SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
The present studies describe the fabrication and characterization of highly porous and interconnected poly(alpha-hydroxy acid) foam scaffolds produced using a phase separation multisolvent system, followed by a sublimation process. Fabrication parameters, including solvent composition, polymer concentration, freezing temperature, polymer type, and polymer molecular weight, were optimized to produce the desired foam microstructure. Analyses of selected samples with scanning electron microscopic images and mercury intrusion porosimetry indicated polymer foams with pore size ranges of 100-350 microm, a porosity >90%, and an interconnecting open-pore foam structure. Scaffold degradation profiles varied according to the type and molecular weight of the polymers. Cytocompatibility assays demonstrated that the preferred foam structures were nontoxic and osteoprecursor cells seeded into the scaffolds exhibited the ability to attach, propagate, and differentiate into a calcified structure.
AIMS: To identify the cytochrome P450 (CYP) isoforms responsible for the metabolism of simvastatin hydroxy acid (SVA), the most potent metabolite of simvastatin (SV). METHODS: The metabolism of SVA was characterized in vitro using human liver microsomes and recombinant CYPs. The effects of selective chemical inhibitors and CYP antibodies on SVA metabolism were assessed in human liver microsomes. RESULTS: In human liver microsomes, SVA underwent oxidative metabolism to three major oxidative products, with values for Km and Vmax ranging from about 50 to 80 microM and 0.6 to 1.9 nmol x min(-1) x mg(-1) protein, respectively. Recombinant CYP3A4, CYP3A5 and CYP2C8 all catalysed the formation of the three SVA metabolites, but CYP3A4 was the most active. CYP2D6 as well as CYP2C19, CYP2C9, CYP2A6, CYP1A2 did not metabolize SVA. Whereas inhibitors that are selective for CYP2D6, CYP2C9 or CYP1A2 did not significantly inhibit the oxidative metabolism of SVA, the CYP3A4/5 inhibitor troleandomycin markedly (about 90%) inhibited SVA metabolism. Quercetin, a known inhibitor of CYP2C8, inhibited the microsomal formation of SVA metabolites by about 25-30%. Immunoinhibition studies revealed 80-95% inhibition by anti-CYP3A antibody, less than 20% inhibition by anti-CYP2C19 antibody, which cross-reacted with CYP2C8 and CYP2C9, and no inhibition by anti-CYP2D6 antibody. CONCLUSIONS: The metabolism of SVA in human liver microsomes is catalysed primarily (> or = 80%) by CYP3A4/5, with a minor contribution (< or = 20%) from CYP2C8. CYP2D6 and other major CYP isoforms are not involved in the hepatic metabolism of SVA.
Original 4-oxo-1,3-dioxanes and 2-oxetanones have been prepared from 3-hydroxy acids. Some pharmacological data and results from agricultural screenings are given.
We propose a multiple alignment of the sequence of formate dehydrogenase with the D-specific 2-hydroxy acid dehydrogenases family. Structurally conserved regions are predicted for those sequences corresponding to important regions of the catalytic and the coenzyme binding domains defined from the known three-dimensional structure of the formate dehydrogenase, namely the nicotinamide binding site (beta D to beta F) and the beta A-loop-alpha B region containing the typical glycine pattern of the adenosine binding site, the catalytic histidine/aspartic acid pair and an arginine probably involved in the interaction with the carboxyl group of the substrate.
The structures of two brucinium (2,3-dimethoxy-10-oxostrychnidinium) salts of the alpha-hydroxy acids L-malic acid and L-tartaric acid, namely brucinium hydrogen (S)-malate pentahydrate, C23H27N2O4+.C4H5O5-.5H2O, (I), and anhydrous brucinium hydrogen (2R,3R)-tartrate, C23H27N2O4+.C4H5O6-,(II), have been determined at 130 K. Compound (I) has two brucinium cations, two hydrogen malate anions and ten water molecules of solvation in the asymmetric unit, and forms an extensively hydrogen-bonded three-dimensional framework structure. In compound (II), the brucinium cations form the common undulating brucine sheet substructures, which accommodate parallel chains of head-to-tail hydrogen-bonded tartrate anion species in the interstitial cavities.
OBJECTIVE: A double-blind, single-site, split-face clinical study was organized and carried out in order to evaluate the efficacy, tolerability, and safety of a glycolic acid containing scalp lotion in conjunction with a betamethasone (as the 17-valerate) scalp application against conditions of psoriasis. BACKGROUND: Alpha-hydroxy acids (AHA) have been proposed as therapeutic modalities against skin exfoliative conditions such as ichthyosis, xeroderma, and psoriasis. AHAs are hereby clinically investigated as therapeutic modalities adjuvant to corticosteroids in order to diminish systemic and topical adverse side-effects most frequently associated with use of the latter. METHODS: Twenty patients suffering from scalp psoriasis and other psoriatic conditions were included in a double-blind, split-face clinical study, using combinations of a 10% (w/w) glycolic acid scalp lotion, placebo lotion (excipients only), and a 0.1% (w/w) betamethasone scalp application, applied twice daily without any bandage for a period of 8 weeks. Clinical assessments were carried out by highly experienced physician evaluations based on a four-grade scale, prior to treatment and after 2, 4, 6 and 8 weeks. RESULTS: Improvement was observed in all cases included in the study following treatment with the 10% glycolic acid lotion. However, when equal parts of the 0.1% betamethasone lotion were combined, most of the treated sites were healed. Moreover, the duration of treatment required for healing was in this case reduced to approximately half of that needed when the glycolic acid or the betamethasone lotions were used separately for treatment. CONCLUSIONS: The present clinical study demonstrates for the first time that the effective and well tolerated therapeutic efficacy of glycolic acid scalp lotions is enhanced when used in conjunction with a 0.1% betamethasone scalp application against scalp psoriasis. This potential offers the practising dermatologist with novel treatment modes against severe skin conditions by combining topical corticosteroid with exfoliative agent therapy.
A sensitive and reliable procedure for the simultaneous determination of simvastatin (SV) and its active beta-hydroxy acid metabolite (SVA) in human plasma was developed and validated. The analytes were extracted simultaneously from 0.5 ml aliquots of human plasma samples by methyl tert-butyl ether (MTBE) via Chem Elut cartridge extraction [also called liquid-solid extraction (LSE) or liquid-liquid cartridge extraction (LLCE)], separated through a Kromasil C(18) column (50 x 2 mm i.d. 5 microm) and detected by tandem mass spectrometry with a turbo ionspray interface. Stable isotope-labeled SV and SVA, (13)CD(3)-SV and (13)CD(3)-SVA, were used as internal standards. SV and SVA were detected in positive and negative ion modes, respectively, via within-run polarity switching. The use of Chem Elut cartridges not only provided a simple and efficient means of plasma sample extraction but also successfully reduced the interconversion between SV and SVA to an undetectable (for lactonization of SVA) or negligible (<0.07%, for hydrolysis of SV) level. The method showed excellent reproducibility, with intra- and inter-assay precisions <4.5% (RSD), and intra- and inter-assay accuracy between 94% and 107% of nominal values, for both analytes. The extraction recoveries were 78% and 87% on average for SV and SVA, respectively. The analyte was found to be stable in plasma through three freeze (-70 degrees C)-thaw (4 degrees C) cycles and for at least 3 h under bench-top storage condition in an ice-bath (4 degrees C), and also in the reconstitution solution at 4 degrees C for at least 24 h. The method has a lower limit of quantitation (LOQ) of 50 pg ml(-1) with a linear calibration range of 0.05-50 ng ml(-1) for both analytes, and has proved to be very reliable for the analysis of clinical samples.
A water-soluble, enantiopure lanthanide complex, SSS-[Ln x L3], has been assessed as an effective chiral derivatizing agent for the determination of the enantiomeric purity of alpha-hydroxy acids in aqueous solution. The complex displays superior chemical shift non-equivalence (DeltaDeltadelta approximately 2-11 ppm) for the diastereomeric resonances of interest compared to lanthanide shift reagents reported in the literature (DeltaDeltadelta <0.1 ppm, typically). 1H NMR studies have also revealed that SSS-[Ln x L3] can be used to determine the absolute configuration of alpha-amino acids at physiological pH, in water. The ability of SSS-[Ln x L3] to signal anion binding and, in particular, to distinguish between diastereomers through optical techniques such as lanthanide luminescence and circular dichroism has also been assessed.
The colloidal structures of beta carboxylic acid topical vesicle formulations were determined and the changes during evaporation after applications were estimated from phase diagrams. The results showed significant difference during evaporation between salicylic acid on one hand and three water soluble acids; malic, tartaric, and citric acid, on the other. The water soluble acids showed an increase in the acid concentration in the aqueous solution to levels that must be considered harmful, while salicylic acid showed no increase in concentration in the individual phases even after 99% evaporation of water.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
D-Alanine and diaminopimelic acid originating from bacterial peptidoglycans and hydroxy fatty acids from lipopolysaccharides (endotoxins) were analysed by gas chromatography using a chiral column (Chirasil-Val as stationary phase) and selected-ion monitoring detection with negative-ion chemical-ionization mass spectrometry. The amino acids were analysed as N-heptafluorobutyryl isobutyl esters after rapid hydrolysis of peptidoglycan followed by isolation of the amino acids with disposable ion-exchange columns. Racemization of amino acid enantiomers was controlled by using deuterium chloride in the hydrolysis. The hydroxy acids were analysed as O-pentafluorobenzoyl methyl esters. Most of the bacteria present in airborne dust from a poultry confinement building were found to be Gram-positive according to the analytical chemical method whereas the Limulus amoebocyte lysate test suggested the presence of appreciable amounts of lipopolysaccharides of Gram-negative bacteria. Further studies are required to compare the utility of these two methods for determining endotoxins in complex environments.
The lithium enolates of trimethylsilyl but-3-enoate and 3-methylbut-3-enoate reacted with aldehydes and saturated or aromatic ketones at -70 degrees C to give exclusively the alpha-condensation products in excellent yields. The unsaturated beta-hydroxy acids thus obtained were directly identified, and the usual conversion into their methyl esters with diazomethane was not necessary. Unsaturated ketones underwent Michael reaction through alpha-addition leading to the unsaturated 5-oxo acids.
In comparison with mature animals, pre-weanling rats have markedly higher and longer lasting serum levels of beta-phenyllactate following the intraperitoneal injection of a moderate dose. A corresponding age-dependent difference in the rate of oxidation of beta-phenyllactate and other alpha-hydroxy acids was observed in experiments with homogenates and supernatant fractions of rat kidney.
Cholesterol lowering statin drugs are the most frequently prescribed agents for reducing morbidity and mortality related to coronary heart disease. This publication presents a validated, highly sensitive and selective isocratic HPLC method for the quantitative determination of the major statin drug simvastatin (SIM) and its metabolite simvastatin hydroxy acid (SIMA). Detection was performed on an electrospray ionization triple quadrupole mass spectrometer equipped with an ESI interface operated in positive and negative ionization mode. The multiple reaction-monitoring mode (MRM) was used to provide MS/MS detection. The linearity for the calibration curve in the concentration range of 0.10-16.00 ng/mL for SIM and 0.10-16.00 ng/mL for SIMA is presented. Inter- and intra-day precision and accuracy of the proposed method were characterized by relative standard deviation (R.S.D.) and percentage deviation, respectively; with both lower than 7% for all analytes. The limit of quantitation was 0.03 ng/mL for SIM and 0.02 ng/mL for SIMA. The devised method was employed in the pharmacokinetic study of SIM and the pharmacokinetic parameters of all analytes are also presented.