From Bioorganic Chemistry to Catalysis

Research projects of the Department of Chemistry, University of Basel are reviewed ranging from the synthesis of complex natural products to the development of metalorganic catalysts and organocatalyst

Porphyrin accumulation induced by 5-aminolaevulinic acid esters in tumour cells growing in vitro and in vivo

The ability of 5-aminolaevulinic acid and some of its esterified derivatives to induce porphyrin accumulation has been examined in CaNT murine mammary carcinoma cells growing in culture and as tumours in vivo. Topical or intravenous administration of 5-aminolaevulinic acid-esters to mice bearing subcutaneous tumours produced lower porphyrin levels in the tumour than an equimolar dose of 5-aminolaevulinic acid. Reducing the dose of intravenous hexyl- or benzyl-ALA and topical hexyl-5-aminolaevulinic acid resulted in a dose-dependent reduction in porphyrin accumulation. A number of normal tissues accumulated higher concentrations of porphyrins than tumour tissue following intravenous administration of 5-aminolaevulinic acid-esters. Esterase activity in these normal tissues was greater than that in tumour tissue. In contrast to the situation in vivo, all of the 5-aminolaevulinic acid-esters examined were at least as effective as 5-aminolaevulinic acid when applied to cloned CaNT cells in vitro, with the drug concentration required for maximum porphyrin accumulation varying with ester chain-length. Tumour cells growing in culture released esterase activity into the medium. These findings suggest that the efficacy of 5-aminolaevulinic esters may vary depending on the esterase activity of the target tissue, and suggest caution when interpreting the findings of in vitro studies using these and similar prodrugs

Estimating Cost Savings when Implementing a Product Platform Approach

Many market forces are driving companies to improve their targeting of increasingly small market niches. To accomplish this efficiently, products are organized into product families that typically share common platforms. To reorganize the current product offerings or new products into a product family, using a platform approach, requires estimating the savings for such a modification. One of the problems encountered in estimating development and design cost is the lack of availability of hard information during the initial design phases. The purpose of this paper is to estimate the design and development cost, when moving towards a platform approach, using simple models. The activity based product family cost models are developed from existing single product design activities, which are modified and extended to reflect activities related to development of product platform and subsequent product family members supported by the platform. Uncertainty related to cost associated with activities are included in the model, which is solved using Monte Carlo simulation. The approach is demonstrated using a hard disk drive spindle motor platform development for a family of hard disks.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Rosamond Lehmann A modern writer

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C3d immunohistochemistry on formalin-fixed tissue is a valuable tool in the diagnosis of bullous pemphigoid of the skin

Background: Direct immunofluorescence (DIF) testing is an important procedure in the diagnosis of autoimmune bullous dermatoses. We investigated the expression of C3d in formalin-fixed, paraffin-embedded tissue of autoimmune bullous dermatoses. Methods: The immunohistochemical expression of C3d in bullous pemphigoid (BP) (n = 32), pemphigoid gestationis (PG) (n = 3), pemphigus (n = 14), dermatitis herpetiformis Duhring (DHD) (n = 10), linear immunoglobulin A (IgA) dermatosis (n = 4), mixed forms of BP and linear IgA dermatosis (n = 2), and 44 controls was analyzed on formalin-fixed tissue. Results: Thirty-one of 32 cases (97%) of BP and 3 out of 3 cases (100%) of PG showed a linear positivity of C3d along the basement membrane. Only 3 out of 14 (21%) cases of pemphigus showed an intraepidermal intercellular expression of C3d. The two mixed forms of linear IgA dermatosis and BP showed a linear positivity of C3d along the basement membrane. All cases of DHD, linear IgA dermatosis and all of the controls were negative for C3d. Conclusions: C3d immunohistochemistry is a valuable tool in the diagnosis of BP and PG of the skin with a sensitivity of at least 97%. Mixed forms of linear IgA dermatosis, and BP, DHD and linear IgA dermatosis can only be identified by DIF. A positive result may prompt serologic confirmation of BP without further need for DIF. Pfaltz K, Mertz K, Rose C, Scheidegger P, Pfaltz M, Kempf W. C3d immunohistochemistry on formalin-fixed tissue is a valuable tool in the diagnosis of bullous pemphigoid of the skin