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Biomedical subjects

H Peter

Publications and source records attributed to H Peter.

At least 19 recordsLinked to original sources
PubMed1992

Desferrithiocin is an effective iron chelator in vivo and in vitro but ferrithiocin is toxic.

The efficacy and toxicity of the siderophore desferrithiocin (DFT), which has shown potential application in iron chelation therapy, were assessed in vivo and in vitro. DFT was evaluated in vivo in two ways: firstly, by measuring the effect of a single dose of DFT (10-100 mg/kg) on 59Fe excretion in iron-loaded rats labelled with 59Fe; and secondly, by examining the effect of the daily oral administration for 2 weeks of DFT (10-25 mg/kg/d) on the growing rat. DFT and its ferric complex, ferrithiocin (FT), were assessed in vitro from their effects on transferrin and iron uptake and mobilization from rat hepatocytes in culture using transferrin doubly labelled with 125I and 59Fe. Both oral and subcutaneous DFT were highly effective in promoting iron excretion in vivo, but showed evidence of toxicity after oral administration for 2 weeks at 25 mg/kg/d. In addition, DFT was much more effective than desferrioxamine or pyridoxal isonicotinyl hydrazone in reducing hepatocyte iron in vitro. However, FT was cytotoxic, causing membrane disruption and release of intracellular aspartate aminotransferase. It was concluded that DFT should not be considered for chronic iron chelation therapy without extensive further evaluation.

Administration, Oral↗
PubMed1991

Formation of DNA adducts in F-344 rats after oral administration or inhalation of [14C]methyl bromide.

The genotoxic effects of methyl bromide were investigated in a DNA-binding study. [14C]Methyl bromide was administered to male and female F-344 rats orally, or by inhalation from a closed exposure system. DNA adducts were detected in the liver, lung, stomach and forestomach. [14C]3-Methyladenine, [14C]7-methylguanine and [14C]O6-methylguanine were identified using a combination of three different methods of hydrolysing DNA, followed by HPLC or gas chromatography-mass spectrometry. After both oral and inhalation exposure, the highest levels of methylated guanines, especially those of [14C]O6-methylguanine, were found in the stomach and forestomach of the rats. These results clearly demonstrate a systemic DNA-alkylating potential of methyl bromide.

Administration, Inhalation↗
PubMed1991

DNA binding of methyl iodide in male and female F344 rats.

The genotoxic potency of methyl iodide was investigated in a DNA binding study. Male and female F344 rats were exposed to 14C-labelled methyl iodide orally or by inhalation in a closed exposure system. DNA adducts were detected in the liver, lung, stomach and forestomach of the exposed animals. [14C]3-Methyladenine, [14C]7-methylguanine and [14C]O6-methylguanine could be identified by a combination of three different methods of hydrolysing DNA and subsequent HPLC or GC/MS analysis. The highest values of methylated guanines were determined in the stomach and forestomach of the animals following both oral and inhalative exposure. These results demonstrate a systemic genotoxic effect of methyl iodide.

Adenine↗
PubMed1991

Distribution of ethylene oxide in human blood and its implications for biomonitoring.

The distribution of radioactivity following the incubation of human blood with radio-labelled ethylene oxide was investigated in vitro. After incubation, the individual blood samples were separated into lymphocytes and high (Mr greater than 10,000) and low (Mr less than 10,000) molecular fractions of erythrocyte cytoplasm and blood plasma. The radioactivity was determined in each sample by liquid scintillation counting. In erythrocyte cytoplasm, the distribution of radioactivity showed marked interindividual differences and two distinct groups could be distinguished. The coincidence of these groups with 'conjugators' and 'non-conjugators', in terms of the enzymatic conjugation of methyl halides to glutathione in erythrocytes, suggests a common principle, such as enzyme polymorphism. Such polymorphism has been described for glutathione S-transferase mu in the human liver, an enzyme that efficiently conjugates epoxides. In the other blood compartments, the interindividual differences were either less significant or were not detectable. Binding products with various macromolecules in blood, such as haemoglobin or lymphocyte DNA, are being discussed as biological monitors for occupational exposure to ethylene oxide. The observation that erythrocytes exhibit interindividual differences as described above make binding products with haemoglobin less suitable for biological monitoring of ethylene oxide exposure than, for example, DNA adducts in lymphocytes.

Blood Cells↗
PubMed1991

[Behavior analysis in myasthenia gravis].

A first step in approaching the autoimmune-disease myasthenia gravis from behavior therapy is reported. 23 patients were investigated by a two to four hours lasting structured behavior analytic interview (SBAI) and a set of standardized questionnaires, used routinely for neurotic reactions. A marked disability was found in occupation. Significant social phobic and depressive reactions became obvious in the interview but not in the questionnaire data. Half of the subjects reported interactions between emotions, cognitions and motoric behavior. Onset of sufficient treatment was preceded by a diagnostic Odyssey, lasting up to 9 years. Our results correspond to the sparse literature. Further basic research on the subject has to be done that may lead to first experimental behavior therapeutic trials.

Activities of Daily Living↗
PubMed1990

A comparative investigation of the metabolism of methyl bromide and methyl iodide in human erythrocytes.

Human erythrocyte cytoplasm was incubated in head space vials with either methyl bromide or methyl iodide. The decline in concentration of the two methyl halides was monitored by gas chromatography. Simultaneously, the production of S-methylglutathione was determined by thin layer chromatography. In parallel experiments, boiled erythrocyte cytoplasm was used in order to determine non-enzymatic conjugation. Furthermore, inhibition experiments with sulfobromophthalein were performed. The results were compared with previous findings on the metabolism of methyl chloride. In contrast to methyl chloride, both methyl bromide and methyl iodide showed a significant non-enzymatic conjugation with glutathione. In addition, an enzymatic conjugation could be observed in the erythrocyte cytoplasm of the majority of the population, whereas a minority lacks this enzymatic activity. This is consistent with findings on methyl chloride. Inhibition experiments show that a minor form of the erythrocyte glutathione transferase may be responsible for the enzymatic conjugation. Of the three monohalogenated methanes, methyl bromide is the substrate with the highest affinity for the conjugating enzyme(s). In the case of methyl iodide, non-enzymatic reaction overweighs the enzymatic process. There are possible implications of the results for occupational health and the toxicity of the substances.

Cytoplasm↗
PubMed1990

Note on the preference of aliphatic epoxides for the N-7 position of guanine in DNA.

The reactivity of aliphatic epoxides like ethylene oxide, chloroethylene oxide or propylene oxide towards N-3 and N-7 in both purine bases was calculated by the MNDO method and correlated with their HOMO coefficients. A greater chemical susceptibility of the N-3 position in both purines to aliphatic epoxides when compared with the N-7 position was found. On this background the preference of aliphatic epoxides for the N-7 position of guanine in DNA was explained by the existence of intramolecular hydrogen bonds in adenine and guanine and the steric orientation of the N-3 (minor groove) and N-7 (major groove) positions of both purines in alpha-helical DNA.

Adenine↗
PubMed1990

Autogenous rib graft for reconstruction of alveolar bone defects in cleft patients. Long-term follow-up results.

In a retrospective study (mean follow-up 76 months), the use of a free autogenous rib graft for reconstruction of anterior residual bone defects in seventeen cleft patients is evaluated on a long term basis. The results show recurrence of a palatal oronasal fistula in 2 out of 17 patients. 6 patients had acceptable results, while 9 had good to excellent scores at all sites. The costal graft material does not prevent permanent upper cuspids from erupting into this bone, after its incorporation. It is concluded that autogenous rib bone is a good material for secondary bone grafting of the residual alveolar and palatal defect in cleft patients.

Alveolar Process↗
PubMed1990

A comparative evaluation of iron clearance models.

A comparative study of the non-iron-overloaded, bile duct-cannulated rat and of the Cebus monkey as iron-clearance models is presented. The ability of desferrioxamine, desferrithiocin, and a pyridoxal isonicotinoyl hydrazone (PIH) analogue to clear the metal from these two animals is evaluated. Data suggest that although rodents represent a viable first-line animal screen, there is no strict correspondence between the effectiveness of a chelator in rodents and that in primates. Rodent data should be interpreted carefully as it relates to potential human trials. Iron-loading response, the similarity between multiple human and Cebus serum and hematological values, and the ability to easily observe changes in behavioral patterns clearly render the Cebus monkey the best preclinical screen.

Animals↗
PubMed1990

Inhalation pharmacokinetics of isoprene in rats and mice.

Studies on inhalation pharmacokinetics of isoprene were conducted in rats (Wistar) and mice (B6C3F1) to investigate possible species differences in metabolism of this compound. Pharmacokinetic analysis of isoprene inhaled by rats and mice revealed saturation kinetics of isoprene metabolism in both species. For rats and mice, linear pharmacokinetics apply at exposure concentrations below 300 ppm isoprene. Saturation of isoprene metabolism is practically complete at atmospheric concentrations of about 1000 ppm in rats and about 2000 ppm in mice. In the lower concentration range where first-order metabolism applies, metabolic clearance (related to the concentration in the atmosphere) of inhaled isoprene per kilogram body weight was 6200 mL/hr for rats and 12,000 mL/hr for mice. The estimated maximal metabolic elimination rates were 130 mumole/hr/kg for rats and 400 mumole/hr/kg for mice. This shows that the rate of isoprene metabolism in mice is about two or three times that in rats. When the untreated animals are kept in a closed all-glass exposure system, the exhalation of isoprene into the system can be measured. This shows that the isoprene endogenously produced by the animals is systemically available within the animal organism. From such experiments the endogenous production rate of isoprene was calculated to be 1.9 mumole/hr/kg for rats and 0.4 mumole/hr/kg for mice. Our data indicate that the endogenous production of isoprene should be accounted for when discussing a possible carcinogenic or mutagenic risk of this compound.

Administration, Inhalation↗