Carbonyl compounds in different stages of vinification and exposure risk assessment through Merlot wine consumption.

The objective of this research was to estimate for the first time the transformations that the free form of some target carbonyl compounds may undergo during winemaking and assess the exposure risk to these compounds through the consumption of the Merlot commercial wines under study. Acrolein and furfural were found in grapes and the respective wines, although levels were observed to decline throughout the winemaking process. Formaldehyde was found in all stages of wine production in levels lower than the limit of quantification of the method and ethyl carbamate was not found in samples. Acetaldehyde seems to be a precursor of acetoin and 2,3-butanediol, since the levels of this aldehyde decreased along winemaking and the formation of the ester and alcohol was verified. Furfural levels decreased, while the occurrence of furan-containing compounds increased during winemaking. The formation of acetaldehyde during alcoholic fermentation and the potential environmental contamination of grapes with acrolein and furfural are considered as the critical points related to the presence of toxic carbonyl compounds in the wine. Acrolein was found in the samples under study in sufficient quantities to present risk to human health, while other potentially toxic carbonyl compounds did not result in risk. This study indicated for the first time the presence of acrolein in grapes suggesting that environmental pollution can play an important role in the levels of this aldehyde detected in wines. Reduction of the emission of this aldehyde to the environment may be achieved by replacing wood burning by another heat source in fireplaces or wood stones, and abandoning the practice of burning garbage and vegetation.

DNA Adduct Formation in the Lungs and Brain of Rats Exposed to Low Concentrations of [13C2]-Acetaldehyde.

Air pollution is a major environmental risk for human health. Acetaldehyde is present in tobacco smoke and vehicle exhaust. In this study, we show that [13C2]-acetaldehyde induces DNA modification with the formation of isotopically labeled 1, N2-propano-2'-deoxyguanosine adducts in the brain and lungs of rats exposed to concentrations of acetaldehyde found in the atmosphere of megacities. The adduct, with the addition of two molecules of isotopically labeled acetaldehyde [13C4]-1, N2-propano-dGuo, was detected in the lung and brain tissues of exposed rats by micro-HPLC/MS/MS. Structural confirmation of the products was unequivocally performed by nano-LC/ESI+-HRMS3 analyses. DNA modifications induced by acetaldehyde have been regarded as a key factor in the mechanism of mutagenesis and may be involved in the cancer risks associated with air pollution.

Subarachnoid hemorrhage in a Japanese cocaine abuser: Cocaine-related sudden death.

Based on a prospective case-control study of forensic autopsies, the causes of cocaine (COC)-related sudden death (SD) are cardiovascular events in 62.0% of cases, cerebrovascular events in 14.0%, and others. A forensic autopsy of a male in his early forties revealed subarachnoid hemorrhage (SAH) at the base of the brain. A cerebral arterial aneurysm was not detected even though hemorrhage was clearly observed in the anterior cerebral artery (ACA) bifurcation area. The brain weighed 1488 g and was edematous. We histopathologically examined the left-ACA, right-ACA, and anterior communicating artery (Acom). Thickening of the internal vessel wall was observed as a pathological change. The internal elastic lamina of the right-ACA, near the peripheral part of Acom, was meandered with a jagged appearance. A toxicology examination detected COC and its metabolites, particularly benzoylecgonin, in blood and urine samples. Therefore, the present case was regarded as a non-fatal intoxication case, but also a COC-related death. Ethanol was also detected, indicating that COC was taken in combination with alcohol. The cause of COC-related death in the present case was SAH. COC use is known to induce aneurysmal SAH; however, whether an aneurysm had formed in the present case was unclear. Meander, extension, and degeneration of the internal elastic lamina of the right-ACA were observed near the bifurcation from the Acom. This area corresponded macroscopically with that considered to be the bleeding point from the blood vessel. Therefore, the present case was diagnosed as COC-related SD.

Now you see me, now you don't: The case of a vanishing outflow gradient in a patient with hypertrophic cardiomyopathy.

Cardiogenic shock is well described in hypertrophic cardiomyopathy (HCM) as acute hemodynamic collapse can develop in the setting of acute worsening of left ventricular outflow tract (LVOT) obstruction. We present the case of a 60-year-old man with drug refractory LVOT obstruction due to hypertrophic cardiomyopathy. On the evening prior to planned alcohol septal ablation, the patient presented in cardiogenic shock. Interestingly, his previously recorded LVOT gradients of 50 mm Hg at rest and 118 mm Hg at peak exercise were absent. With recovery of left ventricular function, significant left ventricular outflow obstruction returned. The patient then underwent successful septal reduction therapy. © 2016 Wiley Periodicals, Inc.

The "first hit" toward alcohol reinforcement: role of ethanol metabolites.

This review analyzes literature that describes the behavioral effects of 2 metabolites of ethanol (EtOH): acetaldehyde and salsolinol (a condensation product of acetaldehyde and dopamine) generated in the brain. These metabolites are self-administered into specific brain areas by animals, showing strong reinforcing effects. A wealth of evidence shows that EtOH, a drug consumed to attain millimolar concentrations, generates brain metabolites that are reinforcing at micromolar and nanomolar concentrations. Salsolinol administration leads to marked increases in voluntary EtOH intake, an effect inhibited by mu-opioid receptor blockers. In animals that have ingested EtOH chronically, the maintenance of alcohol intake is no longer influenced by EtOH metabolites, as intake is taken over by other brain systems. However, after EtOH withdrawal brain acetaldehyde has a major role in promoting binge-like drinking in the condition known as the "alcohol deprivation effect"; a condition seen in animals that have ingested alcohol chronically, are deprived of EtOH for extended periods, and are allowed EtOH re-access. The review also analyzes the behavioral effects of acetate, a metabolite that enters the brain and is responsible for motor incoordination at low doses of EtOH. Also discussed are the paradoxical effects of systemic acetaldehyde. Overall, evidence strongly suggests that brain-generated EtOH metabolites play a major role in the early ("first-hit") development of alcohol reinforcement and in the generation of relapse-like drinking.

Acetaldehyde self-administration by a two-bottle choice paradigm: consequences on emotional reactivity, spatial learning, and memory.

Acetaldehyde, the first alcohol metabolite, is responsible for many pharmacological effects that are not clearly distinguishable from those exerted by its parent compound. It alters motor performance, induces reinforced learning and motivated behavior, and produces different reactions according to the route of administration and the relative accumulation in the brain or in the periphery. The effective activity of oral acetaldehyde represents an unresolved field of inquiry that deserves further investigation. Thus, this study explores the acquisition and maintenance of acetaldehyde drinking behavior in adult male rats, employing a two-bottle choice paradigm for water and acetaldehyde solution (from 0.9% to 3.2% v/v), over 8 weeks. The behavioral consequences exerted by chronic acetaldehyde intake are assessed by a set of different tests: trials in an open-field arena and elevated-plus maze provided information on both general motor and explorative activity, and anxiety-driven behavioral responses. The Morris water maze allowed the exploration of cognitive processes such as spatial learning and memory. Determination of acetaldehyde levels in the brain was carried out at the end of the drinking paradigm. Our results indicate that rats exposed for the first time to acetaldehyde at 0.9% displayed a regular and stable daily drinking pattern that reached higher values and a "peaks and drops" shaped-trend when acetaldehyde concentration was increased to 3.2%. Accordingly, an increase in acetaldehyde levels in the brain was determined compared to non-acetaldehyde drinking rats. Acetaldehyde intake during the free-choice paradigm exerted an anxiogenic response in the open-field arena and elevated-plus maze, which in turn correlates with an enhancement in cognitive flexibility and spatial orientation skills, when an adaptive response to a stressful environmental challenge was required. These findings further support the idea that acetaldehyde is indeed a centrally active and behaviorally relevant metabolite of alcohol.

In vivo effects of metaldehyde on Pacific oyster, Crassostrea gigas: comparing hemocyte parameters in two oyster families.

Pollutants via run-off into the ocean represent a potential threat to marine organisms, especially bivalves such as oysters living in coastal environments. These organisms filter large volumes of seawater and may accumulate contaminants within their tissues. Pesticide contamination in water could have a direct or indirect toxic action on tissues or cells and could induce alteration of immune system. Bivalve immunity is mainly supported by hemocytes and participates directly by phagocytosis to eliminate pathogens. Some studies have shown that pesticides can reduce immune defences and/or modify genomes in vertebrates and invertebrates. Metaldehyde is used to kill slugs, snails and other terrestrial gastropods. Although metaldehyde has been detected in surface waters, its effects on marine bivalves including the Pacific oyster, Crassostrea gigas, have never been studied. Given the mode of action of this molecule and its targets (molluscs), it could be potentially more toxic to oysters than other pesticides (herbicides, fungicides, insecticides, etc.). Effects of metaldehyde on oyster hemocyte parameters were thus monitored through in vivo experiments based on a short-term exposure. In this work, metaldehyde at 0.1 µg/L, which corresponds to an average concentration detected in the environment, modulated hemocyte activities of Pacific oysters after an in vivo short-term contact. Individuals belonging to two families showed different behaviours for some hemocyte activities after contamination by metaldehyde. These results suggested that effects of pollutants on oysters may differ from an individual to another in relation to genetic diversity. Finally, it appears essential to take an interest in the effects of metaldehyde on a wide variety of aquatic invertebrates including those that have a significant economic impact.

Increase in nucleus accumbens dopamine levels following local ethanol administration is not mediated by acetaldehyde.

AIMS: Ethanol (EtOH) activates the mesolimbic dopamine system and increases dopamine levels in the nucleus accumbens (nAc), which is believed to underlie the rewarding effects of alcohol. Accumulating evidence now implicates that acetaldehyde, the first metabolite of EtOH, may play an important role in mediating some of the rewarding properties of its parent compound. The objective of this study was to investigate if the increase in accumbal dopamine output observed when administering EtOH locally in the nAc by reversed microdialysis is mediated by acetaldehyde. METHODS: Acetaldehyde (1, 10, 100 or 200 µM) or EtOH (300 mM) was administered via reversed microdialysis in the nAc of male Wistar rats. In a separate experiment, animals were administered EtOH (300 mM) in the nAc, following pre-treatment with the acetaldehyde-sequestering agent d-penicillamine (50 mg/kg injected intraperitoneally 60 min before drug challenge). Microdialysates from the nAc were collected every 20 min and dopamine content was quantified using high-performance liquid chromatography. RESULTS: Acetaldehyde administered in the nAc did not influence accumbal dopamine levels at any of the concentrations applied, whereas EtOH induced a significant increase in accumbal dopamine. The dopamine-elevating properties of EtOH were not attenuated by pre-treatment with d-penicillamine. CONCLUSION: The current results show that EtOH administered in the nAc induces an elevation in accumbal dopamine levels, which is not mimicked by acetaldehyde alone, nor is it influenced by acetaldehyde sequestering. This would suggest that the increase in accumbal dopamine following nAc EtOH administration is not mediated by acetaldehyde.

What is in that drink: the biological actions of ethanol, acetaldehyde, and salsolinol.

Alcohol abuse and alcoholism represent substantial problems that affect a large portion of individuals throughout the world. Extensive research continues to be conducted in an effort to identify the biological basis of the reinforcing properties of alcohol in order to develop effective pharmacotherapeutic and behavioral interventions. One theory that has developed within the alcohol field over the past four decades postulates that the reinforcing properties of alcohol are due to the action of the metabolites/products of alcohol within the central nervous system (CNS). The most extreme version of this theory suggests that the biologically active metabolites/products of alcohol, created from the breakdown from alcohol, are the ultimate source of the reinforcing properties of alcohol. The contrary theory proposes that the reinforcing properties of alcohol are mediated completely through the interaction of the ethanol molecule with several neurochemical systems within the CNS. While there are scientific findings that offer support for both of these stances, the reinforcing properties of alcohol are most likely generated through a complex series of peripheral and central effects of both alcohol and its metabolites. Nonetheless, the development of a greater understanding for how the metabolites/products of alcohol contribute to the reinforcing properties of alcohol is an important factor in the development of efficacious pharmacotherapies for alcohol abuse and alcoholism. This chapter is intended to provide a historical perspective of the role of acetaldehyde (the first metabolite of alcohol) in alcohol reinforcement as well as review the basic research literature on the effects of acetaldehyde (and acetaldehyde metabolites/products) within the CNS and how these function with regard to alcohol reward.

The role of acetaldehyde in ethanol reinforcement assessed by Pavlovian conditioning in newborn rats.

RATIONALE: Animal studies indicate that central acetaldehyde, dependent on catalase metabolism of ethanol (EtOH), modulates ethanol reinforcement. Brain catalase activity and acetaldehyde (ACD) production are significantly higher in rat pups compare d with adults. Interestingly, infant rats show high EtOH affinity for alcohol consumption and are particularly sensitive to the drug's reinforcing effects. OBJECTIVES: We tested whether central ACD is necessary and sufficient to induce appetitive conditioning in newborn rats through the artificial nipple technique. METHODS: Vehicle, EtOH (100 mg%), and acetaldehyde (0.35 µmol) were administered into the cisterna magna (1 µl). Half of the animals also received a central administration of 75 µg (experiment 1) or 40 µg of D-penicillamine (experiment 2). Afterwards, pups were exposed to an olfactory cue (conditioned stimulus). One hour later, neonates were tested with an artificial nipple in the presence of the conditioned cue. Nipple attachment duration, mean grasp duration, and number of nipple disengagements served as dependent variables. RESULTS: Positive responses to the scented nipple occurred in neonates conditioned with EtOH or ACD (experiments 1 and 2). In experiment 1, there were indications that D-penicillamine weakened the reinforcing effects of EtOH and ACD. In experiment 2, D-penicillamine (40 µg) significantly inhibited appetitive conditioned responses dependent upon EtOH or ACD. CONCLUSIONS: Appetitive conditioning was observed when employing either central EtOH or ACD as unconditioned stimuli. Central abduction of ACD inhibited conditioned appetitive responsiveness to the surrogate nipple. Central ACD is involved in the determination or modulation of EtOH's motivational properties during early stages in development.

Acetaldehyde disrupts tight junctions in Caco-2 cell monolayers by a protein phosphatase 2A-dependent mechanism.

Acetaldehyde is accumulated at high concentrations in the colonic lumen following ethanol administration. Previous studies demonstrated that acetaldehyde disrupts intestinal epithelial tight junctions and increases paracellular permeability. In the present study, we investigated the role of PP2A in the acetaldehyde-induced disruption of intestinal epithelial tight junctions. Caco-2 cell monolayers were exposed to 200-600 µM acetaldehyde for varying times, and the epithelial barrier function was evaluated by measuring transepithelial electrical resistance and inulin permeability. Acetaldehyde treatment resulted in a time-dependent increase in inulin permeability and redistribution of occludin and ZO-1 from the intercellular junctions. Treatment of cells with fostriecin (a PP2A-selective inhibitor) or knockdown of PP2A by siRNA blocked acetaldehyde-induced increase in inulin permeability and redistribution of occludin and ZO-1. The effects of fostriecin and acetaldehyde were confirmed in mouse intestine ex vivo. Acetaldehyde-induced tight junction disruption and barrier dysfunction were also attenuated by a PP2A-specific inhibitory peptide, TPDYFL. Coimmunoprecipitation studies showed that acetaldehyde increased the interaction of PP2A with occludin and induced dephosphorylation of occludin on threonine residues. Fostriecin and TPDYFL significantly reduced acetaldehyde-induced threonine dephosphorylation of occludin. Acetaldehyde failed to change the level of the methylated form of PP2A-C subunit. However, genistein (a tyrosine kinase inhibitor) blocked acetaldehyde-induced association of PP2A with occludin and threonine dephosphorylation of occludin. These results demonstrate that acetaldehyde-induced disruption of tight junctions is mediated by PP2A translocation to tight junctions and dephosphorylation of occludin on threonine residues.

[Shifts in the mice blood-forming system and energy exchange of erythrocytes due to chronic exposure to chemical agents (acetone, ethanol, acetaldehyde) and radiation in concentrations and doses modeling the conditions in extended orbital mission].

The paper presents the results of an investigation with mice subjected to isolated and successive exposure to a blend of chemical agents (acetone, ethanol, acetaldehyde) at MPC levels defined for piloted space vehicles followed by fractionated gamma-irradiation by daily 1 cGy (30 cGy total). The selected chemicals are the primary contributors to total air contamination and present in the prioritized list of compounds to be monitored to ensure air quality on piloted space vehicles. Radiation levels were determined with allowance for mice radiosensitivity to simulate the actual absorbed dose accumulated by crewmembers of orbital mission of up to a year in duration (10 cGy). Based on the findings in the hematopoietic system and erythrocyte biochemistry, energy exchange and redox parameters, pre-irradiation exposure to chemical agents within the MPC limits accentuated radiosensitivity gravely and, therefore, made mouse organism less tolerant to radiation. It was shown that adaptation of the hematopoietic system calls forth activation and significant straining of regulatory mechanisms equally in opposing to a single factor or combination of chemical and radiation exposure. The marked tension of these mechanisms persisted till day 30 of recovery.

Effect of (L)-cysteine on acetaldehyde self-administration.

Acetaldehyde (ACD), the first metabolite of ethanol, has been implicated in several behavioural actions of alcohol, including its reinforcing effects. Recently, we reported that l-cysteine, a sequestrating agent of ACD, reduced oral ethanol self-administration and that ACD was orally self-administered. This study examined the effects of l-cysteine pre-treatment during the acquisition and maintenance phases of ACD (0.2%) self-administration as well as on the deprivation effect after ACD extinction and on a progressive ratio (PR) schedule of reinforcement. In a separate PR schedule of reinforcement, the effect of l-cysteine was assessed on the break-point produced by ethanol (10%). Furthermore, we tested the effect of l-cysteine on saccharin (0.2%) reinforcement. Wistar rats were trained to self-administer ACD by nose poking on a fixed ratio (FR1) schedule in 30-min daily sessions. Responses on an active nose-poke caused delivery of ACD solution, whereas responses on an inactive nose-poke had no consequences. l-cysteine reduced the acquisition (40 mg/kg), the maintenance and the deprivation effect (100 mg/kg) of ACD self-administration. Furthermore, at the same dose, l-cysteine (120 mg/kg) decreased both ACD and ethanol break point. In addition, l-cysteine was unable to suppress the different responses for saccharin, suggesting that its effect did not relate to an unspecific decrease in a general motivational state. Compared to saline, l-cysteine did not modify responses on inactive nose-pokes, suggesting an absence of a non-specific behavioural activation. Taken together, these results could support the hypotheses that ACD possesses reinforcing properties and l-cysteine reduces motivation to self-administer ACD.

Acetaldehyde oral self-administration: evidence from the operant-conflict paradigm.

BACKGROUND: Acetaldehyde (ACD), ethanol's first metabolite, has been reported to interact with the dopaminergic reward system, and with the neural circuits involved in stress response. Rats self-administer ACD directly into cerebral ventricles, and multiple intracerebroventricular infusions of ACD produce conditioned place preference. Self-administration has been largely employed to assess the reinforcing and addictive properties of most drugs of abuse. In particular, operant conditioning is a valid model to investigate drug-seeking and drug-taking behavior in rats. METHODS: This study was aimed at the evaluation of (i) the motivational properties of oral ACD in the induction and maintenance of an operant-drinking behavior; (ii) ACD effect in a conflict situation employing the punishment-based Geller-Seifter procedure; and (iii) the onset of a relapse drinking behavior, following ACD deprivation. The lever-pressing procedure in a sound-attenuated operant-conditioning chamber was scheduled into 3 different periods: (i) training-rewarded responses with a fixed ratio 1; (ii) conflict-rewarded responses periodically associated with a 0.2 mA foot-shock; and (iii) relapse-rewarded lever presses following 1-week ACD abstinence. RESULTS: Our results show that oral self-administrated ACD induced: a higher rate of punished responses in Geller-Seifter procedures; and the establishment of a relapse behavior following ACD deprivation. CONCLUSIONS: In conclusion, our results indicate that ACD is able to induce an operant-drinking behavior, which is also maintained besides the conflict procedure and enhanced by the deprivation effect, supporting the hypothesis that ACD itself possesses motivational properties, such as alcohol and other substances of abuse.

High ethanol and acetaldehyde impair spatial memory in mouse models: opposite effects of aldehyde dehydrogenase 2 and apolipoprotein E on memory.

Aldehyde dehydrogenase 2 deficiency may directly contribute to excess acetaldehyde (AcH) accumulation after ethanol (EtOH) drinking and AcH mediates some of the behavioral effects of EtOH. Apolipoprotein E has been suggested to be involved in the alteration of attention and memory. We have chosen Aldh2-knockout (Aldh2-KO), ApoE-KO, and their wild-type (WT) control mice to examine the effects of EtOH and AcH on spatial memory and to compare the possible relationship between genetic deficiency and memory using two behavioral assessments. Mice were trained for 4 days, with EtOH (0.5, 1.0, 2.0 g/kg) being given intraperitoneally on day 4. A probe trial was given on day 5 in the non-EtOH state in the Morris water maze (MWM). The results showed that 2.0 g/kg EtOH increased errors, indicating memory impairment on the eight-arm radial maze (RAM) for all the mice studied. One gram per kilogram EtOH impaired the performance of Aldh2-KO and ApoE-KO mice, but not WT mice. We found similar effects of EtOH on the MWM performance, with 2.0 g/kg EtOH increasing the latencies. One gram per kilogram EtOH increased the latencies of Aldh2-KO and WT mice, but not ApoE-KO mice. The 2.0 g/kg EtOH-induced memory impairment in Aldh2-KO mice was greater, suggesting an AcH effect. Furthermore, time spent on the probe trial was shorter in mice that had previously received 2.0 g/kg EtOH. ApoE-KO mice learned more slowly, while Aldh2-KO mice learned more quickly. Both the RAM and MWM results suggest that high EtOH and AcH impair spatial memory in mice, while lower doses do not have consistent memory effects. In addition, we conclude that genetic differences might underlie some of EtOH's effects on memory.

Anxiogenic and stress-inducing effects of peripherally administered acetaldehyde in mice: similarities with the disulfiram-ethanol reaction.

UNLABELLED: Peripheral accumulation of acetaldehyde, the first metabolite of ethanol, produces autonomic responses in humans called "flushing". The aversive characteristics of flushing observed in some populations with an isoform of aldehyde dehydrogenase (ALDH2) less active, are the basis for treating alcoholics with disulfiram, an ALDH inhibitor. Although ethanol and centrally formed acetaldehyde have anxiolytic effects, peripheral accumulation of acetaldehyde may be aversive in part because it is anxiogenic. OBJECTIVES: We investigated the effect of direct administration of acetaldehyde on behavioral measures of anxiety and on hormonal markers of stress in mice. The impact of disulfiram on the anxiolytic actions of ethanol was evaluated. Acetate (a metabolite of acetaldehyde) was also studied. METHODS: CD1 male mice received acetaldehyde (0, 25, 50, 75 or 100 mg/kg) at different time intervals and were assessed in the elevated plus maze and in the dark-light box. Corticosterone release after acetaldehyde administration was also assessed. Additional experiments evaluated the impact of disulfiram on the anxiolytic effect of ethanol (0 or 1 mg/kg), and the effect of acetate on the plus maze. RESULTS: Direct administration of acetaldehyde (100 mg/kg) had an anxiogenic effect at 1, 11 or 26 min after IP administration. Acetaldehyde was ten times more potent than ethanol at inducing corticosterone release. Disulfiram did not affect behavior on its own, but blocked the anxiolytic effect of ethanol at doses of 30 and 60 mg/kg, and had an anxiogenic effect at the highest dose (90 mg/kg) when co-administered with ethanol. Acetate did not affect any of the anxiety parameters. CONCLUSIONS: Peripheral administration or accumulation of acetaldehyde produces anxiogenic effects and induces endocrine stress responses. This effect is not mediated by its metabolite acetate.

[Evaluation on molluscicidal effect of suspension concentrate of metaldehyde and niclosamide].

OBJECTIVE: To evaluate the molluscicidal effect of suspension concentrate of 26% metaldehyde and niclosamide (MNSC) in laboratory and field. METHODS: The experiment of MNSC against Oncomelania snails were performed by immersion and spray methods with different time in laboratory and field, and the wettable powder of 50% niclosamide ethanolamine salt (WPN) and fresh water were set as the controls. RESULTS: In laboratory, by immersion method (immersion for 24 h), LC50 of MNSC was 0.058 3 mg/L, which was lower than 0.094 7 mg/L of WPN. For the concentrations of 2.0 mg/L and 1.0 mg/L of MNSC by immersion method (immersion for 24, 48 h and 72 h, respectively), the death rates of snails were all 100%. In laboratory, by the spray method, the snail death rates were higher than 97% on the 3rd and 7th day when the dosage of MNSC was higher than 1.0 g/m2. In the field, by the immersion method, the snail death rates of MNSC (2 g/m3) for 24, 48 h and 72 h were 97.78% -100% in Hubei Province and 97.50% - 100% in Anhui Province, respectively, the rates of WPN were 98.89% - 100% and 97.56% - 100%, respectively, and the snail death rates of MNSC and WPN were both 100% in Jiangsu Province. In the field, by the spray method, the snail death rates of MNSC for 1, 3 d and 7 d were 83.12% - 94.64% in Jiangsu Province, 67.81% - 86.67% in Hubei Province and 72.80% - 100% in Anhui Province, respectively. The snail death rates of WPN for 1, 3 d and 7 d were 78.40% - 86.11%, 77.27% - 87.50% and 83.81% - 98.51%, respectively. In Hunan Province, the snail death rates of MNSC and WPN after spraying for 7 d were 94.94% and 94.20%, respectively, after spraying for 15 d, the rates were 86.67% and 89.38%, respectively. CONCLUSIONS: The molluscicidal effect of MNSC is as the same as WPN by immersion and spray methods in laboratory and field. MNSC has the characteristics of good water solubility, quick dispersing and easy using. In addition, the efficiency component of MNSC is half of WPN. So MNSC is a novel form of molluscicide which is worthy of promotion in field.

Effect of opioid receptor blockade on acetaldehyde self-administration and ERK phosphorylation in the rat nucleus accumbens.

We have previously shown that acetaldehyde (ACD), the first metabolite of ethanol, regulates its motivational properties and possesses reinforcing effects by itself. A large and still growing body of evidence indicates that the endogenous opioidergic system plays a critical role in the motivational effects of ethanol and suggests a role for extracellular signal-regulated kinase (ERK) in these effects of both ethanol and ACD. The present study was undertaken to examine if opioid-mediated mechanisms are involved in the reinforcing properties of ACD and in ACD-elicited ERK activation. To this end, Wistar rats were trained to orally self-administer ACD (0.2%) by nose poking. Responses on active nose poke caused delivery of ACD solution, whereas responses on inactive nose poke had no consequences. The effect of pretreatment with a nonselective opioid receptor antagonist, naltrexone (NTX), was evaluated during (1) maintenance of ACD self-administration, (2) deprivation effect after ACD extinction, and (3) ACD self-administration under a progressive-ratio schedule of reinforcement. Additionally, we tested the effect of NTX on saccharin (0.05%) reinforcement, as assessed by oral self-administration, and on ACD-elicited ERK phosphorylation in the nucleus accumbens (Acb), as assessed by immunohistochemistry. Finally, we examined the effect of a µ(1)-selective opioid receptor antagonist, naloxonazine (NLZ), on the maintenance phase of ACD and saccharin self-administration. The results indicate that NTX (0.4-0.8mg/kg) reduced the maintenance, the deprivation effect, and the break points of ACD self-administration without suppressing saccharin self-administration. Moreover, NTX decreased ACD-elicited ERK activation in the Acb shell and core. NLZ (10-15mg/kg) reduced the maintenance phase of ACD self-administration without interfering with saccharin self-administration, whereas both NTX and NLZ failed to modify responses on inactive nose poke indicating the lack of a nonspecific behavioral activation. Overall, these results indicate that the opioid system is implicated in the reinforcing properties of ACD and suggest an involvement of ERK. The finding that NTX and NLZ reduce ACD but not saccharin self-administration indicates that these effects are specific to ACD.

Leptin and acetaldehyde synergistically promotes αSMA expression in hepatic stellate cells by an interleukin 6-dependent mechanism.

BACKGROUND: The mechanisms whereby patients with obesity/overweight are more susceptible to alcohol-associated liver fibrosis are unclear. Leptin, a peptide hormone secreted by white adipose tissue is increased in association with overweight/obesity and is recognized as mediator of liver fibrosis. We sought to assess whether leptin contributes to alcoholic liver fibrosis by in vitro studies in hepatic stellate cells (HSC). METHODS: Rat HSCs in second or third passage were utilised. Leptin, Acetaldehyde or combination with leptin and acetaldehyde were incubated for specific periods in cultured HSCs. Profibrogenic gene and protein expression were determined and associated-signalling pathways were assessed. Interleukin 6 (IL-6) antibody neutralization was used to evaluate the role of IL-6. RESULTS: Leptin did not promote acetaldehyde-induced gene expression of collagen I, transforming growth factor ß1 (TGFß1) and tissue inhibitor of metalloproteinase 1 (TIMP1) in vitro. However, combined treatment of leptin with acetaldehyde synergistically enhanced the protein expression of smooth muscle actin (αSMA), an activation marker of HSCs, and of Interleukin-6 (IL-6). The combination of leptin and acetaldehyde also augmented MAPK/p38 and MAPK/ERK1/2 phosphoprotein expression. IL-6 neutralization down-regulated protein expression of pp38, pERK1/2 and αSMA, while exogenous rat recombinant IL-6 administration up-regulated αSMA. Similarly, MAPK/p38 and MAPK/ERK1/2 inhibition attenuated αSMA expression. H(2)O(2) induction by acetaldehyde was not potentiated by co-treatment with leptin nor did IL-6 neutralization reduce acetaldehyde-induced H(2)O(2) production. CONCLUSIONS: We conclude that leptin potentiates acetaldehyde-induced HSC activation and αSMA expression by an IL-6-dependent mechanism.

Circulating glycolaldehyde induces oxidative damage in the kidney of rats.

Renal failure is a key pathological issue in diabetic patients. Increased levels of advanced glycation end-products (AGEs) have been associated to diabetic complications, including diabetic nephropathy. Models of AGE-treated animals have been applied to evaluate the effect of such molecules on oxidative parameters involved in the pathogenesis and evolution of diabetes disease. However, little is known about the effect of glycating agents other than glucose. Here we investigate the effect of intravenously administrated glycolaldehyde (GA) on oxidative stress parameters of the kidney. Male Wistar rats received a single injection of GA in different doses (10, 50 or 100mg/kg) and were sacrificed after 6, 12 or 24h. Activities of antioxidant enzymes catalase, superoxide dismutase and glyoxalase I were assayed. Damage to proteins and lipids were also assayed. The content of N(epsilon)-(carboxymethyl)lysine (CML) was quantified. Glycolaldehyde induced a decrease in the activity of all enzymes studied. Lipoperoxidation and protein carbonylation raised, accompanied by a decrease in sulfhydryl groups. Despite the oxidative stress generated by GA, no change was found in the content of CML, suggesting that accumulation of AGEs in the kidney might occur at later steps in the development of diabetic nephropathy.