Ventriculo-peritoneal shunting is the most commonly used method for the treatment of paediatric hydrocephalus. Despite improved shunts and surgical techniques there are still complications. This retrospective study focuses on diagnoses and treatment of shunt malfunction and infections. Cost/benefit of using an adjustable shunt was assessed. Two adjustable cerebrospinal fluid shunts and their compatible antisiphon devices were compared in-vitro. In 21 of 46 children the standard shunt was changed to an adjustable one due to over-drainage. Adjustment of the shunt was performed in 73% of the children thereby avoiding surgery in several cases. This was a financial advantage. Ascites or an abdominal pseudocyst without infection was detected in eight children due to resorption difficulties. A ventriculo-atrial shunt was inserted for a period of time. In three children it could successfully be reverted to a ventriculo-peritoneal. In six children papilloedema was the only sign of shunt dysfunction. At revision the intracranial pressure ranged from 25 to 52 cm H2O. Fundoscopic examination in children older than 8 years may detect symptomless shunt malfunction. During a 13-year period 39 shunt infections were diagnosed. Skin bacteria were found in 80%. Prolonged and anaerobic cultures increased the detection rate by more than one third. The intraventricular infections were treated with intraventricular and systemic antibiotics resulting in quick sterilisation. No relapses were encountered. In five older children with distal catheter infection Propionibacterium acne was found. These were treated with intravenous antibiotics and exchanging of the shunt system. Strata NSCTM and Codman HakimTM worked according to the manufacturers except at the lowest setting. The resistance was below and in the lower range of the physiological one respectively. The antisiphon device of Strata shunt had to be placed in line with shunt to function properly.

The thesis deals with a theme of probiotic mikroorganisms which are aplicated as a dietary supplement. Health benefit on the host have been known for a long time, however, there might be some negative effects affecting a consumer. In connection with this observation defining requirements and evaluating of safety of probiotics in food was necessary. The new probiotic dietary supplement can not be expanded on the market without these processes. Every strain must be tested separately on each property. The ability of rezistance against conditions inside human gastrointestinal tract belongs to the most basic tests. The aim of the practical part is testing this ability of rezistance in vitro by simulated conditions. The model of gastrointestinal juices was designed according to the Czechoslovak codex. The form contributes to the higher rezistance of probiotics within implementing to the host. Also a dosage form of probiotics was involved to a in vitro testing.

Les mycotoxines sont des métabolites fongiques toxiques qui contaminent une variété d’aliments destinés à l’alimentation humaine et animale, notamment les céréales. Les porcs et les humains sont très sensibles aux mycotoxines. La mycotoxine zéaralénone (ZEN) se retrouve dans les aliments pour animaux et dans l'alimentation humaine principalement la suite d’une contamination fongique des céréales par Fusarium spp. la ZEA peut se fixer au 17-β-estradiol récepteur en raison de sa flexibilité, explique ses effets délétères sur les fonctions reproductives. Différentes stratégies de décontamination ont été développées pour réduire l’exposition des animaux d’élevage aux mycotoxines, parmi lesquelles des méthodes de conversion enzymatique de ZEN par certains micro-organismes. Cependant, les données préliminaires indiquent que certains de ces produits de biotransformation peuvent être reconvertis en ZEN. Des données récentes indiquent que Bacillus spp. S62-W peut phosphoryler ZEN sur ses 14e ou 16e carbones, la convertissant respectivement en ZEN-14-phosphate (ZEN-14-P) ou en ZEN-16-phosphate (ZEN-16-P). Cependant, la toxicité résiduelle et la stabilité de ZEN-14-P et de ZEN-16-P par rapport à ZEN sont encore inconnues. Cette étude visait à étudier la cytotoxicité, le stress oxydatif, l'activité pro-inflammatoire et l'activité œstrogénique des ZEN phosphorylés en utilisant des cellules épithéliales intestinales et endométriales porcines et humaines, ainsi que des explants d’utérus de cochettes prépubères. Nous avons également analysé les voies métaboliques de biotransformation des ZEN phosphorylés par les cellules porcines et humaines. Nos résultats ont démontré que l’exposition à ZEN-14-P ou à ZEN-16-P diminue significativement la viabilité des cellules intestinales porcines IPEC-J2 et des cellules endométriales humaines d’Ishikawa. ZEN, les produits de phosphorylation ont induit de manière significative un stress oxydatif dans les cellules IPEC-J2 à 10 µM. De même, 5 μM ou 25 μM de ZEN-14-P et ZEN-16-P ont activé de manière significative l'expression de cytokines pro-inflammatoires TNF-α, IL-1β, IL-6 et IL-8 dans les cellules IPEC-J2 différenciées. Pour ce qui est des effets œstrogéniques, de manière similaire à ZEN, l'activité intracellulaire de la phosphatase alcaline a été augmentée de façon significative et dose dépendante par ZEN-14-P et ZEN-16-P, dans les cellules d'Ishikawa. Ces produits de phosphorylation ont également, à l’image de ZEN, activé de manière significative l'expression de gènes sensibles aux œstrogènes ALPP, ALPG, PGR, ESR1, ESR2 et GPER1 dans les cellules d'Ishikawa. Enfin, l’exposition à ZEN ou aux ZEN phosphorylés a induit la prolifération des glandes endométriales dans les explants utérins de cochettes prépubères. L'analyse LC-MS/MS des surnageants de culture cellulaire de IPEC-J2 et Ishikawa indique que, bien que les ZEN phosphorylés aient été partiellement hydrolysés en ZEN, leurs métabolites de phase I et de phase II sont différents de ceux de ZEN. Globalement, ces résultats indiquent que la phosphorylation ne réduit pas la toxicité de ZEN pour les lignées cellulaires porcine et humaine. De plus, les voies métaboliques impliquées dans la biotransformation de ZEN et celle des produits de phosphorylation sont différentes, ce qui suggère une toxicité intrinsèque des ZEN phosphorylés. / Pigs and humans are highly susceptible to mycotoxins, which are toxic fungal metabolites that contaminate a variety of food and feedstuffs. Among these, Zearalenone (ZEN) is found in the feed and food supply from Fusarium fungal contamination in cereals. ZEN is functionally similar to 17-β estradiol, and therefore exerts deleterious effects on reproductive functions. Different decontamination strategies are developed to reduce the exposure of farm animals to mycotoxins. At many of these, there are methods of biotransformation of ZEN by the enzymatic activity of certain microorganisms. Bacillus sp. S62 reportedly phosphorylates ZEN on its 14th or 16th carbons, yielding, ZEN-14-P and ZEN-16-P. However, the residual toxicity and stability of ZEN-14-P and ZEN-16-P compared to ZEN are still unknown. This study aimed to investigate the cytotoxicity, oxidative stress, pro-inflammatory activity, and estrogenic activity of phosphorylated ZENs, as well as its metabolic fate when incubated either with intestinal or reproductive cells. Our results showed that ZEN-14-P and ZEN-16-P did not decrease the cytotoxic effect of ZEN in porcine intestinal IPEC-J2 cells and human endometrial Ishikawa cells. ZEN and both phosphorylated ZENs significantly induced oxidative stress in IPEC-J2 cells at 10 µM. Likewise, 5 μM or 25 μM ZEN-14-P and ZEN-16-P altered the expression of pro-inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-8 in differentiated IPEC-J2 cells. In addition, intracellular activity of alkaline phosphatase increased by ZEN, ZEN-14-P and ZEN-16-P in Ishikawa cells. ZEN, ZEN-14-P and ZEN-16-P activated the expression of estrogen-responsive genes ALPP, ALPG, PGR, ESR1, ESR2, and GPER1 at 10 μM in Ishikawa cells. Furthermore, ZEN and phosphorylated ZENs induced the proliferation of endometrial glands in prepubertal gilt uterine explants at 30 µM. Finally, LC-MS/MS analysis of the supernatant of IPEC-J2 and Ishikawa cell cultures exposed to ZEN or its phosphorylated metabolites showed that the latter were partially hydrolyzed back to ZEN, but their phase-I and phase-II metabolites still differ from the ones of ZEN. Overall, these results suggest that phosphorylation does not reduce the toxicity of ZEN for pigs and humans. Moreover, different metabolic fate is involved in the biotransformation of ZEN and phosphorylation products.

Coronary artery disease (CAD) affects every fifth person in the world. The gold-standard treatment for CAD is stent implantation, however, the existing therapy is not sufficient due to many reasons. For instance, in-stent restenosis, biocompatibility, controlled degradation rate, protein adsorption, and adequate endothelialization are still the main concerns. In the last two decades, the field of stent technology has been grown rapidly and many new stent types and in vitro testing methods for stent characterization have been developed to minimize the aforementioned issues. In this vicinity, there are still many unaddressed issues: i) the quantitative analysis of corrosion is conducted with simpler samples made of stent material instead of stents, in most cases due to the absence of a mathematical model to calculate the entire stent surface area (ESSA); ii) in vitro stent testing in environments that are very far from actual physiological environments; iii) Evaluation of the influence of in-vitro test conditions on coated metallic stents; iv) absence of flow-induced shear stress (FISS) corrosion model, to mention a few. This thesis presents the novel ESSA model, the fluid dynamic experimental setup with the integration of various sensors and pH control, the influence of in vitro degradation behavior of the titanium oxynitride (TiOxNy) coated stainless steel stents and anodized AZ31 samples, and the FISS corrosion model. The results show some important contributions in this field, however, there is still a huge potential for the development of promising stent characterization solutions. / Die koronare Herzkrankheit (KHK) betrifft jeden fünften Menschen auf der Welt. Der Goldstandard bei der Behandlung von KHK ist die Stent-Implantation, doch die bestehende Therapie ist aus vielen Gründen nicht ausreichend. So sind beispielsweise die Restenose im Stent, die Biokompatibilität, die kontrollierte Abbaugeschwindigkeit, die Proteinadsorption und die angemessene Endothelialisierung nach wie vor die Hauptprobleme. In den letzten zwei Jahrzehnten hat sich die Stenttechnologie rasant weiterentwickelt, und es wurden viele neue Stenttypen und In-vitro-Testmethoden zur Stentcharakterisierung entwickelt, um die oben genannten Probleme zu minimieren. In dieser Umgebung gibt es noch viele ungelöste Probleme: i) die quantitative Analyse der Korrosion wird mit einfacheren Proben aus Stentmaterial anstelle von Stents durchgeführt, in den meisten Fällen aufgrund des Fehlens eines mathematischen Modells zur Berechnung der gesamten Stentoberfläche (ESSA); ii) In-vitro-Stent-Tests in Umgebungen, die sehr weit von der tatsächlichen physiologischen Umgebung entfernt sind; iii) Bewertung des Einflusses von In-vitro-Testbedingungen auf beschichtete metallische Stents; iv) Fehlen eines FISS-Korrosionsmodells (flow-induced shear stress), um nur einige zu nennen. In dieser Arbeit werden das neuartige ESSA-Modell, der strömungsdynamische Versuchsaufbau mit der Integration verschiedener Sensoren und pH-Kontrolle, der Einfluss des In-vitro-Degradationsverhaltens der mit Titanoxynitrid (TiOxNy) beschichteten Edelstahlstents und anodisierten AZ31-Proben sowie das FISS-Korrosionsmodell vorgestellt. Die Ergebnisse zeigen einige wichtige Beiträge in diesem Bereich, jedoch gibt es noch ein großes Potenzial für die Entwicklung von vielversprechenden Lösungen zur Charakterisierung von Stents.

Do metal particles (including particles of pure metals, alloys, metal oxides and compounds) pose a hazard or risk to human health? In the light of this question, this thesis summarizes results from research conducted on metal particles, and describes the elaboration and implementation of an in vitro test methodology to study metal release from particles through corrosion and dissolution processes in synthetic biological media relevant for human exposure through inhalation/ingestion and dermal contact. Bioaccessible metals are defined as the pool of released metals from particles that potentially could be made available for absorption by humans or other organisms. Studies of bioaccessible metals from different metal particles within this thesis have shown that the metal release process is influenced by material properties, particle specific properties, size distribution, surface area and morphology, as well as the chemistry of synthetic biological test media simulating various human exposure scenarios. The presence of metal particles in proximity to humans and the fact that metals can be released from particles to a varying extent is the hazard referred to in the title. The bioavailable metal fraction of the released metals (the fraction available for uptake/absorption by humans through different exposure routes) is usually significantly smaller than the bioaccessible pool of released metals, and is largely related to the chemical form and state of oxidation of the released metals. Chemical speciation measurements of released chromium for instance revealed chromium to be complexed to its non-available form in simulated lung fluids. Such measurements provide an indirect measure of the potential risk for adverse health effects, when performed at relevant experimental conditions. A more direct way to assess risks is to conduct toxicological in-vitro testing of metal particles, for instance on lung cell cultures relevant for human inhalation. Induced toxicity of metal particles on lung cells includes both the effect of the particles themselves and of the released metal fraction (including bioaccessible and bioavailable metals), the latter shown to be less predominant. The toxic response was clearly influenced by various experimental conditions such as sonication treatment of particles and the presence of serum proteins. Thorough characterization of metal particles assessing parameters including chemical surface composition, degree of agglomeration in solution, size distribution, surface area and morphology was performed and discussed in relation to generated results of bioaccessibility, bioavailability and induced toxicity. One important conclusion was that neither the surface composition nor the bulk composition can be used to assess the extent of metals released from chromium-based alloy particles. These findings emphasize that information on physical-chemical properties and surface characteristics of particles is essential for an in-depth understanding of metal release processes and for further use and interpretation of bioaccessibility data to assess hazard and reduce any risks induced by human exposure to metal particles. / QC 20100803