Tomkova J.,Faculty Hospital |
Svidrnoch M.,Palacky University |
Maier V.,Palacky University |
Ondra P.,Faculty Hospital
Journal of Separation Science | Year: 2017
A new ultra high performance liquid chromatography with electrospray ionization time of flight mass spectrometry method for the selective and sensitive separation, identification, and determination of selected designer benzodiazepines (namely, pyrazolam, phenazepam, etizolam, flubromazepam, diclazepam, deschloroetizolam, bentazepam, nimetazepam, and flubromazolam) in human serum was developed. The separation of the studied designer benzodiazepines was achieved on C18 chromatographic column using gradient elution within 6 min without any significant matrix interferences. Liquid–liquid extraction with butyl acetate was applied for serum samples cleanup and preconcentration of studied designer benzodiazepines. The method was validated in terms of linearity, limit of detection, limit of quantification, matrix effects, specificity, precision, accuracy, recovery, and sample stability. The limit of detection values were 0.10–0.15 ng/mL. The method was applied to a spiked serum sample to demonstrate its applicability for systematic toxicology analysis. Furthermore, a capillary chromatographic method with micellar electrokinetic chromatography was used for the estimation of partition coefficients of studied designer benzodiazepines as important parameters to evaluate their pharmacological and toxicological properties. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Bartos V.,Faculty Hospital in Zilina |
Kullova M.,Faculty Hospital
Klinicka Onkologie | Year: 2017
Background: An interesting clinical feature of basal cell carcinoma (BCC) of the skin is a marked interpatient variation in tumor number, lesion accrual and anatomic distribution. We analyzed a proportion of patients with multiple BCCs in the cohort of pathology report-confirmed cases of BCC and investigated clinicopathological differences between individuals suffering from multiple tumor lesions and patients with a single tumor. Material and Methods: All consecutive patients with primary cutaneous BCCs, who were histologically dia gnosed at our Department of Pathology during a 10-year period were enrolled into the study. Results: A cohort of 899 participants with a total of 1,239 histologically proven primary BCCs were assessed. Of them, 728 (81%) had single BCC and 171 (19%) had multiple BCCs. Multiple lesions occurred more frequently in men than women. Mean number of tumors per patient was 1.5 in males and 1.2 in females. Among participants with multiple BCC manifestation, there was a steady increase of the male-to-female ratio with rising tumor number per individual. In the multiple BCC subgroup, the tumors were found more commonly in the trunk and upper limbs, and less frequently in the face. Histologically, these BCCs much more commonly included superficial subtype. There was a positive correlation between the non-aggressive histologic phenotype of BCC and multiple tumor presentations on the one hand, and the aggressive histologic phenotype of BCC and a single tumor occurrence on the other. Conclusion: Our analysis shows that clinicopathological features associated with multiple BCC manifestations include male gender, tumor location in the trunk and upper extremities, and superficial histological subtype. Focus on this risk profile may be beneficial for clinical screening and may help clinicians in the selection of individuals, who should be followed-up more closely.
Hasto J.,Faculty Hospital |
Minarik P.,Aventis Pharma
Neuroendocrinology Letters | Year: 2011
Attachment theory is a very influential general concept of human social and emotional development, which emphasizes the role of early mother-infant interactions for infant's adaptive behavioural and stress copying strategies, personality organization and mental health. Individuals with disrupted development of secure attachment to mother/primary caregiver are at higher risk of developing mental disorders. This theory consists of the complex developmental psycho-neurobiological model of attachment and emerges from principles of psychoanalysis, evolutionary biology, cognitive-developmental psychology, ethology, physiology and control systems theory. The progress of modern neuroscience enables interpretation of neurobiological aspects of the theory as multi-level neural interactions and functional development of important neural structures, effects of neuromediattors, hormones and essential neurobiological processes including emotional, cognitive, social interactions and the special key role of mentalizing. It has multiple neurobiological, neuroendocrine, neurophysiological, ethological, genetic, developmental, psychological, psychotherapeutic and neuropsychiatric consequences and is a prototype of complex neuroscientific concept as interpretation of modern integrated neuroscience. ©2011 Neuroendocrinology Letters.
Mazurova Y.,Charles University |
Guncova I.,Charles University |
Latr I.,Faculty Hospital |
Rudolf E.,Charles University
CNS and Neurological Disorders - Drug Targets | Year: 2011
The evidence for the existence of neurogenesis in the adult mammalian brain, including humans is now widely accepted. Despite the fact that adult neural stem cells appear to be very promising, a wide range of their unrevealed properties, abilities but also limitations under physiological and especially pathological conditions still need to be investigated and explained. Huntington's disease (HD) is characterized by successive degeneration of relatively well-defined neuronal population. Moreover, the most affected region, the caudate nucleus, is adjacent to the subependymal zone (SEZ) neurogenic region. Therefore, the possibility to harness the endogenous neural stem cell capacity for repairing, or at least restricting, the fatal neurodegenerative process in HD patients using promoted neurogenesis in the adult SEZ represent the exciting new possibility in clinical management of this disorder. On the other hand, many questions have to be answered before neuronal replacement therapies using endogenous precursors become a reality, particularly in relation to neurodegenerative diseases. Fundamental for all experimental, functional and future clinical studies is detailed morphological description of structures involved in the process of neurogenesis. The objectives of this review are to describe neurogenesis in the adult murine and human brain (with particular emphasis to morphological aspects of this process) and to determine to what extent it is affected in animal models of HD and in the human HD brain. Due to very limited evidence referring to the impact of striatal pathology of HD phenotype on the adult neurogenesis in the SEZ, some results gained from our studies on two rat models of HD, i.e. the neurotoxic lesion and transgenic HD rats, and on human HD brains are discussed. © 2011 Bentham Science Publishers.
Kumar B.,Pandit Ravishankar Shukla University |
Satnami M.L.,Pandit Ravishankar Shukla University |
Ghosh K.K.,Pandit Ravishankar Shukla University |
Kuca K.,Faculty Hospital
Journal of Physical Organic Chemistry | Year: 2012
We studied the cleave of bis(p-nitrophenyl) phosphate (BNPP) over a pH range of 7.0-12.0 in the presence of cationic micelles of cetyldiethylethanolammonium bromide, cetyldimethylethanolammonium bromide, cetylpyridinium bromide, cetyltrimethylammonium bromide, and cetylpyridinium chloride by using different α-nucleophiles, viz acetohydroxamate, benzohydroxamate, salicylhydroxamate, butane-2,3-dione monooximate, and α-benzoin oximate ions. With the use of α-nucleophiles in cationic micellar media, the hydrolytic cleavage of BNPP was found to be approximately 10 5-fold faster than its spontaneous hydrolysis. All reactions followed pseudo-first-order kinetics. The effect of various concentrations of cationic micelles for the reaction of BNPP and α-nucleophiles has been studied. The variation of k obs values of the reactions depends on the micellar structure, that is, head groups, hydrophobic tail length, and counter ion. Copyright © 2012 John Wiley & Sons, Ltd.
Krahulik D.D.,Faculty Hospital |
Zapletalova J.,Faculty Hospital |
Frysak Z.,Faculty Hospital |
Vaverka M.,Faculty Hospital
Journal of Neurosurgery | Year: 2010
Object. Traumatic brain injury (TBI) is a major cause of serious morbidity and mortality. The incidence is 100-500/100,000 inhabitants/year. Chronic pituitary dysfunction is increasingly recognized after TBI. To define the incidence of endocrine dysfunction and risk factors, the authors describe a prospectively assessed group of patients in whom they documented hormonal functions, early diagnosis, and treatment of neuroendocrine dysfunction after TBI. Methods. Patients aged 18-65 years were prospectively observed from the time of injury to 1 year postinjury; the Glasgow Coma Scale score ranged from 3 to 14. Patients underwent evaluation of hormonal function at the time of injury and at 3, 6, and 12 months postinjury. Magnetic resonance imaging was also conducted at 1 year postinjury. Results. During the study period, 89 patients were observed. The mean age of the patients was 36 years, there were 23 women, and the median Glasgow Coma Scale score was 7. Nineteen patients (21%) had primary hormonal dysfunction. Major deficits included growth hormone dysfunction, hypogonadism, and diabetes insipidus. Patients in whom the deficiency was major had a worse Glasgow Outcome Scale score, and MR imaging demonstrated empty sella syndrome more often than in patients without a deficit. Conclusions. To the authors' knowledge, this is the third largest study of its kind worldwide. The incidence of chronic hypopituitarism after TBI was higher than the authors expected. After TBI, patients are usually observed on the neurological and rehabilitative wards, and endocrine dysfunction can be overlooked. This dysfunction can be life threatening and other clinical symptoms can worsen the neurological deficit, extend the duration of physiotherapy, and lead to mental illness. The authors recommend routine pituitary hormone testing after moderate or severe TBI within 6 months and 1 year of injury.
Cardozo L.,King's College |
Amarenco G.,Hopital Tenon |
Pushkar D.,Moscow State University |
Mikulas J.,Faculty Hospital |
And 3 more authors.
BJU International | Year: 2013
Objective To determine the relationship between severity of baseline overactive bladder (OAB) symptoms and requests for solifenacin dose increases, and the efficacy of 5 and 10 mg solifenacin doses in relieving OAB symptoms in patients who requested a dose increase. Patients and Methods In a 16-week clinical study, patients with OAB were randomized to double-blind treatment with solifenacin or placebo once daily. At week 8, all patients could request a dose increase; these patients entered a second phase of 8 weeks in which those in the solifenacin group were randomized to either 5 or 10 mg doses. The primary efficacy variable was mean change in the number of urgency episodes with or without incontinence per 24 h, measured using the Patient Perception of Intensity of Urgency Scale (PPIUS; grades 3 and 4). Results Of 591 patients receiving solifenacin at 8 weeks, 275 (46.5%) requested a dose increase to 10 mg, and were further randomized to receive 10 mg (n = 140) or to remain on 5 mg (n = 135). Patients who requested a dose increase at week 8 generally had more severe OAB symptoms at baseline and a smaller response at week 8 to the initial solifenacin 5 mg dosage than those who did not. Greater reductions in the mean number of severe urgency episodes (PPIUS grades 3 and 4) were observed from week 8 to the end of treatment for patients requesting a dose increase and randomized to 10 mg solifenacin compared with those randomized to remain on 5 mg (mean reductions -0.9 vs -0.4, respectively), although these did not reach statistical significance. Statistically significant reductions were observed in mean total urgency score (TUS; -2.7 vs -0.6; P = 0.010), mean maximum PPIUS urgency rating (-0.3 vs -0.1; P = 0.034) and mean micturition frequency (-0.8 vs -0.1; P = 0.037). For all other OAB variables, greater changes were observed in the solifenacin 10 mg group but these did not reach statistical significance. Of those who requested a dose increase, eight (5.7%) patients randomized to receive 10 mg and one (0.7%) patient randomized to remain on 5 mg reported new or worsening cases of dry mouth. Conclusions Increasing the solifenacin dose to 10 mg further improved OAB symptoms in patients who requested a dose increase after 8 weeks' treatment with 5 mg solifenacin. The present study supports the view that patients with severe OAB symptoms benefit from a higher antimuscarinic dose. © 2013 BJU International.
Cramer L.,Applied Cachexia Research |
Hildebrandt B.,Charite Medical School |
Kung T.,Applied Cachexia Research |
Wichmann K.,Applied Cachexia Research |
And 13 more authors.
Journal of the American College of Cardiology | Year: 2014
Background Patients with colorectal cancer (CRC) often present with dyspnea and fatigue. These are also frequent symptoms in patients with chronic heart failure (CHF).Objectives We hypothesized that similar patterns of cardiovascular perturbations are present in CRC and CHF.Methods We prospectively studied 50 patients with CRC, 51 patients with CHF, and 51 control subjects. The CRC group was divided into 2 subgroups: patients who underwent chemotherapy (n = 26) and chemotherapy-naive patients (n = 24). We assessed exercise capacity (spiroergometry), cardiac function (echocardiography), heart rate variability (Holter electrocardiography), body composition (dual-energy x-ray absorptiometry), and blood parameters.Results Compared with the control arm, the left ventricular ejection fraction (CRC group 59.4%; control group 62.5%) and exercise performance as assessed by peak oxygen consumption (peak VO2) (CRC group 21.8 ml/kg/min; control group 28.0 ml/kg/min) were significantly reduced in CRC patients (both p < 0.02). Markers of heart rate variability were markedly impaired in CRC patients compared with control subjects (all p < 0.008). Compared with the control group, the CRC group also showed reduced lean mass in the legs and higher levels of the endothelium-derived C-terminal-pro-endothelin-1 (both p < 0.02). Major determinants of cardiovascular function were impaired in chemotherapy-treated patients and in the chemotherapy-naive patients, particularly with regard to exercise capacity, left ventricular ejection fraction, lean mass, and heart rate variability (all p < 0.05 vs. control subjects).Conclusions Some aspects of cardiovascular function are impaired in patients with CRC. More importantly, our findings were evident independently of whether patients were undergoing chemotherapy. © 2014 American College of Cardiology Foundation.
Valentova M.,Applied Cachexia Research |
Von Haehling S.,Applied Cachexia Research |
Von Haehling S.,Faculty Hospital
Expert Opinion on Investigational Drugs | Year: 2014
The European Society of Cardiology held their annual congress in Amsterdam between the 31st of August and 4 September 2013 to discuss the latest developments in the field. The meeting included an update of the latest treatments currently under investigation for the treatment of heart failure. Updates were provided on the RELAX-AHF study that had, for the first time, demonstrated an improvement in post-discharge outcome in patients with acute heart failure treated with seralaxin. The meeting also gave the opportunity to highlight the latest goings on from the promising agent omecamtiv mecarbil as shown in the ATOMIC-AHF study. Indeed, its unique inotropic effect showed a potential to improve dyspnea without increasing myocardial oxygen consumption. Other presentations at the meeting included: a recent study evaluating ultrafiltration in the treatment of acute HF with renal impairment and the effects of the vasodilator cinaciguat. The unremarkable results from the recent ASTRONAUT study with aliskiren were also touched upon. It is important to note that while the data from seralaxin and omecamtiv mecarbil has been promising, the long term benefits of these therapies in heart failure still need to be evaluated. The authors also highlight the need for these promising agents to be further evaluated in women and other ethnic groups. © 2014 Informa UK, Ltd.
Guncova I.,Charles University |
Latr I.,Faculty Hospital |
Mazurova Y.,Charles University
Acta Histochemica | Year: 2011
Although Huntington's disease (HD) occurs only in humans, the use of animal models is crucial for HD research. New genetic models may provide novel insights into HD pathogenesis, but their relevance to human HD is problematic, particularly owing to a lower number of typically degenerated and dying striatal neurons and consequent insignificant reactive gliosis. Hence, neurotoxin-induced animal models are widely used for histopathological studies. Unlike in humans, the neurodegenerative process (NDP) of the HD phenotype develops very fast after the application of quinolinic acid (QA). For that reason, we compared three groups of rats in more advanced stages (1-12 months) of the QA lesion with 3 representative HD cases of varying length and grade. The outcomes of our long-term histological study indicate that significant parallels may be drawn between HD autopsies and QA-lesioned rat brains (particularly between post-lesional months 3 and 9) in relation to (1) the progression of morphological changes related to the neuronal degeneration, primarily the rarefaction of neuropil affecting the density as well as the character of synapses, resulting in severe striatal atrophy and (2) the participation of oligodendrocytes in reparative gliosis. Conversely, the development and character of reactive astrogliosis is principally conditioned by the severity of striatal NDP in the context of neuron-glia relationship. Despite the above-described differences, morphological patterns in which the components of striatal parenchyma react to the progression of NDP are similar in both human and rat brains. Our study specifies the possibilities of interpreting the morphological findings gained from the QA-induced animal model of HD in relation to HD post-mortem specimens. © 2010 Elsevier GmbH.