Search PubMed⌕ Search

Biomedical subjects

Bruce Campbell

Publications and source records attributed to Bruce Campbell.

At least 19 recordsLinked to original sources
PubMed2006

Coalescence stability of emulsions containing globular milk proteins.

This review summarizes a large set of related experimental results about protein adsorption and drop coalescence in emulsions, stabilized by globular milk proteins, beta-lactoglobulin (BLG) or whey protein concentrate (WPC). First, we consider the effect of drop coalescence on the mean drop size, d32, during emulsification. Two regimes of emulsification, surfactant-rich (negligible drop coalescence) and surfactant-poor (significant drop coalescence) are observed in all systems studied. In the surfactant-rich regime, d32 does not depend on emulsifier concentration and is determined mainly by the interfacial tension and the power dissipation density in the emulsification chamber, epsilon. In the surfactant-poor regime and suppressed electrostatic repulsion, d32 is a linear function of the inverse initial emulsifier concentration, 1/C(INI), which allows one to determine the threshold emulsifier adsorption needed to stabilize the oil drops during emulsification, Gamma* (the latter depends neither on oil volume fraction nor on epsilon). Second, we study how the BLG adsorption on drop surface changes while varying the protein and electrolyte concentrations, and pH of the aqueous phase. At low electrolyte concentrations, the protein adsorbs in a monolayer. If the pH is away from the isoelectric point (IEP), the electrostatic repulsion keeps the adsorbed BLG molecules separated from each other, which precludes the formation of strong intermolecular bonds during shelf-storage as well as after heating of the emulsion. At higher electrolyte concentration, the adsorption Gamma increases, as a result of suppressed electrostatic repulsion between the protein molecules; monolayer or multilayer is formed, depending on protein concentration and pH. The adsorption passes through a maximum (around the protein IEP) as a function of pH. Third, the effect of various factors on the coalescence stability of "fresh" emulsions (up to several hours after preparation) was studied. Important conclusion from this part of the study is the establishment of three different cases of emulsion stabilization: (1) electrostatically-stabilized emulsions with monolayer adsorption, whose stability is described by the DLVO theory; (2) emulsions stabilized by steric repulsion, created by protein adsorption multilayers - a simple model was adapted to describe the stability of these emulsions; and (3) emulsions stabilized by steric repulsion, created by adsorption monolayers. Fourth, we studied how the emulsion stability changes with storage time and after heating. At high electrolyte concentrations, we find a significant decrease of the coalescence stability of BLG-emulsions after one day of shelf-storage (aging effect). The results suggest that aging is related to conformational changes in the protein adsorption layer, which lead to formation of extensive lateral non-covalent bonds (H-bonds and hydrophobic interactions) between the adsorbed molecules. The heating of BLG emulsions at high electrolyte concentration leads to strong increase of emulsion stability and to disappearance of the aging effect, which is explained by the formation of disulfide bonds between the adsorbed molecules. The emulsion heating at low electrolyte concentration does not affect emulsion stability - this result is explained with the electrostatic repulsion between the adsorbed molecules, which keeps them separated so that no intermolecular disulfide bonds are formed. Parallel experiments with WPC-stabilized emulsions show that these emulsions are less sensitive to variations of pH and thermal treatment; no aging effect is detected up to 30 days of storage. The observed differences between BLG and WPC are explained with the different procedures of preparation of these protein samples (freeze-drying and thermally enhanced spray-drying, respectively). Our data for emulsion coalescence stability are compared with literature results about the flocculation stability of BLG emulsions, and the observed similarities/differences are explained by considering the structure of the protein adsorption layers.

Computer Simulation↗
PubMed2006

Suppression of serum luteinizing hormone in postmenopausal women by an orally administered nonpeptide antagonist of the gonadotropin-releasing hormone receptor (NBI-42902).

CONTEXT: Parenteral administration of peptide GnRH analogs is widely used in clinical practice for the suppression of pituitary gonadotropins. NBI-42902 is an orally available, high-affinity nonpeptide antagonist of the human GnRH receptor. OBJECTIVE: The objective was to evaluate the safety, pharmacokinetics, and inhibitory effects on gonadotropin secretion of NBI-42902 in postmenopausal women. DESIGN: This was a phase I, double-blind, placebo-controlled, single-dose study with sequential dose escalation. PARTICIPANTS: Fifty-six healthy, postmenopausal women were included. FSH levels were greater than 40 IU/liter, and body mass index was within 20% of ideal values for all subjects. INTERVENTIONS: Subjects were administered 5, 10, 25, 50, 75, 100, 150, or 200 mg NBI-42902 as an oral solution. MAIN OUTCOME MEASURES: Safety, tolerability, and serum LH and FSH concentrations were evaluated. RESULTS: NBI-42902 was well tolerated. Serum LH concentrations rapidly declined, and dose-dependent suppression was observed. Maximal change from baseline LH concentrations ranged from -19 +/- 5% in the 5-mg group to -55 +/- 2% in the 150-mg group. Suppression of FSH was less pronounced (-15 to -22% of baseline). NBI-42902 was rapidly absorbed after oral administration with a terminal elimination half-life ranging from 2.7 +/- 0.3 to 4.8 +/- 0.8 h. A clear relationship between plasma NBI-42902 concentrations and LH suppression was evident. CONCLUSIONS: Dose-dependent LH suppression was achieved by oral administration of a nonpeptide GnRH antagonist suggesting that compounds such as NBI-42902 may enable adjustable gonadotropin suppression as part of novel treatment strategies for benign gynecological conditions.

Administration, Oral↗
PubMed2006

Effect of thermal treatment, ionic strength, and pH on the short-term and long-term coalescence stability of beta-lactoglobulin emulsions.

We present experimental results about the effects of thermal treatment, ionic strength, and pH on the protein adsorption and coalescence stability of freshly prepared (2 h after emulsification) and 6-day-stored emulsions, stabilized by the globular protein beta-lactoglobulin (BLG). In all emulsions studied, the volume fraction of the dispersed soybean oil is 30% and the mean drop diameter is d(32) approximately 40 microm. The protein concentration, C(BLG), is varied between 0.02 and 0.1 wt %, the electrolyte concentration, C(EL), between 1.5 mM and 1 M, and pH between 4.0 and 7.0. The emulsion heating is performed at 85 degrees C, which is above the denaturing temperature of BLG. The results show that, at C(BLG) > or = 0.04 wt %, C(EL) > or = 150 mM, and pH > or = 6.2, the heating leads to higher protein adsorption and to irreversible attachment of the adsorbed molecules, which results in enhanced steric repulsion between the protein adsorption multilayers and to higher emulsion stability. At low electrolyte concentration, C(EL) < or = 10 mM, the emulsion stability is determined by electrostatic interactions and is not affected significantly by the emulsion heating. The latter result is explained by electrostatic repulsion between the adsorbed protein molecules, which keeps them separated from each other and thus precludes the formation of disulfide covalent bonds in the protein adsorption layer. The coalescence stability of heated and nonheated emulsions is practically the same and does not depend on C(EL), when pH is around the isoelectric point (IEP) of the protein molecules. This is explained with the adsorption of uncharged BLG molecules, in compact conformation, which stores the reactive sulfhydryl groups hidden inside the molecule interior, thus preventing the formation of covalent intermolecular bonds upon heating. We studied also the effect of storage time on the stability of heated and nonheated emulsions. The stability of nonheated emulsions (C(BLG) = 0.1 wt %, C(EL) > or = 150 mM, and pH = 6.2) significantly decreases after 1 day of storage (aging effect). In contrast, no aging effect is observed after emulsion heating. FTIR spectra of heated and nonheated, fresh and aged emulsions suggest that the aging effect is caused by slow conformational changes of the protein molecules in the adsorption layer, accompanied with partial loss of the ordered secondary structure of the protein and with the formation of lateral noncovalent bonds (H-bonds and hydrophobic interactions) between the adsorbed molecules. After thermal treatment of the BLG emulsions, the molecules preserve their original secondary structure upon storage, which eliminates the aging effect.

Animals↗
PubMed2005

Effects of electrolyte concentration and pH on the coalescence stability of beta-lactoglobulin emulsions: experiment and interpretation.

Experimental results are presented about the effects of ionic strength and pH on the mean drop-size after emulsification and on the coalescence stability of emulsions, stabilized by a globular protein beta-lactoglobulin (BLG). The mean drop-size is determined by optical microscopy, whereas the coalescence stability is characterized by centrifugation. In parallel experiments, the zeta-potential and protein adsorption on drop surface are determined. The experiments are performed at two different BLG concentrations, 0.02 and 0.1 wt%. The electrolyte concentration in the aqueous phase, C(EL), is varied between 1.5 mM and 1 M, and pH is varied between 4.0 and 7.0. The experiments show that the mean drop-size after emulsification depends slightly on C(EL), at fixed protein concentration and natural pH = 6.2. When pH is varied, the mean drop-size passes through a maximum at fixed protein and electrolyte concentrations. A monolayer protein adsorption is registered in the studied ranges of C(EL) and pH at low BLG concentration of 0.02 wt%. In contrast, a protein multilayer is formed at higher BLG concentration, 0.1 wt%, above a certain electrolyte concentration (C(EL) > 100 mM, natural pH). The experimental results for the emulsion coalescence stability are analyzed by considering the surface forces acting between the emulsion drops. The electrostatic, van der Waals, and steric interactions are taken into account to calculate the barriers in the disjoining pressure isotherm at the various experimental conditions studied. The comparison of the theoretically calculated and the experimentally determined coalescence barriers shows that three qualitatively different cases can be distinguished. (1) Electrostatically stabilized emulsions, with monolayer protein adsorption, whose stability can be described by the DLVO theory. (2) Sterically stabilized emulsions, in which the drop-drop repulsion is created mainly by overlapping protein adsorption multilayers. A simple theoretical model is shown to describe emulsion stability in these systems. (3) Sterically stabilized emulsions with a monolayer adsorption on drop surface.

Adsorption↗
PubMed2004

Evaluation of the precision of drop-size determination in oil/water emulsions by low-resolution NMR spectroscopy.

The accuracy of the recently reported low-resolution NMR method (Goudappel, G. J. W.; et al. J. Colloid Interface Sci. 2001, 239, 535) for the determination of drop-size distribution in oil-in-water emulsions is evaluated by comparing the NMR results with precise data from video-enhanced optical microscopy. A series of 27 soybean-oil-in-water emulsions, differing in their mean drop size, polydispersity, oil volume fraction, and emulsifier, is studied. Soybean oil is selected as a typical component of food emulsions. The experimental error of our optical procedure for drop-size determination is estimated to be around 0.3 microm, which allows us to use the microscopy data as a reference for the mean drop-size and distribution width of the studied emulsions, with known experimental error. The main acquisition parameters in the NMR experiment are varied to find their optimal values and to check how the experimental conditions affect the NMR results. Comparison of the results obtained by the two methods shows that the low-resolution NMR method underestimates the mean drop size, d33, by approximately 20%. For most of the samples, NMR measures relatively precisely the distribution width (+/-0.1 to 0.2 dimensionless units), but for approximately 20% of the samples, larger systematic deviation was registered (underestimate by 0.3-0.4 units). No correlation is found between the emulsion properties and the relative difference between the microscopy and NMR data. Possible reasons for the observed discrepancy between NMR and optical microscopy are discussed, and some advantages and limitations of the low-resolution NMR method are considered.

Emulsions↗
PubMed2004

Surface forces in model oil-in-water emulsions stabilized by proteins.

We have employed two complementary techniques, namely, the magnetic chaining technique (MCT) and a variant of the Mysels cell to obtain data concerning the repulsive interaction profiles between protein layers formed at liquid-liquid interfaces. For BSA-stabilized systems, a long-ranged repulsion is operative. It is not of an electrostatic origin, but originates most probably from the formation of multiple protein layers at the interface. The interactions between beta-casein layers formed at the water/oil interface are governed by electrostatic repulsion. Due to the relatively large final thickness of approximately 20 nm, the van der Waals contribution to the total disjoining pressure is inferior. The oscillatory component is also negligible for the studied protein concentration of 0.1 wt.%. For both proteins, the extracted information describes the situation where the protein-covered surfaces are approached/manipulated in a quasi-static manner. We observe a very good agreement between the data obtained from MCT and Mysels cell. The comparison of our results with literature data from surface force apparatus (SFA) experiments reveals a substantial difference in the force laws existing between protein-stabilized liquid droplets and mica surfaces covered by proteins. We explain this discrepancy in terms of the different protein absorption on solid and liquid interfaces. We also measured the threshold force necessary to induce irreversible flocculation in beta-casein and beta-lactoglobulin (BLG) stabilized emulsions. Under similar conditions, the threshold flocculation force is higher for beta-casein than for BLG stabilized droplets. The flocs formed from BLG covered droplets are tight and remain without visible change for at least 48 h. We speculate that the flocculation is due to formation of protein aggregates between the approaching droplets.

Adsorption↗
PubMed2004

Long-term ovarian function in sheep after ovariectomy and autotransplantation of cryopreserved cortical strips.

Transplantation of cryopreserved ovarian tissue offers a means of preserving reproductive function in girls/women whose ovarian function is compromised by radio- and/or chemotherapy for cancer. Studies in small laboratory rodents have demonstrated that fertility can be restored by transplanting whole cryopreserved ovaries. In large animals, it is not possible to freeze or transplant ovaries without vascular anastomosis. However, primordial oocytes in cortical strips survive freezing, thawing and culture in vitro. We have used sheep as an experimental model for the human because the size of the ovary and length of folliculogenesis (4-6 months) are similar. Following orthotopic transplantation the grafts, become vascularised within a few days and ovulatory cycles become established by 4 months. Several lambs have been born in ewes after autotransplantation of the grafts which continue to function for up to 2 years. The levels of FSH remain consistently raised after transplantation due to a reduced secretion of inhibin A, reflecting the reduction in the size of the ovarian pool of follicles.

Animals↗