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Testing of transdermal permeation of selected xenobiotics
Stará, Veronika ; Herink, Josef (advisor) ; Vopršalová, Marie (referee)
This thesis first briefly mentions the characteristics of the skin and contains a review of current knowledge on the in vitro permeation testing of drugs through the skin. It describes the basic data about nerve agents and the possibilities of prophylaxis poisoning warfare agents focusing on preventive transdermal administration. The experimental work is focused on in vitro testing abilities oxime HI-6 and posibly other reactivators enzyme acetylcholinesterase penetrate through pig skin. Experiments were conducted in static diffusion cells Franz type. The amount of test substance leaked through the skin is determined in the sample of receptor fluid by HPLC. Keywords permeation in vitro; transdermal; pig skin; Franz cell; substance HI-6; antidota; nerve agents; acetylcholinesterase
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Signs of the temporolimbic dysfunction in gamblers
Hončová, Veronika ; Herink, Josef (advisor) ; Kovařík, Miroslav (referee)
Charles University of Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medicinal Sciences Student: Bc. Veronika Hončová Supervisor: Doc. MUDr. Josef Herink, DrSc. Consultant: MUDr. Jela Hrnčiarová Title: Signs of the temporolimbic dysfunction in gamblers Background: The aim of this thesis was to determine whether pathological gamblers exhibit symptoms related to epileptic spectrum disorder. Methods: To investigate, symptoms of the temporolimbic dysfunction were examined by means of the structured questionnaires CPSI (Complex Partial Symptoms Inventory) and LSCL-33 (Limbic System Checklist-33). Mann-Whitney U test and Spearman's correlation coefficient were used for statistical evaluation. Results: The mean score in the questionnaire CPSI of gamblers was 38,9 points, which is an abnormal score. With the questionnaire LSCL-33, the mean score of 21,5 points, corresponds to suspected findings. From the mean results it can be concluded that pathological gamblers may have a higher incidence of the symptoms of the temporolimbic dysfunction. When comparing the groups of gamblers with smokers, it was evaluated that in the questionnaire CPSI was a statistically significant difference between the appearances of symptoms of epileptic spectrum disorder, while it was not in the...
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Comparison of efficacy of acetylcholinesterase inhibitors tacrine, rivastigmine and donepezil for the treatment of cognitive disorders induced by 3-quinuclidinyl benzylate in rat
Pavlíčková, Stela ; Vopršalová, Marie (advisor) ; Herink, Josef (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Mgr. Stela Pavlíčková Supervisor: PharmDr.Marie Vopršálová, CSc. Supervisor specialist: RNDr. Jan Misík, Ph.D. Title of rigorosa thesis: Comparison of efficacy of acetylcholinesterase inhibitors tacrine, rivastigmine and donepezil for the treatment of cognitive disorders induced by 3-quinuclidinyl benzylate in rat Alzheimer's disease is a severe neurodegenerative disorder connected with neuronal death, brain tissue loss and functional disruption of the cholinergic system. Pathophysiological changes are manifested especially as deterioration of memory and other cognitive functions. Current treatment consists mainly of pro-cognitive drugs - acetylcholinesterase inhibitors (previously - tacrine, today - donepezil, rivastigmine and galantamine) and NMDA (N-methyl-D- aspartate) antagonist memantine which can delay the disease progression. The aim of this study was to evaluate the therapeutic effect of three selected acetylcholinesterase inhibitors - tacrine, rivastigmine and donapezil on pharmacologically induced cognitive disorder in rats. As an amnesic drug, 3-quinuclidinyl benzilate was used and the effect of selected inhibitors was investigated using two different behavioral methods -...
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The temporolimbic dysfunction in alcohol dependent persons
Mičulková, Jana ; Herink, Josef (advisor) ; Kudláčková, Zděnka (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Bc. Jana Mičulková Consultant: Doc. MUDr. Josef Herink, DrSc. Title of Thesis: The temporo-limbic dysfunction in alcohol dependent persons This thesis is concerned on the temporo-limbic dysfunction of persons dependent on alcohol. The theoretical part summarizes the information about the neuroanatomical correlates, alcohol dependence syndrome, epidemiology of alcohol addiction in the Czech republic and the relationship between alcohol and epilepsy. The practical part includes evaluation of questionnaires filled out by alcohol dependent persons. These questionnaires are concerned on recognizing epilepsy spectrum disorder. The results are compared with the results obtained from previous studies in the healthy population and are used to evaluate other aims of this thesis. Keywords: alcohol dependence, epilepsy, epilepsy spectrum disorder, limbic system, questionnaire investigation
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The effect of acetylcholinesterase reactivators on urinary bladder contraction
Rambousková, Lucia ; Vopršalová, Marie (advisor) ; Herink, Josef (referee)
Candidate: Mgr. Lucia Rambousková Title of thesis: The effect of acetylcholinesterase reactivators on urinary bladder contraction Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Supervisor: PharmDr. Marie Vopršálová, CSc. Consultant specialist: PharmDr. Vendula Šepsová, Ph.D Acetylcholinesterase (AChE) reactivators major mechanism is attributed to their ability to reactivate phosporylated enzyme, AChE. It has been thought that oxime might have additional direct pharmacological effect, other than AChE reactivation. The oximes may exert effects by interaction with cholinergic receptors. The most of them have antiniconitic or antimuscarinic properties, thus they protect against higher concentration of acetylcholine. The aim of this study was to evaluate the effect of reactivators K 203 and K 027. A contraction study on the rat urinary bladder has been chosen to investigate effect on muscarinic and purinergic receptors. Isolated strips of urinary bladder in the organ bath were used. There were three types of stimulation - electric stimulation (EFS), muscarinic receptor agonist methacholine (MCh) and purinergic receptor agonist adenosine triphosphate (ATP). In conclusion oxime K 027 has tendency to reduce the contraction (during EFS and MCh...
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Intestinal microbiota and mood disorders
Ambrožová, Lucie ; Herink, Josef (advisor) ; Jílek, Petr (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Lucie Ambrožová Supervisor: Doc. MUDr. Josef Herink, DrSc. Title of diploma thesis: Intestinal microbiota and mood disorders The intestinal microbiom is composed mainly of two dominated strains - Bacteroidetes and Firmicutes. The other strains are just not numerous like the previous ones. The specimens have the invariable core of microbiom which doesn't change in time. Nevertheless they have also the transient gut bacteria, which change during their life. Intestinal microbiom is influenced by many factors. Between them we can categorize for example the way of the childbirth, the breast - feeding, the alimentation, the state of health, and the medicaments. Every specimen has own specific microbiom. It was found that human population is possible to divide into three intestinal groups or enterotypes. To each enterotype dominates different bacterial strain. It was proved that intestinal microbiom communicates with the brain and it works also vice versa. This communication system is called "brain - intestine" and takes several ways in several body systems (such as nervous, endocrine, metabolic, and immune). To normal development of the brain is needed the right colonisation of non...
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Sleep disorders - resistant forms
Koláčková, Pavla ; Semecký, Vladimír (advisor) ; Herink, Josef (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Pavla Koláčková Supervisor: Doc. RNDr. Vladimír Semecký, CSc. Name of dissertation: Sleep disorders - resistant forms The diploma thesis is about sleep disorders. Sleep disorders are a global problem, lots of people have these problems. This diploma thesis focuses on American International Classification of Sleep Disorders (ICSD) and its application in clinical practice. We have chosen methods that describe the current conditions of patients who have been in sleep clinics. The thesis contains questionnaires, relevant case study and personal interviews. The main contribution of this diploma thesis is a subjective assessment of patients' treatment including pharmacotherapy and psychotherapy. The results of this thesis include statistics of patients who are visiting psychiatric clinic in Centre of disorders of sleep and biorhythm in University Hospital in Hradec Králové and of their case studies of which we have selected the most interesting ones that describe this problem best. In this thesis we have found out that the statistical distribution of patients is different in comparison with epidemiology studies. The results are influenced by sleeping disorders treated in a sleep...
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Cytopathological diagnostics cervico - vaginal disease
Bartoňová, Simona ; Semecký, Vladimír (advisor) ; Herink, Josef (referee)
Cervical cancer is the most common malignant tumors in the Czech Republic in women older than 35 years. Created on the basis of pathological changes of epithelial cells or so called precancer, manifested no symptoms. Timely is, they can only be detected by specialized colposcopy, cytology and biopsy examinations. In advanced cancer, are present typical symptoms: lower abdominal pain, bleeding after sexual intercourse or vaginal discharge. The main cause of this disease is an infection caused by high - risk types of human papilomaviruses. These viruses have the ability and persistence occur in 90 % of cases detected. Diagnosis of cancer of the cervix must be comprehensively evaluated the results of a Pap test, biopsy examination and positive HPV typing. The thesis deals with cytological examination called Pap test, cervical smears and their microscopic diagnosis to distinguish the early stages. Alteration of the cells was evaluated according to the classification of Bethesda 2014. Further deals with immunohistochemical examination of cervical biopsies, which makes it easier to demonstrate the type of dysplasia. Reactions demonstrating the positivity of p16 was performed on sections, previously described immunohistochemical procedure. The aim was to identify patients over 30 years of samples taken in...
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Utilisation of nutrinional substrates in mechanically ventilated critically ill patients
Valentová, Gabriela ; Hronek, Miloslav (advisor) ; Herink, Josef (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Department of Biological and Medical Sciences Candidate Mgr. Gabriela Valentová Consultant Doc. PharmDr. Miloslav Hronek, PhD. Title of Thesis Utilisation of nutrinional substrates in mechanically ventilated critically ill patients Critically ill patients have significantly different metabolism compared to healthy individuals. Patients are experiencing hypometabolic phase which turns into hypermetabolic phase later on. It is desirable to supply patients with a nutrition that will reflect these metabolic changes and that will sufficiently cover the individual needs of each patient in order to decrease the risk of adverse effects and to improve the prognosis of the patient. The goal of this clinical study was to compare the nutrition of critically ill mechanically ventilated patients from surgical ICU of Teaching Hospital in Hradec Králové with results obtained from the results of calorimetric examination. Balance between the nutritional support and the immediate energy needs of the patient allows us to evaluate the level of coverage of the nutritional needs within our group of patients. In total 17 critically ill mechanically ventilated patients were examined. They were given nutrition according to the detailed...
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Molecular mechanisms of the sensitivity of tumor cells to an inbibitor of protein kinase Src dasatinib
Žáková, Petra ; Semecký, Vladimír (advisor) ; Herink, Josef (referee)
Signal transmission is an efficient mechanism that allows fast and specific response of eukaryotic cells to small changes in the extracellular and intracellular information. Many cascade of protein kinases in signaling pathways are deregulated in human diseases and represent a valuable target for their therapy. This work has been devoted to inhibit Src kinase activity after application of dasatinib on melanoma cells in cell culture. Dasatinib is multikinase inhibitor of protein tyrosine kinases, and with high efficiency inhibits Src and other members of this family of kinases. Dasatinib is already in use as anticancer drug in some tumors, while another is in late stage clinical trials. Results showed mainly the effect of Src inhibition on two main signaling pathways important for survival and proliferation of melanoma cells, MAPK and AKT. In the literature it is not known many links MAPK and Src at melamomu, but recently has been reported that the Src inhibiting translocation of ERK1 / 2 in the core, thereby accelerating the proliferation of melanoma cells.
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