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We report a case of bispectral index (BIS) falling to zero during absolute alcohol embolization of an intracranial arteriovenous malformation (AVM) under anesthesia. This case highlights the unusual effect of a therapeutic dose of parenteral alcohol on the central nervous system using BIS monitoring.A 29-yr-old male with a left parieto-occipital arteriovenous malformation underwent neuroendovascular embolization under general anesthesia. During injection of absolute alcohol injection into the AVM nidus, the patient developed hypertension and tachycardia coincident with a profound and sustained reduction of BIS values to zero, despite a stable level of anesthesia. Immediate angiography revealed no evidence of hemorrhage or new changes in the patient's cerebral vasculature. Post-procedure, the patient remained drowsy for several hours with signs of alcohol intoxication. He had full neurological recovery.In the presence of normal cerebral angiographic findings, suppression of BIS values may serve as an early indicator of CNS responses to intracranial injection of absolute alcohol for embolization of an arteriovenous malformation.

The effects of a mega dose of ascorbic acid (AA) on alcohol induced peroxidative damages were investigated in guinea pigs. In the present study, four groups of male guinea pigs were maintained for 30 days as follows. (1) Control group (1 mg AA/100 g body wt); (2) Ethanol group (1 mg AA/100 g body wt. + 9 g ethanol/kg body wt); (3) AA group (25 mg AA/100 g body wt); (4) AA + ethanol group (25 mg AA/100 g body wt. + 9 g ethanol/kg). Results revealed that alcohol induced significant lipid peroxidation, since the lipid peroxidation products malondialdehyde (MDA), hydroperoxides and conjugated dienes were elevated. The activities of scavenging enzymes superoxide dismutase (SOD), catalase were reduced. However, supplementation of AA along with alcohol reduced the lipid peroxidation products in the liver and enhanced the activities of scavenging enzymes. Activities of glutathione peroxidase and reductase were also greater in guinea pigs given alcohol + AA in comparison with those given alcohol alone. Administration of ascorbic acid also reduced the activity of gamma-glutamyl transpeptidase (GGT), the marker enzyme of alcohol induced toxicity. The vitamin E level, which was reduced by alcohol intake, was raised by the co-administration of AA and alcohol. These studies suggest that a mega dose of AA helps in the prevention of alcohol induced oxidative stress by enhancing the antioxidant capacity and also by reducing the lipid peroxidation products.

Ethanol affects many functions of the brain and peripheral organs. Here we show that ethanol opens G-protein-activated, inwardly rectifying K + (GIRK) channels, which has important implications for inhibitory regulation of neuronal excitability and heart rate. At pharmacologically relevant concentrations, ethanol activated both brain-type GIRK1/2 and cardiac-type GIRK1/4 channels without interaction with G proteins or second messengers. Moreover, weaver mutant mice, which have a missense mutation in the GIRK2 channel, showed a loss of ethanol-induced analgesia. These results suggest that the GIRK channels in the brain and heart are important target sites for ethanol.

SummaryMechanism of central actions of antidepressants were studied in experimental animals.Tests were made on general behavior, anticonvulsant activity in maximal electroshock seizure, antireserpinic action, antagonistic action to methamphetamine‐excitation, anesthesia induced by hexobarbital, hypertension due to noradrenalin, hypotension induced by acetylcholine, anti‐tremorine action and antagonism for physostigmine in unanesthetized mice and rabbits. In these tests, it seemed that the mechanism of antidepressants is related to the changes of biogenic amines in the brain and to the central autonomic functions. Namely, imipramine, amitriptyline and nialamide were related intimately to the changes of biogenic amine and to the inhibitory effects of parasympathetic functions. Diazepam was connected with the tranquilizing effects and the inhibitory effects of parasympathetic functions, and dimethylaminoethanol had no relation to the autonomic functions.

It is the first and important practice for the study of the psychotropic drugs to observe the spontaneous movement of animals. Although many methods have been known for measuring the spontaneous movements, most of them are to find the change of motor activity of a single animal. Many investigators reported the automatic measurement of the motor activity. Photoelectric method was first used by Siegel et al. (1), which was improved by Dews et al. (2) in mice. Takagi et al. (3) traced the spontaneous movement of a mouse using a modified photoelectric apparatus. The central nervous system stimulant effect of 2-dimethylaminoethanol (DMAE) was first reported by Pfeiffer et al. (4) and had been confirmed by Konigsmark et al. (5), Himwich (6) and Brown and Gangloff (7). It was also confirmed by clinical trials. Pfeiffer et al. (8) proposed the hypothesis that DMAE played the role of a precursor of acetylcholine in the central nervous system. Groth et al. (9) found that DMAE was incorporated in the mouse brain more rapidly than choline and probably converted to brain choline. However, Pepeu et al. (10) and Kiplinger et al. (11) had different views from that of Pfeiffer. In this paper, we have developed a method of recording the spontaneous activity of grouped mice, in order to take an accurate measurement of a little change of motor activity by drugs. We investigated the effect of DMAE and its acyl esters on the spontaneous movement of the grouped and/or individual mice.

(R)-1-(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-3-methylamino-propan-2-ol ((R)-OHDMI) and (S,S)-1-cyclopentyl-2-(5-fluoro-2-methoxy-phenyl)-1-morpholin-2-yl-ethanol (CFMME) were synthesized and found to be potent inhibitors of norepinephrine reuptake. Each was labelled efficiently in its methyl group with carbon-11 (t(1/2)=20.4 min) as a prospective radioligand for imaging brain norepinephrine transporters (NET) with positron emission tomography (PET). The uptake and distribution of radioactivity in brain following intravenous injection of each radioligand into cynomolgus monkey was examined in vivo with PET. After injection of (R)-[(11)C]OHDMI, the maximal whole brain uptake of radioactivity was very low (1.1% of injected dose; I.D.). For occipital cortex, thalamus, lower brainstem, mesencephalon and cerebellum, radioactivity ratios to striatum at 93 min after radioligand injection were 1.35, 1.35, 1.2, 1.2 and 1.0, respectively. After injection of [(11)C]CFMME, radioactivity readily entered brain (3.5% I.D.). Ratios of radioactivity to cerebellum at 93 min for thalamus, occipital cortex, region of locus coeruleus, mesencephalon and striatum were 1.35, 1.3, 1.3, 1.2 and 1.2, respectively. Radioactive metabolites in plasma were measured by radio-HPLC. (R)-[(11)C]OHDMI represented 75% of plasma radioactivity at 4 min after injection and 6% at 30 min. After injection of [(11)C]CFMME, 84% of the radioactivity in plasma represented parent at 4 min and 20% at 30 min. Since the two new hydroxylated radioligands provide only modest regional differentiation in brain uptake and form potentially troublesome lipophilic radioactive metabolites, they are concluded to be inferior to existing radioligands, such as (S,S)-[(11)C]MeNER, (S,S)-[(18)F]FMeNER-D(2) and (S,S)-[(18)F]FRB-D(4), for the study of brain NETs with PET in vivo.

AbstractOromandibular dystonia is a focal dystonia involving the masticatory and tongue muscles, causing difficulties in speech or mastication. We treated 13 patients with this condition by injecting diluted lidocaine and alcohol intramuscularly. This method is aimed at reducing muscle spindle afferent activity. The symptoms had been resistant to other therapies such as pharmacotherapy or dental treatment. All patients showed clinical improvement after this therapy with reduced EMG activities in the affected muscles, whereas control injection of normal saline gave no changes in EMG activities. The overall subjective improvement was 57.7 ± 25.1% (mean ± standard deviation) in a self‐rating scale. The mean response of the jaw elevator muscles (70 ± 13.1%) was significantly higher (p < 0.02, t test) than that of the depressor muscles (38 ± 28.4%). Despite the precise mechanism being unknown, this difference might be related to the smaller number of muscle spindles in the depressor than the elevator muscles. This therapy is useful for the treatment of drug‐resistant oromandibular dystonia.