A doença de Wilson (DW) é distúrbio da excreção biliar de cobre, de herança autossômica recessiva, devido a mutações no gene ATP7B. O cobre que não se liga à apoceruloplasmina circula no organismo ligado a aminoácidos, deposita-se principalmente no fígado e no cérebro e é excretado pelos rins. A cuprúria maior que 100ug/24h pode auxiliar no diagnóstico, embora cerca 20% dos pacientes com DW apresentem níveis anormais de cuprúria basal. A administração da d-penicilamina (DPA) pode promover, em crianças, valores maiores que 1.600ug/24h. A fim de se conhecer os níveis de cuprúria de possíveis indivíduos heterozigotos adultos, foram avaliados 25 pais e 25 mães de pacientes (média 61 anos em homens; 57 anos em mulheres) com diagnóstico de DW. Foram obtidos os níveis séricos de enzimas hepáticas, cobre e ceruloplasmina, e quantificada a cuprúria de 24h. A seguir, os indivíduos receberam DPA 1,0g por via oral dividido em duas tomadas, durante nova coleta de urina para dosagem de cuprúria de 24h. Esta análise foi realizada pelo método de espectrometria de absorção atômica eletrotérmica. Os níveis de enzimas hepáticas foram semelhantes nos dois grupos, exceto o nível médio de fosfatase alcalina que foi maior nas mulheres (H= 68,72 UI/L; M=81,68 UI/L). Os níveis de ceruloplasmina (H=21,72mg/dL; M=27,78mg/dL) e de cobre sérico (H=71,38 ?g/dl; M=88,0 ug/dl) foram maiores em mulheres do que em homens (p<0,001). Os níveis de cuprúria basal foram 22,43ug/24h (média) e 21,40ug/24h (mediana); e, após a DPA, de 523,54 ug/24h (média) e 511,5 ug/24h (mediana). A cuprúria média basal masculina foi de 26,19. ug/24h, enquanto a feminina foi de 18,28. ug/24h (p=0,005). Com o presente estudo, ficou definida possível faixa de variação da cuprúria antes e depois da administração de dpenicilamina em pais de portadores com doença de Wilson; que os pais apresentaram cupremia e níveis de ceruloplasmina menores e cuprúria basal maior do que as mães; que as faixas de variação de normalidade para os parâmetros ceruloplasmina, cobre sérico e urinário deveriam ser diferenciadas de acordo com o sexo. / Wilson disease is a biliary copper excretion disturbance, of recessive autossomic heritage, due to ATP7B gene mutations. The copper not bound to apoceruloplasmin circulates in the organism bound to amino acids and accumulates mainly in the liver and brain being excreted by the kidneys. Urinary copper higher than 100ug/24h can be useful in the diagnosis, but only about 20% of Wilson disease patients have abnormal basal levels. In this case, d-penicillamine (DPA) administration can lead, in children, to levels higher than 1.600ug/24h. Twenty five fathers and twenty five mothers of wilson disease patients (mean 61 years for male, and 57 years for female) were assessed in order to obtain urinary copper levels of probable heterozygote adults. Fasting liver enzymes, copper and ceruloplasmin serum levels were obtained along with 24h urinary copper excretion. After, patients got DPA 1.0g by oral route, twice a day, while collecting urine for 24h urinary copper excretion dosage. These analyses were performed by elethrotermic atomic absortion spectrometry method. Liver enzyme levels were similar in men and women but those of alkaline phosphatase were higher in women (M= 68.72 UI/L; F=81.68 UI/L). Serum ceruloplasmin (F=21.72mg/dl; F=27.78mg/dl) and copper (M=71.38 ug/dl; F=88.0 ug/dl) levels were higher in women than in men (p<0.001). Urinary copper levels before DPA were, 43ug/24h (mean) and 21.40 ug/24h (median); and, after DPA, 523.54 ug/24h (mean) and 511.5 ug/24h (median). Basal urinary copper levels in men were 26.9 ug/24h, and in women were 18.67 ug/24h (p=0.005). With the results of this study, we defined a possible range for urinary copper before and after oral intake of DPA in parents of Wilson disease patients. Furthermore, fathers had lower levels of serum copper and of ceruloplasmin, and greater levels of baseline cupriuresis than mothers; and finally the normal range for serum copper and ceruloplasmin, and urinary copper should be differentiated according to the gender.

In cities today, vast amounts of nutrients are being wasted. Improvement in nutrient management within agriculture can contribute to a more sustainable society. Reusing nutrients in agriculture could aid in creating a more circular system, where organic fertilizers can be used instead of chemical fertilizers. Urine is a liquid which has a high nutrient content. According to the Swedish environmental protection agency, human urine can replace mineral fertilizers, by using methods such as source separation, where urine is divided from faeces. This is a cheap, effective and sustainable fertilizer management system that can be easily achieved. In this study, urine fertilizers were compared with ecological and conventional fertilizers (NPK and cow manure). The study examined the effect of different urine fertilizers compared with organic and inorganic ones on plant growth, nutrient content, pH value and microbial growth. The plant growth experiment was carried out in the greenhouse facilities in Alnarp, Sweden. The results from the experiment show that cow manure has a better outcome when it comes to plant growth, but Aurin, one of the urine fertilizers, had the highest uptake of nitrate. Non-diluted urine had a stable result in all analyses. According to this study human urine is a fertilizer which can be used in crop cultivation systems, and can deliver good agricultural results.

Normal human urine contains many anions and cations. Ionic concentrations in urine have classically been determined by spectrophotometry of color reactions, flame emission spectrophotometry, atomic absorption spectrophotometry, high performance liquid chromatography, or potentiometry with ion-specific electrodes. Capillary ion electrophoresis (CIE) is a form of capillary electrophoresis which uses the differential electrophoretic mobility of ions to perform a separation of an ionic mixture. Various salts can be added to urine specimens to abnormally elevate ionic concentrations and interfere with either immunoassay urine drug screening procedures or gas chromatographic/mass spectrometric confirmation techniques. Application of CIE for the direct detection of endogenous anions and anionic adulterants in human urine specimens was the purpose of this investigation. CIE was performed using a Waters Quanta 4000 Capillary Electrophoresis System with either direct or indirect ultraviolet absorption detection at 254 nm. CIE of 30 random normal urine specimens and 21 urine specimens suspected of adulteration was performed. Duplicate aliquots were assayed by CIE and by colorimetric technique for nitrite. Sixteen specimens had elevated concentrations of nitrite and/or nitrate. The correlation coefficient between nitrite CIE and colorimetric results was 0.9895. Three specimens had detectable concentrations of chromate and were suspected of being adulterated with "Urine Luck," an adulterant found to contain chromate. Two specimens suspected of being adulterated with bleach were found to only contain chloride, sulfate, and phosphate. CIE is applicable to forensic analysis of urine anion concentrations. CIE can easily quantitate numerous endogenous anions and offers a method to detect and/or confirm anion adulteration of urine specimens.

Majstorović, Z. Utsöndring av stenbildande substanser i urin – kan stickprov er-sätta dygnsmängder? Examensarbete i Biomedicinsk laboratorievetenskap 15 högskolepoäng. Malmö högskola: Hälsa och samhälle, Utbildningsområde Bio-medicinsk laboratorievetenskap, 2011.Syfte. Utredning av njurstenspatienter omfattar alltid undersökning av utsönd-ringen av stenbildande substanser i urin. Samlingen av urin under ett dygn hos njurstenpatienter innebär ofta problem för patienten eftersom det inte är så sällan att de glömmer samla urin i dunken eller samlar för lång eller kort tid. Syftet med min undersökning är att undersöka om det finns alternativ till att samla urin under 24 timmar i de fall där utsöndringen av stenbildande substanser är konstant över dygnet. Frågeställningen är om utsöndringen av stenbildande substanser kan upp-skattas genom att relatera deras koncentration i urin till koncentrationen av kreati-nin i urin eftersom utsöndringen av kreatinin är relativt konstant över dygnet. I så fall bör koncentrationen av stenbildande substanser i urin kunna relateras till kon-centrationen av kreatinin i urin på samma sätt som vid narkotikaanalys. Metod. Försökspersonerna samlade all urin i exakt 24 timmar. Den första urinportionen sparades i ett separat kärl medan all efterföljande urin samlades i en separat dunk . Efter ca en vecka gjordes en ny urinsamling, denna gång bara i en dunk. Dygnsut-söndringarna jämfördes med varandra och med kreatininindex i stickprovet. Re-sultat. Ett starkt samband fanns mellan kreatininindex av kalcium och dygnut-söndringen av kalcium. Sambandet var något mindre starkt för magnesium och saknades för fosfat och kalium. Slutsats. Resultaten talar mot att kreatininindex generellt kan användas för att skatta utsöndringen av njurstensbildande substanser. Däremot verkar kreatininindex relativt väl förutsäga utsöndringen av kalcium och i viss mån även magnesium. / Majstorović, Z. Secretion of stone-forming substances in the urine - can spot urine sample replace 24 hour urine collection? Degree project in Biomedical Laboratory Science, 15 credits points. Malmö University, Health and Society, Department of Biomedical Laboratory Science, 2011.Objective. Clinical investigation of kidney stone patients always includes moni-toring of the secretion of stone-forming substances in the urine. However, 24 h urine collection is difficult for the patient and prone to error. The purpose of this study is to examine whether there are alternatives to the collecting of urine under the period of 24 hours in cases where the secretion of stone-forming substances is constant across days. The question is whether the excretion of stone-forming sub-stances can be estimated by relating the concentration of urine to the creatinine concentration of urine, since the excretion of creatinine is relatively constant over a day. If so, the concentration of stone-forming substances in urine could be relat-ed to the concentration of creatinine in urine in the same way as drug analyses commonly are. Method. The subjects collected a 24h collection of urine. The first urine portion was stored in a container, while all subsequent urine was collected in a separate container. After about a week, another timed collection of urine was performed, but this time only in one container. The 24 h solute excretions were compared to each other and to the solute creatinine index. Results. A strong cor-relation was found between the creatinine index of calcium and the 24 h excretion of calcium. A somewhat weaker correlation was found for magnesium and a lack of correlation for phosphate and potassium. Conclusion. Results indicate that creatinine indexes in general do not predict 24 h excretions. However, creatinine index appears to predict the excretion of calcium and, to some extent, magnesium.

Human excreta contain plant nutrients and have the potentialto be used as a fertiliser in agriculture. Urine contributesthe major proportion of the nutrients (N, P and K) in domesticwastewater whereas faeces contribute a smaller amount andinvolves greater health risks if reused due to the possiblepresence of enteric pathogens. Human urine does not generallycontain pathogens that can be transmitted through theenvironment. Source-separation of urine and faeces is possible by usingurine-separating (or urine-diverting) toilets, available assimple dry toilets or porcelain flush toilets with dividedbowls. The risk for transmission of disease when handling andreusing the urine is largely dependent on thecross-contamination by faeces. In this research, the presenceof human faeces in urine samples was successfully determined byanalysing for faecal sterols. Cross-contamination was evidentin 22% of the samples from urine collection tanks, and in thesequantified to an average (± SD) of 9.1 ± 5.6 mgfaeces per litre urine. Testing for indicator bacteria wasshown to be an unsuitable method for determining faecalcontamination in human urine sinceE. colihad a rapid inactivation in the urine and faecalstreptococci were found to grow within the system. The fate of any enteric pathogens present in urine iscrucial for the risk for transmission of infectious diseases.Gram-negative bacteria (e.g.SalmonellaandE. coli) were rapidly inactivated (time for 90%reduction, T90&lt;5 days) in source-separated urine at itsnatural pH-value of 9. Gram-positive faecal streptococci weremore persistent with a T90of approximately 30 days. Clostridia sporenumbers were not reduced at all during 80 days. Similarly,rhesusrotavirus andSalmonella typhimuriumphage 28B were not inactivated inurine at low temperature (5°C), whereas at 20°C theirT90-values were 35 and 71 days, respectively.Cryptosporidiumoocysts were less persistent with a T90of 29 days at 4°C. Factors that affect thepersistence of microorganisms in source-separated human urineinclude temperature, pH, dilution and presence of ammonia. By using Quantitative Microbial Risk Assessment (QMRA), therisks for bacterial and protozoan infections related tohandling and reuse of urine were calculated to be&lt;10-3for all exposure routes independent of the urinestorage time and temperature evaluated. The risk for viralinfection was higher, calculated at 0.56 for accidentalingestion of 1 ml of unstored urine. If the urine was stored at20°C for 6 months the risk for viral infection was reducedto 5.4 × 10-4. By following recommendations for storage and reuse, whichare dependent on the type of crop to be fertilised, it ispossible to significantly decrease the risk for infections. Sofar, the level of risk that is acceptable is unknown. Theacceptable risk will be one of the main factors determining thefuture utilisation of source-separated human urine inagriculture. <b>Keywords:</b>urine-separation, urine, wastewater systems,wastewater reuse, recycling, enteric pathogens, faecal sterols,indicator bacteria, hygiene risks, microbial persistence,microbial risk assessment, QMRA, fertiliser, crop.

<p>Human excreta contain plant nutrients and have the potentialto be used as a fertiliser in agriculture. Urine contributesthe major proportion of the nutrients (N, P and K) in domesticwastewater whereas faeces contribute a smaller amount andinvolves greater health risks if reused due to the possiblepresence of enteric pathogens. Human urine does not generallycontain pathogens that can be transmitted through theenvironment.</p><p>Source-separation of urine and faeces is possible by usingurine-separating (or urine-diverting) toilets, available assimple dry toilets or porcelain flush toilets with dividedbowls. The risk for transmission of disease when handling andreusing the urine is largely dependent on thecross-contamination by faeces. In this research, the presenceof human faeces in urine samples was successfully determined byanalysing for faecal sterols. Cross-contamination was evidentin 22% of the samples from urine collection tanks, and in thesequantified to an average (± SD) of 9.1 ± 5.6 mgfaeces per litre urine. Testing for indicator bacteria wasshown to be an unsuitable method for determining faecalcontamination in human urine since<i>E. coli</i>had a rapid inactivation in the urine and faecalstreptococci were found to grow within the system.</p><p>The fate of any enteric pathogens present in urine iscrucial for the risk for transmission of infectious diseases.Gram-negative bacteria (e.g.<i>Salmonella</i>and<i>E. coli</i>) were rapidly inactivated (time for 90%reduction, T₉₀<5 days) in source-separated urine at itsnatural pH-value of 9. Gram-positive faecal streptococci weremore persistent with a T₉₀of approximately 30 days. Clostridia sporenumbers were not reduced at all during 80 days. Similarly,<i>rhesus</i>rotavirus and<i>Salmonella typhimurium</i>phage 28B were not inactivated inurine at low temperature (5°C), whereas at 20°C theirT₉₀-values were 35 and 71 days, respectively.<i>Cryptosporidium</i>oocysts were less persistent with a T₉₀of 29 days at 4°C. Factors that affect thepersistence of microorganisms in source-separated human urineinclude temperature, pH, dilution and presence of ammonia.</p><p>By using Quantitative Microbial Risk Assessment (QMRA), therisks for bacterial and protozoan infections related tohandling and reuse of urine were calculated to be<10^-3for all exposure routes independent of the urinestorage time and temperature evaluated. The risk for viralinfection was higher, calculated at 0.56 for accidentalingestion of 1 ml of unstored urine. If the urine was stored at20°C for 6 months the risk for viral infection was reducedto 5.4 × 10^-4.</p><p>By following recommendations for storage and reuse, whichare dependent on the type of crop to be fertilised, it ispossible to significantly decrease the risk for infections. Sofar, the level of risk that is acceptable is unknown. Theacceptable risk will be one of the main factors determining thefuture utilisation of source-separated human urine inagriculture.</p><p><b>Keywords:</b>urine-separation, urine, wastewater systems,wastewater reuse, recycling, enteric pathogens, faecal sterols,indicator bacteria, hygiene risks, microbial persistence,microbial risk assessment, QMRA, fertiliser, crop.</p>

L’alimentation et l’excrétion constituent deux besoins physiologiques fondamentaux de tout être humain. En analysant leur matérialisation depuis l’échelle cellulaire jusqu’à celle des grands cycles biogéochimiques planétaires, nous proposons de considérer que l’alimentation et l’excrétion humaines participent d’un système dont les modalités de réalisations dans les différentes sociétés humaines permettent de caractériser des régimes socio-écologiques. Nous avons plus particulièrement analysé les systèmes alimentation/excrétion des territoires urbains au regard de leur soutenabilité et proposons une méthodologie de caractérisation fondée principalement sur l’analyse du flux de la substance qui nous paraît la plus pertinente, à savoir l’azote, et sur les modalités de gestion des urines humaines qui représentent près des trois quarts de ce flux. Nous montrons que les systèmes alimentation/excrétion des différentes communautés humaines présentent une très grande variété selon les lieux et époques considérés et proposons de les distinguer entre autres en fonction de leur circularité, c’est-à-dire par le taux de retour sur des sols agricoles des excrétats. En prenant l’agglomération parisienne comme cas d’étude, nous montrons que son système alimentation/excrétion a été de plus en plus circulaire au cours du XIXe siècle, culminant au tout début du XXe siècle aux alentours de 50 % de circularité, avant de se linéariser progressivement au cours du XXe siècle. En ce début de XXIe siècle, nous caractérisons le système alimentation/excrétion de l’agglomération parisienne comme non soutenable car linéaire à plus de 95 %, intensif, inefficace et polluant aux échelles locales et globales. Ces caractéristiques sont généralisées au sein du monde occidental et interpellent sur la possibilité d’une transition socio-écologique vers des systèmes alimentation/excrétion soutenables. Or, depuis les années quatre-vingt-dix, une prise de conscience relative à l’urine a réémergé, principalement en Suède puis dans l’Europe germanique. Elle s’est traduite par de nombreuses réalisations et recherches autour de la séparation à la source des urines. Nous montrons que ce dispositif est actuellement le seul, dans le monde occidental, à avoir permis de nouveau la mise en œuvre de systèmes alimentation/excrétion circulaires. Pouvant être déclinée sous de multiples formes en fonction des contextes, la séparation à la source des urines bénéficie, malgré le verrouillage socio-technique de l’agglomération parisienne autour du tout-à-l’égout, d’un contexte favorable à son développement. Nous avons élaboré un scénario prospectif explorant ainsi la possibilité que l’agglomération parisienne dépasse, en quelques décennies, l’extremum de circularité qu’elle avait connu à la Belle Époque et que les acteurs de ce territoire réalisent, en cohérence avec une transition socio-écologique des autres systèmes énergétiques, hydrauliques et de transport, un régime socio-écologique soutenable de leur système alimentation/excrétion. Cette thèse fait partie du programme de recherche et action OCAPI (www.leesu.fr/OCAPI) / Nutrition and excretion are fundamental physiological needs for all human beings. Analysis of their materiality, from the cellular scale up to the great planetary-scale biogeochemical cycles, shows that nutrition and excretion form a system. The focus of our study is the sustainability of the nutrition/excretion systems of urban areas, which we have sought to assess by analysing substance flows. The most relevant of these substances seems to be nitrogen, so by assessing urban nitrogen flows we can characterise the different possible socioecological regimes and their sustainability. We identify a wide diversity of nutrition/excretion systems depending on the places and eras considered. We propose to distinguish them in terms of their circularity, in other words by the rate at which nitrogen from excreta returns to agricultural land. Using the Paris urban area as our case study, we show that its nutrition/excretion system became increasingly circular in the 19th century, reaching maximum circularity right at the start of the 20th century, before becoming steadily more linear in the course of the 20th century. In these early years of the 21st century, the nutrition/excretion system of the Paris urban area is essentially linear, and still generates significant pollution at both local and global scales. Its environmental footprint is exacerbated by a diet that is very protein rich, mostly animal in origin, and by the non-consumption of a significant proportion of the food produced. All these factors make it unsustainable. These characteristics are found throughout the Western world and raise questions about the possibility of a socioecological transition to sustainable systems of nutrition and excretion. Since the 1990s, initially in Sweden, followed by Nordic and German-speaking Europe, awareness has been growing of the role of urine. Urine is responsible for three-quarters of urban nitrogenous excretions and is a safe substance: following a period of storage, it can be used as agricultural fertiliser. This new awareness has been followed by extensive experimentation and research on urine source separation. We show that this is currently the only method in the Western world to have accomplished a return to circular systems of nutrition/excretion. Urine source separation can be done in multiple ways, depending on circumstances, and conditions in France are favourable to its development, despite the sociotechnical lock-in to mixed sewage management systems. In a forward-looking scenario, we therefore explore the possibility that the Paris urban area could return to, and within a few decades even surpass, the heights of circularity that it attained during the Belle Époque. In that case, alongside a socioecological transition in the other systems – water, energy, transport – the people of this territory could establish a sustainable regime for their system of nutrition/excretion. This thesis is part of the OCAPI research and action programme (www.leesu.fr/OCAPI)

A l’heure actuelle aucun consensus n’existe sur l’utilisation des substrats énergétiques lors d’un exercice en altitude. Certaines études ont montré une utilisation accrue des glucides en altitude comparée à la plaine mais les intensités d’exercices utilisées sont discutables et l’utilisation de méthodes biochimiques traditionnelles ont permis de doser qu’un nombre restreint de molécules. Aujourd’hui grâce à la métabolomique, il est possible d’analyser les variations d’un grand nombre de métabolites simultanément. Le but de cette thèse est d’étudier l’incidence de l’altitude modérée sur l’utilisation des substrats énergétiques à l’effort à l’aide de la métabolomique par résonnance magnétique nucléaire du proton. Des échantillons de plasmas et d’urines ont été collectés lors d’exercices d’endurance en plaine et en altitude modérée chez des sujets non acclimatés. Nos premiers résultats, dans les plasmas, ont montré une baisse de la glycémie et une utilisation accrue des acides aminés ramifiés entre avant et après un exercice d’endurance en altitude, ce qui n’a pas été observé en plaine. Ces résultats ont ensuite été confirmé lors d’un exercice d’endurance jusqu’à épuisement. De plus, nous avons montré que l’utilisation des urines permet de mettre en avant les résultats obtenus dans les plasmas, ce qui est très encourageant pour la compréhension des adaptations métaboliques en altitude par des méthodes non invasives. Pour finir, nous avons utilisé une méthode statistique innovante appelée « analyse en composantes communes et poids spécifiques ». Les résultats ont permis d’observer les variabilités communes entre les paramètres physiologiques mesurés et les variations des métabolites plasmatiques. / Although it is known that altitude impairs performance in endurance sports, there is no consensus on the involvement of energy substrates in this process. Some studies have shown an increased use of carbohydrates at altitude compared at plain but the intensities of exercises used are debatable and the use of traditional biochemical methods allowed to dose only a limited number of molecules. Today, thanks to metabolomics, it is possible to analyze the variations of a large number of metabolites simultaneously. The aim of this thesis is to investigate the incidence of moderate altitude on the use of energy substrates on stress using proton nuclear magnetic resonance metabolomics. Plasma and urine samples were collected during endurance exercises at plain and at moderate altitude in non-acclimatized subjects. Our first results in plasma showed decreased blood glucose and increased use of branched amino acids between before and after endurance exercise at altitude, which was not observed at plain. These results were then confirmed during an endurance exercise until exhaustion. Moreover, we have shown that the use of urine allows to highlight the results obtained in the plasmas, which is very encouraging for the understanding of the metabolic adaptations at altitude by noninvasive methods. Finally, we used an innovative statistical method called “ common components and specific weights analysis”. The results allowed us to observe the common variability between the measured physiological parameters and the variations of the plasma metabolites.

Sur la seule base de critères cliniques et anatomopathologiques, l’évolution des tumeurs superficielles de la vessie (TSV) est imprévisible. Aucun marqueur ne permet, à ce jour, l’identification des tumeurs à fort potentiel de récidive et d’évolution vers des formes agressives. Dans une première partie, nous avons étudié, chez 127 patients, le polymorphisme des microsatellites dans les cellules urinaires pour la mise en évidence de pertes d'hétérozygotie (LOH, Loss Of Heterozygosity) et 2- en tant que marqueur de suivi. Les résultats ont été comparés à la cytologie urinaire : la sensibilité des LOH est nettement supérieure à celle de la cytologie dans les TSV. La présence de LOH au niveau de TP53 et des marqueurs du chromosome 9p est associée à un risque accru de récidive. Parmi les patients ayant récidivé, l’étude des LOH était positive dans 78% des prélèvements urinaires. Dans 20% des cas, les LOH se sont positivées avant la récidive visible à la cystoscopie. Dans une deuxième partie, nous avons développé une technique urinaire quantitative rapide pour l’étude des profils de méthylation de promoteur de 5 gènes suppresseurs de tumeur. Les résultats prometteurs (sensibilité=62%) de la qPCR-HRM sont corrélés à la technique de référence et pourraient être améliorés en élargissant le panel de gènes étudiés. L’analyse des altérations génétiques et épigénétiques améliore la compréhension des mécanismes de la carcinogenèse dans les carcinomes urothéliaux. Ces altérations pourraient être utilisées comme marqueurs diagnostiques et pronostiques. La biologie moléculaire pourrait trouver toute sa place dans la prise en charge de cette pathologie. / On the basis of clinical and pathological criteria, the evolution of superficial bladder tumours (SBT) is unpredictable. Currently, no marker exists permitting the identification of tumours with high potential for recurrence and progression to more aggressive forms. Firstly, we looked for loss of heterozygosity (LOH) at microsatellite polymorphisms in the bladder cells of 127 patients, with the aim of identifying a marker potentially useful in 1) diagnosis and prognosis and 2) the monitoring of patients following trans-urethral resection. Compared to urine cytology, the sensitivity of LOH detection was significantly higher for SBT. The presence of LOH at TP53 and markers of chromosome 9p was associated with an increased risk of recurrence. Among the patients who relapsed, results of LOH analysis were positive in 78% of urine samples, 20% of which were positive before the relapse was detected by cystoscopy. Secondly, we developed a technique for the rapid and quantitative urinary analysis of patterns of promoter methylation of 5 tumour suppressor genes. The promising results (sensitivity of 62%) of the qPCR-HRM correlate well with the gold standard and could be improved by expanding the panel of genes studied. Analysis of genetic and epigenetic alterations improves the understanding of mechanisms of carcinogenesis in urothelial carcinomas. These alterations could be used as diagnostic and prognostic markers. Molecular biology could therefore prove useful in the management of this pathology.

Ziel der Arbeit war eine Steigerung der Wasseraufnahme und Harndilution durch Supplementierung von Natriumchlorid (NaCl) oder pH-Wert-Senkung durch Zugabe von Ammoniumchlorid (NH4Cl) zur Reduktion des Harnsteinbildungspotenzials. Durch die NaCl-Zulage wurde die Harnmenge signifikant gesteigert und das spezifische Gewicht des Harns gesenkt. Eine NaCl-Gabe stellt somit einen möglichen ergänzenden therapeutischen Ansatz für eine vermehrte Ausscheidung von Kristallen dar. Eine Ansäuerung des Harns durch Zulage von NH4Cl ließ sich nicht erreichen.