Quaternary benzo[c]phenanthridine alkaloids (QBA), fagaronine (FA), sanguinarine (SA), chelerythrine (CHE) and the QBA extract from Macleya cordata (EX) exerted differential inhibitory effect on the hydrolytic activity of particular dipeptidyl peptidase (DPP)-like enzyme isolated from human blood plasma and from human and rat glioma cell lines. The low-MW form of DPP-IV-like enzyme activity, corresponding most probably to DPP-8, observed only in glioma cells but not in human plasma, was inhibited preferentially by SA, CHE and EX, and only slightly by FA. The alkaloid inhibitory effect was concentration-dependent in the range 25-150 M and directly pH-related. In addition, a subtle but consistent inhibition of the intermediate-MW form of DPP-IV-like enzyme activity, ascribed to DPP-IV/CD26, observed only in human plasma and of the attractin (high-MW form of DPP-IV-like enzyme activity, expressed in U87 glioma cells) by the studied alkaloids was observed. We conclude that some of the QBA biological effects could be determined by tissue and cell type specific dipeptidyl peptidase IV-like molecules expression pattern., A. Šedo, R. Malík, J. Vičar, V. Šimánek, J. Ulrichová., and Obsahuje bibliografii
The purpose of this study was to determine preventive and protective effects of chronic orally administration with quetiapine (QUE) against anxiety-like behavior and cognitive impairments in rats exposed to the enhanced single prolonged stress (ESPS), an animal model that is used to study post-traumatic stress disorder (PTSD), and to detect changes in the expression of cortical phosphorylated p44/42 extracellular-regulated protein kinase (pERK1/2). Before or after exposure to ESPS paradigm, consisting of 2-h constraint, 20-min forced swimming, etherinduced loss of consciousness, and an electric foot shock, rats were given orally QUE (10 mg/kg daily) for 14 days. Animals were then tested in the open field (OF), elevated plus-maze (EPM), and Morris water maze (MWM). Brains were removed for immunohistochemical staining of pERK1/2. ESPS exposure resulted in pronounced anxiety-like behavior compared to unexposed animals. ESPS-exposed animals also displayed marked learning and spatial memory impairments. However, QUE treatment (both before and after ESPS exposure) significantly ameliorated anxiety-like behavior, learning and spatial memory impairments. ESPS also markedly reduced the expression of pERK1/2 in the prefrontal cortex, medial amygdala nucleus, and cingulate gyrus. Both before and after ESPS exposure QUE treatments significantly elevated the reduced pERK1/2 expression in the three brain regions. QUE has preventive and protective effects against stress-associated symptoms and the changes in pERK1/2 functions may be associated with the pathophysiology of traumatic stress and the therapeutic efficacy of anti-PTSD therapy., H.-N. Wang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Beside heart failure and metabolic syndrome, atrial fibrillation is termed the cardiovascular epidemic of the 21st century. Its increased morbidity and mortality is alarming. The present, most effective therapy of atrial fibrillation is catheter ablation. Successful ablation of atrial fibrillation prevents the occurrence and progression of electrical, structural and mechanic myocardium remodelling, improves function of the left ventricle, and prevents the risk of thrombembolism. Onset of sinus rhythm activates the reversal remodelling leading to wall reconstruction and atrium reduction. The paper reviews the technique and presents own experience with catheter ablation., R. Lábrová, J. Špinar, N. Honzíková., and Obsahuje bibliografii a bibliografické odkazy
This work discusses the clinical performance of chromogranin A, free metanephrine and normetanephrine determination in plasma using a radioimmunoanalytical methods for the diagnosis of pheochromocytoma and paraganglioma. Blood samples were collected from 55 patients (46 pheochromocytomas, 9 paragangliomas). A sampling of biological materials was performed preoperatively and about one week, six months and one year after adrenal gland surgery. The comparative group without a diagnosis of pheochromocytoma/paraganglioma consisted of 36 pheochromocytoma/paraganglioma patients more than 4 months after adrenal gland surgery, and of 87 patients, 16 of them with multiple endocrine neoplasia, 9 with medullary and 5 with parafolicullar carcinoma of the thyroid gland. The rest were patients with various adrenal gland disorders. Chromogranin A, metanephrine and normetanephrine were determined in the EDTA-plasma using a radioimmunoassay kits Cisbio Bioassays, France and IBL International GmbH, Germany. Clinical sensitivity was 96 % for the combination of metanephrine and normetanephrine, and 93 % for chromogranin A. Clinical specificity was 100 % for the combination metanephrine and normetanephrine, and 96 % for chromogranin A. Falsely elevated levels of chromogranin A were observed in 1 patient with chronic renal insufficiency and 9 analyses were influenced by the administration of proton pump inhibitors. These results were excluded of CGA specificity. Both the combination of plasma free metanephrine, normetanephrine and chromogranin A as determined by radioimmunoassays, which are simple without the necessity of special laboratory material, are effective markers of pheochromocytoma or paraganglioma. Chromogranin A exerts association to malignity and all markers are associated with tumor mass., R. Bílek, T. Zelinka, P. Vlček, J. Dušková, D. Michalský, K. Novák, E. Václavíková, J. Widimský Jr., and Obsahuje bibliografii
Raloxifen is a selective estrogen receptor modulator which prevents bone loss in ovariectomized female mice in a fashion similar to estrogens. Since testosterone-deficient male mice also lose bone mass, we were interested in testing the effects of raloxifen on bones in intact and castrated male mice. Bone density was significantly reduced in castrated animals (1.36±0.04 g/ml) as compared to intact animals (1.42±0.03 g/ml) (p<0.01). When castrated mice with extraordinarily low concentrations of testosterone and with reduced weight of seminal vesicles were treated with raloxifen, the changes in bone density and bone minerals resulting from castration (1.36±0.04 g/ml) were entirely prevented (1.40±0.01 g/ml). Cortical bone was lost in orchidectomized mice, and this decrease in cortical thickness of the femur was prevented by raloxifen administration. Raloxifen in a dose used in humans for treatment of osteoporosis decreased the weight of seminal vesicles, an organ which is highly sensitive to the androgenic effect, decreased the concentration of testosterone (12.5±2.8 μmol/l) (p<0.01) but not to the same level as in the case of castrated animals (0.6±0.3 μmol/l), and did not have any effect on bone density or mineral content in intact mice. The results of the present study may thus be interpreted as supporting the hypothesis that raloxifen is an effective agent against the deleterious effects of castration-induced osteopenia in male mice and also support the hypothesis that estrogens may have physiological skeletal effects in male mice., P. D. Broulík, K. Broulíková., and Obsahuje bibliografii a bibliografické odkazy
The analysis of information coding in neurons requires methods that measure different properties of neuronal signals. In this paper we review the recently proposed measure of randomness and compare it to the coefficient of variation, which is the frequently employed measure of variability of spiking neuronal activity. We focus on the problem of the spontaneous activity of neurons, and we hypothetize that under defined conditions, spontaneous activity is more random than evoked activity. This hypothesis is supported by contrasting variability and randomness obtained from experimental recordings of olfactory receptor neurons in rats., L. Košťál, P. Lánský., and Obsahuje biblografii a biblografické odkazy
The development of neurogenic pulmonary edema (NPE) can be elicited by an immediate epidural balloon compression of the thoracic spinal cord. To evaluate whether a slower balloon inflation could prevent NPE development, we examined the extent of NPE in animals lesioned with a rapid (5 μl - 5 μl - 5 μl) or slow rate (3 μl - 2 μl - 2 μl - 2 μl - 2 μl - 2 μl - 2 μl) of balloon inflation. These groups were compared with the NPE model (immediate inflation to 15 μl) and with healthy controls. Slow balloon inflation prevented NPE development, whereas the pulmonary index and histology revealed a massive pulmonary edema in the group with a rapid rate of balloon inflation. Pulmonary edema was preceded by a considerable decrease in heart rate during the inflation procedure. Moreover, rapid inflation of balloon in spinal channel to either 5 μl or 10 μl did not cause NPE. Thus, a slow rate of balloon inflation in the thoracic epidural space prevents the development of neurogenic pulmonary edema, most likely due to the better adaptation of the organism to acute circulatory changes (rapid elevation of systemic blood pressure accompanied by profound heart rate reduction) during the longer balloon inflation period. It should be noted that spinal cord transection at the same level did not cause neurogenic pulmonary edema., J. Šedý ... [et al.]., and Obsahuje seznam literatury
Increased phosphorylation of Akt substrate of 160 kDa (AS160) is essential to trigger the full increase in insulin-stimulated glucose transport in skeletal muscle. The primary aim of this study was to characterize the time course for reversal of insulin-stimulated AS160 phosphorylation in rat skeletal muscle after insulin removal. The time courses for reversal of insulin effects both upstream (Akt phosphorylation) and downstream (glucose uptake) of AS160 were also determined. Epitrochlearis muscles were incubated in vitro using three protocols which differed with regard to insulin exposure: No Insulin (never exposed to insulin), Transient Insulin (30 min with 1.8 nmol/l insulin, then incubation without insulin for 10, 20 or 40 min), or Sustained Insulin (continuously incubated with 1.8 nmol/l insulin). After removal of muscles from insulin, Akt and AS160 phosphorylation reversed rapidly, each with a half-time of <10 min and essentially full reversal by 20 min. Glucose uptake reversed more slowly (half time between 10 and 20 min with essentially full reversal by 40 min). Removal of muscles from insulin resulted in a rapid reversal of the increase in AS160 phosphorylation which preceded the reversal of the increase in glucose uptake, consistent with AS160 phosphorylation being essential for maintenance of insulin-stimulated glucose uptake., N. Sharma, E. B. Arias, G. D. Cartee., and Obsahuje bibliografii a bibliografické odkazy
During the screening of apolipoprotein (apo) E gene polymorphism with PCR and subsequent restriction analysis, we have identified a female carrier with a mutant allele Arg136 ® Cys. This proband had normal lipid parameters and no history of coronary artery disease (CAD). We did not confirm the previously described connection between apo E Arg136 ® Cys mutation and elevated lipid levels. In the case of this mutation, other factors (environmental and/or genetic) are important for the development of lipid metabolism disorders., J. A. Hubáček, J. Piťha, Z. Škodová, R. Poledne., and Obsahuje bibliografii
a1_In the present paper we describe five tests, 3 of which were designed to be similar to tasks used with rodents. Results obtained from control subjects, patients with selective thermo-coagulation lesions to the medial temporal lobe and results from non-human primates and rodents are discussed. The tests involve memory for spatial locations acquired by moving around in a room, memory for objects subjects interacted with, or memory for objects and their locations. Two of the spatial memory tasks were designed specifically as analogs of the Morris water task and the 8-arm radial-maze tasks used with rats. The Morris water task was modeled by hiding a sensor under the carpet of a room (Invisible Sensor Task). Subjects had to learn its location by using an array of visual cues available in the room. A path integration task was developed in order to study the non-visual acquisition of a cognitive representation of the spatial location of objects. In the non-visual spatial memory task, we blindfolded subjects and led them to a room where they had to find 3 objects and remember their locations. We designed an object location task by placing 4 objects in a room that subjects observed for later recall of their locations. A recognition task, and a novelty detection task were given subsequent to the recall task. An 8-arm radial-maze was recreated by placing stands at equal distance from each other around the room, and asking subjects to visit each stand once, from a central point. A non-spatial working memory task was designed to be the non-spatial equivalent of the radial maze. Search paths recorded on the first trial of the Invisible Sensor Task, when subjects search for the target by trial and error are reported., a2_An analysis of the search paths revealed that patients with lesions to the right or left hippocampus or parahippocampal cortex employed the same type of search strategies as normal controls did, showing similarities and differences to the search behavior recorded in rats. Interestingly, patients with lesions that included the right parahippocampal cortex were impaired relative to patients with lesions to the right hippocampus that spared the parahippocampal cortex, when recall of the sensor was tested after a 30 min delay (Bohbot et al. 1998). No differences were obtained between control subjects and patients with selective thermal lesions to the medial temporal lobe, when tested on the radial-maze, the non-spatial analogue to the radial-maze and the path integration tasks. Differences in methodological procedures, learning strategies and lesion location could account for some of the discrepant results between humans and non-human species. Patients with lesions to the right hippocampus, irrespective of whether the right parahippocampal cortex was spared or damaged, had difficulties remembering the particular configuration and identity of objects in the novelty detection of the object location task. This supports the role of the human right hippocampus for spatial memory, in this case, involving memory for the location of elements in the room; learning known to require the hippocampus in the rat., V.D. Bohbot, R. Jech, E. Růžička, L. Nadel, M. Kalina, K. Štěpánková , J. Bureš., and Obsahuje bibliografii