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Biomedical subjects

S L Hem

Publications and source records attributed to S L Hem.

At least 37 records · Page 2Linked to original sources

Contribution of electrostatic and hydrophobic interactions to the adsorption of proteins by aluminium-containing adjuvants.

The effect of ionic strength and ethylene glycol on the adsorption of bovine serum albumin (BSA) or lysozyme by a commercial aluminium hydroxide or aluminium phosphate adjuvant was studied at pH 7.4 and 25 degrees C. The adsorption of BSA by aluminium hydroxide adjuvant and lysozyme by aluminium phosphate adjuvant was found to be inversely related to ionic strength. This indicates that electrostatic attractive forces contribute to adsorption. The adsorption of lysozyme by aluminium phosphate adjuvant was reduced by the addition of ethylene glycol. However, no change in the adsorption of BSA by aluminium hydroxide adjuvant was noted when up to 40% ethylene glycol was present. This behaviour indicates that hydrophobic forces contribute to the adsorption of lysozyme but not of BSA. However, virtually no adsorption was observed when the protein and the adjuvant had the same surface charge. Thus, attractive forces may not be sufficient to produce adsorption of an antigen by an aluminium-containing adjuvant if electrostatic repulsive forces are present.

Adjuvants, Immunologic↗

Comparison of 24 different adjuvants for inactivated HIV-2 split whole virus as antigen in mice. Induction of titres of binding antibodies and toxicity of the formulations.

The objective of this study was the comparison of the quantity and quality of the humoral immune response against inactivated whole human immunodeficiency virus type 2. Twenty-four different adjuvants were tested. The toxicity of these preparations was determined. Due to the large number of experiments, the animal model used was the NMRI mouse. Sera were assayed for the presence of antibodies by ELISA and Western blot. The toxicity of the adjuvants was determined by observing lethal side-effects occurring within two days after injection of the immunogenic preparations. The results show that polymethylmethacrylate nanoprticles were the best overall adjuvant, inducing the highest titres of antibodies compared with other adjuvants as well as producing a significantly better immune response against a number of individual HIV-2 antigens without any observable toxic side-effects. However, this adjuvant did not induce antibodies against the outer envelope protein gp120, whereas such antibodies were induced by aluminium compounds, Freund's complete and incomplete adjuvants, and fumed silica (Aerosil). This result suggests the necessity of using vaccines with two or more different adjuvants in order to induce the required immune response against physically different antigens.

AIDS Vaccines↗

Relationship between protein adsorptive capacity and the X-ray diffraction pattern of aluminium hydroxide adjuvants.

Thermal treatment during the preparation of aluminium hydroxide adjuvants affects the primary crystallite size of the adjuvant. The primary crystallite size can be characterized by the line broadening of the (020) reflection of the X-ray diffraction pattern. Studies of protein adsorption using bovine serum albumin as a model protein revealed a direct relationship between the albumin adsorptive capacity and the width at half height (WHH) of the (020) reflection in the X-ray diffraction pattern.

Adjuvants, Immunologic↗

Effect of protein adsorption on the surface charge characteristics of aluminium-containing adjuvants.

The effect of adsorbing two model proteins, bovine serum albumin and lysozyme, on the point of zero charge of aluminium-containing vaccine adjuvants was studied. At physiological pH, the adsorption of the negatively charged albumin (isoelectric point = 5.0) by aluminium hydroxide adjuvant (point of zero charge = 11.1) resulted in a decrease in the point of zero charge. In contrast, the adsorption of positively charged lysozyme (isoelectric point = 9.6) by the negatively charged aluminium phosphate adjuvant (point of zero charge = 5.0) resulted in an increase in the point of zero charge. The surface charge characteristics of the aluminium-containing adjuvant dominated at low protein coverage. In contrast, the surface charge characteristics of the adsorbed protein dominated at high protein coverage. Therefore, the physicochemical properties of the antigen-adjuvant complex and not the adjuvant alone should be considered during vaccine preparation.

Adjuvants, Immunologic↗

Characterization of antacid compounds containing both aluminum and magnesium. II. Codried powders.

The composition and antacid properties of six samples of codried antacids containing both aluminum and magnesium were determined. Aluminum hydroxide-magnesium carbonate codried gel and aluminum hydroxide-magnesium hydroxide codried gel were non-homogeneous, as the samples contained combinations of hydrotalcite, amorphous aluminum hydroxide, magnesium hydroxide, magnesium hydroxycarbonate, and magnesium carbonate. All samples passed the preliminary antacid test and had high acid neutralizing capacities. However, the rate of acid neutralization varied between samples. In some cases the rate of acid neutralization at a dose of 400 mg was too slow to raise the pH to 3.0 as required by the Rossett-Rice test.

Aluminum↗

Characterization of antacid compounds containing both aluminum and magnesium. I. Crystalline powders.

The composition and antacid properties of 10 samples of crystalline antacids containing both aluminum and magnesium were determined. The composition was found to vary significantly, even within the same type of antacid. For example, three of four hydrotalcite samples exhibit evidence of the presence of a minor phase of amorphous aluminum hydroxide. Almagate and almagcit, which are claimed to be unique compounds, were found to be composed of hydrotalcite, magnesium hydroxycarbonate, and/or magnesium carbonate and amorphous aluminum hydroxide. All three magaldrate samples examined contained a minor phase of amorphous aluminum hydroxide. All 10 samples passed the preliminary antacid test and had high acid neutralizing capacities. However, the rate of acid neutralization varied between samples. In some cases the rate of acid neutralization at a dose of 400 mg was too slow to raise the pH to 3.0 as required by the Rossett-Rice test.

Aluminum↗

The effect of aluminum hydroxide dissolution on the bleeding of aluminum lake dyes.

The effect of pH on the bleeding of FD&C yellow No. 5 aluminum lake and FD&C red No. 40 aluminum lake was investigated. The pH-bleeding profiles corresponded to the pH-solubility profile of aluminum hydroxide. The similarity of the bleeding profiles of both lake dyes and the pH-solubility profile of aluminum hydroxide indicates that pH related bleeding, other than that occurring by competition with anions, is a result of dissolution of the aluminum hydroxide substrate. This dissolution is related to the properties of the substrate rather than to the structure of adsorbed dye.

Aluminum Hydroxide↗

Contribution of soluble aluminium species to absorption of aluminium from the rat gut in situ.

1. Rat gut perfusion studies in vivo at pH 4, 6 or 8 using aluminium chloride or equimolar aluminium chloride and sodium citrate showed that elevated plasma aluminium concentrations were associated with aluminium solubility in the perfusion. Elevated plasma aluminium levels and soluble aluminium in the perfusate occurred with perfusion of equimolar aluminium chloride and sodium citrate at all three pH values. 2. Partitioning studies in vitro, utilizing water and ethyl acetate, revealed that uncomplexed aluminium exhibited maximum partitioning into the ethyl acetate phase at pH 2.5. When complexed with citrate, aluminium exhibited partitioning over a much broader pH range, pH 2.5-8.0. 3. A direct linear relationship was observed between the soluble aluminium concentration of the perfusate and the increase in the plasma aluminium level, suggesting that soluble aluminium is absorbed by a passive diffusion mechanism.

Aluminum↗

Predicting the adsorption of proteins by aluminium-containing adjuvants.

The adsorption of two model proteins, albumin and lysozyme, by boehmite or amorphous aluminium hydroxyphosphate adjuvants was studied. Electrostatic, attraction has a major role in adsorption. At physiological pH, boehmite, which has a point of zero charge above 7.35, extensively adsorbed albumin, which has an isoelectric point of 4.8, but was not effective in adsorbing lysozyme (isoelectric point, 11.0). Conversely, amorphous aluminium hydroxyphosphate (point of zero charge, 4.0) was effective in adsorbing lysozyme but adsorbed relatively little albumin. The results suggest that the selection of either boehmite or amorphous aluminium hydroxyphosphate as an adjuvant should be based in part on the isoelectric point of the antigen.

Adjuvants, Immunologic↗

Effect of competing anions on binding of bile salts by cholestyramine.

The binding of bile salts by cholestyramine may be influenced by other anions, as the Langmuir adsorption coefficients for three bile salts tested were similar to the model anion, citrate. However, the selectivity coefficient indicated preferential binding of cholate anion in comparison to citrate anion. Binding experiments confirmed cholestyramine's preference for bile salts as the presence of other anions reduced but did not prevent the binding of cholate anion. Binding of cholate anion was reduced in direct relationship to the citrate anion concentration. Prior exposure of cholestyramine to citrate anion caused the binding of cholate anion to decrease slightly. Sequential exposure of cholestyramine to simulated gastric fluid and simulated intestinal fluid containing cholate anion resulted in a decrease in cholate binding which was attributed to competition with anions present in the gastrointestinal fluids. Components of tomato juice and orange juice, fluids, commonly used to enhance ingestion of cholestyramine, also reduced the binding of cholate anion.

Adsorption↗

The importance of surface charge in the optimization of antigen-adjuvant interactions.

The adsorptive behavior of the recombinant malarial antigens R32tet32, R32NS181 and NS181V20 to aluminum hydroxide and aluminum phosphate gels was studied as a function of pH and buffer ions. The Plasmodium falciparum antigen, R32NS181, and the P. vivax antigen, NS181V20, with isoelectric points (pI) of 5.9 and 5.5, respectively, adsorbed readily to the positively charged boehmite form of aluminum hydroxide gel. These two antigens displayed reversible, linear adsorption behavior in the pH range 5-9, with maximal adsorption observed at the lowest pH studied. The addition of acetate buffer ions had little effect on adsorption, while the presence of phosphate decreased adsorption for R32NS181 and NS181V20 by 25 and 40% respectively. The adsorptive behavior of these two antigens with the negatively charged adjuvant, aluminum phosphate, was markedly decreased. The converse situation was observed with the R32tet32 antigen, whose pI is estimated to be 12.8. There was minimal interaction of this antigen with aluminum hydroxide gel except in the presence of phosphate counter ions and significant, nonreversible adsorption with aluminum phosphate gel. Enhanced adsorption of R32tet32 to aluminum hydroxide gel in the presence of phosphate is suggested to be the result of a covalent bond between a surface aluminum and a phosphate anion that modifies the surface charge of the aluminum hydroxide gel. These results indicate that the role of complementary surface charges, both for the ionization state of the protein and for the aluminum adjuvants, is the key in optimizing conditions for significant antigen-adjuvant interactions.

Adjuvants, Immunologic↗

Aluminum compounds used as adjuvants in vaccines.

The structure of nine commercially manufactured aluminum-containing adjuvants was investigated by X-ray diffraction, infrared spectroscopy, transmission electron micrography, and energy dispersive spectrometry. Seven samples which were labeled as aluminum hydroxide were identified as boehmite, a crystalline aluminum oxyhydroxide [AlO(OH)]. However, the degree of crystallinity varied between the samples. Two samples which were labeled as aluminum phosphate were found to be amorphous aluminum hydroxyphosphate. Buffer anions and sulfate anions substitute for hydroxyls in the amorphous aluminum hydroxide formed by the in situ alum precipitation method. Finally, the aluminum-containing adjuvant in diphtheria and tetanus toxoid, U.S.P., produced by three manufacturers was characterized.

Adjuvants, Pharmaceutic↗

In vitro adsorption of bile salts by colestipol hydrochloride.

The acid-base titration of colestipol hydrochloride exhibits no sharp inflection points, indicating a weakly basic anion-exchange copolymer. The swelling of colestipol hydrochloride in water and the adsorption of cholate anion are inversely related to pH and are, therefore, related to the ionization state of the copolymer. The Langmuir adsorption parameters at pH 7.5 and 37 degrees C are similar for cholate, glycocholate, and taurocholate anions. Adsorption capacity was not related to particle size and exceeded the adsorptive capacity of the external surface by three orders of magnitude. Therefore, it is believed that the swelling of colestipol hydrochloride makes extensive internal surface area available for adsorption of bile salts. The rate of adsorption depends on the concentration of sodium cholate to which the colestipol hydrochloride is exposed. Adsorption was complete within 5 min when the concentration was below the adsorptive capacity. In contrast, adsorption at levels of sodium cholate at or above the adsorptive capacity was not complete within a 3-hr test period.

Adsorption↗

Effect of anions on adsorption of bile salts by colestipol hydrochloride.

The Langmuir affinity constant and adsorptive capacity for the adsorption of citrate anion or cholate anion by colestipol hydrochloride at pH 7.5, 37 degrees C, were similar. Prior exposure of colestipol hydrochloride to citrate anion caused the adsorption of cholate anion to decrease slightly in comparison to a control utilizing only cholate anion. The concentration of citrate anion was found to be directly related to the decrease in cholate anion adsorption. Simultaneous exposure of colestipol hydrochloride to citrate and cholate anions at pH 7.5, 37 degrees C, resulted in the same adsorption of cholate anion as sequential exposure to citrate anion followed by cholate anion. Sequential exposure of colestipol hydrochloride to simulated gastric fluid and simulated intestinal fluid containing cholate anion resulted in a small decrease in cholate adsorption which was attributed to competition with phosphate anion in simulated intestinal fluid. Pepsin in the simulated gastric fluid did not affect adsorption of cholate anion from simulated intestinal fluid. Preexposure to components of tomato juice and orange juice also slightly reduced the adsorption of cholate anion by colestipol hydrochloride.

Adsorption↗

Validation of fiber-optic Doppler anemometry (FODA) for characterizing the droplet size of emulsions.

Fiber-optic Doppler anemometry (FODA) is a useful tool to characterize polydisperse systems such as emulsions. The mean droplet radius of a model emulsion determined by FODA matched the mean radius determined by sizing droplets from a freeze-fractured freeze-etched scanning electron photomicrograph. The mean droplet radius determined by the Coulter technique was four times too large because the small droplets were not detected. The utility of FODA was further illustrated by its ability to accurately size droplets and monitor the coalescence upon aging of an intravenous lipid emulsion.

Emulsions↗

Effect of shear on the apparent viscosity of amorphous carbonate ion containing aluminum hydroxide suspensions.

The application of shear to carbonate ion containing aluminum hydroxide suspensions caused a change in the apparent viscosity by two possible mechanisms: change in the surface charge because of desorption of specifically adsorbed carbonate ion, and aggregate dispersal and formation of more extensive particle networks. The desorption of specifically adsorbed carbonate ion is related to the expansion of the air-liquid interface during shear. Shear-inducing processing equipment which generates a minimal amount of new air-liquid interface was found to produce the least change in pH and, consequently, in surface charge. However, viscosity increases caused by aggregate dispersal and formation of more extensive particle networks may occur without a shear-induced change in surface charge.

Aluminum Hydroxide↗

Role of water in the aging of aluminum hydroxide suspensions.

The rate of acid neutralization of anhydrous suspensions of amorphous aluminum hydroxide in methanol did not change during aging. At low water content, when all of the water was adsorbed, an initial decrease in the rate of acid neutralization was observed but no further change occurred during aging. When enough water was present to exceed the adsorptive capacity and produce water in the bulk methanol, the initial rate of acid neutralization decreased and a decrease in the rate of acid neutralization also occurred during aging. The decrease in rate of acid neutralization during aging is believed to be due to polymorphic transformation of the amorphous aluminum hydroxide and aggregation. The change caused by aggregation could be reversed by dehydration or sonication, but the change due to polymorphic transformation could not be reversed.

Aluminum Hydroxide↗