25-day-old rats. Ganaxolone, a neuroactive steroid in clinical trials, served as a reference drug. Pretreatment with either steroid suppressed generalized tonicclonic seizures in both age groups, their efficacy was comparable. HOHP as well as ganaxolone were more active in 12- than in 25-day-old rats (effective doses were 40 and 60 mg/kg, respectively). Minimal clonic seizures, which can be elicited only in 25-day-old rats, were not influenced by any drug. Very short duration of anticonvulsant action of HPOP demonstrated in 12-day-old animals indicates that this drug might be used only in acute treatment in epileptology., P. Mareš, H. Kubová, A. Kasal., and Obsahuje bibliografii a bibliografické odkazy