Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonketotic hyperglycinemia (NKH), a metabolic disorder due to defects in the glycine cleavage system, leads to the accumulation of toxic levels of glycine. Glycine levels in these patients may be lowered by sodium benzoate treatment. Benzoic acid binds to glycine to form hippurate, which is subsequently eliminated through the kidneys. At high concentrations, hippuric acid can crystallize in the kidneys and cause renal failure. Therefore, it is desirable to have benzoic acids concentrations within a therapeutic range. In the gas chromatography method described, the drug from the acidified serum or plasma sample is extracted using ethyl acetate. The organic phase containing drug is separated and dried under a stream of nitrogen. After trimethylsilyl derivatization, benzoic acid analysis is done on a gas chromatograph mass spectrometer. Quantitation of the drug in a sample is achieved by comparing responses of the unknown sample to the responses of the calibrators using selected ion monitoring. Benzoic acid D(5) is used as an internal standard.
Methods Mol Biol 2010
PMID:Determination of benzoic acid in serum or plasma by gas chromatography-mass spectrometry (GC/MS). 2007 64

Cocaine, a stimulant, is a commonly abused drug. Cocaine and its metabolites are measured in various biological specimens for clinical and forensic purposes. Urine or plasma or serum is spiked with deuterated internal standards cocaine-d3, benzoylecgonine-d3, ecgonine methyl ester-d3, and cocaethylene-d3 and buffered with phosphate buffer. The drugs in the sample are extracted by cation-exchange solid phase extraction. The drugs from the solid phase cartridge are eluted and the eluent is dried under the stream of nitrogen. The residue is incubated with pentafluoropropionic acid anhydride and pentafluoropropanol to form pentafluoropropionyl derivatives of ecgonine methyl ester and benzoylecgonine. Cocaine and cocaethylene are refractory to derivatization. The extract is dried, reconstituted in ethyl acetate, and injected into gas chromatography mass-spectrometry analyzer. Quantitation of the drugs in the samples is made, using selected ion monitoring, from a 3-point calibration curve.
Methods Mol Biol 2010
PMID:Quantitation of cocaine, benzoylecgonine, ecgonine methyl ester, and cocaethylene in urine and blood using gas chromatography-mass spectrometry (GC-MS). 2007 67

A liquid-liquid extraction (LLE) of drugs and internal standard (promazine) is performed by mixing urine at basic pH with 1-chlorobutane. There are no hydrolysis or derivatization steps. After centrifugation the organic (upper) layer is transferred to another tube and evaporated. The dried extract is reconstituted with ethyl acetate and 1 microL is injected onto the GCMS. Drugs are volatilized in the GC inlet and separated on a capillary column. In the EI source drugs become positively charged and fragment. Mass analysis of ionized fragments occurs with a single quadrupole. The resulting full scan mass spectra are automatically searched against three libraries.
Methods Mol Biol 2010
PMID:Broad spectrum drug screening using electron-ionization gas chromatography-mass spectrometry (EI-GCMS). 2007 71

Neuroblastoma, in most cases, is characterized by increased production of catecholamines and their metabolites. Laboratory diagnosis and clinical follow-up include the measurement of urinary homovanillic acid (HVA) and vanillylmandelic acid (VMA). In the following procedure, urine samples are diluted to give a creatinine concentration of 2 mg/dL. Deuterated internal standards are added to the diluted urine samples followed by acidification using HCl. Ethyl acetate is used to extract HVA and VMA from the acidified samples, and the extract is dried. The residue is treated with bis-(trimethylsilyl)trifluoroacetamide (BSTFA), 1% trimethylchlorosilane (TMCS), and pyridine to prepare trimethylsilyl derivatives of HVA and VMA. The derivatized samples are injected to into gas-chromatograph mass spectrometer. The concentration of HVA and VMA is determined by comparing responses of unknown sample to the responses of calibrators using selected ion monitoring.
Methods Mol Biol 2010
PMID:Quantitation of homovanillic acid (HVA) and vanillylmandelic acid (VMA) in urine using gas chromatography-mass spectrometry (GC/MS). 2007 77

Hydroxyurea is an antineoplastic drug, which is also widely used in the treatment of sickle cell disease. Various methods including colorimetry, high performance liquid chromatography, and gas chromatography-mass spectrometry (GC-MS) are available for the assay of hydroxyurea. In the gas chromatography method described, the drug is extracted from serum, plasma, or urine using ethyl acetate and phosphate buffer (pH 6). The organic phase containing drug is separated and dried under a stream of nitrogen. After trimethylsilyl derivatization, samples are analyzed using GC-MS. Quantitation of the drug in a sample is achieved by comparing responses of the unknown sample to the responses of the calibrators using selected ion monitoring. Tropic acid is used as an internal standard.
Methods Mol Biol 2010
PMID:Determination of hydroxyurea in serum or plasma using gas chromatography-mass spectrometry (GC-MS). 2007 79

Deficiencies in any of the 50 degradative enzymes found in lysosomes results in the accumulation of undegraded material and subsequently cellular dysfunction. Early identification of deficiencies before irreversible organ and tissue damages occur leads to better clinical outcomes. In the method which follows, lysosomal alpha-glucosidase, alpha-galactosidase, beta-glucocerebrosidase, acid sphingomyelinase, and galactocerebrosidase are extracted from dried blood spots and incubated individually with an enzyme-specific cocktail containing the corresponding substrate and internal standard. Each enzyme cocktail is prepared using commercially available mixture of substrate and internal standard at the predetermined optimized molar ratio. After incubation, the enzymatic reactions are quenched using an ethyl acetate/methanol solution and all five enzyme solutions are combined. The mixtures of the reaction products are prepared using liquid-liquid and solid-phase extractions and quantified simultaneously using selected ion monitoring on LC-MS-MS system.
Methods Mol Biol 2010
PMID:Multiplex lysosomal enzyme activity assay on dried blood spots using tandem mass spectrometry. 2007 85

Chemotherapy remains the staple of treatment for many types of leukemia. Despite the positive impact on extending overall survival in patients with hematological malignancies, new treatment strategies are needed to reduce the nonspecific toxicity and improve the efficacy of treatment. Celastrol, derived from the 'Thunder God Vine' and Pro-EGCG, a pre-drug version of green tea polyphenol EGCG have shown potent biological activity in vitro and in vivo. Whether these natural products augment the efficacy of conventional chemotherapy in the treatment of leukemia cells has yet to be demonstrated. Here we demonstrate that these natural products could sensitize the effect of chemotherapy in both K-562 and Jurkat T human leukemia cells. Accordingly, this potent biological activity was associated with increased levels of leukemia cell killing, caspase 3 activation, and poly(ADP-ribose) polymerase cleavage. Furthermore, the higher levels of apoptotic indices were associated with decreased levels of Bcr-Abl oncoprotein in K-562 cells. Taken together, our findings present a compelling rationale for the development of combination strategies using natural products in the treatment of hematological malignancies.
Int J Mol Med 2010 Mar
PMID:Celastrol and an EGCG pro-drug exhibit potent chemosensitizing activity in human leukemia cells. 2012 53

The both, ground-state (mu(g)) and the excited-state (mu(e)) dipole moments of three 1,4-disubstituted anthraquinones, namely 1,4-diaminoanthracene-9,10-dione (1,4-DAAQ), 1-amino-4-hydroxyanthracene-9,10-dione (1,4-AHAQ), and 1,4-dihydroxyanthracene-9,10-dione (1,4-DHAQ) were estimated in binary solvent mixtures (methylcyclohexane-ethyl acetate and ethyl acetate-acetonitrile). The dipole moments (mu(g) and mu(e)) were estimated from Lippert-Mataga, Bakhshiev, Kawski-Chamma-Viallet, McRae, and Suppan equations by using the variation of Stokes shift with the solvent's relative permittivity and refractive index. The ground-state dipole moments were also calculated theoretically by Gaussian 03 software using B3LYP/6-31 G* level of theory. Further, the change in dipole moment values Deltamu were also calculated by using the variation of Stokes shift with the molecular-microscopic empirical solvent polarity parameter (E(T)(N)). The excited-state dipole moments observed are larger than their ground-state counterparts, indicating a substantial redistribution of the pi-electron densities in a more polar excited state for all the molecules investigated.
Spectrochim Acta A Mol Biomol Spectrosc 2010 Apr
PMID:Estimation of the ground and the first excited singlet-state dipole moments of 1,4-disubstituted anthraquinone dyes by the solvatochromic method. 2013 71

In eukaryotes, the ubiquitin-proteasome system (UPS) is responsible for the degradation of most proteins. Proteasome inhibition, which has been associated with various diseases, can cause alterations in various intracellular processes including the expression of heat shock protein (hsp) genes. In this study, we show that celastrol, a quinone methide triterpene and anti-inflammatory agent, inhibited proteasome activity and enhanced HSP accumulation in Xenopus laevis A6 kidney epithelial cells. Treatment of cells with celastrol induced the accumulation of ubiquitinated protein and inhibited chymotrypsin-like activity. This was accompanied by a dose- and time-dependent accumulation of HSP30 and HSP70. Celastrol-induced HSP accumulation was mediated by HSF1-DNA binding activity since this response was inhibited by the HSF1 activation inhibitor, KNK437. Simultaneous exposure of cells with celastrol plus either mild heat shock or the proteasome inhibitor, MG132, produced an enhanced accumulation of HSP30 that was greater than the sum of the individual stressors alone. Immunocytochemical analysis revealed that celastrol-induced HSP30 accumulation occurred in the cytoplasm in a granular pattern supplemented with larger circular HSP30 staining structures. HSP30 was also noted in the nucleus with less staining in the nucleolus. In some cells, celastrol induced the collapse of the actin cytoskeleton and conversion to a rounder morphology. In conclusion, this study has shown that celastrol inhibited proteasome activity and induced HSF1-mediated expression of hsp genes in amphibian cells.
Comp Biochem Physiol A Mol Integr Physiol 2010 Jun
PMID:Celastrol can inhibit proteasome activity and upregulate the expression of heat shock protein genes, hsp30 and hsp70, in Xenopus laevis A6 cells. 2018 6

The preparation, characterization, and in vitro release of 5-aminosalicylic acid (5-ASA) from methacrylic acid (MAA)/perlite composites (APC) prepared via a sol-gel route are reported. The free-radical graft polymerization of methacrylic acid (MAA) onto perlite particles was studied experimentally. The grafting procedure consisted of surface activation with 3-(trimethoxysilyl) propyl methacrylate (TSPA), followed by free-radical graft polymerization of methacrylic acid (MAA) in ethyl acetate with 2,2'-azobisisobutyronitrile (AIBN) initiator. The composition of the composites hybrid materials was determined by FTIR spectroscopy. Equilibrium swelling studies were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF, respectively). The dried composites were immersed in a saturated solution of 5-ASA in water overnight and dried over a period of three days at room temperature and the in vitro release profiles were established separately in both (SGF, pH 1) and (SIF, pH 7.4). The 5-ASA concentration of the solution was measured using a UV-Vis spectrophotometer (205 nm) at different time intervals. The in vitro drug release test revealed that the release rate of 5-ASA in buffer solutions increased with the silica content in the composites; on the contrary, the increase of the content of 3-(trimethoxysilyl)propyl methacrylate (TSPA), a coupling agent, decreased the drug release rate.
Int J Mol Sci 2010 Apr 12
PMID:Colon-specific drug delivery behavior of pH-responsive PMAA/perlite composite. 2048 34


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