Based on the biological significance of the ubiquitin-proteasome pathway (UPP) and its potential role during sepsis, burns and ischemia-reperfusion injury, we hypothesized that the systemic response to traumatic shock (TS) is accompanied by tissue-specific UPP alterations. Therefore, we studied tissue ubiquitin pools, chymotryptic- and tryptic-like proteasome peptidase activities and ubiquitin-protein ligation (UbPL) rates in skeletal muscle, heart, lung, liver, spleen and kidney using a clinically relevant porcine model (bilateral femur fracture/hemorrhage followed by fluid resuscitation). TS induced a systemic reduction of tissue- specific high molecular mass ubiquitin-protein conjugates (>50 kDa). Free ubiquitin was unaffected. The dynamic organ patterns of ubiquitin pools paralleled the typical physiological response to TS and resuscitation. Reduction of ubiquitin-protein conjugates was most pronounced in heart and lung (p<0.05 vs. control) and accompanied by significant increases in proteasome peptidase and UbPL activities in these organs. Unlike all other tissues, spleen proteasome peptidase and UbPL activities were significantly reduced 10 h after TS. These findings support the concept that the UPP could play an important role in regulation of cell functions during the early whole-body response to TS. The UPP might be a therapeutic target to improve the metabolic care after TS, particularly in the heart, lung, and spleen., M. B. Patel, S. A. Earle, M. Majetschak., and Obsahuje bibliografii a bibliografické odkazy
Renal sympathetic hyperactivity is critically involved in hypertension pathophysiology; renal denervation (RDN) presents a novel strategy for treatment of resistant hypertension cases. This study assessed effects of two RDN systems to detect acute intravascular, vascular and peri-vascular changes in the renal artery, and renal nerve alterations, in the sheep. The procedures using a single-point or multi-point ablation catheters, Symplicity FlexTM, Medtronic versus EnligHTNTM, St. Jude Medical were compared; the intact contralateral kidneys served as controls. Histopathological and immunohistochemical assessments were performed 48 h after RDN procedures; the kidney and suprarenal gland morphology was also evaluated. Special staining methods were applied for histologic analysis, to adequately score the injury of renal artery and adjacent renal nerves. These were more pronounced in the animals treated with the multi-point compared with the single-point catheter. However, neither RDN procedure led to complete renal nerve ablation. Forty-eight hours after the procedure no significant changes in plasma and renal tissue catecholamines were detected. The morphologic changes elicited by application of both RDN systems appeared to be dependent on individual anatomical variability of renal nerves in the sheep. Similar variability in humans may limit the therapeutic effectiveness of RDN procedures used in patients with resistant hypertension., M. Táborský, D. Richter, Z. Tonar, T. Kubíková, A. Herman, J. Peregrin, L. Červenková, Z. Husková, L. Kopkan., and Obsahuje bibliografii
This study used an experimental early rehabilitation model combining an enriched environment, multisensory (visual, acoustic and olfactory) stimulation and motor training after traumatic brain injury (via fluid-percussion model) to simulate early multisensory rehabilitation. This therapy will be used by brain injured patients to improve neural plasticity and to restore brain integration functions. Motor dysfunction was evaluated using a composite neuroscore test. Direct structural effects of traumatic brain injury were examined using Fluoro-Jade staining, which allows identification of degenerating neural cell bodies and processes. Animals in the rehabilitation model group performed significantly better when tested for neuromotor function than the animals in standard housing in the 7-day and 15-day interval after injury (7d: p=0.005; 15d: p<0.05). Statistical analysis revealed significantly lower numbers of Fluoro-Jade positive cells (degenerating neurons) in the rehabilitation model group (n=5: mean 13.4) compared to the standard housing group (n=6: mean 123.8) (p<0.005). It appears that the housing of animals in the rehabilitation model led to a clear functional increase in neuromotor functions and to reduced neural loss compared with the animal group in standard housing., M. Lippert-Grüner. M. Maegele, J. Pokorný, D. N. Angelov, O. Švestková, M. Wittner, S. Trojan., and Obsahuje bibliografii a bibliografické odkazy
Reduced physical activity and abundant energy intake are two most common factors leading to uncontrolled body weight gain. But these factors are not under entire internal consciousness control; they are also partially genetically determined and are affected by for example food marketing practices. In addition to these two widely accepted factors, there are some other factors, whose could also contribute to the recent increase of obesity prevalence. For example, non-exercise activity thermogenesis, sleeping habits, more stable inside room temperatures (using of heating and air conditioning), high prescription of medications with weight gain as side effect, psychosocial factors, unfavourable socioeconomic status and unpleasant urban environment are the background factors which should not be omitted if obesity/BMI determination should be fully understood and kept under control. In conclusion, unhealthy life style is necessary, but not sufficient for obesity development., J. A. Hubáček., and Obsahuje seznam literatury
a1_Diabetes mellitus is a risk factor of cardiovascular diseases. ECG of patients with diabetes mellitus type 1 (DM 1) shows tachycardia (block of parasympathetic innervation) and abnormal repolarization (increased QT interval and QT dispersion (QTd)) indicating a risk of ventricular tachycardia and sudden death in young people with DM 1. The aim of the present report was to measure 145 parameters of the heart electric field in 22 patients (14 men, 8 women) with DM 1 without complications (mean age 32.8±11.4 years) and in 22 controls (11 men, 11 women, mean age 30.1±3.4 years). The duration of diabetes was 13.9 ±7.8 years. The parameters were regist ered by the diagnostic system Cardiag 112.2 and statistically evaluated by the Student and Mann-Whitney test. Tachycardia (86.3±2.7 beats.min-1), shortening of both QRS (79.9±1.6 ms) and QT (349.0±5.9 ms) and increased QT dispersion (115±36 ms) were observed in DM 1 when compared with the controls (75.0±2.1 beats. min -1, QRS 89.9±2.7 ms, QT 374.0±4.4 ms, QTd 34.0±12.0 ms, p<0.01). The QTc was 415.2±4.1 ms in DM 1 and 401.4±6.6 ms in controls (NS)., a2_Other significant findings in DM 1 were: higher maximum of depolarization isopotential maps (DIPMmax) in the initial phase of QRS and less positive in the terminal phase, more negative minimum (DIPMmin) during QRS similarly as the minimum in depolarization isointegral maps (DIIMmin) and the minimum in isointegral map of the Q wave (Q-IIMmin), lower maximum in repolarization isopotential maps (RIPMmax) and less negative minimum (RIPMmin), more negative amplitude of Q wave (Q-IPMAM) and more pronounced spread of depolarization (activation time). Our results confirmed a decreased parasympathetic to sympathetic tone ratio (tachycardia, shortening of the activation time) and revealed different depolarization and repolarization patterns in DM 1. The differences in heart electric field parameters measured by the BSPM method in DM 1 and in the controls indicate the importance of ECG examination of diabetic patients type 1 in the prevention of cardiovascular diseases., D. Žďárská, P. Pelíšková, J. Charvát, J. Slavíček, M. Mlček, E. Medová, O. Kittnar., and Obsahuje bibiografii a bibliografické odkazy
ECG body surface mapping (BSM) parameters in patients with diabetes mellitus Type 1 (DM1) are significantly different comparing to healthy non-diabetic subjects. Hypothesis that these changes are more pronounced in DM1 patients with autonomic neuropathy (AN) was tested. The parameters of BSM were registered by diagnostic system Cardiag 112.2 in 54 DM1 patients including 25 with AN and 30 control subjects. AN was diagnosed according to Ewing criteria when two or more Ewing tests were abnormal. In classic 12-lead ECG the heart rate was increased, QRS and QT shortened (p<0.01) and QTC prolonged in DM1 patients. The VCG measurement of QRS-STT angles and spatial QRS-STT angle showed non-significant differences. The absolute values of maximum and minimum in depolarization and repolarization isopotential, isointegral, isoarea maps were significantly different in DM1 patients in comparison with controls (p<0.01). The changes were more pronounced in DM1 patients with AN than in DM patients without AN (p<0.05). The QT duration measured in 82 leads of thorax was significantly shortened in 68 leads of both groups of DM 1 patients (p<0.01) when compared with controls. In 34 of them this shortening was more pronounced in DM1 patients with AN than in DM1 patients without AN (p<0.05). The results showed that the method of ECG BSM is capable to confirm the presence of autonomic neuropathy in diabetic patients., S. Palová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Women with gestational diabetes mellitus (GDM) are at increased risk for cardiovascular diseases (CVD) events compared with women without GDM. The aim of the present study was to evaluate 200 parameters of the heart electric field in 35 women with GDM under optimal glycemic compensation compared to 32 healthy pregnant women. All examinations were performed in the 36th week of gestation. The parameters in ECG body surface mapping (BSM) were registered by the diagnostic system Cardiag 112.2. The absolute values of maximum and minimum in depolarization and repolarization isopotential, isointegral and isoarea maps were not significantly different between the groups. These findings correspond to the result of heart rate variability examination. However BSM revealed the significant prolongation of QRS complex (p=0.05), shortening of ventricular myocardial activation time (ICHVAT) (p=0.01), prolongation of mean QT duration (p=0.01) and increase of QT interval dispersion (p=0.01) in women with GDM. Duration of QRS and ICHVAT significantly correlated with interventricular septum and posterior wall thickness in GDM group, QTd interval correlated significantly with HbA1C level. We conclude that despite of optimal metabolic control several significant abnormalities detected by ECG BSM are still present in patients with GDM., E. Žákovičová, O. Kittnar, J. Slavíček, E. Medová, P. Šváb, J. Charvát., and Obsahuje bibliografii
Enzymes that hydrolyze extracellular ATP, i.e. ecto-ATPase and ecto-ATP diphosphohydrolase (ATPDase), can be differentiated by ability of the latter to hydrolyze ADP and by slightly different kinetic properties of the two enzymes. Synaptic plasma membrane fractions isolated from rat hippocampus and caudate nucleus exhibit ADP-hydrolyzing activity, as revealed by the enzyme assay, and the presence of ecto-ATPase protein, as revealed by immunological identification on Western blot. These findings indicate that both enzymes are co-expressed in the synaptic membrane compartment of hippocampal and caudate nucleus neurons. Kinetic analysis was performed to determine the relative contribution of each enzyme to the total ATP-hydrolyzing activity, while an inhibition study was carried out in order to exclude the interference of other nonspecific ATPase and phosphatase activities. Based on the kinetic properties, sensitivity to inhibitors and VATP/VADP ratio of about 2, we concluded that a substantial portion of ATP-hydrolyzing activity in both synaptic membrane preparations can be ascribed to the catalytic action of ATPDase. On the other hand, the highest catalytic efficacy when ATP is the substrate and the greater abundance of ecto-ATPase protein in caudate nucleus preparation suggest that the relative contribution of ecto-ATPase to the total ATP-hydrolyzing activity in the caudate nucleus is higher than in the hippocampus., N. Nedeljkovic, A. Banjac, A. Horvat, M. Stojiljkovic, G. Nikezic., and Obsahuje bibliografii