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At least 73 records · Page 4Linked to original sources

Plasma, urinary and biliary residues in cattle following intramuscular injection of nortestosterone laurate.

The synthetic androgen 19-nortestosterone (beta-NT) has been used illegally as a growth promoter in cattle production in the European Union. Elimination of beta-NT and its metabolites in plasma, urine and bile was studied in three cattle with cannulated gallbladders following intramuscular injection at a single site of 500 mg of the laurate ester (NTL) containing 300.5 mg beta-NT. Using enzyme immunoassay quantification, plasma Cmax of free beta-NT was 0.5 +/- 0.15 microgram/L (mean +/- SEM). Concentrations of free beta-NT in plasma were consistently greater than the assay limit of quantification (0.12 microgram/L) for 32.7 +/- 13.42 days. Mean residence time for the beta-NT in plasma was 68.5 +/- 20.75 days. Following sample preparation by immunoaffinity chromatography, high-resolution GC-MS was used to quantify beta-NT and alpha-NT in urine and bile. beta-NT was detected irregularly in urine from two of the three animals post injection. The principal metabolite present in the urine, alpha-NT, was detected for 160.3 +/- 22.67 days post injection. Cmax for alpha-NT in urine was 13.7 +/- 5.14 micrograms/L. Mean urinary AUC0-183 days for alpha-NT was 845.7 +/- 400.90 (microgram h)/L. In bile, alpha-NT was the only metabolite detected for 174.3 +/- 8.67 days post treatment. Cmax for alpha-NT in bile was 40.8 +/- 12.70 micrograms/L and mean biliary AUC0-183 days for alpha-NT was 1982.6 +/- 373.81 (microgram h)/L. Concentrations of alpha-NT in bile samples were greater than those in urine samples taken at the same time. The mean ratio of biliary:urinary AUC0-183 days was 3.0 +/- 0.72. It is concluded that bile is a superior fluid for detection of alpha-NT following injection of NTL, owing to the longer period during which residues may be detected after administration.

Animals↗

Unexpected reaction profile observed in the synthesis of propyl laurate when using Candida rugosa lipases immobilized in microemulsions based organogels.

1-Propyl laurate synthesis should not be used as standard reaction test of immobilized enzymes in microemulsion-based organogels (MBGs) prepared using lecithin/1-propanol as surfactant when extremely active enzymes with high load are used. In these cases, an anomalous kinetic reaction constant value is observed over short reaction times. Such an anomalous profile is strongly dependent on the concentration of catalyst in the crude powder and, consequently, is not appreciated when either commercial or low activity lipase samples are employed.

Candida↗

Characterization of rabbit liver cytochrome P-450 (laurate omega-1 hydroxylase) synthesized in transformed yeast cells.

Three cDNAs for chimeras between cytochrome P-450s (pHP3 and pHP2-1) were constructed and inserted between the alcohol dehydrogenase promoter and terminator regions of the yeast expression vector pAAH5 to form expression plasmids, pAH3P2, pAH3E2, and pAH3A2. pAH3P2 contained the entire coding sequence of cytochrome P-450 (pHP2-1) except for the 3rd, the 8th, the 36th, and the 42nd residues of the total of 490 amino acids. Nucleotide sequences of pAH3P2 were replaced with those of cytochrome P-450 (pHP3) in the region coding for the NH2-terminal 210 and 262 amino acid residues to yield pAH3E2 and pAH3A2, respectively. The three expression plasmids were introduced into Saccharomyces cerevisiae AH22 cells and cytochrome P-450 s (3P2, 3E2, and 3A2) were purified from the microsomal fractions of the transformed yeast cells. In the oxidized state either of the cytochromes exhibited a low- and high-spin mixed-type spectrum of cytochrome P-450. The reduced CO complex of the cytochromes showed a Soret absorption maximum at 450 nm. When laurate or caprate was added to ferric cytochrome P-450 s (3P2 and 3E2), the spectrum was converted to that of the typical high-spin type, indicating the binding of the fatty acids to the substrate site of the cytochromes. On the other hand, the addition of the fatty acids to ferric cytochrome P-450 (3A2) induced no spectral change. Only chemicals having a carboxyl group caused such spectral conversion of cytochrome P-450 (3P2) among dodecyl compounds examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Pretransitional scaling close to a double critical point in a potassium laurate, 1-decanol, and heavy water lyotropic liquid crystal.

Light scattering measurements were done close to the double critical point of the isotropic boundary of the lyotropic liquid crystal potassium laurate, 1-decanol, and heavy water. From scaling analysis we find susceptibility and correlation length exponents that are clearly higher than the mean-field values usually found in other studies on this and similar systems. In order to recover mean-field analysis, we use a parabolic version of the Landau-de Gennes free energy in account of the convex nature of the phase diagram. We also observe pretransitional characteristic domain sizes greater than the correlation length. Furthermore, we show that the transition goes into a new two-phase coexistence region, between the convex tips of pure isotropic and discotic nematic boundaries.

Journal Article↗

Double-blind, placebo-controlled study of the efficacy of nandrolone laurate in the treatment of dobermanns with subclinical hepatitis.

Twenty-one three-year-old dobermanns with subclinical hepatitis were treated with nandrolone laurate or a placebo in a double-blind trial. The dogs were scored clinically before and after four months of treatment and they were evaluated by clinical biochemistry and liver biopsies. After the treatment no significant differences were observed between the two groups in any of the clinical biochemistry values; eight of the 21 dogs had no histological evidence of hepatitis and five other dogs had improved, but there was no significant difference between the responses of the two groups.

Androgens↗

Optimization of suppository preparation containing sodium laurate and taurine that can safely improve rectal absorption of rebamipide.

We previously reported that the fatty base suppository containing sodium laurate (C12) and taurine (Tau) (C12-Tau suppository) could enhance the colonic absorption of rebamipide, a poorly water-soluble and poorly absorbable drug, without any serious mucosal damages in rats. In the preset study, in order to make C12-Tau suppositories available for practical use, the scaling-up studies of animal and formulation size were performed, compared with the suppositories containing sodium caprate (C10) (C10 suppository) at the same amounts as those contained in the commercial products. Twenty-mg C12 improved the dissolution of rebamipide from suppository remarkably and the addition of 30-mg Tau only slightly decreased the dissolution rate. The absorption of rebamipide from rabbit rectum was more markedly improved by suppositories containing C12 than C10 suppositories. Although Tau tended to attenuate the absorption-enhancing effect of C12, several C12-Tau suppositories kept high bioavailability values, which were much higher than control. Histopathological studies showed that Tau exerted the cytoprotective action and that C12-Tau suppositories were better than C10 suppositories in safety. Considering the balance between efficacy and safety, the suppository containing 10- or 20-mg C12 with 30-mg Tau is better than C10 suppositories as commercial products and could be promising for practical use in human.

Administration, Rectal↗

Inhibitory effect of prostaglandin E1 on laurate-induced peripheral vascular occlusive sequelae in rabbits: optimized topical formulation with beta-cyclodextrin derivative and penetration enhancer HPE-101.

Prostaglandin E1 (PGE1) and its inclusion complexes with beta-cyclodextrin (beta-CyD) and O-carboxymethyl-O-ethyl-beta-cyclodextrin (CME-beta-CyD) were made as topical preparations. The PGE1 preparations, when applied with a penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentane-2-one (HPE-101), markedly increased the regional blood flow in the ear of rabbits and were longer acting than when administered by the intravenous route. Topical application of the PGE1 preparations significantly protected rabbits against laurate-induced peripheral vascular occlusive sequelae; the protective potency increased in the order of PGE1 alone = beta-CyD complex < CME-beta-CyD complex preparation. The PGE1 preparations elicited skin reactions such as erythema and oedema depending on their vasodilating actions. These reactions disappeared gradually after removal of the preparations, and hence may not be serious obstacles for their safe use. These results suggest that combinations of CME-beta-CyD and HPE-101 work synergistically to facilitate the entry of PGE1 into the skin, and consequently enhance the therapeutic potential of PGE1 in the topical preparation tested.

Administration, Topical↗

Influence of glucose solubility and dissolution rate on the kinetics of lipase catalyzed synthesis of glucose laurate in 2-methyl 2-butanol.

The lipase catalyzed acylation of glucose by dodecanoic acid in 2-methyl 2-butanol was studied. The initial reaction rate was strongly dependent on the dissolved glucose concentration in the medium. Several methods were shown to increase dissolved glucose concentrations and initial reaction rates, namely, the use of solid beta-glucose, amorphous solid glucose, and supersaturated glucose solution. Supersaturated glucose solutions in 2-methyl 2-butanol showed a high stability even in the presence of solid crystalline glucose. During the reaction, the dissolved glucose concentration falls as the reaction proceeds, before recovering later as more of the excess solid dissolves. However, the ester synthesis rate continues to fall even after glucose concentration reaches its minimum, so glucose dissolution rate limitation is not responsible for the synthesis rate decline. Experiments with added molecular sieves show that the main reason is the accumulation of product water. In the presence of molecular sieves, 70% of glucose was converted to ester, independent of the initial soluble glucose in the medium.

Acylation↗

Different mechanisms of regioselection of fatty acid hydroxylation by laurate (omega-1)-hydroxylating P450s, P450 2C2 and P450 2E1.

P450 2C2 as well as P450 2E1 [Fukuda, T. et al. (1993) J. Biochem. 113, 7-12] catalyzed the hydroxylation of medium chain fatty acids, although the regioselectivity of substrates of the former contrasted with that of the latter. Whereas P450 2E1 hydroxylated C9-C18 fatty acids at the omega-1 position and to a much lesser extent at the omega and omega-2 positions, P450 2C2 hydroxylated C9-C13 fatty acids at different positions dependent on the chain length of fatty acids. Among the fatty acids used as the substrate, undecanoate was hydroxylated at the omega-1 position almost exclusively by P450 2C2. The proportion of omega-hydroxylated products produced by P450 2C2 was markedly increased with decreasing chain length of fatty acids, while the hydroxylation positions were enlarged to the omega-3 position with tridecanoate. When the conserved Thr at the putative distal helix was replaced with Ser, the substrate regioselectivity of the two P450s was affected in different manners. The mutation of P450 2C2 did not change the hydroxylation positions of C9-C12 fatty acids, but caused a significant decrease in the proportion of the omega-1 hydroxy analog in the total products. In sharp contrast to P450 2C2, the mutated P450 2E1 gave additional products to those with the wild-type P450, and the number of different products increased with increasing chain length of the fatty acids. Thus, the products of palmitate hydroxylation were identified as omega-1, omega-2, omega-3, omega-4, omega-5, omega-6, and omega-7 monohydroxy isomers using gas chromatography-electron impact mass spectrometry.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of phenobarbital treatment and cytochrome P-450 inhibitors on the laurate omega- and (omega - 1)-hydroxylase activities of rat liver microsomes.

The omega- and (omega - 1)-hydroxylase activities for lauric acid were investigated in rat liver microsomes. Treatment of rats with phenobarbital selectively induced the hydroxylation of the fatty acid (omega - 1)-hydroxylase activity two- to threefold, but had little effect on the omega-hydroxylation reaction. SKF 525-A, metyrapone, and alpha-naphthoflavone inhibited (omega - 1)-hydroxylation, but had only neglible effects on omega-hydroxylation. Metyrapone at 10(-4) inhibited the specific activity of (omega - 1)-hydroxylase 70% in phenobarbital-pretreated rats, but produced only a 10% inhibition of the omega-hydroxylation activity. alpha-Naphthoflavone at 10(-4)M inhibited (omega - 1)-hydroxylase activity 60% in untreated and beta-haphthoflavone-pretreated rats, while omega-hydroxylase activity was decreased only 20%. A selective effect was also observed when microsomes were stored overnight at 4 degrees C. Declines of 50% and 70% were observed in the (omega - 1)-hydroxylase activities after 24 and 48 hr, respectively, whereas omega-hydroxylation decreased only 10-20%. The differential effects on omega- and (omega - 1)-hydroxylase activities of a variety of conditions suggest that distinct cytochromes P-450 mediate the two fattty acid hydroxylases in liver microsomes.

Animals↗

Polyethylene glycol400 laurate synthesized by immobilized lipase in a solvent-free system.

Conditions for the esterification of polyethylene glycol400 (PEG400) with lauric acid by immobilized lipase from Candida sp. 1619 in a solvent-free system were investigated. The esterification degree was increased greatly through the dehydration that occurred during the reaction. When the amount of lauric acid added exceeded the stoichiometric amount the yield of product was further improved by fed-batch feeding of PEG400. In the reaction system that was composed of 5.0 mmol of lauric acid, 2.5 mmol of PEG400, 20 mg of immobilized lipase (200 u), 0.2 ml of water, at 40 degrees C shaken for 48 h in a 100-ml conical flask without a plug, the esterification degree of 98.9% was reached. When the amount of lauric acid used was increased to 60 mmol, the PEG400 in reaction system was completely esterified. The recovery yield of product was 95% by hexane extraction and the product was identified as diester by means of TLC.

Candida↗