Ethanol induced oxidative stress and membrane injury in rat erythrocytes.

The aim of this study was to observe membrane injury and to investigate the mechanism of antioxidant defence systems against acute ethanol toxicity. Erythrocyte superoxide dismutase and Na+, K(+)-ATPase activities were significantly decreased and catalase levels were significantly increased one hour after ethanol intoxication of male swiss albino rats. These data demonstrated that superoxide dismutase and catalase are susceptible to lipid peroxidation and that these enzymes protect tissues from free radicals. The possible mechanism involved in Na+, K(+)-ATPase and Ca(2+)-ATPase inhibition are discussed in relation to the development of ethanol toxicity and the role of lipid peroxidative processes.

Erythrocyte Na+,K(+)-ATPase activity does not predict therapeutic response to calcium antagonists in essential hypertension.

We investigated whether pre- and posttreatment analysis of erythrocyte membrane Na+,K(+)-ATPase (EC 3.6.1.37) activity would be a useful marker for screening hypertensive patients to determine who might benefit from treatment with calcium antagonists. Erythrocyte Na+,K(+)-ATPase activity and sodium and potassium (ENa, EK) contents were determined in controls and in patients with untreated essential hypertension before and after 4 weeks of treatment with nitrendipine. Na+,K(+)-ATPase activity was significantly (P < 0.0001) less in untreated hypertensive patients (n = 15; 104.60 +/- 29.37 nmol of phosphate produced per milligram of protein per hour) than in controls (n = 15, 171.87 +/- 34.42). After 4 weeks of nitrendipine treatment Na+,K(+)-ATPase activity was greater than in the pretreatment group: 158.13 +/- 26.80 (P < 0.001). Pretreatment ENa contents (22.34 +/- 4.77 mmol/L) were significantly (P < 0.0001) higher than in the normotensive group (13.14 +/- 3.32 mmol/L), but there was no significant difference between the controls and the posttreatment group (14.84 +/- 3.49 mmol/L). The control and pretreatment groups showed negative correlations between enzyme activity and systolic/diastolic blood pressure (P < 0.0001). The control and the posttreatment groups showed an inverse correlation between enzyme activity and ENa contents: r = -0.608 (P < 0.05) and r = -0.724 (P < 0.001), respectively. Although Na+,K(+)-ATPase is restored in hypertensive patients receiving nitrendipine treatment, relative changes in enzyme activity in relation to relative reduction in blood pressure response to treatment were not correlated.

Free amino acid level determinations in normal and schizophrenic brain.

1. Some disturbances in brain amino acids are reported with regard to pathological changes in schizophrenia: a reduction in GABA content and a reduced activity at some glutamatergic synapses. 2. Comparison of post-mortem brain tissue from control subjects and schizophrenic patients can provide evidence for amino acid alterations in disease. 3. The present study was undertaken to measure free amino acid concentrations in 20 brain regions obtained at autopsy, from normal persons and schizophrenics. Amino acids were extracted, esterified and separated by gas chromatography. 4. The distribution and levels of amino acids in normal persons is in accordance with similar values reported in human post-mortem brain samples by other investigators. 5. The differences in amino acids found in schizophrenic brain samples support the view of disturbed neurotransmission especially with regard to GABAergic and glutamatergic systems in schizophrenia and suggest the possible involvement of other amino acids as well.

[Biotransformation of tramadol in man and animal (author's transl)]. / Metabolismus von Tramadol bei Mensch und Tier.

Following p.o. administration of 14C-labelled rac.-1-(e)-(m-methoxyphenyl)-2-(e)-dimethylaminomethyl-cyclohexan-1-(a)-ol hydrochloride (tramadol hydrochloride, CG 315, Tramal) to mice, hamsters, rats, guinea pigs, rabbits, dogs and man the metabolic pathways were investigated and the results compared. After synthesis of the reference substances the metabolites were identified by co-chromatography using both TLC (thin-layer chromatography) and HPLC (high-performance liquid chromatography) methods, by co-crystallization and by gas chromatography-mass spectrometry. In all species the main metabolic pathways are N- and O-demethylation (phase I reactions) and conjugation of O-demethylated compounds (phase II reactions). 11 metabolites are known, 5 arising by phase I reactions (M1 to M5) and 6 by phase II reactions (glucuronides and sulfates of M1, M4 and M5). The 5 phase I metabolites are mono-O-demethyl-tramadol (M1), mono-N-demethyl-tramadol (M2), di-N-demethyl-tramadol (M3), tri-N,O-demethyl-tramadol (M4) and di-N,O-demethyl-tramadol (M5). The biotransformation scheme of tramadol is qualitatively identical in man, dog, rabbit, guinea pig, rat, hamster and mouse. In all species M1 and M1-conjugates, M5 and M5-conjugates and M2 are the main metabolites, whereas M3, M4 and M4-conjugates were only formed in minor quantities. Following p.o. administration to man and animals 14C-tramadol are rapidly and almost completely absorbed. The unchanged drug and metabolites are mainly excreted via kidneys. The cumulative renal excretion of total radioactivity accounts for approximately 90% in man and varies from 86 to 100% in mouse, hamster, rat, guinea pig, rabbit and dog; the residual of the applied radioactivity appears in the feces. Apparently tramadol is metabolized much more rapidly in animals than in man. For that reason there are appreciable differences between man and animals in the amount of tramadol excreted unchanged in the urine (about 30% and 1% of the p.o. dose, respectively). After incubation with beta-glucuronidase and arylsulfatase at least 81% of the excreted radioactivity could be extracted from the urine of man animals (with the exception of the guinea pig and the rabbit). In man all extractable metabolites were identified.