PubMed Health⌕ Search

Biomedical subjects

J A Berger

Publications and source records attributed to J A Berger.

At least 19 recordsLinked to original sources

Ultranonlocality in time-dependent current-density-functional theory: application to conjugated polymers.

We solve the long-standing problem of the large overestimation of the static polarizability of conjugated polymers obtained using the local density approximation within density-functional theory. The local approximation is unable to describe the highly nonlocal exchange and correlation (xc) effects found in these quasi-one-dimensional systems. Time-dependent current-density-functional theory enables a local current description of ultranonlocal xc effects using the Vignale-Kohn functional [G. Vignale and W. Kohn, Phys. Rev. Lett. 77, 2037 (1996)]. Except for the model hydrogen chain, our results are in excellent agreement with the best available correlated methods.

Journal Article↗

A Case Study: Linda.

An oncology chaplain illustrates the Discipline for Pastoral Care Giving by recalling interactions with a breast cancer patient.

Breast Neoplasms↗

Clinical psychology students' self-reported willingness to interact with persons living with HIV.

Previous research has indicated that health care workers, including those in mental health, have negative attitudes toward people living with HIV and AIDS and may be unwilling to work with them in a professional capacity. Ajzen's theory of planned behavior (1985) was used as a model for better understanding the specific components of these attitudes. In this project doctoral students in clinical psychology read a vignette describing a person who is HIV positive and then completed a set of measures regarding willingness to interact professionally, level of knowledge and attitudes toward HIV and AIDS, and attitudes regarding drug abusers and promiscuity. Results indicated that participants were generally willing to provide therapy for an HIV positive client, although some participants indicated that they would experience some anxiety in doing so. Level of anxiety could be predicted by attitudes toward AIDS and whether the participants believed that accepting an infected client would have negative effects for them personally or professionally.

Adult↗

Determination of phloroglucinol in human plasma by gas chromatography-mass spectrometry.

A specific and sensitive method has been developed for the determination of phloroglucinol in plasma; it involves an optimized procedure for blood sampling designed to minimize the in vitro oxidation of the molecule, and gas chromatography-mass spectrometry after silylation of the compound. The method allowed a reliable determination of phloroglucinol in plasma. The precision and accuracy of the assay, reported as coefficients of variation, were below 15%. Using a plasma sample of 0.25 ml, the limit of quantitation was 5 ng/ml with a precision of 17.4%, which is sensitive enough for pharmacokinetic studies. Stability studies under different conditions revealed that ascorbic acid limits the degradation of phloroglucinol in plasma during storage at freezer temperatures.

Drug Stability↗

Measurement of trazodone in plasma and brain of rat by capillary gas chromatography with a nitrogen-selective detector.

A specific and highly sensitive method for the measurement of trazodone in plasma and brain of rat is presented. The compound and the internal standard were extracted from alkalinized samples with hexane and analysed by capillary gas chromatography with nitrogen-selective detection. The method was demonstrated to be accurate and precise. The limits of determination were 2 ng/ml for plasma and 24 ng/g for brain, which makes this procedure suitable for pharmacokinetic analysis.

Animals↗

Antinociceptive activity of metapramine in mice. Relationship with its pharmacokinetic properties.

The antinociceptive effect of acutely and chronically (every brain elimination half-life time) administered metapramine, a tricyclic antidepressant without anticholinergic or cardiotoxic effects, was studied in three different pain tests. In the hot plate test, its action was more potent when jumping was used as a pain parameter (acute ED50 = 19 +/- 3 mg/kg, i.p.) than when pain was assessed by licking of forepaws (only 20 mg/kg, i.p. was weakly active). Five chronic doses of 15 mg/kg were as active in the tail-flick test as an acute dose of 20 mg/kg (only active dose). Metapramine was more effective in the PBQ-induced writhing test after acute (ED50 = 9.9 +/- 0.1 mg/kg, i.p.) and chronic administration. A significant linear correlation was found between the effect in this test and plasma and overall brain levels of metapramine. No correlation was observed with levels of its three desmethylated metabolites. The usefullness of using a well-defined pattern of administration based on pharmacokinetic parameters and the involvement of monoaminergic mechanisms and of some metabolites of metapramine are discussed.

Animals↗

Identification of several human urinary metabolites of 6-benzoyl benzoxazolinone by gas chromatography/mass spectrometry.

The biotransformation of 6-benzoyl benzoxazolinone (6-BB), a non-narcotic peripheral analgesic, was studied in eight healthy volunteers after oral administration of a single dose of 1 g. Urinary metabolites were extracted either with ethyl acetate at different pH values or by percolating at pH 5 through Amberlite XAD 2 ion-exchange resin. Eluates were concentrated under vacuum, purified by thin-layer chromatography and analysed by gas chromatography/mass spectrometry or direct insertion probe mass spectrometry. Metabolites were identified with reference to the mass spectra of various synthesized compounds assumed to be metabolites of 6-BB, as N-methylated or monohydroxylated compounds. Another metabolic pathway was cleavage of the benzoxazolinone heterocycle giving 2-amino-5-benzoyl phenol after hydrolysis and decarboxylation. N-methyl, N-acetyl and hydroxylated metabolites having an amino-5-benzoyl phenol structure were also found.

Adult↗

Kinetics of allopurinol and its metabolite oxypurinol after oral administration of allopurinol alone or associated with benzbromarone in man. Simultaneous assay of hypoxanthine and xanthine by gas chromatography-mass spectrometry.

Allopurinol, oxypurinol, hypoxanthine and xanthine were assayed simultaneously using a highly specific method combining gas chromatography and mass spectrometry. Two hypo-uricaemic prescriptions were compared: i) 300 mg of allopurinol (AL); and ii) 100 mg of allopurinol plus 20 mg of benzbromarone (AL + BZB). When administered acutely, their effects on blood uric acid levels were similar. Analysis of the pharmacokinetic parameters of allopurinol and its metabolite after each treatment showed dose-linearity for the metabolite but not for the drug itself. The area under the concentration time curve for allopurinol was 40.3 +/- 9.3 mumol l-1 h after AL, against 8.4 +/- 3.9 mumol-1 h after AL + BZB, while for oxypurinol it was 948.0 +/- 125.4 mumol l-1 h after AL and 285.2 +/- 77.9 mumol l-1 h after AL + BZB. The difference in dosage form may partly account for this difference, but the benzbromarone also seems to be involved. Its role on the blood uric acid lowering action of the drug association is complex. Although benzbromarone appreciably favors the elimination of oxypurinol, which should result in a weakening of its hypo-uricaemic action, this is offset by enhanced elimination of hypoxanthine and xanthine. Renal clearance of xanthine was significantly increased under AL + BZB (173.1 +/- 65.6 ml/min against 112.2 +/- 32.9 ml/min after AL). Similarly, blood xanthine levels were proportionately higher in the presence of benzbromarone. The action of the two agents may thus be synergistic and not antagonistic, a pharmacological justification for the therapeutic use of this drug association.

Adult↗

Biotransformation study of para-substituted phenylpiperazines in beagle dogs by gas chromatography-mass spectrometry.

1. Beagle dogs were treated orally (10 mg/kg) with para-chloro-, para-fluoro- and para-methyl-phenylpiperazine derivatives, and urine was collected for 72 h after treatment. 2. Metabolites were extracted, converted into trimethylsilyl (TMS) derivatives and examined by g.l.c.-mass spectrometry. 3. The metabolites fall into two main groups, N-desphenylated metabolites, which result from N-desphenylation, and N-phenyl metabolites. 4. Two kinds of hydroxylated metabolites were found. Some lost the original para substituent (Cl, F or CH3); others retained it. 5. These results are consistent with the NIH shift reaction.

Animals↗

Plasma and blood assay of xanthine and hypoxanthine by gas chromatography-mass spectrometry: physiological variations in humans.

Plasma and blood xanthine and hypoxanthine levels were assayed using a sensitive and specific method involving gas chromatography-mass spectrometry, associated with an optimized sample preparation procedure. Physiological variation was studied in 224 subjects with no purine metabolism disorders. An age dependency for both compounds was found, comparable with that known for uric acid. The mean plasma levels for the 224 subjects were 0.65 +/- 0.24 microM for xanthine and 1.65 +/- 0.78 microM for hypoxanthine. Corresponding mean blood levels were 0.59 +/- 0.21 microM for xanthine and 1.72 +/- 0.74 microM for hypoxanthine. Plasma and blood levels were significantly different, by ca. 10%. Rapid in vitro release of hypoxanthine from erythrocytes and continuation of intraerythrocytal metabolism lead to overestimation exceeding 10% within half an hour after sample blood collection. Hence samples must be deproteinized promptly. Blood can therefore be conveniently used for oxypurine assay instead of plasma when prompt spinning of samples is difficult to manage, as is usually encountered in clinical practice.

Adolescent↗

Pharmacokinetics of metapramine and its demethylated metabolites in plasma and brain of mice.

Previous studies on pharmacokinetic parameters of tricyclic antidepressants (TCAs) in rodents have shown different results from those obtained for the same drugs in man. The kinetics of metapramine (META) and its major demethylated metabolites (METs) were studied in the SWISS CD 1 mouse after acute administration in order to establish the pharmacokinetic parameters in plasma and brain. The plasma half-life (T1/2) was very short (87 min) compared with the half-life (7 h) in man. The metabolism of META was intensive as was the transfer of META and its metabolites into the brain. The kinetic profiles of the substances were quite similar both in plasma and in brain, namely a bicompartment open model. META was rapidly absorbed (Tmax = 10 min) into and quickly eliminated (T 1/2 = 40 min) from the brain. These parameters were used to schedule sampling (blood and brain) at the appropriate time after acute administration of increased doses. The administered doses were significantly correlated to firstly the plasma or brain levels of META, secondly the plasma levels of the main monodemethylated metabolite (MET I), and thirdly the plasma or brain levels of META + METs. Finally, the evolution of plasma and brain levels of the substances was studied after repeated injections (i.e. every 40 min) and confirmed the high affinity of META and its metabolites for the brain regions.

Animals↗