Notes: The ability of cells to control the balance between the generation and quenching of reactive oxygen species is important in combating potentially damaging effects of oxidative stress. One mechanism that cells use to maintain redox homeostasis is the antioxidant response pathway. Antioxidant response elements (AREs) are cis-acting elements located in regulatory regions of antioxidant and phase II detoxification genes. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is a member of the Cap ‘n’ Collar family of transcription factors that binds to the ARE and regulates the transcription of specific ARE-containing genes such as NAD(P)H:quinone oxidoreductase 1, glutamylcysteine synthetase and heme oxygenase. Activation of Nrf2 results in release from its negative repressor, Kelch-like ECH-associated protein 1 (Keap1), and allows Nrf2 to translocate into the nucleus to induce gene expression. In this study, we demonstrate that increasing Nrf2 activity by various methods, including chemical induction, Nrf2 overexpression or Keap1 siRNA knockdown, protects cells against specific types of oxidative damage. Cells were protected against 6-hydroxydopamine- and 3-morpholinosydnonimine-mediated toxicity but not against 1-methyl-1-4-phenylpyridinium toxicity. As oxidative stress is a hallmark of several neurodegenerative disorders, including Parkinson's disease, pharmacological agents that selectively target the Keap1-Nrf2 pathway may provide a novel neuroprotective strategy for the treatment of these diseases.

Notes: Summary. Fibrin sealant, which consists mainly of fibrinogen and thrombin, provides rapid haemostasis as well as tissue sealing and adhesion. Commercial, viralinactivated products are available in Europe, Canada, and Japan. Liquid fibrin sealant (LFS) has been used clinically in haemophiliacs to perform dental procedures, orthopedic surgeries, non-orthopaedic surgeries, and circumcisions. LFS use is expected to increase as commercial products will soon be available in the US. Recombinant sources and transgenic animal bioreactor systems will replace plasma-derived products and become the predominant sources for this product in the next decade. Other areas of innovation include the development of fibrin sealant bandages or dressings, expandable foams, and spray powders which will provide the haemophiliac the ability to rapidly attain control of traumatic haemorrhages prior to hospital treatment with a significant reduction in the use of IV clotting factors. Fibrin sealant products have the potential to provide life-saving control of haemorrhage, reduction in factor dependency, lower viral exposure risk, and medical care cost reduction.

Notes: Background Corticosteroid therapy has become the mainstay in the treatment of asthma. However, the risk-benefit balance in the patient calls for assessment of the state of inflammation in the airways. In this respect serum eosinophil cationic protein (ECP) might be a marker, which can easily be measured in a clinical setting. Studies have indicated a relation between level of serum ECP and activity and severity in asthma.Objective To investigate the feasibility to guide steroid therapy on the basis of the level of serum ECP in patients with chronic asthma.Methods Twenty adult patients on maintenance inhaled steroid therapy visited the chest clinic once every 2 months over a 12-month period. At each visit a short history, blood sample for ECP and number of eosinophils, baseline spirometry, and histamine inhalation provocation test (PC20) were obtained. On the basis of level of ECP, adjustments in daily dose of steroids were considered. Data were compared with those of a previous 6-month ECP evaluation study in these same patients.Results In 10 patients mean dose of inhaled steroids was decreased 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:09547894:CEA519:ges" location="ges.gif"/〉 25%. ECP rose slightly (antilogged mean from 9.06 to 11.8μg/L) and lung function decreased slightly (mean FEV1%predicted from 85.5 to 81.6). In seven patients mean dose of inhaled or oral (n= 2) steroids was increased 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:09547894:CEA519:ges" location="ges.gif"/〉 25%. In this group ECP decreased but remained elevated at 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:09547894:CEA519:ges" location="ges.gif"/〉20μg/L (antilogged mean from 30.5 to 25.6μg/L) and lung function improved (mean FEV1%predicted from 67.2 to 74.5). In both groups patients' scores of asthmatic well-being increased significantly, and PC20 did not show a trend. Exacerbation rate remained the same in the decreased and the no change group (n= 3, in which no substantial change in steroid dose occurred), but was reduced by about 50% in the increased group.Conclusion From this observational study it is concluded that adjusting steroid therapy guided by serum ECP-level may be helpful in tailoring asthma treatment.

Notes: Sera from 204 adult patients with chronic airways obstruction were analysed with the Phadiatop®, a new allergosorbent test with a paper disc containing the most relevant inhalant allergens, the PRIST for total IgE determinations, and a panel of seven RAST tests with the common inhalant allergens in The Netherlands as reference. The aim was to evaluate the Phadiatop as screening test in the in vitro diagnostic procedures in an epidemiological setting. The Phadiatop was classified positive or negative according to percentage binding, total IgE was considered elevated at values 〉 100 kU/1 and the RAST panel positive when at least one RAST result was class 〉 1. The prevalence of inhalant atopy came to 27.9%. The predictive value of the Phadiatop for a positive RAST panel was 96.4%, and for a negative RAST panel 97.3%. For the PRIST these values were 51.9% and 87.2% respectively. The correlation between the log percentages binding of the Phadiatop and the RAST panel was 0.93. It is concluded that the Phadiatop is a valuable test for the screening of inhalant atopy, and as the percentage binding of the Phadiatop may reflect the degree of sensitization it could also be applied as a quantitative measure especially for epidemiological purposes.

Notes: Abstract The complete sequence of the plasmid pHly152-encoded hemolysin (hly) determinant of Escherichia coli is presented and compared with a recently sequenced chromosomal hly determinant [1]. High sequence homology between the two hly determinants is observed withìn all four structural genes, hlyC, A, B and D, but little sequence similarities are found in the 3′- and 5′-noncoding flanking regions. In addition, the noncoding region upstream of hlyC which carries the promoter for hlyC, A and B, was sequenced for several chromosomal hly determinants. The comparison of these sequences indicates three distinct classes of promoter regions which share common putative −10 and −35 boxes at roughly the same location relative to the start of hlyC.