A quantitative system, amenable to automation, for determining the presence of group A streptococci in broth culture is described. After separation from the broth, the cells' protein coats are removed by digestion with 0.1% trypsin, and they are then stained with anti-A fluorescent antibody (FA). Excess FA is removed, and bound FA is put into solution by dissociation with demineralized distilled water. The amount of FA bound to the cells is quantitated by fluorometry of the solution. The level of nonspecific staining is measured by staining the cells with fluorescein-conjugated normal rabbit globulin absorbed with group A cells, dissociating, and quantifying, as above. The two quantities are subtracted to measure specific binding of FA to group A cells. A clinical trial showed 92% agreement with microscopists.

Bacterial Proteins↗

PubMedDate not supplied

Measuring the health of seniors.

Explore the source record for details and available documents.

Aged↗

PubMedDate not supplied

Pharmacokinetics of glucuronidation of propranolol following oral administration in humans.

Pharmacokinetic and bioavailability parameters of propranolol were estimated in 10 healthy adult subjects after single oral doses of two commercial tablet formulations of propranolol hydrochloride (2 X 40 mg). Plasma concentrations of propranolol were determined by a high-performance liquid-chromatographic (HPLC) assay. Peak plasma concentrations of propranolol glucuronide were 6-8 times those of the corresponding peak propranolol plasma concentrations. The mean resident time (MRT) of propranolol and of propranolol glucuronide was determined for each subject for both formulations. The MRT of the parent drug was found to be longer than the MRT of the glucuronide metabolite for each of the subjects examined. Statistical moment analysis indicated that this phenomenon is attributable to extensive presystemic glucuronidation of the parent drug.

Administration, Oral↗

PubMedDate not supplied

A bioequivalency study of two trifluoperazine tablet formulations using RIA and GC-MS.

Two sensitive analytical procedures, a radioimmunoassay (RIA) and a mass fragmentographic (GC-MS) method, were used to quantitate plasma trifluoperazine concentrations over 24 h in five healthy male volunteers following single 5 mg doses of two trifluoperazine tablet formulations (A and B) in a two-way cross-over design. Bioavailability in terms of area under the plasma concentration versus time curve to 24h or extrapolated to infinity, maximum plasma concentration and time to maximum plasma concentration using either RIA or GC-MS was not statistically significantly different from one formulation to the other. Also, there were no statistically significant differences between GC-MS and RIA values for AUC24(0) and Cmax for each of the two formulations examined. However, the mean AUC24(0) RIA/GC-MS ratios for formulations A and B were 3.1 and 3.4, respectively, while the mean Cmax RIA/GC-MS ratios were 1.7 and 2.1, respectively. These differences in AUC and Cmax are probably mainly due to the relative non-specificity of the RIA antiserum. Thus, where GC-MS is preferred for pharmacokinetic studies, both analytical procedures can be used for comparative single-dose bioequivalence studies of trifluoperazine. However, both the methods should be tested in patients in order to establish the suitability of one procedure over the other for the study of plasma level versus clinical response correlations.

Adult↗

PubMedDate not supplied

Comparison of a new GLC-AFID method with a GLC-MS selected ion monitoring technique and a radioimmunoassay for the determination of plasma concentrations of imipramine and desipramine.

A gas-liquid chromatographic procedure employing an alkali flame ionization detector (GLC-AFID) for the quantitation of imipramine and its major active metabolite, desipramine, in plasma was developed. This method validated a previously reported radioimmunoassay for imipramine and desipramine. The GLC-AFID method was also compared with a GLC-mass spectrometric procedure which employed selected ion monitoring (GLC/MS-SIM) in which specific ions for imipramine and desipramine were monitored. The two methods using gas chromatographic separation were shown to be suitable for therapeutic monitoring of these drugs in patients. The direct immunoassay, which measures the total imipramine plus desipramine, is very useful when large numbers of samples are to be analysed rapidly and it compares favorably with the other two analytical procedures.

Desipramine↗

PubMedDate not supplied

Risk factor and behavioral differences between vascular and Alzheimer's dementias: the pathway to end-stage disease.

Differences between vascular dementia and Alzheimer's dementia may be present in both risk factors and in behavioral manifestations. Behavioral distinctions may be apparent only at particular stages of the disease process, but comparisons at different stages require a large number of subjects. The California Alzheimer Disease Diagnostic and Treatment Center Program has collected data on a large number of subjects with dementia. We examined differences in risk factors and in behaviors in 502 subjects with vascular dementia and 810 subjects with probable Alzheimer's dementia. With respect to risk factors, vascular dementia subjects were more likely to have a history of general anesthesia. We found no difference in history of closed head trauma, family history of dementia, or cigarette smoking, suggesting that these factors are less likely to have a disease-specific etiologic role. With respect to behaviors, subjects with vascular dementia were more likely to have depression in all stages of dementia. Subjects with Alzheimer's dementia were more likely to exhibit wandering in the middle or late stages. Subjects were similar in five other behavioral factors in the three stages studied. We conclude that general anesthesia is a risk factor for vascular dementia and that depression is more prevalent in vascular dementia, while wandering is more characteristic of Alzheimer's dementia.

Aged↗

PubMedDate not supplied

Metabolism of methoxyphenamine in man and in monkey.

Metabolites of methoxyphenamine in the urine of human subjects and monkeys were separated by gas-liquid chromatography and identified by comparison of their chromatographic and mass spectrometric behavior with those of synthetic compounds. Aromatic O-demethylation, aromatic ring hydroxylation (both followed by glucuronide conjugation), and N-demethylation were shown to occur in man as well as in monkey. In man these were the principal metabolites, whereas in the monkey three additional unidentified major metabolites were formed.

Adult↗

PubMedDate not supplied

Identification of 3-O-methyl-alpha-methyldopamine as a urinary metabolite of 3,4-methylenedioxyamphetamine in dog and monkey.

3-O-Methyl-alpha-methyldopamine has been separated by gas-liquid chromatography (GC) as a metabolite of MDA in the urine of dog and monkey. The metabolite was identified as its mono- and di-trifluoroacetyl derivatives by comparison of their GC and GC-mass spectral properties with those of synthetic compounds. The amount of metabolite increased on hydrolyzing the urine from dosed dogs and monkeys with a preparation containing beta-glucuronidase and sulfatase.

3,4-Methylenedioxyamphetamine↗

PubMedDate not supplied

Identification of phase-I and phase-II metabolites of fluphenazine in rat bile. Intact glucuronide and sulfate conjugates.

In rat bile following ip administration of fluphenazine (FLU) dihydrochloride (20 mg/kg body weight), phase-I metabolites 7-hydroxyfluphenazine (7-HOFLU) and FLU sulfoxide (FLUSO), together with unmetabolized FLU, were isolated and identified by HPLC and fast atom bombardment spectrometry (FAB/MS) and also by comparison with authentic compounds. Two intact glucuronide conjugates of FLU were isolated and identified as phase-II metabolites: 7-hydroxyfluphenazine ring glucuronide (glucuronic acid linked to the aromatic hydroxyl group of 7-hydroxyfluphenazine), and FLU glucuronide (glucuronide linked to the aliphatic group of the side chain of FLU) by HPLC and FAB/MS in comparison with authentic compounds. Further confirmed by FAB/MS were several sulfate conjugates of FLU that were isolated and identified indirectly as phase-II sulfate metabolites: FLU sulfate, 7-hydroxyfluphenazine sulfate and/or 7-hydroxyfluphenazine ring sulfate, and FLU sulfoxide sulfate by HPLC and FAB/MS; their aglycones were identified after sulfatase hydrolysis as FLU, 7-HOFLU and FLUSO. A further phase-II metabolite, for which no authentic standard was available, was tentatively identified as a monoglucuronide of dihydroxy derivative of FLU. To our knowledge, this report provides the first direct evidence of the presence of intact phase-II metabolites of FLU in rat bile.

Animals↗

PubMedDate not supplied

The metabolism of p-methoxyamphetamine in dog and monkey. O-demethylation as a major route.

p-Hydroxyamphetamine (PHA) and p-hydroxybenzoic acid (PHBA) have been isolated by gas-liquid chromatography (GC) as urinary metabolites of p-methoxyamphetamine (PMA) in dogs and rhesus monkeys. The amounts of PMA excreted unchanged in the total 24-hr urine samples in dogs and monkeys were 26% and 3%, respectively, of the total administered doses. The amounts of the pharmacologically active metabolite PHA excreted in 24-hr urine samples were 13% in the dog and 44% in the monkey. In the dog, 72% of the PHA was present as free (unconjugated) PHA, whereas in the monkey the amount of PHA present in the free form was only 14%.

Amphetamines↗

PubMedDate not supplied

The identification of urinary metabolites of doxepin in patients.

The metabolism of doxepin was investigated in three patients who provided cumulative urine samples on each of 3 successive days. These samples were examined by means of stereoselective HPLC or HPLC combined with mass spectrometry through a plasmaspray interface (LCMS). In addition, sufficient quantities of the major metabolites were isolated from the urine by column chromatography. The isolated metabolites were examined by HPLC, proton nuclear magnetic resonance spectroscopy (1H-NMR), and chemical ionization and/or electron impact mass spectrometry (EIMS). The resultant spectra and chromatographic properties were compared with authentic reference standards. The metabolites were identified as (E)-2-hydroxydoxepin, (E)-2-hydroxy-N-desmethyldoxepin, (Z)- and (E)-N-desmethyldoxepin, and (Z)- and (E)-doxepin N-oxide. There was no evidence of hydroxylation at the oxymethylene bridge. A further metabolite previously unreported was tentatively identified by LCMS and EIMS as an aromatic hydroxy-N-desmethyldoxepin hydrated at the exocyclic double bond. This metabolite was present in very low amounts, precluding its analysis by 1H-NMR. Moreover, this type of compound dehydrated readily in vitro, and numerous attempts to synthesize reference materials were unsuccessful. The tentative identification of this hydrated metabolite lends significant support to a possible mechanism responsible for the enrichment of cis-N-desmethyldoxepin over time in plasma.

Aged↗