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At least 1,711 records · Page 95Linked to original sources
PubMed2003

Effect of colloidal carriers on ascorbyl palmitate stability.

Active compounds can be protected against degradation by incorporation into colloidal carrier systems. The stabilizing effect of carrier systems for ascorbyl palmitate (AP) was investigated using microemulsions (ME), liposomes and solid lipid nanoparticles (SLN). Analysis of chemical stability by HPLC showed that AP is most resistant against oxidation in non-hydrogenated soybean lecithin liposomes, followed by SLN, w/o and o/w ME, and hydrogenated soybean lecithin liposomes. The molecular environment of the AP-like nitroxide probe (C(16)-Tempo) in colloidal carriers was characterized using electron paramagnetic resonance (EPR) spectroscopy. We have found that the nitroxide groups are located in environments with different polarity and mobility. The hydrophilic part of AP is the reactive moiety, and high stability is obtained in systems in which this part is exposed to a less polar environment. Additionally, the determined accessibility of nitroxide groups to reduction correlated well with the chemical stability of AP. It is more deeply immersed in the interface when entrapped in a liquid-state carrier than when applied in gel-state particles. Encapsulation of AP in SLN core leads to greater stability. We conclude that the location of the sensitive group of the drug-molecule in a carrier system is crucial for its stability.

Ascorbic Acid↗
PubMed1989

Stability of symmetric idiotypic networks--a critique of Hoffmann's analysis.

Hoffmann (1982) analysed a very simple model of suppressive idiotypic immune networks and showed that idiotypic interactions are stabilizing. He concluded that immune networks provide a counterexample to the general analysis of large dynamic systems (Gardner and Ashby, 1970; May, 1972). The latter is often verbalized as: an increase in size and/or connectivity decreases the system stability. We here analyse this apparent contradiction by extending the Hoffmann model (with a decay term), and comparing it to an ecological model that was used as a paradigm in the general analysis. Our analysis confirms that the neighbourhood stability of such idiotypic networks increases with connectivity and/or size. However, the contradiction is one of interpretation, and is not due to exceptional properties of immune networks. The contradiction is caused by the awkward normalization used in the general analysis.

Animals↗
PubMed1994

Stabilization of thoracic spine fractures resulting in complete paraplegia. A long-term retrospective analysis.

STUDY DESIGN: The impact of surgical stabilization on initial rehabilitation and complications in patients with traumatic thoracic level paraplegia was investigated. One hundred thirteen patient records were retrospectively reviewed. SUMMARY OF BACKGROUND DATA: Forty-six patients had been treated with surgical stabilization and fusion. Nineteen patients had been treated by laminectomy alone. Forty-eight patients had been treated nonoperatively. The most common mechanism of injury was a motor vehicle accident (52.6%). The mean follow-up was 8.4 years. METHODS: All inpatient and outpatient records at Craig Hospital were reviewed for patients who had sustained a thoracic spine fracture (T2-T9) that resulted in complete paraplegia (Frankel A). All patients were followed for a minimum of 5 years. Data were collected regarding initial length of inpatient rehabilitation, as well as early and late complications that affected rehabilitation and function during follow-up. This information was analyzed by treatment group. RESULTS: There was a statistically significant difference in the length of initial rehabilitation days between the surgically stabilized group and the laminectomy-only group. There was a trend toward fewer in-patient rehabilitation days between the surgically stabilized group and the nonoperatively treated group. The surgically treated group had twice as many complications as the nonoperative group. CONCLUSIONS: The surgical stabilization of thoracic (T2-T9) spine fractures with complete paraplegia tends to decrease initial rehabilitation days but is associated with increased overall complications. The treatment of this patient group clearly must be individualized.

Adult↗
PubMed2000

The photodegradation of vitamins A and E in parenteral nutrition mixtures during infusion.

BACKGROUND & AIMS: Vitamins A and E are the most light-sensitive vitamins. Vitamin A is degraded by photolysis, while vitamin E degrades by photo-oxidation. The composition of the parenteral nutrition mixture and the container could therefore influence degradation during daylight administration. The aim of this study was therefore to determine the influence of fat emulsion and the type of bag on the photo-degradation of vitamins A and E in Parenteral Nutrition (PN) mixtures during simulated infusion in daylight. METHODS: Representative adult PN mixtures, with and without fat emulsion, were prepared. Samples for analysis were taken from infusates and each bag during simulated infusion. Degradation of vitamins A and E was determined by stability-indicating HPLC analysis. RESULTS: Results indicated that vitamin A loss proceeded rapidly during infusion, resulting in up to 80% loss in 6 hours, even with light protection of the bag. The presence of fat emulsion did not provide significant light protection. Vitamin E degradation was substantial if mixtures were prepared in EVA bags but was largely prevented if PN mixtures were compounded and stored in multi-layered bags. CONCLUSIONS: It is recommended that all PN bags should be light-protected during infusion in daylight. The use of multi-layered bags will prevent vitamin E losses during infusion.

Chromatography, High Pressure Liquid↗
PubMed1984

Factorial design of experiment for stability studies in the development of a tablet formulation.

The stability of chlorpromazine hydrochloride in some hypothetical tablet formulations was evaluated through a fractional factorial design of the type N = 2(6-3). The factors studied were the type of filler (X1), lubricant (X2), binder (X3), disintegrant (X4), the absence or presence of light ( X5 ) and/or humidity ( X6 ). Statistical analysis of the stability data allowed the derivation of a regression equation which determined the magnitude and direction of change of each factor level to optimize drug stability. The significance of the factors could be arranged in the following order: X5 greater than X2 greater than X3 greater than X6 greater than X1. The effects of X4 and the two-factor interaction X2X3 were found to be insignificant. The best multi-component excipient mixture was evaluated on the basis of the information deduced from the factorial design.

Analysis of Variance↗
PubMedDate not supplied

Development of a microencapsulated form of cefuroxime axetil using pH-sensitive acrylic polymers.

Cefuroxime axetil (CA) was encapsulated in pH-sensitive acrylic microspheres in order to formulate a suspension dosage form. Using this microencapsulated form it was expected to prevent leaching of the drug from the microspheres into the suspension medium and to assure the release of the drug in the first part of the intestine, thus avoiding changes to its bioavailability. For this purpose, CA was microencapsulated within several types of acrylic polymers by the solvent evaporation and the solvent extraction techniques. The acrylic polymers selected were: Eudragit E (positively charged and soluble at pH 5), Eudragit L-55 (negatively charged and soluble at pH > 5.5) and Eudragit RL (neutral, insoluble, but readily permeable). The influence of the polymer electrical charge on the stability and in vitro release of CA was investigated. Though Eudragit E microspheres presented good morphological characteristics and dissolution behaviour, the analysis of the stability of CA in the presence of Eudragit E by HPLC, indicated a negative interaction between both compounds. However, formulations made of Eudragit L-55 and RL in the ratios 100:0 and 90:10 were adequate in terms of the stability of the encapsulated CA. The dissolution studies showed a critical pH between 5.2 and 6.0, which allowed the complete release of CA in a short period. Furthermore, these polymer microspheres were shown to be efficient in masking the taste of CA.

Acrylic Resins↗
PubMed1998

Enzyme stability in systems with organic solvents.

This review deals with enzyme stability in organic solvent systems. Based on the current state of the problem, catalytic activity is chosen as the main tool for testing enzyme stability. Various enzyme properties being regarded as their "stability" at present, a classification of the types of enzyme stability most often discussed in the literature is put forward. Aggregation state of the biocatalytic system formed a basis for the analysis of enzyme stability in organic solvent systems. Regularities of enzyme function in homogeneous solutions in water--organic co-solvent mixtures and suspensions in practically anhydrous solvents are discussed, kinetic data being analyzed in parallel to results of structural studies. Based on the elaborated regularities, up-to-date methods for enzyme stabilization in organic solvent systems are considered.

Catalysis↗
PubMed2003

High-pressure FTIR study of the stability of horseradish peroxidase. Effect of heme substitution, ligand binding, Ca++ removal, and reduction of the disulfide bonds.

The pressure stability of horseradish peroxidase isoenzyme C and the identification of possible stabilizing factors are presented. The effect of heme substitution, removal of Ca(2+), binding of a small substrate molecule (benzohydroxamic acid), and reduction of the disulfide bonds on the pressure stability were investigated by FTIR spectroscopy. HRP was found to be extremely stable under high pressure with an unfolding midpoint of 12.0 +/- 0.1 kbar. While substitution of the heme for metal-free mesoporphyrin did not change the unfolding pressure, Ca(2+) removal and substrate binding reduced the midpoint of the unfolding by 2.0 and 1.2 kbar, respectively. The apoprotein showed a transition as high as 10.4 kbar. However, the amount of folded structure present at the atmospheric pressure was considerably lower than that in all the other forms of HRP. Reduction of the disulfide bonds led to the least pressure stable form, with an unfolding midpoint at 9.5 kbar. This, however, is still well above the average pressure stability of proteins. The high-pressure stability and the analysis of the pressure-induced spectral changes indicate that the protein has a rigid core, which is responsible for the high stability, while there are regions with less stability and more conformational mobility.

Amides↗
PubMed1998

Directed evolution of a thermostable esterase.

We have used in vitro evolution to probe the relationship between stability and activity in a mesophilic esterase. Previous studies of these properties in homologous enzymes evolved for function at different temperatures have suggested that stability at high temperatures is incompatible with high catalytic activity at low temperatures through mutually exclusive demands on enzyme flexibility. Six generations of random mutagenesis, recombination, and screening stabilized Bacillus subtilis p-nitrobenzyl esterase significantly (>14 degreesC increase in Tm) without compromising its catalytic activity at lower temperatures. Furthermore, analysis of the stabilities and activities of large numbers of random mutants indicates that these properties are not inversely correlated. Although enhanced thermostability does not necessarily come at the cost of activity, the process by which the molecule adapts is important. Mutations that increase thermostability while maintaining low-temperature activity are very rare. Unless both properties are constrained (by natural selection or screening) the evolution of one by the accumulation of single amino acid substitutions typically comes at the cost of the other, regardless of whether the two properties are inversely correlated or not correlated at all.

Amino Acid Substitution↗
PubMed1987

Isomeric equilibria in complexes of adenosine 5'-triphosphate with divalent metal ions. Solution structures of M(ATP)2- complexes.

Solution structures of M(ATP)2- complexes are reviewed. First the self-stacking properties of ATP4- and M(ATP)2- are shortly described. It is emphasized that for an evaluation of solution structures of M(ATP)2- complexes only results from diluted solutions (below 1 mM) should be used. Next, a comprehensive set of stability data obtained under such conditions from potentiometric pH titrations is summarized for the complexes of Mg2+, Ca2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+ and Cd2+ with ATP, and for comparison also with pyrimidine nucleoside 5'-triphosphates (YTPs), i.e. CTP, UTP and TTP. The stabilities for the M(ATP)2- complexes are mostly larger than those for the corresponding M(YTP)2- species; this increased stability results from the metal ion back-binding to the base residue in M(ATP)2-, i.e. macrochelates are formed. Detailed analysis of the stability data allows calculation of the percentage of the closed form for the several M(ATP)2- complexes: back-binding is most pronounced in Cu(ATP)2- (67 +/- 2%), remarkable in Zn(ATP)2- (28 +/- 7%), and not observable for Ca(ATP)2- (2 +/- 6%). Comparison of these results with those from 1H-NMR and ultraviolet spectrophotometric studies allows the conclusion that two types of base back-bound macrochelates are formed: one with a direct, i.e. innersphere, M2+/N-7 coordination, and one with a water molecule between the metal ion and N-7, i.e. an outersphere interaction occurs [e.g. to about 10% in Mg(ATP)2-] through hydrogen bonding of a coordinated water to N-7. The formation degree of both forms of these closed isomers is quantified. The biological implications of these results are indicated and the versatility of ATP as a ligand is discussed by summarizing pertinent examples.

Adenosine Triphosphate↗
PubMed1995

Specificity of ligand-dependent androgen receptor stabilization: receptor domain interactions influence ligand dissociation and receptor stability.

The molecular basis for the different physiological effects of testosterone (T) and dihydrotestosterone (DHT) was investigated using recombinantly expressed wild-type and mutant androgen receptor (AR). Rates of androgen dissociation from nuclear and cytoplasmic AR were compared with hormone- and concentration-dependent receptor degradation rates. T dissociates from AR 3 times faster than DHT or methyltrienolone (R1881) and is less effective in stabilizing the receptor. Analysis of AR deletion mutants and AR/glucocorticoid receptor chimeras indicates that the AR NH2-terminal domain has a specific role in stabilizing the receptor by slowing the rate of ligand dissociation and AR degradation. Amino acid mutations that abolish receptor dimerization, nuclear localization, or DNA-binding activity have no significant effect on androgen dissociation or AR degradation. A naturally occurring steroid-binding domain mutation (Val889 to Met) that causes androgen insensitivity, but does not alter equilibrium androgen binding affinity, lowered the androgen-binding capacity as a result of increased rates of androgen dissociation and AR degradation. Thus, AR stabilization and function require prolonged receptor occupancy with androgen, with a similar extent of stabilization observed at higher concentrations of faster dissociating androgens and lower concentrations of slower dissociating androgens. Retention of receptor-bound androgen is enhanced by an interaction between the AR NH2-terminal and steroid-binding domains. The ligand specificity and concentration dependence of receptor stabilization provide an explanation for physiological differences in the actions of T and DHT.

Animals↗
PubMed2002

Output power and polarization characteristics for a diode-side-pumped Nd:YAG rod laser with a diffusive optical pump cavity.

We fabricated and analyzed the output power and polarization characteristics of an efficient diode-side-pumped Nd:YAG rod laser with a diffusive optical cavity. The resonator stability conditions are analyzed graphically in the symmetric and asymmetric configurations for a plane-parallel resonator. On the basis of an analysis of the stability condition and mode size for the r and theta polarizations, we clarify how the stable laser operation is possible for various resonator configurations. In particular, we show that the critical stability region of around g1*g2* = 0 provides a stable resonator in the symmetric resonator, even with a slight asymmetry. Experimentally, the output power and polarization characteristics are confirmed in association with the resonator stability condition.

Journal Article↗
PubMed1976

Relationship between composition and stability of bovine milk lysozyme.

The amino acid analysis, peptide mapping, and heat stability of bovine milk lysozyme are presented. The bovine milk lysozyme molecule contains approximately 154 amino acids and is strikingly different in amino acid content from human milk lysozyme and egg white lysozyme. Tryptic hydrolysis yielded 26 peptides, all of which are unique from tryptic peptides of human milk lysozyme and egg white lysozyme. In addition, bovine milk lysozyme was more heat stable than human milk lysozyme at pH 4.0 but more labile at pH 7.0 and 9.0. Possible explanations for the differences in heat stability are discussed.

Amino Acids↗
PubMed1977

Fibrin and fibrinogen proteolysis products: comparison between gel filtration and SDS polyacrylamide electrophoresis analysis.

The proteolysis of purified human fibrinogen, stabilized and non-stabilized fibrin by plasmin were investigated by gel filtration analysis and SDS polyacrylamide electrophoresis of the reaction products. Plasmin proteolysis of fibrinogen followed the sequential steps previously reported and the two analytical methods yielded concordant results. Large molecular weight proteolysis products, of substantially greater molecular weight than native fibrinogen, were identified by gel filtration analysis following dissolution of stabilized and non-stabilized fibrin clots; with further incubation with plasmin, these proteolysis products gradually diminished in size. On the other hand, SDS polyacrylamide electrophoresis of these fibrin digests demonstrated that while non-stabilized fibrin yielded breakdown products similar in size to those obtained after proteolysis of fibrinogen, stabilized fibrin digests showed moieties of greater molecular size estimated to be of molecular weight 400,000 to 800,000. The final breakdown products of stabilized fibrin differed from those of fibrinogen and nonstabilized fibrin in that fragment D was present in the "double D" cross-linked form.

Antigens↗
PubMed2004

Analysis of void volumes in proteins and application to stability of the p53 tumour suppressor protein.

We have developed a new method for the analysis of voids in proteins (defined as empty cavities not accessible to solvent). This method combines analysis of individual discrete voids with analysis of packing quality. While these are different aspects of the same effect, they have traditionally been analysed using different approaches. The method has been applied to the calculation of total void volume and maximum void size in a non-redundant set of protein domains and has been used to examine correlations between thermal stability and void size. The tumour-suppressor protein p53 has then been compared with the non-redundant data set to determine whether its low thermal stability results from poor packing. We found that p53 has average packing, but the detrimental effects of some previously unexplained mutations to p53 observed in cancer can be explained by the creation of unusually large voids.

Amino Acid Substitution↗
PubMed2006

A combined FEM/genetic algorithm for vascular soft tissue elasticity estimation.

Tissue elasticity reconstruction is a parameter estimation effort combining imaging, elastography, and computational modeling to build maps of soft tissue mechanical properties. One application is in the characterization of atherosclerotic plaques in diseased arteries, wherein the distribution of elastic properties is required for stress analysis and plaque stability assessment. In this paper, a computational scheme is proposed for elasticity reconstruction in soft tissues, combining finite element modeling (FEM) for mechanical analysis of soft tissues and a genetic algorithm (GA) for parameter estimation. With a model reduction of the discrete elasticity values into lumped material regions, namely the plaque constituents, a robust, adaptive strategy can be used to solve inverse elasticity problems involving complex and inhomogeneous solution spaces. An advantage of utilizing a GA is its insistence on global convergence. The algorithm is easily implemented and adaptable to more complex material models and geometries. It is meant to provide either accurate initial guesses of low-resolution elasticity values in a multi-resolution scheme or as a replacement for failing traditional elasticity estimation efforts.

Algorithms↗
PubMed1991

Organization and stability of a polytopic membrane protein: deletion analysis of the lactose permease of Escherichia coli.

The overall topology of polytopic membrane proteins is thought to result from either the oriented insertion of the N-terminal alpha-helical domain followed by passive insertion of subsequent helices or from the function of independent topogenic determinants dispersed throughout the molecules. By using the lactose permease of Escherichia coli, a well-characterized membrane protein with 12 transmembrane domains and the N and C termini on the cytoplasmic surface of the membrane, we have studied the insertion and stability of in-frame deletion mutants. So long as the first N-terminal and the last four C-terminal putative alpha-helical domains are retained, stable polypeptides are inserted into the membrane, even when an odd number of helical domains is deleted. Moreover, even when an odd number of helices is deleted, the C terminus remains on the cytoplasmic surface of the membrane, as judged by lacY-phoA fusion analysis. In addition, permease molecules devoid of even or odd numbers of putative transmembrane helices retain a specific pathway for downhill lactose translocation. The findings imply that relatively short C-terminal domains of the permease contain topological information sufficient for insertion in the native orientation regardless of the orientation of the N terminus.

Alkaline Phosphatase↗
PubMed1996

Stabilization of proteins by glycosylation examined by NMR analysis of a fucosylated proteinase inhibitor.

Here we investigate the effects of the naturally occurring threonine-linked L-fucose moiety on the structure, dynamics and stability of the proteinase inhibitor PMP-C (Pars intercerebralis major peptide C). The three-dimensional structure of PMP-C fucosylated on Thr 9 has been determined by NMR spectroscopy and simulated annealing. The fucose ring is very well ordered, held in place by hydrophobic and hydrogen bond interactions with Thr 16 and Arg 18. Comparing the NMR data and the structure of the fucosylated inhibitor with those of the nonfucosylated form shows that conformational changes only occur in the vicinity of the fucose moiety. Nevertheless, a comparative analysis of the exchange rates of amide protons indicates that fucosylation is responsible for an overall decrease of the dynamic fluctuations of the molecule. This correlates well with an increase in stability of approximately 1 kcal mol-1 as monitored by thermal denaturation.

Cyclotides↗