[Chemical constituents of Bulgaria inquinans (Fries)].
Three compounds were isolated from Bulgaria inquinans. They were identified as ergosterol, galacitiol and ethanedioic acid.
Drugs, Chinese Herbal↗
Biomedical subjects
D Cui
Publications and source records attributed to D Cui.
[Physiological effects of cabin temperature decrease on human].
To study effects of cabin temperature on human body, changes in rectal temperature, local skin temperature, local skin heat fluxes and skin infrared thermogram were observed in 5 male subjects dressed in different thermal insulation clothings under 20 degrees C, 15 degrees C and 10 degrees C cabin temperatures. The results showed that, average skin temperature and tip temperature obviously dropped, and skin heat fluxes increased with falling of cabin temperature, and changes of local skin infrared thermogram were significant. Subjective feeling were comfortable and cool at cabin temperature of 20 degrees C and 15 degrees C respectively. While subjective feeling was cold and there was a thermal debt of body 144 kJ/m2 at 10 degrees C which indicated that it was slightly cold but tolerable. The results may be valuable in determining the lowest tolerable limit of cabin temperature.
Acclimatization↗
Characterization of the novel benzisothiazole ring-cleaved products of the antipsychotic drug ziprasidone.
Characterization of two novel benzisothiazole ring cleaved metabolites of the antipsychotic drug, ziprasidone (ZIP), in rat has been described. Metabolites designated M6 and M9 were isolated from urine and bile of the rat dosed with radiolabeled ZIP and purified by reversed phase HPLC. The chemical structures of these metabolites were assigned based on tandem mass spectrometry in combination with chemical derivatization techniques. M6 and M9 were unaffected upon treatment with N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide. Reaction of M9 with aqueous TiCl3 also did not change the HPLC retention time or the CID spectrum of metabolite M9. These data excluded the possibility that these metabolites were owing to N-oxidation and/or aromatic hydroxylation. M6 and M9 were generated only when in vitro incubations of ZIP were conducted with human liver S-9 fraction in the presence of S-adenosyl-L-methionine. Based on these data, metabolites M6 and M9 were identified as S-methyl-dihydro-ZIP and S-methyl-dihylro-ZIP-sulfoxide, respectively. The structure of M9 was unambiguously confirmed by comparing the LC/MS retention time and mass spectral data with synthetic standard. A mechanism for the formation of these metabolites from ZIP is proposed.
Animals↗
Amyloid A protein amyloidosis induced in apolipoprotein-E-deficient mice.
Apolipoprotein E (apoE) is a constituent of lipoproteins other than low-density lipoprotein, and it principally acts in the transport and metabolism of plasma cholesterol and triglyceride. ApoE is a minor constituent of various kinds of amyloidoses and may play a role as a pathological chaperone for fibrillogenesis of amyloid fibril protein with the amyloid P component and proteoglycans. In this study, we examined the role of apoE in amyloidogenesis in vivo in apoE-deficient mutant mice with amyloid A protein (AA) amyloidosis induced by inflammatory stimulation. Amyloid deposition was seen in six of nine C57BL/6J control mice and in six of eight apoE-deficient mutant mice after the intraperitoneal and subcutaneous injections of the mixture of complete Freund's adjuvant and Mycobacterium butyricum. Moreover, amyloid deposition in apoE-deficient mice as well as C57BL/6J control mice started 48 or 72 hours after injection of amyloid-enhancing factor and silver nitrate, although the amount of amyloid deposit in C57BL/6J control mice was slightly larger than that in apoE-deficient mice. These amyloid deposits reacted with anti-mouse AA antibody were seen in the perifollicular area of the spleen. Immunoreactivity of apoE was seen irregularly in the amyloid deposits of C57BL/6J control mice but not in the amyloid deposit of apoE-deficient mice. From these results, we concluded that apoE is not always necessary for amyloid deposition and that the existence of apoE might slightly accelerate AA amyloid deposition in the earliest phase of AA amyloid deposition.
Amyloidosis↗
Metabolism and excretion of a new antianxiety drug candidate, CP-93,393, in cynomolgus monkeys: identification of the novel pyrimidine ring cleaved metabolites.
The metabolism and excretion of a new anxiolytic/antidepressant drug candidate, CP-93,393, ((7S, 9aS)-1-(2-pyrimidin-2-yl-octahydro-pyrido[1, 2-a]-pyrazin-7-yl-methyl)-pyrrolidine-2,5-dione) were investigated in cynomolgus monkeys after oral administration of a single 5 mg/kg dose of 14C-CP-93,393. Urine, bile, feces, and blood samples were collected and assayed for total radioactivity, parent drug, and metabolites. Total recovery of the administered dose after 6 days was 80% with the majority recovered during the first 48 hr. An average of 69% of the total radioactivity was recovered in urine, 4% in bile, and 7% in feces. Mean Cmax and AUC(0-infinity) values for the unchanged CP-93,393 were 143.2 ng/ml and 497.7 ng.hr/ml, respectively, in the male monkeys and 17.2 ng/ml and 13.7 ng.hr/ml, respectively, in the female monkeys. HPLC analysis of urine, bile, feces, and plasma from both male and female monkeys indicated extensive metabolism of CP-93,393 to several metabolites. The identification of metabolites was achieved by chemical derivatization, beta-glucuronidase/sulfatase treatment, and by LC/MS/MS, and the quantity of each metabolite was determined by radioactivity detector. CP-93,393 undergoes metabolism by three primary pathways, aromatic hydroxylation, oxidative degradation of the pyrimidine ring, and hydrolysis of the succinimide ring followed by a variety of secondary pathways, such as oxidation, methylation, and conjugation with glucuronic acid and sulfuric acid. The major metabolites, oxidation on the pyrimidine ring to form 5-OH-CP-93,393 (M15) followed by glucuronide and sulfate conjugation (M7 and M13), accounted for 35-45% of the dose in excreta. Two metabolites (M25 and M26) were formed by further oxidation of M15 followed by methylation of the resulting catechol intermediate presumably by catechol-O-methyl transferase. A novel metabolic pathway, resulting in the cleavage of the pyrimidine ring, was also identified. The metabolites (M18, M20, and M21) observed from this pathway accounted for 8-15% of the dose. Aliphatic hydroxylation of the succinimide ring was a very minor pathway in monkey. 5-Hydroxy-CP-93,393 (M15, 37-49%), its sulfate and glucuronide conjugates (M7 and M13, approximately 34%), and the pyrimidine ring cleaved product (M18, approximately 8%) were the major metabolites in monkey plasma. The identified metabolites accounted for approximately 90, 93, 97, and 92% of the total radioactivity present in urine, bile, plasma, and feces, respectively. The major in vivo oxidative metabolites were also observed after in vitro incubations with monkey liver microsomes.
Adrenergic alpha-2 Receptor Antagonists↗
Sequence-specific interactions of wound-inducible nuclear factors with mannopine synthase 2' promoter wound-responsive elements.
A 318 bp mannopine synthase 2' (mas2') promoter element from the T-DNA of Agrobacterium tumefacians can direct wound-inducible and root-preferential expression of a linked uidA gene in transgenic tobacco plants. Wound inducibility is further enhanced by sucrose in the medium. Promoter deletion analysis indicated that the sucrose enhancement is conferred by a region extending from -318 to -213. DNase I footprinting indicated that an A/T-rich DNA sequence in this region is protected by tobacco nuclear factors. Regions extending from -103 to +66 and from -213 to -138 directed wound-inducibile expression of a linked uidA gene when placed downstream of a CaMV 35S enhancer or upstream of a truncated (-209) CaMV 35S promoter, respectively. DNase I footprinting analyses indicated that proteins from wounded tobacco leaves specifically bound to three contiguous motifs downstream of the mas2' TATA box. In addition to a common retarded band formed by the upstream wound-responsive element complexed with proteins from either wounded or unwounded tobacco leaves, two unique retarded bands were observed when this element was incubated with protein from wounded leaves. Methylation interference analysis additionally identified an unique motif composed of promoter elements and nuclear factors derived specifically from wounded tobacco leaves. We propose a model to describe the involvement of nuclear factors with mas2' promoter elements in wound-inducible gene expression.
Agrobacterium tumefaciens↗
Interaction of synthetic peptide corresponding to signal sequence of glucitol permease of Escherichia coli and its analogue with liposomes.
The N-terminal signal sequence of glucitol permease of Escherichia Coli (Gut22) and its analogue (Gut22Ana) were synthesized. The analogue had a Pro residue substituting for the His at the 7th position of Gut22 and a Val residue substituting for the Glu at the 10th position. The intrinsic fluorescence emission spectra indicated that the binding of Gut22 with lipid bilayer was much stronger than that of Gut22Ana. The leakage experiments with calcein-loaded liposomes showed that Gut22 strongly perturbed lipid bilayers while Gut22Ana did not. The apparent partition constant of Gut22 for partitioning into phosphatidylserine/phosphatidylcholine bilayers was measured; the effect of membrane potential on the interaction of Gut22 with lipid bilayers was studied and the conformation changes of Gut22 and Gut22Ana upon interacting with liposomes were studied by the method of circular dichroism analysis.
Amino Acid Sequence↗
[The changes of glucocorticoid receptor and beta-adrenoreceptor of lung tissues in SD rat asthma models and the effects of antiasthmatics on them].
OBJECTIVE: To observe the changes of glucocorticoid receptor (GR) and beta-adrenoreceptor (beta-AR) of lung tissue and the effects of oral procaterol, salbutamol and intraperitoneal (i.p.) or inhaled (i.h.) dexamethasone (Dex). METHOD: The GR or beta-AR were determined by using 3H-dexamethasone and 3H-Dihydroalprenolol as ligand respectively, in groups of rat asthma models at 1, 3, 7, 14th day and groups received antiasthmatics on the 7th day after daily consecutive challenges. RESULTS: The GR Bmax of asthma groups increased significantly after the first challenge, but decreased since the third day to a lower level than that of healthy control. The KD also decreased significantly since the third day. The beta-AR Bmax of asthma group gradually decreased to a significant low level on the 14th day. The Dex i.p. group had the lowest GR Bmax and the Dex i.h. group had the highest beta-AR Bmax among the treated. In the procaterol and salbutamol group, there had no decrease of GR Bmax compared with that of controls. CONCLUSIONS: The GR and beta-AR levels of lung tissues changed after daily challenges. The GC played a down-regulation role on GR and an up-regulation role on beta-AR in lung tissues. The Dex i.h. had more advantages than Dex i.p. in terms of GR and beta-AR regulations.
Adrenergic beta-Agonists↗
Synthesis and application of hepatitis E virus peptides to diagnosis.
Based on computer analysis of hydrophobicity and prediction of secondary structures for the full-length putative proteins encoded by open reading frame-1 (ORF-1), ORF-2 and ORF-3 of hepatitis E virus (HEV), we selected antigenic regions with hydrophilicity, beta-turn, and beta-sheet, and synthesized 7 peptides of possible epitope-containing regions of the polypeptide encoded by all 3 ORFs of HEV genomic RNA by Merrifield's method of solid-phase synthesis. The synthetic peptides were screened and identified by solid-phase enzyme-linked immunosorbent assay (ELISA). Three of the peptides (EH174 from ORF-1, EH286 from ORF-2 and EH362 from ORF-3) showed antigenic activity and possible application for the development of anti-HEV test kits (the peptide-based ELISA). The laboratory experiments and clinical trials showed that the kits, using a set of 3 synthetic HEV peptides as coating antigens, were of high specificity and exhibited good reproducibility. The small-scale seroepidemiological survey indicated high seroprevalence (14.3%) of anti-HEV in Tibetan populations. Additionally, the results also demonstrated good agreement with clinical findings, suggesting that the test kits will be of major use for immunodiagnosis and seroepidemiological surveys of HEV infection.
Amino Acid Sequence↗
Influence of intracellular Mn on the contractile inhibition caused by db cAMP, forskolin, and porcine relaxin in the circular muscle of the estrogen-treated rat uterus.
Whether Mn ion permeates into circular muscle cells of the estrogen-treated rat uterus and how contractile inhibitions caused by db cAMP, forskolin, and relaxin are affected by treatment with Mn were examined. By exposing the muscle strip to 0.35 mM Mn added to Mg-free Krebs solution, the magnitude of phasic contractions evoked by electrical stimulation was reduced to 21.8 +/- 14.7% (n = 22) of control. Mn influx was measured by fura-2 fluorescence quenching at the Ca isosbestic excitation wavelength (360 nm). The contractile inhibitions caused by 30 microM db cAMP and 0.2 microM forskolin were enhanced after pretreatment with 0.35 mM Mn for 10 min, whereas the inhibition caused by 100 mU relaxin underwent enhancement or attenuation. These results are discussed in relation to those reported previously for the longitudinal muscle in which the influences of treatment with Mn were somewhat different.
Animals↗
[Chemical constituents of stems and leaves of Fritillaria ussuriensis Maxim].
Three compounds were isolated from stems and leaves of Fritillaria ussuriensis. They were identified as adenosine, galacitiol and succinic acid.
Adenosine↗
Pretreatment with porcine relaxin and Mg ions enhances inhibitory effects of dibutyryl cyclic AMP in longitudinal muscle of estrogen-treated rat myometrium.
Phasic contractions were evoked in Mg-free Krebs solution by electrical stimulation in the longitudinal myometrial strip taken from estrogen-treated rats, and the application of 30 microM dibutyryl cyclic AMP (db cAMP) for 15 min depressed the amplitude of contraction to 81 +/- 18% (+/- SD, n = 23) of the control. The contractile depression caused by db cAMP was not significantly altered by pretreatment with either 1 mM Mg (40 min) or 100 mU porcine relaxin (15 min) alone; however it was markedly enhanced to 22 +/- 30% (n = 7) of the control response by the combined pretreatment with Mg and relaxin. The enhancement lasted for longer than 2 h thereafter in Mg-free Krebs solution. It was discussed that some memory factor was induced by relaxin in the presence of 1 mM Mg to respond strongly to db cAMP.
Animals↗
Effects of Mg and Mn ions on the inhibitory action of cyclic nucleotides in the longitudinal myometrium of rat.
Contractile response, membrane activity, and fluorescence signal from mag-fura-2 were measured on the longitudinal myometrium taken from estrogen-treated rat, and the influence of Mg and Mn ions on the inhibitory effects caused by db cAMP, 8-bromo cGMP, and db cGMP was investigated. Taking the Kd value of mag-fura-2 with Mg to be 2.0 mM, the intracellular Mg concentration was estimated to be 380 microM in the tissue incubated with Mg-free Krebs solution and 420 microM in the tissue exposed to Ca-free 40 mM K solution containing 15 mM Mg for 5 min, respectively. The phasic contractions generated by electrical stimulation in Mg-free Krebs solution were more strongly depressed by 30 microM db cAMP, 10 microM 8-bromo cGMP, and 1 mM db cGMP after the Mg loading treatment. The muscle was exposed to Ca-free 40 mM K solution containing 0.6 mM Mn for 10 min, and it was assumed that the muscle was loaded with Mn ions. After the Mn loading treatment, the contractile depression caused by 8-bromo cGMP and db cGMP was enhanced, whereas that by db cAMP was attenuated. These results were discussed in relation to the influence of intracellular load with Mg or Mn on the inhibitory actions caused by isoprenaline, forskolin, and relaxin.
Animals↗
Model-free numerical deconvolution of recirculating indicator concentration curves.
This paper investigates two model-free methods for numerical deconvolution of recirculating indicator concentration curves. The two methods, damped least squares and discrete orthogonal polynomial deconvolution, are applied to simulated data to verify the reliability of the algorithms. Both deconvolution methods provide damping that results in estimated transport functions that are smooth and reasonable estimates of the actual simulated transport function. On convolution with the simulated input curve, the estimated transport functions provide good fits to the simulated output curve. In addition, methods for identifying an optimal solution and for truncating the artifactually long oscillatory tails of the estimated transport functions are proposed, which appear to allow for reasonably accurate estimation of the mean transit times and variances of the transport functions as well. When either method was applied to indicator dilution data obtained from the pulmonary artery and left atrium, it was computationally stable while producing transport functions that when convolved with the input concentration curves provided good fits to the output concentration curves. The combined simulation and experimental results suggest that the proposed methods should be useful for estimating circulation transport functions from indicator dilution data.
Algorithms↗
Miniature urea sensor based on H(+)-ion sensitive field effect transistor and its application in clinical analysis.
An urea-ENFET (Enzyme field effect transistor) probe was made by covering one of the grids of the dual ISFET (Ion sensitive field effect transistor) with a membrane of cross-linked bovine serum albumin (BSA)-urease and the other with cross-linked BSA, and the response characteristics of the probe was then tested through differential measurements. In different concentrations of phosphate buffer, the sensor responded to various concentrations of urea solution within 10-60s. From the calibration curve plotted on logarithmic scales a linear concentration range of 1.0-8.0 mg/dl was acquired, and the correlation coefficient and response sensitivity were 0.997 and 50mV/dec. (mg/dl), respectively. However, in dilute urea solution, the sensor responded linearly to the contents of urea over the range of concentration of 0.1-1.0 mg/dl with a correlation coefficient of 0.998 and a response sensitivity of 12-15mV/mg/dl. The standard deviation and the variation coefficient for 20 performances responding to 100mg/dl urea in 0.01M pH7.0 phosphate buffer were found to be 1.39mV and 1.44%, respectively. The urea-ENFET was used for the determination of BUN (Blood urea nitrogen) and the BUN values were compared with those determined by enzymatic method, the repression equation and correlation coefficient for 50 assays were y = -0.1272 + 0.9695x and r = 0.9912, respectively. When the urea-ENFET was used for determining urea either in buffer solution or in serum for 250 runs over a period of 1.5 months (the enzyme FET was stored at 4 degrees C between measurements during this period), the observed decrease of response sensitivity was only about 10%.(ABSTRACT TRUNCATED AT 250 WORDS)
Biosensing Techniques↗
Metabolic chiral inversion of stiripentol in the rat. I. Mechanistic studies.
To study enantioselective aspects of the disposition of stiripentol (STP), a chiral allylic alcohol undergoing development as an antiepileptic drug, a stereoselective synthesis was developed and the configuration of the two enantiomers determined to be (R)-(+) and (S)-(-). Following a single oral dose (300 mg kg-1) of the individual enantiomers to adult male Sprague-Dawley rats, it was found that (R)-STP was transformed extensively to its antipode, whereas little inversion was detected when (S)-STP was administered. Studies on the mechanism of this apparently unidirectional chiral inversion revealed that the phenomenon was dependent on the presence of the side-chain C==C double bond, because the enantiomers of the corresponding saturated alcohol (D2602) did not interconvert in vivo. Experiments with analogs of STP labeled with deuterium or oxygen-18 at the chiral center showed that, whereas the deuterium was retained in vivo, partial loss of the 18O occurred from both enantiomers of the drug. Pretreatment of rats with pentachlorophenol (40 mumol kg-1 i.p.), an inhibitor of sulfation (and possibly other conjugation reactions), led to a marked decrease in the rate of conversion of (R)-STP to its antipode, suggesting that the chiral inversion phenomenon may be mediated, at least in part, by an enantioselective conjugation process.
Administration, Oral↗