Midazolam protects B35 neuroblastoma cells through Akt-phosphorylation in reactive oxygen species derived cellular injury / 대한마취과학회지

BACKGROUND: Soman, a potent irreversible acetylcholinesterase (AChE) inhibitor, induces delayed neuronal injury by reactive oxygen species (ROS). Midazolam is used in patients with pathologic effects of oxidative stresses such as infection, hemodynamic instability and hypoxia. We investigated whether midazolam protects the Central Nervous System (CNS) from soman intoxication. The present study was performed to determine whether midazolam protects B35 cells from ROS stress for the purpose of exploring an application of midazolam to soman intoxication. METHODS: Glucose oxidase (GOX) induced ROS stress was used in a B35 neuroblastoma cell model of ROS induced neuronal injury. To investigate the effect of midazolam on cell viability, LDH assays and fluorescence activated cell sorting (FACS) analysis was performed. Western blotting was used for evaluating whether Akt-phosphorylation is involved in cell-protective effects of midazolam. RESULTS: GOX derived ROS injury decreased cell viability about 1.6-2 times compared to control; midazolam treatment (5 and 10 microg/ml) dose-dependently increased cell viability during ROS injury. On western blots, Akt-phosphorylation was induced during pretreatment with midazolam; it was diminished during co-treatment with LY-294002, an inhibitor of Akt-phosphorylation. FACS analysis confirmed that the cell protective effect of midazolam is mediated by an anti-apoptotic effect. GOX-induced apoptosis was inhibited by midazolam and the finding was diminished by LY-294002. CONCLUSIONS: Midazolam protects neuronal cells from GOX-induced ROS injury; this effect is mediated by an anti-apoptotic effect through Akt-phosphorylation. This shows that midazolam may be useful in soman intoxication.

Inhibitory effect of soman on stress induced hyperthermia in rats and the influence of central and peripheral cholinergic antagonists / 中国应用生理学杂志

<p><b>AIM</b>To determine the effect of soman on stress induced hyperthermia and the influence of central and peripheral cholinergic antagonists.</p><p><b>METHODS</b>Effects of subcutaneous injection of soman, scopolamine, methylscopolamine and pyridostigmine on stress-induced hyperthermia were observed in rats by radio telemetry in an open-field environment. Plasma cholinesterase (ChE) activity was measured by a spectrophotometry.</p><p><b>RESULTS</b>(1) Core temperature of the control group increased by 0.96 degrees C when exposed to open-field, whereas core temperature only increased by 0.55 degrees C in soman treated animals. Scopolamine, a central cholinergic antagonist, nearly abolished inhibitory effects of soman on core temperature when exposed to open-field. Methylscopolamine, a peripheral cholinergic antagonist, coadministered with soman reduced significantly the hyperthermic response to open-field exposure compared with rats dosed with soman. (2) Pyridostigmine, a peripheral anti-ChE agent that caused a 52% decrease in plasma ChE activity led to a significant enhancement of the hyperthermic response to open-field exposure. Methyl scopolamine nearly abolished the effects of pyridostigmine on stress-induced hyperthermia response.</p><p><b>CONCLUSION</b>Inhibitory effect of soman on the open field hyperthermia suggested that soman treatment hampered the ability of the rat to develop a normal hyperthermic response when placed in the open-field environment. Its inhibitory effects were mediated primarily through a central muscarinic pathway. In addition, peripheral cholinergic nerve was involved in the control of stress hyperthermic response.</p>

Comparative efficacy of exogenous acetylcholinesterase administration on soman and dichlorvos toxicity in rats.

Cholinesterase (ChE) activity in the blood serum of rats was elevated to 15, 25, and 45 times by the sc administration of 1000, 2000 and 3000 electric eel acetylcholinesterase (AChE) units respectively. Apparently no ill-effect to animals was observed. The maximal activity of the enzyme occurred in 90 min after its administration and was directly proportional to the administered dose. The increase activity of ChE in the serum on the exogenous administration of AChE persisted for 18 hr. The exogenously raised serum ChE, protected rats against lethal dose of dichlorvos, but not against lethal dose of soman. The possible mechanism of differential response in discussed.

Effect of soman administration on beta-esterases in blood, liver microsomes and brain regions of rats.

Activities of enzymes cholinesterase (ChE) and carboxylesterase (CaE) were assayed in serum, liver microsomes and three regions of brain, viz; cerebrum, cerebellum and brain stem (with mid brain) in male albino rats at 0.5 and 2 h periods after administration of 1/2 LD 50 dose of soman (0.22 mg/kg) intraperitoneally in olive oil as vehicle. At 0.5 h, in serum, ChE activity declined to 33% of its initial level whereas CaE activity was almost completely inhibited. However, in the liver microsomes at this period, ChE activity was greatly inhibited (18% of initial level) whereas CaE activity was nearly unaffected. At 2 h period, both the enzymes in the serum were almost completely inhibited. In the brain regions (excepting in cerebellum), both the enzymes were nearly similarly inhibited (by 55% to 65% of the initial level) at both the periods. The time related differential response of these two beta-esterases in acute soman intoxication probably occurred in the peripheral tissues like blood and liver but not in the CNS.

Intracranial Lipoma

Intracranial lipoma is a rare condition, though lipoma in other sites can be found throughout the body. Many authors have reported intracranial lipoma since Rokitansky and Soman who described first in autopsy and living patient respectively. Intracranial lipoma can be diagnosed simply be simple skull and computed tomography. The authors experienced three cases of intracranial lipoma diagnosed by simple skull, tomography, cerebral angiography and computed tomography, and reported with a brief review of the literature.