EtOH Pretreatment Research Articles

Effects of Etching Time and Ethanol Wet Bonding on Bond Strength and Metalloproteinase Activity in Radicular Dentin.

(1) Background: The objective of this in vitro study was to evaluate the impact of different etching times and ethanol pre-treatments on the immediate bond strength of a hydrophilic multi-mode universal adhesive (Clearfil Universal Bond Quick, Kuraray, UBQ) and on the consequent gelatinolytic activity of metalloproteinases (MMPs) on radicular dentin. (2) Methods: Sixty single-root teeth were selected and divided into four groups according to the adhesive protocol applied for fiber post cementation: (G1) 15 s H3PO4 application + UBQ; (G2) 30 s H3PO4 application + UBQ; (G3) 15 s H3PO4 application + ethanol pre-treatment + UBQ; (G4) 30 s H3PO4 + ethanol pre-treatment + UBQ. After adhesive procedures, fiber posts were luted into the post space with a dual-curing cement (DC Core, Kuraray) and light-cured for 40 s. To perform the push-out test and nanoleakage analyses for both coronal end apical areas, 1 mm slices were prepared, following a 24 h storage period in artificial saliva. Additionally, an in situ zymographic assay was conducted to explore endogenous MMP activity within the radicular layer. Results were statistically analyzed with ANOVA and Tukey post hoc tests. Statistical significance was set at p < 0.05. (3) Result: ANOVA revealed a statistically significant difference in push-out bond strength related to the pre-treatment variable but did not highlight any significance of etching time. Specimens pre-treated with ethanol wet bond application showed higher bond strength (p < 0.01). In situ zymography quantification analyses revealed that all tested groups, independently of etching time end ethanol pre-treatment, activated MMP gelatinolytic activity. A significant increase in MMP activity was detected for the 30 s etching time. However, ETOH pre-treatment significantly reduced MMP activity within the adhesive interface (p < 0.01). (4) Conclusions: The tested adhesive showed similar results regardless of the etching time protocol. The gelatinolytic activity of MMPs was observed in all the groups. Further investigations and extended follow-ups are required to validate the results of the present study in vivo.

Influence of typical pretreatment on cotton stalk conversion activity and bio-oil property during low temperature (180–220 ℃) hydrothermal process

• Pretreatment could enhance cotton stalk (CS) hydrothermal conversion activity. • CS surface microstructure changed by pretreatments benefits hydrothermal bio generation. • The best bio-oil properties and CS conversion activity was realize by NaOH/EtOH pretreatment. • Pretreatment could be used as an important way to regulate the composition of bio-oil. Conversion of agricultural and forestry waste biomass into high value-added bio-oil by mild hydrothermal method is of great significance to reduce the diesel consumption and alleviate the shortage of high-quality fuel oil supply. Most of the current research focuses on the parameter adjustment in the hydrothermal process, including temperature, time, catalyst and cosolvent, but the influence of the structure of raw materials on the hydrothermal conversion activity and the properties of hydrothermal oil is less. In this study, several typical pretreatment methods (including ball milling, alkali + ball milling, urea/NaOH and NaOH + ethanol) were used to change the structural characteristics of agricultural waste cotton stalks (CS), and the treated CS were used for hydrothermal conversion at low temperature (180–220 ℃). Taking the yield of hydrothermal bio-oil as index, the results show that various pretreatment can effectively improve the hydrothermal conversion activity of CS, improve the combustion performance of hydrothermal bio-oil and adjust the composition of hydrothermal oil. The hydrothermal bio-oil obtained by NaOH + EtOH pretreatment has the best properties, the yield is 7.41 % (wt, 220 ℃, 2 h), the calorific value is 24.16 MJ/kg, and the energy recovery is 10.98 %, which is higher than untreated CS bio-oil (with yield of 3.90 wt% at 220 ℃ and 2 h, calorific value is 23.32 MJ/kg and energy recovery of 10.98 %). The research will strengthen the role of lignocellulosic raw material structure in the hydrothermal process, which will play an important role in promoting the industrialization process of hydrothermal technology in the field of biomass, especially considering the optimization of operating parameters of various raw materials in the future industrialization.

The protective effect of platelet released growth factors and bone augmentation (Bio-Oss®) on ethanol impaired osteoblasts

BackgroundChronic alcohol consumption is a known limiting factor for bone healing. One promising strategy to improve bone augmentation techniques with Bio-Oss® in oral and maxillofacial surgery might be the supportive application of platelet-concentrated biomaterials as platelet-released growth factor (PRGF). To address this matter, we performed an in vitro study investigating the protective effects of PRGF and Bio-Oss® in ethanol (EtOH) treated osteoblasts. MethodsThe SAOS-2 osteosarcoma cell line, with and without EtOH pretreatment was used. The cell viability, proliferation and alkali phosphatase activity (ALP) after application of 0%, 5% and 10% PRGF and Bio-Oss® were assessed. ResultsThe application of PRGF and Bio-Oss® in EtOH impaired osteoblasts showed a significant beneficial influence increasing the viability of the osteoblasts in cell culture. The synergistic effect of Bio-Oss® and 5% PRGF on the proliferation of osteoblasts was also demonstrated. Bio-Oss® only in combination with PRGF increases the alkaline phosphatase (ALP) activity in EtOH pretreated cells. ConclusionsThese results indicate that the simultaneous application of PRGF and Bio-Oss® inhibits EtOH induced bone healing impairment. Furthermore, in the cells, PRGF induced a protective mechanism which might promote bone regeneration.

Adolescent but not adult ethanol binge drinking modulates cocaine withdrawal symptoms in mice

BackgroundEthanol (EtOH) binge drinking is an increasingly common behavior among teenagers that induces long-lasting neurobehavioral alterations in adulthood. An early history of EtOH abuse during adolescence is highly correlated with cocaine addiction in adulthood. Abstinence of cocaine abuse can cause psychiatric symptoms, such as anxiety, psychosis, depression, and cognitive impairments. This study assessed the consequences of adolescent exposure to EtOH on the behavioral alterations promoted by cocaine withdrawal in adulthood.MethodsWe pretreated juvenile (34–47 days old) or adult (68–81 days old) mice with EtOH (1.25 g/kg) following a binge-drinking pattern. Then, after a three-week period without drug delivery, they were subjected to a chronic cocaine treatment in adulthood and tested under cocaine withdrawal by the ensuing paradigms: open field, elevated plus maze, prepulse inhibition, tail suspension test, and object recognition. Another set of mice were treated with the same EtOH binge-drinking procedure during adolescence and were tested immediately afterwards under the same behavioral paradigms.ResultsAdolescent EtOH pretreatment undermined the anxiogenic effects observed after cocaine abstinence, reduced prepulse inhibition, and increased immobility scores in the tail suspension test following cocaine withdrawal. Moreover, the memory deficits evoked by these substances when given separately were enhanced in cocaine-withdrawn mice exposed to EtOH during adolescence. EtOH binge drinking during adolescence also induced anxiety, depressive symptoms, and memory impairments when measured immediately afterwards. In contrast, neither EtOH nor cocaine alone or in combination altered any of these behaviors when given in adulthood.ConclusionsEtOH binge drinking induces short- and long-term behavioral alterations and modulates cocaine withdrawal symptoms when given in adolescent mice.

Tolerance to Ethanol or Nicotine Results in Increased Ethanol Self-Administration and Long-Term Depression in the Dorsolateral Striatum.

Ethanol (EtOH) and nicotine are the most widely coabused drugs. Tolerance to EtOH intoxication, including motor impairment, results in greater EtOH consumption and may result in a greater likelihood of addiction. Previous studies suggest that cross-tolerance between EtOH and nicotine may contribute to the abuse potential of these drugs. Here we demonstrate that repeated intermittent administration of either EtOH or nicotine in adult male Sprague Dawley rats results in tolerance to EtOH-induced motor impairment and increased EtOH self-administration. These findings suggest that nicotine and EtOH cross-tolerance results in decreased aversive and enhanced rewarding effects of EtOH. Endocannabinoid signaling in the dorsolateral striatum (DLS) has been implicated in both EtOH tolerance and reward, so we investigated whether nicotine or EtOH pretreatment might modulate endocannabinoid signaling in this region. Using similar EtOH and nicotine pretreatment methods resulted in increased paired-pulse ratios of evoked EPSCs in enkephalin-positive medium spiny neurons in DLS slices. Thus, EtOH and nicotine pretreatment may modulate glutamatergic synapses in the DLS presynaptically. Bath application of the CB1 receptor agonist Win 55,2-212 increased the paired-pulse ratio of evoked EPSCs in control slices, while Win 55,2-212 had no effect on paired-pulse ratio in slices from either EtOH- or nicotine-pretreated rats. Consistent with these effects, nicotine pretreatment occluded LTD induction by high-frequency stimulation of the corticostriatal inputs to the dorsolateral striatum. These results suggest that nicotine and EtOH pretreatment modulates striatal synapses to induce tolerance to the motor-impairing effects of EtOH, which may contribute to nicotine and EtOH coabuse.

Analysis of the pretreatment effect of ethanol on the stratum corneum- and hair follicular-penetration of drugs using the hair follicle-plugging method.

The hair follicle-plugging method was used to analyze the effects of EtOH on skin permeation pathways. In vitro permeation experiments were performed on 4 model drugs [isosorbide mononitrate (ISMN), ionized lidocaine (ionized LC), fluorescein (FL), and fluorescein isothiocyanate (FITC)-dextran 4 kDa (FD-4)] using excised pig ear skin. The skin permeations of ionized LC, FL, and FD-4 were decreased by hair follicle-plugging. Hair follicle-plugging prevented the skin permeation of FL and FD-4 in EtOH-pretreated skin, but did not prevent that of ISMN. On the other hand, the effect of hair follicle-plugging on the permeation of ionized LC was different among the pretreatment conditions. These results indicate that the EtOH pretreatment greatly affected the aqueous pathway in the stratum corneum and hair follicles.

Preinjury alcohol exposure attenuates the neuroinflammatory response to traumatic brain injury

BackgroundTraumatic brain injury (TBI) initiates a neuroinflammatory response that increases the risk of TBI-related mortality. Acute alcohol intoxication at the time of TBI is associated with improved survival. Ethanol is recognized as a systemic immunomodulator that may also impart neuroprotection. The effects of alcohol on TBI-induced neuroinflammation, however, are unknown. We hypothesized that ethanol treatment prior to TBI may provide neuroprotection by diminishing the neuroinflammatory response to injury. Materials and methodsMice underwent gavage with ethanol (EtOH) or water (H2O) prior to TBI. Animals were subjected to blunt TBI or sham injury (Sham). Posttraumatic rapid righting reflex (RRR) and apnea times were assessed. Cerebral and serum samples were analyzed by ELISA for inflammatory cytokine levels. Serum neuron-specific enolase (NSE), a biomarker of injury severity, was also measured. ResultsNeurologic recovery from TBI was more rapid in H2O-treated mice compared with EtOH-treated mice. However, EtOH/TBI mice had a 4-fold increase in RRR time compared with EtOH/Sham, whereas H2O/TBI mice had a 15-fold increase in RRR time compared with H2O/Sham. Ethanol intoxication at the time of TBI significantly increased posttraumatic apnea time. Preinjury EtOH treatment was associated with reduced levels of proinflammatory cytokines IL-6, KC, MCP-1, and MIP-1α post TBI. NSE was significantly increased post injury in the H2O/TBI group compared with H2O/Sham but was not significantly reduced by EtOH pretreatment. ConclusionsAlcohol treatment prior to TBI reduces the local neuroinflammatory response to injury. The decreased neurologic and inflammatory impact of TBI in acutely intoxicated patients may be responsible for improved clinical outcomes.

Effect of Ethanol Pretreatment on Skin Permeation of Drugs

It has been demonstrated that ethanol (EtOH) can enhance skin permeation of drugs when simultaneously applied with drugs. However, only a few studies have reported on the pretreatment effect of EtOH on skin permeations. In this study, the pretreatment effects of EtOH on skin permeation of drugs were investigated by measuring changes in skin permeation and electrical skin resistance. Permeabilities of deuterium oxide (D2O), isosorbide mononitrate (ISMN), isosorbide dinitrate (ISDN), calcein sodium (CA-Na), and fluorescein isothiocyanate-dextran 4 kDa (FD-4, 3.3-4.4 kDa) were evaluated through Yucatan micropig skin pretreated with different concentrations of EtOH solution. From the results, almost constant skin permeabilities of D2O and ISDN were observed independent of EtOH concentration. Skin permeabilities of ISMN, CA, and FD-4 increased with low concentrations of EtOH, but decreased with high concentrations of EtOH. At 99.5% EtOH pretreatment, skin permeabilities of hydrophilic compounds (ISMN, CA, and FD-4) decreased to non-detectable levels. In addition, low molecular ion transports were almost constant at any EtOH concentration. Since molecular (ion) sizes of ISMN, CA, and FD-4 are larger than Na+, Cl-, and D2O, permeation pathway sizes for hydrophilic compounds in the skin barrier may be remarkably decreased by pretreatment with high concentrations of EtOH. However, the permeability coefficient of ISDN was not influenced by any EtOH concentration, since ISDN is a lipophilic, low-molecular compound that permeated through the lipophilic stratum corneum pathway. The present results show useful information for repeatedly and topically applied formulations containing EtOH, and also contribute to the effective use of alcohol formulations.

Transdermal iontophoresis of insulin: V. Effect of terpenes

To increase the skin permeation of large peptides like insulin, it is necessary to utilize a combination of enhancement strategies. In this regard, this study investigated the effect of terpenes/EtOH combination in comparison to EtOH and neat terpene on transdermal iontophoretic permeation of insulin. Ex-vivo experiments were conducted using full thickness rat skin after pre-treatment for 2 h with 5% of menthol, menthone, cineole and pulegone in EtOH; EtOH alone; neat menthone with and without iontophoresis (0.5 mA/cm2; 6 h). FT-IR studies were carried out using rat epidermal sheets after pre-treatment with enhancer solution for 2 h and tritiated water permeation studies was used to investigate the alteration in skin barrier property after enhancer or current treatment. The lag time was significantly reduced (P<0.05) with terpene/EtOH pre-treatment in comparison to passive control and EtOH pre-treatment, although there was no significant difference (P>0.05) among the terpenes. Synergistic enhancement in flux was observed with terpene/EtOH, and menthone/EtOH showed highest enhancement among the terpene/EtOH combinations. On the other hand, enhancement with neat menthone was higher than with menthone/EtOH. FT-IR studies showed that terpene/EtOH, EtOH and neat terpene act at the intercellular lipids. The skin barrier property was significantly (P<0.05) compromised with neat menthone treatment. Iontophoresis had a lesser effect on skin barrier property compared to chemical enhancer pre-treatment. Terpene/EtOH caused synergistic enhancement of insulin permeation when combined with iontophoresis and was influenced by the type and concentration of terpene.

Alcohol (Ethanol) Inhibits IL-8 and TNF: Role of the p38 Pathway

Acute ethanol (EtOH) intoxication has been identified as a risk factor for infectious complications in trauma and burn victims. However, the mechanism of this immune dysfunction has yet to be elucidated. The monocyte/macrophage production of cytokines, in particular IL-8 and TNF-alpha, is critical in the regulation of the acute inflammatory response to infectious challenge. IL-8 is a potent chemoattractant and activator of neutrophils. TNF-alpha, a proinflammatory cytokine, initiates expression of endothelial cell surface adhesion molecules and neutrophil migration. p38, a member of the mitogen-activated protein kinases, plays an important role in mediating intracellular signal transduction in endotoxin-induced inflammatory responses. We examined the effects of LPS and ethanol on p38 activation and the corresponding IL-8 and TNF-alpha production in human mononuclear cells. LPS-induced IL-8 and TNF-alpha production was inhibited in a similar pattern by pretreatment with either EtOH or SB202190 (1 microM), a specific inhibitor of p38 kinase. Western blot analysis, using a dual phospho-specific p38 mitogen-activated protein kinase Ab, demonstrated that EtOH pretreatment inhibited LPS-induced p38 activation. These results demonstrate that alcohol suppresses the normal host immune inflammatory response to LPS. This dysregulation appears to be mediated in part via inhibition of p38 activation. Inhibition of IL-8 and TNF-alpha production by acute EtOH intoxication may inhibit inflammatory focused neutrophil migration and activation and may be a mechanism explaining the increased risk of trauma- and burn-related infections.

Effects of Ethanol Hangover on the Operant Self-Administration of Cocaine in Rats

To assess the interaction of experimentally induced ethanol hangover and cocaine self-administration, rats maintained to self-administer cocaine (0.5 mg/kg/inj) were given either saline or 2 or 4 g/kg ethanol (10% w/v, IP) 15 h prior to cocaine access (dose range tested 0.03–1.0 mg/kg/inj). Cocaine was shown to be dose-dependently self-administered in a significant inverted U-shaped function. EtOH hangover had a significant effect on the dose-dependent effects of cocaine, resulting in a general flattening of the inverted U-shaped function with increasing intensity of hangover. A significant dose-dependent reduction in the number of reinforcer deliveries occurred at the peak of the cocaine dose–response function (0.06 mg/kg/inj) following the 2 and 4 g/kg EtOH pretreatment doses when compared to saline pretreatment. These data suggest that hangover may alter the ability for moderate doses of cocaine to “prime” and maintain stable self-administration behavior.

Effect of ethanol pretreatment on mercury distribution in organs of fetal guinea pigs following in utero exposure to mercury vapor

Ethanol (Et-OH), which is an inhibitor of catalase, reduces oxidation of mercury vapor (Hg 0) into ionic mercury (Hg 2+). Consequently, exposure of pregnant animals to Hg 0 with pretreatment of Et-OH causes penetration of larger amount of Hg 0 to the fetus. The fate of Hg 0 in the fetus of pregnant guinea pigs, thus penetrated, was investigated. Et-OH pretreatment of the dams resulted in the transfer of more mercury to the fetuses and led to a marked increase in mercury in the fetal liver. Furthermore, according to the mercury distribution in the fetal organs, the animals in the Et-OH-pretreated group fell into two subgroups: a group of fetuses (subgroup 1) had higher mercury concentrations in the brain, heart and kidney compared with the group which was exposed to Hg 0 without Et-OH-pretreatment (Hg 0 group) and another group (subgroup 2) with similar organ mercury concentrations to that of the Hg 0 group. Determination of metallothionein (MT) concentrations showed that MT concentration in the fetal liver of subgroup 2 was significantly higher than that of subgroup 1 and the Hg 0 group. Further, the Sephadex G-75 chromatography of the cytosol of the fetal liver in subgroup 2 revealed that most of mercury, about 66%, was bound to metallothionein-like protein. On the other hand, in the cytosol of fetal liver of subgroup 1, a small amount, about 10% appeared in fractions corresponding to MT. These findings suggest that fetal hepatic MT plays a significant defense role against mercury crossing the placenta and is involved in regulating for the mercury distribution in the fetus.

Interaction of Protein Phosphatases and Ethanol on Phospholipase C-Mediated Intracellular Signal Transduction Processes in Rat Hepatocytes: Role of Protein Kinase A

Phospholipase C (PLC)-mediated signal transduction processes in rat hepatocytes are subject to modulation by protein phosphatases (PPases) and protein kinases, including protein kinase A (PKA) and protein kinase C. Ethanol (EtOH) stimulates PLC activity in liver cells in the absence of hormones, and EtOH pretreatment inhibits the subsequent stimulation of PLC by hormonal stimuli. There is evidence that protein kinase activities are involved in these actions of EtOH. We investigated the effects of okadaic acid (OKA), a PPase inhibitor, and 8-(4-chlorophenylthio)adenosine 3′:5′-cyclic monophosphate (cpt-cAMP), a cell permeant cAMP analog that activates PKA, on EtOH-induced PLC activation. In addition, we studied the combined effects of cpt-cAMP and EtOH/OKA on vasopressin-induced PLC activation. PLC activation (cytosolic Ca2+ mobilization and inositol trisphosphate accumulation) induced by EtOH and vasopressin was inhibited by treatment with OKA, and was potentiated by cpt-cAMP. OKA treatment prevented the effect of cpt-cAMP. Pretreatment with EtOH caused inhibition of vasopressin-induced PLC activation. EtOH also decreased the enhancing effect of cpt-cAMP on the responses to vasopressin. The susceptibility to enhancement by cpt-cAMP plotted as a function of the initial rate of vasopressin-induced Ca2+ mobilization in EtOH-treated cells was similar to the pattern observed in OKA-treated cells. These data suggest that interactions of OKA and PKA on EtOH-induced PLC activation occurred at the level of G-protein, and indicate that EtOH may act as an inhibitory agent of PPase.

Interaction of Protein Phosphatases and Ethanol on Phospholipase C‐Mediated Intracellular Signal Transduction Processes in Rat Hepatocytes: Role of Protein Kinase A

Phospholipase C (PLC)-mediated signal transduction processes in rat hepatocytes are subject to modulation by protein phosphatases (PPases) and protein kinases, including protein kinase A (PKA) and protein kinase C. Ethanol (EtOH) stimulates PLC activity in liver cells in the absence of hormones, and EtOH pretreatment inhibits the subsequent stimulation of PLC by hormonal stimuli. There is evidence that protein kinase activities are involved in these actions of EtOH. We investigated the effects of okadaic acid (OKA), a PPase inhibitor, and 8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate (cpt-cAMP), a cell permeant cAMP analog that activates PKA, on EtOH-induced PLC activation. In addition, we studied the combined effects of cpt-cAMP and EtOH/OKA on vasopressin-induced PLC activation. PLC activation (cytosolic Ca2+ mobilization and inositol trisphosphate accumulation) induced by EtOH and vasopressin was inhibited by treatment with OKA, and was potentiated by cpt-cAMP. OKA treatment prevented the effect of cpt-cAMP. Pretreatment with EtOH caused inhibition of vasopressin-induced PLC activation. EtOH also decreased the enhancing effect of cpt-cAMP on the responses to vasopressin. The susceptibility to enhancement by cpt-cAMP plotted as a function of the initial rate of vasopressin-induced Ca2+ mobilization in EtOH-treated cells was similar to the pattern observed in OKA-treated cells. These data suggest that interactions of OKA and PKA on EtOH-induced PLC activation occurred at the level of G-protein, and indicate that EtOH may act as an inhibitory agent of PPase.

In vivo potentiation of 1,2-dibromoethane hepatotoxicity by ethanol through inactivation of glutathione- s-transferase

In the rat, a single ethanol (EtOH) pretreatment (2.5 g/kg b.w., per os) was able to strongly enhance the cytotoxicity of 1,2-dibromoethane (DBE) (87 mg/kg b.w., per os). The principal metabolic routes of DBE involve both oxidative and conjugative transformations. Microsomal cytochrome P 450 content and dimethyl nitrosamine demethylase activity were not changed, while a significant loss of cytosolic total GSH-transferase was observed in rats killed 6 h after EtOH pretreatment. Pretreatment with methylpyrazole, an inhibitor of alcoholdehydrogenase prevented the effects provoked by ethanol. The major EtOH metabolite, acetaldehyde, seemed thus to play a fundamental role in the mechanism responsible for the potentiation of DBE toxicity mediated by EtOH. To further support this hypothesis, disulfiram (75 mg/kg b.w.), an inhibitor of aldehyde dehydrogenase, was given i.p. to rats. When DBE was administered to disulfiram- and EtOH-pretreated rats, a marked increase of liver cytolysis was shown and cytosolic GSH-transferase activity was further inhibited if compared to that induced by EtOH treatment alone. The results are consistent with the hypothesis that EtOH given to rats increases DBE liver toxicity because its major metabolite, acetaldehyde, reduces the DBE conjugation to GSH transferase, with consequent shift of DBE metabolism to the oxidative route and accumulation of reactive oxidative intermediates no longer effectively conjugated with GSH.

Adverse effects of vagotomy on ethanol-induced gastric injury in the rat. Absence of a role for glutathione redox cycle.

Truncal vagotomy is known to aggravate the damaging effects of alcohol-induced gastric injury and prevent the occurrence of adaptive cytoprotection against such injury by a mild irritant. This study was undertaken to determine whether aberrations in glutathione (GSH) metabolism were responsible for these vagotomy-induced effects. Fasted rats (6-8/group) were subjected to truncal vagotomy and pyloroplasty or sham vagotomy and pyloroplasty. One week later they were given 2 ml of oral saline or the mild irritant, 25% ethanol (EtOH). Thirty minutes following such treatment, animals were either sacrificed or orally received 2 ml of 100% EtOH and then were sacrificed 5 min later. At sacrifice, in each experimental group, stomachs were removed and either evaluated macroscopically for the degree of injury involving the glandular gastric epithelium or samples of the mucosa were prepared for measurement of total GSH levels or GSH peroxidase (GPX) and GSH reductase (GRT) activity. In nonvagotomized animals, saline treatment prior to 100% EtOH exposure resulted in injury to the glandular epithelium involving approximately 18%. Treatment with 25% EtOH prior to 100% EtOH exposure virtually abolished this injury. In vagotomized animals, 100% EtOH elicited almost three times the amount of injury observed in the nonvagotomized state and the protective effect of 25% EtOH pretreatment was prevented. Effects of the various treatment modalities on GPX and GRT activity were not significantly different from control values. When mucosal GSH results were plotted against the presence or absence of gastric injury among the various groups studied, no significant correlation was apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of chronic ethanol consumption on α-adrenergic-induced contractions in rat thoracic aorta

1. 1. The effects of chronic oral administration of ethanol (EtOH, 80 mM daily during 15–18 days) on the modulation exerted by the endothelium on the contractions induced by phenylephrine (Ph) and clonidine (C) were studied in rat aortic rings with and without endothelium. 2. 2. The maximal contraction induced by a 70 mM KCl depolarizing solution was similar in control and EtOH treated-rings. 3. 3. EtOH pretreatment significantly enhanced the contractile response to Ph in vessels with intact endothelium, but did not significantly affect the response of endothelium-denuded rings. 4. 4. This effect reflects a reduction of the modulation exerted by the endothelial cells on α 1-adrenergic vasoconstriction. 5. 5. C did not contract control aortic rings with endothelium, but after EtOH treatment, the response reached about 20% of the maximal KCl-induced contraction. 6. 6. EtOH pretreatment significantly enhanced the contractile response to C both in endothelium-denuded and intact aortic rings. 7. 7. The results indicate that chronic EtOH consumption significantly potentiates α-andrenergic-induced contractions in rat aortic rings, probably through interference with the production and/or the release of EDRF.

Acute tolerance to ethanol using drug discrimination and open-field procedures in rats

This study examined the phenomenon of acute tolerance to ethanol (ETOH) using drug discrimination learning (DDL), and open-field (OF) procedures. In DDL, rats were trained to discriminate between ETOH (1.2 g/kg) and saline. Doses of ETOH lower (0.6 and 0.9 g/kg), or higher (1.8 and 2.4 g/kg) than the training dose were tested to examine possible influence of ETOH pretreatment doses on the expression of acute tolerance. To assess concentrations of ETOH in the organism, a rebreathed air procedure was used. Equal concentrations after different ETOH doses were achieved by postponing the tests until sufficient time had elapsed. Only doses of ETOH higher than the training dose produced acute tolerance in the DDL procedure. For the response-time data no acute tolerance was observed. In the OF experiment, the occurrence of acute tolerance was examined for different spontaneous behaviours in drug-naive animals. At equal ETOH concentrations, the group examined during the descending phase of intoxication (1.8 g/kg, 60 min post-injection), reared significantly more than the group tested during the ascending phase (1.5 g/kg, 10 min post-injection). Other OF behaviours did not differ significantly between the two time intervals. Thus, it is suggested that acute tolerance is seen both in ETOH naive and in ETOH pre-exposed rats. However, in DDL acute tolerance was observed only when doses higher than training dose of ETOH were evaluated.

Ethanol effects on brain concentrations of amitriptyline and the relationship to psychomotor function.

The effect of amitriptyline (AMI), ethanol (ETOH), and ETOH followed by AMI on both general activity (open field) and motor performance (two rotorod tasks) was tested in reference to a saline-injected control. The combination (ETOH plus AMI) produced greater impairment on all three tasks than did either drug alone. ETOH pretreatment also produced a 223% increase in the total tricyclic antidepressant (TCA) brain concentration. The decrement in motor performance was logarithmically related to total TCA brain concentrations in both animals treated with AMI alone and those pretreated with ETOH prior to AMI. The concentration which consistently produced behavioral impairment was similar to those previously reported to cause cognitive and electroencephalographic dysfunction in humans.

Ethanol narcosis in mice: effects of L-dopa, its metabolites and other experimental variables.

Ethanol-induced narcosis was studied in mice as a function of pretreatment with L-dopa and its metabolites administered alone or in conjunction with Ro-4-4602, an inhibitor of aromatic-L-amino acid decarboxylase. These studies suggest that L-dopa prolongation of ETOH narcosis in mice may be due to formation of one or more toxic metabolites rather than to a direct involvement of dopamine. Ethanol narcosis also was studied in mice as a function of age of animals, concentration of ETOH, ambient temperature and saline pretreatment. Since manipulation of these variables produced alterations in ETOH narcosis, the need for their rigid control is indicated.