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At least 127 records · Page 7Linked to original sources

PubMed1998

Effect of salts on the solubility of thermolysin: a remarkable increase in the solubility as well as the activity by the addition of salts without aggregation or dispersion of thermolysin.

Thermolysin is remarkably activated in the presence of high concentrations (1-5 M) of neutral salts [Inouye, K. (1992) J. Biochem. 112, 335-340]. The activity is enhanced 13-15 times with 4 M NaCl at pH 7.0 and 25 degrees C. In this study, the effect of neutral salts on the solubility of thermolysin has been examined. Although the solubility was only 1.0-1.2 mg/ml in 40 mM Tris-HCl buffer, pH 7.5, in the temperature range between 0 and 60 degrees C, it was increased greatly by the addition of salts. With NaCl, the solubility showed a bell-shaped behavior with increasing NaCl concentration, and the maximum solubility (10 mg/ml) was at 2.0-2.5 M NaCl. With LiCl and NaI, it increased progressively to 20-50 mg/ml with increasing salt concentration up to 5 M. The solubility observed in the presence of salts decreased with increasing temperature from 0 to 60 degrees C, and also with the order of chaotropic anion effect. The molecular weight of thermolysin was estimated to be 33.0(+/-2.5) x 10(3) in the presence of 0-3 M NaCl, suggesting that thermolysin exists as a monomer in the presence or absence of 3 M NaCl. The possibility that aggregation and/or dispersion of thermolysin might be related to the remarkable activation by salt was ruled out.

Acrylates↗

PubMed1986

Coulter Counter measurements of solubility and dissolution rate of sparingly soluble compounds using micellar solutions.

A Coulter Counter, Model TAII, was used to determine both solubility and surface specific dissolution rate of two sparingly soluble materials suspended in micellar solutions. The equilibrium solubility increased linearly with surfactant concentration, thereby making it possible by extrapolation to characterize materials with an aqueous solubility down to 1 ppm or less. At high concentrations (greater than 0.1% w/v) the effect of surfactant concentration on the surface specific dissolution rate was less than that predicted from the increased bulk solubility.

Felodipine↗

PubMed1995

Enthalpy and entropy contributions to the solubility of sulphamethoxypyridazine in solvent mixtures showing two solubility maxima.

The solubility of sulphamethoxypyridazine was measured at several temperatures in mixtures of water:ethanol and ethanol:ethyl acetate. Sulphamethoxypyridazine was chosen as a model drug to compare the solvation effects of proton donor-proton acceptor (water and ethanol) and proton acceptor (ethyl acetate) solvents and mixtures of these solvents because this drug contains functional groups capable of Lewis acid-base interaction. A plot of the mole fraction solubility against the solubility parameter (delta 1 = 30.87 MPa1/2 (20:80 v/v water:ethanol) and another at delta 1 = 20.88 MPa1/2 (30:70 v/v ethanol:ethyl acetate) at all the temperatures under study. The enthalpies and entropies of mixing as well as the enthalpies and entropies of transfer of sulphamethoxypyridazine from ethanol of mixing as well as the enthalpies and entropies of transfer of sulphamethoxypyridazine from ethanol to water:ethanol and ethanol:ethyl acetate mixtures were calculated to compare solvation characteristics of the solvent mixtures toward the drug. As ethanol is added to water, the entropy increases and the structure of the solvent mixture became less ordered, favouring the interaction of the drug with the solvent mixture. On the other hand, in the case of the ethanol:ethyl acetate mixture, solubility is favoured by the more negative enthalpy values. This way, the same result, i.e. a solubility maximum, is obtained by different routes. In the ethanol:water mixtures, the dissolution process if entropy-controlled while enthalpy is the driving force in the case of ethanol:ethyl acetate mixtures. The two solvent systems show enthalpy-entropy compensation. Water deviates from the linear relationship due possibly to its hydrophobic effect.

Acetates↗

PubMed2000

Alterations in detergent solubility of heterotrimeric G proteins after chronic activation of G(i/o)-coupled receptors: changes in detergent solubility are in correlation with onset of adenylyl cyclase superactivation.

Prolonged G(i/o) protein-coupled receptor activation has been shown to lead to receptor internalization and receptor desensitization. In addition, it is well established that although acute activation of these receptors leads to inhibition of adenylyl cyclase (AC), long-term activation results in increased AC activity (especially evident on removal of the inhibitory agonist), a phenomenon defined as AC superactivation or sensitization. Herein, we show that chronic exposure to agonists of G(i)-coupled receptors also leads to a decrease in cholate detergent solubility of G protein subunits, and that antagonist treatment after such chronic agonist exposure leads to a time-dependent reversal of the cholate insolubility. With Chinese hamster ovary and COS cells transfected with several G(i/o)-coupled receptors (i.e., mu- and kappa-opioid, and m(4)-muscarinic), we observed that although no overall change occurred in total content of G(alphai)- and beta(1)-subunits, chronic agonist treatment led to a marked reduction in the ability of 1% cholate to solubilize G(betagamma) as well as G(alphai). This solubility shift is exclusively observed with G(alphai), and was not seen with G(alphas). The disappearance and reappearance of G(alphai) and G(betagamma) subunits from and to the detergent-soluble fractions occur with similar time courses as observed for the onset and disappearance of AC superactivation. Lastly, pertussis toxin, which blocks acute and chronic agonist-induced AC inhibition and superactivation, also blocks the shift in detergent solubility. These results suggest a correlation between the solubility shift of the heterotrimeric G(i) protein and the generation of AC superactivation.

Adenylate Cyclase Toxin↗

PubMed2004

Differential antioxidant properties of red wine in water soluble and lipid soluble peroxyl radical generating systems.

Red wine and its components have been shown to possess cardioprotective and anti-atherogenic effects. Additionally, red wine and many of its components like catechin, epicatechin, rutin, transresveratrol and quercetin possess antioxidant properties. Oxidized low density lipoprotein (LDL) is involved in the development of an atherosclerotic lesion. Red wine, therefore, may be anti-atherogenic because of its antioxidant effects on LDL modification. This study examined the antioxidant effects of catechin, epicatechin, rutin, transresveratrol, quercetin and Merlot wines on LDL oxidation. Merlot was chosen because although other red wines have been tested, limited information exists for this variety. Oxidation was carried out with AAPH (2,2'-Azo-bis(2-amidinopropane) dihydrochloride) and AMVN (2,2'-Azo-bis(2,4-dimethylvaleronitrile)), as water and lipid soluble peroxyl radical generating systems (FRGS), respectively. This allowed us to determine the lipophilic antioxidant characteristics of the wine and its components. Conjugated diene assays were used to measure LDL oxidation over 6 hrs. In an AAPH system, all polyphenolic compounds except transresveratrol displayed an antioxidant effect. LDL oxidation by AAPH was also inhibited by aliquots of Merlot wine. No antioxidant effects were observed in an AMVN environment except for a mild antioxidant effect by quercetin. Surprisingly, incubation of LDL with Merlot wine strongly protected against oxidation by AMVN. In summary, the five phenolic compounds displayed antioxidant effects in a water soluble free radical generating system, but only quercetin showed this in a lipid soluble one. However, red wine inhibited LDL oxidation by both water and lipid soluble free radical generating systems. Our data suggest, therefore, that red wines contain unidentified antioxidants that provide protection against LDL oxidation within a lipid soluble environment.

Amidines↗

PubMed2005

Characterization of the solubility of a poorly soluble hydroxylated metabolite in human urine and its implications for potential renal toxicity.

The solubility, in human urine, of the major hydroxylated metabolite (M1) of an experimental cognition enhancer was characterized through a series of in vitro experiments in an effort to estimate the probability of crystalluria occurring following oral administration of the parent compound. The aim of these experiments was to determine if a safety margin existed between clinically observed urine concentrations and the solubility of M1. The mean urine concentrations of M1 in young and elderly subjects following oral administration of the parent compound at the highest doses tested, were 4865 +/- 2368 ng/mL and 2764 +/- 791 ng/mL, respectively. In vitro solubility experiments with M1 were conducted in drug-free human urine (37 degrees C) from four male and four female healthy subjects under conditions of high and low urine osmolality. Mean concentrations (n = 16) of M1 in human urine to which solid M1 was added, were 3656 +/- 621 ng/mL, 4678 +/- 1169 ng/mL and 5378 +/- 2474 ng/mL after stirring for 24, 48 and 72 h, respectively, indicating that the ex vivo mean solubility of M1 in human urine is no greater then approximately 5 microg/mL. Addition of solid M1 to urine from human subjects dosed with the parent compound resulted in mean urine M1 concentrations 23.5% greater than those observed in vivo. The results from both experiments indicated a significant overlap between urine concentrations of M1 in vivo following the highest oral administration of the parent drug and M1 solubility measured in vitro, suggesting a high potential for in vivo saturation of urine with M1 with subsequent precipitation, crystalluria, and nephrotoxicity. Consequently, the results of these studies have placed restrictions on the dose that could be administered during clinical development of this compound.

Animals↗

PubMed2005

The effect of cyclodextrins on the aqueous solubility of a new MMP inhibitor: phase solubility, 1 H-NMR spectroscopy and molecular modeling studies, preparation and stability study of nebulizable solutions.

PURPOSE: Ro 28-2653 (RO) is a synthetic inhibitor of matrix metalloproteinases (MMPs), which is potentially effective against bronchial remodeling. Given that this molecule has very poor aqueous solubility, different cyclodextrins (CDs) have been tested to increase its solubility. The aim of this study was to prepare and to characterize inclusion complexes between RO and CDs, in order to develop nebulizable solutions. METHODS: The complex formation was investigated by phase solubility studies. (1)H-NMR spectroscopy and molecular modeling studies were carried out to elucidate the structure of the inclusion complex between RO and dimethyl-beta-CD (DIMEB). Nebulizable solutions of RO were developed with CDs and a stability study was performed over 9 months. RESULTS: The phase solubility studies showed that beta-CD and its derivatives form a 1:2 complex with RO, whereas gamma-CD includes RO with a 1:1 stoichiometry and a weak stability constant. T-ROESY spectra showed that DIMEB is able to complex two RO substituents (nitrophenyl and biphenyl groups) with preferential orientations, while molecular modeling demonstrated that the configurations observed with (1)H-NMR are energetically favorable, especially owing to H-bond formation between RO and DIMEB. Two CDs were selected to develop nebulizable solutions of RO and the stability study demonstrated that RO degradation in solution is strongly dependent on the concentration of the 1:2 inclusion complex. CONCLUSIONS: CDs are able to include RO and to improve its aqueous solubility. The beta-CD derivatives can be used to formulate nebulizable solutions of RO, the stability of which depends on the concentration of the 1:2 complex.

Cyclodextrins↗

PubMed2000

Serum concentrations of soluble Fas antigen and soluble Fas ligand in mother and newborn.

We measured soluble Fas antigen and soluble Fas ligand, which are considered to be an apoptotic substance, in maternal serum, umbilical cord serum and amniotic fluid during cesarean section at full term pregnancy. Seventeen healthy parturients with no fetal distress were studied. Soluble Fas antigen showed no different levels between these measurement sites. Soluble Fas ligand showed a difference, in which umbilical serum level was significantly higher than maternal serum and amniotic fluid levels. The present results suggest high serum levels of soluble Fas ligand in newborn. However, the reason for this evidence is entirely unknown.

Adult↗

PubMed2005

Optimized expression of soluble cyclomaltodextrinase of thermophilic origin in Escherichia coli by using a soluble fusion-tag and by tuning of inducer concentration.

Cyclomaltodextrinases are multidomain and often dimeric proteins from the alpha-amylase family (glycoside hydrolase family 13) which frequently have been very difficult to express in active form in Escherichia coli. To express the soluble form of this type of proteins in larger quantities the expression has to be optimized. We have used and combined two strategies to increase the yield of soluble recombinant cyclomaltodextrinase expressed from a gene originating from the thermophilic Gram-positive bacterium Anoxybacillus flavithermus. One strategy involved tuning of the inducer concentration while the other involved fusion of the gene encoding the target protein to the gene encoding the solubility-enhancing protein NusA. The enzyme activity could be increased 6-7 times solely by finely tuning the IPTG concentration, but the activity level was very sensitive to the amount of inducer applied. Hence, the IPTG concentration may have to be optimized for every protein under the conditions used. The fusion protein-strategy gave a slightly lower total activity but the level of soluble recombinant protein obtained was in this case significantly less sensitive to the inducer concentration applied. Moreover, the activity could be increased about 2-fold by cleaving off the solubility-tag (NusA) by enterokinase.

Cloning, Molecular↗

PubMed2003

Soluble Fas antigen and soluble Fas ligand in early neonatal life.

BACKGROUND: After birth, apoptosis rates might slow down, compared to those in utero. Thus, factors, attenuating the apoptotic process, like the soluble forms of Fas/FasL system, may increase. AIM-STUDY DESIGN: Soluble Fas (sFas) and soluble Fas ligand (sFasL) concentrations were measured in maternal serum (MS), umbilical cord (UC) and neonatal serum in the first (1N) and fifth (5N) days after birth in order to evaluate the alterations of these molecules during the early neonatal period. SUBJECTS AND METHODS: Soluble molecules were estimated in 35 healthy, appropriate for gestational age, full-term neonates, their mothers and in 25 healthy, nonpregnant women, age-matched to the mothers (controls), using enzyme immunoassays. RESULTS: sFas concentrations in MS (p < 0.01), UC (p < 0.0001), 1N (p < 0.0003) and 5N (p < 0.02) were lower than those in controls. Neonatal sFas concentrations showed a significant increase from UC to 5N (p < 0.001). In contrast, sFasL concentrations were significantly elevated in all neonatal samples (UC, 1N and 5N) compared to those in MS and controls (p < 0.0001), showing also a significant elevation from UC to 5N (p < 0.0001). CONCLUSION: Our results demonstrate increasing serum concentrations of the soluble molecules sFas and sFasL during the first days after birth, indicating possibly a gradual decrease of apoptosis in early neonatal life.

Adult↗

PubMedDate not supplied

Single dilution ELISAs using soluble piroplasm, cellular schizont and soluble schizont antigens for the detection of antibodies against Theileria annulata.

Single dilution ELISAs were standardised for the determination of antibody titres against Theileria annulata using three antigens namely soluble piroplasm, cellular schizont or soluble schizont antigens. Antibody titres of 20 cattle serum samples of known identity were determined by multi-dilution ELISA using the three antigens. The ratio of the optical density (OD) of known positive and known negative sera at different serum dilutions were calculated and termed as positive/negative (P/N) ratios. Coefficients of correlation (r) were calculated between the P/N ratios at different dilutions of known sera and their log10 antibody titres by multi-dilution ELISA. The value of "r" was the highest at the dilution of 1:400. From the log10 antibody titres of known sera and their P/N ratios at the dilution of 1:400, regression equations (Y = a + bX, where Y = predicted log10 titre, X = the P/N ratio at 1:400 dilution) were calculated separately for the three antigens. Thus, the equations Y = 1.63 + 1.35X for soluble piroplasm, Y = 2.67 + 0.547X for cellular schizont and Y = 1.817 + 0.663X for soluble schizont antigens were derived. Test sera were diluted to 1:400 and their OD were read in duplicate wells and converted to P/N ratios. The antibody titres were predicted from the P/N ratios using the above mentioned regression equations. Twenty randomly selected sera tested by single and multidilution ELISAs showed non-significant differences (P < 0.01) between antibody titres. Antibody titres of 90 unknown field sera of cattle were determined by single dilution ELISA. The piroplasm antigen detected higher antibody titres followed by cellular schizont and soluble schizont antigens. The study revealed that a single dilution ELISA could be successfully used for field epidemiological studies of tropical theileriosis.

Animals↗

PubMed1994

Isolation of an Arabidopsis thaliana Mutant, mto1, That Overaccumulates Soluble Methionine (Temporal and Spatial Patterns of Soluble Methionine Accumulation).

We isolated Arabidopsis thaliana mutants that are resistant to ethionine, a toxic analog of methionine (Met). One of the mutants was analyzed further, and it accumulated 10- to 40-fold more soluble Met than the wild type in the aerial parts during the vegetative growth period. When the mutant plants started to flower, however, the soluble Met content in the rosette region decreased to the wild-type level, whereas that in the inflorescence apex region and in immature fruits was 5- to 8-fold higher than the wild type. These results indicate that the concentration of soluble Met is temporally and spatially regulated and suggest that soluble Met is translocated to sink organs after the onset of reproductive growth. The causal mutation, designated mto1, was a single, nuclear, semidominant mutation and mapped to chromosome 3. Accumulation profiles of soluble amino acids suggested that the mutation affects a later step(s) in the Met biosynthesis pathway. Ethylene production of the mutants was only 40% higher than the wild-type plants, indicating that ethylene production is tightly regulated at a step after Met synthesis. This mutant will be useful in studying the translocation of amino acids, as well as regulation of Met biosynthesis and other metabolic pathways related to Met.

Journal Article↗

PubMed1966

Soluble antigens of vaccinia-infected mammalian cells. I. Separation of virus-induced soluble antigens into two classes on the basis of physical characteristics.

Cohen, Gary H. (University of Pennsylvania, Philadelphia), and Wesley C. Wilcox. Soluble antigens of vaccinia-infected mammalian cells. I. Separation of virus-induced soluble antigens into two classes on the basis of physical characteristics. J. Bacteriol. 92:676-686. 1966-Infection of mammalian cells with members of the poxvirus group elicits production of a number of virus-induced, soluble antigens. Immunoelectrophoresis and immunodiffusion techniques employing soluble antigen preparations obtained from vaccinia virus-infected KB cells revealed at least seven well-defined immunoprecipitin bands. On the basis of fractionation and subsequent characterization of the soluble antigen mixture by gel filtration, calcium phosphate chromatography, isoelectric precipitation, disc electrophoresis, and ultracentrifugation studies, two distinct classes of virus-induced antigens differing markedly in molecular weight were recognized. A high molecular weight class (200,000 and greater) contained at least three virus-induced antigens; a low molecular weight class (50,000 to 100,000 range) contained at least four immunoprecipitins. Further separation of the antigens within the two groups was accomplished. The two classes were distinguished also by their ability to stimulate synthesis of virus-neutralizing antibody. Antisera prepared against the high molecular weight class proved effective in neutralizing vaccinia virus. In contrast, the low molecular weight antigens showed little, if any, ability to induce formation of neutralizing antibody.

Antibodies↗

PubMed1987

Lipid-soluble and water-soluble beta-blockers. Comparison of the central nervous system depressant effect.

The sedative effects of a relatively lipid-soluble and a water-soluble beta-blocker were compared in 20 male hypertensives, 30 to 60 years old. In a blinded, randomized, crossover study, critical flash fusion frequency and computerized Stroop Word Test were used to assess psychomotor function parameters during a drug-free control day and then following 14 days of either metoprolol, 150 mg daily, or atenolol, 100 mg daily, treatment. Both drugs caused subtle but significant reductions in both parameters of sedation (critical flash fusion frequency and computerized Stroop Word Testing). Sedation was significantly related to serum concentrations of both drugs. The maximum drug-induced change was 17.2% +/- 9% for metoprolol and 19.6% +/- 3% for atenolol. The duration of effect was six hours after atenolol and two hours after metoprolol. Blood pressure control for all patients was similar during both treatment phases. These results demonstrate that relative lipid solubility does not reliably predict the neurologic effects of beta-blockers. The intensity of drug-induced sedation was similar, but the water-soluble agent produced a longer duration of sedative activity.

Adult↗

PubMed1981

Extended solubility approach: solubility parameters for crystalline solid compounds.

A method is suggested to obtain solubility parameters for crystalline solid compounds involving a quadratic equation based on the original Scatchard-Hildebrand solubility expression. The geometric mean delta 1 delta 2, of the Hildebrand approach is replaced by w12 = K delta 1 delta 2, and log alpha 2/(V2 phi 2(2)/2.3RT) is regressed against delta 1 in a second-degree power series for parabens and benzoic acid in a series of normal alcohols. The method provides reasonable solubility parameters for the solid solutes and affords a convenient calculation of the solubility of drugs in a homologous series of solvents.

Benzoates↗

PubMed1981

Solubility and partitioning IV: Aqueous solubility and octanol-water partition coefficients of liquid nonelectrolytes.

The aqueous solubility and octanol-water partition coefficient of over 100 nonelectrolyte organic liquid solutes are related by the simple equation log Sw = -1.016 log PC +0.515, where Sw is the molar solubility of liquid solutes in water and PC is the experimental partition coefficient of the solutes in the octanol-water system. The liquids studied represent a wide variety of organic compounds including aliphatic and aromatic hydrocarbons, alcohols, esters, ethers, aldehydes, and ketones. This finding is in agreement with that reported by Hansch and coworkers. However, these results are significant because only the experimental values for the aqueous solubilities and octanol-water partition coefficients are included, as opposed to the calculated partition coefficients used by Hansch. This relationship is extremely useful in understanding the overall solubility and partitioning phenomenon for organic liquids are provides a basis for studying crystalline solids and gases.

Chemical Phenomena↗

PubMed1983

Solubility and partitioning VI: octanol solubility and octanol-water partition coefficients.

A simple equation for the estimation of the aqueous solubility of crystalline solutes was previously derived based on the assumption that the presence of water does not significantly alter the crystal properties of the solute. The data presented verify the solubility equation for a set of 36 nonelectrolytes and weak electrolytes. Using the same set of solutes, the two major assumptions used to derive the equation were also verified: that the octanol solubility of nonelectrolytes is exponentially proportional to the melting point of the solute and that the octanol-water solubility ratio is a good approximation of the octanol-water partition coefficient.

Chemical Phenomena↗

PubMed2006

Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers.

Role of various water-soluble carriers was studied for dissolution enhancement of a poorly soluble model drug, rofecoxib, using solid dispersion approach. Diverse carriers viz. polyethylene glycols (PEG 4000 and 6000), polyglycolized fatty acid ester (Gelucire 44/14), polyvinylpyrollidone K25 (PVP), poloxamers (Lutrol F127 and F68), polyols (mannitol, sorbitol), organic acid (citric acid) and hydrotropes (urea, nicotinamide) were investigated for the purpose. Phase-solubility studies revealed AL type of curves for each carrier, indicating linear increase in drug solubility with carrier concentration. The sign and magnitude of the thermodynamic parameter, Gibbs free energy of transfer, indicated spontaneity of solubilization process. All the solid dispersions showed dissolution improvement vis-à-vis pure drug to varying degrees, with citric acid, PVP and poloxamers as the most promising carriers. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Fickian diffusion. Solid state characterization of the drug-poloxamer binary system using XRD, FTIR, DSC and SEM techniques revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement in dissolution rate.

Calorimetry, Differential Scanning↗