Baroreflex control of heart rate was studied in inbred salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahl rats that were subjected to chronic dietary sodium chloride loading (for 4 weeks) either in youth or only in adulthood, i.e. from the age of 4 or 12 weeks. Using phenylephrine administration to pentobarbital-anesthetized male rats we have demonstrated the decreased baroreflex sensitivity (lower slope for reflex bradycardia) in young prehypertensive SS/Jr rats fed a low-salt diet as compared to age-matched SR/Jr animals. High salt intake further suppressed baroreflex sensitivity in young SS/Jr but not in SR/Jr rats. Baroreflex sensitivity decreased with age in SR/Jr rats, whereas it increased in SS/Jr rats fed a low-salt diet. Thus at the age of 16 weeks baroreflex sensitivity was much higher in SS/Jr than in SR/Jr animals. High salt intake lowered baroreflex sensitivity even in adult SS/Jr rats without affecting it in adult SR/Jr rats. Nevertheless, baroreflex sensitivity was significantly lower in young SS/Jr rats with a severe salt hypertension than in adult ones with a moderate blood pressure elevation. It is concluded that the alterations of baroreflex sensitivity in young inbred SS/Jr rats (including the response to high salt intake) are similar to those described earlier for outbred salt-sensitive Dahl rats. We have, however, disclosed contrasting age-dependent changes of baroreflex sensitivity in both inbred substrains of Dahl rats., J. Nedvídek, J. Zicha., and Obsahuje bibliografii
1a_It has been known for many years that baroreflex sensitivity is lowered in hypertensive patients. There are several known factors implicating this association, e.g. high blood pressure leads to remodeling of the carotid arterial wall, to its stiffness and to a diminished activation of baroreceptors; leptin released from a fatty tissue activates the sympathetic nervous system etc. On the other hand, low baroreflex sensitivity (BRS, usually quantified in ms/mmHg) can be inborn. Studies on primary hypertension in children and adolescents have brought new information about the role of baroreflex in the development of an early stage of primary hypertension. BRS lower than 3.9 ms/mmHg was found in 5 % of healthy subjects. This value approaches the critical value for the risk of sudden cardiac death in patients after myocardial infarction and corresponds to the value present in hypertensive patients. A decreased BRS and BRSf (baroreflex sensitivity expressed in mHz/mmHg, index independent of the mean cardiac interval), was found not only in children with hypertension, but also in those with white-coat hypertension. This is in accordance with a single interpretation. The decrease of BRS/BRSf precedes a pathological blood pressure increase., 2a_The contribution of obesity and BRS/BRSf to the development of hypertension in adolescents was also compared. Both factors reach a sensitivity and a specificity between 60 % and 65 %, but there is no correlation between the values of the body mass index and BRS either in the group of hypertensive patients or in healthy controls. If a receiver operating curve (sensitivity versus specificity) is plotted for both values together using logistic regression analysis, a sensitivity higher than 70 % and a specificity over 80 % are reached. This means that low baroreflex sensitivity is an independent risk factor for the development of primary hypertension. Studies demonstrate that adolescents with increased blood pressure and with BRS under 7 ms/mmHg should be given care and intensively motivated to change their lifestyle including a change in diet and increase in physical activity., and N. Honzíková, B. Fišer.
Sympathetic overactivity and low parasympathetic activity is an autonomic dysfunction (AD) which enhances cardiac mortality. In the present study, the impact of AD on the mortality in patients after myocardial infarction was evaluated. We examined 162 patients 7-21 days after myocardial infarction, 20 patients of whom died in the course of two years. Baroreflex sensitivity (BRS) was estimated by spectral analysis of spontaneous fluctuations of systolic blood pressure and cardiac intervals (Finapres, 5 min recording, controlled breathing 20/min). The heart rate variability was determined as SDNN index (mean of standard deviations of RR intervals for all 5-min segments of 24-hour ECG recordings). BRS < 3 ms/mm Hg and/or SDNN index < 30 ms were taken as markers of AD. The risk stratification was performed according to the number of the following standard risk factors of increased risk of cardiac mortality (SRF): ejection fraction < 40 %, positive late potentials and the presence of ventricular extrasystoles > 10/h. No difference in mortality between patients with AD (4 %) and without AD (4.5 %) was found in 92 patients without SRF, the mortality in 6 patients with three SRF was 66.6 %. Five of these patients had AD. Out of 64 patients with one or two SRF, 32 had AD. The mortality of patients without AD was 6.25 % and 31.2 % of those with AD (p<0.025). It is concluded that AD enhanced two-years mortality five fold in our patients with moderate risks., N. Honzíková, B. Semrád, B. Fišer, R. Lábrová., and Obsahuje bibliografii
At present, there are insufficient information about baroreflex sensitivity (BRS) and factors that determine BRS in premature newborns. The objective of this study was to determine the relationship between BRS and the characteristics that reflecting the intrauterine development (gestational age and birth weight), as well as postnatal development (postconception age and the actual weight of the child at the time of measurement). We examined 57 premature infants, who were divided into groups according to gestational age and postconception age as well as birth weight, and weight at the time of measurement. Continuous and noninvasive registration of peripheral blood pressure (BP) was perf ormed in every child within 2-5 m in under standard conditions using a Portapres (FMS) device. The results showed a close correlation of baroreflex sensitivity, heart rate and respiratory rate with gestational age, postconception age, birth weight and actual weight at the time of measureme nt premature newborns. An increase in the characteristics (ages and weights) resulted in increased BRS and diastolic arterial pressure (DAP), and in decreased heart and respiratory rates. Baroreflex sensitivity in the first week was in the group of very premature newborns the lowest (4.11 ms/mmHg) and in the light premature newborns was almost double (8.12 ms/mmHg). BRS increases gradually in relation to postnatal (chronological) and to postconception age as well as to birth and actual weight. The multifact or analysis of BRS identified birth weight and postconception age as the best BRS predictors. The two independent variables together explained 40 % of interindividual BRS variability., K. Haskova, M. Javorka, B. Czippelova, M. Zibolen, K. Javorka., and Obsahuje bibliografii
Prenatal exposure to methamphetamine (METH) increases nociceptive sensitivity in adult rats. As the strong analgesics have high abuse potential and drugs of abuse are known to have analgesic properties, the aim was to study analgesic effect of different psychostimulants in control and prenatally METHexposed rats. Latencies of withdrawal reflexes of hind limbs and the tail on thermal nociceptive stimuli were repeatedly measured in 15-min intervals after the application of 5 mg/kg s.c. of amphetamine (AMPH), methamphetamine (METH), cocaine (COC), 3,4-methylenedioxymethamphetamine (MDMA) or morphine (MOR). In all groups, AMPH induced on hind limbs stronger analgesia than METH and MDMA whereas COC and MOR were practically without any effect. On the tail, effect of AMPH did not differ from that of MOR. All psychostimulants increased defecation in comparison with MOR and in all groups the number of defecation boluses positively correlated with analgesia of the hind limbs. We did not confirm that prenatal exposure to METH makes adult rats more sensitive either to same drug or to other psychostimulants. The different analgesic potencies of psychostimulants and MOR at different body sites indicate the possible existence of a somatotopic organization of pain inhibition, which is controlled by different mechanisms., A. Yamamotová, R. Šlamberová., and Obsahuje seznam literatury
The study investigated whether specific changes in phase synchrony in the beta 2 frequency band of EEG (25-35 Hz) occurred during a recognition task. The level of synchrony was examined between one hundred and eighty loci in the frontal and temporal lobes of eight epileptic patients with intracerebral electrodes; the EEG records were obtained during a visual oddball task. In each pair of records, the correlation curves were created from the sequence of correlation coefficients calculated. These curves consisted of irregular oscillations between the maximal and minimal r-values. Transient highly synchronized activity was observed during the whole time course of the experiment in all record pairs investigated and a significant relationship was found between the number of such episodes and the mean correlation coefficient (Spearman R 0.84; N 3240; p<0.001). On averaged curves, which were calculated using stimulus onsets as the trigger of averaging, a significant increase of the mean correlation coefficient in the post-stimulus epoch was found (p<0.01 after both target and non-target stimuli; t-test for dependent samples). As the cognitive demand significantly increases after stimulus presentation, the results are considered to be the first evidence from intracranial recording of increased synchronization in the beta 2 frequency band related to the cognitive activity., M. Kukleta ... [et al.]., and Obsahuje seznam literatury
In this study, we focused on an analysis of biguanides effects on mitochondrial enzyme activities, mitochondrial membrane potential and membrane permeabili ty transition pore function. We used phenformin, which is more efficient than metformin, and evaluated its effect on rat liver mitochondria and isolated hepatocytes. In contrast to prev iously published data, we found that phenformin, after a 5 min pr e-incubation, dose-dependently inhibits not only mitochondrial complex I but also complex II and IV activity in isolated mitochondria. The enzymes complexes inhibition is paralleled by the decreased respiratory control index and mitochondrial membrane potent ial. Direct measurements of mitochondrial swelling revealed that phenformin increases the resistance of the permeability transition pore to Ca 2+ ions. Our data might be in agreement with the hypothesis of Schäfer (1976) that binding of biguanides to membrane phospholipids alters membrane properties in a non-specific manner and, subsequently, different enzyme activities are modified via lipid phase. However, our measurements of anisotropy of fluorescence of hydrophobic membrane probe diphenylhexatriene have not shown a measurable effect of membrane fluidity with the 1 mM concentration of phenformin that strongly inhibited complex I activity. Our data therefore suggest that biguanides could be considered as agents with high efficacy but low specifity., Z. Drahota ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The incidence of diabetes mellitus is rising worldwide. The aim of this prospective epidemiological study was to compare the effects of natural and surgical menopause on parameters of glucose metabolism. In a group of 587 repeatedly examined women, with a baseline age of 45-55 years, the following subgroups of women were separated: those after bilateral oophorectomy (BO, n=37) and those in natural menopause (NAT, n=380) including women menopausal already at baseline (POST, n=89). The study parameters including glycemia, insulinemia, HOMA-IR and betacell function using HOMA-β were determined at baseline and 6 years later. Over the study period, there was a marked rise in prediabetic and diabetic values of fasting glycemia; the percentage of women with diabetic values increased in the NAT (from 0.8 % to 3.9 %) and POST (from 2.2 % to 9.0 %) subgroups, with the highest prevalence in the BO subgroup (from 8.1 % to 10.8 %). While, among women with non-diabetic fasting glycemia, an increase in fasting glycemia was observed in all study subgroups, it was more marked in the BO subgroup than in the NAT and POST ones (p=0.02 both). This difference between NAT and BO was also found in the long-term trend of development of glycemia in non-diabetic women (p=0.014). Compared with natural menopause, bilateral oophorectomy may have an adverse effect on glucose metabolism., M. Lejsková, J. Piťha, S. Adámková, O. Auzký, T. Adámek, E. Babková, V. Lánská, Š. Alušík., and Obsahuje bibliografii
We investigated the gastric response to an ulcerogenic irritant and the change in gastric functions in an experimental rat model of obstructive jaundice, with or without biliary drainage. After biliary obstruction for 14 days, rats with ligated bile duct (BDL) were randomly divided into three groups: BDL group without biliary drainage, BDL followed by choledochoduodenostomy (CD) or a choledochovesical fistula (CVF). The gastric functions were evaluated 2 weeks after the surgery. Gastric damage, induced by orogastric administration of ethanol, was evaluated 30 min later using a lesion index and microscopic scoring was then performed on fixed stomachs. Basal gastric acid secretion was measured by the pyloric ligation method.The lesion index and maximum lesion depth did not differ in the BDL and sham groups, while they were significantly reduced in the CD group. Gastric acid output and secretory volume were reduced in the BDL group compared to the sham group, while these reductions were abolished in the CD group. Afferent denervation with capsaicin further reduced the ulcer index in the later group. Our data suggest that gastric mucosal susceptibility to injury is dependent on the normal flow of bile into the duodenal lumen, which appears to be a requirement for adaptive gastric cytoprotection., A. Cingi, R. Ahiskali, B. K. Oktar, M. A. Gülpinar, C. Yegen, B.Ç. Yegen., and Obsahuje bibliografii
The complex architecture of the liv er biliary network represents a structural prerequisite for the formation and secretion of bile as well as excretion of toxic substances through bile ducts. Disorders of the biliary tract affect a significant portion of the worldwide population, often leading to cholestatic liver diseases. Cholestatic liver disease is a condition that results from an impairment of bile formation or bile flow to the gallbladder and duodenum. Cholestasis leads to dramatic changes in biliary tree architecture, worsening liver disease and systemic illness. Recent studies show that the preva lence of cholestatic liver diseases is increasing. The availability of well characterized animal models, as well as development of visualization approaches constitutes a critical asset to develop novel pathogenetic concepts and new treatment strategies., L. Sarnova, M. Gregor., and Obsahuje bibliografii
Bilirubin is the final product of heme catabolism in the systemic circulation. For decades, increased serum/plasma bilirubin levels were considered an ominous sign of an underlying liver disease. However, data from recent years convincin gly suggest that mildly elevated bilirubin concentrations are as sociated with protection against various oxidative stress-mediated diseases, atherosclerotic conditions being the most clinically relevant. Although scarce data on beneficial effects of bilirubin had been published also in the past, it took until 1994 when the first clinical study demonstrated an increased risk of coronary heart disease in subjects with low serum bilirubin levels, and bilirubin was found to be a risk factor for atherosclerotic diseases independent of standard risk factors. Consistent with t hese results, we proved in our own studies, that subjects with mild elevation of serum levels of unconjugated bilirubin (benign hyperbilirubinemia, Gilbert syndrome) have much lower prevalence/incidence of cor onary heart as well as peripher al vascular disease. We have also demonstrated that this association is even more general, with serum bilirubin being a biomarker of numerous other diseases, often associated with increased risk of atherosclerosis. In addition, very recent data have demonst rated biological pathways modulated by bilirubin, which are responsible for observed strong clinical associations., L. Vítek., and Obsahuje bibliografii
ECM is composed of different collagenous and non-collagenous proteins. Collagen nanofibers play a dominant role in maintaining the biological and structural integrity of various tissues and organs, including bone, skin, tendon, blood vessels, and cartilage. Artificial collagen nanofibers are increasingly significant in numerous tissue engineering applications and seem to be ideal scaffolds for cell growth and proliferation. The modern tissue engineering task is to develop three-dimensional scaffolds of appropriate biological and biomechanical properties, at the same time mimicking the natural extracellular matrix and promoting tissue regeneration. Furthermore, it should be biodegradable, bioresorbable and non-inflammatory, should provide sufficient nutrient supply and have appropriate viscoelasticity and strength. Attributed to collagen features mentioned above, collagen fibers represent an obvious appropriate material for tissue engineering scaffolds. The aim of this minireview is, besides encapsulation of the basic biochemical and biophysical properties of collagen, to summarize the most promising modern methods and technologies for production of collagen nanofibers and scaffolds for artificial tissue development., L. Koláčná, J. Bakešová, F. Varga, E. Košťáková, L. Plánka, A. Nečas, D. Lukáš, E. Amler, V. Pelouch., and Obsahuje bibliografii
Spinal cord injury results in a permanent neurological deficit due to tissue damage. Such a lesion is a barrier for “communication” between the brain and peripheral tissues, effectors as well as receptors. One of the primary goal s of tissue engineering is to bridge the spinal cord injury and re-establish the damaged connections. Hydrogels are biocompatible implants used in spinal cord injury repair. They can create a permissive environment and bridge the lesion cavities by providing a scaffold for the regeneration of neurons and their axons, glia and other tissue elements. The advantage of using artificial materials is the possibility to modify their physical and chemical properties in order to develop the best implant suitable for spinal cord injury repair. As a result, several types of hydrogels have been tested in experimental studies so far. We review our work that has been done during the last 5 years with various types of hydrogels and their applications in experimental spinal cord injury repair., A. Hejčl, P. Lesný, M. Přádný, J. Michálek, P. Jendelová, J. Štulík, E. Syková., and Obsahuje bibliografii a bibliografické odkazy
Noble gases are known for their inertness. They do not react chemically with any element at normal temperature and pressure. Through that, some of them are known to be biologically active by their sedative, hypnotic and analgesic properties. Common inhalation anesthetics are characterized by some disadvantages (toxicity, decreased cardiac output, etc). Inhalation of xenon introduces anesthesia and has none of the above disadvantages, hence xenon seems to be the anesthetic gas of the future (with just one disadvantage - its cost). It is known that argon has similar anesthetic properties (under hyperbaric conditions), which is much cheaper and easily accessible. The question is if this could be used in clinical practice, in anesthesia of patients who undergo treatment in the hyperbaric chamber. Xenon was found to be organ-protective. Recent animal experiments indicated that xenon decreases infarction size after ischemic attack on brain or heart. The goal of our study is to check if hyperbaric argon has properties similar to those of xenon., J. Růžička, J. Beneš, L. Bolek, V. Markvartová., and Obsahuje bibliografii
Selenium is a trace element that is essential for living organism. Its beneficial effect is, however, expressed in a very narrow dosage range: the high and low doses of selenium are connected with pathological manifestations. The toxicity depends on the chemical form of selenium, state of organism, interactions with heavy metals and on the stage of ontogenetic development. Whereas one dose of sodium selenite (20 μmol/kg b.w.) is lethal in adult rats, suckling rats are entirely resistant. However, within one week after administration of the same dose, cataract of eye lens developed. The highest incidence of cataract was observed in 10-day-old animals and it decreased until day 20. From postnatal day 20 to day 40 the rats were resistant to both the lethal and cataractogenic effects of selenium. The incidence of cataract may be suppressed by premature weaning, lower hydration of suckling, change of water soluble/water insoluble lens protein ratio, thyroxine treatment, and by interaction with mercury. By means of its oxidative and reduction properties, selenium is involved in the maintenance of the cell redox homeostasis. Typical example is its possible cardioprotective effect: selenium decreased number of arrhythmias, reduced infarct size and improved the contractile recovery after ischemia/reperfusion injury. Selenium supplementation may thus increase cardiac tolerance to ischemic damage., I. Ošťádalová., and Obsahuje seznam literatury
A new generator of two successive shock waves focused to a common focal point has been developed. Cylindrical pressure waves created by multichannel electrical discharges on two cylindrical composite anodes are focused by a metallic parabolic reflector - cathode, and near the focus they are transformed to strong shock waves. Schlieren photos of the focal region have demonstrated that mutual interaction of the two waves results in generation of a large number of secondary short-wavelength shocks. Interaction of the focused shockwaves with liver tissues and cancer cell suspensions was investigated. Localized injury of rabbit liver induced by the shock waves was demonstrated by magnetic resonance imaging. Histological analysis of liver samples taken from the injured region revealed that the transition between the injured and the healthy tissues is sharp. Suspension of melanoma B16 cells was exposed and the number of the surviving cells rapidly decreased with increasing number of shocks and only 8 % of cells survived 350 shocks. Photographs of cells demonstrate that even small number of shocks results in perforation of cell membranes., J. Beneš, P. Šunka, J. Králová, J. Kašpar, P. Poučková., and Obsahuje bibliografii
Obesity is a strong cardiometabolic (CM) risk factor in children. We tested potential CM risk in obese/overweight children and the effect of an intensive lifestyle intervention using newer CM markers: atherogenic index of plasma AIP [Log(TG/HDL-C)], apoB/apoAI ratio and a marker of insulin resistance HOMA-IR. The participants (194 girls, 115 boys, average age 13) were enrolled in an intensive, one-month, inpatient weight reduction program. The program consisted of individualised dietary changes and the exercise program comprised aerobic and resistance training. Anthropometrical and biochemical parameters in plasma and CM risk biomarkers - (AIP, apoB/apoAI ratio and HOMA-IR) were examined before and after the intervention. AIP and HOMA-IR significantly correlated with BMI while apoB/apoAI ratio did not. Only AIP and HOMA-IR showed systematic increases according to the level of obesity by BMI quartiles. Lifestyle intervention significantly improved anthropometrical and biochemical values and the biomarkers too. The response of lipid parameters to the intervention was considerably higher in boys than in girls. The children were stratified into three risk categories according to AIP, where 13.8 % of boys and 5.3 % of girls fell into high risk category. The monitored biomarkers may complement each other in the prognosis of CM risk. AIP was strongly related to obesity and to lipid and glycid metabolism, while the relationship of the apoB/apoAI ratio to obesity and glycid metabolism was not significant. The obese children benefited from the intensive lifestyle intervention which improved the anthropometrical and biochemical parameters and CM risk biomarkers., M. Vrablík, M. Dobiášová, L. Zlatohlávek, Z. Urbanová, R. Češka., and Obsahuje bibliografii
Primary graft dysfunction (PGD) is a life-threatening complication among heart transplant recipients and a major cause of early mortality. Although the pathogenesis of PGD is still unclear, ischemia/reperfusion injury has been identified as a predominant factor. Both necrosis and apoptosis contribute to the loss of cardiomyocytes during ischemia/reperfusion injury, and this loss of cells can ultimately lead to PGD. The aim of our prospective study was to find out whether cell death, necrosis and apoptosis markers present in the donor myocardium can predict PGD. The prospective study involved 64 consecutive patients who underwent orthotopic heart transplantation at our institute between September 2010 and January 2013. High-sensitive cardiac troponin T (hs-cTnT) as a marker of minor myocardial necrosis was detected from arterial blood samples before the donor’s pericardium was opened. Apoptosis (caspase-3, active + pro-caspase-3, bcl-2, TUNEL) was assessed from bioptic samples taken from the right ventricle prior graft harvesting. In our study, 14 % of transplant recipients developed PGD classified according to the standardized definition proposed by the ISHLT Working Group. We did not find differences between the groups in regard to hs-cTnT serum levels. The mean hs-cTnT value for the PGD group was 57.4±22.9 ng/l, compared to 68.4±10.8 ng/l in the group without PGD. The presence and severity of apoptosis in grafted hearts did not differ between grafts without PGD and hearts that subsequently developed PGD. In conclusion, our findings did not demonstrate any association between measured myocardial cell death, necrosis or apoptosis markers in donor myocardium and PGD in allograft recipients. More detailed investigations of cell death signaling pathways in transplanted hearts are required., O. Szarszoi, J. Besik, M. Smetana, J. Maly, M. Urban, J. Maluskova, A. Lodererova, L. Hoskova, Z. Tucanova, J. Pirk, I. Netuka., and Obsahuje bibliografii
Pneumatic tourniquets are widely used in pediatric extremity surgery to provide a bloodless field and facilitate dissection. This prospective study was carried out to examine possible effect of different anesthesia techniques on oxidative stress and endothelial dysfunction connected with ischemia-reperfusion injury during extremity operations at children's age. Patients were randomized into three groups of 15 patients each: general inhalational anesthesia with sevoflurane (group S), total intravenous anesthesia with propofol (group T) and regional anesthesia (group R). Venous blood samples for determination of the malondialdehyde in plasma and erythrocytes, protein carbonyl groups concentration as well as plasma nitrites and nitrates level and xanthine oxidase activity were obtained at four time points: be fore peripheral nerve block and induction of general anesthesia (baseline), 1 min before tourniquet release, 5 and 20 min after tourniquet release. This study demonstrates that total intravenous anesthesia with propofol and regional anesthesia techniques provide better antioxidant defense and reduce endothelial dysfunct ion than general inhalational anesthesia with sevoflurane during tourniquet application in pediatric extremity surgery., I. Budic ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The present article introduces a novel method of characterizing the macromechanical cartilage properties based on dynamic testing. The proposed approach of instrumented impact testing shows the possibility of more detailed investigation of the acting dynamic forces and corresponding deformations within the wide range of strain rates and loads, including the unloading part of stress-strain curves and hysteresis loops. The presented results of the unconfined compression testing of both the native joint cartilage tissues and potential substitute materials outlined the opportunity to measure the dissipation energy and thus to identify the initial mechanical deterioration symptoms and to introduce a better definition of material damage. Based on the analysis of measured specimen deformation, the intact and pathologically changed cartilage tissue can be distinguished and the differences revealed., F. Varga, M. Držík, M. Handl, J. Chlpík, P. Kos, E. Filová, M. Rampichová, A. Nečas, T. Trč, E. Amler., and Obsahuje bibliografii
Diabetes is a recognized risk factor of heart disease. The abnormalities related to a decreased heart performance probably arise at cellular and molecular levels already in the asymptomatic phase of diabetes. However, the early alterations initiating a sequence of events that culminates in the clinical signs have not been fully elucidated yet. This review deals with some biophysical methods applied to investigation of left ventricular myocytes in rats with streptozotocin diabetes, as well as our most important findings concerning diabetes-induced cell changes which cannot be captured by other techniques. The observed decrease in sarcolemmal membrane fluidity is causatively associated with increased glycation and glycoxidation. On the other hand, an increase in the mitochondrial membrane fluidity may be attributed to augmented energy transduction through the membranes. We reported for the first time concurrent measurements of membrane potential and dynamics, and respiratory chain activities in rat heart mitochondria, as well as calcium transients in the myocytes from diabetic hearts together with the assessed quantitative relationships among these variables. We were able to detect some significant alterations that may underlie myocyte dysfunction and subsequent remodeling of the heart. We suppose that not all these changes reflect mechanisms leading to pathology; some may represent adaptive and compensatory responses to diabetes., I. Waczulíková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
To determine the role of postinspiratory inspiratory activity of the diaphragm in the biphasic ventilatory response to hypoxia in unanesthetized rats, we examined diaphragmatic activity at its peak (DI), at the end of expiration (DE), and ventilation in adult unanesthetized rats during poikilocapnic hypoxia (10 % O2) sustained for 20 min. Hypoxia induced an initial increase in ventilation followed by a consistent decline. Tidal volume (VT), frequency of breathing (fR), DI and DE at first increased, then VT and DE decreased, while fR and DI remained enhanced. Phasic activation of the diaphragm (DI - DE) increased significantly at 10, 15 and 20 min of hypoxia. These results indicate that 1) the ventilatory response of unanesthetized rats to sustained hypoxia has a typical biphasic character and 2) the increased end-expiratory activity of the diaphragm limits its phasic inspiratory activation, but this increase cannot explain the secondary decline in tidal volume and ventilation., H. Maxová, M. Vízek., and Obsahuje bibliografii
Cardiac resynchronization therapy is not commonly used in the early postoperative period in pati ents undergoing cardiac surgery who have left ventricular (LV) dysfunction and a history of heart failure. We performed a prospective randomized clinical trial to compare atrial synchronous right ventricular (DDD RV) and biventricular (DDD BIV) pacing within 72 hours after cardiac surgery in patients with an EF ≤ 35 %, a QRS interval longer than 120 msec and who had LV dyssynchrony detected by real-time three-dimensional echocardiography (RT3DE). Epicardial pacing was provided by a modified Medtronic INSYNC III pacemaker. An LV epicardial pacing lead was implanted on the latest activated segment of the LV based on RT3DE. The study included 18 patients with ischemic heart diseas e, with or without valvular heart disease (14 men, 4 women, average age 71 years). Patients undergoing DDD BIV pacing had a statistically significant greater CO and CI (CO 6.7±1.8 l/min, CI 3.4±0.7 l/min/m²) than patients undergoing DDD RV pacing (CO 5.5±1.4 l/min, CI 2.8±0.7 l/min/m²), p<0.001. DDD BIV paci ng in the early postoperative period after cardiac surgery corrects LV dyssynchrony and has better hemodynamic results than DDD RV pacing., F. Straka ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The production of the pineal hormone melatonin is synchronized with day-night cycle via multisynaptic pathway including suprachiasmatic nucleus linking several physiological functions to diurnal cycle. The recent data indicate that impaired melatonin production is involved in several cardiovascular pathologies including hypertension and ischemic heart disease. However, the mechanisms of melatonin effect on cardiovascular system are still not completely understood. The activation of melatonin receptors on endothelial and vascular smooth muscle cells and antioxidant properties of melatonin could be responsible for the melatonin effects on vascular tone. However, the data from in vitro studies are controversial making the explanation of the melatonin effect on blood pressure in vivo difficult. In vivo, melatonin also attenuates sympathetic tone by direct activation of melatonin receptors, scavenging free radicals or increasing NO availability in the central nervous system. The central and peripheral antiadrenergic action of chronic melatonin treatment might eliminate the mechanisms counter-regulating decreased blood pressure, providing thus additional cardioprotective mechanism. The extraordinary antioxidant activity and antilipidemic effects of melatonin may enhance the modulation of blood pressure by melatonin and probably play the most important role in the amelioration of target organ damage by chronic melatonin treatment. Further investigation of these mechanisms should provide novel knowledge about pathophysiological mechanisms of cardiovascular diseases, additional explanation for their circadian and seasonal variability and potentially generate new impulses for the development of therapeutic arsenal., Ľ. Paulis, F. Šimko., and Obsahuje bibliografii a bibliografické odkazy
The goal of the research is to investigate the special effect of ovarian-menstrual cycle phases on the level of women’s blood pressure and characteristics of Mayer waves. 77 women aged 18-19 were tested under condition close to the state of basal metabolism in follicular phase (I), ovulation (II) and luteal phase (III) of ovarian-menstrual cycle. In phases II and III, the increase of mean and diastolic blood pressure level, in comparison with phase I in the prone position at rest and with psycho-emotional loading, were observed. The distinctions between variation parameters of R-R interval duration, stroke volume and its synchronization in phases II and III, in comparison with phase I, were observed in the prone position at rest, during tilt-test and with psycho-emotional loading. The substantial level of relationship between the power of Mayer waves and mean and diastolic blood pressure, mainly in phase I under conditions of all types, is observed. The maximum peak amplitude of stroke volume spectrogram is associated with pressure levels in the range of 0.04-0.15 Hz (ρ from -0.33 to -0.64). The obtained results indicate the possible participation of spontaneous baroreflex sensitivity characteristics in keeping blood pressure level in women., O. I. Lutsenko, S. O. Kovalenko., and Obsahuje bibliografii
Type 2 diabetes mellitus (T2DM) is associated with increased fracture risk; the underlying mechanism remains unexplained. This study aimed to investigate the relationships between body composition and bone and glucose metabolism in postmenopausal women wit h T2DM. Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD) and body composition. A total of 68 postme nopausal women with T2DM and 71 controls were eligible for the study. In contrast to normal BMD in T2DM, a similar prevalence of low-trauma fractures was observed in both groups. T2DM women had significantly higher Trunk fat% and A/G ratio and significantly lower Legs LM% and Legs FM%. Legs LM% was significantly lower in fractured T2DM group and negatively correlated with glycaem ia and HbA1c (p<0.01). Serum osteocalcin was significantly lower in T2DM and inversely correlated with FM%, Trunk FM% and A/G ratio (p<0.01) and positively correlated with Legs FM% and total LM% (p<0.05). In conclusion, abdominal obesity and decrease in mu scle mass may contribute to low bone formation in T2DM women. Further research is needed to unravel underlying pathophysiological mechanisms and to determine whether maintenance of muscle mass, especially in the lower extremities and/or reduction of centra l fat mass can prevent fractures., I. Raška Jr., M. Rašková, V. Zikán, J. Škrha., and Obsahuje bibliografii
Variants within the FTO gene are important determinants of body mass index (BMI), but their role in determination of BMI changes after combined dietary/physical ac tivity intervention is unclear. We have analyzed 107 unrelated overweight non-diabetic Czech females (BMI over 27.5 kg/m2 , age 49.2±12.3 years). FTO variants rs17817449 (first intron) and rs17818902 (third intron) were genotyped. The life style mo dification program (10 weeks) consisted of an age- matched reduction of energy intake and exercise program (aerobic exercise 4 times a week, 60 min each). The mean BMI before intervention was 32.8±4.2 kg/m2 and the mean achieved weight loss was 4.8±3.5 kg (5.3±3.5 %, max. -15.5 kg, min. +2.0 kg, p<0. 01). No significant association between BMI decrease and FTO variants was found. Also waist-to-hip ratio, body composition (body fat, water, active tissue), lipid parameters (total, LDL and HDL cholesterol, triglycerides) glucose and hsCRP change s were independent on FTO variants. FTO variants rs17817449 and rs17818902 are not associated with BMI changes after combined short time dietary/physical activity intervention in overweight females., D. Dlouhá ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
In the present paper we describe changes of anatomical parameters in inbred Lewis strain rats, namely their body weight, body weight gain per week, absolute and relative heart, thyroid gland and skeletal muscle weights, that are assumed to reflect experimentally altered thyroid status. The hyperthyroid state was induced by DL-thyroxine or Na 3,3',5-triiodo-L-thyronine, while methimazole was employed for inducing hypothyroidism. We have found that when compared to euthyroid rats, hypothyroidism resulted in a significantly lower body weight gain, absolute and relative heart weight and, in contrast, in a significant increase of absolute and relative thyroid gland weight. On the other hand, hyperthyroidism led to a significant increase of absolute and relative heart weight and to a significant reduction of absolute and relative thyroid gland weight. However, the body mass was not significantly altered in hyperthyroidism as compared with euthyroid rats. We conclude that our protocol leads to chronic hyper- or hypothyroidism as demonstrated by body, heart and thyroid gland weight changes. These anatomical data can thus be utilized as supplemental criteria for the assessment of the thyroid state of experimental rats., T. Soukup, G. Zachařová, V. Smerdu, I. Jirmanová., and Obsahuje bibliografii
The aim of the current study was to clarify the effect of high sucrose diet (HSD) on bile formation (BF) in rats with hereditary hypertriglyceridemia (HHTg). Potentially positive effects were studied for boldine, a natural choleretic agent. Administration of HSD to HHTg rats led to increased triglyceride deposition in the liver. HSD reduced BF as a consequence of decreased biliary secretion of bile acids (BA) and glutathione. Responsible mechanism was down-regulation of hepatic transporters for BA and glutathione, Bsep and Mrp2, respectively. Moreover, gene expressions of transporters for other constituents of bile, namely Abcg5/8 for cholesterol, Abcb4 for phospholipids, and Oatp1a4 for xenobiotics, were also reduced by HSD. Boldine partially attenuated cholestatic effect of HSD by promotion of biliary secretion of BA through up-regulation of Bsep and Ntcp, and by increase in biliary secretion of glutathione as a consequence of its increased hepatic disposition. This study demonstrates mechanisms of impaired BF during nonalcoholic fatty liver disease induced by HSD. Altered function of responsible transporters suggests also potential for changes in kinetics of drugs, which may complicate pharmacotherapy in subjects with high intake of sucrose, and with fatty liver disease. Sucrose induced alterations in BF may be alleviated by administration of boldine., M. Zagorova, A. Prasnicka, Z. Kadova, E. Dolezelova, L. Kazdova, J. Cermanova, L. Rozkydalova, M. Hroch, J. Mokry, S. Micuda., and Obsahuje bibliografii
This minireview briefly surveys the complexity of regulations governing the bone metabolism. The impact of clinical studies devoted to osteoporosis is briefly summarized and the emphasis is put on the significance of experimental mouse models based on an extensive use of genetically modified animals. Despite possible arising drawbacks, the studies in mice are of prime importance for expanding our knowledge on bone metabolism. With respect to human physiology and medicine, one should be always aware of possib le limitations as the experimental results may not be, or may be only to some extent, transposed to humans. If applicable to humans, results obtained in mice provide new clues for assessing un foreseen treatment strategies for patients. A recent publication representing in our opinion the important breakthrough in the field of bone metabolism in mice is commented in detail. It provides an evidence that skeleton is endocrine organ that affects energy metabolism and osteocalcin, a protein specifically synthesized and secreted by osteoblasts, is a hormone involved. If confirmed by other groups and applicable to humans, this study provides the awaited connection of long duration between bone disorders on one hand and obesity and diabetes on the other., O. Raška, K. Bernášková, I. Raška Jr., and Obsahuje seznam literatury
The aim of the study was to compare the bone mineral density (BMD) and body composition between ambulatory male MS patients and control subjects and to evaluate the relationships among body composition, motor disability, glucocorticoids (GC) use, and bone health. Body composition and BMD were measured by dual-energy X-ray absorptiometry in 104 ambulatory men with MS (mean age: 45.2 years) chronically treated with low-dose GC and in 54 healthy age-matched men. Compared to age-matched controls, MS patients had a significantly lower total body bone mineral content (TBBMC) and BMD at all measured sites except for the radius. Sixty five male MS patients (62.5 %) met the criteria for osteopenia and twenty six of them (25 %) for osteoporosis. The multivariate analysis showed a consistent dependence of bone measures (except whole body BMD) on BMI. The total leg lean mass % was as an independent predictor of TBBMC. The Expanded Disability Status Scale (EDSS), cumulative GC dose and age were independent determinants for BMD of the proximal femur. We conclude that decreasing mobility in male MS patients is associated with an increasing degree of osteoporosis and muscle wasting in the lower extremities. The chronic low-dose GC treatment further contributes to bone loss., V. Zikán ... [et al.]., and Obsahuje seznam literatury
The peak bone mass and the rate of bone loss are in part genetically determined. It has been suggested that bone mineral density (BMD) may be related to allelic variation in the apolipoprotein E (ApoE) gene locus. ApoE is important in the receptor-mediated clearance of chylomicron particles from the plasma, Apo E4 having the highest and Apo E2 the lowest receptor affinity. Chylomicrons are the main carrier of vitamin K in the plasma; vitamin K plays an important role in the carboxylation of osteocalcin. We have tested the hypothesis that persons with E4 variant would have lower BMD and increased bone turnover than those with E2 variant. A total of 18 ApoE 2/2 and ApoE 4/4 homozygotes were selected from 873 patients who were examined for the ApoE genotype. BMD in lumbar vertebral, femoral neck and distal forearm was measured and plasma concentrations of osteocalcin and C-terminal fragments of collagen (CTx) were determined. BMD values (expressed as T-score) at the three specified sites were -0.12± 1.72, -0.52± 1.32 and -0.52± 0.81 in ApoE 2/2 group and -0.24± 1.22, 0.00± 0.84 and -0.17± 1.07 in the ApoE 4/4 group. Plasma osteocalcin and CTx were within normal limits in both groups. In conclusion, we did not observe any association of ApoE genotype with BMD and biochemical markers of bone metabolism in ApoE 2/2 and ApoE 4/4 homozygotes., T. Štulc, R. Češka, A. Hořínek, J. Štěpán., and Obsahuje bibliografii
Exercise induced bone response although established, little is known about the molecular components that mediate bone response to mechanical loading (ML). In our recent QTL study, we identified one such possible molecular component responding to ML: cartilage oligomeric matrix protein (COMP). To address the COMP role in mediating ML effects on bone formation, COMP expression was evaluated as a function of duration and age in response to ML in female B6 mice. A 9N load was applied using a four-point bending device at 2Hz frequency for 36 cycles, once per day for 2-, 4- and 12-days on the right tibia. The left tibia was used as an internal control. Loading caused an increase in COMP expression by 1.3-, 2- and 4-fold respectively after 2-, 4- and 12-days of loading. This increase was also seen in 16 and 36-week old mice. Based on these findings, we next used COMP knockout (KO) mice to evaluate the cause and effect relationship. Quantitative analysis revealed 2 weeks of ML induced changes in vBMD and bone size in the KO mice (5.9 % and 21 % vs. unloaded bones) was not significantly different from control mice (7 % and 24 % vs. unloaded bones). Our results imply that COMP is not a key upstream mediator of the anabolic effects of ML on the skeleton., A. Sengul, S. Mohan, C. Kesavan., and Obsahuje seznam literatury
Bone is a target tissue for hormones, such as the sex steroids, parathormon, vitamin D, calcitonin, glucocorticoids, and thyroid hormones. In the last decade, other “non-classic” hormones that modulate the bone tissue have been identified. While incretins (GIP and GLP-1) inhibit bone remodeling, angiotensin acts to promote remodeling. Bone morphogenetic protein (BMP) has also been found to have anabolic effects on the skeleton by activating bone formation during embryonic development, as well as in the postnatal period of life. Bone has also been identified as an endocrine tissue that produces a number of hormones, that bind to and modulate extra-skeletal receptors. Osteocalcin occupies a central position in this context. It can increase insulin secretion, insulin sensitivity and regulate metabolism of fatty acids. Moreover, osteocalcin also influences phosphate metabolism via osteocyte-derived FGF23 (which targets the kidneys and parathyroid glands to control phosphate reabsorption and metabolism of vitamin D). Finally, osteocalcin stimulates testosterone synthesis in Leydig cells and thus may play some role in male fertility. Further studies are necessary to confirm clinically important roles for skeletal tissue in systemic regulations., I. Zofkova., and Obsahuje bibliografii
We investigated the renal response to direct renal nerve stimulation, 2 weeks following reversal of 24-h unilateral (left) ureteric obstruction. Renal nerve stimulation caused a 13-15 % fall in renal blood flow, in 4 groups of anesthetized rats following ureteric obstruction (n=9) or a sham operation (n=7) both with (n=9) and without (n=7) treatment with the mixed ETA/B receptor antagonist, bosentan. In the sham-operated rats, renal nerve stimulation did not change glomerular filtration rate but reduced urine flow rate (37±3 %, P<0.001), and absolute (38±4 %, P<0.001) and fractional (35±5 %, P<0.01) sodium excretion. Following unilateral ureteric obstruction, renal nerve stimulation increased glomerular filtration rate by 22±3 % (P<0.01), but reduced urine flow rate (14±2 %, P<0.001) and fractional sodium excretion (23±5 %, P<0.01). Bosentan treatment had no effect on baseline or renal responses to renal nerve stimulation in the sham group but normalized the renal response to renal nerve stimulation in the unilateral ureteric obstruction group. We conclude that 14 days after a 24-h period of unilateral ureteric obstruction there is an increase in GFR in response to direct renal nerve stimulation, which is due, in part, to the actions of endothelin at the time of obstruction., F. T. Hammad, A. M. Wheatley, G. Davis., and Obsahuje bibliografii
Our previous experiments revealed that water intoxication and osmotic BBB disruption in the rat allow penetration of high- molecular substances into the brain and that resulting changes in the internal environment of th e CNS lead to pathological development, such as the loss of integrity of myelin. The aim of the present study was to determine whether the previously described phenomena are associated with increased water content in the brain. To answer the question following methods were used: a) water intoxication : intraperitoneal administration of distilled water, b) osmotic BBB disruption: application of mannitol (20 %) selectively into the internal carotid artery, c) brain wet weight was measured after decapitation, and subsequently (after six days in thermostat set at 86 °C) the dry weight were estimated d) in animals with 20 % and 30 % hyperhydration the degree of myelin deterioration was estimated e) animal locomotor activity was tested by continuous behavior tracking and analysis. Brai n water content after water intoxication and following the administration of mannitol was higher than in the control group. Different degrees of hyperhydration led to different levels of brain water content and to different degrees of myelin impairment. Hyperhydration corresponding to 20 % of the body weight brought about lower locomotor activity. Increased water content in the brain after the BBB osmotic disruption is surprising because this method is frequently used in the clinical practice., P. Kozler, V. Riljak, J. Pokorný., and Obsahuje bibliografii a bibliografické odkazy
Functional magnetic resonance imaging (fMRI) was used to demonstrate the brain activation during volitional control of breathing in nine healthy human subjects. This type of breathing was induced by acoustic stimuli dictating the respiratory frequency. During the period of dictated breathing not only the frontal and temporal lobes of the brain, but also the parietal lobes were bilaterally activated. The frontal lobe was activated bilaterally in all subjects, with frequent activation of Brodmann areas 4 and 6. In the parietal lobe, activation could mostly be demonstrated in gyrus postcentralis and the same was true for area 22 in the temporal lobe., V. Šmejkal, R. Druga, J. Tintěra., and Obsahuje bibliografii
Over a century ago, hyperplasia and hypertrophy of astrocytes was noted as a histopathological hallmark of multiple sclerosis and was hypothesized to play an important role in the development and course of this disease. However until today, the factual contribution of astrocytes to multiple sclerosis is elusive. Astrocytes may play an active role during degeneration and demyelination by controlling local inflammation in the CNS, provoking damage of oligodendrocytes and axons, and glial scarring but might also be beneficial by creating a permissive environment for remyelination and oligodendrocyte precursor migration, proliferation, and differentiation. Recent findings from our lab suggest that brain lipid binding protein (FABP7) is implicated in the course of multiple sclerosis and the regulation of astrocyte function. The relevance of our findings and data from other groups are highlighted and discussed in this paper in the context of myelin repair., M. Kipp ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Our objective was to evaluate the utility of the natriuretic peptides BNP (brain natriuretic peptide) and NT-proBNP as markers of pulmonary artery systolic pressure (PASP) in trekkers ascending to high altitude (HA). 20 participants had BNP and NT- proBNP assayed and simultaneous echocardiographic assessment of PASP performed during a trek to 5150 m. PASP increased significantly (p=0.006) with ascent from 24±4 to 39±11 mm Hg at 5150 m. At 5150 m those with a PASP ≥ 40 mm Hg (n=8) (versus those with PASP<40 mm Hg) had higher post-exercise BNP (pg/ml): 54.5±36 vs. 13.4±17 (p=0.012). Their resting BNP at 5150 m was also higher: 57.3±43.4 vs. 12.6±13 (p=0.017). In those with a pathological ( ≥ 400 pg/ml) rise in NT-proBNP at 5150 m (n=4) PASP was significantly higher: 45.9±7.5 vs. 32.2±6.2 mm Hg (p=0.015). BNP and NT-proBNP may reflect elevated PASP, a central featur e of high altitude pulmonary oedema, at HA., D. R. Woods ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The purpose of the present study was to investigate whether peripheral brain-derived neurotrophic factor (BDNF) treatment induced metabolic adaptations in mouse skeletal muscle. BDNF (20 mg/kg/day) was injected subcutaneously for successive 14 days. BDNF treatment significantly reduced the total food intake and inhibited the weight gain in comparison to the control group. The glucose transporter 4 (GLUT4) protein expression in the gastrocnemius muscle was significantly increased by BDNF treatment in comparison to the control and pair-fed groups. Neither the oxidative nor the glycolytic enzyme activities in the gastrocnemius muscle changed after the BDNF treatment. These results suggest that the peripheral BDNF treatment promotes the skeletal muscle GLUT4 protein expression as well as hypophagia., M. Suwa ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Severe meconium aspiration sy ndrome (MAS) in newborns is often treated by exogenous surfac tant. Because its efficacy is reduced by meconium-induced inflammation, glucocorticoid budesonide was added into surfac tant preparation Curosurf to enhance efficacy of the surfactant therapy in experimental model of MAS. Oxygen-ventilated rabbits were intratracheally given meconium (25 mg/ml, 4 ml/kg) to induce respiratory failure. Thirty minutes later, animals were treated by intratracheal budesonide (0.25 mg/kg) ; or surfactant lung lavage (10 ml/kg, 5 mg phospholipids/ml) repeated twice, followed by undiluted Curosurf (100 mg phospholipids/kg) ; or by the above mentioned surfactant treatment with the last surfactant dose fortified with budesonide (0.25 mg/kg) ; or were untreated. Animals were ventilated for additional 5 hours and respiratory parameters were measured regularly. After sacrificing animals, wet-dry lung weight ratio was evaluated and plasma levels of interleukins (IL)-1beta, -6, -8, and TNF-alpha were measured by ELISA method. Efficacy of the given therapies to enhance lung functions and to diminish lung edema formation and in flammation increased from budesonide-only and surf actant-only therapy to surfactant+budesonide therapy. Combined therapy improved gas exchange from 30 min of administration, and showed a longer- lasting effect than surfactant-only therapy. In conclusions, budesonide additionally improv ed the effects of exogenous surfactant in experimental MAS., P. Mikolka ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Colonic mucosal protection is provided by the mucus gel, mainly composed of mucins. Several factors can modulate the formation and the secretion of mucins, and among them butyrate, an end-product of carbohydrate fermen tation. However, the specific effect of butyrate on the various colonic mucins, and the consequences in terms of the mucus layer thickness are not known. Our aim was to determine whether butyrate modulates colonic MUC genes expression in vivo and whether this results in changes in mucus synthesis and mucus layer thickness. Mice received daily for 7 days rectal enemas of butyrate (100 mM) versus saline. We demonstrated that butyrate stimulated the gene expression of both secreted (Muc2) and membrane-linked (Muc1, Muc3, Muc4) mucins. Butyrate especially induced a 6-fold increase in Muc2 gene expression in proximal colon. However, butyrate enemas did not modify the number of epithelial cells containing the protein Muc2, and caused a 2-fold decrease in the thickness of adherent mucus layer. Further studies should help understanding whether this last phenomenon, i.e. the decrease in adherent mucus gel thickness, results in a diminished protective function or not., E. Gaudier ... [et al.]., and Obsahuje seznam literatury
We determined and characterized the Mg2+-dependent, Ca2+-stimulated ATPase (Ca-ATPase) activity in cell plasma membranes from the myometrium of pregnant women, and compared these characteristics to those of the active Ca2+-transport already demonstrated in this tissue. Similarly to the Ca2+-transport system, the Ca2+-ATPase is Mg2+-dependent, stimulated by calmodulin, and inhibited by vanadate. The Km for Ca2+ activation is 0.40 m M, very similar to that found for active calcium transport, i.e. 0.25 m M. Consequently, this Ca2+-ATPase can be responsible for the active calcium transport across the plasma membranes of smooth muscle cells., F. Carrera, T. Proverbio, R. Marín, F. Proverbio., and Obsahuje bibliografii
Intracellular free Ca2+ is one of important biological signals regulating a number of cell functions. It has been discussed widely and extensively in several cell types during the past two decades. Attention has been paid to the Ca2+ transportation in mesenchymal stem cells in recent years as mesenchymal stem cells have gained considerable interest due to their potential for cell replacement therapy and tissue engineering. In this paper, roles of intracellular Ca2+ oscillations and its transporters in mesenchymal stem cells have been reviewed., B. Ye., and Obsahuje bibliografii a bibliografické odkazy
The present study was devised to assess the effects of cadmium chloride (CdCl2) administration on certain andrological, endocrinological and biochemical alterations in adult male rabbits (n=24). The animals were assigned to control (n=8) and experimental (n=16) group. Experimental group was orally administered with 1.5 mg/kg body weight of CdCl2. The trials were carried out for a total of 5 weeks and blood sampling was carried out on weekly basis. A gradual decrease was noticed for body weight in the experimental group from week 1 to 5, being significantly lower in week 4 and 5 (P<0.05). A similar decremented trend was noticed for serum testosterone level being significantly lower in experimental group in week 4 and 5 (P<0.001). Significantly lower values were noticed for prolactin in experimental group in week 4 and 5 (P<0.05), than in the control. On the contrary, serum cortisol level showed a gradual increase in experimental group, from week 1 to 5, being significantly higher in week 4 and 5 (P<0.05). Regarding the biochemical attributes, all the parameters under study revealed a gradually ascending trend. Statistical significance was, however, achieved in varying weeks and at varying levels. The total protein and albumin were significantly higher in week 4 and 5 (P<0.01); alanine aminotransferase in week 2 (P<0.01), 3 (P<0.001), 4 (P<0.01) and 5 (P<0.001); aspartate aminotransferase in week 1, 2, 3, 4 and 5 (P<0.01); and alkaline phosphatase in week 1, 2 (P<0.01), 3, 4 and 5 (P<0.0001), respectively. Overall mortality rate in experimental group was 68.75 (11/16). In a nutshell, Cd exposure results in adverse effects on all physiological parameters of body and may lead to lethal consequences., S. Sajjad, H. Malik, U. Farooq, F. Rashid, H. Nasim, S. Tariq, S. Rehman., and Obsahuje bibliografii
Exocytotic machinery in neuronal and endocrine tissues is sensitive to changes in intracellular Ca2+ concentration. Endocrine cell models, that are most frequently used to study the mechanisms of regulated exocytosis, are pancreatic beta cells, adrenal chromaffin cells and pituitary cells. To reliably study the Ca2+ sensitivity in endocrine cells, accurate and fast determination of Ca2+ dependence in each tested cell is required. With slow photo-release it is possible to induce ramp-like increase in intracellular Ca2+ concentration ([Ca2+]i) that leads to a robust exocytotic activity. Slow increases in the [Ca2+] i revealed exocytotic phases with different Ca2+ sensitivities that have been largely masked in step-like flash photo-release experiments. Strikingly, in the cells of the three described model endocrine tissues (beta, chromaffin and melanotroph cells), distinct Ca2+ sensitivity ‘classes’ of secretory vesicles have been observed: a highly Ca2+ -sensitive, a medium Ca2+ -sensitive and a low Ca2+ - sensitive kinetic phase of secretory vesicle exocytosis. We discuss that a physiological modulation of a cellular activity, e.g. by activating cAMP/PKA transduction pathway, can switch the secretory vesicles between Ca2+ sensitivity classes. This significantly alters late steps in the secretory release of hormones even without utilization of an additional Ca2+ sensor protein., J. Dolenšek, M. Skelin, M. S. Rupnik., and Obsahuje bibliografii a bibliografické odkazy
Experimental and epidemiological studies suggest that calcium intake is inversely related to weight gain. Calcium of dairy origin has been shown to be more effective in promoting weight loss. However, clinical studies yielded controversial results concerning the role of calcium intake in weight change. The aim of this study was to ascertain whether the addition of calcium can affect the outcome of 3-week weight management (WM) with a hypocaloric diet characterized by a decreased calcium intake. Overweight/obese women (n=67; BMI 32.2±4.1 kg/m2; age 49.1±12.1 years) underwent a 4-week comprehensive WM program. WM included a 7 MJ/day diet resulting in a stable weight during the first week and a 4.5 MJ/day diet with mean daily calcium intake 350 mg during the second to fourth week. Participants were divided into three age- and BMI-matched groups who received placebo or calcium (500 mg/day). Calcium was administered either as carbonate or calcium of dairy origin (Lactoval). There was no significant difference in weight loss in response to WM between the placebo-treated and calcium-treated groups. However, addition of calcium to the diet resulted in a lower hunger score in the Eating Inventory as well as a decrease in plasma resistin levels. Body composition measured by bioimpedance demonstrated that added calcium leads to preservation of fat-free mass. Nevertheless, a greater loss of fat-free mass in the placebo group might be partly due to a greater loss of water., K. Kabrnová-Hlavatá, V. Hainer, M. Gojová, P. Hlavatý, V. Kopský, J. Nedvídková, M. Kunešová, J. Pařízková, M. Wagenknecht, M. Hill, J. Drbohlav., and Obsahuje bibliografii a bibliografické odkazy
Previous data concerning the action of calcium (Ca) on gastric acid secretion (GAS) indicated that calcium ions increase GAS elicited by gastrin released through a vagal mechanism, and also by a direct effect on parietal cells. Our research showed that the stimulating effect of calcium on gastric acid secretion can be antagonized by verapamil administration, which reduces gastric acid secretion . In the present study we followed the effect induced by administration of calcium and Ca-chelating agents (disodium EDTA) on gastric acid secretion and on carbonic anhydrase (CA) activity. We selected two groups of healthy volunteers: Group I (n=21) received a single i.v. dose of CaCl2 (15 mg/kg b.w.), whereas Group II (n=22) received a single i.v. dose of disodium EDTA (5 mg/kg b.w.). We determined blood calcium before and after treatment, gastric acid secretion at 2 hours, erythrocyte CA II activity, and CA IV activity in membrane parietal cells, which were isolated from gastric mucosa obtained by endoscopic biopsy. Assessment of carbonic anhydrase activity was achieved by the stopped-flow method. In Group I calcium administration increased blood calcium, HCl output, CA II and CA IV activity as compared to initial values. In Group II, disodium EDTA reduced blood calcium, HCl output, CA II and CA IV activity as compared to initial values. The results demonstrated that increased blood calcium and GAS values after calcium administration correlated with the increase of erythrocyte CA II and parietal cell CA IV activity, while disodium EDTA induced a reversed process. Our results also show that cytosolic CA II and membrane CA IV values are sensitive to calcium changes and they directly depend on these levels. Our data suggest that intra- and extracellular pH changes induced by carbonic anhydrase might account for the modulation of the physiological and pathological secretory processes in the organism., I. Puscas, M. Coltau, M. Baican, G. Domuta, A. Hecht., and Obsahuje bibliografii
The rationale for the topical application of capsaicin and other vanilloids in the treatment of pain is that such compounds selectively excite and subsequently desensitize nociceptive neurons. This desensitization is triggered by the activation of vanilloid receptors (TRPV1), which leads to an elevation in intracellular free Ca2+ levels. Depending on the vanilloid concentration and duration of exposure, the Ca2+ influx via TRPV1 desensitizes the channels themselves, which may represent not only a feedback mechanism protecting the cell from toxic Ca2+ overload, but also likely contributes to the analgesic effects of capsaicin. This review summarizes the current state of knowledge concerning the mechanisms that underlie the acute capsaicin-induced Ca2+-dependent desensitization of TRPV1 channels and explores to what extent they may contribute to capsaicin-induced analgesia. In view of the polymodal nature of TRPV1, we illustrate how the channels behave in their desensitized state when activated by other stimuli such as noxious heat or depolarizing voltages. We also show that the desensitized channel can be strongly reactivated by capsaicin at concentrations higher than those previously used to desensitize it. We provide a possible explanation for a high incidence of adverse effects of topical capsaicin and point to a need for more accurate clinical criteria for employing it as a reliable remedy., L. Vyklický, K. Nováková-Toušová, J. Benedikt, A. Samad, F. Touška, V. Vlachová., and Obsahuje bibliografii a bibliografické odkazy