Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Valerates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 901 records · Page 50Linked to original sources
PubMed1999

Absorption and bioavailability of oestradiol from a gel, a patch and a tablet.

OBJECTIVES: To compare oestradiol and oestrone concentrations and bioavailability after a single dose and at a steady state during oral oestradiol valerate, transdermal oestradiol gel and transdermal oestradiol patch treatments. METHODS: Two open, randomised, cross-over studies were conducted. In the first study, 12 healthy postmenopausal women received 1.5 mg oestradiol as a transdermal gel or a 2 mg oestradiol valerate tablet daily for 14 days. In the second study, 15 postmenopausal women were treated for 18 days with 1.5 mg oestradiol gel or a transdermal patch releasing oestradiol 50 microg/24 h (replaced every 72 h). Venous blood samples for serum oestradiol and oestrone measurements with RIA were taken until 24 or 72 h after the first and last doses. RESULTS: The tablet and the transdermal gel yielded similar serum oestradiol profiles with a peak concentration 4-5 h after administration. The patch resulted in relatively stable oestradiol levels during the mid third of the wearing time whereas much lower levels were observed in the beginning and towards the end. There was no difference in the fluctuation between the peak and trough oestradiol levels between the gel (56 or 67%) and the tablet (54%) while the fluctuation was greater with the patch (89%). The bioavailability of oestradiol from the gel was 61% as compared with the tablet and 109% as compared with the patch. The gel was not bioequivalent with the tablet or the patch. CONCLUSIONS: The doses used of the transdermal gel and the patch roughly corresponded to each other with regard to the amount of oestradiol absorbed whereas the bioavailability from the tablet was significantly higher than from the gel. The lack of bioequivalence, the different serum oestradiol profiles and the large intersubject variability suggest that individual dose adjustments may be needed when changing administration form.

Administration, Cutaneous↗
PubMed1997

750 MHz 1H NMR spectroscopy characterisation of the complex metabolic pattern of urine from patients with inborn errors of metabolism: 2-hydroxyglutaric aciduria and maple syrup urine disease.

750 MHz 1H NMR spectroscopy has been used to characterise in detail the abnormal low molecular weight metabolites of urine from two patients with inborn errors of metabolism. One case of the rare condition 2-hydroxyglutaric aciduria has been examined. There is at present no rapid routine method to detect this genetic defect, although NMR spectroscopy of urine is shown to provide a distinctive pattern of resonances. Assignment of a number of prominent urinary metabolites not normally seen in control urine could be made on the basis of their known NMR spectral parameters including the diagnostic marker 2-hydroxyglutaric acid, which served to confirm the condition. In addition, 750 MHz 1H NMR spectroscopy has been used to characterise further the abnormal metabolic profile of urine from a patient with maple syrup urine disease. This abnormality arises from a defect in branched chain keto-acid decarboxylase activity and results in a build up in the urine of high levels of branched chain oxo- and hydroxy-acids resulting from altered metabolism of the branched chain amino acids, valine, leucine and isoleucine. A number of previously undetected abnormal metabolites have been identified through the use of one-dimensional and two-dimensional J-resolved and COSY 750 MHz 1H NMR spectroscopy, including ethanol, 2-hydroxy-isovalerate, 2,3-dihydroxy-valerate, 2-oxo-3-methyl-n-valerate and 2-oxo-isocaproate. NMR spectroscopy of urine, particularly when combined with automatic data reduction and computer pattern recognition using a combination of biochemical markers, promises to provide an efficient alternative to other techniques for the diagnosis of inborn errors of metabolism.

Amino Acid Metabolism, Inborn Errors↗
PubMed2001

Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (Comparison with steroids).

Tacrolimus (FK506) ointment showed remarkable efficacy against atopic dermatitis in animal models and clinical trials. The suppressive effect of tacrolimus on the production of the cytokines involved in atopic dermatitis (IL-2, IL-3, IL-4, IL-5, IFN-gamma and GM-CSF) from human peripheral blood mononuclear cells (PBMC) was investigated. We constructed a new cytokine production system in which T cells are activated by direct stimulation in vitro with anti-CD3/CD2 or anti-CD3/CD28 antibody combination. Tacrolimus inhibited the production of these cytokines by both stimulations. In a comparative study with steroids (alclometasone dipropionate and betamethason valerate) in anti-CD3/CD2 system, tacrolimus and both steroids inhibited Th1 cytokines (IL-2, IFN-gamma), Th2 cytokines (IL-4, IL-5) and IL-3, GM-CSF (produced by both Th1 and Th2). The suppressive effect of tacrolimus on cytokine production was stronger than that of alclometasone dipropionate and equal to or stronger than that of betamethason valerate. The effective dose of tacrolimus (IC50, 0.02-0.11 ng/ml) is almost the same as for Th1 and Th2 cytokines, and 1 ng/ml of tacrolimus suppressed all cytokines completely. These results suggest that tacrolimus suppresses the allergic cytokines from T cells, and that tacrolimus ointment is effective against atopic dermatitis through the inhibition of cytokine production.

Betamethasone↗
PubMed1994

Effects of various salts and pH on the stability of the nucleosome in chromatin fragments.

The stability of nucleosomes in long chromatin fragments was observed by differential scanning calorimetry over a wide range of solution conditions. The thermal denaturation of chromatin was characterized in general as three major transitions, although the process clearly is more complex. The three major transitions were (1) denaturation of the nucleosome, (2) base unstacking of DNA in the resulting denatured nucleoprotein, and (3) base unstacking of naked DNA. In very low salt concentrations (e.g., 2 mM sodium cacodylate), these three processes were essentially coincident (near 76 degrees C), but in medium salt concentrations (e.g., 100 mM NaCl) the nucleosome denaturation occurred first at about 69 degrees C and then base unstacking occurred at 85 degrees C. As [NaCl] was increased, all three processes were resolved with the observation of increasing amounts of naked DNA being melted, until at 2000 mM NaCl the calorimetric profile showed mainly the melting of DNA. The transition temperature for nucleosome denaturation decreased from 76 to 63 degrees C as the salt concentration increased from 1 to 600 mM. Destabilization of the nucleosome by increasing [NaCl] was also evident above 100 mM as a decrease in enthalpic change attributable to nucleosome denaturation. Similarly, as [NaCl] was increased above 100 mM, less and less denatured nucleoprotein was evident as more and more of the DNA melted as naked DNA. The fatty acid salts, sodium valerate and sodium caproate, destabilized the nucleosome but not the denatured nucleoprotein that resulted from the collapse of the nucleosome. In the series acetate, butyrate, valerate, caproate, it was clear that destabilization of the nucleosome increased as hydrophobicity (chain length) increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Calorimetry, Differential Scanning↗
PubMed2000

Identification of an essential tyrosine residue in nitroalkane oxidase by modification with tetranitromethane.

The flavoprotein nitroalkane oxidase from Fusarium oxysporum catalyzes the oxidation of nitroalkanes to the respective aldehydes or ketones with production of nitrite and hydrogen peroxide. The enzyme is irreversibly inactivated by incubation with tetranitromethane, a tyrosine-directed reagent, at pH 7.3. The inactivation is time-dependent and shows first-order kinetics for two half-lives of inactivation. Further inactivation can be achieved upon a second addition of tetranitromethane. A saturation kinetic pattern is observed when the rate of inactivation is determined versus the concentration of tetranitromethane, indicating that a reversible enzyme-inhibitor complex is formed before irreversible inactivation occurs. Values of 0.096 +/- 0.013 min(-1) and 12.9 +/- 3.8 mM were determined for the first-order rate constant for inactivation and the dissociation constant for the reversibly formed complex, respectively. The competitive inhibitor valerate protects the enzyme from inactivation by tetranitromethane, suggesting an active-site-directed inactivation. The UV-visible absorbance spectrum of the inactivated enzyme is perturbed with respect to that of the native enzyme, suggesting that treatment with tetranitromethane resulted in nitration of the enzyme. Comparison of tryptic maps of nitroalkane oxidase treated with tetranitromethane in the presence and absence of valerate shows a single peptide differentially labeled in the inactivated enzyme. The spectral properties of the modified peptide are consistent with nitration of a tyrosine residue. The amino acid sequence of the nitrated peptide is L-L-N-E-V-M-C-(NO(2)-Y)-P-L-F-D-G-G-N-I-G-L-R. The possible role of this tyrosine in substrate binding is discussed.

Amino Acid Sequence↗
PubMedDate not supplied

SEC-MALS characterization of microbial polyhydroxyalkanoates.

Characterization of poly-3-hydroxybutyric acid (PHB) and poly-3-hydroxybutyric-co-valeric acid (PHBV, 13% valerate) in chloroform was performed using size exclusion chromatography coupled to a multi-angle light scattering detector (SEC-MALS). Absolute molar mass averages, molar mass distribution, and the radius of gyration were determined. Three sample preparation methods were examined: dissolution in chloroform (1) at room temperature, (2) at 60 degrees C, and (3) after thermal pretreatment of samples (annealing at 180 degrees C with subsequent quenching in liquid nitrogen). Dissolution at 60 degrees C and dissolution of thermally pretreated samples gave molecularly dissolved PHB and PHBV. At 60 degrees C using acid free chloroform, there was no indication of degradation for up to 120 min dissolution time, whereas thermal degradation of polymers did take place during annealing at 180 degrees C. The degradation rate constants for number and weight average degree of polymerization at 180 degrees C were slightly higher for PHB (5.19 x 10(-5) min(-1), 4.95 x 10(-5) min(-1)) than for PHBV (4.99 x 10(-5) min(-1), 4.54 x 10(-5) min(-1)). The dependence of the radii of gyration on molar mass showed that both polymers form random coils in chloroform. The relationship between the absolute molar masses and relative SEC results was determined. DSC and NMR characterization also gave evidence of the progress of degradation.

Biodegradation, Environmental↗
PubMed2006

Improved bioproduction of short-chain fatty acids (SCFAs) from excess sludge under alkaline conditions.

The production of short-chain fatty acids (SCFAs) from excess sludge was conducted in batch fermentation tests at different pH values ranging from 4.0 to 11.0. Experimental results of the impacts of different pHs on SCFAs production showed that during the first 8-day fermentation time the total SCFAs production at either pH 9.0 or pH 10.0 was much greater than that at acidic or neutral pH, and the maximal yield of 256.2 mg SCFAs-COD per gram of volatile suspended solids (VSS) was at pH 10.0, which was, respectively, over3 and 4times that at pH 5.0 and uncontrolled pH. Clearly, SCFAs production from excess sludge could be significantly improved and maintained stable by controlling the fermentation pH at 10.0. The composition of SCFAs and the percent distribution of individual SCFAs accounting for total SCFAs at pH 10.0 were analyzed. The SCFAs consisted of acetic, propionic, iso-butyric, n-butyric, iso-valeric, and n-valeric acids, and acetic acid was the most prevalent product with a fraction of 40-55%. Because the results of this study were differentfrom those of previous studies of SCFAs production, the mechanism of increased SCFAs production under alkaline conditions was investigated. Results showed that as soluble COD increased, more soluble protein was provided as the substrate for producing SCFAs. In addition, less or even no SCFAs were consumed by methanogens at alkaline pH, so the SCFAs production was therefore remarkably improved. Further investigation revealed thatthe formation of SCFA at pH 10.0 was dominated by biological effects rather than by chemical hydrolysis.

Biodegradation, Environmental↗
PubMed2003

Conformationally constrained analogues of bleomycin A5.

The bleomycin (BLM) group antitumor antibiotics are glycopeptide-derived natural products shown to cause sequence selective lesions in DNA. Prior studies have indicated that the linker region, composed of the methylvalerate and threonine residues, may be responsible for a conformational bend in the agent required for efficient DNA cleavage. We have synthesized a number of conformationally constrained methylvalerate analogues and incorporated them into deglycobleomycin A(5) congeners using our recently reported procedure for the solid phase construction of (deglyco)bleomycin and its analogues. These analogues were designed to probe the effects of conformational constraint of the native valerate moiety. Initial experiments indicated that the constrained molecules, none of which mimic the conformation proposed for the natural valerate linker, possessed DNA cleavage activity, albeit with potencies less than that of (deglyco)BLM and lacking sequence selectivity. Further experiments demonstrated that these analogues failed to produce alkali-labile lesions in DNA or sequence selective oxidative damage in RNA. However, two of the conformationally constrained deglycoBLM analogues were shown to mediate RNA cleavage in the absence of added Fe(2+). The ability of the analogues to mediate the oxygenation of small molecules was also assayed, and it was shown that they were as competent in the transfer of oxygen to low molecular weight substrates as the parent compound.

Antibiotics, Antineoplastic↗
PubMed1986

Adriamycin analogues. Preparation and biological evaluation of some N-(trifluoroacetyl)-14-O-[(N-acetylamino)acyl]adriamycin derivatives.

In connection with structure-activity studies related to the novel DNA-nonbinding adriamycin analogues N-(trifluoroacetyl)adriamycin 14-valerate (AD 32) and N-(trifluoroacetyl)adriamycin 14-O-hemiadipate (AD 143), we have now prepared a series of N-(trifluoroacetyl)adriamycin derivatives with N-acylamino acid esters at the 14-carbinol position. Target compounds were made by reaction of N-(trifluoroacetyl)-14-iododaunorubicin with the sodium salts of N-acylamino acids generally in dimethylformamide-ethylene glycol solvent. Products were evaluated for in vitro growth-inhibitory activity and, to a limited extent, in vivo antitumor activity in the murine P388 leukemia system. ID50 values for the target compounds vs. cultured CCRF-CEM cells were generally in the same range as those for the above-mentioned DNA nonbinding adriamycin analogues. Of the four compounds tested for in vivo activity, although none was as effective as N-(trifluoroacetyl)adriamycin 14-valerate, all showed significant activity in the P388 assay system, with three of the compounds, at the doses used, being essentially equiactive with an optimal dose of adriamycin. Studies on the rate of esterase-mediated deacylation of the products, in a defined system containing unfractionated mouse serum as the source of enzyme, showed no relationship between the in vitro and in vivo activities of these compounds and the relative ease at which the side-chain ester substituents were hydrolyzed.

Animals↗
PubMed1982

Adriamycin analogues. Preparation of 9,10-anhydrodaunorubicin, 9,10-anhydroadriamycin, and some related compounds.

The title compounds, as well as 9,10-anhydro-N-(trifluoroacetyl)adriamycin 14-valerate (9,10-anhydro-AD 32), were prepared starting from daunorubicin, adriamycin, and N-(trifluoroacetyl)adriamycin 14-valerate (AD 32), respectively. In addition, 9-deoxydaunorubicin and 9-deoxy-AD 32 were obtained by catalytic hydrogenation of the appropriate olefin. All of the products were significantly less active than the parent drugs in inhibiting the growth of CCRF-CEM (human lymphoblastic leukemic) cells in culture. The results suggest the importance of the tertiary alcohol function, as found in the parent compounds at the anthracycline 9 position, in contributing to the expression of biological activity of these agents.

Animals↗
PubMed1987

Synthesis and structure-activity studies of corticosteroid 17-heterocyclic aromatic esters. 1. 9 alpha, 11 beta-dichloro series.

The preparation and topical antiinflammatory potencies of a series of 9 alpha, 11 beta-dichloro-16-methyl corticosteroid 17-heteroaryl carboxylates are described. The 17-acyl group was introduced to the 9 alpha, 11 beta-dichloro 21-acetate by direct acylation with the appropriate heteroaryl carbonyl chloride in the presence of 4-(dimethylamino)pyridine. Alternatively, the 21-functionalized 17-hydroxy delta 9(11) compound was acylated at 17, followed by C-ring chlorination. The most extensively studied heterocyclic acyl functionality was the 2-furoyl, but the 3-furoyl, and 2- and 3-thenoyl derivatives were also investigated. Antiinflammatory potencies were measured in mice by a 5-day modification of the Tonelli croton oil ear assay. The most potent topical antiinflammatory compounds were 17-heteroaryl esters in the 16 alpha-methyl series where the 21-substituent was chloro or fluoro. Thus 2p [21-chloro 17-(2'-furoate)] was 8 times as potent as betamethasone valerate, while 2s [21-fluoro 17-(2'-furoate)], 2r [21-chloro 17-(2'-theonate)], and 2v [6 alpha-fluoro 21-chloro 17-(2'-furoate)] were 3 times as potent as betamethasone valerate.

Administration, Topical↗
PubMed1987

17-Heteroaroyl esters of corticosteroids. 2. 11 beta-Hydroxy series.

The preparation and topical antiinflammatory potencies of a series of 17-furoyl and -thenoyl esters of 9 alpha-fluoro-11 beta-hydroxy-16 methyl and 9 alpha-chloro-11 beta-hydroxy-16-methyl corticosteroids are described. The 17 alpha-esters were introduced to the 9 alpha-fluoro 11-ketones or to the appropriate delta 9(11) compounds by direct acylation with the appropriate heteroaryl carbonyl chloride in the presence of 4-(dimethylamino)pyridine. Functionalization of the C ring was completed by standard methods. The most extensively studied heterocyclic acyl group was 2-furoyl, but 3-furoyl and 2- and 3-thenoyl derivatives were also investigated. Antiinflammatory potencies were measured in mice by a 5-day modification of the Tonelli croton oil ear assay. The most potent topical antiinflammatory agents were 1e, dexamethasone 17-(2'-furoate) 21-propionate, and 2c, the 21-chloro 17-(2'-furoate) in the 9 alpha-chloro series, both being 6 times as potent as betamethasone 17-valerate. Several other 9 alpha-chloro-11 beta-hydroxy-17-heteroaryl carboxylates (2a, 2b, 2d, and 2g) were at least 4 times as potent as betamethasone 17-valerate. Evaluation of 2c in the clinic confirmed that the compound is a potent topical antiinflammatory agent in humans.

Adrenal Cortex Hormones↗
PubMed2003

Lacticin 3147 favours isoleucine transamination by Lactococcus lactis IFPL359 in a cheese-model system.

The bacteriocin, lacticin 3147, increased isoleucine transamination by Lactococcus lactis IFPL359 in a cheese model system. The formation of alpha-keto-beta-methyl-n-valeric acid and 2-hydroxy-3-methyl-valeric acid increased by three times in cheese slurries at 12 degrees C and cheese aroma intensity increased as well, which corresponded with a higher 2-methylbutanal formation.

Amino Acids↗
PubMed1998

Quantification of tyrosinase, TRP-1, and Trp-2 transcripts in human melanocytes by reverse transcriptase-competitive multiplex PCR--regulation by steroid hormones.

We have introduced a reverse transcriptase polymerase chain reaction based method to measure mRNA levels of the melanogenesis enzymes tyrosinase, tyrosinase-related-protein 1 (TRP-1), and tyrosinase-related-protein 2 (TRP-2). Expression was determined by reverse transcriptase-competitive multiplex polymerase chain reaction of (i) melanogenesis enzyme transcripts and the "housekeeping" gene glyceraldehyde-3-phosphate dehydrogenase, and (ii) two internal standards consisting of mutated melanogenesis enzyme cDNA and mutated gene glyceraldehyde-3-phosphate dehydrogenase cDNA. This was investigated on in vitro cultured melanocytes in the presence of three different steroids; one glucocorticoid (betamethasone-17-valerate) and two sex steroids (diethylstilbestrol and estradiol). All three steroids lead to an increase of about 1.5-2.5-fold of tyrosinase transcripts. The amount of TRP-1 transcripts was likewise enhanced, but only moderately (approximately 1.5-fold). In contrast, TRP-2 transcripts were reduced by approximately 40% in number after betamethasone-17-valerate treatment, whereas the two sex steroids, diethylstilbestrol and estradiol, caused an upregulation of about 20-fold of the initial TRP-2 transcript level. We therefore suggest that hyperpigmentation during pregnancy or under contraceptive treatment is mediated by a direct induction of melanogenesis via sex steroids.

Betamethasone↗
PubMed1998

Regulation of RANTES and IL-8 production in normal human dermal fibroblasts by active vitamin D3 (tacalcitol).

1. The production of chemokines, RANTES and IL-8 in cultured human dermal fibroblasts and the effects of tacalcitol (1alpha,24(R)-dihydroxyvitamin D3) were studied using an enzyme-linked immunosorbent assay. 2. In the unstimulated condition, RANTES and IL-8 were at a trace level in the culture supernatant. On stimulation with TNF-alpha alone for 24 h, RANTES and IL-8 production were induced. Tacalcitol suppressed RANTES and IL-8 production dose-dependently at concentrations between 10(-12) M and 10(-7) M. 3. When the cells were treated with TNF-alpha and IFN-gamma in combination, RANTES production was enhanced, but IL-8 production was not changed, compared to TNF-alpha-treated cells. Tacalcitol decreased IL-8 production dose-dependently as observed in the TNF-alpha-treated cells. On the other hand, RANTES production was enhanced by 10(-11) M and 10(-10) M of tacalcitol, and dose-dependently suppressed by tacalcitol concentrations higher than 10(-9) M. 4. Active vitamin D3 compounds, betamethasone valerate and cyclosporin A were compared with respect to their effects on chemokine production. Three active vitamin D3 compounds, tacalcitol, 1alpha,25-dihydroxyvitamin D3 and MC903 (calcipotriol), inhibited the production of RANTES and IL-8, with very similar potencies. Betamethasone valerate also inhibited these chemokine productions, but with greater potency than active vitamin D3 compounds. Cyclosporin A significantly stimulated RANTES production at 10(-6) M and IL-8 production at 10(-7) M and 10(-6) M. 5. The results of this study suggest that active vitamin D3 compounds exert some beneficial effects in the treatment of inflammatory skin diseases via regulation of the production of chemokines by dermal fibroblasts.

Betamethasone↗
PubMed1976

Microbiological degradation of bile acids. Nitrogenous hexahydroindane derivatives formed from cholic acid by Streptomyces rubescens.

The metabolism of cholic acid (I) by Streptomyces rubescens was investigated. This organism effected ring A cleavage, side-chain shortening and amide bond formation and gave the following metabolites: (4R)-4-[4alpha-(2-carboxyethyl)-3aalpha-hexahydro-7abeta-methyl-5-oxoindan-1 beta-yl]valeric acid (IIa) and its mono-amide (valeramide) (IIb); and 2,3,4,6, 6abeta,7,8,9,9aalpha,9bbeta-decahydro-6abeta-methyl-1H-cyclopenta[f]quinoline-3,7-dione(IIIe)and its homologues with the beta-oriented side chains, valeric acid, valeramide, butanone and propionic acid, in the place of the oxo group at C-7, i.e.compounds (IIIa), (IIIb), (IIIc) and (IIId) respectively. All the nitrogenous metabolites were new compounds, and their structures were established by partial synthesis except for the metabolite (IIIc). The mechanism of formation of these metabolites is considered. A degradative pathway of cholic acid (I) into the metabolites is also tentatively proposed.

Cholic Acids↗
PubMed1983

Assessment of the flux of mitochondrial acetyl-CoA in liver and kidney by using the differential production of 14CO2 from tracers of (1-14C)- and (2-14C)-labelled 4-methyl-2-oxovalerate.

A procedure is described to convert rates of (14)CO(2) production into rates of mitochondrial acetyl-CoA production from a (14)C-labelled substrate. The principle is illustrated in perfused rat liver and kidney by the differential yield of (14)CO(2) from 4-methyl-2-oxo[1-(14)C]valerate and 4-methyl-2-oxo[2-(14)C]valerate.

Acetyl Coenzyme A↗
PubMed1983

Bovine serum albumin decreases 4-methyl-2-oxovalerate utilization by isolated rat hepatocytes.

Binding of 4-methyl-2-oxo[1-14C]valerate to defatted bovine serum albumin inhibited the utilization of this 2-oxo acid by fed-rat hepatocytes in vitro. With 0-50g of albumin/l in the presence of 0.05mM 2-oxo acid or on increasing the 2-oxo acid concentration from 0 to 2mM in the presence of 26g of albumin/l, the extent of inhibition was essentially dependent on the change in the free 2-oxo acid concentration. Intrahepatocyte 4-methyl-2-oxo[1-14C]valerate concentrations were similar to extracellular free 2-oxo acid concentrations, suggesting equilibration so that the plasma membrane appears not to be rate-limiting for the utilization of this substrate by the isolated liver cells.

Animals↗