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Biomedical subjects

J Hannemann

Publications and source records attributed to J Hannemann.

28 records · Page 2Linked to original sources
PubMed1990

Cyclosporine A induced lipid peroxidation and influence on glucose-6-phosphatase in rat hepatic and renal microsomes.

The in vitro effect of cyclosporine A (CsA) on lipid peroxidation (LPO) in hepatic and renal microsomes (male Wistar rats) were investigated either with different CsA concentrations (0.3-1000 micrograms/ml), incubation time 3 h or for different periods of time (0.5-3.0 h) at a CsA concentration of 1000 micrograms/ml. LPO was monitored by measuring the formation of malondialdehyde (MDA) using the thiobarbituric acid assay. Furthermore the influence of CsA on the microsomal enzyme glucose-6-phosphatase was investigated. CsA caused a time- and concentration-dependent increase of LPO in hepatic and renal microsomes. The lowest CsA concentration which produced a significant increase in MDA production amounted to 1 microgram/ml for hepatic microsomes and 3 micrograms/ml for renal microsomes. Under identical experimental conditions, the MDA production by hepatic microsomes was 3 to 5 fold higher than by renal microsomes. Addition of the radical scavenger alpha-tocopherol (1 mM) to the incubation medium decreased the CsA-caused microsomal MDA production. Regarding the microsomal enzyme, CsA decreased the specific activity of glucose-6-phosphatase in a time- and concentration-dependent fashion. Compared to microsomal MDA production, higher CsA concentrations were necessary to effect on specific enzyme activity. The results suggest, that production of free radicals and subsequently lipid peroxidation could participate in cyclosporine A induced hepato- and nephrotoxicity.

Animals↗
PubMed1988

Cisplatin-induced lipid peroxidation and decrease of gluconeogenesis in rat kidney cortex: different effects of antioxidants and radical scavengers.

The present in vitro study was performed to investigate the effect of the nephrotoxic anticancer agent cisplatin (CP) on lipid peroxidation, on pyruvate-stimulated gluconeogenesis and on p-aminohippurate (PAH) accumulation in rat renal cortical slices. In addition, the inhibitory effects of the antioxidants and radical scavengers N,N'-diphenyl-p-phenylenediamine (DPPD), (+)-cyanidanol-3 or alpha-tocopherol on CP-induced lipid peroxidation and CP-induced decrease of gluconeogenesis and the inhibitory effect of DPPD on CP-induced decrease of PAH accumulation were evaluated. Slices were incubated in a CP-containing medium for different periods of time (7.5-300 min) and at different concentrations (0.025-1.5 mg/ml). Lipid peroxidation was monitored by measuring the production of malondialdehyde (MDA). Accumulation of PAH was expressed as slice to medium concentration ratio. Pyruvate-stimulated gluconeogenesis, measured as glucose production, was determined after a subsequent 60- or 15-min incubation in a pyruvate-containing, CP-free medium. CP led to a time- and concentration-dependent increase in MDA production, a time- and concentration-dependent decrease of pyruvate-stimulated gluconeogenesis and a time-dependent decrease of PAH accumulation in renal cortical slices. Decrease of gluconeogenesis preceded MDA production and decrease of PAH accumulation. Antioxidants reduced CP-induced MDA production and CP-induced decrease of accumulation of PAH, but did not reverse CP-induced decrease of gluconeogenesis. This might indicate, that the generation of free radicals and subsequent lipid peroxidation may play a role, at least in part, in inducing CP nephrotoxicity. There could be more than one mechanism of CP-induced nephrotoxicity, since decrease of gluconeogenesis preceded MDA production and decrease of PAH accumulation and could not be inhibited by antioxidants and radical scavengers.

Animals↗
PubMed1988

Inhibition of lactate-dehydrogenase by cisplatin and other platinum-compounds: enzyme leakage of LDH is not a suitable method to measure platinum-compound-induced kidney cell damage in vitro.

The effects of three platinum-compounds on the activity of hog muscle lactate-dehydrogenase (LDH), cytosolic LDH released from rat renal cortical slices and cytosolic LDH isolated from rat kidney cells were investigated. In vitro, cisplatin inhibited the activity of LDH in a concentration-dependent manner. At a concentration of 0.25 mg/ml, cisplatin, transplatin and cisplatin-hydrolysis-products inhibited the activity of LDH time-dependently. These observations make it doubtful to use LDH-enzyme leakage experiments to demonstrate damage of kidney cells by platinum-compounds. The nonnephrotoxic compound transplatin had an enhanced inhibitory effect on the activity of LDH compared to the nephrotoxic compounds cisplatin or cisplatin-hydrolysis-products (transplatin greater than cisplatin greater than cisplatin-hydrolysis-products). Thus, LDH-enzyme inhibition seems not to be related to the nephrotoxicity of cisplatin.

Animals↗
PubMed1985

Cephaloridine-induced lipid peroxidation initiated by reactive oxygen species as a possible mechanism of cephaloridine nephrotoxicity.

Rat kidney microsomes reduced cephaloridine when incubated anaerobically with NADPH. Superoxide anion was generated in a concentration- and time-dependent manner when cephaloridine was incubated with rat kidney microsomes. Cephaloridine increased the in vitro peroxidation of rat kidney microsomal lipids in a concentration- and time-dependent manner. Cephaloridine-induced lipid peroxidation was inhibited by a combination of superoxide dismutase and catalase, by the hydroxyl radical scavengers, mannitol, (+)-cyanidanol-3 and by the singlet oxygen scavenger histidine in a concentration-dependent manner. It is proposed that cephaloridine nephrotoxicity may occur through the transfer of an electron from reduced cephaloridine to oxygen and subsequent formation of the superoxide anion, hydrogen peroxide, the hydroxyl radical and singlet oxygen. These activated oxygen species then are very likely to react with membrane lipids to induce lipid peroxidation and nephrotoxicity.

Anaerobiosis↗
PubMedDate not supplied

[Quality management within the competence network of paediatric oncology and haematology].

The competence network paediatric oncology and haematology aims at improving the structure of paediatric oncology and haematology as a whole focussing in particular on the quality of clinical trials and study centres. This implicates the following measures: (1) Employment of research and trial assistants in order to improve the quality of documentation and study management in the participating hospitals. (2) Building up of an Internet portal to provide medical information for non-professionals, for patients and their families as well as for health professionals. (3) The project "Study Assistance" supports study centers during the process of writing and examining new treatment protocols so that they are in compliance with the Good Clinical Practice criteria, formal criteria and statutory provisions. It presently works on a structural standardisation of study protocols and case record forms in order to improve their usability. In addition, the working group "Quality Assurance in GPOH Study Centres" is engaged in developing a quality management system for study centers.

Clinical Trials as Topic↗
PubMedDate not supplied

[The "quality house pediatric oncology" as an instrument for improving the performance of the trial centers].

The project group "Central Trial Support" of the German Competence Network Pediatric Oncology and Haematology supports the members of the Society of Pediatric Oncology and Haematology in their effort to cope with the growing statutory, ethical and administrative requirements for therapy optimization studies (investigator-initiated, non-profit clinical trials). By these quality improvement measures the studies will become more revisable and reliable, but at the same time their processing will become more and more complex. The basic instrument of the project group "Central Trial Support" will be the so-called "Quality House" which has been built up in order to improve the performance of the associated study centres and to help put a systematic quality management system into practice. The "Quality House Pediatric Oncology" comprises detailed descriptions of the activities of all trial center co-workers. Its process map details all operational sequences which constitute an efficiently performing trial center. The so-called value adding processes are explained step by step, and the associated specific tasks are assigned to each respective co-worker. At each process step, the person in charge will have explanatory descriptions at her/his disposal and - if necessary - further problem solving means as well as references to possible optimization measures (e. g. Standard Operating Procedures and other documents). The German Competence Network Pediatric Oncology and Haematology will be implementing this electronic quality management system in trial centers which will convince both sponsors and authorities of the compliance with requirements and standards.

Child↗