Zur Kasuistik des Sellheimschen Kastratoidismus

Ohne Zusammenfassung     

Einzelreferate und Buchbesprechungen

Ohne Zusammenfassung     

Einzelreferate und Buchbesprechungen

Ohne Zusammenfassung     

Differently charged polypeptides in the prevention of post-surgical peritoneal adhesions

Objective. Peritoneal adhesions develop after almost all surgical interventions in the abdomen. We have developed an efficient treatment against post-surgical adhesions consisting of a combination of positively charged poly-L-lysine and negatively charged poly-L-glutamate. The aim of the present study was to further develop the concept of applying oppositely charged polypeptides in the prevention of adhesion formation, by evaluating different doses of the peptides, alterations in the way of administration, and also testing alternative components. Material and methods. Eighty-five NMRI mice were divided into six groups. A standardized peritoneal injury model was used. The groups received physiologic sodium chlorine, poly-L-lysine+poly-L-glutamate, low molecular weight poly-L-lysine+poly-L-glutamate, locally administered poly-L-lysine+poly-L-glutamate, in vitro mixed poly-L-lysine+poly-L-glutamate and poly-L-arginine+poly-L-glutamate, respectively. After 7 days, the extent of adhesion formation was determined during relaparotomy and was expressed as the mean percentage of the total wound length. Results. A significant decrease (p <0.001) in the peritoneal adhesion rate was detected in all groups, with the exception of the group administered poly-L-arginine. Among those animals that received poly-L-lysine and poly-L-glutamate, the low dose of poly-L-lysine administration resulted in the most pronounced anti-adhesive effect. Conclusions. The most effective polypeptide combination was poly-L-lysine and poly-L-glutamate, also showing effectiveness when used at low doses and by local application. The differences in adhesion prevention and the possible underlying mechanisms are discussed and the key role of poly-L-lysine is elucidated.     

Substantial discrepancies in 17β‐oestradiol concentrations obtained with three different commercial direct radioimmunoassay kits in rat sera

The extensive use of oestrogen for contraception and amelioration of post‐menopausal symptoms has made it the subject of substantial recent research efforts, and ovariectomized (ovx) rats treated with exogenous ovarial hormones are important when investigating the effects and mechanisms of oestrogen actions. The crucial need to control and monitor plasma levels of 17β‐oestradiol calls for accurate, precise and robust assay methods. The performance of direct radioimmunoassays (RIAs) in measurement of 17β‐oestradiol has been reported previously for human samples, but to our knowledge not for rat samples. In the current study, 552 serum samples from ovx, native and hormone‐treated rats were used to compare the performance of three commercially manufactured direct RIAs from the companies DPC (Siemens Healthcare Diagnostics Inc., formerly Diagnostic Products Corporation), DSL (Diagnostic Systems Labs) and MPB (MP Biomedicals, formerly ICN Biomedicals). Substantial differences in results between the three assay methods were found when measuring serum 17β‐oestradiol concentrations. The following formulas describing the relation between the different methods were obtained using weighted Deming's orthogonal regression (based on pg/mL): DSL = 0.43*DPC+12.3, MPB = 2.1*DPC+84.7 and DSL = 4.8*MPB+22.2. Furthermore, a preceding diethyl ether extraction step of the serum appears to impair the performance of the RIAs in the present samples (based on pg/mL): DPC_ex = 0.39*DPC_unex+0.76, DSL_ex = 0.32*DSL_unex?1.7 and MPB_ex = 0.22*MPB_unex+1.4.     

Bone marrow transplantation for severe aplastic anemia: a randomized controlled study of conditioning regimens

The addition of antithymocyte globulin (ATG) to a regimen of high-dose cyclophosphamide has been advocated to enhance engraftment after allogeneic bone marrow transplantation (BMT) for severe aplastic anemia (SAA). In a prospective clinical trial, 134 patients were randomly assigned to receive cyclophosphamide alone or in combination with ATG. All patients received T-cell–replete bone marrow from an HLA-matched sibling. With a median follow-up of 6 years, the 5-year probabilities of survival were 74% for the cyclophosphamide alone group and 80% for the cyclophosphamide plus ATG group (P = .44). Graft failure and graft-versus-host disease (GVHD) rates were similar in both groups. With the survival rates achieved, this study is not adequately powered to detect significant differences between the 2 treatment groups. In conclusion, the results of allogeneic BMT for SAA have improved over time related to advances in supportive care. The addition of ATG to the preparative regimen did not significantly improve the outcome.     

Chaperone domains convert prolyl isomerases into generic catalysts of protein folding

The cis/trans isomerization of peptide bonds before proline (prolyl bonds) is a rate-limiting step in many protein folding reactions, and it is used to switch between alternate functional states of folded proteins. Several prolyl isomerases of the FK506-binding protein family, such as trigger factor, SlyD, and FkpA, contain chaperone domains and are assumed to assist protein folding in vivo. The prolyl isomerase activity of FK506-binding proteins strongly depends on the nature of residue Xaa of the Xaa-Pro bond. We confirmed this in assays with a library of tetrapeptides in which position Xaa was occupied by all 20 aa. A high sequence specificity seems inconsistent with a generic function of prolyl isomerases in protein folding. Accordingly, we constructed a library of protein variants with all 20 aa at position Xaa before a rate-limiting cis proline and used it to investigate the performance of trigger factor and SlyD as catalysts of proline-limited folding. The efficiencies of both prolyl isomerases were higher than in the tetrapeptide assays, and, intriguingly, this high activity was almost independent of the nature of the residue before the proline. Apparently, the almost indiscriminate binding of the chaperone domain to the refolding protein chain overrides the inherently high sequence specificity of the prolyl isomerase site. The catalytic performance of these folding enzymes is thus determined by generic substrate recognition at the chaperone domain and efficient transfer to the active site in the prolyl isomerase domain.