yes / Fluorescence spectroscopy on a series of aqueous solutions of poly(acrylic acid) containing a luminescent label showed that polymers with molar mass, Mn < 16.5 kDa did not exhibit a pH responsive conformational change, which is typical of higher molar mass poly(acrylic acid). Below this molar mass, polymers remained in an extended conformation, regardless of pH. Above this molar mass, a pH-dependent conformational change was observed. Diffusion-ordered nuclear magnetic resonance spectroscopy confirmed that low molar mass polymers did not undergo a conformational transition, although large molar mass polymers did exhibit pH-dependent diffusion. / Engineering and Physical Sciences Research Council (EPSRC) funded CASE award PhD. Part funded by flocculant manufacturer SNF (UK) Ltd.

<p>The gastric mucosa is frequently exposed to endogenously secreted hydrochloric acid of high acidity. Gastric mucosal defense mechanisms are arranged at different levels of the gastric mucosa and must work in unison to maintain its integrity. </p><p>In this thesis, several mechanisms underlying gastric mucosal resistance to strong acid were investigated in anesthetized rats and mice. The main findings were as follows:</p><p>Only when acid secretion occurred did the pH gradient in the mucus gel withstand back-diffusion of luminal acid (100 mM or 155 mM HCl), and keep the juxtamucosal pH (pH_jm) neutral. Thus, when no acid secretion occurred and the luminal pH was 0.8-1, the pH gradient was destroyed. </p><p>Bicarbonate ions, produced concomitant with hydrogen ions in the parietal cells during acid secretion and blood-borne to the surface epithelium, were carried transepithelially through a DIDS-sensitive transport. </p><p>Prostaglandin-dependent bicarbonate secretion seemed to be less important in maintaining a neutral pH_jm. </p><p>Removal of the loosely adherent mucus layer did not influence the maintenance of the pH_jm. Hence, only the firmly adherent mucus gel layer, approximately 80µm thick, seemed to be important for the pH_jm. </p><p>Staining of the mucus gel with a pH-sensitive dye revealed that secreted acid penetrated the mucus gel from the crypt openings toward the gastric lumen only in restricted paths (channels). One crypt opening was attached to one channel, and the channel was irreversibly formed during acid secretion. </p><p>Gastric mucosal blood flow increased on application of strong luminal acid (155 mM HCl). This acid-induced hyperemia involved the inducible but not the neural isoform of nitric oxide synthase. These results suggest a novel role for iNOS in gastric mucosal protection and indicate that iNOS is constitutively expressed in the gastric mucosa. </p><p>It is concluded that a pH gradient in the gastric mucus gel can be maintained during ongoing acid secretion, since the acid penetrates the mucus only in restricted channels and bicarbonate is carried from the blood to the lumen via a DIDS-sensitive transporter.</p>

The gastric mucosa is frequently exposed to endogenously secreted hydrochloric acid of high acidity. Gastric mucosal defense mechanisms are arranged at different levels of the gastric mucosa and must work in unison to maintain its integrity. In this thesis, several mechanisms underlying gastric mucosal resistance to strong acid were investigated in anesthetized rats and mice. The main findings were as follows: Only when acid secretion occurred did the pH gradient in the mucus gel withstand back-diffusion of luminal acid (100 mM or 155 mM HCl), and keep the juxtamucosal pH (pHjm) neutral. Thus, when no acid secretion occurred and the luminal pH was 0.8-1, the pH gradient was destroyed. Bicarbonate ions, produced concomitant with hydrogen ions in the parietal cells during acid secretion and blood-borne to the surface epithelium, were carried transepithelially through a DIDS-sensitive transport. Prostaglandin-dependent bicarbonate secretion seemed to be less important in maintaining a neutral pHjm. Removal of the loosely adherent mucus layer did not influence the maintenance of the pHjm. Hence, only the firmly adherent mucus gel layer, approximately 80µm thick, seemed to be important for the pHjm. Staining of the mucus gel with a pH-sensitive dye revealed that secreted acid penetrated the mucus gel from the crypt openings toward the gastric lumen only in restricted paths (channels). One crypt opening was attached to one channel, and the channel was irreversibly formed during acid secretion. Gastric mucosal blood flow increased on application of strong luminal acid (155 mM HCl). This acid-induced hyperemia involved the inducible but not the neural isoform of nitric oxide synthase. These results suggest a novel role for iNOS in gastric mucosal protection and indicate that iNOS is constitutively expressed in the gastric mucosa. It is concluded that a pH gradient in the gastric mucus gel can be maintained during ongoing acid secretion, since the acid penetrates the mucus only in restricted channels and bicarbonate is carried from the blood to the lumen via a DIDS-sensitive transporter.

L’objectif de cette thèse est de contribuer à la compréhension du mécanisme d’oxydation de Br- dans lequel le radical HO• intervient. Le rendement du radical HO• étant alors intimement lié au rendement d’oxydation de Br-, c’est sur lui que l'influence de différents paramètres physicochimiques a été étudiée : température, TEL, débit de dose, pH, nature du gaz saturant. Les solutions ont été irradiées avec 4 types de rayonnement : rayons X de 13 à 18 keV, électrons de 7 et 10 MeV, faisceaux d’ions C6+ de 975 MeV et He2+ de 70 MeV. Le développement d’un autoclave optique avec circulation de solution compatible avec le rayonnement de TEL élevé a permis de réaliser les premières expériences à TEL élevé constant et à température élevée. Cette cellule s’est avérée être aussi compatible avec les expériences pompe-sonde picoseconde réalisées avec l’accélérateur ELYSE.Le rendement de capture du radical hydroxyle a donc été estimé à TEL élevé mais aussi à haute température. Une meilleure compréhension du mécanisme d’oxydation de Br- en est issue, notamment en milieu acide et en comparant les résultats cinétiques avec les simulations Monte Carlo pour les temps inférieurs à la µs, et Chemsimul pour les produits stables (formation de Br2•- et de Br3-). / The purpose of this thesis is to contribute to the understanding of the oxidation mechanism of Br- in which the HO• radical is involved. The HO• radiolytic yield is strongly connected with the oxidation yield of Br-, and therefore we have studied the influence of different physical and chemical parameters on this global yield: temperature, LET, dose rate, pH, saturation gas. The solutions have been irradiated with 4 types of ionizing rays: X- rays (from 13 to 18 keV), electrons (from 7 to 10 MeV), C6+-ions beam of 975 MeV and He2+-ions beam of 70 MeV.The development of an optical autoclave with solution flow, compatible with high LET ionizing rays has allowed us conduct the first experiments at constant high LET and high temperature. This cell has turned out to be compatible with the picosecond pump-probe experiments performed with the ELYSE accelerator.The HO• scavenging yield has been, therefore, estimated at both high LET and high temperature. A better understanding of the Br- oxidation mechanism has been achieved, in acid medium, in particular, by comparing the kinetics results with Monte Carlo Simulations for time scales inferior to the microsecond and with Chemsimul for the stable products (Br2•- and Br3- formations).