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Biomedical subjects

A Biber

Publications and source records attributed to A Biber.

27 records · Page 2Linked to original sources

Urinary mutagenicity after controlled exposure to environmental tobacco smoke (ETS).

20 non-smokers on a defined diet low in polycyclic aromatic hydrocarbons (PAH) were exposed to environmental tobacco smoke (ETS) in an unventilated room for 8 h. The urinary mutagenicity in the 24-h urine samples as tested with the Salmonella (TA98) microsome assay did not significantly increase after exposure to either 10 ppm CO or 20-25 ppm CO. We conclude that exposure of non-smokers to ETS does not lead to an increase in their urinary mutagenicity, provided the exposure conditions are within a realistic range.

Adult↗

Calmodulin content in specific brain areas.

A radioimmunoassay was used to measure the calmodulin content in eleven brain areas of the rat. Calmodulin showed an uneven distribution. Various cortical regions, striatum, hippocampus, amygdala and substantia grisea were highest in calmodulin content (15 micrograms/mg protein). Locus coeruleus, nucleus tractus solitarii (+A2 region) and A1 region, contained 7 micrograms calmodulin per mg protein and the cerebellum 4 micrograms/mg.

Animals↗

Radioimmunoassay of oxidized calmodulin in chloramine-T treated tissue samples.

We found that a short incubation of calmodulin with chloramine-T alters its antigenic structure. Antisera elicited by performic acid oxidized calmodulin only bind with chloramine-T treated calmodulin. Based on this finding we have developed an assay for the determination of calmodulin in small tissue samples. Tissue homogenates are incubated with 10 mmol/l chloramine-T before calmodulin quantification. Immune complexes are isolated by sodium sulphate precipitation. [125I]calmodulin is used as tracer.

3',5'-Cyclic-AMP Phosphodiesterases↗

Myelin basic protein in cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases.

Cerebrospinal fluid (CSF) from 105 patients was analyzed by radioimmunoassay for the presence of material cross-reactive with peptide 89-169 of bovine myelin basic protein (BP). In a group of 72 multiple sclerosis patients, 52 showed higher BP content than the control group, i.e. more than 2 ng/ml CSF. Increased BP or BP fragments could be detected in CSF from almost all patients who recently (within 2 weeks) had had an acute episode, or after deterioration in the progressive form of the disease. Fifteen to 30 days after the onset of exacerbation or in a stable period, BP content decreases and in the slowly progressive form was in the range of the control group with one exception. BP content was also elevated in the CSF of patients with other neurological diseases. The presence of BP in the CSF from patients with isolated retrobulbar neuritis is of particular interest. Thus the presence of material cross-reactive with BP fragment 89-169 is not specific for multiple sclerosis, but is a useful parameter in diagnosis and evaluation of MS.

Cerebrovascular Disorders↗

Pharmacokinetics of [14C]-labelled Losigamone and enantiomers after oral administration to healthy subjects.

Losigamone ((+/-)-(R*,S*)-5-(2-chlorophenylhydroxymethyl)-4-methoxy-2 (5H)-furanone; AO-33) is a new potential antiepileptic drug undergoing clinical development. In a crossover study, 200 mg [14C]-labelled Losigamone, as well as 100 mg of each of the unlabelled enantiomers, was administered to 5 healthy volunteers as an oral suspension. The objectives of the study were to determine the mode of elimination, the excretion balance, metabolic profile, the in vitro and in vivo binding to plasma proteins and the pharmacokinetics of both enantiomers in plasma. From the plasma concentration-time profiles of [14C]-radioactivity and unchanged Losigamone it can be concluded that the absorption of Losigamone occurs very rapidly and the plasma concentration of the parent compound versus total radioactivity was consistently about 40%. An overall recovery of total radioactivity of about 97% with 85% in urine and 12% in faeces was found. Protein binding was 50%. Losigamone was extensively metabolized, with only traces of unchanged drug found in urine. The predominant metabolic pathways are hydroxylation and conjugation. After administration of the pure enantiomers, significant differences in pharmacokinetics were observed. The mean oral clearance of the (-)-enantiomer was 1863 ml/min and of the (+)-enantiomer was 171 ml/min. There was no chiral inversion after administration of the enantiomers.

Administration, Oral↗

The effect of acute and chronic administration of nicotine on lipoprotein lipase activity.

Nicotine was injected intraperitoneally to rats and 2 h later lipoprotein lipase was determined in isolated perfused hearts. There was a significant increase in heparin releasable lipoprotein lipase activity which represents the functional pool without increase in total enzyme activity. When 1 microliter/h of a solution of nicotine (120 mg/ml) was delivered for 3 days from subcutaneously implanted miniosmotic pumps, total lipoprotein lipase activity in the heart increased 1.5-3.0 fold. Endogenous lipoprotein lipase activity in plasma doubled and there was a significant fall in plasma triglyceride levels. The effect of nicotine on heart lipoprotein lipase activity was evident also after 6 days of continuous delivery and was accompanied by a fall in adipose tissue lipoprotein lipase activity. No effect was seen when the dose of nicotine was halved. A positive correlation was seen between plasma nicotine levels and heart lipoprotein lipase activity, while adipose tissue lipoprotein lipase correlated negatively with plasma nicotine levels. Chronic administration of nicotine was accompanied by either weight loss or diminished weight gain. It is concluded that in the rat the acute effect of nicotine on the shift of lipoprotein lipase to the functional pool could be related to enhanced beta-adrenergic stimulation. The chronic effect of nicotine could have been mediated by the loss in body weight, due to reduced caloric intake.

Animals↗

[Pharmacokinetic properties of Bilobalide and Ginkgolides A and B in healthy subjects after intravenous and oral administration of Ginkgo biloba extract (EGb 761)].

The pharmacokinetics of Ginkgolide A, Ginkgolide B and Bilobalide, which are compounds extracted from the dried leaves of the Ginkgo biloba tree, were investigated in 12 young healthy volunteers (six men and six women; mean +/- SD age = 25 +/- 5 years) after single-dose administration of Ginkgo biloba extract. Subjects were given, on three occasions, Ginkgo biloba extract as a solution either orally (in fasting conditions and after a standard meal) or intravenously; corresponding to single doses of Ginkgolide A, Ginkgolide B and Bilobalide ranging from 0.90 mg to 3.36 mg. After each dosing, blood and urine samples were collected for up to 36 h and 48 h, for measurements of Ginkgolide A, Ginkgolide B and Bilobalide. Plasma and urine concentrations of these compounds were quantitatively measured by gas chromatography/mass spectrometry using negative chemical ionization, by applying a very sensitive method which allowed plasma concentrations as low as 0.2 ng/ml of each compound to be measured. When given orally, while fasting, the extents of bioavailability are high, as shown by bioavailability coefficients (FAUC) mean (+/- SD) values equal to 0.80 (+/- 0.09), 0.88 (+/- 0.21) and 0.79 (+/- 0.30) for Ginkgolide A, Ginkgolide B and Bilobalide respectively. Food intake does not change AUC quantitatively but increases Tmax. For the three compounds of interest, after oral dosing while fasting, differences can be noted for the elimination half-lives (T1/2Z), which exhibit mean values equal to 4.50, 10.57 and 3.21 h, as well as mean residence times (MRT), equal to 5.86, 11.25 and 4.89 h, for Ginkgolide A, Ginkgolide B and Bilobalide respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗