Dynamics of lipid adsorption at the electrified water∣1,2-dichloroethane interface

A recently introduced setup to measure the dynamic interfacial tension of expanding drops was used to compare the adsorption behaviour of a series of lipids at the electrified water∣dichloroethane interface. Phospholipids with saturated carbon chains of different length (DMPC, DPPC, DSPC, DAPC, DBPC), an unsaturated phospholipid (DOPC) and an ethanolamine (DSPE) were compared. It was found that the adsorption decreases with increasing chain length. Also, the increase of the flow rate reduces the degree of adsorption effectively. On the timescale of the experiments, the DSPE, DAPC and DBPC adsorption showed no potential dependence, whereas the adsorption of DOPC was stronger than that of the saturated lipids. Adsorption was modelled using the Langmuir adsorption isotherm; the potential dependence of adsorption is discussed.     

Logics and Logistics of Community Intervention Against Osteoporosis: An Evidence Basis

Under designations like small areas action research and intervention, directed ‘ground-up’ health promotion and prevention in the population form an important part of the ongoing medical systems development. There is recent evidence of the success of community intervention against cardiovascular disease. In osteoporosis, however, there is still a lack of conclusive data on both the logics and logistics of such an approach. Since 1988, a county health policy program has been formulated and implemented in Östergötland, Sweden, following the principles and guidelines of the WHO HFA 2000 declaration. Vadstena (n ? 7,600) was chosen for a local and generalizable osteoporosis prevention project mediated by the primary care organization by means of health promotion and education in the community. In the present report we emphasize that community intervention is an important new advancement of the medical systems, where the basic research questions include operational and management aspects as equally vital and measurable requisites and results as other performance and outcome variables. We found that a community intervention trial against osteoporosis is both motivated and feasible and in this report wish to provide evidence on these crucial issues of logics and logistics.     

Occupational allergic contact dermatitis and composition of acrylates in dentin bonding systems

Background Dentin-bonding systems contain sensitizing acrylates. They are increasingly used in dentistry, but only few cases of allergy have been encountered. Objective This study reports observations on eleven patients sensitized by acrylates in dentin-bonding compounds. Furthermore, the composition of dentin-bonding products was analysed and compared with the information given in the material safety data sheets. Methods Patch testing was performed to reveal allergic contact dermatitis, and chamber provocation tests to reveal possible respiratory sensitivity. Gas chromatography/mass spectrometry was used to analyse the chemical composition of the bonding products. Results The most common sensitizer in our material of eleven patients was 2-hydroxyethyl methacrylate (2-HEMA). Another putative sensitizer, BIS-GMA, used in dentin adhesives, did not cause sensitization. The typical allergic dermatitis localized to the fingertips (pulpitis). Seven of the eleven patients also developed paresthesia of the fingertips. One patient with positive patch test reactions to (meth)acrylates had pharyngitis hut no skin symptoms. One patient was sensitized because she had been patch tested with too high a concentration (undiluted) of dentin-bonding components. Material safety sheets gave inaccurate or wrong information about the contents. Conclusion Dentin-bonding acrylates are strong sensitizers, and even a single exposure may sensitize.     

Reduced dermal infiltration of cytokine-expressing inflammatory cells in atopic dermatitis after short-term topical tacrolimus treatment

BACKGROUND: In several clinical studies, topical calcineurin inhibitors have been shown to be effective in the treatment of atopic dermatitis (AD). They target signaling pathways that control gene expression, particularly the expression of cytokines. OBJECTIVE: We examined the cellular infiltrate in skin lesions of 10 patients with AD and characterized the cytokine pattern expressed by the infiltrating cells before and after short-term topical therapy with tacrolimus 1% ointment. METHODS: Skin biopsies were examined for histologic alterations (hematoxylin and eosin staining), composition of the cellular inflammatory infiltrate (immunofluorescence), and cytokine expression (ribonuclease protection assay, ELISA, immunofluorescence) before as well as 1 and 3 weeks after initiation of tacrolimus therapy. For comparison, biopsies from nonlesional AD and normal skin were analyzed. Systemic immunologic effects were assessed by analyzing peripheral blood leukocytes (immunofluorescence) as well as in vitro stimulated pan-T-cell cytokine production (ELISA). RESULTS: All patients showed a significant improvement of their skin lesions associated with a marked regression of spongiosis, acanthosis, and density of the cellular infiltrate in the dermis. The last was a result of reduced infiltration of T cells, B cells, and eosinophils. In contrast, the numbers of mast cells did not change. Moreover, the expression of the T H 2 cytokines IL-5, IL-10, and IL-13 in CD4 + T cells was reduced after therapy. Interestingly, tacrolimus therapy was also associated with a reduction of CD8 + T cells expressing the T H 1 cytokine IFN-gamma. Furthermore, the numbers of epidermal CD1a + dendritic cells increased after treatment. In the peripheral blood, a decrease of granulocytes (eosinophils and neutrophils) but no changes in the distribution of lymphocyte subpopulations were noticed. CONCLUSION: Topical tacrolimus treatment has anti-inflammatory effects on AD skin as indicated by reduced infiltration of cytokine expressing inflammatory cells. No evidence for drug-induced systemic immunosuppression was obtained.     

The interleukin-13 production by peripheral blood T cells from atopic dermatitis patients does not require CD2 costimulation

BACKGROUND: Although allergic mechanisms appear to be important, the pathogenesis of both extrinsic and intrinsic forms of atopic dermatitis (AD) is unknown. METHODS: We compared the cytokine production of peripheral blood mononuclear cells of extrinsic AD (EAD) and intrinsic AD (IAD) patients and normal control individuals after stimulation with anti-CD3 and/or anti-CD28 monoclonal antibodies (mAbs) in the presence or absence of anti-CD2-blocking mAb. The cytokine production was measured by immunoassays in supernatants of 24-hour cultures. RESULTS: EAD patients showed a decreased capacity to synthesize interferon gamma and granulocyte-macrophage colony-stimulating factor upon anti-CD3 mAb stimulation as compared with IAD patients. Both EAD and IAD patients demonstrated an increased production of interleukin (IL)-5 and IL-13. As expected, interferon gamma, granulocyte-macrophage colony-stimulating factor, and IL-5 levels were reduced in the presence of anti-CD2-blocking mAbs. CD28 costimulation restored the release in cultures with anti-CD2 mAbs added, suggesting that CD2 and CD28 have redundant functions in T cell activation and subsequent cytokine production. Strikingly, the IL-13 production was not blocked by anti-CD2 mAbs and also not increased by agonistic anti-CD28 mAb, in particular within the EAD patient group. CONCLUSION: The signalling pathway initiated by the T cell receptor complex leading to increased IL-13 production in AD patients appears to be highly sensitive and is largely independent on CD2 costimulatory signals.     

The “Scandinavian Star” ferry disaster 1990 -a challenge to forensic odontology

Summary With 158 victims, the fire on board the Scandinavian Star was one of the world's worst ferry disasters. A team of identification experts, including dentists, were employed to secure evidence for identification and to remove the victims from the ferry. Four parallel teams, each with 2 dentists, examined and autopsied the victims at the Institute of Forensic Medicine, University of Oslo. Using the INTERPOL Disaster Victim Identification forms and aided by computers, all victims were identified within 17 days. Dental identity could be established in 107 cases (68%).     

Plasma levels of enterolactone and percentage mammographic density among postmenopausal women.

AIMS: Certain phytoestrogens, such as lignans, may protect against developing breast cancer. Enterolactone is a lignan metabolite produced by the intestinal flora from dietary precursors such as whole grains, vegetables, and fruits. Enterolactone has been shown to have weak estrogenic and antiestrogenic properties. We decided to examine the association between plasma levels of enterolactone and mammographic density, a biomarker for breast cancer risk. METHODS: We included data from postmenopausal women ages 55 and older who participated in a cross-sectional mammogram study in Troms?, Norway. Mammograms, plasma enterolactone measurements, as well as information on anthropometric and hormonal/reproduction factors were available on 616 women. We assessed mammographic density using a previously validated computer-assisted method. We estimated correlation coefficients and conducted multiple regression analyses. RESULTS: Mean mammographic density increased slightly across quartiles of enterolactone; the women in the highest quartile had, on average, 3.1% (absolute difference) higher percentage mammographic density compared with the lowest quartile (P(trend) < 0.01). After adjustment for age, body mass index, number of full-term pregnancies, age at first birth, and use of postmenopausal hormone therapy, the mean difference in density was reduced to 2.0% (P(trend) = 0.05). Results were similar when restricted to the 454 current hormone nonusers. The fully adjusted statistical model explained 28.3% of the total variability in mammographic percentage density, with body mass index contributing 18.2% and enterolactone only 0.9%. CONCLUSION: In our study, higher levels of enterolactone were associated with slightly higher percentage mammographic density. Our results suggest that if higher enterolactone levels reduce the risk of developing breast cancer in postmenopausal women, then this effect is not through lowering mammographic density.     

Pharmacokinetics of levosimendan and its active metabolite OR-1896 in rapid and slow acetylators.

OBJECTIVE: The purpose of this study was to investigate the pharmacokinetics of levosimendan and to determine the primary pharmacokinetic parameters of the pharmacologically active metabolite OR-1896 in rapid and slow acetylators. METHODS: Levosimendan was administered as a constant rate (0.1 microg/(kg min)) i.v. infusion for 24h in six rapid and six slow acetylators based on N-acetyltransferase 2 genotyping. At the end of the infusion, a small amount (2.5 microg/kg) of (13)C-labeled OR-1896 was administered by i.v. infusion for 10 min. Blood samples were taken at predefined sampling points 14 days post-infusion and levosimendan and its metabolite concentrations were determined by LC-MS/MS. RESULTS: Steady-state concentrations of levosimendan were achieved within 4-8h and no differences were found in the pharmacokinetics of the parent compound between the rapid and slow acetylators. The maximum concentrations of amino phenylpyridazinone metabolite OR-1855 and N-acetylated conjugate OR-1896 were observed approximately 24h after terminating the infusion. AUC of OR-1896 was approximately 3.5 times higher in the rapid acetylators compared to the slow acetylators (P = 0.002, 95% confidence interval for group ratio from 2.0 to 8.2). The mean +/- S.D. fraction of levosimendan metabolized to OR-1896 was 6.8 +/- 2.8% in the rapid and 4.3 +/- 2.4% in the slow acetylators (P = 0.12). (13)C-OR-1855 concentrations were detected in plasma after administration of (13)C-OR-1896 indicating deacetylation from OR-1896 to OR-1855. CONCLUSIONS: Plasma OR-1896 levels during and after levosimendan treatment are dependent on the acetylation status of the subject-rapid acetylators having 3.5 times higher concentrations than slow acetylators.