Leonard Goldberg

Inhibition of ethanol metabolism in vivo by administration of pyrazole

Abstract In experiments in rats, the in vivo effect of pyrazole on ethanol metabolism was studied. Pyrazole acts as a competitive ADH inhibitor. Ethanol at a dose of 32.6 m-mole/kg was administered. Blood samples were withdrawn at regular intervals, and ethanol analyzed by the automated ADH method and by gas chromatography. Pyrazole in doses of 0.07–8.82 m-mole/kg inhibited the elimination of ethanol by 20 to 90 per cent compared to the control experiments. In the control experiments, ethanol was eliminated in 4 hr, but, after a dose of 8.82 m-mole/kg pyrazole, elimination time was prolonged to between 35 and 50 hr. Inhibition of ethanol metabolism was confirmed by studies with 14 C-1-ethanol, which showed a decrease in the excretion rate after pyrazole, with a subsequent decrease in the excretion of 14 CO 2 . The specificity of the inhibitor is discussed.

The nucleic acid content of mouse ascites tumor cells

Abstract Nucleic acid determinations were carried out on cells of Ehrlich ascites tumor of mice. Ascites fluid was withdrawn a certain period of time after the inoculation of 0.8 × 10 6 –39 × 10 6 cells, and the nucleic acid content was determined per ml fluid and per cell after counting the number of cells. The following results were obtained: 1. 1. The content of nucleic acids in 65 animals was on an average: NA = 4.09 × 10 −6 μg P per cell PNA = 2.68 × 10 −6 μg P per cell DNA = 1.42 × 10 −6 μg P per cell PNA/NA = 65.6 per cent PNA/DNA = 1.94 The variability between animals was low (14.1 per cent for PNA, 21.3 per cent for DNA). 2. 2. In spite of the variation in the inoculated number of cells from 0.8 × 10 6 to 39 × 10 6 , and a corresponding decrease in the median survival time from 11 to 5 days, there was no difference in cell nucleic acid content observed when sacrificing the animals on the median survival time ± 2 days. 3. 3. Starvation for 48 hrs had no effect on the PNA content of the tumor cells in spite of having a deteriorating action on the general condition of the animals. 4. 4. The isolation of nuclei performed with 1 per cent citric acid had no influence on the DNA content, the values per nucleus were the same as per whole cell. 5. 5. The DNA content of tumor cells was about twice and the PNA content about fivefold the value obtained on non-tumorous exudate cells, which were: PNA = 0.44 × 10 −6 μg P per cell DNA = 0.77 × 10 −6 μg P per cell PNA/DNA = 0.59 6. 6. U.V. examination at 257 mμ showed a rather uniform and high absorption in ascites tumor cells, while solid Ehrlich carcinoma cells had highly varying absorption.

Changes in EEG, blood levels, mood scales and performance scores during long term treatment with diazepam, phenobarbital or placebo in patients

1. The patient population consisting of fifteen patients was divided into three groups, namely: diazepam group, phenobarbital group and placebo group. After three weeks the medicated groups were switched to placebo for a week and the placebo group was given phenobarbital. 2. The parameters to be assessed once a week comprised frequency-analyzed EEG recordings, performance in two attention tests and subjectively estimated mood modalities. 3. The EEG analysis suggested that EEG patterns: a) were drug-dependent, with a differential distribution for each drug of the four frequency bands analyzed; b) showed no change during the three-week treatment period; c) changed on cessation of medication or on switch from placebo to active medication; d) were task-dependent and changed in a systematic way with the level of activation (stress, vigilance or relaxation). 4. The results would allow a better understanding of the clinical course, the choice of therapeutic measures and of the underlying mechanisms of action.

Activation levels, EEG, and behavioural responses

Fifteen male alcoholic patients, who were divided into 3 different groups and treated for 3 weeks with placebo, phenobarbital or diazepam, were examined once a week in 3 different states of activation, varying from relaxation to moderate and high demand attention. Frequency-analyzed EEG recording, pulse rate, drug plasma levels, mood and performance were evaluated. The aim of this paper was to find an explanation in the EEG for responding correctly or in a non-adequate way to stimuli. Based on the activation theory of vigilant behaviour, the EEG recordings of the first examination were analyzed before, during and after the presentation of specific stimuli and related to 4 types of responses (hit, miss, false response, correct rejection) to ascertain whether prestimulus patterns were connected with different types of behavioural poststimulus responses. The EEG patterns were found to be dependent on the type of drug administered as well as on the complexity of the task performed. In all 3 treatment groups, low EEG changes before stimulus onset seemed to be the necessary condition for adequate behavioural responses. A high variability between time-points seemed to indicate a subvigilant state which led to non-adequate responses and possibly to internally induced stimuli in the vigilance test to overcome this state. In the stress phase, however, the missed responses were possibly due to selective attention to the simultaneously appearing non-relevant stimuli. The conclusion must be drawn that, at least in alcoholic patients in the acute withdrawal phase, the EEG prior to and during the stimulus presentation plays a decisive role in determining the type of emerging behavioural response: the differential high variability of the EEG is response-specific, whereas the actual power values depend on the medication given and the task performed.