Chronic kidney disease (CKD) is a life-threatening disease arising as a frequent complication of diabetes, obesity and hypertension. Since it is typically undetected for long periods, it often progresses to end-stage renal disease. CKD is characterized by the development of progressive glomerulosclerosis, interstitial fibrosis and tubular atrophy along with a decreased glomerular filtration rate. This is associated with podocyte injury and a progressive rise in proteinuria. As endothelin-1 (ET-1) through the activation of endothelin receptor type A (ETA) promotes renal cell injury, inflammation, and fibrosis which finally lead to proteinuria, it is not surprising that ETA receptors antagonists have been proven to have beneficial renoprotective effects in both experimental and clinical studies in diabetic and non-diabetic CKD. Unfortunately, fluid retention encountered in large clinical trials in diabetic CKD led to the termination of these studies. Therefore, several advances, including the synthesis of new antagonists with enhanced pharmacological activity, the use of lower doses of ET antagonists, the addition of diuretics, plus simply searching for distinct pathological states to be treated, are promising targets for future experimental studies. In support of these approaches, our group demonstrated in adult subtotally nephrectomized Ren-2 transgenic rats that the addition of a diuretic on top of renin-angiotensin and ETA blockade led to a further decrease of proteinuria. This effect was independent of blood pressure which was normalized in all treated groups. Recent data in non-diabetic CKD, therefore, indicate a new potential for ETA antagonists, at least under certain pathological conditions., I. Vaněčková, S. Hojná, M. Kadlecová, Z. Vernerová, L. Kopkan, L. Červenka, J. Zicha., and Seznam literatury
Disturbed circadian activity of the sympathetic system may be involved in negative consequences of chronodisruption on the cardiovascular system. We studied daily changes in pressure response to adrenergic stimulation in rats exposed to repeated phase advance shifts (PAS) of light/dark (LD) regimen. Blood pressure (BP), heart rate (HR) and locomotor activity was measured by radiotelemetry in normotensive Wistar rats exposed to repeated PAS (three 8-h shifts per week) lasting for 12 weeks. Norepinephrine was administered subcutaneously in the middle of L and D during week 12 of PAS exposure. In the control LD cycle, cardiovascular parameters exhibited significant daily rhythms with expected higher values during D than L phase. Rats exposed to PAS showed disturbed rhythms without a BP and HR increase. Administration of norepinephrine to control rats revealed daily variability in the cardiovascular response with higher stimulation of BP during L than D. This daily pattern of BP response to norepinephrine was diminished in the PAS group. The damped daily variability in pressure response to norepinephrine and augmented response during the light phase of the day suggest that the increased and desynchronized activity of the sympathetic system may worsen responses of the cardiovascular system to load in individuals exposed to irregular LD conditions., L. Molcan, A. Vesela, M. Zeman., and Obsahuje bibliografii
Repetitive transcranial magnetic stimulation (rTMS) is non-invasive neuromodulation method. We applied rTMS for the treatment of farmacoresistant chronic orofacial pain. We compared the effect of 10 Hz an d 20 Hz stimulation. The study included 23 patients for 20 Hz stimulation and 36 patients for 10 Hz stimulation with pharmacoth erapy resistant chronic facial pain aged 33-65 years with pain duration of at least 6 months. Monitoring of treatment effects was performed within 15 minutes of each rTMS application (days 1-5) and finally stimulation (active vs. sham coil). If compared with data with 10 Hz rTMS study (n=36) and with 20 Hz rTMS (n=23) trials using a parallel design. Only the results obtained in a series of five rTMS treatments in the first step (active n=24, sham n=12), that 20 Hz frequency rTMS using a higher intensity (95 % of motor threshold) to be equally effective relative to VAS (Visual analogue scale) and QST (quantitative sensory testing). In conclusions, the better results with the relief of orofacial pain were obtained with 20 Hz stimulation if compared with 10 Hz stimulation. It was proved with subjective (VAS) and object ive evaluation (QST). rTMS can be used in the treatment of chronic intractable pain., J. Fricová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
T wave morphology (TWM) descriptors derived from Holter electrocardiograms during hemodialysis (HD) are of potential value for cardiac risk assessment in HD patients. Our knowledge on autonomic regulation of TWM descriptors is limited. The purpose of this study was to investigate the association between TWM parameters and heart rate variability (HRV) during intradialytic monitoring. In each of 81 patients on maintenance HD, continuous electrocardiograms were recorded 5 times during HD on alternate weeks. TWM descriptors were calculated every 5 s in overlapping 10-s ECG segments and Low Frequency (LF) (0.04 Hz to 0.15 Hz), High Frequency (HF) (0.15 Hz to 0.40 Hz) powers of the spectrum of HRV were calculated every five min. The calculated values of TWM and HRV were averaged during the first hour of the recordings and subsequently over all recordings in each subject. Analyzable data for HRV and TWM were available in 71 HD patients (aged 61±15, 36 % diabetics, 32 % females). LF in normalized units correlated positively with Total Cosine R to T (r=0.374, p=0.001) and negatively with T wave morphology dispersion (r=-0.253, p=0.033) after adjusting for heart rate. A heart rate independent association between repolarisation descriptors and HRV exists in HD patients. Autonomic modulation needs to be considered when using TWM characteristics for risk profiling of HD patients., D. Poulikakos, D. Banerjee, M. Malik., and Obsahuje bibliografii
Increased blood pressure variability (BPV) and decreased interbeat interval (heart rate, respectively) variability (IBIV, HRV respectively) are associated with cardiovascular disorders. The aim of this study was to evaluate the reproducibility of BPV and IBIV (HRV) in young healthy individuals. Blood pressure and inter-beat intervals (instantaneous values of heart rate, respectively) were recorded beat-to-beat at rest (5 min, Finapres, breathing at 0.33 Hz) in 152 subjects (19-24 years) 3 times in periods of one week. Systolic (SBPV0.1r/SBPV0.1a) and diastolic (DBPV0.1r/DBPV0.1a) blood pressure variability in relative (r.u.) and absolute (mmHg2/Hz) units and inter-beat interval (IBIV0.1r/IBIV0.1a,), or heart rate (HRV0.1r/HRV0.1a) variability in relative (r.u.) and absolute (ms2/Hz, resp. mHz2) units were determined by the spectral method as spectral power at the frequency of 0.1 Hz and 0.33 Hz (SBPV0.33r/SBPV0.33a, DBPV0.33r/DBPV0.33a, IBIV0.33r/IBIV0.33a, HRV0.33r/HRV0.33a). All indices of BPV and IBIV (resp. HRV) revealed a lower intraindividual than interindividual variability (ANOVA; p<0.001). The mean values of all indices in each subject significantly correlated with distribution of individual values in the same subject (Pearson's correlation coefficient; p<0.001). Blood pressure and inter-beat interval (heart rate) variability is an individual characteristic feature., M. Jíra ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Sensorineural hearing loss and vertigo, resulting from lesions in the sensory epithelium of the inner ear, have a high incidence worldwide. The sensory epithelium of the inner ear may exhibit extreme degeneration and is transformed to flat epithelium (FE) in humans and mice with profound sensorineural hearing loss and/or vertigo. Various factors, including ototoxic drugs, noise exposure, aging, and genetic defects, can induce FE. Both hair cells and supporting cells are severely damaged in FE, and the normal cytoarchitecture of the sensory epithelium is replaced by a monolayer of very thin, flat cells of irregular contour. The pathophysiologic mechanism of FE is unclear but involves robust cell division. The cellular origin of flat cells in FE is heterogeneous; they may be transformed from supporting cells that have lost some features of supporting cells (dedifferentiation) or may have migrated from the flanking region. The epithelial-mesenchymal transition may play an important role in this process. The treatment of FE is challenging given the severe degeneration and loss of both hair cells and supporting cells. Cochlear implant or vestibular prosthesis implantation, gene therapy, and stem cell therapy show promise for the treatment of FE, although many challenges remain to be overcome., Lu He, Jing-Ying Guo, Ke Liu, Guo-Peng Wang, Shu-Sheng Gong., and Obsahuje bibliografii
To investigate the effect of light cue on the resetting of the peripheral clocks, we examined the resetting processes of clock genes (Per1, Per2, Bmal1, Cry1, Dec1, and Rev-erbα) in the liver and heart of rats after the feeding and light-dark (LD) reversal via a 24-h light period transition. The liver clock was reset quickly within 3 days, while the heart clock needed a longer time course of 5-7 days to be completely re-entrained. Moreover, the reentrainment of Per1 and Per2 in the liver clock was more rapid than that of the other four clock genes, suggesting the important role of these two clock genes in initiating the circadian resetting of the hepatic clock. However, the resetting rates of these two clock genes were as similar as the others in the heart clock. Therefore, the resetting mechanisms underlining these two peripheral clocks may be totally distinct. Furthermore, the reentrainment of the liver and heart clocks were relatively lengthened after the feeding and LD reversal via a light period transition compared to a dark period transition, suggesting a simultaneous shift of feeding schedule and the LD cycle may facilitate the circadian resetting in rats., T. Wu ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The cardiovascular system is described by parameters including blood flow, blood distribution, blood pressure, heart rate and pulse wave velocity. Dynamic changes and mutual interactions of these parameters are important for understanding the physiological mechanisms in the cardiovascular system. The main objective of this study is to introduce a new technique based on parallel continuous bioimpedance measurements on different parts of the body along with continuous blood pressure, ECG and heart sound measurement during deep and spontaneous breathing to describe interactions of cardiovascular parameters. Our analysis of 30 healthy young adults shows surprisingly strong deep-breathing linkage of blood distribution in the legs, arms, neck and thorax. We also show that pulse wave velocity is affected by deep breathing differently in the abdominal aorta and extremities. Spontaneous breathing does not induce significant changes in cardiovascular parameters., P. Langer, P. Jurák, V. Vondra, J. Halámek, M. Mešťaník, I. Tonhajzerová, I. Viščor, L. Soukup, M. Matejkova, E. Závodná, P. Leinveber., and Obsahuje bibliografii
Determination of response of cortisol and its metabolites to different stimuli may be important for adrenal gland disorders. To date, only one metabolite, cortisone, has been followed in stimulation tests of the adrenal gland. We aimed to describe a response of cortisol metabolites to the standard short Synacthen test (HDST), insulin tolerance test (ITT), low dose Synacthen test (LDST) and medium dose Synacthen test (MDST). Sixty healthy subjects were investigated: 30 men and 30 women. Plasma for measurements of cortisol and its metabolites was obtained before and 30th and 60th min after Synacthen and insulin administration. The cut-off 500 nmol/l of cortisol was reached after stimulation in all of tests, the maximal stimulation level was reached in 60th min in all of the tests except for LDST. The response of cortisol and its metabolites at 30th and 60th min strongly correlated in all of the tests except for LDST. Cortisol and its metabolites increased after stimulation; in contrast, cortisone and its metabolites decreased. We showed that the response of the cortisol metabolites during the Synacthen tests and ITT well correlated, and the MDST showed similar response compared to HDST. The decrease in cortisone metabolites may correspond to the regeneration of cortisol from cortisone in response to stimulation test., K. Simunkova, M. Duskova, M. Kosak, M. Krsek, V. Hana, M. Hill, H. Jandikova, H. Pospisilova, M. Sramkova, E. Bifulco, L. Starka., and Obsahuje bibliografii