Cellular kinetics of prednimustine versus chlorambucil plus prednisolone in vitro

Summary Intracellular concentrations of prednimustine (PM), chlorambucil (CLB), phenylacetic acid mustard (PAAM) and prednisolone (P) were measured in different experimental tumor cell lines that had been incubated with either PM or CLB+P. For intracellular analytical determination, we modified a high-pressure liquid chromatographic method for the detection of these substances in plasma. Intact PM could be detected in the intracellular compartment of the incubated tumor cells. PM-incubated cells from PM-injected rats exhibited a higher intracellular concentration-time integral (PAAM) and longer concentration-time profiles for drugs with alkylating capacity than did cells exposed to the CLB+P mixture or to CLB. PAAM was not detectable after incubation of cells with PM, whereas in CLB-incubated cells the AUC of PAAM exceeded that of the parent drug CLB. Our in vitro results therefore favour the concept of a facilitated intracellular uptake and an increased antiproliferative effect for PM versus CLB and CLB+P.Dedicated to Prof. Dr. H. J. Dengler on the occasion of his 65th birthday. This study was supported by the Ministry of Science and Research of Nordrhein-Westfalen     

Hypotensive effect of the active fragment derived from factor XII is mediated by an activation of the plasma kallikrein-kinin system

Plasma protein fraction (PPF) contaminated by factor XII active fragment (XIIf) may cause hypotensive reactions when infused to patients. This study was planned to assess in conscious normotensive rats whether the blood pressure response to the factor XIIf is mediated by an activation of the plasma kallikrein-kinin system or by stimulation of prostaglandin synthesis. To test whether the factor XIIf-induced blood pressure fall is due partially to an enhanced generation of vasodilating prostaglandins, the blood pressure effect of XIIf (1 microgram i.v.) was investigated 15 min after treatment with indomethacin (5 mg i.v.), an inhibitor of cyclo-oxygenase. Factor XIIf reduced mean blood pressure similarly in indomethacin- and vehicle-treated rats (-23 +/- 4 mmHg, n = 5, and -23 +/- 5 mmHg, n = 4, respectively). Other rats received factor XIIf 15 min after depletion of circulating prekallikrein by the administration of dextran sulfate. Thirty minutes after a 0.25 mg i.v. dose of this agent, plasma prekallikrein activity averaged 0.12 +/- 0.015 mumol/min/ml (n = 6) as compared to 2.48 +/- 0.31 mumol/min/ml in control rats (n = 4, P less than .001). Factor XIIf decreased mean blood pressure by only 4 +/- 2 mm Hg in rats pretreated with dextran sulfate. Thus, it was possible to blunt the acute hypotensive effect of factor XIIf by depleting circulating prekallikrein, but not by inhibiting prostaglandin production. This strongly suggests that the blood pressure effects of factor XIIf is mediated by a stimulation of the plasma kallikrein-kinin system.     

Immunoreactivity of an antibody to a beta/A4 sequence with Alzheimer paired helical filaments and tau protein.

beta/A4, a peptide that forms the extracellular amyloid fibrils of Alzheimer senile plaques, has also been proposed to be a component of Alzheimer paired helical filaments (PHFs). We compared BR88, an antiserum to amino acids 1-12 of beta/A4, with BR126, an antiserum to the sequence SEKLDFKDRVQS in tau protein, since tau protein is the only confirmed component of PHFs. In enzyme-linked immunosorbent assays (ELISAs), both antibodies reacted with pronase-treated PHFs better after PHFs were treated with guanidine. tau protein shares no sequence homology with beta/A4. Nevertheless, BR88 cross-reacted with human recombinant tau isoforms by ELISA and Western blot analysis with potencies comparable to those for anti-tau antibodies. BR88 reacted with a beta/A4 peptide as well on a molar basis as with tau protein and showed some reactivity to the tubulin-binding region of tau protein. In conclusion, the beta/A4 antiserum BR88 cross-reacts with tau protein, possibly explaining its reactivity with PHFs.     

ManagementHandbuch für die psychotherapeutische Praxis – MHP.

Ohne Zusammenfassung     

Exposure to allergens of different cattle breeds and their relevance in occupational allergy

Introduction  

Cattle are an important source of allergens in the working area of farmers. Asthma caused by cow allergens is a significant occupational problem. Yet in allergological testing, the results of in vivo and in vitro diagnostic tests are often inconsistent even in cases with clearly cattle-related symptoms.