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F R Ungemach

Publications and source records attributed to F R Ungemach.

At least 37 records · Page 2Linked to original sources
PubMed1994

The consequences of nitrofurantoin-induced oxidative stress in isolated rat hepatocytes: evaluation of pathobiochemical alterations.

Oxidative stress was induced in isolated rat hepatocytes by incubation with nitrofurantoin in the absence and presence of the GSSG reductase inhibitor BCNU. In both cases nitrofurantoin markedly reduced glutathione but exerted cytotoxicity as measured by LDH release and loss of intracellular potassium only in BCNU pretreated cells. The onset of cytotoxicity was accompanied by an increase of lipid peroxidation. Oxidation of protein thiols, however, could not be detected in the early phase of cell damage. The cytoprotective activity of N-acetyl-cysteine > dithiothreitol = deferoxamine revealed the substantial importance of glutathione for cellular defence and the sensitivity of not yet identified thiol-dependent targets of oxidative stress.

Acetylcysteine↗
PubMed1994

The role of glutathione and protein thiols in CBrCl3-induced cytotoxicity in isolated rat hepatocytes.

The role of glutathione (GSH) and protein thiols in the pathobiochemical process of CBrCl3 cytotoxicity was investigated in isolated hepatocytes. Administration of 0.5, 1.0 and 1.5 mmol/l CBrCl3 affected cellular viability as assessed by trypan blue exclusion, release of lactate dehydrogenase and loss of intracellular potassium in a dose-dependent manner. Intracellular glutathione and the capacity to reduce 3-(4,5-dimethylthiazolyl-2-)-2,5-diphenyltetrazolium bromide (MTT, thiazolyl blue) decreased almost independently of the CBrCl3 concentration. Protein thiols were not markedly oxidized in the presence of CBrCl3. However, compromising cellular defence mechanisms by either inhibition of glutathione regeneration or depletion of glutathione enhanced the cytotoxicity of CBrCl3 and induced a loss of protein thiols in the late phase of cellular injury. Under these conditions the thiol-dependent Na+,K+ATPase revealed high sensitivity towards CBrCl3. Thus, glutathione proved to exert effective cytoprotection, and sulfhydryl groups of particular proteins were supposed to be an important target of radical attack.

Animals↗
PubMed1992

[In vitro studies of intestinal absorption and biotransformation of furazolidone].

The intestinal biotransformation and absorption of the nitrofuran furazolidone were investigated in isolated gut cells and in the isolated perfused gut. In case of inhibiting furazolidone metabolism by high oxygen tension almost equal concentrations of the parent compound were measured on the mucosal and serosal side of the perfused gut segments. Lowering oxygen supply in order to adjust it to physiological conditions caused a complete degradation of furazolidone in isolated gut cells. Accordingly, hardly any unchanged furazolidone was detected on the serosal side of the isolated perfused gut. An open-chain cyanometabolite was formed in both systems indicating a reductive metabolic process which induces highly reactive intermediates. This metabolite also reached the serosal side of the gut representing the systemic circuit. Thus, the low systemic bioavailability is due to the considerable intestinal metabolism rather than a limited absorption. Unknown metabolites will reach the systemic circuit, the toxic potential of which is still obscure. Independent of its metabolic degradation, thus probably due to its redox cycle furazolidone inhibited intestinal functions as e. g. the flow of water and the transport of sodium.

Animals↗
PubMed1992

[Evaluation of fixed glucocorticoid-antibiotic combinations].

Fixed combinations of glucocorticoids and antibiotics are widely used for the treatment of bacterial infections because they can cause a rapid relief of the inflammatory symptoms. However, hitherto a decisive improvement of the clinical efficacy of the combination as compared to single antibiotic therapy could not be proved. Without a real clinical advantage the combined use of glucocorticoids causes severe side effects like immune suppression with increased risk of infections, gastrointestinal lesions and depression of endogenous hydrocortisone which all will occur even after short-term use and may last for several weeks. Glucocorticoids exhibit a markedly longer duration of action than antibiotics with the risk of cumulation of the glucocorticoid. Thus, there is no kinetic compatibility as it has to be claimed for a rational combination. Due to the negative risk-benefit relation the systemic use of such combinations has to be rejected. For the topical treatment of skin disorders, however, the short-term use of combinations of corticosteroids and antibiotics with comparable pharmacokinetics on the skin like aminoglycoside antibiotics can be of clinical benefit.

Administration, Topical↗
PubMed1991

Investigations on the biotransformation of mebendazole using an isolated perfused rat gut system.

1. The intestinal metabolism of the benzimidazole, mebendazole (MEB), has been investigated using isolated perfused jejunal segments of rats. Significant absorption and intestinal metabolism of the substance was observed. 2. The metabolites, the reduced alpha-hydroxy-analogue, its glucuronide, and the decarbamoylated 2-amino-analogue, were transported into the resorbate collected at the serosal side or were resecreted into the gut lumen. 3. The intestinal decarbamoylation of mebendazole increased up to 20-fold after pretreatment with 3-methylcholanthrene (MC), and complete re-secretion of this metabolite into the gut lumen led to a total loss of the absorption of mebendazole and metabolites across the gut wall. 4. The results indicate the ability of the gut to metabolize mebendazole by phase I and II reactions. 5. An almost complete loss of bioavailability after induction of the gut enzyme system by MC was observed.

Animals↗
PubMed1986

[Creatine content and lipid analysis in radiosensitive organs after whole body x-irradiation of mice--a contribution to the further development of biological radiation dosimetry].

The authors intended to test the suitability of creatine level and/or certain criteria of lipid analysis in radiosensitive organs for an individual (i.e. considering biologic variations of radiosensitivity), qualitative and quantitative demonstration of an irradiation damage. It was found that creatine determination and several criteria of lipid peroxidation are not suitable for a biologic radiation dosimetry due to the absence of organ dependent, radiation dose dependent, and time dependent changes. The reasons are discussed.

Animals↗
PubMed1985

[Doping control in race horses].

Doping in performance horses is defined as the "illegal application of any substance, except normal diet, that might modify the natural and present capacities of the horse at the time of the race." The prohibition of doping is mainly based on the protection of animals. Doping can be performed with various aims: "doping to win" can be regarded as the classical method by mobilization of overphysiological capacities. Such positive doping may be classified as an acute form using psychomotoric stimulants, as a chronic form using anabolic hormones, and as a paradoxical form using small doses of neuroleptics or tranquilizers in excitable horses. In larger doses these sedatives are acting for "doping to loose" in a more subtle manner as compared to hypnotics. According to the doping regulations there is no difference between therapy and doping at the time of the race. Thus at the race all medications to restore normal performance have to be regarded as doping. This fact especially concerns the therapy of lamenesses with non-steroidal antiinflammatory drugs or local anesthetics. A particular problem is "inadvertent" doping due to unknown side effects, combinations of drugs, galenic supplements or food additives. Accidental doping may further be caused by the unawareness of elimination times. At the moment no exact withdrawing times can be defined due to the manifold interindividual variations at different levels of the pharmacokinetics. As a border-line case of doping the application of endogenous substances, like electrolytes or glucose, may be regarded. Though their parenteral application is prohibited prior to the race, only bicarbonate or "blood doping" may be considered to be effective as positive doping. Special doping methods are the use of "masking" substances or diuretics in order to make more difficult the detection of illegal drugs as well as physical doping procedures which are often hardly to define and which thus are only in part included in the doping regulations.

Anabolic Agents↗
PubMed1985

[Efficacy of the paramunity inducers PIND-AVI and PIND-ORF as radioprotective agents].

A significant reduction of mortality after lethal irradiation (7,8 and 9 Gy X-ray total-body irradiation) was achieved by continuous therapeutic subcutaneous application of the biologic inducers PIND-AVI and PIND-ORF. This was obtained by a stimulation of the investigated spleen parameters and a stimulation of leucocytes and phagocytosis. The inducers had no significant influence on the radiogenic reduction of blood cells and bone marrow cells, of the relative spleen and thymus weight and of the DNA and protein level of spleen and thymus. The regeneration of blood leucocytes (preponderantly by PIND-AVI) and of the spleen (preponderantly by PIND-ORF) was accelerated, but not the thymus regeneration which was already rather low. The leucocyte phagocytosis which increased generally after irradiation was markedly stimulated by paramunization. This stimulation was also observed after a latent time in animals submitted to sham irradiation. Its temporal appearance and its quantitative and qualitative properties corresponded to the effects of inducers after X-ray irradiation. Both inducers were found to be harmless in all experiments.

Animals↗
PubMed1983

Simultaneous occurrence of receptors for estradiol, progesterone, and dihydrotestosterone in canine mammary tumors.

Fifty-nine canine mammary tumors have been simultaneously assayed for their histological nature and their content of cytosolic receptors for estradiol (ER), progesterone (PGR), and dihydrotestosterone (DHTR). The tumors were histologically defined as benign tumors, malignant mixed tumors, sarcomas, and simple or complex carcinomas. The tumors exhibited a high incidence of steroid receptors (ER in 61% of the tumors, PGR in 69%, DHTR in 36%). It could be demonstrated that, in cytosols of canine mammary tumors, binding sites for different steroids may simultaneously occur. Twenty four percent of the tumors were able to bind specifically all three hormones tested. No tumor class displayed a specific receptor profile in regard to the receptor incidence, KD, and binding capacity. Also no correlation could be detected between histological grading of carcinomas and receptor incidence. In these tumors, however, the amount of ER and PGR binding showed changes dependent on differentiation. Noteworthy tumors simultaneously removed from the same bitch and with identical histological diagnosis were different in their receptor characteristics.

Animals↗
PubMed1980

Thymidine transport in hepatocytes. An assay for hepatotoxicity.

Thymidine transport and phosphorylation were investigated in isolated rat hepatocytes and AS 30 D hepatoma cells. In contrast to hepatoma cells, hepatocytes exhibited a minimum of thymidine phosphorylation due to a 100-fold smaller thymidine kinase activity. In hepatocytes thymidine is transported by two transport systems: a specific concentrative "high affinity" system and an unspecific non-concentrative "low affinity" system. In hepatoma cells only the "low affinity" system could be detected. A single dose of 20 or 50 mg diethylnitrosamine/kg body weight induced in hepatocytes a remakable increas of thymidine kinase activity and a decrease of the transport by the "high affinity" system. Thymidine transport and phosphorylation by hepatocytes are considered to be sensitive markers for early recognition of toxin-induced liver regeneration.

Animals↗