Climate change, a reality, a myth, a conspiracy, remains a point of research and concern, specifically with regards to the impact it has on human health. Reports concerning climate change are accepted by many but are also rejected by prominent figures of society and powerful enterprises flourishing in the race for economic development. Yet all living organisms on Earth are dependent on its natural resources and delicate balance of co-existence. A disruption of ecological balance will bring about changes to biomes and niches. These changes will affect disease patterns and well-being for all. Vulnerable groups will be most affected. If these changes have occurred and continue to occur what provision should be made to reduce population vulnerability? What investment should be made to public healthcare to assist vulnerable population groups and improve adaptability? This study was conducted with the aide of the South African Red Cross Society in three large South African provinces, Limpopo, Mpumalanga and Kwa-Zulu Natal, each known for its rich diverse ecologies and tropical to sub-tropical climates. The study aimed to determine the level of awareness amongst the healthcare workers with emphasis on education. The participants were counsellors working closely with the National Department of Health and local clinics. A total of 101 participants completed a close-ended questionnaire. The results indicated a strong workforce of young people with post-matric qualifications and strong views. Qualitative research was used with descriptive statistics to analyse and describe the data collected. It was, therefore, recommended that investment be made into this growing workforce in healthcare, as well as healthcare as a whole, since climate change, as documented, will threaten food security and water availability, see altered diseases patterns including emerging and re-emergence of infectious diseases and cardiovascular concerns brought on by heat stress. Funding must support education and training to strengthen awareness and preparedness so as to empower this workforce so that they may assist local populations to better adapt to the changes, become more resilient and, thereby, reduce their vulnerability and risk / Health Studies / M.Sc. (Life Sciences)

The quality of marine bathing water is currently assessed by monitoring the levels of faecal indicator bacteria. Among other drawbacks, results are retrospective using the traditional culture based methods. A rapid method is thus needed as an early warning to bathers for bacterial contamination in marine bathing waters. Total lipopolysaccharide (LPS) was chosen here as a potential general biomarker for bacterial contamination. Levels of total LPS, measured using a Kinetic QCL™ Limulus Amebocyte Lysate (LAL) assay, highly correlated with enumerated Escherichia coli and Bacteroides species. Levels of LPS in excess of 50 EU mL-1 were found to equate with water that was unsuitable for bathing under the current European Union regulations. Results showed that monitoring the levels of total LPS has a potential applicability as a rapid method for screening the quality of marine bathing water. More importantly, the LAL assay overcome the retrospective results when using culture based assessment since the LAL assay takes less than 30 minutes. Although false positive events were not detected, the occurrence of a false positive has been hypothesised, hence a more specific faecal biomarker was also investigated. LPS of five Bacteroides species (B. fragilis, B. caccae, B. ovatus, B. xylanisolvens and B. finegoldii) isolated from marine bathing waters samples were successfully profiled and showed high similarity between isolates in LPS gel electrophoresis banding pattern. Similar results were shown when investigating the endotoxic activity of Bacteroides species with the Kinetic QCL™ LAL assay. The potential biological relevance of Bacteroides LPS was also investigated in cell culture models indicating that Bacteroides showed similar induction of proinflammatory cytokines (TNF-α, IL-6 and IL-1α) and generally the biological activity was approximately 100 fold less than E. coli LPS. In addition, an ELISA assay was designed for the detection of Bacteroides LPS. Results showed that the Bacteroides LPS has a high potential to be used as a faecal biomarker, however, further work is required to develop a fully functional assay. The potential biological relevance of LPS present in contaminated bathing waters was also investigated in cell culture models. Results showed that there is a significant difference in the production of proinflammatory cytokines in comparison to “clean” bathing waters. Thus, results suggest that the European Directive regulations should be extended to cover the levels of total LPS in bathing waters to assure safety to the users of marine recreational water.

Adverse health effects from exposure to air pollution, although at present only partly understood, are a global challenge and of widespread concern. Quantifying human exposure to air pollutants is challenging, as ambient concentrations of air pollutants at potentially harmful levels are ubiquitous and subject to high spatial and temporal variability. At the same time, individuals have their very own unique activity-patterns. Hence exposure results from intertwined relationships between environmental and human systems add complexity to the assessment process. It is essential to develop a deeper understanding of individual exposure pathways and situations occurring in people’s everyday lives. This is important especially with regard to exposure and health impact assessment which provide the basis for public health advice and policy development. This thesis describes the development and application of a personal monitoring method to assess exposure to fine particulate matter in a variety of microenvironments. Tools and methods applied are tested with respect to feasibility, intrusiveness, performance and potential for future applications. The development of the method focuses on the application in everyday environments and situations in an attempt to capture as much of the total exposure as possible, across a complete set of microenvironments. Seventeen volunteers took part in the pilot study, collected data and provided feedback on methodology and tools applied. The low-cost particle counter applied showed good agreement with reference instruments when studied in two different environments. Based on the assessment of the two instruments functions to derive particle mass concentration from the original particle number counts have been defined. The application of the devices and tools received positive feedback from the volunteers. Limitations are mainly related to the non-weatherproof design of the particle counter. The collection of time-activity patterns with GPS and time-activity diaries is challenging and requires careful processing. Resulting personal exposure profiles highlight the influence of individual activities and contextual factors. Highest concentrations were measured in indoor environments where people also spent the majority of time. Differences between transport modes as well as between urban and rural areas were identified.

Organic contaminants from industrial and/or domestic effluents may be harmful to humans directly or indirectly by degrading the quality of the aquatic environment. Consequently these contaminants must be reduced to levels that are not harmful to humans and the environment before disposal. Chemical, physical and biological methods exist for the removal of these pollutants from effluents. Among the available chemical methods, heterogeneous photocatalytic oxidation has been found particularly effective in removing a large number of persistent organics in water. In this study, photocatalytic degradation was explored for the removal of reactive azo-dye (textile dye), triclocarban (disinfectant), clopyralid (herbicide) and three endocrine disrupting compounds (EDCs) (estrone, 17ß-estradiol and 17α-ethinylestradiol) from synthetic effluents. The major factors affecting the photocatalytic processes including the initial concentration of the target compounds, the amount of catalyst, the light intensity, the type of catalyst, the electron acceptor, the irradiation time and the pH were studied. Other oxidation techniques including (O3, H2O2, UV) were also studied. Generally UV light is used in combination with titanium dioxide, as photocatalyst, to generate photoinduced charge separation leading to the creation of electron-hole pairs. The holes act as electron acceptors hence the oxidation of organics occur at these sites. These holes can also lead to the formation of hydroxyl radicals which are also effective oxidants capable of degrading the organics. The results obtained in this study indicated that photolysis (i.e. UV only) was found to have no effect on the degradation of reactive azo-dye (RO16). However, complete photocatalytic degradation of 20 mg/L (3.24×10-2 mM) RO16 was achieved in 20 minutes in the presence of 1g/L TiO2 Degussa P25 at pH 5.5. Comparison between various types of catalysts (i.e. Degussa P25, VP Aeroperl, Hombifine N) gave varied results but Degussa P25 was the most effective photocatalyst hence it was selected for this study. For RO16 the optimum catalyst concentration was 0.5 g/L TiO2 with initial concentration of 20 mg/L RO16. It was found that the disappearance of RO16 satisfactorily followed the pseudo first-order kinetics according to Langmuir-Hinshelwood (L-H) model. The rate constant was k= 0.0928 mol/min. Photodegradation of TCC was studied in 70%v acetonitrile: 30%v water solutions. UV light degraded TCC effectively and the reaction rates increased with decreasing initial concentration of TCC. UV/TiO2 gave unsatisfactory degradation of triclocarban (TCC) since only 36% were removed in 60 minutes with initial concentration of TCC 20 mg/L. The degradation of clopyralid and the EDCs was studied using three oxidation systems UV/TiO2, UV/H2O2 and O3. Complete degradation of clopyralid (3,6-DCP) was achieved with UV/TiO2 in about 90 minutes at an optimum catalyst concentration of 1g/L. Zero-order kinetics was found to describe the first stage of the photocatalytic reaction in the concentration range 0.078-0.521 mM. At pH 5 the rate constant was 2.09×10⁻⁶ ± 4.32×10⁻⁷ M.s⁻¹. Complete degradation of all the three EDCs was achieved with UV/H₂O₂ in 60 minutes at catalyst concentration of (2.94×10⁻² M). On the other hand complete degradation of the EDCs was achieved in just 2 minutes with ozonation. For high concentration EDCs, TiO₂/UV gave low efficiency of degradation as compared with ozone and H2O2/UV. First-order kinetics was found to describe the photocatalytic reaction of the EDCs.

The wide scale use of ZnO nanoparticles (NPs) in the world consumer market has resulted in likelihood of exposure to human beings. The present study was aimed to assess the in vitro and in vivo interactions of ZnO NPs in the mammalian system and to elucidate the possible mechanism of their toxicity. Our in vitro results using human epidermal cells (A431), primary human epidermal keratinocytes and human liver cells (HepG2) demonstrated that cells exposed to ZnO NPs exhibit a decrease in cell viability which was independent of NP dissolution. ZnO NPs also induced oxidative DNA damage as evidenced by an increase in the Fpg sensitive sites. The reactive oxygen species triggered a decrease in mitochondrial membrane potential and an increase in the ratio of Bax/Bcl2 leading to apoptosis through the intrinsic pathway. In addition, ZnO NPs induced phosphorylation of JNK, P38 and P53ser15. The results from our in vivo studies using a mouse model showed that ZnO NPs induce lipid peroxidation, oxidative DNA damage and apoptosis in liver which further confirmed our in vitro findings. The data from the present study provide valuable insights into the cellular interactions of ZnO NPs and the underlying molecular mechanism of their toxicity. The results also stress the need for a comprehensive environmental health and safety assessment of engineered nanomaterials to ensure safer nanotechnology based products.

Dans des études animales, nous avons étudié le développement des métastases osseuses, leur vascularisation ainsi que des biomatériaux de comblement ou pouvant cibler l'angiogenèse. Nous avons utilisé le poly 2-hydroxyéthyl méthacrylate (pHEMA) connu pour sa biocompatibilité, pour fabriquer des microbilles fluorescentes portant à leur surface des charges anioniques ou cationiques. Les microbilles ont été incubées avec une lignée de cellules endothéliales qui internalisent de préférence les microbilles portant une charge anionique. Un silicone radio-opaque a été utilisé pour caractériser l'architecture en 3D des vaisseaux sanguins à différents stades d'évolution des métastases osseuses chez le rat. Nous avons montré au niveau des os tumoraux une hypervascularisation et une désorganisation importante de l'architecture vasculaire avec un réseau très dense de micro vaisseaux à l'aspect tortueux s'étendant dans toute la zone trabéculaire, envahissant la corticale et la diaphyse en sens rétrograde. Dans une autre étude, l'acide zolédronique, un puissant bisphosphonate ayant aussi un effet anti-angiogénique, a été utilisé de façon préventive dans un modèle de métastase osseuse chez le rat. Il permet la conversion des métastases du carcinome MatLyLu, initialement ostéolytiques, en formes ostéocondensantes en limitant les perforations corticales. Enfin, chez le lapin, dans un modèle de comblement osseux par le bêta tricalcium phosphate (β−TCP), nous avons montré que des anti-inflammatoires non stéroïdiens, utilisés en chirurgie osseuse, ne retardent pas l'ostéogenèse au contact du biomatériau. La vascularisation joue un rôle important dans le remodelage osseux normal mais aussi dans les ostéopathies bénignes et malignes ainsi que dans l'ostéointégration des biomatériaux utilisés pour le traitement des pertes de substance osseuse.

S'entendre annoncer, lors d'une consultation médicale, que la mort est proche, n'est pas sans effet subjectif. Effroi et traumatisme : violence faite à cette illusion d'immortalité protectrice qui soutient le sujet dans sa quotidienneté, ouverture faite sur le gouffre de la déréliction. La clinique que l'on rencontre dans une unité de soins palliatifs met en évidence les effets subjectifs, trop souvent délétères, d'une telle annonce. C'est à partir de celle-ci que se déploie cette interrogation concernant le sujet et ce qu'il parvient à faire -ou non- de cette annonce. Nous serons alors amenés à rendre compte de ce que la mort réelle, annoncée du lieu de l'Autre, a cet effet de produire une néantisation de la fonction symbolique qu'il supporte, en ce que son manque vient subitement à manquer. La clinique propre aux soins palliatifs montre alors les incidences subjectives d'une telle vacillation et les possibles recours du sujet dans ses tentatives pour pallier au défaut del'Autre.

Les algies pelviennes aigues constituent le premier motif de consultation aux urgences gynécologiques. Les étiologies possibles de ces algies pelviennes aigues sont nombreuses et incluent à la fois des affections gynécologiques et non gynécologiques. Certaines de ces affections peuvent, en l'absence de diagnostic précoce et d'un traitement adapté, avoir des conséquences très graves. Dans ce travail, nous avons développé un autoquestionnaire standardisé de manière qualitative dédié aux urgences gynécologiques par des entretiens structurés. Nous avons ensuite construit des modèles de prédiction clinique dédiés (i) au diagnostic de rupture tubaire chez les patientes porteuses de grossesses extra-utérines et (ii) au diagnostic de torsion d'annexe à partir de cet autoquestionnaire. Après avoir défini le concept d'urgence potentiellement à risque en gynécologie, nous avons proposé (iii) un modèle de prédiction clinique de celles-ci basé sur notre autoquestionnaire standardisé. A l'issue du développement de ces modèles, nous avons sélectionné certains items de l'autoquestionnaire standardisé afin d'en proposer une version simplifiée. L'utilisation de nos modèles pour le tri et le diagnostic des patientes aux urgences gynécologiques pourrait permettre d'optimiser la prise en charge des patientes. Dans les groupes à haut risque de pathologie, les patientes pourraient bénéficier d'une prise en charge plus rapide avec une éventuelle diminution de la morbidité secondaire à la pathologie. Pour les patientes classées à bas risque, une désescalade des examens complémentaires et des chirurgies inutiles pourrait aussi permettre une diminution de la morbidité d'origine iatrogène.

Les aquaporines (AQPs) sont des petites protéines formant des canaux hydriques àtravers les membranes cellulaires. Les AQPs 0, 1, 2 ,4 ,5 ,6 et 8 assurent le transport sélectif de l'eautandis que les AQPs 3, 7, 9 et 10 permettent également le passage du glycérol. Nous avons étudié leurexpression dans l'épiderme, la couche supérieure de notre peau supposée imperméable. Dans lesmélanocytes, des cellules dendritiques responsables de la pigmentation, seule l'AQP1 est exprimée.Nous avons montré que les kératinocytes, les cellules majoritaires de l'épiderme, expriment enprolifération les AQPs 3 et 10, alors que les kératinocytes différenciés expriment les AQPs 3 et 9. Lalocalisation de l'AQP3 a été précédemment rapportée à la membrane plasmique des kératinocytes, de lacouche basales à la couche épineuse. Nous avons localisé l'AQP9 dans les kératinocytes différenciés dela couche granuleuse au contenu riche en glycérol et réduit en eau. De fait nous pensons que l'AQP9 ysert de transporteur de glycérol. Enfin contrairement à d'autres auteurs, nous n'avons pu mettre enévidence de lien entre prolifération tumorale et expression des aquaporines.

Dans le cadre des comportements addictifs, une démarche descriptive est souvent le préambule nécessaire à toute démarche compréhensive. L'épidémiologie est donc un outil qui s'avère précieux notamment quand il s'agit d'estimer i) l'existence de comportements addictifs dans une population spécifique et de mesurer la pertinence nosographique de la notion "d'usage nocif", ii) la pertinence d'utilisation d'une pathologie comme modèle d'étude des mécanismes addictifs. Ainsi, nous avons dans un premier temps estimé l'existence de comportements addictifs dans une population spécifiques "les femmes enceintes". Il apparaît que les outils de type "questionnaire" sont facilement utilisables avec une forte adhérence des participantes. Les marqueurs biologiques pour l'alcool n'étaient ici pas satisfaisants contraitement à celui du tabagisme qui a dévoilé la présence importante du tabagisme passif. Cette enquête révèle également que la moitié des parturientes en Auvergne consomment au moins une fois de l'alcool au cours de leur grossesse et que la conséquence la plus grave de cette consommation, à savoir le Syndrome d'Alcoolisation Fœtale, touche au moins 1,8 naissance sur mille. Ainsi cette étude épidémiologique a permis la mesure des indicateurs d'intérêt sanitaire pour une médecine sociale et préventive et des actions ciblées de santé publique. Dans un second temps, nous avons évalué le profil addictif d'une autre population spécifique "les patients atteints par la maladie de Parkinson" en comparaison à une population indemne de la maladie. nous avons constaté que l'hypersexualité ou le jeu pathologique ne semblent pas être des comportements surreprésentés chez les patients Parkinsoniens tandis que la prise addictive de leur traitement dopaminergique est fréquente. En perspective de cette recherche épidémiologique, il est apparu que les patients Parkinsoniens peuvent représenter un modèle pour une meilleure compréhension du fonctionnement des comportements addictifs.