Molecular aspects of calcium-phosphate metabolism in renal complications of diabetes mellitus.

Úvod: Diplomová práce se zabývá kalcio-fosfátovým metabolismem a jeho roli při rozvoji chronických diabetických komplikací. Zkoumá kalcium sensitivní receptor, který může mít klíčový význam v ovlivnění kalciového metabolismu. Kalcium senzitivní receptor se pravděpodobně podílí na intrabuněčné signalizaci a metabolických pochodech, které vedou k proliferaci extracelulární matrix a k počátku diabetické nefropatie. Byly zkoumány 2 polymorfismy tohoto genu pro kalcium senzitivní receptor (intron 4 a codon 990). Materiál a Metody: Do studie bylo zařazeno 313 diabetických pacientů, z toho 41 pacientů s diabetem 1.typu, 106 pacientů s diabetem 2.typu, 110 pacientů diabetiků 2. typu, kteří trpěli diabetickou nefropatií a 56 pacientů s nediabetickým renálním selháním (NDRD). Dále bylo vyšetřeno 72 nediabetických pacientů s chronickým renálním selháním (CKD) a 96 zdravých dárců krve (ZK). Klasifikace jednotlivých diagnóz je uvedena v části teorie. DNA byla izolována QIAamp DNA Blood Mini Kitu a vysolovací metodou. Pomocí PCR byly amplifikovány specifické fragmenty genu pro CaSR. Pro detekci byl použit polymorfismus délky restrikčních fragmentů a TaqMan sondy. Pro určení hladiny exprese mRNA byla použita metoda real-time PCR. Výsledky: U polymorfismu "codon 990" jsme zjistili statisticky významnost ve frekvenci...Introduction: This thesis deals with the calcium-phosphate metabolism and its role in the development of chronic diabetic complications. It examines calcium sensitive receptor, which can be crucial in affecting calcium metabolism. Calcium-sensitive receptor may play a role in intracellular signaling and metabolic pathways that lead to cell proliferation and extracellular matrix early diabetic nephropathy. We investigated two polymorphisms of the gene for calcium-sensitive receptor (intron 4 and codon 990). Material and Methods: The study included 313 diabetic patients, 41 patients with type 1 diabetes, 106 patients with type 2 diabetes, 110 diabetic patients with type 2 diabetes who had diabetic nephropathy and 56 patients with renal failure non-diabetic (NDRD). It was also examined 72 non-diabetic patients with chronic renal failure (CKD) and 96 healthy blood donors (ZK). Classification of diagnoses is listed in the theory. DNA was isolated by QIAamp DNA Blood Mini Kit and salting method. The specific fragments of gene for the CaSR were amplified by PCR. For detection, restriction fragment length polymorphism and TaqMan probes were used. The expression levels of mRNA were determined by real-time PCR. Results: For the codon 990 polymorphism, we found statistical significance of the genotype frequencies (AA,...Department of Anthropology and Human GeneticsKatedra antropologie a genetiky člověkaFaculty of SciencePřírodovědecká fakult

Gilbetr syndrome

The mail focus of this thesis is to assess a genealogical frequency of homo- and heterozygotes for a mutation in a promotor region of UGT 1A1 gene. This mutation is typical for Gilbert's syndrome. It explains a genesis, symptoms, pathology and also a therapy of this syndrome. It discusses a possibly protective effect of this polymorphic mutation that might result in a lower incidence of vascular diseases (myocardial infarction, stroke, atherosclerosis, pulmonary embolism). An important contribution is also an attenuation of stress due to hyperbilirubinaemia. This thesis was worked out in a cooperation with GENVIA Ltd

Gilbert Syndrome.

Diplomová práce se zaměřuje na zjištění možné souvislosti mezi genotypem typickým pro Gilbertův syndrom a konkrétní chorobou. Zkoumá možný ochranný vliv alely 7TA. Vysvětluje vznik, symptomy, patologii tohoto syndromu a jeho souvislosti s medicínou. Diskuse zahrnuje možný ochranný účinek této polymorfní mutace, který se může projevit sníženou četností cévních onemocnění (infarkt myokardu, cévní mozková příhoda, ateroskleróza, atd.). Významný by mohl být rovněž podíl hyperbilirubinémie na snížení oxidačního stresu. Práce byla prováděna ve spolupráci s laboratoří GENVIA s.r.o.This thesis focuses on finding a possible link between genotype typical for Gilberts syndrome and specific diseases. It nvestigates a possible protective effect of the 7TA allele. It explains the origin, symptoms, pathology of this syndrome and its consequences for clinical medicine. Possible protective effect of this polymorphic mutation including reduced incidence of vascular diseases (myocardial infarction, stroke, atherosclerosis, etc.). is discussed. Reduced oxidative stress in hyperbilirubinaemia can be the mechanism behind. The work was carried out in the co-operation with the GENVIA laborator.Katedra antropologie a genetiky člověkaDepartment of Anthropology and Human GeneticsPřírodovědecká fakultaFaculty of Scienc

State liability for damage incurred due to the decision or incorrect official procedure

Odpovědnost státu za škodu způsobenou rozhodnutím nebo nesprávným úředním postupem Abstrakt English Thesis is interested in a legal institution of state liability for damage incurred due to the decision or incorrect official procedure as one of the particular case of a civil liability. It evaluates its legal forms on the one hand and specifics of proceedings concerning compensation for damage on the other, de lege lata in the area of the Czech national law. The thesis offers an European sight of the institute of liability for damage of EU member states too and introduces the fundamental rulings of European Court of Justice. An interesting component of the thesis is a case study in state liability for damage incurred due to incorrect official procedure of legislator in the area of Czech residential rent rates. At the end of the thesis several reflections of potential changes of legislation de lege ferenda are presented

Protection against radiation at the out-patients and at the operating theatres - the role of the radiological assistant in safeguarding against radiation

The eim of this Bachelor's thesi s is to evaluate the radiation protection in arnbulatory care centers arnbulatory roorns consequences of excessive radiation on the rnolecular and organ level are also reviewed. New legislature, conceming the protection ofwornen is also discussed. The deterrnination in roorns), pararneters rnentioned frorn approximation principles The arnbulatory rooIUS. rneasurernents values frorn 2005. cornprises tab les, selected thesis radi ation ambulatory in comparison to operating rooms. First, the legislature of radiation protection is discussed. Then, different protective tools used in ambulatory care centers and operating rooms are listed. The excessÍve molecular concerning ofwomen Tne determination of effective dose (in ambulatory care centers and operating rooms), data processing, and different apparatus parameters are mentioned in another part. The groups used in this study were divided in respect to the age and diagnose. The data from the measurements can be used for approx.imation of radiation effective dose. The general princi ples of radiological assistant role in radiation protection are discussed consecutively, as well as the possibilities ofradiation reduction. Tne radiation protection is reviewed in respect to differences between ambulatory care centers and operating..

Molecular aspects of calcium-phosphate metabolism in renal complications of diabetes mellitus.

Introduction: This thesis deals with the calcium-phosphate metabolism and its role in the development of chronic diabetic complications. It examines calcium sensitive receptor, which can be crucial in affecting calcium metabolism. Calcium-sensitive receptor may play a role in intracellular signaling and metabolic pathways that lead to cell proliferation and extracellular matrix early diabetic nephropathy. We investigated two polymorphisms of the gene for calcium-sensitive receptor (intron 4 and codon 990). Material and Methods: The study included 313 diabetic patients, 41 patients with type 1 diabetes, 106 patients with type 2 diabetes, 110 diabetic patients with type 2 diabetes who had diabetic nephropathy and 56 patients with renal failure non-diabetic (NDRD). It was also examined 72 non-diabetic patients with chronic renal failure (CKD) and 96 healthy blood donors (ZK). Classification of diagnoses is listed in the theory. DNA was isolated by QIAamp DNA Blood Mini Kit and salting method. The specific fragments of gene for the CaSR were amplified by PCR. For detection, restriction fragment length polymorphism and TaqMan probes were used. The expression levels of mRNA were determined by real-time PCR. Results: For the codon 990 polymorphism, we found statistical significance of the genotype frequencies (AA,..

Histological Changes of the Middle Ear Ossicles Harvested During Cholesteatoma Surgery

Background: In the cholesteatoma surgery ossicles can be replaced to reconstruct middle ear function. It is important that these ossicles are free of squamous epithelium, to prevent residual disease. This study focuses on the histological findings of the malleus and incus harvested during cholesteatoma surgery. Materials and Methods: Eighty middle ears ossicles were examined in vivo and histologically to consider the relationship of cholesteatoma to ossicles, grade of bone destruction and invasion of cholesteatoma to deeper layers of bone. Results: Serious ossicular destruction was observed more frequently in incus compared to malleus (p = 0.0065). Difference of ossicles destruction between children and adults was not significant (p = 0.3032). Deep invasion of cholesteatoma into the vascular spaces or inner core of the bone was not observed. Conclusions: Autograft ossicles from cholesteatomatous ears should not necessarily be rejected for reconstruction of the ossicular chain. Regarding the histological finding, the authors suggest mechanical cleaning of the ossicle surface to eliminate residual disease

The Influence of Repeated Blood Withdrawals before Surgery on Clinical Outcome

The aim of this study was to find the influence of blood withdrawals and diet iron on elective surgery. Male Wistar rats (n=24) were divided: 1. group (SLD) ate standard laboratory diet (SLD), 2. group (FE) an iron enriched diet (FE) with one blood withdrawal after 9 weeks. 3. group (SLD-w) SLD and 4. group (FE-w) ate the FE diet; with 9 withdrawals once a week. The rats were sacrificed 18 hour after partial hepatectomy (PH) in the 10th week. Liver DNA synthesis (3H-thymidin – kBq/mg DNA) was performed. Serum hepcidin (pg/ml), iron concentration, respiratory burst of polymorfonucleares (RB, spontaneous; stimulated, %), count of blood cells were determined. FE-w had a higher (2.36±0.36) liver DNA synthesis after PH vs. SLD (1.21±0.49). Higher hemoglobin in erythrocytes (pg) was in FE-w and SLD-w vs. FE and SLD. PMN count in SLD-w, FE-w increased vs. SLD, FE. Hepcidin after PH decreased in SLD (78.0), FE (68.0), FE-w (97.0), but increased in SLD-w (217). Serum iron increased in SLD-w. RB after PH increased in FE-w (4.5; 47.6) vs. SLD (1.15; 29.1), FE (3.20;17.8), SLD-w (3.30;13.7). Conclusions: The iron diet with stimulation of haematopoesis by withdrawals improves an organism’s condition expressed as better response to elective surgery and better PMN functions

Sodium Accumulation and Blood Capillary Rarefaction in the Skin Predispose Spontaneously Hypertensive Rats to Salt Sensitive Hypertension

Recent studies in humans and rats suggested that increased Na+ storage in the skin without parallel water retention may predispose to salt-sensitive hypertension. In the current studies, we compared tissue Na+ storage in salt sensitive spontaneously hypertensive rats (SHR) versus salt resistant normotensive Brown Norway (BN-Lx) rats. After salt loading (10 days drinking 1% NaCl solution), the SHR showed significant parallel increase in Na+-to-water as well as (Na++K+)-to-water ratios suggesting increased storage of osmotically inactive Na+ in the skin while no significant changes in skin electrolyte concentrations were observed in BN-Lx rats. SHR rats after salt treatment exhibited a nonsignificant decrease in skin blood capillary number (rarefaction) while BN-Lx rats showed significantly increased skin blood capillary density. Analysis of dermal gene expression profiles in BN-Lx rats after salt treatment showed significant up-regulation of genes involved in angiogenesis and proliferation of endothelial cells contrary to the SHR. Since the skin harbors most of the body’s resistance vessels it is possible that blood capillary rarefaction may lead to increased peripheral resistance and salt sensitivity in the SHR