Action Of Alcohol Research Articles

The TMEM132B-GABAA receptor complex controls alcohol actions in the brain.

Alcohol is the most consumed and abused psychoactive drug globally, but the molecular mechanisms driving alcohol action and its associated behaviors in the brain remain enigmatic. Here, we have discovered a transmembrane protein TMEM132B that is a GABAA receptor (GABAAR) auxiliary subunit. Functionally, TMEM132B promotes GABAAR expression at the cell surface, slows receptor deactivation, and enhances the allosteric effects of alcohol on the receptor. In TMEM132B knockout (KO) mice or TMEM132B I499A knockin (KI) mice in which the TMEM132B-GABAAR interaction is specifically abolished, GABAergic transmission is decreased and alcohol-induced potentiation of GABAAR-mediated currents is diminished in hippocampal neurons. Behaviorally, the anxiolytic and sedative/hypnotic effects of alcohol are markedly reduced, and compulsive, binge-like alcohol consumption is significantly increased. Taken together, these data reveal a GABAAR auxiliary subunit, identify the TMEM132B-GABAAR complex as a major alcohol target in the brain, and provide mechanistic insights into alcohol-related behaviors.

Development and Performance Evaluation of a New Conformance Control Agent Gel.

How to effectively plug the multi-scale fractured water channeling has always been the key to achieving efficient water flooding of fractured low-permeability oil reservoirs. In this paper, a new type of supramolecular-polymer composite gel is developed, which is suitable for plugging multi-scale fractured water channeling. The supramolecular-polymer composite gel is composed of a polymer (such as polyacrylamide), cross-linking agent (such as polyethyleneimine), supramolecular gel factor (such as cyclodextrin) and polarity regulator (such as ethyl alcohol). The mass fraction of polyacrylamide, polyethyleneimine, cyclodextrin and ethyl alcohol are 0.15%, 0.2%, 1% and 0.2%, respectively. At the initial state, the viscosity of the composite gelant system is less than 20 mPa·s. It has good injection performance in micro-scale fractures and can enter the deep part of a fractured reservoir. At 40 °C, the composite gelant system can form a gel with a double network structure after gelation. One of the networks is formed by the covalent interaction between polyacrylamide and polyethyleneimine, the other network is formed by the self-assembly of cyclodextrins under the action of the ethyl alcohol. The comprehensive performance of the composite gel is greatly improved. The strength of the composite gel is >5 × 104 mPa·s, and it has good plugging strength in large-scale fractures. The composite gel can be used as a conformance control agent for fractured low-permeability oilfields.

Gender-responsive health promotion for women: regulating the sociopolitical landscape of alcohol product marketing

Abstract This perspective piece calls for health promotion action to regulate alcohol product marketing targeting women and create environments where it is possible to mitigate the harms of alcohol and protect women’s health. Drawing on the Global Alcohol Action Plan in the context of the Australian National Women’s Health Strategy 2020–30, we consider critical actions for gender-responsive health promotion to protect women from the ways alcohol companies market their products utilizing women’s gendered social roles and entrenched stereotypes. We show how these subtle yet powerful gendered approaches to alcohol marketing have the potential for harm yet are not covered by the current mechanisms of the self-regulated Alcohol Beverages Advertising Code. We draw on the World Health Organization’s 2024 Framework on Gender-Responsive Approaches to the Acceptability Availability and Affordability of Alcohol and make a call to regulate alcohol marketing targeting women.

Mechanism Actions of Coniferyl Alcohol in Improving Cardiac Dysfunction in Renovascular Hypertension Studied by Experimental Verification and Network Pharmacology.

Renovascular hypertension (RH), a secondary hypertension, can significantly impact heart health, resulting in heart damage and dysfunction, thereby elevating the risk of cardiovascular diseases. Coniferol (CA), which has vascular relaxation properties, is expected to be able to treat hypertension-related diseases. However, its potential effects on cardiac function after RH remain unclear. In this study, in combination with network pharmacology, the antihypertensive and cardioprotective effects of CA in a two-kidney, one-clip (2K1C) mice model and its ability to mitigate angiotensin II (Ang II)-induced hypertrophy in H9C2 cells were investigated. The findings revealed that CA effectively reduced blood pressure, myocardial tissue damage, and inflammation after RH. The possible targets of CA for RH treatment were screened by network pharmacology. The interleukin-17 (IL-17) and tumor necrosis factor (TNF) signaling pathways were identified using a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The inflammatory response was identified using a Gene Ontology (GO) enrichment analysis. Western blot analysis confirmed that CA reduced the expression of IL-17, matrix metallopeptidase 9 (MMP9), cyclooxygenase 2 (COX2), and TNF α in heart tissues and the H9C2 cells. In summary, CA inhibited cardiac inflammation and fibrohypertrophy following RH. This effect was closely linked to the expression of MMP9/COX2/TNF α/IL-17. This study sheds light on the therapeutic potential of CA for treating RH-induced myocardial hypertrophy and provides insights into its underlying mechanisms, positioning CA as a promising candidate for future drug development.

Combined effects of alcohol and lead on cerebrospinal fluid production

Currently, due to the development of industry, a high incidence of heavy metal salt poisoning is observed, especially in people with alcohol dependence. The study aims to investigate the combined effects of these pathogens on the central nervous system. The study demonstrates changes in intracranial pressure and cerebrospinal fluid production in isolated and combined poisoning of lead and ethanol based on experimental models on 10 and 40 days of exposure, 3 main groups were formed – the group of lead salts, ethanol, combined intoxication, after which the main indicators were measured. The effect of separate and combined action of alcohol and lead on cerebrospinal fluid production and haemodynamic indices in experimental animals was studied. It was found at 40-day intoxication indices remained above normal, systemic arterial pressure was 131.8 mmHg, and the rate of cerebrospinal fluid production was 0.073±0.002 ml/min. Combined 10-day combined action of alcohol and lead enhances their excitatory effect, which is characterised by an increase in systemic arterial pressure (to the level of 135.6 mmHg) and general psycho-somatic agitation, the rate of cerebrospinal fluid production was 0.077±0.008 ml/min. The 40-day co-exposure manifested mainly toxic effects of lead, as shown by a decrease in cerebrospinal fluid production of 0.049±0.001 ml/min, and a decrease in blood pressure to a level of 93.6 mmHg. The results of this study will make it possible to develop treatment protocols for patients with ethanol and heavy metal salt poisoning, especially in the field of anti-oedema therapy

Continuities and change in alcohol policy at the global level: a documentary analysis of the 2010 Global Strategy for Reducing the Harmful Use of Alcohol and the Global Alcohol Action Plan 2022–2030

BackgroundThere are only two major statements which define alcohol policy development at the global level. There has not been any comparative analysis of the details of these key texts, published in 2010 and 2022 respectively, including how far they constitute similar or evolving approaches to alcohol harm.MethodsPreparatory data collection involved examination of documents associated with the final policy statements. A thematic analysis across the two policy documents was performed to generate understanding of continuity and change based on comparative study. Study findings are interpreted in the contexts of the evolving conceptual and empirical literatures.ResultsBoth documents exhibit shared guiding principles and identify similar governance challenges, albeit with varying priority levels. There is more emphasis on the high-impact interventions on price, availability and marketing in 2022, and more stringent targets have been set for 2030 in declaring alcohol as a public health priority therein, reflecting the action-oriented nature of the Plan. The identified roles of policy actors have largely remained unchanged, albeit with greater specificity in the more recent statement, appropriately so because it is concerned with implementation. The major exception, and the key difference in the documents, regards the alcohol industry, which is perceived primarily as a threat to public health in 2022 due to commercial activities harmful to health and because policy interference has slowed progress.ConclusionsThe adoption of the Global Alcohol Action Plan 2022-30 potentially marks a pivotal moment in global alcohol policy development, though it is unclear how fully it may be implemented. Perhaps, the key advances lie in advancing the ambitions of alcohol policy and clearly identifying that the alcohol industry should not be seen as any kind of partner in public health policymaking, which will permit progress to the extent that this influences what actually happens in alcohol policy at the national level.

A growing need for advocacy skills and knowledge in promoting population health and well-being

Public health advocacy plays a crucial role in promoting and protecting the health and well-being of communities. It involves the efforts of individuals, organizations, communities, and coalitions to influence public health policies, practices, and systems to address health disparities, improve health outcomes, and create healthier environments. Advocacy strategies used in public health include raising awareness about health issues, mobilizing communities, engaging policy- and decision-makers and media, and influencing legislation. Public health advocates utilize various communication channels, such as traditional and social media, and community forums, to disseminate information and build support for their cause. They also collaborate with stakeholders, including government agencies, non-profit organizations, and community leaders, to amplify their impact. Public health advocacy has been successful in achieving significant improvements in health outcomes. Examples include the adoption and implementation of smoke-free policies, the adoption of evidence-based alcohol strategy and policy, such as the WHO Global Alcohol Action Plan (2022-2030), and many more. However, challenges exist, such as lack of advocacy knowledge and skills among public health workforce, resistance from powerful interest groups (e.g., unhealthy industries), limited resources, and the need for sustained efforts to address complex health issues. In conclusion, public health advocacy is a vital component of efforts to improve population health. It involves advocating for policies and practices that address the social determinants of health and promote health equity. Public health advocates can create positive change and contribute to healthier communities. Continued support and investment in public health advocacy are therefore essential.

Research on Phenol compounds and impact of Nootropic mixture herbal product on duration of action of Ethanol anesthesia

According to scientific literature data, chemical composition of the biologically active substances of nootropic mixture herbal product is reach. It includes various groups of biologically active substances (BASes). Phenol compounds and flavonoids are dominating BASes. Nootrops are often used for medical rehabilitation as well as for rehabilitation after craniocerebral trauma, insult, neuroinfection, neurotropic intoxication, poisoning, alcohol withdrawal syndrome, and drug withdrawal syndrome. In such a way, it is expedient to research possibilities of using of new nootropic mixture herbal product against alcohol poisoning. The phenol compounds have been determined by the HPLC-UV/VIS method basing on retention times and the UV-spectrum of standard samples. Antialcoholic activity is studied basing on impact of the nootropic mixture herbal product on duration of action of ethanol anesthesia on white outbred male rats. The fluid extract is extracted from the nootropic mixture herbal product by extracting dry raw agents on ethyl alcohol, which concentration is of 70%. Nootropic drug Piracetamisa comparator drug. 12 phenol compounds are discovered in the nootropic mixture herbal product alcohol extract. Dominating components of nootropic mixture herbal product composition are luteolin-7-glycoside (0.6322%) and rutin (0.3769%) in terms of dry raw material. The analysis of aqueous extracts has shown that there are the same 12 BASes but their contentsis much fewer. Summarized contents of phenol compounds in nootropic mixture herbal product aqueous extractions is of 0.0333%. 0.0157% of rutinis half of them in terms of dry raw material. Results of the experiment establish that the developed nootropic mixture herbal product reduced toxic action of alcohol reduces duration of action of ethanol anesthesia by 18% in comparison with that of control animals.

LY2444296, a κ-opioid receptor antagonist, selectively reduces alcohol drinking in male and female Wistar rats with a history of alcohol dependence

Alcohol use disorder (AUD) remains a major public health concern. The dynorphin (DYN)/κ-opioid receptor (KOP) system is involved in actions of alcohol, particularly its withdrawal-associated negative affective states. This study tested the ability of LY2444296, a selective, short-acting, KOP antagonist, to decrease alcohol self-administration in dependent male and female Wistar rats at 8 h abstinence. Animals were trained to orally self-administer 10% alcohol (30 min/day for 21 sessions) and were made dependent via chronic intermittent alcohol vapor exposure for 6 weeks or exposed to air (nondependent). After 6 weeks, the effect of LY2444296 (0, 3, and 10 mg/kg, p.o.) was tested on alcohol self-administration at 8 h of abstinence. A separate cohort of rats was prepared in parallel, and their somatic withdrawal signs and alcohol self-administration were measured after LY2444296 administration at 8 h, 2 weeks, and 4 weeks abstinence. LY2444296 at 3 and 10 mg/kg significantly reduced physical signs of withdrawal in dependent rats at 8 h abstinence, only. Furthermore, 3 and 10 mg/kg selectively decreased alcohol self-administration in dependent rats at only 8 h abstinence. These results highlight the DYN/KOP system in actions of alcohol during acute abstinence, suggesting KOP antagonism could be beneficial for mitigating acute withdrawal signs and, in turn, significantly reduce excessive alcohol consumption associated with AUD.

Alcohol Exposure Induces Nucleolar Stress and Apoptosis in Mouse Neural Stem Cells and Late-Term Fetal Brain.

Prenatal alcohol exposure (PAE) is a leading cause of neurodevelopmental disability through its induction of neuronal growth dysfunction through incompletely understood mechanisms. Ribosome biogenesis regulates cell cycle progression through p53 and the nucleolar cell stress response. Whether those processes are targeted by alcohol is unknown. Pregnant C57BL/6J mice received 3 g alcohol/kg daily at E8.5-E17.5. Transcriptome sequencing was performed on the E17.5 fetal cortex. Additionally, primary neural stem cells (NSCs) were isolated from the E14.5 cerebral cortex and exposed to alcohol to evaluate nucleolar stress and p53/MDM2 signaling. Alcohol suppressed KEGG pathways involving ribosome biogenesis (rRNA synthesis/processing and ribosomal proteins) and genes that are mechanistic in ribosomopathies (Polr1d, Rpl11; Rpl35; Nhp2); this was accompanied by nucleolar dissolution and p53 stabilization. In primary NSCs, alcohol reduced rRNA synthesis, caused nucleolar loss, suppressed proliferation, stabilized nuclear p53, and caused apoptosis that was prevented by dominant-negative p53 and MDM2 overexpression. Alcohol's actions were dose-dependent and rapid, and rRNA synthesis was suppressed between 30 and 60 min following alcohol exposure. The alcohol-mediated deficits in ribosomal protein expression were correlated with fetal brain weight reductions. This is the first report describing that pharmacologically relevant alcohol levels suppress ribosome biogenesis, induce nucleolar stress in neuronal populations, and involve the ribosomal/MDM2/p53 pathway to cause growth arrest and apoptosis. This represents a novel mechanism of alcohol-mediated neuronal damage.

Studies on the Inhibition Mechanism of Linalyl Alcohol against the Spoilage Microorganism Brochothrix thermosphacta.

The aim of this study was to investigate the bacterial inhibitory ability and mechanism of action of linalyl alcohol against B. thermosphacta. Linalyl alcohol causes the leakage of intracellular material by disrupting the cell wall and exposing the hydrophobic phospholipid bilayer, which binds to bacterial membrane proteins and alters their structure. In addition, linalyl alcohol causes cell membrane damage by affecting fatty acids and proteins in the cell membrane. By inhibiting the synthesis of macromolecular proteins, the normal physiological functions of the bacteria are altered. Linalyl alcohol binds to DNA in both grooved and embedded modes, affecting the normal functioning of B. thermosphacta, as demonstrated through a DNA interaction analysis.

LIVER HEALTH IS OVERLOOKED BY ALCOHOL DRINKERS IN BRAZIL.

Chronic excessive use of alcohol is an important risk factor for several health and social conditions. A cross-sectional survey, in a sample representative of the Brazilian population,was conducted to evaluate the frequency of consumption of alcoholic beverages and behaviors concerning liver diseases. Participants were prospectively interviewed using a questionnaire regarding alcohol consumption and actions toward liver health. The study accepted at most one sampling error of ±2 percentage points and considered a 95% confidence interval. One thousand nine hundred ninety-five subjects (1.048 women, mean age 44 years) from all Brazilian regions were interviewed. Most of the Brazilian subjects believe that alcohol abuse (63-87%) is the leading cause of cirrhosis and liver cancer, however, most responders (56%) had never been screened to assess liver damage related to alcohol consumption. A total of 55% of Brazilians drink alcoholic beverages. Among Brazilians who drink alcoholic beverages, 44% consume three or more drinks at a time, 11% consume more than 10 doses a day. Among those who consume 1 to 2 drinks a day, women (42%) consume more than men (32%) and more than the national average (37%). There is a high frequency of alcohol consumption, especially among young people, and individuals from lower social classes, with frequent consumption among women. Despite the knowledge of its adverse impact on liver health, less than half of the Brazilians have been evaluated at least once for liver disease. Education and prevention strategies need to be implemented to reduce theharmful use of alcohol.

GABAergic mechanisms in alcohol dependence.

The target of alcohol's effect on the central nervous system has been sought for more than 50 years in the brain's GABA system. The behavioral and emotional effects of alcohol in humans and rodents are very similar to those of barbiturates and benzodiazepines, and GABAA receptors have been shown to be one of the sites of alcohol action. The mechanisms of GABAergic inhibition have been a hotspot of research but have turned out to be complex and controversial. Genetics support the involvement of some GABAA receptor subunits in the development of alcohol dependence and in alcohol use disorders (AUD). Since the effect of alcohol on the GABAA system resembles that of a GABAergic positive modulator, it may be possible to develop GABAergic drug treatments that could substitute for alcohol. The adaptation mechanisms of the GABA system and the plasticity of the brain are a big challenge for drug development: the drugs that act on GABAA receptors developed so far also may cause adaptation and development of additional addiction. Human polymorphisms should be studied further to get insight about how they affect receptor function, expression or other factors to make reasonable predictions/hypotheses about what non-addictive interventions would help in alcohol dependence and AUD.

Commonly used anesthetics modify alcohol and (-)-trans-delta9-tetrahydrocannabinol in vivo effects on rat cerebral arterioles

BackgroundEthyl alcohol and cannabis are widely used recreational substances with distinct effects on the brain. These drugs increase accidental injuries requiring treatment under anesthesia. Moreover, alcohol and cannabis are often used in anesthetized rodents for biomedical research. Here, we compared the influence of commonly used forms of anesthesia, injectable ketamine/xylazine (KX) versus inhalant isoflurane, on alcohol- and (-)-trans-delta9-tetrahydrocannabinol (THC) effects on cerebral arteriole diameter evaluated in vivo.MethodsStudies were performed on male and female Sprague–Dawley rats subjected to intracarotid catheter placement for drug infusion, and cranial window surgery for monitoring pial arteriole diameter. Depth of anesthesia was monitored every 10–15 min by toe-pinch. Under KX, the number of toe-pinch responders was maximal after the first dose of anesthesia and diminished over time in both males and females. In contrast, the number of toe-pinch responders under isoflurane slowly raised over time, leading to increase in isoflurane percentage until deep anesthesia was re-established. Rectal temperature under KX remained stable in males while dropping in females. As expected for gaseous anesthesia, both males and females exhibited rectal temperature drops under isoflurane.ResultsInfusion of 50 mM alcohol (ethanol, EtOH) into the cerebral circulation rendered robust constriction in males under KX anesthesia, this alcohol action being significantly smaller, but still present under isoflurane anesthesia. In females, EtOH did not cause measurable changes in pial arteriole diameter regardless of the anesthetic. These findings indicate a strong sex bias with regards to EtOH induced vasoconstriction.Infusion of 42 nM THC in males and females under isoflurane tended to constrict cerebral arterioles in both males and females when compared to isovolumic infusion of THC vehicle (dimethyl sulfoxide in saline). Moreover, THC-driven changes in arteriole diameter significantly differed in magnitude depending on the anesthetic used.Simultaneous administration of 50 mM alcohol and 42 nM THC to males constricted cerebral arterioles regardless of the anesthetic used. In females, constriction by the combined drugs was also observed, with limited influence by anesthetic presence.ConclusionsWe demonstrate that two commonly used anesthetic formulations differentially influence the level of vasoconstriction caused by alcohol and THC actions in cerebral arterioles.

Progesterone activation of β1-containing BK channels involves two binding sites

Progesterone (≥1 µM) is used in recovery of cerebral ischemia, an effect likely contributed to by cerebrovascular dilation. The targets of this progesterone action are unknown. We report that micromolar (µM) progesterone activates mouse cerebrovascular myocyte BK channels; this action is lost in β1-/- mice myocytes and in lipid bilayers containing BK α subunit homomeric channels but sustained on β1/β4-containing heteromers. Progesterone binds to both regulatory subunits, involving two steroid binding sites conserved in β1-β4: high-affinity (sub-µM), which involves Trp87 in β1 loop, and low-affinity (µM) defined by TM1 Tyr32 and TM2 Trp163. Thus progesterone, but not its oxime, bridges TM1-TM2. Mutation of the high-affinity site blunts channel activation by progesterone underscoring a permissive role of the high-affinity site: progesterone binding to this site enables steroid binding at the low-affinity site, which activates the channel. In support of our model, cerebrovascular dilation evoked by μM progesterone is lost by mutating Tyr32 or Trp163 in β1 whereas these mutations do not affect alcohol-induced cerebrovascular constriction. Furthermore, this alcohol action is effectively counteracted both in vitro and in vivo by progesterone but not by its oxime.

Practical Aspects of Clinical Manifestations, Pathogenesis and Therapy of Alcoholic Liver Disease and Non-alcoholic Fatty Liver Disease: Expert Opinion

Aim: to present the results of an expert discussion of modern aspects of the clinical manifestations, pathogenesis and treatment of alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD).Key points. ALD and NAFLD are characterized by high prevalence and have a significant impact on public health. For the diagnosis of liver pathology, it is important to determine the stage of fibrosis and the severity of the exacerbation of the disease. In the treatment of ALD, it is recommended to achieve abstinence, proper nutrition, the appointment of B vitamins, drugs with cytoprotective activity. In severe hepatitis, corticosteroids may be prescribed. In the treatment of NAFLD, diet and lifestyle modification, weight loss, the use of insulin sensitizers, vitamin E, statins (in the presence of hyperlipidemia) and drugs with metabolic activity are effective.Currently, a point of view is being actively expressed about the synergism of the action of alcohol and the metabolic syndrome on the development of fibrosis, cirrhosis, and hepatocellular carcinoma. The current international consensus recommends a change in the nomenclature of NAFLD and ALD and proposes the terms “metabolically associated steatotic liver disease” and “metabolically associated alcoholic liver disease”.Conclusion. The closeness of the clinical manifestations and pathogenesis of NAFLD and ALD justifies attention to drugs with metabolic activity, which are recommended by the Russian Gastroenterological Association and Russian Scientific Liver Society for the treatment of these diseases. The experts support the suggestion to quantify alcohol consumption in patients with NAFLD in order to change the management of patients, if necessary.

Dual-color miniscope imaging of microvessels and neuronal activity in the hippocampus CA1 region of freely moving mice following alcohol administration.

Moderate-to-heavy episodic ("binge") drinking is the most common form of alcohol consumption in the United States. Alcohol at binge drinking concentrations reduces brain artery diameter in vivo and in vitro in many species including rats, mice, and humans. Despite the critical role played by brain vessels in maintaining neuronal function, there is a shortage of methodologies to simultaneously assess neuron and blood vessel function in deep brain regions. Here, we investigate cerebrovascular responses to ethanol by choosing a deep brain region that is implicated in alcohol disruption of brain function, the hippocampal CA1, and describe the process for obtaining simultaneous imaging of pyramidal neuron activity and diameter of nearby microvessels in freely moving mice via a dual-color miniscope. Recordings of neurovascular events were performed upon intraperitoneal injection of saline versus 3 g/kg ethanol in the same mouse. In male mice, ethanol mildly increased the amplitude of calcium signals while robustly decreasing their frequency. Simultaneously, ethanol decreased microvessel diameter. In females, ethanol did not change the amplitude or frequency of calcium signals from CA1 neurons but decreased microvessel diameter. A linear regression of ethanol-induced reduction in number of active neurons and microvessel constriction revealed a positive correlation (R = 0.981) in females. Together, these data demonstrate the feasibility of simultaneously evaluating neuronal and vascular components of alcohol actions in a deep brain area in freely moving mice, as well as the sexual dimorphism of hippocampal neurovascular responses to alcohol.

Home cage voluntary alcohol consumption increases binge drinking without affecting abstinence-related depressive-like behaviors or operant responding in crossed high alcohol-preferring mice (cHAPs)

Chronic alcohol consumption can lead to tolerance and escalation of drinking in humans and animals, but mechanisms underlying these changes are not fully characterized. Preclinical models can delineate which mechanisms are involved. The chronic intermittent ethanol exposure (CIE) procedure uses forced exposure to vaporized alcohol that elicits withdrawal and increased responding for alcohol in operant tasks in C57BL/6J inbred mice. Chronic two-bottle choice (2BC) drinking in the same strain elicits abstinent-related depression-like behavior, suggestive of allostatic changes. Selected lines such as crossed High Alcohol Preferring (cHAP) mice voluntarily drink to blood alcohol concentrations comparable to those attained in CIE and could be used to assess how alcohol affects these same endpoints without the confounds of involuntary vapor inhalation. In three experiments, we assess how 2BC drinking in cHAP mice affects abstinence-related depressive- and anxiety-like behavior, operant responding for alcohol, and binge consumption using drinking-in-the-dark (DID). We hypothesized that cHAPs with home-cage drinking experience would exhibit more depressive behavior after abstinence, increased responding for alcohol in the operant box, and increased DID intake. Of these, a drinking history increased DID intake in female cHAPs only and increased sucrose preference and intake following abstinence, but had no effects on operant responding or NSFT latency and FST immobility following forced abstinence. These results are consistent with recent findings using slice electrophysiology showing tolerance to alcohol's actions on the dorsolateral striatum following 2BC drinking in female, but not male cHAP mice. Overall, these data suggest that cHAPs may require procedures allowing rapid intoxication, such as DID, to demonstrate changes in alcohol's rewarding effects.

Influencing the global governance of alcohol: Alcohol industry views in submissions to the WHO consultation for the Alcohol Action Plan 2022-2030.

In 2020, the Secretariat of the World Health Organization (WHO) conducted an open consultation, with public submissions, for the purpose of developing an Alcohol Action Plan to "strengthen implementation" of the WHO's 2010 Global Strategy to Reduce the Harmful Use of Alcohol. The consultation process and public submissions provided an opportunity to critically examine alcohol industry perspectives and arguments in relation to the global governance of alcohol. 48 alcohol industry submissions to the WHO's 2020 consultation were included for analysis. Directed content analysis was used to examine the policy positions and arguments made by industry actors. Thematic analysis was employed to further explore the framing of industry arguments. In framing their arguments, alcohol industry actors positioned themselves as important stakeholders in policy debates; differentiated "normal" drinking from consumption that merits intervention; argued that alcohol policy should be made at the national, rather than global, level; and supported industry self-regulation or co-regulation rather than cost-effective public health measures to prevent harms from alcohol. The alcohol industry's submissions to the WHO's 2020 consultation could be seen as efforts to stymie improvements in the global governance of alcohol, and repeats several framing strategies that the industry has used in other forums, both national and global. However, their arguments appear to have had little traction in the creation of the Alcohol Action Plan. Changes from the Working Document to the adopted Action Plan show little acceptance by WHO of industry arguments.

Activity of volatiles induced by microbes and natural plants stifled the growth of Pythium aphanidermatum - the damping off in Tomato

BackgroundVolatilomes from natural plants and microbes imparts diverse antifungal properties to suppress the growth of plant pathogens and therefore can be a suitable alternative of chemical fungicides. The present experiment was to study effect of volatiles produced by natural plants and microbes on the fungal growth of Pythium aphanidermatum, which is a tomato seedling pathogen.ResultsIsolate of P. aphanidermatum, causing damping off in tomato were isolated and incubated at 25 ± 2 °C. The isolate was tested for the anti-oomycetes activities of volatiles in vitro. The volatiles produced by the leaves of Mentha spicata and Cymbopogon citratus showed the maximum inhibitory effect of 45.56 and 24.70 percent, respectively on the mycelial growth of P. aphanidermatum, whereas, the pathogen was not inhibited on exposure to the volatiles of macro-basidiomycetes fungi. The volatiles of T. asperellum showed the maximum inhibitory effect of 69.26 percent against P. aphanidermatum. The study also included the identification of Volatile Organic Compounds (VOCs) involved in the suppression of pathogens by Headspace Gas Chromatography Mass Spectrometry (HS GCMS). The results revealed the production of carvone by the leaves of M. spicata; citronellol and geraniol by C. citratus; isopentyl alcohol and limonene by T. asperellum with increased peak area percentage and these compounds possessed antifungal properties. The vaporous action of isopentyl alcohol completely suppressed the mycelial growth of P. aphanidermatum, which is highly correlated to the T. asperellum extract on pathogenic growth. While the compounds, carvone, and citronellol showed the maximum inhibitory effect of 89.02 and 85.49 percent, respectively when used at 500 ppm and also altered the sporulation behavior of P. aphanidermatum.ConclusionResults showed that volatiles of M. spicata and T. asperellum have anti-oomycetes action on pathogenic growth leading to a distortion of sporulation of P. aphanidermatum. High antifungal properties make VOCs suitable for incorporation as a new integrated plant disease management programs.