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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We developed a simplified method for quantitative measurement of trinitroglycerin in human plasma using hexane extraction and analysis by gas-liquid chromatography with electron-capture detection. This assay was linear from 0.5-60 ng/ml. Sensitivity and reproducibility were +/- 0.5 ng/ml. We used this assay to evaluate the pharmacodynamics of trinitroglycerin in 14 patients. Maximum plasma levels were similar with trinitroglycerin given by constant intravenous infusion (1.6 +/- 0.4 ng/ml (SEM)), transcutaneously (2.3 +/- 0.6 ng/ml), or sublingually (1.6 +/- 0.6 ng/ml). Despite similar levels and hemodynamic responses after intravenous trinitroglycerin, the dose range was wide (37.5-175 microg/min, n = 5), emphasizing the need to individualize therapy. In normal volunteers on no other drugs, the plasma level time course followed changes in heart rate better than blood pressure changes. Use of the trinitroglycerin assay may enhance optimization of trinitroglycerin therapy when administered by different methods.
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PMID:Quantitative determination of trinitroglycerin in human plasma. 10 4

A sensitive and selective assay has been developed for the identification and quantitation of 3-amino-1-phenyl butane (3-APB), a metabolite of labetalol, in biological fluids using electron impact gas chromatography/mass-selective detection. Samples were extracted with n-hexane, derivatized with heptafluorobutyric anhydride and chromatographed on a cross-linked fused-silica capillary column. A positive EI spectrum was obtained using a mass-selective detector. Identification of the metabolite was accomplished using an authentic standard; quantitation was performed in the selected ion monitoring mode using ions m/z 345 (M+) and 132. The assay was linear over the calibration range of 0.5-1000 ng of the analyte and the intra-sample coefficients of variation were less than 12% in all cases. The absolute recovery of 3-APB following extraction from urine and bile was found to be 102.9 +/- 4.9% and 98.3 +/- 1.45% (mean +/- SEM) respectively. The minimum quantitation limit of the assay was 0.5 ng ml-1 (approximately 2 pg injected). Application of the assay in a pharmacokinetic-pharmacodynamic study of labetalol in sheep is demonstrated. The metabolite was detected in urine and bile samples obtained from adult non-pregnant sheep following labetalol administration. The cumulative amount of 3-APB excreted in urine over 24 h was found to be 71.55 micrograms in one animal following a 100 mg dose of labetalol. Evidence for biliary excretion, glucuronidation and sulfation of 3-APB was also found.
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PMID:Identification and quantitation of an oxidative metabolite of labetalol in sheep: pharmacokinetic and metabolic implications. 145 68

Reversed-phase HPLC assays with on-column UV detection and post-column fluorescent detection of ion pair-extracted material were developed and used for the quantitative assay of methadone, its presumed metabolites, and acid- and alkali-hydrolyzable conjugates of these metabolites in biological fluids with assay sensitivities of 10-20 ng/mL. Plasma, urine, and bile were monitored in dogs after intravenous bolus administration of 0.8, 1.0, 2.0, and 2.2 mg/kg methadone hydrochloride. Plasma-time data showed two sequential half-lives of 8.3 +/- 3.4 (SEM) and 128 +/- 37 min, with apparent dose-independent pharmacokinetics in the studied dose range. Total body clearances were 899 +/- 103 (SEM) mL/min. Renal clearances (6-82 mL/min) of methadone were highly variable within and among studies but showed no significant variation with urinary pH or flow rate. The percentages of the dose excreted in the urine as methadone and (+)-2-ethyl-1,5-dimethyl-3,3-diphenylpyrroline (2) were 3.6 +/- 0.5% (SEM) and 4.1 +/- 0.4% (SEM), respectively, but there were no significant concentrations of 2 in plasma. The presumed metabolites 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (3), 1,5-dimethyl-3,3-diphenyl-2-pyrrolidone (4), (-)-alpha-N-normethadol (7), 4-dimethylamino-2,2-diphenylvaleric acid (8), p-hydroxymethadone (9), and (-)-alpha-methadol (10) were not observed in the plasma of dogs given methadone. Quantities of presumed metabolites 3, 4, 7, 8, 9, and 10 were negligible in urine (less than 0.03% of dose). No acid-hydrolyzable conjugates, or generators on acidification, of 3, 4, 7, 8, or 10 were detectable in urine. No alkali-hydrolyzable conjugates, or generators on alkalinization, of 3, 4, 8, or 10 were detectable in urine. There was no significant biliary secretion of unchanged methadone; 2 in bile amounted to only 2% of the dose. In bile and urine, 50% and 17-27%, respectively, of the radiolabeled dose was not extractable into hexane. In a non-bile-cannulated dog, 35% of the total radiolabeled intravenous dose was present in the feces. As much as 88% of an intravenous radiolabeled dose could be accounted for, even though only small amount of methadone was disposed through the metabolic routes claimed in the literature. The intravenous administration of 2 resulted in two sequential half-lives of 3 and 270 min and no apparent pharmacokinetic dose dependency. Amounts of 2 excreted unchanged in urine and bile were 23% and 5-16% of the dose, respectively. Renal and total body clearances were 170 and 1150 mL/min.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacokinetics of morphine and its surrogates. VII: High-performance liquid chromatographic analyses and pharmacokinetics of methadone and its derived metabolites in dogs. 408 82

Conversion of thyroxine (T(4)) to 3,5,3'-triiodothyronine (T(3)) in rat brain has recently been shown in in vivo studies. This process contributes a substantial fraction of endogenous nuclear T(3) in the rat cerebral cortex and cerebellum. Production of T(4) metabolites besides T(3) in the brain has also been suggested. To determine the nature of these reactions, we studied metabolism of 0.2-1.0 nM [(125)I]T(4) and 0.1-0.3 nM [(131)I]T(3) in whole homogenates and subcellular fractions of rat cerebral cortex and cerebellum. Dithiothreitol (DTT) was required for detectable metabolic reactions: 100 mM DTT was routinely used. Ethanol extracts of incubation mixtures were analyzed by paper chromatography in t-amyl alcohol:hexane:ammonia and in 1-butanol:acetic acid. Rates of production of iodothyronines from T(4) and T(3) were greater at pH 7.5 than at 6.4 or 8.6 and greater at 37 degrees C than at 22 degrees or 4 degrees C. Lowering the pH, reducing the protein or DTT concentrations, and preheating homogenates to 100 degrees C all increased excess I(-) production but reduced iodothyronine production. In cerebral cortical homogenates from normal rats, products of T(4) degradation were as follows (percent added T(4)+/-SEM in nine experiments): T(3), 1.9+/-0.5%; 3,3',5'-triiodothyronine (rT(3)), 34.0+/-2.4%; 3,3'-diiodothyronine (3,3'-T(2)), 5.8+/-1.6%; 3'-iodothyronine (3'-T(1)), </=2.5%; and excess I(-), 4.7+/-1.2%. In the same experiments, products of T(3) degradation were 3,3'-T(2), 63.3+/-5.5%, and 3'-T(1), 12.6+/-1.4%. Cerebral cortical homogenates from hyperthyroid rats and normals were similar in regard to T(4) to T(3) deiodination. In contrast, in cerebral cortical homogenates from hypothyroid rats, phenolic ring deiodination rates were increased and tyrosyl ring deiodination rates were decreased compared with normals.T(4) to T(3) conversion rates in cerebellar homogenates were greater than rates in cerebral cortical homogenates from the same normal rats and less than rates in cerebellar homogenates from hypothyroid rats. T(4) and T(3) tyrosyl ring deiodination rates were greatly diminished in cerebellar homogenates compared with cerebral cortical homogenates in normal and hypothyroid rats. High-speed (1,000-160,000 g) pellets from cerebral cortical homogenates were enriched in phenolic and tyrosyl ring deiodinating activities relative to cytosol. Fractional conversion of T(4) to T(3) was inhibited by T(4), iopanoic acid, and rT(3), but not by T(3). Tyrosyl ring deiodination reactions were inhibited by T(3), T(4), and iopanoic acid, but not by rT(3). These studies demonstrate separate phenolic and tyrosyl ring iodothyronine deiodinase enzymes in rat brain. The brain phenolic ring deiodinase serves in vivo as a T(4) 5'-deiodinase and closely resembles anterior pituitary T(4) 5'-deiodinase in physiological and biochemical characteristics. The physiological significance of the tyrosyl ring iodothyronine deiodinase enzyme is unclear; it shares several properties with rat hepatic T(4) 5-deiodinase.
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PMID:Phenolic and tyrosyl ring deiodination of iodothyronines in rat brain homogenates. 740 Mar 28

The hydrothermal crystallization of X-type zeolite with a Si/Al ratio of 1.15 was achieved from the Na(2)O-Al(2)O(3)-SiO(2)-H(2)O system at 368 K under static conditions. The post-synthesis modification was carried out by a conventional ion-exchange technique to obtain K(+)-, Rb(+)-, and Cs(+)-exchanged samples with different degrees of exchange. All the samples were characterized using chemical analysis, IR, SEM, powder XRD, low-temperature nitrogen adsorption, and equilibrium sorption uptakes of different probe molecules. The relative intensities of the XRD peaks of cation-exchanged zeolite were found to be affected to different extents, depending on the nature and the concentration of nonframework cationic size, without any shift in the positions of reflection. The sorptive properties of the K-, Rb-, and Cs-exchanged samples were studied using nitrogen, water, and different C(6) hydrocarbons including bulkier benzene derivative 1,3,5-trimethylbenzene (TMB) as probe molecules. The trend observed in chemical potential estimated as a function of nitrogen coverage indicates different sorption selectivity because of differences in the cationic size and population. Sorption uptake kinetics for probe molecules such as water, n-hexane, cyclohexane, benzene, and TMB were also studied. The samples with higher degrees of exchange and/or cationic size have shown a decrease in hydrophilic character due to the formation of irregular networks of water molecules connected with preadsorbed water molecules, framework oxygen ions, and nonframework cations. Among C(6) hydrocarbons including TMB, the benzene molecule is found to be the most promising probe for the estimation of openness of structure and surface heterogeneity as well. Copyright 2001 Academic Press.
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PMID:Adsorption Behavior of N(2), Water, C(6) Hydrocarbons, and Bulkier Benzene Derivative (TMB) on Na-X Zeolite and Its K(+)-, Rb(+)-, and Cs(+)-Exchanged Analogues. 1123 52

The hexane extract of Syzygium samarangense (Ss.Hex) dose-dependently (10-1000 microg/ ml) relaxed the spontaneously contracting isolated rabbit jejunum. Four rare C-methylated flavonoids with a chalcone and a flavanone skeleton were isolated from Ss.Hex and were subsequently tested for spasmolytic activity. All flavonoids, identified as 2'-hydroxy-4',6'-dimethoxy-3'-methylchalcone (1), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (2), 2',4'-dihydroxy-6'-methoxy-3'-methylchalcone (3), and 7-hydroxy-5-methoxy-6,8-dimethyl-flavanone (4), showed dose-dependent spasmolytic activity in the rabbit jejunum with IC50 values of 148.3 +/- 69.4, 77.2 +/- 43.5, 142.4 +/- 58.6 and 178.5 +/- 37.5 microg/ml (mean +/- SEM), respectively. The dihydrochalcone derivative of compound 1, 2'-hydroxy-4',6'-dimethoxy-3'-methyldihydrochalcone (5), when tested for spasmolytic activity, did not significantly relax the smooth muscle relative to the other compounds. Verapamil, a standard spasmolytic, has an IC50 value of 0.16 +/- 0.04 microg/ml. This is the first report of the relaxant activity of chalcones, specifically of compounds 1-3.
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PMID:Spasmolytic flavonoids from Syzygium samarangense (Blume) Merr. & L.M. Perry. 1578 47

Acorus calamus Linn. (Araceae) is a native of Central Asia and Eastern Europe and has widespread use in the traditional system of medicine for gastrointestinal disorders such as colic pain and diarrhoea. This study was aimed at providing a possible pharmacological basis to the use of this plant as an antispasmodic and antidiarrhoeal. In the isolated rabbit jejunum preparation the crude extract (Ac.Cr), which tested positive for the presence of alkaloid, saponins and tannins, caused inhibition of spontaneous and high K(+) (80 mm)-induced contractions, with respective EC(50) values of 0.42 +/- 0.06 and 0.13 +/- 0.04 mg/mL (mean +/- SEM; n = 6-8), thus showing spasmolytic activity, mediated possibly through calcium channel blockade (CCB). The CCB activity was confirmed when pre-treatment of the tissue with Ac.Cr (0.3-1.0 mg/mL) caused a rightward shift in the Ca(++) dose-response curves similar to that caused by verapamil, a standard calcium channel blocker. Activity-directed fractionation revealed that the CCB activity was concentrated in the n-hexane fraction while the ethylacetate fraction was less potent. These results suggest that the spasmolytic effect of the plant extract is mediated through the presence of CCB-like constituent(s) which is concentrated in the n-hexane fraction and this study provides a strong mechanistic base for its traditional use in gastrointestinal disorders such as colic pain and diarrhoea.
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PMID:Antispasmodic effect of Acorus calamus Linn. is mediated through calcium channel blockade. 1700 6

Enzymes are less stable in harsh conditions and hence to overcome this nature, several methodologies are being developed. It was found that crosslinked enzyme crystals are the most promising strategy for the stabilization of the enzymes [Emilia Abraham, T., Jegan Roy, J., Bindhu, L.V., Jayakumar, K.K., 2004. Crosslinked enzyme crystals of glucoamylase as a potent catalyst for biotransformations. Carbohydr. Res. 339, 1099-1104; Navia, M., St. Clair, N., 1997. Crosslinked enzyme crystals. Biosens. Bioelectron. 12, 7]. A cost effective methodology of crystallization of protease (Bacillus subtilis) with ammonium sulphate (65%, w/v) and then crosslinking the crystals with glutaraldehyde (4%, v/v) in isopropanol for 20min gave a stable and active enzyme. SEM studies showed that the protease is in small cubic shaped crystals of 1-2 microm size. Crosslinked enzyme crystal (CLEC) of protease has good stability in polar and nonpolar organic solvents, such as hexane, toluene, benzene and carbon tetrachloride and it had high thermal stability up to 60 degrees C and hence can be used as a catalyst for the biotransformation of compounds which are not soluble in aqueous medium. The CLECs were entrapped in the alginate:guar gum (3:1) composite beads which were resistant to low pH conditions in the stomach and hence was found to be useful for the oral drug delivery. This method can be used to deliver the protein and peptide drugs which require high concentrations at the delivery stage, and which normally degrades in the stomach before reaching the jejunum. Application of these pH-sensitive beads for the controlled release of subtilisin in in vitro was studied and found to be a viable strategy.
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PMID:Encapsulation of crosslinked subtilisin microcrystals in hydrogel beads for controlled release applications. 1762 42

Highly ordered hierarchical calcium carbonate is an important phase involved in calcification by a wide variety of invertebrate organisms, and its formation is of technological interest in the development of functional materials. In this article, porous CaCO(3) hierarchical microspheres with a hedgehoglike appearance have been fabricated on the flexible substrate under mild conditions. There are two points that play important roles in the regular organization of the terminal products: one is the biphase interfaces, which are generated by organic solvent n-hexane and an aqueous saturated solution of Ca(OH)(2), and the other is hydroxyl-terminated monolayers assembled on the flexible PET (poly(ethylene terephthalate)) substrate. The SEM images show that novel CaCO(3) hierarchical microspheres consist of densely stacked "shuttles" by the oriented self-organization of CaCO(3) nanoparticles. The IR and XRD spectra indicate that the as-synthesized products are composed of a calcite phase obtained by an ACC (amorphous calcium carbonate)-to-calcite transformation. In view of the results, a nanoparticle-mediated self-organization process induced by biphase interfaces and SAMs template is proposed for the integration of functional materials and nanodevices.
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PMID:Fabrication of hierarchical CaCO3 mesoporous spheres: particle-mediated self-organization induced by biphase interfaces and SAMs. 2002 Jul 62

Nanohybrid organo-inorgano clay mineral-polydimethylsiloxane (PDMS) membranes were prepared by the reaction of pure and/or modified natural clay minerals (Sepiolite and montmorillonite) with PDMS in hexane, followed by evaporation of the solvent at 70 degrees C. The membranes were characterized by means of XRD, SEM, ATD-TG and solid state (29)Si magic angle spinning (MAS) and cross-polarization (CP) CP/MAS NMR. The morphology of the membranes depends on the content loading of clay mineral. For low content, the membrane composition is homogeneous, with well dispersed nanoparticles of clay into the polymer matrix, whereas for higher clay content, the membranes are constituted also of a mixture of well dispersed nanoparticles into the polymer, but in the presence of agglomerations of small clay particles. Quantitative (29)Si MAS NMR demonstrated a strong correlation between the clay content of the membrane and the average length of the PDMS chain, indicating that the nanohybrid material is made of clay particles covalently linked to the PDMS structure. This is particularly the case for Sepiolite with has a high density of Q(2) silanol sites. The separation performances of the prepared membranes were tested for CO(2)/CH(4) and O(2)/N(2) mixtures. The observed separation factors showed an increase of the selectivity in the case of CO(2)/CH(4) in comparison with membranes made from PDMS alone under the same conditions.
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PMID:Nanoporous polymer--clay hybrid membranes for gas separation. 2006 May 40


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