The pH-dependent phase distribution of wood pitch components in papermaking processes

Wood contains only a very small amount of lipophilic extractives, commonly known as wood pitch. The pitch is known to cause severe problems in papermaking processes. The amount of pitch in process waters can be decreased by seasoning of the raw material prior to pulping, pulp washing, removal of pitch by flotation, adsorption of pitch onto various mineral surfaces, and retention of pitch to the fibre material by cationic polymers. The aim of this study was to determine the influence of pH on some of the methods used for pitch control. Experiments were performed using laboratory-made wood pitch emulsions with varying pH, salt concentration, hemicellulose concentration and pitch composition. These emulsions were used to study the phase distribution of resin and fatty acids, the colloidal stability of pitch with and without steric stabilisation by galactoglucomannans, and the interactions between wood pitch and mineral particles. Purification of unbleached and peroxidebleached mill process water was performed by froth flotation in combination with a foaming agent. The distribution of resin and fatty acids (RFAs) between colloidal pitch droplets and the water phase was very dependent on pH. At pH 3, almost all of the RFAs were attached to the pitch droplets, while increasing the pH led to increasing concentration of dissolved RFAs in the water phase. The presence of salt shifted the release of RFAs towards higher pH, while lower ratio of neutral pitch in the emulsion resulted in release of RFAs at lower pH. It was also seen that the dissolution and adsorption of RFAs at sudden pHchanges takes place very quickly. Colloidal pitch was more stable against electrolyte-induced aggregation at higher pH, due to its higher anionic charge. The concentration of cationic polymers needed to aggregate colloidal pitch also increased with increasing pH. The surface characteristics of solid particles, such as amount of charged groups, were very important for understanding their interactions with colloidal wood pitch. Water-soluble galactoglucomannans stabilised the colloidal pitch sterically against aggregation, but could not completely prevent interactions between wood pitch and hydrophilic particles. Froth flotation of unbleached and peroxidebleached process water showed that the pitch could be removed more effectively and selectively at low pH, compared to at neutral pH. The pitch was removed more effectively, using lower concentrations of foaming agent, from peroxide-bleached water than from unbleached water. The results show that pH has a major impact on various pulping and papermaking processes. It determines the anionic charge of the colloidal pitch and the solubility of certain pitch components. Because of this, the pH influences the effectiveness of pitch retention and removal of pitch. The results indicate that pitch problems could be diminished by acknowledging the importance of pH in various papermaking processes.

Correlation of discocyte frequency and ATP concentration in preserved blood: A morphological indicator of red blood cell viability

Red blood cells (RBC) are viable if kept in an adequate preservative solution, although gradual changes in morphology and metabolism may occur. There is a gradual decrease in adenosine-5'-triphosphate (ATP) concentration, pH, glucose consumption, and enzyme activity during preservation. The normal discocyte shapes are initially replaced by echinocytes and stomatocytes and, at final stages, by spherocytes, the last step before splenic sequestration. Post-transfusional survival has been correlated with the ATP concentration. RBC preserved in ADSOL, a solution containing adenine, dextrose, sodium chloride, and mannitol, are viable for transfusion for up to 6 weeks. Erythrocytes from 10 blood units taken from healthy adult donors were preserved for 12 weeks in ADSOL at 4oC. We now report a significant correlation (r2 = 0.98) between the percentage of discocytes (89 to 7%) and ATP (100 to 10%) concentration in ADSOL-preserved RBC. The results suggest that the percent of discocyte shapes used as an indicator of ATP concentration may be a useful indicator for quality control of RBC viability in centers which have limited assay facilities.

Chronic postnatal administration of methylmalonic acid provokes a decrease of myelin content and ganglioside N-acetylneuraminic acid concentration in cerebrum of young rats

Levels of methylmalonic acid (MMA) comparable to those of human methylmalonic acidemia were achieved in blood (2-2.5 mmol/l) and brain (1.35 µmol/g) of rats by administering buffered MMA, pH 7.4, subcutaneously twice a day from the 5th to the 28th day of life. MMA doses ranged from 0.76 to 1.67 µmol/g as a function of animal age. Control rats were treated with saline in the same volumes. The animals were sacrificed by decapitation on the 28th day of age. Blood was taken and the brain was rapidly removed. Medulla, pons, the olfactory lobes and cerebellum were discarded and the rest of the brain ("cerebrum") was isolated. Body and "cerebrum" weight were measured, as well as the cholesterol and triglyceride concentrations in blood and the content of myelin, total lipids, and the concentrations of the lipid fractions (cholesterol, glycerolipids, phospholipids and ganglioside N-acetylneuraminic acid (ganglioside-NANA)) in the "cerebrum". Chronic MMA administration had no effect on body or "cerebrum" weight, suggesting that the metabolites per se neither affect the appetite of the rats nor cause malnutrition. In contrast, MMA caused a significant reduction of plasma triglycerides, but not of plasma cholesterol levels. A significant diminution of myelin content and of ganglioside-NANA concentration was also observed in the "cerebrum". We propose that the reduction of myelin content and ganglioside-NANA caused by MMA may be related to the delayed myelination/cerebral atrophy and neurological dysfunction found in methylmalonic acidemic children.

Effect of pH, dextrose and yeast extract on cadmium toxicity on Saccharomyces cerevisiae PE-2

The aim of this study was to evaluate the effects of pH, dextrose and yeast extract on the cadmium toxicity on Saccharomyces cerevisiae PE-2. In the first assay, the YED mediums with different pH (2, 3, 4, 5, 6, 7, and 8) containing 0.0 and 0.05 mmol Cd L-1 were inoculated with yeast suspension and incubated at 30 °C for 18 hours. During the anaerobic growth, the biomass concentration was determined. The yeast trehalose content, cell viability, and the growth rate were assessed at the beginning and at the end of the growth stages. In the second assay the YED mediums were diluted to the total, ½, and ¼ content of dextrose and yeast and 0.0 and 0.05 mmol Cd L-1 were added. The pH of the mediums was adjusted to 5. The culture mediums were inoculated and incubated at 30 °C for 18 hours. The yeast growth was not affected by cadmium at high pH, but at low pH the yeast becomes more sensitive to the toxic effect. The yeast susceptibility to cadmium was enhanced by the decrease of yeast extract strength and the increase of dextrose strength.

Effect of standard and neutral-pH peritoneal dialysis solutions upon fibroblasts proliferation

Introduction: Continuous exposition of the peritoneal membrane to conventional dialysis solutions is an important risk factor for inducing structural and functional alterations. Objective: To compare in vitro mouse fibroblast NIH-3T3 cell viability after exposition to a neutral pH dialysis solution in comparison to cells exposed to a standard solution. Methods: Experimental study to compare the effects of a conventional standard or a neutral-pH, low-glucose degradation products peritoneal dialysis solution on the viability of exposed fibroblasts in cell culture. Both solutions were tested in all the commercially available glucose concentrations. Cell viability was evaluated with tetrazolium salt colorimetric assay. Results: Fibroblast viability was significantly superior in the neutral pH solution in comparison to control, in all three glucose concentrations (Optical density in nm-means ± SD: 1.5% 0.295 ± 0.047 vs. 0.372 ± 0.042, p < 0.001; 2.3% 0.270 ± 0.036 vs. 0.337 ± 0.051, p < 0.001; 4.25% 0.284 ± 0.037 vs. 0.332 ± 0.032, p < 0.001; control vs. neutral pH respectively, Student t Test). There was no significant difference in cell viability between the three concentrations of glucose when standard solution was used (ANOVA p = 0.218), although cell viability was higher after exposition to neutral pH peritoneal dialysis fluid at 1.5% in comparison to 2.3 and 4.25% glucose concentrations (ANOVA p = 0.008: Bonferroni 1.5% vs. 2.3% p = 0.033, 1.5% vs. 4.25% p = 0.014, 2.3% vs. 4.25% p = 1.00). Conclusion: Cell viability was better in neutral pH dialysis solution, especially in the lower glucose concentration. A more physiological pH and lower glucose degradation products may be responsible for such results.

The effect of pH and ethanol on the astringent sub-qualities of red wine, and the implications for optimum grape maturity /

The first objective of this study was to identify appropriate sensory descriptors to assess the astringent sub-qualities of red wine. The influence of pH and ethanol on the sensation of astringency in red wine was evaluated, using a de-alcoholized red wine. A portion of the wine was adjusted to the pH values of 3.2, 3.4, 3.6 and 3.8, and another portion was adjusted to ethanol concentrations of 0%, 6%, 12%, and 15%. In addition, the pH 3.4 and 3.6 treatments were adjusted to an ethanol concentration of 12% and 15% all wines were then assessed sensorially and seventeen terms were identified, through panel discussion, to describe the mouth-feel and taste qualities: velvet, aggressive, silk/satin, dry, fleshy, unripe, pucker viscosity, abrasive, heat, chewy, acidity, grippy/adhesive, bitter, balance, overall astringency, and mouth-coat. Descriptive analysis profiling techniques were used to train the panel and measure the intensity of these attributes. It was found that decreasing pH values (averaged across all ethanol concentrations) showed an increase in the overall astringency of the wine. The combined treatments of ethanol and pH, real wine parameters (pH 3.4 and 3.6; 12% and 15% ethanol) did not have an effect on the perception of the astringent sub-qualities of the wine. A time intensity study was also included using the pH and ethanol adjusted wines, which showed that as the ethanol level of the wines increased so did the time to maximum intensity. The second objective was to identify appropriate sensory descriptors to evaluate the influence of grape maturity and maceration technique (grape skin contact) on the astringency sub-qualities of red vinifera wines from Niagara. The grapes were harvested across two dates, representing an early harvest and a late harvest. A portion of the Cabernet Sauvignon grapes wine was divided into three maceration treatments of oneweek maceration, standard two-week maceration, three-week maceration, and MCM. Another portion of both the early and late harvest Cabernet Sauvignon grapes were chaptalized to yield a final ethanol concentration of 14.5%. The wines were assessed sensorially and thirteen terms were identified, through panel discussion, to describe the mouth-feel and taste qualities: carbon dioxide, pucker, acidity, silk/chamois, dusty/chalky/powdery, sandpaper, numbing, grippy/adhesive, dry, mouthcoat, bitter, balance and, overall astringency. Descriptive analysis techniques were used to train the panel and measure the intensity of these attributes. The data revealed few significant differences in the mouth-feel of the wines with respect to maturity; which included differences in overall astringency and balance. There were varietal differences between Cabernet Sauvignon, Cabernet Franc, and Pinot Noir and differences for Cabernet Sauvignon wines due to the length and manner of maceration and as a result of chaptalization. Statistical analysis revealed a more complex mouth-feel for the Pinot Noir wines; and an increase in the intensity of the astringent sub-qualities as a result of the addition of sugar to the wines. These findings have implications for how processing decisions, such as optimum grape maturity and vinification methods may affect red wine quality.

A comparative study of the change in diatom inferred ph of a staircase of lakes in the Algoma District, Northern Ontario /

Four staircase lakes occupying a single watershed located in the Algoma District, north of Lake Superior were chosen for this study. I examined the subfossil diatom assemblage in the top twenty centimeters of the surface sediments in each of these four lakes in an attempt to reconstruct their respective past pH history. From these analyses it was possible to test the hypothesis that the rate of change of diatom inferred pH was not significantly different in lakes located one below the other in a single "staircase" within a single watershed system. My results indicated that the four Z lakes had been acid for at least the last century. The water color of the three upper Z lakes (Z1, Z2 and Z3) was brown (>30 Pt Co units). The bottom lake (Z4) was the only clear water lake in the system «5 Pt Co units). This bottom staircase lake had no muskeg development around its shoreline. The alkaliphilous diatoms in the Z watershed system were important in determining the diatom inferred pH of the four Z lakes. The centric diatoms were extremely rare in the clearwater bottom lake (Z4). The ecology of the Eupodiscales is perhaps important in the interpretation of sediment in the more acid environment. Lake Z4 was the only one that had a progressive as well as a significant decrease in its downcore diatom inferred pH since the early 1960's. This lead me to speculate that the humic substances present in the upper three brown water lakes (Z1, Z2 and Z3) were perhaps Important in buffering them against a further decrease in water pH even though they were located within an area which was sensitive to acid precipitation.

A comparison between diatom inferred ph changes and diatom populations in brownwater and clearwater lakes

The objective of this study was to determine whether clearwater and brownwater lakes differed in their rate of acidification as inferred by subfossil diatoms analyzed in recent downcore sediments. Differences between associations of diatom populations in brownwater and clearwater environments were characterized. Sediment cores were taken from four lakes located north and east of Lake Superior, near Wawa, Ontario. Two of these lakes were humicrich, brownwater lakes ( lakes U1 and CB2). The two other lakes were clearwater lakes ( lakes Xl and CF). The regression of Nygaard log index-alpha for surficial diatom sediments on observed pH ( Inferred pH = 6.57 - 0.82 log index-alpha ), was utilized to infer lake pH in recent sediments of these lakes. Upon analyzing the downcore diatoms, it was discovered that no significant change, in downcore diatom inferred pH, could be detected in the two brownwater lakes. In contrast, the two clearwater lakes showed significant shifts in downcore diatom inferred pH. In one of these lakes, pH had dropped from 5.3 to 4.5, in the top 9.0 cm of the core, while in the second lake, pH had dropped from 5.4 to 5.0 in the top 1.5 cm of the core. These findings suggested that humic substances, found in brownwater lakes, imparted a buffering capacity to these lake waters. In the clearwater lakes, the decrease in pH was very probably a consequence of acid precipitation. The Ambrosia rise ( circa 1890 ) occurred at the same depth in both brownwater lakes ( 11.0 - 12.0 cm). In both clearwater lakes, the Ambrosia rise occurred at a depth of 14.0 - 15.0 cm. This suggested a lower sedimentation rate in the brownwater lakes. pH influenced the total percentage composition of diatom pH indicator groups. Greater numbers of alkaliphilous taxa were found in less acidic lakes ( e.g. Lake Ul ), While greater numbers of acidloving forms were found in highly acidic lakes ( e.g. Lake Xl ). There was a greater abundance of indifferent forms in the brownwater lakes, than in the clearwater lakes. A number of diatom genera and species were found to be associated with either clearwater or brownwater conditions. The centric diatom, ~elosira distans, significantly increased in abundance in the recent sediments of both clearwater lakes. This may be indicating a shift toward a more oligotrophic state within these acidic, clearwater lakes. This study suggested that a pH index based on subfossil diatoms may be a sensitive indicator of changing lake pH. This study also indicated that humic substances may playa more important role, than previously acknowledged, in controlling the pH dynamics of lake waters, and in determining diatom populations.

The production of 4-adminobutyrate in response to treatments reducing cytosolic pH and the regulation of intracellular pH

GABA (4-aminobutyrate) is synthesized through the decarboxylation of LGlu- (L-Glu-+ H+ ---> GABA + C02), and compared to many free amino acids is present in high concentrations in plant cells. GABA levels rise rapidly and dramatically in response to varied stress conditions including anaerobiosis. Recent papers suggest that GABA production and associated H+ consumption are parts of a metabolic pH-stat mechanism which ameliorates the intracellular pH decline associated with anaerobiosis or other treatments. To test this hypothesis GABA production and efflux have been measured in isolated Asparagus sprengeri cells in response to three treatments which potentially cause intracellular acidification. Acid loads were imposed using 60 min of (i) anaerobiosis, (ii) H+/LGlu- cotransport, and (iii) treatment with permeant weak acids (butyric, acetic and propionic). Both intra- and extracellular GABA concentrations increased more than 100% after anaerobiosis, almost 1000% after H+/L-Glu- cotransport (light or dark) and almost 5000/0 after addition of 5 mM butyric acid at pH 5.0. HPLC analysis of amino acids indicates that as GABA concentrations increased in response to butyric acid addition, glutamate concentrations decreased. Time-course studies demonstrated that added butyric acid stimulates GABA production by 2800/0 within 15 seconds. A fluorescent determination of cytosolic pH indicates that addition of butyric or other weak acids resulted in a rapid reduction in cytosolic pH of 0.6 pH units. The half time for the response to butyric acid addition is 2.1 seconds, indicating that the decline in cytosolic pH is rapid enough to account for the rapid stimulation of GABA production. The acid load in response to butyric acid addition was assayed by measurements of 14C-butyric acid uptake. Calculations indicate that GABA production accounted for 45% of the imposed acid load. The biological significance of GABA efflux is not yet understood. The results support the original hypothesis suggesting a role for GABA production in cellular pH regulation.

The regulation of oat coleoptile phosphoenolpyruvate carboxylase and malic enzyme by Hâ ½ and metabolites : kinetic evidence for and against a cytosolic pH-stat

Phosphoenolpyruvate carboxylase (PEPC) and malic enzyme activities in soluble protein extracts of Avena coleoptiles were investigated to determine whether their kinetics were consistent with a role in cytosol pH regulation. Malic enzyme activity was specific for NADP+ and Mn2+. Maximal labelled product formation from [14C]-substrates required the presence of all coenzymes, cofactors and substrates. Plots of rate versus malate concentration, and linear transformations there- 2 of, indicated typical Michaelis-Menten kinetics at non-saturating malate levels and substrate inhibition at higher malate levels. pH increases between 6.5 and 7.25 increased near-optimal activity, decreased the degree of substrate inhibition and the Kmapp(Mn2+) but did not affect the Vmax or Kmapp(malate). Transformed data of PEPC activity demonstrated non-linear plots indicative of non-Michaelian kinetics. pH increases between 7.0 and 7.6 increased the Vmax and decreased the Km app (Mg2+) but did not affect the Kmapp(PEP). Various carboxylic acids and phosphorylated sugars inhibited PEPC and malic enzyme activities, and these effects decreased with pH increases. Metabolite inhibited malic enzyme activity was non-competitive and resulted mainly from Mn2+ chelation. In contrast, metabolite inhibited PEPC activity was unique for each compound tested, being variously dependent on the PEP concentration and the pH employed. These results indicate that fluctuations in pH and metabolite levels affect PEPC and malic enzyme activities similarly and that 3 the in vitro properties of PEPC are consistent with its proposed role in a pH-stat, whereas the in vitro properties of the malic enzyme cannot be interpreted in terms of a role in pH regulation.

The utility of sedimentary diatoms as a measure of historical lake ph

As a result of increased acid precipitation, the pH of a large number of Canadian Shield lakes has been falling. Prior to this study there was no documentation available to explain the history of lake acidification for the Algoma area lakes. In order to obtain this information the diatom inferred pH technique was developed in this study. During two field seasons, July 1981 and July 1982, short sediment cores (circa 25-30 cm) were collected from 28 study lakes located north of Lake Superior, District Algoma, Ontario. The surface sediment diatoms (0-1 cm) from each of these lakes were carefully identified, enumerated, and classified in terms of their pH indicator status. The surface sediment diatom analysis indicated that lake pH is one of the most important factors affecting the species composition and relative abundance of diatom populations. Thus diatom assemblages can be sensitive indicators of lake acidification. When Nygaard's index alpha was plotted against observed lake pH, a statistically significant relationship resulted (r=-0.89; p=pha regression equation was used to construct the pH histories of 4 lakes (lakes X4, CS, U3, and WI). The repeatability of this technique was confirmed by comparing two downcore paleo-pH profiles of Lake WI. These two paleo-pH profiles represented almost identical paleo-pH patterns for Lake WI. The paleo-pH study of Lake X4 revealed that the lake has been rather acidic (pH <5.6) for the last 200 years. It appears that the recent increase in acid precipitation 3 over the last 30 years has not altered the water pH compared to the lake's pH history. However, the paleo-pH study of another acidic lake (Lake CS) indicated that its pH has significantl}* dropped over the last 30 years . During this time the Lake CS pH has dropped almost 2 pH units (7.1 to 5.2). The other two lakes studied for downcore pH were circumneutral in nature . One of these lakes (Lake U3) displayed a relatively stable pH history while the other lake (Lake WI) displayed significant pH fluctuations over post-Ambrosia time. The variable pH history of Lake WI was probably associated with the Algoma sintering plant plume and forest fires. A significant relationship between surface sediment diatoms and observed lake pH and secondly a statistically significant relationship between index alpha and observed pH suggested that diatoms are one of the best indicators of lake pH. Thus diatom inferred pH technique has great potential in explaining the rate of lake acidification.

Synthèse de brosses de polyélectrolytes par polymérisation initiée depuis une surface de mica et étude de leur réponse en fonction du pH et de la force ionique

Cette thèse rapporte le greffage chimique de brosses de polymères neutres de poly(acrylate de tert-butyle) (PtBA) et de brosses chargées d’acide polyacrylique (PAA) sur des substrats de mica afin d’étudier leur conformation en fonction de la densité de greffage, du pH et de la force ionique. Le greffage est réalisé par polymérisation contrôlée par transfert d’atome (ATRP) initiée depuis la surface de mica afin de contrôler la croissance du polymère et sa densité de greffage. L’étude de la conformation des brosses de PtBA et de PAA a été menée avec la technique AFM en mesurant les épaisseurs des films à sec et gonflés sous différentes conditions de solvant, de pH et de force ionique. Une monocouche d’amorceurs est tout d’abord greffée sur du mica porteur de groupes hydroxyles créés par plasma (Ar/H2O). Cette couche a été caractérisée par des mesures d’angle de contact et par la technique TOF-SIMS. L’amorceur greffé a ensuite permis d’initier l’ATRP directement depuis la surface pour former des brosses neutres de PtBA liés de façon covalente au mica. La croissance linéaire de l’épaisseur du film avec la masse molaire du polymère en solution et le taux de conversion montre que la polymérisation est contrôlée. De plus, la ré-initiation des chaînes greffées atteste du caractère vivant de la polymérisation. L’hydrolyse des brosses de PtBA, confirmée par des mesures d’angle de contact, d’épaisseur et par FT-IR, conduit à des brosses de PAA. Les différentes couches greffées sont stables à l’air, en milieu organique et en milieu aqueux et leur gonflement est réversible. Le degreffage de la couche de PAA est observé suite à une longue exposition à pH basique. Cette étude représente le premier exemple de brosses greffées chimiquement sur du mica par polymérisation initiée depuis la surface. La variation des paramètres de la réaction de greffage de l’amorceur, tels que la concentration et la durée de réaction, a permis de contrôler le taux de recouvrement de l’amorceur et la densité de greffage du polymère. Une grande gamme de taux de recouvrement de l’amorceur est accessible et se traduit par un intervalle de densités de greffage allant de faibles à élevées (e.g. 0,04 chaîne/nm2 à 0,5 chaîne/nm2). L’étude de la conformation des chaînes de PtBA dans le DMF montre que cet intervalle de densités recouvre le régime crêpe au régime brosse. Le gonflement de brosses de PAA et la variation de la hauteur de la brosse L ont été étudiés en fonction de la densité de greffage, du pH et du sel ajouté cs (NaCl). Une transition brusque de collapsée à étirée est observée avec l’augmentation du pH, indépendamment de la densité de greffage. A pH neutre, les brosses sont collapsées et se comportent comme des brosses neutres en mauvais solvant. A pH basique, les brosses sont gonflées et chargées et se trouvent dans un régime de Pincus caractéristique des polyélectrolytes forts. En présence de sel, les charges sont partiellement écrantées et les répulsions électrostatiques dominent toujours dans la brosse. Cette étude contribue à une meilleure compréhension du comportement complexe des brosses de polyélectrolytes faibles et apporte un soutien expérimental à la théorie sur le comportement de ces brosses.

Mesure de la concentration en métaux traces dans la solution de sol par microlysimétrie

La présente étude porte sur l’évaluation d’une méthode d’acquisition de la solution de sol présente à l’interface sol-racine, dans la rhizosphère. Cette interface constitue le lieu privilégié de prise en charge par les plantes des contaminants, tels que les métaux traces. Comme les plantes acquièrent ces éléments à partir de la phase liquide, la solution de sol de la rhizosphère est une composante clé pour déterminer la fraction de métaux traces biodisponibles. La microlysimétrie est la méthode in situ la plus appropriée pour aborder les difficultés liées à l’échelle microscopique de la rhizosphère. Ainsi, dans les études sur la biodisponibilité des métaux traces au niveau de la rhizosphère, les microlysimètres (Rhizon©) gagnent en popularité sans, toutefois, avoir fait l’objet d’études exhaustives. L’objectif de cette étude est donc d’évaluer la capacité de ces microlysimètres à préserver l’intégrité chimique de la solution, tout en optimisant leur utilisation. Pour ce faire, les microlysimètres ont été soumis à une série d’expériences en présence de solutions et de sols, où la quantité de solution prélevée et le comportement des métaux traces (Cd, Cu, Ni, Pb, Zn) ont été étudiés. Les résultats montrent que les microlysimètres fonctionnent de façon optimale lorsque le contenu en eau du sol est au-dessus de la capacité au champ et lorsqu’il y a peu de matière organique et d’argile. Les sols sableux ayant un faible contenu en C organique reproduisent mieux le volume prélevé et la solution sous la capacité au champ peut être récoltée. L’utilisation des microlysimètres dans ces sols est donc optimale. Dans les essais en solution, les microlysimètres ont atteint un équilibre avec la solution après 10 h de prélèvement. En respectant ce délai et les conditions optimales préalablement établies (pH acide et COD élevé), les microlysimètres préservent la composition chimique de la solution. Dans les essais en sol, cet équilibre n’a pas été atteint après dix jours et huit prélèvements. Le contenu en matière organique et l’activité microbienne semblent responsables de la modification des concentrations en métaux au cours de ces prélèvements, notamment, dans l’horizon FH où les microlysimètres performent très mal. En revanche, dans l’horizon B, les concentrations tendent à se stabiliser vers la fin de la série de prélèvements en se rapprochant des valeurs de référence. Bien que des valeurs plus élevées s’observent pour les microlysimètres, leurs concentrations en métaux sont comparables à celles des méthodes de référence (extrait à l’eau, lysimètres de terrain avec et sans tension). En somme, les microlysimètres se comportent généralement mieux dans l’horizon B. Même si leur utilisation est plus optimale dans un sol sableux, cet horizon est privilégié pour de futures études sur le terrain avec les microlysimètres.

Caractérisation de la pharmacocinétique de formulations sensibles au pH et de formulations destinées au traitement des intoxications médicamenteuses

La préparation de formulations à libération contrôlée est le domaine des sciences pharmaceutiques qui vise à modifier l’environnement immédiat des principes actifs pour en améliorer l’efficacité et l’innocuité. Cet objectif peut être atteint en modifiant la cinétique de circulation dans le sang ou la distribution dans l’organisme. Le but de ce projet de recherche était d’étudier le profil pharmacocinétique (PK) de différentes formulations liposomales. L’analyse PK, généralement employée pour représenter et prédire les concentrations plasmatiques des médicaments et de leurs métabolites, a été utilisée ici pour caractériser in vivo des formulations sensibles au pH servant à modifier la distribution intracellulaire de principes actifs ainsi que des liposomes destinés au traitement des intoxications médicamenteuses. Dans un premier temps, la PK d’un copolymère sensible au pH, à base de N-isopropylacrylamide (NIPAM) et d’acide méthacrylique (MAA) a été étudiée. Ce dernier, le p(NIPAM-co-MAA) est utilisé dans notre laboratoire pour la fabrication de liposomes sensibles au pH. L’étude de PK conduite sur les profils de concentrations sanguines de différents polymères a défini les caractéristiques influençant la circulation des macromolécules dans l’organisme. La taille des molécules, leur point de trouble ainsi que la présence d’un segment hydrophobe à l’extrémité des chaînes se sont avérés déterminants. Le seuil de filtration glomérulaire du polymère a été évalué à 32 000 g/mol. Finalement, l’analyse PK a permis de s’assurer que les complexes formés par la fixation du polymère à la surface des liposomes restaient stables dans le sang, après injection par voie intraveineuse. Ces données ont établi qu’il était possible de synthétiser un polymère pouvant être adéquatement éliminé par filtration rénale et que les liposomes sensibles au pH préparés avec celui-ci demeuraient intacts dans l’organisme. En second lieu, l’analyse PK a été utilisée dans le développement de liposomes possédant un gradient de pH transmembranaire pour le traitement des intoxications médicamenteuses. Une formulation a été développée et optimisée in vitro pour capturer un médicament modèle, le diltiazem (DTZ). La formulation liposomale s’est avérée 40 fois plus performante que les émulsions lipidiques utilisées en clinique. L’analyse PK des liposomes a permis de confirmer la stabilité de la formulation in vivo et d’analyser l’influence des liposomes sur la circulation plasmatique du DTZ et de son principal métabolite, le desacétyldiltiazem (DAD). Il a été démontré que les liposomes étaient capables de capturer et de séquestrer le principe actif dans la circulation sanguine lorsque celui-ci était administré, par la voie intraveineuse. L’injection des liposomes 2 minutes avant l’administration du DTZ augmentait significativement l’aire sous la courbe du DTZ et du DAD tout en diminuant leur clairance plasmatique et leur volume de distribution. L’effet de ces modifications PK sur l’activité pharmacologique du médicament a ensuite été évalué. Les liposomes ont diminué l’effet hypotenseur du principe actif administré en bolus ou en perfusion sur une période d’une heure. Au cours de ces travaux, l’analyse PK a servi à établir la preuve de concept que des liposomes possédant un gradient de pH transmembranaire pouvaient modifier la PK d’un médicament cardiovasculaire et en diminuer l’activité pharmacologique. Ces résultats serviront de base pour le développement de la formulation destinée au traitement des intoxications médicamenteuses. Ce travail souligne la pertinence d’utiliser l’analyse PK dans la mise au point de vecteurs pharmaceutiques destinés à des applications variées. À ce stade de développement, l’aspect prédictif de l’analyse n’a pas été exploité, mais le côté descriptif a permis de comparer adéquatement diverses formulations et de tirer des conclusions pertinentes quant à leur devenir dans l’organisme.

Optimisation de la concentration en électrolytes au sein des matrices à base de HASCA pour la libération prolongée

Le sel sodique du carboxyméthylamidon à haute teneur en amylose, HASCA (Amylose 60%-amylopectine 40%), est un polymère hydrophile ionique utilisé pour obtenir des comprimés matriciels à libération prolongée. Il est caractérisé par la formation d'un hydrogel lors de la mise en contact avec le milieu de dissolution. La libération du principe actif (PA) à travers ce polymère est principalement contrôlée par la diffusion fickienne et la relaxation du réseau polymérique. De plus, la solubilité du PA est un facteur qui permet de moduler la libération, cependant, la solubilité d’un médicament dépend de la forme utilisée et du pH. Les bases ou les acides libres présentent une solubilité moins élevée que leurs sels. Nous proposons d’étudier l’effet d’une combinaison entre le sel et la forme acide ou le sel et la forme alcaline dans le même comprimé matriciel d’HASCA. Comme objectif de ce travail, nous étudions l’influence de la nature du polymère sur le profil de libération de PA dans un milieu aqueux en gradient de pH à cause de la nature des matrices à base d’HASCA caractérisées par la présence de groupement carboxyliques, ionisés ou non selon l’acidité du milieu de dissolution. Nous étudions également l’influence de la nature du PA (base libre ou son sel vs acide libre ou son sel) sur le profil de libération, ceci en sélectionnant des PAs modèles représentatifs de chaque catégorie. L’influence de changement de proportions entre la forme libre (acide ou base) et son sel sur le profil de libération est aussi investiguée. Pour ce, des comprimés à base de HASCA avec des proportions différentes de, soit le naproxène acide et le naproxène de sodium (PA acide et son sel), soit la tétracycline et le chlorhydrate de tétracycline (PA alcalin et son sel) ont été utilisés. Ceux-ci sont évalués lors des tests de dissolution dans un milieu simulant le milieu gastro-intestinal, selon les normes de l’USP (spectrophotométrie UV). Nous avons également menés des études de vitesse de dissolution intrinsèque sur les PAs purs, afin de déterminer leur solubilité et vitesse de libération dans les même pH de dissolution étudiés. Nous avons réussit d’obtenir des comprimés matriciels à base de HASCA convenables à être administrés une fois par jour en utilisant une combinaison du naproxène acide et son sel comme PA. Tandis que les résultats ont montré qu’en utilisant la tétracycline et son sel, les temps de libération étaient trop élevés pour permettre la réalisation d’une formulation convenable pour une administration quotidienne unique