The main objective of this master thesis entitled The study of polyneuropathy in Leonberger dogs (LPN) was to determine the variability of ortholog of CMT2 gene in a selected population of this breed. The number of individual samples studied was 211. The entire set of DNA samples was divided to the cases (110 samples) and controls (101 samples). Partial objectives were the study of information available on the hereditary neuropathies, the selection of candidate gene polymorphisms and their association analysis with the disease. The candidate gene studied is associated with the autosomal recessive form of axonal neuropathy in humans with early onset of symptoms. Compound mutation was discovered in the gene (substitution and 1 bp deletion). The normal allele predominated in healthy individuals. In contrast, both mutant alleles always predominated in diseased individuals. Statistical comparison of genotypes depending on the health status did not show a clear correlation with disease (p = 0,1562).

Hereditary peripheral neuropathy, known asCharcot Marie Tooth disease (CMT) and with an incidence of 1:2500 -1:10 000, is the most common hereditary neuromuscular disorder. Type CMT 1A is the most common form of CMT refering to the group of primary demyelinitateing motor and sensory peripheral neuropathies. CMT phenotype is clinically characterized by chronic slowly progressive distal muscle weakness and atrophy with hypo or areflexia and mild to moderate acral sensory loss. The lower limbs are predominantly affected. The aims of this study were to describe the first and most common signs of CMT1A during the first decade of life, to characterize their progression, and evaluate the sensitivity of CMTNS (Charcot-Marie- Tooth neuropath scale) for CMT1A young children. Sixteen children aged 3 to 10 years with genetically proven CMT 1A were examined. All patients were clinically examined, underwent electrophysiological examination, and were scored by CMTNS. Eight were followed for up to two years. Our data shows that CMT 1A in children under the age of 10 years causes only a mild disability. Initial signs of CMT 1A were difficulty in heel walking (15/16, 93%) and lower limb hypo or areflexia ( 13/16, 81%). The test of heel walking can be easily used as a screening test for hereditary neuropathies in pediatrics....

Neuropathic pain represents a possible outcome of neural tissue injury; it occurs also as a concomitant symptom of different diseases or as a side effect of several treatments. Up to date, it constitutes a great challenge in clinical practice, as currently available treatments are still unsatisfactory. Mechanism-based treatment approaches are promising strategy in neuropathic pain management. However, there is still a lack of information about the exact mechanisms involved in the development and/or maintenance of neuropathic pain. This Doctoral Thesis is aimed to explore the mechanisms underlying the development of neuropathic pain states in different models. The principal part of this work is focused on the study of anti-inflammatory effect of Angiotensin II receptor type 1 (AT1R) blocker, losartan, in two different models of peripheral neuropathy: paclitaxel-induced peripheral neuropathy (PIPN) and spinal nerve ligation (SNL). The work also aimed to access the involvement of spinal transient receptor potential vanilloid type 1 (TRPV1) channels in the process of neuronal activation induced by paclitaxel (PAC) and chemokine CCL2 treatment. In order to fulfil the abovementioned aims, behavioral, immunohistochemical and molecular methods were used. For every model of peripheral neuropathy, the...

The ulnar neuropathy of the elbow (UNE) is the second most common compression neuropathy in the upper extremity. The studies of impact of bone morphology on the origin of the ulnar neuropathy are inconsistent. According to the recently published retrospective analysis of 880 cases of the cubital tunnel syndrome, the incidence of the ulnar neuropathy is more often on the left side, independent of handedness. The theoretical part of this thesis contains a summary of recent literature with an emphasis on the etiology, basics of diagnostics, treatment and rehabilitation of the UNE. The experimental part is made of the measurement of ten parameters of humerus bones. The aim of this experiment was to decide whether some of these measures were different compared to the other side. There were statistically significant differences in 4 of 9 crucial parameters, where the right side was bigger than the left side, therefore we believe the influence of bone morphology on the origin of the UNE cannot be excluded. The results may help towards a better understanding of the etiopathogenesis of the origin of the UNE and therefore be a valuable starting point for other studies of prevention, diagnosis and therapy of the UNE.

Inborn errors of metabolism represent a heterogenous group of rare conditions, most having an incidence of less than 1 in 100,000 births. Because of their low prevalence, they are on the margin of attention of general research and even more so of large pharmaceutical companies. Study of rare diseases is the only way to design therapeutic options in order to improve quality of life of affected patients. Present Thesis particularly focuses on disturbances in mitochondrial energy metabolism. The main goals were the characterization of mitochondrial biogenesis within foetal development, as well as in childhood and adulthood. Another aim was to define clinical, biochemical and molecular aspects of mitochondrial optic neuropathies in childhood and adulthood. This work supported the earlier observations that gestational week 22 is the edge of viability, which has to be taken into account in upcoming discussions about guidelines on resuscitation of preterm neonates. Secondly, over last four years, we managed to examine and describe large cohort of patients with optic neuropathies based on a mitochondrial dysfunction. We have managed to characterize the biochemical and molecular-genetic background in more than 200 patients, and both selected cases (LHON/MELAS overlap syndrome) and cohort studies (MELAS,...

The aim was to assess exercise habits, handle the issue condition in patients with hereditary neuropathy and to clarify the possibility of using fitness training in this disease. We managed to show a reduced fitness of patients with hereditary neuropathy and its relationship with the severity of neurologic disability and mobility habits of individuals. The study results also show the positive effect of physical stress on condition of patients with hereditary neuropathy. Powered by TCPDF (www.tcpdf.org)

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Simona Benčová Supervisors: Dr. Claire Demiot, Dr. Aurore Danigo Assoc. Prof. Přemysl Mladěnka, Ph.D Title of diploma thesis: Transcriptomic analysis of cutaneous inflammatory biomarkers in a mouse model of small fiber neuropathy. Peripheral neuropathy is an expanding public health problem conditioned by various diseases and associated with several adverse effects such as the occurrence of chronic pain or increased risk of pressure ulcers (PUs). The aim of this study is to explore, whether the inflammatory state of the skin is modified during peripheral neuropathy and in the course of the formation of a pressure ulcer. The transcriptomic analysis was performed with two different models of mice: PU model and uninjured model, to determine genes that differ in expression and in particular, those involved in inflammation. Small fiber neuropathy was induced in young mice by intraperitoneal injection of resiniferatoxin (50 µg/kg, i.p.) - transient receptor potential vanilloid 1 (TRPV1) agonist. PUs were induced by applying two magnetic plates on the dorsal skin. Gene expression was obtained based on RNA microarray and the results were subsequently verified by qPCR. The transcriptomic analysis of PU...

Title: Evaluation of selected postural stability parameters of diabetic patients Objectives: The main objective of this thesis is to describe the level of postural stability using the selected parameters in diabetes mellitus type 2 and to try to find a relationship between the severity of disease. We also want to compare the level of postural stability for such an illness with respect to the values of selected parameters of the healthy population. Methods: It is a descriptive study. The theoretical part was the basis of the processing problems of diabetes mellitus, with a focus on neuropathy. After that we evaluate data of selected parameters of postural stability in diabetes mellitus type 2. The second part involves the experiment, which refers to the evaluation of this issue in terms of posturographic analysis. A group of 30 type 2 diabetic patients were divided according to their diabetologist disease severity into 4 groups. A control group of healthy subjects included a sample of 7 probands. The patient group was composed of 18 men and 12 women, whose average age was 62.63 ± 15.55 years, average weight 91.17 ± 19.97 kg, who were subjected to measurement using a pressure plate FootScan (RScan International, Belgium). Results: We managed to prove, that subjects with diabetic neuropathy have...

(English) Modulation of synaptic transmission in dorsal horn of spinal cord plays a key role in nociceptive signalling. Recent studies have indicated a great importance of presynaptic TRPV1 receptors (transient receptor potential vanilloid) in spinal cord. These receptors act as molecular integrator of nociceptive stimulation on periphery. The way of their activation and the effect on modulation of the synaptic transmission are not clarified yet. Previous studies demonstrated the influence of many inflammatory mediators and cytokins on TRPV1 receptors. The aim of our research was to show changes in activation of presynaptic TRPV1 receptors in the spinal cord following the application of endogenous agonist N-oleoyl dopamine (OLDA) in a model of peripheral neuropathy, after incubation with cytokine TNFα and to show the effect of precursor of anandamide N-acylphosphatidylethanolamine (NAPE). In our experiments, we have recorded miniature excitatory postsynaptic currents (mEPSC) from neurons of acute spinal cord slices by the patch-clamp method. The first series of experiments tested sensitivity to application of the endogenous agonist OLDA 5 days after evoking peripheral neuropathy. The frequency of mEPSC increased significantly - to 250 % of base level after applying a low concentration of OLDA (0,2...

In the first part of the thesis Objectification of disorders of the fine motor skills of the upper extremities in the patients with hereditary neuropathies there are mentioned some brief informations about characteristics, classifications, clinical symptoms, deformities and testing of upper extremities, rehabilitation and treatment of CMT neuropathy. The practical part of this thesis is concerned with testing and evaluating of strength, fine motor skills and sensation of the upper extremities in the patients with CMT. For the measurement of the hand strenght the dynamometry and the functional muscle test are used. The Jebsen-Taylor test, the Nine-Hole Peg Test and the examination of static and dynamic handgrip rating are used. For the examination of the sensation the Nottingham Sensory Assessment is used. CMT neuropathy score and Overall Neuropathy Disability Scaleare are used for the classification of disability. The aim of this thesis is the comparison of the muscle strength and the function of the dominant and non-dominant hand. Partial aim of thesis is detection of the correlations between tests. According to the results CMT disease leads to the muscle strenght weakness and to worsening of the fine motor skills mainly of the dominant upper extremity. This may be the result of overwork weakness. For...