Orientador: João Batista de Miranda / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T13:37:30Z (GMT). No. of bitstreams: 1 Ferreira_DanielBecharaJacob_M.pdf: 1620645 bytes, checksum: 6452df17927d464b10dd8a697e2a2126 (MD5) Previous issue date: 2011 / Resumo: Introdução: A osteotomia valgizante no terço proximal da tíbia é considerada um método confiável para o tratamento de pacientes jovens com osteoartrite medial do joelho, associado a alinhamento em varo. Entretanto, procedimentos realizados para a correção de desalinhamentos no plano frontal podem alterar o alinhamento do plano sagital. Vários fatores estão relacionados ao aumento da inclinação posterior do planalto tibial pós-osteotomia valgizante no terço proximal da tíbia. Hipótese: O posicionamento posterior da placa-calço está relacionado com menor alteração da inclinação posterior do planalto tibial. Modelo do estudo: Estudo clínico retrospectivo. Métodos: Foram realizadas 42 osteotomias entre abril de 2007 e agosto de 2008. Imagens radiográficas em perfil do joelho foram obtidas no pré-operatório e no pós-operatório recente. Determinou-se o ângulo formado entre a tangente do planalto tibial medial e uma linha perpendicular ao eixo da cortical posterior da tíbia por medidas goniométricas manuais, antes e após cirurgia. Determinou-se também a posição relativa da placa-calço em relação à cortical posterior da tíbia. Resultados: Houve aumento de aproximadamente 34% no valor da inclinação posterior do planalto tibial após a cirurgia, com a média subindo de 7,6° para 10,2° (p = 0,0006). Existe correlação entre o ângulo de inclinação do planalto tibial pré-operatório e o seu valor pós-cirúrgico (r = 0,4131 e p = 0,0065). A posição relativa e o tamanho do implante não influenciaram as alterações do alinhamento sagital. Conclusão: Nesta população amostral houve aumento estatisticamente significativo da angulação da superfície articular tibial proximal, no plano sagital, após osteotomia valgizante no terço proximal da tíbia. O posicionamento posterior da placa-calço não foi relacionado a um menor aumento desta angulação / Abstract: Background: The high tibial osteotomy is considered a reliable method for the treatment of young patients with medial knee osteoarthritis associated with varus alignment. However, procedures performed to correct misalignments in the frontal plane can change the alignment of the sagittal plane. Several factors are related to the increase in the posterior inclination of the tibial plateau after high tibial osteotomy. Hypothesis: The posterior positioning of the Puddu plate causes less alteration of the posterior inclination of the tibial plateau. Study design: Retrospective clinical trial. Methods: Forty-two opening-wedge high tibial osteotomies were carried out. Lateral radiographic images of the knee were obtained preoperatively and right after surgery. The angle between the tangent of the medial tibial plateau and a line perpendicular to the axis of the posterior tibial cortex was determined by manual goniometric measurements before and after surgery. We also determined the relative position of the Puddu plate in relation to the posterior tibial cortex. Results: There was an increase of approximately 34% in the tibial slope after surgery, with the mean value rising from 7.6° to 10.2°. This difference was statistically significant (p = 0.0006). There is a correlation between the preoperative and postoperative inclination angles of the tibial plateau (r = 0.4131, p = 0.0065). The relative position and the size of the implant did not influence the changes in sagittal alignment. Conclusion: There was a statistically significant increase in the angulation of the proximal tibial articular surface in the sagittal plane after high tibial osteotomy. The posterior positioning of the Puddu plate was not related to a smaller increase of this angle / Mestrado / Fisiopatologia Cirúrgica / Mestre em Ciências

Title: Measurement of muscle activity during gait at patients with knock knees Objective: The aim of this study was to compare muscle activation between two groups of volunteers with and without knock-knees during level ground and incline walking on treadmill by surface electromyography. Muscles were measured on both legs, specificly tibialis anterior muscle, gastrocnemius lateralis muscle, vastus medialis muscle, adductor magnus muscle, semimembranosus muscle and tensor fasciae latae muscle. The goal of this experiment was to discover which muscles are more or less aktive according to the other group of participants. Then based on the conclusion could be possible to affect these changes by physiotherapy in future. Methods: The surface electromyography was used for measurement muscle activation. There were 12 volunteers, 9 women and 3 men, participate on this study in age from 21 to 27. Intermalleolar distance was used as a screening investigation for sorting into two groups whether the knock-knees are present or not. Result: There were different muscle activation between both groupes. Some muscles had increased activation others had lowest activation. However, this increase can be considered as statistically significant only in case of averrage amplitude muscle activity during midstance of step by...

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and toxicology Student: Lucie Rozkydalová Supervisor of Diploma thesis: Prof. PharmDr. František Štaud, PhD. Specialized supervisor: Pr. Pierre Cuq PharmD. PhD., Laure-Anaïs Vincent Title of diploma thesis: Differential resistance of melanoma to vinca-alkaloids Malignant melanoma (MM) represents the most dangerous and very aggressive skin tumor with fast development of drug resistance which is the main obstacle in successful treatment of MM. According to previous studies (microarray data analysis), KIT gene, which plays key role in melanoma pathophysiology, was chosen as one of the potential causes of failure of treatment by vinca alkaloids (VAs) because of its complete underexpression in melanoma CAL1 resistant cells (CAL1R-VAs) in comparison with parental cells (CAL1-wt). Moreover, KIT also interacted with NF-κB and cyclin D1-2 proteins involved in chemoresistance of melanoma - inside molecular network built using IPA software. Although KIT underexpression in resistant CAL1 R-VAs cell lines were confirmed (qRTPCR), KIT repression using specific siRNA transfection did not show any effect on in vitro sensibility of CAL1-wt cells to VAs. It signifies that KIT is not directly involved in melanoma resistance...

Niemann-Pick disease type C (NPC) is a rare, severe disease with autosomal recessive inheritance. Disease is caused by pathogenic mutations located in genes NPC1/NPC2. These genes encode lysosomal non enzymatic NPC1/NPC2 proteins that are part of lipid transport. As a result of malfunction of these proteins intracellular accumulation of lipids occurs, in particular free cholesterol and glycolipids. Causal therapy is currently still unsatisfactory therefore new therapies are evolved. However these therapies depend on whether the patient cells contain at least residual amount of transcript NPC1 gene. In a group of patiens, for which a fibroblast culture was available, I analyzed the effect of pathogenic mutations on the expression level of the transcript. Results showed that for all pathogenic mutations transcript level is low, but detectable. Moreover, I characterized the structure of the NPC1 gene promoter. By sequence analysis I found polymorphisms rs8099071, rs28403610, rs2981422, rs1652354, rs1788774, rs1788772 in promoter. On the basis of the composition of polymorphisms in individual patiens, I estimate six different haplotypes. I performed mutation analysis in DNA of recently diagnosed patient. I found only one pathogenic mutation p.I1061T (c.3182T> C) in the NPC1 gene. Therefore I tested...

Title: Assess the degree of valgus and varus knee joint in the second stage students in primary school in the Karlovarský region. Objective: The aim of this study was to explore and assess the degree of weakening of the lower limbs in the knee joint area in children of second stage of primary school in Karlovarský region. The effort was get as much information from the test subjects to understand and determining problems in the lower limbs. It measured two types of impairment, valgus and varus knee. Part of this study was to find what sports activities affect the creation or increase of individual weakness in the recreational and competitive level. Methods: The thesis is conducted as an empirical quantitative research, which focuses on finding descriptive and associative relationships between variables. From a methodological point of view this is a type of observation. To determine the necessary data was used planimetric method: trigonometric measurement. Measurements were attended by 531 children, including 243 boys and 288 girls aged from 11 to 16. This has involved completing a questionnaire form with basic somatic details and types of sporting activities. Results: The results show significant differences between girls and boys with genu valgum and genu varum. Girls also reached higher values...

In this work endocrine disrupting potential of Delor 103, a commercial mixture of PCB congeners, was studied along with its effect on production of laccase by the ligninolytic fungus Trametes versicolor. Using a gene-reporter yeast assay for evaluation of hormonal activity Delor 103 showed an androgenic activity with an EC50 value of 2.29. 10-2 mg/l. Chlorbenzoic acids, Delor 103 potential metabolites resulting from microbial degradation, displayed on the other hand an estrogenic activity, indicating possible changes in hormonal activity of Delor 103 during its microbial degradation. The addition of Delor 103 to mineral medium T. versicolor cultures resulted in an up to 257times higher laccase activities detected in fungal cultures. Delor 103 induced enzymes showed different pI values from those of control cultures. In a complex malt-extract glucose medium (MEG) the stimulation effect of Delor 103 was kept down. Further, the production of laccase and synthesis of different pI forms depended strongly on the growth phase of fungal cultures. Exponencially growing cultures of T. versicolor were able to produce up to 7 different pI forms of laccase in responce to Delor 103 whereas stationary cultures produced only 4 enzyme forms with higher pI values. Stimulation of laccase activities in T. versicolor,...

PREIMPLANTATION GENETIC HAPLOTYPING IN GENETICALLY RISK FAMILIES Abstract of Irena Borgulova's PhD study Page 1/1 ABSTRACT Preimplantation genetic diagnosis (PGD) is at the intersection of assisted reproduction and clinical genetics. PGD precedes prenatal diagnosis because consists in biopsy of a single embryonic cell and its examination excluding genetic risks before embryo transfer back to mother uterus. Methods within PGD can offer all spectrums of possible investigations of a single cell, whether focused on monogenic disorders, chromosomal aberration or abnormality of whole genome. Monogenic diseases in embryos can be detected by direct or indirect linkage analysis. Indirect linkage analysis has the advantage compared to direct analysis that it is able to indentify pertinent aberration of examined chromosome. Indirect linkage analysis is characterised by preimplantation genetic haplotyping (PGH) which is prime and important constituent of PGD cycle. PGH is based on family anamnesis for determination of pathologic/ high-risk (mutation-associated) haplotype and healthy/ low-risk (without mutation) haplotype by comparison with the haplotypes of other family members. PGD cycle requires in vitro fertilisation (IVF). IVF cycle includes hormonal stimulation, biopsy of oocytes and their fertilisation outside...

Bilirubin is a major product of the heme catabolism in the vascular bed with substantial antioxidant properties. These importantly contribute to pathogenesis of diseases associated with increased oxidative stress, including cardiovascular or cancer diseases. In the first part of this PhD project serum bilirubin concentrations were examined in the 1 % representative sample of the general Czech population, together with determination of the prevalence of Gilbert's syndrome. Bilirubin concentrations were determined also within individual polymorphisms of the UGT1A1 gene (OMIM*191740) responsible for bilirubin biotransformation in the liver, including their association with the basic risk factors for atherosclerosis. We also assessed the activity of the standard liver enzymes (representing another significant risk factor for the development of cardiovascular diseases) with surprisingly high proportion of subjects with elevated values. Simultaneously, we determined the concentrations of serum bilirubin in a group of patients with an acute coronary syndrome, who manifested with significantly lower concentrations as compared to general population. In the second part of this research project, the relationship between plasma concentrations of bilirubin and individual variants of UGT1A1 gene polymorphisms...

iv Abstract Regulation of gene expression is a key ability of every single cell in its development, differentiation and homeostasis. On the other hand, rather sparse amount of information is available for protists and our understanding of regulation of gene expression in eukaryotes is limited to a few model organisms. Our research is aimed at oxymonads, poorly studied group of anaerobic protists, which inhabit digestive tract of some animals. In this study we focus on the genus Monocercomonoides. Gene expression is modulated at multiple levels by many mechanisms. This thesis is focused on structure of promoter regions, 5' untranslated regions and basal transcription and translation initiation factors. Our results are compared to the closest studied relatives of Monocercomonoides - Trichomonas vaginalis and Giardia intestinalis. We have identified several conserved motifs in promoter regions of Monocercomonoides, including TATA box and TATA-like motif. These motifs potentially play a role in the transcription regulation. 5' untranslated regions are relatively short (typically 20 - 30 nucleotides) and GC content in these regions is low compared to model organisms. In selected genes, the quality of the automatic prediction of UTR was verified by RACE. We have annotated sets of basic transcription (23 proteins)...

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell disorders with ineffective hematopoiesis. It is characterized by morphological dysplasia, peripheral cytopenias affecting one or more cell lineages and an increased risk of transformation into acute myeloid leukemia (AML). The early stages of MDS can be considered a premalignant disease. The pathogenesis of MDS has not been fully explained yet, but due to the development of molecular genetic and cytogenetic methods, the origin and development of the disease is gradually being elucidated. In addition to the cytogenetic changes that are part of the prognostic system (IPSS-R), the somatic mutations found in different genes come to the forefront of interest. However, they are not routinely used in clinical practice. One of the objectives of this study was monitoring of mutations in TP53 gene in lower-risk MDS patients who generally have a good prognosis and for whom these findings have a particularly relevant prognostic significance. We investigated a total of 154 patients with lower-risk MDS, and 13% of them had a mutation. After dividing patients according to the presence of del(5q), we observed significant differences in the incidence of the mutations. The mutations were detected in 23.6% of patients with...