Search PubMed⌕ Search

Biomedical subjects

J L White

Publications and source records attributed to J L White.

At least 91 records · Page 5Linked to original sources

Ferritin: design and formation of an iron-storage molecule.

Although essential for most forms of life, too much iron is harmful. To cope with these antagonistic phenomena an iron-storage molecule, ferritin, has evolved. The structure of horse spleen apoferritin, which has recently been refined, consists of 24 symmetrically related subunits forming a near-spherical hollow shell. In ferritin the central cavity is occupied by an iron core of 'ferrihydrite', a geologically ephemeral mineral found in hot or cold springs and in mine workings, or produced in the laboratory by heating solutions of ferric salts. Ferritin itself forms most readily from apoferritin, in the presence of dioxygen, from FeII, not FeIII. Access to its interior is through small intersubunit channels, and the protein influences both the rate of FeII-oxidation and the form of oxide produced.

Animals↗

Mechanism of freeze-thaw instability of aluminum hydroxycarbonate and magnesium hydroxide gels.

The effect of freeze-thaw cycles on the physical stability of aluminum hydroxycarbonate and magnesium hydroxide gels was studied. Coagulation following a freeze-thaw cycle, leading to the formation of visible aggregates, affected the content uniformity of both gels. The freeze-thaw cycles did not affect the crystal form or surface characteristics of the gels as determined by X-ray powder diffraction and point of zero charge, but caused a slight reduction in the rate of acid neutralization and a large increase in the rate of sedimentation. The greatest effect was observed after the first freeze-thaw cycle. While the duration of freezing was not a factor, the rate of freezing was important and was inversely related to the aggregate size. The aggregates which formed following a freeze-thaw cycle were not redispersed by shaking, but were reversed by ultrasonic treatment or homogenization. The adsorption of polymers or surface-active agents prior to freezing reduced and, in some cases, prevented the formation of aggregates. The physical instability produced by a freeze-thaw cycle was explained by the modified DLVO theory. The force exerted on the particles by the growing ice crystals forced the particles into the primary minimum, producing strong interparticle attraction. On thawing, simple agitation did not provide enough force to overcome the attractive force of the primary minimum. Adsorption of polymers or surface-active agents increased the steric repulsive force and prevented the particles from reaching the primary minimum.

Aluminum Hydroxide↗

Desorption of carbonate from aluminum hydroxycarbonate gel by nitrogen purging.

Carbonate was completely desorbed from amorphous aluminum hydroxycarbonate gel by purging with nitrogen. The reversibility of carbonate adsorption suggests that aluminum hydroxycarbonate particles are composed of planes of aluminum hydroxide with carbonate adsorbed at edge aluminum sites. A slow-reacting phase which was identified as a precursor of gibbsite, formed when the carbonate/aluminum molar ratio was less than 0.20.

Adsorption↗

Properties of carbonate-containing aluminum hydroxide produced by precipitation at constant pH.

Carbonate-containing aluminum hydroxide was precipitated at constant pH at intervals of 0.5 pH units from pH 6 to 10 by pumping 0.5 M AlCl3 into the reaction vessel at a constant rate of 2 mL/min and infusing 2 M Na2CO3 at a rate necessary to maintain the desired pH. The pH of precipitation affected both the particle size and the composition of the precipitate. The particle size of the precipitate decreased as the pH of precipitation was increased from 6 to 10. The precipitates formed between pH 7.5 and 9.5 contained crystalline sodium aluminum hydroxycarbonate (dawsonite) in addition to amorphous carbonate-containing aluminum hydroxide.

Aluminum Hydroxide↗

Exchange of sodium by magnesium in aluminum hydroxycarbonate gel.

Approximately 90% of the sodium present in a washed aluminum hydroxycarbonate gel was removed by exchange with magnesium. This behavior supports recent structural studies which have suggested that cations such as sodium serve as counterions in aluminum hydroxycarbonate gel. However, sodium could not be removed from dihydroxyaluminum sodium carbonate by exchange with magnesium because sodium is part of the crystal structure. It is hypothesized that aluminum hydroxycarbonate gels which resist removal of sodium are actually mixtures containing dihydroxyaluminum sodium carbonate in addition to aluminum hydroxycarbonate.

Aluminum Hydroxide↗

Adsorption of phosphate by aluminum hydroxycarbonate.

Phosphate is specifically adsorbed by aluminum hydroxycarbonate by anion ligand exchange. IR analysis indicated that phosphate exchanged with specifically adsorbed carbonate. Adsorption is favored by low pH and is inversely related to particle size. Adsorption of phosphate decreases the rate of acid neutralization of aluminum hydroxycarbonate. The results are applied to the treatment of hyperphosphatemia and hypophosphatemia.

Adsorption↗

Adsorption of pepsin by aluminum hydroxide I: Adsorption mechanism.

Adsorption of pepsin by gibbsite and boehmite, non-acid-reactive forms of aluminum hydroxide, was observed and related to the surface area of the adsorbent. Adsorption was pH dependent, with maximum adsorption occurring between pH 2.7-3.3 for gibbsite and pH 2.7-4.3 for boehmite. Electrostatic attraction was an important adsorption mechanism at the pH conditions encountered in the GI tract; the isoelectric point of pepsin was approximately 1, giving it a negative charge, and the point of zero charge for the adsorbents was greater than 9, giving them a positive charge. However, the pH-adsorption profile can not be fully explained by electrostatic considerations. Desorption studies indicate the importance of specific adsorption because pepsin was not desorbed by washing with acidified water, but was partly desorbed by exchange with phosphate. The IR spectrum of adsorbed pepsin also suggested that specific adsorption of pepsin occurred through anionic ligand exchange involving carboxylate groups of pepsin and surface aluminum ions.

Adsorption↗

Adsorption of pepsin by aluminum hydroxide II: Pepsin inactivation.

Pepsin adsorbed on gibbsite or boehmite, non-acid-reactive forms of aluminum hydroxide, had a significantly lower activity than pepsin in solution. IR and desorbed pepsin activity studies showed that the reduced activity of adsorbed pepsin was not due to denaturation of pepsin on adsorption. Steric occlusion of the active site, following pepsin adsorption, was responsible for the lower activity of pepsin adsorbed on gibbsite. The porous morphology of boehmite caused diffusional resistance and steric exclusion, contributing to the decreased activity of adsorbed pepsin. The specific inactivation of pepsin by adsorption on aluminum hydroxide may be important in ulcer therapy.

Adsorption↗

Stabilization of aluminum hydroxide gel by specifically adsorbed carbonate.

Ion-free aluminum hydroxide gel, prepared by the hydrolysis of aluminum tri-sec-butoxide, was observed by IR, X-ray analysis, and pH-stat titration to undergo rapid structural changes leading to the formation of pseudoboehmite and bayerite. The rate of development of order was directly related to the water-aluminum molar ratio. The Al--O bands at 625 and 470 cm-1 were the most sensitive indicators of the development of order in the gel structure. Direct evidence for the stabilizing effect of specifically adsorbed carbonate was obtained when carbon dioxide was introduced during the hydrolysis of aluminum tri-sec-butoxide. The resulting aluminum hydroxycarbonate gel possessed excellent antacid properties, retained its amorphous nature upon aging, and contained no cations other than aluminum. Hydrolysis of aluminum tri-sec-butoxide in the presence of stoichiometric amounts of sodium bicarbonate resulted in the immediate formation of crystalline sodium aluminum hydroxycarbonate (dawsonite).

Adsorption↗

Effect of surface charge and particle size on gel structure of aluminum hydroxycarbonate gel.

The effect of surface charge and particle size on the gel structure of aluminum hydroxycarbonate gel was studied through the use of a specially designed tension cell. Surface charge has a major effect on the coefficient of bulk compressibility. The charged state is more compressible at lower tensions while the neutral gel is more compressible at higher tensions. In addition, physical properties of gels having a small particle size are more profoundly influenced by interparticle forces than are gels consisting of larger particles. The effect of surface charge and particle size on gel structure is applied to physical properties such as viscosity and dewatering.

Aluminum Hydroxide↗

Effect of the pH-zero point of charge relationship on the interaction of ionic compounds and polyols with aluminum hydroxide gel.

The adsorption of magnesium nitrate, docusate sodium, and mannitol by chloride-containing aluminum hydroxide gel or aluminum hydroxycarbonate gel can be directly related to the surface charge characteristics of the aluminum hydroxide gel as determined by the pH-zero point of charge (ZPC) relationship. Magnesium cation is completely adsorbed under pH conditions where the gel has a negative surface charge, i.e. when the pH is above the ZPC. Docusate sodium is more strongly adsorbed when the pH-ZPC relationship causes the surface charge of aluminum when the pH-ZPC relationship causes the surface charge of aluminum hydroxycarbonate gel to be positive indicating adsorption of the docusate anion. However, adsorption also occurred when the pH was above the ZPC suggesting that adsorption of the hydrophobic portion of docusate anion by van der Waals forces also contributes to the overall adsorption mechanism. Mannitol is adsorbed under all pH conditions. However, greater adsorption occurs when the pH is above the ZPC. Maximum hydrogen bonding is believed to occur when mannitol acts as the proton donor and the negative aluminum hydroxycarbonate gel surface serves as the proton acceptor.

Adsorption↗

Formation of hydrotalcite in mixtures of aluminum hydroxycarbonate and magnesium hydroxide gels.

IR and X-ray analysis demonstrate that hydrotalcite forms during the aging of aluminum hydroxycarbonate gel and magnesium hydroxide gel mixtures. The formation of hydrotalcite produces a change in the pH-stat titrigram and a sharp increase in the pH of the mixture. Hydrotalcite was noted earlier in mixtures having a high molar ratio of magnesium to aluminum, a high total gel concentration, a high initial pH, or in mixtures stored at elevated temperatures. The addition of sorbitol to the mixtures substantially delayed the appearance of hydrotalcite. Nonacid-reactive hydrotalcite formed when mixtures of chloride-containing aluminum hydroxide gel and magnesium hydroxide gel were aged.

Aluminum Hydroxide↗

Neutralization of acid in the rumen by magnesium oxide and magnesium carbonate.

Two reagent and two feed grade magnesium oxides and reagent grade magnesium carbonate, sodium bicarbonate, and calcium carbonate were evaluated to ascertain their ability to neutralize acid in the rumen. Rumen fluid pH was increased in vitro, compared to the control, by antacid compounds, and their increased ranked: calcium carbonate less than feed grade magnesium oxide A less than light magnesium oxide and feed grade magnesium oxide B less than heavy magnesium oxide less than magnesium carbonate less than sodium bicarbonate. Titrations at constant pH's ranging from 3.0 to 7.5 indicated that these magnesium compounds were reactive at pH's normally in the rumen although reactivity decreased with increasing pH. Intraruminal doses of feed grade magnesium oxide A and calcium carbonate did not change rumen fluid pH for other compounds ranked: feed grade magnesium oxide B less than magnesium carbonate less than heavy magnesium oxide. Feeding of heavy magnesium oxide or magnesium carbonate increased rumen fluid pH as compared to the control diet. Feeding feed grade magnesium oxide B in three quantities to cattle resulted in proportional increased in fecal pH and fluidity of feces. Two feed grade magnesium oxides differed in their ability to neutralize acid in the rumen.

Animals↗

Evaluation of antacid suspensions containing aluminum hydroxide and magnesium hydroxide.

Liquid antacid suspensions containing aluminum hydroxide and magnesium hydroxide were evaluated for composition, antacid properties, and product quality. The equivalent aluminum oxide and magnesium hydroxide content was determined by chelatometric titration, and sodium content was determined by flame photometry. Antacid properties measured were acid-consuming capacity, antacid effectiveness (preliminary antacid test, acid-neutralizing capacity test), and pH-stat titration. Content uniformity, consistency of the antacid properties, and microbiological content were examined for each product. Data are presented for 36 products for which samples from four or more lots were obtained. The ratio of percentage of equivalent aluminum oxide to percentage of magnesium hydroxide ranged from 1:0.6 to 1:3.5; this range allows for selection of the desired balance between the laxative effect of magnesium hydroxide and the constipating effect of aluminum hydroxide. Based on a daily dose of 280 meq of antacid, the sodium content of the products tested ranged from less than 2% to approximately 45% of the 500 mg per day of sodium allowed in a sodium-restricted diet. The concept of bioavailability was related to the amount of the antacid reacting at pH 3, 37 degrees C during the estimated gastric residence time of 15 minutes. Antacid suspensions are available which will react almost completely (neutralizing greater than 90% of the theoretical quantity of acid) during the estimated gastric residence time. Approximately 4% of the samples contained unacceptable numbers of bacteria. An antacid suspension cannot be adequately evaluated by a single test; choice of a product should be based on an evaluation that integrates several characteristics including sodium content, time and volume required to neutralize a given amount of acid, and uniformity of content.

Aluminum Hydroxide↗

Sepiolite, a potential excipient for drugs subject to oxidative degradation.

Sepiolite, a member of the fibrous mineral group of clays, is relatively free of surface ferric iron and does not accelerate significantly the oxidative degradation of hydrocortisone. The compatibility of sepiolite with drugs that can undergo oxidative degradation is in sharp contrast to the catalytic effect of attapulgite, another fibrous mineral, which contains a significant amount of surface ferric iron and which therefore accelerates oxidative degradation. Sepiolite adsorbs hydrocortisone by a weak adsorption mechanism, which was shown by IR spectroscopy to be chiefly due to hydrogen bonding. However, accelerated oxidative degradation of the adsorbed hydrocortisone does not occur. Maximum adsorption occurs at pH 7-8.5. Desorption occurs readily by washing with water. Sepiolite has similar rheological properties to attapulgite. The results of this study suggest that sepiolite may be useful as a pharmaceutical excipient for drugs that undergo oxidative degradation.

Adsorption↗