Effects Of Acute Intoxication Research Articles

Acute effects of ethanol on mineral metabolism and trabecular bone in Sprague-Dawley rats.

In order to assess the effects of acute ethanol intoxication on bone, 45 female Sprague-Dawley rats were studied. Five rats were sacrificed at baseline. The remainder received either ethanol (2 g/kg of body weight) intraperitoneally or isotonic saline. Rats were sacrificed in groups of 10 (5 intoxicated and 5 placebo) at 1, 4, 8, and 24 hours after injection. At the time of sacrifice, a blood sample was obtained and the 4th vertebra was excised for histomorphometric analysis of undecalcified bone. Effect of ethanol was assessed by an analysis of variance test using a Scheffé procedure. In ethanol-treated rats we observed (mean +/- SD, ethanol versus controls, maximum difference point, P value) a significant decrease in osteiod surface with osteoblasts (42.86 +/- 15.61% versus 64.57 +/- 6.24%, P < 0.05); osteoclast number (0.05 +/- 0.02 n/mm2 versus 0.17 +/- 0.09 n/nm2, P < 0.05), and osteocalcin (36.9 +/- 2.21 ng/ml versus 45.8 +/- 5.1 ng/ml, P < 0.05). Osteoclast surface was initially reduced (0.129 +/- 0.09% versus 0.425 +/- 0. 26%, P < 0.01) but showed a subsequent increase (0.765 +/- 0.24% versus 0.226 +/- 0.17%, P < 0.01) attributable to alcohol. There was also a significant decrease in serum Ca (8.51 +/- 0.23 mg/dl versus 9.10 +/- 0.29 mg/dl, P < 0.01) and parathyroid hormone values (23.51 +/- 5.72 pg/ml versus 76.39 +/- 11.66 pg/ml, P < 0.001). We conclude that acute alcohol intoxication in rats induces early striking changes in bone histology and analytical parameters, not completely reversed after 24 hours. These data are consistent with a toxic effect induced by alcohol on bone.

Ontogenetic differences in the expression of olfactory-conditioned aversions resulting from a state of acute alcohol intoxication in the rat

Three experiments examined the effects of acute alcohol intoxication on olfactory conditioning in infant (16 days old) and adult rats (60–65 days old). In both age groups, alcohol administration (2 g.kg, IG) prior to conditioning procedures failed to affect subsequent expression of methyl-conditioned aversions in a two-way odor locational test. Nevertheless, whenever this same alcohol dose was administered prior to testing procedures, the expression of the olfactory conditioning was substantially impaired in infants but unaffected in adults. The factorial design allowed rejection of the possibility that ontogenetic differences in alcohol-induced state-dependent retention might explain this developmental difference (Experiment 1). A subsequent experiment (Exp. 2a) revealed major age-related differences in terms of peak blood alcohol levels (BALs) that resulted from the 2 g/kg alcohol dose previously employed. As revealed by gas chromatography, infants exhibited significantly higher BALs than adults at time of conditioning and/or testing. Therefore, in Experiment 2b, the alcohol dose administered in adults was increased until BALs were comparable to those attained in infants given 2 g/kg. This was accomplished with a 2.5 g/kg alcohol dose, employed in Experiment 2c to evaluate responsiveness of adults in conditioning circumstances identical to those of Experiment 1. Yet even with this dose the adults' expression of the conditioned olfactory aversion was unaffected by the alcohol at the time of testing. Experiment 3 analyzed the effects of alcohol intoxication on infantile and adult motor responses elicited by methyl and a novel odor (lemon), which might conceivably have affected performance in the two-way odor locational tests used to assess olfactory conditioning. The results failed to support possibility that the previously observed ontogenetic differences in the expression of olfactory-conditioned aversions were due to alcohol's effect on sensorimotor responsiveness. In accordance with prior studies, the present results seem to indicate age-related sensitivity to alcohol's effects on cognitive processes.

Alterations in CNS Gene Expression in a Rodent Model of Moderate Traumatic Brain Injury Complicated by Acute Alcohol Intoxication

The combined effects of acute alcoholic intoxication and moderate traumatic brain injury (TBI) on zif/268, glial fibrillary acidic protein (GFAP), and preproenkephalin (PPE) mRNA expression were examined. Adult male Wistar rats received ip injections of a 5% alcohol solution (2.4 g/kg in a final volume of 20 ml isotonic saline) 10 min prior to fixed-head, mechanical injury. Using Northern analysis, a transient three- to fourfold induction of zif/268 mRNA levels was observed 45 min after injury in both TBI and alcohol-treated rats. This induction occurred in regions close to the impact site, namely, the olfactory bulb (OB) and frontal cortex (FTCTX) but not in the more distal piriform/amygdala cortex (P/A). No PPE mRNA changes were observed at 45 min for any experimental group. By 6 h, zif/268 transcript levels returned to or fell below basal levels in the OB and FTCTX while GFAP mRNA levels began to increase in TBI rats. At 24 h, GFAP mRNA levels were greatly increased in all three brain regions of TBI rats. However, alcohol inhibited the temporal induction of GFAP mRNA in the FTCTX and P/A triggered by TBI at 6 and 24 h. These results suggest that although acute alcohol intoxication prior to TBI does not influence gene expression patterns immediately after injury, it may minimize the transcriptional activation of astrocytes particularly in more distant brain regions that were influenced by the impact in nonintoxicated rats.

Effects of Ethanol on Ion Channels

Ion channels play critical roles in nervous system function, from initiating rapid synaptic activity to propagation of action potentials. Studies have indicated that many of the effects of ethanol on the nervous system are likely caused by the actions of ethanol on ion channels. Ion channels are multimeric structures that gate ions through subtle changes in tertiary structure. Ethanol readily enters molecular sites within multimeric ion channels, modifying intermolecular forces and bonds that are important for the open-close-inactivation kinetic properties of channels. The diversity of channel composition caused by the multimeric structure results in subtypes of channels that have a spectrum of sensitivity to ethanol that translates into brain regional differences in ethanol sensitivity, in part caused by differences in ion channel subunit composition. Ethanol has been shown to affect both receptor-activated ion channels and voltage-gated ion channels. The acute intoxicating and incoordinating effects of ethanol are probably related to inhibition of subtypes of NMDA-glutamate receptor ion channels and potentiation of certain subtypes of GABAA receptor ion channels. Effects on these channels, as well as glycine, nicotinic cholinergic, serotonergic, and other ion channels, likely contribute to the euphoric, sedative, and other acute actions of ethanol. Changes in ion channel subunit composition, density, and properties probably also contribute to ethanol tolerance, dependence, withdrawal hyperexcitability, and neurotoxicity. A substantial number of studies have implicated glutamate NMDA receptor, GABAA, and L-type voltage-gated calcium channels in the adaptive changes in the brain during chronic ethanol exposure. The diversity of ion channels subunits, their prominent role in brain function, and ethanol action are likely to make them important contributors to alcoholism and alcohol abuse.

Effect of acute alcohol intoxication on the opioid system in humans

We investigated the possible relation between the endogenous opioid system and acute alcoholic intoxication in 21 subjects, of whom 13 were drinkers who came to the emergency service with evident symptoms of drunkenness, and 8 were nondrinkers who consumed 1 g alcohol per kg body weight over a short period. Different patterns of changes were found in the two groups for plasma concentrations of β-endorphin and adrenocorticotropic hormone. In drinkers, plasma levels of both substances increased, whereas in nondrinkers both concentrations decreased, the declines being especially notable 15, 30, and 45 min after ingestion. We found no differences between the two groups in plasma cortisol concentrations. The different levels of these substances may reflect differences in drinking behavior between the two groups.

Alcohol and head injury: an issue revisited.

The pathophysiologic changes associated with acute and chronic alcohol exposure in the setting of traumatic brain injury are complex. Experimental data indicate that ethanol intoxication can exacerbate brain injury through several mechanisms including hemodynamic and respiratory depression, blood-brain barrier disruption, and derangements in hemostasis. Alcohol, however, is also a potent inhibitor of N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity, and thus is neuroprotective. In contrast to the effects of acute intoxication, chronic alcohol exposure appears to result in upregulation of NMDA receptor activity and downregulation of gamma-aminobutyric acid (GABA) receptor function. This imbalance, it is hypothesized, can result in a surge of excitotoxicity following alcohol withdrawal. Trauma-related excitotoxic cell damage may be significantly potentiated by this alcohol-induced receptor imbalance that is unmasked as withdrawal occurs. Clinical and epidemiologic investigations of alcohol and outcome after head injury have not consistently demonstrated a measurable effect from either acute or chronic alcohol use. Multiple factors including the timing of intoxication in relation to time of injury, the degree and chronicity of intoxication, as well as the influence of other secondary injury processes appear to determine the net effect of alcohol in a given individual. Further clinical and experimental investigations aimed at defining the impact of alcohol use on outcome after head injury are warranted.

Effects of acute ethanol intoxication on experimental brain injury in the rat: neurobehavioral and phosphorus-31 nuclear magnetic resonance spectroscopy studies

Using the lateral fluid-percussion model of experimental brain injury in the rat, the authors investigated the effect of acute ethanol (EtOH) intoxication on cardiovascular changes, neurological motor deficits, brain bioenergetics, and mortality associated with traumatic brain injury. Two hours after gastric administration of EtOH (low dose in 20 animals, 1.5 g/kg; high dose in 28, 3.0 g/kg) or saline (equal volume), animals were subjected to a fluid-percussion brain injury centered over the left parietal cortex. These injuries were of either moderate (X = 2.2 atm; 10 animals/treatment) or high severity (X = 3.0 atm; 18 animals/saline, 10 animals/low-dose EtOH, and 18 animals/high-dose EtOH). Neurological motor function was evaluated daily over a 1-week period, while a subset of eight animals receiving high-dose EtOH and subjected to brain injury of high severity were monitored for 4 hours using phosphorus-31 nuclear magnetic resonance spectroscopy to determine intracellular pH, free magnesium, and brain cytosolic phosphorylation potential. A significant (p < 0.05) and prolonged (up to 1 hour) hypotension was observed in animals pretreated with either low- or high-dose EtOH. Neither low-dose (blood-EtOH concentration = 110 +/- 40 mg/dl) nor high-dose (blood-EtOH = 340 +/- 70 mg/dl) EtOH had any effect on survival or neurological motor function after moderate brain injury. Following severe brain injury, animals pretreated with high-dose (blood-EtOH concentration = 352 +/- 65 mg/dl) EtOH showed a significantly increased mortality and markedly worsened neurological deficits at 24 hours postinjury. Following injury, free magnesium and cytosolic phosphorylation potential declined in both groups by approximately 50% to 60%, with no significant differences between groups with respect to these variables. In contrast, brain intracellular pH in the EtOH-treated animals was consistently higher than in the control group after injury. These data suggest that prior exposure to EtOH, particularly at high concentrations, may have detrimental effects on neurobehavioral function and survival in the acute period (up to 24 hours) after severe brain injury, and may be associated with posttraumatic cerebral alkalosis.

Effect of Acute Ethanol Ingestion on Orthostatic Vital Signs

Study objective: To determine the effect of acute ethanol intoxication on the results of orthostatic tilt testing. Design: Prospective, randomized crossover study. Subjects received ethanol (1.1 gm/kg) or an equal volume of water added to nonalcoholic beer. Orthostatic vital signs, ethanol concentration, and relative volume status were checked initially and hourly for 8 hours. Participants: Twenty healthy human volunteers, 10 men, and 10 women. Results: Peak ethanol concentration was 116±18 mg/dL (mean± SD) 1 hour after ingestion. ANOVA for repeated measures revealed a significant difference in orthostatic pulse changeand relative volume deficit between the ethanol and placebo groups ( P<.05). Post hoc testing revealed significant differences between the two groups at two, five, seven and eight hours post ingestion for pulse change, and two to eight hours for volume status (Bonferroni's corrected t test, P<.0055). At 2 and 5 to 8 hours, there were significantly more positive tilt tests (±30 beat/minute increase) in the ethanol group than in the placebo group ( P<.05). Starting at 2 hours, the ethanol group had a statistically significant relative fluid deficit averaging .5 L by 3 hours. There was no difference in postural blood pressure changes between the two groups. Conclusion: In healthy volunteers, ethanol intoxication resulted in exaggerated postural pulse changes and in a greater proportion of positive orthostatic tilt test results than in a placebo group. These changes were accompanied by significant relative fluid deficits. [Tomaszewski C, Cline DM, Whitley TW, Grant T: Effect of acute ethanol ingestion on orthostatic vital signs. Ann Emerg Med May 1995;25:636-641.]

Staurosporine, a Protein Kinase Inhibitor, Increases the Intoxicating Potencies of Ethanol and Other n‐Alkanols in Rana pipiens Tadpoles

Central nervous system protein kinases are the intracellular effectors for many of the signal transduction pathways essential to neurotransmission. Although the in vitro activity of at least one of these important enzymes, protein kinase C, is diminished by therapeutic concentrations of ethanol and other central depressants, the relationship of this effect to intoxication in vivo is not known. If intoxication by ethanol involves central protein kinase inhibition, then other inhibitors of these enzymes should enhance ethanol's intoxicating potency. To test this hypothesis, we compared the median effective concentrations of ethanol and two other n-alkanols for loss-of-righting reflex in Rana pipiens tadpoles pretreated with staurosporine and in untreated controls. Alkanol concentrations were confirmed by gas chromatography and staurosporine concentrations by ultraviolet absorbance spectrophotometry. Results obtained with 650 animals demonstrate that pretreatment with staurosporine concentrations in the nanomolar range significantly decrease the median effective concentration for ethanol (56% of control; p < 0.001), butanol (38% of control; p < 0.001), and octanol (59% of control; p < 0.001). This finding supports that central protein kinase inhibition may be involved in the acute intoxicating effects of ethanol and other n-alkanols.

Development of a Rabbit Model to Investigate the Effects of Acute Nitrogen Dioxide Intoxication

1. In previous studies a rat inhalation model was developed to investigate the effects of intervention after acute NO2 exposure. The object of the present study was to investigate whether acute NO2 intoxication induced comparable effects in rabbits as it does in rats. Where the effects of intervention in both species are similar, then the conclusions drawn from these studies may have more relevance for the treatment of man. 2. Biochemical variables in bronchoalveolar lavage and supernatant from lung homogenate, which may be relevant for the evaluation of lung injury and repair, were investigated and compared with histology. 3. After NO2 exposure for 10 min, the pulmonary effects observed became more pronounced with increasing NO2 concentrations (0, 125, 175, 250, 400, 600 or 800 ppm) [1 ppm NO2 is 1.88 mg m-3]. The effects in rabbits were found to be broadly comparable with those in rats. 4. To achieve severe lung injury in rabbits without mortality, enabling investigations of the effects of intervention over several days, exposure to a NO2 concentration of 600 ppm for 10 min was most appropriate, while a concentration of 175 ppm NO2 was needed to attain comparable effects in rats. 5. The repair phase starts later, namely at 3 days after exposure in rats, compared to 5 days in rabbits.

Effect of acute ethanol intoxication on glucoregulation during prolonged insulin-induced hypoglycemia.

This study examined the interaction of acute ethanol administration on glucose homeostasis during insulin-induced hypoglycemia (IIH). Glucose kinetics and net hepatic balances of alanine, glycerol, and lactate were estimated in three groups of dogs: group I underwent 3 h of IIH; group II received a continuous ethanol infusion in addition to IIH; group III received ethanol for 3 h. In group I, IIH resulted in a sustained twofold increase in glucose rate of appearance (Ra) and net hepatic uptake (NHU) of glycerol and lactate but no change in NHU of alanine. In group II, glucose Ra rose transiently, NHU of alanine and glycerol increased two- and fivefold, respectively, whereas NHU of lactate dropped 60%. In group III, no alterations in plasma glucose levels, glucose Ra, and NHU of alanine and glycerol were observed, but NHU of lactate switched to a net output. These results demonstrate that ethanol alone or with IIH exclusively inhibited NHU of lactate, and this was responsible, in a stoichiometric fashion, for the failure of the delayed increase in glucose Ra during IIH.

SYNAPTIC MEMBRANE RESPONSES TO ACUTE AND CHRONIC ALCOHOL INTOXICATION IN HIGH ALCOHOL SENSITIVE (HAS) AND LOW ALCOHOL SENSITIVE (LAS) SELECTIVELY BRED RATS

HAS (high alcohol sensitive) and LAS (low alcohol sensitive) lines of rats have been selectively bred based on their differences in ethanol-induced sleep time. In the present study, the two lines were compared to examine another central effect of acute alcohol intoxication: namely, hypothermia. As the disturbances in membrane microorganization have been associated with the nervous system's sensitivity and tolerance to ethanol, the synaptic plasma membrane fluidity and acute sensitivity to ethanol were also evaluated by fluorescence polarization of DPH probes in the HAS and LAS rats. The two lines did not differ in the magnitude of their hypothermic response after acute injection of ethanol (3 g/kg body wt, i.p.). Although membranes in the HAS line were slightly more rigid than in the LAS line, the level of membrane disordering after acute ethanol addition was identical for the two lines in the region examined with the DPH probe. Following the chronic intoxication of the rats, the two lines developed tolerance to the hypnotic and hypothermic effects of ethanol. In the same way, a membrane resistance (i.e. tolerance) to the disordering effect of acute ethanol addition developed in the region probed with DPH. In general, the LAS line showed a more pronounced level of tolerance than the HAS line at both the functional and membrane level. These results suggest that different measures used to assess the depressant action of ethanol, such as sleep time, hypothermia or membrane disordering, may not be related and could indicate different genetic origins.(ABSTRACT TRUNCATED AT 250 WORDS)

MK-801 prevents cyanide-induced changes of Fos levels in rat brain.

The effect of acute cyanide intoxication on levels of transcriptional regulatory proteins Fos and c-Jun in rat cortex, hippocampus, cerebellum and brain stem was studied. Western blot analysis showed a differential effect of cyanide on Fos levels in the selected brain areas. The most prominent changes were seen 60 min. following ip. injection of KCN in all brain areas except the brain stem, which showed the maximal change 120 min. following cyanide. Fos levels were doubled in cortex and cerebellum and decreased to below 70% of the control levels in hippocampus. Levels of c-Jun were not altered 60 min. following cyanide treatment. Pretreatment with the NMDA receptor antagonist, MK-801, prevented the cyanide-induced changes of Fos. The differential effect of cyanide on Fos levels in different brain areas and the blockade of these changes by MK-801 suggest involvement of multiple neuronal pathways, including the excitatory amino acid (EAA) neurotransmitter system. It is concluded that cyanide alters levels of the transcriptional regulatory protein Fos through activation of the EAA neurotransmitter system and, thus, may affect gene expression in neuronal or glia cells.

Effects of acute ethanol intoxication during pregnancy on central dopaminergic system in male rats

Pregnant albino rats received 2 IP injections, spaced by 4 h, of either ethanol (2.9 g/kg in 24% v/v saline solution) or saline, on gestational day (GD) 8. During adulthood, male rats prenatally exposed to alcohol exhibited an increased stereotyped behavioral response to 12 mg/kg of amphetamine (AMPH) or 1 mg/kg of apomorphine (APO), whereas the stereotypy induced by 6 mg/kg of AMPH showed no difference between control and experimental animals. Also, the hypoactivity response elicited by small doses of APO was not significantly affected by the prenatal treatment with alcohol. Analysis of dopaminergic function in the striatum and nucleus accumbens demonstrated no change on dopamine (DA) levels in both structures in alcohol pre-exposed 55- and 180-day-old rats. A reduction in striatum 3–4 dihydroxyphenylacetic acid levels was observed at both ages. These results indicate that an acute intoxication with alcohol on GD 8 induces a long-lasting decrease in striatal but not in nucleus accumbens DA metabolism. As a consequence, a lower striatal DA release might produce a compensatory supersensivity of postsynaptic DA sites. This interpretation is consistent and correlates with behavioral results.

Gill morphology and ATPase activity in the goldfishcarassius carassiusvar.auratusexposed to experimental lead intoxication

Abstract The effect of acute lead intoxication (5 mg 1‐1) on the structure and function of the gills in Carassius carassius var. auratus was studied. The gills absorbed Pb very quickly and the storage increased progressively in the longest treated specimens. Light and electron microscopy observations on gill filaments from unexposed fish showed an organization similar to that described for other teleosteans. Gill histological and cytological alterations induced by lead were detected after 24 h of treatment and became more evident after 48 h. The salient changes were the following: 1) free parts of secondary lamellae increased in length and had irregular outlines; 2) an increased number of mucocytes, prevalently distributed over the superficial layer of the primary epithelium; 3) chloride and epithelial cell ultrastructure were particularly damaged; the degenerating chloride cells were more numerous; 4) K+‐NPPase activity was not particularly affected; on the contrary, Ca2+‐ATPase increased particularly in...

The Effect of Acute Alcohol Intoxication and Chronic Alcohol Abuse on Outcome From Trauma

To determine the effect of acute alcohol intoxication and chronic alcohol abuse on morbidity and mortality from trauma. Prospective cohort study. Blunt or penetrating trauma patients at least 18 years of age admitted to one trauma center or dying at the injury scene. Mortality, complications (infection, pneumonia, respiratory failure, or multiple organ failure), and length of hospital stay. Acute intoxication had no effect on risk of dying--at the injury scene, within the first 24 hours of hospitalization, after the first 24 hours, or overall. Acute intoxication also did not increase the risk of complications and was associated with shorter lengths of stay. Patients with both biochemical and behavioral evidence of chronic alcohol abuse had a twofold increased risk of complications, particularly pneumonia and any infection, compared with those with no evidence of chronic alcohol abuse. Chronic, but not acute, alcohol abuse adversely affects outcome from trauma. Attention to the problem of chronic alcohol abuse in trauma patients is necessary, and screening trauma patients for chronic alcohol abuse appears to be warranted.

The effect of acute alcohol intoxication and chronic alcohol abuse on outcome from trauma

The effect of acute alcohol intoxication and chronic alcohol abuse on outcome from trauma

Effect of acute versus chronic intoxication on clinical features of theophylline poisoning in children: Shannon M, Lovejoy FH Jr J Pediatr 121:125–130 July 1992

Effect of acute versus chronic intoxication on clinical features of theophylline poisoning in children: Shannon M, Lovejoy FH Jr J Pediatr 121:125–130 July 1992

Effects of acute alcohol intoxication on gluconeogenesis and its hormonal responsiveness in isolated, perfused rat liver

Rats were acutely administered ethanol as a primed constant infusion in order to produce sustained blood ethanol levels of 8–12 or 55–65 mM. At the end of ethanol infusion the livers were either freeze-clamped in vivo or isolated and perfused for metabolic studies. The rate ofgluconeogenesis and its responsiveness to phenylephrine (10μM), prostaglandin F 2α (5μM) and glucagon (10 nM), as well as the redox state of the cytosolic NAD +-NADH system were assessed in livers isolated from acutely ethanol-treated rats, and subsequently perfused without ethanol. For liver clamped in vivo, high- but not low-ethanol treatment decreased the ATP content by 31% and slightly increased ADP and AMP content, resulting in a decreased energy charge (11%). Glutamate and aspartate content was also increased in high-dose ethanol-infused rats with no changes in malate and 2-oxoglutarate content. Gluconeogenesis with saturating concentrations of lactate (4 mM) + pyruvate (0.4 mM) was delayed in reaching a plateau in the livers of high-dose ethanol-treated rats and its response to all three stimulators was impaired. Low-dose ethanol treatment only decreased the liver response to phenylephrine. While the perfused livers of low-dose ethanol-treated rats displayed no changes in adenine nucleotide content, the livers of high-dose ethanol-treated rats had a decreased ATP (35%) and an increased AMP (77%) content, paralleled by a fall in the total adenine nucleotides (14%) and energy charge (14%). No differences were observed between the saline- and ethanol-treated rats with respect to malate-aspartate shuttle intermediate concentration in perfused livers. Also, the livers of high-, but not low-dose ethanol-treated rats had a more negative value of NAD +-NADH redox state as compared to the livers of control rats. The data suggest that acute ethanol intoxication produces changes in liver metabolism and its responsiveness to hormones/agonists that are demonstrable for at least 2 hr after isolation and perfusion of the liver.

The acute phase response of rats to soman intoxication

The capacity of an organophosphate to elicit phase response (APR) was assessed by studying the effects of acute soman intoxication on two major processes which characterize inflammation, cytokine production in macrophages and the expression of acute phase protein (APP) genes in the liver. It was established that the concentration of lymphostimulatory substances secreted by the macrophages of soman-intoxicated rats was increased to a level characteristic of the primary inflammatory reaction. Macrophage activation was followed by increased transcription rates of APP genes and the corresponding mRNA and protein synthesis in the liver. The pattern of the DNA-protein complexes obtained with nuclear extracts and the cis-element of the rat haptoglobin gene in the gel-retardation assay suggested that the molecular events which underlie the expression of APP genes of intoxicated rats are similar to those that occur during the APR. From these findings we concluded that soman intoxication was a metabolic injury which elicited the typical APR.