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Biomedical subjects

B Svensson

Publications and source records attributed to B Svensson.

280 records · Page 16Linked to original sources

Metabolic activation of eugenol by myeloperoxidase and polymorphonuclear leukocytes.

Eugenol has recently been associated with the toxic effects of clove cigarettes on human lungs. We have studied the metabolism and adverse effects of eugenol on human polymorphonuclear leukocytes (PMNs). Myeloperoxidase, isolated and purified from human PMNs, catalyzed the oxidation of eugenol to a reactive intermediate which is likely to be a quinone methide. Eosinophil peroxidase, lactoperoxidase, prostaglandin H synthase, horseradish peroxidase, and rat intestinal peroxidase also supported this hydrogen peroxide dependent reaction. Glutathione inhibited the formation of this metabolite, resulting in the formation of glutathione disulfide and a small amount of eugenol-glutathione conjugates. In cellular incubations, phorbol ester stimulated PMNs catalyzed the covalent binding of [3H]eugenol to cellular protein, which was partially inhibitable by azide. Intracellular glutathione levels decreased by 90% over a period of 30 min in phorbol ester stimulated PMNs exposed to 100 microM eugenol compared with decreases of 30% (phorbol ester alone) or 5% (eugenol alone) in control incubations. In addition, eugenol was more cytotoxic to PMNs in the presence of phorbol ester than in its absence, and eugenol inhibited the phorbol ester stimulated oxidative burst in PMNs as reflected by a decrease in oxygen consumption, superoxide formation, and hydrogen peroxide formation. These results suggest that PMNs are capable of activating eugenol to a reactive intermediate and also suggest a mechanism whereby eugenol can potentially interfere with and adversely affect vital PMN functions.

Biotransformation↗

Inhibition of catalytic and glucan-binding activities of a streptococcal GTF forming insoluble glucans.

The ability of a range of potential inhibitors to affect the catalytic activity or binding of dextran by a glucosyltransferase (GTF-I) that synthesises insoluble alpha1,3-linked glucan was tested. Acarbose, deoxynojirimycin, N-dodecyldeoxynojirimycin and Tris, which are thought to interfere with the active site of the enzyme of GTF and related glycosidases, inhibited glucan synthesis but not glucan binding. Tris was found to act as a competitive inhibitor of GTF-I. The effectiveness of the active site inhibitors was not altered by immobilisation of GTF-I on saliva-coated hydroxyapatite. In contrast, three amine hydrofluorides were markedly less effective against immobilised GTF than soluble GTF. The pH of the reaction mixture was found to have a strong influence on inhibition by acarbose, Tris and amine hydrofluorides, a finding that is of direct relevance to use of inhibitors in vivo.

1-Deoxynojirimycin↗

Sequence analysis of the D1 and D2 reaction center proteins of photosystem II.

A compilation of 38 sequences for the D1 and 15 sequences for the D2 reaction center proteins of photosystem II is presented. The sequences have been compared and a similarity index that takes into account the degree of conservation and the quality of the changes in each position has been calculated. The similarity index is used to identify and describe functionally important domains in the D1/D2 heterodimer. Comparative hydropathy plot are presented for the aminoacid sidechains that constitute the binding domain of the tyrosine radicals, TyrZ and TyrD, in photosystem II. The structure around TyrZ is more hydrophilic than the structure around TyrD. The hydrophilic residues are clustered in the part of the binding pocket for TyrZ that is turned towards the lumenal side of the thylakoid membrane. Most prominent is the presence of two conserved carboxylic aminoacids, D1-Asp 170 and D1-Glu 189. Their respective carboxyl-groups come close in space and are proposed to constitute a metal binding site together with D1-Gln 165. The distance between the proposed metal binding site and the center of the ring of TyrZ is approximately 7 A. The cavity that constitutes the binding site for TyrD is composed of residues from the D2 protein. Its character is more hydrophobic than the TyrZ site and the environment around TyrD lacks the cluster of putative metal binding side-chains.

Amino Acid Sequence↗

Treatment of early RA in clinical practice: a comparative study of two different DMARD/corticosteroid options.

OBJECTIVES: To study the outcome in clinical practice of first DMARD and/or corticosteroid (CS) treatment in patients with recent onset rheumatoid arthritis (RA). PATIENTS: 245 patients with active RA, not previously treated with DMARDs or CS, were randomised to one of two treatment groups, T1 = 7.5-15 mg of prednisolone (PRE) daily for one to three months followed, if needed, by methotrexate (MTX) in a weekly dose of 5-15 mg in addition to the lowest possible dose of PRE or T2 = sulfasalazine (SAL), supplemented with lowest possible CS dose if needed. METHODS: The EULAR individual response criteria were applied and remission was defined as a final DAS28 < 2.6. Function was assessed by the HAQ and radiographic progression by Larsen scores. A patient who managed to remain on the allocated treatment for two years was described as a "completer". RESULTS: After 2 years of treatment, 70% of the patients in T1 and 63% in T2 were responders (30% and 33% "good responders", respectively). In T1 29% and in T2 19% were in remission. There was a significant functional improvement in both groups but radiographic progression occurred. The mean decrease in HAQ and increase in the Larsen score were similar in the two groups. One-third of the patients were non-completers, 19% from T1 and 47% from T2. Non-completers had, compared with completers, a significantly lower rate of individual response and remission. Completers and non-completers had similar functional improvement and similar radiological progression. CONCLUSIONS: Individual response and remission was reduced in patients who did not complete their first DMARD/CS treatment option. Treatment failures were significantly more frequent in the sulfasalazine plus optional CS than in the CS plus optional methotrexate treatment group.

Adult↗

High incidence of polymyalgia rheumatica and giant cell arteritis in a Swedish community.

The minimum incidence of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) was studied during one year in a stable Caucasian population in southern Sweden. The data obtained show an incidence rate higher than that previously found in Sweden and almost as high as the rate recently found in Denmark. In addition, the finding of a low incidence of ocular complications during 3 years of follow-up suggests the positive influence of training primary health care physicians to identify and treat these patients early. Furthermore, the previously described transition from pure PMR into GCA was not seen which might imply a further effect of early treatment.

Adrenal Cortex Hormones↗

Random locomotion and phagocytosis of monocytes in undiluted normal serum and in undiluted SLE serum.

Time-lapse filming was performed with normal monocytes in normal serum and in SLE serum, with and without yeast cell phagocytosis. Undiluted sera were used. After incubation of the monocytes with SLE serum we found a decreased velocity of random movement and a change of morphology to more condensed, rounded-up and un-spread cells with a decreased yeast cell phagocytosis. No obvious correlation was found between the SLE serum induced impairment of monocyte function and disease activity, complement levels or the presence of immune complexes. We conclude that monocyte in vitro membrane functions, such as random motility, spreading and yeast cell phagocytosis, are impaired in the presence of undiluted SLE serum.

Adult↗

No effect of acetylcystein on refractory rheumatoid arthritis.

Acetylcystein has some chemical similarities with Penicillamine and other thiol containing compounds with effect on rheumatoid arthritis. We report an open trial on seven patients with refractory rheumatoid arthritis in which no beneficial effect could be seen after up to twelve months treatment in doses 600-1200 mg acetylcystein daily. No definite laboratory changes were seen, apart from a tendency towards higher IgA levels at the end of the treatment period.

Acetylcysteine↗

D-penicillamine in early rheumatoid arthritis: experience from a 2-year double blind placebo controlled study.

OBJECTIVE: To evaluate the usefulness of early treatment with D-Penicillamine (DPA) in rheumatoid arthritis. METHODS: The patients were recruited from a Swedish early RA cohort comprising 180 patients. All patients experiencing active and/or erosive disease 2 years from onset were asked to participate in a 2-year placebo-controlled DPA trial. Previous treatment with slow-acting anti-rheumatic drugs (SAARDs) or oral corticosteroids was not allowed. The main outcome variable was radiographic progression in the hands and feet evaluated according to Larsen. Clinical assessment including the Ritchie index, active joint count, and the HAQ-disability index was performed every 6th month. Patients were included in the analyses of efficacy until the endpoint of therapy. RESULTS: 111/180 patients were eligible for treatment, and 74 agreed to participate in the trial. 21/33 patients on DPA and 22/41 on placebo completed the study. More patients taking placebo stopped due to lack of response (p < 0.01). 27% of the patients on DPA were withdrawn due to side effects. Radiographic deterioration increased but most clinical variables improved in both trial arms. A large inter-individual variation was observed. The only significant difference in trend over 2 years between DPA and placebo was found for joint tenderness. However, the median trends for most clinical variables showed a more positive effect for DPA. The 37 patients who refused to participate in the trial in general fared somewhat worse than patients taking DPA and somewhat better than patients taking placebo. The remission rate was about the same in all 3 groups (12-13.5%). CONCLUSIONS: About two-thirds of all early definite RA patients were eligible for treatment using current criteria. Psychological readiness for early therapy was fairly modest with a high refusal rate. The difference in efficacy between DPA and placebo was small, but was in favour of DPA for most clinical variables. However, only joint tenderness showed a significantly better trend. No significant slowing of radiographic progression by DPA was found.

Antirheumatic Agents↗