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Biomedical subjects

R M Caprioli

Publications and source records attributed to R M Caprioli.

At least 73 records · Page 4Linked to original sources
PubMed1981

Determination of plasma fentanyl by GC-mass spectrometry and pharmacokinetic analysis.

GC-mass spectrometry was used to measure extremely low levels of fentanyl in dog plasma. Deuterated fentanyl was synthesized for use as an internal standard. Fentanyl was hydrolyzed to despropionyl fentanyl by 20% DCl in in deuterium oxide. Mass spectrometric analysis of the product revealed that the molecular ion was three mass units higher than that of the authentic despropionyl fentanyl, indicating that the deuterium exchange reactions occurred at this stage. Deuterated despropionyl fentanyl was reesterified by propionyl chloride to fentanyl-d3. The drug was assayed in biological fluids by extraction into ethyl acetate followed by analysis with GC-chemical-ionization mass spectrometry. The lowest measurable plasma fentanyl level is 500 pg/ml. The method is highly selective and is suitable for monitoring the time course of plasma drug levels. Evaluation of pharmacokinetic data from experiments using nine dogs revealed a triphasic phenomenon. No measurable amounts of the major metabolites, depropionyl fentanyl and norfentanyl, were detected.

Animals↗
PubMed1981

Phagocytosis, cellular distribution, and carcinogenic activity of particulate nickel compounds in tissue culture.

The uptake, toxicity, and morphological transformation efficacy of various water-insoluble nickel compounds were examined in tissue culture. Particles (2.2 to 4.8 micrometers) of crystalline Ni3S2, crystalline NiS, and crystalline Ni3Se2 were actively phagocytized by cultured cells as determined by light and electron microscopy. However, particles of similar size consisting of amorphous NiS and metallic nickel were not significantly phagocytized despite long exposure periods to high concentrations. X-ray fluorescence spectrometry measurements of metal levels in subcellular fractions isolated from cells treated with crystalline Ni3S2, crystalline NiS, or amorphous NiS confirmed that amorphous NiS did not significantly enter the cells, either as a phagocytized particle or in a solubilized form, while the other two crystalline nickel compounds were actively taken up. Cells treated with amorphous NiS contained nickel levels generally less than 10% of the nickel levels in whole cells and in cytoplasmic fractions, or nuclear fractions of cells treated with either crystalline NiS or crystalline Ni3S2. The phagocytized nickel particles were always observed in the cytoplasm with light and electron microscopy, but substantial nickel levels were measured in the nuclear fraction. These and other results suggest that the nickel particles were broken down in the cytoplasm to a size range no longer detectable with the electron microscope and then subsequently entered the nucleus. Control experiments suggest that at least 20% of the nickel measured in the nucleus isolated from cells treated with Ni3S2 is no longer part of a sedimentable particle with the same particle size and/or solubility properties of the parent compound. A substantial portion of the nickel associated with the nuclear fraction coprecipitated with trichloroacetic acid-insoluble material, suggesting that nickel binds strongly to cellular macromolecules. The phagocytized particulate nickel compounds were more cytotoxic as determined by reduction of cell-plating efficiency and induced more morphological transformations in the Syrian hamster embryo cell transformation assay than did the particulate nickel compounds which were not phagocytized. Manganese dust inhibited the morphological transformation induced by Ni3S2 and also reduced the phagocytosis of Ni3S2 particles.

Animals↗
PubMed1980

Analysis of dipeptide mixtures by the combination of ion-pair reversed-phase high-performance liquid chromatographic and gas chromatographic-mass spectrometric techniques.

Reversed-phase high-performance liquid chromatography using aliphatic carboxylic acids as surfactants was used to separate basic, acidic and neutral dipeptides. The enhancement of the capacity factors of basic dipeptides versus the chain length of carboxylic acid followed sigmoidal curves. The capacity factor of dipeptides fell precipitously with addition of salts until it decreased to a value which was unaffected by the addition of more salts. For the identification of dipeptides produced by the hydrolysis of proteases (dipeptidylaminopeptidases), gas chromatographic-mass spectrometric techniques were used for acidic and neutral dipeptides. Basic dipeptides could be positively identified either by normal chromatographic procedures or by collecting the suspected peaks for further characterization by alternate techniques.

Acetonitriles↗
PubMed1980

Comparison of the mechanisms of two distinct aldolases from Escherichia coli grown on gluconeogenic substrates.

Escherichia coli grown on gluconeogenic compounds as carbon sources produced two chemically and physically distinct types of fructose-1,6-biphosphate aldolases (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphatelyase, EC 4.1.2.13), while these bacteria produced only a single enzyme when grown on glucose or fructose. We have investigated this enzyme in several strains of Escherichia coli (Crookes, K-12, and B) grown on glucose, fructose lactate, pyruvate, alanine and glycerol by comparing chemical properties and mechanisms of action. Comparison of these mechanisms was accomplished by following the fate of 18O in the keto position of fructose 1,6-bisphosphate during the aldolase catalyzed cleavage reaction. The results show that the two enzymes have different mechanisms of action and are consistent with a Schiff-base mechanism for the one which was induced by gluconeogenic substrates and metal-chelate mechanism for the constitutive enzyme.

Alanine↗
PubMed1980

CSF neurotransmitter studies. An infant with ascorbic acid-responsive tyrosinemia.

A female newborn infant with Marfan-like habitus experienced lethargy and hypothermia associated with tyrosinemia that was not corrected by the administration of ascorbic acid at 50 mg/day but that subsequently responded to ascorbic acid at 500 mg/day. Cerebrospinal fluid analysis for neurotransmitter metabolites showed elevated concentrations of homovanillic acid and 5-hydroxyindoleacetic acid when the child was symptomatic and normal concentrations after successful ascrobic acid therapy. These observations suggest that a high level of tyrosine in serum can affect the metabolism in the brain of dopamine and serotonin.

Ascorbic Acid↗
PubMed1980

Quantitation of plasma azathioprine and 6-mercaptopurine levels in renal transplant patients.

The plasma of renal transplant patients was analyzed by high performance liquid chromatography (HPLC) for the presence of azathioprine and its primary metabolite, 6-mercaptopurine, after either oral or i.v. administration of azathioprine. Azathioprine was demonstrated in plasma at peak concentrations of 0.6 microgram/ml 15 min after i.v. injections of 100 to 200 mg. Within 90 min of injection, the azathioprine level fell to 10 ng/ml. Azathioprine was not detected in plasma at any time after an oral dose of 100 mg, indicating that the plasma concentration is less than 0.5 ng/ml, which is the sensitivity limit of this assay. 6-Mercaptopurine appeared in the plasma after either oral or i.v. azathioprine administration. Furthermore, decreased renal graft function has no effect on the rate of disappearance of azathioprine from plasma. These results demonstrate that high performance liquid chromatography can be used to determine azathioprine and 6-mercaptopurine levels in man, and that alteration in renal function does not influence early stages of azathioprine degradation.

Administration, Oral↗
PubMed1979

Biogenic amine metabolism in Tourette syndrome.

Biogenic amine metabolism in the central nervous system of 9 children with Tourette syndrome was evaluated by quantitation of their metabolites in cerebrospinal fluid by a gas chromatographic/mass spectrometric method. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) were measured in CSF before and after oral administration of probenecid. Dopamine metabolism appeared defective, as both baseline and accumulated levels of HVA after probenecid were decreased. Serotonin metabolism also appeared defective in some patients with low baseline and low accumulated levels of 5-HIAA after probenecid. Taken together with other clinical features of this disease, the results suggest an underlying disorder of dopamine and serotonin metabolism in Tourette syndrome.

Biogenic Amines↗
PubMed1979

Human urinary metabolites of 1-(tetrahydro-2-furanyl)-5-fluorouracil (ftoraful).

Two hydroxylated metabolites were isolated from the urine of a patient who had received ftorafur (5 g/sq m). These metabolites were identified by mass spectrometry and nuclear magnetic resonance spectroscopy as trans-3'- and cis-4'-hydroxyftorafur. The compounds were not converted to 4-fluorouracil when incubated in plasma, base (pH 9), or water. Because of their stability, it is unlikely that these metabolites are in vivo precursors of 5-fluorouracil. There are indications that less stable, unisolatable, hydroxylated ftorafur derivatives are intermediates in the conversion of ftorafur to 5-fluorouracil.

Chemical Phenomena↗
PubMed1978

Hydrolysis of proteins using dipeptidyl aminopeptidases: analysis of the N-terminal portion of spinach plastocyanin.

The exopeptidases dipeptidyl aminopeptidases I and IV were used to hydrolyze the N-terminal portion of spinach plastocyanin to dipeptides. The enzymes were used individually as well as in a mixture and the dipeptides were analyzed by combined gas chromatography-mass spectrometry. Data are presented for native plastocyanin and the S-methylated protein. Of the 98 residues which make up this protein, the first 44 were released in the form of 22 dipeptides by the combined action of DAP I and DAP IV. These dipeptides were aligned by homology to other plastocyanins of known sequence. The results demonstrate the versatility of the two enzymes in hydrolyzing proteins to obtain information on their primary sequence.

Amino Acid Sequence↗
PubMed1975

Classification of fructose-1,6-bisphosphate aldolases based on 18O retention in the cleavage reaction.

Oxygen (18) was used as a mechanistic probe in the investigation of several different sources of fructose 1,6-bisphosphate aldolases (EC 4.1.2.13) which, due to differences in some physical and chemical properties, could not be clearly put in either Class I or Class II. Aldolases may be identified as belonging to a particular class on the basis of the amount of 180 retained in the dihydroxyacetone phosphate produced in the cleavage of [2-Oxygen (18)] fructose 1,6-biphosphate. The mechanism of Class I aldolases involves an obligatory exchange of the C-2 oxygen atom of fructose 1,6-bisphosphate, leading to the absence of 180 in the product. For Class II aldolases, the C-2 oxygen atom is retained in the aldol cleavage reaction. Aldolases from spinach and L. casei base intermediate. Aldosase from C. perfringens was found to be Class II, suggesting a metal-chelate intermediate. Results with Euglena aldolase confirmed that this organism contained both types of aldolases with approximately 78% Class II. The data show that despite a wide variety of physical and chemical properties, there are important mechanistic similarities within each class of enzyme and significant differences between the two classes. The determination of 180 retention in the product of the cleavage reaction using [2-180] fructose 1,6-biphosphate is an accurate means of classifying these enzymes since it is a measure of a property which is directly related to the mechanisms of the reactions.

Animals↗