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A Olsson

Publications and source records attributed to A Olsson.

At least 73 records · Page 4Linked to original sources

Determination of enantiomeric purity of nicotine in pharmaceutical preparations by 13C-NMR in the presence of a chiral lanthanide shift reagent.

A method for the determination of enantiomeric composition of nicotine samples, based on 13C-NMR spectroscopy in the presence of the chiral lanthanide shift reagent, tris[3-(trifluoromethylhydroxymethylene)-(+)-camphorato]ytte rbium [Yb(tfc)3], was developed. Observation at 100.6 MHz of the C2' resonance of nicotine in the presence of 0.15-0.20 mol of the ytterbium complex, either in ordinary 13C[1H]-NMR spectra or in carbon spectra enhanced by polarization transfer (refocused INEPT), allowed precise determination of the ratios of (S)- to (R)-nicotine. At least 1% of (R)-nicotine could be determined in samples of (S)-nicotine, milligram amounts being required for the analysis. Use of the 13C-NMR spectra is more advantageous than use of 1H-NMR spectra. Thus, Yb(tfc)3 induced separation of the proton resonances of the enantiomers of nicotine, and the shifted resonances of nicotine enantiomers could be assigned by use of 1H-13C heteronuclear chemical shift correlation, but the proton resonances were broad, their chemical shifts were sensitive to small variations of the ratio between Yb(tfc)3 and nicotine, and signals of the enantiomer present in small amounts were easily obscured by impurities. Therefore, although 13C-NMR is more time consuming, this method is more suitable for routine analysis. The method was applied for the determination of enantiomeric purity of (S)-nicotine in pharmaceutical formulations, including chewing gums, skin absorption patches, inhalators, and nasal sprays.

Magnetic Resonance Spectroscopy↗

Specific binding and uptake of extracellular nicotinamide in human leukemic K-562 cells.

Extracellular nicotinamide is well recognized as the primary precursor to the cellular synthesis of NAD. NAD is a pivotal molecule in regulating the energy and redox potentials of cells via synthesis of ATP and NAD(P)/NAD(P)H ratios. NAD turnover in cells is very rapid due to NAD catabolism via ADP-ribosylation reactions. These facts suggest that the cellular uptake and transport of nicotinamide may not be a passive process but a highly regulated cellular event. We have utilized radiometric procedures to characterize the uptake of [14C]nicotinamide in human leukemic K-562 cells. At physiologically relevant doses of nicotinamide (< 100 microM), the uptake was saturable with a Km of 2.3 +/- 1.0 microM and a Vmax of about 1.5 +/- 0.5 pmol/10(6) cells/min. Kinetic studies revealed that nicotinamide was first taken up intracellularly and then immediately converted to NAD and 1-methyl nicotinamide. All of the nicotinamide taken up into the cell was bound tightly to plasma membranes (25,000 g pellet) with Kd values between 3.2 and 12.7 microM and a Bmax of 1.56 pmol/10(6) cells. The specificity of nicotinamide binding was demonstrated by competitive inhibition experiments using NAD analogs, nicotinamide derivatives, and agonists or antagonists of plasma membrane receptors. We conclude that there is specific binding of nicotinamide, followed by intracellular uptake and immediate synthesis to NAD.

Binding, Competitive↗

The Malmö biological bank.

Currently there are no available biological markers that have been satisfactorily validated clinically as 'intermediate end-points' for evaluation of the impact of diet on cancer. Therefore, there is high scientific value in banking biological specimens for future use in the Malmö Diet and Cancer Study. The banking procedures we have developed are adequate for assessing factors that estimate dietary intake (e.g. vitamins, lipids or micronutrients) as well as non-dietary variables (e.g. immunologic and ecogenetic factors of biologically effective doses of xenobiotic exposures) that may regulate the biological expression of dietary variables. This approach is further justified by state-of-the-art technology that includes assessment of the concept of gene-environment interactions. Purified viable mononuclear leucocytes, granulocytes, erythrocytes, plasma and serum are being stored from each individual entering the study under the guidelines of a strict quality control programme. Storage of tumour/normal tissues from incident cancer cases are also being stored and quality controlled. It is hoped that these banking procedures will encourage a high activity in biomarker development in the future.

Algorithms↗

The Malmö biomarker programme.

Evaluation of pro-oxidant/antioxidant dietary factors in relation to individual susceptibility to cancer and cardiovascular disease is justified based on a review of the literature. This working hypothesis is amendable to further scientific validation from biomarkers with end-point sensitivity to oxygen radicals. So far, the biomarker programme developed around this theme may be divided into three distinct classes: (1) Markers of genotoxic exposure estimate DNA damage either directly as a biologically effective dose, or indirectly by estimating aberrant cellular functions that lead to accumulation of DNA damage. The examples included are ADP-ribosylation in mononuclear leucocytes (R. Pero, A. Olsson), oxidative DNA damage (K. Frenkel), gene expression in lymphocytes (S. Garte, G. Cosma), serum alpha macroglobulin (W. Troll) and oxidized DNA damage and repair (N. Christie). (2) Markers of genetic predisposition have been shown to have genetic inheritance patterns that relate to individual susceptibility to cancer or cardiovascular disease. The examples included are glutathione transferase mu phenotyping (R. Pero, J. Seidegård) and poly (ADP-ribose) polymerase pseudogene polymorphism (M. Smulson). (3) Markers of dietary status have been validated to estimate the amount of a particular nutrient or xenobiotic in the diet that has been taken up and metabolized or distributed to body fluids or tissues. The example included here is niacin nutriture (E. Jacobson, M. Jacobson). This biomarker is presented in Section 5 (pp. 59-62) of the Malmö Diet and Cancer Programme Minisymposium reported in this issue of the journal.

Animals↗

[Acupuncture nurse].

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Acupuncture Analgesia↗

Plasma homocysteine in women on oral oestrogen-containing contraceptives and in men with oestrogen-treated prostatic carcinoma.

The mechanism by which oral oestrogen-containing contraceptives in women and oestrogen treatment of prostatic carcinoma in men increases the risk of vascular disease is unclear. These agents decrease serum concentrations of vitamin B12, pyridoxal 5-phosphate, and folate, all of which are essential for the metabolism of the atherogenic amino acid homocysteine. We found serum vitamin B12 concentrations to be lower in 17 women using oral contraceptives (219 +/- 84 pmol l-1) than in 13 age-matched female controls (385 +/- 129, p less than 0.001), but similar values were obtained in the two groups both for fasting plasma homocysteine concentrations (9.1 +/- 2.4 vs 9.2 +/- 3.6 mumol l-1) and for the increase in these concentrations after methionine loading (19.2 +/- 7.5 vs 17.8 +/- 5.2 mumol l-1). In five men with prostatic carcinoma, high-dose oestrogen treatment decreased serum vitamin B12 concentrations by a mean of 30% (p less than 0.05) within 4 weeks, during which fasting plasma homocysteine concentrations decreased (13.8 +/- 4.5 vs 10.5 +/- 2.8 mumol l-1) and response to methionine loading increased (12.4 +/- 3.4 vs 17.3 +/- 5.1 mumol l-1), though the latter changes were non-significant. Our findings do not support the hypothesis that hyperhomocysteinemia explains cardiovascular risk in women using oral oestrogen-containing contraceptives, or in oestrogen-treated men with prostatic carcinoma.

Adolescent↗

Caregivers' experience of providing care for demented persons living at home.

Caregivers providing home-care for demented persons answered a questionnaire concerning what was satisfactory or problematic when providing home-care. They were also asked what needs/wishes they had for themselves and for the demented persons. The findings reflected the impact of a functioning interpersonal relationship between the caregiver and the demented person and his family. The difficulties in handling problematic behaviour, and the necessity to be able to stimulate and provide activities for the demented were also emphasized. Moreover, the caregivers stressed their role as supporters of the patients' families, their need for more and better cooperation with the staff of the psychogeriatric clinic, and their need for training and supervision in how to manage their relationship with the demented person. Hence, it seems urgent to try to practise and evaluate systematic clinical guidance to provide knowledge and systematic supervision about how to manage demented persons in their own social context so that they can stay in their homes.

Adolescent↗

Liquid chromatographic determination of the enantiomers of ibuprofen in plasma using a chiral AGP column.

A reversed-phase high-performance liquid chromatographic method has been developed for the determination of the R- and S-enantiomers of ibuprofen. The enantiomers and the internal standard 4-pentylphenylacetic acid are extracted from plasma, separated and quantified on a Chiral-AGP column using ultraviolet detection. The simplicity, sensitivity and precision of the method makes it convenient for use in pharmacokinetic studies.

Animals↗