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Baronnet, Véronique. "Environnement économique industriel et règlementaire du médicament". Paris 5, 1993. http://www.theses.fr/1993PA05P035.
Pełny tekst źródłaLaurencé, Céline. "Analyse prédictive du devenir des médicaments dans l'environnement". Thesis, Paris Est, 2011. http://www.theses.fr/2011PEST1094.
Pełny tekst źródłaPharmaceuticals as well as personal care products are classified as emerging pollutants of increasing concern due to possible negative impacts on ecosystems. They are constantly introduced in sewage treatment plants either through excretion, or disposal by flushing of unused or expired medication, or directly within the sewage effluents of plants or hospitals. They end up in surface and ground waters and can even be found in drinking water. Many studies report on adverse effects on terrestrial and aquatic organisms. Pharmaceuticals have complex chemical structures capable of reacting in an aqueous medium under the action of chemical, biological or physical agents. Thus, the transformation products (TPs) gradually replace the parent drug in the environment. In addition these transformation products constitute markers of past or current presence of the drug in the environment. Faced with this problem, we believe it is necessary to synthesize the transformation products of the parent compounds to development their detection. The proposed method consists, firstly, to prepare the largest number of (TPs) of a particular drug using three complementary approaches : bioconversion, electro-Fenton and electrochemical oxidation. A second step is to identify the structures which are the most likely present in the environment. Expected advances are the development of a predictive methodology applicable to the study of any molecule involved in environmental risk
Marchand-Pilard, Marie. "Propositions d’évolutions de l’encadrement juridique des rejets de médicaments humains dans l’eau". Electronic Thesis or Diss., Paris 8, 2022. http://www.theses.fr/2022PA080009.
Pełny tekst źródłaHuman drugs are chemicals designed to last long enough to have the desired effects on the body while resisting unwanted alterations to avoid adverse effects. These properties, closely studied by European and national authorities, make it possible to guarantee safe, effective, and quality pharmaceuticals but, conversely, pose a challenge for their end of life. These molecules “go through” the human body by undergoing degrees of alteration that can range from complete elimination to an unchanged status, ending up in whole or in part in wastewater (via our excretions). Added to this are unused pharmaceuticals that are improperly disposed of, effluents from industrial drug production sites and healthcare establishments, and WWTP sewage sludge, which can also contains drugs. However, whether under the regulations specific to medicines or those intended for the management of water, waste or sewage sludge, neither France nor the EU have an appropriate regulatory framework to manage these emerging pollutants, which is reflected in the treatments implemented in the WWTPs. As a result, drug residues are found in all European [and global] waters, some of which have harmful effects on aquatic environments. This thesis thus seeks to give recommendations aimed at combating this pollution in the EU and in France without reducing essential access to medicines
Legendre, Claire. "Adaptation cellulaire et moléculaire des cellules d'hépatome humain HepaRG à un environnement hypoxique". Rennes 1, 2009. http://www.theses.fr/2009REN1S055.
Pełny tekst źródłaReduced oxygen level, or hypoxia, is frequently encountered in solid tumours and contributes to drug resistance. Hypoxia is also associated with invasive phenotype and correlated to poor prognosis and mortality. The role of hypoxia in hepatocellular carcinoma biology is not fully understood. Therefore, there is a need for developing in vitro models mimicking hypoxic conditions find within solid tumours using hepatic tumour cells. Highly differentiated human hepatoma HepaRG cells respond to hypoxia by a switch from aerobic to anaerobic glycolysis. Moreover, we showed that hypoxia also repressed drug-metabolizing enzymes expression. These repressions could therefore strongly compromise chemotherapy effectiveness on tumour cells within hypoxic environment. Furthermore, HepaRG cells cultured under hypoxic versus normoxic conditions might represent a new strategy to test different types of therapeutic molecules in order to predict their effectiveness
Arpin-Pont, Lauren. "Les produits pharmaceutiques et de soin personnel en milieu marin : prédiction des concentrations environnementales et étude des effets sur le métabolisme endogène d’organismes exposés". Electronic Thesis or Diss., Montpellier, 2015. http://www.theses.fr/2015MONTS172.
Pełny tekst źródłaThe last twenty years, the issue of PPCP contamination of the marine environment caused a growing concern among scientific community. PPCP enter the environment mainly through wastewater treatment plants (WTP), not able to remove completely these substances. The first objective of the thesis was to assess the current state of knowledge on the PPCP occurrence in the different compartments of the marine environment (seawater, sediments and organisms) through a literature review. The contamination of the marine environment is generally assessed by “one-time” measures in situ. However, such monitoring campaigns are time-consuming and costly. Some approaches based on the determination of the predicted environmental concentrations (PEC) could be applied alternatively or complementarily to in situ measures. The PEC calculation is the first step of environmental risk assessment (ERA), to assess the exposure of non target organisms to these substances. However, this estimation needs to be refined to be accurate, by integrating site-specific information. The second aim of the thesis was to propose refined PEC calculation methodologies of pharmaceuticals and their metabolites in a coastal zone using an adapted hydrodynamic model. Two model compounds were chosen, carbamazepine and venlafaxine. In order to assess the environmental risk of pharmaceuticals, it is needful to assess their effects on organisms. Nowadays, few ecotoxicological data are available on marine organisms, contrary to freshwater organisms. Regulatory concept of ERA is often based on a set of short term standard tests carried out at high concentrations. Other tests, implemented at lower organizational levels, are more sensitive to low exposure levels and are more relevant for the marine risk assessment. The last objective was to study the effects of diclofenac on PG production, based on its mode of action, on marine mussels exposed
Idder, Salima. "État de la contamination des eaux du département de la Dordogne par les résidus de médicaments". Electronic Thesis or Diss., Bordeaux 1, 2012. http://www.theses.fr/2012BOR14652.
Pełny tekst źródłaThe beginning of the 21th century saw a growing interest for pharmaceuticals in aquaticsystems. The development of new analytical technologies allowing detection and quantification ofcompounds at ultra-trace levels mostly contributed to this expansion. These technologicalimprovements allowed to evidence and quantify many xenobiotics in various aquaticcompartments. Since about fifteen years, research teams focused their attention to human orveterinary pharmaceuticals. These contaminants are among emerging pollutants and no regulationexists in Europe concerning their presence in the environment. The presence of few tenths ofpharmaceuticals has been demonstrated. Living organisms in aquatic bodies are thereforeexposed to mixtures of compounds certainly at low doses (often between few ng and fewhundreds of ng) but continuously and the effects of this exposure are few documented. Thecontamination of aquatic systems by pharmaceuticals is usually the sign of an importanturbanization and streams with strong domestic pressures are often chosen as sampling sites inscientific studies. Nevertheless, the data concerning rural areas are still scarce although theyrepresent four fifth of the French territory.This work aims to establish a current situation of water resources of a rural territory, theDordogne administrative department. The occurrence of 40 pharmaceuticals including lipidregulators, antibiotics, β-blockers, non-steroidal anti-inflammatories, anticancer drugs, etc inseveral streams has studied with a multi-residue analytical method involving an on-linepreconcentration, a chromatographic separation followed by tandem MS/MS detection. Themethod has been validated for surface waters according to COFRAC requirements.Many sites were sampled every month during one year (2011) on six major streams of theDordogne department. The various campaigns allowed identifying the main areas contaminatedby pharmaceuticals and some linear correlations with other parameters (ammonium ion,phosphorus, etc.) have been evidenced.Beside the results obtained over all the Dordogne department, a focus on the presence ofpharmaceuticals in Isle river, around Périgueux, the main urban area of Dordogne, was led. Thissurvey allowed characterizing the introduction ways of pharmaceuticals and better understandingthe impact of the city of Périgueux on the river Isle
Olvera, Vargas Hugo. "Study on the fate of pharmaceuticals in aqueous media : synthesis, characterization and detection of biotic and abiotic transformation products using electrochemical advanced oxidation processes and bioconversions". Electronic Thesis or Diss., Paris Est, 2014. http://www.theses.fr/2014PEST1179.
Pełny tekst źródłaThe present project contributes with valuable data for a better fundamental understanding on the fate of pharmaceutical residues in the environment, dealing with the main challenges concerning this increasingly worrying environmental issue. The used Electrochemical Advanced Oxidation Processes (EAOPs), electro-Fenton (EF) and anodic oxidation (AO), showed to be a very efficient alternative for the mineralization of acid solutions of the pharmaceuticals RNTD and FRSM, attaining almost complete mineralization of the drugs after 6h of electrolysis. A comparative study on the mineralization of RNTD solutions by EF and SPEF processes in a 2.5 L capacity pre-pilot flow plant demonstrates the higher oxidation capacity of SPEF, achieving very good mineralization rates, thus evidencing the potentiality of this technology at greater scale for the treatment of wastewaters containing pharmaceutical products. The application of an EF pre-treatment coupled with a biological process for the degradation of both drugs was conducted. EF pre-pretreatment was capable of enhancing the solution biodegradability envisaging a biological treatment, which efficiently removed the short-chain carboxylic acids that had been formerly generated during the pre-applied electrolysis. In this way, the combination of both processes was confirmed as a very promising technology for the treatment of pharmaceuticals-containing wastewater. Several transformation products (TPs) were detected and identified during the electrochemical oxidation of the studied drugs. Toxicity tests based on the bioluminescence of the marine bacteria V. fischeri. evidenced the toxicity some of these oxidation by-products, since the toxicity of the solution increased on the first stages of the electrolysis. However, the abatement of the toxicity in the final stages of the electrochemical treatments, demonstrated the effectiveness of these technologies for both the mineralization and detoxification of the RNTD and FRSM solutions. The use of the fungi Cunninghanella echinulate for the bioconversion of FRSM led to the formation of three main bio-transofrmation products: the previously identified saluamide and pyridinium, and the new detected keto-alcohol derivate. These TPs were generated by both, biological and electrochemical approches, evidencing their high probability to be found in environmental compartments as the most likely TPs of FRSM by different oxidation conditions. This study is thus presented as a very useful alternative for the assessment of the fate of pharmaceutical residues in the environment
Gbaguidi, Bénédicte. "Caractérisation structurale de LmrP, protéine membranaire associée à la résistance bactérienne aux antibiotiques, dans son environnement lipidique". Doctoral thesis, Universite Libre de Bruxelles, 2007. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210714.
Pełny tekst źródłaIdder, Salima. "État de la contamination des eaux du département de la Dordogne par les résidus de médicaments". Thesis, Bordeaux 1, 2012. http://www.theses.fr/2012BOR14652/document.
Pełny tekst źródłaThe beginning of the 21th century saw a growing interest for pharmaceuticals in aquaticsystems. The development of new analytical technologies allowing detection and quantification ofcompounds at ultra-trace levels mostly contributed to this expansion. These technologicalimprovements allowed to evidence and quantify many xenobiotics in various aquaticcompartments. Since about fifteen years, research teams focused their attention to human orveterinary pharmaceuticals. These contaminants are among emerging pollutants and no regulationexists in Europe concerning their presence in the environment. The presence of few tenths ofpharmaceuticals has been demonstrated. Living organisms in aquatic bodies are thereforeexposed to mixtures of compounds certainly at low doses (often between few ng and fewhundreds of ng) but continuously and the effects of this exposure are few documented. Thecontamination of aquatic systems by pharmaceuticals is usually the sign of an importanturbanization and streams with strong domestic pressures are often chosen as sampling sites inscientific studies. Nevertheless, the data concerning rural areas are still scarce although theyrepresent four fifth of the French territory.This work aims to establish a current situation of water resources of a rural territory, theDordogne administrative department. The occurrence of 40 pharmaceuticals including lipidregulators, antibiotics, β-blockers, non-steroidal anti-inflammatories, anticancer drugs, etc inseveral streams has studied with a multi-residue analytical method involving an on-linepreconcentration, a chromatographic separation followed by tandem MS/MS detection. Themethod has been validated for surface waters according to COFRAC requirements.Many sites were sampled every month during one year (2011) on six major streams of theDordogne department. The various campaigns allowed identifying the main areas contaminatedby pharmaceuticals and some linear correlations with other parameters (ammonium ion,phosphorus, etc.) have been evidenced.Beside the results obtained over all the Dordogne department, a focus on the presence ofpharmaceuticals in Isle river, around Périgueux, the main urban area of Dordogne, was led. Thissurvey allowed characterizing the introduction ways of pharmaceuticals and better understandingthe impact of the city of Périgueux on the river Isle
Fahy, Lucine. "Etude des conséquences d’un environnement hypoxique sur le développement et la chimiorésistance des leucémies aiguës lymphoblastiques T (LAL-T)". Thesis, Sorbonne Paris Cité, 2019. https://theses.md.univ-paris-diderot.fr/FAHY_Lucine_2_complete_20190627.pdf.
Pełny tekst źródłaBackground: T cell acute lymphoblastic leukemia (T-ALL) is a malignant hematological disorder characterized by an increased proliferation of T lymphocyte precursors that are unable to complete their maturation. Treatments are effective in 90% of children T-ALL cases. However, children with relapse have a very poor prognosis. Resistance to chemotherapy is thus a major therapeutic challenge in the treatment of T-ALL that can be driven by interactions between leukemic cells and the microenvironment. Bone marrow microenvironment, a crucial site of propagation and maintenance of leukemia, is hypoxic with oxygen levels varying from 0.1 to 5%. As hypoxic solid tumors are more resistant to radiotherapy and chemotherapy, the aims of the study were to investigate to which extent oxygen levels impact on leukemia development and chemoresistance and to characterize the implicated molecular mechanisms. Methods: Mouse models and patients derived samples of T-ALL were cultured in low (1% and 3.5%) and high (21%) oxygen levels. Growth, apoptosis, cell cycle, metabolism and chemoresistance were measured as well as in vivo leukemia propagation using immune deficient mice as ways to define the impact of oxygen levels on T-ALL.Results: Results show that hypoxia inhibits the growth of T-ALL by slowing down cell cycle progression and decreasing metabolism, making them less sensitive to anti-leukemic drugs and preserving their ability to initiate leukemia in vivo after treatment. Knocking down (KD) HIF1α counteracted the effects observed in hypoxic T-ALL and restored their chemosensitivity. Interestingly activation of mTOR was diminished in hypoxic leukemic cells and HIF-1α KD restored mTOR activation in these low O2 conditions. Moreover, inhibiting mTOR in HIF1aKD T-ALL enhanced their chemoresistance, indicating a functional relationship between these two pathways.Conclusion: This work shows that hypoxic niches can play a protective role during the treatment of T-ALL through a HIF1α/mTOR molecular loop. Inhibition of HIF1α and/or activation of the mTOR pathway may help suppress the chemoresistance of T-ALL in hypoxic niches
Bui, Van Hoi. "Contribution à l’étude de la présence et du devenir des résidus de médicaments dans les compartiments aquatiques". Electronic Thesis or Diss., Bordeaux 1, 2013. http://www.theses.fr/2013BOR14930.
Pełny tekst źródłaThe presence of pharmaceuticals was evaluated in Seine surface waters and in eight wastewater treatment plants (WWTP) effluents (4 WWTP within MEDSEINE - GIP Seine – Aval project and 4 WWTP within TOXSTEP – ANSES project. A hundred molecules was systematically reseached in both types of waters by applying the analytical methodologies (SPE solid phase extraction followed by LC-MS/MS analysis). A seasonal monitoring of pharmaceutical residues was also carried out. The pharmaceutically residues have been systematically quantified in this both types of water. The concentrations in suface of waters are significative for some molecules: 1 – 108 ng/L for diclofenac, 2 – 324 ng/L for ibuprofen and the values are weakly for some molecules: 2 – 13 for sulfapyridine, 1 – 5 for nordiazepam. Non steroidal anti-inflammatory drugs, β-blockers, macrolides and fluoroquinolones are mostly founded in the effluents of WWTP. Their concentrations were measured in the range: 62 ng/L – 10 µg/L for sotalol, 39 ng/L – 8 µg/L for atenolol, 32 ng/L – up to 127 µg/L for paracetamol.Moreover, the stability of pharmaceuticals was evaluated with light radiation . UV irradiation (at 254 nm) potentially used in the final WWTP before discharge in particularly areas have been applied (with a dose up to 1500 J/m2). Sunlight simulations have also been done. The phenomenon of photodegradation at 254 nm has been observed for some molecules such as : diclofenac, ketoprofen (>90% degraded), ciprofloxacine, norfloxacine (up to 75% degraded). Azithromycinem clarithromycine, carbamazepine and atenolol are most stable molecules observed. Exposing under simulated sunlight, diclofenac, ketoprofen, ciprofloxacine and norfloxacine are also sensitive molecules (>90 % degraded) after 24 hours of exposure (172.8 kJ/m2). Carbamazepine, sulfamethoxazole, atenolol, metoprolol and bisoprolol are most stable molecules observed
Palakas, Somchit. "Etudes fonctionnelles dans son environnement membranaire natif d'un transporteur multispécifique, la "Multidrug Resistance-associated Protein 1" (MRP1, ABCC1) : application à la recherche de radiopharmaceutiques potentiels". Tours, 2004. http://www.theses.fr/2004TOUR3309.
Pełny tekst źródłaMRP1 (ABCC1) is a multispecific membrane transporter who plays an important role in cellular detoxification and absorption/distribution/elimination processes of drugs, and confers to certain cancer cells, the multidrug resistance phenotype (MDR) to anticancer agents. In search of radiopharmaceuticals for in vivo imaging of MDR phenotype by scintigraphic exploration, perturbation of MRP1 ATPase and transport functions have been investigated using microsomes issued from human small cell lung cancer cells (GLC4/Adr). Transport of [3H]LTC4, [ 3H]E217βG and [3H]GSH by MRP1 as well as its ATPase activity stimulated by its transported substrates have been characterized. Both functional probes are inhibited in the presence of QCRL-3, a specific monoclonal antibody of MRP1. Furthermore, we have demonstrated that apigenine and its five newly synthesized halogenated derivatives interact with MRP1 only in the presence of GSH
Bustany, Sophie. "Caractérisation des mécanismes de résistance aux traitements anticancéreux des hémopathies lymphoïdes B exprimant la cycline D1 : impact du microenvironnement tumoral". Caen, 2014. http://www.theses.fr/2014CAEN4064.
Pełny tekst źródłaCyclin D1 overexpression is an important oncogenic event in the initiation and the development of mantle cell lymphoma (MCL) and multiple myeloma (MM). Cyclin D1 regulates numerous cellular functions (cell cycle, DNA damage response, mitochondrial metabolism, interactions between cancerous cells and microenvironment) but its consequences on the regulation of cell chemosensitivity are not well understood. We report that cyclin D1 enhances the tumorigenecity of MCL cells without modifying cell proliferation. Lenalidomide blocks this process by increasing cyclin D1 degradation and inducing caspase-dependent apoptosis. On the contrary, cyclin D1 expression in MM cells is associated with disruption of redox homeostasis, increase of reticulum endoplasmic-stress and activation of caspase-dependent apoptosis, which enhance cell chemosensitivity after a treatment with proteasome inhibitors or corticoids. Besides, cyclin D1 expression perturbs cell adhesion, chemotaxis and, consequently, cell adhesion-mediated drug resistance. Immunomodulators counteract these perturbations and enhance the efficacy of the others antimyeloma drugs. All these results identify new pathways which could be targeted to ameliorate the efficacy of patient’s treatments
Vieux, Rachel. "Déterminants de la fonction rénale d'enfants nés grands prématurés dans leur environnement néonatal et dans l'enfance". Thesis, Nancy 1, 2011. http://www.theses.fr/2011NAN10095/document.
Pełny tekst źródłaBackground: Physiological development of renal may be altered in preterm infants by environmental factors. Their imprinting could persist beyond the neonatal period. Objectives: 1) to determine reference values of glomerular filtration rate (GFR) during the first month of life in preterm newborns, 2) to determine the impact of perinatal factors and of the drugs often prescribed on their renal function, 3) to determine the effect of the perinatal imprinting, and of the growth and height catch-up, on their renal function in early childhood. Sample: Multicentre cohort of children born very preterm at 27-31 weeks of gestation, with a measure of their renal function during the neonatal period, and at 4 years of age. Results: 1) 275 infants included. Median reference GFR value (mL/min/1.73m²) was: 7.9 on day7 to 37.9 on day 28. 2) GFR was significantly reduced on day 7 in ibuprofen-infused infants in comparison to Controls: 12.8±6.2 vs. 18.1±12.1 ml/min/1.73 m², p < 0.001. This decrease persisted throughout the first month of life, and tubular function was also altered. Among all antenatal drugs and drugs administered during the first week of life, alone ibuprofen was significantly associated with a GFR < median reference value on day 7. 3) Height >= -1 SD in early childhood was associated with a high albuminuria in 119 four year-old preterm-born children. Conclusion: i) These GFR reference values are to be used in clinical research, ii) Neonatal therapeutic environment impairs renal function and delays its maturation, iii) The height at age four is an independent risk factor of high albuminuria in preterm-born children
Berger, Tristan. "L'accès aux informations environnementales et sanitaires : le cas des substances chimiques, des OGM et des médicaments". Thesis, Paris 1, 2020. http://www.theses.fr/2020PA01D006.
Pełny tekst źródłaThalidomide, asbestos, tobacco, PCB, benzene, valproate, dexfenfluramine, ECB, PIP implants, chlordecone, BPA, glyphosate, etc., there is now a long list of environmental and health risks that both affected risk management and undermined the public’s trust towards institutions. In this context, the issue of transparency related to environmental and health risks has continued to grow, not only for the purpose of directly informing citizens, but also for the purpose of building a counterexpertise, with a growing number of organizations or researchers seeking to review and check official expertise, and to challenge the action or the inertia of public authorities or companies. As a result, expert agencies increasingly receive requests to access environmental and health information, including to detailed datasets and techniques to test their reliability. Despite the progress that has characterized public rights to access information over the past forty years and the display of an open data policy, this thesis is based on the observation that access to information regimes are not effective. Going beyond the causes traditionally analyzed by doctrine (length of the delays, culture of secrecy, complexity), the thesis seeks to identify systemic limits to public access to environmental and health information. In particular, it highlights three sets of structural factors. First, the system for assessing product safety, entrusted to companies, inherently carries a risk of conflicts of interest and therefore undermines the reliability of the data to which the public is entitled. Second, the claim of intellectual property rights on data produced by companies, subjects them to a privatization process. Third, the lack of enforcement power of expert agencies, caught in a stranglehold between the exclusive rights of companies and the rights of public access. Three case studies – chemicals, GMOs and medicines – are used to highlight these structural limitations to access rights and, simultaneously, to deepen ecological and health democracy
Rodriguez, Christophe. "Dynamique adaptative des virus hautement variables à un nouvel environnement réplicatif". Phd thesis, Université Paris-Est, 2012. http://tel.archives-ouvertes.fr/tel-00916824.
Pełny tekst źródłaPouzol, Tanguy. "Monitoring and modelling of pharmaceuticals in wastewater : Daily and hourly loads in both hospital and urban wastewater". Thesis, Lyon, 2018. http://www.theses.fr/2018LYSEI009/document.
Pełny tekst źródłaDaily and hourly loads of 15 pharmaceutical molecules at the inlet of a wastewater treatment plant have been measured over 3 years and modelled for both an urban catchment of 16 000 inhabitants and a hospital of 450 beds. Some molecules are never or rarely quantified. Daily loads range from 0.6 to 564 g/day depending of the molecule and the 24 h measurement campaign. Seasonal or weekly patterns are not identified. Pharmaceuticals hourly loads dynamics are distinctive from one another and from wastewater flow. The measured hourly loads are severely impacted by the random behaviour of the patients when the daily mass consumed is low. Thus, the average dynamics is difficult to identify. The main hypothesis to model pharmaceuticals loads in wastewater is that they result from the following steps: pharmaceuticals sales or distributions, human consumption, metabolism and excretion. Pharmaceuticals sales for the urban catchment and distribution for the hospital have been collected at different space and timescales (respectively 1, 6 and 223 pharmacies and daily, weekly and monthly). Larger scales are more reliable for magnitude but the variability of the smaller ones is closer to the variability observed in the measurements. The quantities of pharmaceuticals sold or distributed range from 0.4 to 1 600 theoretical patients per day. Associating measured daily loads with sales or distributions, no linear correlation is found. A minute time step stochastic model is proposed and applied to both sites. It produces reliable and accurate results for both daily and hourly loads. However, results are difficult to interpret when only a few patients are consuming a pharmaceutical. Also, the model does not reproduce the inherent specificity of the hospital. In addition, the model is also able to predict the domestic wastewater flow of an urban catchment with great accuracy for both daily volumes and dynamics
Calvo, Julien. "Etude de l'impact des adipocytes de la moelle osseuse sur le développement et la chimiorésistance des leucémies aigues lymphoblastiques T (LAL-T)". Thesis, Université de Paris (2019-....), 2019. http://www.theses.fr/2019UNIP7114.
Pełny tekst źródłaT-cell acute lymphoblastic leukemia (T-ALLs) is a T cell progenitor proliferation malignancy that mostly occurs in children and young adults. Over the years, intrinsic and extrinsic factors have been demonstrated to play a role in initiation and onset of the leukemic proliferation. Among other organs, T-ALL expands in most cases in various Bone Marrow (BM) sites. These niches have a complex cellular composition with hematopoietic, stromal, endothelial, nervous cells and also adipocytes that form the Medullar Adipose Tissue (MAT). Two types of MAT exist in the BM niches. The constitutive MAT takes place in long bones extremities whereas the regulated MAT arises and grows as a results of external stimuli like aging and BM ablation. Mice harbor both constitutive MAT enriched and deprived BM niches respectively in tail and thoracic vertebrae. Hence, using in vivo models we observed that mouse and human T-ALL develop slowly in tail compared to thoracic vertebrae. Tail-derived T-ALL cells display lowered cell surface marker expression, decreased metabolism and cell cycle progression demonstrating a dormancy phenotype. Functionally tail-derived T-ALL cells exhibit a deficient short-term ex vivo growth and a delayed in vivo propagation. These features are non-cell autonomous as T-ALL from tail and thorax share identical genomic abnormalities, and also functional disparities disappear in vivo and in prolonged in vitro assays. Importantly, tail-derived T-ALL display higher intrinsic resistance to cell cycle-related drugs, i.e. Vincristine sulfate and Cytarabine. Moreover, T-ALL recovered from gonadal adipose tissues or from co-cultures with adipocytes share metabolic, cell cycle and phenotypic or chemoresistance features with tail-derived T-ALL. These results demonstrate that BM niches differentially orchestrate T-ALL propagation and that adipocyte enriched BM protects T-ALL during drug treatments. To support these findings, single cell RNA sequencing analysis suggests that a few thoracic derived T-ALL cells exhibit a similar mRNA expression pattern to those from the tail. Altogether, these results emphasize the hypothesis of chemoresistance inducing niche among the thoracic hematopoietic-enriched adipocytes-deprived BM
Dupont, Chloé. "Achromobacter & Pandoraea : diversité et évolution adaptative de populations persistantes au cours de la mucoviscidose et dans l'environnement". Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT105/document.
Pełny tekst źródłaBacterial persistence involves adaptation to environmental conditions and constraints, sometimes associated with genotype and phenotype diversification of bacterial populations. In the context of chronic infections, Cystic Fibrosis (CF) is a human disease among the most studied in terms of persistence and adaptation of opportunistic pathogens. Some environmental opportunistic pathogens like Achromobacter and Pandoraea genera are considered as emerging in CF and are able to chronically colonize CF Respiratory Tract (CFRT). Adaptation mechanisms required for colonization and persistence were studied for P. aeruginosa but remain largely unknown for emerging bacteria. We studied Achromobacter spp. persistence in the CFRT of 13 patients and in a dental care unit water network, and Pandoraea pulmonicola persistence in the CFRT of one patient, during colonization periods up to 7 years. In parallel, we studied Achromobacter population genomic and phenotypic diversity in sputum samples from 9 patients. Finally, we made an environmental investigation to study the diversity and the ecology of Achromobacter spp. in household of 3 Achromobacter chronically colonized CF patients. During these studies, Achromobacter and Pandoraea species were identified by molecular methods and genome dynamic and phenotypic diversity were studied.Diversity of Achromobacter species colonizing the CFRT is described and included an undescribed species. Chronically colonized patients had a unique Achromobacter or Pandoraea clone in their CFRT, supporting the initial acquisition of one environmental clone which persists over time. A large genomic and phenotypic diversity has been observed over time and also at the intra-specimen level. A wide antibiotic susceptibility profile diversity was observed within samples and its clinical impact remains to be assessed. Finally, Achromobacter species diversity was observed in patient domestic environment but the Achromobacter clone adapted to the patient CFRT was not isolated. These results suggested that after initial colonization and specialisation the CFRT, colonizing clones might secondarily be unable to survive in the environment.A colonizing clone quickly adapts to the specific local conditions of the CFRT and undergoes intense genomic and phenotypic diversification with genotype specialization to the different ecological niches of the heterogeneous CFRT, resulting in a diversified clonal population. This diversity certainly insures the population persistence according to the “bet hedging” theory stating that regardless of the environmental pressures, a bacteria or a subgroup of bacteria will be able to persist.Key words : Achromobacter, adaptation, antibiotic susceptibility, chronic colonization, Cystic Fibrosis, diversity, ecology, environment, epidemiology, evolution, genomic, Pandoraea, persistence, phenotype, water network
Vancauwenberghe, Eric. "Rôle du canal TRPA1 dans le microenvironnement tumoral des cancers prostatiques humains". Thesis, Lille 1, 2016. http://www.theses.fr/2016LIL10210.
Pełny tekst źródłaProstate cancer (PCa) is the second most common cancer in men. The tumor microenvironment (TME) plays an important role in prostate carcinogenesis and metastasis independently of androgens. There is a close communication between tumor epithelial cells and stroma through the secretion of soluble factors promoting survival and metastasis of cancer cells. Modulating the secretion of these factors could therefore be a potential therapeutic option in the treatment of prostate cancers. Ion channels and the intracellular calcium are known to modulate secretion. In this context, we have shown that the TRPA1 channel is expressed in fibroblasts associated to cancers (CAF) in human prostate. Here, we describe that the activation of TRPA1 channel by epithelial factors leads to an increase in intracellular calcium levels promoting expression and secretion of growth factors. Our data show that these latter induce the epithelial-mesenchymal transition, migration and resistance to chemotherapeutic agents in cancer cells. Finally, we identified polymorphisms and mutations in TRPA1 channel allowing its activation by environmental factors and secretion of growth factors inducing resistance to apoptosis of prostate cancer cells. All these data suggest that TRPA1 channel constitutes a potential target for future therapies of PCa to interrupt the epithelial-stromal interactions of TME and prevent the development of these cancers
Deynoux, Margaux. "Incidence de l'hypoxie sur le métabolisme oxydatif des leucémies aiguës myéloïdes : établissement et caractérisation d'un modèle in vitro de niche leucémique". Thesis, Tours, 2019. http://www.theses.fr/2019TOUR3303.
Pełny tekst źródłaIn acute myeloid leukemia, a high level of ROS is known to favor blasts proliferation, whereas a low level promotes stem cells quiescence. The low oxygenation, or hypoxia, of the bone marrow niche could contribute to chemoresistance of AML cells by reducing the oxidative stress. Hypoxia-inducible factors (HIF) are involved in the control of the cell metabolism and antioxidant enzymes. HIFs inhibition leads to AML cells stress and death. The purpose of this work was to study a link between hypoxia, oxidative metabolism and chemoresistance in an in vitro model of leukemic cell culture. The acquisition of a hypoxic profile by hematopoietic stem cells (HSC) cultured with medullary mesenchymal stromal cells (MSC), has been shown. We hypothesized that AML cells may also acquire such profile in a coculture with human MSCs. To demonstrate that, we cultivated primary AML cells or the MV4-11 cell line on primary human MSCs or the HS-27a cell line. Like HSCs, we identified three leukemic populations according to their adhesion capacity to MSCs: in suspension, adherent to MSCs and embedded in MSCs. Embedded cells, the most adherent, have stronger CXCR4 expression compared to the others. They are also 2- to 7-fold more resistance to cytarabine. However, no change in the stem cell phenotype profile and in the clonogenic, repopulation or xenograft capacities, could be associated with the embedded cells compared to other populations. In contrast, embedded cells present a hypoxic profile, a weak proliferation with increased G0 phase, and lower ROS level that may rely on lower mitochondrial mass. This suggests that chemoresistance mainly relies on hypoxia or cell metabolism rather than a higher stem cell capacity. Furthermore, we have shown that acriflavine, a non-specific HIF inhibitor, could synergize with the cytarabine to eliminate embedded chemoresistant cells. Our results show that the MSC supernatant or a simple contact are not sufficient to induce metabolic change and resistance to cytarabine. We assume that hypoxia in the niche may modulate the oxidative metabolism and the chemoresistance by direct mechanisms and/or indirect ones through CXCR4 expression, a chemokine receptor shown to be involved in the regulation of the oxidative stress in HSC
Mullot, Jean-Ulrich. "Modélisation des flux de médicaments dans les effluents hospitaliers". Paris 11, 2009. http://www.theses.fr/2009PA114825.
Pełny tekst źródłaThe management of water contamination by pharmaceutical residues requires knowledge of the loads entering the sewage network: this study try to describe and model the contribution of the hospital sewage. A prioritization method was first applied to select a limited number of target molecules, then analyzed in the wastewater of 3 hospitals and in the influent and effluents of WWTPs. All target molecules investigated, except one, were detected at least once in hospital wastewater at concentrations ranging from a few ng. L-1 to a few mg. L-1. These measures have helped to provide models, using easily available data in hospitals, to obtain a probabilistic prediction of drug residues loads emerging from hospitals. Finally, for each molecule, the part of hospital source in the total load of urban pollution has been assessed to provide a contrasted picture of this contribution
Miollis, Frédérick de. "Développement d’un système de culture in vitro 3D et microfluidique pour étudier les interactions tumeur-stroma et la résistance aux drogues de l’adénocarcinome du pancréas". Thesis, Lille, 2021. http://www.theses.fr/2021LILUI015.
Pełny tekst źródłaPancreatic cancer is one of the deadliest cancers with an extremely poor prognosis. In 2020, the 5-year survival rate remains very low (only 3 to 9%) and the median is less than 6 months. Despite significant progress in the patient care, current therapies do not have the expected effectiveness. This is due to the strong chemoresistance observed in this cancer. The key factor of this resistance is the complex tumor microenvironment mainly composed of stroma and a dense extracellular matrix limiting the access of therapies to the tumor. The current models’ limitations, particularly in terms of physiological relevance, are a major obstacle in understanding this chemoresistance. In response to this issue, researchers are turning to different approaches by developing brand new models that are alternatives to those already available (in vitro and in vivo).The objectives of this work were: (i) to develop an in vitro 3D microfluidic culture device allowing to reproduce the tumor microenvironment both biologically and mechanically, as well as to model the flows and mass transport present in a pancreatic tumor, and (ii) to approach the morphological changes of the co-culture by studying epithelio-mesenchymal markers and to study the impact of FOLFIRINOX chemotherapy in this model.First, we have shown numerically and experimentally the feasibility of such an in vitro model. The chosen extracellular matrix is a combination of collagen I and hyaluronic acid creating a rigid structure close to in vivo conditions. It allows long-term culture maintenance under the effect of the perfusion as well as the activation of pancreatic stellate cells. The chosen perfusion rate allows to apply an interstitial flow in the model equivalent to the one observed in the in vivo microenvironment, inducing hydrostatic pressure and shear stress on the cancerous cells.Then, we demonstrated the biological contribution of this model by showing an increased chemoresistance to the FOLFIRINOX protocol of tumor cells both in mono- and in co-culture in the microfluidic device. We also show the establishment of a process presenting characteristics of epithelial-mesenchymal transition and a possible promotion of a dedifferentiated phenotype of tumor cells by activated pancreatic stellate cells.In conclusion, we present in this thesis an original microfluidic model allowing to mimic a tumor (co-culture of epithelial and mesenchymal cells) and to study the kinetics of a complex multidrug chemotherapy. In the future, the device should allow us to further study the mechanisms of drug resistance and tumor-stroma interactions in pancreatic cancer
Besse, Jean-Philippe. "Impact environnemental des médicaments à usage humain sur le milieu récepteur : évaluation de l'exposition et des effets pour les écosystèmes d'eau douce". Thesis, Metz, 2010. http://www.theses.fr/2010METZ023S/document.
Pełny tekst źródłaA high number of pharmaceuticals are used in France and can reach the aquatic environment. This observation have contributed to a growing concern for authorities in targeting and quantifying these substances in freshwaters. Considering the high number of molecules used in France, it is necessary, prior to implement any comprehensive monitoring survey in freshwaters, to build a list of priority pharmaceuticals in terms of their risk for the aquatic environment. The work conducted here aims at proposing reliable lists of priority pharmaceuticals, based on expected environmental concentrations and biological effects on aquatic non-target organisms. Several methodologies were implemented, depending on the type of pharmaceuticals assessed and the availability of data. Finally, 300 parent molecules and 50 human metabolites were screened and scientifically sound priority lists were built. Moreover, this work allowed to draw the following conclusions : The issue of pharmaceutical mixtures and their interactions with other environmental polutants needs to be addressed. Preventing the rejection of human pharmaceuticals in the aquatic environment should be a priority. For a good management of the environmental risk of pharmaceuticals, an agreement between public health authorities, environment authorities on one hand, and pharmaceutical industries and professionals on the other hand, is necessary
Mahdi, Ahmed Moussa. "Elimination de substances pharmaceutiques d'effluents urbains par un procédé d'oxydation avancée basé sur le radical sulfate". Electronic Thesis or Diss., Aix-Marseille, 2013. http://www.theses.fr/2013AIXM4746.
Pełny tekst źródłaThis work is devoted to the study of an alternative advanced oxidation process (AOP) generating sulfate radical (SO4•-) for the removal of pharmaceuticals in municipal wastewater effluents. Four nitrogen containing pharmaceuticals (carbamazepine, diclofenac, sulfamethoxazole and ciprofloxacin) belonging to different therapeutic classes were chosen as model contaminants. The evaluation of the kinetic performance of processes based on the generation of HO• (H2O2/Fe(II) and UV-C/H2O2 ) and SO4•- (HSO5-/Co2+, UV-C/S2O82- and UV-C/HSO5- ) was conducted in biologically treated effluent. Comparison of photochemical and non- photochemical processes performed under the same optimal conditions showed that the processes generating SO4•- are less inhibited by the environmental matrix than processes producing HO•. This electron transfer reaction is demonstrated by the identification of transformation products using liquid chromatography coupled to high resolution mass spectrometer. Oxidation of parent compounds starts by an electron transfer reaction on the nitrogen groups thereby generating a cation radical which further reacts with water or O2. The sulfamethoxazole degradation pathway gives more insights into this mechanism due to the primary amine moiety (aniline) which is converted into nitro function. This treatment system can be regarded as a new strategy for the treatment of urban wastewater contaminated by pharmaceutical residues through the generation of SO4•-
Lê, Laetitia Minh Mai. "Exploitation des données spectrales dans la sécurisation du circuit des médicaments anticancéreux". Thesis, Paris 11, 2014. http://www.theses.fr/2014PA112148/document.
Pełny tekst źródłaMost of the anticancer drugs are defined by a narrow therapeutic margin; therefore medical errors can have major consequences on patients. Thus, it’s necessary to guarantee the good drug at the good dose by the implementation of a quality control of the preparation before administration. These potentially carcinogenic, mutagenic or teratogenic drugs present a risk for exposed people especially healthcare workers.The aim of this study was to develop tools which can optimize the safety of the cytotoxic medication circuit in hospitals, for the patient as much as for healthcare workers. In order to respond to these problematics, analytical tools have been associated with different methods of data interpretation of chemometric and risk management.To improve healthcare workers’ safety, environmental monitoring looking for traces of platinum compound cytotoxic drugs were performed to identify the most contaminated areas. Based on these contaminations and working conditions, a methodology of multi-criteria risk analysis has been developed to quantify the risk of exposure of healthcare workers. Regarding the risk, various corrective measures were considered. Thus, studies based on the detergent efficiency of decontamination protocols used to clean workplace surfaces and cytotoxic vials were conducted.In parallel, assays were performed on two anticancer molecules to secure cytotoxic preparations before administration: 5-fluorouracile and gemcitabine. Regarding their non-destructive, non-invasive properties and therefore, more secured handling, Raman and near infrared spectroscopy were explored. Spectral data (spectral zones and pretreatments) were optimized by multivariate analyses ComDim to develop models of regression PLS predicting the concentration of the active ingredient in solution. Results showed the feasibility and the complementarity of these two spectroscopies in the quantitative determination of the cytotoxic drugs.These works participate in the continuous approach of quality assurance implemented in numerous health institutions. We hope that they will contribute to durably decrease risks associated to cytotoxic drugs for both patients and healthcare workers
Dandachi, Iman. "Multi drug resistant organisms in Lebanese livestock". Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0286/document.
Pełny tekst źródłaNowadays, the epidemiology of multi-drug resistance has changed and is no more confined to the hospital settings. Food producing animals are increasingly regarded as potent reservoirs of multi-drug resistant organisms i.e. beta lactamase producers and colistin-resistant Gram-negative bacilli. The emergence of multi-drug resistance in animals is thought to be mainly driven by the overuse of antibiotics as growth promoters and prophylaxis. The dissemination of resistant organisms in animals is sparked by the concern of being transferred to humans where they can be candidates for infections with limited therapeutic options. The zoonotic transmission of resistant organisms from animals to humans occurs mainly via direct/indirect contact but also via environmental routes. In Lebanon, several studies were conducted in hospitals and showed a high prevalence of multi-drug resistance; unlikely, these studies are scarce in animals. The aim of this thesis research was thus to describe the epidemiology of multi-drug resistant organisms in Lebanese Livestock Multi-locus sequence typing and whole genome sequencing were used to describe the prevalence of multi-drug resistant organisms and the corresponding mechanisms of resistance in the isolated strains from chicken, pigs, farmers and environment. Chicken and swine farms showed to be potent reservoirs of ESBL and mcr-1 genes in Lebanon. The dissemination of multi-drug resistance appears to be multi-clonal and related to the spread of plasmid carrying resistance genes. Colistin use in veterinary medicine in Lebanon should be banned
Grandal, Rejo Beatriz. "Beyond Breast Cancer : The Interplay of Immunity, Comedications, and Comorbidities in Treatment Response and Outcomes". Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPASL063.
Pełny tekst źródłaCancer caused almost 10 million deaths in 2020 and is predicted to affect nearly 24.5 million people by 2035 due to lifestyle changes, aging, and environmental factors. Breast cancer (BC) is the most frequent cancer diagnosis and the first cause of oncology mortality among females. The incidence of BC escalates with increasing âge, paralleling the rising prevalence of co-existing conditions (comorbidities) and chronic médication prescriptions (comedications), reported in roughly half of ail cancer patients. Administering chemotherapy prior to surgery (NAC) allows clinicians to evaluate in vivo tumor chemosensitivity. The objective of this thesis is to perform a comprehensive analysis to investigate the intricate relationships among tumor-infiltrating lymphocytes (TILs), checkpoints, genetic déterminants, breast cancer subtypes, comedications, comorbidities, treatment response, and oncological outcomes in patients with breast cancer. This objective will be achieved via an intégrative examination of datasets from real-world evidence (RWE) and a post-hoc analysis of randomized controlled trials (RCTs). The opening section of this thesis provides a comprehensive review of the neoadjuvant treatment paradigm in breast cancer, focusing on the interconnectedness of tumor biology, TILs,chemosensitivity, and survival. This research offers valuable insights into the intricate network that governs treatment outcomes. The subséquent segment seeks to study the rôle of comedications in cancer treatment by examining the associations between comedication use, comorbidities, immune infiltration, and treatment response. This chapter aims to identify unsuspected interactions that may improve patient outcomes by discovering novel therapeutic applications for existing drugs (drug repurposing). Moreover, we undertake an in-depth examination of the effects of regularly prescribed concomitant médications on BC survival using data from the French National Health Data System (SNDS). We endeavor to delineate a detailed map of potential interactions between concomitant médications and survival in the context of the entire French population. In conclusion, BC epitomizes a complex network of tumor and microenvironment interactions, with numerous influencing factors yet to be fully elucidated. Neoadjuvant settings and vast database intégration can identify novel therapeutic targets and drug-drug interactions, which are vital for advancing cost-effective, safe précision medicine
Bejjani-Ghauch, Alice. "Apport de l’analyse élémentaire (IBA) et moléculaire (ToF-SIMS) par faisceaux d’ions à l’étude de matériaux d’intérêt environnemental et pharmaceutique". Thesis, Lyon 1, 2009. http://www.theses.fr/2009LYO10302.
Pełny tekst źródłaThe aim of this study is to analyze heterogeneous organic matter by exhibiting analytical difficulties by classical techniques under solid state. The first part of this work is dedicated to the study of pesticides photodegradation impregnated in soils by ToF-SIMS technique. A comparative investigation of the induced phenomenon obtained with the same pesticides deposited as thin layer on a neutral support helped in studying the degradation kinetics of those pesticides especially their half-lives. The second part is dedicated to the development of new analytical method for the analysis of commercialized pharmaceutical compounds without prior sample preparation. We have demonstrated the possibility of active ingredient (A.I.) quantification in the presence of the excipients by the following analytical techniques: IBA techniques if the A.I. contains an heteroatom, however, absent in the excipients. The precision (< 7%) is found to be in the majority of the studied cases within the analytical standards of the quality control processes. ToF-SIMS technique for all drugs however within a specific range of concentration defined by the calibration curves for improved sensitivities. These restrictions in the dynamic concentration range depend on the nature of the mixtures A.I. / Excipients on hand and show evidence of the matrix effect on the other hand. A deep investigation on the matrix nature should improve the sample preparation method for more performance analysis. To our knowledge, it is the first time that the above mentioned techniques whose analytical advantages and limitations have been discussed were applied to such solid matrix samples
Togola, Anne. "Présence et devenir des substances pharmaceutiques dans les écosystèmes aquatiques". Bordeaux 1, 2006. http://www.theses.fr/2006BOR13314.
Pełny tekst źródłaPharmaceutical substances belong to the class of the emerging contaminants which have started recently to be studied in natural environments. The widespread use and the large consumed quantities of these compounds can lead to important inputs into the aquatic environment through wastewater treatment plants. The first part of this work consisted in the development and the comparison of various procedures concerning sampling (spot sampling and passive sampling), extraction step (Solid Phase Extraction , Microwave-assisted extraction) and analysis (Gas chromatography / mass spectrometry), needed for pharmaceutical analysis in various aquatic compartments (dissolved, particulate and sedimentary phases, biological organisms). Thus a first assessment of pharmaceutical contamination of various aquatic systems (Seine, Loire, Adour and Garonne estuaries, Mediterranean coastal water…) has been undertaken. A contamination of aquatic compartments with pharmaceutical substances has been highlighted for all studied systems. Concentrations ranging from few ng. L-1 to several μg. L-1 have been measured, depending on compounds, sampling stations and seasonal variations. This work has allowed to document the origins (quantification and qualification of inputs) and the fate (degradation phenomena) of those compounds. It has also highlighted partition phenomena between the different phases (ie particulate matter and dissolved phase) and the bioaccumulation capability of some of those substances
Aminot, Yann. "Étude de l'impact des effluents urbains sur la qualité des eaux de la Garonne estuarienne : application aux composés pharmaceutiques et aux filtres UV". Electronic Thesis or Diss., Bordeaux 1, 2013. http://www.theses.fr/2013BOR14161.
Pełny tekst źródłaUbiquitous presence of pharmaceuticals in the environment is of great concern. In this Ph.D. work, occurrence and fate of these organic contaminants were studied in the estuarine Garonne River, receiving treated effluents of the Bordeaux urban area (France). After developing and validating the analytical methods for multi-residue detection of 53 pharmaceuticals in water and sediment, composition and variability of the Bordeaux wastewater treatment plant influents and effluents were characterized. Presence of analytes in river water, suspended solids and sediments was then investigated on a periurban river located in the suburbs of Bordeaux. Besides, a long-term monitoring of estuarine Garonne River revealed the relative importance of local and upstream inputs and clearly showed a seasonal in-situ degradation of certain pharmaceuticals. This degradation was further confirmed and examined through batch experiments simulating the mixing conditions of wastewater and estuarine river water, highlighting the importance of suspended solid concentration in biodegradation rates
Kazma, Rémi. "Les interactions gène-environnement dans les études génétiques des maladies complexes". Phd thesis, Université Paris Sud - Paris XI, 2010. http://tel.archives-ouvertes.fr/tel-00502881.
Pełny tekst źródłaKazma, Rémi. "Les interactions gène-environnement dans les études génétiques des maladies complexes". Phd thesis, Paris 11, 2010. http://www.theses.fr/2010PA11T016.
Pełny tekst źródłaSoldatenko, Alexandra. "Les implications juridiques des nanotechnologies". Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAA033.
Pełny tekst źródłaWhile a significant number of products containing nanomaterials is already in widespread use, we have little understanding of risks and benefits they can bring to the society in the long term. The objective of this PhD thesis is to answer the following question: which regulatory framework can ensure a high level of protection against real or suspected risks of nanotechnologies while promoting competitiveness and innovation ? Although the European Union and the United States have attempted to find nuanced solutions according to the needs, capacities and challenges, which are proper to each sector concerned and their respective legal traditions, the emerging regulatory framework for nanotechnologies is characterised by a high degree of fragmentation
Tian, Roger Bi Diangoné. "Sources environnementales de Mycobacterium ulcerans en Côte d'Ivoire". Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM5040.
Pełny tekst źródłaBuruli ulcer is the third mycobacteriosis in the world after tuberculosis, leprosy. Buruli ulcer is widespread in at least 33 countries including West Africa which has the highest prevalence. Among the countries in which Buruli ulcer is reported, Ivory Coast which we come from has the highest incidence of 36% reported in the World Health Organization. Buruli ulcer is caused by Mycobacterium ulcerans, an environmental mycobacterium whose reservoir and source of transmission to humans, are not understood. Our review of the literature focused on environmental sources of this mycobacterium in West Africa, which converge stagnant aquatic environment. On this basis, we conducted an extensive campaign of environmental sampling in Ivory Coast and detected by real-time PCR M. ulcerans in stagnant water, soil and feces of an herbivorous mammal Thryonomys swinderianus. Then we experimentally proved that M. ulcerans could survive in the soil for at least four months. These results suggest that, in Ivory Coast, stagnant water, soil and animal could play a role in the life cycle of the bacterium. In the second work, we have upgraded aquatic tropical plants by the use of extracts in the culture medium of M. ulcerans, slow growing mycobacteria to accelerate its growth. In the third work, we proposed the methylene blue, less expensive, easy to access as an alternative treatment for Buruli ulcer. It is appropriate to resume the experiment on methylene blue by other teams of researchers and after reproducing our experimental data, suggest the topical use of purified, non-toxic methylene blue in human clinical
Bui, Van Hoi. "Contribution à l’étude de la présence et du devenir des résidus de médicaments dans les compartiments aquatiques". Thesis, Bordeaux 1, 2013. http://www.theses.fr/2013BOR14930/document.
Pełny tekst źródłaThe presence of pharmaceuticals was evaluated in Seine surface waters and in eight wastewater treatment plants (WWTP) effluents (4 WWTP within MEDSEINE - GIP Seine – Aval project and 4 WWTP within TOXSTEP – ANSES project. A hundred molecules was systematically reseached in both types of waters by applying the analytical methodologies (SPE solid phase extraction followed by LC-MS/MS analysis). A seasonal monitoring of pharmaceutical residues was also carried out. The pharmaceutically residues have been systematically quantified in this both types of water. The concentrations in suface of waters are significative for some molecules: 1 – 108 ng/L for diclofenac, 2 – 324 ng/L for ibuprofen and the values are weakly for some molecules: 2 – 13 for sulfapyridine, 1 – 5 for nordiazepam. Non steroidal anti-inflammatory drugs, β-blockers, macrolides and fluoroquinolones are mostly founded in the effluents of WWTP. Their concentrations were measured in the range: 62 ng/L – 10 µg/L for sotalol, 39 ng/L – 8 µg/L for atenolol, 32 ng/L – up to 127 µg/L for paracetamol.Moreover, the stability of pharmaceuticals was evaluated with light radiation . UV irradiation (at 254 nm) potentially used in the final WWTP before discharge in particularly areas have been applied (with a dose up to 1500 J/m2). Sunlight simulations have also been done. The phenomenon of photodegradation at 254 nm has been observed for some molecules such as : diclofenac, ketoprofen (>90% degraded), ciprofloxacine, norfloxacine (up to 75% degraded). Azithromycinem clarithromycine, carbamazepine and atenolol are most stable molecules observed. Exposing under simulated sunlight, diclofenac, ketoprofen, ciprofloxacine and norfloxacine are also sensitive molecules (>90 % degraded) after 24 hours of exposure (172.8 kJ/m2). Carbamazepine, sulfamethoxazole, atenolol, metoprolol and bisoprolol are most stable molecules observed
Olvera, Vargas Hugo. "Study on the fate of pharmaceuticals in aqueous media : synthesis, characterization and detection of biotic and abiotic transformation products using electrochemical advanced oxidation processes and bioconversions". Thesis, Paris Est, 2014. http://www.theses.fr/2014PEST1179/document.
Pełny tekst źródłaThe present project contributes with valuable data for a better fundamental understanding on the fate of pharmaceutical residues in the environment, dealing with the main challenges concerning this increasingly worrying environmental issue. The used Electrochemical Advanced Oxidation Processes (EAOPs), electro-Fenton (EF) and anodic oxidation (AO), showed to be a very efficient alternative for the mineralization of acid solutions of the pharmaceuticals RNTD and FRSM, attaining almost complete mineralization of the drugs after 6h of electrolysis. A comparative study on the mineralization of RNTD solutions by EF and SPEF processes in a 2.5 L capacity pre-pilot flow plant demonstrates the higher oxidation capacity of SPEF, achieving very good mineralization rates, thus evidencing the potentiality of this technology at greater scale for the treatment of wastewaters containing pharmaceutical products. The application of an EF pre-treatment coupled with a biological process for the degradation of both drugs was conducted. EF pre-pretreatment was capable of enhancing the solution biodegradability envisaging a biological treatment, which efficiently removed the short-chain carboxylic acids that had been formerly generated during the pre-applied electrolysis. In this way, the combination of both processes was confirmed as a very promising technology for the treatment of pharmaceuticals-containing wastewater. Several transformation products (TPs) were detected and identified during the electrochemical oxidation of the studied drugs. Toxicity tests based on the bioluminescence of the marine bacteria V. fischeri. evidenced the toxicity some of these oxidation by-products, since the toxicity of the solution increased on the first stages of the electrolysis. However, the abatement of the toxicity in the final stages of the electrochemical treatments, demonstrated the effectiveness of these technologies for both the mineralization and detoxification of the RNTD and FRSM solutions. The use of the fungi Cunninghanella echinulate for the bioconversion of FRSM led to the formation of three main bio-transofrmation products: the previously identified saluamide and pyridinium, and the new detected keto-alcohol derivate. These TPs were generated by both, biological and electrochemical approches, evidencing their high probability to be found in environmental compartments as the most likely TPs of FRSM by different oxidation conditions. This study is thus presented as a very useful alternative for the assessment of the fate of pharmaceutical residues in the environment
Coetsier, Clémence. "Approche intégrée de la gestion environnementale des produits pharmaceutiques dans des rejets de stations d’épuration urbaines et leur milieu récepteur : occurrence, impact et traitements tertiaires d'élimination". Montpellier 2, 2009. http://www.theses.fr/2009MON20105.
Pełny tekst źródłaPharmaceutical products (PPs), widely consumed by population and discharged in the environment through wastewater treatment process (WTP), are sources of aquatic ecosystems contamination. Environmental risk assessment for these substances involves the accurate quantification of their concentrations and the evaluation of their toxicity for exposed species. Our study dealing with a dozen of representative pharmaceutical compounds was conducted in Southeast France. A LC-MS/MS detection method was developed and a sampling campaign was carried out on 7 urban WTP and the natural waters where they discharge (rivers of the Gard and pond) in order to assess PPs contamination level. Toxicity of PPs was estimated using bioluminescent and growth inhibition tests (Microtox, ToxScreen and Protoxkit). Experiments were conducted to evaluate UV photolysis and activated carbon adsorption capacities for the removal of these compounds. Measurements for samples collected highlight the occurrence of PPs in WTP effluent of Southeast region at concentrations ranging from 10 to 1000 ng. L-1 and reaching hundreds of ng. L-1 in the downstream surface waters. Comparison between the level of exposure and experimental toxicity values completed by literature data suggests that only 3 compounds (propranolol, ibuprofen and diclofénac) may induce a low risk at a local scale (rivers of Gard). Complementary treatments of the STP effluents by UV photolysis and activated carbon adsorption prove to be efficient to remove most of the 12 studied PPs and should be considered to reduce the presence and the impact of pharmaceutical products in the environment
Durance, Loïc. "Développement d'une méthode de stérilisation par la chaleur de solutions injectables conditionnées en polyéthylène basse densité". Amiens, 2003. http://www.theses.fr/2003AMIED003.
Pełny tekst źródłaThe solutions for injection are usually packaged in glass flasks and sterilised by moist steam. Is the current tendency to substitute glass by the plastic because it reduce the obstruction of conditioning while increasing its shock-proofness and allows a board elimination of the wastes by incineration. Only some plastics meet both public health regulations and ecological requirements. Among them, low density polyethylene (LDPE) offers various advantages. It possesses virtually no additive, which limits the interaction hazards between plastic and chemical substances used in injection preparations. Its destruction does not bring chlorine-containing waste or other toxic matter into the atmosphere. Moreover, it is fully adapted to the various manufacturing technologies for large-scale production as the blow-fill-an-seal. However, the temperature value admitted for sterilisation is 121°C, whereas LDPE exhibits a melting point at about 117°C. Therfore, we have developped an alternative cycle of sterilisation based on F0 concept at a temperature lower than 121°C and such as it respected the LDPE containers integrity. The efficiency on the micro-organisms destruction have been calculated aid of stocks spores of Bacillus Stearothermophilus introduced into the recipients which contained water for injection as base solution. The sterilised products have been followed throughout this period. The information obtained by this work have the aim of documenting a manufacturing authorization file about products for injection for its recording with the benefit of a pharmaceutical industry of Amiens
Arpin-Pont, Lauren. "Les produits pharmaceutiques et de soin personnel en milieu marin : prédiction des concentrations environnementales et étude des effets sur le métabolisme endogène d’organismes exposés". Thesis, Montpellier, 2015. http://www.theses.fr/2015MONTS172/document.
Pełny tekst źródłaThe last twenty years, the issue of PPCP contamination of the marine environment caused a growing concern among scientific community. PPCP enter the environment mainly through wastewater treatment plants (WTP), not able to remove completely these substances. The first objective of the thesis was to assess the current state of knowledge on the PPCP occurrence in the different compartments of the marine environment (seawater, sediments and organisms) through a literature review. The contamination of the marine environment is generally assessed by “one-time” measures in situ. However, such monitoring campaigns are time-consuming and costly. Some approaches based on the determination of the predicted environmental concentrations (PEC) could be applied alternatively or complementarily to in situ measures. The PEC calculation is the first step of environmental risk assessment (ERA), to assess the exposure of non target organisms to these substances. However, this estimation needs to be refined to be accurate, by integrating site-specific information. The second aim of the thesis was to propose refined PEC calculation methodologies of pharmaceuticals and their metabolites in a coastal zone using an adapted hydrodynamic model. Two model compounds were chosen, carbamazepine and venlafaxine. In order to assess the environmental risk of pharmaceuticals, it is needful to assess their effects on organisms. Nowadays, few ecotoxicological data are available on marine organisms, contrary to freshwater organisms. Regulatory concept of ERA is often based on a set of short term standard tests carried out at high concentrations. Other tests, implemented at lower organizational levels, are more sensitive to low exposure levels and are more relevant for the marine risk assessment. The last objective was to study the effects of diclofenac on PG production, based on its mode of action, on marine mussels exposed
Fancello, Laura. "A viral metagenomic approach to study taxonomic and functional diversity of viral communities from the environment to humans". Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM5046/document.
Pełny tekst źródłaViruses are the most abundant and diverse organisms but little is known about their diversity. Recently, viral metagenomics has allowed performing broad unselective exploration of uncultivated viral communities, bypassing the limits of classical viral detection tools. However, most viral metagenomes are generated from temperate regions (for environmental studies) or from modern stool samples, sera/blood and naso-/oro- pharyngeal samples (for human-associated studies). Therefore, the purpose of my thesis is to study viral communities in the least investigated environments or human samples, using viral metagenomics.The first part of my thesis is a review of the main computational tools for the analysis of viral metagenomes. The second part of my thesis presents the first viromes generated from the Sahara desert. In the third part, I investigate human-associated viral communities: i) the first virome from a human coprolite; ii) the first viromes generated from human pericardial fluids, in idiopathic pericarditis cases; ii) a functional-level investigation of previously described viral metagenomes from cystic fibrosis patient sputa that focuses on antimicrobial resistance genes carried by bacteriophages to better understand the emergence of multidrug-resistance bacteria in the airways of cystic fibrosis patients.This thesis work provides original data on unexplored viral communities and shows the potential of viral metagenomics to give insights on viral diversity, reveal the presence of expected and unexpected viruses and decipher their role in the ecosystem
Aminot, Yann. "Étude de l'impact des effluents urbains sur la qualité des eaux de la Garonne estuarienne : application aux composés pharmaceutiques et aux filtres UV". Thesis, Bordeaux 1, 2013. http://www.theses.fr/2013BOR14161/document.
Pełny tekst źródłaUbiquitous presence of pharmaceuticals in the environment is of great concern. In this Ph.D. work, occurrence and fate of these organic contaminants were studied in the estuarine Garonne River, receiving treated effluents of the Bordeaux urban area (France). After developing and validating the analytical methods for multi-residue detection of 53 pharmaceuticals in water and sediment, composition and variability of the Bordeaux wastewater treatment plant influents and effluents were characterized. Presence of analytes in river water, suspended solids and sediments was then investigated on a periurban river located in the suburbs of Bordeaux. Besides, a long-term monitoring of estuarine Garonne River revealed the relative importance of local and upstream inputs and clearly showed a seasonal in-situ degradation of certain pharmaceuticals. This degradation was further confirmed and examined through batch experiments simulating the mixing conditions of wastewater and estuarine river water, highlighting the importance of suspended solid concentration in biodegradation rates
Mahdi, ahmed Moussa. "Elimination de substances pharmaceutiques d'effluents urbains par un procédé d'oxydation avancée basé sur le radical sulfate". Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM4746.
Pełny tekst źródłaThis work is devoted to the study of an alternative advanced oxidation process (AOP) generating sulfate radical (SO4•-) for the removal of pharmaceuticals in municipal wastewater effluents. Four nitrogen containing pharmaceuticals (carbamazepine, diclofenac, sulfamethoxazole and ciprofloxacin) belonging to different therapeutic classes were chosen as model contaminants. The evaluation of the kinetic performance of processes based on the generation of HO• (H2O2/Fe(II) and UV-C/H2O2 ) and SO4•- (HSO5-/Co2+, UV-C/S2O82- and UV-C/HSO5- ) was conducted in biologically treated effluent. Comparison of photochemical and non- photochemical processes performed under the same optimal conditions showed that the processes generating SO4•- are less inhibited by the environmental matrix than processes producing HO•. This electron transfer reaction is demonstrated by the identification of transformation products using liquid chromatography coupled to high resolution mass spectrometer. Oxidation of parent compounds starts by an electron transfer reaction on the nitrogen groups thereby generating a cation radical which further reacts with water or O2. The sulfamethoxazole degradation pathway gives more insights into this mechanism due to the primary amine moiety (aniline) which is converted into nitro function. This treatment system can be regarded as a new strategy for the treatment of urban wastewater contaminated by pharmaceutical residues through the generation of SO4•-
De, Conto Véronique. "Importance du microenvironnement dans les modèles cérébraux in vitro pour le criblage phénotypique". Thesis, Université de Lille (2018-2021), 2021. http://www.theses.fr/2021LILUS046.
Pełny tekst źródłaAbout 90% of drug candidates fail in clinical trials, for efficacy- and toxicity-related reasons, which often involve the Central Nervous System (CNS). This high failure rate highlights a lack of relevance in experimental models used upstream, including human in vitro models. Indeed, they do not take into account the complexity of the CNS, in which neurons are organized in 3 dimensions (3D) and interact with their microenvironment, composed of cells, soluble factors and extracellular matrix (ECM). The objectives of this PhD were i) to study the influence of these three microenvironment components on neuronal cells in cerebral in vitro models by automatized cellular imaging, and ii) to develop more relevant cerebral in vitro models for phenotypic screening, to assess neurotoxic or therapeutic effects, in the frame of Parkinson’s Disease (PD).First, the BIOMIMESYS® Brain technology has been developed. This acid hyaluronic based-matrix allows the simulation of the ECM and a 3D culture of cerebral cells in 96-well plates. The sensitivity of Luhmes cells, a dopaminergic neuronal cell line, to PD inducers has been studied: the cells displayed a lower sensitivity in BIOMIMESYS® Brain compared to cells cultured in 2 dimensions (2D). This difference was explained by two phenomena: a partial retention of toxic molecules in the matrix, and a lower neuronal maturity compared to cells cultured in 2D.The importance of the cellular microenvironment has been studied through a co-culture of Luhmes cells and primary human astrocytes in 2D. This co-culture has then been transposed in BIOMIMESYS® matrix, to form a complex model including both the glial and the matricial microenvironments.In parallel, the influence of the molecular microenvironment has been studied on the SH-SY5Y cells, a cell line derived from a neuroblastoma, commonly used for neurotoxicity assessment. In this study, the 24 major differentiation media described in the literature to differentiate these cells into neurons have been screened. The 3 most differentiating conditions in terms of proliferation slowdown and neurite elongation have been selected: retinoic acid, staurosporine, and cyclic Adenosine Monophosphate (cAMP) combined to B21 supplement. The neuronal protein marker expression and the cell sensitivity to compounds of known-toxicity have been measured, in 2D and in 3D in BIOMIMESYS® Brain. Both maturity and sensitivity of these neurons varied according to the differentiation medium, and were higher in B21+cAMP. The 3D cell culture modified also the cell response, with a lower sensitivity of cells cultured in 2D.This PhD highlighted that the microenvironment of neurons, including the ECM, the glial cells and the soluble factors, can modify the neuronal response in vitro, and should thus be considered carefully in academic research and as early as possible in the drug discovery industrial process