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  1. Honokiol activates the LKB1–AMPK signaling pathway and attenuates the lipid accumulation in hepatocytes

    SciTech Connect

    Seo, Min Suk; Kim, Jung Hwan; Kim, Hye Jung

    Honokiol is a bioactive neolignan compound isolated from the species of Magnolia. This study was designed to elucidate the cellular mechanism by which honokiol alleviates the development of non-alcoholic steatosis. HepG2 cells were treated with honokiol for 1 h, and then exposed to 1 mM free fatty acid (FFA) for 24 h to simulate non-alcoholic steatosis in vitro. C57BL/6 mice were fed with a high-fat diet for 28 days, and honokiol (10 mg/kg/day) was daily treated. Honokiol concentration-dependently attenuated intracellular fat overloading and triglyceride (TG) accumulation in FFA-exposed HepG2 cells. These effects were blocked by pretreatment with an AMP-activated proteinmore » kinase (AMPK) inhibitor. Honokiol significantly inhibited sterol regulatory element-binding protein-1c (SREBP-1c) maturation and the induction of lipogenic proteins, stearoyl-CoA desaturase-1 (SCD-1) and fatty acid synthase (FAS) in FFA-exposed HepG2 cells, but these effects were blocked by pretreatment of an AMPK inhibitor. Honokiol induced AMPK phosphorylation and subsequent acetyl-CoA carboxylase (ACC) phosphorylation, which were inhibited by genetic deletion of liver kinase B1 (LKB1). Honokiol stimulated LKB1 phosphorylation, and genetic deletion of LKB1 blocked the effect of honokiol on SREBP-1c maturation and the induction of SCD-1 and FAS proteins in FFA-exposed HepG2 cells. Honokiol attenuated the increases in hepatic TG and lipogenic protein levels and fat accumulation in the mice fed with high-fat diet, while significantly induced LKB1 and AMPK phosphorylation. Taken together, our findings suggest that honokiol has an anti-lipogenic effect in hepatocytes, and this effect may be mediated by the LKB1–AMPK signaling pathway, which induces ACC phosphorylation and inhibits SREBP-1c maturation in hepatocytes. - Highlights: • Honokiol attenuates lipid accumulation induced by free fatty acid in hepatocyte. • Honokiol inhibits the increase in lipogenic enzyme levels induced by free

  2. Honokiol induces autophagic cell death in malignant glioma through reactive oxygen species-mediated regulation of the p53/PI3K/Akt/mTOR signaling pathway

    SciTech Connect

    Lin, Chien-Ju

    Honokiol, an active constituent extracted from the bark of Magnolia officinalis, possesses anticancer effects. Apoptosis is classified as type I programmed cell death, while autophagy is type II programmed cell death. We previously proved that honokiol induces cell cycle arrest and apoptosis of U87 MG glioma cells. Subsequently in this study, we evaluated the effect of honokiol on autophagy of glioma cells and examined the molecular mechanisms. Administration of honokiol to mice with an intracranial glioma increased expressions of cleaved caspase 3 and light chain 3 (LC3)-II. Exposure of U87 MG cells to honokiol also induced autophagy in concentration- andmore » time-dependent manners. Results from the addition of 3-methyladenine, an autophagy inhibitor, and rapamycin, an autophagy inducer confirmed that honokiol-induced autophagy contributed to cell death. Honokiol decreased protein levels of PI3K, phosphorylated (p)-Akt, and p-mammalian target of rapamycin (mTOR) in vitro and in vivo. Pretreatment with a p53 inhibitor or transfection with p53 small interfering (si)RNA suppressed honokiol-induced autophagy by reversing downregulation of p-Akt and p-mTOR expressions. In addition, honokiol caused generation of reactive oxygen species (ROS), which was suppressed by the antioxidant, vitamin C. Vitamin C also inhibited honokiol-induced autophagic and apoptotic cell death. Concurrently, honokiol-induced alterations in levels of p-p53, p53, p-Akt, and p-mTOR were attenuated following vitamin C administration. Taken together, our data indicated that honokiol induced ROS-mediated autophagic cell death through regulating the p53/PI3K/Akt/mTOR signaling pathway. - Highlights: • Exposure of mice with intracranial gliomas to honokiol induces cell apoptosis and autophagy. • Honokiol triggers autophagy of human glioma cells via the PISK/AKT/mTOR signaling pathway. • P53 induces autophagy via regulating the AKT/mTOR pathway in honokiol-treated glioma cells. • ROS

  3. Reversible blindness associated with alcoholic ketoacidosis.

    PubMed

    Yanagawa, Youichi; Kiyozumi, Teturou; Hatanaka, Kousuke; Itoh, Toshitaka; Sakamoto, Toshihisa; Okada, Yoshiaki

    2004-04-01

    To report a case of reversible blindness associated with severe alcoholic ketoacidosis. Observational case report. A 44-year-old male presented with gradual bilateral blindness that developed within a 24-hour period. He suffered from ethanol-induced severe ketoacidosis and shock and was resuscitated with epinephrine and sodium bicarbonate. The treatment of acidosis led to a rapid resolution of the patient's blindness. It is important to understand the role of severe acidosis as the sole causative factor of reversible bilateral blindness.

  4. Honokiol bis-dichloroacetate (Honokiol DCA) demonstrates activity in vemurafenib-resistant melanoma in vivo.

    PubMed

    Bonner, Michael Y; Karlsson, Isabella; Rodolfo, Monica; Arnold, Rebecca S; Vergani, Elisabetta; Arbiser, Jack L

    2016-03-15

    The majority of human melanomas bears BRAF mutations and thus is treated with inhibitors of BRAF, such as vemurafenib. While patients with BRAF mutations often demonstrate an initial dramatic response to vemurafenib, relapse is extremely common. Thus, novel agents are needed for the treatment of these aggressive melanomas. Honokiol is a small molecule compound derived from Magnolia grandiflora that has activity against solid tumors and hematopoietic neoplasms. In order to increase the lipophilicity of honokiol, we have synthesized honokiol DCA, the dichloroacetate ester of honokiol. In addition, we synthesized a novel fluorinated honokiol analog, bis-trifluoromethyl-bis-(4-hydroxy-3-allylphenyl) methane (hexafluoro). Both compounds exhibited activity against A375 melanoma in vivo, but honokiol DCA was more active. Gene arrays comparing treated with vehicle control tumors demonstrated induction of the respiratory enzyme succinate dehydrogenase B (SDHB) by treatment, suggesting that our honokiol analogs induce respiration in vivo. We then examined its effect against a pair of melanomas, LM36 and LM36R, in which LM36R differs from LM36 in that LM36R has acquired vemurafenib resistance. Honokiol DCA demonstrated in vivo activity against LM36R (vemurafenib resistant) but not against parental LM36. Honokiol DCA and hexafluoro inhibited the phosphorylation of DRP1, thus stimulating a phenotype suggestive of respiration through mitochondrial normalization. Honokiol DCA may act in vemurafenib resistant melanomas to increase both respiration and reactive oxygen generation, leading to activity against aggressive melanoma in vivo.

  5. Reversible catalytic dehydrogenation of alcohols for energy storage

    PubMed Central

    Bonitatibus, Peter J.; Chakraborty, Sumit; Doherty, Mark D.; Siclovan, Oltea; Jones, William D.; Soloveichik, Grigorii L.

    2015-01-01

    Reversibility of a dehydrogenation/hydrogenation catalytic reaction has been an elusive target for homogeneous catalysis. In this report, reversible acceptorless dehydrogenation of secondary alcohols and diols on iron pincer complexes and reversible oxidative dehydrogenation of primary alcohols/reduction of aldehydes with separate transfer of protons and electrons on iridium complexes are shown. This reactivity suggests a strategy for the development of reversible fuel cell electrocatalysts for partial oxidation (dehydrogenation) of hydroxyl-containing fuels. PMID:25588879

  6. Reversible catalytic dehydrogenation of alcohols for energy storage

    DOE PAGES

    Bonitatibus, Jr., Peter J.; Chakraborty, Sumit; Doherty, Mark D.; ...

    2015-01-14

    Reversibility of a dehydrogenation/hydrogenation catalytic reaction has been an elusive target for homogeneous catalysis. In this paper, reversible acceptorless dehydrogenation of secondary alcohols and diols on iron pincer complexes and reversible oxidative dehydrogenation of primary alcohols/reduction of aldehydes with separate transfer of protons and electrons on iridium complexes are shown. Finally, this reactivity suggests a strategy for the development of reversible fuel cell electrocatalysts for partial oxidation (dehydrogenation) of hydroxyl-containing fuels.

  7. Reversible Inhibition of Spore Germination by Alcohols 1

    PubMed Central

    Trujillo, Ralph; Laible, Nancy

    1970-01-01

    Low levels of alcohols have been found to inhibit the process of spore germination. The extent of germination is dependent upon the concentration of alcohol present in the germinating medium. This inhibition is reversible since removal of the alcohol from the spore environment allows germination to proceed. PMID:4993360

  8. Safety and Toxicology of Magnolol and Honokiol.

    PubMed

    Sarrica, Andrea; Kirika, Natalja; Romeo, Margherita; Salmona, Mario; Diomede, Luisa

    2018-06-20

    Magnolia officinalis and Magnolia obovata bark extracts have been used for thousands of years in Chinese and Japanese traditional medicines and are still widely employed as herbal preparations for their sedative, antioxidant, anti-inflammatory, antibiotic, and antispastic effects. Neolignans, particularly magnolol and honokiol, are the main substances responsible for the beneficial properties of the magnolia bark extract (MBE). The content of magnolol and honokiol in MBE depends on different factors, including the Magnolia plant species, the area of origin, the part of the plant employed, and the method used to prepare the extract. The biological and pharmacological activities of magnolol and honokiol have been extensively investigated. Here we review the safety and toxicological properties of magnolol and honokiol as pure substances or as components of concentrated MBE, including the potential side-effects in humans after oral intake. In vitro and in vivo genotoxicity studies indicated that concentrated MBE has no mutagenic and genotoxic potential, while a subchronic study performed according to OECD (Organisation for Economic Co-operation and Development) guidelines established a no adverse effect level for concentrated MBE > 240 mg/kg b.w/d. Similar to other dietary polyphenols, magnolol and honokiol are subject to glucuronidation, and despite a relatively quick clearance, an interaction with pharmaceutical active principles or other herbal constituents cannot be excluded. However, intervention trials employing concentrated MBE for up to 1 y did not report adverse effects. In conclusion, over the recent years different food safety authorities evaluated magnolol and honokiol and considered them safe. Georg Thieme Verlag KG Stuttgart · New York.

  9. Alcohol consumption stimulates early steps in reverse cholesterol transport.

    PubMed

    van der Gaag, M S; van Tol, A; Vermunt, S H; Scheek, L M; Schaafsma, G; Hendriks, H F

    2001-12-01

    Alcohol consumption is associated with increased HDL cholesterol levels, which may indicate stimulated reverse cholesterol transport. The mechanism is, however, not known. The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol pathway: cellular cholesterol efflux and plasma cholesterol esterification. Eleven healthy middle-aged men consumed four glasses (40 g of alcohol) of red wine, beer, spirits (Dutch gin), or carbonated mineral water (control) daily with evening dinner, for 3 weeks, according to a 4 x 4 Latin square design. After 3 weeks of alcohol consumption the plasma ex vivo cholesterol efflux capacity, measured with Fu5AH cells, was raised by 6.2% (P < 0.0001) and did not differ between the alcoholic beverages. Plasma cholesterol esterification was increased by 10.8% after alcohol (P = 0.008). Changes were statistically significant after beer and spirits, but not after red wine consumption (P = 0.16). HDL lipids changed after alcohol consumption; HDL total cholesterol, HDL cholesteryl ester, HDL free cholesterol, HDL phospholipids and plasma apolipoprotein A-I all increased (P < 0.01). In conclusion, alcohol consumption stimulates cellular cholesterol efflux and its esterification in plasma. These effects were mostly independent of the kind of alcoholic beverage

  10. Effects of Magnolol and Honokiol on Adhesion, Yeast-Hyphal Transition, and Formation of Biofilm by Candida albicans

    PubMed Central

    Sun, Lingmei; Liao, Kai; Wang, Dayong

    2015-01-01

    Background The first step in infection by Candida albicans is adhesion to host cells or implanted medical devices and this followed by hyphal growth and biofilm formation. Yeast-to-hyphal transition has long been identified as a key factor in fungal virulence. Following biofilm formation, C. albicans is usually less sensitive or insensitive to antifungals. Therefore, development of new antifungals with inhibitory action on adhesion, yeast-hyphal transition and biofilm formation by C. albicans is very necessary. Methods The effects of magnolol and honokiol on hypha growth were investigated using different induction media. Their inhibitory effects were determined using the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5- carboxanilide assay, and biofilm thickness and viability were observed by a confocal scanning laser microscope. Mammalian cells were used in adhesion assays. Genes related to hyphae development and cell adhesions were analyzed by real-time reverse transcription-polymerase chain reaction. The exogenous cyclic adenosine monophosphate was used to determine the mechanisms of action of magnolol and honokiol. Caenorhabditis elegans was used as an in vivo model to estimate the antifungal activities of magnolol and honokiol. Results and conclusions Magnolol and honokiol inhibited adhesion, the transition from yeast to hypha, and biofilm formation by C. albicans through the Ras1-cAMP-Efg1 pathway. Moreover, magnolol and honokiol prolonged the survival of nematodes infected by C. albicans. Magnolol and honokiol have potential inhibitory effects against biofilm formation by C. albicans. General Significance This study provides useful information towards the development of new strategies to reduce the incidence of C. albicans biofilm-associated infection. PMID:25710475

  11. Effects of magnolol and honokiol on adhesion, yeast-hyphal transition, and formation of biofilm by Candida albicans.

    PubMed

    Sun, Lingmei; Liao, Kai; Wang, Dayong

    2015-01-01

    The first step in infection by Candida albicans is adhesion to host cells or implanted medical devices and this followed by hyphal growth and biofilm formation. Yeast-to-hyphal transition has long been identified as a key factor in fungal virulence. Following biofilm formation, C. albicans is usually less sensitive or insensitive to antifungals. Therefore, development of new antifungals with inhibitory action on adhesion, yeast-hyphal transition and biofilm formation by C. albicans is very necessary. The effects of magnolol and honokiol on hypha growth were investigated using different induction media. Their inhibitory effects were determined using the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5- carboxanilide assay, and biofilm thickness and viability were observed by a confocal scanning laser microscope. Mammalian cells were used in adhesion assays. Genes related to hyphae development and cell adhesions were analyzed by real-time reverse transcription-polymerase chain reaction. The exogenous cyclic adenosine monophosphate was used to determine the mechanisms of action of magnolol and honokiol. Caenorhabditis elegans was used as an in vivo model to estimate the antifungal activities of magnolol and honokiol. Magnolol and honokiol inhibited adhesion, the transition from yeast to hypha, and biofilm formation by C. albicans through the Ras1-cAMP-Efg1 pathway. Moreover, magnolol and honokiol prolonged the survival of nematodes infected by C. albicans. Magnolol and honokiol have potential inhibitory effects against biofilm formation by C. albicans. This study provides useful information towards the development of new strategies to reduce the incidence of C. albicans biofilm-associated infection.

  12. Honokiol confers immunogenicity by dictating calreticulin exposure, activating ER stress and inhibiting epithelial-to-mesenchymal transition.

    PubMed

    Liu, Shing-Hwa; Lee, Wen-Jane; Lai, De-Wei; Wu, Sheng-Mao; Liu, Chia-Yu; Tien, Hsing-Ru; Chiu, Chien-Shan; Peng, Yen-Chun; Jan, Yee-Jee; Chao, Te-Hsin; Pan, Hung-Chuan; Sheu, Meei-Ling

    2015-04-01

    Peritoneal dissemination is a major clinical obstacle in gastrointestinal cancer therapy, and it accounts for the majority of cancer-related mortality. Calreticulin (CRT) is over-expressed in gastric tumors and has been linked to poor prognosis. In this study, immunohistochemistry studies revealed that the up-regulation of CRT was associated with lymph node and distant metastasis in patients with gastric cancer specimens. CRT was significantly down-regulated in highly metastatic gastric cancer cell lines and metastatic animal by Honokiol-treated. Small RNA interference blocking CRT by siRNA-CRT was translocated to the cells in the early immunogenic response to Honokiol. Honokiol activated endoplasmic reticulum (ER) stress and down-regulated peroxisome proliferator-activated receptor-γ (PPARγ) activity resulting in PPARγ and CRT degradation through calpain-II activity, which could be reversed by siRNA-calpain-II. The Calpain-II/PPARγ/CRT axis and interaction evoked by Honokiol could be blocked by gene silencing or pharmacological agents. Both transforming growth factor (TGF)-β1 and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced cell migration, invasion and reciprocal down-regulation of epithelial marker E-cadherin, which could be abrogated by siRNA-CRT. Moreover, Honokiol significantly suppressed MNNG-induced gastrointestinal tumor growth and over-expression of CRT in mice. Knockdown CRT in gastric cancer cells was found to effectively reduce growth ability and metastasis in vivo. The present study provides insight into the specific biological behavior of CRT in epithelial-to-mesenchymal transition (EMT) and metastasis. Taken together, our results suggest that the therapeutic inhibition of CRT by Honokiol suppresses both gastric tumor growth and peritoneal dissemination by dictating early translocation of CRT in immunogenic cell death, activating ER stress, and blocking EMT. Copyright © 2015 Federation of European Biochemical Societies. Published by

  13. Magnolol and honokiol from Magnolia officinalis enhanced antiviral immune responses against grass carp reovirus in Ctenopharyngodon idella kidney cells.

    PubMed

    Chen, Xiaohui; Hu, Yang; Shan, Lipeng; Yu, Xiaobo; Hao, Kai; Wang, Gao-Xue

    2017-04-01

    Medicinal plants have been widely used for a long history. Exploration of pharmacologically active compounds from medicinal plants present a broad prevalent of application. By examining viral mRNA expression in GCRV-infected Ctenopharyngodon idella kidney (CIK) cells treated with thirty kinds of plant extracts, we identified Magnolia officinalis Rehd et Wils. was able to preferably suppress viral replication. Further studies demonstrated that the main ingredients of magnolia bark, namely, magnolol and honokiol presented protective pharmacological function when treated GCRV-infected CIK cells with a concentration of 2.00 μg/ml and 1.25 μg/ml, respectively. Furthermore, reverse transcript quantitative polymerase chain reaction (RT-qPCR) and western blot showed that both magnolol and honokiol were efficient to restrain the replication of GCRV in CIK cells at non-toxic concentration (2.51 ± 0.51 μg/ml for magnolol, and 3.18 ± 0.61 μg/ml for honokiol). Moreover, it was found that magnolol and honokiol promoted the expression of immune-related genes. Magnolol obviously significantly increased the expression of interferon (IFN) regulatory factor (IRF)7 rather than that of IRF3 in the GCRV-infected cells, leading to the activation of type I IFN (IFN-I). Simultaneously, magnolol drastically facilitated the expression of interleukin (IL)-1β, but failed to induce the molecules in nuclear factor (NF)-κB pathways. Differently, honokiol strikingly motivated not only the expression of IL-1β, but also those of tumor necrosis factor α (TNFα) and NF-κB. Interestingly, though honokiol motivated the expression of IFN-β promoter stimulator 1 (IPS-1), IRF3 and IRF7, it failed to up-regulate the expression of IFN-I, indicating that honokiol enhanced the host innate antiviral response to GCRV infection via NF-κB pathways. Collectively, the present study revealed that magnolol and honokiol facilitated the expression of innate immune-related genes to strengthen the

  14. Honokiol trimers and dimers via biotransformation catalyzed by Momordica charantia peroxidase: novel and potent α-glucosidase inhibitors.

    PubMed

    He, Ye; Wang, Xiao-Bing; Fan, Bo-Yi; Kong, Ling-Yi

    2014-01-15

    Ten honokiol oligomers (1-10), including four novel trimers (1-4) and four novel dimers (5-8), were obtained by means of biotransformation of honokiol catalyzed by Momordica charantia peroxidase (MCP) for the first time. Their structures were established on the basis of spectroscopic methods. The biological results demonstrated that most of the oligomers were capable of inhibiting α-glucosidase with significant abilities, which were one to two orders of magnitude more potent than the substrate, honokiol. In particular, compound 2, the honokiol trimer, displayed the greatest inhibitory activity against α-glucosidase with an IC50 value of 1.38μM. Kinetic and CD studies indicated that 2 inhibited α-glucosidase in a reversible, mixed-type manner and caused conformational changes in the secondary structure of the enzyme protein. These findings suggested that 2 might be exploited as a promising drug candidate for the treatment of diabetes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Elimination of Cancer Stem-Like Cells and Potentiation of Temozolomide Sensitivity by Honokiol in Glioblastoma Multiforme Cells

    PubMed Central

    Lai, I-Chun; Shih, Ping-Hsiao; Yao, Chih-Jung; Yeh, Chi-Tai; Wang-Peng, Jacqueline; Lui, Tai-Ngar; Chuang, Suang-En; Hu, Tsai-Shu; Lai, Tung-Yuan; Lai, Gi-Ming

    2015-01-01

    Glioblastoma multiforme (GBM) is the most common adult malignant glioma with poor prognosis due to the resistance to radiotherapy and chemotherapy, which might be critically involved in the repopulation of cancer stem cells (CSCs) after treatment. We had investigated the characteristics of cancer stem-like side population (SP) cells sorted from GBM cells, and studied the effect of Honokiol targeting on CSCs. GBM8401 SP cells possessed the stem cell markers, such as nestin, CD133 and Oct4, and the expressions of self-renewal related stemness genes, such as SMO, Notch3 and IHH (Indian Hedgehog). Honokiol inhibited the proliferation of both GBM8401 parental cells and SP cells in a dose-dependent manner, the IC50 were 5.3±0.72 and 11±1.1 μM, respectively. The proportions of SP in GBM8401 cells were diminished by Honokiol from 1.5±0.22% down to 0.3±0.02% and 0.2±0.01% at doses of 2.5 μM and 5 μM, respectively. The SP cells appeared to have higher expression of O 6-methylguanine-DNA methyltransferase (MGMT) and be more resistant to Temozolomide (TMZ). The resistance to TMZ could be only slightly reversed by MGMT inhibitor O 6-benzylguanine (O 6-BG), but markedly further enhanced by Honokiol addition. Such significant enhancement was accompanied with the higher induction of apoptosis, greater down-regulation of Notch3 as well as its downstream Hes1 expressions in SP cells. Our data indicate that Honokiol might have clinical benefits for the GBM patients who are refractory to TMZ treatment. PMID:25763821

  16. Antimicrobial activity of honokiol and magnolol isolated from Magnolia officinalis.

    PubMed

    Ho, K Y; Tsai, C C; Chen, C P; Huang, J S; Lin, C C

    2001-03-01

    The antimicrobial activity of honokiol and magnolol, the main constituents of Magnolia officinalis was investigated. The antimicrobial activity was assayed by the agar dilution method using brain heart infusion medium and the minimum inhibitory concentration (MIC) were determined for each compound using a twofold serial dilution assay. The results showed that honokiol and magnolol have a marked antimicrobial effect (MIC = 25 microg/mL) against Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Micrococcus luteus and Bacillus subtilis, but did not show antimicrobial activity (MIC > or = 100 microg/mL) for Shigella flexneii, Staphylococcus epidermidis, Enterobacter aerogenes, Proteus vulgaris, Escherichia coli and Pseudomonas aeruginosa. Our results indicate that honokiol and magnolol, although less potent than tetracycline, show a significant antimicrobial activity for periodontal pathogens. Hence we suggest that honokiol and magnolol might have the potential to be an adjunct in the treatment of periodontitis. Copyright 2001 John Wiley & Sons, Ltd.

  17. Comparative metabolism of honokiol in mouse, rat, dog, monkey, and human hepatocytes.

    PubMed

    Jeong, Hyeon-Uk; Kim, Ju-Hyun; Kong, Tae Yeon; Choi, Won Gu; Lee, Hye Suk

    2016-04-01

    Honokiol has antitumor, antioxidative, anti-inflammatory, and antithrombotic effects. Here we aimed to identify the metabolic profile of honokiol in mouse, rat, dog, monkey, and human hepatocytes and to characterize the enzymes responsible for the glucuronidation and sulfation of honokiol. Honokiol had a high hepatic extraction ratio in all five species, indicating that it was extensively metabolized. A total of 32 metabolites, including 17 common and 15 different metabolites, produced via glucuronidation, sulfation, and oxidation of honokiol allyl groups were tentatively identified using liquid chromatography-high resolution quadrupole Orbitrap mass spectrometry. Glucuronidation of honokiol to M8 (honokiol-4-glucuronide) and M9 (honokiol-2'-glucuronide) was the predominant metabolic pathway in hepatocytes of all five species; however, interspecies differences between 4- and 2'-glucuronidation of honokiol were observed. UGT1A1, 1A8, 1A9, 2B15, and 2B17 played major roles in M8 formation, whereas UGT1A7 and 1A9 played major roles in M9 formation. Human cDNA-expressed SULT1C4 played a major role in M10 formation (honokiol-2'-sulfate), whereas SULT1A1*1, 1A1*2, and 1A2 played major roles in M11 formation (honokiol-4-sulfate). In conclusion, honokiol metabolism showed interspecies differences.

  18. Honokiol exerts dual effects on browning and apoptosis of adipocytes.

    PubMed

    Lone, Jameel; Yun, Jong Won

    2017-12-01

    Induction of brown adipocyte-like phenotype (browning) in white adipocytes and promotion of apoptosis by dietary and pharmacological compounds is considered a novel strategy against obesity. Here, we show that honokiol exerts dual modulatory effects on adipocytes via induction of browning in 3T3-L1 white adipocytes and apoptosis as well as activation of HIB1B brown adipocytes combined with inhibition of apoptosis. Honokiol-induced browning and apoptosis were investigated by determining expression levels of brown adipocyte-specific genes and proteins by RT-PCR and immunoblot analysis, respectively. Apoptotic data were validated by immunofluorescence and ROS levels were measured by FACS analysis. Honokiol treatment induced browning by elevating expression levels of brown adipocyte-specific genes such as Cidea, Cox8, Fgf21, Pgc-1α, and Ucp1. Honokiol promoted apoptosis of 3T3-L1 white adipocytes and inhibited apoptosis of HIB1B brown adipocytes via opposite regulation of the pro-apoptotic protein BAX and anti-apoptotic protein Bcl-2. Honokiol also significantly increased protein expression levels of ACOX1, CPT1, p-HSL, and p-PLIN and reduced ROS levels, suggesting its possible role in fat oxidation and lipid catabolism. Honokiol-induced browning could be mediated by activation of ERK, as inhibition of ERK by FR180204 abolished expression of PGC-1α and UCP1. Our findings suggest that honokiol exhibits a modulatory role in adipocytes via induction of browning and apoptosis in white adipocytes, promotion of catabolic lipid metabolism, as well as activation and inhibition of apoptosis in HIB1B brown adipocytes, thereby exhibiting therapeutic potential against obesity. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  19. Honokiol protects pancreatic β cell against high glucose and intermittent hypoxia-induced injury by activating Nrf2/ARE pathway in vitro and in vivo.

    PubMed

    Li, Chen-Guang; Ni, Chang-Lin; Yang, Min; Tang, Yun-Zhao; Li, Zhu; Zhu, Yan-Juan; Jiang, Zhen-Huan; Sun, Bei; Li, Chun-Jun

    2018-01-01

    Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with glucose intolerance, insulin resistance and type 2 diabetes mellitus (T2DM). Although several studies have revealed that intermittent hypoxia (IH) in OSAHS may further aggravate pancreatic β cell damage and promote the evolution of type 2 diabetes (T2DM) by increasing oxidative stress, the underlying mechanisms are unclear. Honokiol, a potent radical scavenger, has been demonstrated to ameliorate oxidative stress in many cases. The present study aimed to explore the potential mechanism of IH and diabetes synergistically damage and destruct the pancreatic β cell, examine the effects of honokiol on ameliorating pancreatic β cell injury in this context and explore the mechanism of such effects. High glucose (HG) cultured INS-1 cells were exposed to 50 μM of honokiol for 24, 48 and 72 h with or without IH intervention. T2DM rats were treated with honokiol and exposed to 80 s of IH followed by 160 s of normoxia for 8 weeks. The cell proliferation, apoptosis and oxidative stress were measured. Blood glucose, insulin, glucagon and HOMA-IR (Homeostasis model assessment -insulin resistence) were also detected, and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were detected by immunofluorescence staining and western blotting. Honokiol can reduce oxidative stress, cytotoxicity and apoptosis in the INS-1 cells of rats receiving HG treatment or both HG and IH treatment. IH can further aggravate pancreas dysfunction, cause a marked elevation in fasting blood glucose, glucagon, HOMA-IR and oxidative stress levels in DM rats. In addition, honokiol can effectively activate the Nrf2/ARE pathway and reverse this pancreatic dysfunction in vivo and in vitro. These findings indicate that honokiol acts as a potent ROS scavenger via Nrf2/ARE pathway and effectively attenuates oxidative stress and improves pancreatic β cell function of DM rats under IH

  20. [Alcoholic ketoacidosis and reversible neurological complications due to hypophosphataemia].

    PubMed

    Fernández López, Ma T; García Bargo, Ma D; Rivero Luis, Ma T; Álvarez Vázquez, P; Saenz Fernández, C A; Mato Mato, J A

    2012-01-01

    A 57-year-old man with chronic alcoholism was admitted to our hospital due to disturbance of consciousness and polyradiculitis. Laboratory examination revealed metabolic acidosis, hypokalemia and hypophosphataemia. Alcoholic ketoacidosis is a common disorder in alcoholic patients. All patients present with a history of heavy alcohol misuse, preceding a bout of particularly excesive intake, which had been terminated by nausea, vomiting and abdominal pain. The most important laboratory results are: normal or low glucose level, metabolic acidosis with a raised anion GAP, low or absent blood alcohol level and urinary ketones. The greatest threats to patients are: hypovolemia, hypokaliemia, hypoglucemia and acidosis. Alcohol abuse may result in a wide range of electrolyte and acid-base disorders including hypophosphataemia, hypomagnesemia, hypocalcemia, hypokalemia, metabolic acidosis and respiratory alkalosis. Disturbance of consciousness in alcoholic patients is observed in several disorders, such drunkenness, Wernicke encephalopathy, alcohol withdrawal syndrome, central pontine myelinolysis, hepatic encephalopathy, hypoglucemia and electrolyte disorders.

  1. Acute and sub-chronic toxicity studies of honokiol microemulsion.

    PubMed

    Zhang, Qianqian; Li, Jianguo; Zhang, Wei; An, Quan; Wen, Jianhua; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

    2015-04-01

    The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD50) was 50.5mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication. Copyright © 2015. Published by Elsevier Inc.

  2. Time and dose-response effects of honokiol on UVB-induced skin cancer development.

    PubMed

    Guillermo, Ruth F; Chilampalli, Chandeshwari; Zhang, Xiaoying; Zeman, David; Fahmy, Hesham; Dwivedi, Chandradhar

    2012-06-01

    Honokiol has shown chemopreventive effects in chemically-induced and UVB-induced skin cancer in mice. In this investigation, we assessed the time-effects of a topical low dose of honokiol (30 μg), and then the effects of different honokiol doses (30, 45, and 60 μg) on a UVB-induced skin cancer model to find an optimal dose and time for desirable chemopreventive effects. UVB radiation (30 mJ/cm(2), 5 days/week for 25 or 27 weeks) was used to induce skin carcinogenesis in SKH-1 mice. For the time-response experiment 30 μg honokiol in acetone was applied topically to the animals before the UVB exposure (30 min, 1 h, and 2 h) and after the UVB exposure (immediately, 30 min, and 1 h). Control groups were treated with acetone. For the dose-response study, animals were treated topically with acetone or honokiol (30, 45, and 60 μg) one hour before the UVB exposure. In the time-response experiment, honokiol inhibited skin tumor multiplicity by 49-58% while reducing tumor volumes by 70-89%. In the dose-response study, honokiol (30, 45, and 60 μg) significantly decreased skin tumor multiplicity by 36-78% in a dose-dependent manner, while tumor area was reduced by 76-94%. Honokiol (60 μg) significantly reduced tumor incidence by 40% as compared to control group. Honokiol applied in very low doses (30 μg) either before or after UVB radiation shows chemopreventive effects. Honokiol (30, 45, and 60 μg) prevents UVB-induced skin cancer in a dose-dependent manner. Honokiol can be an effective chemopreventive agent against skin cancer.

  3. Honokiol inhibits pathological retinal neovascularization in oxygen-induced retinopathy mouse model

    SciTech Connect

    Vavilala, Divya Teja; O’Bryhim, Bliss E.; Ponnaluri, V.K. Chaithanya

    2013-09-06

    Highlights: •Aberrant activation of HIF pathway is the underlying cause of ischemic neovascularization. •Honokiol has better therapeutic index as a HIF inhibitor than digoxin and doxorubicin. •Daily IP injection of honokiol in OIR mouse model reduced retinal neovascularization. •Honokiol also prevents vaso-obliteration, the characteristic feature of the OIR model. •Honokiol enhanced physiological revascularization of the retinal vascular plexuses. -- Abstract: Aberrant activation of the hypoxia inducible factor (HIF) pathway is the underlying cause of retinal neovascularization, one of the most common causes of blindness worldwide. The HIF pathway also plays critical roles during tumor angiogenesis and cancer stem cell transformation.more » We have recently shown that honokiol is a potent inhibitor of the HIF pathway in a number of cancer and retinal pigment epithelial cell lines. Here we evaluate the safety and efficacy of honokiol, digoxin, and doxorubicin, three recently identified HIF inhibitors from natural sources. Our studies show that honokiol has a better safety to efficacy profile as a HIF inhibitor than digoxin and doxorubicin. Further, we show for the first time that daily intraperitoneal injection of honokiol starting at postnatal day (P) 12 in an oxygen-induced retinopathy (OIR) mouse model significantly reduced retinal neovascularization at P17. Administration of honokiol also prevents the oxygen-induced central retinal vaso-obliteration, characteristic feature of the OIR model. Additionally, honokiol enhanced physiological revascularization of the retinal vascular plexuses. Since honokiol suppresses multiple pathways activated by HIF, in addition to the VEGF signaling, it may provide advantages over current treatments utilizing specific VEGF antagonists for ocular neovascular diseases and cancers.« less

  4. Dynamic Multi-Component Covalent Assembly for the Reversible Binding of Secondary Alcohols and Chirality Sensing

    PubMed Central

    You, Lei; Berman, Jeffrey S.; Anslyn, Eric V.

    2011-01-01

    Reversible covalent bonding is often employed for the creation of novel supramolecular structures, multi-component assemblies, and sensing ensembles. In spite of remarkable success of dynamic covalent systems, the reversible binding of a mono-alcohol with high strength is challenging. Here we show that a strategy of carbonyl activation and hemiaminal ether stabilization can be embodied in a four-component reversible assembly that creates a tetradentate ligand and incorporates secondary alcohols with exceptionally high affinity. Evidence is presented that the intermediate leading to binding and exchange of alcohols is an iminium ion. Further, to demonstrate the use of this assembly process we explored chirality sensing and enantiomeric excess determinations. An induced twist in the ligand by a chiral mono-ol results in large Cotton effects in the circular dichroism spectra indicative of the alcohol’s handedness. The strategy revealed in this study should prove broadly applicable for the incorporation of alcohols into supramolecular architecture construction. PMID:22109274

  5. [Pharmacokinetics of magnolol and honokiol in Weichang'an pill].

    PubMed

    Chen, Yu-Ling; Wang, Shu-Ping; Wang, Lei; Jin, Zhao-Xiang; Zhang, Jing-Ze; Chen, Hong; Gao, Wen-Yuan

    2016-05-01

    To conduct multiple-reaction monitoring(MRM) quantitative analysis with high-performance liquid chromatography coupled with mass spectrometry method, establish the quantification method of magnolol and honokiol in blood sample under negative ion mode with ibuprofen as internal standard, investigate the pharmacokinetic process of lignans constituents after oral administration of Weichang'an pill(WCA) at different doses, and provide theoretical basis to further reveal the material basis of WCA's anti-diarrhea effect. In the plasma samples, the linear relationship was good over the concentration range of 5.25 to 1 344.00 μg•L ⁻¹ for magnolol and 10.08 to 2 580.00 μg•L ⁻¹ for honokiol. The results of precision, stability, and extraction recovery tests showed that the determination method of plasma concentration for such compositions was stable and reliable. Dose-dependence was shown for magnolol and honokiol in the plasma concentration-time profile. The results indicated that the time to reach the maximum plasma concentration(Tmax) for lignanoids was 0.55-1.42 h, when the maximum plasma concentration(Cmax) could reach 996.36-2 330.96,189.87-1 469.43 μg•L ⁻¹ respectively for magnolol and honokiol. The lignanoids could be absorbed rapidly in the blood after oral administration of WAC pills, providing experimental basis to prove rapid and long-acting anti-diarrhea effect of WAC pills after oral administration. Copyright© by the Chinese Pharmaceutical Association.

  6. Combination of honokiol and magnolol inhibits hepatic steatosis through AMPK-SREBP-1 c pathway.

    PubMed

    Lee, Ju-Hee; Jung, Ji Yun; Jang, Eun Jeong; Jegal, Kyung Hwan; Moon, Soo Young; Ku, Sae Kwang; Kang, Seung Ho; Cho, Il Je; Park, Sook Jahr; Lee, Jong Rok; Zhao, Rong Jie; Kim, Sang Chan; Kim, Young Woo

    2015-04-01

    Honokiol and magnolol, as pharmacological biphenolic compounds of Magnolia officinalis, have been reported to have antioxidant and anti-inflammatory properties. Sterol regulatory element binding protein-1 c (SREBP-1 c) plays an important role in the development and processing of steatosis in the liver. In the present study, we investigated the effects of a combination of honokiol and magnolol on SREBP-1 c-dependent lipogenesis in hepatocytes as well as in mice with fatty liver due to consumption of high-fat diet (HFD). Liver X receptor α (LXRα) agonists induced activation of SREBP-1 c and expression of lipogenic genes, which were blocked by co-treatment of honokiol and magnolol (HM). Moreover, a combination of HM potently increased mRNA of fatty acid oxidation genes. HM induced AMP-activated protein kinase (AMPK), an inhibitory kinase of the LXRα-SREBP-1 c pathway. The role of AMPK activation induced by HM was confirmed using an inhibitor of AMPK, Compound C, which reversed the ability of HM to both inhibit SREBP-1 c induction as well as induce genes for fatty acid oxidation. In mice, HM administration for four weeks ameliorated HFD-induced hepatic steatosis and liver dysfunction, as indicated by plasma parameters and Oil Red O staining. Taken together, our results demonstrated that a combination of HM has beneficial effects on inhibition of fatty liver and SREBP-1 c-mediated hepatic lipogenesis, and these events may be mediated by AMPK activation. © 2014 by the Society for Experimental Biology and Medicine.

  7. Combination of honokiol and magnolol inhibits hepatic steatosis through AMPK-SREBP-1 c pathway

    PubMed Central

    Lee, Ju-Hee; Jung, Ji Yun; Jang, Eun Jeong; Jegal, Kyung Hwan; Moon, Soo Young; Ku, Sae Kwang; Kang, Seung Ho; Cho, Il Je; Park, Sook Jahr; Lee, Jong Rok; Zhao, Rong Jie; Kim, Sang Chan

    2015-01-01

    Honokiol and magnolol, as pharmacological biphenolic compounds of Magnolia officinalis, have been reported to have antioxidant and anti-inflammatory properties. Sterol regulatory element binding protein-1 c (SREBP-1 c) plays an important role in the development and processing of steatosis in the liver. In the present study, we investigated the effects of a combination of honokiol and magnolol on SREBP-1 c-dependent lipogenesis in hepatocytes as well as in mice with fatty liver due to consumption of high-fat diet (HFD). Liver X receptor α (LXRα) agonists induced activation of SREBP-1 c and expression of lipogenic genes, which were blocked by co-treatment of honokiol and magnolol (HM). Moreover, a combination of HM potently increased mRNA of fatty acid oxidation genes. HM induced AMP-activated protein kinase (AMPK), an inhibitory kinase of the LXRα-SREBP-1 c pathway. The role of AMPK activation induced by HM was confirmed using an inhibitor of AMPK, Compound C, which reversed the ability of HM to both inhibit SREBP-1 c induction as well as induce genes for fatty acid oxidation. In mice, HM administration for four weeks ameliorated HFD-induced hepatic steatosis and liver dysfunction, as indicated by plasma parameters and Oil Red O staining. Taken together, our results demonstrated that a combination of HM has beneficial effects on inhibition of fatty liver and SREBP-1 c-mediated hepatic lipogenesis, and these events may be mediated by AMPK activation. PMID:25125496

  8. Design, synthesis and antibacterial evaluation of honokiol derivatives.

    PubMed

    Wu, Bo; Fu, Su-Hong; Tang, Huan; Chen, Kai; Zhang, Qiang; Peng, Ai-Hua; Ye, Hao-Yu; Cheng, Xing-Jun; Lian, Mao; Wang, Zhen-Ling; Chen, Li-Juan

    2018-02-15

    Staphylococcus aureus is a major and dangerous human pathogen that causes a range of clinical manifestations of varying severity, and is the most commonly isolated pathogen in the setting of skin and soft tissue infections, pneumonia, suppurative arthritis, endovascular infections, foreign-body associated infections, septicemia, osteomyelitis, and toxic shocksyndrome. Honokiol, a pharmacologically active natural compound derived from the bark of Magnolia officinalis, has antibacterial activity against Staphylococcus aureus which provides a great inspiration for the discovery of potential antibacterial agents. Herein, honokiol derivatives were designed, synthesized and evaluated for their antibacterial activity by determining the minimum inhibitory concentration (MIC) against S. aureus ATCC25923 and Escherichia coli ATCC25922 in vitro. 7c exhibited better antibacterial activity than other derivatives and honokiol. The structure-activity relationships indicated piperidine ring with amino group is helpful to improve antibacterial activity. Further more, 7c showed broad spectrum antibacterial efficiency against various bacterial strains including eleven gram-positive and seven gram-negative species. Time-kill kinetics against S. aureus ATCC25923 in vitro revealed that 7c displayed a concentration-dependent effect and more rapid bactericidal kinetics better than linezolid and vancomycin with the same concentration. Gram staining assays of S. aureus ATCC25923 suggested that 7c could destroy the cell walls of bacteria at 1×MIC and 4×MIC. Copyright © 2017. Published by Elsevier Ltd.

  9. Advances on Semisynthesis, Total Synthesis, and Structure-Activity Relationships of Honokiol and Magnolol Derivatives.

    PubMed

    Yang, Chun; Zhi, Xiaoyan; Xu, Hui

    2016-01-01

    Honokiol and magnolol (an isomer of honokiol) are small-molecule polyphenols isolated from the barks of Magnolia officinalis, which have been widely used in traditional Chinese and Japanese medicines. In the last decade, a variety of biological properties of honokiol and magnolol (e.g., anti-oxidativity, antitumor activity, anti-depressant activity, anti-inflammatory activity, neuroprotective activity, anti-diabetic activity, antiviral activity, and antimicrobial activity) have been reported. Meanwhile, certain mechanisms of action of some biological activities were also investigated. Moreover, many analogs of honokiol and magnolol were prepared by structural modification or total synthesis, and some exhibited very potent pharmacological activities with improved water solubility. Therefore, the present review will provide a systematic coverage on recent developments of honokiol and magnolol derivatives in regard to semisynthesis, total synthesis, and structure-activity relationships from 2000 up to now.

  10. Posterior reversible encephalopathy syndrome in chronic alcoholism with acute psychiatric symptoms.

    PubMed

    Kimura, Ryo; Yanagida, Makoto; Kugo, Aki; Taguchi, Satoki; Matsunaga, Hidenori

    2010-01-01

    To highlight the association between posterior reversible encephalopathy syndrome (PRES) and chronic alcoholism. We present a case report, a review of the literature and a discussion. We report on the case of a 51-year-old man with chronic alcoholism, who suddenly developed visual disturbance and confusion. Magnetic resonance imaging (MRI) on admission demonstrated abnormal findings. However, clinical symptoms and imaging promptly improved, indicating the diagnosis of PRES. PRES should be considered when making a diagnosis for disturbed consciousness in alcoholic patients. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Alcohol reversibly disrupts TNF-α/TACE interactions in the cell membrane

    PubMed Central

    Song, Kejing; Zhao, Xue-Jun; Marrero, Luis; Oliver, Peter; Nelson, Steve; Kolls, Jay K

    2005-01-01

    Background Alcohol abuse has long been known to adversely affect innate and adaptive immune responses and pre-dispose to infections. One cellular mechanism responsible for this effect is alcohol-induced suppression of TNF-α (TNF) by mononuclear phagocytes. We have previously shown that alcohol in part inhibits TNF-α processing by TNF converting enzyme (TACE) in human monocytes. We hypothesized that the chain length of the alcohol is critical for post-transcriptional suppression of TNF secretion. Methods Due to the complex transcriptional and post-transcriptional regulation of TNF in macrophages, to specifically study TNF processing at the cell membrane we performed transient transfections of A549 cells with the TNF cDNA driven by the heterologous CMV promoter. TNF/TACE interactions at the cell surface were assessed using fluorescent resonance energy transfer (FRET) microscopy. Results The single carbon alcohol, methanol suppressed neither TNF secretion nor FRET efficiency between TNF and TACE. However, 2, 3, and 4 carbon alcohols were potent suppressors of TNF processing and FRET efficiency. The effect of ethanol, a 2-carbon alcohol was reversible. Conclusion These data show that inhibition of TNF-α processing by acute ethanol is a direct affect of ethanol on the cell membrane and is reversible upon cessation or metabolism. PMID:16246259

  12. Chemopreventive effects of combination of honokiol and magnolol with α-santalol on skin cancer developments.

    PubMed

    Chilampalli, C; Zhang, X; Kaushik, R S; Young, A; Zeman, D; Hildreth, M B; Fahmy, H; Dwivedi, C

    2013-06-01

    α-Santalol is active component of sandalwood oil and has been shown to have chemopreventive effects against chemically and UVB-induced skin cancer development in mice. α-Santalol is also shown to have skin permeation enhancing effects. Honokiol and magnolol isolated from Magnolia officinalis bark extract have also been shown to have chemopreventive effects against chemically and UVB-induced skin cancer in mice. This study was conducted to investigate the combination effects of α-santalol, honokiol and magnolol to study any additive/synergistic effects to lower the doses required for chemoprevention. Pretreatment of combinations of α-santalol with honokiol and magnolol significantly decreased tumor multiplicity upto 75% than control, α-santalol, honokiol and magnolol alone in SKH-1 mice. Combination of α-santalol with honokiol and magnolol also decreased cell viability, proliferation, and enhanced apotosis in comparison to α-santalol, honokiol and magnolol alone in Human epidrmoid carcinoma A431 cells. Overall, the results of present study indicated combinations of α-santalol with honokiol and magnolol could provide chemoprevention of skin cancer at lower doses than given alone.

  13. Honokiol Increases CD4+ T Cell Activation and Decreases TNF but Fails to Improve Survival Following Sepsis.

    PubMed

    Klingensmith, Nathan J; Chen, Ching-Wen; Liang, Zhe; Burd, Eileen M; Farris, Alton B; Arbiser, Jack L; Ford, Mandy L; Coopersmith, Craig M

    2017-10-11

    Honokiol is a biphenolic isolate extracted from the bark of the magnolia tree that has been used in traditional Chinese and Japanese medicine, and has more recently been investigated for its anti-inflammatory and anti-bacterial properties. Honokiol has previously been demonstrated to improve survival in sepsis models that have rapid 100% lethality. The purpose of this study was to determine the impact of Honokiol on the host response in a model of sepsis that more closely approximates human disease. Male and female C57BL/6 mice underwent cecal ligation and puncture (CLP) to induce polymicrobial intraabdominal sepsis. Mice were then randomized to receive an injection of either Honokiol (120 mg/kg/day) or vehicle and were sacrificed after 24 hours for functional studies or followed 7 days for survival. Honokiol treatment after sepsis increased the frequency of CD4 T cells and increased activation of CD4 T cells as measured by the activation marker CD69. Honokiol also increased splenic dendritic cells. Honokiol simultaneously decreased frequency and number of CD8 T cells. Honokiol decreased systemic TNF without impacting other systemic cytokines. Honokiol did not have a detectable effect on kidney function, lung physiology, liver function or intestinal integrity. In contrast to prior studies of Honokiol in a lethal model of sepsis, Honokiol did not alter survival at seven days (70% mortality for Honokiol vs. 60% mortality for vehicle). Honokiol is thus effective in modulating the host immune response and inflammation following a clinically relevant model of sepsis but is not sufficient to alter survival.

  14. Reversing the sequence: reducing alcohol consumption by overcoming alcohol attentional bias.

    PubMed

    Fadardi, Javad Salehi; Cox, W Miles

    2009-05-01

    The aims of the research were to (a) compare the alcohol attentional bias (AAB) of social, hazardous, and harmful drinkers and (b) assess the effects of alcohol attention-control training on the AAB and alcohol consumption of hazardous and harmful drinkers. Participants were social drinkers (N=40), hazardous drinkers (N=89), and harmful drinkers (N=92). Paper-and-pencil measures were used to collect information about participants' socio-demographic characteristics, health status, motivational structure, drinking-related locus of control and situational self-confidence, readiness to change, affect, and alcohol consumption. Computerized classic, alcohol- and concerns-Stroop tests were administered. All participants were tested individually, with the order of tests counterbalanced across participants. After the baseline assessment, the hazardous and harmful drinkers were trained with the Alcohol Attention-Control Training Program (AACTP) for two and four sessions, respectively. Both samples completed a post-training assessment, and the harmful drinkers also completed 3-month follow-up. Results indicated that (a) the harmful drinkers had larger AAB than the hazardous and the social drinkers; (b) the attentional training reduced the hazardous and harmful drinkers' AAB; and (c) the harmful drinkers showed post-training reductions in alcohol consumption and improvements on the other drinking-related indices. The harmful drinkers' improvements were maintained at the 3-month follow-up.

  15. Poly/vinyl alcohol/ membranes for reverse osmosis

    NASA Technical Reports Server (NTRS)

    Katz, M. G.; Wydeven, T., Jr.

    1981-01-01

    A description is presented of the results of studies of the water and salt transport properties of PVA membranes, taking into account radiation crosslinked PVA membranes, diffusive salt permeability through PVA membranes, and heat treated PVA membranes. The experimental findings support an occurrence of independent water, and salt permeation processes. It is suggested that the salt permeation is governed by a solution-diffusion transport mechanism. The preparation of thin skinned, asymmetric PVA membranes is also discussed. The employed method has a certain similarity to the classical phase inversion method, which is widely applied in the casting of asymmetric reverse osmosis membranes. Instead of using a gelling bath composed of a nonsolvent for the membrane material and miscible with the solvent from which the membrane is cast, a 'complexing' bath is used, which is a solution of a complexing agent in water.

  16. A sustained depressive state promotes a guanfacine reversible susceptibility to alcohol seeking in rats.

    PubMed

    Riga, Danai; Schmitz, Leanne J M; van der Harst, Johanneke E; van Mourik, Yvar; Hoogendijk, Witte J G; Smit, August B; De Vries, Taco J; Spijker, Sabine

    2014-04-01

    High rates of comorbidity between alcohol use disorder (AUD) and major depressive disorder (MDD) are reported. Preclinical models examining effects of primary depression on secondary AUD are currently absent, preventing adequate testing of drug treatment. Here, we combined social defeat-induced persistent stress (SDPS) and operant alcohol self-administration (SA) paradigms to assess causality between these two neuropsychiatric disorders. We then exploited guanfacine, an FDA-approved adrenergic agent reported to reduce drug craving in humans, against SDPS-induced modulation of operant alcohol SA. Wistar rats were socially defeated and isolated for a period of ≥9 weeks, during which depression-like symptomatology (cognitive and social behavioral symptoms) was assessed. Subsequently, animals were subjected to a 5-month operant alcohol SA paradigm, examining acquisition, motivation, extinction, and cue-induced reinstatement of alcohol seeking. The effects of guanfacine on motivation and relapse were measured at >6 months following defeat. SDPS rats exhibited significant disruption of social and cognitive behavior, including short-term spatial and long-term social memory, several months following defeat. Notably, SDPS increased motivation to obtain alcohol, and cue-induced relapse vulnerability. Guanfacine reversed the SDPS-induced effects on motivation and relapse. Together, our model mimics core symptomatology of a sustained depressive-like state and a subsequent vulnerability to alcohol abuse. We show that SDPS is strongly associated with an enhanced motivation for alcohol intake and relapse. Finally, we show that the clinically employed drug guanfacine has potential as a novel treatment option in comorbid patients, as it effectively reduced the enhanced sensitivity to alcohol and alcohol-associated stimuli.

  17. A Sustained Depressive State Promotes a Guanfacine Reversible Susceptibility to Alcohol Seeking in Rats

    PubMed Central

    Riga, Danai; Schmitz, Leanne JM; van der Harst, Johanneke E; van Mourik, Yvar; Hoogendijk, Witte JG; Smit, August B; De Vries, Taco J; Spijker, Sabine

    2014-01-01

    High rates of comorbidity between alcohol use disorder (AUD) and major depressive disorder (MDD) are reported. Preclinical models examining effects of primary depression on secondary AUD are currently absent, preventing adequate testing of drug treatment. Here, we combined social defeat-induced persistent stress (SDPS) and operant alcohol self-administration (SA) paradigms to assess causality between these two neuropsychiatric disorders. We then exploited guanfacine, an FDA-approved adrenergic agent reported to reduce drug craving in humans, against SDPS-induced modulation of operant alcohol SA. Wistar rats were socially defeated and isolated for a period of ⩾9 weeks, during which depression-like symptomatology (cognitive and social behavioral symptoms) was assessed. Subsequently, animals were subjected to a 5-month operant alcohol SA paradigm, examining acquisition, motivation, extinction, and cue-induced reinstatement of alcohol seeking. The effects of guanfacine on motivation and relapse were measured at >6 months following defeat. SDPS rats exhibited significant disruption of social and cognitive behavior, including short-term spatial and long-term social memory, several months following defeat. Notably, SDPS increased motivation to obtain alcohol, and cue-induced relapse vulnerability. Guanfacine reversed the SDPS-induced effects on motivation and relapse. Together, our model mimics core symptomatology of a sustained depressive-like state and a subsequent vulnerability to alcohol abuse. We show that SDPS is strongly associated with an enhanced motivation for alcohol intake and relapse. Finally, we show that the clinically employed drug guanfacine has potential as a novel treatment option in comorbid patients, as it effectively reduced the enhanced sensitivity to alcohol and alcohol-associated stimuli. PMID:24192553

  18. Maximizing dermal targeting and minimizing transdermal penetration by magnolol/honokiol methoxylation.

    PubMed

    Lin, Chwan-Fwu; Hwang, Tsong-Long; Al-Suwayeh, Saleh A; Huang, Yu-Ling; Hung, Yi-Yun; Fang, Jia-You

    2013-03-10

    Magnolol and honokiol, predominant active compounds in the family Magnoliaceae, are known to exhibit strong anti-inflammatory activities against dermal disorders. We attempted to modify the structures of magnolol and honokiol by methoxylation to optimize the skin delivery ability. Absorption of these permeants into and through the skin was performed at both an infinite dose and saturated solubility. Superoxide anion and elastase released from human neutrophils were the biomarkers used to examine anti-inflammatory potencies of these permeants. The safety of the permeants was evaluated by keratinocyte viability and in vivo bioengineering techniques. Topical magnolol and honokiol at an infinite dose (7.5 mM) showed skin accumulations of 0.22 and 0.16 nmol/mg, respectively. Methoxylation significantly enhanced their skin absorption. Deposition amounts of dimethylmagnolol and dimethylhonokiol were respectively 15- and 7-fold greater than those of magnolol and honokiol. Contrary to the skin accumulation results, the transdermal penetration across skin decreased following methoxylation. No transdermal delivery occurred for dimethylhonokiol. Skin uptake of 4'-O-methylhonokiol was 2-fold higher than that of 2-O-methylhonokiol, although they are isomers. Methoxylated permeants demonstrated selective absorption into follicles, which showed 3-5-fold higher follicular amounts compared to magnolol and honokiol. The relative order of anti-inflammatory activities was honokiol>2-O-methylmagnolol>dimethylhonokiol>magnolol. The other compounds exhibited negligible or negative responses in activated neutrophils. Magnolol and honokiol induced slight but significant keratinocyte cytotoxicity and stratum corneum disruption. Daily administration of methoxylated permeants, especially dimethylhonokiol, produced no skin irritation for up to 7 days. Methoxylated magnolol and honokiol can be efficient and safe candidates for treating inflammatory skin disorders. Copyright © 2013 Elsevier B

  19. Effects of magnolol and honokiol derived from traditional Chinese herbal remedies on gastrointestinal movement

    PubMed Central

    Zhang, Wei-Wei; Li, Yan; Wang, Xue-Qing; Tian, Feng; Cao, Hong; Wang, Min-Wei; Sun, Qi-Shi

    2005-01-01

    AIM: To study the effects of magnolol and honokiol on isolated smooth muscle of gastrointestinal tract and their relationship with Ca2+, and on the gastric emptying and the intestinal propulsive activity in mice. METHODS: Routine experimental methods using isolated gastric fundus strips of rats and isolated ileum segments of guinea pigs were adopted to measure the smooth muscle tension. The effects of magnolol 10-3, 10-4, 10-5 mol/L, and honokiol 10-4, 10-5, 10-6 mol/L on the contractility of gastric fundus strips of rats and ileum of guinea pigs induced by acetylcholine (Ach) and 5-hydroxytryptamine (5-HT) was assessed respectively. The method using nuclein and pigment methylene blue was adopted to measure the gastric retention rate of nuclein and the intestinal propulsive ratio of a nutritional semi-solid meal for assessing the effect of magnolol and honokiol (0.5, 2, 20 mg/kg) on gastric emptying and intestinal propulsion. RESULTS: Magnolol and honokiol significantly inhibited the contractility of isolated gastric fundus strips of rats treated with Ach or 5-HT and isolated ileum guinea pigs treated with Ach or CaCl2, and both of them behaved as non-competitive muscarinic antagonists. Magnolol and honokiol inhibited the contraction induced by Ach in Ca2+-free medium and extracellular Ca2+-dependent contraction induced by Ach. Each group of magnolol and honokiol experiments significantly decreased the residual rate of nuclein in the stomach and increased the intestinal propulsive ratio in mice. CONCLUSION: The inhibitory effect of magnolol and honokiol on contractility of the smooth muscles of isolated gastric fundus strips of rats and isolated ileum of guinea pigs is associated with a calcium-antagonistic effect. Magnolol and honokiol can improve the gastric emptying of a semi-solid meal and intestinal propulsive activity in mice. PMID:16038044

  20. Antinociceptive actions of honokiol and magnolol on glutamatergic and inflammatory pain

    PubMed Central

    2009-01-01

    The antinociceptive effects of honokiol and magnolol, two major bioactive constituents of the bark of Magnolia officinalis, were investigated on animal paw licking responses and thermal hyperalgesia induced by glutamate receptor agonists including glutamate, N-methyl-D-aspartate (NMDA), and metabotropic glutamate 5 receptor (mGluR5) activator (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), as well as inflammatory mediators such as substance P and prostaglandin E2 (PGE2) in mice. The actions of honokiol and magnolol on glutamate-induced c-Fos expression in the spinal cord dorsal horn were also examined. Our data showed that honokiol and magnolol blocked glutamate-, substance P- and PGE2-induced inflammatory pain with similar potency and efficacy. Consistently, honokiol and magnolol significantly decreased glutamate-induced c-Fos protein expression in superficial (I-II) laminae of the L4-L5 lumbar dorsal horn. However, honokiol was more selective than magnolol for inhibition of NMDA-induced licking behavioral and thermal hyperalgesia. In contrast, magnolol was more potent to block CHPG-mediated thermal hyperalgesia. These results demonstrate that honokiol and magnolol effectively decreased the inflammatory pain. Furthermore, their different potency on inhibition of nociception provoked by NMDA receptor and mGluR5 activation should be considered. PMID:19832997

  1. Reversal of Alcohol-Induced Dysregulation in Dopamine Network Dynamics May Rescue Maladaptive Decision-making

    PubMed Central

    Schindler, Abigail G.; Soden, Marta E.; Zweifel, Larry S.

    2016-01-01

    Alcohol is the most commonly abused substance among adolescents, promoting the development of substance use disorders and compromised decision-making in adulthood. We have previously demonstrated, with a preclinical model in rodents, that adolescent alcohol use results in adult risk-taking behavior that positively correlates with phasic dopamine transmission in response to risky options, but the underlying mechanisms remain unknown. Here, we show that adolescent alcohol use may produce maladaptive decision-making through a disruption in dopamine network dynamics via increased GABAergic transmission within the ventral tegmental area (VTA). Indeed, we find that increased phasic dopamine signaling after adolescent alcohol use is attributable to a midbrain circuit, including the input from the pedunculopontine tegmentum to the VTA. Moreover, we demonstrate that VTA dopamine neurons from adult rats exhibit enhanced IPSCs after adolescent alcohol exposure corresponding to decreased basal dopamine levels in adulthood that negatively correlate with risk-taking. Building on these findings, we develop a model where increased inhibitory tone on dopamine neurons leads to a persistent decrease in tonic dopamine levels and results in a potentiation of stimulus-evoked phasic dopamine release that may drive risky choice behavior. Based on this model, we take a pharmacological approach to the reversal of risk-taking behavior through normalization of this pattern in dopamine transmission. These results isolate the underlying circuitry involved in alcohol-induced maladaptive decision-making and identify a novel therapeutic target. SIGNIFICANCE STATEMENT One of the primary problems resulting from chronic alcohol use is persistent, maladaptive decision-making that is associated with ongoing addiction vulnerability and relapse. Indeed, studies with the Iowa Gambling Task, a standard measure of risk-based decision-making, have reliably shown that alcohol-dependent individuals make

  2. Antihyperalgesic Properties of Honokiol in Inflammatory Pain Models by Targeting of NF-κB and Nrf2 Signaling.

    PubMed

    Khalid, Sidra; Ullah, Muhammad Z; Khan, Ashraf U; Afridi, Ruqayya; Rasheed, Hina; Khan, Adnan; Ali, Hussain; Kim, Yeong S; Khan, Salman

    2018-01-01

    The present study investigates the possible anti-nociceptive effect of intraperitoneal (i.p.) honokiol: a phenolic compound originally isolated from Magnolia officinalis , in acute and chronic inflammatory pain models. Doses of 0.1, 5, and 10 mg/kg honokiol were administered in carrageenan induced pain and the dose (honokiol 10 mg/kg i.p.) with most significant response among behavioral tests was selected for further experiments. The i.p. administration of honokiol inhibits mechanical hyperalgesia, mechanical allodynia, and thermal hyperalgesia, without causing any apparent toxicity. To elucidate the effect of honokiol on various cytokines and antioxidant enzymes, quantitative real-time-PCR was performed to determine the expression levels of pro-inflammatory cytokines and antioxidant enzymes. It is demonstrated that honokiol significantly reduced the expression levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF). Similarly, honokiol was also found to potentiate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 2 (SOD2), and heme oxygenase-1 (HO-1) levels. Additionally, honokiol significantly reduced plasma nitrite levels as compared to complete Freund's adjuvant (CFA) induced group. X-ray analysis and hematoxylin and eosin (H&E) staining of inflamed and treated paws showed that honokiol reduced the inflammation with significantly less leukocyte infiltration and soft tissue inflammation. In order to explore the possible mechanism of action of honokiol, agonists [piroxicam (5 mg/kg), tramadol (50 mg/kg), and gabapentin (5 mg/kg) i.p.] as well as antagonists [naloxone (4 mg/kg), olanzapine (10 mg/kg), and flumazenil (0.2 mg/kg) i.p.] were used to study involvement of various receptors on the anti-nociceptive effect of honokiol. The potential side effects of honokiol on muscle activity were assessed. An adverse effect testing of honokiol by liver

  3. Honokiol promotes non-rapid eye movement sleep via the benzodiazepine site of the GABA(A) receptor in mice.

    PubMed

    Qu, Wei-Min; Yue, Xiao-Fang; Sun, Yu; Fan, Kun; Chen, Chang-Rui; Hou, Yi-Ping; Urade, Yoshihiro; Huang, Zhi-Li

    2012-10-01

    Decoctions of the Chinese herb houpu contain honokiol and are used to treat a variety of mental disorders, including depression. Depression commonly presents alongside sleep disorders and sleep disturbances, which appear to be a major risk factor for depression. Here, we have evaluated the somnogenic effect of honokiol and the mechanisms involved. Honokiol was administered i.p. at 20:00 h in mice. Flumazenil, an antagonist at the benzodiazepine site of the GABA(A) receptor, was administered i.p. 15 min before honokiol. The effects of honokiol were measured by EEG and electromyogram (EMG), c-Fos expression and in vitro electrophysiology. Honokiol (10 and 20 mg·kg⁻¹) significantly shortened the sleep latency to non-rapid eye movement (non-REM, NREM) sleep and increased the amount of NREM sleep. Honokiol increased the number of state transitions from wakefulness to NREM sleep and, subsequently, from NREM sleep to wakefulness. However, honokiol had no effect on either the amount of REM sleep or EEG power density of both NREM and REM sleep. Honokiol increased c-Fos expression in ventrolateral preoptic area (VLPO) neurons, as examined by immunostaining, and excited sleep-promoting neurons in the VLPO by whole-cell patch clamping in the brain slice. Pretreatment with flumazenil abolished the somnogenic effects and activation of the VLPO neurons by honokiol. Honokiol promoted NREM sleep by modulating the benzodiazepine site of the GABA(A) receptor, suggesting potential applications in the treatment of insomnia, especially for patients who experience difficulty in falling and staying asleep. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  4. SIRT3 activator Honokiol attenuates β-Amyloid by modulating amyloidogenic pathway

    PubMed Central

    Lynd, Tyler; Briggs, Gwyneth; Adamek, Danielle; Jones, Ellery; Heiner, Jake; Majrashi, Mohammed; Moore, Timothy; Amin, Rajesh; Suppiramaniam, Vishnu

    2018-01-01

    Honokiol (poly-phenolic lignan from Magnolia grandiflora) is a Sirtuin-3 (SIRT3) activator which exhibit antioxidant activity and augment mitochondrial functions in several experimental models. Modern evidence suggests the critical role of SIRT3 in the progression of several metabolic and neurodegenerative diseases. Amyloid beta (Aβ), the precursor to extracellular senile plaques, accumulates in the brains of patients with Alzheimer’s disease (AD) and is related to the development of cognitive impairment and neuronal cell death. Aβ is generated from amyloid-β precursor protein (APP) through sequential cleavages, first by β-secretase and then by γ-secretase. Drugs modulating this pathway are believed to be one of the most promising strategies for AD treatment. In the present study, we found that Honokiol significantly enhanced SIRT3 expression, reduced reactive oxygen species generation and lipid peroxidation, enhanced antioxidant activities, and mitochondrial function thereby reducing Aβ and sAPPβ levels in Chinese Hamster Ovarian (CHO) cells (carrying the amyloid precursor protein-APP and Presenilin PS1 mutation). Mechanistic studies revealed that Honokiol affects neither protein levels of APP nor α-secretase activity. In contrast, Honokiol increased the expression of AMPK, CREB, and PGC-1α, thereby inhibiting β-secretase activity leading to reduced Aβ levels. These results suggest that Honokiol is an activator of SIRT3 capable of improving antioxidant activity, mitochondrial energy regulation, while decreasing Aβ, thereby indicating it to be a lead compound for AD drug development. PMID:29324783

  5. Posterior reversible encephalopathy syndrome in alcoholic hepatitis: Hepatic encephalopathy a common theme

    PubMed Central

    John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita

    2017-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a neuro-radiologic diagnosis that has become more widely recognized and reported over the past few decades. As such, there are a number of known risk factors that contribute to the development of this syndrome, including volatile blood pressures, renal failure, cytotoxic drugs, autoimmune disorders, pre-eclampsia, and eclampsia. This report documents the first reported case of PRES in a patient with severe alcoholic hepatitis with hepatic encephalopathy and delves into a molecular pathophysiology of the syndrome. PMID:28127211

  6. A case of posterior reversible encephalopathy syndrome associated with acute pancreatitis and chronic alcoholism.

    PubMed

    Baek, Hyun Seok; Lee, Se-Jin

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is known to be caused by a variety of clinical disorders. The authors encountered a case of PRES associated with acute pancreatitis and chronic alcoholism. A 49-year-old man presented with altered mental status. Magnetic resonance imaging (MRI) displayed vasogenic edema at the bilateral posterior temporal and parieto-occipital lobes and cerebellum. Laboratory tests and abdominal computed tomography (CT) revealed acute pancreatitis. The patient recovered completely, and follow-up brain MRI and abdominal CT exhibited resolution of the previous lesions. We suggest that acute pancreatitis might be an etiology of PRES. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. In vitro growth inhibition of human cancer cells by novel honokiol analogs.

    PubMed

    Lin, Jyh Ming; Prakasha Gowda, A S; Sharma, Arun K; Amin, Shantu

    2012-05-15

    Honokiol possesses many pharmacological activities including anti-cancer properties. Here in, we designed and synthesized honokiol analogs that block major honokiol metabolic pathway which may enhance their effectiveness. We studied their cytotoxicity in human cancer cells and evaluated possible mechanism of cell cycle arrest. Two analogs, namely 2 and 4, showed much higher growth inhibitory activity in A549 human lung cancer cells and significant increase of cell population in the G0-G1 phase. Further elucidation of the inhibition mechanism on cell cycle showed that analogs 2 and 4 inhibit both CDK1 and cyclin B1 protien levels in A549 cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Polyethylene glycol-based ultrasound-assisted extraction of magnolol and honokiol from Cortex Magnoliae Officinalis.

    PubMed

    He, Lei; Fan, Tao; Hu, Jianguo; Zhang, Lijin

    2015-01-01

    In this study, a kind of green solvent named polyethylene glycol (PEG) was developed for the ultrasound-assisted extraction (UAE) of magnolol and honokiol from Cortex Magnoliae Officinalis. The effects of PEG molecular weight, PEG concentration, sample size, pH, ultrasonic power and extraction time on the extraction of magnolol and honokiol were investigated to optimise the extraction conditions. Under the optimal extraction conditions, the PEG-based UAE supplied higher extraction efficiencies of magnolol and honokiol than the ethanol-based UAE and traditional ethanol-reflux extraction. Furthermore, the correlation coefficient (R(2)), repeatability (relative standard deviation, n = 6) and recovery confirmed the validation of the proposed extraction method, which were 0.9993-0.9996, 3.1-4.6% and 92.3-106.8%, respectively.

  9. A novel reverse osmosis membrane modified by polyvinyl alcohol with maleic anhydride crosslinking

    NASA Astrophysics Data System (ADS)

    Samnani, Mohit; Rathod, Harshad; Raval, Hiren

    2018-03-01

    In the era of increasing energy crisis, it is inevitable to decrease process energy consumption to increase process viability and curtail green-house gas emission. The Reverse Osmosis plant requires significant energy to transfer water overcoming the osmotic pressure. This paper focuses on increasing the water flux for Thin Film Composite Reverse Osmosis (TFC RO) membrane without compromising salt rejection performance leading to the environmentally friendly and economically attractive process. The virgin TFC RO membrane was exposed to solution of sodium hypochlorite of concentration 2000 mg l-1 for 1 h to activate the surface of the membrane, followed by the treatment with the mixture of polyvinyl alcohol and maleic anhydride with varying concentrations for 1 h and curing in the oven at 80 °C temperature for 10 min. Out of all the treated membranes, the membrane treated with 2000 mg l-1 polyvinyl alcohol and 1000 mg l-1 maleic anhydride demonstrated the highest salt rejection of 96.83 % with 2% increase as compared to the virgin TFC RO membrane. The water flux of the membrane was around 44% higher than the virgin TFC RO membrane. The membrane samples were characterized by atomic force micrographs, ATR-FTIR, Nuclear magnetic resonance and Dynamic mechanical analysis.

  10. Reversal of alcohol-induced effects on response control due to changes in proprioceptive information processing.

    PubMed

    Stock, Ann-Kathrin; Mückschel, Moritz; Beste, Christian

    2017-01-01

    Recent research has drawn interest to the effects of binge drinking on response selection. However, choosing an appropriate response is a complex endeavor that usually requires us to process and integrate several streams of information. One of them is proprioceptive information about the position of limbs. As to now, it has however remained elusive how binge drinking affects the processing of proprioceptive information during response selection and control in healthy individuals. We investigated this question using neurophysiological (EEG) techniques in a response selection task, where we manipulated proprioceptive information. The results show a reversal of alcohol-induced effects on response control due to changes in proprioceptive information processing. The most likely explanation for this finding is that proprioceptive information does not seem to be properly integrated in response selection processes during acute alcohol intoxication as found in binge drinking. The neurophysiological data suggest that processes related to the preparation and execution of the motor response, but not upstream processes related to conflict monitoring and spatial attentional orienting, underlie these binge drinking-dependent modulations. Taken together, the results show that even high doses of alcohol have very specific effects within the cascade of neurophysiological processes underlying response control and the integration of proprioceptive information during this process. © 2015 Society for the Study of Addiction.

  11. Honokiol and magnolol stimulate glucose uptake by activating PI3K-dependent Akt in L6 myotubes.

    PubMed

    Choi, Sun-Sil; Cha, Byung-Yoon; Lee, Young-Sil; Yonezawa, Takayuki; Teruya, Toshiaki; Nagai, Kazuo; Woo, Je-Tae

    2012-01-01

    Honokiol and magnolol, ingredients of Magnolia officinalis, which is used in traditional Chinese and Japanese medicines, have been reported to have antioxidant, anticancer, and antiangiogenic effects. Effects of these compounds on glucose metabolism in adipocytes have also been reported. However, their effects on skeletal muscle glucose uptake and the underlying molecular mechanisms are still unknown. Here, we investigated the direct effects and signaling pathways activated by honokiol and magnolol in skeletal muscle cells using L6 myotubes. We found that honokiol and magnolol dose-dependently acutely stimulated glucose uptake without synergistic effects of combined administration in L6 myotubes. Treatment with honokiol and magnolol also stimulated glucose transporter-4 translocation to the cell surface. Honokiol- and magnolol-stimulated glucose uptake was blocked by the phosphatidylinositol-3 kinase inhibitor, wortmannin. Both honokiol and magnolol stimulated Akt phosphorylation, a key element in the insulin signaling pathway, which was completely inhibited by wortmannin. These results suggest that honokiol and magnolol might have beneficial effects on glucose metabolism by activating the insulin signaling pathway. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

  12. Transcriptomic analysis of Saccharomyces cerevisiae upon honokiol treatment.

    PubMed

    Zhu, Xiaolong; Zou, Shenshen; Li, Youbin; Liang, Yongheng

    2017-09-01

    Honokiol (HNK), one of the main medicinal components in Magnolia officinalis, possesses antimicrobial activity against a variety of pathogenic bacteria and fungi. However, little is known of the molecular mechanisms underpinning the antimicrobial activity. To explore the molecular mechanism of its antifungal activity, we determined the effects of HNK on the mRNA expression profile of Saccharomyces cerevisiae using a DNA microarray approach. HNK markedly induced the expression of genes related to iron uptake and homeostasis. Conversely, genes associated with respiratory electron transport were downregulated, mirroring the effects of iron starvation. Meanwhile, HNK-induced growth deficiency was partly rescued by iron supplementation and HNK reacted with iron, producing iron complexes that depleted iron. These results suggest that HNK treatment induced iron starvation. Additionally, HNK treatment resulted in the upregulation of genes involved in protein synthesis and drug resistance networks. Furthermore, the deletion of PDR5, a gene encoding the plasma membrane ATP binding cassette (ABC) transporter, conferred sensitivity to HNK. Overexpression of PDR5 enhanced resistance of WT and pdr5Δ strains to HNK. Taken together, these findings suggest that HNK, which can be excluded by overexpression of Pdr5, functions in multiple cellular processes in S. cerevisiae, particularly in inducing iron starvation to inhibit cell growth. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  13. Inhibitory effects of magnolol and honokiol on human calcitonin aggregation

    PubMed Central

    Guo, Caiao; Ma, Liang; Zhao, Yudan; Peng, Anlin; Cheng, Biao; Zhou, Qiaoqiao; Zheng, Ling; Huang, Kun

    2015-01-01

    Amyloid formation is associated with multiple amyloidosis diseases. Human calcitonin (hCT) is a typical amyloidogenic peptide, its aggregation is associated with medullary carcinoma of the thyroid (MTC), and also limits its clinical application. Magnolia officinalis is a traditional Chinese herbal medicine; its two major polyphenol components, magnolol (Mag) and honokiol (Hon), have displayed multiple functions. Polyphenols like flavonoids and their derivatives have been extensively studied as amyloid inhibitors. However, the anti-amyloidogenic property of a biphenyl backbone containing polyphenols such as Mag and Hon has not been reported. In this study, these two compounds were tested for their effects on hCT aggregation. We found that Mag and Hon both inhibited the amyloid formation of hCT, whereas Mag showed a stronger inhibitory effect; moreover, they both dose-dependently disassembled preformed hCT aggregates. Further immuno-dot blot and dynamic light scattering studies suggested Mag and Hon suppressed the aggregation of hCT both at the oligomerization and the fibrillation stages, while MTT-based and dye-leakage assays demonstrated that Mag and Hon effectively reduced cytotoxicity caused by hCT aggregates. Furthermore, isothermal titration calorimetry indicated Mag and Hon both interact with hCT. Together, our study suggested a potential anti-amyloidogenic property of these two compounds and their structure related derivatives. PMID:26324190

  14. Antioxidant Activity of Magnolol and Honokiol: Kinetic and Mechanistic Investigations of Their Reaction with Peroxyl Radicals.

    PubMed

    Amorati, Riccardo; Zotova, Julija; Baschieri, Andrea; Valgimigli, Luca

    2015-11-06

    Magnolol and honokiol, the bioactive phytochemicals contained in Magnolia officinalis, are uncommon antioxidants bearing isomeric bisphenol cores substituted with allyl functions. We have elucidated the chemistry behind their antioxidant activity by experimental and computational methods. In the inhibited autoxidation of cumene and styrene at 303 K, magnolol trapped four peroxyl radicals, with a kinh of 6.1 × 10(4) M(-1) s(-1) in chlorobenzene and 6.0 × 10(3) M(-1) s(-1) in acetonitrile, and honokiol trapped two peroxyl radicals in chlorobenzene (kinh = 3.8 × 10(4) M(-1) s(-1)) and four peroxyl radicals in acetonitrile (kinh = 9.5 × 10(3) M(-1) s(-1)). Their different behavior arises from a combination of intramolecular hydrogen bonding among the reactive OH groups (in magnolol) and of the OH groups with the aromatic and allyl π-systems, as confirmed by FT-IR spectroscopy and DFT calculations. Comparison with structurally related 3,3',5,5'-tetramethylbiphenyl-4,4'-diol, 2-allylphenol, and 2-allylanisole allowed us to exclude that the antioxidant behavior of magnolol and honokiol is due to the allyl groups. The reaction of the allyl group with a peroxyl radical (C-H hydrogen abstraction) proceeds with rate constant of 1.1 M(-1) s(-1) at 303 K. Magnolol and honokiol radicals do not react with molecular oxygen and produce no superoxide radical under the typical settings of inhibited autoxidations.

  15. Synthesis of magnolol and honokiol derivatives and their effect against hepatocarcinoma cells

    PubMed Central

    Carta, Paola; Fabbri, Davide; Dettori, Maria Antonietta; Cruciani, Sara; Serra, Pier Andrea

    2018-01-01

    The hepatocellular carcinoma is one of the most common malignant tumour with high level of mortality rate due to its rapid progression and high resistance to conventional chemotherapies. Thus, the search for novel therapeutic leads is of global interest. Herein, a small set of derivatives of magnolol 1 and honokiol 2, the main components of Magnolia grandiflora and Magnolia obovata, were evaluated in in vitro assay using tumoral hepatocytes. The pro-drug approach was applied as versatile strategy to the improve bioactivity of the compounds by careful transformation of the hydroxyl groups of magnolol 1 and honokiol 2 in suitable ester derivatives. Compounds 10 and 11 resulted to be more potent than the parental honokiol 2 at concentration down to 1 μM with complete viability of treated fibroblast cells up to concentrations of 80 μM. The combination of a butyrate ester and a bare phenol-OH group in the honokiol structure seemed to play a significant role in the antiproliferative activity identifying an interesting pharmacological clue against hepatocellular carcinoma. PMID:29415009

  16. Embryo-fetal development toxicity of honokiol microemulsion intravenously administered to pregnant rats.

    PubMed

    Zhang, Qianqian; Ye, Xiangfeng; Wang, Lingzhi; Peng, Bangjie; Zhang, Yingxue; Bao, Jie; Li, Wanfang; Wei, Jinfeng; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

    2016-02-01

    The aim of this study was to evaluate the embryo-fetal development toxicity of honokiol microemulsion. The drug was intravenously injected to pregnant SD rats at dose levels of 0, 200, 600 and 2000 μg/kg/day from day 6-15 of gestation. All the pregnant animals were observed for body weights and any abnormal changes and subjected to caesarean-section on gestation day (GD) 20; all fetuses obtained from caesarean-section were assessed by external inspection, visceral and skeletal examinations. No treatment-related external alterations as well as visceral and skeletal malformations were observed in honokiol microemulsion groups. There was no significant difference in the body weight gain of the pregnant rats, average number of corpora lutea, and the gravid uterus weight in the honokiol microemulsion groups compared with the vehicle control group. However, at a dose level of 2000 μg/kg/day, there was embryo-fetal developmental toxicity observed, including a decrease in the body length and tail length of fetuses. In conclusion, the no-observed-adverse-effect level (NOAEL) of honokiol microemulsion is 600 μg/kg/day, 75 times above the therapeutic dosage and it has embryo-fetal toxicity at a dose level of 2000 μg/kg/day, which is approximately 250 times above the therapeutic dosage. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Overcoming Resistance to Cetuximab with Honokiol, A Small-Molecule Polyphenol.

    PubMed

    Pearson, Hannah E; Iida, Mari; Orbuch, Rachel A; McDaniel, Nellie K; Nickel, Kwangok P; Kimple, Randall J; Arbiser, Jack L; Wheeler, Deric L

    2018-01-01

    Overexpression and activation of the EGFR have been linked to poor prognosis in several human cancers. Cetuximab is a mAb against EGFR that is used for the treatment in head and neck squamous cell carcinoma (HNSCC) and metastatic colorectal cancer. Unfortunately, most tumors have intrinsic or will acquire resistance to cetuximab during the course of therapy. Honokiol is a natural compound found in the bark and leaves of the Chinese Magnolia tree and is established to have several anticancer properties without appreciable toxicity. In this study, we hypothesized that combining cetuximab and honokiol treatments could overcome acquired resistance to cetuximab. We previously developed a model of acquired resistance to cetuximab in non-small cell lung cancer H226 cell line. Treatment of cetuximab-resistant clones with honokiol and cetuximab resulted in a robust antiproliferative response. Immunoblot analysis revealed the HER family and their signaling pathways were downregulated after combination treatment, most notably the proliferation (MAPK) and survival (AKT) pathways. In addition, we found a decrease in phosphorylation of DRP1 and reactive oxygen species after combination treatment in cetuximab-resistant clones, which may signify a change in mitochondrial function. Furthermore, we utilized cetuximab-resistant HNSCC patient-derived xenografts (PDX) to test the benefit of combinatorial treatment in vivo There was significant growth delay in PDX tumors after combination treatment with a subsequent downregulation of active MAPK, AKT, and DRP1 signaling as seen in vitro Collectively, these data suggest that honokiol is a promising natural compound in overcoming acquired resistance to cetuximab. Mol Cancer Ther; 17(1); 204-14. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Antimicrobial Effects and Resistant Regulation of Magnolol and Honokiol on Methicillin-Resistant Staphylococcus aureus

    PubMed Central

    Kim, Su Young; Kim, Ju; Jeong, Seung-Il; Jahng, Kwang Yeop; Yu, Kang-Yeol

    2015-01-01

    The antimicrobial killing activity toward methicillin-resistant Staphylococcus aureus (MRSA) has been a serious emerging global issue. In a continuing search for compounds with antibacterial activity against several microorganisms including S. aureus and MRSA, an n-hexane extract of Magnolia officinalis was found to contain magnolol. This compound exhibited potent activity against S. aureus, standard methicillin-susceptible S. aureus (MSSA), and MRSA as well as clinical MRSA isolates. When combined with oxacillin, the antibacterial activities of magnolol and honokiol against the MRSA strain were increased compared to single treatment without antibiotics at 10 µg/mL and 25 µg/mL, respectively. These activities of magnolol and honokiol were dose dependent. Also, magnolol showed synergistic effects with oxacillin against 13 clinical isolates of MRSA. It was determined that magnolol and honokiol had a synergistic effect with oxacillin against MRSA strain. Furthermore, the magnolol inhibited the expression of the resistant genes, mecA, mecI, femA, and femB, in mRNA. We concluded that the antibacterial activity of magnolol against MRSA strain is more related to the mecI's pathway and components of the cell wall than mecR1. Therefore, the results obtained in this study suggest that the combination of magnolol and antibiotics could lead to the development of new combination antibiotics against MRSA infection. PMID:26357651

  19. Antimicrobial Effects and Resistant Regulation of Magnolol and Honokiol on Methicillin-Resistant Staphylococcus aureus.

    PubMed

    Kim, Su Young; Kim, Ju; Jeong, Seung-Il; Jahng, Kwang Yeop; Yu, Kang-Yeol

    2015-01-01

    The antimicrobial killing activity toward methicillin-resistant Staphylococcus aureus (MRSA) has been a serious emerging global issue. In a continuing search for compounds with antibacterial activity against several microorganisms including S. aureus and MRSA, an n-hexane extract of Magnolia officinalis was found to contain magnolol. This compound exhibited potent activity against S. aureus, standard methicillin-susceptible S. aureus (MSSA), and MRSA as well as clinical MRSA isolates. When combined with oxacillin, the antibacterial activities of magnolol and honokiol against the MRSA strain were increased compared to single treatment without antibiotics at 10 µg/mL and 25 µg/mL, respectively. These activities of magnolol and honokiol were dose dependent. Also, magnolol showed synergistic effects with oxacillin against 13 clinical isolates of MRSA. It was determined that magnolol and honokiol had a synergistic effect with oxacillin against MRSA strain. Furthermore, the magnolol inhibited the expression of the resistant genes, mecA, mecI, femA, and femB, in mRNA. We concluded that the antibacterial activity of magnolol against MRSA strain is more related to the mecI's pathway and components of the cell wall than mecR1. Therefore, the results obtained in this study suggest that the combination of magnolol and antibiotics could lead to the development of new combination antibiotics against MRSA infection.

  20. Characterization of metabolic profile of honokiol in rat feces using liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and (13)C stable isotope labeling.

    PubMed

    Dong, Yinfeng; Tang, Minghai; Song, Hang; Li, Rong; Wang, Chunyu; Ye, Haoyu; Qiu, Neng; Zhang, Yongkui; Chen, Lijuan; Wei, Yuquan

    2014-03-15

    As fecal excretion is one of important routes of elimination of drugs and their metabolites, it is indispensable to investigate the metabolites in feces for more comprehensive information on biotransformation in vivo. In this study, a sensitive and reliable approach based on ultra-performance liquid chromatography/quadrupole-time-of-flight-mass spectrometry (UHPLC-Q-TOF-MS) was applied to characterize the metabolic profile of honokiol in rat feces after the administration of an equimolar mixture of honokiol and [(13)C6]-labeled honokiol. Totally 42 metabolites were discovered and tentatively identified in rat feces samples, 26 metabolites were first reported, including two novel classes of metabolites, methylated and dimeric metabolites of honokiol. Moreover, this study provided basic comparative data on the metabolites in rat plasma, feces and urine, which gave better understanding of the metabolic fate of honokiol in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Detection of new human metabolic urinary markers in chronic alcoholism and their reversal by aqueous extract of Tinospora cordifolia stem.

    PubMed

    Mittal, Ashwani; Dabur, Rajesh

    2015-05-01

    We have studied urine metabolic signature of chronic alcoholism (CA) before and after treatment with an Ayurvedic drug Tinospora cordifolia aqueous extract (TCE). Urinary metabolites of chronic alcoholics and apparently healthy subjects were profiled using HPLC-Q-TOF-MS. Discrimination models from the initial data sets were able to correctly assign the unknown samples to the CA, treated or healthy groups in validation sets with r(2) > 0.98. Metabolic signature in CA patients include changed tryptophan, fatty acids and pyrimidines metabolism. Several novel biomarkers of alcoholism were observed in urine for the first time which includes, 5-hydroxyindole, phenylacetic acid, picolinic acid, quinaldic acid, histidine, cystathionine, riboflavin, tetrahydrobiopterin and chenodeoxyglycocholic acid, in addition to previously reported biomarkers. Treatment of CA with TCE reverted the levels of most of the biomarkers except tetrahydrobiopterin levels. These results suggested that the measurement of these urine metabolites could be used as a non-invasive diagnostic method for the detection of CA. As TCE treatment significantly reversed the affected pathways without any side effect. Overall, the present data depicts that TCE may be used either alone or adjunct in reducing alcohol-induced disorders. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  2. Alcohol

    MedlinePlus

    ... because that's how many accidents occur. What Is Alcoholism? What can be confusing about alcohol is that ... develop a problem with it. Sometimes, that's called alcoholism (say: al-kuh-HOL - ism) or being an ...

  3. Mitochondria-targeted ubiquinone (MitoQ) enhances acetaldehyde clearance by reversing alcohol-induced posttranslational modification of aldehyde dehydrogenase 2: A molecular mechanism of protection against alcoholic liver disease.

    PubMed

    Hao, Liuyi; Sun, Qian; Zhong, Wei; Zhang, Wenliang; Sun, Xinguo; Zhou, Zhanxiang

    2018-04-01

    Alcohol metabolism in the liver generates highly toxic acetaldehyde. Breakdown of acetaldehyde by aldehyde dehydrogenase 2 (ALDH2) in the mitochondria consumes NAD + and generates reactive oxygen/nitrogen species, which represents a fundamental mechanism in the pathogenesis of alcoholic liver disease (ALD). A mitochondria-targeted lipophilic ubiquinone (MitoQ) has been shown to confer greater protection against oxidative damage in the mitochondria compared to untargeted antioxidants. The present study aimed to investigate if MitoQ could preserve mitochondrial ALDH2 activity and speed up acetaldehyde clearance, thereby protects against ALD. Male C57BL/6J mice were exposed to alcohol for 8 weeks with MitoQ supplementation (5mg/kg/d) for the last 4 weeks. MitoQ ameliorated alcohol-induced oxidative/nitrosative stress and glutathione deficiency. It also reversed alcohol-reduced hepatic ALDH activity and accelerated acetaldehyde clearance through modulating ALDH2 cysteine S-nitrosylation, tyrosine nitration and 4-hydroxynonenol adducts formation. MitoQ ameliorated nitric oxide (NO) donor-mediated ADLH2 S-nitrosylation and nitration in Hepa-1c1c7 cells under glutathion depletion condition. In addition, alcohol-increased circulating acetaldehyde levels were accompanied by reduced intestinal ALDH activity and impaired intestinal barrier. In accordance, MitoQ reversed alcohol-increased plasma endotoxin levels and hepatic toll-like receptor 4 (TLR4)-NF-κB signaling along with subsequent inhibition of inflammatory cell infiltration. MitoQ also reversed alcohol-induced hepatic lipid accumulation through enhancing fatty acid β-oxidation. Alcohol-induced ER stress and apoptotic cell death signaling were reversed by MitoQ. This study demonstrated that speeding up acetaldehyde clearance by preserving ALDH2 activity critically mediates the beneficial effect of MitoQ on alcohol-induced pathogenesis at the gut-liver axis. Copyright © 2017 The Authors. Published by Elsevier B

  4. Anti-biofilm and bactericidal effects of magnolia bark-derived magnolol and honokiol on Streptococcus mutans.

    PubMed

    Sakaue, Yuuki; Domon, Hisanori; Oda, Masataka; Takenaka, Shoji; Kubo, Miwa; Fukuyama, Yoshiyasu; Okiji, Takashi; Terao, Yutaka

    2016-01-01

    Dental caries affects people of all ages and is a worldwide health concern. Streptococcus mutans is a major cariogenic bacterium because of its ability to form biofilm and induce an acidic environment. In this study, the antibacterial activities of magnolol and honokiol, the main constituents of the bark of magnolia plants, toward planktonic cell and biofilm of S. mutans were examined and compared with those of chlorhexidine. The minimal inhibitory concentrations of magnolol, honokiol and chlorhexidine for S. mutans were 10, 10 and 0.25 µg/mL, respectively. In addition, each agent showed bactericidal activity against S. mutans planktonic cells and inhibited biofilm formation in a dose- and time-dependent manner. Magnolol (50 µg/mL) had greater bactericidal activity against S. mutans biofilm than honokiol (50 µg/mL) and chlorhexidine (500 µg/mL) at 5 min after exposure, while all showed scant activity against biofilm at 30 s. Furthermore; chlorhexidine (0.5-500 µg/mL) exhibited high cellular toxicity for the gingival epithelial cell line Ca9-22 at 1 hr, whereas magnolol (50 µg/mL) and honokiol (50 µg/mL) did not. Thus; it was found that magnolol has antimicrobial activities against planktonic and biofilm cells of S. mutans. Magnolol may be a candidate for prevention and management of dental caries. © 2015 The Societies and John Wiley & Sons Australia, Ltd.

  5. The natural products magnolol and honokiol are positive allosteric modulators of both synaptic and extra-synaptic GABAA receptors

    PubMed Central

    Alexeev, Mikhail; Grosenbaugh, Denise K.; Mott, David D.; Fisher, Janet L.

    2012-01-01

    The National Center for Complementary and Alternative Medicine (NCCAM) estimates that nearly 40% of adults in the United States use alternative medicines, often in the form of an herbal supplement. Extracts from the tree bark of magnolia species have been used for centuries in traditional Chinese and Japanese medicines to treat a variety of neurological diseases, including anxiety, depression, and seizures. The active ingredients in the extracts have been identified as the bi-phenolic isomers magnolol and honokiol. These compounds were shown to enhance the activity of GABAA receptors, consistent with their biological effects. The GABAA receptors exhibit substantial subunit heterogeneity, which influences both their functional and pharmacological properties. We examined the activity of magnolol and honokiol at different populations of both neuronal and recombinant GABAA receptors to characterize their mechanism of action and to determine whether sensitivity to modulation was dependent upon the receptor’s subunit composition. We found that magnolol and honokiol enhanced both phasic and tonic GABAergic neurotransmission in hippocampal dentate granule neurons. In addition, all recombinant receptors examined were sensitive to modulation, regardless of the identity of the α, β, or γ subunit subtype, although the compounds showed particularly high efficacy at δ-containing receptors. This direct positive modulation of both synaptic and extra-synaptic populations of GABAA receptors suggests that supplements containing magnolol and/or honokiol would be effective anxiolytics, sedatives, and anti-convulsants. However, significant side-effects and risk of drug interactions would also be expected. PMID:22445602

  6. Pro-Apoptotic Activity of New Honokiol/Triphenylmethane Analogues in B-Cell Lymphoid Malignancies.

    PubMed

    Mędra, Aleksandra; Witkowska, Magdalena; Majchrzak, Agata; Cebula-Obrzut, Barbara; Bonner, Michael Y; Robak, Tadeusz; Arbiser, Jack L; Smolewski, Piotr

    2016-07-30

    Honokiol and triphenylmethanes are small molecules with anti-tumor properties. Recently, we synthesized new honokiol analogues (HAs) that possess common features of both groups. We assessed the anti-tumor effectiveness of HAs in B-cell leukemia/lymphoma cells, namely in chronic lymphocytic leukemia (CLL) cells ex vivo and in pre-B-cell acute lymphoblastic leukemia (Nalm-6), Burkitt lymphoma (BL; Raji), diffuse large B-cell lymphoma (DLBCL; Toledo) and multiple myeloma (MM; RPMI 8226) cell lines. Four of these compounds appeared to be significantly active against the majority of cells examined, with no significant impact on healthy lymphocytes. These active HAs induced caspase-dependent apoptosis, causing significant deregulation of several apoptosis-regulating proteins. Overall, these compounds downregulated Bcl-2 and XIAP and upregulated Bax, Bak and survivin proteins. In conclusion, some of the HAs are potent tumor-selective inducers of apoptosis in ex vivo CLL and in BL, DLBCL and MM cells in vitro. Further preclinical studies of these agents are recommended.

  7. Ketamine and MAG Lipase Inhibitor-Dependent Reversal of Evolving Depressive-Like Behavior During Forced Abstinence From Alcohol Drinking.

    PubMed

    Holleran, Katherine M; Wilson, Hadley H; Fetterly, Tracy L; Bluett, Rebecca J; Centanni, Samuel W; Gilfarb, Rachel A; Rocco, Lauren E R; Patel, Sachin; Winder, Danny G

    2016-07-01

    Although alcoholism and depression are highly comorbid, treatment options that take this into account are lacking, and mouse models of alcohol (ethanol (EtOH)) intake-induced depressive-like behavior have not been well established. Recent studies utilizing contingent EtOH administration through prolonged two-bottle choice access have demonstrated depression-like behavior following EtOH abstinence in singly housed female C57BL/6J mice. In the present study, we found that depression-like behavior in the forced swim test (FST) is revealed only after a protracted (2 weeks), but not acute (24 h), abstinence period. No effect on anxiety-like behavior in the EPM was observed. Further, we found that, once established, the affective disturbance is long-lasting, as we observed significantly enhanced latencies to approach food even 35 days after ethanol withdrawal in the novelty-suppressed feeding test (NSFT). We were able to reverse affective disturbances measured in the NSFT following EtOH abstinence utilizing the N-methyl D-aspartate receptor (NMDAR) antagonist and antidepressant ketamine but not memantine, another NMDAR antagonist. Pretreatment with the monoacylglycerol (MAG) lipase inhibitor JZL-184 also reduced affective disturbances in the NSFT in ethanol withdrawn mice, and this effect was prevented by co-administration of the CB1 inverse agonist rimonabant. Endocannabinoid levels were decreased within the BLA during abstinence compared with during drinking. Finally, we demonstrate that the depressive behaviors observed do not require a sucrose fade and that this drinking paradigm may favor the development of habit-like EtOH consumption. These data could set the stage for developing novel treatment approaches for alcohol-withdrawal-induced mood and anxiety disorders.

  8. [Alcohol].

    PubMed

    Zima, T

    1996-07-14

    Alcohol is one of the most widely used addictive substances. It can be assumed that everybody encounters alcohol--ethanol in various forms and concentrations in the course of their lives. A global and social problem of our civilization is alcohol consumption which has a rising trend. Since 1989 the consumption of alcoholic beverages is rising and the mean annual consumption of concentrated ethanol per head is cea 10 litres. In ethanol abuse the organism is damaged not only by ethanol alone but in particular by substances formed during its metabolism. Its detailed knowledge is essential for the knowledge and investigations of the metabolic and toxic effect of ethanol on the organism. Ingested alcohol is in 90-98% eliminated from the organism by three known metabolic pathways: 1-alcohol dehydrogenase, 2-the microsomal ethanol oxidizing system and 3-catalase. Alcohol is a frequent important risk factor of serious "diseases of civilization" such as IHD, hypertension, osteoporosis, neoplastic diseases. Cirrhosis of the liver and chronic pancreatitis are the well known diseases associated with alcohol ingestion and also their most frequent cause. It is impossible to list all organs and diseases which develop as a result of alcohol consumption. It is important to realize that regular and "relatively" small amounts in the long run damage the organism and may be even fatal.

  9. Simultaneous determination of Magnolol and Honokiol by amino acid ionic liquid synchronous fluorescence spectrometry

    NASA Astrophysics Data System (ADS)

    Liu, Wei; Zhu, Xiashi

    2018-05-01

    A novel method based on amino acid ionic liquids (AAILs) as an additive synchronous fluorescence spectrometry is proposed for simultaneous determination of magnolol (MN) and honokiol (HN) in traditional Chinese medicine Houpu. The overlapping fluorescence spectrum of MN and HN could be completely separated in the AAILs medium. Experiment parameters (the type and concentration of AAILs, pH values and temperature) were discussed. The detection limits of MN and HN reached 1.46 ng/mL, 0.92 ng/mL and the recovery rates ranged from 98.6%-100.7%, 99.7%-100.6%, respectively. This methods was successfully employed for simultaneously determination of MN and HN in real samples. No significant differences could be found in the results of this method and the pharmacopoeia of People's Republic of China 2015 (Ch.P.2015). The experiment mechanisms were discussed by the Gaussian simulation and fluorescence quantum yield.

  10. Honokiol protects against renal ischemia/reperfusion injury via the suppression of oxidative stress, iNOS, inflammation and STAT3 in rats.

    PubMed

    Yu, Yongwu; Li, Mingxv; Su, Ning; Zhang, Zhiyong; Zhao, Haidan; Yu, Hai; Xu, Yingluan

    2016-02-01

    Honokiol is the predominant active ingredient in the commonly used traditional Chinese medicine, Magnolia, which has been confirmed in previous studies to exhibit anti-oxidation, antimicrobial, antitumor and other pharmacological effects. However, its effects on renal ischemia/reperfusion injury (IRI) remain to be elucidated. The present study aimed to examine the effects of honokiol on renal IRI, and to investigate its potential protective mechanisms in the heart. Male adult Wistar albino rats were induced into a renal IRI model. Subsequently, the levels of serum creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), and the levels of serum nitrite and the kidney nitrite were examined in the IRI group. The levels of oxidative stress, inducible nitric oxide synthase (iNOS), inflammatory factors and caspase-3 were evaluated using a series of commercially available kits. The levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and the protein expression levels of STAT3 were determined using western blotting. Pretreatment with honokiol significantly reduced the levels of serum creatinine, BUN, ALT, AST and ALP, and the level of nitrite in the kidney of the IRI group, compared with the control group. The levels of malondialdehyde, the activity of myeloperoxidase, and the gene expression and activity of iNOS were reduced in the IRI rats, compared with the sham-operated rats, whereas the levels of superoxide dismutase and catalase were increased following treatment with honokiol in the IRI rats. In addition, the expression levels of tumor necrosis factor-α and interleukin-6 in the IRI rats were increased by honokiol. Treatment with honokiol suppressed the protein expression levels of p-STAT3 and caspase-3 in the IRI rats. These findings indicated that honokiol protects against renal IRI via the suppression of oxidative stress, iNOS, inflammation and STAT3 in

  11. Surface modification of polyamide reverse osmosis membrane with sulfonated polyvinyl alcohol for antifouling

    NASA Astrophysics Data System (ADS)

    Zhang, Yang; Wan, Ying; Pan, Guoyuan; Shi, Hongwei; Yan, Hao; Xu, Jian; Guo, Min; Wang, Zhe; Liu, Yiqun

    2017-10-01

    Sulfonated polyvinyl alcohol (SPVA) was synthesized by esterification reaction of PVA and sulfuric acid, and the structure was characterized by FTIR spectrum. Then a series of TFC membranes modified with cross-linked SPVA layer were fabricated by coating method, with glutaraldehyde as the cross-linker. The resulting TFC membranes were characterized by SEM, AFM, ATR-FTIR, XPS, streaming potential as well as static contact angle. The TFC membranes modified with SPVA exhibit decreased water flux and increased NaCl rejection with SPVA content increasing in the coating aqueous solution. The optimal PA-SPVA-0.5 sample exhibits a NaCl rejection of 99.18%, which is higher than the 98.32% of the virgin PA membrane. More importantly, the PA-SPVA-0.5 membrane shows much more improved fouling resistance to BSA and CTAB than virgin PA membrane and the TFC sample modified with PVA (PA-PVA-0.5). PA-SPVA-0.5 membrane loses about 8% of the initial flux after BSA fouling for 12 h, which is much lower than those of virgin PA and PA-PVA-0.5 membranes (28% and 15%, respectively). Furthermore, the flux recovery of the PA-SPVA-0.5 membrane reaches above 95% after cleaning. Thus, the PA-SPVA-0.5 membrane shows potential applications as antifouling RO membrane for desalination and purification.

  12. Fiber-Optic Bio-sniffer (Biochemical Gas Sensor) Using Reverse Reaction of Alcohol Dehydrogenase for Exhaled Acetaldehyde.

    PubMed

    Iitani, Kenta; Chien, Po-Jen; Suzuki, Takuma; Toma, Koji; Arakawa, Takahiro; Iwasaki, Yasuhiko; Mitsubayashi, Kohji

    2018-02-23

    Volatile organic compounds (VOCs) exhaled in breath have huge potential as indicators of diseases and metabolisms. Application of breath analysis for disease screening and metabolism assessment is expected since breath samples can be noninvasively collected and measured. In this research, a highly sensitive and selective biochemical gas sensor (bio-sniffer) for gaseous acetaldehyde (AcH) was developed. In the AcH bio-sniffer, a reverse reaction of alcohol dehydrogenase (ADH) was employed for reducing AcH to ethanol and simultaneously consuming a coenzyme, reduced form of nicotinamide adenine dinucleotide (NADH). The concentration of AcH can be quantified by fluorescence detection of NADH that was consumed by reverse reaction of ADH. The AcH bio-sniffer was composed of an ultraviolet light-emitting diode (UV-LED) as an excitation light source, a photomultiplier tube (PMT) as a fluorescence detector, and an optical fiber probe, and these three components were connected with a bifurcated optical fiber. A gas-sensing region of the fiber probe was developed with a flow-cell and an ADH-immobilized membrane. In the experiment, after optimization of the enzyme reaction conditions, the selectivity and dynamic range of the AcH bio-sniffer were investigated. The AcH bio-sniffer showed a short measurement time (within 2 min) and a broad dynamic range for determination of gaseous AcH, 0.02-10 ppm, which encompassed a typical AcH concentration in exhaled breath (1.2-6.0 ppm). Also, the AcH bio-sniffer exhibited a high selectivity to gaseous AcH based on the specificity of ADH. The sensor outputs were observed only from AcH-contained standard gaseous samples. Finally, the AcH bio-sniffer was applied to measure the concentration of AcH in exhaled breath from healthy subjects after ingestion of alcohol. As a result, a significant difference of AcH concentration between subjects with different aldehyde dehydrogenase type 2 (ALDH2) phenotypes was observed. The AcH bio-sniffer can be

  13. New in vitro insights on a cell death pathway induced by magnolol and honokiol in aristolochic acid tubulotoxicity.

    PubMed

    Bunel, Valérian; Antoine, Marie-Hélène; Stévigny, Caroline; Nortier, Joëlle; Duez, Pierre

    2016-01-01

    Aristolochic acids (AA) are nephrotoxic agents found in Aristolochia species whose consumption leads to the onset of a progressive tubulointerstitial fibrosis. This AA-nephropathy was first reported during the Belgian outbreak of the 1990's in which more than a hundred patients consumed slimming pills containing an Aristolochia species and Magnolia officinalis. The patients developed an end-stage kidney disease requiring dialysis or transplantation. Magnolol and honokiol are bioactive compounds from M. officinalis known for their potent antioxidant activity. As they can alleviate oxidative stress, we investigated their respective effects on AA-mediated tubulotoxicity using HK-2 cells. Magnolol and honokiol were able to reduce the oxidative stress associated with AA-treatment. Cytotoxicity alleviation was further investigated and overall cell viability measurements unexpectedly revealed that both compounds worsened the survival of AA-treated cells. Flow cytometry analyses of annexin V/PI stained cells indicated that the lignans efficiently prevented AA-induced apoptosis; but favored necrosis. Microscopy observations highlighted extensive vacuolization; other types of cell death, including autophagy, paraptosis or accelerated senescence were excluded. Ki-67 index and cell cycle analysis indicated that both magnolol and honokiol inhibited proliferation by blocking the cell cycle at the G1 phase; they also prevented the AA-induced G2/M arrest. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Alcohol.

    ERIC Educational Resources Information Center

    Schibeci, Renato

    1996-01-01

    Describes the manufacturing of ethanol, the effects of ethanol on the body, the composition of alcoholic drinks, and some properties of ethanol. Presents some classroom experiments using ethanol. (JRH)

  15. Alcohol

    MedlinePlus

    ... created when grains, fruits, or vegetables are fermented . Fermentation is a process that uses yeast or bacteria ... change the sugars in the food into alcohol. Fermentation is used to produce many necessary items — everything ...

  16. Magnolol and honokiol regulate the calcium-activated potassium channels signaling pathway in Enterotoxigenic Escherichia coli-induced diarrhea mice.

    PubMed

    Deng, Yanli; Han, Xuefeng; Tang, Shaoxun; Xiao, Wenjun; Tan, Zhiliang; Zhou, Chuanshe; Wang, Min; Kang, Jinghe

    2015-05-15

    To explore the regulatory mechanisms of magnolol and honokiol on calcium-activated potassium channels signaling pathway in Enterotoxigenic Escherichia coli (ETEC)-induced diarrhea mice, the concentrations of serum chloride ion (Cl(-)), sodium ion (Na(+)), potassium ion (K(+)) and calcium ion (Ca(2+)) were measured. Additionally, the mRNA expressions of calmodulin 1 (CaM), calcium/calmodulin-dependent protein kinase II alpha subunit (CaMKIIα) and beta subunit (CaMKIIβ), ryanodine receptor 1, inositol 1,4,5-trisphosphate receptors (IP3 receptors), protein kinases C (PKC), potassium intermediate/small conductance calcium-activated channels (SK) and potassium large conductance calcium-activated channels(BK)were determined. A diarrhea mouse model was established using ETEC suspensions (3.29×10(9)CFU/ml) at a dosage of 0.02ml/g live body weight (BW). Magnolol or honokiol was intragastrically administered at dosages of 100 (M100 or H100), 300 (M300 or H300) and 500 (M500 or H500) mg/kg BW according to a 3×3 factorial arrangement. Magnolol and honokiol increased the Cl(-) and K(+) concentrations, further, upregulated the CaM, BKα1 and BKβ3 mRNA levels but downregulated the IP3 receptors 1, PKC, SK1, SK2, SK3, SK4 and BKβ4 mRNA expressions. Magnolol and honokiol did not alter the CaMKIIα, CaMKIIβ, ryanodine receptor 1, IP3 receptor 2, IP3 receptor 3, BKβ1 and BKβ2 mRNA expressions. These results clarify that magnolol and honokiol, acting through Ca(2+) channel blockade, inhibit the activation of IP3 receptor 1 to regulate the IP3-Ca(2+) store release, activate CaM to inhibit SK channels, and effectively suppress PKC kinases to promote BKα1 and BKβ3 channels opening and BKβ4 channel closing, which modulates the intestinal ion secretion. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Modulation of Rat Hepatic CYP1A and 2C Activity by Honokiol and Magnolol: Differential Effects on Phenacetin and Diclofenac Pharmacokinetics In Vivo.

    PubMed

    Kim, Sang-Bum; Kim, Kyu-Sang; Ryu, Heon-Min; Hong, Seong-Ho; Kim, Bo-Kyoung; Kim, Dae-Duk; Park, Jin Woo; Yoon, In-Soo

    2018-06-17

    Honokiol (2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol) and magnolol (4-Allyl-2-(5-allyl-2-hydroxy-phenyl)phenol) are the major active polyphenol constituents of Magnolia officinalis (Magnoliaceae) bark, which has been widely used in traditional Chinese medicine (Houpu Tang) for the treatment of various diseases, including anxiety, stress, gastrointestinal disorders, infection, and asthma. The aim of this study was to investigate the direct effects of honokiol and magnolol on hepatic CYP1A and 2C-mediated metabolism in vitro using rat liver microsomes and in vivo using the Sprague-Dawley rat model. Honokiol and magnolol inhibited in vitro CYP1A activity (probe substrate: phenacetin) more potently than CYP2C activity (probe substrate: diclofenac): The mean IC 50 values of honokiol for the metabolism of phenacetin and diclofenac were 8.59 μM and 44.7 μM, while those of magnolol were 19.0 μM and 47.3 μM, respectively. Notably, the systemic exposure (AUC and C max ) of phenacetin, but not of diclofenac, was markedly enhanced by the concurrent administration of intravenous honokiol or magnolol. The differential effects of the two phytochemicals on phenacetin and diclofenac in vivo pharmacokinetics could at least be partly attributed to their lower IC 50 values for the inhibition of phenacetin metabolism than for diclofenac metabolism. In addition, the systemic exposure, CL, and V ss of honokiol and magnolol tended to be similar between the rat groups receiving phenacetin and diclofenac. These findings improve our understanding of CYP-mediated drug interactions with M. officinalis and its active constituents.

  18. Magnolol and Honokiol Attenuate Apoptosis of Enterotoxigenic Escherichia Coli-Induced Intestinal Epithelium by Maintaining Secretion and Absorption Homeostasis and Protecting Mucosal Integrity.

    PubMed

    Deng, Yanli; Han, Xuefeng; Tang, Shaoxun; Li, Chengjian; Xiao, Wenjun; Tan, Zhiliang

    2018-05-21

    BACKGROUND The cortex of Magnolia officinalis has long been used as an element of traditional Chinese medicine for the treatment of anxiety, chronic bronchitis, and gastrointestinal dysfunction. This study aimed to elucidate the underlying mechanism of its functional ingredients (magnolol and honokiol) in modifying the secretion and absorption homeostasis and protecting mucosal integrity in an Enterotoxigenic Escherichia coli (ETEC)-induced diarrhea mouse model. MATERIAL AND METHODS This study established a diarrhea mouse model infected by ETEC at a dosage of 0.02 ml/g live body weight (BW) in vivo. Magnolol or honokiol was followed by an intraperitoneal administration at dosages of 100, 300, and 500 mg/kg BW according to a 3×3 factorial arrangement. The useful biomarkers for evaluating the integrity of intestinal tract and histologic injury were analyzed and morphological development (including villus height, crypt depth, and ratio of villus height to crypt depth) and the expressions of inflammatory cytokines were determined by real-time PCR. RESULTS The results showed that magnolol and honokiol (500 mg/kg BW) reduced the concentrations of NO, DAO, and DLA, and iNOS activity, and the mRNA expressions of the interferon gamma (IFN-γ) and interleukin 10 (IL-10), and inhibited intestinal epithelial cell apoptosis. Magnolol and honokiol (300 mg/kg BW) elongated the villus height and crypt depth and decreased the number of goblet cells and the ratio of villus height to crypt depth. CONCLUSIONS The current results indicate that magnolol and honokiol enhance the intestinal anti-inflammatory capacities, elongate the villus height and crypt depth, and reduce goblet cell numbers to inhibit the intestinal epithelium apoptosis and effectively protect the intestinal mucosa. These results show that magnolol and honokiol protect the intestinal mucosal integrity and regulate gastrointestinal dysfunction.

  19. UPLC-MS/MS-ESI assay for simultaneous determination of magnolol and honokiol in rat plasma: application to pharmacokinetic study after administration emulsion of the isomer.

    PubMed

    Sheng, Yi-Ling; Xu, Jing-Hua; Shi, Cai-Hong; Li, Wei; Xu, Hai-Yan; Li, Ning; Zhao, Yu-Qing; Zhang, Xiang-Rong

    2014-09-29

    Magnolia officinalis is one of the commonly used in traditional Chinese medicine for the treatment of fever, chronic bronchitis and stomach ailments. Magnolol and honokiol are isomers with hydroxylated biphenol compound in the extract of Magnolia officinalis. This study aims to determine the isomers in rat plasma and evaluate their pharmacokinetic pattern after administration emulsion. Sprague Dawley male rats received either an intravenous (i.v.25, mg/kg) or oral (50mg/kg) dose of the emulsion of the isomer. A sensitive and specific ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for the investigation of the pharmacokinetics of magnolol and honokiol in rats. Kaempferol was employed as an internal standard. The plasma samples were deproteinized with acetonitrile, the post-treatment samples were analyzed on an Agela C18 column interfaced with a triple quadrupole tandem mass spectrometer in negative electrospray ionization mode. Acetonitrile and 5 mmol/L ammonium acetate buffer solution (65: 35, v/v) was used as the mobile phase at a flow rate of 0.2 mL/min. Following oral administration of emulsion to rats, magnolol attained mean peak plasma concentrations of 426.4 ± 273.8 ng/mL at 1.20 h, whereas honokiol reached peak plasma concentrations of 40.3 ± 30.8 ng/mL at 0.45 h. The absolute bioavailability of magnolol and honokiol is 17.5 ± 9.7% and 5.3 ± 11.7%. By comparison, the AUC0-∞ of magnolol was 5.4 times higher than that of honokiol after intravenous administration, but AUC0-∞ of magnolol was about 18-fold higher than honokiol after oral administration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Alcohol

    MedlinePlus

    ... to do. Wondering if adding a glass of wine or beer might help lower your blood glucose if it is high? The effects of alcohol can be unpredictable and it is not recommended as a treatment for high blood glucose. The risks likely outweigh any benefit that may be seen in blood glucose alone. ...

  1. Paid protection? Ethics of incentivised long-acting reversible contraception in adolescents with alcohol and other drug use.

    PubMed

    Won, Tiana; Blumenthal-Barby, Jennifer; Chacko, Mariam

    2017-03-01

    Pregnant adolescents have a higher risk of poor maternal and fetal outcomes, particularly in the setting of concomitant maternal alcohol and other drug (AOD) use. Despite numerous programmes aimed at reducing overall teen pregnancy rates and the recognition of AOD use as a risk factor for unintended pregnancy in adolescents, interventions targeting this specific group have been sparse. In adult drug-using women, financial incentives for contraception have been provided but are ethically controversial. This article explores whether a trial could ethically employ monetary incentives in adolescents with AOD use to promote the use of long-acting reversible contraception (LARC), with special attention to the relevant distinctions between adults and adolescents. We conclude that a trial of incentives to promote LARC in this patient population is ethically permissible if the incentives are small, are tied to completion of an educational activity to minimise the quick fix temptation and potential for non-attendance to the risks and benefits of LARC and are provided only to the adolescent after an assessment of her reasoning to rule out coercion (eg, by guardians) as motivation. Information about treatment for AOD use and follow-up care in case of problems with the contraceptive or desire for removal should also be provided. Before implementing such a trial, qualitative research with input from providers, potential patients and their parents should be conducted to inform the programme's specific structure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. The synergy of honokiol and fluconazole against clinical isolates of azole-resistant Candida albicans.

    PubMed

    Jin, J; Guo, N; Zhang, J; Ding, Y; Tang, X; Liang, J; Li, L; Deng, X; Yu, L

    2010-09-01

    To evaluate the interaction of fluconazole (FLC) and honokiol (HNK) in vitro and vivo against azole-resistant (azole-R) clinical isolates of Candida albicans. A checkerboard microdilution method was used to study the in vitro interaction of FLC and HNK in 24 azole-R clinical isolates of C. albicans. In vivo antifungal activity was performed to further analyse the interaction between FLC and HNK. In the in vitro study, synergism was observed in all 24 FLC-resistant strains tested as determined by fractional inhibitory concentration index (FICI), and in 22 strains by Delta E models. No antagonistic activity was observed in any of the strains tested. These positive interactions were also confirmed by using the time-killing test for the selected strain C. albicans YL371, which shows strong susceptible to the combination of HNK and FLC. In the in vivo study, the mice with candidiasis were treated successfully by a combination therapy of HNK with FLC, the results showed a decrease of the colony forming unit in infected and treated animals compared to the controls, at the conditions of the treatment used in this study. Synergistic activity of HNK and FLC against clinical isolates of FLC-resistant C. albicans was observed in vitro and in vivo. This report might provide a potential therapeutic method to overcome the problem of drug-resistance in C. albicans.

  3. Chronic cytoprotection: pentadecapeptide BPC 157, ranitidine and propranolol prevent, attenuate and reverse the gastric lesions appearance in chronic alcohol drinking rats.

    PubMed

    Prkacin, I; Aralica, G; Perovic, D; Separovic, J; Gjurasin, M; Lovric-Bencic, M; Stancic-Rokotov, D; Ziger, T; Anic, T; Sikiric, P; Seiwerth, S; Staresinic, M; Mise, S; Rotkvic, I; Jagic, V; Rucman, R; Petek, M; Turkovic, B; Marovic, A; Sjekavica, I; Sebecic, B; Boban-Blagaic, A; Ivasovic, Z

    2001-01-01

    Unlike severe gastric damage acutely induced by ethanol administration in rat, the ulcerogenic effect of chronic alcohol administration (3.03 g/kg b.w. or 7.28 g/kg b.w.) given in drinking water, producing liver lesions and portal hypertension, is far less investigated. Therefore, focus was on the antiulcer effect of the gastric pentadecapeptide BPC 157, GEPPPGKPADDAGLV, M.W. 1419, known to have a beneficial effect in variety of gastrointestinal lesions models (10 microg or 10 ng/kg b.w. i.p. or i.g.), ranitidine (10 mg/kg b.w. i.g.) and propranol (10 mg/kg b.w. i.g.) or saline (5 ml/kg b.w. i.p./i.g.; control). They were given once daily (1) throughout 10 days preceding alcohol consumption, (2) since beginning of alcohol drinking till the end of the study, (3) throughout the last month of alcohol consumption, 2 months after alcohol drinking had been initiated. Gastric lesions were assessed, at the end of 3 months drinking [(1), (2)] or with respect to therapeutic effect of medication before medication or at the end of therapy. Pentadecapeptide BPC 157, ranitidine and propranolol may prevent gastric lesion development if given prophylactically, before alcohol drinking. Likewise, they attenuate the lesion appearance given once daily throughout the drinking period. Importantly, when given therapeutically, they may antagonize otherwise pertinent lesion presence in stomach mucosa of the drinking rats. Thus, these results demonstrate that pentadecapeptide BPC 157, ranitidine and propranol may prevent, attenuate or reverse the gastric lesions appearance in chronically alcohol drinking rats, and may be used for further therapy, while the other studies showed that their effect (except to ranitidine) is parallel with their beneficial effect on liver lesion and portal hypertension.

  4. Honokiol and magnolol production by in vitro micropropagated plants of Magnolia dealbata, an endangered endemic Mexican species.

    PubMed

    Domínguez, Fabiola; Chávez, Marco; Garduño-Ramírez, María Luisa; Chávez-Avila, Víctor M; Mata, Martín; Cruz-Sosa, Francisco

    2010-02-01

    An efficient protocol for the in vitro propagation of Magnolia dealbata Zucc., an important medicinal plant that is the source of the anxiolytic and anticancer compounds honokiol and magnolol, was established. This plant is wild-crafted, and conservationists have expressed concerns with regard to the sustainability of production. In the present work, two factors were found to be of importance for the regeneration of M. dealbata and the production of honokiol and magnolol. These factors were the type of explants and the combination and concentration of plant-growth regulators. Green, compact, nodular organogenic callus was obtained from leaf explants in a medium fortified with Murashige and Skoog salts and supplemented with 1.5 mg/L 2,4-dicholorophenoxyacetic acid and 1.5 mg/L kinetin. Shoots multiplication from callus cultures was achieved in the Murashige and Skoog (MS) medium with 1.5 mg/L thidiazuron (TDZ). Phenol secretion was controlled by the addition of 250 mg/L of activated charcoal. For rooting, shoots were transferred to MS medium supplemented with several auxins. After root induction, the plants were hardened in earthen pots containing sand, soil, and vermiculite. The contents of honokiol (HK) and magnolol (MG) were determined in different plant materials by high-performance liquid chromatography-diode-array detection techniques. This analysis revealed that the honokiol and magnolol content in aerial and underground parts of micropropagated M. dealbata were higher than that observed in wild plants (both 6 months old). Our results suggest that conservation of M. dealbata is possible by means of in vitro multiplication of leaf-derived callus. The usefulness of M. dealbata regeneration and production of HK and MG may be attributed to the proper selection of explant sourcing and identification of the correct growth medium to support adequate growth. This careful selection of explants and growth medium leads to a very useful source of plant material for

  5. Dietary intervention, but not losartan, completely reverses non-alcoholic steatohepatitis in obese and insulin resistant mice.

    PubMed

    Verbeek, Jef; Spincemaille, Pieter; Vanhorebeek, Ilse; Van den Berghe, Greet; Vander Elst, Ingrid; Windmolders, Petra; van Pelt, Jos; van der Merwe, Schalk; Bedossa, Pierre; Nevens, Frederik; Cammue, Bruno; Thevissen, Karin; Cassiman, David

    2017-02-23

    Dietary intervention is the cornerstone of non-alcoholic steatohepatitis (NASH) treatment. However, histological evidence of its efficacy is limited and its impact on hepatic pathways involved in NASH is underreported. The efficacy of the angiotensin receptor type 1 blocker losartan is controversial because of varying results in a few animal and human studies. We evaluated the effect of dietary intervention versus losartan on NASH and associated systemic metabolic features in a representative mouse model. Male C57BL/6 J mice with high fat-high sucrose diet (HF-HSD) induced NASH, obesity, insulin resistance and hypercholesterolemia were subjected to dietary intervention (switch from HF-HSD to normal chow diet (NCD)) (n = 9), continuation HF-HSD together with losartan (30 mg/kg/day) (n = 9) or continuation HF-HSD only (n = 9) for 8 weeks. 9 mice received NCD during the entire experiment (20 weeks). We assessed the systemic metabolic effects and performed a detailed hepatic histological and molecular profiling. A P-value of < 0.05, using the group with continuation of HF-HSD only as control, was considered as statistically significant. Dietary intervention normalized obesity, insulin resistance, and hypercholesterolemia (for all P < 0.001), and remarkably, completely reversed all histological features of pre-existent NASH (for all P < 0.001), including fibrosis measured by quantification of collagen proportional area (P < 0.01). At the hepatic molecular level, dietary intervention targeted fibrogenesis with a normalization of collagen type I alpha 1, transforming growth factor β1, tissue inhibitor of metalloproteinase 1 mRNA levels (for all P < 0.01), lipid metabolism with a normalization of fatty acid translocase/CD36, fatty acid transport protein 5, fatty acid synthase mRNA levels (P < 0.05) and markers related to mitochondrial function with a normalization of hepatic ATP content (P < 0.05) together with sirtuin1 and

  6. Synthesis of fruity ethyl esters by acyl coenzyme A: alcohol acyltransferase and reverse esterase activities in Oenococcus oeni and Lactobacillus plantarum.

    PubMed

    Costello, P J; Siebert, T E; Solomon, M R; Bartowsky, E J

    2013-03-01

    To assess the abilities of commercial wine lactic acid bacteria (LAB) to synthesize potentially flavour active fatty acid ethyl esters and determine mechanisms involved in their production. Oenococcus oeni AWRI B551 produced significant levels of ethyl hexanoate and ethyl octanoate following growth in an ethanolic test medium, and ester formation generally increased with increasing pH (4.5 > 3.5), anaerobiosis and precursor supplementation. Cell-free extracts of commercial O. oeni strains and Lactobacillus plantarum AWRI B740 were also tested for ester-synthesizing capabilities in a phosphate buffer via: (i) acyl coenzyme A: alcohol acyltransferase (AcoAAAT) activity and (ii) reverse esterase activity. For both ester-synthesizing activities, strain-dependent variation was observed, with AcoAAAT activity generally greater than reverse esterase. Reverse esterase in O. oeni AWRI B551 also esterified 1-propanol to produce propyl octanoate, and deuterated substrates ([(2)H(6)]ethanol and [(2)H(15)]octanoic acid) to produce the fully deuterated ester, [(2)H(5)]ethyl [(2)H(15)]octanoate. Wine LAB exhibit ethyl ester-synthesizing capability and possess two different ester-synthesizing activities, one of which is associated with an acyl coenzyme A: alcohol acyltransferase. This study demonstrates that wine LAB exhibit enzyme activities that can augment the ethyl ester content of wine. This knowledge will facilitate greater control over the impacts of malolactic fermentation on the fruity sensory properties and quality of wine. © 2012 Australian Wine Research Institute © 2012 The Society for Applied Microbiology.

  7. Effects of large volume injection of aliphatic alcohols as sample diluents on the retention of low hydrophobic solutes in reversed-phase liquid chromatography.

    PubMed

    David, Victor; Galaon, Toma; Aboul-Enein, Hassan Y

    2014-01-03

    Recent studies showed that injection of large volume of hydrophobic solvents used as sample diluents could be applied in reversed-phase liquid chromatography (RP-LC). This study reports a systematic research focused on the influence of a series of aliphatic alcohols (from methanol to 1-octanol) on the retention process in RP-LC, when large volumes of sample are injected on the column. Several model analytes with low hydrophobic character were studied by RP-LC process, for mobile phases containing methanol or acetonitrile as organic modifiers in different proportions with aqueous component. It was found that starting with 1-butanol, the aliphatic alcohols can be used as sample solvents and they can be injected in high volumes, but they may influence the retention factor and peak shape of the dissolved solutes. The dependence of the retention factor of the studied analytes on the injection volume of these alcohols is linear, with a decrease of its value as the sample volume is increased. The retention process in case of injecting up to 200μL of upper alcohols is dependent also on the content of the organic modifier (methanol or acetonitrile) in mobile phase. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Biodegradable self-assembled PEG-PCL-PEG micelles for hydrophobic honokiol delivery: I. Preparation and characterization

    NASA Astrophysics Data System (ADS)

    Gong, ChangYang; Wei, XiaWei; Wang, XiuHong; Wang, YuJun; Guo, Gang; Mao, YongQiu; Luo, Feng; Qian, ZhiYong

    2010-05-01

    This study aims to develop self-assembled poly(ethylene glycol)-poly(ɛ-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) micelles to encapsulate hydrophobic honokiol (HK) in order to overcome its poor water solubility and to meet the requirement of intravenous administration. Honokiol loaded micelles (HK-micelles) were prepared by self-assembly of PECE copolymer in aqueous solution, triggered by its amphiphilic characteristic assisted by ultrasonication without any organic solvents, surfactants and vigorous stirring. The particle size of the prepared HK-micelles measured by Malvern laser particle size analyzer were 58 nm, which is small enough to be a candidate for an intravenous drug delivery system. Furthermore, the HK-micelles could be lyophilized into powder without any adjuvant, and the re-dissolved HK-micelles are stable and homogeneous with particle size about 61 nm. Furthermore, the in vitro release profile showed a significant difference between the rapid release of free HK and the much slower and sustained release of HK-micelles. Moreover, the cytotoxicity results of blank micelles and HK-micelles showed that the PECE micelle was a safe carrier and the encapsulated HK retained its potent antitumor effect. In short, the HK-micelles were successfully prepared by an improved method and might be promising carriers for intravenous delivery of HK in cancer chemotherapy, being effective, stable, safe (organic solvent and surfactant free), and easy to produce and scale up.

  9. Reversibility of object recognition but not spatial memory impairment following binge-like alcohol exposure in rats.

    PubMed

    Cippitelli, Andrea; Zook, Michelle; Bell, Lauren; Damadzic, Ruslan; Eskay, Robert L; Schwandt, Melanie; Heilig, Markus

    2010-11-01

    Excessive alcohol use leads to neurodegeneration in several brain structures including the hippocampal dentate gyrus and the entorhinal cortex. Cognitive deficits that result are among the most insidious and debilitating consequences of alcoholism. The object exploration task (OET) provides a sensitive measurement of spatial memory impairment induced by hippocampal and cortical damage. In this study, we examine whether the observed neurotoxicity produced by a 4-day binge ethanol treatment results in long-term memory impairment by observing the time course of reactions to spatial change (object configuration) and non-spatial change (object recognition). Wistar rats were assessed for their abilities to detect spatial configuration in the OET at 1 week and 10 weeks following the ethanol treatment, in which ethanol groups received 9-15 g/kg/day and achieved blood alcohol levels over 300 mg/dl. At 1 week, results indicated that the binge alcohol treatment produced impairment in both spatial memory and non-spatial object recognition performance. Unlike the controls, ethanol treated rats did not increase the duration or number of contacts with the displaced object in the spatial memory task, nor did they increase the duration of contacts with the novel object in the object recognition task. After 10 weeks, spatial memory remained impaired in the ethanol treated rats but object recognition ability was recovered. Our data suggest that episodes of binge-like alcohol exposure result in long-term and possibly permanent impairments in memory for the configuration of objects during exploration, whereas the ability to detect non-spatial changes is only temporarily affected. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Reversibility of object recognition but not spatial memory impairment following binge-like alcohol exposure in rats

    PubMed Central

    Cippitelli, Andrea; Zook, Michelle; Bell, Lauren; Damadzic, Ruslan; Eskay, Robert L.; Schwandt, Melanie; Heilig, Markus

    2010-01-01

    Excessive alcohol use leads to neurodegeneration in several brain structures including the hippocampal dentate gyrus and the entorhinal cortex. Cognitive deficits that result are among the most insidious and debilitating consequences of alcoholism. The object exploration task (OET) provides a sensitive measurement of spatial memory impairment induced by hippocampal and cortical damage. In this study, we examine whether the observed neurotoxicity produced by a 4-day binge ethanol treatment results in long-term memory impairment by observing the time course of reactions to spatial change (object configuration) and non-spatial change (object recognition). Wistar rats were assessed for their abilities to detect spatial configuration in the OET at 1 week and 10 weeks following the ethanol treatment, in which ethanol groups received 9–15 g/kg/day and achieved blood alcohol levels over 300 mg/dl. At 1 week, results indicated that the binge alcohol treatment produced impairment in both spatial memory and non-spatial object recognition performance. Unlike the controls, ethanol treated rats did not increase the duration or number of contacts with the displaced object in the spatial memory task, nor did they increase the duration of contacts with the novel object in the object recognition task. After 10 weeks, spatial memory remained impaired in the ethanol treated rats but object recognition ability was recovered. Our data suggest that episodes of binge-like alcohol exposure result in long-term and possibly permanent impairments in memory for the configuration of objects during exploration, whereas the ability to detect non-spatial changes is only temporarily affected. PMID:20849966

  11. Reversal of alcohol induced testicular hyperlipidemia by supplementation of ascorbic acid and its comparison with abstention in male guinea pigs.

    PubMed

    Radhakrishnakartha, Harikrishnan; Appu, Abhilash Puthuvelvippel; Madambath, Indira

    2014-02-01

    Chronic ethanol exposure causes hyperlipidemia. The present study was designed to investigate the impact of ascorbic acid supplementation on ethanol induced hyperlipidemia in testis and to compare it with that of abstinence from taking alcohol. Thirty-six male guinea pigs were divided into two groups and were maintained for 90 days as follows (1) control (C) (2) ethanol treated group (E) (4 g/kg body wt/day). Ethanol was administered for 90 days and on 90th day, alanine amino transaminase (ALT), aspartate amino transaminase (AST) and γ-glutamyltransferase (GGT) in serum was assayed. The animals in the ethanol group were further divided into an ascorbic acid supplemented group (25 mg/100 g body wt/day) (E+AA) and an ethanol abstention group (EAG) and those in the control group were divided into a control group and a control+ascorbic acid group (C+AA). There was significant increase in levels of testicular cholesterol, free fatty acid, phospholipids and triglycerides in the ethanol group. There was also a significant increase in the activity of HMG CoA reductase and decrease in activity of testicular glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme in ethanol-ingested animals that further led to decreased levels of serum testosterone. Alcohol administration also enhanced the activity of testicular alcohol dehydrogenase (ADH). Ascorbic acid supplementation and abstention altered all these parameters induced by chronic alcohol administration. Histological studies were also in line with the above results. Ascorbic acid was able to reinstate the cholesterol homeostasis in testis which could have further restored the testicular steroidogenesis. The present study demonstrated that ascorbic acid is effective in reducing the hyperlipidemia induced by chronic alcohol administration and produced a better recovery than abstention.

  12. Determination of eight artificial sweeteners and common Stevia rebaudiana glycosides in non-alcoholic and alcoholic beverages by reversed-phase liquid chromatography coupled with tandem mass spectrometry.

    PubMed

    Kubica, Paweł; Namieśnik, Jacek; Wasik, Andrzej

    2015-02-01

    The method for the determination of acesulfame-K, saccharine, cyclamate, aspartame, sucralose, alitame, neohesperidin dihydrochalcone, neotame and five common steviol glycosides (rebaudioside A, rebaudioside C, steviol, steviolbioside and stevioside) in soft and alcoholic beverages was developed using high-performance liquid chromatography and tandem mass spectrometry with electrospray ionisation (HPLC-ESI-MS/MS). To the best of our knowledge, this is the first work that presents an HPLC-ESI-MS/MS method which allows for the simultaneous determination of all EU-authorised high-potency sweeteners (thaumatin being the only exception) in one analytical run. The minimalistic sample preparation procedure consisted of only two operations; dilution and centrifugation. Linearity, limits of detection and quantitation, repeatability, and trueness of the method were evaluated. The obtained recoveries at three tested concentration levels varied from 97.0 to 105.7%, with relative standard deviations lower than 4.1%. The proposed method was successfully applied for the determination of sweeteners in 24 samples of different soft and alcoholic drinks.

  13. Portal hypertension and liver lesions in chronically alcohol drinking rats prevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116), and propranolol, but not ranitidine.

    PubMed

    Prkacin, I; Separovic, J; Aralicia, G; Perovic, D; Gjurasin, M; Lovric-Bencic, M; Stancic-Rokotov, D; Staresinic, M; Anic, T; Mikus, D; Sikiric, P; Seiwerth, S; Mise, S; Rotkvic, I; Jagic, V; Rucman, R; Petek, M; Turkovic, B; Marovic, A; Sebecic, B; Boban-Blagaic, A; Kokic, N

    2001-01-01

    markedly attenuated (values less than in drinking controls, still higher than in healthy rats, i.e. circumference and area of hepatocytes nucleus). On the other hand, ranitidine application attenuated only steatosis development. In summary, despite continuous chronic alcohol drinking, pentadecapeptide BPC 157, and propranolol may prevent portal hypertension as well as reverse already established portal hypertension along with related liver disturbances.

  14. Rescuing prefrontal cAMP-CREB pathway reverses working memory deficits during withdrawal from prolonged alcohol exposure.

    PubMed

    Dominguez, G; Dagnas, M; Decorte, L; Vandesquille, M; Belzung, C; Béracochéa, D; Mons, N

    2016-03-01

    Both human and animal studies indicate that alcohol withdrawal following chronic alcohol consumption (CAC) impairs many of the cognitive functions which rely on the prefrontal cortex (PFC). A candidate signaling cascade contributing to memory deficits during alcohol withdrawal is the protein kinase A (PKA)/cAMP-responsive element binding (CREB) cascade, although the role of PKA/CREB cascade in behavioral and molecular changes during sustained withdrawal period remains largely unknown. We demonstrated that 1 week (1W) or 6 weeks (6W) withdrawal after 6-month CAC impairs working memory (WM) in a T-maze spontaneous alternation task and reduces phosphorylated CREB (pCREB) in the PFC but not the dorsal CA1 region (dCA1) of the hippocampus compared with CAC and water conditions. In contrast, both CAC-unimpaired and withdrawn-impaired mice exhibited decreased pCREB in dCA1 as well as reduced histone H4 acetylation in PFC and dCA1, compared with water controls. Next, we showed that enhancing CREB activity through rolipram administration prior to testing improved WM performance in withdrawn mice but impaired WM function in water mice. In addition, WM improvement correlates positively with increased pCREB level selectively in the PFC of withdrawn mice. Results further indicate that direct infusion of the PKA activator (Sp-cAMPS) into the PFC significantly improves or impairs, respectively, WM performance in withdrawn and water animals. In contrast, Sp-cAMPS had no effect on WM when infused into the dCA1. Collectively, these results provide strong support that dysregulation of PKA/CREB-dependent processes in prefrontal neurons is a critical molecular signature underlying cognitive decline during alcohol withdrawal.

  15. In vitro synergism of magnolol and honokiol in combination with antibacterial agents against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA).

    PubMed

    Zuo, Guo-Ying; Zhang, Xin-Juan; Han, Jun; Li, Yu-Qing; Wang, Gen-Chun

    2015-12-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a problematic pathogen posing a serious therapeutic challenge in the clinic. It is often multidrug-resistant (MDR) to conventional classes of antibacterial agents and there is an urgent need to develop new agents or strategies for treatment. Magnolol (ML) and honokiol (HL) are two naturally occurring diallylbiphenols which have been reported to show inhibition of MRSA. In this study their synergistic effects with antibacterial agents were further evaluated via checkerboard and time-kill assays. The susceptibility spectrum of clinical MRSA strains was tested by the disk diffusion method. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of ML and HL were assayed by broth microdilution. The synergy was evaluated through checkerboard microdilution and time-killing experiments. ML and HL showed similar activity against both MSSA and MRSA with MIC/MBC at 16 ~ 64 mg/L, with potency similar to amikacin (AMK) and gentamicin (GEN). When they were used in combination with conventional antibacterial agents, they showed bacteriostatic synergy with FICIs between 0.25 ~ 0.5, leading to the combined MICs decreasing to as low as 1 ~ 2 and 1 ~ 16 mg/L for ML (HL) and the agents, respectively. MIC50 of the combinations decreased from 16 mg/L to 1 ~ 4 mg/L for ML (HL) and 8 ~ 128 mg/L to 2 ~ 64 mg/L for the antibacterial agents, which exhibited a broad spectrum of synergistic action with aminoglycosides (AMK, etilmicin (ETM) and GEN), floroquinolones (levofloxacin (LEV), ciprofloxacin and norfloxacin), fosfomycin (FOS) and piperacillin. The times of dilution (TOD, the extent of decreasing in MIC value) were determined up to 16 for the combined MIC. A more significant synergy after combining was determined as ML (HL) with AMK, ETM, GEN and FOS. ML (HL) combined with antibacterial agents did not show antagonistic effects on any of the ten MRSA strains. Reversal effects of MRSA resistance to

  16. H2-P, a honokiol derivative, exerts anti-angiogenesis effects via c-MYC signaling pathway in glioblastoma.

    PubMed

    Wang, Ting; Chen, Wei; Wu, Jialin

    2018-04-01

    H2-P, a derivative of honokiol, was first synthesized in our laboratory. Compared with honokiol, H2-P has even high anti-tumor activity. In the present study, we evaluated the ability of H2-P to inhibit the survival rate in four gliomas cell lines. The result showed that H2-P could significantly inhibit proliferation of gliomas cells in a dose-dependent manner (IC50 U251  = 9.03, IC50 SHG-44  = 10.74, IC50 U78  = 19.87, and IC50 c6  = 22.56 nM). Furthermore, to determine the mechanism underlying the anti-gliomas effects of H2-P, six kinase activities was detected by Z'-LYTE™ system. The high-throughput screening shown that effect targets of H2-P were MEK and VEGFR2. We also studied the inhibition of H2-P vascular endothelial cells (EA.HY926). The data shown that H2-P could increase endothelial cells apoptosis rate, while inhibiting endothelial cell proliferation (IC50 EA.hy926  = 16.11 nM) and migration. Besides, we investigated anti-angiogenesis of H2-P in the rat thoracic aorta rings, chicken chorioallantoic membrane (CAM), and capillary tube formation models. H2-P showed strong inhibition of angiogenesis. Moreover, we found that H2-P also could reduce tumor volume in mice significantly (P < 0.01), and downregulate gene expression level of VEGFR2, MEK, and c-MYC in tumor. These data suggest that H2-P have an excellent anti-tumor activity by exerting anti-angiogenesis effects via c-MYC signaling pathway in glioblastoma (GBM). © 2017 Wiley Periodicals, Inc.

  17. Reversed phase liquid chromatography with UV absorbance and flame ionization detection using a water mobile phase and a cyano propyl stationary phase Analysis of alcohols and chlorinated hydrocarbons.

    PubMed

    Quigley, W W; Ecker, S T; Vahey, P G; Synovec, R E

    1999-10-01

    The development of liquid chromatography with a commercially available cyano propyl stationary phase and a 100% water mobile phase is reported. Separations were performed at ambient temperature, simplifying instrumental requirements. Excellent separation efficiency using a water mobile phase was achieved, for example N=18 800, or 75 200 m(-1), was obtained for resorcinol, at a retention factor of k'=4.88 (retention time of 9.55 min at 1 ml min(-1) for a 25 cmx4.6 mm i.d. column, packed with 5 mum diameter particles with the cyano propyl stationary phase). A separation via reversed phase liquid chromatography (RP-LC) with a 100% water mobile phase of six phenols and related compounds was compared to a separation of the same compounds by traditional RP-LC, using octadecylsilane (ODS), i.e. C18, bound to silica and an aqueous mobile phase modified with acetonitrile. Nearly identical analysis time was achieved for the separation of six phenols and related compounds using the cyano propyl stationary phase with a 100% water mobile phase, as compared to traditional RP-LC requiring a relatively large fraction of organic solvent modifier in the mobile phase (25% acetonitrile:75% water). Additional understanding of the retention mechanism with the 100% water mobile phase was obtained by relating measured retention factors of aliphatic alcohols, phenols and related compounds, and chlorinated hydrocarbons to their octanol:water partition coefficients. The retention mechanism is found to be consistent with a RP-LC mechanism coupled with an additional retention effect due to residual hydroxyl groups on the cyano propyl stationary phase. Advantages due to a 100% water mobile phase for the chemical analysis of alcohol mixtures and chlorinated hydrocarbons are reported. By placing an absorbance detector in-series and preceding a novel drop interface to a flame ionization detector (FID), selective detection of a separated mixture of phenols and related compounds and aliphatic

  18. Comparison of single-step reverse transepithelial all-surface laser ablation (ASLA) to alcohol-assisted photorefractive keratectomy.

    PubMed

    Aslanides, Ioannis M; Padroni, Sara; Arba Mosquera, Samuel; Ioannides, Antonis; Mukherjee, Achyut

    2012-01-01

    To evaluate postoperative pain, corneal epithelial healing, development of corneal haze, refractive outcomes, and corneal aberrations in a novel one-step, modified transepithelial photorefractive keratectomy (PRK), termed All-surface laser ablation (ASLA), compared to conventional, alcohol-assisted PRK. Sixty eyes of 30 myopic patients were prospectively recruited to a randomized fellow eye study. Patients underwent conventional alcohol-assisted PRK in one eye (control group) and ASLA-modified transepithelial PRK in the other (30 eyes in each treatment arm). Primary endpoints were postoperative pain and haze scores at 1 day, 3 days, 1 week, and 1, 3, 6, and 12 months. Secondary endpoints included visual acuity at 1, 3, 6, and 12 months, corneal aberrations at 3, 6, and 12 months, and early and late onset haze. Refractive predictability, safety, and efficacy of the two methods were considered. The average age of the cohort was 29 years (standard deviation [SD]: 9; range: 18-46), and the average spherical equivalent refractive error was -4.18 diopters (SD: 1.9). At 3 days after surgery, the average pain score was 64% lower in the ASLA group (P < 0.0005). At this point, 96% of ASLA eyes had no epithelial defect, whereas 43% in the alcohol-assisted group did not achieve complete epithelial healing, and required replacement of bandage contact lens. The haze level was consistently lower in the ASLA group at all time points from 1 to 6 months. This study shows that the ASLA technique may have a future role in refractive surgery, due to the fact that it offers faster epithelial healing, lower pain scores, and significantly less haze formation.

  19. Comparison of single-step reverse transepithelial all-surface laser ablation (ASLA) to alcohol-assisted photorefractive keratectomy

    PubMed Central

    Aslanides, Ioannis M; Padroni, Sara; Mosquera, Samuel Arba; Ioannides, Antonis; Mukherjee, Achyut

    2012-01-01

    Purpose To evaluate postoperative pain, corneal epithelial healing, development of corneal haze, refractive outcomes, and corneal aberrations in a novel one-step, modified transepithelial photorefractive keratectomy (PRK), termed All-surface laser ablation (ASLA), compared to conventional, alcohol-assisted PRK. Materials and methods Sixty eyes of 30 myopic patients were prospectively recruited to a randomized fellow eye study. Patients underwent conventional alcohol-assisted PRK in one eye (control group) and ASLA-modified transepithelial PRK in the other (30 eyes in each treatment arm). Primary endpoints were postoperative pain and haze scores at 1 day, 3 days, 1 week, and 1, 3, 6, and 12 months. Secondary endpoints included visual acuity at 1, 3, 6, and 12 months, corneal aberrations at 3, 6, and 12 months, and early and late onset haze. Refractive predictability, safety, and efficacy of the two methods were considered. Results The average age of the cohort was 29 years (standard deviation [SD]: 9; range: 18–46), and the average spherical equivalent refractive error was −4.18 diopters (SD: 1.9). At 3 days after surgery, the average pain score was 64% lower in the ASLA group (P < 0.0005). At this point, 96% of ASLA eyes had no epithelial defect, whereas 43% in the alcohol-assisted group did not achieve complete epithelial healing, and required replacement of bandage contact lens. The haze level was consistently lower in the ASLA group at all time points from 1 to 6 months. Conclusion This study shows that the ASLA technique may have a future role in refractive surgery, due to the fact that it offers faster epithelial healing, lower pain scores, and significantly less haze formation. PMID:22815640

  20. Separation and Determination of Honokiol and Magnolol in Chinese Traditional Medicines by Capillary Electrophoresis with the Application of Response Surface Methodology and Radial Basis Function Neural Network

    PubMed Central

    Han, Ping; Luan, Feng; Yan, Xizu; Gao, Yuan; Liu, Huitao

    2012-01-01

    A method for the separation and determination of honokiol and magnolol in Magnolia officinalis and its medicinal preparation is developed by capillary zone electrophoresis and response surface methodology. The concentration of borate, content of organic modifier, and applied voltage are selected as variables. The optimized conditions (i.e., 16 mmol/L sodium tetraborate at pH 10.0, 11% methanol, applied voltage of 25 kV and UV detection at 210 nm) are obtained and successfully applied to the analysis of honokiol and magnolol in Magnolia officinalis and Huoxiang Zhengqi Liquid. Good separation is achieved within 6 min. The limits of detection are 1.67 µg/mL for honokiol and 0.83 µg/mL for magnolol, respectively. In addition, an artificial neural network with “3-7-1” structure based on the ratio of peak resolution to the migration time of the later component (Rs/t) given by Box-Behnken design is also reported, and the predicted results are in good agreement with the values given by the mathematic software and the experimental results. PMID:22291059

  1. Magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas

    PubMed Central

    Cheng, Yu-Chen; Hueng, Dueng-Yuan; Huang, Hua-Yin; Chen, Jang-Yi; Chen, Ying

    2016-01-01

    Glioblastoma (GBM) is a malignant brain tumor associated with a high mortality rate. The aim of this study is to investigate the synergistic effects of honokiol (Hono) and magnolol (Mag), extracted from Magnolia officinalis, on cytotoxicity and inhibition of human GBM tumor progression in cellular and animal models. In comparison with Hono or Mag alone, co-treatment with Hono and Mag (Hono-Mag) decreased cyclin A, D1 and cyclin-dependent kinase 2, 4, 6 significantly, leading to cell cycle arrest in U87MG and LN229 human glioma cells. In addition, phosphorylated phosphoinositide 3-kinase (p-PI3K), p-Akt, and Ki67 were decreased after Hono-Mag treatment, showing proliferation inhibition. Hono-Mag treatment also reduced p-p38 and p-JNK but elevated p-ERK expression. Besides, Hono-Mag treatment induced autophagy and intrinsic and extrinsic apoptosis. Both ERK and autophagy inhibitors enhanced Hono-Mag-induced apoptosis in LN229 cells, indicating a rescuer role of ERK. In human GBM orthotopic xenograft model, the Hono-Mag treatment inhibited the tumor progression and induced apoptosis more efficiently than Temozolomide, Hono, or Mag group. In conclusion, the Hono-Mag exerts a synergistic anti-tumor effect by inhibiting cell proliferation and inducing autophagy and apoptosis in human GBM cells. The Hono-Mag may be applied as an adjuvant therapy to improve the therapeutic efficacy of GBM treatment. PMID:27074557

  2. Inhibitory Effects of Honokiol on the Voltage-Gated Potassium Channels in Freshly Isolated Mouse Dorsal Root Ganglion Neurons.

    PubMed

    Sheng, Anqi; Zhang, Yan; Li, Guang; Zhang, Guangqin

    2018-02-01

    Voltage-gated potassium (K V ) currents, subdivided into rapidly inactivating A-type currents (I A ) and slowly inactivating delayed rectifier currents (I K ), play a fundamental role in modulating pain by controlling neuronal excitability. The effects of Honokiol (Hon), a natural biphenolic compound derived from Magnolia officinalis, on K V currents were investigated in freshly isolated mouse dorsal root ganglion neurons using the whole-cell patch clamp technique. Results showed that Hon inhibited I A and I K in concentration-dependent manner. The IC 50 values for block of I A and I K were 30.5 and 25.7 µM, respectively. Hon (30 µM) shifted the steady-state activation curves of I A and I K to positive potentials by 17.6 and 16.7 mV, whereas inactivation and recovery from the inactivated state of I A were unaffected. These results suggest that Hon preferentially interacts with the active states of the I A and I K channels, and has no effect on the resting state and inactivated state of the I A channel. Blockade on K + channels by Hon may contribute to its antinociceptive effect, especially anti-inflammatory pain.

  3. Exploring the reversal of enantioselectivity on a zinc-dependent alcohol dehydrogenase† †Electronic supplementary information (ESI) available. See DOI: 10.1039/C7OB00482F Click here for additional data file.

    PubMed Central

    Maria-Solano, Miguel A.; Romero-Rivera, Adrian

    2017-01-01

    Alcohol Dehydrogenase (ADH) enzymes catalyse the reversible reduction of prochiral ketones to the corresponding alcohols. These enzymes present two differently shaped active site pockets, which dictate their substrate scope and selectivity. In this study, we computationally evaluate the effect of two commonly reported active site mutations (I86A, and W110T) on a secondary alcohol dehydrogenase from Thermoanaerobacter brockii (TbSADH) through Molecular Dynamics simulations. Our results indicate that the introduced mutations induce dramatic changes in the shape of the active site, but most importantly they impact the substrate–enzyme interactions. We demonstrate that the combination of Molecular Dynamics simulations with the tools POVME and NCIplot corresponds to a powerful strategy for rationalising and engineering the stereoselectivity of ADH variants. PMID:28436515

  4. Alcoholism and Alcohol Abuse

    MedlinePlus

    ... their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that causes ... the liver, brain, and other organs. Drinking during pregnancy can harm your baby. Alcohol also increases the ...

  5. Comparative inhibitory effects of magnolol, honokiol, eugenol and bis-eugenol on cyclooxygenase-2 expression and nuclear factor-kappa B activation in RAW264.7 macrophage-like cells stimulated with fimbriae of Porphyromonas gingivalis.

    PubMed

    Murakami, Yukio; Kawata, Akifumi; Seki, Yuya; Koh, Teho; Yuhara, Kenji; Maruyama, Takehisa; Machino, Mamoru; Ito, Shigeru; Kadoma, Yoshinori; Fujisawa, Seiichiro

    2012-01-01

    The anti-inflammatory activity of magnolol and related compounds is currently a focus of interest. In the present study, the inhibitory effects of these compounds on cyclooxygenase (COX-2) expression and nuclear factor-kappa B (NF-κB) activation were investigated in RAW264.7 macrophage-like cells stimulated with the fimbriae of Porphyromonas gingivalis, an oral anaerobe. The cytotoxicity of magnolol, honokiol, eugenol and bis-eugenol against RAW264.7 cells was determined using a cell counting kit (CCK-8). The regulatory effect of these compounds on the expression of COX-2 mRNA, stimulated by exposure to the fimbriae was investigated by real-time polymerase chain reaction (PCR). NF-κB activation was evaluated by enzyme-linked immunosorbent assay (ELISA)-like microwell colorimetric transcription factor activity assay (Trans-AM) and western blot analysis. The radical-scavenging activity was determined using the induction period method in the methyl methacrylate-azobisisobutyronitrile (AIBN) polymerization system under nearly anaerobic conditions. The phenolic bond dissociation enthalpy (BDE) and orbital energy were calculated at the density functional theory (DFT) B3LYP/6-31G* level. The cytotoxicity against RAW264.7 cells declined in the order bis-eugenol>eugenol> honokiol>magnolol, whereas the radical-scavenging activity declined in the order honokiol, bis-eugenol>magnolol> eugenol. Magnolol and honokiol significantly inhibited the fimbria-induced expression of COX-2 at non-cytotoxic concentrations. Both the fimbria-stimulated binding of NF-κB to its consensus sequence and phosphorylation-dependent proteolysis of inhibitor κB-α were markedly inhibited by magnilol and honokiol, whereas eugenol and bis-eugenol did not inhibit COX-2 expression and NF-κB activation. Magnolol and honokiol possessed a high electronegativity (χ) value. Magnolol and honokiol exhibit antioxidative activity, low cytotoxicity, and anti-inflammatory activity. These compounds may be

  6. Repeated diazepam administration reversed working memory impairments and glucocorticoid alterations in the prefrontal cortex after short but not long alcohol-withdrawal periods.

    PubMed

    Dominguez, G; Henkous, N; Pierard, C; Belzung, C; Mons, N; Beracochea, Daniel

    2018-04-30

    The study was designed to assess whether repeated administration of diazepam (Valium®, Roche)-a benzodiazepine exerting an agonist action on GABA A receptors-may alleviate both the short (1 week, 1W) and long-term (6 weeks, 6W) deleterious effects of alcohol withdrawal occurring after chronic alcohol consumption (6 months; 12% v/v) in C57/BL6 male mice. More pointedly, we first evidenced that 1W and 6W alcohol-withdrawn mice exhibited working memory deficits in a sequential alternation task, associated with sustained exaggerated corticosterone rise and decreased pCREB levels in the prefrontal cortex (PFC). In a subsequent experiment, diazepam was administered i.p. for 9 consecutive days (1 injection/day) during the alcohol withdrawal period at decreasing doses ranging from 1.0 mg/kg to 0.25 mg/kg. Diazepam was not detected in the blood of withdrawn mice at the time of memory testing, occurring 24 hours after the last diazepam injection. Repeated diazepam administration significantly improved alternation rates and normalized levels of glucocorticoids and pCREB activity in the PFC in 1W but not in 6W withdrawn mice. Thus, repeated diazepam administration during the alcohol-withdrawal period only transitorily canceled out the working memory impairments and glucocorticoid alterations in the PFC of alcohol-withdrawn animals.

  7. Honokiol Dimers and Magnolol Derivatives with New Carbon Skeletons from the Roots of Magnolia officinalis and Their Inhibitory Effects on Superoxide Anion Generation and Elastase Release

    PubMed Central

    Chen, Hung-Chung; Kuo, Ping-Chung; Lee, E-Jian; Lee, Kuo-Hsiung; Wu, Tian-Shung

    2013-01-01

    Two honokiol dimers, houpulins A and B (1 and 2), and two magnolol derivatives, houpulins C and D (3 and 4), were isolated and characterized from an ethanol extract obtained from the roots of Magnolia officinalis. The chemical structures were determined based on spectroscopic and physicochemical analyses, which included 1D and 2D NMR, as well as mass spectrometry data. These four oligomers possess new carbon skeletons postulated to be biosynthesized from the coupling of three or four C6-C3 subunits. In addition, the new oligomers were evaluated for inhibition of superoxide anion generation and elastase release, and houpulin B (2) was identified as a new anti-inflammatory lead compound. PMID:23667420

  8. Reversal of alcohol dependence-induced deficits in cue-guided behavior via mGluR2/3 signaling in mice.

    PubMed

    Barker, Jacqueline M; Lench, Daniel H; Chandler, L Judson

    2016-01-01

    Alcohol use disorders are associated with deficits in adaptive behavior. While some behavioral impairments that are associated with alcohol use disorders may predate exposure to drugs of abuse, others may result directly from exposure to drugs of abuse, including alcohol. Identifying a causal role for how alcohol exposure leads to these impairments will enable further investigation of the neurobiological mechanisms by which it acts to dysregulate adaptive behavior. In the present study, we examined the effects of chronic intermittent ethanol exposure (CIE) on the use of reward-paired cues to guide consummatory behaviors in a mouse model, and further, how manipulations of mGluR2/3 signaling-known to be dysregulated after chronic alcohol exposure-may alter the expression of this behavior. Adult male C57B/6J mice were trained to self-administer 10 % ethanol and exposed to CIE via vapor inhalation. After CIE exposure, mice were trained in a Pavlovian task wherein a cue (tone) was paired with the delivery of a 10 % sucrose unconditioned stimulus. The use of the reward-paired cue to guide licking behavior was determined across training. The effect of systemic mGluR2/3 manipulation on discrimination between cue-on and cue-off intervals was assessed by administration of the mGluR2/3 agonist LY379268 or the antagonist LY341495 prior to a testing session. Exposure to CIE resulted in reductions in discrimination between cue-on and cue-off intervals, with CIE-exposed mice exhibiting significantly lower consummatory behavior during reward-paired cues than air controls. In addition, systemic administration of an mGluR2/3 agonist restored the use of reward-paired cues in CIE-exposed animals without impacting behavior in air controls. Conversely, administration of an mGluR2/3 antagonist mimicked the effects of CIE on cue-guided licking behavior, indicating that mGluR2/3 signaling can bidirectionally regulate the ability to use reward-paired cues to guide behavior. Together

  9. Reverse Algols

    NASA Technical Reports Server (NTRS)

    Leung, K. C.

    1989-01-01

    Reverse Algols, binary systems with a semidetached configuration in which the more massive component is in contact with the critical equipotential surface, are examined. Observational evidence for reverse Algols is presented and the parameters of seven reverse Algols are listed. The evolution of Algols and reverse Algols is discussed. It is suggested that, because reverse Algols represent the premass-reversal semidetached phase of close binary evolution, the evolutionary time scale between regular and reverse Algols is the ratio of the number of confirmed systems of these two Algol types.

  10. Sevelamer Improves Steatohepatitis, Inhibits Liver and Intestinal Farnesoid X Receptor (FXR), and Reverses Innate Immune Dysregulation in a Mouse Model of Non-alcoholic Fatty Liver Disease.

    PubMed

    McGettigan, Brett M; McMahan, Rachel H; Luo, Yuhuan; Wang, Xiaoxin X; Orlicky, David J; Porsche, Cara; Levi, Moshe; Rosen, Hugo R

    2016-10-28

    Bile acid sequestrants are synthetic polymers that bind bile acids in the gut and are used to treat dyslipidemia and hyperphosphatemia. Recently, these agents have been reported to lower blood glucose and increase insulin sensitivity by altering bile acid signaling pathways. In this study, we assessed the efficacy of sevelamer in treating mice with non-alcoholic fatty liver disease (NAFLD). We also analyzed how sevelamer alters inflammation and bile acid signaling in NAFLD livers. Mice were fed a low-fat or Western diet for 12 weeks followed by a diet-plus-sevelamer regimen for 2 or 12 weeks. At the end of treatment, disease severity was assessed, hepatic leukocyte populations were examined, and expression of genes involved in farnesoid X receptor (FXR) signaling in the liver and intestine was analyzed. Sevelamer treatment significantly reduced liver steatosis and lobular inflammation. Sevelamer-treated NAFLD livers had notably fewer pro-inflammatory infiltrating macrophages and a significantly greater fraction of alternatively activated Kupffer cells compared with controls. Expression of genes involved in FXR signaling in the liver and intestine was significantly altered in mice with NAFLD as well as in those treated with sevelamer. In a mouse model of NAFLD, sevelamer improved disease and counteracted innate immune cell dysregulation in the liver. This study also revealed a dysregulation of FXR signaling in the liver and intestine of NAFLD mice that was counteracted by sevelamer treatment. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Reverse indentation size effects in gamma irradiated blood compatible blend films of chitosan-poly (vinyl alcohol) for possible medical applications.

    PubMed

    Bisen, D S; Bhatt, Rinkesh; Bajpai, A K; Bajpai, R; Katare, R

    2017-02-01

    In the present work binary blends of polyvinyl alcohol (PVA) and chitosan (CS) were prepared by solution cast method and characterized by analytical methods like FTIR, XRD and SEM for seeking structural and morphological information. The blends were exposed to gamma radiation and evaluated for their improved mechanical strength. It was found that the tensile strength and microhardness increased after irradiation of CS-PVA films. Plastic effect due to absorption of water molecules and scissoring effect due to gamma irradiation were found to decrease the softness or increase the microhardness of the blends. Improved mechanical properties were attributed to intermolecular and intramolecular hydrogen bonds and adhesive nature of the blends also. The blends were also investigated for water intake behavior and in vitro blood compatibility property on the basis of certain in vitro tests like protein adsorption, haemolysis and blood clot formation on the un-irradiated and irradiated blend samples. The increased % swelling with time could be assigned to the fact that increasing water content facilitates the phase separation process within the blend which results in advancement in interstitial nano-void spaces which are occupied by water molecules. The blood compatibility results showed that when the amount of CS was varied from 0.5% to 2%, the amount of blood clot and percent haemolysis decreased while the protein adsorption increased with increasing CS content of the blend films. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. SciTech Connect

    Yin Huquan; Kim, Youn-Chul; Chung, Young-Suk

    Ethanol induces hepatic steatosis via a complex mechanism that is not well understood. Among the variety of molecules that have been proposed to participate in this mechanism, the sterol regulatory element (SRE)-binding proteins (SREBPs) have been identified as attractive targets for therapeutic intervention. In the present study, we evaluated the effects of honokiol on alcoholic steatosis and investigated its possible effect on the inhibition of SREBP-1c maturation. In in vitro studies, H4IIEC3 rat hepatoma cells developed increased lipid droplets when exposed to ethanol, but co-treatment with honokiol reversed this effect. Honokiol inhibited the maturation of SREBP-1c and its translocation tomore » the nucleus, the binding of nSREBP-1c to SRE or SRE-related sequences of its lipogenic target genes, and the expression of genes for fatty acid synthesis. In contrast, magnolol, a structural isomer of honokiol, had no effect on nSREBP-1c levels. Male Wistar rats fed with a standard Lieber-DeCarli ethanol diet for 4 weeks exhibited increased hepatic triglyceride and decreased hepatic glutathione levels, with concomitantly increased serum alanine aminotransferase and TNF-{alpha} levels. Daily administration of honokiol (10 mg/kg body weight) by gavage during the final 2 weeks of ethanol treatment completely reversed these effects on hepatotoxicity markers, including hepatic triglyceride, hepatic glutathione, and serum TNF-{alpha}, with efficacious abrogation of fat accumulation in the liver. Inhibition of SREBP-1c protein maturation and of the expression of Srebf1c and its target genes for hepatic lipogenesis were also observed in vivo. A chromatin immunoprecipitation assay demonstrated inhibition of specific binding of SREBP-1c to the Fas promoter by honokiol in vivo. These results demonstrate that honokiol has the potential to ameliorate alcoholic steatosis by blocking fatty acid synthesis regulated by SREBP-1c.« less

  13. Alcoholism - resources

    MedlinePlus

    Resources - alcoholism ... The following organizations are good resources for information on alcoholism : Alcoholics Anonymous -- www.aa.org Al-Anon Family Groups www.al-anon.org National Institute on Alcohol ...

  14. Alcoholic neuropathy

    MedlinePlus

    Neuropathy - alcoholic; Alcoholic polyneuropathy ... The exact cause of alcoholic neuropathy is unknown. It likely includes both a direct poisoning of the nerve by the alcohol and the effect of poor nutrition ...

  15. Honokiol abrogates leptin-induced tumor progression by inhibiting Wnt1-MTA1-β-catenin signaling axis in a microRNA-34a dependent manner

    PubMed Central

    Avtanski, Dimiter B.; Nagalingam, Arumugam; Kuppusamy, Panjamurthy; Bonner, Michael Y.; Arbiser, Jack L.; Saxena, Neeraj K.; Sharma, Dipali

    2015-01-01

    Obesity greatly influences risk, progression and prognosis of breast cancer. As molecular effects of obesity are largely mediated by adipocytokine leptin, finding effective novel strategies to antagonize neoplastic effects of leptin is desirable to disrupt obesity-cancer axis. Present study is designed to test the efficacy of honokiol (HNK), a bioactive polyphenol from Magnolia grandiflora, against oncogenic actions of leptin and systematically elucidate the underlying mechanisms. Our results show that HNK significantly inhibits leptin-induced breast-cancer cell-growth, invasion, migration and leptin-induced breast-tumor-xenograft growth. Using a phospho-kinase screening array, we discover that HNK inhibits phosphorylation and activation of key molecules of leptin-signaling-network. Specifically, HNK inhibits leptin-induced Wnt1-MTA1-β-catenin signaling in vitro and in vivo. Finally, an integral role of miR-34a in HNK-mediated inhibition of Wnt1-MTA1-β-catenin axis was discovered. HNK inhibits Stat3 phosphorylation, abrogates its recruitment to miR-34a promoter and this release of repressor-Stat3 results in miR-34a activation leading to Wnt1-MTA1-β-catenin inhibition. Accordingly, HNK treatment inhibited breast tumor growth in diet-induced-obese mouse model (exhibiting high leptin levels) in a manner associated with activation of miR-34a and inhibition of MTA1-β-catenin. These data provide first in vitro and in vivo evidence for the leptin-antagonist potential of HNK revealing a crosstalk between HNK and miR34a and Wnt1-MTA1-β-catenin axis. PMID:26036628

  16. Alcohol advertising bans and alcohol abuse.

    PubMed

    Young, D J

    1993-07-01

    Henry Saffer [Saffer (1991) Journal of Health Economics 10, 65-79] concludes that bans on broadcast advertising for alcoholic beverages reduce total alcohol consumption, motor vehicle fatalities, and cirrhosis deaths. A reexamination of his data and procedures reveals a number of flaws. First, there is evidence of reverse causation: countries with low consumption/death rates tend to adopt advertising bans, creating a (spurious) negative correlation between bans and consumption/death rates. Second, even this correlation largely disappears when the estimates are corrected for serial correlation. Third, estimates based on the components of consumption--spirits, beer and wine--mostly indicate that bans are associated with increased consumption.

  17. Reversible Sterilization

    ERIC Educational Resources Information Center

    Largey, Gale

    1977-01-01

    Notes that difficult questions arise concerning the use of sterilization for alleged eugenic and euthenic purposes. Thus, how reversible sterilization will be used with relation to the poor, mentally ill, mentally retarded, criminals, and minors, is questioned. (Author/AM)

  18. Reverse Dynamization

    PubMed Central

    Glatt, Vaida; Bartnikowski, Nicole; Quirk, Nicholas; Schuetz, Michael; Evans, Christopher

    2016-01-01

    Background: Reverse dynamization is a technology for enhancing the healing of osseous defects. With use of an external fixator, the axial stiffness across the defect is initially set low and subsequently increased. The purpose of the study described in this paper was to explore the efficacy of reverse dynamization under different conditions. Methods: Rat femoral defects were stabilized with external fixators that allowed the stiffness to be modulated on living animals. Recombinant human bone morphogenetic protein-2 (rhBMP-2) was implanted into the defects on a collagen sponge. Following a dose-response experiment, 5.5 μg of rhBMP-2 was placed into the defect under conditions of very low (25.4-N/mm), low (114-N/mm), medium (185-N/mm), or high (254-N/mm) stiffness. Reverse dynamization was evaluated with 2 different starting stiffnesses: low (114 N/mm) and very low (25.4 N/mm). In both cases, high stiffness (254 N/mm) was imposed after 2 weeks. Healing was assessed with radiographs, micro-computed tomography (μCT), histological analysis, and mechanical testing. Results: In the absence of dynamization, the medium-stiffness fixators provided the best healing. Reverse dynamization starting with very low stiffness was detrimental to healing. However, with low initial stiffness, reverse dynamization considerably improved healing with minimal residual cartilage, enhanced cortication, increased mechanical strength, and smaller callus. Histological analysis suggested that, in all cases, healing provoked by rhBMP-2 occurred by endochondral ossification. Conclusions: These data confirm the potential utility of reverse dynamization as a way of improving bone healing but indicate that the stiffness parameters need to be selected carefully. Clinical Relevance: Reverse dynamization may reduce the amount of rhBMP-2 needed to induce healing of recalcitrant osseous lesions, reduce the time to union, and decrease the need for prolonged external fixation. PMID:27098327

  19. Reverse Logistics

    DTIC Science & Technology

    2001-05-01

    reverse logistics was to pick up the damage or obsolete items from the vendor and discard them into a land fill. Estee Lauder Companies, Inc. dumped as...Quality Center, Benchmarking and Leveraging “Best Practices” Strategies , Houston, TX, AQPC, 1995. 2. Brauner, Marygail, “Evaluating Five Proposed Price

  20. Black Alcoholism.

    ERIC Educational Resources Information Center

    Watts, Thomas D.; Wright, Roosevelt

    1988-01-01

    Examines some aspects of the problem of alcoholism among Blacks, asserting that Black alcoholism can best be considered in an ecological, environmental, sociocultural, and public health context. Notes need for further research on alcoholism among Blacks and for action to reduce the problem of Black alcoholism. (NB)

  1. Impairments in learning by monetary rewards and alcohol-associated rewards in detoxified alcoholic patients.

    PubMed

    Jokisch, Daniel; Roser, Patrik; Juckel, Georg; Daum, Irene; Bellebaum, Christian

    2014-07-01

    Excessive alcohol consumption has been linked to structural and functional brain changes associated with cognitive, emotional, and behavioral impairments. It has been suggested that neural processing in the reward system is also affected by alcoholism. The present study aimed at further investigating reward-based associative learning and reversal learning in detoxified alcohol-dependent patients. Twenty-one detoxified alcohol-dependent patients and 26 healthy control subjects participated in a probabilistic learning task using monetary and alcohol-associated rewards as feedback stimuli indicating correct responses. Performance during acquisition and reversal learning in the different feedback conditions was analyzed. Alcohol-dependent patients and healthy control subjects showed an increase in learning performance over learning blocks during acquisition, with learning performance being significantly lower in alcohol-dependent patients. After changing the contingencies, alcohol-dependent patients exhibited impaired reversal learning and showed, in contrast to healthy controls, different learning curves for different types of rewards with no increase in performance for high monetary and alcohol-associated feedback. The present findings provide evidence that dysfunctional processing in the reward system in alcohol-dependent patients leads to alterations in reward-based learning resulting in a generally reduced performance. In addition, the results suggest that alcohol-dependent patients are, in particular, more impaired in changing an established behavior originally reinforced by high rewards. Copyright © 2014 by the Research Society on Alcoholism.

  2. Alcoholism (image)

    MedlinePlus

    Alcoholism is a chronic illness marked by dependence on alcohol consumption that interferes with physical or mental health, and social, family or job responsibilities. This addiction can lead to liver, circulatory and neurological problems. Pregnant women who ...

  3. Alcohol Abuse

    ERIC Educational Resources Information Center

    O'Farrell, Timothy J.; Fals-Stewart, William

    2003-01-01

    We received 38 controlled studies of marital and family therapy (MFT) in alcoholism treatment. We conclude that, when the alcoholic is unwilling to seek help, MFT is effective in helping the family cope better and motivating alcoholics to enter treatment. Specifically, (a) Al-Anon facilitation and referral help family members cope better; (b)…

  4. Sex-Role Affiliation among Male Alcoholics.

    ERIC Educational Resources Information Center

    Penick, Elizabeth C.; And Others

    1984-01-01

    Compared sex role attributes of male alcoholic veterans to those of 81 nonalcoholic veterans and 386 college students. Results showed male alcoholics were sex-typed more frequently as feminine than masculine. Results were interpreted as a consequence, not a cause of the disorder and were considered reversible with sustained sobriety. (JAC)

  5. Alcoholic cardiomyopathy

    PubMed Central

    Guzzo-Merello, Gonzalo; Cobo-Marcos, Marta; Gallego-Delgado, Maria; Garcia-Pavia, Pablo

    2014-01-01

    Alcohol is the most frequently consumed toxic substance in the world. Low to moderate daily intake of alcohol has been shown to have beneficial effects on the cardiovascular system. In contrast, exposure to high levels of alcohol for a long period could lead to progressive cardiac dysfunction and heart failure. Cardiac dysfunction associated with chronic and excessive alcohol intake is a specific cardiac disease known as alcoholic cardiomyopathy (ACM). In spite of its clinical importance, data on ACM and how alcohol damages the heart are limited. In this review, we evaluate available evidence linking excessive alcohol consumption with heart failure and dilated cardiomyopathy. Additionally, we discuss the clinical presentation, prognosis and treatment of ACM. PMID:25228956

  6. Health risks of alcohol use

    MedlinePlus

    Alcoholism - risks; Alcohol abuse - risks; Alcohol dependence - risks; Risky drinking ... pubmed/23698791 . National Institute on Alcohol Abuse and Alcoholism website. Alcohol use disorder. www.niaaa.nih.gov/ ...

  7. Contingency management in the treatment of adolescent alcohol drinking problems.

    PubMed

    Brigham, S L; Rekers, G A; Rosen, A C; Swihart, J J; Pfrimmer, G; Ferguson, L N

    1981-09-01

    Three case studies demonstrated that social and monetary reinforcement for abstinence reduced the rate of excessive alcohol drinking in adolescents. The self-monitoring and extrinsic reinforcement procedures (ABA reversal design) resulted in complete abstinence in a 15-year-old boy with a 10-year history of excessive alcohol abuse and hospitalization for an alcohol-induced psychosis. In the cases of the 13-year-old and 15-year-old girls with extensive alcohol abuse histories, the behavioral interventions decreased the rate of alcohol consumption during treatment phases, but alcohol abuse increased markedly with the removal of the intervention procedures.

  8. Alcohol and pregnancy

    MedlinePlus

    Drinking alcohol during pregnancy; Fetal alcohol syndrome - pregnancy; FAS - fetal alcohol syndrome ... lead to lifelong damage. DANGERS OF ALCOHOL DURING PREGNANCY Drinking a lot of alcohol during pregnancy can ...

  9. Alcohol Energy Drinks

    MedlinePlus

    ... Home / About Addiction / Alcohol / Alcohol Energy Drinks Alcohol Energy Drinks Read 34001 times font size decrease font size increase font size Print Email Alcohol energy drinks (AEDs) or Caffeinated alcoholic beverages (CABs) are ...

  10. Alcohol conversion

    DOEpatents

    Wachs, Israel E.; Cai, Yeping

    2002-01-01

    Preparing an aldehyde from an alcohol by contacting the alcohol in the presence of oxygen with a catalyst prepared by contacting an intimate mixture containing metal oxide support particles and particles of a catalytically active metal oxide from Groups VA, VIA, or VIIA, with a gaseous stream containing an alcohol to cause metal oxide from the discrete catalytically active metal oxide particles to migrate to the metal oxide support particles and to form a monolayer of catalytically active metal oxide on said metal oxide support particles.

  11. Alcoholic ketoacidosis

    MedlinePlus

    Tests may include: Arterial blood gases (measures the acid/base balance and oxygen level in blood) Blood alcohol ... PA: Elsevier Saunders; 2014:chap 185. Seifter JL. Acid-base disorders. In: Goldman L, Schafer AI, eds. Goldman- ...

  12. Alcohol Intolerance

    MedlinePlus

    ... ingredients commonly found in alcoholic beverages, especially in beer or wine, can cause intolerance reactions. These include: Sulfites or other preservatives Chemicals, grains or other ingredients Histamine, a byproduct of fermentation or brewing In some cases, reactions can be ...

  13. Alcohol withdrawal

    MedlinePlus

    ... Seeing or feeling things that aren't there (hallucinations) Seizures Severe confusion ... alcohol withdrawal. You will be watched closely for hallucinations and other signs of delirium tremens. Treatment may ...

  14. Reversible Thermoset Adhesives

    NASA Technical Reports Server (NTRS)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  15. Isobutyl alcohol

    Integrated Risk Information System (IRIS)

    Isobutyl alcohol ; CASRN 78 - 83 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic E

  16. Allyl alcohol

    Integrated Risk Information System (IRIS)

    Allyl alcohol ; CASRN 107 - 18 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  17. Propargyl alcohol

    Integrated Risk Information System (IRIS)

    Propargyl alcohol ; CASRN 107 - 19 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  18. Alcoholism and Minority Populations.

    ERIC Educational Resources Information Center

    Watts, Thomas D.; Wright, Roosevelt, Jr.

    1991-01-01

    Briefly discusses some aspects of the role of the state and the position of minorities in respect to alcoholism policies and services. Includes case study of a Black alcoholic. Refers readers to studies on Black alcoholism, Native American alcoholism, Hispanic alcoholism, and Asian-American alcoholism. (Author/NB)

  19. Reverse Correlation in Neurophysiology

    ERIC Educational Resources Information Center

    Ringach, Dario; Shapley, Robert

    2004-01-01

    This article presents a review of reverse correlation in neurophysiology. We discuss the basis of reverse correlation in linear transducers and in spiking neurons. The application of reverse correlation to measure the receptive fields of visual neurons using white noise and m-sequences, and classical findings about spatial and color processing in…

  20. Paracetamol, alcohol and the liver

    PubMed Central

    Prescott, Laurie F

    2000-01-01

    where it is alleged that paracetamol hepatotoxicity was enhanced in chronic alcoholics, the reverse should have been the case because alcohol was actually taken at the same time as the paracetamol. Chronic alcoholics are likely to be most vulnerable to the toxic effects of paracetamol during the first few days of withdrawal but maximum therapeutic doses given at this time have no adverse effect on liver function tests. Although the possibility remains that chronic consumption of alcohol does increase the risk of paracetamol hepatotoxicity in man (perhaps by impairing glutathione synthesis), there is insufficient evidence to support the alleged major toxic interaction. It is astonishing that clinicians and others have unquestion-ingly accepted this supposed interaction in man for so long with such scant regard for scientific objectivity. PMID:10759684

  1. Alcohol Alert: Genetics of Alcoholism

    MedlinePlus

    ... Reilly, M.T.; et al. Mpdz is a quantitative trait gene for drug withdrawal seizures. Nature Neuroscience 7(7):699–700, 2014. PMID: 15208631 . 12 Hurley, T.D., and Edenberg, H.J. Genes encoding enzymes involved in ethanol metabolism. Alcohol Research & Health 34:339–344, 2012 13 Yokoyama, A.; ...

  2. Interstellar Alcohols

    NASA Technical Reports Server (NTRS)

    Charnley, S. B.; Kress, M. E.; Tielens, A. G. G. M.; Millar, T. J.

    1995-01-01

    We have investigated the gas-phase chemistry in dense cores where ice mantles containing ethanol and other alcohols have been evaporated. Model calculations show that methanol, ethanol, propanol, and butanol drive a chemistry leading to the formation of several large ethers and esters. Of these molecules, methyl ethyl ether (CH3OC2H5) and diethyl ether (C2H5)2O attain the highest abundances and should be present in detectable quantities within cores rich in ethanol and methanol. Gas-phase reactions act to destroy evaporated ethanol and a low observed abundance of gas-phase C,H,OH does not rule out a high solid-phase abundance. Grain surface formation mechanisms and other possible gas-phase reactions driven by alcohols are discussed, as are observing strategies for the detection of these large interstellar molecules.

  3. Neuropeptide Y Opposes Alcohol Effects on GABA Release in Amygdala and Blocks the Transition to Alcohol Dependence

    PubMed Central

    Gilpin, Nicholas W.; Misra, Kaushik; Herman, Melissa A.; Cruz, Maureen T.; Koob, George F.; Roberto, Marisa

    2011-01-01

    Background During the transition to alcohol and drug addiction, neuromodulator systems in the extended amygdala are recruited to mediate aspects of withdrawal and relapse via convergence on inhibitory GABA neurons in central amygdala (CeA). Methods This study investigated the role of neuropeptide Y (NPY) in excessive alcohol drinking by making rats dependent on alcohol via alcohol vapor inhalation. This study also utilized intracellular and whole-cell recording techniques to determine the effects of NPY on GABAergic inhibitory transmission in CeA, synaptic mechanisms involved in these NPY effects, and NPY interactions with alcohol in the CeA of alcohol-naïve and alcohol-dependent rats. Results Chronic NPY treatment blocked excessive operant alcohol-reinforced responding associated with alcohol dependence, as well as gradual increases in alcohol responding by intermittently tested non-dependent controls. NPY decreased baseline GABAergic transmission and reversed alcohol-induced enhancement of inhibitory transmission in CeA by suppressing GABA release via actions at presynaptic Y2 receptors. Conclusions These results highlight NPY modulation of GABAergic signaling in central amygdala as a promising pharmacotheraputic target for the treatment of alcoholism. GABA neurons in the CeA likely constitute a major point of convergence for neuromodulator systems recruited during the transition to alcohol dependence. PMID:21459365

  4. Alcoholism and Suicide.

    ERIC Educational Resources Information Center

    Roy, Alec; Linnoila, Markku

    1986-01-01

    Reviews knowledge about suicide in alcoholism: how commonly suicide among alcoholics occurs; which alcoholics commit suicide and why; suicide among alcoholic women and alcoholic physicians; possible predisposing biological factors; possible linkages with depression, adverse life events, and personality disorder; and future research and directions.…

  5. Changes in alcohol policies and public opinions in Finland 2003-2013.

    PubMed

    Österberg, Esa; Lindeman, Mikaela; Karlsson, Thomas

    2014-05-01

    There is a constant and ongoing interplay between public opinions and public policies, alcohol policies being no exception. This article describes the development of public opinions regarding alcohol policy in Finland during a 10-year period between 2003 and 2013. Fluctuations in the alcohol policy opinion climate are put in context by looking at concurrent changes in alcohol policies and in total alcohol consumption. The study is based on data from opinion surveys on alcohol policies commissioned by the National Institute for Health and Welfare and the Finnish Social and Health Association. The opinion polls include questions about the general acceptance of prevailing alcohol policies, appropriate sales channels of different alcoholic beverage categories and opinions about the legal age limits and prices of alcoholic beverages. In the study, changes in alcohol policy during 2003-2013 are surveyed, and their relationship with changes in alcohol policy opinion is examined. There seem to be a strong positive correlation during the study period between the level of alcohol consumption and the share of those wanting a more restrictive alcohol policy in Finland. It seems that an increased level of awareness of alcohol-related issues among the general public created a more restrictive opinion climate on alcohol policy issues after the big alcohol excise duty decrease in 2004. The reverse seems to happen but in a lesser degree when alcohol excise duties has been increased after the year 2007. © 2014 Australasian Professional Society on Alcohol and other Drugs.

  6. Reverse Core Engine with Thrust Reverser

    NASA Technical Reports Server (NTRS)

    Chandler, Jesse M. (Inventor); Suciu, Gabriel L. (Inventor)

    2017-01-01

    An engine system has a gas generator, a bi-fi wall surrounding at least a portion of the gas generator, a casing surrounding a fan, and the casing having first and second thrust reverser doors which in a deployed position abut each other and the bi-fi wall.

  7. Reversibility of female sterilization.

    PubMed

    Siegler, A M; Hulka, J; Peretz, A

    1985-04-01

    The discussion considers the current status of reversibility of sterilization in the US and describes clinical and experimental efforts for developing techniques designed for reversibility. It focuses on regret following sterilization, reversal potential of current sterilization techniques, patient selection, current reversal techniques, results of sterilization procedures, experimental approaches to reversal of current techniques of sterilization, and sterilization procedures devised for reversibility, in humans and in animals. Request is the 1st stage of reversal, but a request for sterilization reversal (SR) does not always mean regret for a decision made at the time. Frequently it is a wish to restore fertility because life circumstances have changed after a sterilization that was ppropriate at the time it was performed. Schwyhart and Kutner reviewed 22 studies published between 1949-69 in which they found that the percentage of patients regretting the procedure ranged from 1.3-15%. Requests for reversal remain low in most countries, but if sterilization becomes a more popular method of contraception, requests will also increase. The ideal operation considered as a reversaible method of sterilization should include an easy, reliable outpatient method of tubal occlusion with miniml risk or patient discomfort that subsequently could be reversed without the need for a major surgical intervention. Endoscopic methods have progressed toward the 1st objective. A recent search of the literature uncovered few series of SR of more than 50 cases. The 767 operations found were analyzed with regard to pregnancy outcome. The precent of live births varied from 74-78.8%, and the occurance of tubal pregnancies ranged from 1.7-6.5%. All of the confounding variables in patient selection and small numbers of reported procedures preclude any conclusion about the different techniques or the number of operations that give a surgeon a level of expertise. Few authors classify their

  8. Ultrasonic Time Reversal Mirrors

    NASA Astrophysics Data System (ADS)

    Fink, Mathias; Montaldo, Gabriel; Tanter, Mickael

    2004-11-01

    For more than ten years, time reversal techniques have been developed in many different fields of applications including detection of defects in solids, underwater acoustics, room acoustics and also ultrasound medical imaging and therapy. The essential property that makes time reversed acoustics possible is that the underlying physical process of wave propagation would be unchanged if time were reversed. In a non dissipative medium, the equations governing the waves guarantee that for every burst of sound that diverges from a source there exists in theory a set of waves that would precisely retrace the path of the sound back to the source. If the source is pointlike, this allows focusing back on the source whatever the medium complexity. For this reason, time reversal represents a very powerful adaptive focusing technique for complex media. The generation of this reconverging wave can be achieved by using Time Reversal Mirrors (TRM). It is made of arrays of ultrasonic reversible piezoelectric transducers that can record the wavefield coming from the sources and send back its time-reversed version in the medium. It relies on the use of fully programmable multi-channel electronics. In this paper we present some applications of iterative time reversal mirrors to target detection in medical applications.

  9. The alcoholism generator.

    PubMed

    Miller, Michael W; Spear, Linda P

    2006-09-01

    Alcohol exposure largely affects 3 populations: fetuses, adolescents, and adults. These 3 developmental stages are inextricably intertwined such that elevated alcohol exposure at any time increases the probability of exposure at the others. This circular interdependency is called the alcoholism generator. Furthermore, exposure to large amounts of alcohol at these 3 times can cause cognitive dysfunction, largely through mechanisms of alcohol-induced perturbations in neurogenesis and synaptogenesis. Breaking this cycle is key to reducing problem alcohol drinking and the associated sequelae.

  10. Hydrogenation of carbonyl compounds of relevance to hydrogen storage in alcohols

    NASA Astrophysics Data System (ADS)

    Suárez, Andrés

    2018-02-01

    Alcohols are a promising source for the sustainable production of hydrogen that may also serve as rechargeable liquid organic hydrogen carriers (LOHCs). Metal-catalyzed acceptorless dehydrogenation of alcohols produces carbonyl derivatives as H2-depleted by-products, which by means of a hydrogenation reaction can be reconverted to the initial alcohols. Hence, reversible H2-storage systems based on pairs of secondary alcohols/ketones and primary alcohols/carboxylic acid derivatives may be envisaged. In this contribution, the hydrogenation of carbonyl derivatives, including ketones, esters, amides and carboxylic acids, is reviewed from the perspective of the hydrogen storage in alcohols.

  11. Mechanisms of neuroimmune gene induction in alcoholism.

    PubMed

    Crews, Fulton T; Vetreno, Ryan P

    2016-05-01

    Alcoholism is a primary, chronic relapsing disease of brain reward, motivation, memory, and related circuitry. It is characterized by an individual's continued drinking despite negative consequences related to alcohol use, which is exemplified by alcohol use leading to clinically significant impairment or distress. Chronic alcohol consumption increases the expression of innate immune signaling molecules (ISMs) in the brain that alter cognitive processes and promote alcohol drinking. Unraveling the mechanisms of alcohol-induced neuroimmune gene induction is complicated by positive loops of multiple cytokines and other signaling molecules that converge on nuclear factor kappa-light-chain-enhancer of activated B cells and activator protein-1 leading to induction of additional neuroimmune signaling molecules that amplify and expand the expression of ISMs. Studies from our laboratory employing reverse transcription polymerase chain reaction (RT-PCR) to assess mRNA, immunohistochemistry and Western blot analysis to assess protein expression, and others suggest that ethanol increases brain neuroimmune gene and protein expression through two distinct mechanisms involving (1) systemic induction of innate immune molecules that are transported from blood to the brain and (2) the direct release of high-mobility group box 1 (HMGB1) from neurons in the brain. Released HMGB1 signals through multiple receptors, particularly Toll-like receptor (TLR) 4, that potentiate cytokine receptor responses leading to a hyperexcitable state that disrupts neuronal networks and increases excitotoxic neuronal death. Innate immune gene activation in brain is persistent, consistent with the chronic relapsing disease that is alcoholism. Expression of HMGB1, TLRs, and other ISMs is increased several-fold in the human orbital frontal cortex, and expression of these molecules is highly correlated with each other as well as lifetime alcohol consumption and age of drinking onset. The persistent and

  12. Alcohol policy and taxation in South Africa: an examination of the economic burden of alcohol tax.

    PubMed

    Ataguba, John Ele-Ojo

    2012-01-01

    Alcohol consumption accounts for over 4% of the global burden of disease and an even higher figure in developing countries. Several policies have been proposed to curb the negative impact of alcohol misuse. Apart from South Africa, which has witnessed a rapid development in alcohol policy, such policies are poorly developed in most African countries. South Africa uses taxation as a policy lever, in line with international evidence, to reduce alcohol consumption. However, the problem of alcohol abuse still exists. The objective of this article is to present an analysis of alcohol tax incidence for the first time in South Africa. This was done for each category of alcohol tax (wines, spirits, beer and traditional brew [sorghum beer]) and for alcohol tax as a whole. The paper also uses the results to point to the areas where a greater understanding of the issues surrounding alcohol abuse needs to be developed. Data were drawn from the 2005/06 South African Income and Expenditure Survey. Reported expenditures on alcohol beverages were used to obtain the tax component paid by households. This was done under certain assumptions relating to alcohol content and the price per litre of alcohol. Per adult equivalent consumption expenditure was used as the measure of relative living standards and concentration curves and Kakwani indices to assess relative progressivity of alcohol taxes. Statistical dominance tests were also performed. Most sorghum beer and malt beer drinkers were in the poorer quintiles. The reverse was the case for wines and spirits. Overall, alcohol tax in South Africa was regressive (Kakwani index -0.353). The individual categories were found to be regressive. The most regressive tax was that on sorghum beer (Kakwani index -1.01); the least regressive was that on spirits (Kakwani index -0.09), although this was not statistically significant at conventional levels. These results were confirmed by the test of dominance. In South Africa, there has been a

  13. An algebra of reversible computation.

    PubMed

    Wang, Yong

    2016-01-01

    We design an axiomatization for reversible computation called reversible ACP (RACP). It has four extendible modules: basic reversible processes algebra, algebra of reversible communicating processes, recursion and abstraction. Just like process algebra ACP in classical computing, RACP can be treated as an axiomatization foundation for reversible computation.

  14. Asymmetric Thrust Reversers

    NASA Technical Reports Server (NTRS)

    Chandler, Jesse M. (Inventor); Suciu, Gabriel L. (Inventor)

    2018-01-01

    An aircraft includes a propulsion supported within an aft portion of a fuselage A thrust reverser is mounted in the aft portion of the fuselage proximate the propulsion system for directing thrust in a direction to slow the aircraft. The thrust reverser includes an upper blocker door movable about a first pivot axis to a deployed position and a lower blocker door movable about a second pivot axis not parallel to the first pivot axis.

  15. Fetal Alcohol Exposure

    MedlinePlus

    ... categories: 4 » Fetal Alcohol Syndrome (FAS) » Partial FAS (pFAS) » Alcohol-Related Neurodevelopmental Disorder (ARND) » Alcohol-Related Birth ... either prenatally, after birth, or both Partial FAS (pFAS) Partial FAS (pFAS) involves prenatal alcohol exposure, and ...

  16. Children of Alcoholics.

    ERIC Educational Resources Information Center

    Krois, Deborah Helen

    Although alcoholism has long been considered a serious problem, the impact of parental alcoholism on children has only recently begun to receive attention from researchers and clinicians. A review of the empirical literature on children of alcoholics was conducted and it was concluded that children raised in an alcoholic family are at increased…

  17. Clearinghouse: alcohol and poppers.

    PubMed

    1999-03-01

    Ten articles from magazines and journals are referenced on the subjects of alcohol and poppers. Topics include alcohol consumption and HIV/AIDS-related risky sexual behavior, alcohol and drug abuse, and self-esteem, gender, and alcohol use. Contact information is provided.

  18. Fetal alcohol syndrome

    MedlinePlus

    ... a baby when a mother drinks alcohol during pregnancy. Causes Using alcohol during pregnancy can cause the same risks as using alcohol in general. But it poses extra risks to the unborn baby. When a pregnant woman drinks ... use during pregnancy. Larger amounts of alcohol appear to increase the ...

  19. Internet Alcohol Marketing and Underage Alcohol Use.

    PubMed

    McClure, Auden C; Tanski, Susanne E; Li, Zhigang; Jackson, Kristina; Morgenstern, Matthis; Li, Zhongze; Sargent, James D

    2016-02-01

    Internet alcohol marketing is not well studied despite its prevalence and potential accessibility and attractiveness to youth. The objective was to examine longitudinal associations between self-reported engagement with Internet alcohol marketing and alcohol use transitions in youth. A US sample of 2012 youths aged 15 to 20 was surveyed in 2011. An Internet alcohol marketing receptivity score was developed, based on number of positive responses to seeing alcohol advertising on the Internet, visiting alcohol brand Web sites, being an online alcohol brand fan, and cued recall of alcohol brand home page images. We assessed the association between baseline marketing receptivity and both ever drinking and binge drinking (≥6 drinks per occasion) at 1-year follow-up with multiple logistic regression, controlling for baseline drinking status, Internet use, sociodemographics, personality characteristics, and peer or parent drinking. At baseline, ever-drinking and binge-drinking prevalence was 55% and 27%, respectively. Many (59%) reported seeing Internet alcohol advertising, but few reported going to an alcohol Web site (6%) or being an online fan (3%). Higher Internet use, sensation seeking, having family or peers who drank, and past alcohol use were associated with Internet alcohol marketing receptivity, and a score of 1 or 2 was independently associated with greater adjusted odds of initiating binge drinking (odds ratio 1.77; 95% confidence interval, 1.13-2.78 and odds ratio 2.15; 95% confidence interval, 1.06-4.37 respectively) but not with initiation of ever drinking. Although high levels of engagement with Internet alcohol marketing were uncommon, most underage youths reported seeing it, and we found a prospective association between receptivity to this type of alcohol marketing and future problem drinking, making additional research and ongoing surveillance important. Copyright © 2016 by the American Academy of Pediatrics.

  20. Internet Alcohol Marketing and Underage Alcohol Use

    PubMed Central

    McClure, Auden C.; Tanski, Susanne E.; Li, Zhigang; Jackson, Kristina; Morgenstern, Matthis; Li, Zhongze; Sargent, James D.

    2016-01-01

    BACKGROUND AND OBJECTIVE Internet alcohol marketing is not well studied despite its prevalence and potential accessibility and attractiveness to youth. The objective was to examine longitudinal associations between self-reported engagement with Internet alcohol marketing and alcohol use transitions in youth. METHODS A US sample of 2012 youths aged 15 to 20 was surveyed in 2011. An Internet alcohol marketing receptivity score was developed, based on number of positive responses to seeing alcohol advertising on the Internet, visiting alcohol brand Web sites, being an online alcohol brand fan, and cued recall of alcohol brand home page images. We assessed the association between baseline marketing receptivity and both ever drinking and binge drinking (≥6 drinks per occasion) at 1-year follow-up with multiple logistic regression, controlling for baseline drinking status, Internet use, sociodemographics, personality characteristics, and peer or parent drinking. RESULTS At baseline, ever-drinking and binge-drinking prevalence was 55% and 27%, respectively. Many (59%) reported seeing Internet alcohol advertising, but few reported going to an alcohol Web site (6%) or being an online fan (3%). Higher Internet use, sensation seeking, having family or peers who drank, and past alcohol use were associated with Internet alcohol marketing receptivity, and a score of 1 or 2 was independently associated with greater adjusted odds of initiating binge drinking (odds ratio 1.77; 95% confidence interval, 1.13–2.78 and odds ratio 2.15; 95% confidence interval, 1.06–4.37 respectively) but not with initiation of ever drinking. CONCLUSIONS Although high levels of engagement with Internet alcohol marketing were uncommon, most underage youths reported seeing it, and we found a prospective association between receptivity to this type of alcohol marketing and future problem drinking, making additional research and ongoing surveillance important. PMID:26738886

  1. Alcoholic liver disease.

    PubMed

    Penny, Steven M

    2013-01-01

    In the United States, approximately 100,000 deaths are attributed to alcohol abuse each year. In 2009, the World Health Organization listed alcohol use as one of the leading causes of the global burden of disease and injury. Alcoholic liver disease, a direct result of chronic alcohol abuse, insidiously destroys the normal functions of the liver. The end result of the disease, cirrhosis, culminates in a dysfunctional and diffusely scarred liver. This article discusses the clinical manifestations, imaging considerations, and treatment of alcoholic liver disease and cirrhosis. Normal liver function, liver hemodynamics, the disease of alcoholism, and the deleterious effects of alcohol also are reviewed.

  2. The economics of alcohol.

    PubMed

    Lehto, J

    1997-03-01

    The use of economic arguments with regard to four aspects of alcohol policy is described and discussed. The first aspect is the impact of a potential reduction in alcohol consumption on employment by alcohol production and trade. It is shown that employment is quite independent of the level of consumption. The second aspect is the opportunity for serving the public health and state finance interests at the same time by developing alcohol taxation. The third aspect is the relationship between the public revenue from alcohol and the public costs for alcohol-related problems. A "polluter pays" principle with regard to alcohol would mean higher taxation of alcoholic beverages. The fourth aspect is the need for cost-effectiveness analyses to support the choices by the decision makers between different alcohol policy options. It is concluded that such analyses could have impact on the priorities in public health policy on alcohol.

  3. Neural correlates of alcohol-approach bias in alcohol addiction: the spirit is willing but the flesh is weak for spirits.

    PubMed

    Wiers, Corinde E; Stelzel, Christine; Park, Soyoung Q; Gawron, Christiane K; Ludwig, Vera U; Gutwinski, Stefan; Heinz, Andreas; Lindenmeyer, Johannes; Wiers, Reinout W; Walter, Henrik; Bermpohl, Felix

    2014-02-01

    Behavioral studies have shown an alcohol-approach bias in alcohol-dependent patients: the automatic tendency to faster approach than avoid alcohol compared with neutral cues, which has been associated with craving and relapse. Although this is a well-studied psychological phenomenon, little is known about the brain processes underlying automatic action tendencies in addiction. We examined 20 alcohol-dependent patients and 17 healthy controls with functional magnetic resonance imaging (fMRI), while performing an implicit approach-avoidance task. Participants pushed and pulled pictorial cues of alcohol and soft-drink beverages, according to a content-irrelevant feature of the cue (landscape/portrait). The critical fMRI contrast regarding the alcohol-approach bias was defined as (approach alcohol>avoid alcohol)>(approach soft drink>avoid soft drink). This was reversed for the avoid-alcohol contrast: (avoid alcohol>approach alcohol)>(avoid soft drink>approach soft drink). In comparison with healthy controls, alcohol-dependent patients had stronger behavioral approach tendencies for alcohol cues than for soft-drink cues. In the approach, alcohol fMRI contrast patients showed larger blood-oxygen-level-dependent responses in the nucleus accumbens and medial prefrontal cortex, regions involved in reward and motivational processing. In alcohol-dependent patients, alcohol-craving scores were positively correlated with activity in the amygdala for the approach-alcohol contrast. The dorsolateral prefrontal cortex was not activated in the avoid-alcohol contrast in patients vs controls. Our data suggest that brain regions that have a key role in reward and motivation are associated with the automatic alcohol-approach bias in alcohol-dependent patients.

  4. HIV/AIDS and Alcohol

    MedlinePlus

    ... Abuse and Alcoholism (NIAAA) Main Menu Search Search form Search Alcohol & Your Health Overview of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol Exposure Support & Treatment Alcohol Policy Special Populations & Co-occurring Disorders Publications & Multimedia Brochures & ...

  5. Childhood sexual abuse history and role reversal in parenting.

    PubMed

    Alexander, P C; Teti, L; Anderson, C L

    2000-06-01

    This study explored the main and interactive effects of sexual abuse history and relationship satisfaction on self-reported parenting, controlling for histories of physical abuse and parental alcoholism. The community sample consisted of 90 mothers of 5- to 8-year-old children. The sample was limited to those mothers currently in an intimate relationship, 19 of whom reported a history of childhood sexual abuse. Participants completed the Child Behavior Checklist, the Parenting Stress Inventory, the Family Cohesion Index, and questions assessing parent-child role reversal, history of abuse and parental alcoholism, and current relationship satisfaction. Results of analyses and multivariate analyses of covariance suggested that sexual abuse survivors with an unsatisfactory intimate relationship were more likely than either sexual abuse survivors with a satisfactory relationship or nonabused women to endorse items on a questionnaire of role reversal (defined as emotional overdependence upon one's child). Role reversal was not significantly predicted by histories of physical abuse or parental alcoholism or child's gender. While parenting stress was inversely predicted by the significant main effect of relationship satisfaction, neither parenting stress nor child behavior problems were predicted by the main effect of sexual abuse history or by the interaction between sexual abuse history and relationship satisfaction. These results suggest the unique relevance of sexual abuse history and relationship satisfaction in the prediction of a specific type of parent-child role reversal--namely, a mother's emotional overdependence upon her child.

  6. Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes.

    PubMed

    Tolstrup, Janne Schurmann; Nordestgaard, Børge Grønne; Rasmussen, Søren; Tybjaerg-Hansen, Anne; Grønbaek, Morten

    2008-06-01

    Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1-11) among men with the ADH1B.1/1 genotype compared to 7.5 drinks (95% CI: 6.4-8.7) among men with the ADH1B.1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7-5.7) among men with the ADH1B.1/1 genotype compared to men with the ADH1B.1/2 genotype. Furthermore, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1-1.8) among men with the ADH1C.1/2 genotype and 1.4 (95% CI: 1.0-1.9) among men with the ADH1B.2/2 genotype, compared with men with the ADH1C.1/1 genotype. Results for ADH1B and ADH1C genotypes among men and women were similar. Finally, because slow ADH1B alcohol degradation is found in more than 90% of the white population compared to less than 10% of East Asians, the population attributable risk of heavy drinking and alcoholism by ADH1B.1/1 genotype was 67 and 62% among the white population compared with 9 and 24% among the East Asian population.

  7. Russian alcohol policy in the making.

    PubMed

    Levintova, Marya

    2007-01-01

    This paper examines implementation of the 2005 federal alcohol control law in the Russian Federation. The documents on the Russian Federation federal legislation on the control of the production and turnover of ethyl alcohol, and ethyl alcohol containing products, news reports, research, and historical documents were gathered and analysed for implementation barriers. Consumption of alcoholic beverages, especially spirits, has been one the most significant public health problems in Russia for many centuries. Prior attempts to control alcohol consumption have been unsuccessful, in part due to the government's reliance on alcohol revenue, and its inability to implement creative and manageable solutions in the light of the high drinking rates. Implementation of this legislation has been a challenge in Russia because of administrative oversight, lack of organizational preparation, and corruption. The law discussed in this paper presented a window of opportunity to ameliorate the deteriorating health status and reverse the impending mortality crisis. However, a number of barriers presented substantial setbacks toward realization of this legislation.

  8. Tubulin Dimer Reversible Dissociation

    PubMed Central

    Schuck, Peter; Sackett, Dan L.

    2016-01-01

    Tubulins are evolutionarily conserved proteins that reversibly polymerize and direct intracellular traffic. Of the tubulin family only αβ-tubulin forms stable dimers. We investigated the monomer-dimer equilibrium of rat brain αβ-tubulin using analytical ultracentrifugation and fluorescence anisotropy, observing tubulin in virtually fully monomeric and dimeric states. Monomeric tubulin was stable for a few hours and exchanged into preformed dimers, demonstrating reversibility of dimer dissociation. Global analysis combining sedimentation velocity and fluorescence anisotropy yielded Kd = 84 (54–123) nm. Dimer dissociation kinetics were measured by analyzing the shape of the sedimentation boundary and by the relaxation of fluorescence anisotropy following rapid dilution of labeled tubulin, yielding koff in the range 10−3–10−2 s−1. Thus, tubulin dimers reversibly dissociate with moderately fast kinetics. Monomer-monomer association is much less sensitive than dimer-dimer association to solution changes (GTP/GDP, urea, and trimethylamine oxide). PMID:26934918

  9. Influence of affordability of alcohol on educational disparities in alcohol-related mortality in Finland and Sweden: a time series analysis.

    PubMed

    Herttua, Kimmo; Östergren, Olof; Lundberg, Olle; Martikainen, Pekka

    2017-12-01

    Prices of alcohol and income tend to influence how much people buy and consume alcohol. Price and income may be combined into one measure, affordability of alcohol. Research on the association between affordability of alcohol and alcohol-related harm is scarce. Furthermore, no research exists on how this association varies across different subpopulations. We estimated the effects of affordability of alcohol on alcohol-related mortality according to gender and education in Finland and Sweden. Vector-autoregressive time series modelling was applied to the quarter-annual aggregations of alcohol-related deaths and affordability of alcohol in Finland in 1988-2007 and in Sweden in 1991-2008. Alcohol-related mortality was defined using information on both underlying and contributory causes of death. We calculated affordability of alcohol index using information on personal taxable income and prices of various types of alcohol. Among Finnish men with secondary education, an increase of 1% in the affordability of total alcohol was associated with an increase of 0.028% (95% CI 0.004 to 0.053) in alcohol-related mortality. Similar associations were also found for affordability for various types of alcohol and for beer only in the lowest education group. We found few other significant positive associations for other subpopulations in Finland or Sweden. However, reverse associations were found among secondary-educated Swedish women. Overall, the associations between affordability of alcohol and alcohol-related mortality were relatively weak. Increased affordability of total alcoholic beverages was associated with higher rates of alcohol-related mortality only among Finnish men with secondary education. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Global alcohol policy and the alcohol industry.

    PubMed

    Anderson, Peter

    2009-05-01

    The WHO is preparing its global strategy on alcohol, and, in so doing, has been asked to consult with the alcohol industry on ways it could contribute in reducing the harm done by alcohol. This review asks which is more effective in reducing harm: the regulatory approaches that the industry does not favour; or the educational approaches that it does favour. The current literature overwhelmingly finds that regulatory approaches (including those that manage the price, availability, and marketing of alcohol) reduce the risk of and the experience of alcohol-related harm, whereas educational approaches (including school-based education and public education campaigns) do not, with industry-funded education actually increasing the risk of harm. The alcohol industry should not be involved in making alcohol policy. Its involvement in implementing policy should be restricted to its role as a producer, distributor, and marketer of alcohol. In particular, the alcohol industry should not be involved in educational programmes, as such involvement could actually lead to an increase in harm.

  11. Reverse shoulder arthroplasty.

    PubMed

    Jarrett, Claudius D; Brown, Brandon T; Schmidt, Christopher C

    2013-07-01

    The reverse shoulder arthroplasty is considered to be one of the most significant technological advancements in shoulder reconstructive surgery over the past 30 years. It is able to successfully decrease pain and improve function for patients with rotator cuff-deficient shoulders. The glenoid is transformed into a sphere that articulates with a humeral socket. The current reverse prosthesis shifts the center of rotation more medial and distal, improving the deltoid's mechanical advantage. This design has resulted in successful improvement in both active shoulder elevation and in quality of life. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Sequential Polarity-Reversing Circuit

    NASA Technical Reports Server (NTRS)

    Labaw, Clayton C.

    1994-01-01

    Proposed circuit reverses polarity of electric power supplied to bidirectional dc motor, reversible electro-mechanical actuator, or other device operating in direction depending on polarity. Circuit reverses polarity each time power turned on, without need for additional polarity-reversing or direction signals and circuitry to process them.

  13. Salivary alcohol dehydrogenase in non-smoking and smoking alcohol-dependent persons.

    PubMed

    Waszkiewicz, Napoleon; Jelski, Wojciech; Zalewska, Anna; Szulc, Agata; Szmitkowski, Maciej; Zwierz, Krzysztof; Szajda, Sławomir Dariusz

    2014-09-01

    Increasing attention to the importance of saliva testing is not surprising because smoking and alcohol drinking act synergistically on oral tissues, and their metabolite levels, e.g., acetaldehyde, are much higher in saliva than in blood. The activity of salivary alcohol dehydrogenase (ADH) comes from oral microbiota, mucosa, and salivary glands. The purpose of this study was to investigate the involvement of ADH in the oral health pathology of smoking (AS) and non-smoking (ANS) alcohol-dependent males. The results indicated that the AS group had a more significant and longer duration (until the 30th day of alcohol abstinence) decrease in ADH activity and output than the ANS group (until the 15th day of alcohol abstinence) compared to controls (social drinkers; C). The decreased salivary flow (SF) in alcoholics was observed longer in the ANS group (until the 30th day of alcohol abstinence), whereas in the AS group SF normalized at the 15th day, probably due to the irritating effect of tobacco smoke on the oral mucosa. Because saliva was centrifuged to remove cells and debris (including microbial cells), the detected salivary ADH activity was derived from salivary glands and/or oral mucosa. A more profound and longer decrease in ADH activity/output in smoking than non-smoking alcoholics was likely due to the damaged salivary glands and/or oral mucosa, caused by the synergistic effect of alcohol drinking and smoking. The lower values of salivary ADH in smoking than non-smoking alcoholics might also be partly due to the reversed/inhibited ADH reaction by high levels of accumulated acetaldehyde. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Alcohol and Alzheimer's Disease-Does Alcohol Dependence Contribute to Beta-Amyloid Deposition, Neuroinflammation and Neurodegeneration in Alzheimer's Disease?

    PubMed

    Venkataraman, Ashwin; Kalk, Nicola; Sewell, Gavin; Ritchie, Craig W; Lingford-Hughes, Anne

    2017-03-09

    To investigate the underlying neurobiology between alcohol use, misuse and dependence and cognitive impairment, particularly Alzheimer's disease (AD). Review of the literature using searches of Medline, Pubmed, EMBASE, PsycInfo, and meeting abstracts and presentations. The role of alcohol as a risk factor and contributor for cognitive decline associated with AD has received little attention. This is despite the high prevalence of alcohol use, the potential reversibility of a degree of cognitive impairment and the global burden of AD. Until now the focus has largely been on the toxic effects of alcohol, neuronal loss and the role of thiamine. We propose alcohol adds to the cognitive burden seen in dementia through additional mechanisms to neurodegenerative processes or may contribute at various mechanistic points in the genesis and sustenance of AD pathology via neuroinflammation. We describe the common underlying neurobiology in alcohol and AD, and examine ways alcohol likely contributes to neuroinflammation directly via stimulation of Toll-like receptors and indirectly from small bowel changes, hepatic changes, withdrawal and traumatic brain injury to the pathogenesis of AD. Alcohol use, misuse and dependence cause cognitive impairment. We propose alcohol adds to the cognitive burden seen in dementia through additional mechanisms to neurodegenerative processes or may contribute at various mechanistic points in the genesis and sustenance of AD pathology via neuroinflammation. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  15. [Cognitive impairment of alcohol-dependent subjects].

    PubMed

    Bernardin, Florent; Maheut-Bosser, Anne; Paille, François

    2014-04-01

    Chronic excessive alcohol consumption induces multiple brain damages. Secondary cognitive disorders include executive functions, episodic memory and visuospatial capacities. The severity of these alcohol induced disorders may vary between sub-clinical manifestations (that may, nevertheless, interfere with medical management) and more important ones like Korsakoff syndrome or dementia. The latter are usually irreversible but many of these manifestations are potentially reversible with persistent abstinence. It therefore appears of particular importance to clearly define neuropsychological management in order to identify and evaluate the type and severity of alcohol-related cognitive disorders. The patients may then be offered rehabilitation for these cognitive impairments. This is the first step of a complete addiction program based especially on cognitive behavioral therapies.

  16. [Out of addictions: Alcohol, or alcohol to alcohol].

    PubMed

    Simmat-Durand, L; Vellut, N; Lejeune, C; Jauffret-Roustide, M; Mougel, S; Michel, L; Planche, M

    2017-08-01

    Pathways from alcoholism to recovery are documented; less often are those from drug addiction to alcoholism. Biographical approaches allow analyzing how people change their uses and talk about their trajectories of recovery. Three hundred and forty-one people (34% women) in the Paris area were questioned on their trajectories with a biographical questionnaire. Some open questions were aimed to understand the connection they made between events in their lives, how recovered they felt and what they considered strengths or obstacles. All the participants had stopped at least one product. Their mean age was 43, and 26% were over 50. How can the differences between one substance addicts and dual abusers be explained? Can we hypothesize a better result for the patients with a single dependence to alcohol in their lives for the following two reasons? (1) They could really be taken in charge for their alcoholism whereas the dual abusers mostly receive cared for their illicit drug problems with an under estimation of their problem with alcohol. In this case, they turn to alcohol after weaning themselves from their drug dependence so as to return to a social consumption, especially when they are given an opiate treatment. (2) Conversely could we suggest that the dual substance abusers had different trajectories from their childhood (more adverse events, more social difficulties, mental health problems), and that this accumulation explains their skipping from one substance or behaviour to another without any real recovery for decades? All respondents were polydrug users. Eighty-two had been dependent mainly on alcohol. One hundred and twenty-one people had been drug addicts (mostly heroin), which they had stopped on average ten years before the survey. The last group included 138 persons who had been heroin or cocaine addicts and alcoholics in their lives, a third of whom had been dependent on alcohol before their drug addiction (35%), a tenth on both at the same time (10

  17. Fetal alcohol effects in alcoholic veteran patients.

    PubMed

    Tishler, P V; Henschel, C E; Ngo, T A; Walters, E E; Worobec, T G

    1998-11-01

    Fetal alcohol syndrome is often associated with severe physical and neuropsychiatric maldevelopment. On the other hand, some offspring of women who drank during pregnancy appear to be affected in minimal ways and function relatively well within society. We questioned whether this effect of prenatal alcohol in the adult is generally minimal. To bear on this, we determined whether we could distinguish alcohol-exposed from nonexposed individuals in a population of male veterans, selected because of both their accepted level of function within society (e.g., honorable discharge from the military) and their admission to an alcohol treatment unit (thus, a greater likelihood of parental alcoholism, because of its familial aggregation). Consecutively admitted alcoholics (cases; n = 77) with likely maternal alcohol ingestion during their pregnancy or the first 10 years of life were matched with alcoholics with no maternal alcohol exposure during these periods (controls; n = 161). Each subject completed questionnaires regarding personal birthweight, alcohol, drug, educational and work histories, and family (including parental) alcohol and drug histories. We measured height, weight, and head circumference; checked for facial and hand anomalies; and took a frontal facial photograph, from which measurements of features were made. Data were analyzed by univariate statistics and stepwise logistic regression. No case had bona fide fetal alcohol syndrome. With univariate statistical analyses, the cases differed from the controls in 10 variables, including duration of drinking, width of alae nasae, being hyperactive or having a short attention span, and being small at birth. By stepwise logistic regression, the variables marital status, small size at birth, duration of drinking, and the presence of a smooth philtrum were marginally (the first two) or definitely (the last two) significant predictors of case status. Analysis of only the 37 cases in whom maternal prenatal drinking was

  18. Fetal Alcohol Spectrum Disorders.

    PubMed

    Williams, Janet F; Smith, Vincent C

    2015-11-01

    Prenatal exposure to alcohol can damage the developing fetus and is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities. In 1973, fetal alcohol syndrome was first described as a specific cluster of birth defects resulting from alcohol exposure in utero. Subsequently, research unequivocally revealed that prenatal alcohol exposure causes a broad range of adverse developmental effects. Fetal alcohol spectrum disorder (FASD) is the general term that encompasses the range of adverse effects associated with prenatal alcohol exposure. The diagnostic criteria for fetal alcohol syndrome are specific, and comprehensive efforts are ongoing to establish definitive criteria for diagnosing the other FASDs. A large and growing body of research has led to evidence-based FASD education of professionals and the public, broader prevention initiatives, and recommended treatment approaches based on the following premises:▪ Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.▪ Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.▪ Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.▪ During pregnancy:◦no amount of alcohol intake should be considered safe;◦there is no safe trimester to drink alcohol;◦all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and◦binge drinking poses dose-related risk to the developing fetus. Copyright © 2015 by the American Academy of Pediatrics.

  19. Time reversal communication system

    DOEpatents

    Candy, James V.; Meyer, Alan W.

    2008-12-02

    A system of transmitting a signal through a channel medium comprises digitizing the signal, time-reversing the digitized signal, and transmitting the signal through the channel medium. The channel medium may be air, earth, water, tissue, metal, and/or non-metal.

  20. Engineering Encounters: Reverse Engineering

    ERIC Educational Resources Information Center

    McGowan, Veronica Cassone; Ventura, Marcia; Bell, Philip

    2017-01-01

    This column presents ideas and techniques to enhance your science teaching. This month's issue shares information on how students' everyday experiences can support science learning through engineering design. In this article, the authors outline a reverse-engineering model of instruction and describe one example of how it looked in our fifth-grade…

  1. Sex Reversal in Birds.

    PubMed

    Major, Andrew T; Smith, Craig A

    2016-01-01

    Sexual differentiation in birds is controlled genetically as in mammals, although the sex chromosomes are different. Males have a ZZ sex chromosome constitution, while females are ZW. Gene(s) on the sex chromosomes must initiate gonadal sex differentiation during embryonic life, inducing paired testes in ZZ individuals and unilateral ovaries in ZW individuals. The traditional view of avian sexual differentiation aligns with that expounded for other vertebrates; upon sexual differentiation, the gonads secrete sex steroid hormones that masculinise or feminise the rest of the body. However, recent studies on naturally occurring or experimentally induced avian sex reversal suggest a significant role for direct genetic factors, in addition to sex hormones, in regulating sexual differentiation of the soma in birds. This review will provide an overview of sex determination in birds and both naturally and experimentally induced sex reversal, with emphasis on the key role of oestrogen. We then consider how recent studies on sex reversal and gynandromorphic birds (half male:half female) are shaping our understanding of sexual differentiation in avians and in vertebrates more broadly. Current evidence shows that sexual differentiation in birds is a mix of direct genetic and hormonal mechanisms. Perturbation of either of these components may lead to sex reversal. © 2016 S. Karger AG, Basel.

  2. Reverse coherent information.

    PubMed

    García-Patrón, Raúl; Pirandola, Stefano; Lloyd, Seth; Shapiro, Jeffrey H

    2009-05-29

    In this Letter we define a family of entanglement distribution protocols assisted by feedback classical communication that gives an operational interpretation to reverse coherent information, i.e., the symmetric counterpart of the well-known coherent information. This leads to the definition of a new entanglement distribution capacity that exceeds the unassisted capacity for some interesting channels.

  3. Women and Alcohol

    MedlinePlus

    ... this page please turn JavaScript on. Feature: Rethinking Drinking Women and Alcohol Past Issues / Spring 2014 Table ... susceptible to alcohol-related heart disease. Pregnancy and Drinking Any drinking during pregnancy is risky. Heavy drinking ...

  4. Alcohol use disorder

    MedlinePlus

    ... help you stop drinking completely. These programs usually offer: Education about alcohol use and its effects Counseling and therapy to discuss how to control your thoughts and behaviors Physical ... programs offer housing options for people with alcohol problems. Depending ...

  5. Alcohol Use Disorders

    MedlinePlus

    ... 2017-2021 Our Work Our Funding Our Staff Jobs & Training Our Location Contact Us You are here Home » Alcohol & Your Health » Alcohol Use Disorder In ... Or caused job troubles? Or school problems? Continued to drink even ...

  6. Antidepressants and Alcohol

    MedlinePlus

    ... the concern? Why is it bad to mix antidepressants and alcohol? Answers from Daniel K. Hall-Flavin, M.D. It's best to avoid combining antidepressants and alcohol. It may worsen your symptoms, and ...

  7. Genetics of Alcoholism.

    PubMed

    Zhu, Ena C; Soundy, Timothy J; Hu, Yueshan

    2017-05-01

    Consuming excessive amounts of alcohol has the potential to modify an individual's brain and lead to alcohol dependence. Alcohol use leads to 88,000 deaths every year in the U.S. alone and can lead to other health issues including cancers, such as colorectal cancer, and mental health problems. While drinking behavior varies due to environmental factors, genetic factors also contribute to the risk of alcoholism. Certain genes affecting alcohol metabolism and neurotransmitters have been found to contribute to or inhibit the risk. Geneenvironment interactions may also play a role in the susceptibility of alcoholism. With a better understanding of the different components that can contribute to alcoholism, more personalized treatment could cater to the individual. This review discusses the major genetic factors and some small variants in other genes that contribute to alcoholism, as well as considers the gene-environmental interactions. Copyright© South Dakota State Medical Association.

  8. In Focus: Alcohol and Alcoholism Audiovisual Guide.

    ERIC Educational Resources Information Center

    National Clearinghouse for Alcohol Information (DHHS), Rockville, MD.

    This guide reviews audiovisual materials currently available on alcohol abuse and alcoholism. An alphabetical index of audiovisual materials is followed by synopses of the indexed materials. Information about the intended audience, price, rental fee, and distributor is included. This guide also provides a list of publications related to media…

  9. Alcohol and Family Violence.

    ERIC Educational Resources Information Center

    Covington, Stephanie S.

    There is growing acknowledgement of the association between family violence and alcohol use. A study was conducted to examine the role that abuse plays in the lives of women and to investigate the relationship between alcohol and violence. Data were collected from 35 recovering female alcoholics and 35 nonalcoholic women on their sexual experience…

  10. Alcohol and the law.

    PubMed

    Karasov, Ariela O; Ostacher, Michael J

    2014-01-01

    Society has had an interest in controlling the production, distribution, and use of alcohol for millennia. The use of alcohol has always had consequences, be they positive or negative, and the role of government in the regulation of alcohol is now universal. This is accomplished at several levels, first through controls on production, importation, distribution, and use of alcoholic beverages, and second, through criminal laws, the aim of which is to address the behavior of users themselves. A number of interventions and policies reduce alcohol-related consequences to society by regulating alcohol pricing, targeting alcohol-impaired driving, and limiting alcohol availability. The legal system defines criminal responsibility in the context of alcohol use, as an enormous percentage of violent crime and motor death is associated with alcohol intoxication. In recent years, recovery-oriented policies have aimed to expand social supports for recovery and to improve access to treatment for substance use disorders within the criminal justice system. The Affordable Care Act, also know as "ObamaCare," made substantial changes to access to substance abuse treatment by mandating that health insurance include services for substance use disorders comparable to coverage for medical and surgical treatments. Rather than a simplified "war on drugs" approach, there appears to be an increasing emphasis on evidence-based policy development that approaches alcohol use disorders with hope for treatment and prevention. This chapter focuses on alcohol and the law in the United States. © 2014 Elsevier B.V. All rights reserved.

  11. Biological Vulnerability to Alcoholism.

    ERIC Educational Resources Information Center

    Schuckit, Marc A.

    1987-01-01

    Reviews the role of biological factors in the risk for alcoholism. Notes the importance of the definition of primary alcoholism and highlights data indicating that this disorder is genetically influenced. In studies of men at high risk for the future development of alcoholism, vulnerability shows up in reactions to ethanol brain wave amplitude and…

  12. Television: Alcohol's Vast Adland.

    ERIC Educational Resources Information Center

    2002

    Concern about how much television alcohol advertising reaches underage youth and how the advertising influences their attitudes and decisions about alcohol use has been widespread for many years. Lacking in the policy debate has been solid, reliable information about the extent of youth exposure to television alcohol advertising. To address this…

  13. Alcoholism and Lesbians

    ERIC Educational Resources Information Center

    Gedro, Julie

    2014-01-01

    This chapter explores the issues involved in the relationship between lesbianism and alcoholism. It examines the constellation of health and related problems created by alcoholism, and it critically interrogates the societal factors that contribute to the disproportionately high rates of alcoholism among lesbians by exploring the antecedents and…

  14. Electrocardiogram Changes with Acute Alcohol Intoxication: A Systematic Review.

    PubMed

    Raheja, Hitesh; Namana, Vinod; Chopra, Kirti; Sinha, Ankur; Gupta, Sushilkumar Satish; Kamholz, Stephan; Moskovits, Norbert; Shani, Jacob; Hollander, Gerald

    2018-01-01

    Acute alcohol intoxication has been associated with cardiac arrhythmias but the electrocardiogram (ECG) changes associated with acute alcohol intoxication are not well defined in the literature. Highlight the best evidence regarding the ECG changes associated with acute alcohol intoxication in otherwise healthy patients and the pathophysiology of the changes. A literature search was carried out; 4 studies relating to ECG changes with acute alcohol intoxication were included in this review. Of the total 141 patients included in the review, 90 (63.8%) patients had P-wave prolongation, 80 (56%) patients had QTc prolongation, 19 (13.5%) patients developed T-wave abnormalities, 10 (7%) patients had QRS complex prolongation, 3 (2.12%) patients developed ST-segment depressions. The most common ECG changes associated with acute alcohol intoxication are (in decreasing order of frequency) P-wave and QTc prolongation, followed by T-wave abnormalities and QRS complex prolongation. Mostly, these changes are completely reversible.

  15. Operant self-administration of alcohol and nicotine in a preclinical model of co-abuse

    PubMed Central

    Lê, A.D.; Funk, Douglas; Lo, Steven; Coen, Kathleen

    2017-01-01

    Rationale and objectives Alcohol and nicotine are often taken together. In humans, intake of nicotine, via smoked tobacco, increases alcohol drinking, and alcohol increases smoking. Chronic nicotine treatment increases alcohol self-administration (SA) in laboratory animals; the reverse relationship is less clear. Most animal work modeling this has used passive administration, which lacks relevance to human co-abuse. Here, we describe a model based on sequential operant SA of alcohol and nicotine. Methods Animals are first trained on alcohol SA (0.19 ml of 12% w/v/delivery) and then receive separate alcohol (8% w/v) and nicotine (15 μg/kg/infusion) SA sessions on the same day (“daily dual access”). Animals then receive access to alcohol and then to nicotine (or in the reverse order) in alternating 5 min periods in 2h sessions (“alternating access”). We then determine if alternating access modifies the effects of naltrexone on responding for alcohol and nicotine. Results We found that with daily dual access, nicotine significantly increased alcohol SA when alcohol access occurred prior to nicotine access, and that nicotine SA significantly decreased when the alcohol SA session preceded it. During alternating access, nicotine also significantly increased alcohol intake. Naltrexone (0.3 or 1 mg/kg) significantly reduced alcohol SA during these alternating access sessions in animals that also received nicotine SA, but had minimal effects on animals receiving alcohol SA alone. Naltrexone did not affect nicotine SA under any condition. Conclusions This sequential access procedure effectively models the effects of nicotine on alcohol intake noted in humans. PMID:24696081

  16. Reversing Glass Wettability

    NASA Technical Reports Server (NTRS)

    Frazier, D. O.; Smith, J. E., Jr.; Kaukler, W. F.

    1985-01-01

    Treatment reverses wettability of glassware: Liquids that normally wet glass no longer do, and those that do not wet glass are made to do so. Useful in research on container effects in nucleation and growth of secondary phase from solution. Treatment consists of spreading 3 percent (by weight) solution of silicone oil in hexane isomers over glass, drying in air, and curing at 300 degrees C in vacuum for one hour.

  17. Lassa Virus Reverse Genetics.

    PubMed

    Martínez-Sobrido, Luis; Paessler, Slobodan; de la Torre, Juan Carlos

    2017-01-01

    The Old World (OW) arenavirus Lassa (LASV ) is estimated to infect several hundred thousand people yearly in West Africa, resulting in high numbers of Lassa fever (LF), a viral hemorrhagic fever (HF) disease associated with high morbidity and mortality. To date, no licensed vaccines are available to LASV infections, and anti-LASV drug therapy is limited to an off-label use of ribavirin (Rib) that is only partially effective. The development of reverse genetics has provided investigators with a novel and powerful approach for the investigation of the molecular, cell biology, and pathogenesis of LASV. The use of cell-based LASV minigenome (MG) systems has allowed examining the cis- and trans-acting factors involved in genome replication and gene transcription and the identification of novel drugable LASV targets. Likewise, it is now feasible to rescue infectious recombinant (r)LASV entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify antiviral drugs against LASV and the implementation of novel strategies to develop live-attenuated vaccines (LAV). In this chapter we will summarize the state-of-the-art experimental procedures for implementation of LASV reverse genetics. In addition, we will briefly discuss some significant translational research developments that have been made possible upon the development of LASV reverse genetics.

  18. Reversible infantile mitochondrial diseases.

    PubMed

    Boczonadi, Veronika; Bansagi, Boglarka; Horvath, Rita

    2015-05-01

    Mitochondrial diseases are usually severe and progressive conditions; however, there are rare forms that show remarkable spontaneous recoveries. Two homoplasmic mitochondrial tRNA mutations (m.14674T>C/G in mt-tRNA(Glu)) have been reported to cause severe infantile mitochondrial myopathy in the first months of life. If these patients survive the first year of life by extensive life-sustaining measures they usually recover and develop normally. Another mitochondrial disease due to deficiency of the 5-methylaminomethyl-2-thiouridylate methyltransferase (TRMU) causes severe liver failure in infancy, but similar to the reversible mitochondrial myopathy, within the first year of life these infants may also recover completely. Partial recovery has been noted in some other rare forms of mitochondrial disease due to deficiency of mitochondrial tRNA synthetases and mitochondrial tRNA modifying enzymes. Here we summarize the clinical presentation of these unique reversible mitochondrial diseases and discuss potential molecular mechanisms behind the reversibility. Understanding these mechanisms may provide the key to treatments of potential broader relevance in mitochondrial disease, where for the majority of the patients no effective treatment is currently available.

  19. Burnout: Recognize and Reverse.

    PubMed

    Anne, Samantha

    2014-07-01

    Physician burnout may be underrecognized and can cause significant detrimental effects on personal health and job satisfaction. Burnout has been associated with medical errors, alcohol and drug abuse, and neglect and abandonment of career goals. With self-awareness, development of coping mechanisms, and the adoption of a strong social and professional support network, burnout can be combated. This article focuses on recognizing characteristics of burnout and providing strategies to cope to avoid reaching a high degree of burnout. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

  20. Alcohol and the Intestine

    PubMed Central

    Patel, Sheena; Behara, Rama; Swanson, Garth R.; Forsyth, Christopher B.; Voigt, Robin M.; Keshavarzian, Ali

    2015-01-01

    Alcohol abuse is a significant contributor to the global burden of disease and can lead to tissue damage and organ dysfunction in a subset of alcoholics. However, a subset of alcoholics without any of these predisposing factors can develop alcohol-mediated organ injury. The gastrointestinal tract (GI) could be an important source of inflammation in alcohol-mediated organ damage. The purpose of review was to evaluate mechanisms of alcohol-induced endotoxemia (including dysbiosis and gut leakiness), and highlight the predisposing factors for alcohol-induced dysbiosis and gut leakiness to endotoxins. Barriers, including immunologic, physical, and biochemical can regulate the passage of toxins into the portal and systemic circulation. In addition, a host of environmental interactions including those influenced by circadian rhythms can impact alcohol-induced organ pathology. There appears to be a role for therapeutic measures to mitigate alcohol-induced organ damage by normalizing intestinal dysbiosis and/or improving intestinal barrier integrity. Ultimately, the inflammatory process that drives progression into organ damage from alcohol appears to be multifactorial. Understanding the role of the intestine in the pathogenesis of alcoholic liver disease can pose further avenues for pathogenic and treatment approaches. PMID:26501334

  1. Genetics and alcoholism.

    PubMed

    Edenberg, Howard J; Foroud, Tatiana

    2013-08-01

    Alcohol is widely consumed; however, excessive use creates serious physical, psychological and social problems and contributes to the pathogenesis of many diseases. Alcohol use disorders (that is, alcohol dependence and alcohol abuse) are maladaptive patterns of excessive drinking that lead to serious problems. Abundant evidence indicates that alcohol dependence (alcoholism) is a complex genetic disease, with variations in a large number of genes affecting a person's risk of alcoholism. Some of these genes have been identified, including two genes involved in the metabolism of alcohol (ADH1B and ALDH2) that have the strongest known affects on the risk of alcoholism. Studies continue to reveal other genes in which variants affect the risk of alcoholism or related traits, including GABRA2, CHRM2, KCNJ6 and AUTS2. As more variants are analysed and studies are combined for meta-analysis to achieve increased sample sizes, an improved picture of the many genes and pathways that affect the risk of alcoholism will be possible.

  2. [Physical diseases in alcoholism].

    PubMed

    Takase, Kojiro

    2015-09-01

    Rapid excessive alcohol drinking frequently causes disturbance of consciousness due to head trauma, brain edema, hypoglycemia, hyponatremia, hepatic coma and so on, provoked by acute alcohol intoxication. Rapid differential diagnosis and management are extremely important to save a life. On the other hands, the chronic users of alcohol so called alcoholism has many kinds of physical diseases such as liver diseases (i.e., fatty liver, alcoholic hepatitis, alcoholic liver cirrhosis and miscellaneous liver disease), diabetes mellitus, injury to happen in drunkenness, pancreas disease (i.e., acute and chronic pancreatitis and deterioration of chronic pancreatitis), gastrontestinal diseases (i.e., gastroduodenal ulcer), and so on. Enough attention should be paid to above mentioned diseases, otherwise they would turn worse more with continuation and increase in quantity of the alcohol. It should be born in its mind that the excessive drinking becomes the weapon threatening life.

  3. Alcoholic and non-alcoholic steatohepatitis

    PubMed Central

    Neuman, Manuela G.; French, Samuel W.; French, Barbara A.; Seitz, Helmut K.; Cohen, Lawrence B.; Mueller, Sebastian; Osna, Natalia A.; Kharbanda, Kusum K.; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J.; McKillop, Iain H.; Kirpich, Irina A.; McClain, Craig J.; Bataller, Ramon; Nanau, Radu M.; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomas, Paul G.; Ganesan, Murali; Malnick, Steve

    2015-01-01

    This paper is based upon the “Charles Lieber Satellite Symposia” organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its comorbidities with chronic viral hepatitis in the presence or absence of human deficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible

  4. Alcohol disrupts sleep homeostasis.

    PubMed

    Thakkar, Mahesh M; Sharma, Rishi; Sahota, Pradeep

    2015-06-01

    Alcohol is a potent somnogen and one of the most commonly used "over the counter" sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to unravel the mechanism of alcohol-induced sleep disruptions. We have conducted a series of experiments using two different species, rats and mice, as animal models. We performed microdialysis, immunohistochemical, pharmacological, sleep deprivation and lesion studies which suggest that the sleep-promoting effects of alcohol may be mediated via alcohol's action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that sleep disruptions observed during acute withdrawal, are caused due to impaired

  5. Microbial alcohol-conferred hemolysis is a late response to alcohol stress.

    PubMed

    Shuster, Amir; Korem, Moshe; Jacob-Hirsch, Jasmine; Amariglio, Ninette; Rechavi, Gideon; Rosenberg, Mel

    2011-06-01

    We have reported previously that growth on alcohol vapors confers hemolytic properties on certain yeast species and strains ['microbial alcohol-conferred hemolysis' (MACH)]. In a recent study, we analyzed the genetic basis of MACH in Saccharomyces cerevisiae using the EUROSCARF mutant collection. The data suggested that intact mitochondrial and respiratory chain functions are critical for the observed alcohol-mediated hemolysis. We proposed that the uncontrolled cellular uptake of alcohol results in yeast 'hyper-respiration', leading to elaboration of hemolytic molecules such as hydrogen peroxide and lytic lipids. In the current study, we have further analyzed the molecular mechanisms involved in the MACH phenomenon in S. cerevisiae, using DNA microarrays. The patterns of regulation were confirmed by quantitative reverse transcriptase PCR. The results presented here lend further support to this hypothesis, based on upregulation of the genes responsible for coping with vast amounts of hydrogen peroxide produced as a byproduct of excessive oxidation of alcohol. These results, taken together, show that alcohol-mediated hemolysis in yeast appears to be related to the overproduction of hemolytic byproducts, particularly hydrogen peroxide, which accumulates during long-term exposure of S. cerevisiae to both ethanol and n-butanol. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  6. Geomagnetic Field During a Reversal

    NASA Technical Reports Server (NTRS)

    Heirtzler, J. R.

    2003-01-01

    It has frequently been suggested that only the geomagnetic dipole, rather than higher order poles, reverse during a geomagnetic field reversal. Under this assumption the geomagnetic field strength has been calculated for the surface of the Earth for various steps of the reversal process. Even without an eminent a reversal of the field, extrapolation of the present secular change (although problematic) shows that the field strength may become zero in some geographic areas within a few hundred years.

  7. Geomagnetic Reversals during the Phanerozoic.

    PubMed

    McElhinny, M W

    1971-04-09

    An antalysis of worldwide paleomagnetic measurements suggests a periodicity of 350 x 10(6) years in the polarity of the geomagnetic field. During the Mesozoic it is predominantly normal, whereas during the Upper Paleozoic it is predominantly reversed. Although geomagnetic reversals occur at different rates throughout the Phanerozoic, there appeaars to be no clear correlation between biological evolutionary rates and reversal frequency.

  8. Alcohol Alert: Link Between Stress and Alcohol

    MedlinePlus

    ... Alert Number 85 Print Version The Link Between Stress and Alcohol Today, more and more servicemen and ... in alleviating and perpetuating stress. Common Types of Stress Most causes of stress can be grouped into ...

  9. Women's alcohol use and alcoholism in Korea.

    PubMed

    Kim, Wooksoo; Kim, Sungjae

    2008-07-01

    Recently South Korean society has experienced an increase in alcohol use related problems, as well as alcohol use among women. The purpose of this paper is to describe the cultural context of and to summarize the current state of knowledge of women's drinking in South Korea. Subscribing to Confucian principles, traditional Korean society has allowed drinking for men, but not for women. However, as society has changed, contemporary women drink at a younger age and consume larger amounts of alcohol than their prior generations. The current trends suggest an urgent need for research on the etiology and trajectory of women's alcohol use among various populations and the need to develop intervention programs tailored to the specific needs of women.

  10. Personality disorders, alcohol use, and alcohol misuse.

    PubMed

    Maclean, Johanna Catherine; French, Michael T

    2014-11-01

    Personality disorders (PDs) are psychiatric conditions that manifest early in life from a mixture of genetics and environment, are highly persistent, and lead to substantial dysfunction for the affected individual and those with whom s/he interacts. In this study we offer new information on the associations between PDs and alcohol use/misuse. Specifically, we consider all 10 PDs recognized by the American Psychiatric Association; carefully address important sources of bias in our regression models; and study heterogeneity across PDs, drinking pattern, and gender. To investigate the relationships between PDs and alcohol consumption we analyze data from the 2004/2005 National Epidemiological Survey of Alcohol and Related Conditions (N=34,653). We construct measures of any drinking, drinking quantity, and patterns of misuse that could lead to significant social costs including drinking to intoxication, driving after drinking, drinking during the day, and alcohol abuse/dependence. Results show that persons with PDs are significantly more likely to use and misuse alcohol, although associations vary across gender. Moreover, antisocial, borderline, histrionic, and narcissistic PDs display the strongest links with alcohol use and misuse, and the relationships are strongest among the heaviest drinkers. These findings have important public health implications and underscore the potential social costs associated with mental health conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Reversal bending fatigue testing

    DOEpatents

    Wang, Jy-An John; Wang, Hong; Tan, Ting

    2014-10-21

    Embodiments for apparatuses for testing reversal bending fatigue in an elongated beam are disclosed. Embodiments are configured to be coupled to first and second end portions of the beam and to apply a bending moment to the beam and create a pure bending condition in an intermediate portion of the beam. Embodiments are further configured to cyclically alternate the direction of the bending moment applied to the beam such that the intermediate portion of the beam cyclically bends in opposite directions in a pure bending condition.

  12. Reversible brazing process

    DOEpatents

    Pierce, Jim D.; Stephens, John J.; Walker, Charles A.

    1999-01-01

    A method of reversibly brazing surfaces together. An interface is affixed to each surface. The interfaces can be affixed by processes such as mechanical joining, welding, or brazing. The two interfaces are then brazed together using a brazing process that does not defeat the surface to interface joint. Interfaces of materials such as Ni-200 can be affixed to metallic surfaces by welding or by brazing with a first braze alloy. The Ni-200 interfaces can then be brazed together using a second braze alloy. The second braze alloy can be chosen so that it minimally alters the properties of the interfaces to allow multiple braze, heat and disassemble, rebraze cycles.

  13. Exposure to Televised Alcohol Ads and Subsequent Adolescent Alcohol Use

    ERIC Educational Resources Information Center

    Stacy, Alan W.; Zogg, Jennifer B.; Unger, Jennifer B.; Dent, Clyde W.

    2004-01-01

    Objective : To assess the impact of televised alcohol commercials on adolescents' alcohol use. Methods : Adolescents completed questionnaires about alcohol commercials and alcohol use in a prospective study. Results : A one standard deviation increase in viewing television programs containing alcohol commercials in seventh grade was associated…

  14. Final report of the safety assessment of Alcohol Denat., including SD Alcohol 3-A, SD Alcohol 30, SD Alcohol 39, SD Alcohol 39-B, SD Alcohol 39-C, SD Alcohol 40, SD Alcohol 40-B, and SD Alcohol 40-C, and the denaturants, Quassin, Brucine Sulfate/Brucine, and Denatonium Benzoate.

    PubMed

    2008-01-01

    Alcohol Denat. is the generic term used by the cosmetics industry to describe denatured alcohol. Alcohol Denat. and various specially denatured (SD) alcohols are used as cosmetic ingredients in a wide variety of products. Many denaturants have been previously considered, on an individual basis, as cosmetic ingredients by the Cosmetic Ingredient Review (CIR) Expert Panel, whereas others, including Brucine and Brucine Sulfate, Denatonium Benzoate, and Quassin, have not previously been evaluated. Quassin is a bitter alkaloid obtained from the wood of Quassia amara. Quassin has been used as an insect antifeedant and insecticide and several studies demonstrate its effectiveness. At oral doses up to 1000 mg/kg using rats, Quassin was not toxic in acute and short-term tests, but some reversible piloerection, decrease in motor activity, and a partial loss of righting reflex were found in mice at 500 mg/kg. At 1000 mg/kg given intraperitoneally (i.p.), all mice died within 24 h of receiving treatment. In a cytotoxicity test with brine shrimp, 1 mg/ml of Quassin did not possess any cytotoxic or antiplasmodial activity. Quassin administered to rat Leydig cells in vitro at concentrations of 5-25 ng/ml inhibited both the basal and luteinizing hormone (LH)-stimulated testosterone secretion in a dose-related fashion. Quassin at doses up to 2.0 g/kg in drinking water using rats produced no significant effect on the body weights, but the mean weights of the testes, seminal vesicles, and epididymides were significantly reduced, and the weights of the anterior pituitary glands were significantly increased. The sperm counts and levels of LH, follicle-stimulating hormone (FSH), and testosterone were significantly lower in groups treated with Quassin. Brucine is a derivative of 2-hydroxystrychnine. Swiss-Webster mice given Brucine base, 30 ml/kg, had an acute oral LD(50) of 150 mg/kg, with central nervous system depression followed by convulsions and seizures in some cases. In those

  15. Reversal of liver fibrosis: From fiction to reality.

    PubMed

    Zoubek, Miguel Eugenio; Trautwein, Christian; Strnad, Pavel

    2017-04-01

    In chronic liver diseases, an ongoing hepatocellular injury together with inflammatory reaction results in activation of hepatic stellate cells (HSCs) and increased deposition of extracellular matrix (ECM) termed as liver fibrosis. It can progress to cirrhosis that is characterized by parenchymal and vascular architectural changes together with the presence of regenerative nodules. Even at late stage, liver fibrosis is reversible and the underlying mechanisms include a switch in the inflammatory environment, elimination or regression of activated HSCs and degradation of ECM. While animal models have been indispensable for our understanding of liver fibrosis, they possess several important limitations and need to be further refined. A better insight into the liver fibrogenesis resulted in a large number of clinical trials aiming at reversing liver fibrosis, particularly in patients with non-alcoholic steatohepatitis. Collectively, the current developments demonstrate that reversal of liver fibrosis is turning from fiction to reality. Copyright © 2017. Published by Elsevier Ltd.

  16. Alcohol Activates the Hedgehog Pathway and Induces Related Pro-carcinogenic Processes in the Alcohol-Preferring Rat Model of Hepatocarcinogenesis

    PubMed Central

    Chan, Isaac S.; Guy, Cynthia D.; Machado, Mariana V.; Wank, Abigail; Kadiyala, Vishnu; Michelotti, Gregory; Choi, Steve; Swiderska-Syn, Marzena; Karaca, Gamze; Pereira, Thiago A.; Yip-Schneider, Michele T.; Schmidt, C. Max; Diehl, Anna Mae

    2014-01-01

    Background Alcohol consumption promotes hepatocellular carcinoma (HCC). The responsible mechanisms are not well understood. Hepatocarcinogenesis increases with age and is enhanced by factors that impose a demand for liver regeneration. Because alcohol is hepatotoxic, habitual alcohol ingestion evokes a recurrent demand for hepatic regeneration. The alcohol-preferring (P) rat model mimics the level of alcohol consumption by humans who habitually abuse alcohol. Previously, we showed that habitual heavy alcohol ingestion amplified age-related hepatocarcinogenesis in P-rats, with over 80% of alcohol-consuming P rats developing HCCs after 18 months of alcohol exposure, compared to only 5% of water-drinking controls. Methods Herein, we used quantitative real time PCR and quantitative immunocytochemistry to compare liver tissues from alcohol-consuming P rats and water-fed P rat controls after 6, 12, or 18 months of drinking. We aimed to identify potential mechanisms that might underlie the differences in liver cancer formation, and hypothesized that chronic alcohol ingestion would activate Hedgehog (HH), a regenerative signaling pathway that is over-activated in HCC. Results Chronic alcohol ingestion amplified age-related degenerative changes in hepatocytes, but did not cause appreciable liver inflammation or fibrosis even after 18 months of heavy drinking. HH signaling was also enhanced by alcohol exposure, as evidenced by increased levels of mRNAs encoding HH ligands, HH-regulated transcription factors, and HH-target genes. Immunocytochemistry confirmed increased alcohol-related accumulation of HH ligand-producing cells and HH-responsive target cells. HH-related regenerative responses were also induced in alcohol-exposed rats. Three of these processes (i.e., deregulated progenitor expansion, the reverse-Warburg effect, and epithelial-to-mesenchymal transitions) are known to promote cancer growth in other tissues. Conclusions Alcohol-related changes in Hedgehog signaling

  17. Alcohol and B1 vitamin deficiency-related stillbirths.

    PubMed

    Bâ, Abdoulaye

    2009-05-01

    The present study attempts to determine whether prenatal thiamine (B1 vitamin) deficiency and prenatal alcohol exposure are risk factors for stillbirths. From conception to parturition, Wistar rat dams were exposed to the following treatments: (1) Rat dams consuming a thiamine-deficient diet; (2) 12% alcohol/water drinking mothers; (3) mothers drinking 12% alcohol/water + thiamine hydrochloride mixture. Appropriate pair-fed controls and ad libitum controls were assessed. Gestation outcome and fetal parameters, including spontaneous abortion, still-born fetuses, litter size and birth weight, were assessed from the dams of each experimental group. Both alcohol and thiamine deficiency during pregnancy increased fetal death (48.26%vs. 84.47%), reduced litter size (44.54%vs. 72.7%), respectively, and lowered birth weight. Thiamine administration reversed the effects of alcohol-induced fetal death, suggesting that a part of deleterious actions of alcohol on fetal death was mediated by thiamine deficiency. Prenatal thiamine deficiency increased singularly spontaneous abortion with abundant bleeding (40%), rising the occurrence of stillbirth. Such a pathology was not observed in alcohol group. The results indexed thiamine deficiency as a potent risk factor for stillbirths. The vitamin supply during pregnancy prevents stillbirths related to chronic alcoholism and different facets of malnutrition.

  18. [Biological markers of alcoholism].

    PubMed

    Marcos Martín, M; Pastor Encinas, I; Laso Guzmán, F J

    2005-09-01

    Diagnosis of alcoholism is very important, given its high prevalence and possibility of influencing the disease course. For this reason, the so-called biological markers of alcoholism are useful. These are analytic parameters that alter in the presence of excessive alcohol consumption. The two most relevant markers are the gamma-glutamyltranspeptidase and carbohydrate deficient transferrin. With this clinical comment, we aim to contribute to the knowledge of these tests and promote its use in the clinical practice.

  19. Fetal Alcohol Syndrome "Chemical Genocide."

    ERIC Educational Resources Information Center

    Asetoyer, Charon

    In the Northern Plains of the United States, 100% of Indian reservations are affected by alcohol related problems. Approximately 90% of Native American adults are currently alcohol users or abusers or are recovering from alcohol abuse. Alcohol consumption has a devastating effect on the unborn. Fetal Alcohol Syndrome (FAS) is an irreversible birth…

  20. Prenatal alcohol exposure affects vasculature development in the neonatal brain.

    PubMed

    Jégou, Sylvie; El Ghazi, Faiza; de Lendeu, Pamela Kwetieu; Marret, Stéphane; Laudenbach, Vincent; Uguen, Arnaud; Marcorelles, Pascale; Roy, Vincent; Laquerrière, Annie; Gonzalez, Bruno José

    2012-12-01

    In humans, antenatal alcohol exposure elicits various developmental disorders, in particular in the brain. Numerous studies focus on the deleterious effects of alcohol on neural cells. Although recent studies suggest that alcohol can affect angiogenesis in adults, the impact of prenatal alcohol exposure on brain microvasculature remains poorly understood. We used a mouse model to investigate effects of prenatal alcohol exposure on the cortical microvascular network in vivo and ex vivo and the action of alcohol, glutamate, and vascular endothelial growth factor A (VEGF) on activity, plasticity, and survival of microvessels. We used quantitative reverse transcriptase polymerase chain reaction, Western blot, immunohistochemistry, calcimetry, and videomicroscopy. We characterized the effect of prenatal alcohol exposure on the cortical microvascular network in human controls and fetal alcohol syndrome (FAS)/partial FAS (pFAS) patients at different developmental stages. In mice, prenatal alcohol exposure induced a reduction of cortical vascular density, loss of the radial orientation of microvessels, and altered expression of VEGF receptors. Time-lapse experiments performed on brain slices revealed that ethanol inhibited glutamate-induced calcium mobilization in endothelial cells, affected plasticity, and promoted death of microvessels. These effects were prevented by VEGF. In humans, we evidenced a stage-dependent alteration of the vascular network in the cortices of fetuses with pFAS/FAS. Whereas no modification was observed from gestational week 20 (WG20) to WG22, the radial organization of cortical microvessels was clearly altered in pFAS/FAS patients from WG30 to WG38. Prenatal alcohol exposure affects cortical angiogenesis both in mice and in pFAS/FAS patients, suggesting that vascular defects contribute to alcohol-induced brain abnormalities. Copyright © 2012 American Neurological Association.

  1. Income inequality and alcohol attributable harm in Australia.

    PubMed

    Dietze, Paul M; Jolley, Damien J; Chikritzhs, Tanya N; Clemens, Susan; Catalano, Paul; Stockwell, Tim

    2009-02-25

    inequality and the rates of some types of alcohol-attributable hospitalisation and death at a local area level in Australia. While alcohol-attributable harms generally increased with increasing income inequality, alcohol-attributable hospitalisations actually showed the reverse relationship at low levels of income inequality. The curvilinear patterns we observed are inconsistent with monotonic trends found in previous research making our findings incompatible with previous explanations of the relationship between income inequality and health related harms.

  2. How reverse shoulder arthroplasty works.

    PubMed

    Walker, Matthew; Brooks, Jordan; Willis, Matthew; Frankle, Mark

    2011-09-01

    The reverse total shoulder arthroplasty was introduced to treat the rotator cuff-deficient shoulder. Since its introduction, an improved understanding of the biomechanics of rotator cuff deficiency and reverse shoulder arthroplasty has facilitated the development of modern reverse arthroplasty designs. We review (1) the basic biomechanical challenges associated with the rotator cuff-deficient shoulder; (2) the biomechanical rationale for newer reverse shoulder arthroplasty designs; (3) the current scientific evidence related to the function and performance of reverse shoulder arthroplasty; and (4) specific technical aspects of reverse shoulder arthroplasty. A PubMed search of the English language literature was conducted using the key words reverse shoulder arthroplasty, rotator cuff arthropathy, and biomechanics of reverse shoulder arthroplasty. Articles were excluded if the content fell outside of the biomechanics of these topics, leaving the 66 articles included in this review. Various implant design factors as well as various surgical implantation techniques affect stability of reverse shoulder arthroplasty and patient function. To understand the implications of individual design factors, one must understand the function of the normal and the cuff-deficient shoulder and coalesce this understanding with the pathology presented by each patient to choose the proper surgical technique for reconstruction. Several basic science and clinical studies improve our understanding of various design factors in reverse shoulder arthroplasty. However, much work remains to further elucidate the performance of newer designs and to evaluate patient outcomes using validated instruments such as the American Society for Elbow Surgery, simple shoulder test, and the Constant-Murley scores.

  3. Reverse photoacoustic standoff spectroscopy

    DOEpatents

    Van Neste, Charles W [Kingston, TN; Senesac, Lawrence R [Knoxville, TN; Thundat, Thomas G [Knoxville, TN

    2011-04-12

    A system and method are disclosed for generating a reversed photoacoustic spectrum at a greater distance. A source may emit a beam to a target and a detector measures signals generated as a result of the beam being emitted on the target. By emitting a chopped/pulsed light beam to the target, it may be possible to determine the target's optical absorbance by monitoring the intensity of light collected at the detector at different wavelengths. As the wavelength of light is changed, the target may absorb or reject each optical frequency. Rejection may increase the intensity at the sensing element and absorption may decrease the intensity. Accordingly, an identifying spectrum of the target may be made with the intensity variation of the detector as a function of illuminating wavelength.

  4. 46,XX sex reversal.

    PubMed

    Zenteno-Ruiz, J C; Kofman-Alfaro, S; Méndez, J P

    2001-01-01

    In humans, sexual differentiation is directed by SRY, a master regulatory gene located at the Y chromosome. This gene initiates the male pathway or represses the female pathway by regulating the transcription of downstream genes; however, the precise mechanisms by which SRY acts are largely unknown. Moreover, several genes have recently been implicated in the development of the bipotential gonad even before SRY is expressed. In some individuals, the normal process of sexual differentiation is altered and a sex reversal disorder is observed. These subjects present the chromosomes of one sex but the physical attributes of the other. Over the past years, considerable progress has been achieved in the molecular characterization of these disorders by using a combination of strategies including cell biology, animal models, and by studying patients with these pathologic entities.

  5. Multiple stimulus reversible hydrogels

    DOEpatents

    Gutowska, Anna; Krzyminski, Karol J.

    2003-12-09

    A polymeric solution capable of gelling upon exposure to a critical minimum value of a plurality of environmental stimuli is disclosed. The polymeric solution may be an aqueous solution utilized in vivo and capable of having the gelation reversed if at least one of the stimuli fall below, or outside the range of, the critical minimum value. The aqueous polymeric solution can be used either in industrial or pharmaceutical environments. In the medical environment, the aqueous polymeric solution is provided with either a chemical or radioisotopic therapeutic agent for delivery to a specific body part. The primary advantage of the process is that exposure to one environmental stimuli alone will not cause gelation, thereby enabling the therapeutic agent to be conducted through the body for relatively long distances without gelation occurring.

  6. Multiple stimulus reversible hydrogels

    DOEpatents

    Gutowska, Anna; Krzyminski, Karol J.

    2006-04-25

    A polymeric solution capable of gelling upon exposure to a critical minimum value of a plurality of environmental stimuli is disclosed. The polymeric solution may be an aqueous solution utilized in vivo and capable of having the gelation reversed if at least one of the stimuli fall below, or outside the range of, the critical minimum value. The aqueous polymeric solution can be used either in industrial or pharmaceutical environments. In the medical environment, the aqueous polymeric solution is provided with either a chemical or radioisotopic therapeutic agent for delivery to a specific body part. The primary advantage of the process is that exposure to one environmental stimuli alone will not cause gelation, thereby enabling the therapeutic agent to be conducted through the body for relatively long distances without gelation occurring.

  7. Sex Reversal in Amphibians.

    PubMed

    Flament, Stéphane

    2016-01-01

    Amphibians have been widely used to study developmental biology due to the fact that embryo development takes place independently of the maternal organism and that observations and experimental approaches are easy. Some amphibians like Xenopus became model organisms in this field. In the first part of this article, the differentiation of the gonads in amphibians and the mechanisms governing this process are reviewed. In the second part, the state of the art about sex reversal, which can be induced by steroid hormones in general and by temperature in some species, is presented. Also information about pollutants found in the environment that could interfere with the development of the amphibian reproductive apparatus or with their reproductive physiology is given. Such compounds could play a part in the amphibian decline, since in the wild, many amphibians are endangered species. © 2016 S. Karger AG, Basel.

  8. Biochemical Reversal of Aging

    NASA Astrophysics Data System (ADS)

    Ely, John T. A.

    2006-03-01

    We cite our progress on biochemical reversal of aging. However, it may be circa 2 years before we have necessary substances at low cost. Meanwhile, without them, a number of measures can be adopted providing marked improvement for the problems of aging in modern societies. For example, enzymes are needed to excrete toxins that accelerate aging; Hg is the ultimate toxin that disables all enzymes (including those needed to excrete Hg itself). Low Hg level in the urine, due to loss of excretory ability, causes the diagnosis of Hg toxicity to almost always be missed. Hg sources must be removed from the body! Another example is excess sugar; hyperglycemia decreases intracellular ascorbic acid (AA) by competitively inhibiting the insulin- mediated active transport of AA into cells. Thus, immunity is impaired by low leucocyte AA. AA is needed for new proteins in aging tissues. Humans must supplement AA; their need same as in AA-synthesizing mammals.

  9. Reverse total shoulder arthroplasty

    PubMed Central

    Familiari, Filippo; Rojas, Jorge; Nedim Doral, Mahmut; Huri, Gazi; McFarland, Edward G.

    2018-01-01

    Since the introduction of reverse total shoulder arthroplasty (RTSA) in 1987 (in Europe) and 2004 (in the United States), the number of RTSAs performed annually has increased. Although the main indication for RTSA has been rotator cuff tears, indications have expanded to include several shoulder conditions, many of which involve dysfunction of the rotator cuff. RTSA complications have been reported to affect 19% to 68% of patients and include acromial fracture, haematoma, infection, instability, mechanical baseplate failure, neurological injury, periprosthetic fracture and scapular notching. Current controversies in RTSA include optimal baseplate positioning, humeral neck-shaft angle (135° versus 155°), glenosphere placement (medial, lateral or bony increased offset RTSA) and subscapularis repair. Improvements in prosthesis design, surgeon experience and clinical results will need to occur to optimize this treatment for many shoulder conditions. Cite this article: EFORT Open Rev 2018;3:58–69 DOI: 10.1302/2058-5241.3.170044 PMID:29657846

  10. Reverse Osmosis Optimization

    SciTech Connect

    McMordie Stoughton, Kate; Duan, Xiaoli; Wendel, Emily M.

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). ¬The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them tomore » make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.¬« less

  11. Reverse Osmosis Optimization

    SciTech Connect

    None

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them tomore » make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.« less

  12. Reverse slapper detonator

    DOEpatents

    Weingart, Richard C.

    1990-01-01

    A reverse slapper detonator (70), and methodology related thereto, are provided. The detonator (70) is adapted to be driven by a pulse of electric power from an external source (80). A conductor (20) is disposed along the top (14), side (18), and bottom (16) surfaces of a sheetlike insulator (12). Part of the conductor (20) comprises a bridge (28), and an aperture (30) is positioned within the conductor (20), with the bridge (28) and the aperture (30) located on opposite sides of the insulator (12). A barrel (40) and related explosive charge (50) are positioned adjacent to and in alignment with the aperture (30), and the bridge (28) is buttressed with a backing layer (60). When the electric power pulse vaporizes the bridge (28), a portion of the insulator (12) is propelled through the aperture (30) and barrel (40), and against the explosive charge (50), thereby detonating it.

  13. On the association between nandrolone-mediated testosterone reduction during alcohol intoxication and attenuated voluntary alcohol intake in rats.

    PubMed

    Etelälahti, T J; Eriksson, C J P

    2013-11-01

    Human studies have indicated that the use of anabolic androgenic steroids may be associated with the abuse of alcohol and other drugs. Also, experimental animal research has indicated that chronic nandrolone administration subsequently increases voluntary alcohol drinking. The aim of our study was to test our hypothesis that alcohol-induced testosterone elevation, especially associated with stress conditions derived by nandrolone treatment, could be the underlying factor in causing increased alcohol drinking. Male alcohol-preferring AA and low drinking Wistar rats were randomly divided into control and nandrolone decanoate treated (15 mg/kg for 14 days) groups. Basal serum testosterone and corticosterone were determined before the first nandrolone treatment, after 7 days of treatment, and after an additional (7-day) washout period, during which also the acute effect of alcohol (1.5 g/kg) on steroid hormones was determined. Hereafter followed a (5-week) voluntary alcohol consumption period, during the last 2 weeks of which the rats were treated again with nandrolone. Both normal and reversed dark- vs. light-cycle experimental designs were used. Contrary to our hypothesis, nandrolone treatment decreased voluntary alcohol consumption in both AA and Wistar rats. Also, instead of stress causation, elevated basal testosterone and lowered basal corticosterone levels were observed after nandrolone treatment in both AA rats and Wistars. During acute alcohol intoxication the frequency of testosterone decreases was higher in the nandrolone-treated groups compared with control AA and Wistar rats. Present data support the hypothesis that nandrolone-treatment mediated attenuation of alcohol intake in both AA and Wistar rats may be the result of negative reinforcement caused by alcohol-mediated testosterone reduction. © 2013.

  14. Alcohol use by alcoholics with and without a history of parental alcoholism.

    PubMed

    Worobec, T G; Turner, W M; O'Farrell, T J; Cutter, H S; Bayog, R D; Tsuang, M T

    1990-12-01

    The association between parental history of alcoholism and the nature of alcoholism was assessed using a more reliable measure of family history (Family Tree Questionnaire) and a more comprehensive inventory of alcoholism (Alcohol Use Inventory) than used in earlier studies. Parental alcoholism was associated with more severe alcoholism on most parameters of alcohol use (age of onset, quantity, frequency, preoccupation, and sustained use) and alcohol-related problems (social, vocational, physical, cognitive, and loss of control). The association between parental history of alcoholism and more severe alcoholism in the probands was independent of age of onset of alcoholism, current age, socioeconomic background, and marital status. Parental history positive (PH+) alcoholics were more reliant on alcohol to manage their moods but did not differ significantly from parental history negative (PH-) alcoholics in the use of alcohol to improve sociability or mental functioning or to cope with marital problems. Surprisingly, the degree of concern, guilt, and worry over the negative consequences of drinking was not significantly different for PH+ alcoholics although the negative consequences were clearly much more severe for this group. While the data are inconclusive about the reasons for more severe alcoholism in PH+ alcoholics, greater reliance on ethanol to manage moods and a relative insensitivity to negative consequences could theoretically account for the vulnerability to more severe alcoholism found in PH+ alcoholics.

  15. Alcohol advertising and youth.

    PubMed

    Saffer, Henry

    2002-03-01

    The question addressed in this review is whether aggregate alcohol advertising increases alcohol consumption among college students. Both the level of alcohol-related problems on college campuses and the level of alcohol advertising are high. Some researchers have concluded that the cultural myths and symbols used in alcohol advertisements have powerful meanings for college students and affect intentions to drink. There is, however, very little empirical evidence that alcohol advertising has any effect on actual alcohol consumption. The methods used in this review include a theoretical framework for evaluating the effects of advertising. This theory suggests that the marginal effect of advertising diminishes at high levels of advertising. Many prior empirical studies measured the effect of advertising at high levels of advertising and found no effect. Those studies that measure advertising at lower, more disaggregated levels have found an effect on consumption. The results of this review suggest that advertising does increase consumption. However, advertising cannot be reduced with limited bans, which are likely to result in substitution to other available media. Comprehensive bans on all forms of advertising and promotion can eliminate options for substitution and be potentially more effective in reducing consumption. In addition, there is an increasing body of literature that suggests that alcohol counteradvertising is effective in reducing the alcohol consumption of teenagers and young adults. These findings indicate that increased counteradvertising, rather than new advertising bans, appears to be the better choice for public policy. It is doubtful that the comprehensive advertising bans required to reduce advertising would ever receive much public support. New limited bans on alcohol advertising might also result in less alcohol counteradvertising. An important topic for future research is to identify the counteradvertising themes that are most effective with

  16. Alcohol's Effects on the Body

    MedlinePlus

    ... Council Strategic Plan 2017-2021 Our Work Our Funding Our Staff Jobs & Training Our Location Contact Us You are here Home » Alcohol & Your Health » Alcohol's Effects on the Body Alcohol's Effects on the Body ...

  17. Alcohol and older drivers' crashes.

    DOT National Transportation Integrated Search

    2014-09-01

    Researchers have examined the effects of alcohol consumption : on older adults functioning, and some have : addressed alcohols effects on older drivers crash risk. : Generally, the findings have shown that alcohol is less : likely to be a fa...

  18. Responsible alcohol service programs evaluation

    DOT National Transportation Integrated Search

    1991-06-01

    TEAM is a responsible alcohol service program developed for public assembly facilities. Its objectives are to promote responsible alcohol service, enhance safety and enjoyment of fans, reduce potential liability, and reduce alcohol-impaired driving. ...

  19. Alcohol Use Screening

    MedlinePlus

    ... an interactive version of this tool. Select your gender. Female Male How often do you have a drink containing alcohol? Never Monthly or Less Two to four times a month Two to Three Times a Week Four or more times a week How many drinks containing alcohol do you have on a ...

  20. Women and Alcohol

    MedlinePlus

    ... about 5 percent alcohol content »» 5 ounces of wine with about 12 percent alcohol content »» 1.5 ... large cup of beer, an overpoured glass of wine, or a single mixed drink could contain much ...

  1. Alcohol and Choice.

    ERIC Educational Resources Information Center

    Kraushaar, Kevin W.

    Increased constraints on access to alcohol resulted from the closure of the sole hotels in two "experimental" towns. This afforded a natural experiment to study the effects of the change in availability of alcohol on consumption. Dependent measures were derived from public records of liquor sales by all licensed premises, and from…

  2. Adolescents' Perceptions of Alcohol

    ERIC Educational Resources Information Center

    Roy, Amit; Ikonen, Risto; Keinonen, Tuula; Kumar, Kuldeep

    2017-01-01

    Purpose: Rising trends in alcohol consumption and early drinking initiation pose serious health risks especially for adolescents. Learner's prior knowledge about alcohol gained from the social surroundings and the media are important sources that can impact the learning outcomes in health education. The purpose of this paper is to map adolescents'…

  3. Molecular basis of alcoholism.

    PubMed

    Most, Dana; Ferguson, Laura; Harris, R Adron

    2014-01-01

    Acute alcohol intoxication causes cellular changes in the brain that last for hours, while chronic alcohol use induces widespread neuroadaptations in the nervous system that can last a lifetime. Chronic alcohol use and the progression into dependence involve the remodeling of synapses caused by changes in gene expression produced by alcohol. The progression of alcohol use, abuse, and dependence can be divided into stages, which include intoxication, withdrawal, and craving. Each stage is associated with specific changes in gene expression, cellular function, brain circuits, and ultimately behavior. What are the molecular mechanisms underlying the transition from recreational use (acute) to dependence (chronic)? What cellular adaptations result in drug memory retention, leading to the persistence of addictive behaviors, even after prolonged drug abstinence? Research into the neurobiology of alcoholism aims to answer these questions. This chapter will describe the molecular adaptations caused by alcohol use and dependence, and will outline key neurochemical participants in alcoholism at the molecular level, which are also potential targets for therapy. © 2014 Elsevier B.V. All rights reserved.

  4. Neurologic complications of alcoholism.

    PubMed

    Noble, James M; Weimer, Louis H

    2014-06-01

    This review serves as an overview of neurologic conditions associated with alcohol abuse or withdrawal, including epidemiology, clinical symptoms, diagnostic approach, and treatment. Frequent alcohol abuse and frank alcoholism are very common among adults in the United States. Although rates decline with each decade, as many as 10% of the elderly drink excessively. Given the ubiquitous nature of alcoholism in society, its complications have been clinically recognized for generations, with recent advances focusing on improved understanding of ethanol's biochemical targets and the pathophysiology of its complications. The chronic effects of alcohol abuse are myriad and include neurologic complications through both direct and indirect effects on the central and peripheral nervous systems. These disorders include several encephalopathic states related to alcohol intoxication, withdrawal, and related nutritional deficiencies; acute and chronic toxic and nutritional peripheral neuropathies; and myopathy. Although prevention of alcoholism and its neurologic complications is the optimal strategy, this article reviews the specific treatment algorithms for alcohol withdrawal and its related nutritional deficiency states.

  5. Colby Alcohol Reports.

    ERIC Educational Resources Information Center

    Seitzinger, Janice

    Due to a variety of internal and external events the Student Affairs Committee of Colby College (Maine) studied alcohol use on campus and recommended solutions in two major areas, educational and social. Five educational strategies were recommended: (1) development of clear policies regarding alcohol and other drugs; (2) enforcement of…

  6. The Fetal Alcohol Syndrome.

    ERIC Educational Resources Information Center

    Umbreit, John; Ostrow, Lisa S.

    1980-01-01

    Fetal alcohol syndrome is a pattern of altered growth and morphogenesis found in about half the offspring of severely and chronically alcoholic women who continue drinking throughout their pregnancy. Of children studied, mild to moderate mental retardation was the most common disorder, occurring in 44 percent of the cases. (PHR)

  7. Fetal Alcohol Syndrome.

    ERIC Educational Resources Information Center

    Zerrer, Peggy

    The paper reviews Fetal Alcohol Syndrome (FAS), a series of effects seen in children whose mothers drink alcohol to excess during pregnancy. The identification of FAS and its recognition as a major health problem in need of prevention are traced. Characteristics of children with FAS are described and resultant growth retardation, abnormal physical…

  8. Reverse Genetics for Mammalian Orthoreovirus.

    PubMed

    Stuart, Johnasha D; Phillips, Matthew B; Boehme, Karl W

    2017-01-01

    Reverse genetics allows introduction of specific alterations into a viral genome. Studies performed with mutant viruses generated using reverse genetics approaches have contributed immeasurably to our understanding of viral replication and pathogenesis, and also have led to development of novel vaccines and virus-based vectors. Here, we describe the reverse genetics system that allows for production and recovery of mammalian orthoreovirus, a double-stranded (ds) RNA virus, from plasmids that encode the viral genome.

  9. 49 CFR 230.89 - Reverse gear.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Reverse gear. 230.89 Section 230.89 Transportation... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants... quadrant. Proper counterbalance shall be provided for the valve gear. (b) Air-operated power reverse gear...

  10. Alcoholics' selective attention to alcohol stimuli: automated processing?

    PubMed

    Stormark, K M; Laberg, J C; Nordby, H; Hugdahl, K

    2000-01-01

    This study investigated alcoholics' selective attention to alcohol words in a version of the Stroop color-naming task. Alcoholic subjects (n = 23) and nonalcoholic control subjects (n = 23) identified the color of Stroop versions of alcohol, emotional, neutral and color words. Manual reaction times (RTs), skin conductance responses (SCRs) and heart rate (HR) were recorded. Alcoholics showed overall longer RTs than controls while both groups were slower in responding to the incongruent color words than to the other words. Alcoholics showed longer RTs to both alcohol (1522.7 milliseconds [ms]) and emotional words (1523.7 ms) than to neutral words (1450.8 ms) which suggests that the content of these words interfered with the ability to attend to the color of the words. There was also a negative correlation (r = -.41) between RT and response accuracy to alcohol words for the alcoholics, reflecting that the longer time the alcoholics used to respond to the color of the alcohol words, the more incorrect their responses were. The alcoholics also showed significantly greater SCRs to alcohol words (0.16 microSiemens) than to any of the other words (ranging from 0.04-0.08 microSiemens), probably reflecting the emotional significance of the alcohol words. Finally, the alcoholics evidenced smaller HR acceleration to alcohol (1.9 delta bpm) compared to neutral (2.8 delta bpm), which could be related to difficulties alcoholics experience in terminating their attention to the alcohol words. These findings indicate that it is difficult for alcoholics to regulate their attention to alcohol stimuli, suggesting that alcoholics' processing of alcohol information is automated.

  11. Reversible micromachining locator

    DOEpatents

    Salzer, Leander J.; Foreman, Larry R.

    1999-01-01

    This invention provides a device which includes a locator, a kinematic mount positioned on a conventional tooling machine, a part carrier disposed on the locator and a retainer ring. The locator has disposed therein a plurality of steel balls, placed in an equidistant position circumferentially around the locator. The kinematic mount includes a plurality of magnets which are in registry with the steel balls on the locator. In operation, a blank part to be machined is placed between a surface of a locator and the retainer ring (fitting within the part carrier). When the locator (with a blank part to be machined) is coupled to the kinematic mount, the part is thus exposed for the desired machining process. Because the locator is removably attachable to the kinematic mount, it can easily be removed from the mount, reversed, and reinserted onto the mount for additional machining. Further, the locator can likewise be removed from the mount and placed onto another tooling machine having a properly aligned kinematic mount. Because of the unique design and use of magnetic forces of the present invention, positioning errors of less than 0.25 micrometer for each machining process can be achieved.

  12. Reversible micromachining locator

    DOEpatents

    Salzer, L.J.; Foreman, L.R.

    1999-08-31

    This invention provides a device which includes a locator, a kinematic mount positioned on a conventional tooling machine, a part carrier disposed on the locator and a retainer ring. The locator has disposed therein a plurality of steel balls, placed in an equidistant position circumferentially around the locator. The kinematic mount includes a plurality of magnets which are in registry with the steel balls on the locator. In operation, a blank part to be machined is placed between a surface of a locator and the retainer ring (fitting within the part carrier). When the locator (with a blank part to be machined) is coupled to the kinematic mount, the part is thus exposed for the desired machining process. Because the locator is removably attachable to the kinematic mount, it can easily be removed from the mount, reversed, and reinserted onto the mount for additional machining. Further, the locator can likewise be removed from the mount and placed onto another tooling machine having a properly aligned kinematic mount. Because of the unique design and use of magnetic forces of the present invention, positioning errors of less than 0.25 micrometer for each machining process can be achieved. 7 figs.

  13. Alcohol and CV Health: Jekyll and Hyde J-Curves.

    PubMed

    O'Keefe, Evan L; DiNicolantonio, James J; O'Keefe, James H; Lavie, Carl J

    2018-02-16

    A routine of light or moderate alcohol consumption (≤1 drink/day for women and 1 to 2 drinks/day for men) is associated with a lower risk for all-cause mortality, coronary artery disease (CAD), type 2 diabetes mellitus (T2D), heart failure (HF), and stroke. Conversely, heavy drinking, (>4 drinks/day) is associated with an increased risk for death and cardiovascular (CV) disease (CVD). Excessive alcohol intake trails behind only smoking and obesity among the 3 leading causes of premature deaths in the United States (US). Heavy alcohol use is a common cause of reversible hypertension (HTN), nonischemic dilated cardiomyopathy, atrial fibrillation (AF), and stroke (both ischemic and hemorrhagic). Among males aged 15 to 59 years, alcohol abuse is perhaps the leading cause of premature death. As such, the risk-to-benefit ratio of drinking is less favorable in younger individuals. A daily habit of light to moderate drinking is ideal for those who choose to consume alcohol regularly. Red wine in particular before or during the evening meal is linked with the best long-term CV outcomes. Most of the studies on alcohol and health are observational, and correlation does not prove causation. Health care professionals should not advise nondrinkers to begin drinking because of the paucity of randomized outcome data coupled with the potential for alcohol abuse even among seemingly low risk individuals. Copyright © 2017. Published by Elsevier Inc.

  14. Profiles of impaired, spared, and recovered neuropsychologic processes in alcoholism.

    PubMed

    Oscar-Berman, Marlene; Valmas, Mary M; Sawyer, Kayle S; Ruiz, Susan Mosher; Luhar, Riya B; Gravitz, Zoe R

    2014-01-01

    Long-term chronic alcoholism is associated with disparate and widespread residual consequences for brain functioning and behavior, and alcoholics suffer a variety of cognitive deficiencies and emotional abnormalities. Alcoholism has heterogeneous origins and outcomes, depending upon factors such as family history, age, gender, and mental or physical health. Consequently, the neuropsychologic profiles associated with alcoholism are not uniform among individuals. Moreover, within and across research studies, variability among subjects is substantial and contributes to characteristics associated with differential treatment outcomes after detoxification. In order to refine our understanding of alcoholism-related impaired, spared, and recovered abilities, we focus on five specific functional domains: (1) memory; (2) executive functions; (3) emotion and psychosocial skills; (4) visuospatial cognition; and (5) psychomotor abilities. Although the entire brain might be vulnerable in uncomplicated alcoholism, the brain systems that are considered to be most at risk are the frontocerebellar and mesocorticolimbic circuitries. Over time, with abstinence from alcohol, the brain appears to become reorganized to provide compensation for structural and behavioral deficits. By relying on a combination of clinical and scientific approaches, future research will help to refine the compensatory roles of healthy brain systems, the degree to which abstinence and treatment facilitate the reversal of brain atrophy and dysfunction, and the importance of individual differences to outcome. © 2014 Elsevier B.V. All rights reserved.

  15. Profiles of Impaired, Spared, and Recovered Neuropsychological Processes in Alcoholism

    PubMed Central

    Oscar-Berman, Marlene; Valmas, Mary M.; Sawyer, Kayle S.; Ruiz, Susan Mosher; Luhar, Riya B.; Gravitz, Zoe R.

    2015-01-01

    Long-term chronic alcoholism is associated with disparate and widespread residual consequences for brain functioning and behavior, and alcoholics suffer a variety of cognitive deficiencies and emotional abnormalities. Alcoholism has heterogeneous origins and outcomes, depending upon factors such as family history, age, gender, and mental or physical health. Consequently, the neuropsychological profiles associated with alcoholism are not uniform among individuals. Moreover, within and across research studies, variability among participants is substantial and contributes to characteristics associated with differential treatment outcomes after detoxification. In order to refine our understanding of alcoholism-related impaired, spared, and recovered abilities, we focus on five specific functional domains: (1) memory, (2) executive functions, (3) emotion and psychosocial skills, (4) visuospatial cognition, and (5) psychomotor abilities. The brain systems that are most vulnerable to alcoholism are the frontocerebellar and mesocorticolimbic circuitries. Over time, with abstinence from alcohol, the brain appears to become reorganized to provide compensation for structural and behavioral deficits. By relying on a combination of clinical and scientific approaches, future research will help to refine the compensatory roles of healthy brain systems, the degree to which abstinence and treatment facilitate the reversal of brain atrophy and dysfunction, and the importance of individual differences to outcome. PMID:25307576

  16. Does alcohol have any effect on male reproductive function? A review of literature.

    PubMed

    La Vignera, Sandro; Condorelli, Rosita A; Balercia, Giancarlo; Vicari, Enzo; Calogero, Aldo E

    2013-03-01

    Although alcohol is widely used, its impact on the male reproductive function is still controversial. Over the years, many studies have investigated the effects of alcohol consumption on sperm parameters and male infertility. This article reviews the main preclinical and clinical evidences. Studies conducted on the experimental animal have shown that a diet enriched with ethanol causes sperm parameter abnormalities, a number of alterations involving the reproductive tract inhibition, and reduced mouse oocyte in vitro fertilization rate. These effects were partly reversible upon discontinuation of alcohol consumption. Most of the studies evaluating the effects of alcohol in men have shown a negative impact on the sperm parameters. This has been reported to be associated with hypotestosteronemia and low-normal or elevated gonadotropin levels suggesting a combined central and testicular detrimental effect of alcohol. Nevertheless, alcohol consumption does not seem to have much effect on fertility either in in vitro fertilization programs or population-based studies. Finally, the genetic background and other concomitant, alcohol consumption-related conditions influence the degree of the testicular damage. In conclusion, alcohol consumption is associated with a deterioration of sperm parameters which may be partially reversible upon alcohol consumption discontinuation.

  17. Family Based Prevention of Alcohol and Risky Sex for Older Teens

    ClinicalTrials.gov

    2018-05-08

    Alcohol Drinking; Alcohol Intoxication; Alcohol Poison; Alcohol-Related Disorders; Alcohol Impairment; Alcohol Withdrawal; Alcohol Abstinence; Alcohol; Harmful Use; Sex Behavior; Sexual Aggression; Sexual Harassment; Relation, Interpersonal

  18. Developmental Relations and Patterns of Change between Alcohol Use and Number of Sexual Partners from Adolescence through Adulthood

    ERIC Educational Resources Information Center

    Dogan, Shannon J.; Stockdale, Gary D.; Widaman, Keith F.; Conger, Rand D.

    2010-01-01

    We explored two unanswered questions about the role of alcohol use in sexual behavior. First, we considered whether alcohol use temporally precedes and predicts changes in sexual behavior assessed as the number of sexual partners, whether the reverse pattern holds, or whether the association reflects a common, external cause. Second, we assessed…

  19. Supported metal catalysts for alcohol/sugar alcohol steam reforming

    SciTech Connect

    Davidson, Stephen; Zhang, He; Sun, Junming

    Despite extensive studies on hydrogen production via steam reforming of alcohols and sugar alcohols, catalysts typically suffer a variety of issues from poor hydrogen selectivity to rapid deactivation. Here, we summarize recent advances in fundamental understanding of functionality and structure of catalysts for alcohol/sugar alcohol steam reforming, and provide perspectives on further development required to design highly efficient steam reforming catalysts.

  20. Alcoholism: genes and mechanisms.

    PubMed

    Oroszi, Gabor; Goldman, David

    2004-12-01

    Alcoholism is a chronic relapsing/remitting disease that is frequently unrecognized and untreated, in part because of the partial efficacy of treatment. Only approximately one-third of patients remain abstinent and one-third have fully relapsed 1 year after withdrawal from alcohol, with treated patients doing substantially better than untreated [1]. The partial effectiveness of strategies for prevention and treatment, and variation in clinical course and side effects, represent a challenge and an opportunity to better understand the neurobiology of addiction. The strong heritability of alcoholism suggests the existence of inherited functional variants of genes that alter the metabolism of alcohol and variants of other genes that alter the neurobiologies of reward, executive cognitive function, anxiety/dysphoria, and neuronal plasticity. Each of these neurobiologies has been identified as a critical domain in the addictions. Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.

  1. Preference Reversal in Multiattribute Choice

    ERIC Educational Resources Information Center

    Tsetsos, Konstantinos; Usher, Marius; Chater, Nick

    2010-01-01

    A central puzzle for theories of choice is that people's preferences between options can be reversed by the presence of decoy options (that are not chosen) or by the presence of other irrelevant options added to the choice set. Three types of reversal effect reported in the decision-making literature, the attraction, compromise, and similarity…

  2. Play: The Reversal Theory Perspective.

    ERIC Educational Resources Information Center

    Kerr, J. H.

    The intention of this theoretical paper is to present a reversal theory interpretation of play phenomena. Reversal theory, a developing theory in psychology, concerns the complex relationship between experience and motivation. One of the central charactieristics of the theory is that it attempts to understand why so much of human behavior is…

  3. Marital Interaction in Alcoholic and Nonalcoholic Couples: Alcoholic Subtype Variations and Wives’ Alcoholism Status

    PubMed Central

    Floyd, Frank J.; Daugherty, Michelle Klotz; Fitzgerald, Hiram H.; Cranford, James A.; Zucker, Robert A.

    2008-01-01

    The authors examined problem-solving marital interactions of alcoholic and nonalcoholic couples (N = 132). Four alcoholic groups (husband alcoholic with antisocial personality disorder or not, paired with alcoholic or nonalcoholic wives) were compared with each other and with a both-spouses-nonalcoholic group. Consistent with the alcoholic subtypes hypothesis, couples with an antisocial alcoholic husband had higher levels of hostile behavior regardless of wives’ alcoholism status. In contrast, rates of positive behaviors and the ratio of positive to negative behaviors were greatest among couples in which either both or neither of the spouses had alcoholic diagnoses and were lowest among alcoholic husbands with nonalcoholic wives. Discussion focuses on possible mechanisms linking antisocial alcoholism and discrepant alcoholic diagnoses to poorer marital outcomes. PMID:16492103

  4. Nutritional evaluation of alcoholic inpatients admitted for alcohol detoxification.

    PubMed

    Teixeira, Joana; Mota, Teresa; Fernandes, João Cabral

    2011-01-01

    To assess nutritional risk of alcoholic patients admitted for alcohol detoxification. Screening of nutritional risk of alcoholic patients using the Malnutrition Universal Screening Tool. Fifty-three percentage patients at presentation were rated as being at medium or high risk of malnutrition. Malnutrition should be actively considered and screened for in alcoholic patients admitted for alcohol detoxification due to its high prevalence and benefits obtained from treatment.

  5. The Geomagnetic Field During a Reversal

    NASA Technical Reports Server (NTRS)

    Heirtzler, James R.

    2003-01-01

    By modifying the IGRF it is possible to learn what may happen to the geomagnetic field during a geomagnetic reversal. If the entire IGRF reverses then the declination and inclination only reverse when the field strength is zero. If only the dipole component of the IGRF reverses a large geomagnetic field remains when the dipole component is zero and he direction of the field at the end of the reversal is not exactly reversed from the directions at the beginning of the reversal.

  6. Theories of the Alcoholic Personality.

    ERIC Educational Resources Information Center

    Cox, W. Miles

    Several theories of the alcoholic personality have been devised to determine the relationship between the clusters of personality characteristics of alcoholics and their abuse of alcohol. The oldest and probably best known theory is the dependency theory, formulated in the tradition of classical psychoanalysis, which associates the alcoholic's…

  7. Alcohol and Staff Leisure Time.

    ERIC Educational Resources Information Center

    Camping Magazine, 1992

    1992-01-01

    Discusses the problem of alcohol use and abuse by camp staff. Describes alcohol policies of two different camps. Camp Highlands allows responsible drinking but not intoxication. Camp Olympia requires total abstinence from alcohol. A policy that clearly expresses the camp's philosophy toward alcohol and spells out all expectations and results is…

  8. Alcohol Policies on College Campuses.

    ERIC Educational Resources Information Center

    Mitchell, Rebecca J.; Toomey, Traci L.; Erickson, Darin

    2005-01-01

    State and local alcohol policies can minimize opportunities for people to use alcohol, thereby reducing consumption and alcohol-related problems. Little is known, however, about the prevalence of campus policies aimed at reducing college students' alcohol use and related problems. The authors surveyed school administrators in Minnesota and…

  9. Fecal microbiota manipulation prevents dysbiosis and alcohol-induced liver injury in mice.

    PubMed

    Ferrere, Gladys; Wrzosek, Laura; Cailleux, Frédéric; Turpin, Williams; Puchois, Virginie; Spatz, Madeleine; Ciocan, Dragos; Rainteau, Dominique; Humbert, Lydie; Hugot, Cindy; Gaudin, Françoise; Noordine, Marie-Louise; Robert, Véronique; Berrebi, Dominique; Thomas, Muriel; Naveau, Sylvie; Perlemuter, Gabriel; Cassard, Anne-Marie

    2017-04-01

    Alcoholic liver disease (ALD) is a leading cause of liver failure and mortality. In humans, severe alcoholic hepatitis is associated with key changes to intestinal microbiota (IM), which influences individual sensitivity to develop advanced ALD. We used the different susceptibility to ALD observed in two distinct animal facilities to test the efficiency of two complementary strategies (fecal microbiota transplantation and prebiotic treatment) to reverse dysbiosis and prevent ALD. Mice were fed alcohol in two distinct animal facilities with a Lieber DeCarli diet. Fecal microbiota transplantation was performed with fresh feces from alcohol-resistant donor mice to alcohol-sensitive receiver mice three times a week. Another group of mice received pectin during the entire alcohol consumption period. Ethanol induced steatosis and liver inflammation, which were associated with disruption of gut homeostasis, in alcohol-sensitive, but not alcohol resistant mice. IM analysis showed that the proportion of Bacteroides was specifically lower in alcohol-sensitive mice (p<0.05). Principal coordinate analysis showed that the IM of sensitive and resistant mice clustered differently. We targeted IM using two different strategies to prevent alcohol-induced liver lesions: (1) pectin treatment which induced major modifications of the IM, (2) fecal microbiota transplantation which resulted in an IM very close to that of resistant donor mice in the sensitive recipient mice. Both methods prevented steatosis, liver inflammation, and restored gut homeostasis. Manipulation of IM can prevent alcohol-induced liver injury. The IM should be considered as a new therapeutic target in ALD. Sensitivity to alcoholic liver disease (ALD) is driven by intestinal microbiota in alcohol fed mice. Treatment of mice with alcohol-induced liver lesions by fecal transplant from alcohol fed mice resistant to ALD or with prebiotic (pectin) prevents ALD. These findings open new possibilities for treatment of human

  10. Alcoholic cardiomyopathy: Pathophysiologic insights

    PubMed Central

    Piano, Mariann R.; Phillips, Shane A.

    2014-01-01

    Alcoholic cardiomyopathy is a specific heart muscle disease found in individuals with a history of long-term heavy alcohol consumption. Alcoholic cardiomyopathy is associated with a number of adverse histological, cellular, and structural changes within the myocardium. Several mechanisms are implicated in mediating the adverse effects of ethanol, including the generation of oxidative stress, apoptotic cell death, impaired mitochondrial bioenergetics/stress, derangements in fatty acid metabolism and transport, and accelerated protein catabolism. In this review, we discuss the evidence for such mechanisms and present the potential importance of drinking patterns, genetic susceptibility, nutritional factors, race, and sex. The purpose of this review is to provide a mechanistic paradigm for future research in the area of alcoholic cardiomyopathy. PMID:24671642

  11. Alcohol and masculinity.

    PubMed

    Lemle, R; Mishkind, M E

    1989-01-01

    Alcohol use--and abuse--has always been more prevalent among males than among females. The sex role prescription for men to affirm their masculinity by drinking is a major determinant of this sex difference. This paper reviews the intricate interrelationship between masculinity and both social and alcoholic drinking. A large body of evidence indicates that social drinking is a primary cultural symbol of manliness; portrayals in the media strengthen this association. Less evidence exists to connect masculinity issues with alcoholic dependence, but there has been much speculation: Three psychodynamic theories of alcoholism--the repressed homosexuality, dependency, and power theories--hypothesized that men who drink addictively have the most fragile masculine identities. The 1980s have witnessed a widespread recognition of the dangers of equating drinking and manliness, and societal changes suggest that drinking may be gradually losing its masculine aura.

  12. Alcohol and lipid metabolism

    PubMed Central

    Sozio, Margaret; Crabb, David W.

    2008-01-01

    Many new mechanisms for alcoholic steatosis have been suggested by work reported in the last five years. These include alterations of transcriptional controls of lipid metabolism, better understanding of the effects of abnormal methionine metabolism on the endoplasmic reticulum stress response, unraveling of the basis for sensitization of the Kupffer cell to lipopolysaccharide, a better understanding of the role of cytokines and adipokines in alcoholic liver disease, and implication of the innate immune and complement systems in responses to alcohol. Much of this work has been facilitated by work with knockout mice. Undoubtedly, there are interrelationships among these various pathogenic mechanisms that ultimately will provide a more cohesive picture of how heavy alcohol use deranges hepatic lipid metabolism. PMID:18349117

  13. Overview of Alcohol Consumption

    MedlinePlus

    ... Council Strategic Plan 2017-2021 Our Work Our Funding Our Staff Jobs & ... drink to socialize, celebrate, and relax. Alcohol often has a strong effect on people – and throughout history, we’ve struggled ...

  14. Alcohol Facts and Statistics

    MedlinePlus

    ... preventable causes of death in the United States: Comparative risk assessment of dietary, lifestyle, and metabolic risk ... Follow Get Updates Donations Share Join a Clinical Study Alcohol Treatment Navigator Site Map Accessibility Privacy FOIA ...

  15. Alcohol and Heart Health

    MedlinePlus

    ... Obesity, And What You Can Do Understanding the American Obesity Epidemic Stress Management How Does Stress Affect You? ... increases such dangers as alcoholism, high blood pressure , obesity , ... risks, the American Heart Association cautions people NOT to start drinking ... ...

  16. Fetal Alcohol Syndrome

    MedlinePlus

    ... Infants and Toddlers Kids and Teens Pregnancy and Childbirth Women Men Seniors Your Health Resources Healthcare Management ... Categories: Family Health, Infants and Toddlers, Pregnancy and Childbirth, WomenTags: alcohol abuse, female, Obstetrical, Pregnant Women, prenatal ...

  17. Alcoholic liver disease

    MedlinePlus

    ... FF, ed. Ferri's Clinical Advisor 2018 . Philadelphia, PA: Elsevier; 2018:59-60. Carithers RL, McClain C. Alcoholic ... Gastrointestinal and Liver Disease . 10th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 86. Haines EJ, Oyama LC. ...

  18. Older Adults and Alcohol

    MedlinePlus

    ... occurring Disorders Publications & Multimedia Brochures & Fact Sheets NIAAA Journal Alcohol Alert Bulletin Professional Education Materials Classroom Resources Publicaciones en Español Presentations and Videocasts Research Major Initiatives Guidelines & Resources Extramural Research Intramural Research ...

  19. Breath alcohol test

    MedlinePlus

    ... a glass tube. The tube is filled with bands of yellow crystals. The bands in the tube change colors (from yellow to ... Results Mean With the balloon method: 1 green band means that the blood-alcohol level is 0. ...

  20. Alcohol advertising and youth.

    PubMed

    Martin, Susan E; Snyder, Leslie B; Hamilton, Mark; Fleming-Milici, Fran; Slater, Michael D; Stacy, Alan; Chen, Meng-Jinn; Grube, Joel W

    2002-06-01

    This article presents the proceedings of a symposium at the 2001 Research Society on Alcoholism meeting in Montreal, Canada. The symposium was organized and chaired by Joel W. Grube. The presentations and presenters were (1) Introduction and background, by Susan E. Martin; (2) The effect of alcohol ads on youth 15-26 years old, by Leslie Snyder, Mark Hamilton, Fran Fleming-Milici, and Michael D. Slater; (3) A comparison of exposure to alcohol advertising and drinking behavior in elementary versus middle school children, by Phyllis L. Ellickson and Rebecca L. Collins; (4) USC health and advertising project: assessment study on alcohol advertisement memory and exposure, by Alan Stacy; and (5) TV beer and soft drink advertising: what young people like and what effects? by Meng-Jinn Chen and Joel W. Grube.

  1. Analysis of Alcohols.

    ERIC Educational Resources Information Center

    McCullough, Brother Thomas

    1984-01-01

    Presents a novel approach to identification of unknown alcohols using experimental measurements of boiling point and viscosity which are easily obtained without expensive equipment of instrumentation. Provides instructions for preparing capillary viscometer, listing special hints for obtaining good results. (JM)

  2. Alcohol during Pregnancy

    MedlinePlus

    ... Disease Control and Prevention (CDC) National Council on Alcoholism and Drug Dependence (NCADD) Substance Abuse and Mental Health Services Administration (SAMSHA) Last reviewed: April, 2016 Pregnancy Is it safe? Other Pregnancy topics ') document.write(' ...

  3. Reversible simulation of irreversible computation

    NASA Astrophysics Data System (ADS)

    Li, Ming; Tromp, John; Vitányi, Paul

    1998-09-01

    Computer computations are generally irreversible while the laws of physics are reversible. This mismatch is penalized by among other things generating excess thermic entropy in the computation. Computing performance has improved to the extent that efficiency degrades unless all algorithms are executed reversibly, for example by a universal reversible simulation of irreversible computations. All known reversible simulations are either space hungry or time hungry. The leanest method was proposed by Bennett and can be analyzed using a simple ‘reversible’ pebble game. The reachable reversible simulation instantaneous descriptions (pebble configurations) of such pebble games are characterized completely. As a corollary we obtain the reversible simulation by Bennett and, moreover, show that it is a space-optimal pebble game. We also introduce irreversible steps and give a theorem on the tradeoff between the number of allowed irreversible steps and the memory gain in the pebble game. In this resource-bounded setting the limited erasing needs to be performed at precise instants during the simulation. The reversible simulation can be modified so that it is applicable also when the simulated computation time is unknown.

  4. How decision reversibility affects motivation.

    PubMed

    Bullens, Lottie; van Harreveld, Frenk; Förster, Jens; Higgins, Tory E

    2014-04-01

    The present research examined how decision reversibility can affect motivation. On the basis of extant findings, it was suggested that 1 way it could affect motivation would be to strengthen different regulatory foci, with reversible decision making, compared to irreversible decision making, strengthening prevention-related motivation relatively more than promotion-related motivation. If so, then decision reversibility should have effects associated with the relative differences between prevention and promotion motivation. In 5 studies, we manipulated the reversibility of a decision and used different indicators of regulatory focus motivation to test these predictions. Specifically, Study 1 tested for differences in participants' preference for approach versus avoidance strategies toward a desired end state. In Study 2, we used speed and accuracy performance as indicators of participants' regulatory motivation, and in Study 3, we measured global versus local reaction time performance. In Study 4, we approached the research question in a different way, making use of the value-from-fit hypothesis (Higgins, 2000, 2002). We tested whether a fit between chronic regulatory focus and focus induced by the reversibility of the decision increased participants' subjective positive feelings about the decision outcome. Finally, in Study 5, we tested whether regulatory motivation, induced by decision reversibility, also influenced participants' preference in specific product features. The results generally support our hypothesis showing that, compared to irreversible decisions, reversible decisions strengthen a prevention focus more than a promotion focus. Implications for research on decision making are discussed.

  5. [Alcohol and pregnancy].

    PubMed

    Seror, E; Chapelon, E; Bué, M; Garnier-Lengliné, H; Lebeaux-Legras, C; Loudenot, A; Lejeune, C

    2009-10-01

    Alcohol consumption during pregnancy is a major cause of mental retardation in Western countries. Fetal alcohol syndrome (FAS) is mainly characterized by pre- and postnatal stunted growth, neurocognitive disorders, and facial dysmorphism. It compromises the intellectual and behavioral prognosis of the child. Prevention tools exist, through better information of health professionals, for optimal care of high-risk women before, during, and after pregnancy, which would decrease the incidence of SAF in the future.

  6. Supercritical fluid reverse micelle separation

    DOEpatents

    Fulton, John L.; Smith, Richard D.

    1993-01-01

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W.sub.o that determines the maximum size of the reverse micelles. The maximum ratio W.sub.o of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions.

  7. Supercritical fluid reverse micelle separation

    DOEpatents

    Fulton, J.L.; Smith, R.D.

    1993-11-30

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W[sub o] that determines the maximum size of the reverse micelles. The maximum ratio W[sub o] of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions. 27 figures.

  8. Stress and Alcohol

    PubMed Central

    Keyes, KM.; Hatzenbuehler, ML.; Grant, Bridget F.; Hasin, Deborah S.

    2012-01-01

    Exposure to stress often is psychologically distressing. The impact of stress on alcohol use and the risk of alcohol use disorders (AUDs) depends on the type, timing during the life course, duration, and severity of the stress experienced. Four important categories of stressors that can influence alcohol consumption are general life stress, catastrophic/fateful stress, childhood maltreatment, and minority stress. General life stressors, including divorce and job loss, increase the risk for AUDs. Exposure to terrorism or other disasters causes population-level increases in overall alcohol consumption but little increase in the incidence of AUDs. However, individuals with a history of AUDs are more likely to drink to cope with the traumatic event. Early onset of drinking in adolescence, as well as adult AUDs, are more common among people who experience childhood maltreatment. Finally, both perceptions and objective indicators of discrimination are associated with alcohol use and AUDs among racial/ethnic and sexual minorities. These observations demonstrate that exposure to stress in many forms is related to subsequent alcohol consumption and AUDs. However, many areas of this research remain to be studied, including greater attention to the role of various stressors in the course of AUDs and potential risk moderators when individuals are exposed to stressors. PMID:23584105

  9. Neuropathology of alcoholism.

    PubMed

    Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

    2014-01-01

    Chronic alcohol consumption results in structural changes to the brain. In alcoholics without coexisting thiamine deficiency or liver disease this is largely restricted to a loss of white-matter volume. When it occurs, neuronal loss is limited in anatomic distribution and only detected with quantitative techniques. This relative paucity of neurodegeneration is reflected in studies of gene and protein expression in postmortem brain where findings are subtle and discordant between studies. In alcoholics with coexisting pathologies, neuronal loss is more marked and affects a wider range of anatomic regions, especially subcortical nuclei. Although this more widespread damage may reflect a more severe drinking history, there is evidence linking thiamine deficiency and the consequences of liver disease to the pathogenesis of alcohol-related brain damage. Furthermore, a range of other factors, such as cigarette smoking and mood disorders, that are common in alcoholics, have the potential to influence studies of brain pathology and should be considered in further studies of the neuropathology of alcoholism. © 2014 Elsevier B.V. All rights reserved.

  10. Computer-aided diagnosis of alcoholism-related EEG signals.

    PubMed

    Acharya, U Rajendra; S, Vidya; Bhat, Shreya; Adeli, Hojjat; Adeli, Amir

    2014-12-01

    Alcoholism is a severe disorder that affects the functionality of neurons in the central nervous system (CNS) and alters the behavior of the affected person. Electroencephalogram (EEG) signals can be used as a diagnostic tool in the evaluation of subjects with alcoholism. The neurophysiological interpretation of EEG signals in persons with alcoholism (PWA) is based on observation and interpretation of the frequency and power in their EEGs compared to EEG signals from persons without alcoholism. This paper presents a review of the known features of EEGs obtained from PWA and proposes that the impact of alcoholism on the brain can be determined by computer-aided analysis of EEGs through extracting the minute variations in the EEG signals that can differentiate the EEGs of PWA from those of nonaffected persons. The authors advance the idea of automated computer-aided diagnosis (CAD) of alcoholism by employing the EEG signals. This is achieved through judicious combination of signal processing techniques such as wavelet, nonlinear dynamics, and chaos theory and pattern recognition and classification techniques. A CAD system is cost-effective and efficient and can be used as a decision support system by physicians in the diagnosis and treatment of alcoholism especially those who do not specialize in alcoholism or neurophysiology. It can also be of great value to rehabilitation centers to assess PWA over time and to monitor the impact of treatment aimed at minimizing or reversing the effects of the disease on the brain. A CAD system can be used to determine the extent of alcoholism-related changes in EEG signals (low, medium, high) and the effectiveness of therapeutic plans. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Zero field reversal probability in thermally assisted magnetization reversal

    NASA Astrophysics Data System (ADS)

    Prasetya, E. B.; Utari; Purnama, B.

    2017-11-01

    This paper discussed about zero field reversal probability in thermally assisted magnetization reversal (TAMR). Appearance of reversal probability in zero field investigated through micromagnetic simulation by solving stochastic Landau-Lifshitz-Gibert (LLG). The perpendicularly anisotropy magnetic dot of 50×50×20 nm3 is considered as single cell magnetic storage of magnetic random acces memory (MRAM). Thermally assisted magnetization reversal was performed by cooling writing process from near/almost Curie point to room temperature on 20 times runs for different randomly magnetized state. The results show that the probability reversal under zero magnetic field decreased with the increase of the energy barrier. The zero-field probability switching of 55% attained for energy barrier of 60 k B T and the reversal probability become zero noted at energy barrier of 2348 k B T. The higest zero-field switching probability of 55% attained for energy barrier of 60 k B T which corespond to magnetif field of 150 Oe for switching.

  12. Perspectives on the neuroscience of alcohol from the National Institute on Alcohol Abuse and Alcoholism.

    PubMed

    Reilly, Matthew T; Noronha, Antonio; Warren, Kenneth

    2014-01-01

    Mounting evidence over the last 40 years clearly indicates that alcoholism (alcohol dependence) is a disorder of the brain. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has taken significant steps to advance research into the neuroscience of alcohol. The Division of Neuroscience and Behavior (DNB) was formed within NIAAA in 2002 to oversee, fund, and direct all research areas that examine the effects of alcohol on the brain, the genetic underpinnings of alcohol dependence, the neuroadaptations resulting from excessive alcohol consumption, advanced behavioral models of the various stages of the addiction cycle, and preclinical medications development. This research portfolio has produced important discoveries in the etiology, treatment, and prevention of alcohol abuse and dependence. Several of these salient discoveries are highlighted and future areas of neuroscience research on alcohol are presented. © 2014 Elsevier B.V. All rights reserved.

  13. Comparing Alcohol Marketing and Alcohol Warning Message Policies Across Canada.

    PubMed

    Wettlaufer, Ashley; Cukier, Samantha N; Giesbrecht, Norman

    2017-08-24

    In order to reduce harms from alcohol, evidence-based policies are to be introduced and sustained. To facilitate the dissemination of policies that reduce alcohol-related harms by documenting, comparing, and sharing information on effective alcohol polices related to restrictions on alcohol marketing and alcohol warning messaging in 10 Canadian provinces. Team members developed measurable indicators to assess policies on (a) restrictions on alcohol marketing, and (b) alcohol warning messaging. Indicators were peer-reviewed by three alcohol policy experts, refined, and data were collected, submitted for validation by provincial experts, and scored independently by two team members. The national average score was 52% for restrictions on marketing policies and 18% for alcohol warning message policies. Most provinces had marketing regulations that went beyond the federal guidelines with penalties for violating marketing regulations. The provincial liquor boards' web pages focused on product promotion, and there were few restrictions on sponsorship activities. No province has implemented alcohol warning labels, and Ontario was the sole province to have legislated warning signs at all points-of-sale. Most provinces provided a variety of warning signs to be displayed voluntarily at points-of-sale; however, the quality of messages varied. Conclusions/Importance: There is extensive alcohol marketing with comparatively few messages focused on the potential harms associated with alcohol. It is recommended that governments collaborate with multiple stakeholders to maximize the preventive impact of restrictions on alcohol marketing and advertising, and a broader implementation of alcohol warning messages.

  14. 27 CFR 4.36 - Alcoholic content.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Alcoholic content. 4.36 Section 4.36 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF WINE Labeling Requirements for Wine § 4.36 Alcoholic content. (a) Alcoholic content shall be...

  15. 27 CFR 4.36 - Alcoholic content.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Alcoholic content. 4.36 Section 4.36 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF WINE Labeling Requirements for Wine § 4.36 Alcoholic content. (a) Alcoholic content shall be...

  16. 27 CFR 7.71 - Alcoholic content.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Alcoholic content. 7.71 Section 7.71 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF MALT BEVERAGES Interim Regulations for Alcoholic Content Statements § 7.71 Alcoholic content. ...

  17. 27 CFR 7.71 - Alcoholic content.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Alcoholic content. 7.71 Section 7.71 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF MALT BEVERAGES Interim Regulations for Alcoholic Content Statements § 7.71 Alcoholic content. ...

  18. Cycling injuries and alcohol.

    PubMed

    Airaksinen, Noora K; Nurmi-Lüthje, Ilona S; Kataja, J Matti; Kröger, Heikki P J; Lüthje, Peter M J

    2018-05-01

    Most of the cycling accidents that occur in Finland do not end up in the official traffic accident statistics. Thus, there is minimal information on these accidents and their consequences, particularly in cases in which alcohol was involved. The focus of the present study is on cycling accidents and injuries involving alcohol in particular. Data on patients visiting the emergency department at North Kymi Hospital because of a cycling accident was prospectively collected for two years, from June 1, 2004 to May 31, 2006. Blood alcohol concentration (BAC) was measured on admission with a breath analyser. The severity of the cycling injuries was classified according to the Abbreviated Injury Scale (AIS). A total of 217 cycling accidents occurred. One third of the injured cyclists were involved with alcohol at the time of visiting the hospital. Of these, 85% were males. A blood alcohol concentration of ≥ 1.2 g/L was measured in nearly 90% of all alcohol-related cases. A positive BAC result was more common among males than females (p < 0.001), and head injuries were more common among cyclists where alcohol was involved (AI) (60%) than among sober cyclists (29%) (p < 0.001). Two thirds (64%) of the cyclists with AI were not wearing a bicycle helmet. The figure for serious injuries (MAIS ≥ 3) was similar in both groups. Intoxication with an alcohol level of more than 1.5 g/L and the age of 15 to 24 years were found to be risk factors for head injuries. The mean cost of treatment was higher among sober cyclists than among cyclists with AI (€2143 vs. €1629), whereas in respect of the cost of work absence, the situation was the opposite (€1348 vs. €1770, respectively). Cyclists involved with alcohol were, in most cases, heavily intoxicated and were not wearing a bicycle helmet. Head injuries were more common among these cyclists than among sober cyclists. As cycling continues to increase, it is important to monitor cycling accidents, improve

  19. Acute Alcohol Consumption, Alcohol Outlets, and Gun Suicide

    PubMed Central

    Branas, Charles C.; Richmond, Therese S.; Ten Have, Thomas R.; Wiebe, Douglas J.

    2014-01-01

    A case–control study of 149 intentionally self-inflicted gun injury cases (including completed gun suicides) and 302 population-based controls was conducted from 2003 to 2006 in a major US city. Two focal independent variables, acute alcohol consumption and alcohol outlet availability, were measured. Conditional logistic regression was adjusted for confounding variables. Gun suicide risk to individuals in areas of high alcohol outlet availability was less than the gun suicide risk they incurred from acute alcohol consumption, especially to excess. This corroborates prior work but also uncovers new information about the relationships between acute alcohol consumption, alcohol outlets, and gun suicide. Study limitations and implications are discussed. PMID:21929327

  20. Acute alcohol consumption, alcohol outlets, and gun suicide.

    PubMed

    Branas, Charles C; Richmond, Therese S; Ten Have, Thomas R; Wiebe, Douglas J

    2011-01-01

    A case-control study of 149 intentionally self-inflicted gun injury cases (including completed gun suicides) and 302 population-based controls was conducted from 2003 to 2006 in a major US city. Two focal independent variables, acute alcohol consumption and alcohol outlet availability, were measured. Conditional logistic regression was adjusted for confounding variables. Gun suicide risk to individuals in areas of high alcohol outlet availability was less than the gun suicide risk they incurred from acute alcohol consumption, especially to excess. This corroborates prior work but also uncovers new information about the relationships between acute alcohol consumption, alcohol outlets, and gun suicide. Study limitations and implications are discussed.

  1. Alcohol and the pancreas.

    PubMed

    Schenker, S; Montalvo, R

    1998-01-01

    Alcoholic pancreatitis may be one of the most serious adverse consequences of alcohol abuse. Its diagnosis, as it has for many years, depends primarily on clinical acumen in interpreting properly the symptoms and signs of abdominal distress, buttressed by elevated pancreatic enzymes (amylase and lipase). More recently, the use of computerized tomography (CT) in selected situations has been both of confirmatory and prognostic value. Severity of abnormality by CT correlates reasonably well with a variety of clinical-laboratory clusters (APACHE system, Ranson's criteria, etc.) and aids in therapy. The pathogenesis of alcoholic pancreatitis is not fully defined. The ultimate picture is one of tissue autolysis by activated proteolytic enzymes. The triggers for such activation, however, are still not known. They are represented by three main theories: (1) large duct obstruction and/or increased permeability relative to pancreatic secretion, (2) small duct obstruction due to proteinaceous precipitates, and (3) a direct toxic-metabolic effect of ethanol on pancreatic acinar cells. While not mutually exclusive, we favor the last hypothesis as being most consistent with the effects of ethanol on other organ systems. The direct effects of ethanol and/or its metabolites may be mediated, at least in part, via oxidative stress or the generation of fatty acid ethyl esters. Autolysis (regardless of proximate mechanism(s)) leads to inflammation likely mediated via release of various cytokines. It also should be appreciated that "acute" pancreatitis (the topic of this chapter) likely represents an acute process within a chronic pancreatic exposure and injury from alcoholic abuse. The key question of why pancreatitis develops in only a small number of alcohol abusers is not resolved. Therapy depends on the severity of alcoholic pancreatitis, which is defined by clinical-laboratory and often CT criteria. Mild pancreatitis usually resolves acutely with alcohol abstention and supportive

  2. The influence of alcohol-specific communication on adolescent alcohol use and alcohol-related consequences.

    PubMed

    Reimuller, Alison; Hussong, Andrea; Ennett, Susan T

    2011-12-01

    Alcohol-specific communication, a direct conversation between an adult and an adolescent regarding alcohol use, contains messages about alcohol relayed from the adult to the child. The current study examined the construct of alcohol-specific communication and the effect of messages on adolescent alcohol use and alcohol-related consequences. Parent-adolescent dyads were assessed biannually for 3 years (grades 9-11 at wave 6) to examine these relations in a large longitudinal study of adolescents initially in grades 6 through 8. An exploratory factor analysis identified two factors among alcohol-specific communication items, permissive messages and negative alcohol messages. Results showed previous level of adolescent alcohol use moderated the relation between permissive messages and alcohol use outcomes. Plotting of these interactions showed greater alcohol use and consequences with increasing permissive messages in adolescents with higher versus lower levels of previous alcohol use. Results suggest that parental messages regarding alcohol use may impact adolescent alcohol use beyond the effect of general parenting style and parental alcohol use.

  3. The Influence of Alcohol-specific Communication on Adolescent Alcohol Use and Alcohol-related Consequences

    PubMed Central

    Reimuller, Alison; Hussong, Andrea; Ennett, Susan T.

    2013-01-01

    Alcohol-specific communication, a direct conversation between an adult and an adolescent regarding alcohol use, contains messages about alcohol relayed from the adult to the child. The current study examined the construct of alcohol-specific communication and the effect of messages on adolescent alcohol use and alcohol-related consequences. Parent-adolescent dyads were assessed biannually for 3 years (grades 9-11 at wave 6) to examine these relations in a large longitudinal study of adolescents initially in grades 6 through 8. An exploratory factor analysis identified two factors among alcohol-specific communication items, permissive messages and negative alcohol messages. Results showed previous level of adolescent alcohol use moderated the relation between permissive messages and alcohol use outcomes. Plotting of these interactions showed greater alcohol use and consequences with increasing permissive messages in adolescents with higher versus lower levels of previous alcohol use. Results suggest that parental messages regarding alcohol use may impact adolescent alcohol use beyond the effect of general parenting style and parental alcohol use. PMID:21667141

  4. Reverse Current in Solar Flares

    NASA Technical Reports Server (NTRS)

    Knight, J. W., III

    1978-01-01

    An idealized steady state model of a stream of energetic electrons neutralized by a reverse current in the pre-flare solar plasma was developed. These calculations indicate that, in some cases, a significant fraction of the beam energy may be dissipated by the reverse current. Joule heating by the reverse current is a more effective mechanism for heating the plasma than collisional losses from the energetic electrons because the Ohmic losses are caused by thermal electrons in the reverse current which have much shorter mean free paths than the energetic electrons. The heating due to reverse currents is calculated for two injected energetic electron fluxes. For the smaller injected flux, the temperature of the coronal plasma is raised by about a factor of two. The larger flux causes the reverse current drift velocity to exceed the critical velocity for the onset of ion cyclotron turbulence, producing anomalous resistivity and an order of magnitude increase in the temperature. The heating is so rapid that the lack of ionization equilibrium may produce a soft X-ray and EUV pulse from the corona.

  5. Focus on: epigenetics and fetal alcohol spectrum disorders.

    PubMed

    Kobor, Michael S; Weinberg, Joanne

    2011-01-01

    Epigenetic changes-stable but potentially reversible alterations in a cell's genetic information that result in changes in gene expression but do not involve changes in the underlying DNA sequence-may mediate some of the detrimental effects of prenatal alcohol exposure and contribute to the deficits and abnormalities associated with fetal alcohol spectrum disorders. These epigenetic processes are linked to the chromatin (i.e., DNA, histone proteins, and other associated proteins) and commonly involve chemical modifications (e.g., methylation) of these molecules, which may result in altered expression of the affected genes. Even alcohol exposure prior to conception appears to be able to induce epigenetic changes in the parental genetic material that can be passed on to the offspring and affect offspring outcome. Similarly, epigenetic processes may occur as a result of maternal alcohol consumption during the period between fertilization of the egg and implantation in the uterus. The period most sensitive to alcohol's adverse effects appears to be gastrulation, which corresponds to prenatal weeks 3 to 8 in the human and prenatal days 7 to 14 in the mouse, when cells are differentiating to form organs. One way in which alcohol exposure may induce epigenetic changes, particularly abnormal DNA methylation, is by affecting a set of biochemical reactions called the methionine-homocysteine cycle.

  6. Alcohol policies on college campuses.

    PubMed

    Mitchell, Rebecca J; Toomey, Traci L; Erickson, Darin

    2005-01-01

    State and local alcohol policies can minimize opportunities for people to use alcohol, thereby reducing consumption and alcohol-related problems. Little is known, however, about the prevalence of campus policies aimed at reducing college students' alcohol use and related problems. The authors surveyed school administrators in Minnesota and Wisconsin to assess the frequency of alcohol policies and whether institutional characteristics were likely to predict campus policies. They also compared administrators' responses to policies posted on college Web sites. Most schools prohibited beer kegs and provided alcohol-free housing for students. A minority of schools prohibited all alcohol use on campus or at Greek organizations or banned advertisements in school newspapers for alcohol or off-campus bars. The prevalence of policies varied with school characteristics, and agreement was poor between Web-site policy information and that provided by administrators. Further research on the prevalence of college alcohol policies might be useful for assessing trends and future prevention needs on campuses.

  7. Activation of brain NOP receptors attenuates acute and protracted alcohol withdrawal symptoms in the rat.

    PubMed

    Economidou, Daina; Cippitelli, Andrea; Stopponi, Serena; Braconi, Simone; Clementi, Stefano; Ubaldi, Massimo; Martin-Fardon, Rèmi; Weiss, Friedbert; Massi, Maurizio; Ciccocioppo, Roberto

    2011-04-01

    Alcohol withdrawal refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with Nociceptin/orphanin FQ (N/OFQ) significantly reduces alcohol consumption and attenuates alcohol-seeking behavior induced by environmental conditioning factors or by stress in rats. In this study, we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats. For this purpose, animals were subjected to a 6-day chronic alcohol intoxication (by intragastric administration), and at 8, 10, and 12 hours following cessation of alcohol exposure, they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0, and 3.0 μg/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal-induced anxiety, another group of rats was subjected to ethanol intoxication and after 1 week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment, an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12 hour later were tested in the EPM following ICV N/OFQ (0.0, 1.0, and 2.0 μg/rat). Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals. These findings suggest that the N/OFQ-NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms. Copyright © 2011 by the Research Society on Alcoholism.

  8. Exposure to alcohol advertisements and teenage alcohol-related problems.

    PubMed

    Grenard, Jerry L; Dent, Clyde W; Stacy, Alan W

    2013-02-01

    This study used prospective data to test the hypothesis that exposure to alcohol advertising contributes to an increase in underage drinking and that an increase in underage drinking then leads to problems associated with drinking alcohol. A total of 3890 students were surveyed once per year across 4 years from the 7th through the 10th grades. Assessments included several measures of exposure to alcohol advertising, alcohol use, problems related to alcohol use, and a range of covariates, such as age, drinking by peers, drinking by close adults, playing sports, general TV watching, acculturation, parents' jobs, and parents' education. Structural equation modeling of alcohol consumption showed that exposure to alcohol ads and/or liking of those ads in seventh grade were predictive of the latent growth factors for alcohol use (past 30 days and past 6 months) after controlling for covariates. In addition, there was a significant total effect for boys and a significant mediated effect for girls of exposure to alcohol ads and liking of those ads in 7th grade through latent growth factors for alcohol use on alcohol-related problems in 10th grade. Younger adolescents appear to be susceptible to the persuasive messages contained in alcohol commercials broadcast on TV, which sometimes results in a positive affective reaction to the ads. Alcohol ad exposure and the affective reaction to those ads influence some youth to drink more and experience drinking-related problems later in adolescence.

  9. Exposure to Alcohol Advertisements and Teenage Alcohol-Related Problems

    PubMed Central

    Dent, Clyde W.; Stacy, Alan W.

    2013-01-01

    OBJECTIVE: This study used prospective data to test the hypothesis that exposure to alcohol advertising contributes to an increase in underage drinking and that an increase in underage drinking then leads to problems associated with drinking alcohol. METHODS: A total of 3890 students were surveyed once per year across 4 years from the 7th through the 10th grades. Assessments included several measures of exposure to alcohol advertising, alcohol use, problems related to alcohol use, and a range of covariates, such as age, drinking by peers, drinking by close adults, playing sports, general TV watching, acculturation, parents’ jobs, and parents’ education. RESULTS: Structural equation modeling of alcohol consumption showed that exposure to alcohol ads and/or liking of those ads in seventh grade were predictive of the latent growth factors for alcohol use (past 30 days and past 6 months) after controlling for covariates. In addition, there was a significant total effect for boys and a significant mediated effect for girls of exposure to alcohol ads and liking of those ads in 7th grade through latent growth factors for alcohol use on alcohol-related problems in 10th grade. CONCLUSIONS: Younger adolescents appear to be susceptible to the persuasive messages contained in alcohol commercials broadcast on TV, which sometimes results in a positive affective reaction to the ads. Alcohol ad exposure and the affective reaction to those ads influence some youth to drink more and experience drinking-related problems later in adolescence. PMID:23359585

  10. Anticonvulsants for alcohol withdrawal.

    PubMed

    Minozzi, Silvia; Amato, Laura; Vecchi, Simona; Davoli, Marina

    2010-03-17

    Alcohol abuse and dependence represents a most serious health problem worldwide with major social, interpersonal and legal interpolations. Besides benzodiazepines, anticonvulsants are often used for the treatment of alcohol withdrawal symptoms. Anticonvulsants drugs are indicated for the treatment of alcohol withdrawal syndrome, alone or in combination with benzodiazepine treatments. In spite of the wide use, the exact role of the anticonvulsants for the treatment of alcohol withdrawal has not yet bee adequately assessed. To evaluate the effectiveness and safety of anticonvulsants in the treatment of alcohol withdrawal. We searched Cochrane Drugs and Alcohol Group' Register of Trials (December 2009), PubMed, EMBASE, CINAHL (1966 to December 2009), EconLIT (1969 to December 2009). Parallel searches on web sites of health technology assessment and related agencies, and their databases. Randomized controlled trials (RCTs) examining the effectiveness, safety and overall risk-benefit of anticonvulsants in comparison with a placebo or other pharmacological treatment. All patients were included regardless of age, gender, nationality, and outpatient or inpatient therapy. Two authors independently screened and extracted data from studies. Fifty-six studies, with a total of 4076 participants, met the inclusion criteria. Comparing anticonvulsants with placebo, no statistically significant differences for the six outcomes considered.Comparing anticonvulsant versus other drug, 19 outcomes considered, results favour anticonvulsants only in the comparison carbamazepine versus benzodiazepine (oxazepam and lorazepam) for alcohol withdrawal symptoms (CIWA-Ar score): 3 studies, 262 participants, MD -1.04 (-1.89 to -0.20), none of the other comparisons reached statistical significance.Comparing different anticonvulsants no statistically significant differences in the two outcomes considered.Comparing anticonvulsants plus other drugs versus other drugs (3 outcomes considered), results

  11. Reverse hybrid total hip arthroplasty.

    PubMed

    Wangen, Helge; Havelin, Leif I; Fenstad, Anne M; Hallan, Geir; Furnes, Ove; Pedersen, Alma B; Overgaard, Søren; Kärrholm, Johan; Garellick, Göran; Mäkelä, Keijo; Eskelinen, Antti; Nordsletten, Lars

    2017-06-01

    Background and purpose - The use of a cemented cup together with an uncemented stem in total hip arthroplasty (THA) has become popular in Norway and Sweden during the last decade. The results of this prosthetic concept, reverse hybrid THA, have been sparsely described. The Nordic Arthroplasty Register Association (NARA) has already published 2 papers describing results of reverse hybrid THAs in different age groups. Based on data collected over 2 additional years, we wanted to perform in depth analyses of not only the reverse hybrid concept but also of the different cup/stem combinations used. Patients and methods - From the NARA, we extracted data on reverse hybrid THAs from January 1, 2000 until December 31, 2013. 38,415 such hips were studied and compared with cemented THAs. The Kaplan-Meier method and Cox regression analyses were used to estimate the prosthesis survival and the relative risk of revision. The main endpoint was revision for any reason. We also performed specific analyses regarding the different reasons for revision and analyses regarding the cup/stem combinations used in more than 500 cases. Results - We found a higher rate of revision for reverse hybrids than for cemented THAs, with an adjusted relative risk of revision (RR) of 1.4 (95% CI: 1.3-1.5). At 10 years, the survival rate was 94% (CI: 94-95) for cemented THAs and 92% (95% CI: 92-93) for reverse hybrids. The results for the reverse hybrid THAs were inferior to those for cemented THAs in patients aged 55 years or more (RR =1.1, CI: 1.0-1.3; p < 0.05). We found a higher rate of early revision due to periprosthetic femoral fracture for reverse hybrids than for cemented THAs in patients aged 55 years or more (RR =3.1, CI: 2.2-4.5; p < 0.001). Interpretation - Reverse hybrid THAs had a slightly higher rate of revision than cemented THAs in patients aged 55 or more. The difference in survival was mainly caused by a higher incidence of early revision due to periprosthetic femoral fracture in

  12. Invertebrate models of alcoholism.

    PubMed

    Scholz, Henrike; Mustard, Julie A

    2013-01-01

    For invertebrates to become useful models for understanding the genetic and physiological mechanisms of alcoholism related behaviors and the predisposition towards alcoholism, several general requirements must be fulfilled. The animal should encounter ethanol in its natural habitat, so that the central nervous system of the organism will have evolved mechanisms for responding to ethanol exposure. How the brain adapts to ethanol exposure depends on its access to ethanol, which can be regulated metabolically and/or by physical barriers. Therefore, a model organism should have metabolic enzymes for ethanol degradation similar to those found in humans. The neurons and supporting glial cells of the model organism that regulate behaviors affected by ethanol should share the molecular and physiological pathways found in humans, so that results can be compared. Finally, the use of invertebrate models should offer advantages over traditional model systems and should offer new insights into alcoholism-related behaviors. In this review we will summarize behavioral similarities and identified genes and mechanisms underlying ethanol-induced behaviors in invertebrates. This review mainly focuses on the use of the nematode Caenorhabditis elegans, the honey bee Apis mellifera and the fruit fly Drosophila melanogaster as model systems. We will discuss insights gained from those studies in conjunction with their vertebrate model counterparts and the implications for future research into alcoholism and alcohol-induced behaviors.

  13. Stress, epigenetics, and alcoholism.

    PubMed

    Moonat, Sachin; Pandey, Subhash C

    2012-01-01

    Acute and chronic stressors have been associated with alterations in mood and increased anxiety that may eventually result in the development of stress-related psychiatric disorders. Stress and associated disorders, including anxiety, are key factors in the development of alcoholism because alcohol consumption can temporarily reduce the drinker's dysphoria. One molecule that may help mediate the relationship between stress and alcohol consumption is brain-derived neurotrophic factor (BDNF), a protein that regulates the structure and function of the sites where two nerve cells interact and exchange nerve signals (i.e., synapses) and which is involved in numerous physiological processes. Aberrant regulation of BDNF signaling and alterations in synapse activity (i.e., synaptic plasticity) have been associated with the pathophysiology of stress-related disorders and alcoholism. Mechanisms that contribute to the regulation of genetic information without modification of the DNA sequence (i.e., epigenetic mechanisms) may play a role in the complex control of BDNF signaling and synaptic plasticity-for example, by modifying the structure of the DNA-protein complexes (i.e., chromatin) that make up the chromosomes and thereby modulating the expression of certain genes. Studies regarding the epigenetic control of BDNF signaling and synaptic plasticity provide a promising direction to understand the mechanisms mediating the interaction between stress and alcoholism.

  14. Genetics of alcoholism.

    PubMed

    Edenberg, Howard J; Foroud, Tatiana

    2014-01-01

    Multiple lines of evidence strongly indicate that genetic factors contribute to the risk for alcohol use disorders (AUD). There is substantial heterogeneity in AUD, which complicates studies seeking to identify specific genetic factors. To identify these genetic effects, several different alcohol-related phenotypes have been analyzed, including diagnosis and quantitative measures related to AUDs. Study designs have used candidate gene analyses, genetic linkage studies, genomewide association studies (GWAS), and analyses of rare variants. Two genes that encode enzymes of alcohol metabolism have the strongest effect on AUD: aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B each has strongly protective variants that reduce risk, with odds ratios approximately 0.2-0.4. A number of other genes important in AUD have been identified and replicated, including GABRA2 and alcohol dehydrogenases 1B and 4. GWAS have identified additional candidates. Rare variants are likely also to play a role; studies of these are just beginning. A multifaceted approach to gene identification, targeting both rare and common variations and assembling much larger datasets for meta-analyses, is critical for identifying the key genes and pathways important in AUD. © 2014 Elsevier B.V. All rights reserved.

  15. Stress, Epigenetics, and Alcoholism

    PubMed Central

    Moonat, Sachin; Pandey, Subhash C.

    2012-01-01

    Acute and chronic stressors have been associated with alterations in mood and increased anxiety that may eventually result in the development of stress-related psychiatric disorders. Stress and associated disorders, including anxiety, are key factors in the development of alcoholism because alcohol consumption can temporarily reduce the drinker’s dysphoria. One molecule that may help mediate the relationship between stress and alcohol consumption is brain-derived neurotrophic factor (BDNF), a protein that regulates the structure and function of the sites where two nerve cells interact and exchange nerve signals (i.e., synapses) and which is involved in numerous physiological processes. Aberrant regulation of BDNF signaling and alterations in synapse activity (i.e., synaptic plasticity) have been associated with the pathophysiology of stress-related disorders and alcoholism. Mechanisms that contribute to the regulation of genetic information without modification of the DNA sequence (i.e., epigenetic mechanisms) may play a role in the complex control of BDNF signaling and synaptic plasticity—for example, by modifying the structure of the DNA–protein complexes (i.e., chromatin) that make up the chromosomes and thereby modulating the expression of certain genes. Studies regarding the epigenetic control of BDNF signaling and synaptic plasticity provide a promising direction to understand the mechanisms mediating the interaction between stress and alcoholism. PMID:23584115

  16. Addictions Neuroclinical Assessment: A reverse translational approach.

    PubMed

    Kwako, Laura E; Momenan, Reza; Grodin, Erica N; Litten, Raye Z; Koob, George F; Goldman, David

    2017-08-01

    Incentive salience, negative emotionality, and executive function are functional domains that are etiologic in the initiation and progression of addictive disorders, having been implicated in humans with addictive disorders and in animal models of addictions. Measures of these three neuroscience-based functional domains can capture much of the effects of inheritance and early exposures that lead to trait vulnerability shared across different addictive disorders. For specific addictive disorders, these measures can be supplemented by agent specific measures such as those that access pharmacodynamic and pharmacokinetic variation attributable to agent-specific gatekeeper molecules including receptors and drug-metabolizing enzymes. Herein, we focus on the translation and reverse translation of knowledge derived from animal models of addiction to the human condition via measures of neurobiological processes that are orthologous in animals and humans, and that are shared in addictions to different agents. Based on preclinical data and human studies, measures of these domains in a general framework of an Addictions Neuroclinical Assessment (ANA) can transform the assessment and nosology of addictive disorders, and can be informative for staging disease progression. We consider next steps and challenges for implementation of ANA in clinical care and research. This article is part of the Special Issue entitled "Alcoholism". Published by Elsevier Ltd.

  17. The economics of alcohol abuse and alcohol-control policies.

    PubMed

    Cook, Philip J; Moore, Michael J

    2002-01-01

    Economic research has contributed to the evaluation of alcohol policy through empirical analysis of the effects of alcohol-control measures on alcohol consumption and its consequences. It has also provided an accounting framework for defining and comparing costs and benefits of alcohol consumption and related policy interventions, including excise taxes. The most important finding from the economics literature is that consumers tend to drink less ethanol, and have fewer alcohol-related problems, when alcoholic beverage prices are increased or alcohol availability is restricted. That set of findings is relevant for policy purposes because alcohol abuse imposes large "external" costs on others. Important challenges remain, including developing a better understanding of the effects of drinking on labor-market productivity.

  18. Compensatory recruitment of neural resources in chronic alcoholism.

    PubMed

    Chanraud, Sandra; Sullivan, Edith V

    2014-01-01

    Functional recovery occurs with sustained sobriety, but the neural mechanisms enabling recovery are only now emerging. Theories about promising mechanisms involve concepts of neuroadaptation, where excessive alcohol consumption results in untoward structural and functional brain changes which are subsequently candidates for reversal with sobriety. Views on functional adaptation in chronic alcoholism have expanded with results from neuroimaging studies. Here, we first describe and define the concept of neuroadaptation according to emerging theories based on the growing literature in aging-related cognitive functioning. Then we describe findings as they apply to chronic alcoholism and factors that could influence compensation, such as functional brain reserve and the integrity of brain structure. Finally, we review brain plasticity based on physiologic mechanisms that could underlie mechanisms of neural compensation. Where possible, we provide operational criteria to define functional and neural compensation. © 2014 Elsevier B.V. All rights reserved.

  19. Inhibition of histone acetylation by curcumin reduces alcohol-induced fetal cardiac apoptosis.

    PubMed

    Yan, Xiaochen; Pan, Bo; Lv, Tiewei; Liu, Lingjuan; Zhu, Jing; Shen, Wen; Huang, Xupei; Tian, Jie

    2017-01-05

    Prenatal alcohol exposure may cause cardiac development defects, however, the underlying mechanisms are not yet clear. In the present study we have investigated the roles of histone modification by curcumin on alcohol induced fetal cardiac abnormalities during the development. Q-PCR and Western blot results showed that alcohol exposure increased gene and active forms of caspase-3 and caspase-8, while decreased gene and protein of bcl-2. ChIP assay results showed that, alcohol exposure increased the acetylation of histone H3K9 near the promoter region of caspase-3 and caspase-8, and decreased the acetylation of histone H3K9 near the promoter region of bcl-2. TUNEL assay data revealed that alcohol exposure increased the apoptosis levels in the embryonic hearts. In vitro experiments demonstrated that curcumin treatment could reverse the up-regulation of active forms of caspase-3 and caspase-8, and down-regulation of bcl-2 induced by alcohol treatment. In addition, curcumin also corrected the high level of histone H3K9 acetylation induced by alcohol. Moreover, the high apoptosis level induced by alcohol was reversed after curcumin treatment in cardiac cells. These findings indicate that histone modification may play an important role in mediating alcohol induced fetal cardiac apoptosis, possibly through the up-regulation of H3K9 acetylation near the promoter regions of apoptotic genes. Curcumin treatment may correct alcohol-mediated fetal cardiac apoptosis, suggesting that curcumin may play a protective role against alcohol abuse caused cardiac damage during pregnancy.

  20. Neuroplasticity in Human Alcoholism

    PubMed Central

    Fein, George; Cardenas, Valerie A.

    2015-01-01

    Alcoholism is characterized by a lack of control over excessive alcohol consumption despite significant negative consequences. This impulsive and compulsive behavior may be related to functional abnormalities within networks of brain regions responsible for how we make decisions. The abnormalities may result in strengthened networks related to appetitive drive—or the need to fulfill desires—and simultaneously weakened networks that exercise control over behaviors. Studies using functional magnetic resonance imaging (fMRI) in abstinent alcoholics suggest that abstinence is associated with changes in the tone of such networks, decreasing resting tone in appetitive drive networks, and increasing resting tone in inhibitory control networks to support continued abstinence. Identifying electroencephalographic (EEG) measures of resting tone in these networks initially identified using fMRI, and establishing in longitudinal studies that these abstinence-related changes in network tone are progressive would motivate treatment initiatives to facilitate these changes in network tone, thereby supporting successful ongoing abstinence. PMID:26259093

  1. Receptivity to alcohol marketing predicts initiation of alcohol use.

    PubMed

    Henriksen, Lisa; Feighery, Ellen C; Schleicher, Nina C; Fortmann, Stephen P

    2008-01-01

    This longitudinal study examined the influence of alcohol advertising and promotions on the initiation of alcohol use. A measure of receptivity to alcohol marketing was developed from research about tobacco marketing. Recall and recognition of alcohol brand names were also examined. Data were obtained from in-class surveys of sixth, seventh, and eighth graders at baseline and 12-month follow-up. Participants who were classified as never drinkers at baseline (n = 1,080) comprised the analysis sample. Logistic regression models examined the association of advertising receptivity at baseline with any alcohol use and current drinking at follow-up, adjusting for multiple risk factors, including peer alcohol use, school performance, risk taking, and demographics. At baseline, 29% of never drinkers either owned or wanted to use an alcohol branded promotional item (high receptivity), 12% students named the brand of their favorite alcohol ad (moderate receptivity), and 59% were not receptive to alcohol marketing. Approximately 29% of adolescents reported any alcohol use at follow-up; 13% reported drinking at least 1 or 2 days in the past month. Never drinkers who reported high receptivity to alcohol marketing at baseline were 77% more likely to initiate drinking by follow-up than those were not receptive. Smaller increases in the odds of alcohol use at follow-up were associated with better recall and recognition of alcohol brand names at baseline. Alcohol advertising and promotions are associated with the uptake of drinking. Prevention programs may reduce adolescents' receptivity to alcohol marketing by limiting their exposure to alcohol ads and promotions and by increasing their skepticism about the sponsors' marketing tactics.

  2. Receptivity to alcohol marketing predicts initiation of alcohol use

    PubMed Central

    Henriksen, Lisa; Feighery, Ellen C.; Schleicher, Nina C.; Fortmann, Stephen P.

    2008-01-01

    Purpose This longitudinal study examined the influence of alcohol advertising and promotions on the initiation of alcohol use. A measure of receptivity to alcohol marketing was developed from research about tobacco marketing. Recall and recognition of alcohol brand names were also examined. Methods Data were obtained from in-class surveys of 6th, 7th, and 8th graders at baseline and 12-month follow-up. Participants who were classified as never drinkers at baseline (n=1,080) comprised the analysis sample. Logistic regression models examined the association of advertising receptivity at baseline with any alcohol use and current drinking at follow-up, adjusting for multiple risk factors, including peer alcohol use, school performance, risk taking, and demographics. Results At baseline, 29% of never drinkers either owned or wanted to use an alcohol branded promotional item (high receptivity), 12% students named the brand of their favorite alcohol ad (moderate receptivity) and 59% were not receptive to alcohol marketing. Approximately 29% of adolescents reported any alcohol use at follow-up; 13% reported drinking at least 1 or 2 days in the past month. Never drinkers who reported high receptivity to alcohol marketing at baseline were 77% more likely to initiate drinking by follow-up than those were not receptive. Smaller increases in the odds of alcohol use at follow-up were associated with better recall and recognition of alcohol brand names at baseline. Conclusions Alcohol advertising and promotions are associated with the uptake of drinking. Prevention programs may reduce adolescents’ receptivity to alcohol marketing by limiting their exposure to alcohol ads and promotions and by increasing their skepticism about the sponsors’ marketing tactics. PMID:18155027

  3. Alcohol and risky behaviors.

    PubMed

    Corte, Colleen M; Sommers, Marilyn Sawyer

    2005-01-01

    The purpose of this chapter is to review and critique the literature on risky drinking, driving, and sexual behaviors. To complete this review, electronic searches using databases from the disciplines of nursing, medicine, and psychology were used with keywords alcohol and risky behavior, risky drinking, risky driving, risky sex, and sexual aggression, as well as other relevant terms. The basic tenets of contemporary theoretical models of risky behaviors are used as a framework for reviewing the literature. Most relevant to the discussion are the relationships among the behaviors, risk and protective factors, and major unresolved theoretical and methodological issues. In the literature, sensation seeking was differentially associated with risky drinking, driving, and sex, but causal assertions are premature. Important conceptual and physiological issues are clarified. First, unconventionality contributes to risky drinking, risky driving, and, among adolescents, risky sex. Second, the pharmacologic effects of alcohol on cognitive processing contribute to risky sex, but only among persons who feel conflicted about risky sex (e.g., condom use). This perception may be particularly true for men who have a belief that alcohol will enhance sex. Third, sexual aggression appears to stem from a variety of factors, including the pharmacologic effects of alcohol on aggression and stereotypes about drinking women. Exploration of risk and protective factors adds breadth and depth to the discussion of risk taking. Risk factors include (1) high tolerance for deviance, (2) unconventional attitudes and behaviors such as early alcohol use and precocious sex, (3) peer norms for deviance, (4) high sensation seeking, and, to a lesser extent, (5) disturbed risk perception and positive beliefs about alcohol. Protective factors appear to mitigate risk and include (1) conventional attitudes and behaviors and (2) having peers that model conventional attitudes and behaviors. Although

  4. ALCOHOL AND THE SOLDIER

    PubMed Central

    Saldanka, D.; Goel, D.S.

    1992-01-01

    One hundred and fifteen cases of alcohol dependence syndrome admitted during a two year period in a zonal referral hospital were studied. Vie majority of the subject were between the age of 30 to 50 years and had more than 10 year's history of alcohol abuse. 19.26% of the subjects had to be invalided out of service. 66.09% remained under various categories of observation after the treatment. At the end of two year′s follow-up only 12% of them had recovered completely. Preventive measures in the light of state policies are discussed. PMID:21776144

  5. Fermentative alcohol production

    DOEpatents

    Wilke, Charles R.; Maiorella, Brian L.; Blanch, Harvey W.; Cysewski, Gerald R.

    1982-01-01

    An improved fermentation process for producing alcohol which includes the combination of vacuum fermentation and vacuum distillation. Preferably, the vacuum distillation is carried out in two phases, one a fermentor proper operated at atmospheric pressure and a flash phase operated at reduced pressure with recycle of fermentation brew having a reduced alcohol content to the fermentor, using vapor recompression heating of the flash-pot recycle stream to heat the flash-pot or the distillation step, and using "water load balancing" (i.e., the molar ratio of water in the fermentor feed is the same as the molar ratio of water in the distillation overhead).

  6. Acute Alcoholic Hepatitis: Therapy.

    PubMed

    Phillips, Paulina K; Lucey, Michael R

    2016-08-01

    Alcoholic hepatitis (AH) causes great morbidity and mortality in the United States and throughout the world. Advances in therapy have proven difficult. In part, this reflects challenges in diagnosis, including the distinction between AH and acute-on-chronic liver failure. Liver biopsy is the best method to clarify the cause in circumstances whereby conflicting clinical data confound the diagnosis. All treatment of AH begins with abstinence from alcohol. All patients with AH should be given sufficient nutrition. Prednisolone has become the principal agent for treating patients with severe AH. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Vasectomy reversal: a clinical update

    PubMed Central

    Patel, Abhishek P; Smith, Ryan P

    2016-01-01

    Vasectomy is a safe and effective method of contraception used by 42–60 million men worldwide. Approximately 3%–6% of men opt for a vasectomy reversal due to the death of a child or divorce and remarriage, change in financial situation, desire for more children within the same marriage, or to alleviate the dreaded postvasectomy pain syndrome. Unlike vasectomy, vasectomy reversal is a much more technically challenging procedure that is performed only by a minority of urologists and places a larger financial strain on the patient since it is usually not covered by insurance. Interest in this procedure has increased since the operating microscope became available in the 1970s, which consequently led to improved patency and pregnancy rates following the procedure. In this clinical update, we discuss patient evaluation, variables that may influence reversal success rates, factors to consider in choosing to perform vasovasostomy versus vasoepididymostomy, and the usefulness of vasectomy reversal to alleviate postvasectomy pain syndrome. We also review the use of robotics for vasectomy reversal and other novel techniques and instrumentation that have emerged in recent years to aid in the success of this surgery. PMID:26975488

  8. Information on Blood Alcohol Concentration: Evaluation of Two Alcohol Nomograms.

    ERIC Educational Resources Information Center

    Werch, Chudley E.

    1988-01-01

    Compared utility of two common alcohol nomograms on impacting decisions regarding drinking, driving after drinking, knowledge of relationship between personal alcohol consumption and the legal level of intoxication, and consumer evaluation measures, to utility of alcohol information warning card. Nomograms were no more effective than cards warning…

  9. Fetal Alcohol Syndrome and Fetal Alcohol Effects in Child Development.

    ERIC Educational Resources Information Center

    Pancratz, Diane R.

    This literature review defines Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) and considers their causes, diagnoses, prevalence, and educational ramifications. Effects of alcohol during each of the trimesters of pregnancy are summarized. Specific diagnostic characteristics of FAS are listed: (1) growth deficiency, (2) a…

  10. Smoking Cessation in Recovering Alcoholics

    MedlinePlus

    ... from alcohol abuse may be more addicted to nicotine. As a result, they often smoke more cigarettes. ... alcoholism treatment. You may be more addicted to nicotine than other smokers, but very few people succeed ...

  11. Alcohol and Memory: Retrieval Processes

    ERIC Educational Resources Information Center

    Birnbaum, Isabel M.; And Others

    1978-01-01

    The influence of alcohol intoxication on the retrieval of information from memory was investigated in nonalcoholic subjects Intoxicated subjects recalled fewer categories and words within categories. The retrieval stage of memory did not appear to be affected by alcohol. (SW)

  12. The Origin of Alcohol Proof

    ERIC Educational Resources Information Center

    Jensen, William B.

    2004-01-01

    The origin of the "proof" system for measuring the ethanol content of alcoholic beverages is presented. The proof system was originally established for purposes of taxing liquors according to their alcohol content and is different in different countries.

  13. Effectiveness of passive alcohol sensors

    DOT National Transportation Integrated Search

    1996-03-01

    Author's abstract: The purpose of this study was to evaluate the effectiveness of passive alcohol sensors for youth alcohol enforcement conducted as part of normal or typical police operations. Three municipal police departments of 100 or more sworn ...

  14. Production of hydrogen from alcohols

    DOEpatents

    Deluga, Gregg A [St. Paul, MN; Schmidt, Lanny D [Minneapolis, MN

    2007-08-14

    A process for producing hydrogen from ethanol or other alcohols. The alcohol, optionally in combination with water, is contacted with a catalyst comprising rhodium. The overall process is preferably carried out under autothermal conditions.

  15. Kids and Alcohol (For Parents)

    MedlinePlus

    ... should know the facts about alcohol and your attitudes and beliefs about substance abuse. So use this ... odor of alcohol sudden change in mood or attitude change in attendance or performance at school loss ...

  16. Reverse innovation in maternal health.

    PubMed

    Firoz, Tabassum; Makanga, Prestige Tatenda; Nathan, Hannah L; Payne, Beth; Magee, Laura A

    2017-09-01

    Reverse innovation, defined as the flow of ideas from low- to high-income settings, is gaining traction in healthcare. With an increasing focus on value, investing in low-cost but effective and innovative solutions can be of mutual benefit to both high- and low-income countries. Reverse innovation has a role in addressing maternal health challenges in high-income countries by harnessing these innovative solutions for vulnerable populations especially in rural and remote regions. In this paper, we present three examples of 'reverse innovation' for maternal health: a low-cost, easy-to-use blood pressure device (CRADLE), a diagnostic algorithm (mini PIERS) and accompanying mobile app (PIERS on the Move), and a novel method for mapping maternal outcomes (MOM).

  17. Reverse Transfection Using Gold Nanoparticles

    NASA Astrophysics Data System (ADS)

    Yamada, Shigeru; Fujita, Satoshi; Uchimura, Eiichiro; Miyake, Masato; Miyake, Jun

    Reverse transfection from a solid surface has the potential to deliver genes into various types of cell and tissue more effectively than conventional methods of transfection. We present a method for reverse transfection using a gold colloid (GC) as a nanoscaffold by generating nanoclusters of the DNA/reagentcomplex on a glass surface, which could then be used for the regulation of the particle size of the complex and delivery of DNA into nuclei. With this method, we have found that the conjugation of gold nanoparticles (20 nm in particle size) to the pEGFP-N1/Jet-PEI complex resulted in an increase in the intensity of fluorescence of enhanced green fluorescent protein (EGFP) (based on the efficiency of transfection) from human mesenchymal stem cells (hMSCs), as compared with the control without GC. In this manner, we constructed a method for reverse transfection using GC to deliver genes into the cells effectively.

  18. Reverse current in solar flares

    NASA Technical Reports Server (NTRS)

    Knight, J. W.; Sturrock, P. A.

    1977-01-01

    We examine the proposal that impulsive X-ray bursts are produced by high-energy electrons streaming from the corona to the chromosphere. It is known that the currents associated with these streams are so high that either the streams do not exist or their current is neutralized by a reverse current. Analysis of a simple model in which the reverse current is stable indicates that the primary electron stream leads to the development of an electric field in the ambient corona which (a) decelerates the primary beam and (b) produces a neutralizing reverse current. It appears that, in some circumstances, this electric field could prevent the primary beam from reaching the chromosphere. In any case, the electric field acts as an energy exchange mechanism, extracting kinetic energy from the primary beam and using it to heat the ambient plasma. This heating is typically so rapid that it must be expected to have important dynamical consequences.

  19. Ice ages and geomagnetic reversals

    NASA Technical Reports Server (NTRS)

    Wu, Patrick

    1992-01-01

    There have been speculations on the relationship between climatic cooling and polarity reversals of the earth's magnetic field during the Pleistocene. Two of the common criticisms on this relationship have been the reality of these short duration geomagnetic events and the accuracy of their dates. Champion et al. (1988) have reviewed recent progress in this area. They identified a total of 10 short-duration polarity events in the last 1 Ma and 6 of these events have been found in volcanic rocks, which also have K-Ar dates. Supposing that the speculated relationship between climatic cooling and geomagnetic reversals actually exist, two mechanisms that assume climatic cooling causes short period magnetic reversals will be investigated. These two methods are core-mantle boundary topography and transfer of the rotational energy to the core.

  20. The posterior reversible encephalopathy syndrome.

    PubMed

    Sanjay, K Mandal; Partha, P Chakraborty

    2008-09-01

    The posterior/potentially reversible encephalopathy syndrome is a unique syndrome encountered commonly in hypertensive encephalopathy. A 13-year-old boy presented with of intermittent high grade fever, throbbing headache and non-projective vomiting for 5 days. The patient had a blood pressure of 120/80 mmHg but fundoscopy documented grade 3 hypertensive retinopathy. The patient improved symptomatically following conservative management. However, on the 5(th) post-admission day headache reappeared, and blood pressure measured at that time was 240/120 mmHg. Neuroimaging suggested white matter abnormalities. Search for the etiology of secondary hypertension led to the diagnosis of pheochromocytoma. Repeated MRI after successful surgical excision of the tumor patient showed reversal of white matter abnormalities. Reversible leucoencephalopathy due to pheochromocytoma have not been documented in literature previously.

  1. The Discovery of Reverse Transcriptase.

    PubMed

    Coffin, John M; Fan, Hung

    2016-09-29

    In 1970 the independent and simultaneous discovery of reverse transcriptase in retroviruses (then RNA tumor viruses) by David Baltimore and Howard Temin revolutionized molecular biology and laid the foundations for retrovirology and cancer biology. In this historical review we describe the formulation of the controversial provirus hypothesis by Temin, which ultimately was proven by his discovery of reverse transcriptase in Rous sarcoma virus virions. Baltimore arrived at the same discovery through his studies on replication of RNA-containing viruses, starting with poliovirus and then moving to vesicular stomatitis virus, where he discovered a virion RNA polymerase. Subsequent studies of reverse transcriptase led to the elucidation of the mechanism of retrovirus replication, the discovery of oncogenes, the advent of molecular cloning, the search for human cancer viruses, and the discovery and treatment of HIV/AIDS.

  2. [Alcohol intoxication in old age].

    PubMed

    Menecier, Pascal; Rotheval, Loetita

    Acute alcohol intoxication occurs in elderly subjects. Drunkenness appears in banal clinical forms in geriatrics: falls, dizziness or confusion. Elderly people are more vulnerable to alcohol and need less alcohol to become intoxicated. Age does not exclude the possibility of receiving alcohol addiction treatment. Broaching the subject with an elderly person, the day after a drunken episode, is useful and recommended. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    PubMed Central

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  4. Time-reversed, flow-reversed ballistics simulations

    SciTech Connect

    Zernow, L.; Chapyak, E. J.; Scheffler, D. R.

    2001-01-01

    Two-dimensional simulations of planar sheet jet formation are studied to examine the hydrodynamic issues involved when simulations are carried out in the inverse direction, that is, with reversed time and flow. Both a realistic copper equation of state and a shockless equation of state were used. These studies are an initial step in evaluating this technique as a ballistics design tool.

  5. Stagnation point reverse flow combustor

    NASA Technical Reports Server (NTRS)

    Zinn, Ben T. (Inventor); Neumeier, Yedidia (Inventor); Seitzman, Jerry M. (Inventor); Jagoda, Jechiel (Inventor); Weksler, Yoav (Inventor)

    2008-01-01

    A method for combusting a combustible fuel includes providing a vessel having an opening near a proximate end and a closed distal end defining a combustion chamber. A combustible reactants mixture is presented into the combustion chamber. The combustible reactants mixture is ignited creating a flame and combustion products. The closed end of the combustion chamber is utilized for directing combustion products toward the opening of the combustion chamber creating a reverse flow of combustion products within the combustion chamber. The reverse flow of combustion products is intermixed with combustible reactants mixture to maintain the flame.

  6. Marburg Virus Reverse Genetics Systems

    PubMed Central

    Schmidt, Kristina Maria; Mühlberger, Elke

    2016-01-01

    The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems. PMID:27338448

  7. Marburg Virus Reverse Genetics Systems.

    PubMed

    Schmidt, Kristina Maria; Mühlberger, Elke

    2016-06-22

    The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems.

  8. Alcoholism: Development, Consequences, and Interventions.

    ERIC Educational Resources Information Center

    Estes, Nada J.; Heinemann, M. Edith

    This book is intended to contribute to the theoretical knowledge of alcoholism workers so that the needs of people with alcohol related problems may be met with greater understanding. Contributors to the book represent a variety of disciplines and address a broad spectrum of topics. Part One deals with developmental perspectives of alcoholism,…

  9. Photobiomodulation on alcohol induced dysfunction

    NASA Astrophysics Data System (ADS)

    Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

    2007-05-01

    Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

  10. Measuring Alcohol Expectancies in Youth

    ERIC Educational Resources Information Center

    Randolph, Karen A.; Gerend, Mary A.; Miller, Brenda A.

    2006-01-01

    Beliefs about the consequences of using alcohol, alcohol expectancies, are powerful predictors of underage drinking. The Alcohol Expectancies Questionnaire-Adolescent form (AEQ-A) has been widely used to measure expectancies in youth. Despite its broad use, the factor structure of the AEQ-A has not been firmly established. It is also not known…

  11. Geriatric Alcoholism and Drug Abuse

    ERIC Educational Resources Information Center

    Schuckit, Marc A.

    1977-01-01

    This paper reviews the literature and presents new data on alcohol and drug problems in older individuals. Drug abusers include users of opiates, inadvertent misusers, and deliberate abusers of nonopiates. Two to 10 percent of the elderly are alcoholic, and these are usually individuals beginning alcohol abuse after age 40. (Author)

  12. Exposure to televised alcohol ads and subsequent adolescent alcohol use.

    PubMed

    Stacy, Alan W; Zogg, Jennifer B; Unger, Jennifer B; Dent, Clyde W

    2004-01-01

    To assess the impact of televised alcohol commercials on adolescents' alcohol use. Adolescents completed questionnaires about alcohol commercials and alcohol use in a prospective study. A one standard deviation increase in viewing television programs containing alcohol commercials in seventh grade was associated with an excess risk of beer use (44%), wine/liquor use (34%), and 3-drink episodes (26%) in eighth grade. The strength of associations varied across exposure measures and was most consistent for beer. Although replication is warranted, results showed that exposure was associated with an increased risk of subsequent beer consumption and possibly other consumption variables.

  13. Alcohol and Traffic Safety.

    ERIC Educational Resources Information Center

    Dickman, Frances Baker, Ed.

    1988-01-01

    Seven papers discuss current issues and applied social research concerning alcohol traffic safety. Prevention, policy input, methodology, planning strategies, anti-drinking/driving programs, social-programmatic orientations of Mothers Against Drunk Driving, Kansas Driving Under the Influence Law, New Jersey Driving While Impaired Programs,…

  14. Alcohol - Multiple Languages

    MedlinePlus

    ... and Driving Laws - العربية (Arabic) PDF Karen Chemical Dependency Taskforce of Minnesota How Beer and Alcohol Affect ... Affect the Body - العربية (Arabic) PDF Karen Chemical Dependency Taskforce of Minnesota Burmese (myanma bhasa) Expand Section ...

  15. Benzyl Alcohol Topical

    MedlinePlus

    ... lice. Benzyl alcohol lotion will not kill lice eggs, so the medication must be used a second ... kill the lice that may hatch from these eggs. ... to remove the dead lice and nits (empty egg shells) after this treatment. You may also need ...

  16. Alcohol, drugs, and driving

    DOT National Transportation Integrated Search

    1974-03-01

    An invitational symposium was held October 13-15, 1972, at a remote Vermont inn and was attended by 35 research and/or administrative specialists in alcohol, drugs and/or highway safety. The basic purpose was publication of the proceedings to incorpo...

  17. Inpatient alcohol withdrawal syndrome.

    PubMed

    Monte-Secades, R; Rabuñal-Rey, R; Guerrero-Sande, H

    2015-03-01

    A 55-year-old man was admitted for a femur fracture; an alcohol fetor was noted on admission. The following day, the patient began to experience tremors and nervousness. Intravenous haloperidol was administered. Shortly afterwards, the patient experienced two generalized seizures and then began to experience delirium and uncontrollable agitation. The patient was diagnosed with alcohol withdrawal syndrome; high doses of intravenous midazolam were prescribed and infused. A few hours later, the patient presented signs of respiratory depression, requiring a transfer to the intensive care unit. After a review of the medical history, it was determined that the patient had been admitted on 3 previous occasions due to alcohol withdrawal and had progressed to delirium tremens after experiencing seizures. Can the risk of alcohol withdrawal syndrome and the need for prophylactic treatment be assessed on admission? Were appropriate monitoring and treatment measures employed? Would it have been possible to change his outcome? Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  18. Weight loss and alcohol

    MedlinePlus

    ... of wine 1.5 ounces (45 mL, or one shot) of hard liquor The sizes of alcoholic drinks at a restaurant or bar are often larger than the standard amounts listed above. In some cases, 1 drink may actually have 2 or more servings ...

  19. NATIONAL ALCOHOL SURVEY (NAS)

    EPA Science Inventory

    National Alcohol Survey (NAS) is designed to assess the trends in drinking practices and problems in the national population, including attitudes, norms, treatment and experiences and adverse consequences. It also studies the effects of public policy on drinking practices (i.e., ...

  20. Drugs, Alcohol & Pregnancy.

    ERIC Educational Resources Information Center

    Dye, Christina

    Expectant parents are introduced to the effects of a variety of drugs on the unborn baby. Material is divided into seven sections. Section 1 deals with the most frequently used recreational drugs, including alcohol, marijuana, narcotics, depressants, stimulants, inhalants, and hallucinogens. Sections 2 and 3 focus on the effects of prescription…

  1. Nickel-hydrogen cell reversal characteristics

    NASA Technical Reports Server (NTRS)

    Lurie, Charles

    1994-01-01

    Nickel-hydrogen cell reversal characteristics are being studied as part of a TRW program directed towards development of a high current battery cell bypass switch. The following are discussed: cell bypass switch; nickel-hydrogen cell reversal characteristics; and nickel-hydrogen cell chemistry: discharge/reversal and overdischarge (reversal) with nickel and hydrogen precharge.

  2. 27 CFR 7.71 - Alcoholic content.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Alcoholic content. 7.71 Section 7.71 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF MALT BEVERAGES Interim Regulations for Alcoholic Content Statements § 7.71 Alcoholic content. ...

  3. 27 CFR 5.37 - Alcohol content.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Alcohol content. 5.37 Section 5.37 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF DISTILLED SPIRITS Labeling Requirements for Distilled Spirits § 5.37 Alcohol content. (a)...

  4. 27 CFR 4.36 - Alcoholic content.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Alcoholic content. 4.36 Section 4.36 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Labeling Requirements for Wine § 4.36 Alcoholic content. (a) Alcoholic content shall be...

  5. 27 CFR 5.37 - Alcohol content.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Alcohol content. 5.37 Section 5.37 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF DISTILLED SPIRITS Labeling Requirements for Distilled Spirits § 5.37 Alcohol content. (a)...

  6. 27 CFR 4.36 - Alcoholic content.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Alcoholic content. 4.36 Section 4.36 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Labeling Requirements for Wine § 4.36 Alcoholic content. (a) Alcoholic content shall be...

  7. 27 CFR 7.71 - Alcoholic content.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Alcoholic content. 7.71 Section 7.71 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF MALT BEVERAGES Interim Regulations for Alcoholic Content Statements § 7.71 Alcoholic content. ...

  8. 27 CFR 4.36 - Alcoholic content.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Alcoholic content. 4.36 Section 4.36 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Labeling Requirements for Wine § 4.36 Alcoholic content. (a) Alcoholic content shall be...

  9. 27 CFR 7.71 - Alcoholic content.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Alcoholic content. 7.71 Section 7.71 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF MALT BEVERAGES Interim Regulations for Alcoholic Content Statements § 7.71 Alcoholic content. ...

  10. 27 CFR 19.366 - Alcohol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Alcohol. 19.366 Section 19.366 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE..., and Removal of Products § 19.366 Alcohol. (a) Containers. A proprietor may put alcohol for industrial...

  11. Protective role of taurine in developing offspring affected by maternal alcohol consumption

    PubMed Central

    Ananchaipatana-Auitragoon, Pilant; Ananchaipatana-Auitragoon, Yutthana; Siripornpanich, Vorasith; Kotchabhakdi, Naiphinich

    2015-01-01

    Maternal alcohol consumption is known to affect offspring growth and development, including growth deficits, physical anomalies, impaired brain functions and behavioral disturbances. Taurine, a sulfur-containing amino acid, is essential during development, and continually found to be protective against neurotoxicity and various tissue damages including those from alcohol exposure. However, it is still unknown whether taurine can exert its protection during development of central nervous system and whether it can reverse alcohol damages on developed brain later in life. This study aims to investigate protective roles of taurine against maternal alcohol consumption on growth and development of offspring. The experimental protocol was conducted using ICR-outbred pregnant mice given 10 % alcohol, with or without maternal taurine supplementation during gestation and lactation. Pregnancy outcomes, offspring mortality and successive bodyweight until adult were monitored. Adult offspring is supplemented taurine to verify its ability to reverse damages on learning and memory through a water maze task performance. Our results demonstrate that offspring of maternal alcohol exposure, together with maternal taurine supplementation show conserved learning and memory, while that of offspring treated taurine later in life are disturbed. Taurine provides neuroprotective effects and preserves learning and memory processes when given together with maternal alcohol consumption, but not shown such effects when given exclusively in offspring. PMID:26648819

  12. [Gender differences in alcoholism].

    PubMed

    Avila Escribano, José Juan; González Parra, David

    2007-01-01

    Recent epidemiological studies indicate that alcohol consumption in women has increased in the last few years, which suggests that alcoholism in women will also increase in the near future. Moreover, this disease shows differential characteristics in women, and knowledge of these characteristics is important so that treatment can begin as early as possible. The objective of the present study was to explore clinical differences in alcohol use disorders according to patients' gender. It was carried out with a sample of 370 patients, 325 men (87.8%) and 45 women (12.2%), with mean ages of 42.83 and 44.6 years, respectively. The patients were assessed through the Europasi interview and analytical studies with liver enzyme profiles and blood tests. The most notable results were: women began alcohol consumption significantly later than men (19.61 and 16.9 years, respectively; p < 0.008); they were significantly older than men when the consumption pattern became problematic (30.93 and 24.68 years, respectively; p < 0.003); they had been drinking for fewer years (13.26 versus 17.85 years; p < 0.02); and they drank fewer grams of alcohol (117.7 and 133.8 g., respectively; n.s.). Women scored significantly higher than men on the Europasi psychiatric scale (2.91 and 1.97, respectively; p < 0.007) and men had more legal problems than women (1.2 and 1.0, respectively; p < 0.000). In the biological tests the GGT enzyme values were higher in men (137.51) than in women (96.7), but this difference was not significant, and the VCM value was significantly higher for women (98.1) than for men (95.05). Another important finding was that the percentage of women who had sought private professional help was higher than that of men (15% versus 4.6%; p < 0.01).

  13. Postdependent state in rats as a model for medication development in alcoholism.

    PubMed

    Meinhardt, Marcus W; Sommer, Wolfgang H

    2015-01-01

    Rational development of novel therapeutic strategies for alcoholism requires understanding of its underlying neurobiology and pathophysiology. Obtaining this knowledge largely relies on animal studies. Thus, choosing the appropriate animal model is one of the most critical steps in pre-clinical medication development. Among the range of animal models that have been used to investigate excessive alcohol consumption in rodents, the postdependent model stands out. It was specifically developed to test the role of negative affect as a key driving force in a perpetuating addiction cycle for alcoholism. Here, we will describe our approach to make rats dependent via chronic intermittent exposure to alcohol, discuss the validity of this model, and compare it with other commonly used animal models of alcoholism. We will summarize evidence that postdependent rats fulfill several criteria of a 'Diagnostic and Statistical Manual of Mental Disorders IV/V-like' diagnostic system. Importantly, these animals show long-lasting excessive consumption of and increased motivation for alcohol, and evidence for loss of control over alcohol intake. Our conclusion that postdependent rats are an excellent model for medication development for alcoholism is underscored by a summary of more than two dozen pharmacological tests aimed at reversing these abnormal alcohol responses. We will end with open questions on the use of this model. In the tradition of the Sanchis-Segura and Spanagel review, we provide comic strips that illustrate the postdependent procedure and relevant phenotypes in this review. © 2014 Society for the Study of Addiction.

  14. Reversible thermosalience of 4-aminobenzonitrile.

    PubMed

    Alimi, Lukman O; van Heerden, Dewald P; Lama, Prem; Smith, Vincent J; Barbour, Leonard J

    2018-05-31

    Crystals of 4-aminobenzonitrile grown by sublimation undergo reversible thermosalient phase changes during cooling and subsequent heating. Single-crystal diffraction studies have been carried out at 20 K intervals during cooling from 300 to 100 K in order to explain the structural change that occurs.

  15. Reversible colour change in Arthropoda.

    PubMed

    Umbers, Kate D L; Fabricant, Scott A; Gawryszewski, Felipe M; Seago, Ainsley E; Herberstein, Marie E

    2014-11-01

    The mechanisms and functions of reversible colour change in arthropods are highly diverse despite, or perhaps due to, the presence of an exoskeleton. Physiological colour changes, which have been recorded in 90 arthropod species, are rapid and are the result of changes in the positioning of microstructures or pigments, or in the refractive index of layers in the integument. By contrast, morphological colour changes, documented in 31 species, involve the anabolism or catabolism of components (e.g. pigments) directly related to the observable colour. In this review we highlight the diversity of mechanisms by which reversible colour change occurs and the evolutionary context and diversity of arthropod taxa in which it has been observed. Further, we discuss the functions of reversible colour change so far proposed, review the limited behavioural and ecological data, and argue that the field requires phylogenetically controlled approaches to understanding the evolution of reversible colour change. Finally, we encourage biologists to explore new model systems for colour change and to engage scientists from other disciplines; continued cross-disciplinary collaboration is the most promising approach to this nexus of biology, physics, and chemistry. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

  16. CAPSULE REPORT: REVERSE OSMOSIS PROCESS

    EPA Science Inventory

    A failure analysis has been completed for the reverse osmosis (RO) process. The focus was on process failures that result in releases of liquids and vapors to the environment. The report includes the following: 1) A description of RO and coverage of the principles behind the proc...

  17. 76 FR 17140 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-28

    ... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Special Emphasis Panel; RFA-AA-11-02 Alcohol Induced Metabolic and Hepatic...: Philippe Marmillot, PhD, Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism...

  18. Epigenetic Events in Liver Cancer Resulting From Alcoholic Liver Disease

    PubMed Central

    French, Samuel W.

    2013-01-01

    Epigenetic mechanisms play an extensive role in the development of liver cancer (i.e., hepatocellular carcinoma [HCC]) associated with alcoholic liver disease (ALD) as well as in liver disease associated with other conditions. For example, epigenetic mechanisms, such as changes in the methylation and/or acetylation pattern of certain DNA regions or of the histone proteins around which the DNA is wrapped, contribute to the reversion of normal liver cells into progenitor and stem cells that can develop into HCC. Chronic exposure to beverage alcohol (i.e., ethanol) can induce all of these epigenetic changes. Thus, ethanol metabolism results in the formation of compounds that can cause changes in DNA methylation and interfere with other components of the normal processes regulating DNA methylation. Alcohol exposure also can alter histone acetylation/deacetylation and methylation patterns through a variety of mechanisms and signaling pathways. Alcohol also acts indirectly on another molecule called toll-like receptor 4 (TLR4) that is a key component in a crucial regulatory pathway in the cells and whose dysregulation is involved in the development of HCC. Finally, alcohol use regulates an epigenetic mechanism involving small molecules called miRNAs that control transcriptional events and the expression of genes important to ALD. PMID:24313165

  19. Focus On: Epigenetics and Fetal Alcohol Spectrum Disorders

    PubMed Central

    Kobor, Michael S.; Weinberg, Joanne

    2011-01-01

    Epigenetic changes—stable but potentially reversible alterations in a cell’s genetic information that result in changes in gene expression but do not involve changes in the underlying DNA sequence—may mediate some of the detrimental effects of prenatal alcohol exposure and contribute to the deficits and abnormalities associated with fetal alcohol spectrum disorders. These epigenetic processes are linked to the chromatin (i.e., DNA, histone proteins, and other associated proteins) and commonly involve chemical modifications (e.g., methylation) of these molecules, which may result in altered expression of the affected genes. Even alcohol exposure prior to conception appears to be able to induce epigenetic changes in the parental genetic material that can be passed on to the offspring and affect offspring outcome. Similarly, epigenetic processes may occur as a result of maternal alcohol consumption during the period between fertilization of the egg and implantation in the uterus. The period most sensitive to alcohol’s adverse effects appears to be gastrulation, which corresponds to prenatal weeks 3 to 8 in the human and prenatal days 7 to 14 in the mouse, when cells are differentiating to form organs. One way in which alcohol exposure may induce epigenetic changes, particularly abnormal DNA methylation, is by affecting a set of biochemical reactions called the methionine–homocysteine cycle. PMID:23580038

  20. On the automaticity of response inhibition in individuals with alcoholism.

    PubMed

    Noël, Xavier; Brevers, Damien; Hanak, Catherine; Kornreich, Charles; Verbanck, Paul; Verbruggen, Frederick

    2016-06-01

    Response inhibition is usually considered a hallmark of executive control. However, recent work indicates that stop performance can become associatively mediated ('automatic') over practice. This study investigated automatic response inhibition in sober and recently detoxified individuals with alcoholism.. We administered to forty recently detoxified alcoholics and forty healthy participants a modified stop-signal task that consisted of a training phase in which a subset of the stimuli was consistently associated with stopping or going, and a test phase in which this mapping was reversed. In the training phase, stop performance improved for the consistent stop stimuli, compared with control stimuli that were not associated with going or stopping. In the test phase, go performance tended to be impaired for old stop stimuli. Combined, these findings support the automatic inhibition hypothesis. Importantly, performance was similar in both groups, which indicates that automatic inhibitory control develops normally in individuals with alcoholism.. This finding is specific to individuals with alcoholism without other psychiatric disorders, which is rather atypical and prevents generalization. Personalized stimuli with a stronger affective content should be used in future studies. These results advance our understanding of behavioral inhibition in individuals with alcoholism. Furthermore, intact automatic inhibitory control may be an important element of successful cognitive remediation of addictive behaviors.. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Reverse amblyopia with atropine treatment.

    PubMed

    Hainline, Bryan C; Sprunger, Derek C; Plager, David A; Neely, Daniel E; Guess, Matthew G

    2009-01-01

    Occlusion, pharmacologic pernalization and combined therapy have been documented in controlled studies to effectively treat amblyopia with few complications. However, there remain concerns about the effectiveness and complications when, as in this case, there are not standardized treatment protocols. A retrospective chart review of 133 consecutive patients in one community based ophthalmology practice treated for amblyopia was performed. Treatments evaluated were occlusion only, atropine penalization, and combination of occlusion and atropine. Reverse amblyopia was defined as having occured when the visual acuity of the sound eye was 3 LogMar units worse than visual acuity of the amblyopia eye after treatment. Improvement in vision after 6 months and 1 year of amblyopia therapy was similar among all three groups: 0.26 LogMar lines and 0.30 in the atropine group, 0.32 and 0.34 in the occlusion group, and 0.24 and 0.32 in the combined group. Eight (6%) patients demonstrated reverse amblyopia. The mean age of those who developed reverse amblyopia was 3.5 years, 1.5 years younger than the mean age of the study population, 7/8 had strabismic amblyopia, 6/8 were on daily atropine and had a mean refractive error of +4.77 diopters in the amblyopic eye and +5.06 diopters in the sound eye. Reverse amblyopia did not occur with occlusion only therapy. In this community based ophthalmology practice, atropine, patching, and combination therapy appear to be equally effective modalities to treat ambyopia. Highly hyperopic patients under 4 years of age with dense, strabismic amblyopia and on daily atropine appeared to be most at risk for development of reverse amblyopia.

  2. Exon microarray analysis of human dorsolateral prefrontal cortex in alcoholism.

    PubMed

    Manzardo, Ann M; Gunewardena, Sumedha; Wang, Kun; Butler, Merlin G

    2014-06-01

    Alcohol abuse is associated with cellular and biochemical disturbances that impact upon protein and nucleic acid synthesis, brain development, function, and behavioral responses. To further characterize the genetic influences in alcoholism and the effects of alcohol consumption on gene expression, we used a highly sensitive exon microarray to examine mRNA expression in human frontal cortex of alcoholics and control males. Messenger RNA was isolated from the dorsolateral prefrontal cortex (dlPFC; Brodmann area 9) of 7 adult alcoholic (6 males, 1 female, mean age 49 years) and 7 matched controls. Affymetrix Human Exon 1.0 ST array was performed according to standard procedures and the results analyzed at the gene level. Microarray findings were validated using quantitative reverse transcription polymerase chain reaction, and the ontology of disturbed genes characterized using Ingenuity Pathway Analysis (IPA). Decreased mRNA expression was observed for genes involved in cellular adhesion (e.g., CTNNA3, ITGA2), transport (e.g., TF, ABCA8), nervous system development (e.g., LRP2, UGT8, GLDN), and signaling (e.g., RASGRP3, LGR5) with influence over lipid and myelin synthesis (e.g., ASPA, ENPP2, KLK6). IPA identified disturbances in network functions associated with neurological disease and development including cellular assembly and organization impacting on psychological disorders. Our data in alcoholism support a reduction in expression of dlPFC mRNA for genes involved with neuronal growth, differentiation, and signaling that targets white matter of the brain. Copyright © 2014 by the Research Society on Alcoholism.

  3. Alcohol use in films and adolescent alcohol use.

    PubMed

    Waylen, Andrea; Leary, Sam; Ness, Andrew; Sargent, James

    2015-05-01

    To investigate whether exposure to alcohol use in films (AUFs) is associated with early alcohol use, binge drinking, and alcohol-related problems in British adolescents. Cross-sectional study with 5163 15-year-olds from the Avon Longitudinal Study of Parents and Children in the United Kingdom. We measured adolescent exposure to AUFs, age at onset of alcohol use, and binge-drinking behavior. We adjusted for early childhood social, family and behavioral factors, adolescent tobacco use, and peer drinking. After adjustment, adolescents with the highest exposure to AUFs were 1.2 (95% confidence interval [CI]: 1.1-1.3) times more likely to have tried alcohol compared with those least exposed and 1.7 (95% CI: 1.5-2.0) times more likely to binge drink. They were 2.4 (95% CI: 1.9-3.1) times more likely to drink weekly and 2.0 (95% CI: 1.7-2.4) times more likely to have alcohol-related problems than those least exposed. Exposure to AUFs is associated with higher risk of alcohol use and alcohol-related problems in UK adolescents. Our findings provide evidence to support the argument that a review of film-rating categories and alcohol ratings for all films may help reduce problem-related alcohol consumption in young people. Copyright © 2015 by the American Academy of Pediatrics.

  4. [Alcohol and alcoholism among Brazilian adolescent public-school students].

    PubMed

    de Souza, Delma P Oliveira; Areco, Kelsy N; da Silveira Filho, Dartiu Xavier

    2005-08-01

    To estimate the prevalence of alcohol consumption and alcoholism among working and non-working adolescents. Cross-sectional study with a systematic, stratified sample 993 working adolescents and 1,725 non-working adolescents. The study included students enrolled in 1998 in the state public network schools of a city in Center-Western Brazil. An anonymous, self-administered questionnaire was completed by subjects in the classroom. Univariate and bivariate analyses and logistic regression were used. We found prevalences of 71.3% for alcohol consumption and 13.4% for alcoholism in the total sample, and higher prevalences among working students (81.0% and 14.9%) than among non-workers (65.8% and 12.6%). In addition to the association between alcohol use and work, we found both differences and similarities between the two groups. Alcoholism is not associated with work but is associated with male sex (OR=1.61; 95% CI: 1.18-2.19) and family history of alcohol use among both non-workers (OR=2.19; 95% CI: 1.60-2.99) and workers (OR=2.10; 95% CI: 1.42-3.12). The results of the present study indicate a high prevalence of alcohol consumption and alcoholism, which is higher among working adolescents. Sociodemographic, family, and work-related factors must be considered when attempting to implement educational measures aimed at changing alcohol-related behaviors in this population.

  5. Exposure to alcohol advertising and alcohol consumption among Australian adolescents.

    PubMed

    Jones, Sandra C; Magee, Christopher A

    2011-01-01

    Underage drinking is a major problem in Australia and may be influenced by exposure to alcohol advertising. The objective of the present study was to collect data on 12-17 year old Australian adolescents' exposure to different types of alcohol advertising and examine the association between exposure to advertising and alcohol consumption. A cross-sectional survey of 1113 adolescents aged 12-17 years recruited with a variety of methods to gain a cross-section of participants across metropolitan, regional and rural New South Wales (including independent schools, mall intercepts and online). Participants answered a series of questions assessing adolescents' exposure to alcohol advertising across eight media (including television, Internet and point-of-sale). Alcohol consumption was assessed using three questions (initiation, recent consumption and frequency of consumption in the previous 12 months). The majority indicated that they had been exposed to alcohol advertisements on television, in newspapers and magazines, on the Internet, on billboards/posters and promotional materials and in bottleshops, bars and pubs; exposure to some of these types of alcohol advertisements was associated with increased alcohol consumption, with differences by age and gender. The results are consistent with studies from other countries and suggest that exposure to alcohol advertisements among Australian adolescents is strongly associated with drinking patterns. Given current high levels of drinking among Australian youth, these findings suggest the need to address the high levels of young people's exposure to alcohol advertising.

  6. Reversion phenomena of Cu-Cr alloys

    NASA Technical Reports Server (NTRS)

    Nishikawa, S.; Nagata, K.; Kobayashi, S.

    1985-01-01

    Cu-Cr alloys which were given various aging and reversion treatments were investigated in terms of electrical resistivity and hardness. Transmission electron microscopy was one technique employed. Some results obtained are as follows: the increment of electrical resistivity after the reversion at a constant temperature decreases as the aging temperature rises. In a constant aging condition, the increment of electrical resistivity after the reversion increases, and the time required for a maximum reversion becomes shorter as the reversion temperature rises. The reversion phenomena can be repeated, but its amount decreases rapidly by repetition. At first, the amount of reversion increases with aging time and reaches its maximum, and then tends to decrease again. Hardness changes by the reversion are very small, but the hardness tends to soften slightly. Any changes in transmission electron micrographs by the reversion treatment cannot be detected.

  7. The Weakness of Stern Alcohol Control Policies.

    PubMed

    Poikolainen, Kari

    2016-01-01

    To test the total consumption model claiming that alcohol-related ill health can best be diminished by a policy of severe restrictions and high price. The associations between an index measuring the severity of the alcohol policy, total alcohol consumption and number of disability-adjusted life years (DALYs) lost due to alcohol were compared in 30 OECD countries in 2005. No significant correlations were found between alcohol policy index, alcohol consumption and the number of DALYs due to alcohol use. In regression analysis, alcohol policy index and alcohol consumption were not related to alcohol-related DALYs. Excise tax rate was not related to alcohol-related DALYs (25 countries with tax rate data). These findings suggest that the total consumption model fails. Alcohol-related ill health seems to be mainly due to alcohol dependence, both clinical and subclinical, not to moderate drinking. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  8. [Elderly women and alcohol].

    PubMed

    Moscato, Alba

    It is important to understand the reasons for alcohol abuse in elderly people and in particular women. Psychological suffering must be envisaged. This behaviour can be considered as a necessary narcissistic retreat when ageing. The mental health of these women should be taken into account when providing them with help when they want it. This involves understanding them and supporting them as they adjust to the passage of time. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Genetics, systems, and alcohol.

    PubMed

    McClearn, G E

    1993-03-01

    Under a variety of rubrics (e.g., complexity, self-constructing systems, dissipative structures), interest has recently burgeoned in applying principles of complex systems to a wide variety of scientific issues. A major concern is with emergent properties of systems not derivable from the properties of components of the systems. In this paper, some elementary aspects of "systems" considerations are applied to phenomena of alcohol pharmacogenetics. It is likely that whole new families of informative phenotypes can be generated by this approach.

  10. Alcohol advertising and adolescents.

    PubMed

    Strasburger, Victor C

    2002-04-01

    Considerable research now exists that the media may exert a powerful influence on adolescents' drug-taking behavior. Teens view an average of 2,000 beer and wine ads per year in the US. In addition, television shows, movies, and music videos contain considerable amounts of alcohol use. This article will discuss the available research and offers suggestions to make the media healthier for teenagers.

  11. [Nationwide survey of alcohol drinking and alcoholism among Japanese adults].

    PubMed

    Osaki, Yoneatsu; Matsushita, Sachio; Shirasaka, Tomonobu; Hiro, Hisanori; Higuchi, Susumu

    2005-10-01

    To investigate the characteristics of alcohol use among Japanese adults and prevalence of alcohol dependence in Japan, we conducted a nationwide survey on alcohol drinking behavior and alcohol dependence among Japanese adults using a representative sampling method. We sampled 3500 adults from throughout the entire country using a stratified random sampling method with two-step stratification, and carried out a home visit interview survey. A total of 2547 people (72.8%) responded to the survey. The survey period was June, 2003. The questionnaire contained questions about the frequency and quantity of alcohol use, 'hazardous use of alcohol' and 'alcohol dependence' according to the ICD-10 definition, several screening scales on problem use of alcohol (CAGE, KAST, AUDIT), life-time prevalence of 24 alcohol related diseases, smoking status, dysgryphia, and nightcap drinking. The number of respondents was, 1184 males, and 1363 females. Lifetime alcohol drinking, and weekly drinking, and daily drinking rates were 95.1%, 64.4%, and 36.2% for males, 79.0%, 27.5%, and 7.5% for females, respectively. Average daily alcohol consumption was 3.7 units for males, and 2.0 units for females (1 unit = 10 g pure alcohol). The proportion of drinkers who drank alcohol 4 units or more daily was 28.9% for males, and 7.6% for females, and that for 6 units or more was 12.7% for males, and 3.4% for females. The proportion of flasher was 41.2% for males, and 35.0% for females. Among screening questions, problem drinking was most frequently identified using AUDIT (score 12 points or more, 150 persons), followed by KAST (2 points or more, 100 persons) and CAGE (2 points or more, 98 persons). The number of subjects who met the ICD-10 criteria for alcohol dependence was 24, while the number who engaged in hazardous alcohol use was 64. This study revealed that problem drinking and alcohol dependence are a serious problem in Japanese general population. The problem of females drinking may be

  12. Pharmacologic treatment of alcoholism.

    PubMed

    Anton, Raymond F; Schacht, Joseph P; Book, Sarah W

    2014-01-01

    Progress in understanding the neuroscience of addiction has significantly advanced the development of more efficacious medications for the treatment of alcohol use disorders (AUD). While several medications have been approved by regulatory bodies around the world for the treatment of AUD, they are not universally efficacious. Recent research has yielded improved understanding of the genetics and brain circuits that underlie alcohol reward and its habitual use. This research has contributed to pharmacogenetic studies of medication response, and will ultimately lead to a more "personalized medicine" approach to AUD pharmacotherapy. This chapter summarizes work on clinically available medications (both approved by regulatory bodies and investigational) for the treatment of alcohol dependence, as well as the psychiatric disorders that are commonly comorbid with AUD. Studies that have evaluated genetic influences on medication response and those that have employed neuroimaging to probe mechanisms of medication action or response are highlighted. Finally, new targets discovered in animal models for possible pharmacologic intervention in humans are overviewed and future directions in medications development provided. © 2014 Elsevier B.V. All rights reserved.

  13. [DGRW update: alcohol addiction].

    PubMed

    Vogelgesang, M

    2011-10-01

    First, epidemiological data and socioeconomic consequences of alcohol addiction are summarized. Research findings, in particular in intervention and evaluation, from 2009-2011 in the field of alcohol addiction treatment are then discussed concerning their relevance for rehabilitation practice. The search was based on PubMed and PSYNDEX. The interventions most frequently evaluated and found most effective in alcohol addiction treatment are cognitive-behavioural interventions. Further topics dealt with are: pharmacological relapse prevention; technologically based therapies (e. g. e-therapy); systemic interventions; 12-steps; effectiveness of addiction treatment as confirmed in large-scale catamnestic studies; treatment of addiction and comorbidity; various subgroups (like elderly people and women); as well as other new and interesting developments such as rehab case management, dovetailing of medical and vocational interventions, stepped-care interventions, rehab management category groups as well as a new focus on individual treatment experiences and the pre-eminence of the therapeutic relationship. Finally, priority areas of future research are described. © Georg Thieme Verlag KG Stuttgart · New York.

  14. [Non alcoholic steatohepatitis].

    PubMed

    Manero, E; Findor, J A; Avagnina, A; de Elizalde, S; Elsner, B

    1994-01-01

    A prospective study of 21 patients with the diagnosis of non-alcoholic steatohepatitis (NASH) was carried out. All patients had hepatomegaly and in 10 (48%) image studies were consistent with steatosis and/or fibrosis. Biochemically, there was increase of AST, ALT and cholesterol in 48%, of GGT in 52% and of alkaline phosphatase in 38%. 18 patients were obese, 2 of them diabetic, 2 others had a history of exposure to drugs (amiodarone and isopropilic alcohol) and the last one presented hypothyroidism. Liver biopsies were studied using a semiquantitative scale to evaluate the degree of steatosis, inflammation and fibrosis in a scale from 1 to 3. Results showed a medium score of 2.6 for steatosis, 1.5 for inflammation and 1.8 for fibrosis. Four patients had cirrhosis and Mallory bodies were found in 11 cases (52%). NASH is an oligosymptomatic disease that can be found in different clinical conditions, mainly obesity, and is more frequent in women. It is histologically indistinguishable from alcoholic steatohepatitis. It is frequently underdiagnosed clinically and must be taken into account as a possible cause of cryptogenetic cirrhosis.

  15. Varenicline Reduces Alcohol Intake During Repeated Cycles of Alcohol Reaccess Following Deprivation in Alcohol-Preferring (P) Rats.

    PubMed

    Froehlich, Janice C; Nicholson, Emily R; Dilley, Julian E; Filosa, Nick J; Rademacher, Logan C; Smith, Teal N

    2017-08-01

    Most alcoholics experience periods of voluntary alcohol abstinence or imposed alcohol deprivation followed by a return to alcohol drinking. This study examined whether varenicline (VAR) reduces alcohol intake during a return to drinking after periods of alcohol deprivation in rats selectively bred for high alcohol drinking (the alcohol preferring or "P" rats). Alcohol-experienced P rats were given 24-hour access to food and water and scheduled access to alcohol (15% and 30% v/v) for 2 h/d. After 4 weeks, rats were deprived of alcohol for 2 weeks, followed by reaccess to alcohol for 2 weeks, and this pattern was repeated for a total of 3 cycles. Rats were fed either vehicle (VEH) or VAR, in doses of 0.5, 1.0, or 2.0 mg/kg BW, at 1 hour prior to onset of the daily alcohol reaccess period for the first 5 days of each of the 3 alcohol reaccess cycles. Low-dose VAR (0.5 mg/kg BW) reduced alcohol intake during the 5 days of drug treatment in alcohol reaccess cycles 1 and 2. Higher doses of VAR (1.0 mg/kg BW and 2.0 mg/kg BW) reduced alcohol intake during the 5 days of treatment in all 3 alcohol reaccess cycles. The decrease in alcohol intake disappeared with termination of VAR treatment in all alcohol reaccess cycles. The results demonstrate that VAR decreases alcohol intake during multiple cycles of alcohol reaccess following alcohol deprivation in rats and suggests that it may prevent a return to heavy alcohol drinking during a lapse from alcohol abstinence in humans with alcohol use disorder. Copyright © 2017 by the Research Society on Alcoholism.

  16. Pedagogically Bereft! Improving Learning Outcomes for Children with Foetal Alcohol Spectrum Disorders

    ERIC Educational Resources Information Center

    Carpenter, Barry

    2011-01-01

    Foetal alcohol spectrum disorder (FASD) is the most common non-genetic cause of learning disability, affecting around 1% of live births in Europe, and costing an estimated $2.9 million per individual across their lifespan. In adulthood, non-reversible brain damage is often compounded by secondary disabilities in adulthood, such as mental health…

  17. The soy-associated phytoestrogen, genistein, does not protect against alcohol induced osteoporosis in male mice

    USDA-ARS?s Scientific Manuscript database

    Alcohol abuse acts as a risk factor for osteoporosis by increasing osteoclast activity and decreasing osteoblast activity in bone. These effects can be reversed by estradiol. Soy diets are also suggested to have protective effects on bone loss in men and women, as a result of the presence of soy pro...

  18. [Current peculiarities of alcoholic psychosis].

    PubMed

    Aleksin, D S; Egorov, A Iu

    2011-01-01

    The follow-up study of alcoholic psychoses in male patients admitted to a clinical department of a psychiatric hospital in 2005-2007 was carried out. Patients with alcoholic psychoses made up from 15 to 30% of all patients. The number of psychosis had seasonal variations with the elevations in spring and autumn, peaks in January, lune and October. Alcoholic delirium morbidity made up from 69 to 82% of the total number of alcoholic psychoses, alcoholic hallucinosis varied from 14 to 27%. Other forms were presented by single cases. In alcoholic delirium hallucinations had brighter, sated character. The most specific were visual hallucinations in the form of zoohallucinations, hallucinations of an oral cavity ("sensation of threads, hair etc"). The most often observable characters were "extraneous people, animal, demons". In alcoholic hallucinosis, verbal contrast hallucinations, making comment hallucinations, visual illusions were most frequent. The family history of mental disorders and alcoholism was noted in 30% of patients with alcoholic psychosis. The probability of occurrence of alcoholic psychoses depended on the quality of consumed drinks. The presence of a cranial-brain injury in the anamnesis considerably aggravated the disease forecast and increased the risk of seizure syndrome.

  19. [Polythelia in alcoholics. Preliminary report].

    PubMed

    König, P; Haller, R; Dünser, H

    1985-09-30

    We present a study comparing 650 alcoholics with 1074 patients with miscellaneous other psychiatric (665) and medical (409) diagnoses for the frequency of supernumerary nipples (SN). Also 716 adolescents and school-children in a general medical screening were investigated for this phenomenon. In alcoholics SN were found in over 6%, in the non-alcoholic group in approximately 1%. The latter figure correlates well with other findings in literature, 6% being significantly higher. In the group of adolescents/children (1,8-3,2%) polythelia correlates with familial alcoholism, albeit of the father. As polythelia may be part of fetal alcohol-syndrome, the addiction should be expected on the mother's side, the more so, as the local rate of female/male alcoholism is approximately 1:3 (administrative incidence). We suggest that polythelia may be more frequent among alcoholics. Apart from SN occurring in alcoholic embryopathy, alcoholism of the father may be an additional factor for their development. Polythelia may in certain cases offer a diagnostic clue not only for mammo-renal syndromes but also for individual or familial alcoholism.

  20. Alcohol and the young child.

    PubMed

    Bradford, D E

    1984-01-01

    With the increasing availability of alcohol in modern times, the child neglect and abuse portrayed in Hogarth's engraving Gin Lane may once again be witnessed. Reports occur occasionally of alcohol being given deliberately to infants to quieten them, but alcohol poisoning in the slightly older child is not uncommon. The introduction of child-proof containers has altered poisoning figures recently. However, alcohol poisoning tends to occur at ages 3 and 4, that is, about 2 years after the peak of all poisonings in children. This difference may be an indication that alcohol is taken in imitation of parents' drinking, a suggestion which has some support from reported cases of mouthwash poisoning. Holidays and high days where children and alcohol mix, are potentially dangerous periods. Since alcohol poisoning can be fatal, yet if recognised is relatively easily managed, every child with the slightest degree of drowsiness should be suspect until proven or not by blood alcohol. The prevention of alcohol poisoning in the young child consists in protecting the alcohol by lock and key, not setting an example by drinking or gargling in front of children. Many substances such as mouthwash and perfume should also be under supervision. Once actual poisoning has occurred blood sugar is probably more important than the level of blood ethanol and blood sugar levels should be monitored frequently and the child treated with glucose, preferably intravenously.

  1. Reverse Current in Solar Flares

    NASA Technical Reports Server (NTRS)

    Knight, J. W.; Sturrock, P. A.

    1976-01-01

    The theory that impulsive X ray bursts are produced by high energy electrons streaming from the corona to the chromosphere is investigated. Currents associated with these streams are so high that either the streams do not exist or their current is neutralized by a reverse current. Analysis of a simple model indicates that the primary electron stream leads to the development of an electric field in the ambient corona which decelerates the primary beam and produces a neutralizing reverse current. It appears that, in some circumstances, this electric field could prevent the primary beam from reaching the chromosphere. In any case, the electric field acts as an energy exchange mechanism, extracting kinetic energy from the primary beam and using it to heat the ambient plasma. This heating is typically so rapid that it must be expected to have important dynamical consequences.

  2. Reverse osmosis water purification system

    NASA Technical Reports Server (NTRS)

    Ahlstrom, H. G.; Hames, P. S.; Menninger, F. J.

    1986-01-01

    A reverse osmosis water purification system, which uses a programmable controller (PC) as the control system, was designed and built to maintain the cleanliness and level of water for various systems of a 64-m antenna. The installation operates with other equipment of the antenna at the Goldstone Deep Space Communication Complex. The reverse osmosis system was designed to be fully automatic; with the PC, many complex sequential and timed logic networks were easily implemented and are modified. The PC monitors water levels, pressures, flows, control panel requests, and set points on analog meters; with this information various processes are initiated, monitored, modified, halted, or eliminated as required by the equipment being supplied pure water.

  3. Complications in reverse shoulder arthroplasty

    PubMed Central

    Barco, Raul; Savvidou, Olga D.; Sperling, John W.; Sanchez-Sotelo, Joaquín; Cofield, Robert H.

    2016-01-01

    The reported rate of complications of reverse shoulder arthroplasty (RSA) seems to be higher than the complication rate of anatomical total shoulder arthroplasty. The reported overall complication rate of primary RSA is approximately 15%; when RSA is used in the revision setting, the complication rate may approach 40%. The most common complications of RSA include instability, infection, notching, loosening, nerve injury, acromial and scapular spine fractures, intra-operative fractures and component disengagement. Careful attention to implant design and surgical technique, including implantation of components in the correct version and height, selection of the best glenosphere-humeral bearing match, avoidance of impingement, and adequate management of the soft tissues will hopefully translate in a decreasing number of complications in the future. Cite this article: Barco R, Savvidou OD, Sperling JW, Sanchez-Sotelo J, Cofield RH. Complications in reverse shoulder arthroplasty. EFORT Open Rev 2016;1:72-80. DOI: 10.1302/2058-5241.1.160003. PMID:28461931

  4. Complications in reverse shoulder arthroplasty.

    PubMed

    Barco, Raul; Savvidou, Olga D; Sperling, John W; Sanchez-Sotelo, Joaquín; Cofield, Robert H

    2016-03-01

    The reported rate of complications of reverse shoulder arthroplasty (RSA) seems to be higher than the complication rate of anatomical total shoulder arthroplasty.The reported overall complication rate of primary RSA is approximately 15%; when RSA is used in the revision setting, the complication rate may approach 40%.The most common complications of RSA include instability, infection, notching, loosening, nerve injury, acromial and scapular spine fractures, intra-operative fractures and component disengagement.Careful attention to implant design and surgical technique, including implantation of components in the correct version and height, selection of the best glenosphere-humeral bearing match, avoidance of impingement, and adequate management of the soft tissues will hopefully translate in a decreasing number of complications in the future. Cite this article: Barco R, Savvidou OD, Sperling JW, Sanchez-Sotelo J, Cofield RH. Complications in reverse shoulder arthroplasty. EFORT Open Rev 2016;1:72-80. DOI: 10.1302/2058-5241.1.160003.

  5. Reverse engineering of integrated circuits

    DOEpatents

    Chisholm, Gregory H.; Eckmann, Steven T.; Lain, Christopher M.; Veroff, Robert L.

    2003-01-01

    Software and a method therein to analyze circuits. The software comprises several tools, each of which perform particular functions in the Reverse Engineering process. The analyst, through a standard interface, directs each tool to the portion of the task to which it is most well suited, rendering previously intractable problems solvable. The tools are generally used iteratively to produce a successively more abstract picture of a circuit, about which incomplete a priori knowledge exists.

  6. The Alcohol Environment Protocol: A new tool for alcohol policy.

    PubMed

    Casswell, Sally; Morojele, Neo; Williams, Petal Petersen; Chaiyasong, Surasak; Gordon, Ross; Gray-Philip, Gaile; Viet Cuong, Pham; MacKintosh, Anne-Marie; Halliday, Sharon; Railton, Renee; Randerson, Steve; Parry, Charles D H

    2018-01-04

    To report data on the implementation of alcohol policies regarding availability and marketing, and drink driving, along with ratings of enforcement from two small high-income to three high-middle income countries, and one low-middle income country. This study uses the Alcohol Environment Protocol, an International Alcohol Control study research tool, which documents the alcohol policy environment by standardised collection of data from administrative sources, observational studies and interviews with key informants to allow for cross-country comparison and change over time. All countries showed adoption to varying extents of key effective policy approaches outlined in the World Health Organization Global Strategy to Reduce the Harmful Use of Alcohol (2010). High-income countries were more likely to allocate resources to enforcement. However, where enforcement and implementation were high, policy on availability was fairly liberal. Key Informants judged alcohol to be very available in both high- and middle-income countries, reflecting liberal policy in the former and less implementation and enforcement and informal (unlicensed) sale of alcohol in the latter. Marketing was largely unrestricted in all countries and while drink-driving legislation was in place, it was less well enforced in middle-income countries. In countries with fewer resources, alcohol policies are less effective because of lack of implementation and enforcement and, in the case of marketing, lack of regulation. This has implications for the increase in consumption taking place as a result of the expanding distribution and marketing of commercial alcohol and consequent increases in alcohol-related harm. © 2018 The Authors Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.

  7. The economic impact of alcohol abuse and alcoholism.

    PubMed Central

    Burke, T R

    1988-01-01

    The economic effects of alcohol abuse are as damaging to the nation as the health effects, affecting the family, the community, and persons of all ages. Underaged drinking is interfering with children's development, affecting the nation's ability to respond to economic challenge in the future. The college aged may be the most difficult to educate about alcohol abuse because of drinking patterns established at an early age and susceptibility to advertising inducements. Health care costs for families with an alcoholic member are twice those for families without one, and up to half of all emergency room admissions are alcohol related. Fetal alcohol syndrome is one of the top three known causes of birth defects, and is totally preventable. Alcohol abuse and alcoholism are estimated to have cost the nation $117 billion in 1983, while nonalcoholic drug abuse that year cost $60 billion. Costs of alcohol abuse are expected to be $136 billion a year by 1990, mostly from lost productivity and employment. Between 6 and 7 million workers are alcoholic, with an undetermined loss of productivity, profits, and competitiveness of American business. Alcohol abuse contributes to the high health care costs of the elderly beneficiaries of Federal health financing programs. Heavily affected minorities include blacks, Hispanics, and Native Americans. Society tends to treat the medical and social consequences of alcohol abuse, rather than its causes. Although our experience with the consequences of alcohol abuse is greater than that for any other drug, public concern for its prevention and treatment is less than for other major illnesses or abuse of other drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3141948

  8. Alcohol advertising bans and alcohol abuse: an international perspective.

    PubMed

    Saffer, H

    1991-05-01

    This paper examines the effect of banning broadcast advertising of alcoholic beverages. The data used in this study are a pooled time series from 17 countries for the period 1970 to 1983. The empirical results show that countries with bans on spirits advertising have about 16% lower alcohol consumption than countries with no bans and that countries with bans on beer and wine advertising have about 11% lower alcohol consumption than countries with bans only on spirits advertising.

  9. Socioeconomic status as an effect modifier of alcohol consumption and harm: analysis of linked cohort data.

    PubMed

    Katikireddi, Srinivasa Vittal; Whitley, Elise; Lewsey, Jim; Gray, Linsay; Leyland, Alastair H

    2017-06-01

    Alcohol-related mortality and morbidity are high in socioeconomically disadvantaged populations compared with individuals from advantaged areas. It is unclear if this increased harm reflects differences in alcohol consumption between these socioeconomic groups, reverse causation (ie, downward social selection for high-risk drinkers), or a greater risk of harm in individuals of low socioeconomic status compared with those of higher status after similar consumption. We aimed to investigate whether the harmful effects of alcohol differ by socioeconomic status, accounting for alcohol consumption and other health-related factors. The Scottish Health Surveys are record-linked cross-sectional surveys representative of the adult population of Scotland. We obtained baseline demographics and data for alcohol consumption (units per week and binge drinking) from Scottish Health Surveys done in 1995, 1998, 2003, 2008, 2009, 2010, 2011, and 2012. We matched these data to records for deaths, admissions, and prescriptions. The primary outcome was alcohol-attributable admission or death. The relation between alcohol-attributable harm and socioeconomic status was investigated for four measures (education level, social class, household income, and area-based deprivation) using Cox proportional hazards models. The potential for alcohol consumption and other risk factors (including smoking and body-mass index [BMI]) mediating social patterning was explored in separate regression models. Reverse causation was tested by comparing change in area deprivation over time. 50 236 participants (21 777 men and 28 459 women) were included in the analytical sample, with 429 986 person-years of follow-up. Low socioeconomic status was associated consistently with strikingly raised alcohol-attributable harms, including after adjustment for weekly consumption, binge drinking, BMI, and smoking. Evidence was noted of effect modification; for example, relative to light drinkers living in

  10. Grand Rounds: Alcoholic Hepatitis.

    PubMed

    Singal, Ashwani K; Louvet, Alexandre; Shah, Vijay H; Kamath, Patrick S

    2018-06-13

    A 33-year-old Caucasian male was admitted to hospital with recent onset of jaundice of 2-3 weeks duration. He reported heavy use of alcohol for the last 10 years with the last drink a day prior to the onset of symptoms. At admission, he was alert and oriented to time, place, and person, and was deeply jaundiced. His laboratory profile can be summarised as follows: haemoglobin 12.1 g/dl, white blood cell count 18,700 with 81% neutrophils, serum bilirubin 33 (direct 22) mg/dl, aspartate aminotransferase 147 IU/L, alanine aminotransferase 62 IU/L, alkaline phosphatase 117 IU/L, serum albumin 2.8 gm/dl, serum creatinine 0.6 mg/dl, prothrombin time 18.3 (control 14.5) seconds, and international normalized ratio 1.48. He was diagnosed with severe alcoholic hepatitis (Maddrey discriminant function score of 50) and treated with prednisolone for 28 days with symptomatic and biochemical improvement. His Lille score at seven days was 0.4, and his serum bilirubin had decreased to 3.5 mg/dl at the end of treatment. He was also seen by the addiction team during hospitalisation; he agreed to follow through on recommendations. He was dismissed after completing a three-week inpatient rehabilitation programme but relapsed to alcohol use three months later, and was readmitted with alcohol withdrawal. He was readmitted two months later (about six months from the first episode) for a second episode of severe alcoholic hepatitis. At admission, his model for end-stage liver disease score was 32 and he was treated again with corticosteroids. His Lille score at seven days was 0.6 and steroids were discontinued. The hospital course was complicated by spontaneous bacterial peritonitis and pneumonia with development of acute kidney injury. He continued to worsen, developing multiorgan failure. After a course of one month, the family's preference was for him to receive comfort measures. This scenario raises several questions. Copyright © 2018 European Association for the

  11. Recruitment of a Neuronal Ensemble in the Central Nucleus of the Amygdala Is Required for Alcohol Dependence.

    PubMed

    de Guglielmo, Giordano; Crawford, Elena; Kim, Sarah; Vendruscolo, Leandro F; Hope, Bruce T; Brennan, Molly; Cole, Maury; Koob, George F; George, Olivier

    2016-09-07

    Abstinence from alcohol is associated with the recruitment of neurons in the central nucleus of the amygdala (CeA) in nondependent rats that binge drink alcohol and in alcohol-dependent rats. However, whether the recruitment of this neuronal ensemble in the CeA is causally related to excessive alcohol drinking or if it represents a consequence of excessive drinking remains unknown. We tested the hypothesis that the recruitment of a neuronal ensemble in the CeA during abstinence is required for excessive alcohol drinking in nondependent rats that binge drink alcohol and in alcohol-dependent rats. We found that inactivation of the CeA neuronal ensemble during abstinence significantly decreased alcohol drinking in both groups. In nondependent rats, the decrease in alcohol intake was transient and returned to normal the day after the injection. In dependent rats, inactivation of the neuronal ensemble with Daun02 produced a long-term decrease in alcohol drinking. Moreover, we observed a significant reduction of somatic withdrawal signs in dependent animals that were injected with Daun02 in the CeA. These results indicate that the recruitment of a neuronal ensemble in the CeA during abstinence from alcohol is causally related to excessive alcohol drinking in alcohol-dependent rats, whereas a similar neuronal ensemble only partially contributed to alcohol-binge-like drinking in nondependent rats. These results identify a critical neurobiological mechanism that may be required for the transition to alcohol dependence, suggesting that focusing on the neuronal ensemble in the CeA may lead to a better understanding of the etiology of alcohol use disorders and improve medication development. Alcohol dependence recruits neurons in the central nucleus of the amygdala (CeA). Here, we found that inactivation of a specific dependence-induced neuronal ensemble in the CeA reversed excessive alcohol drinking and somatic signs of alcohol dependence in rats. These results identify a

  12. The economic impact of alcohol abuse and alcoholism.

    PubMed

    Burke, T R

    1988-01-01

    The economic effects of alcohol abuse are as damaging to the nation as the health effects, affecting the family, the community, and persons of all ages. Underaged drinking is interfering with children's development, affecting the nation's ability to respond to economic challenge in the future. The college aged may be the most difficult to educate about alcohol abuse because of drinking patterns established at an early age and susceptibility to advertising inducements. Health care costs for families with an alcoholic member are twice those for families without one, and up to half of all emergency room admissions are alcohol related. Fetal alcohol syndrome is one of the top three known causes of birth defects, and is totally preventable. Alcohol abuse and alcoholism are estimated to have cost the nation $117 billion in 1983, while nonalcoholic drug abuse that year cost $60 billion. Costs of alcohol abuse are expected to be $136 billion a year by 1990, mostly from lost productivity and employment. Between 6 and 7 million workers are alcoholic, with an undetermined loss of productivity, profits, and competitiveness of American business. Alcohol abuse contributes to the high health care costs of the elderly beneficiaries of Federal health financing programs. Heavily affected minorities include blacks, Hispanics, and Native Americans. Society tends to treat the medical and social consequences of alcohol abuse, rather than its causes. Although our experience with the consequences of alcohol abuse is greater than that for any other drug, public concern for its prevention and treatment is less than for other major illnesses or abuse of other drugs. Alcohol abuse is a problem being given high priority within the Department in an effort to create a national agenda on the issue and to try to impart a greater sense of urgency about the problems. Ways are being explored to integrate alcoholism activities into more Departmental programs. Employee assistance programs for alcohol

  13. Fetal Alcohol Spectrum Disorders (FASDs): Alcohol Use Quiz

    MedlinePlus

    ... Data & Statistics State-Level Estimates 2016 Research & Tracking Monitoring Alcohol Use International Research Training & Education Online Training Past Activities Articles & Key Findings Materials & Multimedia Fact Sheets & Brochures ...

  14. Alcohol, Diet and Drug Use Preceding Alcoholic Hepatitis.

    PubMed

    Parker, Richard; Neuberger, James M

    2018-05-31

    Alcoholic hepatitis (AH) is a severe manifestation of alcohol-related liver disease characterised by jaundice and liver failure. It is not known what might trigger an episode of AH. We interviewed patients to investigate changes in behaviour before the onset of AH. Structured interviews were performed with patients with AH to examine their alcohol use, diet, drug use and smoking habit. Clinical and laboratory results were noted. Patients were followed up for 12 months after interview. Data from 39 patients was analysed. No single behavioural change occurred before the onset of jaundice, although reductions in alcohol and/or dietary intake were common. Reduction in alcohol use was seen to occur approximately 14 days before the onset of jaundice. Increased alcohol intake was not common. Clinical and laboratory data varied between types of behaviour changes, although these were not statistically significant. No changes in drug use or tobacco were reported before AH. Those who had not reduced alcohol intake or had increased their drinking had better survival. No single type of behaviour change is associated with AH. Contrary to previous assertions, increased alcohol intake was not common; in fact, participants were much more likely to have reduced their alcohol intake. © 2018 S. Karger AG, Basel.

  15. Alcohol and malnutrition in the pathogenesis of experimental alcoholic cardiomyopathy.

    PubMed

    Rossi, M A

    1980-02-01

    In this study, the morphology and the catecholamine levels of the myocardium in both well-nourished and malnourished alcohol-fed rats were examined. Alcohol has been administered to rats for 16 weeks. Rats fed a diet containing alcohol corresponding to 40 per cent. of total calorific intake and inadequate amounts of calories and nutrients developed morphological changes in the heart, while the controls did not. In addition, an increase in cardiac noradrenaline concentration and heart: body weight ratio could be observed. There were no differences in myocardial morphology and catecholamine concentration between well-nourished rats fed alcohol as 35 per cent. of the calorific intake and pair-fed controls. A dispute exists about whether alcohol is directly toxic to the heart or indirectly injurious due to associated dietary deficiency. The present results, taken together, make the theory of cardiotoxicity of alcohol an unlikely one, at least in the case of the rat; and they offer considerable support for the hypothesis that the association between chronic consumption of alcoholic beverages and cardiomyopathy is a result of a primary multifactorial nutritional deficiency, resulting from displacement of nutrient-associated calories by the "empty" calories--devoid of protein, vitamins, and minerals--of alcohol, and/or a secondary nutritional deficiency due to injurious effects of alcohol on the liver, pancreas and intestine. It is suggested that continued exposure to high levels of catecholamine, directly related to malnutrition, may play a role in the development of myocardial pathology.

  16. The presynaptic Munc13-1 binds alcohol and modulates alcohol self-administration in Drosophila

    PubMed Central

    Das, Joydip; Xu, Shiyu; Pany, Satyabrata; Guillory, Ashley; Shah, Vrutant; Roman, Gregg W.

    2013-01-01

    Munc13-1 is a presynaptic active-zone protein essential for neurotransmitter release and involved in presynaptic plasticity in brain. Ethanol, butanol and octanol quenched the intrinsic fluorescence of the C1 domain of Munc13-1 with EC50s of 52 mM, 26 mM and 0.7 mM, respectively. Photoactive azialcohols photolabeled Munc13-1 C1 exclusively at Glu-582, which was identified by mass spectrometry. Mutation of Glu-582 to alanine, leucine and histidine reduced the alcohol binding two- to five-fold. Circular dichroism studies suggested that binding of alcohol increased the stability of the wild type Munc13-1 compared with the mutants. If Munc13-1 plays some role in the neural effects of alcohol in vivo, changes in the activity of this protein should produce differences in the behavioral responses to ethanol. We tested this prediction with a loss-of-function mutation in the conserved Dunc-13 in Drosophila melanogaster. The Dunc-13P84200/+ heterozygotes have 50% wild type levels of Dunc-13 mRNA and display a very robust increase in ethanol self-administration. This phenotype is reversed by the expression of the rat Munc13-1 protein within the Drosophila nervous system. The present studies indicate that Munc13-1 C1 has binding site(s) for alcohols and Munc13-1 activity is sufficient to restore normal self-administration to Drosophila mutants deficient in Dunc-13 activity. PMID:23692447

  17. The Epigenetic Landscape of Alcoholism

    PubMed Central

    Krishnan, Harish R.; Sakharkar, Amul J.; Teppen, Tara L.; Berkel, Tiffani D.M.; Pandey, Subhash C.

    2015-01-01

    Alcoholism is a complex psychiatric disorder that has a multifactorial etiology. Epigenetic mechanisms are uniquely capable of accounting for the multifactorial nature of the disease in that they are highly stable and are affected by environmental factors, including alcohol itself. Chromatin remodeling causes changes in gene expression in specific brain regions contributing to the endophenotypes of alcoholism such as tolerance and dependence. The epigenetic mechanisms that regulate changes in gene expression observed in addictive behaviors respond not only to alcohol exposure, but also to comorbid psychopathology such as the presence of anxiety and stress. This review summarizes recent developments in epigenetic research that may play a role in alcoholism. We propose that pharmacologically manipulating epigenetic targets, as demonstrated in various preclinical models, holds great therapeutic potential in the treatment and prevention of alcoholism. PMID:25131543

  18. The epigenetic landscape of alcoholism.

    PubMed

    Krishnan, Harish R; Sakharkar, Amul J; Teppen, Tara L; Berkel, Tiffani D M; Pandey, Subhash C

    2014-01-01

    Alcoholism is a complex psychiatric disorder that has a multifactorial etiology. Epigenetic mechanisms are uniquely capable of accounting for the multifactorial nature of the disease in that they are highly stable and are affected by environmental factors, including alcohol itself. Chromatin remodeling causes changes in gene expression in specific brain regions contributing to the endophenotypes of alcoholism such as tolerance and dependence. The epigenetic mechanisms that regulate changes in gene expression observed in addictive behaviors respond not only to alcohol exposure but also to comorbid psychopathology such as the presence of anxiety and stress. This review summarizes recent developments in epigenetic research that may play a role in alcoholism. We propose that pharmacologically manipulating epigenetic targets, as demonstrated in various preclinical models, hold great therapeutic potential in the treatment and prevention of alcoholism. © 2014 Elsevier Inc. All rights reserved.

  19. Ancient Magnetic Reversals: Clues to the Geodynamo.

    ERIC Educational Resources Information Center

    Hoffman, Kenneth A.

    1988-01-01

    Discusses the question posed by some that the earth's magnetic field may reverse. States that rocks magnetized by ancient fields may offer clues to the underlying reversal mechanism in the earth's core. (TW)

  20. Rapid evaluation of reverse-osmosis membranes

    NASA Technical Reports Server (NTRS)

    Hollahan, J. R.; Wydeven, T.

    1972-01-01

    Simultaneous reverse-osmosis tests conducted with centrifuges having multiple compartment heads are discussed. Equipment for retaining reverse-osmosis membrane is illustrated. Method of conducting tests is described.

  1. Changes in cinnamyl alcohol dehydrogenase activities from sugarcane cultivars inoculated with Sporisorium scitamineum sporidia.

    PubMed

    Santiago, Rocío; Alarcón, Borja; de Armas, Roberto; Vicente, Carlos; Legaz, María Estrella

    2012-06-01

    This study describes a method for determining cinnamyl alcohol dehydrogenase activity in sugarcane stems using reverse phase (RP) high-performance liquid chromatography to elucidate their possible lignin origin. Activity is assayed using the reverse mode, the oxidation of hydroxycinnamyl alcohols into hydroxycinnamyl aldehydes. Appearance of the reaction products, coniferaldehyde and sinapaldehyde is determined by measuring absorbance at 340 and 345 nm, respectively. Disappearance of substrates, coniferyl alcohol and sinapyl alcohol is measured at 263 and 273 nm, respectively. Isocratic elution with acetonitrile:acetic acid through an RP Mediterranea sea C18 column is performed. As case examples, we have examined two different cultivars of sugarcane; My 5514 is resistant to smut, whereas B 42231 is susceptible to the pathogen. Inoculation of sugarcane stems elicits lignification and produces significant increases of coniferyl alcohol dehydrogenase (CAD) and sinapyl alcohol dehydrogenase (SAD). Production of lignin increases about 29% in the resistant cultivar and only 13% in the susceptible cultivar after inoculation compared to uninoculated plants. Our results show that the resistance of My 5514 to smut is likely derived, at least in part, to a marked increase of lignin concentration by the activation of CAD and SAD. Copyright © Physiologia Plantarum 2012.

  2. Effects of DA-Phen, a dopamine-aminoacidic conjugate, on alcohol intake and forced abstinence.

    PubMed

    Sutera, Flavia Maria; De Caro, Viviana; Cannizzaro, Carla; Giannola, Libero Italo; Lavanco, Gianluca; Plescia, Fulvio

    2016-09-01

    The mesolimbic dopamine (DA) system plays a key role in drug reinforcement and is involved in the development of alcohol addiction. Manipulation of the DAergic system represents a promising strategy to control drug-seeking behavior. Previous studies on 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) showed in vivo effects as a DA-ergic modulator. This study was aimed at investigate DA-Phen effects on operant behavior for alcohol seeking behavior, during reinstatement following subsequent periods of alcohol deprivation. For this purpose, male Wistar rats were tested in an operant paradigm of self-administration; behavioral reactivity and anxiety like-behavior during acute abstinence were evaluated. A characterization of DA-Phen CNS targeting by its quantification in the brain was also carried out. Our findings showed that DA-Phen administration was able to reduce relapse in alcohol drinking by 50% and reversed the alterations in behavioral reactivity and emotionality observed during acute abstinence. In conclusion, DA-Phen can reduce reinstatement of alcohol drinking in an operant-drinking paradigm following deprivation periods and reverse abstinence-induced behavioral phenotype. DA-Phen activity seems to be mediated by the modulation of the DAergic transmission. However further studies are needed to characterize DA-Phen pharmacodynamic and pharmacokinetic properties, and its potential therapeutic profile in alcohol addiction. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Functional inactivation of the orbitofrontal cortex disrupts context-induced reinstatement of alcohol seeking in rats.

    PubMed

    Bianchi, Paula Cristina; Carneiro de Oliveira, Paulo Eduardo; Palombo, Paola; Leão, Rodrigo Molini; Cogo-Moreira, Hugo; Planeta, Cleopatra da Silva; Cruz, Fábio Cardoso

    2018-05-01

    The high rate of relapse to drug use remains a central challenge to treating drug addiction. In human and rat models of addiction, environmental stimuli in contexts associated with previous drug use can provoke a relapse of drug seeking. Pre-clinical studies have used the ABA renewal procedure to study context-induced reinstatement of drug seeking. In the current study, we studied the role of the orbitofrontal cortex (OFC) in context-induced reinstatement to alcohol. We trained male and female rats to self-administer alcohol in context A, extinguished drug-reinforced responding in a distinct context B, and assessed context-induced reinstatement in context A or B (control group). Next, we determined the effect of context-induced renewal of alcohol-seeking behavior on the expression of Fos (a neuronal activity marker) in the OFC. Finally, we determined the effect of reversible inactivation by GABAa and GABAb receptor agonists (i.e., muscimol and baclofen, respectively) in the OFC. There were no differences between male and female rats in context-induced reinstatement of alcohol-seeking behavior. Re-exposure to Context A, but not Context B, reinstated alcohol-seeking behavior and increased expression of the neural activity marker Fos in the OFC. Reversible inactivation of the OFC with muscimol and baclofen attenuated context-induced reinstatement. Our data indicated that the OFC mediates context-induced reinstatement of alcohol-seeking behavior. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Human alcohol-related neuropathology

    PubMed Central

    Kril, Jillian J.

    2015-01-01

    Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol (ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions

  5. 27 CFR 5.37 - Alcohol content.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Alcohol content. 5.37 Section 5.37 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF DISTILLED SPIRITS Labeling Requirements for Distilled Spirits § 5.37 Alcohol content. (a)...

  6. Traffic safety facts 1994 : state alcohol estimates

    DOT National Transportation Integrated Search

    1995-01-01

    Nationwide in 1994, alcohol was involved in 40.8 percent of the traffic fatalities (8.6 percent low alcohol and 32.2 percent high alcohol), translating to 16,589 alcohol-related fatalities. These tables provide estimates of alcohol involvement in fat...

  7. Traffic safety facts 1995 : state alcohol estimates

    DOT National Transportation Integrated Search

    1996-01-01

    Nationwide in 1995, alcohol was involved in 41.3 percent of the traffic fatalities (8.9 percent low alcohol and 32.5 percent high alcohol), translating to 17,274 alcohol-related fatalities. These tables provide estimates of alcohol involvement in fat...

  8. 27 CFR 5.37 - Alcohol content.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Alcohol content. 5.37 Section 5.37 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF DISTILLED SPIRITS Labeling Requirements for Distilled Spirits § 5.37 Alcohol content. (a)...

  9. 27 CFR 21.116 - Methyl alcohol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Methyl alcohol. 21.116 Section 21.116 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21...

  10. 27 CFR 21.113 - Isopropyl alcohol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Isopropyl alcohol. 21.113 Section 21.113 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21...

  11. 27 CFR 21.116 - Methyl alcohol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Methyl alcohol. 21.116 Section 21.116 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21...

  12. 27 CFR 19.398 - Alcohol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Alcohol. 19.398 Section 19.398 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE... Articles Bottling, Packaging, and Removal of Products § 19.398 Alcohol. (a) Containers. Subject to the...

  13. 27 CFR 21.113 - Isopropyl alcohol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Isopropyl alcohol. 21.113 Section 21.113 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21...

  14. 27 CFR 5.37 - Alcohol content.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Alcohol content. 5.37 Section 5.37 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF DISTILLED SPIRITS Labeling Requirements for Distilled Spirits § 5.37 Alcohol content. (a)...

  15. [The expression and significance of VIP and its receptor in the cochlea of different degrees of chronic alcoholism rats].

    PubMed

    Feng, Jing; Liu, Haibing

    2015-07-01

    To determine whether chronic alcoholism alters the expression levels of Vasoactive intestinal polypeptide (VIP) and its receptor (VIPR1) in the cochlea of chronic alcoholism rats. We measured their expression levels in 30 SD rats, in which we created models of different degrees of chronic alcoholism. We investigated the presence of the mRNA of VIP in the cochlea of chronic alcoholism rats and controls by reverse transcription-polymerase chain reaction (RT-PCR) method. We investigated the presence of proteins of VIPR1 in poisoned rats and controls by western blot. We also evaluated the local distribution of VIP cells by immunohistochemistry. We found that the levels of VIP and VIPR1 were downregulated in the chronic alcoholism groups compared to the controls group. The differences in some expression levels were significant different between chronic alcoholism rats and control rats. Moreover, at different degrees of alcohol poisoning in rats, the contents of VIP and VIPR1 differed. Decreased levels of VIP and VIPR1 were detected in the deep chronic alcoholism group compared to the group with low-degree poisoning (P < 0.05). In spiral ganglion cell plasm the expression of VIP and VIPR1 had no significant difference in three groups (P > 0.05). These results suggest that VIP and VIPR1 play an important role in the auditory function in rats with chronic alcoholism. Chronic alcoholism may cause a peptide hormone secretion imbalance in the auditory system, eventually leading to hearing loss.

  16. Employment impacts of alcohol taxes.

    PubMed

    Wada, Roy; Chaloupka, Frank J; Powell, Lisa M; Jernigan, David H

    2017-12-01

    There is strong scientific evidence supporting the effectiveness of increasing alcohol taxes for reducing excessive alcohol consumption and related problems. Opponents have argued that alcohol tax increases lead to job losses. However, there has been no comprehensive economic analysis of the impact of alcohol taxes on employment. To fill this gap, a regional macroeconomic simulation model was used to assess the net impact of two hypothetical alcohol tax increases (a 5-cent per drink excise tax increase and a 5% sales tax increase on beer, wine, and distilled spirits, respectively) on employment in Arkansas, Florida, Massachusetts, New Mexico, and Wisconsin. The model accounted for changes in alcohol demand, average state income, and substitution effects. The employment impact of spending the new tax revenue on general expenditures versus health care was also assessed. Simulation results showed that a 5-cent per drink additional excise tax on alcoholic beverages with new tax revenues allocated to general expenditures increased net employment in Arkansas (802 jobs); Florida (4583 jobs); Massachusetts (978 jobs); New Mexico (653 jobs); and Wisconsin (1167 jobs). A 5% additional sales tax also increased employment in Arkansas (789 jobs; Florida (4493 jobs); Massachusetts (898 jobs); New Mexico (621 jobs); and Wisconsin (991 jobs). Using new alcohol tax revenues to fund health care services resulted in slightly lower net increases in state employment. The overall economic impact of alcohol tax increases cannot be fully assessed without accounting for the job gains resulting from additional tax revenues. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Alcohol Use and Firearm Violence

    PubMed Central

    Branas, Charles C.; Han, SeungHoon; Wiebe, Douglas J.

    2016-01-01

    Although the misuse of firearms is necessary to the occurrence of firearm violence, there are other contributing factors beyond simply firearms themselves that might also be modified to prevent firearm violence. Alcohol is one such key modifiable factor. To explore this, we undertook a 40-year (1975–2014) systematic literature review with meta-analysis. One large group of studies showed that over one third of firearm violence decedents had acutely consumed alcohol and over one fourth had heavily consumed alcohol prior to their deaths. Another large group of studies showed that alcohol was significantly associated with firearm use as a suicide means. Two controlled studies showed that gun injury after drinking, especially heavy drinking, was statistically significant among self-inflicted firearm injury victims. A small group of studies investigated the intersection of alcohol and firearms laws and alcohol outlets and firearm violence. One of these controlled studies found that off-premise outlets selling takeout alcohol were significantly associated with firearm assault. Additional controlled, population-level risk factor and intervention studies, including randomized trials of which only 1 was identified, are needed. Policies that rezone off-premise alcohol outlets, proscribe blood alcohol levels and enhance penalties for carrying or using firearms while intoxicated, and consider prior drunk driving convictions as a more precise criterion for disqualifying persons from the purchase or possession of firearms deserve further study. PMID:26811427

  18. Alcohol myopia and goal commitment

    PubMed Central

    Sevincer, A. Timur; Oettingen, Gabriele

    2014-01-01

    According to alcohol myopia theory, acute alcohol consumption leads people to disproportionally focus on the salient rather than the peripheral aspects of a situation. We summarize various studies exploring how myopic processes resulting from acute alcohol intake affect goal commitment. After consuming alcohol student participants felt strongly committed to an important personal goal even though they had low expectations of successfully attaining the goal. However, once intoxicated participants were sober again (i.e., not myopic anymore) they failed to act on their goal commitment. In line with alcohol myopia theory, strong goal commitment as a result of alcohol intake was mediated by intoxicated (vs. sober) participants disproportionally focusing on the desirability rather than the feasibility of their goal. Further supporting alcohol myopia theory, when the low feasibility of attaining a particular goal was experimentally made salient (either explicitly or implicitly by subliminal priming), intoxicated participants felt less committed than those who consumed a placebo. We discuss these effects of acute alcohol intake in the context of research on the effects of chronic alcohol consumption on goal commitment. PMID:24624106

  19. Fetal Alcohol Spectrum Disorders (FASDs)

    MedlinePlus

    ... other research. DATA & STATISTICS Data and statistics highlights. Interventions CHOICES program and alcohol screening and brief intervention (SBI). EDUCATION & TRAINING Tools, training centers, & educational resources. ...

  20. Static posturography and intravenous alcohol.

    PubMed

    Uimonen, S; Laitakari, K; Bloigu, R; Reinilä, M; Sorri, M

    1994-01-01

    Twelve health subjects were assessed using static posturography before and after intravenous alcohol infusion in a double-blind experiment. The dose was 0.5 g ethanol per kg body weight in 15 minutes, which raised the blood alcohol concentration to a level of approximately 1 mg/mL. Among other parameters, the average body sway velocity (BSV) and area of body sway (BSA) were measured. BSV was the most sensitive parameter for detecting increased body sway after alcohol infusion, and a significant effect of alcohol on its values was seen at 0.46 to 1.0 mg/mL alcohol concentrations. The second best indicator was the BSA. There was a positive correlation between the BSV and the BSA. The other parameters were not affected. The Romberg quotient remained constant during the alcohol test. The test battery used was relevant to distinguish the effect of alcohol on balance. In this study, acute blood alcohol concentrations of around 0.5 to 1.0 mg/mL affected BSV more significantly than BSA. The authors do not, however, recommend the test for forensic purposes in examining drivers with alcohol in their blood, as there is too much interindividual dispersion in the results.

  1. Alcohol Control and Foster Care

    PubMed Central

    Markowitz, Sara; Cuellar, Alison; Conrad, Ryan M.; Grossman, Michael

    2013-01-01

    Parental alcohol consumption is often associated with an increased likelihood of child abuse. As consumption is related to price, the purpose of this paper is to investigate the propensity for increases in the full price of alcohol to influence entry rates and the length of time spent in foster care. Using alcoholic beverage prices and a measure of availability in combination with data on foster care cases, we find that higher alcohol prices are not effective in reducing foster care entry rates; however, once in foster care, the duration of stay may be shortened by higher prices and reduced availability. PMID:25506296

  2. The Combined Effects of Alcohol, Caffeine and Expectancies on Subjective Experience, Impulsivity and Risk-Taking

    PubMed Central

    Heinz, Adrienne J.; de Wit, Harriet; Lilje, Todd C.; Kassel, Jon D.

    2013-01-01

    Caffeinated alcoholic beverage (CAB) consumption is a rapidly growing phenomenon among young adults and is associated with a variety of health-risk behaviors. The current study examined whether either caffeinated alcohol or the expectation of receiving caffeinated alcohol altered affective, cognitive and behavioral outcomes hypothesized to contribute to risk behavior. Young adult social drinkers (N=146) participated in a single session where they received alcohol (peak Breath Alcohol Content = .088 g/dL, SD = .019; equivalent to about 4 standard drinks) and were randomly assigned to one of four further conditions 1) no caffeine, no caffeine expectancy, 2) caffeine and caffeine expectancy, 3) no caffeine but caffeine expectancy, 4) caffeine but no caffeine expectancy. Participants’ habitual CAB consumption was positively correlated with measures of impulsivity and risky behavior, independently of study drugs. Administration of caffeine (mean dose = 220 mg, SD = 38; equivalent to about 2.75 Red Bulls) in the study reduced subjective ratings of intoxication and reversed the decrease in desire to continue drinking, regardless of expectancy. Caffeine also reduced the effect of alcohol on inhibitory reaction time (faster incorrect responses). Participants not expecting caffeine were less attentive after alcohol, whereas participants expecting caffeine were not, regardless of caffeine administration. Alcohol decreased response accuracy in all participants except those who both expected and received caffeine. Findings suggest that CABs may elevate risk for continued drinking by reducing perceived intoxication, and by maintaining the desire to continue drinking. Simply expecting to consume caffeine may reduce the effects of alcohol on inattention, and either expecting or consuming caffeine may protect against other alcohol-related performance decrements. Caffeine, when combined with alcohol, has both beneficial and detrimental effects on mechanisms known to contribute to

  3. Alcohol mixed with energy drink: Use may be a consequence of heavy drinking.

    PubMed

    Rossheim, Matthew E; Thombs, Dennis L; Weiler, Robert M; Barry, Adam E; Suzuki, Sumihiro; Walters, Scott T; Barnett, Tracey E; Paxton, Raheem J; Pealer, Lisa N; Cannell, Brad

    2016-06-01

    In recent years, studies have indicated that consumers of alcohol mixed with energy drink (AmED) are more likely to drink heavily and experience more negative consequences than consumers who avoid these beverages. Although researchers have identified a number of plausible hypotheses that explain how alcohol-energy drink co-ingestion could cause greater alcohol consumption, there has been no postulation about reverse causal relations. This paper identifies several plausible hypotheses for the observed associations between AmED consumption and greater alcohol consumption, and provides initial evidence for one such hypothesis suggesting that heavy drinking may be a determinant of AmED use. Data collected from 511bar patrons were used to examine the plausibility of one of the proposed hypotheses, i.e., AmED is an artifact of heavy drinking. Associations between the consumption of an assortment of alcoholic beverage types and total alcohol consumption were examined at the event-level, to assess whether AmED is uniquely related with greater alcohol consumption. Increased alcohol consumption was associated with greater odds of consuming most alcoholic beverage types; this association was not unique to AmED. Results support the overlooked hypothesis that AmED use is an artifact of heavy drinking. Thus, AmED consumption may be a consequence or marker of heavier drinking. Much of the existing research on alcoholic beverage types is limited in its ability to implicate any specific type of drink, including AmED, as a cause of increased alcohol consumption and related harm. More rigorous study designs are needed to examine causal relationships. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Categorizing and Promoting Reversibility of Mathematical Concepts

    ERIC Educational Resources Information Center

    Simon, Martin A.; Kara, Melike; Placa, Nicora; Sandir, Hakan

    2016-01-01

    Reversibility of concepts, a key aspect of mathematical development, is often problematic for learners. In this theoretical paper, we present a typology we have developed for categorizing the different reverse concepts that can be related to a particular initial concept and explicate the relationship among these different reverse concepts. We…

  5. 14 CFR 25.933 - Reversing systems.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... reversal in flight the engine will produce no more than flight idle thrust. In addition, it must be shown... kind of failure is extremely remote. (3) Each system must have means to prevent the engine from... alone, under the most critical reversing condition expected in operation. (b) For propeller reversing...

  6. 14 CFR 25.933 - Reversing systems.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... reversal in flight the engine will produce no more than flight idle thrust. In addition, it must be shown... kind of failure is extremely remote. (3) Each system must have means to prevent the engine from... alone, under the most critical reversing condition expected in operation. (b) For propeller reversing...

  7. 14 CFR 25.933 - Reversing systems.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... reversal in flight the engine will produce no more than flight idle thrust. In addition, it must be shown... kind of failure is extremely remote. (3) Each system must have means to prevent the engine from... alone, under the most critical reversing condition expected in operation. (b) For propeller reversing...

  8. Cleaning Our World through Reverse Graffiti

    ERIC Educational Resources Information Center

    Randazzo, Gabe; LaJevic, Lisa

    2013-01-01

    Over the last decade artists have begun to experiment with "reverse pollution" techniques, such as reverse graffiti, which focuses on cleaning environmental surfaces. Having recently been introduced to the works of Moose, the artist known for inventing the reverse graffiti technique, the authors decided to design a curriculum to increase…

  9. 77 FR 64117 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-18

    ... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Special Emphasis Panel. Name of Committee: Date: November 5, 2012. Time: 2:30.... Rippe, Ph.D., Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism, 5635...

  10. 78 FR 66015 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-04

    ... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Special Emphasis Panel; AA-2 Deferred Grant Application Review. Date...: National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane (Teleconference), Rockville, MD 20852...

  11. 77 FR 54919 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-06

    ... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Initial Review Group Biomedical Research Review Subcommittee. Date: October... Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Rm 2019, Bethesda, MD 20892, 301-443-2861, marmillotp...

  12. 75 FR 46949 - National Institute on Alcohol Abuse and Alcoholism; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-04

    ... Alcohol Abuse and Alcoholism; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory... intramural programs and projects conducted by the National Institute on Alcohol Abuse and Alcoholism... Branch, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers...

  13. 78 FR 38353 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-26

    ... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Special Emphasis Panel; Review of Applications on HIV- AIDS/Alcohol....273, Alcohol Research Programs; National Institutes of Health, HHS) Dated: June 19, 2013. Carolyn A...

  14. 76 FR 2129 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-12

    ... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... and Alcoholism, Special Emphasis Panel, ``Review of the Prenatal Alcohol in Sudden Infant Death... Officer, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635 Fishers...

  15. 75 FR 10808 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-09

    ... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... and Alcoholism Special Emphasis Panel; Review of Alcohol Resource Grant Applications. Date: April 6...: Richard A Rippe, Ph.D., Scientific Review Officer, National Institute on Alcohol Abuse & Alcoholism...

  16. 75 FR 71711 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-24

    ... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Initial Review Group; Neuroscience Review Subcommittee. Date: March 8-9, 2011..., Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health...

  17. 75 FR 42451 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-21

    ... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... and Alcoholism, Special Emphasis Panel, Review of Alcohol Research Centers' Applications. Date: August...: Richard Rippe, PhD, Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism...

  18. Remote Whispering Applying Time Reversal

    SciTech Connect

    Anderson, Brian Eric

    The purpose of this project was to explore the use of time reversal technologies as a means for communication to a targeted individual or location. The idea is to have the privacy of whispering in one’s ear, but to do this remotely from loudspeakers not located near the target. Applications of this work include communicating with hostages and survivors in rescue operations, communicating imaging and operational conditions in deep drilling operations, monitoring storage of spent nuclear fuel in storage casks without wires, or clandestine activities requiring signaling between specific points. This technology provides a solution in any application where wiresmore » and radio communications are not possible or not desired. It also may be configured to self calibrate on a regular basis to adjust for changing conditions. These communications allow two people to converse with one another in real time, converse in an inaudible frequency range or medium (i.e. using ultrasonic frequencies and/or sending vibrations through a structure), or send information for a system to interpret (even allowing remote control of a system using sound). The time reversal process allows one to focus energy to a specific location in space and to send a clean transmission of a selected signal only to that location. In order for the time reversal process to work, a calibration signal must be obtained. This signal may be obtained experimentally using an impulsive sound, a known chirp signal, or other known signals. It may also be determined from a numerical model of a known environment in which the focusing is desired or from passive listening over time to ambient noise.« less

  19. Caffeinated Alcoholic Beverages – An Emerging Trend in Alcohol Abuse

    PubMed Central

    Franklin, Kelle M; Hauser, Sheketha R; Bell, Richard L.; Engleman, Eric A

    2014-01-01

    Alcohol use disorders are pervasive in society and their impact affects quality of life, morbidity and mortality, as well as individual productivity. Alcohol has detrimental effects on an individual’s physiology and nervous system, and is associated with disorders of many organ and endocrine systems impacting an individual’s health, behavior, and ability to interact with others. Youth are particularly affected. Unfortunately, adolescent usage also increases the probability for a progression to dependence. Several areas of research indicate that the deleterious effects of alcohol abuse may be exacerbated by mixing caffeine with alcohol. Some behavioral evidence suggests that caffeine increases alcohol drinking and binge drinking episodes, which in turn can foster the development of alcohol dependence. As a relatively new public health concern, the epidemiological focus has been to establish a need for investigating the effects of caffeinated alcohol. While the trend of co-consuming these substances is growing, knowledge of the central mechanisms associated with caffeinated ethanol has been lacking. Research suggests that caffeine and ethanol can have additive or synergistic pharmacological actions and neuroadaptations, with the adenosine and dopamine systems in particular implicated. However, the limited literature on the central effects of caffeinated ethanol provides an impetus to increase our knowledge of the neuroadaptive effects of this combination and their impact on cognition and behavior. Research from our laboratories indicates that an established rodent animal model of alcoholism can be extended to investigate the acute and chronic effects of caffeinated ethanol. PMID:25419478

  20. Parental Alcohol Involvement and Adolescent Alcohol Expectancies Predict Alcohol Involvement in Male Adolescents

    PubMed Central

    Cranford, James A.; Zucker, Robert A.; Jester, Jennifer M.; Puttler, Leon I.; Fitzgerald, Hiram E.

    2010-01-01

    Current models of adolescent drinking behavior hypothesize that alcohol expectancies mediate the effects of other proximal and distal risk factors. This longitudinal study tested the hypothesis that the effects of parental alcohol involvement on their children’s drinking behavior in mid-adolescence are mediated by the children’s alcohol expectancies in early adolescence. A sample of 148 initially 9–11 year old boys and their parents from a high-risk population and a contrast group of community families completed measures of drinking behavior and alcohol expectancies over a 6-year interval. We analyzed data from middle childhood (M age = 10.4 years), early adolescence (M age = 13.5 years), and mid-adolescence (M age = 16.5 years). The sample was restricted only to adolescents who had begun to drink by mid-adolescence. Results from zero-inflated Poisson regression analyses showed that 1) maternal drinking during their children’s middle childhood predicted number of drinking days in middle adolescence; 2) negative and positive alcohol expectancies in early adolescence predicted odds of any intoxication in middle adolescence; and 3) paternal alcoholism during their children’s middle childhood and adolescents’ alcohol expectancies in early adolescence predicted frequency of intoxication in middle adolescence. Contrary to predictions, child alcohol expectancies did not mediate the effects of parental alcohol involvement in this high-risk sample. Different aspects of parental alcohol involvement, along with early adolescent alcohol expectancies, independently predicted adolescent drinking behavior in middle adolescence. Alternative pathways for the influence of maternal and paternal alcohol involvement and implications for expectancy models of adolescent drinking behavior were discussed. PMID:20853923

  1. American Alcohol Photo Stimuli (AAPS): A standardized set of alcohol and matched non-alcohol images.

    PubMed

    Stauffer, Christopher S; Dobberteen, Lily; Woolley, Joshua D

    2017-11-01

    Photographic stimuli are commonly used to assess cue reactivity in the research and treatment of alcohol use disorder. The stimuli used are often non-standardized, not properly validated, and poorly controlled. There are no previously published, validated, American-relevant sets of alcohol images created in a standardized fashion. We aimed to: 1) make available a standardized, matched set of photographic alcohol and non-alcohol beverage stimuli, 2) establish face validity, the extent to which the stimuli are subjectively viewed as what they are purported to be, and 3) establish construct validity, the degree to which a test measures what it claims to be measuring. We produced a standardized set of 36 images consisting of American alcohol and non-alcohol beverages matched for basic color, form, and complexity. A total of 178 participants (95 male, 82 female, 1 genderqueer) rated each image for appetitiveness. An arrow-probe task, in which matched pairs were categorized after being presented for 200 ms, assessed face validity. Criteria for construct validity were met if variation in AUDIT scores were associated with variation in performance on tasks during alcohol image presentation. Overall, images were categorized with >90% accuracy. Participants' AUDIT scores correlated significantly with alcohol "want" and "like" ratings [r(176) = 0.27, p = <0.001; r(176) = 0.36, p = <0.001] and arrow-probe latency [r(176) = -0.22, p = 0.004], but not with non-alcohol outcomes. Furthermore, appetitive ratings and arrow-probe latency for alcohol, but not non-alcohol, differed significantly for heavy versus light drinkers. Our image set provides valid and reliable alcohol stimuli for both explicit and implicit tests of cue reactivity. The use of standardized, validated, reliable image sets may improve consistency across research and treatment paradigms.

  2. The Spectrum of Reversible Minimizers

    NASA Astrophysics Data System (ADS)

    Ureña, Antonio J.

    2018-05-01

    Poincaré and, later on, Carathéodory, showed that the Floquet multipliers of 1-dimensional periodic curves minimizing the Lagrangian action are real and positive. Even though Carathéodory himself observed that this result loses its validity in the general higherdimensional case, we shall show that it remains true for systems which are reversible in time. In this way, we also generalize a previous result by Offin on the hyperbolicity of nondegenerate symmetric minimizers. Our arguments rely on the higher-dimensional generalizations of the Sturm theory which were developed during the second half of the twentieth century by several authors, including Hartman, Morse or Arnol'd.

  3. Benefits of Alcohol on Arsenic Toxicity in Rats.

    PubMed

    Singh, Purnima; Dutta, Shubha Ranjan; Passi, Deepak; Bharti, Jaya

    2017-01-01

    It has been demonstrated earlier that exposure to ethanol and/or arsenic compounds (such as sodium arsenite) produces toxic effects as shown by both in vitro and in vivo experiments. Chronic exposure of humans to arsenic through drinking water, pesticides or consumption of alcoholic beverages has produced major health problem and concern in recent years. Water being one of the main ingredients for alcohol formation (beer fermentation process) can lead to contamination with arsenic. Thus, people consuming such alcohol are getting continuously exposed to arsenic compounds as well along with alcohol. The present study was undertaken to investigate the effect of alcohol co-administration on arsenic induced changes in carbohydrate metabolic status in adult male albino rats. Adult male albino rats of Wistar strain (weighing~100g) were divided into three groups (n=8 rats/group) including Control or vehicle treated (C), Arsenic treated (As) and Arsenic treated alcohol co-exposed (As+Alc). Treatment with Sodium-arsenite included intra-peritoneal injection consecutively for 14 days at a dose of 5.55 mg/kg (equivalent to 35% of LD50) per day. Absolute alcohol (15% v/v) was fed at a dose of 0.5 ml/100 g body weight per day for five consecutive days from start of the treatment schedule. Distilled water (D/W) was used as vehicle. Blood Glucose (BG) level, levels of glycogen, Pyruvic Acid (PA), Free Amino Acid Nitrogen (FAAN), total protein, Glutamate Oxalate transaminase (GOT) and Glutamate Pyruvate Transaminase (GPT) activity, and glucose-6-phosphatase (G6Pase) activity were measured in tissues including liver, kidney and muscle. Treatment with arsenic decreased the levels of BG, liver glycogen and PA, tissue protein and G6Pase activity, GOT activity in liver and muscle, and increased free amino acid content in kidney and muscle, GPT activity in liver and kidney. Alcohol administration to rats co-exposed to arsenic treatment reversed these changes. Thus, it is suggested that

  4. Benefits of Alcohol on Arsenic Toxicity in Rats

    PubMed Central

    Dutta, Shubha Ranjan; Passi, Deepak; Bharti, Jaya

    2017-01-01

    reversed these changes. Conclusion Thus, it is suggested that combined administration of alcohol with arsenic can result in the suppression of the down-regulating action of arsenic on glucose homeostasis as evidenced by its hypoglycaemic effect and increased gluconeogenesis and transamination in liver. PMID:28273963

  5. Organic functional group transformations in water at elevated temperature and pressure: Reversibility, reactivity, and mechanisms

    NASA Astrophysics Data System (ADS)

    Shipp, Jessie; Gould, Ian R.; Herckes, Pierre; Shock, Everett L.; Williams, Lynda B.; Hartnett, Hilairy E.

    2013-03-01

    Many transformation reactions involving hydrocarbons occur in the presence of H2O in hydrothermal systems and deep sedimentary systems. We investigate these reactions using laboratory-based organic chemistry experiments at high temperature and pressure (300 °C and 100 MPa). Organic functional group transformation reactions using model organic compounds based on cyclohexane with one or two methyl groups provided regio- and stereochemical markers that yield information about reversibility and reaction mechanisms. We found rapidly reversible interconversion between alkanes, alkenes, dienes, alcohols, ketones, and enones. The alkane-to-ketone reactions were not only completely reversible, but also exhibited such extensive reversibility that any of the functional groups along the reaction path (alcohol, ketone, and even the diene) could be used as the reactant and form all the other groups as products. There was also a propensity for these ring-based structures to dehydrogenate; presumably from the alkene, through a diene, to an aromatic ring. The product suites provide strong evidence that water behaved as a reactant and the various functional groups showed differing degrees of reactivity. Mechanistically-revealing products indicated reaction mechanisms that involve carbon-centered cation intermediates. This work therefore demonstrates that a wide range of organic compound types can be generated by abiotic reactions at hydrothermal conditions.

  6. Kinematic reversal schemes for the geomagnetic dipole.

    NASA Technical Reports Server (NTRS)

    Levy, E. H.

    1972-01-01

    Fluctuations in the distribution of cyclonic convective cells, in the earth's core, can reverse the sign of the geomagnetic field. Two kinematic reversal schemes are discussed. In the first scheme, a field maintained by cyclones concentrated at low latitude is reversed by a burst of cyclones at high latitude. Conversely, in the second scheme, a field maintained predominantly by cyclones in high latitudes is reversed by a fluctuation consisting of a burst of cyclonic convection at low latitude. The precise fluid motions which produce the geomagnetic field are not known. However, it appears that, whatever the details are, a fluctuation in the distribution of cyclonic cells over latitude can cause a geomagnetic reversal.

  7. CDC Vital Signs: Alcohol and Pregnancy

    MedlinePlus

    ... prematurity, and sudden infant death syndrome (SIDS). Doctors, nurses, or other health professionals can help prevent alcohol ... Fetal Alcohol Spectrum Disorders Toolkit American College of Nurse-Midwives – Alcohol and Pregnancy The Arc’s FASD Prevention ...

  8. Alcohol-crash problem in Canada, 2006

    DOT National Transportation Integrated Search

    2009-01-01

    This report examines: data on alcohol in fatally injured drivers and pedestrians; the number and : percent of people who died in alcohol-related crashes; and alcohol involvement in those crashes : in which someone was seriously injured but not killed...

  9. Alcohol-crash problem in Canada, 2008

    DOT National Transportation Integrated Search

    2010-12-01

    This report examines: data on alcohol in fatally injured drivers and pedestrians; the number and : percent of people who died in alcohol-related crashes; and alcohol involvement in those crashes : in which someone was seriously injured but not killed...

  10. Alcohol-crash problem in Canada, 2007

    DOT National Transportation Integrated Search

    2010-03-01

    This report examines: data on alcohol in fatally injured drivers and pedestrians; the number and : percent of people who died in alcohol-related crashes; and alcohol involvement in those crashes : in which someone was seriously injured but not killed...

  11. Screening For Alcohol-Producing Microbes

    NASA Technical Reports Server (NTRS)

    Schubert, Wayne W.

    1988-01-01

    Dye reaction rapidly identifies alcohol-producing microbial colonies. Method visually detects alcohol-producing micro-organisms, and distinguishes them from other microbial colonies that do not produce alcohol. Method useful for screening mixed microbial populations in environmental samples.

  12. Alcohol involvement in fatal traffic crashes 1987

    DOT National Transportation Integrated Search

    1989-03-01

    Author's abstract: This report describes the magnitude of the alcohol related fatal crash problem in the United States, highlights the circumstances under which fatal crashes are associated with alcohol, and presents recent trends in alcohol related ...

  13. Responsible alcohol service programs evaluation summary report

    DOT National Transportation Integrated Search

    1991-06-01

    TEAM is a responsible alcohol service program developed for public assembly facilities. Its objectives are to promote responsible alcohol service, enhance safety and enjoyment of fans, reduce potential liability, and reduce alcohol-impaired driving. ...

  14. Monkey alcohol tissue research resource: banking tissues for alcohol research.

    PubMed

    Daunais, James B; Davenport, April T; Helms, Christa M; Gonzales, Steven W; Hemby, Scott E; Friedman, David P; Farro, Jonathan P; Baker, Erich J; Grant, Kathleen A

    2014-07-01

    An estimated 18 million adults in the United States meet the clinical criteria for diagnosis of alcohol abuse or alcoholism, a disorder ranked as the third leading cause of preventable death. In addition to brain pathology, heavy alcohol consumption is comorbid with damage to major organs including heart, lungs, liver, pancreas, and kidneys. Much of what is known about risk for and consequences of heavy consumption derive from rodent or retrospective human studies. The neurobiological effects of chronic intake in rodent studies may not easily translate to humans due to key differences in brain structure and organization between species, including a lack of higher-order cognitive functions, and differences in underlying prefrontal cortical neural structures that characterize the primate brain. Further, rodents do not voluntarily consume large quantities of ethanol (EtOH) and they metabolize it more rapidly than primates. The basis of the Monkey Alcohol Tissue Research Resource (MATRR) is that nonhuman primates, specifically monkeys, show a range of drinking excessive amounts of alcohol (>3.0 g/kg or a 12 drink equivalent per day) over long periods of time (12 to 30 months) with concomitant pathological changes in endocrine, hepatic, and central nervous system (CNS) processes. The patterns and range of alcohol intake that monkeys voluntarily consume parallel what is observed in humans with alcohol use disorders and the longitudinal experimental design spans stages of drinking from the EtOH-naïve state to early exposure through chronic abuse. Age- and sex-matched control animals self-administer an isocaloric solution under identical operant procedures. The MATRR is a unique postmortem tissue bank that provides CNS and peripheral tissues, and associated bioinformatics from monkeys that self-administer EtOH using a standardized experimental paradigm to the broader alcohol research community. This resource provides a translational platform from which we can better

  15. The effect of alcohol price on dependent drinkers' alcohol consumption.

    PubMed

    Falkner, Carolyn; Christie, Grant; Zhou, Lifeng; King, Julian

    2015-12-18

    To investigate the current purchasing behaviours of a group of dependent drinkers and their potential response to future increases in the price of alcohol. 115 clients undergoing medical detoxification completed an anonymous survey about their daily alcohol consumption, its cost, their response to potential price increases and strategies previously used when unable to afford alcohol. Mean and median number of standard drinks consumed per day was 24, at a median cost of $25 NZD (95%CI $22, $30). Thirty-six per cent (95%CI 26%, 46%) of the group bought alcohol at $1 or less per standard drink, and the median number of drinks consumed per day (30) by this group was significantly higher (p=0.0028) than the rest of the sample (22.5). The most common strategy used if no money was available to purchase alcohol was to forgo essentials. If facing a potential price rise, 77% (95%CI 69%, 85%) would switch wholly or partially to a cheaper product and 13% (95%CI 8%, 21%) would cut down their drinking. Although the majority of our group would be financially impacted by an increase in the minimum price per standard drink, any potential impacts would be most significant in those buying the cheapest alcohol (who also drink the most), suggesting that minimum pricing may be an important harm minimisation strategy in this group. A minimum price per standard drink would limit the possibility of switching to an alternate cheaper product and likely result in an overall reduction in alcohol consumption in this group. Stealing alcohol, or the use of non-beverage alcohol, were seldom reported as previous strategies used in response to unaffordable alcohol and fears of such are not valid reasons for rejecting minimum pricing to reduce general population consumption.

  16. Paradoxical effects of alcohol information on alcohol outcome expectancies.

    PubMed

    Krank, Marvin D; Ames, Susan L; Grenard, Jerry L; Schoenfeld, Tara; Stacy, Alan W

    2010-07-01

    Cognitive associations with alcohol predict both current and future use in youth and young adults. Much cognitive and social cognitive research suggests that exposure to information may have unconscious influences on thinking and behavior. The present study assessed the impact of information statements on the accessibility of alcohol outcome expectancies. The 2 studies reported here investigated the effects of exposure to alcohol statements typical of informational approaches to prevention on the accessibility of alcohol outcome expectancies. High school and university students were presented with information statements about the effects of alcohol and other commercial products. The alcohol statements were taken from expectancy questionnaires. Some of these statements were presented as facts and others as myths. The retention of detailed information about these statements was manipulated by (i) divided attention versus focused attention or (ii) immediate versus delayed testing. Accessibility of personal alcohol outcome expectancies was subsequently measured using an open-ended question about the expected effects of alcohol. Participants reported more alcohol outcomes seen during the information task as personal expectations about the effects of alcohol use than similar unseen items. Paradoxically, myth statements were also more likely to be reported as expectancies than unseen items in all conditions. Additionally, myth statements were generated less often than fact statements only under the condition of immediate testing with strong content processing instructions. These observations are consistent with findings from cognitive research where familiarity in the absence of explicit memory can have an unconscious influence on performance. In particular, the exposure to these items in an informational format increases accessibility of the seen items even when the participants were told that they were myths. The findings have implications for the development of

  17. Paradoxical Effects of Alcohol Information on Alcohol Outcome Expectancies

    PubMed Central

    Krank, Marvin D.; Ames, Susan L.; Grenard, Jerry L.; Schoenfeld, Tara; Stacy, Alan W.

    2014-01-01

    Background Cognitive associations with alcohol predict both current and future use in youth and young adults. Much cognitive and social cognitive research suggests that exposure to information may have unconscious influences on thinking and behavior. The present study assessed the impact of information statements on the accessibility of alcohol outcome expectancies. Methods The 2 studies reported here investigated the effects of exposure to alcohol statements typical of informational approaches to prevention on the accessibility of alcohol outcome expectancies. High school and university students were presented with information statements about the effects of alcohol and other commercial products. The alcohol statements were taken from expectancy questionnaires. Some of these statements were presented as facts and others as myths. The retention of detailed information about these statements was manipulated by (i) divided attention versus focused attention or (ii) immediate versus delayed testing. Accessibility of personal alcohol outcome expectancies was subsequently measured using an open-ended question about the expected effects of alcohol. Results Participants reported more alcohol outcomes seen during the information task as personal expectations about the effects of alcohol use than similar unseen items. Paradoxically, myth statements were also more likely to be reported as expectancies than unseen items in all conditions. Additionally, myth statements were generated less often than fact statements only under the condition of immediate testing with strong content processing instructions. Conclusions These observations are consistent with findings from cognitive research where familiarity in the absence of explicit memory can have an unconscious influence on performance. In particular, the exposure to these items in an informational format increases accessibility of the seen items even when the participants were told that they were myths. The findings have

  18. [Suicidality and alcohol abuse].

    PubMed

    Tijdink, Joeri K; Smulders, Yvo M; Biesaart, Monique C H I; Vinkers, Christiaan H

    2015-01-01

    This article describes the role played by a patient's mental competency in the assessment and treatment of patients who are under the influence of alcohol and expressing suicidal thoughts. The factors that should be taken into consideration in the assessment of suicidality are not always clear: somatic complications or possible discharge from the emergency room. The treating physician at the emergency department should evaluate the mental competency. The risk of suicide should also be assessed by a psychiatrist. In order to make the right decisions about treatment and mental competency, the key concepts of proportionality, effectiveness and subsidiarity in the assessment of mental competency are crucial. These concepts require a personalized, multidisciplinary approach and result in unique decisions which may differ from case to case. In the assessment and treatment of patients under the influence of alcohol who are suicidal and do not want to have a proper medical evaluation, communication between the emergency physician, internist and psychiatrist is crucial to optimize both evaluation and treatment. In this context, tasks and responsibilities should be clearly defined in order to minimize the risk of errors and complications.

  19. Translating Alcohol Research

    PubMed Central

    Batman, Angela M.; Miles, Michael F.

    2015-01-01

    Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient. Translational research is a multistage process of streamlining the movement of basic biomedical research findings into clinical research and then to the clinical target populations. This process demands efficient bidirectional communication across basic, applied, and clinical science as well as with clinical practitioners. Ongoing work suggests rapid progress is being made with an evolving translational framework within the alcohol research field. This is helped by multiple interdisciplinary collaborative research structures that have been developed to advance translational work on AUD. Moreover, the integration of systems biology approaches with collaborative clinical studies may yield novel insights for future translational success. Finally, appreciation of genetic variation in pharmacological or behavioral treatment responses and optimal communication from bench to bedside and back may strengthen the success of translational research applications to AUD. PMID:26259085

  20. Measurement of alcohol craving.

    PubMed

    Kavanagh, David J; Statham, Dixie J; Feeney, Gerald F X; Young, Ross McD; May, Jon; Andrade, Jackie; Connor, Jason P

    2013-02-01

    Despite considerable research activity and application in treatment, the construct of craving remains poorly understood. We propose that cravings and urges are cognitive-emotional events in time, characterised by frequency, duration, intensity and salience. Commonly used measures of alcohol craving are reviewed, and their strengths and weaknesses identified. Most measures confound craving with behaviours, or with separable cognitive phenomena such as expectancies, intentions, or perceived behavioural control. These confounds have limited our advances in understanding the determinants and consequences of craving. Based on the criteria applied in this review, among the better performing multi-item measures are the Penn Alcohol Craving Scale and Obsessive subscale of the Obsessive-Compulsive Drinking Scale. Optimal assessment strategies are likely to involve daily assessments of peak intensity of cravings, desires or urges and of the frequency and duration of craving episodes. Of particular interest are measures of intensity at times when individuals are at risk of drinking or of other functional impacts from craving. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Mechanisms and cell signaling in alcoholic liver disease

    PubMed Central

    Beier, Juliane I.; McClain, Craig J.

    2013-01-01

    Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60%. The poor prognosis of ALD implies that preventing disease progression would be more effective than treating end-stage liver disease. An obvious avenue of prevention would be to remove the damaging agent; however, the infamously high rate of recidivism in alcoholics makes maintaining abstinence a difficult treatment goal to prevent ALD. Indeed, although the progression of ALD is well-characterized, there is no universally accepted therapy available to halt or reverse this process in humans. With better understanding of the mechanism(s) and risk factors that mediate the initiation and progression of ALD, rational targeted therapy can be developed to treat or prevent ALD. The purpose of this review is to summarize the established and proposed mechanisms by which chronic alcohol abuse damages the liver and to highlight key signaling events known or hypothesized to mediate these effects. PMID:20868231

  2. Baclofen for alcohol withdrawal.

    PubMed

    Liu, Jia; Wang, Lu-Ning

    2017-08-20

    Baclofen shows potential for rapidly reducing symptoms of severe alcohol withdrawal syndrome (AWS) in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review published in 2015, Issue 4. To assess the efficacy and safety of baclofen for people with AWS. We updated our searches of the following databases to March 2017: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language. We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies. We used standard methodological procedures expected by Cochrane. We included three RCTs with 141 randomised participants. We did not perform meta-analyses due to the different control interventions. For the comparison of baclofen and placebo (1 study, 31 participants), there was no significant difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores (very low quality evidence). For the comparison of baclofen and diazepam (1 study, 37 participants), there was no significant difference in CIWA-Ar scores (very low quality evidence), adverse events (risk difference (RD) 0.00, 95% confidence interval (CI) -0.10 to 0.10; very low quality evidence), dropouts (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence). For the comparison of

  3. Alcohol vapours sensor based on thin polyaniline salt film and quartz crystal microbalance.

    PubMed

    Ayad, Mohamad M; Torad, Nagy L

    2009-06-15

    A sensor based on the quartz crystal microbalance (QCM) technique was developed for detection of a number of primary aliphatic alcohols such as ethanol, methanol, 1-propanol, and 2-propanol vapours. Detection was based on a sensitive and a thin film of polyaniline, emeraldine salt (ES), coated the QCM electrode. The frequency shifts (Delta f) of the QCM were increased due to the vapour absorption into the ES film. The values of Delta f were found to be linearly correlated with the concentrations of alcohols vapour in mg L(-1). The changes in frequency are due to the hydrophilic character of the ES and the electrostatic interaction as well as the type of the alcohol. The sensor shows a good reproducibility and reversibility. The diffusion and diffusion coefficient (D) of different alcohols vapour were determined. It was found that the sensor follows Fickian kinetics.

  4. A sensor of alcohol vapours based on thin polyaniline base film and quartz crystal microbalance.

    PubMed

    Ayad, Mohamad M; El-Hefnawey, Gad; Torad, Nagy L

    2009-08-30

    Thin films of polyaniline base, emeraldine base (EB), coating on the quartz crystal microbalance (QCM) electrode were used as a sensitive layer for the detection of a number of primary aliphatic alcohols such as ethanol, methanol, 2-propanol and 1-propanol vapours. The frequency shifts (Deltaf) of the QCM were increased due to the vapour adsorption into the EB film. Deltaf were found to be linearly correlated with the concentrations of alcohols vapour in part per million (ppm). The sensitivity of the sensor was found to be governed by the chemical structure of the alcohol. The sensor shows a good reproducibility and reversibility. The diffusions of different alcohols vapour were studied and the diffusion coefficients (D) were calculated. It is concluded that the diffusion of the vapours into the EB film follows Fickian kinetics.

  5. Exercise prescription to reverse frailty.

    PubMed

    Bray, Nick W; Smart, Rowan R; Jakobi, Jennifer M; Jones, Gareth R

    2016-10-01

    Frailty is a clinical geriatric syndrome caused by physiological deficits across multiple systems. These deficits make it challenging to sustain homeostasis required for the demands of everyday life. Exercise is likely the best therapy to reverse frailty status. Literature to date suggests that pre-frail older adults, those with 1-2 deficits on the Cardiovascular Health Study-Frailty Phenotype (CHS-frailty phenotype), should exercise 2-3 times a week, for 45-60 min. Aerobic, resistance, flexibility, and balance training components should be incorporated but resistance and balance activities should be emphasized. On the other hand, frail (CHS-frailty phenotype ≥ 3 physical deficits) older adults should exercise 3 times per week, for 30-45 min for each session with an emphasis on aerobic training. During aerobic, balance, and flexibility training, both frail and pre-frail older adults should work at an intensity equivalent to a rating of perceived exertion of 3-4 ("somewhat hard") on the Borg CR10 scale. Resistance-training intensity should be based on a percentage of 1-repetition estimated maximum (1RM). Program onset should occur at 55% of 1RM (endurance) and progress to higher intensities of 80% of 1RM (strength) to maximize functional gains. Exercise is the medicine to reverse or mitigate frailty, preserve quality of life, and restore independent functioning in older adults at risk of frailty.

  6. Theta, time reversal and temperature

    DOE PAGES

    Gaiotto, Davide; Kapustin, Anton; Komargodski, Zohar; ...

    2017-05-17

    SU(N) gauge theory is time reversal invariant at θ = 0 and θ = π. We show that at θ = π there is a discrete ’t Hooft anomaly involving time reversal and the center symmetry. This anomaly leads to constraints on the vacua of the theory. It follows that at θ = π the vacuum cannot be a trivial non-degenerate gapped state. (By contrast, the vacuum at θ = 0 is gapped, non-degenerate, and trivial.) Due to the anomaly, the theory admits nontrivial domain walls supporting lower-dimensional theories. Depending on the nature of the vacuum at θ = π,more » several phase diagrams are possible. Assuming area law for space-like loops, one arrives at an inequality involving the temperatures at which CP and the center symmetry are restored. We also analyze alternative scenarios for SU(2) gauge theory. The underlying symmetry at θ = π is the dihedral group of 8 elements. If deconfined loops are allowed, one can have two O(2)-symmetric fixed points. In conclusion, it may also be that the four-dimensional theory around θ = π is gapless, e.g. a Coulomb phase could match the underlying anomalies.« less

  7. Questionable Methods in Alcoholism Research.

    ERIC Educational Resources Information Center

    Koocher, Gerald P.

    1991-01-01

    Alcoholism research paradigms that use substantial cash incentives to attract participants and that call for alcoholics to consume ethanol in laboratory raise ethical questions. When using such methods, investigators should be obligated to discuss risk-benefit rationales and detail precautionary behaviors to protect participants. Discussion of…

  8. Orosensory responsiveness and alcohol behaviour.

    PubMed

    Thibodeau, Margaret; Bajec, Martha; Pickering, Gary

    2017-08-01

    Consumption of alcoholic beverages is widespread through much of the world, and significantly impacts human health and well-being. We sought to determine the contribution of orosensation ('taste') to several alcohol intake measures by examining general responsiveness to taste and somatosensory stimuli in a convenience sample of 435 adults recruited from six cohorts. Each cohort was divided into quantiles based on their responsiveness to sweet, sour, bitter, salty, umami, metallic, and astringent stimuli, and the resulting quantiles pooled for analysis (Kruskal-Wallis ANOVA). Responsiveness to bitter and astringent stimuli was associated in a non-linear fashion with intake of all alcoholic beverage types, with the highest consumption observed in middle quantiles. Sourness responsiveness tended to be inversely associated with all measures of alcohol consumption. Regardless of sensation, the most responsive quantiles tended to drink less, although sweetness showed little relationship between responsiveness and intake. For wine, increased umami and metallic responsiveness tended to predict lower total consumption and frequency. A limited examination of individuals who abstain from all alcohol indicated a tendency toward higher responsiveness than alcohol consumers to sweetness, sourness, bitterness, and saltiness (biserial correlation), suggesting that broadly-tuned orosensory responsiveness may be protective against alcohol use and possibly misuse. Overall, these findings confirm the importance of orosensory responsiveness in mediating consumption of alcohol, and indicate areas for further research. Copyright © 2017. Published by Elsevier Inc.

  9. Alcohol and Women. Pamphlet Series.

    ERIC Educational Resources Information Center

    Gomberg, Edith S. Lisansky

    Reasonable and moderate drinking is considered acceptable by the major portion of the population. Although women consume less alcohol than men, alcohol has a greater intoxicating effect for women than for men because of the differences in body water content and proportion of fatty tissue. The prevalence rate of drinking is virtually identical for…

  10. Antecedent Personality Characteristics of Alcoholics.

    ERIC Educational Resources Information Center

    Loper, Rodney G.

    Psychological studies on personality characteristics obtained from individuals prior to being diagnosed as alcoholics are reviewed. Retrospective studies suggesting an association between childhood anti-social behavior and the subsequent problem of alcoholism are presented, supported by studies of the personality inventories of college students…

  11. The Aging and Alcohol Abuse.

    ERIC Educational Resources Information Center

    Brody, Jacob A.

    Demographic data suggest that alcohol abuse among the elderly will increase in proportion to the population growth of that group. Four factors which may cause the elderly to be a highly susceptible group for alcohol problems are: (1) retirement and its boredom, role changes, and financial problems; (2) increased concern with death and losses of…

  12. Alcohol Impairment and Social Drinking.

    ERIC Educational Resources Information Center

    Bates, Marsha E.

    Cognitive abilities of social drinkers are generally thought to be affected by alcohol only during acute intoxication, but several studies suggest that sober-state performance may be affected by the quantity of alcohol consumed per drinking episode. Although the findings regarding sober-state mental deficits in social drinkers are inconclusive,…

  13. Group Process in Alcohol Education.

    ERIC Educational Resources Information Center

    American Driver and Traffic Safety Education Association, Washington, DC.

    This manual describes group process and relates it specifically to alcohol education and to a pilot study conducted in cooperation with the Milwaukee Public Schools. It reports on an effort to prepare teachers to use group process techniques in alcohol education, and on their subsequent use of the process with their high school students. The…

  14. Alcohol, aging, and innate immunity.

    PubMed

    Boule, Lisbeth A; Kovacs, Elizabeth J

    2017-07-01

    The global population is aging: in 2010, 8% of the population was older than 65 y, and that is expected to double to 16% by 2050. With advanced age comes a heightened prevalence of chronic diseases. Moreover, elderly humans fair worse after acute diseases, namely infection, leading to higher rates of infection-mediated mortality. Advanced age alters many aspects of both the innate and adaptive immune systems, leading to impaired responses to primary infection and poor development of immunologic memory. An often overlooked, yet increasingly common, behavior in older individuals is alcohol consumption. In fact, it has been estimated that >40% of older adults consume alcohol, and evidence reveals that >10% of this group is drinking more than the recommended limit by the National Institute on Alcohol Abuse and Alcoholism. Alcohol consumption, at any level, alters host immune responses, including changes in the number, phenotype, and function of innate and adaptive immune cells. Thus, understanding the effect of alcohol ingestion on the immune system of older individuals, who are already less capable of combating infection, merits further study. However, there is currently almost nothing known about how drinking alters innate immunity in older subjects, despite innate immune cells being critical for host defense, resolution of inflammation, and maintenance of immune homeostasis. Here, we review the effects of aging and alcohol consumption on innate immune cells independently and highlight the few studies that have examined the effects of alcohol ingestion in aged individuals. © Society for Leukocyte Biology.

  15. Traffic safety facts 1998 : alcohol

    DOT National Transportation Integrated Search

    1999-01-01

    The National Highway Traffic Safety Administration (NHTSA) defines a fatal traffic crash as being alcohol-related if either a driver or a nonoccupant (e.g., pedestrian) had a blood alcohol concentration (BAC) of 0.01 grams per deciliter (g/dl) or gre...

  16. Traffic safety facts 1995 : alcohol

    DOT National Transportation Integrated Search

    1995-01-01

    The National Highway Traffic Safety Administration (NHTSA) defines a fatal traffic crash as being alcohol-related if either a driver or a nonoccupant (e.g., pedestrian) had a blood alcohol concentration (BAC) of 0.01 grams per deciliter (g/dl) or gre...

  17. Traffic safety facts 1993 : alcohol

    DOT National Transportation Integrated Search

    1994-01-01

    The National Highway Traffic Safety Administration (NHTSA) defines a fatal traffic crash as being alcohol-related if either a driver or a nonoccupant (e.g., pedestrian) had a blood alcohol concentration (BAC) of 0.01 grams per deciliter (g/dl) or gre...

  18. Traffic safety facts 2000 : alcohol

    DOT National Transportation Integrated Search

    2001-01-01

    The National Highway Traffic Safety Administration (NHTSA) defines a fatal traffic crash as being alcohol-related if either a driver or a nonoccupant (e.g., pedestrian) had a blood alcohol concentration (BAC) of 0.01 grams per deciliter (g/dl) or gre...

  19. Traffic safety facts 1994 : alcohol

    DOT National Transportation Integrated Search

    1994-01-01

    The National Highway Traffic Safety Administration (NHTSA) defines a fatal traffic crash as being alcohol-related if either a driver or a nonoccupant (e.g., pedestrian) had a blood alcohol concentration (BAC) of 0.01 grams per deciliter (g/dl) or gre...

  20. Traffic safety facts 1999 : alcohol

    DOT National Transportation Integrated Search

    2000-01-01

    The National Highway Traffic Safety Administration (NHTSA) defines a fatal traffic crash as being alcohol-related if either a driver or a nonoccupant (e.g., pedestrian) had a blood alcohol concentration (BAC) of 0.01 grams per deciliter (g/dl) or gre...