Rapid assay for furancarboxylic acid accumulated in uremic serum using high-performance liquid chromatography and on-line mass spectrometry.
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Chromatography, High Pressure Liquid↗
Biomedical subjects
T Niwa
Publications and source records attributed to T Niwa.
Alterations in estradiol metabolism in MCF-7 cells induced by treatment with indole-3-carbinol and related compounds.
In mammals, estradiol (E2) metabolism primarily involves mutually exclusive hydroxylation at either C-2 or C-16 alpha. We have previously reported a consistent increase in the C-16 alpha hydroxylation activity in human breast cancer and in mouse strains with high levels of mammary tumors. Here we show that the dietary compound indole-3-carbinol (I3C) increases C-2 hydroxylation five-fold in MCF-7 cells in culture but has minimal effect on the reaction at C-16 alpha. Because I3C-induced changes in E2 metabolism result in a metabolite ratio inverse to that observed in women with breast cancer we have separately examined whether this shift conferred an anti-tumorigenic advantage to estrogen target cells. The preferential changes induced by I3C on estradiol metabolism in MCF-7 cells parallel its anti-tumorigenicity in mice. These results suggest that changes in the metabolism of estradiol via the C-2 pathway might play a significant role in decreasing risk for breast cancer in women. Indole-2-carbinol is readily available as a chemical and as a dietary component of cruciferous vegetables. Feasible dietary changes show promise of having clinical utility in the prevention of breast cancer and other hormone-dependent cancers.
Anticarcinogenic Agents↗
Preparation of agglomerated crystals for direct tabletting and microencapsulation by the spherical crystallization technique with a continuous system.
Adhesive and cohesive properties of chlorpromazine hydrochloride (CP) crystals were modified to improve their powder processing, e.g., direct tabletting and microencapsulation, by agglomeration. Moreover, sustained-released gelling microcapsules of CP were devised to prolong the pharmacological effect. The spherical crystallization technique was applied to prepare agglomerates for direct tabletting and microencapsulation to use them as core materials. The ethanolic solution dissolving CP was poured into a stirred cyclohexane, yielding spherically agglomerated crystals. The resultant agglomerates were free-flowing and easily packable spheres with average diameters of 200 to 1000 microns. The agglomerates reserved the high compressibility of the original powder having a small particle size (14 microns). The compression behavior represented by Heckel's equation suggested that the agglomerates were disintegrated to individual primary crystals at low compression pressures, and then they were closely repacked and plastically deformed at higher pressures. After agglomeration, microencapsulation was continuously performed in the same batch by a phase separation method. Coacervate droplets produced by pouring cyclohexane into a dichloromethane solution, dissolving polyvinyl acetate as a coating polymer, were added to the crystallization system under stirring, to prepare the microcapsules. By filling the microcapsules in gelatin hard capsules or tabletting them, their drug release rates became retarded compared with the physical mixture treated in the same way, having the same formulation as the microcapsules. This phenomenon was due to the gelation of polyvinyl acetate of the microcapsules in the dissolution medium, whose glass transition temperature is very low. This novel sustained-release dosage form is termed "gelled microcapsules."
Adhesiveness↗
Progression of glomerular sclerosis in experimental uremic rats by administration of indole, a precursor of indoxyl sulfate.
In uremia there is a marked elevation of serum levels of indoxyl sulfate due to its decreased renal clearance. Indoxyl sulfate is synthesized in the liver from indole which is produced by bacteria in the intestines. To determine the role of indoxyl sulfate in the progression of chronic renal failure, we administered indole, the precursor of indoxyl sulfate, to subtotally nephrectomized uremic rats. The oral administration of indole increased the serum levels of creatinine and blood urea nitrogen and decreased creatinine, inulin, and p-aminohippuric acid clearances. The glomerular sclerosis index in the indole-treated rats was higher than in the control uremic rats. After oral administration, indole could not be detected in the urine, but large amounts of its metabolite, indoxyl sulfate. Thus, indole administration stimulated glomerular sclerosis in a uremic model through the production of indoxyl sulfate.
Animals↗
Plasma interleukin 8 levels are increased by hemodialysis.
The effects of hemodialysis on plasma interleukin 8 (IL-8) levels and the expression of IL-8 mRNA in peripheral blood mononuclear cells (PBMC) were studied in uremic patients undergoing maintenance hemodialysis (HD) using regenerated cellulose dialyzers. The plasma IL-8 levels in the patients after HD sessions were significantly higher than before HD. Comparison of the IL-8 mRNA levels obtained from PBMC before and after HD indicated that the expression of IL-8 mRNA was increased by HD. The enhancement of production of IL-8 in PBMC during HD may be responsible for inflammatory complications and impaired host defense in HD patients.
Adult↗
Isolation and characterization of an alicyclic amine N-sulfotransferase from female rat liver.
An alicyclic amine N-sulfotransferase sulfonating 4-phenyl-1,2,3,6-tetrahydropyridine (PTHP) was purified from female rat liver cytosol and showed a homogenous band with a molecular weight of 30500 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme, designated NST-1, catalyzed sulfonation not only of the alicyclic amine but also dehydroepiandrosterone, a typical substrate of hydroxysteroid sulfotransferase (STs), but had little sulfonating activity towards 2-naphthol, a typical substrate of aryl STs. The N-terminal amino acid sequence for the first 24 residues had a high homology with those of rat liver hydroxysteroid STs. Therefore, it is suggested that NST-1 is classified as a member of the hydroxysteroid ST. Immunoblot analysis of male and female rat liver cytosol, carried out by using rabbit antisera raised against NST-1, indicated that the female cytosol contained a higher level of the enzyme than that of male. The marked sex difference in the expression level of NST-1 was in good accordance with the previous demonstration that female rat liver cytosol catalyzed sulfonation of PTHP to a greater extent than that of male.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Analysis of conjugated bile acids in human biological fluids. Synthesis of hyodeoxycholic acid 3- and 6-glycosides and related compounds.
The glucuronide, glucoside and N-acetylglucosaminide conjugates of hyodeoxycholic acid were synthesized. In addition, murideoxycholic acid 3-glycosides and some of their C-5 epimeric analogs were also prepared. The principal reactions used are 1) the Koenigs-Knorr condensation reaction of 3-oxo-6 alpha-hydroxy and 6-oxo-3 alpha-hydroxy esters with an appropriate alpha-acetohalosugar catalyzed by cadmium carbonate in benzene under reflux, 2) reduction of the resulting bile acid glycoside methyl ester-acetates with tert-butylamine-borane complex, and 3) subsequent hydrolysis with aqueous lithium hydroxide.
Bile Acids and Salts↗
Mucoadhesion of polymer-coated liposomes to rat intestine in vitro.
Multilamellar liposomes consisting of dipalmitoyl phosphatidylcholine (DPPC) and dicetyl phosphate (DCP) in a molar ratio of 8:2 (DPPC:DCP = 8:2) were coated with three different types of polymers: chitosan, polyvinyl alcohol having a long alkyl chain, and poly(acrylic acid) bearing cholesterols. The existence of polymer layers on the liposome surface was confirmed by measuring the zeta potential of the liposomal particles. The mucoadhesive function of the polymer-coated liposomes was evaluated in vitro using rat intestine. A particle counting method using the Coulter counter was adopted to evaluate the adhesive % of liposomes. Chitosan coated liposomes showed the highest adhesive % among the polymer-coated liposomes tested. No adhesive % was observed for the non-coated liposomes. The adhesion of chitosan-coated liposomes to the intestine wall was confirmed by fluorescence microscopy using pyrene loaded liposomes.
1,2-Dipalmitoylphosphatidylcholine↗
Effect of repeated injection of somatomedin C on drug metabolizing enzyme activities in rats.
The effect of somatomedin C on the hepatic drug-metabolizing enzyme system in rat liver after sc injection, a clinically applicable dosing route, was studied. Although liver weight was slightly increased after somatomedin C (1 mg/kg) was injected for 7 days, no significant changes were observed in other dosing group (0.1 and 10 mg/kg). There were no significant effects of somatomedin C on cytochrome P-450 and b5 contents, and NADPH-cytochrome c reductase, aminopyrine demethylase, aniline hydroxylase, and ethoxyresorufin deethylase. Additionally, somatomedin C treatment did not affect the activities of 2 alpha-, 2 beta-, 6 beta- and 16 alpha-hydroxytestosterone and androstenedione formation from testosterone. Changes relation to dosing period were also examined with 1 mg/kg of somatomedin C. In this case, hepatic levels of cytochrome P-450 and b5, NADPH-cytochrome c reductase and drug oxidations did not differ significantly among groups treated for 3, 7, or 14 days. These results suggest that somatomedin C has no effect on the hepatic mixed-function oxidase system.
Animals↗
Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis.
To determine the role of indoxyl sulfate in the progression of glomerular sclerosis, the serum level of indoxyl sulfate was measured in patients with uremia, and the effect of oral administration of indoxyl sulfate on renal function and renal histology was studied in subtotally nephrectomized uremic rats. Further, the effects of a low-protein diet and oral sorbent (AST-120) administration on the serum and urine levels of indoxyl sulfate were studied in different groups of subtotally nephrectomized uremic rats. We noted a marked elevation of serum level of indoxyl sulfate in the patients with uremia. The oral administration of indoxyl sulfate to the uremic rats increased the serum creatinine and blood urea nitrogen levels and decreased creatinine clearance, inulin clearance, and p-aminohippuric acid clearance. The glomerular sclerosis index in the indoxyl sulfate-administered uremic rats was higher than in the control uremic rats. A low-protein diet and AST-120 administration decreased the serum and urine levels of indoxyl sulfate, the blood urea nitrogen level, the urinary protein level, and the glomerular sclerosis index in the uremic rats as compared with those on a high-protein diet. Thus, indoxyl sulfate, a circulating uremic toxin, stimulated the progression of glomerular sclerosis in the uremic model. A low-protein diet and AST-120 reduced the serum and urine levels of indoxyl sulfate and suppressed the progression of glomerular sclerosis.
Aged↗
[Percutaneous ethanol injections for hepatocellular carcinoma].
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Adult↗
Quantification of serum 1,5-anhydroglucitol in uremic and diabetic patients by liquid chromatography/mass spectrometry.
We developed a new method for measuring serum 1,5-anhydroglucitol (1,5-AG), using liquid chromatography/atmospheric pressure chemical-ionization mass spectrometry (LC/MS). With this method we measured serum 1,5-AG concentrations in uremic and diabetic patients and compared these values with those determined by an enzymatic method. Serum 1,5-AG concentrations were significantly less in the undialyzed and dialyzed uremic patients and in diabetic patients; the values in the dialyzed patients decreased after hemodialysis. In uremic patients with high concentrations of serum myo-inositol, the 1,5-AG values determined by LC/MS were significantly lower than those determined enzymatically. There was no significant correlation between 1,5-AG and fructosamine in the uremic patients. These results demonstrate that serum 1,5-AG cannot be used as an index for glycemic control in uremic patients and that the LC/MS method is indicated in uremic patients with high concentrations of myo-inositol.
Adult↗
Analysis of urinary organic acids by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.
We developed a new method for the rapid determination of urinary organic acids using liquid chromatography-atmospheric pressure chemical ionization mass spectrometry. Mass spectra of authentic organic acids obtained in the negative-ion mode showed intense [M-H]- ions with some fragment ions. Urine samples of patients with methylmalonic aciduria, ornithine transcarbamylase deficiency, and phenylketonuria were extracted using anion-exchange columns. The mass chromatograms of the extracts showed some dominant peaks of abnormal metabolites characteristic of each disorder. This is a useful method for the analysis of urinary organic acids for the diagnosis of organic aciduria, because the sample preparation is simple.
Acids↗
Presence of 3-deoxyglucosone, a potent protein crosslinking intermediate of Maillard reaction, in diabetic serum.
3-Deoxyglucosone, a potent protein crosslinking intermediate of the Maillard reaction, was first detected in diabetic serum using gas chromatography/mass spectrometry. Serum concentration of 3-deoxyglucosone was elevated in diabetic patients as compared with healthy subjects. More notably, diabetic patients with nephropathy showed higher serum concentration of 3-deoxyglucosone than those without nephropathy. The increased serum concentration of 3-deoxyglucosone in the diabetic patients suggests that 3-deoxyglucosone may be responsible for the development of diabetic complications such as diabetic nephropathy by promoting the formation of advanced glycation end products.
Adult↗
Effect of human serum on the in vitro anti-HIV-1 activity of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives as related to their lipophilicity and serum protein binding.
Several derivatives of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were examined for their inhibitory effects on the replication of human immunodeficiency virus type 1 (HIV-1) in MT-4 cells in the presence of various concentrations (10-50%) of human serum (HS). Although all HEPT derivatives proved to be highly potent inhibitors of HIV-1 in the presence of 10% fetal bovine serum, some of them were less inhibitory to HIV-1 replication in the presence of HS. The HEPT derivatives were found to be highly bound to HS proteins. Both the anti-HIV-1 activity and HS protein binding of the compounds appeared to be related to their lipophilicity.
Acetylcysteine↗
Presence of N-methyldopamine in parkinsonian and normal human brains.
N-Methyldopamine (epinine) has been identified for the first time in parkinsonian and normal human brains by gas chromatography-mass spectrometry. N-Methylsalsolinol and N-methylnorsalsolinol, which are analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which produces parkinsonism in humans, may be synthesized from N-methyldopamine by the Pictet-Spengler condensation reaction as an alternative metabolic pathway.
Brain↗
Analysis of polyols in uremic serum by liquid chromatography combined with atmospheric pressure chemical ionization mass spectrometry.
Liquid chromatography with atmospheric pressure chemical ionization mass spectrometry in the negative-ion mode was used to analyse polyols in uremic serum obtained from haemodialysis patients. With post-column addition of 1% chloroform-methanol as an ionization accelerating solvent, the chloride addition ions, [M+Cl]-, were detected as base peaks, and the molecular masses of the polyols were easily determined by comparing [M+Cl]- and [M - H]- ions. Concentrations of erythritol, myoinositol, mannitol and sorbitol were markedly increased, and that of 1,5-anhydroglucitol was markedly decreased in the uremic serum compared with normal serum. After haemodialysis, the serum concentration of these polyols decreased significantly. This method was found to be useful in analysing the profile of polyols.
Atmospheric Pressure↗
Analysis of IMP-SPECT in cerebral infarcts.
We performed single photon emission computed tomography with N-isopropyl[123I]-p-iodoamphetamine in 22 normal volunteers (mean age, 68.3 +/- 9.5 years) and 190 patients with unilateral cerebral infarcts (66.1 +/- 11.4 years). We then compared visual and semiquantitative assessment of the left/right ratio of the early images. Cerebral blood flow in the patients with cerebral infarcts was compared with data from normal volunteers. An abnormal left/right ratio was recognized in 110 of 136 (81%) patients in whom X-ray computed tomography (CT) showed an abnormality, while visual inspection revealed abnormalities in only 99 (73%). In 54 patients no abnormality on CT, an abnormal left/right ratio was found in 28 (52%), and visual abnormalities in only 9 (17%). Altogether, the left/right ratio was abnormal in 138 of 190 (73%) patients, and abnormalities were detected visually in 108 (57%). Of 95 patients, 56 (59%) showed markedly larger lesions using the left/right ratio method than with the visual method.
Aged↗