Lever conditioned stimulus-directed autoshaping induced by saccharin-ethanol unconditioned stimulus solution: effects of ethanol concentration and trial spacing.

Science.gov (United States)

Tomie, Arthur; Festa, Eugene D; Sparta, Dennis R; Pohorecky, Larissa A

2003-05-01

Two experiments were designed to evaluate whether brief access to a saccharin-ethanol solution would function as an effective unconditioned stimulus (US) in Pavlovian-autoshaping procedures. In these experiments, the insertion of a lever conditioned stimulus (CS) was followed by the brief presentation of a sipper tube containing saccharin-ethanol US solution. Experience with this Pavlovian-autoshaping procedure engendered lever CS-directed autoshaping conditioned responses (CRs) in all rats. In Experiment 1, the concentration of ethanol [0%, 2%, 4%, 6%, or 8% (vol./vol.)] in 0.1% saccharin was systematically increased within subjects across autoshaping sessions to evaluate the relation between a rat's drinking and lever pressing. In Experiment 2, the mean intertrial interval (ITI) duration (60, 90, 120 s) was systematically increased within subjects across autoshaping sessions to evaluate the effect of ITI duration on drinking and lever pressing. A pseudoconditioning control group received lever CS randomly with respect to the saccharin-ethanol US solution. In Experiment 1, lever-press autoshaping CRs developed in all rats, and the tendency of a rat to drink an ethanol concentration was predictive of the performance of lever-press autoshaping CRs. In Experiment 2, longer ITIs induced more lever CS-directed responding, and CS-US paired procedures yielded more lever CS-directed responding than that observed in CS-US random procedures. Saccharin-ethanol is an effective US in Pavlovian-autoshaping procedures, inducing more CS-directed responding than in pseudoconditioning controls receiving CS-US random procedures. More lever CS-directed responding was observed when there was more drinking of the saccharin-ethanol US solution (Experiment 1); when the CS and US were paired, rather than random (Experiment 2); and with longer mean ITI durations (Experiment 2). This pattern of results is consistent with the hypothesis that lever CS-directed responding reflects performance

Volumetric Behavior of Sodium Saccharin in Water and (0.1, 0.3, and 0.5 m Fructose at (298.15, 303.15, 308.15, and 313.15 K

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Sanjeevan J. Kharat

2017-04-01

Full Text Available In order to get the information regarding the sweetener-water and sweetener-sweetener interactions, densities of sodium saccharin in water and (0.1, 0.3, and 0.5 m fructose have been measured at (298.15, 303.15, 308.15, and 313.15 K by the use of bicapillary pycnometer. From density values, partial molar volumes, expansion coefficient, Hepler’s constant, apparent specific volumes, partial molar volumes of transfer, doublet and triplet interaction coefficients have been calculated. From density study, it has been concluded that strong water-sodium saccharin interactions exist. Sodium saccharin is water structure maker. Strong interactions exist between sodium saccharin and fructose. In presence of fructose, the interactions exist between hydrophilic group (–OH, C=O, and –O– of fructose and sodium ion of sodium saccharin in aqueous solutions of sodium saccharin. All investigated solutions exhibit sweet taste. DOI: http://dx.doi.org/10.17807/orbital.v9i1.921 

Acquisition of i.v. cocaine self-administration in adolescent and adult male rats selectively bred for high and low saccharin intake.

Science.gov (United States)

Perry, Jennifer L; Anderson, Marissa M; Nelson, Sarah E; Carroll, Marilyn E

2007-05-16

Adolescence and excessive intake of saccharin have each been previously associated with enhanced vulnerability to drug abuse. In the present study, we focused on the relationship between these two factors using male adolescent and adult rats selectively bred for high (HiS) and low (LoS) levels of saccharin intake. On postnatal day 25 (adolescents) or 150 (adults), rats were implanted with an intravenous catheter and trained to self-administer cocaine (0.4 mg/kg) using an autoshaping procedure that consisted of two 6-h sessions. In the first 6 h, rats were given non-contingent cocaine infusions at random intervals 10 times per hour, and during the second 6-h session, rats were allowed to self-administer cocaine under a fixed ratio 1 (FR 1) lever-response contingency. Acquisition was defined as a total of at least 250 infusions over 5 consecutive days, and rats were given 30 days to meet the acquisition criterion. Subsequently, saccharin phenotype scores were determined by comparing 24-h saccharin and water consumption in two-bottle tests to verify HiS/LoS status. Adolescent LoS rats had a faster rate of acquisition of cocaine self-administration than adult LoS rats; however, adolescent and adult HiS rats acquired at the same rate. Both HiS and LoS adolescents had significantly higher saccharin phenotype scores than HiS and LoS adults, respectively. Additionally, saccharin score was negatively correlated with the number of days to meet the acquisition criterion for cocaine self-administration, but this was mostly accounted for by the HiS adolescents. These results suggest that during adolescence, compared with adulthood, rats have both an increased avidity for sweets and vulnerability to initiate drug abuse.

Saccharin and aspartame, compared with sucrose, induce greater weight gain in adult Wistar rats, at similar total caloric intake levels.

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Feijó, Fernanda de Matos; Ballard, Cíntia Reis; Foletto, Kelly Carraro; Batista, Bruna Aparecida Melo; Neves, Alice Magagnin; Ribeiro, Maria Flávia Marques; Bertoluci, Marcello Casaccia

2013-01-01

It has been suggested that the use of nonnutritive sweeteners (NNSs) can lead to weight gain, but evidence regarding their real effect in body weight and satiety is still inconclusive. Using a rat model, the present study compares the effect of saccharin and aspartame to sucrose in body weight gain and in caloric intake. Twenty-nine male Wistar rats received plain yogurt sweetened with 20% sucrose, 0.3% sodium saccharin or 0.4% aspartame, in addition to chow and water ad libitum, while physical activity was restrained. Measurements of cumulative body weight gain, total caloric intake, caloric intake of chow and caloric intake of sweetened yogurt were performed weekly for 12 weeks. Results showed that addition of either saccharin or aspartame to yogurt resulted in increased weight gain compared to addition of sucrose, however total caloric intake was similar among groups. In conclusion, greater weight gain was promoted by the use of saccharin or aspartame, compared with sucrose, and this weight gain was unrelated to caloric intake. We speculate that a decrease in energy expenditure or increase in fluid retention might be involved. Copyright © 2012 Elsevier Ltd. All rights reserved.

Aspartame-fed zebrafish exhibit acute deaths with swimming defects and saccharin-fed zebrafish have elevation of cholesteryl ester transfer protein activity in hypercholesterolemia.

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Kim, Jae-Yong; Seo, Juyi; Cho, Kyung-Hyun

2011-11-01

Although many artificial sweeteners (AS) have safety issues, the AS have been widely used in industry. To determine the physiologic effect of AS in the presence of hyperlipidemia, zebrafish were fed aspartame or saccharin with a high-cholesterol diet (HCD). After 12 days, 30% of zebrafish, which consumed aspartame and HCD, died with exhibiting swimming defects. The aspartame group had 65% survivability, while the control and saccharin groups had 100% survivability. Under HCD, the saccharin-fed groups had the highest increase in the serum cholesterol level (599 mg/dL). Aspartame-fed group showed a remarkable increase in serum glucose (up to 125 mg/dL), which was 58% greater than the increase in the HCD alone group. The saccharin and HCD groups had the highest cholesteryl ester transfer protein (CETP) activity (52% CE-transfer), while the HCD alone group had 42% CE-transfer. Histologic analysis revealed that the aspartame and HCD groups showed more infiltration of inflammatory cells in the brain and liver sections. Conclusively, under presence of hyperlipidemia, aspartame-fed zebrafish exhibited acute swimming defects with an increase in brain inflammation. Saccharin-fed zebrafish had an increased atherogenic serum lipid profile with elevation of CETP activity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Changes in saccharin preference behavior as a primary outcome to evaluate pain and analgesia in acetic acid-induced visceral pain in mice.

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de la Puente, Beatriz; Romero-Alejo, Elizabeth; Vela, José Miguel; Merlos, Manuel; Zamanillo, Daniel; Portillo-Salido, Enrique

2015-01-01

Reflex-based procedures are important measures in preclinical pain studies that evaluate stimulated behaviors. These procedures, however, are insufficient to capture the complexity of the pain experience, which is often associated with the depression of several innate behaviors. While recent studies have made efforts to evidence the suppression of some positively motivated behaviors in certain pain models, they are still far from being routinely used as readouts for analgesic screening. Here, we characterized and compared the effect of the analgesic ibuprofen (Ibu) and the stimulant, caffeine, in assays of acute pain-stimulated and pain-depressed behavior. Intraperitoneal injection of acetic acid (AA) served as a noxious stimulus to stimulate a writhing response or depress saccharin preference and locomotor activity (LMA) in mice. AA injection caused the maximum number of writhes between 5 and 20 minutes after administration, and writhing almost disappeared 1 hour later. AA-treated mice showed signs of depression-like behaviors after writhing resolution, as evidenced by reduced locomotion and saccharin preference for at least 4 and 6 hours, respectively. Depression-like behaviors resolved within 24 hours after AA administration. A dose of Ibu (40 mg/kg) - inactive to reduce AA-induced abdominal writhing - administered before or after AA injection significantly reverted pain-induced saccharin preference deficit. The same dose of Ibu also significantly reverted the AA-depressed LMA, but only when it was administered after AA injection. Caffeine restored locomotion - but not saccharin preference - in AA-treated mice, thus suggesting that the reduction in saccharin preference - but not in locomotion - was specifically sensitive to analgesics. In conclusion, AA-induced acute pain attenuated saccharin preference and LMA beyond the resolution of writhing behavior, and the changes in the expression of hedonic behavior, such as sweet taste preference, can be used as a more

Changes in saccharin preference behavior as a primary outcome to evaluate pain and analgesia in acetic acid-induced visceral pain in mice

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de la Puente B

2015-10-01

Full Text Available Beatriz de la Puente, Elizabeth Romero-Alejo, José Miguel Vela, Manuel Merlos, Daniel Zamanillo, Enrique Portillo-Salido Department of Pharmacology, Drug Discovery and Preclinical Development, ESTEVE, Barcelona, SpainAbstract: Reflex-based procedures are important measures in preclinical pain studies that evaluate stimulated behaviors. These procedures, however, are insufficient to capture the complexity of the pain experience, which is often associated with the depression of several innate behaviors. While recent studies have made efforts to evidence the suppression of some positively motivated behaviors in certain pain models, they are still far from being routinely used as readouts for analgesic screening. Here, we characterized and compared the effect of the analgesic ibuprofen (Ibu and the stimulant, caffeine, in assays of acute pain-stimulated and pain-depressed behavior. Intraperitoneal injection of acetic acid (AA served as a noxious stimulus to stimulate a writhing response or depress saccharin preference and locomotor activity (LMA in mice. AA injection caused the maximum number of writhes between 5 and 20 minutes after administration, and writhing almost disappeared 1 hour later. AA-treated mice showed signs of depression-like behaviors after writhing resolution, as evidenced by reduced locomotion and saccharin preference for at least 4 and 6 hours, respectively. Depression-like behaviors resolved within 24 hours after AA administration. A dose of Ibu (40 mg/kg – inactive to reduce AA-induced abdominal writhing – administered before or after AA injection significantly reverted pain-induced saccharin preference deficit. The same dose of Ibu also significantly reverted the AA-depressed LMA, but only when it was administered after AA injection. Caffeine restored locomotion – but not saccharin preference – in AA-treated mice, thus suggesting that the reduction in saccharin preference – but not in locomotion – was specifically

Determination of Aspartame, Caffeine, Saccharin, and Benzoic Acid in Beverages by High Performance Liquid Chromatography.

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Delaney, Michael F.; And Others

1985-01-01

Describes a simple and reliable new quantitative analysis experiment using liquid chromatography for the determinaiton of caffeine, saccharin, and sodium benzoate in beverages. Background information, procedures used, and typical results obtained are provided. (JN)

Synthesis and characterization of some complexes with imidazole and pyrazole from saccharinate transition ions in oxidation state (II)

International Nuclear Information System (INIS)

Pineda Cedeno, Leslie William

2001-01-01

The synthesis and characterization of metal ions saccharinate of the first serie of transition with the imidazole and pyrazole molecules in water and absolute ethanol were studied. In general, it found that in this series of saccharinate of coordinated water molecules are replaced by imidazole and pyrazole molecules with different substitution patterns, generating neutral complex of molecular formula [M(Sac) 2 (L) n (H 2 O) n-4 ] and cationic complex of molecular formula [M(L) n (H 2 O) 2 ]x2Sac, [M(L) n (H 2 O) 3 ]x2Sac, [M(L) n ]x2Sac, where M = V(II), Cr(II), Mc(II), Fe(II), Co(II), Ni(II) y Zn(II); Sac = saccharinate ion; L = imidazole (imd) and pyrazole (pir) and n = 6,4,3 and 2. These compounds are soluble in DMF and insoluble in all other common solvents. In turn, synthesized compounds in water were characterized by X ray crystallography, where preliminary data of refinement cycles, generate formulas of isostructural type [M(imd) 4 (H 2 O) 2 ]x2Sac and [M(Sac) 2 (pir) 2 (H 2 O) 2 ] where M = Co(II), Ni(II). The imidazole complex crystallize in the triclinic crystal system and space group P-1, while the pyrazole complexes crystallize in the monoclinic crystal system and space group P2 (1)/n. Gradual diminution was observed in the bond distances of M-N (saccharinate ion), M-N (imidazole) and M-N (pyrazole). The complex was characterized by spectroscopic methods, magnetic and electrochemical. (author) [es

Unusual saccharin-N,O (carbonyl) coordination in mixed-ligand copper(II) complexes: Synthesis, X-ray crystallography and biological activity

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Mokhtaruddin, Nur Shuhada Mohd; Yusof, Enis Nadia Md; Ravoof, Thahira B. S. A.; Tiekink, Edward R. T.; Veerakumarasivam, Abhi; Tahir, Mohamed Ibrahim Mohamed

2017-07-01

Three tridentate Schiff bases containing N and S donor atoms were synthesized via the condensation reaction between S-2-methylbenzyldithiocarbazate with 2-acetyl-4-methylpyridine (S2APH); 4-methyl-3-thiosemicarbazide with 2-acetylpyridine (MT2APH) and 4-ethyl-3-thiosemicarbazide with 2-acetylpyridine (ET2APH). Three new, binuclear and mixed-ligand copper(II) complexes with the general formula, [Cu(sac)(L)]2 (sac = saccharinate anion; L = anion of the Schiff base) were then synthesized, and subsequently characterized by IR and UV/Vis spectroscopy as well as by molar conductivity and magnetic susceptibility measurements. The Schiff bases were also spectroscopically characterized using NMR and MS to further confirm their structures. The spectroscopic data indicated that the Schiff bases behaved as a tridentate NNS donor ligands coordinating via the pyridyl-nitrogen, azomethine-nitrogen and thiolate-sulphur atoms. Magnetic data indicated a square pyramidal environment for the complexes and the conductivity values showed that the complexes were essentially non-electrolytes in DMSO. The X-ray crystallographic analysis of one complex, [Cu(sac)(S2AP)]2 showed that the Cu(II) atom was coordinated to the thiolate-S, azomethine-N and pyridyl-N donors of the S2AP Schiff base and to the saccharinate-N from one anion, as well as to the carbonyl-O atom from a symmetry related saccharinate anion yielding a centrosymmetric binuclear complex with a penta-coordinate, square pyramidal geometry. All the copper(II) saccharinate complexes were found to display strong cytotoxic activity against the MCF-7 and MDA-MB-231 human breast cancer cell lines.

Acquisition of i.v. cocaine self-administration in adolescent and adult male rats selectively bred for high and low saccharin intake

OpenAIRE

Perry, Jennifer L.; Anderson, Marissa M.; Nelson, Sarah E.; Carroll, Marilyn E.

2007-01-01

Adolescence and excessive intake of saccharin have each been previously associated with enhanced vulnerability to drug abuse. In the present study, we focused on the relationship between these two factors using male adolescent and adult rats bred for high (HiS) and low (LoS) levels of saccharin intake. On postnatal day 25 (adolescents) or 150 (adults), rats were implanted with an intravenous catheter and trained to self-administer cocaine (0.4 mg/kg) using an autoshaping procedure that consis...

Modified high-density lipoproteins by artificial sweetener, aspartame, and saccharin, showed loss of anti-atherosclerotic activity and toxicity in zebrafish.

Science.gov (United States)

Kim, Jae-Yong; Park, Ki-Hoon; Kim, Jihoe; Choi, Inho; Cho, Kyung-Hyun

2015-01-01

Safety concerns have been raised regarding the association of chronic consumption of artificial sweeteners (ASs) with metabolic disorders, especially in the heart and brain. There has been no information on the in vivo physiological effects of AS consumption in lipoprotein metabolism. High-dosage treatment (final 25, 50, and 100 mM) with AS (aspartame, acesulfame K, and saccharin) to human high-density lipoprotein (HDL) induced loss of antioxidant ability along with elevated atherogenic effects. Aspartame-treated HDL3 (final 100 mM) almost all disappeared due to putative proteolytic degradation. Aspartame- and saccharin-treated HDL3 showed more enhanced cholesteryl ester transfer activity, while their antioxidant ability was disappeared. Microinjection of the modified HDL3 exacerbated the inflammatory death in zebrafish embryos in the presence of oxLDL. These results show that AS treatment impaired the beneficial functions of HDL, resulting in loss of antioxidant and anti-atherogenic activities. These results suggest that aspartame and saccharin could be toxic to the human circulation system as well as embryonic development via impairment of lipoprotein function.

Beyond the "First Hit": Marked Inhibition by N-Acetyl Cysteine of Chronic Ethanol Intake But Not of Early Ethanol Intake. Parallel Effects on Ethanol-Induced Saccharin Motivation.

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Quintanilla, María Elena; Rivera-Meza, Mario; Berríos-Cárcamo, Pablo; Salinas-Luypaert, Catalina; Herrera-Marschitz, Mario; Israel, Yedy

2016-05-01

A number of studies have shown that acetaldehyde synthesized in the brain is necessary to induce ethanol (EtOH) reinforcement in naïve animals (acquisition phase). However, after chronic intake is achieved (maintenance phase), EtOH intake becomes independent of acetaldehyde generation or its levels. Glutamate has been reported to be associated with the maintenance of chronic EtOH intake. The levels of brain extracellular glutamate are modulated by 2 glial processes: glutamate reabsorption via an Na(+) -glutamate transporter (GLT1) and a cystine-glutamate exchanger. Chronic EtOH intake lowers GLT1 levels and increases extracellular glutamate. The administration of N-acetyl cysteine (NAC), a precursor of cystine, has been shown to reduce the relapse of several drugs of abuse, while NAC has not been tested on chronic EtOH intake or on EtOH's influence on the motivation for another drug. These were investigated in the present study. (i) Rats bred for their high EtOH intake were allowed access to 10% EtOH and water up to 87 days. NAC was administered (30 and 60 mg/kg daily, intraperitoneally) for 14 consecutive days, either during the acquisition phase or the maintenance phase of EtOH drinking. (ii) In additional experiments, rats were allowed EtOH (10%) and water access for 61 days, after which EtOH was replaced by saccharin (0.3%) to determine both if chronic EtOH consumption influences saccharin intake and whether NAC modifies the post chronic EtOH saccharin intake. NAC did not influence the acquisition ("first hit") of chronic EtOH intake, but greatly inhibited (60 to 70%; p intake when NAC was administered to animals that were consuming EtOH chronically. NAC did not influence saccharin intake in naïve animals. In animals that had consumed EtOH chronically and were thereafter offered a saccharin solution (0.3%), saccharin intake increased over 100% versus that of EtOH-untreated animals, an effect that was fully suppressed by NAC. N-acetyl cysteine, a drug

75 FR 13495 - Saccharin from the People's Republic of China: Preliminary Results of the 2008-2009 Antidumping...

Science.gov (United States)

2010-03-22

... Republic of China: Preliminary Results of the 2008-2009 Antidumping Duty Administrative Review AGENCY... administrative review of the antidumping duty order on saccharin from the People's Republic of China (``PRC'') covering the period July 1, 2008, through June 30, 2009. This administrative review covers one exporter of...

Evaluation of Derivative Ultraviolet Spectrometry for Determining Saccharin in Cola and Other Matrices: An Instrumental Methods Experiment.

Science.gov (United States)

Stolzberg, Richard J.

1986-01-01

Background information and experimental procedures are provided for an experiment in which three samples of saccharin (a nickel plating solution, a dilute cola drink, and a more concentrated cola drink) are analyzed and the data interpreted using five methods. Precision and accuracy are evaluated and the best method is selected. (JN)

The Reinforcing Properties of Ethanol are Quantitatively Enhanced in Adulthood by Peri-Adolescent Ethanol, but not Saccharin, Consumption in Female Alcohol-Preferring (P) Rats

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Toalston, Jamie E.; Deehan, Gerald A.; Hauser, Sheketha R.; Engleman, Eric A.; Bell, Richard L.; Murphy, James M.; McBride, William J.; Rodd, Zachary A.

2015-01-01

Alcohol drinking during adolescence is associated in adulthood with heavier alcohol drinking and an increased rate of alcohol dependence. Past research in our laboratory has indicated that peri-adolescent ethanol consumption can enhance the acquisition and reduce the rate of extinction of ethanol self-administration in adulthood. Caveats of the past research include reinforcer specificity, increased oral consumption during peri-adolescence, and a lack of quantitative assessment of the reinforcing properties of ethanol. The current experiments were designed to determine the effects of peri-adolescent ethanol or saccharin drinking on acquisition and extinction of oral ethanol self-administration and ethanol seeking, and to quantitatively assess the reinforcing properties of ethanol (progressive ratio). Ethanol or saccharin access by alcohol-preferring (P) rats occurred during postnatal day (PND) 30–60. Animals began operant self-administration of ethanol or saccharin after PND 85. After 10 weeks of daily operant self-administration, rats were tested in a progressive ratio paradigm. Two weeks later, self-administration was extinguished in all rats. Peri-adolescent ethanol consumption specifically enhanced the acquisition of ethanol self-administration, reduced the rate of extinction for ethanol self-administration, and quantitatively increased the reinforcing properties of ethanol during adulthood. Peri-adolescent saccharin consumption was without effect. The data indicate that ethanol consumption during peri-adolescence results in neuroadaptations that may specifically enhance the reinforcing properties of ethanol during adulthood. This increase in the reinforcing properties of ethanol could be a part of biological sequelae that are the basis for the effects of adolescent alcohol consumption on the increase in the rate of alcoholism during adulthood. PMID:26074425

The reinforcing properties of ethanol are quantitatively enhanced in adulthood by peri-adolescent ethanol, but not saccharin, consumption in female alcohol-preferring (P) rats.

Science.gov (United States)

Toalston, Jamie E; Deehan, Gerald A; Hauser, Sheketha R; Engleman, Eric A; Bell, Richard L; Murphy, James M; McBride, William J; Rodd, Zachary A

2015-08-01

Alcohol drinking during adolescence is associated in adulthood with heavier alcohol drinking and an increased rate of alcohol dependence. Past research in our laboratory has indicated that peri-adolescent ethanol consumption can enhance the acquisition and reduce the rate of extinction of ethanol self-administration in adulthood. Caveats of the past research include reinforcer specificity, increased oral consumption during peri-adolescence, and a lack of quantitative assessment of the reinforcing properties of ethanol. The current experiments were designed to determine the effects of peri-adolescent ethanol or saccharin drinking on acquisition and extinction of oral ethanol self-administration and ethanol seeking, and to quantitatively assess the reinforcing properties of ethanol (progressive ratio). Ethanol or saccharin access by alcohol-preferring (P) rats occurred during postnatal day (PND) 30-60. Animals began operant self-administration of ethanol or saccharin after PND 85. After 10 weeks of daily operant self-administration, rats were tested in a progressive ratio paradigm. Two weeks later, self-administration was extinguished in all rats. Peri-adolescent ethanol consumption specifically enhanced the acquisition of ethanol self-administration, reduced the rate of extinction for ethanol self-administration, and quantitatively increased the reinforcing properties of ethanol during adulthood. Peri-adolescent saccharin consumption was without effect. The data indicate that ethanol consumption during peri-adolescence results in neuroadaptations that may specifically enhance the reinforcing properties of ethanol during adulthood. This increase in the reinforcing properties of ethanol could be a part of biological sequelae that are the basis for the effects of adolescent alcohol consumption on the increase in the rate of alcoholism during adulthood. Published by Elsevier Inc.

Simultaneous determination of sodium saccharin, aspartame, acesulfame-K and sucralose in food consumed in Korea using high-performance liquid chromatography and evaporative light-scattering detection.

Science.gov (United States)

Lee, Youngsun; Do, Byungkyung; Lee, Gunyoung; Lim, Ho Soo; Yun, Sang Soon; Kwon, Hoonjeong

2017-05-01

Four artificial sweeteners, i.e., sodium saccharin, aspartame, acesulfame-K and sucralose, are permitted for use in Korea, and recent regulatory changes have expanded the number of food categories in which they may be used. Four artificial sweeteners were determined simultaneously in more than 900 food items from 30 food categories that are commercially available in Korean markets, including both domestic and imported products, using high-performance liquid chromatography and evaporative light-scattering detection (ELSD). A new procedure using 75% acetone to remove fat was applied for sample preparation. The levels detected in all samples were below the maximum permitted use levels established in Korea. Despite the increased number of categories, the only one in which sodium saccharin was newly found was takju, an alcoholic beverage. Sodium saccharin was not found in other beverages in the food analysis or in the food label survey, even though its use was reported in a previous study, suggesting that consumer preference outweighs regulatory decisions. When the analytical results were combined with food-consumption data obtained from the Korea National Health and Nutrition Examination Survey 2010-14, the estimated daily intakes of all the sweeteners were considered safe.

Effect of cigarette smoking on nasal mucociliary clearance: A comparative analysis using saccharin test

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Manu Kurian Baby

2014-01-01

Full Text Available Background: Nasal mucociliary clearance (NMC system transports the mucus layer covering the nasal epithelium towards nasopharynx by ciliary beating at a frequency of 7-16 Hz. NMC is altered by septal deviations, upper respiratory infections, and drugs. Few studies have revealed significant depression of ciliary activity in smokers. We conducted this study to compare NMC and influence duration of smoking on NMC in adult smokers and nonsmokers using saccharin test. Materials and Methods: Our study included 30 nonsmokers and 30 smokers (21-40 years who were not on any medications and had no history of any systemic illness. Time elapsing until the first experience of sweet taste at posterior nasopharynx, following placement of saccharin particle approximately 1 cm behind the anterior end of inferior turbinate was recorded as NMC time in minutes using standard method described by Anderson. Mean NMC of both groups were compared using Student′s t -test and influence of duration was analyzed by one-way Analysis of variance (ANOVA. Results: NMC was significantly prolonged in smokers (481.2 ± 29.83; P 5 years = 637.5 ± 28.49 s; F statistic = 20.8968, P = 0.0000. Conclusions: NMC measurement is a simple and useful index for the assessment of effect of smoking on the ciliary activity of respiratory mucosa. Prolonged clearance observed in smokers of our study may be due to slowed ciliary beat frequency or reduction in number of cilia and changes in viscoelastic properties of mucus.

Sweetener Intake by Rats Selectively Bred for Differential Saccharin Intake: Sucralose, Stevia, and Acesulfame Potassium.

Science.gov (United States)

Dess, Nancy K; Dobson, Kiana; Roberts, Brandon T; Chapman, Clinton D

2017-06-01

Behavioral responses to sweeteners have been used to study the evolution, mechanisms, and functions of taste. Occidental low and high saccharin consuming rats (respectively, LoS and HiS) have been selectively outbred on the basis of saccharin intake and are a valuable tool for studying variation among individuals in sweetener intake and its correlates. Relative to HiS rats, LoS rats consume smaller amounts of all nutritive and nonnutritive sweeteners tested to date, except aspartame. The lines also differ in intake of the commercial product Splenda; the roles of sucralose and saccharides in the difference are unclear. The present study extends prior work by examining intake of custom mixtures of sucralose, maltodextrin, and sugars and Splenda by LoS and HiS rats (Experiment 1A-1D), stevia and a constituent compound (rebaudioside A; Experiment 2A-2E), and acesulfame potassium tested at several concentrations or with 4 other sweeteners at one concentration each (Experiment 3A-3B). Results indicate that aversive side tastes limit intake of Splenda, stevia, and acesulfame potassium, more so among LoS rats than among HiS rats. In addition, regression analyses involving 5 sweeteners support the idea that both sweetness and bitterness are needed to account for intake of nonnutritive sweeteners, more so among LoS rats. These findings contribute to well developed and emerging literatures on sweetness and domain-general processes related to gustation. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Production method of carbamazepine/saccharin cocrystal particles by using two solution mixing based on the ternary phase diagram

Science.gov (United States)

Kudo, Shoji; Takiyama, Hiroshi

2014-04-01

In the pharmaceutical field, improvement of drug solubility is required, and an interest in cocrystals is growing. Crystallization methods for industrial production of cocrystals have not been developed enough whereas many cocrystals have been prepared in order to find a new crystal form by screening in the laboratory. The objective of this study was the development of the crystallization method which is useful for the industrial production of cocrystal particles based on the phase diagram. A cocrystal of carbamazepine and saccharin was selected as a model substance. The ternary phase diagram of carbamazepine and saccharin in methanol at 303 K was measured. A cocrystallization method of mixing two kinds of different eutectic solutions was designed based on the ternary phase diagram. In order to adjust the cocrystallization conditions, the determination method of the driving force for cocrystal deposition such as supersaturation based on mass balance was proposed. The cocrystal particles were obtained under all the conditions of the five mixing ratios. From these experimental results, the relationship between the supersaturation and the induction time for nucleation was confirmed as well as conventional crystallization. In conclusion, the crystallization method for industrial production of cocrystal particles including the determination of the supersaturation was suggested.

Bioavailability of indomethacin-saccharin cocrystals.

Science.gov (United States)

Jung, Min-Sook; Kim, Jeong-Soo; Kim, Min-Soo; Alhalaweh, Amjad; Cho, Wonkyung; Hwang, Sung-Joo; Velaga, Sitaram P

2010-11-01

Pharmaceutical cocrystals are new solid forms with physicochemical properties that appear promising for drug product development. However, the in-vivo bioavailability of cocrystals has rarely been addressed. The cocrystal of indomethacin (IND), a Biopharmaceutical Classification System class II drug, with saccharin (SAC) has been shown to have higher solubility than IND at all pH. In this study, we aimed to evaluate the in-vitro dissolution and in-vivo bioavailability of IND-SAC cocrystals in comparison with IND in a physical mixture and the marketed product Indomee. Scale-up of the cocrystals was undertaken using cooling batch crystallisation without seeding. The chemical and physical purity of the up-scaled material was verified using high-performance liquid chromatography, differential scanning calorimetry and powder X-ray diffraction. The IND-SAC cocrystals and IND plus SAC were mixed with lactose and the formulations were placed into gelatin capsules. In-vitro dissolution studies were then performed using the rotating basket dissolution method. The intrinsic dissolution rate of IND and IND-SAC cocrystals was also determined. Finally, a bioavailability study for the formulations was conducted in beagle dogs. The plasma samples were analysed using high-performance liquid chromatography and the pharmacokinetic data were analysed using standard methodologies.   The bulk cocrystals (i.e. scaled-up material) were chemically and physically pure. The in-vitro dissolution rate of the cocrystals was higher than that of IND and similar to that of Indomee at pH 7.4 and pH 1.2. The in-vivo bioavailability of the IND-SAC cocrystals in dogs was significantly higher (ANOVA, P0.05). The study indicates that the improved aqueous solubility of the cocrystals leads to improved bioavailability of IND. Thus, the cocrystals are a viable alternative solid form that can improve the dissolution rate and bioavailability of poorly soluble drugs. © 2010 The Authors. JPP © 2010 Royal

Structural investigation of nitrogen-linked saccharinate-tetrazole

Science.gov (United States)

Gómez-Zavaglia, A.; Ismael, A.; Cabral, L. I. L.; Kaczor, A.; Paixão, J. A.; Fausto, R.; Cristiano, M. L. S.

2011-09-01

The molecular structure of nitrogen-linked saccharinate-tetrazole, N-(1,1-dioxo-1,2-benzisothiazol-3-yl)-amine-1 H-tetrazole (BAT), was investigated in the crystalline state using X-ray crystallography and infrared and Raman spectroscopies, and isolated in argon matrix by infrared spectroscopy. Interpretation of the experimental results was supported by quantum chemical calculations undertaken at the DFT(B3LYP)/6-311++G(3df,3pd) level of theory. In the neat crystalline solid (space group C2/ c, a = 21.7493(3) Å, b = 8.85940(10) Å, c = 10.76900(10) Å, β = 103.3300(10) deg; Z = 8), BAT units exist in the (1 H)-tetrazole aminosaccharin tautomeric form, with the NH spacer establishing a hydrogen bond to the nitrogen in position-4 of the tetrazole group of a neighbour molecule, and the NH group of the tetrazole fragment forming a bifurcated H-bond to the saccharyl nitrogen of the same molecule and to one of the oxygen atoms of a second neighbour molecule. On the other hand, according to both the matrix isolation infrared studies and the theoretical calculations, the isolated BAT molecule exists preferentially as the (1 H)-tetrazole iminosaccharin tautomer, where the main stabilizing interaction is the intramolecular H-bond established between the NH group of the saccharyl ring and the tetrazole nitrogen atom in position 4. A detailed conformational analysis of the studied molecule and full assignment of the vibrational spectra for both the matrix-isolated compound and crystalline sample were undertaken.

Physicochemical and mechanical properties of carbamazepine cocrystals with saccharin.

Science.gov (United States)

Rahman, Ziyaur; Samy, Raghu; Sayeed, Vilayat A; Khan, Mansoor A

2012-01-01

The aim of present research was to investigate the physicochemical, mechanical properties, and stability characteristics of cocrystal of carbamazepine (CBZ) using saccharin (SAC) as a coformer. The cocrystals were prepared by solubility method and characterized by pH-solubility profile, intrinsic dissolution by static disk method, and surface morphology by scanning electron microscopy (SEM), crystallinity by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), and mechanical properties by Heckel analysis. Stability of the cocrystals were assessed by storing them at 60 (°)C for two weeks, 25 (°)C/60%RH, 40 (°)C/75%RH and 40 (°)C/94%RH for one month and compared with the stability of CBZ. The solubility profile of cocrystal was similar to CBZ. The cocrystal and CBZ have shown the same stability profile at all the conditions of studies except at 40 (°)C/94%RH. Unlike the CBZ, cocrystal was stable against dihydrate transformation. The compacts of cocrystal have a greater tensile strength and more compressibility. The Heckel analysis suggested that plastic deformation started at low compression pressure in the cocrystal than CBZ. In summary, the cocrystal form of carbamazepine provides another avenue for product development which is more stable than the parent drug.

Liquid chromatographic determination of saccharin in beverages and desserts: complementary collaborative study.

Science.gov (United States)

Sjöberg, A M

1988-01-01

A complementary collaborative study was conducted on a liquid chromatographic method for determination of saccharin in accordance with the latest international recommendations. One industrial and 6 official food control laboratories analyzed 3 samples of a juice, a soft drink, and a dessert at concentration levels of 26-90 mg/L, 33-73 mg/L, and 56-147 mg/kg, respectively. Blind duplicates and a blank were supplied for each type of material at each concentration level. The beverage was chromatographed directly and the dessert was extracted with ethanol before chromatography. Average recoveries were 95-107%. The reproducibility relative standard deviations were 6.4-7.3% for the juice, 9.2-20.6% for the soft drink, and 13.4-16.2% for the dessert. The outlier percentage was 14.3%. The results were compared with those of an earlier collaborative study by Nordic laboratories and with general collaborative results obtained by AOAC.

The effect of current density and saccharin addition on the grain size of nickel coatings

Energy Technology Data Exchange (ETDEWEB)

Uhm, Young Rang; Park, Keun Yung; Son, Kwang Jae; Shim, Young Ho; Choi, Sun Ju [KAERI, Daejeon (Korea, Republic of)

2012-10-15

Recently, the main advantage of a radioisotope 'fuel' is concentrated, because it is 'burned' at the rate of the isotopes half life. In other words, given a half life of 100 years, a nuclear battery would still produce half of its initial starting power after 100 years. A speck of a radioisotope like nickel 63, for example, contains enough energy to power a nano nuclear battery for decades, and to do so safely. Ni 63, a beta radiation source, is prepared by electrical deposition of radioactive Ni 63 ions on thin non radioactive nickel foil. Ni 63 plating is similar to other electroplating processes that employ soluble metal anodes. It requires the passage of a direct current between two electrodes that are immersed in a conductive, aqueous solution of nickel salts. The charged Ni ions are formed by sulfate, sulfamate, chloride, and a Watts bath. However, the charged Ni 63 ions are formed by dissolving metal Ni 63. To establish the coating condition of Ni 63, non radioactive metal Ni particles were dissolved in an acid solution and electroplated on the Ni sheet. A continuous increase in the grain size versus current density has also been recognized in the direct current electrodeposition of nickel coating. On the other hand, A runa et al. reported that the current density has no significant effect on the grain size of nickel electro deposits. A review of the literature shows that saccharin has often been added to a nickel plating bath since the 1980s to improve the ductility and brightness, and in later periods as a grain refiner agent. In the present paper, not only the preparation of the Ni plating solution prepared by dissolving metal particles but also an optimization of the deposition conditions, such as the influence of current density and saccharin concentration on the grain size, was investigated. The proposed model can also be applied for radioactive Ni 63 electroplating.

The effect of current density and saccharin addition on the grain size of nickel coatings

International Nuclear Information System (INIS)

Uhm, Young Rang; Park, Keun Yung; Son, Kwang Jae; Shim, Young Ho; Choi, Sun Ju

2012-01-01

Recently, the main advantage of a radioisotope 'fuel' is concentrated, because it is 'burned' at the rate of the isotopes half life. In other words, given a half life of 100 years, a nuclear battery would still produce half of its initial starting power after 100 years. A speck of a radioisotope like nickel 63, for example, contains enough energy to power a nano nuclear battery for decades, and to do so safely. Ni 63, a beta radiation source, is prepared by electrical deposition of radioactive Ni 63 ions on thin non radioactive nickel foil. Ni 63 plating is similar to other electroplating processes that employ soluble metal anodes. It requires the passage of a direct current between two electrodes that are immersed in a conductive, aqueous solution of nickel salts. The charged Ni ions are formed by sulfate, sulfamate, chloride, and a Watts bath. However, the charged Ni 63 ions are formed by dissolving metal Ni 63. To establish the coating condition of Ni 63, non radioactive metal Ni particles were dissolved in an acid solution and electroplated on the Ni sheet. A continuous increase in the grain size versus current density has also been recognized in the direct current electrodeposition of nickel coating. On the other hand, A runa et al. reported that the current density has no significant effect on the grain size of nickel electro deposits. A review of the literature shows that saccharin has often been added to a nickel plating bath since the 1980s to improve the ductility and brightness, and in later periods as a grain refiner agent. In the present paper, not only the preparation of the Ni plating solution prepared by dissolving metal particles but also an optimization of the deposition conditions, such as the influence of current density and saccharin concentration on the grain size, was investigated. The proposed model can also be applied for radioactive Ni 63 electroplating

Anti-solvent co-crystallization of carbamazepine and saccharin.

Science.gov (United States)

Wang, In-Chun; Lee, Min-Jeong; Sim, Sang-Jun; Kim, Woo-Sik; Chun, Nan-Hee; Choi, Guang J

2013-06-25

The co-crystal approach has been investigated extensively over the past decade as one of the most promising methods to enhance the dissolution properties of insoluble drug substances. Co-crystal powders are typically produced by mechanical grinding (neat or wet) or a solution method (evaporation or cooling). In this study, high-purity carbamazepine-saccharin (CBZ-SAC) co-crystals were manufactured by a novel method, anti-solvent addition. Among various solvents, methanol was found to perform well with water as the anti-solvent for the co-crystallization of CBZ and SAC. When water was added to the methanol solution of CBZ and SAC at room temperature under agitation, nucleation of CBZ-SAC co-crystals occurred within 2-3 min. Co-crystallization was complete after 30 min, giving a solid yield as high as 84.5% on a CBZ basis. The effects of initial concentrations, focusing on the SAC/CBZ ratio, were examined to establish optimal conditions. The whole anti-solvent co-crystallization process was monitored at-line via ATR-FTIR analysis of regularly sampled solutions. The nucleation and crystal growth of CBZ-SAC co-crystals were detected by a significant increase in absorption in the range of 2400-2260 cm(-1), associated with the formation of hydrogen bonds between the carbonyl group in CBZ and the N-H of SAC. When CBZ hydrates were formed as impurities during anti-solvent co-crystallization, the hydrogen bonding between methanol and water was reduced greatly, primarily due to the incorporation of water molecules into the CBZ crystal lattice. In conclusion, an anti-solvent approach can be used to produce highly pure CBZ-SAC co-crystal powders with a high solid yield. Copyright © 2013 Elsevier B.V. All rights reserved.

Characteristics of indomethacin-saccharin (IMC-SAC) co-crystals prepared by an anti-solvent crystallization process.

Science.gov (United States)

Chun, Nan-Hee; Wang, In-Chun; Lee, Min-Jeong; Jung, Yun-Taek; Lee, Sangkil; Kim, Woo-Sik; Choi, Guang J

2013-11-01

The creation of co-crystals of various insoluble drug substances has been extensively investigated as a promising approach to improve their pharmaceutical performance. In this study, co-crystal powders of indomethacin and saccharin (IMC-SAC) were prepared by an anti-solvent (water) addition and compared with co-crystals by evaporation method. No successful synthesis of a pharmaceutical co-crystal powder via an anti-solvent approach has been reported. Among solvents examined, methanol was practically the only one that resulted in the formation of highly pure IMC-SAC co-crystal powders by anti-solvent approach. The mechanism of a preferential formation of IMC-SAC co-crystal to IMC was explained with two aspects: phase solubility diagram and solution complexation concept. Accordingly, the anti-solvent approach can be considered as a competitive route for producing pharmaceutical co-crystal powders with acceptable properties. Copyright © 2013 Elsevier B.V. All rights reserved.

Saccharin fading is not required for the acquisition of alcohol self-administration, and can alter the dynamics of cue-alcohol memory reconsolidation.

Science.gov (United States)

Puaud, Mickaël; Ossowska, Zofia; Barnard, Jordan; Milton, Amy L

2018-04-01

Animal models of alcohol-seeking are useful for understanding alcohol addiction and for treatment development, but throughput in these models is limited by the extensive pretraining required to overcome the aversive taste of ethanol. Work by Augier et al. (Psychopharmacology 231: 4561-4568, 2014) indicates that Wistar rats will self-administer alcohol without water deprivation, exposure to sweetened ethanol solutions or intermittent access to ethanol. We sought to replicate and extend the work of Augier et al. by comparing the acquisition of instrumental self-administration of ethanol in Lister-Hooded rats that had been previously saccharin faded (SF group) or not (NSF group). We also aimed to determine whether NMDA receptor antagonism with MK-801, given at memory reactivation, reduced subsequent ethanol-seeking behaviour in both groups of animals. Finally, we assessed the ethanol preference of SF and NSF rats using the two-bottle choice procedure. Both SF and NSF groups acquired instrumental self-administration of ethanol, though SF rats consumed fewer of the earned reinforcers. MK-801, given at memory reactivation, had different effects on NSF and SF rats: impairing the capacity of an ethanol-paired conditioned stimulus (CS) to support reinstatement in NSF rats, and enhancing it in SF rats. Finally, neither SF nor NSF rats showed a preference for ethanol. Our data support those of Augier et al. (Psychopharmacology 231: 4561-4568, 2014) that pretraining is unnecessary for rats to acquire instrumental self-administration of ethanol. Indeed, saccharin fading may produce a weaker memory that extinguishes more readily, thus accounting for the different effects of MK-801 on SF and NSF rats.

Coformer selection based on degradation pathway of drugs: a case study of adefovir dipivoxil-saccharin and adefovir dipivoxil-nicotinamide cocrystals.

Science.gov (United States)

Gao, Yuan; Gao, Jing; Liu, Ziling; Kan, Hongliang; Zu, Hui; Sun, Wanjin; Zhang, Jianjun; Qian, Shuai

2012-11-15

Adefovir dipivoxil (AD) is a bis(pivaloyloxymethyl) prodrug of adefovir with chemical stability problem. It undergoes two degradation pathways including hydrolysis and dimerization during storage. Pharmaceutical cocrystallization exhibits a promising approach to enhance aqueous solubility as well as physicochemical stability. In this study we attempted to prepare and investigate the physiochemical properties of AD cocrystals, which were formed with two coformers having different acidity and alkalinity (weakly acidic saccharin (SAC) and weakly basic nicotinamide (NCT)). The presence of different coformer molecules along with AD resulted in altered physicochemical properties. AD-SAC cocrystal showed great improvement in solubility and chemical stability, while AD-NCT did not. Several potential factors giving rise to different solid-state properties were summarized. Different coformers resulted in different cocrystal formation, packing style and hydrogen bond formation. This study could provide the coformer selection strategy based on degradation pathways for some unstable drugs in pharmaceutical cocrystal design. Copyright © 2012 Elsevier B.V. All rights reserved.

21 CFR 180.37 - Saccharin, ammonium saccharin, calcium saccharin, and sodium saccharin.

Science.gov (United States)

2010-04-01

... FOOD OR IN CONTACT WITH FOOD ON AN INTERIM BASIS PENDING ADDITIONAL STUDY Specific Requirements for... when the Commissioner receives the final reports on the ongoing studies in Canada and publishes an...) In beverages, fruit juice drinks, and bases or mixes when prepared for consumption in accordance with...

Volumetric and acoustical behaviour of sodium saccharin in aqueous system over temperature range (20.0-45.0)°C.

Science.gov (United States)

Jamal, Muhammad Asghar; Rashad, Muhammad; Khosa, Muhammad Kaleem; Bhatti, Haq Nawaz

2015-04-15

Densities and ultrasonic velocity values for aqueous solutions of sodium saccharin (SS) has been measured as a function of concentration at 20.0-45.0 °C and atmospheric pressure using DSA-5000 M. The density and ultrasonic velocity values have been further used to calculate apparent molar volume, apparent specific volume, isentropic apparent molar compressibility and compressibility hydration numbers and reported. The values for apparent molar volume obtained at given temperatures showed negative deviations from Debye-Hückel limiting law and used as a direct measure of the ion-ion and ion-solvent interactions. The apparent specific volumes of the solute were calculated and it was found that these values of the investigated solutions lie on the borderline between the values reported for sweet substances. The sweetness response of the sweeteners is then explained in terms of their solution behaviours. Furthermore, the partial molar expansibility, its second derivative, (∂(2)V°/∂T(2)) as Hepler's constant and thermal expansion coefficient have been estimated. Copyright © 2014 Elsevier Ltd. All rights reserved.

Saccharin Sulfonic Acid as an Efficient Catalyst for the Preparation and Deprotection of 1,1-Diacetates

International Nuclear Information System (INIS)

Shirini, F.; Mamaghani, M.; Mostashari-Rad, T.; Abedini, M.

2010-01-01

Saccharin sulfonic acid can be used as an efficient catalyst for the acylation of aldehydes using acetic anhydride. This is also a suitable catalyst for the regeneration of aldehydes from the related acylals in the presence of wet SiO 2 . The significant advantages of this methodology are mild, solvent-free reaction conditions, relatively short reaction times, high yields of the products, selectivity and easy work-up. The Protection and deprotection of organic functional groups are important procceses during multi-step organic synthesis. The choice of a method which is used for the functional group transformations depends on its simplicity, high yields of the desired products, short reaction times, low cost of the process and ease of the work-up procedure. Between the several methods available for the protection of aldehydes, acylal formation is often preferred due to the ease of preparation and the stability of the produced 1,1-diacetate towards basic and neutral conditions. In addition, 1,1-diacetates serve as valuable precursors for asymmetric allylic alkylation and synthesis of natural products as well as for the synthesis of 1-acetoxydienes and 2,2-dichlorovinylacetates for Diels-Alder reactions. Acylals have also been used as cross-linking agents for cellulose in cotton and as bleaching activators in wine-stained fabrics. Moreover, the acylal functionality can be converted to other functional groups by reaction with appropriate nucleophiles

Sub-minute method for simultaneous determination of aspartame, cyclamate, acesulfame-K and saccharin in food and pharmaceutical samples by capillary zone electrophoresis.

Science.gov (United States)

Vistuba, Jacqueline Pereira; Dolzan, Maressa Danielli; Vitali, Luciano; de Oliveira, Marcone Augusto Leal; Micke, Gustavo Amadeu

2015-05-29

This paper reports the development of a sub-minute separation method by capillary zone electrophoresis for the determination of aspartame, cyclamate, acesulfame-K and saccharin in food products and pharmaceutical samples. Separations were performed in a fused uncoated silica capillary with UV detection at 220nm. Samples and standards were injected hydrodynamically using the short-end injection procedure. The electrophoretic system was operated under constant voltage of -30kV. The background electrolyte was composed of 45mmolL(-1) 2-amino-2-(hydroxymethyl)-1,3-propanediol and 15mmolL(-1) benzoic acid at pH 8.4. The separation time for all analytes was less than 1min. Evaluation of analytical parameters of the method showed good linearity (r(2)>0.9972), limit of detection of 3.3-6.4mgL(-1), intermediate precision better than 9.75% (peak area of sample) and recovery in the range of 91-117%. Copyright © 2015 Elsevier B.V. All rights reserved.

“Jello® Shots” and Cocktails as Ethanol Vehicles: Parametric Studies with High- and Low-Saccharin-Consuming Rats

Directory of Open Access Journals (Sweden)

Nancy K. Dess

2013-11-01

Full Text Available Naïve humans and rats voluntarily consume little ethanol at concentrations above ~6% due to its aversive flavor. Developing procedures that boost intake of ethanol or ethanol-paired flavors facilitates research on neural mechanisms of ethanol-associated behaviors and helps identify variables that modulate ethanol intake outside of the lab. The present study explored the impact on consumption of ethanol and ethanol-paired flavors of nutritionally significant parametric variations: ethanol vehicle (gelatin or solution, with or without polycose; ethanol concentration (4% or 10%; and feeding status (chow deprived or ad lib. during flavor conditioning and flavor preference testing. Individual differences were modeled by testing rats of lines selectively bred for high (HiS or low (LoS saccharin intake. A previously reported preference for ethanol-paired flavors was replicated when ethanol had been drunk during conditioning. However, indifference or aversion to ethanol-paired flavors generally obtained when ethanol had been eaten in gelatin during conditioning, regardless of ethanol concentration, feeding status, or caloric value of the vehicle. Modest sex and line variations occurred. Engaging different behavioral systems when eating gelatin, rather than drinking solution, may account for these findings. Implications for parameter selection in future neurobiological research and for understanding conditions that influence ethanol intake outside of the lab are discussed.

Title: Elucidation of Environmental Fate of Artificial Sweeteners (Aspartame, Acesulfame K and Saccharin) by Determining Bimolecular Rate Constants with Hydroxyl Radical at Various pH and Temperature Conditions and Possible Reaction By-Products

Science.gov (United States)

Teraji, T.; Arakaki, T.; Suzuka, T.

2012-12-01

Use of artificial sweeteners in beverages and food has been rapidly increasing because of their non-calorie nature. In Japan, aspartame, acesulfame K and sucralose are among the most widely used artificial sweeteners. Because the artificial sweeteners are not metabolized in human bodies, they are directly excreted into the environment without chemical transformations. We initiated a study to better understand the fate of artificial sweeteners in the marine environment. The hydroxyl radical (OH), the most potent reactive oxygen species, reacts with various compounds and determines the environmental oxidation capacity and the life-time of many compounds. The steady-state OH concentration and the reaction rate constants between the compound and OH are used to estimate the life-time of the compound. In this study, we determine the bimolecular rate constants between aspartame, acefulfame K and saccharin and OH at various pH and temperature conditions using a competition kinetics technique. We use hydrogen peroxide as a photochemical source of OH. Bimolecular rate constant we obtained so far for aspartame was (2.6±1.2)×109 M-1 s-1 at pH = 3.0 and (4.9±2.3)×109 M-1 s-1 at pH = 5.5. Little effect was seen by changing the temperatures between 15 and 40 oC. Activation energy (Ea) was calculated to be -1.0 kJ mol-1 at pH = 3.0, +8.5 kJ mol-1 at pH = 5.5, which could be regarded as zero. We will report bimolecular rate constants at different pHs and temperatures for acesulfame K and saccharin, as well. Possible reaction by-products for aspartame will be also reported. We will further discuss the fate of aspartame in the coastal environment.

Molecular-level elucidation of saccharin-assisted rapid dissolution and high supersaturation level of drug from Eudragit® E solid dispersion.

Science.gov (United States)

Ueda, Keisuke; Kanaya, Harunobu; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

2018-03-01

In this work, the effect of saccharin (SAC) addition on the dissolution and supersaturation level of phenytoin (PHT)/Eudragit® E (EUD-E) solid dispersion (SD) at neutral pH was examined. The PHT/EUD-E SD showed a much slower dissolution of PHT compared to the PHT/EUD-E/SAC SD. EUD-E formed a gel layer after the dispersion of the PHT/EUD-E SD into an aqueous medium, resulting in a slow dissolution of PHT. Pre-dissolving SAC in the aqueous medium significantly improved the dissolution of the PHT/EUD-E SD. Solid-state 13 C NMR measurements showed an ionic interaction between the tertiary amino group of EUD-E and the amide group of SAC in the EUD-E gel layer. Consequently, the ionized EUD-E could easily dissolve from the gel layer, promoting PHT dissolution. Solution-state 1 H NMR measurements revealed the presence of ionic interactions between SAC and the amino group of EUD-E in the PHT/EUD-E/SAC solution. In contrast, interactions between PHT and the hydrophobic group of EUD-E strongly inhibited the crystallization of the former from its supersaturated solution. The PHT supersaturated solution was formed from the PHT/EUD-E/SAC SD by the fast dissolution of PHT and the strong crystallization inhibition effect of EUD-E after aqueous dissolution. Copyright © 2018 Elsevier B.V. All rights reserved.

Mice do not develop conditioned taste aversion because of immunity loss.

Science.gov (United States)

Vidal, Jose

2011-01-01

This study intends to test the generation of conditioned taste aversion and conditioned immunodepression by daily paired administration of saccharin solution with cyclophosphamide, 15 mg/kg, for 4 days. One group of male mice of the outbred CD1 strain drank 0.15% saccharin and received 1 injection of cyclophosphamide, 15 mg/kg, for 4 days (paired group), another group (unpaired group) received the same doses of saccharin and cyclophosphamide noncontingently, the third group (cy60) received saccharin paired with cyclophosphamide, 60 mg/kg, and the fourth group (placebo) received saccharin in the absence of cyclophosphamide. All mice were immunized with keyhole limpet hemocyanin (KLH), 0.2 mg, 1 day before the treatments. Mice of the paired, unpaired and cy60 groups displayed a similarly decreased antibody response to KLH, but mice of the paired group did not develop an aversion to saccharin while mice of the cy60 group did. Besides, repeat presentation of saccharin to mice of the paired group did not alter their antibody response to ovalbumin compared with mice of the unpaired or placebo group. Taste aversion was not elicited in response to impaired immunity and the conditioned stimulus (saccharin) did not impair the antibody response. 2011 S. Karger AG, Basel.

Stress control in electrodeposited CoFe films—Experimental study and analytical model

International Nuclear Information System (INIS)

Brankovic, Stanko R.; Kagajwala, Burhanuddin; George, Jinnie; Majkic, Goran; Stafford, Gery; Ruchhoeft, Paul

2012-01-01

Work investigating the effect of saccharin as an additive on growth stress and structure of electrodeposited CoFe films is presented. The saccharin concentrations were in the range between 0 g L −1 and 1.5 g L −1 . The stress measurements are performed in situ during electrodeposition of CoFe films using cantilever-bending method (curvature measurements). The structure of CoFe films was studied by transmission electron microscopy and X-ray diffraction. Results show that growth stress is a decreasing function of saccharin concentration. No appreciable change in composition, grain size, orientation or texture of CoFe films are observed with increasing saccharin content in solution. The growth stress dependence on saccharin concentration is discussed within the framework of analytical model, which directly links the observed stress decrease with the apparent saccharin coverage of the CoFe film surface during the electrodeposition process.

Optimisation of cognitive performance in rodent operant (touchscreen) testing: Evaluation and effects of reinforcer strength.

Science.gov (United States)

Phillips, Benjamin U; Heath, Christopher J; Ossowska, Zofia; Bussey, Timothy J; Saksida, Lisa M

2017-09-01

Operant testing is a widely used and highly effective method of studying cognition in rodents. Performance on such tasks is sensitive to reinforcer strength. It is therefore advantageous to select effective reinforcers to minimize training times and maximize experimental throughput. To quantitatively investigate the control of behavior by different reinforcers, performance of mice was tested with either strawberry milkshake or a known powerful reinforcer, super saccharin (1.5% or 2% (w/v) saccharin/1.5% (w/v) glucose/water mixture). Mice were tested on fixed (FR)- and progressive-ratio (PR) schedules in the touchscreen-operant testing system. Under an FR schedule, both the rate of responding and number of trials completed were higher in animals responding for strawberry milkshake versus super saccharin. Under a PR schedule, mice were willing to emit similar numbers of responses for strawberry milkshake and super saccharin; however, analysis of the rate of responding revealed a significantly higher rate of responding by animals reinforced with milkshake versus super saccharin. To determine the impact of reinforcer strength on cognitive performance, strawberry milkshake and super saccharin-reinforced animals were compared on a touchscreen visual discrimination task. Animals reinforced by strawberry milkshake were significantly faster to acquire the discrimination than animals reinforced by super saccharin. Taken together, these results suggest that strawberry milkshake is superior to super saccharin for operant behavioral testing and further confirms that the application of response rate analysis to multiple ratio tasks is a highly sensitive method for the detection of behavioral differences relevant to learning and motivation.

Pharmacological effects of ethanol on ingestive behavior of the preweanling rat.

Science.gov (United States)

Kozlov, Andrey P; Nizhnikov, Michael E; Varlinskaya, Elena I; Spear, Norman E

2009-12-14

The present study was designed to test the hypothesis that sensitivity of ingestive behavior of infant rat to the pharmacological effects of ethanol changes between postnatal (P) days 9 and 12. The intake of 0.1% saccharin and water, general motor activity, and myoclonic twitching activity were assessed following administration of three doses of ethanol (0, 0.25, and 0.5 g/kg) while fluids were free available to the animals. The 0.5 g/kg dose of ethanol attenuated saccharin intake in P9 pups and enhanced saccharin intake in P12 rats. On P12 some sex-related differences emerged at 0.5 g/kg of ethanol, with saccharin intake being higher in females than in their male counterparts. Taste reactivity probe revealed that 0.5 g/kg of ethanol increased taste responsiveness to saccharin on P12 but only to infusions presented at a high rate. The results of the present study indicate that ontogenetic changes in sensitivity to the effects of ethanol on ingestive behavior occur during the second postnatal week, with P9 animals being more sensitive to the inhibitory (sedative) effects on saccharin intake and P12 rats being more sensitive to the stimulatory effects of ethanol. We suggest that acute ethanol enhanced saccharin intake via sensitization of oral response to appetitive taste stimulation.

Fenofibrate Administration Reduces Alcohol and Saccharin Intake in Rats: Possible Effects at Peripheral and Central Levels

Directory of Open Access Journals (Sweden)

Mario Rivera-Meza

2017-07-01

Full Text Available We have previously shown that the administration of fenofibrate to high-drinker UChB rats markedly reduces voluntary ethanol intake. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARα agonist, which induces the proliferation of peroxisomes in the liver, leading to increases in catalase levels that result in acetaldehyde accumulation at aversive levels in the blood when animals consume ethanol. In these new studies, we aimed to investigate if the effect of fenofibrate on ethanol intake is produced exclusively in the liver (increasing catalase and systemic levels of acetaldehyde or there might be additional effects at central level. High drinker rats (UChB were allowed to voluntary drink 10% ethanol for 2 months. Afterward, a daily dose of fenofibrate (25, 50 or 100 mg/kg/day or vehicle (as control was administered orally for 14 days. Voluntary ethanol intake was recorded daily. After that time, animals were deprived of ethanol access for 24 h and administered with an oral dose of ethanol (1 g/kg for acetaldehyde determination in blood. Fenofibrate reduced ethanol voluntary intake by 60%, in chronically drinking rats, at the three doses tested. Acetaldehyde in the blood rose up to between 80 μM and 100 μM. Considering the reduction of ethanol consumption, blood acetaldehyde levels and body weight evolution, the better results were obtained at a dose of 50 mg fenofibrate/kg/day. This dose of fenofibrate also reduced the voluntary intake of 0.2% saccharin by 35% and increased catalase levels 2.5-fold in the liver but showed no effects on catalase levels in the brain. To further study if fenofibrate administration changes the motivational properties of ethanol, a conditioned-place preference experiment was carried out. Animals treated with fenofibrate (50 mg/kg/day did not develop ethanol-conditioned place preference (CPP.In an additional experiment, chronically ethanol-drinking rats underwent two cycles of ethanol

Photo-Fenton treatment of saccharin in a solar pilot compound parabolic collector: Use of olive mill wastewater as iron chelating agent, preliminary results.

Science.gov (United States)

Davididou, K; Chatzisymeon, E; Perez-Estrada, L; Oller, I; Malato, S

2018-03-14

The aim of this work was to investigate the treatment of the artificial sweetener saccharin (SAC) in a solar compound parabolic collector pilot plant by means of the photo-Fenton process at pH 2.8. Olive mill wastewater (OMW) was used as iron chelating agent to avoid acidification of water at pH 2.8. For comparative purposes, Ethylenediamine-N, N-disuccinic acid (EDDS), a well-studied iron chelator, was also employed at circumneutral pH. Degradation products formed along treatment were identified by LC-QTOF-MS analysis. Their degradation was associated with toxicity removal, evaluated by monitoring changes in the bioluminescence of Vibrio fischeri bacteria. Results showed that conventional photo-Fenton at pH 2.8 could easily degrade SAC and its intermediates yielding k, apparent reaction rate constant, in the range of 0.64-0.82 L kJ -1 , as well as, eliminate effluent's chronic toxicity. Both OMW and EDDS formed iron-complexes able to catalyse H 2 O 2 decomposition and generate HO. OMW yielded lower SAC oxidation rates (k = 0.05-0.1 L kJ -1 ) than EDDS (k = 2.21-7.88 L kJ -1 ) possibly due to its higher TOC contribution. However, the degradation rates were improved (k = 0.13 L kJ -1 ) by increasing OMW dilution in the reactant mixture. All in all, encouraging results were obtained by using OMW as iron chelating agent, thus rendering this approach promising towards the increase of process sustainability. Copyright © 2018 Elsevier B.V. All rights reserved.

Ethanol-induced conditioned taste aversion in Warsaw Alcohol High-Preferring (WHP) and Warsaw Alcohol Low-Preferring (WLP) rats.

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Dyr, Wanda; Wyszogrodzka, Edyta; Paterak, Justyna; Siwińska-Ziółkowska, Agnieszka; Małkowska, Anna; Polak, Piotr

2016-03-01

The aversive action of the pharmacological properties of ethanol was studied in selectively bred Warsaw Alcohol High-Preferring (WHP) and Warsaw Alcohol Low-Preferring (WLP) rats. For this study, a conditioned-taste aversion test was used. Male WHP and WLP rats were submitted to daily 20-min sessions for 5 days, in which a saccharin solution (1.0 g/L) was available (pre-conditioning phase). Next, this drinking was paired with the injection of ethanol (0, 0.5, 1.0 g/kg), intraperitoneally [i.p.] immediately after removal of the saccharin bottle (conditioning phase). Afterward, the choice between the saccharin solution and water was extended for 18 subsequent days for 20-min daily sessions (post-conditioning phase). Both doses of ethanol did not produce an aversion to saccharin in WLP and WHP rats in the conditioning phase. However, injection of the 1.0 g/kg dose of ethanol produced an aversion in WLP rats that was detected by a decrease in saccharin intake at days 1, 3, 7, and 10 of the post-conditioning phase, with a decrease in saccharin preference for 16 days of the post-conditioning phase. Conditioned taste aversion, measured as a decrease in saccharin intake and saccharin preference, was only visible in WHP rats at day 1 and day 3 of the post-conditioning phase. This difference between WLP and WHP rats was apparent despite similar blood ethanol levels in both rat lines following injection of 0.5 and 1.0 g/kg of ethanol. These results may suggest differing levels of aversion to the post-ingestional effects of ethanol between WLP and WHP rats. These differing levels of aversion may contribute to the selected line difference in ethanol preference in WHP and WLP rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Matrix-isolation FTIR, theoretical structural analysis and reactivity of amino-saccharins: N-(1,1-dioxo-1,2-benzisothiazol-3-yl)- N-methyl amine and - N,N-dimethyl amine

Science.gov (United States)

Almeida, R.; Gómez-Zavaglia, A.; Kaczor, A.; Ismael, A.; Cristiano, M. L. S.; Fausto, R.

2009-12-01

In this work, two novel amino-substituted derivatives of saccharin, N-(1,1-dioxo-1,2-benzisothiazol-3-yl)- N-methyl amine (MBAD) and N-(1,1-dioxo-1,2-benzisothiazol-3-yl)- N, N-dimethyl amine (DMBAD), were synthesized and characterized, and their molecular structure and vibrational properties were investigated by matrix-isolation FTIR spectroscopy and theoretical calculations undertaken using different levels of approximation. The calculations predicted the existence of two conformers of MBAD. The lowest energy form was predicted to be considerably more stable than the second conformer (Δ E > ca. 20 kJ mol -1) and was the sole form contributing to the infrared spectrum of the compound isolated in solid xenon. Both conformers have planar amine moieties. In the case of DMBAD, only one doubly-degenerated-by-symmetry conformer exists, with the amine nitrogen atom considerably pyramidalized. The effect of the electron-withdrawing saccharyl ring on the C-N bond lengths is discussed. The different structural preferences around the amine nitrogen atom in the two molecules were explained in terms of repulsive interactions involving the additional methyl group of DMBAD. Observed structural features are correlated with the reactivity exhibited by the two compounds towards nucleophiles. The experimentally obtained spectra of the matrix-isolated monomers of MBAD and DMBAD were fully assigned by comparison with the corresponding calculated spectra.

Gut Microbiota and a Selectively Bred Taste Phenotype: A Novel Model of Microbiome-Behavior Relationships.

Science.gov (United States)

Lyte, Mark; Fodor, Anthony A; Chapman, Clinton D; Martin, Gary G; Perez-Chanona, Ernesto; Jobin, Christian; Dess, Nancy K

2016-06-01

The microbiota-gut-brain axis is increasingly implicated in obesity, anxiety, stress, and other health-related processes. Researchers have proposed that gut microbiota may influence dietary habits, and pathways through the microbiota-gut-brain axis make such a relationship feasible; however, few data bear on the hypothesis. As a first step in the development of a model system, the gut microbiome was examined in rat lines selectively outbred on a taste phenotype with biobehavioral profiles that have diverged with respect to energy regulation, anxiety, and stress. Occidental low and high-saccharin-consuming rats were assessed for body mass and chow, water, and saccharin intake; littermate controls had shared cages with rats in the experimental group but were not assessed. Cecum and colon microbial communities were profiled using Illumina 16S rRNA sequencing and multivariate analysis of microbial diversity and composition. The saccharin phenotype was confirmed (low-saccharin-consuming rats, 0.7Δ% [0.9Δ%]; high-saccharin-consuming rats, 28.1Δ% [3.6Δ%]). Regardless of saccharin exposure, gut microbiota differed between lines in terms of overall community similarity and taxa at lower phylogenetic levels. Specifically, 16 genera in three phyla distinguished the lines at a 10% false discovery rate. The study demonstrates for the first time that rodent lines created through selective pressure on taste and differing on functionally related correlates host different microbial communities. Whether the microbiota are causally related to the taste phenotype or its correlates remains to be determined. These findings encourage further inquiry on the relationship of the microbiome to taste, dietary habits, emotion, and health.

Control Of Rust Disease In Irradiated Vicia Faba By Using Safe Alternative Methods

International Nuclear Information System (INIS)

Ahmed, B.M.; Helal, I.M.; Mohamed, G.A.

2013-01-01

Infection of Vicia faba with Uromyces viciae-fabae causes significant decrease in growth and total nitrogen content and increase in the phenolic compounds. The study was carried out to investigate the effects of chemicals used as drench application in soil (e.g. saccharin), biotic agents (e.g. Bacillus subtilis) and artificial essential oils (e.g. rosemary) in irradiated (0, 5, 10, 15 Gy) broad bean Vicia faba on the rust fungus Uromyces viciae-fabae. Bacillus subtilis was inoculated to beans at the third leaf then saccharin (5 mM/l) was used as drench application in the soil and the essential oil was used for foliar application at concentrations 0, 500, 1000 and 1500 ppm. All treatments gave positive results to control the disease but differ in the mechanism of action. The control of the disease with saccharin application may be due to the formation of antimicrobial components (wyrone acid) by plant tissues and increase with increasing the concentration of saccharin. In case of using the essential oil, the affect on the microbe was directly observed within 28 h because the oil affect the permeability of cell membrane of the pathogen but in case of Bacillus, it acts as biological control agent induced resistance of plant by affecting the activity of antioxidant enzymes; peroxidase and chitinase. Saccharin and spore suspension induce systemic protection to rust infection after 72 and 96 hours. The disease index and the phenolic compounds were determined because they play important role in the systemic protection of rust disease 96 h after application. The results showed that the phytoalexin wyerone acid was formed in case of biotic agent (Bacillus subtilis) and the chemical (saccharin) but did not form in case of essential oil (rosemary)

Autoshaping of ethanol drinking: an animal model of binge drinking.

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Tomie, Arthur; di Poce, Jason; Derenzo, Christopher C; Pohorecky, Larissa A

2002-01-01

To examine the hypothesis that Pavlovian autoshaping provides an animal learning model of drug abuse, two studies evaluated the induction of ethanol drinking by autoshaping procedures. In Experiment 1, the sipper tube conditioned stimulus (CS) contained saccharin/ethanol solution and was repeatedly paired with food as an unconditioned stimulus (US). The CS-US paired group consumed more of the 0.1% saccharin-6% ethanol solution than did the CS-US random group, revealing that autoshaping conditioned responses (CR) induce ethanol drinking not attributable to pseudo-conditioning. Experiment 2 employed saccharin-fading procedures and showed that the paired vs random group differences in ethanol drinking were maintained, even as the saccharin was eliminated from the solution. The results show that Pavlovian autoshaping procedures induce high volumes of ethanol drinking when the presentation of a sipper tube containing an ethanol solution precedes the response-independent delivery of food. The high volume of ethanol consumed in a brief period of time suggests that Pavlovian autoshaping may be a model of binge drinking.

Effects of cycloheximide on extinction in an appetitively motivated operant conditioning task depend on re-exposure duration.

Science.gov (United States)

Mierzejewski, Pawel; Olczak, Mieszko; Rogowski, Artur; Kostowski, Wojciech; Samochowiec, Jerzy; Filip, Malgorzata; Przegalinski, Edmund; Bienkowski, Przemyslaw

2008-08-29

Little is known about the role of new protein synthesis in extinction of operant responding for natural and chemical reinforcers. In the present study, the authors investigated whether the effects of a protein synthesis inhibitor, cycloheximide (CHX) on extinction of operant responding for sweet reward depended on the duration of re-exposure sessions. In addition, the authors investigated whether the effects of CHX on extinction could generalize to relapse of saccharin seeking induced by discrete cues. CHX injected after short re-exposure sessions (5min) accelerated extinction of non-reinforced responding. In contrast, the drug injected after long re-exposure sessions (30min) partially inhibited extinction. Reinstatement of saccharin seeking induced by the saccharin-paired discrete cues was not altered by the previous treatment with CHX. Concluding, the results of the present study indicate that: (i) the protein synthesis inhibitor, CHX can alter extinction of operant responding for sweet reward in rats; (ii) the effects of CHX on extinction critically depend on the duration of re-exposure/extinction sessions and do not generalize to relapse of saccharin seeking induced by discrete cues.

Dexamethasone: a potent blocker for radiation-induced taste aversion in rats

International Nuclear Information System (INIS)

Cairnie, A.B.; Leach, K.E.

1982-01-01

Rats, trained to drink water during a single 30-min period each day, were then given 0.1% saccharin twice a week and water on other days for 30 min. If 20 rad of radiation (0.2 Gy) were given each time 30 to 40 min after the saccharin the rats developed a profound aversion to saccharin during the course of three weeks, whereas control groups failed to do so. This paradigm was then used to test the ability of drugs, given twice weekly immediately after the saccharin, to prevent the development during three weeks of an aversion when 20 rad was given, 30 to 40 min later. Insulin, domperidone, haloperidol, acetylsalicylic acid, naloxone, chlorpheniramine, cimetidine, and dimethyl sulphoxide were tested without notable success. However dexamethasone, at doses ranging from 0.013 mg/kg to 1.3 mg/kg, significantly attenuated the conditioned taste aversion by up to 60 percent. The results are discussed in terms of a search for an antinauseant and antiemetic drug effective against radiation in man

Radiation-induced taste aversion: effects of radiation exposure level and the exposure-taste interval

International Nuclear Information System (INIS)

Spector, A.C.; Smith, J.C.; Hollander, G.R.

1986-01-01

Radiation-induced taste aversion has been suggested to possibly play a role in the dietary difficulties observed in some radiotherapy patients. In rats, these aversions can still be formed even when the radiation exposure precedes the taste experience by several hours. This study was conducted to examine whether increasing the radiation exposure level could extend the range of the exposure-taste interval that would still support the formation of a taste aversion. Separate groups of rats received either a 100 or 300 R gamma-ray exposure followed 1, 3, 6, or 24 h later by a 10-min saccharin (0.1% w/v) presentation. A control group received a sham exposure followed 1 h later by a 10-min saccharin presentation. Twenty-four hours following the saccharin presentation all rats received a series of twelve 23-h two-bottle preference tests between saccharin and water. The results indicated that the duration of the exposure-taste interval plays an increasingly more important role in determining the initial extent of the aversion as the dose decreases. The course of recovery from taste aversion seems more affected by dose than by the temporal parameters of the conditioning trial

Can overeating induce conditioned taste avoidance in previously food restricted rats?

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Hertel, Amanda; Eikelboom, Roelof

2010-03-30

While feeding is rewarding, the feeling of satiation has been theorized to have a mixed affect. Using a food restriction model of overeating we examined whether bingeing was capable of supporting conditioned taste avoidance (CTA). Adult male Sprague-Dawley rats were maintained on either an ad lib (n=8) or restricted (50% of regular consumption; n=24) food access for 20 days. On Days 9, 14, and 19 all rats were given access to a novel saccharin solution in place of water, and two groups of food restricted rats were given access to either 100% of regular food consumption or ad lib food. Ad lib access in the restricted rats induced significant overeating on all three exposures. After all rats were returned to ad lib feeding, a 24h two-bottle saccharin/water choice test displayed significantly reduced saccharin consumption in the overeating rats, compared to those in the other 3 groups. To determine whether this avoidance was due to a learned association, a second experiment used a latent inhibition paradigm, familiarizing half the rats with the saccharin for 8 days prior to pairing it with overeating. Using the design of Experiment 1, with only the continuously ad lib and the restricted to ad lib feeding groups, it was found that the overeating-induced saccharin avoidance was attenuated by the pre-exposure. These results suggest that self-induced overeating is capable of supporting a learned avoidance of a novel solution suggestive of a conditioned satiety or taste avoidance. (c) 2009 Elsevier Inc. All rights reserved.

GABA(A) receptor modulation during adolescence alters adult ethanol intake and preference in rats.

Science.gov (United States)

Hulin, Mary W; Amato, Russell J; Winsauer, Peter J

2012-02-01

To address the hypothesis that GABA(A) receptor modulation during adolescence may alter the abuse liability of ethanol during adulthood, the effects of adolescent administration of both a positive and negative GABA(A) receptor modulator on adult alcohol intake and preference were assessed. Three groups of adolescent male rats received 12 injections of lorazepam (3.2 mg/kg), dehydroepiandrosterone (DHEA, 56 mg/kg), or vehicle on alternate days starting on postnatal day (PD) 35. After this time, the doses were increased to 5.6 and 100 mg/kg, respectively, for 3 more injections on alternate days. Subjects had access to 25 to 30 g of food daily, during the period of the first 6 injections, and 18 to 20 g thereafter. Food intake of each group was measured 60 minutes after food presentation, which occurred immediately after drug administration on injection days or at the same time of day on noninjection days. When subjects reached adulthood (PD 88), ethanol preference was determined on 2 separate occasions, an initial 3-day period and a 12-day period, in which increasing concentrations of ethanol were presented. During each preference test, intake of water, saccharin, and an ethanol/saccharin solution was measured after each 23-hour access period. During adolescence, lorazepam increased 60-minute food intake, and this effect was enhanced under the more restrictive feeding schedule. DHEA had the opposite effect on injection days, decreasing food intake compared with noninjection days. In adulthood, the lorazepam-treated group preferred the 2 lowest concentrations of ethanol/saccharin more than saccharin alone compared with vehicle-treated subjects, which showed no preference for any concentration of ethanol/saccharin over saccharin. DHEA-treated subjects showed no preference among the 3 solutions. These data demonstrate that GABA(A) receptor modulation during adolescence can alter intake and preference for ethanol in adulthood and highlights the importance of drug history

In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats disrupts brain sexual differentiation

International Nuclear Information System (INIS)

Ikeda, Masahiko; Mitsui, Tetsuo; Setani, Kaoru; Tamura, Masashi; Kakeyama, Masaki; Sone, Hideko; Tohyama, Chiharu; Tomita, Takako

2005-01-01

The effects of in utero and lactational exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on brain sexual differentiation were investigated. TCDD was orally administered to pregnant Holtzman rats on gestation day (GD) 15, and the activity of brain aromatase, a key enzyme for sexual differentiation, was measured in offspring on postnatal day (PND) 2. Changes in sexual dimorphisms of saccharin preference and the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) were examined in adult offspring. In controls, litter means of brain aromatase activity were higher in males than in females. In utero exposure to 200 ng/kg TCDD significantly decreased the sex ratio of aromatase activity (male/female) on PND 2. Offspring were weaned on PND28 and the saccharin test was started on PND84. In controls, saccharin (0.25%) intake (g/kg body weight) was significantly higher in female offspring than in males. In utero exposure to 200 ng/kg TCDD significantly increased saccharin intake in male offspring compared with control males, whereas 800 ng/kg TCDD had no effect. Neither dose of TCDD influenced saccharin intake of female offspring. In controls, SDN-POA volume was significantly greater in males than in females at 14 weeks of age. Exposure to 200 ng/kg TCDD significantly decreased SDN-POA volume in males, whereas 800 ng/kg TCDD had no effect. Neither doses of TCDD influenced the SDN-POA volume in female offspring. These results suggest that in utero and lactational TCDD exposure dose-dependently induces demasculinization in male offspring by inhibiting brain aromatase activity in the hypothalamus-preoptic area during central nervous system development

Gamma radiation-induced conditioned taste aversions in rats: A comparison of the protective effects of area postrema lesions with differing doses of radiation

International Nuclear Information System (INIS)

Ossenkopp, K.P.; Giugno, L.

1989-01-01

Lesions which destroy the area postrema (AP) and damage the adjacent nucleus of the solitary tract (NTS) attenuate or abolish conditioned taste aversions (CTA) induced by a variety of pharmacological agents as well as exposure to radiation. In the present experiment, 4 groups of male rats received lesions of AP and 4 groups were given sham lesions. One sham-lesioned and one AP-lesioned group were given a single pairing of 1-hr access to a novel 0.10% sodium saccharin solution followed immediately with exposure to 0, 100, 200, or 400 rad of gamma radiation, respectively. Four days later all groups were given daily two-bottle preference tests (saccharin vs. water) on 4 consecutive days. The sham-lesioned groups exposed to the radiation (100, 200, or 400 rad) developed profound aversions to the saccharin on all test days (p less than 0.001). In contrast, all of the AP-lesioned groups as well as the sham-irradiated (0 rad) sham-lesioned group exhibited strong, comparable (p greater than 0.30) preferences for saccharin. Thus, lesion of AP abolished the radiation-induced CTA at all dose levels of radiation. These results raise the possibility of pharmacological intervention at the level of AP to prevent radiation-induced CTA in cancer patients undergoing radiation therapy

A mouse model of prenatal ethanol exposure using a voluntary drinking paradigm.

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Allan, Andrea M; Chynoweth, Julie; Tyler, Lani A; Caldwell, Kevin K

2003-12-01

The incidence of fetal alcohol spectrum disorders is estimated to be as high as 1 in 100 births. Efforts to better understand the basis of prenatal ethanol-induced impairments in brain functioning, and the mechanisms by which ethanol produces these defects, will rely on the use of animal models of fetal alcohol exposure (FAE). Using a saccharin-sweetened alcohol solution, we developed a free-choice, moderate alcohol access model of prenatal alcohol exposure. Stable drinking of a saccharin solution (0.066%) was established in female mice. Ethanol then was added to the saccharin in increasing concentrations (2%, 5%, 10% w/v) every 2 days. Water was always available, and mice consumed standard pellet chow. Control mice drank saccharin solution without ethanol. After a stable baseline of ethanol consumption (14 g/kg/day) was obtained, females were impregnated. Ethanol consumption continued throughout pregnancy and then was decreased to 0% in a step-wise fashion over a period of 6 days after pups were delivered. Characterization of the model included measurements of maternal drinking patterns, blood alcohol levels, food consumption, litter size, pup weight, pup retrieval times for the dams, and effects of FAE on performance in fear-conditioned learning and novelty exploration. Maternal food consumption, maternal care, and litter size and number were all found to be similar for the alcohol-exposed and saccharin control animals. FAE did not alter locomotor activity in an open field but did increase the time spent inspecting a novel object introduced into the open field. FAE mice displayed reduced contextual fear when trained using a delay fear conditioning procedure. The mouse model should be a useful tool in testing hypotheses about the neural mechanisms underlying the learning deficits present in fetal alcohol spectrum disorders. Moreover, a mouse prenatal ethanol model should increase the opportunity to use the power of genetically defined and genetically altered mouse

Excitation of lateral habenula neurons as a neural mechanism underlying ethanol-induced conditioned taste aversion.

Science.gov (United States)

Tandon, Shashank; Keefe, Kristen A; Taha, Sharif A

2017-02-15

The lateral habenula (LHb) has been implicated in regulation of drug-seeking behaviours through aversion-mediated learning. In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol-induced conditioned taste aversion (CTA) to saccharin. Ethanol-induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste. In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol-induced CTA. Our results strongly suggest that excitation of LHb neurons is required for ethanol-induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion-mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol-induced aversion, we recorded neural firing in the LHb of freely behaving, water-deprived rats before and after an ethanol-induced (1.5 g kg -1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol-induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced

Excitation of lateral habenula neurons as a neural mechanism underlying ethanol‐induced conditioned taste aversion

Science.gov (United States)

Keefe, Kristen A.; Taha, Sharif A.

2016-01-01

Key points The lateral habenula (LHb) has been implicated in regulation of drug‐seeking behaviours through aversion‐mediated learning.In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol‐induced conditioned taste aversion (CTA) to saccharin.Ethanol‐induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste.In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol‐induced CTA.Our results strongly suggest that excitation of LHb neurons is required for ethanol‐induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Abstract Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion‐mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol‐induced aversion, we recorded neural firing in the LHb of freely behaving, water‐deprived rats before and after an ethanol‐induced (1.5 g kg−1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol‐induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA

Adverse effects of the radioprotector WR2721

International Nuclear Information System (INIS)

Cairnie, A.B.

1983-01-01

S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR2721) has radioprotective properties, but it is also toxic - in man it causes nausea and vomiting. Since radiation also causes nausea and vomiting it is important to know whether WR2721 would increase or decrease the likelihood of nausea and vomiting after radiation. This question was investigated in rats using the phenomenon of aversion to the taste of saccharin, which is readily inducible and is understood to be controlled in rats by the same pathways that control nausea and vomiting in man. The taste aversion was induced by giving 0.2 Gy 60 Co γ radiation 30 min after drinking 0.1% saccharin, or WR2721 immediately after the saccharin, or giving both radiation and WR2721. There were appropriate controls. In sham-irradiated rats, WR2721 (40 or 200 mg/kg, but not 8 mg/kg) produced a significant taste aversion. When WR2721 (40 or 200 mg/kg) was given immediately after the saccharin to irradiated rats it increased the taste aversion significantly, but it did not have any effect at 8 mg/kg. It was concluded that at doses which were optimal for radioprotection (approx.200 mg/kg) or lower, WR2721 increased in rats the taste aversion induced by radiation. By inference if conditioned taste aversion is an appropriate paradigm, WR2721 would increase nausea and vomiting in man induced by radiation

Pavlovian drug-sickness pairings result in the conditioning of an antisickness response.

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Lett, B T

1983-10-01

After a drug conditioned stimulus (CS) has been injected prior to lithium chloride as the unconditioned stimulus (US) on five occasions, the drug CS becomes able to evoke a conditioned antisickness response (CAR). This CAR is implied by the finding that the CS drug mitigates the conditioned saccharin aversion produced by lithium when it is administered in the interval between saccharin consumption and lithium injection. The following drugs were tested and are listed in approximate order of their effectiveness in producing a conditioned antisickness effect: pentobarbital, ethanol, morphine, amphetamine, and chlordiazepoxide.

Sweetness and bitterness taste of meals per se does not mediate gastric emptying in humans.

Science.gov (United States)

Little, Tanya J; Gupta, Nili; Case, R Maynard; Thompson, David G; McLaughlin, John T

2009-09-01

In cell line and animal models, sweet and bitter tastants induce secretion of signaling peptides (e.g., glucagon-like peptide-1 and cholecystokinin) and slow gastric emptying (GE). Whether human GE and appetite responses are regulated by the sweetness or bitterness per se of ingested food is, however, unknown. We aimed to determine whether intragastric infusion of "equisweet" (Study A) or "equibitter" (Study B) solutions slow GE to the same extent, and whether a glucose solution made sweeter by the addition of saccharin will slow GE more potently than glucose alone. Healthy nonobese subjects were studied in a single-blind, randomized fashion. Subjects received 500-ml intragastric infusions of predetermined equisweet solutions of glucose (560 mosmol/kgH(2)O), fructose (290 mosmol/kgH(2)O), aspartame (200 mg), and saccharin (50 mg); twice as sweet glucose + saccharin, water (volumetric control) (Study A); or equibitter solutions of quinine (0.198 mM), naringin (1 mM), or water (Study B). GE was evaluated using a [(13)C]acetate breath test, and hunger and fullness were scored using visual analog scales. In Study A, equisweet solutions did not empty similarly. Fructose, aspartame, and saccharin did not slow GE compared with water, but glucose did (P solution (P > 0.05, compared with glucose alone). In Study B, neither bitter tastant slowed GE compared with water. None of the solutions modulated perceptions of hunger or fullness. We conclude that, in humans, the presence of sweetness and bitterness taste per se in ingested solutions does not appear to signal to influence GE or appetite perceptions.

Estimated intake of intense sweeteners from non-alcoholic beverages in Denmark, 2005

DEFF Research Database (Denmark)

Leth, Torben; Jensen, U.; Fagt, Sisse

2008-01-01

In 2005, 76 out of 177 analysed samples of non-alcoholic beverages were found to contain the intense sweeteners cyclamate, acesulfame-K, aspartame, and saccharin. The content of cyclamate did not exceed the now permitted maximum level in the European Union of 250 mg l(-1) in soft drinks. The esti......In 2005, 76 out of 177 analysed samples of non-alcoholic beverages were found to contain the intense sweeteners cyclamate, acesulfame-K, aspartame, and saccharin. The content of cyclamate did not exceed the now permitted maximum level in the European Union of 250 mg l(-1) in soft drinks...

Role for the Rostromedial Tegmental Nucleus in Signaling the Aversive Properties of Alcohol.

Science.gov (United States)

Glover, Elizabeth J; McDougle, Molly J; Siegel, Griffin S; Jhou, Thomas C; Chandler, L Judson

2016-08-01

While the rewarding effects of alcohol contribute significantly to its addictive potential, it is becoming increasingly appreciated that alcohol's aversive properties also play an important role in the propensity to drink. Despite this, the neurobiological mechanism for alcohol's aversive actions is not well understood. The rostromedial tegmental nucleus (RMTg) was recently characterized for its involvement in aversive signaling and has been shown to encode the aversive properties of cocaine, yet its involvement in alcohol's aversive actions have not been elucidated. Adult male and female Long-Evans rats underwent conditioned taste aversion (CTA) procedures where exposure to a novel saccharin solution was paired with intraperitoneal administration of saline, lithium chloride (LiCl), or ethanol (EtOH). Control rats underwent the same paradigm except that drug and saccharin exposure were explicitly unpaired. Saccharin consumption was measured on test day in the absence of drug administration, and rats were sacrificed 90 to 105 minutes following access to saccharin. Brains were subsequently harvested and processed for cFos immunohistochemistry. The number of cFos-labeled neurons was counted in the RMTg and the lateral habenula (LHb)-a region that sends prominent glutamatergic input to the RMTg. In rats that received paired drug and saccharin exposure, EtOH and LiCl induced significant CTA compared to saline to a similar degree in males and females. Both EtOH- and LiCl-induced CTA significantly enhanced cFos expression in the RMTg and LHb but not the hippocampus. Similar to behavioral measures, no significant effect of sex on CTA-induced cFos expression was observed. cFos expression in both the RMTg and LHb was significantly correlated with CTA magnitude with greater cFos being associated with more pronounced CTA. In addition, cFos expression in the RMTg was positively correlated with LHb cFos. These data suggest that the RMTg and LHb are involved in the expression of

Autoshaping of ethanol drinking in rats: effects of ethanol concentration and trial spacing.

Science.gov (United States)

Tomie, Arthur; Wong, Karlvin; Apor, Khristine; Patterson-Buckendahl, Patricia; Pohorecky, Larissa A

2003-11-01

In two studies, we evaluated the effects of ethanol concentration and trial spacing on Pavlovian autoshaping of ethanol drinking in rats. In these studies, the brief insertion of an ethanol sipper conditioned stimulus (CS) was followed by the response-independent presentation of food unconditioned stimulus (US), inducing sipper CS-directed drinking conditioned responses (CRs) in all rats. In Experiment 1, the ethanol concentration in the sipper CS [0%-16% volume/volume (vol./vol.), in increments of 1%] was systematically increased within subjects across autoshaping sessions. Groups of rats received sipper CS-food US pairings (Paired/Ethanol), a CS-US random procedure (Random/Ethanol), or water sipper CS paired with food US (Paired/Water). In Experiment 2, saccharin-fading procedures were used to initiate, in the Ethanol group, drinking of 6% (vol./vol.) ethanol in 0.1% saccharin or, in the Water group, drinking of tap water in 0.1% saccharin. After elimination of saccharin, and across days, the duration of access to the sipper CS during each autoshaping trial was increased (5, 10, 12.5, 15, 17.5, and 20 s), and subsequently, across days, the duration of the mean intertrial interval (ITI) was increased (60, 90, 120, and 150 s). In Experiment 1, Paired/Ethanol and Random/Ethanol groups showed higher intake of ethanol, in terms of grams per kilogram of body weight, at higher ethanol concentrations, with more ethanol intake recorded in the Paired/Ethanol group. In Experiment 2, the Ethanol group drank more than was consumed by the Water group, and, for both groups, fluid intake increased with longer ITIs. Results support the suggestion that autoshaping contributes to sipper CS-directed ethanol drinking.

Application of Liquid Chromatography-Tandem Mass Spectrometry To Determine Urinary Concentrations of Five Commonly Used Low-Calorie Sweeteners: A Novel Biomarker Approach for Assessing Recent Intakes?

Science.gov (United States)

Logue, Caomhan; Dowey, Le Roy C; Strain, J J; Verhagen, Hans; McClean, Stephen; Gallagher, Alison M

2017-06-07

Although the use of low-calorie sweeteners (LCSs) is widespread, methods of assessing consumption within free-living populations have inherent limitations. Five commonly consumed LCSs, namely, acesulfame-K, saccharin, sucralose, cyclamate, and steviol glycosides, are excreted via the urine, and therefore a urinary biomarker approach may provide more objective LCS intake data. A LC-ESI-MS/MS method of simultaneously determining acesulfame-K, saccharin, sucralose, cyclamate, and the excretory metabolite of steviol glycosides, steviol glucuronide, in human urine was developed and validated. Linearity was observed over a concentration range of 10-1000 ng/mL with coefficients of determination ranging from 0.9969 to 0.9997. Accuracy ranged from 92 to 104%, and intrabatch and interday precisions were within acceptable limits with %CV below 8% for all compounds. A double-blind, randomized crossover dose-response study was conducted to assess the usefulness of urinary LCS excretions (from both fasting spot and a full 24-h urine collection) for investigating recent intakes. Both modes of sampling were useful for distinguishing between the three short-term intakes of acesulfame-K, saccharin, cyclamates, and steviol glycosides (p biomarker approach may be useful for assessing intakes of five commonly consumed LCSs.

Effects of phenobarbital on taste aversion induced by x-radiation

International Nuclear Information System (INIS)

Jolicoeur, F.B.; Wayner, M.J.; Rondeau, D.B.; Merkel, A.D.; Bassano, D.A.

1979-01-01

The effects of phenobarbital on taste aversion induced by x-radiation were examined. Rats were adapted to a 23 hr 50 min water deprivation schedule. On the Treatment Day animals were given a novel 0.125% Na saccharin solution during the 10 min drinking session and were then exposed to 100 rads of x-radiation. The saccharin solution was presented again on six subsequent Test Days. Phenobarbital in doses of 20, 40, 60 and 80 mg/kg was adminstered 15 min prior to drinking on the first Test Day. Results demonstrate the phenobarbital in all doses tested has a significant attenuating effect on radiation induced taste aversion

Suitability of artificial sweeteners as indicators of raw wastewater contamination in surface water and groundwater.

Science.gov (United States)

Tran, Ngoc Han; Hu, Jiangyong; Li, Jinhua; Ong, Say Leong

2014-01-01

There is no quantitative data on the occurrence of artificial sweeteners in the aquatic environment in Southeast Asian countries, particularly no information on their suitability as indicators of raw wastewater contamination on surface water and groundwater. This study provided the first quantitative information on the occurrence of artificial sweeteners in raw wastewater, surface water and groundwater in the urban catchment area in Singapore. Acesulfame, cyclamate, saccharin, and sucralose were ubiquitous in raw wastewater samples at concentrations in the range of ng/L-μg/L, while other sweeteners were not found or found only in a few of the raw wastewater samples. Residential and commercial effluents were demonstrated to be the two main sources of artificial sweeteners entering the municipal sewer systems. Relatively higher concentrations of the detected sweeteners were frequently found in surface waters at the sampling sites located in the residential/commercial areas. No significant difference in the concentrations of the detected sweeteners in surface water or groundwater was noted between wet and dry weather conditions (unpaired T-test, p> 0.05). Relatively higher concentrations and detection frequencies of acesulfame, cyclamate and saccharin in surface water samples were observed at the potentially impacted sampling sites, while these sweeteners were absent in most of the background surface water samples. Similarly, acesulfame, cyclamate, and saccharin were found in most groundwater samples at the monitoring well (GW6), which is located close to known leaking sewer segment; whereas these were absent in the background monitoring well, which is located in the catchment with no known wastewater sources. Taken together, the results suggest that acesulfame, cyclamate, and saccharin can be used as potential indicators of raw wastewater contamination in surface water and groundwater. Copyright © 2013 Elsevier Ltd. All rights reserved.

Failure to produce taste-aversion learning in rats exposed to static electric fields and air ions

Energy Technology Data Exchange (ETDEWEB)

Creim, J.A.; Lovely, R.H.; Weigel, R.J.; Forsythe, W.C.; Anderson, L.E. [Pacific Northwest Labs., Richland, WA (United States)

1995-12-01

Taste-aversion (TA) learning was measured to determine whether exposure to high-voltage direct current (HVdc) static electric fields can produce TA learning in male Long Evans rats. Fifty-six rats were randomly distributed into four groups of 14 rats each. All rats were placed on a 20 min/day drinking schedule for 12 consecutive days prior to receiving five conditioning trials. During the conditioning trials, access to 0.1% sodium saccharin-flavored water was given for 20 min, followed 30 min later by one of four treatments. Two groups of 14 rats each were individually exposed to static electric fields and air ions, one group to +75 kV/m (+2 {times} 10{sup 5} air ions/cm{sup 3}) and the other group to {minus}75 kV/m ({minus}2 {times} 10{sup 5} air ions/cm{sup 3}). Two other groups of 14 rats each served as sham-exposed controls, with the following variation in one of the sham-exposed groups: this group was subdivided into two subsets of seven rats each, so that a positive control group could be included to validate the experimental design. The positive control group (n = 7) was injected with cyclophosphamide 25 mg/kg, i.p., 30 min after access to saccharin-flavored water on conditioning days, whereas the other subset of seven rats was similarly injected with an equivalent volume of saline. Access to saccharin-flavored water on conditioning days was followed by the treatments described above and was alternated daily with water recovery sessions in which the rats received access to water for 20 min in the home cage without further treatment. Following the last water-recovery session, a 20 min, two-bottle preference test (between water and saccharin-flavored water) was administered to each group. The positive control group did show TA learning, thus validating the experimental protocol.

Artificial sweeteners as potential tracers of municipal landfill leachate

International Nuclear Information System (INIS)

Roy, James W.; Van Stempvoort, Dale R.; Bickerton, Greg

2014-01-01

Artificial sweeteners are gaining acceptance as tracers of human wastewater in the environment. The 3 artificial sweeteners analyzed in this study were detected in leachate or leachate-impacted groundwater at levels comparable to those of untreated wastewater at 14 of 15 municipal landfill sites tested, including several closed for >50 years. Saccharin was the dominant sweetener in old (pre-1990) landfills, while newer landfills were dominated by saccharin and acesulfame (introduced 2 decades ago; dominant in wastewater). Cyclamate was also detected, but less frequently. A case study at one site illustrates the use of artificial sweeteners to identify a landfill-impacted groundwater plume discharging to a stream. The study results suggest that artificial sweeteners can be useful tracers for current and legacy landfill contamination, with relative abundances of the sweeteners potentially providing diagnostic ability to distinguish different landfills or landfill cells, including crude age-dating, and to distinguish landfill and wastewater sources. -- Highlights: • Artificial sweeteners detected at 14 of 15 municipal landfill sites. • Concentrations comparable to wastewater even at sites closed for >50 yr. • Saccharin elevated at all sites; potentially diagnostic of landfill impacts. • Potential for age-dating recent (past 2 decades) waste with acesulfame. -- Artificial sweeteners may be useful for tracing landfill leachate contamination and distinguishing it from wastewater impacts

Behavioral Actions of Alcohol: Phenotypic Relations from Multivariate Analysis of Mutant Mouse Data

Science.gov (United States)

Blednov, Yuri A.; Mayfield, R. Dayne; Belknap, John; Harris, R. Adron

2012-01-01

Behavioral studies of genetically diverse mice have proven powerful for determining relationships between phenotypes and have been widely used in alcohol research. Most of these studies rely on naturally occurring genetic polymorphisms among inbred strains and selected lines. Another approach is to introduce variation by engineering single gene mutations in mice. We have tested 37 different mutant mice and their wild type controls for a variety (31) of behaviors and have mined this dataset by K-means clustering and analysis of correlations. We found a correlation between a stress-related response (activity in a novel environment) and alcohol consumption and preference for saccharin. We confirmed several relationships detected in earlier genetic studies including positive correlation of alcohol consumption with saccharin consumption, and negative correlations with conditioned taste aversion and alcohol withdrawal severity. Introduction of single gene mutations either eliminated or greatly diminished these correlations. The three tests of alcohol consumption used (continuous two bottle choice, and two limited access tests: Drinking In the Dark and Sustained High Alcohol Consumption) share a relationship with saccharin consumption, but differ from each other in their correlation networks. We suggest that alcohol consumption is controlled by multiple physiological systems where single gene mutations can disrupt the networks of such systems. PMID:22405477

Development and implementation of the IPCS conceptual framework for evaluating mode of action of chemical carcinogens

International Nuclear Information System (INIS)

Dybing, E.

2002-01-01

The framework developed by the International Programme on Chemical Safety (IPCS) for assessing the mode of action of tumour induction of chemicals in experimental animals has been illustrated with d-limonene, sodium saccharin, di(2-ethylhexyl)phthalate (DEHP) and sulfamethazine as examples. d-Limonene causes renal tumours only in male rats through a response associated with α 2u -globulin. Sodium saccharin induces urinary bladder tumours only in male rats through formation of a urinary precipitate causing erosion of the bladder surface and extensive regenerative hyperplasia. DEHP causes liver tumours in rats and mice through activation of the receptor PPARα leading to peroxisome proliferation and hepatocellular proliferation. Sulfamethazine induces thyroid follicular cell tumours in rats and mice through a mechanism involving altered thyroid hormone homeostasis

Changed preference for sweet taste in adulthood induced by perinatal exposure to bisphenol A-A probable link to overweight and obesity.

Science.gov (United States)

Xu, Xiaobin; Tan, Luei; Himi, Toshiyuki; Sadamatsu, Miyuki; Tsutsumi, Shunsuke; Akaike, Masashi; Kato, Nobumasa

2011-01-01

The preference of obesity has risen dramatically worldwide over the past decades. Some latest reports showed significant increase of obesity in men compared to women. Implication of environmental endocrine disruptors has been focused more and more. Numerous studies in vitro and vivo implied metabolic actions of bisphenol A (BPA), however much less consideration is given to the possibility of BPA exposure-induced change in gender-specific behaviors which result in obesity and overweight. To examine whether perinatal exposure to BPA at relative dose to environmental levels can influence sweet preference of male and female rats and consequently lead to alteration in bodyweight. Rats perinatally exposed to BPA at doses of 0.01, 0.1 and 1.0 mg/L were tested sweet preference for 0.25%, 0.5% saccharin and 15% sucrose by two-bottle choice (water vs. saccharin/sucrose). The food intake, liquid consumption and bodyweight of each rat were monitored daily. At the end of the test, the fat percentage and tail blood pressure were measured. Significant sex difference of preference for 0.25% and 0.5% saccharin was shown in control and all BPA-treated groups (p researches concerning the mechanism are required, the results of the present study are particularly important with regards to the more significant increasing prevalence of obesity in men and the environmental endocrine disruptors. Copyright © 2011 Elsevier Inc. All rights reserved.

Evaluating Suspension Formulations of Theophylline Cocrystals With Artificial Sweeteners.

Science.gov (United States)

Aitipamula, Srinivasulu; Wong, Annie B H; Kanaujia, Parijat

2018-02-01

Pharmaceutical cocrystals have garnered significant interest as potential solids to address issues associated with formulation development of drug substances. However, studies concerning the understanding of formulation behavior of cocrystals are still at the nascent stage. We present results of our attempts to evaluate suspension formulations of cocrystals of an antiasthmatic drug, theophylline, with 2 artificial sweeteners. Stability, solubility, drug release, and taste of the suspension formulations were evaluated. Suspension that contained cocrystal with acesulfame showed higher drug release rate, while a cocrystal with saccharin showed a significant reduction in drug release rate. The cocrystal with saccharin was found stable in suspension for over 9 weeks at accelerated test condition; in contrast, the cocrystal with acesulfame was found unstable. Taste analysis using an electronic taste-sensing system revealed improved sweetness of the suspension formulations with cocrystals. Theophylline has a narrow therapeutic index with a short half-life which necessitates frequent dosing. This adversely impacts patient compliance and enhances risk of gastrointestinal and cardiovascular adverse effects. The greater thermodynamic stability, sweetness, and sustained drug release of the suspension formulation of theophylline-saccharin could offer an alternative solution to the short half-life of theophylline and make it a promising formulation for treating asthmatic pediatric and geriatric patients. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Preparation, structural analysis, and properties of tenoxicam cocrystals.

Science.gov (United States)

Patel, Jagdishwar R; Carlton, Robert A; Needham, Thomas E; Chichester, Clinton O; Vogt, Frederick G

2012-10-15

Cocrystals of tenoxicam, a non-steroidal anti-inflammatory drug, are screened, prepared, and characterized in this study. Nine tenoxicam cocrystals were identified using solvent-drop grinding (SDG) techniques. Structural characterization was performed using powder X-ray diffraction (PXRD), differential scanning calorimetry, and multinuclear solid-state NMR (SSNMR). Thermal analysis, PXRD, and 1D SSNMR are used to detect solvates and phase mixtures encountered in SDG cocrystal screening. 2D SSNMR methods are then used to confirm cocrystal formation and determine structural aspects for selected cocrystals formed with saccharin, salicylic acid, succinic acid, and glycolic acid in comparison to Forms I and III of tenoxicam. Molecular association is demonstrated using cross-polarization heteronuclear dipolar correlation (CP-HETCOR) methods involving (1)H and (13)C nuclei. Short-range (1)H-(13)C CP-HETCOR and (1)H-(1)H double-quantum interactions between atoms of interest, including those engaged in hydrogen bonding, are used to reveal local aspects of the cocrystal structure. (15)N SSNMR is used to assess ionization state and the potential for zwitterionization in the selected cocrystals. The tenoxicam saccharin cocrystal was found to be similar in structure to a previously-reported cocrystal of piroxicam and saccharin. The four selected cocrystals yielded intrinsic dissolution rates that were similar or reduced relative to tenoxicam Form III. Copyright © 2012 Elsevier B.V. All rights reserved.

Sweeteners - sugar substitutes

Science.gov (United States)

... exposed to heat. It is best used in beverages rather than baking. Well-studied, and hasn't ... sweeteners, such as saccharin, in carbonated low-calorie beverages and other products. Most similar to table sugar ...

Electrochemical and surface characterisation of oxide films on nano-grain nickel films electrodeposited on INCOLOY-800

International Nuclear Information System (INIS)

Navin Vinayak, S.; Sunitha, Y.; Rangarajan, S.; Narasimhan, S.V.

2008-01-01

Nano materials have different properties from the corresponding bulk materials because of fine grain size, large fraction of surface atoms, high surface energy and high grain boundary volume fraction. For similar reasons, the nano-alloy coatings show superior high-temperature corrosion resistance and are generally more resistant to stress corrosion cracking. Hence, it is of interest to know the materials performance, if the structural materials used in nuclear reactors are made of nano-grains. In Indian PHWRs, Incoloy-800 is being used as the steam generator tubing material. It's corrosion resistance property is very important as it forms not only the pressure boundary between the radioactive primary water and non-active secondary water but also from the view point of loss of heavy water, in case of any corrosion damage. In this paper, the corrosion resistance of the oxide films formed on nano-grain nickel film electrodeposited on Incoloy-800 (a) in the presence of saccharine (WS) and (b) in the absence of saccharine (WOS) were compared with that formed on Commercial Ni foil, using electrochemical dc polarization and ac impedance techniques. The surface morphology, elemental analysis and grain size were studied with SEM, EDX and XRD techniques respectively. The nano-grain nickel films were prepared on Incoloy-800 by electrodeposition using Watt's Bath with saccharine sodium as a surfactant. The oxide films were developed by exposing them to LiOH solution (pH-10.0) at 245 deg C for 3 days (A-group) and 7 days (B-group). XRD results showed that the grain size of Ni formed in the absence of saccharine (WOS) was ∼ 60 nm and did not change after being autoclaved. But, for Ni formed in the presence of saccharine (WS), the grain size was ∼ 16 nm which increased to 40-50 nm after being autoclaved. With both A and B-group specimens, the PDAP curves showed an active-passive transition, a passive region and a transpassive region in 2N H 2 SO 4 . However, the critical

Water metabolism and modification of tritium excretion in the rat

International Nuclear Information System (INIS)

Ichimasa, Y.; Akita, Y.

1982-01-01

1. The intake and excretion of tritium were studied in rats exposed to tritiated water vapor. The metabolism of tritium was also investigated in rats given single administrations of tritiated water and in rats given daily administrations (per os or i.p.). The results were essentially in accord with those reported previously. 2. Amounts of drinking water consumed and urine excreted by rats drinking water with 0.15% saccharin were 1.5 to 2 times higher than in rats drinking tap water. The tritium activity in various tissues of rats drinking water with 0.15% saccharin decreased to about half of that of rats drinking tap water. A similar tendency was observed also in rats drinking beer. The diuretic agent sodium acetazolamide also enhanced the urinary excretion of tritium. (author)

Acute, but not chronic, exposure to d-cycloserine facilitates extinction and modulates spontaneous recovery of a conditioned taste aversion.

Science.gov (United States)

Mickley, G Andrew; Remus, Jennifer L; Ramos, Linnet; Wilson, Gina N; Biesan, Orion R; Ketchesin, Kyle D

2012-01-18

D-cycloserine, the glutamate N-methyl-D-aspartate receptor partial agonist, has been reported to facilitate the extinction of learned fears acquired in both naturalistic and laboratory settings. The current study extended this literature by evaluating the ability of either chronic or acute administrations of DCS to modulate the extinction and spontaneous recovery of a conditioned taste aversion (CTA). Twenty-three hour fluid-deprived Sprague-Dawley rats acquired a strong CTA following 3 pairings of a conditioned stimulus (CS; 0.3% oral saccharin)+unconditioned stimulus [US; 81 mg/kg (i.p.) lithium chloride (LiCl)]. In separate groups of rats, we then employed 2 different extinction paradigms: (1) CS-only (CSO-EXT) in which saccharin was presented every-other day, or (2) Explicitly Unpaired (EU-EXT) in which both saccharin and LiCl were presented but on alternate days. Previous studies have indicated that the EU-EXT procedure speeds up the extinction process. Further, spontaneous recovery of a CTA emerges following CSO-EXT but the EU-EXT paradigm causes a suppression of spontaneous recovery. DCS (15 mg/kg, i.p.) was administered immediately after daily liquid presentations (saccharin or water, alternate days) during the extinction period. In an acute drug manipulation, DCS (15 mg/kg, i.p.) or saline control injections were administered for 4 days only. This was done during one of 3 different phases of extinction [i.e., static (2-5%), early dynamic (8-16%), or middle dynamic (20-40%) saccharin reacceptance]. Other animals assigned to the chronic DCS condition received daily DCS (15 mg/kg, i.p.) throughout extinction. Changes in saccharin drinking in these animals were compared to the data from rats that received no drug (saline controls). Once rats met our criterion for asymptotic extinction (90% reacceptance of the CS) they entered a 30-day latency period during which they received water for 1 h/day. The day after the completion of the latency period, a final

Nasal mucociliary transportability of male and female smokers.

Science.gov (United States)

Uzeloto, Juliana Souza; Ramos, Dionei; C F Freire, Ana Paula; G D Christofaro, Diego; Mara C Ramos, Ercy

Female smoker's present increased susceptibility to several diseases when compared to the opposite gender. However, there are no studies showing differences in nasal mucociliary transport behavior between male and female smokers. To compare the nasal mucociliary transportability in male and female smokers and non-smokers, taking into consideration age, anthropometric data, smoking load and pulmonary function. The analysis included 139 individuals (33 men and 37 women smokers and 32 men and 37 women non-smokers). All participants answered an initial interview to obtain personal data and smoking load. Anthropometric data and carbon monoxide in the exhaled air were assessed. Individuals also performed pulmonary function test and Saccharin Transit Time test. To compare saccharin transit time values between men and women, smokers and non-smokers, stratification of all independent variables was performed (sociodemographic, smoking and respiratory variables) into two categories: below and above the median values. There was no difference between men and women, smokers and non-smokers, regarding nasal mucociliary transportability. Significant differences were only observed between non-smokers. Among those with less forced vital capacity values (smokers), FCV and FEV1 (men non-smokers) and FEF 25-75% (women non-smokers) on saccharin transit time values. Based on the findings of this study, nasal mucociliary transport in male and female adult smokers, apparently healthy, are similar. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Supramolecular chemistry and crystal engineering*

Indian Academy of Sciences (India)

Administrator

two important prototypes – the large unit cell of elusive saccharin hydrate, .... tures that are able to guide the rational design of .... methanolyated complex could be regenerated to the ..... turn all of chemistry on its ear, since one of chemis-.

Performance and carcass traits of Santa Inês lambs finished with different sources of forage

Directory of Open Access Journals (Sweden)

Adriana Morato Menezes

2013-06-01

Full Text Available The objective of this study was to evaluate performance and biometrics of lambs fed different sources of forage. Twenty-four six-month-old Santa Inês female lambs were randomly allocated to four experimental diets and housed in individual stalls. They weighed on average 26.35±0.20 kg. The diets were coast cross hay (HAY, cassava hay (CAS, dehydrated by-product of pea crop (PEA and saccharin (SAC. The diets were formulated with the same amount of protein and energy with fixed levels of forage (60% and concentrate (40%. Adaptation to the diet took 7 days, with 45 days on experiment. Weights and biometric measurements were obtained every fortnight and feed intake three times a week. Rights half-carcasses were weighed and sectioned into retail cuts, rib, loin, shoulder, belly, neck and leg, which were weighed individually. Weight gain in lambs was significantly different between diets, with those fed saccharin gaining more. Overall, treatments did not significantly affect biometric measurements. There was a significant difference for feed intake and live weight at the end of the experiment. Animals fed PEA and SAC showed the best results. Average positive correlations were found between biometric measurements and live weight. Treatment PEA had heavier hot (14.36 kg and cold (14.01 kg carcass weights than the other groups. Hot carcass kill-out was higher for animals fed PEA as well as ham weight, belly, neck and heart girth. The weight of the abdominal viscera (% for lambs fed CAS was greater than those fed SAC and PEA. The weights of the thoracic viscera as well as the liver, for lambs fed PEA were higher. The by-product of pea yielded best results, followed by saccharin, and can replace traditional forage sources in the region, providing similar results in terms of cuts and body components. These could be an alternative for feeding sheep in the dry season. The substitution of forages using by-product of pea and saccharin led to improved

Low-calorie sweeteners in food and food supplements on the Italian market.

Science.gov (United States)

Janvier, Steven; Goscinny, Séverine; Le Donne, Cinzia; Van Loco, Joris

2015-01-01

This study determines the occurrence and concentration levels of artificial low-calorie sweeteners (LCSs) in food and food supplements on the Italian market. The analysed sample set (290 samples) was representative of the Italian market and comprised of beverages, jams, ketchups, confectionery, dairy products, table-top sweeteners and food supplements. All samples were analysed via UPLC-MS/MS. The method was in-house validated for the analysis of seven LCSs (aspartame, acesulfame-K, saccharin, sucralose, cyclamate, neotame and neohesperidin dihydrochalcone) in food and for five LCSs (aspartame, acesulfame-K, saccharin, cyclamate and sucralose) in food supplements. Except for cyclamate in one beverage which exceeded the maximum level (ML) with 13%, all concentrations measured in food were around or below the ML. In food supplements, 40 of the 52 samples (77%) were found to be above the ML, with exceedances of up to 200% of the ML.

Sensory profile and acceptability for pitanga (Eugenia uniflora L.) nectar with different sweeteners.

Science.gov (United States)

Freitas, Mírian Luisa Faria; Dutra, Mariana Borges de Lima; Bolini, Helena Maria André

2016-12-01

The objective of this study was to evaluate the sensory properties and acceptability of pitanga nectar samples prepared with sucrose and different sweeteners (sucralose, aspartame, stevia with 40% rebaudioside A, stevia with 95% rebaudioside A, neotame, and a 2:1 cyclamate/saccharin blend). A total of 13 assessors participated in a quantitative descriptive analysis and evaluated the samples in relation to the descriptor terms. The acceptability test was carried out by 120 fruit juice consumers. The results of the quantitative descriptive analysis of pitanga nectar showed that samples prepared with sucralose, aspartame, and the 2:1 cyclamate/saccharin blend had sensory profiles similar to that of the sample prepared with sucrose. Consumers' most accepted samples were prepared with sucrose, sucralose, aspartame, and neotame. The sweeteners that have the greatest potential to replace sucrose in pitanga nectar are sucralose and aspartame. © The Author(s) 2016.

The GHR-R antagonist JMV 2959 neither induces malaise nor alters the malaise property of LiCl in the adult male rat.

Science.gov (United States)

Rodriguez, Juan A; Fehrentz, Jean-Alain; Martinez, Jean; Ben Haj Salah, Khoubaib; Wellman, Paul J

2018-01-01

The orexigenic peptide ghrelin (GHR) interacts with ghrelin receptors (GHR-Rs) to modulate brain reinforcement and feeding circuits. Pharmacological inactivation of GHR-Rs via administration of the drug JMV 2959 attenuates the rewarding/reinforcing effects of several drugs of abuse including alcohol, morphine, amphetamine and nicotine. One view of these results is that inactivation of GHR-Rs taps into brain reinforcement/feeding circuits acted upon by drugs of abuse. An alternate explanation is that JMV 2959 may induce malaise, which in turn may limit reinforcement as well as food ingestion. This is a variable of interest given that nicotine alone can induce malaise which may be enhanced by JMV 2959. In the present study, we assessed the capacity of JMV 2959 to produce malaise using a conditioned taste aversion (CTA) task. Adult male rats were allowed to consume a 0.1% sodium saccharin solution and then injected IP with either vehicle, 0.4mg/kg nicotine, 3mg/kg JMV 2959, a combination of 0.4mg/kg nicotine and 3mg/kg JMV 2959, or 32mg/kg lithium chloride (a positive control known to support induction of CTA). Lithium chloride produced a robust avoidance of the saccharin solution in subsequent 2 bottle (water and saccharin) tests, whereas JMV 2959 alone did not induce CTA. The combination of JMV 2959 and nicotine induced a moderate degree of CTA that was similar to that produced by nicotine alone. These results suggest that JMV 2959 is unlikely to limit either reinforcement or food ingestion via induction of malaise. Published by Elsevier Inc.

Antimanic efficacy of retigabine in a proposed mouse model of bipolar disorder

DEFF Research Database (Denmark)

Nielsen, Ditte Dencker; Bak-Jensen, Henriette Husum

2010-01-01

use of amphetamine in humans can result in depression symptoms it was explored if a state of anhedonia could be assessed by testing saccharine preference before and during the withdrawal period of the model. The tested antimanic drugs (lithium, valproate, carbamazepine and lamotrigine) all attenuated...

Effects of sweeteners on individual feed intake characteristics and performance in group-housed weanling pigs

NARCIS (Netherlands)

Sterk, A.R.; Schlegel, P.; Mul, A.J.; Ubbink-Blanksma, M.; Bruininx, E.M.A.M.

2008-01-01

To assess the effects of 2 high intensity sodium saccharine based sweeteners on individual feed intake characteristics and performance of group-housed weaned pigs, 198 26-d-old weanling pigs were given ad libitum access to 3 dietary treatments: containing no additional sweetener (Control), 150 mg

Common Cancer Myths and Misconceptions

Science.gov (United States)

... cancer will shrink or disappear. However, a high-sugar diet may contribute to excess weight gain, and obesity is associated with an increased risk of developing several types of cancer. For more ... sweeteners (sugar substitutes) saccharin (Sweet 'N Low®, Sweet Twin®, NectaSweet®); ...

Simple method for functionalization of silica with alkyl silane and organic ligands

Directory of Open Access Journals (Sweden)

Kasim Mohammed Hello

2018-06-01

Full Text Available 3–(chloropropyltriethoxysilane (CPTES with imidazole and sodium silicate from rice husk ash (RHA successfully reacted within a short time in one–pot synthesis in purely homogenous method. A similar procedure was used for the immobilization of melamine and saccharine to demonstrate a generally applicable method. No reflux was needed, and a green solvent was used as the reaction medium. The surface areas of the prepared materials were very high compared with the materials which have similar structure prepared by the traditional method. The TGA/DTA confirmed that all the materials were highly stable. The FT-IR shows that all expected the functional groups were present. The HRTEM showed that the materials had ordered mesoporous straight-channels which were like the MCM-41. The synthesis procedure is simple, repeatable with different organic ligands and does not require toxic solvents or multiple steps with high products yield. Keywords: Rice husk ash, MCM-41, Imidazole, Melamine, Saccharine

Time-intensity profile of pitanga nectar (Eugenia uniflora L.) with different sweeteners: Sweetness and bitterness.

Science.gov (United States)

Freitas, Mírian Luisa Faria; de Lima Dutra, Mariana Borges; Bolini, Helena Maria André

2016-01-01

Pitanga has been used by the Brazilian food industry mainly for juice production. This fruit shows good economic potential due to its high concentration of vitamins and minerals. The aim of the present work was to characterize the time-intensity profile of pitanga nectar sweetened with different sweeteners to verify differences on the perception of sweet and bitter tastes. The sweeteners used to replace sucrose were sucralose, aspartame, stevia 40% rebaudioside A, stevia 95% rebaudioside A, neotame, and 2:1 cyclamate/saccharin blend. Fifteen assessors were selected according to their discriminating capability and trained to participate in the time-intensity analysis for sweetness and bitterness. The samples prepared with sucralose and 2:1 cyclamate/saccharin blend presented a similar sweetness profile to the sample prepared with sucrose, and the samples prepared with sucralose and aspartame presented a similar bitterness profile to the sample prepared with sucrose. Thus, sucralose would be the most suitable sweetener to replace sucrose in pitanga nectar. © The Author(s) 2015.

NQR investigation and characterization of cocrystals and crystal polymorphs

Energy Technology Data Exchange (ETDEWEB)

Seliger, Janez, E-mail: janez.seliger@fmf.uni-lj.si; Zagar, Veselko [Jozef Stefan Institute (Slovenia); Asaji, Tetsuo [Nihon University, Department of Chemistry, College of Humanities and Sciences (Japan)

2013-05-15

The application of {sup 14}N NQR to the study of cocrystals and crystal polymorphs is reviewed. In ferroelectric and antiferroelectric organic cocrystals {sup 14}N NQR is used to determine proton position in an N-H...O hydrogen bond and proton displacement below T{sub C}. In cocrystal isonicitinamide - oxalic acid (2:1) {sup 14}N NQR is used to distinguish between two polymorphs and to determine the type of the hydrogen bond (N{sup -}...H-O). The difference in the {sup 14}N NQR spectra of cocrystal formers and cocrystal is investigated in case of carbamazepine, saccharin and carbamazepine - saccharin (1:1). The experimental resolution allows an unambiguous distinction between the {sup 14}N NQR spectrum of the cocrystal and the {sup 14}N NQR spectra of the cocrystal formers. The possibility of application of NQR and double resonance for the determination of the inhomogeneity of the sample and for the study of the life time of an unstable polymorph is discussed.

Pairings of ethanol sipper with food induces Pavlovian autoshaping of ethanol drinking in rats: evidence of long-term retention and effects of sipper duration.

Science.gov (United States)

Tomie, Arthur; Sparta, Dennis R; Silberman, Yuval; Interlandi, Jeneen; Mynko, Alise; Patterson-Buckendahl, Patricia; Pohorecky, Larissa A

2002-01-01

This study asks if repeated Pavlovian pairings of a sipper tube (conditioned stimulus, CS) with food (unconditioned stimulus, US) will induce Pavlovian autoshaping conditioned responses (CRs), consisting of drinking of either 6% ethanol or water from the sipper CS. This study also tests predictions derived from the autoshaping model by asking if sipper CS-directed drinking will be retained, despite the absence of training for several weeks, and, in addition, if drinking rate is a negative function of sipper CS duration. Autoshaping procedures, conducted in two daily sessions, consisted of the brief insertion of the sipper tube CS followed by the response-independent presentation of food US. For the Ethanol group (n = 8), the sipper CS contained 6% ethanol, whereas for the Water group (n = 8), the sipper CS contained tap water. Saccharin fading procedures were employed, whereas for both groups, during days 1-19, the sipper CS contained 0.1% saccharin, and thereafter across training days the concentration of saccharin was gradually reduced (0.07, 0.035, 0.0%). Following elimination of saccharin, both groups were maintained in their home cages during a 27-day retention interval, and then re-evaluated for autoshaping of drinking of unsweetened ethanol and water. Thereafter, across days, the duration of access to the sipper CS (5.0, 7.5, 10.0, 15.0 s) during each autoshaping trial was increased. Both groups increased drinking across the first 19 days of training with sipper CS-food US pairings, and, at 0.0% saccharin, the Ethanol group consumed 14.76 ml of 6% ethanol per day, resulting in a daily ethanol consumption of 2.77 g/kg. For both groups, daily levels of drinking before and after the 27-day retention interval were comparable, attesting to the durability of the acquired drinking effects. At each CS duration, the Ethanol group consumed more millilitres of fluid per day than did the Water group, and for the Ethanol group, peak drinking of 24.0 ml of 6% ethanol per

Artificial Sweeteners as Food Additives (Turkish with English Abstract

Directory of Open Access Journals (Sweden)

2015-02-01

Full Text Available In this review some artificial sweeteners (saccharin, cyclamate and aspartame as food additives are looked over for their usage purposes and the effects on health. The problems of public health caused by some artificial sweeteners are assessed according the recent scientific publication on the subject.

Estimated intake of intense sweeteners from non-alcoholic beverages in Denmark

DEFF Research Database (Denmark)

Leth, Torben; Fabricius, N.; Fagt, Sisse

2007-01-01

In 1999, 116 samples of non-alcoholic beverages were analysed for the intense sweeteners cyclamate, acesulfame-K, aspartame and saccharin. High contents of cyclamate close to the maximum permitted level in 1999 of 400 mgl(-1) were found in many soft drinks. The estimated intake of the sweeteners...

The subthalamic nucleus keeps you high on emotion: behavioral consequences of its inactivation

Directory of Open Access Journals (Sweden)

Yann ePelloux

2014-12-01

Full Text Available The subthalamic nucleus (STN belongs to the basal ganglia and is the current target for the surgical treatment of neurological and psychiatric disorders such as Parkinson’s Disease (PD and obsessive compulsive disorders, but also a proposed site for the treatment of addiction. It is therefore very important to understand its functions in order to anticipate and prevent possible side-effects in the patients. Although the involvement of the STN is well documented in motor, cognitive and motivational processes, less is known regarding emotional processes. Here we have investigated the direct consequences of STN inactivation by excitotoxic lesions on emotional processing and reinforcement in the rat. We have used various behavioral procedures to assess affect for neutral, positive and negative reinforcers in STN lesioned rats. STN lesions reduced affective responses for positive (sweet solutions and negative (electric foot shock, Lithium Chloride-induced sickness reinforcers while they had no effect on responses for a more neutral reinforcer (novelty induced place preference. Furthermore, when given the choice between saccharine, a sweet but non caloric solution, and glucose, a more bland but caloric solution, in contrast to sham animals that preferred saccharine, STN lesioned animals preferred glucose over saccharine. Taken altogether these results reveal that STN plays a critical role in emotional processing. These results, in line with some clinical observations in PD patients subjected to STN surgery, suggest possible emotional side-effects of treatments targeting the STN. They also suggest that the increased motivation for sucrose previously reported cannot be due to increased pleasure, but could be responsible for the decreased motivation for cocaine reported after STN inactivation.

Perception of sweet taste is important for voluntary alcohol consumption in mice.

Science.gov (United States)

Blednov, Y A; Walker, D; Martinez, M; Levine, M; Damak, S; Margolskee, R F

2008-02-01

To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: alpha-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild-type mice, whereas Tas1r3 null mice were not different from wild type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion (CTA) to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in CTA to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol.

The synthesis and characterization of polypeptide-adriamycin conjugates and its complexes with adriamycin. Part I

NARCIS (Netherlands)

Heeswijk, W.A.R.; Hoes, C.J.T.; Stoffer, T.; Eenink, M.J.D.; Potman, W.; Feijen, Jan

1985-01-01

Poly(α-l-glutamic acid) (PGA) was grafted with amino acid and oligopeptide spacers up to 5 amino acids with the use of N,N'-carbonyldiimidazole and 2,3-dihydro-1,2-benz-isothiazole-3-on-1, 1-dioxide (saccharin) as an additive, and these polypeptides were characterized. The antitumor antibiotic

Extinction, Spontaneous Recovery and Renewal of Flavor Preferences Based on Taste-Taste Learning

Science.gov (United States)

Diaz, Estrella; De la Casa, L. G.

2011-01-01

This paper presents evidence of extinction, spontaneous recovery and renewal in a conditioned preferences paradigm based on taste-taste associations. More specifically, in three experiments rats exposed to a simultaneous compound of citric acid-saccharin solution showed a preference for the citric solution when the preference was measured with a…

Supramolecular chemistry and crystal engineering

Indian Academy of Sciences (India)

supramolecular architectures, network structures, multi-component host–guest systems, cocrys- tals, and ... structures is illustrated by two important prototypes – the large unit cell of elusive saccharin hydrate ..... N––– H ··· π interaction is not seen in this view. (d) Infinite .... to atmospheric water vapor without color loss or.

The Reproducibility and Comparative Validity of a Non-Nutritive Sweetener Food Frequency Questionnaire

Directory of Open Access Journals (Sweden)

Emily A. Myers

2018-03-01

Full Text Available In order to better assess non-nutritive sweetener (NNS consumption, measurement tools with greater utility are needed. The objective of this investigation is to determine the reproducibility and validity of a newly developed NNS food frequency questionnaire (NNS-FFQ that measures five types of NNS (saccharin, aspartame, acesulfame potassium, sucralose and erythritol. Adult participants (n = 123, 56% female, 75% Caucasian, mean age = 36.8 ± 16.6 completed the NNS-FFQ twice and had 24-h dietary recalls three times over a two-week study period. Reproducibility between two administrations of the NNS-FFQ was assessed via Bland–Altman plots, Spearman’s correlations (rs and paired samples t-tests. Bland–Altman plots, Cohen’s κ, Spearman’s correlations (rs, and paired samples t-tests compared NNS intake between the two methods for validity. For reproducibility analyses, Bland–Altman analyses revealed agreement levels above the 95% acceptance level for total NNS (99.2%, erythritol (99.2%, and aspartame (96.7%. Agreement levels for acesulfame potassium (94.3%, saccharin (94.3%, and sucralose (94.3% were slightly below the acceptable level. For validity analyses, Bland–Altman analyses revealed agreement levels above the 95% acceptance level for total NNS (95.1%, sucralose (95.9%, saccharin (95.9%, and erythritol (95.1%. Agreement levels for aspartame (94.3% and acesulfame potassium (92.7% were slightly below the acceptable level. Although less than desirable agreement was found between the methods for aspartame and acesulfame potassium, some variance was expected due to the habitual nature of the NNS-FFQ as compared to the recent intake reported by recalls. Within the context of this constraint, the NNS-FFQ demonstrates acceptable reproducibility and validity. The NNS-FFQ is a brief questionnaire that could be administered among diverse participants at the individual and population levels to measure habitual NNS intake.

The effect of sweeteners and milk type on the rheological properties ...

African Journals Online (AJOL)

The aim of the study was, to determine effects of sweeteners and milk type on the rheological and sensorial properties of reduced calorie salep drink. In addition to sugar, three different sweeteners; aspartame, saccharine and cyclamate as well as three different milk types; full-fat, low-fat and non-fat; were used for sample ...

Conditions sufficient for the production of oral cocaine or lidocaine self-administration in preference to water.

Science.gov (United States)

Falk, J L; Siris, A; Lau, C E

1996-03-01

Groups of rats were given a chronic history of drinking cocaine solutions of different concentrations in daily, 3-h schedule induced polydipsia sessions. Animals failed to develop a preference for cocaine solution to concurrently presented water. Schedule-induction conditions were maintained, and the animals were divided into separate groups, drinking either cocaine or lidocaine placed in a highly acceptable vehicle (glucose-saccharin solution). Animals preferred their respective drug solutions to concurrently presented water, and these preferences remained stable after the glucose-saccharin vehicle was gradually faded to water, leaving only cocaine or lidocaine, respectively, in the solution. Thus a stable preference for drug solution to water could be instituted in rats for either cocaine or lidocaine solution (putative reinforcing and nonreinforcing agents, respectively) given an appropriate associative history, with high intakes maintained by schedule-induction. Conditions sufficient for the initiation of an oral preference and high intake for a putatively reinforcing drug cannot be assumed to occur owing to the drug's reinforcing property in the absence of demonstrating the ineffectiveness of an appropriate negative control substance.

Effects of cellulosic degradation product concentration on actinide sorption on tuffs from the Borrowdale Volcanic Group, Sellafield, Cumbria

International Nuclear Information System (INIS)

Baston, G.M.N.; Berry, J.A.; Bond, K.A.; Boult, K.A.; Linklater, C.M.

1994-01-01

The Nirex Safety Assessment Research Programme includes an investigation into the effects of cellulosic degradation products on the sorption of radioelements onto geological materials. Previous batch sorption studies have shown that the presence of high concentrations of both authentic cellulosic degradation products (produced by alkaline degradation of wood/tissue) and the well-characterised simulant, gluconate, can cause marked reductions in actinide sorption. This work has now been extended to cover a range of concentrations of both authentic cellulosic degradation products and their simulants, gluconate and iso-saccharinate. Geological samples were from the proposed Nirex underground radioactive waste disposal site at Sellafied, Cumbria. The nuclides studied were thorium and plutonium. In the presence of gluconate or iso-saccharinate, at concentrations above 10 -4 M, the present work has confirmed the trends shown by earlier experiments, with a significant reduction in actinide sorption (R D values reduced by less than a factor of two), and in some cases the results suggested a slight increase (R D values increased by up to a factor of four). (orig.)

Effects of cellulosic degradation product concentration on actinide sorption on tuffs from the Borrowdale Volcanic Group, Sellafield, Cumbria

Energy Technology Data Exchange (ETDEWEB)

Baston, G.M.N. [AEA Technology, Decommissioning and Waste Management, Harwell (United Kingdom); Berry, J.A. [AEA Technology, Decommissioning and Waste Management, Harwell (United Kingdom); Bond, K.A. [AEA Technology, Decommissioning and Waste Management, Harwell (United Kingdom); Boult, K.A. [AEA Technology, Decommissioning and Waste Management, Harwell (United Kingdom); Linklater, C.M. [AEA Technology, Decommissioning and Waste Management, Harwell (United Kingdom)

1994-12-31

The Nirex Safety Assessment Research Programme includes an investigation into the effects of cellulosic degradation products on the sorption of radioelements onto geological materials. Previous batch sorption studies have shown that the presence of high concentrations of both authentic cellulosic degradation products (produced by alkaline degradation of wood/tissue) and the well-characterised simulant, gluconate, can cause marked reductions in actinide sorption. This work has now been extended to cover a range of concentrations of both authentic cellulosic degradation products and their simulants, gluconate and iso-saccharinate. Geological samples were from the proposed Nirex underground radioactive waste disposal site at Sellafied, Cumbria. The nuclides studied were thorium and plutonium. In the presence of gluconate or iso-saccharinate, at concentrations above 10{sup -4} M, the present work has confirmed the trends shown by earlier experiments, with a significant reduction in actinide sorption (R{sub D} values reduced by less than a factor of two), and in some cases the results suggested a slight increase (R{sub D} values increased by up to a factor of four). (orig.)

Investigations on UCS-CS mediation in radiation-induced conditioned taste aversion

International Nuclear Information System (INIS)

Burns, T.C.

1974-01-01

Groups of 8 male Sprague-Dawley rats were used in an investigation of procaine and dimenhydrinate effects on radiation-induced taste aversion learning. Neither the local anesthetic procaine, administered intraperitoneally, nor the antinausea drug dimenhydrinate, administered intramuscularly, blocked acquisition of aversion to saccharin flavored water. Control animals confirmed that saccharin preferences appeared normally in non-irradiated animals, and that the drugs produced no aversion in the absence of radiation. Another investigation, using groups of 5 female Sprague-Dawley rats, showed a failure of dimenhydrinate in blocking the acquisition of a rotation-induced conditioned taste aversion. Two dose levels of the drug were used, 1 mg/kg and 2 mg/kg. At the dimenhydrinate dosage used in the study involving radiation (1.75 mg/kg) and at the higher dosage used in the study involving rotation, there appeared to be a potentiation of the effects of radiation and rotation, respectively. Results of these studies seem to favor a model for UCS-CS mediation as being diffuse and perhaps redundant. The possibility that nausea-producing stimuli may work synergistically was also discussed. (U.S.)

Influência de alguns parâmetros experimentais nos resultados de análises calorimétricas diferenciais - DSC

OpenAIRE

Bernal, Cláudia; Couto, Andréa Boldarini; Breviglieri, Susete Trazzi; Cavalheiro, Éder Tadeu Gomes

2002-01-01

A series of experiments were performed in order to demonstrate to undergraduate students or users of the differential scanning calorimetry (DSC), that several factors can influence the qualitative and quantitative aspects of DSC results. Saccharin, an artificial sweetner, was used as a probe and its thermal behavior is also discussed on the basis of thermogravimetric (TG) and DSC curves.

Influência de alguns parâmetros experimentais nos resultados de análises calorimétricas diferenciais - DSC Influence of some experimental parameters on the results of differential scanning calorimetry - DSC.

OpenAIRE

Cláudia Bernal; Andréa Boldarini Couto; Susete Trazzi Breviglieri; Éder Tadeu Gomes Cavalheiro

2002-01-01

A series of experiments were performed in order to demonstrate to undergraduate students or users of the differential scanning calorimetry (DSC), that several factors can influence the qualitative and quantitative aspects of DSC results. Saccharin, an artificial sweetner, was used as a probe and its thermal behavior is also discussed on the basis of thermogravimetric (TG) and DSC curves.

Risque dû à la consommation des boissons rafraichissantes sans ...

African Journals Online (AJOL)

Les résultats obtenus montrent que 36.66% des échantillons sont non conformes à la réglementation Algérienne. 23.33% sont ... 23.33% are concerning a chemical quality (the exceed of the doses of saccharin for 20% of samples and presence of a Sweetener no permit, the cyclamate in one sample) and 13.33% related to ...

Influência de alguns parâmetros experimentais nos resultados de análises calorimétricas diferenciais - DSC

Directory of Open Access Journals (Sweden)

Bernal Cláudia

2002-01-01

Full Text Available A series of experiments were performed in order to demonstrate to undergraduate students or users of the differential scanning calorimetry (DSC, that several factors can influence the qualitative and quantitative aspects of DSC results. Saccharin, an artificial sweetner, was used as a probe and its thermal behavior is also discussed on the basis of thermogravimetric (TG and DSC curves.

Contaminants of emerging concern in the open sea waters of the Western Mediterranean

International Nuclear Information System (INIS)

Brumovský, Miroslav; Bečanová, Jitka; Kohoutek, Jiří; Borghini, Mireno; Nizzetto, Luca

2017-01-01

Pollution by chemical substances is of concern for the maintenance of healthy and sustainable aquatic environments. While the occurrence and fate of numerous emerging contaminants, especially pharmaceuticals, is well documented in freshwater, their occurrence and behavior in coastal and marine waters is much less studied and understood. This study investigates the occurrence of 58 chemicals in the open surface water of the Western Mediterranean Sea for the first time. 70 samples in total were collected in 10 different sampling areas. 3 pesticides, 11 pharmaceuticals and personal care products and 2 artificial sweeteners were detected at sub-ng to ng/L levels. Among them, the herbicide terbuthylazine, the pharmaceuticals caffeine, carbamazepine, naproxen and paracetamol, the antibiotic sulfamethoxazole, the antibacterial triclocarban and the two artificial sweeteners acesulfame and saccharin were detected in all samples. The compound detected at the highest concentration was saccharin (up to 5.23 ng/L). Generally small spatial differences among individual sampling areas point to a diffuse character of sources which are likely dominated by WWTP effluents and runoffs from agricultural areas or even, at least for pharmaceuticals and artificial food additives, from offshore sources such as ferries and cruising ships. The implications of the ubiquitous presence in the open sea of chemicals that are bio-active or toxic at low doses on photosynthetic organisms and/or bacteria (i.e., terbuthylazine, sulfamethoxazole or triclocarban) deserve scientific attention, especially concerning possible subtle impacts from chronic exposure of pelagic microorganisms. - Highlights: • First report on several classes of emerging contaminants in the open Mediterranean Sea. • 3 pesticides, 11 PPCPs and 2 artificial sweeteners detected in the surface marine water. • Saccharin, naproxen and DEET detected at the highest concentrations. • Spatial distribution independent of distance

Avaliação sensorial, microbiologia e físico-química de suco artificial de laranja adicionado de diferentes agentes adoçantes

Directory of Open Access Journals (Sweden)

Iago Felipe da Silva Leite

2016-11-01

Full Text Available Diante do aumento do consumo de adoçantes por vários fatores e a procura por uma dieta mais saudável,  para a redução dos riscos de doenças como, diabetes, obesidade, entre outras, este trabalho teve como objetivo avaliar a diferença da doçura e aceitação dos diferentes agentes adoçantes em sucos artificiais. Foram formulados sucos em pó sabor laranja e adicionado os diferentes agentes adoçantes (sacarose, demerara, stevia pura, sacarina sódica + ciclamato de sódio e sacarina sódica + ciclamato de sódio + stevia. Realizou-se analises de pH e de sólidos solúveis totais (ºBrix para as diferentes formulações, ocorrendo variações, além das análises microbiológicas para coliformes totais e Salmonella sp/25g, resultando em ausência para ambos Os resultados apontam que as amostras estão próprias para consumo segundo a legislação virgente. A análise foi aplicada no laboratório de análise sensorial da Universidade Federal de Campina Grande e avaliada por 93 provadores. Aplicou-se uma ficha sensorial levando em consideração a aceitação dos agentes adoçantes. Conclui-se que a sacarina sódica + ciclamato de sódio e sacarina sódica + ciclamato de sódio + stevia foi a formulação com maior índice de aprovação.SensoSensory, microbiological and physico-chemical evaluation of artificial orange juice added with different sweetening agents Abstract: The increase in the consumption of sweeteners by several factors. And the demand for a healthier diet with reduced risk of diseases such as, diabetes, obesity, among others, this study aimed to assess the degree of sweetness of difference and acceptance of different sweetening agents. Were formulated artificial juices powdered orange flavor and added different sweeteners (sucrose, demerara, pure stevia, saccharin + sodium cyclamate and sodium saccharin + sodium cyclamate + stevia. We conducted analysis of pH and total soluble solids (° Brix for the different

CoFeRh alloys

International Nuclear Information System (INIS)

Tabakovic, Ibro; Qiu Jiaoming; Riemer, Steve; Sun Ming; Vas'ko, Vlad; Kief, Mark

2008-01-01

The electrochemical behavior of Rh(III) species in CoFe solution containing RhCl 3 , NH 4 Cl, H 3 BO 3 , CoSO 4 , FeSO 4 , saccharin, and NaLS (Na lauryl sulfate) has been investigated. The electrochemistry of Rh(III) species is influenced by each of the compounds present in CoFe plating solution, but especially by addition of saccharin and H 3 BO 3 to the RhCl 3 -NH 4 Cl solution. The nucleation and growth of Rh on GC (glassy carbon), Ru, and Cu electrodes from NH 4 Cl solution was studied using the potentiostatic current-transient methods. The results support a predominantly progressive nucleation of Rh on all three-electrode surfaces. The nucleation kinetic parameters ANo (steady state nucleation rate) and Ns (saturation nuclear number density) were found to vary with potential and are electrode-dependent in order: GC > Ru∼Cu. The electrodeposited Rh films obtained from NH 4 Cl solution and nonmagnetic CoFeRh film obtained from CoFe solution were characterized in terms of the following properties: morphology, surface roughness, crystal structure and chemical composition. The origin of light elements found in Rh and CoFeRh films (O, Cl, S, C, N) was discussed

Endoscopic evaluation of therapeutic effects of “Anuloma-Viloma Pranayama” in Pratishyaya w.s.r. to mucociliary clearance mechanism and Bernoulli's principle

Science.gov (United States)

Bhardwaj, Atul; Sharma, Mahendra Kumar; Gupta, Manoj

2013-01-01

The current endeavor intended to evaluate the effectiveness and mode of action of Anuloma-Viloma Pranayama (AVP), i.e., alternate nasal breathing exercise, in resolving clinical features of Pratishyaya, i.e., rhinosinusitis. The present study was directed to validate the use of classical “saccharin test” in measuring the nasal health by measuring mucociliary clearance time. This study also highlights the effects of AVP by application of Bernoulli principle in ventilation of paranasal sinuses and surface oxygenation of nasal and paranasal sinuses ciliary epithelium. Clinically, endoscopically and radiologically diagnosed patients of Pratishyaya, i.e., rhinosinusitis, satisfying the inclusion criteria were selected to perform AVP as a breathing exercise regularly for 30 min every day in order to evaluate the effectiveness of AVP in resolving features of rhinosinusitis. Saccharin test was performed before and after completion of 40 days trial to assess the nasal ciliary activity, which has been proved to be directly related to the health of ciliary epithelium and nasal health overall as well. AVP may be regarded as a catalyst to conspicuously enhance ventilation and oxygenation of the paranasal sinuses and the positively effect the nasal respiratory epithelium by increasing better surface availability of oxygen and negative pressure in the nasal cavity itself. PMID:24696572

[A comparative study on behaviors of two depression models in rats induced by chronic forced swimming stress].

Science.gov (United States)

Han, Ming-Fei; Gao, Dong; Sun, Xue-Li

2010-01-01

To compare the behaviors of rats with depressions induced by chronic forced swimming stress under two different conditions. Eighteen male rats were randomly divided into 3 groups, with 6 rats in each group. The rats in the control group (C group) were not forced into swimming, while the rats in the stress groups (S1 and S2) were forced to swim for 14 consecutive days. The rats in S1 group and S2 group swam for five minutes every morning, in water with (23 +/- 1) degree C, and (10 +/- 0.5) degree C in temperature, respectively. The weight gain, food intake, open-field test and saccharin solution test were observed on the seventh day and fourteenth day. On the seventh day following chronic swim stress, the rats in the S2 group had significant lower ratio in weight gain and food intake than the controls (P forced swimming. On the fourteenth day, the rats in the S1 group still had lower ratio in weight gain, but had higher ratio in food intake and preference for saccharin solution, and greater number of crossing than the controls. Chronic forced swimming at a lower temperature could induce depression better than at a higher temperature.

Emerging ciliopathies: are respiratory cilia compromised in Usher syndrome?

Science.gov (United States)

Piatti, G; De Santi, M M; Brogi, M; Castorina, P; Ambrosetti, U

2014-01-01

Usher syndrome is a ciliopathy involving photoreceptors and cochlear hair cells (sensory cilia): since sensory and motor ciliopathies can overlap, we analysed the respiratory cilia (motile) in 17 patients affected by Usher syndrome and 18 healthy control subject. We studied the mucociliary transport time with the saccharine test, ciliary motility and ultrastructure of respiratory cilia obtained by nasal brushing; we also recorded the classical respiratory function values by spirometry. All enrolled subjects showed normal respiratory function values. The mean mucociliary transport time with saccharine was 22.33 ± 17.96 min, which is in the range of normal values. The mean ciliary beat frequency of all subjects was 8.81 ± 2.18 Hz, which is a value approaching the lower physiological limit. None of the classical ciliary alterations characterizing the "ciliary primary dyskinesia" was detected, although two patients showed alterations in number and arrangement of peripheral microtubules and one patient had abnormal ciliary roots. Respiratory cilia in Usher patients don't seem to have evident ultrastructural alterations, as expected, but the fact that the ciliary motility appeared slightly reduced could emphasize that a rigid distinction between sensory and motor ciliopathies may not reflect what really occurs. Copyright © 2014 Elsevier Inc. All rights reserved.

Assessing developmental toxicity of caffeine and sweeteners in medaka (Oryzias latipes)

OpenAIRE

Lee, Wenjau; Wang, Yun-Chi

2015-01-01

The use of artificial sweeteners (ASWs) has increased and become more widespread, and consequently ASWs have appeared in aquatic environments around the world. However, their safety to the health of humans and wildlife remains inconclusive. In this study, using medaka embryos (Oryzias latipes), we investigated developmental toxicity of aspartame (ASP) and saccharin (SAC). Since ASWs are often consumed with caffeine (CAF) and CAF with sucrose (SUC), we tested biological activities of these fou...

Theophylline Cocrystals Prepared by Spray Drying: Physicochemical Properties and Aerosolization Performance

OpenAIRE

Alhalaweh, Amjad; Kaialy, Waseem; Buckton, Graham; Gill, Hardyal; Nokhodchi, Ali; Velaga, Sitaram P.

2013-01-01

The purpose of this work was to characterize theophylline (THF) cocrystals prepared by spray drying in terms of the physicochemical properties and inhalation performance when aerosolized from a dry powder inhaler. Cocrystals of theophylline with urea (THF-URE), saccharin (THF-SAC) and nicotinamide (THF-NIC) were prepared by spray drying. Milled THF and THF-SAC cocrystals were also used for comparison. The physical purity, particle size, particle morphology and surface energy of the materials ...

Tumorigenicity of sodium ascorbate in male rats.

Science.gov (United States)

Cohen, S M; Anderson, T A; de Oliveira, L M; Arnold, L L

1998-06-15

Sodium ascorbate, like other sodium salts such as saccharin, glutamate, and bicarbonate, produces urinary alterations when fed at high doses to rats, which results in mild superficial urothelial cytotoxicity and regeneration but not tumors in a standard 2-year bioassay. Sodium saccharin was shown to produce a low incidence of bladder tumors in rats if administered in a two-generation bioassay. In the present study, we evaluated sodium ascorbate in a two-generation bioassay that involved feeding to the male and female parental F344 rats for 4 weeks before mating, feeding the dams during gestation and lactation, and then feeding the weaned (at 28 days of age) male F1 generation rats for the remainder of their lifetime (up to 128 weeks of the experiment). Dietary levels of 1.0, 5.0, and 7.0% sodium ascorbate were tested. At 5.0 and 7.0% sodium ascorbate, there was an increase in urinary bladder urothelial papillary and nodular hyperplasia and the induction of a few papillomas and carcinomas. There was a dose-responsive increase in renal pelvic calcification and hyperplasia and inhibition of the aging nephropathy of rats even at the level of 1% sodium ascorbate. Because the short-term urothelial effects of sodium ascorbate in rats are inhibited by treatments producing urinary acidification to pH sodium ascorbate to evaluate the long-term effects. The combination of 7.0% sodium ascorbate plus 2.78% NH4Cl in the diet was toxic, and the group was terminated early during the course of the experiment. The group fed 5.0% sodium ascorbate plus 2.04% NH4Cl showed complete inhibition of the urothelial effects of sodium ascorbate and significant inhibition of its renal effects. We also demonstrated the presence of a calcium phosphate-containing urinary precipitate in rats fed sodium ascorbate at all doses, in a dose-responsive manner. The formation of the precipitate was inhibited by coadministration with NH4Cl. The proliferative effects of sodium ascorbate on the male rat

Ethanol-induced conditioned taste avoidance: reward or aversion?

Science.gov (United States)

Liu, Chuang; Showalter, John; Grigson, Patricia Sue

2009-03-01

Rats avoid intake of a palatable taste cue when paired with all drugs of abuse tested. Evidence suggests that, at least for morphine and cocaine, rats avoid the taste cue because they are anticipating the rewarding properties of the drug. Thus, the suppressive effects of a rewarding sucrose solution and cocaine, but not those of the putatively aversive agent, lithium chloride (LiCl), are exaggerated in drug-sensitive Lewis rats. Likewise, the suppressive effects of sucrose and morphine, but not those of LiCl, are eliminated by bilateral lesions of the gustatory thalamus. Unlike morphine and cocaine, it is less clear whether rewarding or aversive drug properties are responsible for ethanol-induced suppression of intake of a taste cue. The present set of studies tests whether, like cocaine, ethanol-induced suppression of intake of a taste cue also is greater in the drug-sensitive Lewis rats and whether the suppressive effects of the drug are prevented by bilateral lesions of the taste thalamus. In Experiment 1, fluid-deprived Lewis and Fischer rats were given 5-minute access to 0.15% saccharin and then injected with saline or a range of doses of ethanol (0.5, 0.75, 1.0, or 1.5 g/kg). There was a total of 6 such pairings. In Experiments 2 and 3, Sprague-Dawley rats received bilateral electrophysiologically guided lesions of the gustatory thalamus. After recovery, suppression of intake of the saccharin cue was evaluated following repeated daily pairings with either a high (1.5 g/kg) or a low (0.75 g/kg) dose of ethanol. Ethanol-induced suppression of intake of the saccharin conditioned stimulus (CS) did not differ between the drug-sensitive Lewis rats relative to the less-sensitive Fischer rats. Lesions of the taste thalamus, however, prevented the suppressive effect of the 0.75 g/kg dose of the drug, but had no impact on the suppressive effect of the 1.5 g/kg dose of ethanol. The results suggest that the suppressive effects of ethanol on CS intake are mediated by both

The physiological effect of cobalt on watermelon cultivation

International Nuclear Information System (INIS)

Yao Naihua; Jin Yafang; Sun Yaochen; Huang Yiming

1993-01-01

Cobalt has essential physiological action on both animals and plants. For the latter it can raise plant's nitrogen-fixing ability and saccharine content. Spray of cobalt mixed with other nutritive elements can improve the germinatit of seeds and the yield of fruit. For specifying the nutritive function of cobalt upon watermelon, isotope 60 Co was mixed into a complex leaf nutritive aqua and the regularity of transferring and absorbing cobalt in the watermelon's body was investigated

Electrochemical synthesis of polypyrrole on ferrous and non-ferrous metals from sweet aqueous electrolytic medium

International Nuclear Information System (INIS)

Bazzaoui, M.; Martins, J.I.; Reis, T.C.; Bazzaoui, E.A.; Nunes, M.C.; Martins, L.

2005-01-01

The electrodeposition of polypyrrole (PPy) on oxidizable metals such as aluminum and iron has been achieved in aqueous medium of saccharin and pyrrole. Scanning electron microscopy and X-ray photoelectron spectroscopy analysis reveal a good homogeneity of the obtained PPy film. The electrochemical synthesis of PPy coating has been achieved successfully under potentiodynamic, galvanostatic and potentiostatic techniques. The corrosion experiments performed in HCl show that the PPy coating increases the corrosion potential and decreases the corrosion current density

Discriminative power of an assay for automated in vitro screening of teratogens

DEFF Research Database (Denmark)

Walmod, Peter S; Gravemann, Ute; Nau, Heinz

2004-01-01

-trans-retinoic acid, pentyl-4-yn-valproic acid, saccharin, salicylic acid and valproic acid. All compounds, with the exception of dimethadione inhibited proliferation in a linear dose-dependent manner, and there were statistically significant compound class-dependent differences between the IC(50)-values...... to teratogenicity were: 5-bromo-2(')-deoxyuridine, 6-aminonicotinamide, acrylamide, boric acid, D-(+)-camphor, dimethadione, dimethyl phthalate, diphenhydramine, hydroxyurea, isobutyl-ethyl-valproic acid, lithium chloride, methyl mercury chloride, methotrexate, methoxyacetic acid, penicillin G, all...

Aspartame intake is associated with greater glucose intolerance in individuals with obesity.

Science.gov (United States)

Kuk, Jennifer L; Brown, Ruth E

2016-07-01

This study examined whether sucrose, fructose, aspartame, and saccharin influences the association between obesity and glucose tolerance in 2856 adults from the NHANES III survey. Aspartame intake significantly influenced the association between body mass index (BMI) and glucose tolerance (interaction: P = 0.004), wherein only those reporting aspartame intake had a steeper positive association between BMI and glucose tolerance than those reporting no aspartame intake. Therefore, consumption of aspartame is associated with greater obesity-related impairments in glucose tolerance.

Quantification of four artificial sweeteners in Finnish surface waters with isotope-dilution mass spectrometry

International Nuclear Information System (INIS)

Perkola, Noora; Sainio, Pirjo

2014-01-01

The artificial sweeteners sucralose (SCL), acesulfame (ACS), saccharin (SAC), and cyclamate (CYC) have been detected in environmental waters in Europe and North America. Higher environmental levels are expected in view of the increasing consumption of these food additives. In this study, an isotope-dilution mass spectrometry (IDMS) LC–MS/MS method was developed and validated for quantifying the four artificial sweeteners in boreal lakes (n = 3) and rivers (n = 12). The highest concentrations of ACS, SAC, CYC and SCL were 9,600, 490, 210 and 1000 ng/L, respectively. ACS and SAC were detected in all studied samples, and CYC and SCL in 98% and 56% of the samples. Seasonal trends of ACS and SAC were observed in some rivers. ACS and SCL concentrations in rivers correlated linearly with population equivalents of the wastewater treatment plants in the catchment areas, whereas SAC and CYC concentrations depend more on the source. -- Highlights: • A reliable method for analysing artificial sweeteners in water was validated. • Artificial sweeteners were quantified in boreal rivers and lakes. • Most concentrations were in accordance with previous European studies. • Acesulfame and saccharine concentrations were high in the most contaminated rivers. • Correlation observed between concentrations and mean water throughflow in rivers. -- High concentrations of artificial sweeteners were obtained, which indicates slow or negligible degradation of these compounds in boreal surface waters

Prior exposure to repeated immobilization or chronic unpredictable stress protects from some negative sequels of an acute immobilization.

Science.gov (United States)

Pastor-Ciurana, Jordi; Rabasa, Cristina; Ortega-Sánchez, Juan A; Sanchís-Ollè, Maria; Gabriel-Salazar, Marina; Ginesta, Marta; Belda, Xavier; Daviu, Núria; Nadal, Roser; Armario, Antonio

2014-05-15

Exposure to chronic unpredictable stress (CUS) is gaining acceptance as a putative animal model of depression. However, there is evidence that chronic exposure to stress can offer non-specific stress protection from some effects of acute superimposed stressors. We then compared in adult male rats the protection afforded by prior exposure to CUS with the one offered by repeated immobilization on boards (IMO) regarding some of the negative consequences of an acute exposure to IMO. Repeated exposure to IMO protected from the negative consequences of an acute IMO on activity in an open-field, saccharin intake and body weight gain. Active coping during IMO (struggling) was markedly reduced by repeated exposure to the same stressor, but it was not affected by a prior history of CUS, suggesting that our CUS protocol does not appear to impair active coping responses. CUS exposure itself caused a strong reduction of activity in the open-field but appeared to protect from the hypo-activity induced by acute IMO. Moreover, prior CUS offered partial protection from acute IMO-induced reduction of saccharin intake and body weight gain. It can be concluded that a prior history of CUS protects from some of the negative consequences of exposure to a novel severe stressor, suggesting the development of partial cross-adaptation whose precise mechanisms remain to be studied. Copyright © 2014 Elsevier B.V. All rights reserved.

CoFeRh alloys

Energy Technology Data Exchange (ETDEWEB)

Tabakovic, Ibro [Seagate Technology, Research and Development, Bloomington, MN 55435 (United States)], E-mail: ibro.m.tabakovic@seagate.com; Qiu Jiaoming; Riemer, Steve; Sun Ming; Vas' ko, Vlad; Kief, Mark [Seagate Technology, Research and Development, Bloomington, MN 55435 (United States)

2008-01-01

The electrochemical behavior of Rh(III) species in CoFe solution containing RhCl{sub 3}, NH{sub 4}Cl, H{sub 3}BO{sub 3}, CoSO{sub 4}, FeSO{sub 4}, saccharin, and NaLS (Na lauryl sulfate) has been investigated. The electrochemistry of Rh(III) species is influenced by each of the compounds present in CoFe plating solution, but especially by addition of saccharin and H{sub 3}BO{sub 3} to the RhCl{sub 3}-NH{sub 4}Cl solution. The nucleation and growth of Rh on GC (glassy carbon), Ru, and Cu electrodes from NH{sub 4}Cl solution was studied using the potentiostatic current-transient methods. The results support a predominantly progressive nucleation of Rh on all three-electrode surfaces. The nucleation kinetic parameters ANo (steady state nucleation rate) and Ns (saturation nuclear number density) were found to vary with potential and are electrode-dependent in order: GC > Ru{approx}Cu. The electrodeposited Rh films obtained from NH{sub 4}Cl solution and nonmagnetic CoFeRh film obtained from CoFe solution were characterized in terms of the following properties: morphology, surface roughness, crystal structure and chemical composition. The origin of light elements found in Rh and CoFeRh films (O, Cl, S, C, N) was discussed.

Enhancement of rat bladder contraction by artificial sweeteners via increased extracellular Ca2+ influx

International Nuclear Information System (INIS)

Dasgupta, Jaydip; Elliott, Ruth A.; Doshani, Angie; Tincello, Douglas G.

2006-01-01

Introduction: Consumption of carbonated soft drinks has been shown to be independently associated with the development of overactive bladder symptoms (OR 1.62, 95% CI 1.18, 2.22) [Dallosso, H.M., McGrother, C.W., Matthews, R.J., Donaldson, M.M.K., 2003. The association of diet and other lifestyle factors with overactive bladder and stress incontinence: a longitudinal study in women. BJU Int. 92, 69-77]. We evaluated the effects of three artificial sweeteners, acesulfame K, aspartame and sodium saccharin, on the contractile response of isolated rat detrusor muscle strips. Methods: Strips of detrusor muscle were placed in an organ bath and stimulated with electrical field stimulation (EFS) in the absence and presence of atropine, and with α,β methylene ATP, potassium, calcium and carbachol. Results: Sweeteners 10 -7 M to 10 -2 M enhanced the contractile response to 10 Hz EFS compared to control (p -6 M, aspartame 10 -7 M and sodium saccharin 10 -7 M. Acesulfame K 10 -6 M increased the maximum contractile response to α,β methylene ATP by 35% (± 9.6%) (p -6 M increased the log EC 5 from -2.79 (± 0.037) to -3.03 (± 0.048, p -7 M from -2.74 (± 0.03) to 2.86 (± 0.031, p +2 channels

PERCEPTION OF SWEET TASTE IS IMPORTANT FOR VOLUNTARY ALCOHOL CONSUMPTION IN MICE

OpenAIRE

Blednov, Y.A.; Walker, D.; Martinez, M.; Levine, M.; Damak, S.; Margolskee, R.F.

2007-01-01

To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: α-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solution...

AVAILABILITY AND CHARACTERISTICS OF BETEL PRODUCTS IN THE U.S.†

OpenAIRE

Blank, Melissa; Deshpande, Laxmikant; Balster, Robert L.

2008-01-01

Betel use involves oral placement of shards of areca nut (Areca catechu palm seed containing the cholinergic agonist arecoline) wrapped with slaked lime in a betel leaf (Piper betle plant) or various chopped or powdered products containing areca nut and/or parts of the betel plant. Additives to this mixture include catechu (areca palm extract), spices/sweeteners (e.g., saccharin, cloves), and/or tobacco. Betel use is most common in Asia and East India; however, little is known about the avail...

Synthesis of new piroxicam derivatives and their influence on lipid bilayers.

Science.gov (United States)

Szczęśniak-Sięga, Berenika; Maniewska, Jadwiga; Poła, Andrzej; Środa-Pomianek, Kamila; Malinka, Wiesław; Michalak, Krystyna

2014-01-01

A novel series of potentially biologically active 1,2-benzothiazine 1,1-dioxides--analogs of piroxicam (a recognized non-steroidal anti-inflammatory drug) were synthesized from commercially available saccharin. All of the synthesized compounds were subjected to preliminary evaluation for their ability to interact with lipid bilayers. The influence of the new derivatives of piroxicam on liposomes made of EYPC was investigated by fluorescence spectroscopy with two fluorescent probes--Laurdan and Prodan. All the studied compounds showed an interaction with model membranes.

Shocking revelations and saccharin sweetness in the study of Drosophila olfactory memory.

Science.gov (United States)

Perisse, Emmanuel; Burke, Christopher; Huetteroth, Wolf; Waddell, Scott

2013-09-09

It is now almost forty years since the first description of learning in the fruit fly Drosophila melanogaster. Various incarnations of the classic mutagenesis approach envisaged in the early days have provided around one hundred learning defective mutant fly strains. Recent technological advances permit temporal control of neural function in the behaving fly. These approaches have radically changed experiments in the field and have provided a neural circuit perspective of memory formation, consolidation and retrieval. Combining neural perturbations with more classical mutant intervention allows investigators to interrogate the molecular and cellular processes of memory within the defined neural circuits. Here, we summarize some of the progress made in the last ten years that indicates a remarkable conservation of the neural mechanisms of memory formation between flies and mammals. We emphasize that considering an ethologically-relevant viewpoint might provide additional experimental power in studies of Drosophila memory. Copyright © 2013 Elsevier Ltd. All rights reserved.

Engineering of Metal Microstructures; Process-Microstructure-Property Relationships for Electrodeposits

DEFF Research Database (Denmark)

Jensen, Jens Dahl

2002-01-01

and concentration of additives, current density, and mass transport. The grown films were analysed by a variety of characterisation techniques - including optical light microscopy, electron microscopy, atomic force microscopy, X-ray diffraction, thin film tensile testing, and nano-indentation. Studies of anomalous...... introduced in the deposits with the use of sodium-saccharin, which led to embrittlement of the deposits. By using ultrasonic streaming near the cathode during electrodeposition in the Watts type electrolyte, improved material distribution in machined 3-dimensional groove geometries was observed...

Glucose-responsive neurons of the paraventricular thalamus control sucrose-seeking behavior.

Science.gov (United States)

Labouèbe, Gwenaël; Boutrel, Benjamin; Tarussio, David; Thorens, Bernard

2016-08-01

Feeding behavior is governed by homeostatic needs and motivational drive to obtain palatable foods. Here, we identify a population of glutamatergic neurons in the paraventricular thalamus of mice that express the glucose transporter Glut2 (encoded by Slc2a2) and project to the nucleus accumbens. These neurons are activated by hypoglycemia and, in freely moving mice, their activation by optogenetics or Slc2a2 inactivation increases motivated sucrose-seeking but not saccharin-seeking behavior. These neurons may control sugar overconsumption in obesity and diabetes.

Glucocorticoids interact with the noradrenergic arousal system in the nucleus accumbens shell to enhance memory consolidation of both appetitive and aversive taste learning.

Science.gov (United States)

Wichmann, Romy; Fornari, Raquel V; Roozendaal, Benno

2012-09-01

It is well established that glucocorticoid hormones strengthen the consolidation of long-term memory of emotionally arousing experiences but have little effect on memory of low-arousing experiences. Although both positive and negative emotionally arousing events tend to be well remembered, studies investigating the neural mechanism underlying glucocorticoid-induced memory enhancement focused primarily on negatively motivated training experiences. In the present study we show an involvement of glucocorticoids within the nucleus accumbens (NAc) in enhancing memory consolidation of both an appetitive and aversive form of taste learning. The specific glucocorticoid receptor (GR) agonist RU 28362 (1 or 3ng) administered bilaterally into the NAc shell, but not core, of male Sprague-Dawley rats immediately after an appetitive saccharin drinking experience dose-dependently enhanced 24-h retention of the safe taste, resulting in a facilitated attenuation of neophobia. Similarly, GR agonist infusions given into the NAc shell immediately after pairing of the saccharin taste with a malaise-inducing agent enhanced memory of this negative experience, resulting in an intensified conditioned aversion. Importantly, a suppression of noradrenergic activity within the NAc shell with the β-adrenoceptor antagonist propranolol blocked the facilitating effect of a concurrently administered GR agonist on memory consolidation in both the appetitive and aversive learning task. Thus, these findings indicate that GR activation interacts with the noradrenergic arousal system within the NAc to enhance memory consolidation of emotionally arousing training experiences regardless of valence. Copyright © 2012 Elsevier Inc. All rights reserved.

Lithium-induced malaise does not interfere with adaptation of the hypothalamic-pituitary-adrenal axis to stress.

Science.gov (United States)

Sanchís-Ollé, Maria; Ortega-Sánchez, Juan A; Belda, Xavier; Gagliano, Humberto; Nadal, Roser; Armario, Antonio

2017-04-03

We have recently demonstrated that adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to repeated exposure to a stressor does not follow the rules of habituation and can be fully expressed after a single experience with severe stressors. In the present work we tested the hypothesis that adaptation could be impaired if animals experience malaise during initial exposure to the stressor. To this end, animals were allowed to drink saccharin for 30min before being exposed for 3h to immobilization on boards (IMO), a severe stressor; then they were given either saline or lithium ip after the first hour of IMO. Stress-naïve rats followed exactly the same procedure except IMO. Exposure to IMO caused a strong activation of the HPA axis whereas the effect of lithium was modest. Both IMO and lithium administration resulted in conditioned taste aversion to saccharin when evaluated 4days later. When all animals were exposed to IMO 6days later, reduced HPA response and less impact on body weight was observed in the two groups previously exposed to IMO as compared with stress-naïve rats. Therefore, lithium administration during the first IMO exposure did not affect adaptation of the HPA axis and weight gain. These results indicate that malaise per se only weakly activated the HPA axis and argue against the hypothesis that signs of physical malaise during exposure to the stressor could impair HPA adaptation. Copyright © 2017 Elsevier Inc. All rights reserved.

Reduced alcohol consumption in mice lacking preprodynorphin.

Science.gov (United States)

Blednov, Yuri A; Walker, Danielle; Martinez, Marni; Harris, R Adron

2006-10-01

Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the kappa-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 h) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin, but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild-type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference, or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest that this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).

Gustatory thalamus lesions in the rat: III. Simultaneous contrast and autoshaping.

Science.gov (United States)

Reilly, S; Pritchard, T C

1997-12-01

The performance of rats with electrophysiologically guided electrolytic lesions of the gustatory thalamus (GT) was compared to that of control subjects in two experiments. In Experiment 1, the lesioned rats showed normal simultaneous contrast effects (both positive and negative) during brief, alternating access to 0.15% saccharin and 1.0 M sucrose. There was, however, a substantial lesion-induced impairment in the level of conditioned stimulus-directed maintenance responding on the autoshaping procedure of Experiment 2. These findings are discussed with respect to the anticipatory contrast deficit recently reported in GT-lesioned rats.

Contaminants of emerging concern in the open sea waters of the Western Mediterranean.

Science.gov (United States)

Brumovský, Miroslav; Bečanová, Jitka; Kohoutek, Jiří; Borghini, Mireno; Nizzetto, Luca

2017-10-01

Pollution by chemical substances is of concern for the maintenance of healthy and sustainable aquatic environments. While the occurrence and fate of numerous emerging contaminants, especially pharmaceuticals, is well documented in freshwater, their occurrence and behavior in coastal and marine waters is much less studied and understood. This study investigates the occurrence of 58 chemicals in the open surface water of the Western Mediterranean Sea for the first time. 70 samples in total were collected in 10 different sampling areas. 3 pesticides, 11 pharmaceuticals and personal care products and 2 artificial sweeteners were detected at sub-ng to ng/L levels. Among them, the herbicide terbuthylazine, the pharmaceuticals caffeine, carbamazepine, naproxen and paracetamol, the antibiotic sulfamethoxazole, the antibacterial triclocarban and the two artificial sweeteners acesulfame and saccharin were detected in all samples. The compound detected at the highest concentration was saccharin (up to 5.23 ng/L). Generally small spatial differences among individual sampling areas point to a diffuse character of sources which are likely dominated by WWTP effluents and runoffs from agricultural areas or even, at least for pharmaceuticals and artificial food additives, from offshore sources such as ferries and cruising ships. The implications of the ubiquitous presence in the open sea of chemicals that are bio-active or toxic at low doses on photosynthetic organisms and/or bacteria (i.e., terbuthylazine, sulfamethoxazole or triclocarban) deserve scientific attention, especially concerning possible subtle impacts from chronic exposure of pelagic microorganisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Powder X-ray diffraction method for the quantification of cocrystals in the crystallization mixture.

Science.gov (United States)

Padrela, Luis; de Azevedo, Edmundo Gomes; Velaga, Sitaram P

2012-08-01

The solid state purity of cocrystals critically affects their performance. Thus, it is important to accurately quantify the purity of cocrystals in the final crystallization product. The aim of this study was to develop a powder X-ray diffraction (PXRD) quantification method for investigating the purity of cocrystals. The method developed was employed to study the formation of indomethacin-saccharin (IND-SAC) cocrystals by mechanochemical methods. Pure IND-SAC cocrystals were geometrically mixed with 1:1 w/w mixture of indomethacin/saccharin in various proportions. An accurately measured amount (550 mg) of the mixture was used for the PXRD measurements. The most intense, non-overlapping, characteristic diffraction peak of IND-SAC was used to construct the calibration curve in the range 0-100% (w/w). This calibration model was validated and used to monitor the formation of IND-SAC cocrystals by liquid-assisted grinding (LAG). The IND-SAC cocrystal calibration curve showed excellent linearity (R(2) = 0.9996) over the entire concentration range, displaying limit of detection (LOD) and limit of quantification (LOQ) values of 1.23% (w/w) and 3.74% (w/w), respectively. Validation results showed excellent correlations between actual and predicted concentrations of IND-SAC cocrystals (R(2) = 0.9981). The accuracy and reliability of the PXRD quantification method depend on the methods of sample preparation and handling. The crystallinity of the IND-SAC cocrystals was higher when larger amounts of methanol were used in the LAG method. The PXRD quantification method is suitable and reliable for verifying the purity of cocrystals in the final crystallization product.

Feasibility of electrospray deposition for rapid screening of the cocrystal formation and single step, continuous production of pharmaceutical nanococrystals.

Science.gov (United States)

Emami, Shahram; Siahi-Shadbad, Mohammadreza; Barzegar-Jalali, Mohammad; Adibkia, Khosro

2018-06-01

This study employed electrospray deposition (ESD) for simultaneous synthesis and particle engineering of cocrystals. Exploring new methods for the efficient production of cocrystals with desired particle properties is an essential demand. The possibility of cocrystal formation by ESD was examined for indomethacin-saccharin, indomethacin-nicotinamide, naproxen-nicotinamide, and naproxen-iso-nicotinamide cocrystals. Solutions of the drug and coformer at stoichiometric ratios were sprayed to a high electric field which caused rapid evaporation of the solvent and the formation of fine particles. The phase purity, size, and morphology of products were compared with reference cocrystals. Experiments were performed to evaluate the effects of stoichiometric ratio, concentration and solvent type on the cocrystal formation. Physical stability and dissolution properties of the electrosprayed cocrystals were also compared with reference cocrystals. ESD was found to be an efficient and rapid method to produce cocrystals for all studied systems other than indomethacin-nicotinamide. Pure cocrystals only formed at a specific drug:coformer ratio. The solvent type has a weak effect on the cocrystal formation and morphology. Electrosprayed cocrystals exhibited nano to micrometer sizes with distinct morphologies with comparable physical stability with reference cocrystals. Nanococrystals of indomethacin-saccharin with a mean size of 219 nm displayed a threefold higher dissolution rate than solvent evaporated cocrystal. ESD successfully was utilized to produce pure cocrystals of poorly soluble drugs with different morphologies and sizes ranging from nano to micrometer sizes in one step. This study highlighted the usefulness of ESD for simultaneous preparation and particle engineering of pharmaceutical cocrystals.

Specially designed sweeteners and food for diabetics--a real need?

Science.gov (United States)

Lenner, R A

1976-07-01

In the first part of this study, the effect of four isocaloric mixed breakfast meals on the blood glucose and urinary glucose losses was tested in nine adult diabetics and in three healthy subjects, ages 60 to 75. Three of the test meals consisted of a base diet supplemented with applesauce sweetened with sucrose, fructose, or sorbitol. In the fourth test meal, the starch was increased together with saccharine. In the second part of the study, analyses for free glucose and sucrose in several timed food preparations, ordinary as well as food preparations specially designed for diabetics, were performed. The amount of sucrose equivalents (S(eg)) in one ordinary serving of the various products was estimated. No significant differences among sucrose, fructose, and sorbitol-containing meals with respect to the effect on the blood glucose level or on glucosuria were found. The saccharine-containing meal gave a significantly greater blood glucose increase at 60 min only. The amount of sucrose in ordinary marinated foods, such as herring, cucumber, and common beet was negligible. Water-packed fruits supplied one half of the amount of S(eq) or less, compared with fruits packed in sorbitol-sweetened syrup. The amount of S(eq) in the latter products as well as in fruits packed in unsweetened juice equalled that of the fleshy substance of ordinary sucrose-sweetened products. It was concluded that fructose or sorbitol has no advantages over sucrose, as regards the effect on blood glucose in well-regulated adult diabetics, and that it seems unnecessary to have specially sweetened foods designed for diabetics.

The cannabinoid receptor 2 agonist, β-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice.

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Al Mansouri, Shamma; Ojha, Shreesh; Al Maamari, Elyazia; Al Ameri, Mouza; Nurulain, Syed M; Bahi, Amine

2014-09-01

Several recent studies have suggested that brain CB2 cannabinoid receptors play a major role in alcohol reward. In fact, the implication of cannabinoid neurotransmission in the reinforcing effects of ethanol (EtOH) is becoming increasingly evident. The CB2 receptor agonist, β-caryophyllene (BCP) was used to investigate the role of the CB2 receptors in mediating alcohol intake and ethanol-induced conditioned place preference (EtOH-CPP) and sensitivity in mice. The effect of BCP on alcohol intake was evaluated using the standard two-bottle choice drinking method. The mice were presented with increasing EtOH concentrations and its consumption was measured daily. Consumption of saccharin and quinine solutions was measured following the EtOH preference tests. Finally, the effect of BCP on alcohol reward and sensitivity was tested using an unbiased EtOH-CPP and loss of righting-reflex (LORR) procedures, respectively. BCP dose-dependently decreased alcohol consumption and preference. Additionally, BCP-injected mice did not show any difference from vehicle mice in total fluid intake in a 24-hour paradigm nor in their intake of graded concentrations of saccharin or quinine, suggesting that the CB2 receptor activation did not alter taste function. More importantly, BCP inhibited EtOH-CPP acquisition and exacerbated LORR duration. Interestingly, these effects were abrogated when mice were pre-injected with a selective CB2 receptor antagonist, AM630. Overall, the CB2 receptor system appears to be involved in alcohol dependence and sensitivity and may represent a potential pharmacological target for the treatment of alcoholism. Copyright © 2014 Elsevier Inc. All rights reserved.

Prefrontal blood flow and oxygenation measured by NIRS during long-term memory tasks are impaired by acute hyperglycemia (Conference Presentation)

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Harris, R. Luke; Bell, Lindsay; Reimer, Andrea; Pettersen, Jacqueline A.; Siakaluk, Paul; Duffels, Brian

2017-02-01

Our goal was to use 2-channel frequency domain near-infrared spectroscopy (NIRS) to investigate the hemodynamic and metabolic mechanisms underlying hyperglycemia-associated long-term memory impairment. We hypothesized that prefrontal cortex (PFC) oxygen saturation (%Sat) and perfusion (tHb, i.e. total hemoglobin) would decrease due to hyperglycemia during learning, and then increase during recall. During learning, participants' blood glucose was manipulated with beverages containing either 47.4 mg saccharine control (CON, n = 10), or 50 g dextrose + 23.7 mg saccharine (GLC, n = 10). In the Symbol-Digit Modalities Test (SMDT) participants matched nine symbols to corresponding digits (1-9 inclusive), completing 105 learning and 15 testing trials on day 1 and 15 testing trials on day 2. From learning to recall, CON SMDT performance was unchanged, but GLC SMDT performance was decreased 11% (P = 0.0173). There were significant interactions (2-way ANOVA) between the CON-GLC treatment effects and the learning-recall effects for both PFC perfusion and oxygen saturation. Specifically, comparing learning to recall, CON exhibited no tHb differences but for GLC there was a large tHb decrease during learning with a partial recovery toward CON values during recall (P = 0.0012); and, comparing learning to recall, CON exhibited a large %Sat decrease but GLC exhibited a large %Sat increase (P = 0.021). We speculate that, during learning, after overnight fasting (CON) the PFC demands more hemodynamic and metabolic resources and "works" harder, but with readily available sugar (GLC) the PFC exhibits decreased "effort."

Relaxin-3 receptor (RXFP3 signalling mediates stress-related alcohol preference in mice.

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Andrew W Walker

Full Text Available Stressful life events are causally linked with alcohol use disorders (AUDs, providing support for a hypothesis that alcohol consumption is aimed at stress reduction. We have previously shown that expression of relaxin-3 mRNA in rat brain correlates with alcohol intake and that central antagonism of relaxin-3 receptors (RXFP3 prevents stress-induced reinstatement of alcohol-seeking. Therefore the objectives of these studies were to investigate the impact of Rxfp3 gene deletion in C57BL/6J mice on baseline and stress-related alcohol consumption. Male wild-type (WT and Rxfp3 knockout (KO (C57/B6JRXFP3TM1/DGen littermate mice were tested for baseline saccharin and alcohol consumption and preference over water in a continuous access two-bottle free-choice paradigm. Another cohort of mice was subjected to repeated restraint followed by swim stress to examine stress-related alcohol preference. Hepatic alcohol and aldehyde dehydrogenase activity was assessed in mice following chronic alcohol intake and in naive controls. WT and Rxfp3 KO mice had similar baseline saccharin and alcohol preference, and hepatic alcohol processing. However, Rxfp3 KO mice displayed a stress-induced reduction in alcohol preference that was not observed in WT littermates. Notably, this phenotype, once established, persisted for at least six weeks after cessation of stress exposure. These findings suggest that in mice, relaxin-3/RXFP3 signalling is involved in maintaining high alcohol preference during and after stress, but does not appear to strongly regulate the primary reinforcing effects of alcohol.

Artificial sweeteners and human bladder cancer.

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Howe, G R; Burch, J D; Miller, A B; Morrison, B; Gordon, P; Weldon, L; Chambers, L W; Fodor, G; Winsor, G M

1977-09-17

A positive association between the use of artificial sweetners, particularly saccharin, and risk of bladder cancer in males has been observed in a case-control study of 480 men and 152 women in three Provinces in Canada. The risk ratio for ever versus never used is 1-6 for males (P=0-009, one-tailed test), and a significant dose-response relationship was obtained for both duration and frequency of use. The population attributable risk for males is estimated at 7%, though for diabetics, who have a similar risk ratio for artificial sweetner use as non-diabetics, the attributable risk is 33%.

Esthetic or Functional, Saccharine or Shocking? An Editor Looks at Values in Children's Books.

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Giblin, James Cross

1977-01-01

Discusses artistic or esthetic, social and cultural, functional, and commercial values looked for by children's book editors in selecting and publishing manuscripts. Also reviews changes in social and cultural values as shown by children's books published in 1947, 1957, and 1967. (GT)

Maternal neglect with reduced depressive-like behavior and blunted c-fos activation in Brattleboro mothers, the role of central vasopressin.

Science.gov (United States)

Fodor, Anna; Klausz, Barbara; Pintér, Ottó; Daviu, Nuria; Rabasa, Cristina; Rotllant, David; Balazsfi, Diana; Kovacs, Krisztina B; Nadal, Roser; Zelena, Dóra

2012-09-01

Early mother-infant relationships exert important long-term effects in offspring and are disturbed by factors such as postpartum depression. We aimed to clarify if lack of vasopressin influences maternal behavior paralleled by the development of a depressive-like phenotype. We compared vasopressin-deficient Brattleboro mothers with heterozygous and homozygous normal ones. The following parameters were measured: maternal behavior (undisturbed and separation-induced); anxiety by the elevated plus maze; sucrose and saccharin preference and forced swim behavior. Underlying brain areas were examined by c-fos immunocytochemistry among rest and after swim-stress. In another group of rats, vasopressin 2 receptor agonist was used peripherally to exclude secondary changes due to diabetes insipidus. Results showed that vasopressin-deficient rats spend less time licking-grooming their pups through a centrally driven mechanism. There was no difference between genotypes during the pup retrieval test. Vasopressin-deficient mothers tended to explore more the open arms of the plus maze, showed more preference for sucrose and saccharin and struggled more in the forced swim test, suggesting that they act as less depressive. Under basal conditions, vasopressin-deficient mothers had more c-fos expression in the medial preoptic area, shell of nucleus accumbens, paraventricular nucleus of the hypothalamus and amygdala, but not in other structures. In these areas the swim-stress-induced activation was smaller. In conclusion, vasopressin-deficiency resulted in maternal neglect due to a central effect and was protective against depressive-like behavior probably as a consequence of reduced activation of some stress-related brain structures. The conflicting behavioral data underscores the need for more sex specific studies. Copyright © 2012 Elsevier Inc. All rights reserved.

Near-infrared spectroscopy for cocrystal screening. A comparative study with Raman spectroscopy.

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Allesø, Morten; Velaga, Sitaram; Alhalaweh, Amjad; Cornett, Claus; Rasmussen, Morten A; van den Berg, Frans; de Diego, Heidi Lopez; Rantanen, Jukka

2008-10-15

Near-infrared (NIR) spectroscopy is a well-established technique for solid-state analysis, providing fast, noninvasive measurements. The use of NIR spectroscopy for polymorph screening and the associated advantages have recently been demonstrated. The objective of this work was to evaluate the analytical potential of NIR spectroscopy for cocrystal screening using Raman spectroscopy as a comparative method. Indomethacin was used as the parent molecule, while saccharin and l-aspartic acid were chosen as guest molecules. Molar ratios of 1:1 for each system were subjected to two types of preparative methods. In the case of saccharin, liquid-assisted cogrinding as well as cocrystallization from solution resulted in a stable 1:1 cocrystalline phase termed IND-SAC cocrystal. For l-aspartic acid, the solution-based method resulted in a polymorphic transition of indomethacin into the metastable alpha form retained in a physical mixture with the guest molecule, while liquid-assisted cogrinding did not induce any changes in the crystal lattice. The good chemical peak selectivity of Raman spectroscopy allowed a straightforward interpretation of sample data by analyzing peak positions and comparing to those of pure references. In addition, Raman spectroscopy provided additional information on the crystal structure of the IND-SAC cocrystal. The broad spectral line shapes of NIR spectra make visual interpretation of the spectra difficult, and consequently, multivariate modeling by principal component analysis (PCA) was applied. Successful use of NIR/PCA was possible only through the inclusion of a set of reference mixtures of parent and guest molecules representing possible solid-state outcomes from the cocrystal screening. The practical hurdle related to the need for reference mixtures seems to restrict the applicability of NIR spectroscopy in cocrystal screening.

c-Fos induction in mesotelencephalic dopamine pathway projection targets and dorsal striatum following oral intake of sugars and fats in rats.

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Dela Cruz, J A D; Coke, T; Karagiorgis, T; Sampson, C; Icaza-Cukali, D; Kest, K; Ranaldi, R; Bodnar, R J

2015-02-01

Overconsumption of nutrients high in fats and sugars can lead to obesity. Previous studies indicate that sugar or fat consumption activate individual brain sites using Fos-like immunoreactivity (FLI). Sugars and fats also elicit conditioned flavor preferences (CFP) that are differentially mediated by flavor-flavor (orosensory: f/f) and flavor-nutrient (post-ingestive: f/n) processes. Dopamine (DA) signaling in the medial prefrontal cortex (mPFC), the amygdala (AMY) and the nucleus accumbens (NAc), has been implicated in acquisition and expression of fat- and sugar-CFP. The present study examined the effects of acute consumption of fat (corn oil: f/f and f/n), glucose (f/f and f/n), fructose, (f/f only), saccharin, xanthan gum or water upon simultaneous FLI activation of DA mesotelencephalic nuclei (ventral tegmental area (VTA)) and projections (infralimbic and prelimbic mPFC, basolateral and central-cortico-medial AMY, core and shell of NAc as well as the dorsal striatum). Consumption of corn oil solutions, isocaloric to glucose and fructose, significantly increased FLI in all sites except for the NAc shell. Glucose intake significantly increased FLI in both AMY areas, dorsal striatum and NAc core, but not in either mPFC area, VTA or Nac shell. Correspondingly, fructose intake significantly increased FLI in the both AMY areas, the infralimbic mPFC and dorsal striatum, but not the prelimbic mPFC, VTA or either NAc area. Saccharin and xanthan gum intake failed to activate FLI relative to water. When significant FLI activation occurred, highly positive relationships were observed among sites, supporting the idea of activation of a distributed brain network mediating sugar and fat intake. Copyright © 2014 Elsevier Inc. All rights reserved.

Is catalase involved in the effects of systemic and pVTA administration of 4-methylpyrazole on ethanol self-administration?

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Peana, Alessandra T; Pintus, Francesca A; Bennardini, Federico; Rocchitta, Gaia; Bazzu, Gianfranco; Serra, Pier Andrea; Porru, Simona; Rosas, Michela; Acquas, Elio

2017-09-01

The oxidative metabolism of ethanol into acetaldehyde involves several enzymes, including alcohol dehydrogenase (ADH) and catalase-hydrogen peroxide (H 2 O 2 ). In this regard, while it is well known that 4-methylpyrazole (4-MP) acts by inhibiting ADH in the liver, little attention has been placed on its ability to interfere with fatty acid oxidation-mediated generation of H 2 O 2 , a mechanism that may indirectly affect catalase whose enzymatic activity requires H 2 O 2 . The aim of our investigation was twofold: 1) to evaluate the effect of systemic (i.p. [intraperitoneal]) and local (into the posterior ventral tegmental area, pVTA) administration of 4-MP on oral ethanol self-administration, and 2) to assess ex vivo whether or not systemic 4-MP affects liver and brain H 2 O 2 availability. The results show that systemic 4-MP reduced ethanol but not acetaldehyde or saccharin self-administration, and decreased the ethanol deprivation effect. Moreover, local intra-pVTA administration of 4-MP reduced ethanol but not saccharin self-administration. In addition, although unable to affect basal catalase activity, systemic administration of 4-MP decreased H 2 O 2 availability both in liver and in brain. Overall, these results indicate that 4-MP interferes with ethanol self-administration and suggest that its behavioral effects could be due to a decline in catalase-H 2 O 2 system activity as a result of a reduction of H 2 O 2 availability, thus highlighting the role of central catalase-mediated metabolism of ethanol and further supporting the key role of acetaldehyde in the reinforcing properties of ethanol. Copyright © 2017 Elsevier Inc. All rights reserved.

Bidirectional enantioselective effects of the GABAB receptor agonist baclofen in two mouse models of excessive ethanol consumption.

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Kasten, Chelsea R; Blasingame, Shelby N; Boehm, Stephen L

2015-02-01

The GABAB receptor agonist baclofen has been studied extensively in preclinical models of alcohol-use disorders, yet results on its efficacy have been uncertain. Racemic baclofen, which is used clinically, can be broken down into separate enantiomers of the drug. Baclofen has been shown to produce enantioselective effects in behavioral assays, including those modeling reflexive and sexual behavior. The current studies sought to characterize the enantioselective effects of baclofen in two separate models of ethanol consumption. The first was a Drinking-in-the-Dark procedure that provides "binge-like" ethanol access to mice by restricting access to a 2-h period, 3 h into the dark cycle. The second was a two-bottle choice procedure that utilized selectively bred High Alcohol Preferring 1 (HAP1) mice to model chronic ethanol access. HAP1 mice are selectively bred to consume pharmacologically relevant amounts of ethanol in a 24-h two-bottle choice paradigm. The results showed that baclofen yields enantioselective effects on ethanol intake in both models, and that these effects are bidirectional. Total ethanol intake was decreased by R(+)-baclofen, while total intake was increased by S(-)-baclofen in the binge-like and chronic drinking models. Whereas overall binge-like saccharin intake was significantly reduced by R(+)-baclofen, chronic intake was not significantly altered. S(-)-baclofen did not significantly alter saccharin intake. Neither enantiomer significantly affected locomotion during binge-like reinforcer consumption. Collectively, these results demonstrate that baclofen produces enantioselective effects on ethanol consumption. More importantly, the modulation of consumption is bidirectional. The opposing enantioselective effects may explain some of the variance seen in published baclofen literature. Copyright © 2015 Elsevier Inc. All rights reserved.

Alcohol consumption increases locomotion in an open field and induces Fos-immunoreactivity in reward and approach/withdrawal-related neurocircuitries.

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Wscieklica, Tatiana; de Barros Viana, Milena; Le Sueur Maluf, Luciana; Pouza, Kathlein Cristiny Peres; Spadari, Regina Célia; Céspedes, Isabel Cristina

2016-02-01

Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take the drug, loss of control in limiting intake and, eventually, the emergence of a negative emotional state when access to the drug is prevented. Both dopamine and corticotropin-releasing factor (CRF)-mediated systems seem to play important roles in the modulation of alcohol abuse and dependence. The present study investigated the effects of alcohol consumption on anxiety and locomotor parameters and on the activation of dopamine and CRF-innervated brain regions. Male Wistar rats were given a choice of two bottles for 31 days, one containing water and the other a solution of saccharin + alcohol. Control animals only received water and a solution of 0.2% saccharin. On the 31st day, animals were tested in the elevated plus-maze and open field, and euthanized immediately after the behavioral tests. An independent group of animals was treated with ethanol and used to measure blood ethanol concentration. Results showed that alcohol intake did not alter behavioral measurements in the plus-maze, but increased the number of crossings in the open field, an index of locomotor activity. Additionally, alcohol intake increased Fos-immunoreactivity (Fos-ir) in the prefrontal cortex, in the shell region of the nucleus accumbens, in the medial and central amygdala, in the bed nucleus of the stria terminalis, in the septal region, and in the paraventricular and dorsomedial hypothalamus, structures that have been linked to reward and to approach/withdrawal behavior. These observations might be relevant to a better understanding of the behavioral and physiological alterations that follow alcohol consumption. Copyright © 2016 Elsevier Inc. All rights reserved.

Catalog of risks

Energy Technology Data Exchange (ETDEWEB)

Cohen, B L; Lee, I S [Pittsburgh Univ., PA (USA). Dept. of Physics

1979-06-01

Information on risks is collected from various sources and converted into loss of life expectancy throughout life and in various age ranges. Risks included are radiation, accidents of various types, various diseases, overweight, tobacco use, alcohol and drugs, coffee, saccharin, and The Pill, occupational risks, socioeconomic factors, marital status, geography, serving in U.S. armed forces in Vietnam, catastrophic events, energy production, and technology in general. Information is also included on methods for reducing risks, risks in individual actions, very-hazardous activities, and priorities and perspective. Risks of natural and occupational radiation and exposure to radioactivity from the nuclear industry are compared with risks of similar or competing activities.

A catalog of risks

International Nuclear Information System (INIS)

Cohen, B.L.; Lee, I.S.

1979-01-01

Information on risks is collected from various sources and converted into loss of life expectancy throughout life and in various age ranges. Risks included are radiation, accidents of various types, various diseases, overweight, tobacco use, alcohol and drugs, coffee, saccharin, and The Pill, occupational risks, socioeconomic factors, marital status, geography, serving in U.S. armed forces in Vietnam, catastrophic events, energy production, and technology in general. Information is also included on methods for reducing risks, risks in individual actions, very-hazardous activities, and priorities and perspective. Risks of natural and occupational radiation and exposure to radioactivity from the nuclear industry are compared with risks of similar or competing activities. (author)

Avaliação sensorial de bebidas de goiaba adoçadas com diferentes agentes adoçantes Sensory evaluation of guava drinks sweetened with different sweetening agents

Directory of Open Access Journals (Sweden)

Aline Gurgel Fernandes

2009-06-01

Full Text Available Devido à crescente procura por bebidas à base de frutas tropicais e à expansão do segmento de produtos com valores calóricos reduzidos, este trabalho objetivou avaliar o grau de doçura, sabor, impressão global e a intenção de compra das bebidas de goiaba adoçadas com diferentes agentes adoçantes através de frequência de notas, teste de médias e Mapa de Preferência Interno (MPI. Utilizaram-se polpa de goiaba, água potável e diferentes agentes adoçantes (sacarose, mistura ciclamato/sacarina, aspartame, acesulfame-K, estévia e mistura sacarina/ciclamato sódico/acesulfame-K. A avaliação sensorial foi realizada com 100 provadores não treinados em teste laboratorial através do delineamento de blocos completos balanceados. Objetivando a avaliação das respostas individuais de cada provador, as respostas sensoriais foram avaliadas pela metodologia do MPI, empregando-se a técnica de Análise de Componentes Principais. As bebidas de goiaba adoçadas com sacarose e aspartame apresentaram avaliação sensorial semelhante por parte dos consumidores, apresentando os maiores valores médios no teste de aceitação, enquanto as adoçadas com estévia, com a mistura de três agentes adoçantes e a mistura ciclamato/sacarina apresentaram os valores mais baixos na avaliação sensorial. A utilização do MPI confirmou os resultados obtidos através de frequência de notas e teste de médias.Due to a constant search for tropical fruit drinks and calorie reduced products, this work aimed to evaluate the degree of sweetness, flavor, overall global impression, and purchase intention of guava drinks sweetened with different sweetening agents through the response rank frequency and average test, and internal preference mapping (IPM. Guava pulp, drinking water, and sweetening agents (sucrose, mixture cyclamate/saccharine, aspartame, acesulfame K, stevia and mixture saccharine/sodium cyclamate/acesulfame K were used. The sensory evaluation was

Diet-induced obesity causes ghrelin resistance in reward processing tasks.

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Lockie, Sarah H; Dinan, Tara; Lawrence, Andrew J; Spencer, Sarah J; Andrews, Zane B

2015-12-01

Diet-induced obesity (DIO) causes ghrelin resistance in hypothalamic Agouti-related peptide (AgRP) neurons. However, ghrelin promotes feeding through actions at both the hypothalamus and mesolimbic dopamine reward pathways. Therefore, we hypothesized that DIO would also establish ghrelin resistance in the ventral tegmental area (VTA), a major site of dopaminergic cell bodies important in reward processing. We observed reduced sucrose and saccharin consumption in Ghrelin KO vs Ghrelin WT mice. Moreover, DIO reduced saccharin consumption relative to chow-fed controls. These data suggest that the deletion of ghrelin and high fat diet both cause anhedonia. To assess if these are causally related, we tested whether DIO caused ghrelin resistance in a classic model of drug reward, conditioned place preference (CPP). Chow or high fat diet (HFD) mice were conditioned with ghrelin (1mg/kg in 10ml/kg ip) in the presence or absence of food in the conditioning chamber. We observed a CPP to ghrelin in chow-fed mice but not in HFD-fed mice. HFD-fed mice still showed a CPP for cocaine (20mg/kg), indicating that they maintained the ability to develop conditioned behaviour. The absence of food availability during ghrelin conditioning sessions induced a conditioned place aversion, an effect that was still present in both chow and HFD mice. Bilateral intra-VTA ghrelin injection (0.33μg/μl in 0.5μl) robustly increased feeding in both chow-fed and high fat diet (HFD)-fed mice; however, this was correlated with body weight only in the chow-fed mice. Our results suggest that DIO causes ghrelin resistance albeit not directly in the VTA. We suggest there is impaired ghrelin sensitivity in upstream pathways regulating reward pathways, highlighting a functional role for ghrelin linking appropriate metabolic sensing with reward processing. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Expression of HIV gp120 protein increases sensitivity to the rewarding properties of methamphetamine in mice

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Kesby, James P.; Hubbard, David T.; Markou, Athina; Semenova, Svetlana

2012-01-01

Methamphetamine abuse and human immunodeficiency virus (HIV) infection induce neuropathological changes in corticolimbic brain areas involved in reward and cognitive function. Little is known about the combined effects of methamphetamine and HIV infection on cognitive and reward processes. The HIV/gp120 protein induces neurodegeneration in mice, similar to HIV-induced pathology in humans. We investigated the effects of gp120 expression on associative learning, preference for methamphetamine and non-drug reinforcers, and sensitivity to the conditioned rewarding properties of methamphetamine in transgenic (tg) mice expressing HIV/gp120 protein (gp120-tg). gp120-tg mice learned the operant response for food at the same rate as non-tg mice. In the two-bottle choice procedure with restricted access to drugs, gp120-tg mice exhibited greater preference for methamphetamine and saccharin than non-tg mice, whereas preference for quinine was similar between genotypes. Under conditions of unrestricted access to methamphetamine, the mice exhibited a decreased preference for increasing methamphetamine concentrations. However, male gp120-tg mice showed a decreased preference for methamphetamine at lower concentrations than non-tg male mice. gp120-tg mice developed methamphetamine-induced conditioned place preference at lower methamphetamine doses compared with non-tg mice. No differences in methamphetamine pharmacokinetics were found between genotypes. These results indicate that gp120-tg mice exhibit no deficits in associative learning or reward/motivational function for a natural reinforcer. Interestingly, gp120 expression resulted in increased preference for methamphetamine and a highly palatable non-drug reinforcer (saccharin) and increased sensitivity to methamphetamine-induced conditioned reward. These data suggest that HIV-positive individuals may have increased sensitivity to methamphetamine, leading to high methamphetamine abuse potential in this population. PMID

Artificial sweeteners in a large Canadian river reflect human consumption in the watershed.

Directory of Open Access Journals (Sweden)

John Spoelstra

Full Text Available Artificial sweeteners have been widely incorporated in human food products for aid in weight loss regimes, dental health protection and dietary control of diabetes. Some of these widely used compounds can pass non-degraded through wastewater treatment systems and are subsequently discharged to groundwater and surface waters. Measurements of artificial sweeteners in rivers used for drinking water production are scarce. In order to determine the riverine concentrations of artificial sweeteners and their usefulness as a tracer of wastewater at the scale of an entire watershed, we analyzed samples from 23 sites along the entire length of the Grand River, a large river in Southern Ontario, Canada, that is impacted by agricultural activities and urban centres. Municipal water from household taps was also sampled from several cities within the Grand River Watershed. Cyclamate, saccharin, sucralose, and acesulfame were found in elevated concentrations despite high rates of biological activity, large daily cycles in dissolved oxygen and shallow river depth. The maximum concentrations that we measured for sucralose (21 µg/L, cyclamate (2.4 µg/L [corrected], and saccharin (7.2 µg/L are the highest reported concentrations of these compounds in surface waters to date anywhere in the world. Acesulfame persists at concentrations that are up to several orders of magnitude above the detection limit over a distance of 300 km and it behaves conservatively in the river, recording the wastewater contribution from the cumulative population in the basin. Acesulfame is a reliable wastewater effluent tracer in rivers. Furthermore, it can be used to assess rates of nutrient assimilation, track wastewater plume dilution, separate human and animal waste contributions and determine the relative persistence of emerging contaminants in impacted watersheds where multiple sources confound the usefulness of other tracers. The effects of artificial sweeteners on aquatic biota

The ghrelin signalling system is involved in the consumption of sweets.

Directory of Open Access Journals (Sweden)

Sara Landgren

Full Text Available The gastric-derived orexigenic peptide ghrelin affects brain circuits involved in energy balance as well as in reward. Indeed, ghrelin activates an important reward circuit involved in natural- as well as drug-induced reward, the cholinergic-dopaminergic reward link. It has been hypothesized that there is a common reward mechanism for alcohol and sweet substances in both animals and humans. Alcohol dependent individuals have higher craving for sweets than do healthy controls and the hedonic response to sweet taste may, at least in part, depend on genetic factors. Rat selectively bred for high sucrose intake have higher alcohol consumption than non-sucrose preferring rats and vice versa. In the present study a group of alcohol-consuming individuals selected from a population cohort was investigated for genetic variants of the ghrelin signalling system in relation to both their alcohol and sucrose consumption. Moreover, the effects of GHS-R1A antagonism on voluntary sucrose-intake and operant self-administration, as well as saccharin intake were investigated in preclinical studies using rodents. The effects of peripheral grelin administration on sucrose intake were also examined. Here we found associations with the ghrelin gene haplotypes and increased sucrose consumption, and a trend for the same association was seen in the high alcohol consumers. The preclinical data show that a GHS-R1A antagonist reduces the intake and self-administration of sucrose in rats as well as saccharin intake in mice. Further, ghrelin increases the intake of sucrose in rats. Collectively, our data provide a clear indication that the GHS-R1A antagonists reduces and ghrelin increases the intake of rewarding substances and hence, the central ghrelin signalling system provides a novel target for the development of drug strategies to treat addictive behaviours.

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

Science.gov (United States)

Peana, Alessandra T; Muggironi, Giulia; Fois, Giulia R; Zinellu, Manuel; Sirca, Donatella; Diana, Marco

2012-08-01

Acetaldehyde (ACD), the first metabolite of ethanol, has been implicated in several behavioural actions of alcohol, including its reinforcing effects. Recently, we reported that l-cysteine, a sequestrating agent of ACD, reduced oral ethanol self-administration and that ACD was orally self-administered. This study examined the effects of l-cysteine pre-treatment during the acquisition and maintenance phases of ACD (0.2%) self-administration as well as on the deprivation effect after ACD extinction and on a progressive ratio (PR) schedule of reinforcement. In a separate PR schedule of reinforcement, the effect of l-cysteine was assessed on the break-point produced by ethanol (10%). Furthermore, we tested the effect of l-cysteine on saccharin (0.2%) reinforcement. Wistar rats were trained to self-administer ACD by nose poking on a fixed ratio (FR1) schedule in 30-min daily sessions. Responses on an active nose-poke caused delivery of ACD solution, whereas responses on an inactive nose-poke had no consequences. l-cysteine reduced the acquisition (40 mg/kg), the maintenance and the deprivation effect (100 mg/kg) of ACD self-administration. Furthermore, at the same dose, l-cysteine (120 mg/kg) decreased both ACD and ethanol break point. In addition, l-cysteine was unable to suppress the different responses for saccharin, suggesting that its effect did not relate to an unspecific decrease in a general motivational state. Compared to saline, l-cysteine did not modify responses on inactive nose-pokes, suggesting an absence of a non-specific behavioural activation. Taken together, these results could support the hypotheses that ACD possesses reinforcing properties and l-cysteine reduces motivation to self-administer ACD. Copyright © 2012 Elsevier Inc. All rights reserved.

Oxytocin decreases sweet taste sensitivity in mice.

Science.gov (United States)

Sinclair, Michael S; Perea-Martinez, Isabel; Abouyared, Marianne; St John, Steven J; Chaudhari, Nirupa

2015-03-15

Oxytocin (OXT) suppresses food intake and lack of OXT leads to overconsumption of sucrose. Taste bud cells were recently discovered to express OXT-receptor. In the present study we tested whether administering OXT to wild-type mice affects their licking behavior for tastants in a paradigm designed to be sensitive to taste perception. We injected C57BL/6J mice intraperitoneally (i.p.) with 10mg/kg OXT and assayed their brief-access lick responses, motivated by water deprivation, to NaCl (300mM), citric acid (20mM), quinine (0.3mM), saccharin (10mM), and a mix of MSG and IMP (100mM and 0.5mM respectively). OXT had no effect on licking for NaCl, citric acid, or quinine. A possible effect of OXT on saccharin and MSG+IMP was difficult to interpret due to unexpectedly low lick rates to water (the vehicle for all taste solutions), likely caused by the use of a high OXT dose that suppressed licking and other behaviors. A subsequent experiment focused on another preferred tastant, sucrose, and employed a much lower OXT dose (0.1mg/kg). This modification, based on our measurements of plasma OXT following i.p. injection, permitted us to elevate plasma [OXT] sufficiently to preferentially activate taste bud cells. OXT at this low dose significantly reduced licking responses to 0.3M sucrose, and overall shifted the sucrose concentration - behavioral response curves rightward (mean EC50saline=0.362M vs. EC50OXT=0.466M). Males did not differ from females under any condition in this study. We propose that circulating oxytocin is another factor that modulates taste-based behavior. Copyright © 2014 Elsevier Inc. All rights reserved.

Enduring effects of perinatal nicotine exposure on murine sleep in adulthood.

Science.gov (United States)

Borniger, Jeremy C; Don, Reuben F; Zhang, Ning; Boyd, R Thomas; Nelson, Randy J

2017-09-01

The long-term consequences of early life nicotine exposure are poorly defined. Approximately 8-10% of women report smoking during pregnancy, and this may promote aberrant development in the offspring. To this end, we investigated potential enduring effects of perinatal nicotine exposure on murine sleep and affective behaviors in adulthood (~13-15 wk of age) in C57Bl6j mice. Mothers received a water bottle containing 200 µg/ml nicotine bitartrate dihydrate in 2% wt/vol saccharin or pH-matched 2% saccharin with 0.2% (vol/vol) tartaric acid throughout pregnancy and before weaning. Upon reaching adulthood, offspring were tested in the open field and elevated plus maze, as well as the forced swim and sucrose anhedonia tests. Nicotine-exposed male (but not female) mice had reduced mobility in the open field, but no differences were observed in anxiety-like or depressive-like responses. Upon observing this male-specific phenotype, we further assessed sleep-wake states via wireless EEG/EMG telemetry. Following baseline recording, we assessed whether mice exposed to nicotine altered their homeostatic response to 5 h of total sleep deprivation and whether nicotine influenced responses to a powerful somnogen [i.e., lipopolysaccharides (LPS)]. Males exposed to perinatal nicotine decreased the percent time spent awake and increased time in non-rapid eye movement (NREM) sleep, without changes to REM sleep. Nicotine-exposed males also displayed exaggerated responses (increased time asleep and NREM spectral power) to sleep deprivation. Nicotine-exposed animals additionally had blunted EEG slow-wave responses to LPS administration. Together, our data suggest that perinatal nicotine exposure has long-lasting effects on normal sleep and homeostatic sleep processes into adulthood. Copyright © 2017 the American Physiological Society.

Oxygen With Cold Bubble Humidification Is No Better Than Dry Oxygen in Preventing Mucus Dehydration, Decreased Mucociliary Clearance, and Decline in Pulmonary Function.

Science.gov (United States)

Franchini, Michelle Lisidati; Athanazio, Rodrigo; Amato-Lourenço, Luis Fernando; Carreirão-Neto, Waldir; Saldiva, Paulo Hilario Nascimento; Lorenzi-Filho, Geraldo; Rubin, Bruce K; Nakagawa, Naomi Kondo

2016-08-01

Little is known about the effects of long-term nasal low-flow oxygen (NLFO) on mucus and symptoms and how this variable is affected by dry or cold humidified gas. The aim of this study was to investigate the effects of dry-NLFO and cold bubble humidified-NLFO on nasal mucociliary clearance (MCC), mucus properties, inflammation, and symptoms in subjects with chronic hypoxemia requiring long-term domiciliary oxygen therapy. Eighteen subjects (mean age, 68 years; 7 male; 66% with COPD) initiating NLFO were randomized to receive dry-NLFO (n = 10) or humidified-NLFO (n = 8). Subjects were assessed at baseline, 12 h, 7 days, 30 days, 12 months, and 24 months by measuring nasal MCC using the saccharin transit test, mucus contact angle (surface tension), inflammation (cells and cytokine concentration in nasal lavage), and symptoms according to the Sino-Nasal Outcome Test-20. Nasal MCC decreased significantly (40% longer saccharin transit times) and similarly in both groups over the study period. There was a significant association between impaired nasal MCC and decline in lung function. Nasal lavage revealed an increased proportion of macrophages, interleukin-8, and epidermal growth factor concentrations with decreased interleukin-10 during the study. No changes in the proportion of ciliated cells or contact angle were observed. Coughing and sleep symptoms decreased similarly in both groups. There were no outcome differences comparing dry vs cold bubble humidified NLFO. In subjects receiving chronic NLFO, cold bubble humidification does not adequately humidify inspired oxygen to prevent deterioration of MCC, mucus hydration, and pulmonary function. The unheated bubble humidification performed no better than no humidification. ClinicalTrials.gov; No.: NCT02515786; URL: www.clinicaltrials.gov. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Taste-aversion-prone (TAP) rats and taste-aversion-resistant (TAR) rats differ in ethanol self-administration, but not in ethanol clearance or general consumption.

Science.gov (United States)

Orr, T Edward; Whitford-Stoddard, Jennifer L; Elkins, Ralph L

2004-05-01

Taste-aversion (TA)-prone (TAP) rats and TA-resistant (TAR) rats have been developed by means of bidirectional selective breeding on the basis of their behavioral responses to a TA conditioning paradigm. The TA conditioning involved the pairing of an emetic-class agent (cyclophosphamide) with a novel saccharin solution as the conditioned stimulus. Despite the absence of ethanol in the selective breeding process, these rat lines differ widely in ethanol self-administration. In the current study, blood alcohol concentrations (BACs) were determined after 9 days of limited (2 h per day) access to a simultaneous, two-bottle choice of a 10% ethanol in water solution [volume/volume (vol./vol.)] or plain water. The BACs correlated highly with ethanol intake among TAR rats, but an insufficient number of TAP rats yielded measurable BACs to make the same comparison within this rat line. The same rats were subsequently exposed to 24-h access of a two-bottle choice (10% ethanol or plain water) for 8 days. Ethanol consumption during the 24-h access period correlated highly with that seen during limited access. Subsequent TA conditioning with these rats yielded line-typical differences in saccharin preferences. In a separate group of rats, ethanol clearance was determined by measuring BACs at 1, 4, and 7 h after injection of a 2.5-g/kg dose of ethanol. Ethanol clearance was not different between the two lines. Furthermore, the lines did not differ with respect to food and water consumption. Therefore, the TAP rat-TAR rat differences in ethanol consumption cannot be attributed to line differences in ethanol metabolism or in general consummatory behavior. The findings support our contention that the line differences in ethanol consumption are mediated by differences in TA-related mechanisms. The findings are discussed with respect to genetically based differences in the subjective experience of ethanol.

Strain-dependent sex differences in the effects of alcohol on cocaine-induced taste aversions.

Science.gov (United States)

Jones, Jermaine D; Busse, Gregory D; Riley, Anthony L

2006-04-01

Research using the conditioned taste aversion procedure has reported that a cocaine/alcohol combination induces a significantly stronger taste aversion than either cocaine or alcohol alone. These findings suggest that the co-administration of alcohol intensifies the aversive effects of cocaine. Although the behavioral interaction of cocaine and alcohol is well established, little is known about how the effects of this drug combination might be modulated by a variety of subject variables. The current investigation addressed this by assessing if the ability of alcohol to potentiate cocaine-induced taste aversions is dependent upon the strain and/or sex of the subject. In this series of studies, male and female rats of Long-Evans (Experiment 1) and Sprague-Dawley (Experiment 2) descent were given limited access to a novel saccharin solution to drink and were then injected with either vehicle, cocaine (20 mg/kg), alcohol (0.56 g/kg) or the alcohol/cocaine combination. This procedure was repeated every fourth day for a total of four conditioning trials. All subjects were then compared on an Aversion Test that followed the fourth conditioning cycle. In three of the groups tested (male Long-Evans; male and female Sprague-Dawley), cocaine induced a significant taste aversion that was unaffected by the co-administration of alcohol. However, in female Long-Evans subjects, the addition of alcohol significantly strengthened the avoidance of the saccharin solution. Although the effects of alcohol on cocaine-induced taste aversions are dependent upon an interaction of sex and strain, the basis for this SexxStrain interaction is not known. That such an interaction is evident suggests that attention to such factors in assessing the effects of drug combinations is important to understanding the likelihood of the use and abuse of such drugs.

Prenatal exposure to ethanol during late gestation facilitates operant self-administration of the drug in 5-day-old rats.

Science.gov (United States)

Miranda-Morales, Roberto Sebastián; Nizhnikov, Michael E; Spear, Norman E

2014-02-01

Prenatal ethanol exposure modifies postnatal affinity to the drug, increasing the probability of ethanol use and abuse. The present study tested developing rats (5-day-old) in a novel operant technique to assess the degree of ethanol self-administration as a result of prenatal exposure to low ethanol doses during late gestation. On a single occasion during each of gestational days 17-20, pregnant rats were intragastrically administered ethanol 1 g/kg, or water (vehicle). On postnatal day 5, pups were tested on a novel operant conditioning procedure in which they learned to touch a sensor to obtain 0.1% saccharin, 3% ethanol, or 5% ethanol. Immediately after a 15-min training session, a 6-min extinction session was given in which operant behavior had no consequence. Pups were positioned on a smooth surface and had access to a touch-sensitive sensor. Physical contact with the sensor activated an infusion pump, which served to deliver an intraoral solution as reinforcement (Paired group). A Yoked control animal evaluated at the same time received the reinforcer when its corresponding Paired pup touched the sensor. Operant behavior to gain access to 3% ethanol was facilitated by prenatal exposure to ethanol during late gestation. In contrast, operant learning reflecting ethanol reinforcement did not occur in control animals prenatally exposed to water only. Similarly, saccharin reinforcement was not affected by prenatal ethanol exposure. These results suggest that in 5-day-old rats, prenatal exposure to a low ethanol dose facilitates operant learning reinforced by intraoral administration of a low-concentration ethanol solution. This emphasizes the importance of intrauterine experiences with ethanol in later susceptibility to drug reinforcement. The present operant conditioning technique represents an alternative tool to assess self-administration and seeking behavior during early stages of development. Published by Elsevier Inc.

Sweetened ethanol drinking during social isolation: enhanced intake, resistance to genetic heterogeneity and the emergence of a distinctive drinking pattern in adolescent mice.

Science.gov (United States)

Panksepp, J B; Rodriguez, E D; Ryabinin, A E

2017-03-01

With its ease of availability during adolescence, sweetened ethanol ('alcopops') is consumed within many contexts. We asked here whether genetically based differences in social motivation are associated with how the adolescent social environment impacts voluntary ethanol intake. Mice with previously described differences in sociability (BALB/cJ, C57BL/6J, FVB/NJ and MSM/MsJ strains) were weaned into isolation or same-sex pairs (postnatal day, PD, 21), and then given continuous access to two fluids on PDs 34-45: one containing water and the other containing an ascending series of saccharin-sweetened ethanol (3-6-10%). Prior to the introduction of ethanol (PDs 30-33), increased water and food intake was detected in some of the isolation-reared groups, and controls indicated that isolated mice also consumed more 'saccharin-only' solution. Voluntary drinking of 'ethanol-only' was also higher in a subset of the isolated groups on PDs 46-49. However, sweetened ethanol intake was increased in all isolated strain × sex combinations irrespective of genotype. Surprisingly, blood ethanol concentration (BEC) was not different between these isolate and socially housed groups 4 h into the dark phase. Using lickometer-based measures of intake in FVB mice, we identified that a predominance of increased drinking during isolation transpired outside of the typical circadian consumption peak, occurring ≈8.5 h into the dark phase, with an associated difference in BEC. These findings collectively indicate that isolate housing leads to increased consumption of rewarding substances in adolescent mice independent of their genotype, and that for ethanol this may be because of when individuals drink during the circadian cycle. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Reaction mechanisms and kinetics of processing glucose, xylose and glucose-xylose mixtures under hot compressed water conditions for predicting bio-crude composition

DEFF Research Database (Denmark)

Grigoras, Ionela; Toor, Saqib Sohail; Rosendahl, Lasse Aistrup

Mechanisms for bio-crude formation during the conversion of glucose, xylose and glucose-xylose mixtures as biomass model compounds under hot compressed water conditions are investigated. Studies in literature have shown that the diverse products formed at the early stages of glucose or xylose...... conversion are 5-HMF, erythrose, glyceraldehyde, dihydroxyacetone, pyruvaldehyde, and saccharinic acids resulted through reactions such as dehydration, retro-aldol condensation and isomerization. However, these compounds are mostly water soluble compounds and lack the final steps towards formation of water...... insoluble components at longer reaction times. The effects of pressure, pH, catalyst and reaction time on the main products are examined thoroughly. The possible routes for the formation of oil compounds are developed....

Passion fruit juice with different sweeteners: sensory profile by descriptive analysis and acceptance.

Science.gov (United States)

Rocha, Izabela Furtado de Oliveira; Bolini, Helena Maria André

2015-03-01

This study evaluated the effect of different sweeteners on the sensory profile, acceptance, and drivers of preference of passion fruit juice samples sweetened with sucrose, aspartame, sucralose, stevia, cyclamate/saccharin blend 2:1, and neotame. Sensory profiling was performed by 12 trained assessors using quantitative descriptive analysis (QDA). Acceptance tests (appearance, aroma, flavor, texture and overall impression) were performed with 124 consumers of tropical fruit juice. Samples with sucrose, aspartame and sucralose showed similar sensory profile (P Passion fruit flavor affected positively and sweet aftertaste affected negatively the acceptance of the samples. Samples sweetened with aspartame, sucralose, and sucrose presented higher acceptance scores for the attributes flavor, texture, and overall impression, with no significant (P passion fruit juice.

Electroplating of low stress permalloy for MEMS

International Nuclear Information System (INIS)

Zhang Yonghua; Ding Guifu; Cai Yuli; Wang Hong; Cai Bingchu

2006-01-01

With the wafer-bending method and spectrophotometry, the internal stress in electroplated Ni-Fe alloy for MEMS has been investigated as a function of bath concentration. This investigation demonstrated that low concentration plating solution is useful for the decrease of the residual stress in the electrodeposits, and the stress could further decrease with an increase of saccharin additive content. And the change of stress from tensile to compressive was not observed with the increase of the additive content in plating path. The low stress permalloy (Ni 81 Fe 19 ) was reached in our experimental conditions. A bistable electromagnetic RF MEMS switch with deformation-free bilayer cantilever beam was fabricated successfully by electroplated permalloy

Potentially harmful excipients in neonatal medicines

DEFF Research Database (Denmark)

Nellis, Georgi; Metsvaht, Tuuli; Varendi, Heili

2015-01-01

OBJECTIVES: We aimed to describe administration of eight potentially harmful excipients of interest (EOI)-parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride-to hospitalised neonates in Europe and to identify risk factors for exposure....... METHODS: All medicines administered to neonates during 1 day with individual prescription and demographic data were registered in a web-based point prevalence study. Excipients were identified from the Summaries of Product Characteristics. Determinants of EOI administration (geographical region......, gestational age (GA), active pharmaceutical ingredient, unit level and hospital teaching status) were identified using multivariable logistical regression analysis. RESULTS: Overall 89 neonatal units from 21 countries participated. Altogether 2095 prescriptions for 530 products administered to 726 neonates...

77 FR 21966 - Saccharin From the People's Republic of China: Preliminary Results of Antidumping Duty...

Science.gov (United States)

2012-04-12

... publication of this notice, pursuant to section 751(a)(3)(A) of the Tariff Act of 1930, as amended (``the Act... with section 751(a) of the Tariff Act of 1930, as amended (``the Act''), the Department published in... (August 26, 2011) (``Initiation''). The Initiation covered the following companies: (1) Pingdingshan Coal...

Preparation of PbS and PbO nanopowders from new Pb(II)(saccharine) coordination polymers

International Nuclear Information System (INIS)

Aslani, Alireza; Musevi, Seyid Javad; Şahin, Ertan; Yilmaz, Veysel T.

2014-01-01

Highlights: • The complex of compounds “[Pb(H 2 O)(μ-OAc)(μ-sac)] n ” are synthesized at nano and bulk size structurally diverse and show interesting three-dimensional coordination polymers. • Reduction of the particle size of the coordination polymers to a few dozen nanometers results in lower thermal stability when compared to the single crystalline samples. • This study demonstrates that the metal–organic framework may be suitable precursors for the preparation of nanoscale materials with interesting morphologies. - Abstract: Nanopowders and single crystal of new Pb(II) three-dimensional coordination polymer, [Pb(H 2 O)(μ-OAc)(μ-sac)] n “PASAC” were synthesized by a sonochemical and branched tube methods (Yılmaz et al., Z. Anorg. Allg. Chem. 629 (2003) 172). The new nano-structures of Pb(II) coordination polymer were characterized by X-ray crystallography analysis, scanning electron microscopy (SEM), X-ray powder diffraction (XRD), surface analysis (BET), and IR spectroscopy. The crystal structure of these compounds consists of three-dimensional polymeric units. The thermal stability of compounds was studied by thermal gravimetric analysis (TGA) and differential thermal analyses (DTA). PbS and PbO nano-structures were obtained by calcinations of the nano-structures of this coordination polymer at 600 °C

Combined effect of radiation and environmental contaminants on DNA repair mechanisms

International Nuclear Information System (INIS)

Altmann, H.

1975-11-01

Investigations on the influence of various environmental contamination agents on DNA repair (in combination with irradiation) were reviewed. The agents tested were: detergents (Tween 80, Nonidel P40, Cremophor), aflatoxin B 1 , furocumarines, drugs (indometacin, cyclophosphamide, vincristine, vinblastine, procarbacine), fluorides, irradiated food constituents, food additives (saccharin), metal ions (Cd, Hg), pesticides (2,4,5-trichlorophenoxyethanol) and infective agents (mycoplasmas). Most of the tests were carried out in vitro with γ-irradiated mouse spleen cells. The detergents and aflatoxin were tested also on E. coli, and irradiated glucose solutions were tested in vivo on Swiss albino mice injected with Salmonella typhimurium TA 1530. Most of the tested agents showed some kind of inhibitory or mutagenic effect. The experiments and results are explained briefly with references to earlier investigations

Potential tracers for tracking septic tank effluent discharges in watercourses.

Science.gov (United States)

Richards, Samia; Withers, Paul J A; Paterson, Eric; McRoberts, Colin W; Stutter, Marc

2017-09-01

Septic tank effluent (STE) contributes to catchment nutrient and pollutant loads. To assess the role of STE discharges in impairment of surface water, it is essential to identify the sources of pollution by tracing contaminants in watercourses. We examined tracers that were present in STE to establish their potential for identifying STE contamination in two stream systems (low and high dilution levels) against the background of upstream sources. The studied tracers were microbial, organic matter fluorescence, caffeine, artificial sweeteners and effluent chemical concentrations. The results revealed that tracer concentration ratios Cl/EC, Cl/NH 4 -N, Cl/TN, Cl/TSS, Cl/turbidity, Cl/total coliforms, Cl/sucralose, Cl/saccharin and Cl/Zn had potential as tracers in the stream with low dilution level (P < 0.05). Fluorescence spectroscopy could detect STE inputs through the presence of the tryptophan-like peak, but was limited to water courses with low level of dilution and was positively correlated with stream Escherichia coli (E. coli) and soluble reactive phosphorus (SRP). The results also suggested that caffeine and artificial sweeteners can be suitable tracers for effluent discharge in streams with low and high level of dilution. Caffeine and saccharin were positively correlated with faecal coliforms, E. coli, total P and SRP, indicating their potential to trace discharge of a faecal origin and to be a marker for effluent P. Caffeine and SRP had similar attenuation behaviour in the receiving stream waters suggesting caffeine's potential role as a surrogate indicator for the behaviour of P downstream of effluent inputs. Taken together, results suggest that a single tracer alone was not sufficient to evaluate STE contamination of watercourses, but rather a combination of multiple chemical and physical tracing approaches should be employed. A multiple tracing approach would help to identify individual and cumulative STE inputs that pose risks to stream waters in

Humectancies of d-tagatose and d-sorbitol.

Science.gov (United States)

Lu, Y

2001-06-01

Most toothpastes contain either d-sorbitol or glycerin, or both, as humectants. Both compounds are about half as sweet as sucrose. This level of sweetness is not as intense as desired by most people when brushing teeth. Therefore, many brands of toothpaste add saccharin, a high-intensity sweetener, to increase product sweetness to acceptable levels. While this combination provides the required bulk, humectancy and sweetness, the last characteristic suffers from the widely perceived metallic, or bitter, aftertaste of saccharin. d-tagatose, a full-bulk, low-calorie, sucrose-like sweetener with about twice the sweetness of d-sorbitol, and which does not promote tooth decay, holds promise as a sole sweetener for toothpastes. The only untested aspect of this use of d-tagatose was its humectancy, the characteristic that retains the required level of moisture in toothpaste. The current study was made to investigate this important property, to make a direct comparison of the humectancies of d-tagatose and d-sorbitol as pure substances, and to determine whether the humectancy of d-tagatose is sufficient to counter the crystallizing potentiation of the abrasives used in toothpastes. The humectancies of d-tagatose and d-sorbitol were tested through measuring their water activity (a(w)) vs. water content. By comparing their desorption curves, d-tagatose was seen to have a humectancy equal to that of d-sorbitol when a(w) in the d-tagatose solution was above 0.62. d-Tagatose was then tested in toothpastes containing typical abrasives to determine whether the abrasives would induce crystallization of the sweetener. The addition of 20-25% wt/wt of d-tagatose to the Tom of Maine's toothpastes imparted a satisfactory sweetness. It was found that, within that range of concentration, d-tagatose retained its humectancy, and did not crystallize in the popular brands of commercial toothpastes tested. Thus, d-tagatose could be used as a humectant sweetener in toothpastes, although further

Electroplating condition for Ni nanocrystalline on metal (Ni and Cu) plates

Energy Technology Data Exchange (ETDEWEB)

Park, Keun Yung; Uhm, Young Rang; Son, Kwang Jae; Shim, Young Ho; Choi, Sun Ju [KAERI, Daejeon (Korea, Republic of)

2012-10-15

Ni 63, a beta radiation source, is prepared by the electrical deposition of radioactive Ni 63 ions on a thin non radioactive nickel foil or Cu plate. Given a half life of 100 years, a nuclear battery will still produce half of its initial starting power after 100 years. A speck of a radioisotope like nickel 63, for example, contains enough energy to power a nano nuclear battery for decades, and to do so safely. Ni 63 plating is similar to other electroplating processes that employ soluble metal anodes. It requires the passage of a direct current between two electrodes that are immersed in a conductive, aqueous solution of nickel salts. The charged Ni ions are formed by sulfate, sulfamate, chloride, and a Watts bath. However, the charged Ni 63 ions are formed by dissolving metal Ni 63. To established the coating condition of Ni 63, non radioactive metal Ni particles are dissolved an acid solution and electroplated on a Ni sheet. The nickel plating process is used extensively for decorative, engineering and electro forming purposes because the appearance and other properties of electrodeposited nickel can be varied over a wide range by controlling the composition and operating parameters of the plating solution. A continuous increase in the grain size versus current density has also been recognized in the direct current electrodeposition of nickel coating. On the other hand, A runa et al. reported that the current density has no significant effect on the grain size of nickel electro deposits. A review of the literature shows that saccharin has often been added to a nickel plating bath since the 1980s to improve the ductility and brightness, and in later periods as a grain refiner agent. In the present paper, not only the preparation of a Ni plating solution prepared by dissolving metal particles, but also an optimization of the deposition conditions, such as the current density, saccharin concentration in the bath, and different metal substrates were investigated

Oxytocin Acting in the Nucleus Accumbens Core Decreases Food Intake.

Science.gov (United States)

Herisson, F M; Waas, J R; Fredriksson, R; Schiöth, H B; Levine, A S; Olszewski, P K

2016-04-01

Central oxytocin (OT) promotes feeding termination in response to homeostatic challenges, such as excessive stomach distension, salt loading and toxicity. OT has also been proposed to affect feeding reward by decreasing the consumption of palatable carbohydrates and sweet tastants. Because the OT receptor (OTR) is expressed in the nucleus accumbens core (AcbC) and shell (AcbSh), a site regulating diverse aspects of eating behaviour, we investigated whether OT acts there to affect appetite in rats. First, we examined whether direct AcbC and AcbSh OT injections affect hunger- and palatability-driven consumption. We found that only AcbC OT infusions decrease deprivation-induced chow intake and reduce the consumption of palatable sucrose and saccharin solutions in nondeprived animals. These effects were abolished by pretreatment with an OTR antagonist, L-368,899, injected in the same site. AcbC OT at an anorexigenic dose did not induce a conditioned taste aversion, which indicates that AcbC OT-driven anorexia is not caused by sickness/malaise. The appetite-specific effect of AcbC OT is supported by the real-time polymerase chain reaction analysis of OTR mRNA in the AcbC, which revealed that food deprivation elevates OTR mRNA expression, whereas saccharin solution intake decreases OTR transcript levels. We also used c-Fos immunohistochemistry as a marker of neuronal activation and found that AcbC OT injection increases activation of the AcbC itself, as well as of two feeding-related sites: the hypothalamic paraventricular and supraoptic nuclei. Finally, considering the fact that OT plays a significant role in social behaviour, we examined whether offering animals a meal in a social setting would modify their hypophagic response to AcbC OT injections. We found that a social context abolishes the anorexigenic effects of AcbC OT. We conclude that OT acting via the AcbC decreases food intake driven by hunger and reward in rats offered a meal in a nonsocial setting. © 2016

Electroplating condition for Ni nanocrystalline on metal (Ni and Cu) plates

International Nuclear Information System (INIS)

Park, Keun Yung; Uhm, Young Rang; Son, Kwang Jae; Shim, Young Ho; Choi, Sun Ju

2012-01-01

Ni 63, a beta radiation source, is prepared by the electrical deposition of radioactive Ni 63 ions on a thin non radioactive nickel foil or Cu plate. Given a half life of 100 years, a nuclear battery will still produce half of its initial starting power after 100 years. A speck of a radioisotope like nickel 63, for example, contains enough energy to power a nano nuclear battery for decades, and to do so safely. Ni 63 plating is similar to other electroplating processes that employ soluble metal anodes. It requires the passage of a direct current between two electrodes that are immersed in a conductive, aqueous solution of nickel salts. The charged Ni ions are formed by sulfate, sulfamate, chloride, and a Watts bath. However, the charged Ni 63 ions are formed by dissolving metal Ni 63. To established the coating condition of Ni 63, non radioactive metal Ni particles are dissolved an acid solution and electroplated on a Ni sheet. The nickel plating process is used extensively for decorative, engineering and electro forming purposes because the appearance and other properties of electrodeposited nickel can be varied over a wide range by controlling the composition and operating parameters of the plating solution. A continuous increase in the grain size versus current density has also been recognized in the direct current electrodeposition of nickel coating. On the other hand, A runa et al. reported that the current density has no significant effect on the grain size of nickel electro deposits. A review of the literature shows that saccharin has often been added to a nickel plating bath since the 1980s to improve the ductility and brightness, and in later periods as a grain refiner agent. In the present paper, not only the preparation of a Ni plating solution prepared by dissolving metal particles, but also an optimization of the deposition conditions, such as the current density, saccharin concentration in the bath, and different metal substrates were investigated

Sucrose ingestion causes opioid analgesia

Directory of Open Access Journals (Sweden)

F.N. Segato

1997-08-01

Full Text Available The intake of saccharin solutions for relatively long periods of time causes analgesia in rats, as measured in the hot-plate test, an experimental procedure involving supraspinal components. In order to investigate the effects of sweet substance intake on pain modulation using a different model, male albino Wistar rats weighing 180-200 g received either tap water or sucrose solutions (250 g/l for 1 day or 14 days as their only source of liquid. Each rat consumed an average of 15.6 g sucrose/day. Their tail withdrawal latencies in the tail-flick test (probably a spinal reflex were measured immediately before and after this treatment. An analgesia index was calculated from the withdrawal latencies before and after treatment. The indexes (mean ± SEM, N = 12 for the groups receiving tap water for 1 day or 14 days, and sucrose solution for 1 day or 14 days were 0.09 ± 0.04, 0.10 ± 0.05, 0.15 ± 0.08 and 0.49 ± 0.07, respectively. One-way ANOVA indicated a significant difference (F(3,47 = 9.521, P<0.001 and the Tukey multiple comparison test (P<0.05 showed that the analgesia index of the 14-day sucrose-treated animals differed from all other groups. Naloxone-treated rats (N = 7 receiving sucrose exhibited an analgesia index of 0.20 ± 0.10 while rats receiving only sucrose (N = 7 had an index of 0.68 ± 0.11 (t = 0.254, 10 degrees of freedom, P<0.03. This result indicates that the analgesic effect of sucrose depends on the time during which the solution is consumed and extends the analgesic effects of sweet substance intake, such as saccharin, to a model other than the hot-plate test, with similar results. Endogenous opioids may be involved in the central regulation of the sweet substance-produced analgesia.

A novel regulatory function of sweet taste-sensing receptor in adipogenic differentiation of 3T3-L1 cells.

Directory of Open Access Journals (Sweden)

Yosuke Masubuchi

Full Text Available BACKGROUND: Sweet taste receptor is expressed not only in taste buds but also in nongustatory organs such as enteroendocrine cells and pancreatic beta-cells, and may play more extensive physiological roles in energy metabolism. Here we examined the expression and function of the sweet taste receptor in 3T3-L1 cells. METHODOLOGY/PRINCIPAL FINDINGS: In undifferentiated preadipocytes, both T1R2 and T1R3 were expressed very weakly, whereas the expression of T1R3 but not T1R2 was markedly up-regulated upon induction of differentiation (by 83.0 and 3.8-fold, respectively at Day 6. The α subunits of Gs (Gαs and G14 (Gα14 but not gustducin were expressed throughout the differentiation process. The addition of sucralose or saccharin during the first 48 hours of differentiation considerably reduced the expression of peroxisome proliferator activated receptor γ (PPARγ and CCAAT/enhancer-binding protein α (C/EBPα at Day 2, the expression of aP2 at Day 4 and triglyceride accumulation at Day 6. These anti-adipogenic effects were attenuated by short hairpin RNA-mediated gene-silencing of T1R3. In addition, overexpression of the dominant-negative mutant of Gαs but not YM-254890, an inhibitor of Gα14, impeded the effects of sweeteners, suggesting a possible coupling of Gs with the putative sweet taste-sensing receptor. In agreement, sucralose and saccharin increased the cyclic AMP concentration in differentiating 3T3-L1 cells and also in HEK293 cells heterologously expressing T1R3. Furthermore, the anti-adipogenic effects of sweeteners were mimicked by Gs activation with cholera toxin but not by adenylate cyclase activation with forskolin, whereas small interfering RNA-mediated knockdown of Gαs had the opposite effects. CONCLUSIONS: 3T3-L1 cells express a functional sweet taste-sensing receptor presumably as a T1R3 homomer, which mediates the anti-adipogenic signal by a Gs-dependent but cAMP-independent mechanism.

Kinetics of phosphotungstic acid catalyzed oxidation of propan-1,3-diol and butan-1,4-diol by N-chlorosaccharin

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Sanjay Kumar Singh

2011-09-01

Full Text Available The kinetic studies of N-chlorosaccharin (NCSA oxidation of propan-1,3-diol and butan-1,4-diol have been reported in presence of phophotungstic acid and in aqueous acetic acid medium. The reactions follow first-order in NCSA and one to zero order with respect to substrate and phosphotungstic acid. Increase in the concentration of added perchloric acid increases the rate of oxidation. A negative effect on the oxidation rate is observed for solvent whereas the ionic strength does not influence the rate of reaction. Addition of the reaction product, saccharin, exhibited retarding effect. Various activation parameters have been evaluated. The products of the reactions were identified as the corresponding aldehydes. A suitable scheme of mechanism consistent with the experimental results has been proposed.

Near-infrared spectroscopy for cocrystal screening

DEFF Research Database (Denmark)

Allesø, Morten; Velaga, Sitaram; Alhalaweh, Amjad

2008-01-01

Near-infrared (NIR) spectroscopy is a well-established technique for solid-state analysis, providing fast, noninvasive measurements. The use of NIR spectroscopy for polymorph screening and the associated advantages have recently been demonstrated. The objective of this work was to evaluate...... the analytical potential of NIR spectroscopy for cocrystal screening using Raman spectroscopy as a comparative method. Indomethacin was used as the parent molecule, while saccharin and l-aspartic acid were chosen as guest molecules. Molar ratios of 1:1 for each system were subjected to two types of preparative...... retained in a physical mixture with the guest molecule, while liquid-assisted cogrinding did not induce any changes in the crystal lattice. The good chemical peak selectivity of Raman spectroscopy allowed a straightforward interpretation of sample data by analyzing peak positions and comparing to those...

Discovery and Biological Evaluation of Potent and Selective N-Methylene Saccharin-Derived Inhibitors for Rhomboid Intramembrane Proteases

Czech Academy of Sciences Publication Activity Database

Goel, P.; Jumpertz, T.; Mikles, David C.; Tichá, Anežka; Nguyen, M. T. N.; Verhelst, S.; Hubálek, Martin; Johnson, D. C.; Bachovchin, D. A.; Ogorek, I.; Pietrzik, C. U.; Stříšovský, Kvido; Schmidt, B.; Weggen, S.

2017-01-01

Roč. 56, č. 51 (2017), s. 6713-6725 ISSN 0006-2960 R&D Projects: GA MŠk(CZ) LK11206; GA MŠk LO1302 EU Projects: European Commission(XE) 304154 - Rhomboid substrates Grant - others:EMBO(DE) 2329 Institutional support: RVO:61388963 Keywords : intramembrane protease * rhomboid * inhibitor Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 2.938, year: 2016

Modelling Affective Pain in Mice: Effects of Inflammatory Hypersensitivity on Place Escape/Avoidance Behaviour, Anxiety and Hedonic State

DEFF Research Database (Denmark)

Refsgaard, Louise Konradsen; Hoffmann-Petersen, Julie; Sahlholt, Maj

2016-01-01

and the dark area of a box while being stimulated with a suprathreshold filament on the untreated or treated paw, respectively. This was followed by a 30-min test with unrestricted movement. Anxiety-like behaviour, locomotor activity, and hedonic state were assessed with the elevated zero maze (EZM), an open...... PEAP and other behavioural responses, namely anxiety-like behaviour, locomotor activity, and hedonic state. New Method A novel paradigm assessing the affective component of pain in mice was developed by modifying the setup known from rat studies: Animals were forced to stay 2x5 min in the light...... field setup, and a saccharin preference test, respectively, and correlated with the PEAP behaviour to examine potentially confounding parameters of the novel paradigm. Results In the PEAP, CFA-treated animals spent more time in the light area. CFA also increased anxiety-like behaviour significantly...

Categorizing Mistaken False Positives in Regulation of Human and Environmental Health

DEFF Research Database (Denmark)

Hansen, Steffen Foss; Krayer von Krauss, Martin Paul; Tickner, J.A.

2007-01-01

One of the concerns often voiced by critics of the precautionary principle is that a widespread regulatory application of the principle will lead to a large number of false positives (i.e., over-regulation of minor risks and regulation of nonexisting risks). The present article proposes a general......," including: real risks, "The jury is still out," nonregulated proclaimed risks, "Too narrow a definition of risk," and risk-risk tradeoffs. These categories are defined and examples are presented in order to illustrate their key characteristics. On the basis of our analysis, we were able to identify only...... four cases that could be defined as regulatory false positives in the light of today's knowledge and recognized uncertainty: the Southern Corn Leaf Blight, the Swine Flu, Saccharin, and Food Irradiation in relation to consumer health. We conclude that concerns about false positives do not represent...

Environmental chemicals - how do we assess the risk (question mark)

International Nuclear Information System (INIS)

Somers, E.

Risk assessment is considered as comprising risk identification, risk estimation, and risk evaluation. The methodology of risk estimation is described and the key role of animal experimentation outlined, drawing attention to the inherent problems of extrapolating from animals to humans. The application of risk estimation to regulatory decision-making in Canada is given for chloroform in drinking water; asbestos in dry-wall patching compounds; arsenic emissions in air; nitrogen oxides; mercury in fish; and the food additive saccharin. Risk evaluation represents societal judgement and is ultimately political but a number of techniques can be of value in separating the competing factors, i.e., comparison with natural background or with other risks, balancing risks from alternatives, and risk-benefit analysis. However, the inherent limitations of a completely rational approach to risk assessment must always be recognized. (author)

Mechanism of Oxidation of (p-Substituted Phenylthioacetic Acids with N-Chlorosaccharin

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N. M. I. Alhaj

2011-01-01

Full Text Available The kinetics of oxidation of (phenylthioacetic acid (PTAA with N-chlorosaccharin (NCSA have been studied potentiometrically in 80:20 (v/v acetonitrile-water medium at 298 K. The reaction is first-order each with respect to PTAA and NCSA and shows a negative dependence on [H+]. NCSA itself is shown to be the active oxidizing species. Effects of ionic strength variation, added saccharin, added acrylonitrile, added NaCl and solvent composition variation have been studied. Effect of substituents on the reaction rate has been analysed by employing various (p-sustituted phenylthioacetic acids. The electron-releasing substituent in the phenyl ring of PTAA accelerates the reaction rate while the electron-withdrawing substituent retards the rate. The excellently linear Hammett plot yields a large negative ρ value, supporting the involvement a chlorosulphonium ion intermediate in the rate-determining step.

Chronic Fluoxetine Treatment Upregulates the Activity of the ERK1/2-NF-κB Signaling Pathway in the Hippocampus and Prefrontal Cortex of Rats Exposed to Forced-Swimming Stress.

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Cui, Jingqiu; Yang, Kun; Yu, Xue; Wang, Jing-Lan; Li, Jie; Zhang, Yong; Li, Hengfen

2016-01-01

The aim of this study was to explore whether or not the antidepressant actions of fluoxetine (FLX) are correlated with extracellular signal-regulated kinase 1 and 2 (ERK1/2) and nuclear factor κ-light chain enhancer of activated B cells (NF-κB) in the hippocampus (HC) and prefrontal cortex (PFC) of rats. A total of 108 male Sprague-Dawley rats were randomly divided into 6 groups of 18 rats each. Group 1 was the control group, while group 2 comprised the depressed model in which rats were subjected to 28 days of forced-swimming stress (FST); groups 3-6 were also subjected to 28 days of FST and treated with FLX once a day for 1 day (group 3; F1d), 1 week (group 4; F1w), 2 weeks (group 5; F2w), or 4 weeks (group 6; F4w). The control group was not subjected to FST or treated with FLX. Behavior tests that included the Morris water maze (MWM) and saccharin preference were performed, and ERK1/2 and NF-κB proteins were assayed using Western blot. The rats in the control group and in groups 5 and 6 (F2w and F4w, respectively) had a significantly shorter average escape latency, needed more attempts in order to successfully cross the platform, and had a greater saccharin preference than those in the depressed group (p < 0.05). In the depressed group, the phosphorylated ERK1/2 (p-ERK1/2) and phosphorylated NF-κB (p-NF-κB) expression in the HC and PFC were lower than in the control group (p < 0.05). Treatment with FLX reversed the changes in the expression of p-ERK1/2 and p-NF-κB in rats in the F2w and F4w groups. In this study, FLX treatment for 2 weeks or longer reversed the impaired spatial learning, memory, and anhedonia observed in the depressed model rats and upregulated the activities of the ERK1/2-NF-κB signaling pathway. © 2016 S. Karger AG, Basel.

Disruption of the Glutamate–Glutamine Cycle Involving Astrocytes in an Animal Model of Depression for Males and Females

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Rappeneau, Virginie; Blaker, Amanda; Petro, Jeff R.; Yamamoto, Bryan K.; Shimamoto, Akiko

2016-01-01

Background: Women are twice as likely as men to develop major depression. The brain mechanisms underlying this sex disparity are not clear. Disruption of the glutamate–glutamine cycle has been implicated in psychiatric disturbances. This study identifies sex-based impairments in the glutamate–glutamine cycle involving astrocytes using an animal model of depression. Methods: Male and female adult Long-Evans rats were exposed to chronic social defeat stress (CSDS) for 21 days, using a modified resident-intruder paradigm. Territorial aggression was used for males and maternal aggression was used for females to induce depressive-like deficits for intruders. The depressive-like phenotype was assessed with intake for saccharin solution, weight gain, estrous cycle, and corticosterone (CORT). Behaviors displayed by the intruders during daily encounters with residents were characterized. Rats with daily handling were used as controls for each sex. Ten days after the last encounter, both the intruders and controls were subjected to a no-net-flux in vivo microdialysis to assess glutamate accumulation and extracellular glutamine in the nucleus accumbens (NAc). The contralateral hemispheres were used for determining changes in astrocytic markers, including glial fibrillary acidic protein (GFAP) and glutamate transporter-1 (GLT-1). Results: Both male and female intruders reduced saccharin intake over the course of CSDS, compared to their pre-stress period and to their respective controls. Male intruders exhibited submissive/defensive behaviors to territorial aggression by receiving sideways threats and bites. These males showed reductions in striatal GLT-1 and spontaneous glutamine in the NAc, compared to controls. Female intruders exhibited isolated behaviors to maternal aggression, including immobility, rearing, and selfgrooming. Their non-reproductive days were extended. Also, they showed reductions in prefrontal and accumbal GFAP+ cells and prefrontal GLT-1, compared to

Development and validation of an in-line NIR spectroscopic method for continuous blend potency determination in the feed frame of a tablet press.

Science.gov (United States)

De Leersnyder, Fien; Peeters, Elisabeth; Djalabi, Hasna; Vanhoorne, Valérie; Van Snick, Bernd; Hong, Ke; Hammond, Stephen; Liu, Angela Yang; Ziemons, Eric; Vervaet, Chris; De Beer, Thomas

2018-03-20

A calibration model for in-line API quantification based on near infrared (NIR) spectra collection during tableting in the tablet press feed frame was developed and validated. First, the measurement set-up was optimised and the effect of filling degree of the feed frame on the NIR spectra was investigated. Secondly, a predictive API quantification model was developed and validated by calculating the accuracy profile based on the analysis results of validation experiments. Furthermore, based on the data of the accuracy profile, the measurement uncertainty was determined. Finally, the robustness of the API quantification model was evaluated. An NIR probe (SentroPAT FO) was implemented into the feed frame of a rotary tablet press (Modul™ P) to monitor physical mixtures of a model API (sodium saccharine) and excipients with two different API target concentrations: 5 and 20% (w/w). Cutting notches into the paddle wheel fingers did avoid disturbances of the NIR signal caused by the rotating paddle wheel fingers and hence allowed better and more complete feed frame monitoring. The effect of the design of the notched paddle wheel fingers was also investigated and elucidated that straight paddle wheel fingers did cause less variation in NIR signal compared to curved paddle wheel fingers. The filling degree of the feed frame was reflected in the raw NIR spectra. Several different calibration models for the prediction of the API content were developed, based on the use of single spectra or averaged spectra, and using partial least squares (PLS) regression or ratio models. These predictive models were then evaluated and validated by processing physical mixtures with different API concentrations not used in the calibration models (validation set). The β-expectation tolerance intervals were calculated for each model and for each of the validated API concentration levels (β was set at 95%). PLS models showed the best predictive performance. For each examined saccharine

Roughness development in electrodeposited soft magnetic CoNiFe films in the presence of organic additives

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STEVE RIEMER

2003-05-01

Full Text Available The effects of three additives, sodium lauryl sulfate (NaLS, saccharin (Sacc, and NaLS + Sacc, on roughness development during the electrodeposition of CoNiFe films were investigated. The characterization of these films by atomic force microscopy shows that the electrodeposits produced from NaLS containing solution result in a rough surface. The role of NaLS surfactant is to change the interfacial tension and clean non-polar species like hydrogen bubbles from the surface. In Sacc containing solution, the evolution of a smooth surface is controlled by adsorbed Sacc molecule at the interface. The kinetic roughening of these deposits was investigated by dynamic scaling analysis. It was demonstrated that the roughness of CoNiFe films, obtained in the presence of NaLS + Sacc additives, was also dependent on current density, roughness of substrate, and the temperature of plating bath.

A facile production of microporous carbon spheres and their electrochemical performance in EDLC

Science.gov (United States)

Xia, Xiaohong; Shi, Lei; Liu, Hongbo; Yang, Li; He, Yuede

2012-03-01

In the absence of activation process, we prepared a series of carbon particles from saccharine, in which hydrothermal carbonization method was used. These particles have spherical or near-spherical morphology, controllable monodisperse particle size from the analyses of SEM. Raman and XRD results show that they are nongraphitizable. The BET surface area of these carbon spherules is around 400-500 m2 g-1 and the microporosity is about 84%, suggesting that the carbon particles are rich in micropores. The electrochemical behaviors were characterized by means of galvanostatic charging/discharging, cycle voltammetry and impedance spectroscopy. The results show that the specific capacitance of sucrose-based carbon spherule reached 164 F g-1 in 30% KOH electrolyte and a high volumetric capacitance over 170 F cm-3 was obtained. These carbon spherules could be promising materials for EDLC according to their facile preparation way, low cost and high packing density.

Acquisition of steady-state operant behavior in long-living Ames Dwarf mice.

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Derenne, Adam; Brown-Borg, Holly; Feltman, Kathryn; Corbett, Grant; Lackman, Serena

2011-10-24

Ames dwarf mice have a Prop-1 mutation that has been identified with increased levels of IGF-I in the central nervous system, upregulation of neuroprotective systems, and increased lifespan. To elucidate the behavioral effects of the Prop-1 mutation, 8 Ames dwarf and 7 normal mice (all of whom were 8 months of age or younger) were compared on a differential-reinforcement-of-low-rate-of-responding schedule of reinforcement and a matching-to-sample task. On both tasks, nosepokes were reinforced with access to a saccharin solution. Comparisons were based on several measures of behavioral efficiency: pause durations, intertrial intervals, and numbers of responses. Ames dwarf mice were generally less efficient than normal mice. One possible cause of this outcome is that relatively young Ames dwarf mice show less cognitive development than age-matched normal mice. Copyright © 2011 Elsevier Inc. All rights reserved.

Physical-chemical, caloric and sensory characterization of light jambolan (Syzygium cumini Lamarck jelly

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Ellen Silva Lago-Vanzela

2011-09-01

Full Text Available In Brazil, several little economically explored fruits have good potential as raw material for the agro-industry. This study aimed to produce and determine the physical-chemical and sensory characteristics of light jambolan jelly. This fruit has intense purple color, which gave the jellies - both standard and light - a quite attractive visual aspect. The light jellies exhibited similar physical-chemical characteristics to the ones developed through the conventional method and; with the proportion of sweeteners used, the caloric values of the formulations were reduced to the range of 41 to 53%, attending the requirements of the Brazilian legislation for this type of product. The sensory profile obtained for the 4 light formulations developed, clearly showed the tasters' preference for the jelly elaborated with the association of cyclamate and saccharin. Thus, the results revealed good perspectives for the application of this fruit in the food industry.

Sweet proteins – Potential replacement for artificial low calorie sweeteners

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Kant Ravi

2005-02-01

Full Text Available Abstract Exponential growth in the number of patients suffering from diseases caused by the consumption of sugar has become a threat to mankind's health. Artificial low calorie sweeteners available in the market may have severe side effects. It takes time to figure out the long term side effects and by the time these are established, they are replaced by a new low calorie sweetener. Saccharine has been used for centuries to sweeten foods and beverages without calories or carbohydrate. It was also used on a large scale during the sugar shortage of the two world wars but was abandoned as soon as it was linked with development of bladder cancer. Naturally occurring sweet and taste modifying proteins are being seen as potential replacements for the currently available artificial low calorie sweeteners. Interaction aspects of sweet proteins and the human sweet taste receptor are being investigated.

Diaquabis(dimethyl sulfoxide-κObis(saccharinato-κNcobalt(II

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Fezile S. W. Potwana

2011-12-01

Full Text Available The title complex, [Co(C7H4NO3S2(C2H6OS2(H2O2], contains a Co2+ cation in an octahedral coordination environment. The metal atom is surrounded by two different neutral ligands, namely dimethylsulfoxide (DMSO and water, each coordinating through the O atom. The anionic saccharinate (sac; 1,1,3-trioxo-2,3-dihydro-1λ6,2-benzothiazol-2-ide ligand coordinates through the N atom. Each of the three similar ligand pairs is in a trans configuration with respect to each other. The Co atom lies on a crystallographic center of symmetry and the octahedral geometry is not significantly distorted. A short O—H...O hydrogen bond is present between a water H atom and the ketone O atom; two longer hydrogen bonds (intra- and intermolecular are also present between a water H and a sulfonic O atom, forming a supramolecular assembly through head-to-tail aggregation between adjacent complexes.

Development of pitanga nectar with different sweeteners by sensory analysis: ideal pulp dilution, ideal sweetness, and sweetness equivalence

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Mírian Luisa Faria Freitas

2014-03-01

Full Text Available The objective of this study was to develop pitanga nectar formulations in which sucrose was replaced with different sweeteners. Consumer tests were conducted with 50 fruit juice consumers, and a just-about-right scale was used to determine the ideal pulp dilution and ideal sweetness with sucrose. Furthermore, the adequate concentrations of six sweeteners were determined to obtain the equivalent sweetness of sucrose using relative to these concentrations the magnitude estimation model with 19 selected assessors. The ideal dilution test resulted in 25% pulp, and the ideal sweetness test, 10% sucrose. Sweetener concentrations to replace sucrose were 0.0160%, 0.0541%, 0.1000%, 0.0999%, 0.0017%, and 0.0360%, respectively, for sucralose, aspartame, stevia 40% rebaudioside A, stevia 95% rebaudioside A, neotame, and a 2:1 cyclamate/saccharin blend. These results can be used to prepare pitanga nectar with different sweeteners and obtain the same sweetness intensity in less caloric products than that of nectar prepared with sucrose.

Storage stability of standard and diet figs canned in syrup

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Priscilla Kárim CAETANO

Full Text Available Abstract The current study aimed to evaluate the physicochemical, microbiological and sensory quality of traditional and diet figs canned in syrup, as well as verify their storage stability. Therefore, it was used green figs from the cultivar Roxo de Valinhos. Two treatments were held: standard sucrose syrup and sweetener blends: sodium cyclamate, sucralose and sodium saccharin. The syrups were previously prepared; being 25 °Brix for sucrose syrup; and by dividing the quantity of sucrose potency (100 to the blend of sweeteners potency (125 for sweetener blends. The products were stored at room temperature for 180 days and evaluated once a month through pH, soluble solids, titratable acidity, texture, vacuum and sensory evaluation (i.e. affective test; except for the commercial sterility test that was conducted at 0 to 180 days. Both canned figs in syrup showed no significant difference for pH, titratable acidity, soluble solids, vacuum and texture; therefore, both were considered commercially sterile and kept their sensory characteristics throughout storage.

Water-activity of dehydrated guava slices sweeteners

International Nuclear Information System (INIS)

Ayub, M.; Zeb, A.; Ullah, J.

2005-01-01

A study was carried out to investigate the individual and combined effect of caloric sweeteners (sucrose, glucose and fructose) and non-caloric sweeteners (saccharine, cyclamate and aspartame) along with antioxidants (citric acid and ascorbic acid) and chemical preservatives (potassium metabisulphite and potassium sorbate) on the water-activity (a/sub w/) of dehydrated guava slices. Different dilutions of caloric sweeteners (20, 30, 40 and 50 degree brix (bx) and non-caloric sweeteners (equivalent to sucrose sweetness) were used. Guava slices were osmotically dehydrated in these solutions and then dehydrated initially at 0 and then at 60 degree C to final moisture-content of 20-25%. Guava slices prepared with sucrose: glucose 7:3 potassium metabisulphite, ascorbic acid and citric acid produced best quality products, which have minimum (a/sub w/) and best overall sensory characteristics. The analysis showed that treatments and their various concentrations had a significant effect (p=0.05) on (a/sub w/) of dehydrated guava slices. (author)

Discrimination of sweeteners based on the refractometric analysis

International Nuclear Information System (INIS)

Bodurov, I; Viraneva, A; Yovcheva, T; Vlaeva, I

2017-01-01

In the present work, the refractive characteristics of aqueous solutions of several sweeteners are investigated. These data in combination with ones from other sensors should find application for brief determination of sweeteners content in food and dynamic monitoring of food quality. The refractive indices of pure (distilled) water and aqueous solutions of several commonly used natural and artificial sweeteners (glucose, fructose, sucrose, lactose, sorbitol [E420], isomalt [E953], saccharin sodium [E950], cyclamate sodium and glycerol [E422]) with 10 wt.% concentration are accurately measured at 405 nm, 532 nm and 632.8 nm wavelengths. The measurements are carried out using three wavelength laser microrefractometer based on the total internal reflection method. The critical angle is determined by the disappearance of the diffraction orders from a metal grating. The experimental uncertainty is less than ±0.0001. The dispersion dependences of the refractive indices are obtained using the one-term Sellmeier model. Based on the obtained experimental data additional refractive and dispersion characteristics are calculated. (paper)

Mechanistic Analysis of Cocrystal Dissolution as a Function of pH and Micellar Solubilization.

Science.gov (United States)

Cao, Fengjuan; Amidon, Gordon L; Rodriguez-Hornedo, Nair; Amidon, Gregory E

2016-03-07

The purpose of this work is to provide a mechanistic understanding of the dissolution behavior of cocrystals under the influence of ionization and micellar solubilization. Mass transport models were developed by applying Fick's law of diffusion to dissolution with simultaneous chemical reactions in the hydrodynamic boundary layer adjacent to the dissolving cocrystal surface to predict the pH at the dissolving solid-liquid interface (i.e., interfacial pH) and the flux of cocrystals. To evaluate the predictive power of these models, dissolution studies of carbamazepine-saccharin (CBZ-SAC) and carbamazepine-salicylic acid (CBZ-SLC) cocrystals were performed at varied pH and surfactant concentrations above the critical stabilization concentration (CSC), where the cocrystals were thermodynamically stable. The findings in this work demonstrate that the pH dependent dissolution behavior of cocrystals with ionizable components is dependent on interfacial pH. This mass transport analysis demonstrates the importance of pH, cocrystal solubility, diffusivity, and micellar solubilization on the dissolution rates of cocrystals.

Novel structural hybrids of pyrazolobenzothiazines with benzimidazoles as cholinesterase inhibitors.

Science.gov (United States)

Aslam, Sana; Zaib, Sumera; Ahmad, Matloob; Gardiner, John M; Ahmad, Aqeel; Hameed, Abdul; Furtmann, Norbert; Gütschow, Michael; Bajorath, Jürgen; Iqbal, Jamshed

2014-05-06

Two series of novel pyrazolobenzothiazine-based hybrid compounds were efficiently synthesized starting from saccharin sodium salt. Pyrazolo[4,3-c][1,2]benzothiazine scaffolds were N-arylated by using p-fluorobenzaldehyde, followed by the incorporation of a benzimidazole or similar ring systems by treatment with arylenediamines. These phenylene-connected hybrid compounds were investigated as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Compounds 12d and 12k were the most potent AChE inhibitors with IC50 values of 11 and 13 nM, respectively, while 6j (IC50 = 17 nM) proved to be the most active inhibitor against BuChE with remarkable selectivity for BuChE over AChE. Molecular docking studies were also performed on human AChE and BuChE to suggest possible binding modes in which the inhibitor's extended structure is accommodated along the active site gorge of both enzymes. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Evaluating the environmental impact of artificial sweeteners: a study of their distributions, photodegradation and toxicities.

Science.gov (United States)

Sang, Ziye; Jiang, Yanan; Tsoi, Yeuk-Ki; Leung, Kelvin Sze-Yin

2014-04-01

While having a long tradition as safe food additives, artificial sweeteners are a newly recognized class of environmental contaminants due to their extreme persistence and ubiquitous occurrence in various aquatic ecosystems. Resistant to wastewater treatment processes, they are continuously introduced into the water environments. To date however, their environmental behavior, fate as well as long term ecotoxicological contributions in our water resources still remain largely unknown. As a first step in the comprehensive study of artificial sweeteners, this work elucidates the geographical/seasonal/hydrological interactions of acesulfame, cyclamate, saccharin and sucralose in an open coast system at an estuarine/marine junction. Higher occurrence of acesulfame (seasonal average: 0.22 μg L(-1)) and sucralose (0.05 μg L(-1)) was found in summer while saccharin (0.11  μg L(-1)) and cyclamate (0.10 μg L(-1)) were predominantly detected in winter. Seasonal observations of the four sweeteners suggest strong connections with the variable chemical resistance among different sweeteners. Our photodegradation investigation further projected the potential impact of persistent acesulfame and sucralose compounds under prolonged exposure to intensive solar irradiation. Real-time observation by UPLC-ESI/MS of the degradation profile in both sweeteners illustrated that formation of new photo by-products under prolonged UV irradiation is highly viable. Interestingly, two groups of kinetically behaved photodegradates were identified for acesulfame, one of which was at least six times more persistent than the parent compound. For the first time, acute toxicity for the degradates of both sweeteners were arbitrarily measured, revealing photo-enhancement factors of 575 and 17.1 for acesulfame and sucralose, respectively. Direct comparison of photodegradation results suggests that the phototoxicity of acesulfame degradation products may impact aquatic ecosystems. In an attempt

Disruption of the glutamate-glutamine cycle involving astrocytes in an animal model of depression for males and females

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Virginie Rappeneau

2016-12-01

Full Text Available Background: Women are twice as likely as men to develop major depression (MD. The brain mechanisms underlying this sex disparity are not clear. Disruption of the glutamate-glutamine cycle has been implicated in psychiatric disturbances. This study identifies sex-based impairments in the glutamate-glutamine cycle involving astrocytes using an animal model of depression. Methods: Male and female adult Long-Evans rats were exposed to chronic social defeat stress (CSDS for 21 days, using a modified resident-intruder paradigm. Territorial aggression was used for males and maternal aggression was used for females to induce depressive-like deficits for intruders. The depressive-like phenotype was assessed with intake for saccharin solution, weight gain, estrous cycle, and corticosterone (CORT. Behaviors displayed by the intruders during daily encounters with residents were characterized. Rats with daily handling were used as controls for each sex. Ten days after the last encounter, both the intruders and controls were subjected to a no-net-flux in vivo microdialysis to assess glutamate accumulation and extracellular glutamine in the nucleus accumbens (NAc. The contralateral hemispheres were used for determining changes in astrocytic markers, including glial fibrillary acidic protein (GFAP and glutamate transporter-1 (GLT-1. Results: Both male and female intruders reduced saccharin intake over the course of CSDS, compared to their pre-stress period and to their respective controls. Male intruders exhibited submissive/defensive behaviors to territorial aggression by receiving sideways threats and bites. These males showed reductions in striatal GLT-1 and spontaneous glutamine in the NAc, compared to controls. Female intruders exhibited isolated behaviors to maternal aggression, including immobility, rearing, and self-grooming. Their non-reproductive days were extended. Also, they showed reductions in prefrontal and accumbal GFAP+ cells and prefrontal GLT

Determinação de aditivos, aldeídos furânicos, açúcares e cafeína em bebidas por cromatografia líquida de alta eficiência: validação de metodologias Determination of additives, furanic aldehydes, sugars and caffeine in beverages by high performance liquid chromatographic: validation of methodologies

Directory of Open Access Journals (Sweden)

Francisco Wendel Batista de Aquino

2004-03-01

Full Text Available Metodologias cromatográficas foram adaptadas e validadas para a determinação dos compostos cafeína, furfural, 5-hidroximetilfurfural (5-HMF, sacarina, benzoato de sódio, glicose, frutose, ácido cítrico e ácido ascórbico em cajuínas, xaropes de guaraná, refrigerantes e sucos de fruta produzidos no Ceará. Constatou-se que 66% das cajuínas apresentam baixa qualidade por causa do processo de cozimento, enquanto que para refrigerantes 12% excederam o limite de benzoato de sódio permitido pela legislação brasileira e 29% apresentaram adição ilegal de sacarina. As metodologias foram validadas em função da precisão intralaboratorial, recuperação experimental, linearidade da curva analítica, limite de detecção e de quantificação para cada composto estudado. A precisão e recuperação de cada composto variaram de 2,85 - 8,35 (D.P.R% e 95,1 - 105,5%, respectivamente. As curvas analíticas apresentaram linearidade satisfatória com coeficiente de correlação maior que 0,990. O limite de detecção e quantificação de cada composto foram determinados em nível de µg/L.In this work methodologies chromatographic have been evaluated and validated for the determination of caffeine, furfural, 5-HMF, saccharin, sodium benzoate glucose, fructose, acid citric and acid ascorbic in different food products of Ceara State, Brazil. The study has been evidenced that 66% of the cajuinas, present low quality because of the process of heating, and 12% of the soft drinks presented content of sodium benzoate above the limit tolerated by Brazilian legislation and 29% of the soft drinks illegal saccharin addition. The methodologies were validated in function of the precision, experimental recovery, linearity of the analytical curves, limit of detection and quantification for each compound studied. The precision (R.S.D% of the determination of each compound varied of 2.85 to 8.35 % and recovery was between 95,1 to 105,5 %. The linearity of the

Hypercrosslinked particles for the extraction of sweeteners using dispersive solid-phase extraction from environmental samples.

Science.gov (United States)

Lakade, Sameer S; Zhou, Qing; Li, Aimin; Borrull, Francesc; Fontanals, Núria; Marcé, Rosa M

2018-04-01

This work presents a new extraction material, namely, Q-100, based on hypercrosslinked magnetic particles, which was tested in dispersive solid-phase extraction for a group of sweeteners from environmental samples. The hypercrosslinked Q-100 magnetic particles had the advantage of suitable pore size distribution and high surface area, and showed good retention behavior toward sweeteners. Different dispersive solid-phase extraction parameters such as amount of magnetic particles or extraction time were optimized. Under optimum conditions, Q-100 showed suitable apparent recovery, ranging in the case of river water sample from 21 to 88% for all the sweeteners, except for alitame (12%). The validated method based on dispersive solid-phase extraction using Q-100 followed by liquid chromatography with tandem mass spectrometry provided good linearity and limits of quantification between 0.01 and 0.1 μg/L. The method was applied to analyze samples from river water and effluent wastewater, and four sweeteners (acesulfame, saccharin, cyclamate, and sucralose) were found in both types of sample. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Study on the current status of biomass energy development; Bio mass energy no kaihatsu jokyo chosa

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-03-01

A survey was conducted on the present status of biomass energy in Japan and abroad and the developmental trend of the latest biomass energy technology. Brazil and the U.S. are most advancing in the biomass energy utilization. Brazil uses sugar cane which is plenty in supply as a raw material, and the U.S. does corn which is the surplus crop. Both countries use the conventional ethanol fermentation technology and produce the petroleum substitution liquid fuel which is in greatest need. As to the technology to convert biomass resource into energy, attention has so far been paid to the development of the production process of the liquid fuel. The latest technology for ethanol fermentation using saccharin and starch as raw materials has already been established in Japan, and the energy-saving type alcohol recovery technology has also reached the stage of practical application. Moreover, as to the ethanol conversion technology with cellulose substrate, the development of the saccharification process will be needed in future. 15 figs., 10 tabs.

Determination of essential elements in dietetic sample by neutron activation analysis; Determinacao de elementos essenciais em alimentos dieteticos pela tecnica de analise por ativacao com neutrons

Energy Technology Data Exchange (ETDEWEB)

Siquelli, Murilo V.; Maihara, Vera A. Maihara [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil). Lab. de Analise por Ativacao Neutronica]. E-mail: murilo_siquelli@hotmail.com; vmaihara@ipen.br

2005-07-01

In the last years there has been an increase of the dietetic product consumption by people who suffer from diabetes, heart disease and by people concerned about having a healthy life as well. Despite the increase of dietetic product presents in the diet of the Brazilian population, the use of these products is still controversial. The analysis of the nutritional composition of these products is becoming important because a great number of people is changing their traditional food by dietetic products. In the literature, there is no information about the inorganic composition, mainly related to the essential elements, in the dietetic products: diet and light . In this study are presented preliminary results of the concentrations of Br, Ca, Cr, Fe, Na and Zn determined by Instrumental Neutron Activation Analysis in aspartame, saccharin and cyclamate sodium , and stevia based sweetener samples. Gelatin samples, diet and light, were also analyzed. Methodology validation was done analyzing NIST reference materials Tea Leaves (INCT-TL-1) and Mixed Polish Herbs (INCT-MPH-2). (author)

BIOACTIVE COMPOUNDS IN CONVENTIONAL AND NO ADDED SUGARS RED STRAWBERRY GUAVA (Psidium cattleianum Sabine JELLIES

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GABRIELA NIEMEYER REISSIG

Full Text Available ABSTRACT This study aimed to prepare jellies of conventional type of red strawberry guava (with added sucrose and no added sugar and evaluate the physical and chemical composition and content of bioactive compounds in them. Four jellies formulations were prepared: conventional with addition of sucrose (F1, aspartame (F2, saccharin and cyclamate (F3, acesulfame and sucralose (F4. Physicochemical analysis of pH were carried out, as well as analysis of titratable acidity, total soluble solids, ashes, proteins, lipids, moisture, carbohydrates, calories, lightness, color tone, total phenols, anthocyanins, carotenoids, ascorbic acid and antioxidant activity, by the capture of DPPH and ABTS radicals. Conventional and no added sugars jellies did not differ for total phenols, total anthocyanins and ascorbic acid. However, processing exerted significant influence (p=0.05 on total carotenoids and antioxidant activity. It is feasible to use red strawberry guava for the preparation of conventional and no added sugar jellies. The products, however, show a significant difference in carotenoids content, with the highest content of these and higher antioxidant activity in processed jellies without sugars addition.

The effect of dilute baby shampoo on nasal mucociliary clearance in healthy subjects.

Science.gov (United States)

Isaacs, Seth; Fakhri, Samer; Luong, Amber; Whited, Chad; Citardi, Martin J

2011-01-01

Biofilm formation has been implicated as an etiologic factor in the development of chronic rhinosinusitis (CRS). Nasal irrigation with surfactants including dilute baby shampoo have been proposed as an antibiofilm treatment for CRS patients. The effect of dilute baby shampoo on normal sinonasal mucosal function is unknown. Mucociliary clearance time (MCT), as measured by the time in minutes for a subject to detect a sweet taste after the application of a saccharin granules at the anterior part of the inferior turbinate, was performed before and shortly after nasal irrigation with 50 ml of 1% baby shampoo (Johnson & Johnson, New Brunswick, NJ) in 27 healthy volunteers. Mean MCTs before and after irrigation were 12.09 (±4.83 minutes) and 15.45 (±7.71 minutes) minutes, respectively. The mean difference, 3.37 minutes, was statistically significant (p = 0.031). Pre- and post-MCTs for each subject were not correlated (r = 0.324; p = 0.100). Nasal irrigations with dilute baby shampoo increase MCTs in healthy subjects. The impact of such interventions in CRS patients warrants additional investigation.

Noncaloric Sweeteners in Children: A Controversial Theme

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Samuel Durán Agüero

2018-01-01

Full Text Available Noncaloric sweeteners (NCS are food additives used to provide sweetness without adding calories. Their consumption has become more widespread around the world in all age groups, including children. The aim of this study is to show the state of the art about the intake of noncaloric sweeteners in children, as well as their benefits and consumption risk. Scientific searchers were used (PUBMED, Scopus, and Scielo to analyze articles that included keywords (noncaloric sweeteners/saccharin/cyclamate/acesulfame potassium/aspartame/sucralose/stevia/children in English, Spanish, and Portuguese. Authors conclude that it is imperative that health professionals judiciously and individually evaluate the overall benefits and risks of NCS use in consumers before recommending their use. Different subgroups of the population incorporate products containing NCS in their diet with different objectives, which should be considered when recommending a diet plan for the consumer. In childhood, in earlier age groups, this type of additives should be used as a dietary alternative when other forms of prevention in obesity are not sufficient.

Sulfonamide inhibition studies of the β-carbonic anhydrase from the newly discovered bacterium Enterobacter sp. B13.

Science.gov (United States)

Eminoğlu, Ayşenur; Vullo, Daniela; Aşık, Aycan; Çolak, Dilşat Nigar; Çanakçı, Sabriye; Beldüz, Ali Osman; Supuran, Claudiu T

2016-04-01

The genome of the newly identified bacterium Enterobacter sp. B13 encodes for a β-class carbonic anhydrases (CAs, EC 4.2.1.1), EspCA. This enzyme was recently cloned, and characterized kinetically by this group (J. Enzyme Inhib. Med. Chem. 2016, 31). Here we report an inhibition study with sulfonamides and sulfamates of this enzyme. The best EspCA inhibitors were some sulfanylated sulfonamides with elongated molecules, metanilamide, 4-aminoalkyl-benzenesulfonamides, acetazolamide, and deacetylated methazolamide (KIs in the range of 58.7-96.5nM). Clinically used agents such as methazolamide, ethoxzolamide, dorzolamide, brinzolamide, benzolamide, zonisamide, sulthiame, sulpiride, topiramate and valdecoxib were slightly less effective inhibitors (KIs in the range of 103-138nM). Saccharin, celecoxib, dichlorophenamide and many simple benzenesulfonamides were even less effective as EspCA inhibitors, with KIs in the range of 384-938nM. Identification of effective inhibitors of this bacterial enzyme may lead to pharmacological tools useful for understanding the physiological role(s) of the β-class CAs in bacterial pathogenicity/virulence. Copyright © 2016 Elsevier Ltd. All rights reserved.

Determination of essential elements in dietetic sample by neutron activation analysis

International Nuclear Information System (INIS)

Siquelli, Murilo V.; Maihara, Vera A. Maihara

2005-01-01

In the last years there has been an increase of the dietetic product consumption by people who suffer from diabetes, heart disease and by people concerned about having a healthy life as well. Despite the increase of dietetic product presents in the diet of the Brazilian population, the use of these products is still controversial. The analysis of the nutritional composition of these products is becoming important because a great number of people is changing their traditional food by dietetic products. In the literature, there is no information about the inorganic composition, mainly related to the essential elements, in the dietetic products: diet and light . In this study are presented preliminary results of the concentrations of Br, Ca, Cr, Fe, Na and Zn determined by Instrumental Neutron Activation Analysis in aspartame, saccharin and cyclamate sodium , and stevia based sweetener samples. Gelatin samples, diet and light, were also analyzed. Methodology validation was done analyzing NIST reference materials Tea Leaves (INCT-TL-1) and Mixed Polish Herbs (INCT-MPH-2). (author)

Effects of cellulosic degradation products on uranium sorption in the geosphere

International Nuclear Information System (INIS)

Baston, G.M.N.; Berry, J.A.; Bond, K.A.; Boult, K.A.; Brownsword, M.; Linklater, C.M.

1994-01-01

The current design concept for intermediate- and some low-level radioactive waste disposal in the UK involves emplacement in a cementitious repository deep underground. The movement of radionuclides away from such a repository through the host rock formation towards the biosphere is expected to be retarded to a significant degree by sorption processes. One major issue being studied is the effect on uranium sorption of degradation products arising from organic waste matter, especially cellulosic materials. The sorption of uranium could be reduced by degradation products, either because of complexation, or through the organic materials competing for sorption sites. Because of the complexity of authentic degradation products, work has also been carried out using gluconate and iso-saccharinate as well-characterised simulants. In the presence of high concentrations of either the authentic or simulated degradation products, significant reductions in uranium sorption have been observed. However, in the presence of lower concentrations of these organic materials, such as would be present in the repository, sorption was reduced at most by only a small margin and, in some cases, the results suggested a slight increase. ((orig.))

Effects of cellulosic degradation products on uranium sorption in the geosphere

Energy Technology Data Exchange (ETDEWEB)

Baston, G.M.N. (AEA Technology, Harwell, Didcot, Oxon OX11 0RA (United Kingdom)); Berry, J.A. (AEA Technology, Harwell, Didcot, Oxon OX11 0RA (United Kingdom)); Bond, K.A. (AEA Technology, Harwell, Didcot, Oxon OX11 0RA (United Kingdom)); Boult, K.A. (AEA Technology, Harwell, Didcot, Oxon OX11 0RA (United Kingdom)); Brownsword, M. (AEA Technology, Harwell, Didcot, Oxon OX11 0RA (United Kingdom)); Linklater, C.M. (AEA Technology, Harwell, Didcot, Oxon OX11 0RA (United Kingdom))

1994-10-01

The current design concept for intermediate- and some low-level radioactive waste disposal in the UK involves emplacement in a cementitious repository deep underground. The movement of radionuclides away from such a repository through the host rock formation towards the biosphere is expected to be retarded to a significant degree by sorption processes. One major issue being studied is the effect on uranium sorption of degradation products arising from organic waste matter, especially cellulosic materials. The sorption of uranium could be reduced by degradation products, either because of complexation, or through the organic materials competing for sorption sites. Because of the complexity of authentic degradation products, work has also been carried out using gluconate and iso-saccharinate as well-characterised simulants. In the presence of high concentrations of either the authentic or simulated degradation products, significant reductions in uranium sorption have been observed. However, in the presence of lower concentrations of these organic materials, such as would be present in the repository, sorption was reduced at most by only a small margin and, in some cases, the results suggested a slight increase. ((orig.))

Effect of Surface Roughness and Structure Features on Tribological Properties of Electrodeposited Nanocrystalline Ni and Ni/Al2O3 Coatings

Science.gov (United States)

Góral, Anna; Lityńska-Dobrzyńska, Lidia; Kot, Marcin

2017-05-01

Metal matrix composite coatings obtained by electrodeposition are one of the ways of improving the surfaces of materials to enhance their durability and properties required in different applications. This paper presents an analysis of the surface topography, microstructure and properties (residual stresses, microhardness, wear resistance) of Ni/Al2O3 nanocomposite coatings electrodeposited on steel substrates from modified Watt's-type baths containing various concentrations of Al2O3 nanoparticles and a saccharin additive. The residual stresses measured in the Ni/Al2O3 coatings decreased with an increasing amount of the co-deposited ceramics. It was established that the addition of Al2O3 powder significantly improved the coatings' microhardness. The wear mechanism changed from adhesive-abrasive to abrasive with a rising amount of Al2O3 particles and coating microhardness. Nanocomposite coatings also exhibited a lower coefficient of friction than that of a pure Ni-electrodeposited coating. The friction was found to depend on the surface roughness, and the smoother surfaces gave lower friction coefficients.

Structural and IR-spectroscopic characterization of cadmium and lead(II) acesulfamates

Energy Technology Data Exchange (ETDEWEB)

Echeverria, Gustavo A.; Piro, Oscar E. [Univ. Nacional de La Plata (Argentina). Dept. de Fisica y Inst. IFLP (CONICET- CCT-La Plata); Parajon-Costa, Beatriz S.; Baran, Enrique J. [Univ. Nacional de La Plata (Argentina). Centro de Quimica Inorganica (CEQUINOR/CONICET- CCT-La Plata)

2017-07-01

Cadmium and lead(II) acesulfamate, Cd(C{sub 4}H{sub 4}NO{sub 4}S){sub 2} . 2H{sub 2}O and Pb(C{sub 4}H{sub 4}NO{sub 4}S){sub 2}, were prepared by the reaction of acesulfamic acid and the respective metal carbonates in aqueous solution, and characterized by elemental analysis. Their crystal structures were determined by single crystal X-ray diffraction methods. The Cd(II) compound crystallizes in the monoclinic space group P2{sub 1}/c with Z=4 and the corresponding Pb(II) salt in the triclinic space group P anti 1 with Z=2. In both salts, acesulfamate acts both as a bi-dentate ligand through its nitrogen and carbonyl oxygen atoms and also as a mono-dentate ligand through this same oxygen atom, giving rise to polymeric structures; in the Pb(II) salt the ligand also binds the cation through its sulfoxido oxygen atoms. The FTIR spectra of the compounds were recorded and are briefly discussed. Some comparisons with other related acesulfamate and saccharinate complexes are made.

Morphological characteristics of BRS 501 sweet sorghum under water stress

Directory of Open Access Journals (Sweden)

Luciano Rezende Moreira

2016-12-01

Full Text Available Sorghum [Sorghum bicolor (L. Moench] crop is distinguished from other crops for its tolerance to both water deficit and excess soil moisture, under very dry and/or very hot environmental situations in which the productivity of other cereals becomes uneconomical. This work was conducted to evaluate the effects of irrigation on root conformation at the initial development phase of sweet sorghum. So, BRS 501 cv. was subjected to four irrigation levels based on 80%, 60%, 40% and 20% of the field capacity (CC. The decreased availability of water in the soil negatively affected the majority of the characteristics under evaluation except for the relationship between the root system and the aerial part (SR/PA, average root diameter (DMR and specific root area (ARE. We concluded that the growth of sweet sorghum plants under evaluation is sensible to the decrease of water in the soil, as it is affected by low water availability. This methodology, common to other crops, can be used for saccharine sorghum in order to establish hydric availabilities in new experiments to discriminate the drought-tolerant cultivars.

Simultaneous Determination of Six Food Additives in drinks by high performance liquid chromatography coupled to diode array detector detection

International Nuclear Information System (INIS)

Yan, Q.

2013-01-01

A reversed-phase high performance liquid chromatographic method for the successful separation and determination of 6 synthetic food additives (aspartame, acesulfame potassium, benzoic acid, sodium saccharin, tartrazine and sunset yellow) was developed. A EclipseXDB-C18 column (250x4.6 mm I.D.; 5 micro m) was used and the mobile phase contained methanol and 0.02 mol/L ammonium acetate (pH 6.0) (30:70, v/v) was pumped at a flow rate of 0.7 mL/min at room temperature. Successful separation conditions were obtained for all the compounds using an optimized gradient elution within 10 min. The diode array detector was used to monitor the food additives at 230 nm. The method was thoroughly validated, detection limits for all substances varied between 0.03 and 1.35 micro g/mg, the intra-day precision (as RSD) ranged from 1.57% to 4.72 %, the inter-day precision (as RSD) was between 2.05 % and 4.18 %. Satisfactory recoveries, ranging from 90.00 % to 109.87 %, were obtained. The proposed system was applied to drink samples. (author)

Moessbauer Study of Electrodeposited Fe/Fe-Oxide Multilayers

International Nuclear Information System (INIS)

Kuzmann, E.; Homonnay, Z.; Klencsar, Z.; Vertes, A.; Lakatos-Varsanyi, M.; Miko, A.; Varga, L.K.; Kalman, E.; Nagy, F.

2005-01-01

Iron has been deposited electrochemically by short current pulses in Na-saccharin containing FeII-chloride and sulphate solution electrolytes. Combined electrochemical techniques with initial pulse plating of iron nanolayer and its subsequent anodic oxidation under potential control have been used for production of Fe/Fe-oxide multilayers. 57Fe CEM spectra of pulse plated iron revealed the presence of a minor doublet attributed mainly to γ-FeOOH in addition to the dominant sextet of α-iron. In the case of anodically oxidized pulse plated iron and of samples after repeated deposition of anodically oxidized pulse plated iron an additional minor doublet, assigned to ferrous chloride, also appears in the Moessbauer spectra. A significant change in the magnetic anisotropy of α-iron was observed with the anodic oxidation. The thickness of the layers were estimated from the CEM spectrum data by a modified computer program of the Liljequist method. The coercive field and the power loss versus frequency data showed that the pulse plated iron cores are good inductive elements up to several kHz frequencies

Contaminants of emerging concern in surface waters in Barbados, West Indies.

Science.gov (United States)

Edwards, Quincy A; Kulikov, Sergei M; Garner-O'Neale, Leah D; Metcalfe, Chris D; Sultana, Tamanna

2017-11-14

Contaminants of emerging concern (CECs), including pharmaceuticals, artificial sweeteners, steroid hormones, and current-use pesticides have been detected in surface waters around the world, but to date, there have been no reports in the peer-reviewed literature on the levels of these classes of contaminants in freshwater resources in the Caribbean region. In the present study, multi-residue solid phase extraction (SPE) and liquid chromatography with tandem mass spectroscopy (LC-MS/MS) were used to analyze grab samples of surface waters collected from five different watersheds in Barbados, West Indies. The artificial sweeteners (AS), acesulfame, cyclamate, saccharin, and sucralose were widely detected in the watersheds, indicating contamination from domestic wastewater, and the concentrations of these chemical tracers in water were correlated with the concentrations of the non-prescription pharmaceutical, ibuprofen (R 2 values of 0.4-0.6). Surprisingly, the concentrations of another chemical tracer of domestic wastewater, caffeine were not correlated with ibuprofen or AS concentrations. Several other prescription pharmaceuticals and the steroid hormones, estrone and androstenedione, were detected in selected watersheds at low ng/L concentrations. The fungicide, chlorothalonil was widely detected in surface waters at low (contamination of water resources by pharmaceuticals.

Tobacco smoking, occupational exposure and bladder cancer in Argentina.

Science.gov (United States)

Iscovich, J; Castelletto, R; Estève, J; Muñoz, N; Colanzi, R; Coronel, A; Deamezola, I; Tassi, V; Arslan, A

1987-12-15

The highest rate for bladder cancer in Latin America has been reported from La Plata, Argentina. A case-control study was carried out to investigate the reasons for this high rate. A total of 117 cases, 117 hospital controls and 117 neighbourhood sex- and age-matched controls were interviewed regarding their smoking and drinking habits and occupational exposures. Cigarette smoking and coffee drinking were identified as the major risk factors, and a significant association was also found for truck and railway drivers and for oil refinery workers. The relative risks for male smokers who ever smoked cigarettes vs. non-smokers was 4.3 (95% Cl: 1.9-10.3). The risk associated with black tobacco cigarettes was 2-3 times higher than that of blond cigarettes. For male ex-smokers the risk after 5 years of no smoking is less than one third of that of current smokers. The RR for drinking coffee was 2.4 (95% Cl: 1.4-4.4) after adjusting for the effects of tobacco smoking, and the risk increased with the number of cups per day. No association was found with the use of saccharin.

Stevia preferences in Wistar rats.

Science.gov (United States)

Núñez Martínez, Paula; Argüelles Luis, Juan; Perillán Méndez, Carmen

2016-11-01

The Stevia rebaudiana plant is likely to become a major source of high-potency sweetener for the growing natural-food market. S. rebaudiana is the source of a number of sweet diterpenoid glycosides, but the major sweet constituents are rebaudioside A and stevioside. These two constituents have similar pharmacokinetic and metabolic profiles in rats and humans, and thus, studies carried out with either steviol glycoside are relevant to both. Other studies illustrate the diversity of voluntary sweet intake in mammals. This study was done using a series of two-bottle tests that compared a wide range of sweetener concentrations versus saccharin concentrations and versus water. Wistar rats displayed preferences for stevia extract and pure rebaudioside A solutions over water at a range of concentrations (0.001% to 0.3%), and their intake peak occurred at 0.1% concentration. They also preferred solutions prepared with a commercial rebaudioside A plus erythritol mixture to water, and their peak was at 2% concentration. The present study provides new information about the responses of Wistar rats to stevia compounds and commercial stevia products such as Truvia. These results could help with the appropriate dosage selection for focused behavioral and physiological studies on stevia.

Application of dispersive solid-phase extraction and ultra-fast liquid chromatography-tandem quadrupole mass spectrometry in food additive residue analysis of red wine.

Science.gov (United States)

Chen, Xiao-Hong; Zhao, Yong-Gang; Shen, Hao-Yu; Jin, Mi-Cong

2012-11-09

A novel and effective dispersive solid-phase extraction (dSPE) procedure with rapid magnetic separation using ethylenediamine-functionalized magnetic polymer as an adsorbent was developed. The new procedure had excellent clean-up ability for the selective removal of the matrix in red wine. An accurate, simple, and rapid analytical method using ultra-fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC-MS/MS) for the simultaneous determination of nine food additives (i.e., acesulfame, saccharin, sodium cyclamate, aspartame, benzoic acid, sorbic acid, stevioside, dehydroacetic acid, and neotame) in red wine was also used and validated. Recoveries ranging from 78.5% to 99.2% with relative standard deviations ranging from 0.46% to 6.3% were obtained using the new method. All target compounds showed good linearities in the tested range with correlation coefficients (r) higher than 0.9993. The limits of quantification for the nine food additives were between 0.10 μg/L and 50.0 μg/L. The proposed dSPE-UFLC-MS/MS method was successfully applied in the food-safety risk monitoring of real red wine in Zhejiang Province, China. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Boundary conditions for the maintenance of memory by PKMzeta in neocortex.

Science.gov (United States)

Shema, Reut; Hazvi, Shoshi; Sacktor, Todd C; Dudai, Yadin

2009-02-01

We report here that ZIP, a selective inhibitor of the atypical protein kinase C isoform PKMzeta, abolishes very long-term conditioned taste aversion (CTA) associations in the insular cortex of the behaving rat, at least 3 mo after encoding. The effect of ZIP is not replicated by a general serine/threonine protein kinase inhibitor that is relatively ineffective toward PKMzeta, is independent of the intensity of training and the perceptual quality of the taste saccharin (conditioned stimulus, CS), and does not affect the ability of the insular cortex to re-encode the same specific CTA association again. The memory trace is, however, insensitive to ZIP during or immediately after training. This implies that the experience-dependent cellular plasticity mechanism targeted by ZIP is established following a brief time window after encoding, consistent with the standard period of cellular consolidation, but then, once established, does not consolidate further to gain immunity to the amnesic agent. Hence, we conclude that PKMzeta is not involved in short-term CTA memory, but is a critical component of the cortical machinery that stores long- and very long-term CTA memories.

Glucose enhancement of recognition memory: differential effects on effortful processing but not aspects of 'remember-know' responses.

Science.gov (United States)

Scholey, Andrew; Macpherson, Helen; Sünram-Lea, Sandra; Elliott, Jade; Stough, Con; Kennedy, David

2013-01-01

The administration of a glucose drink has been shown to enhance cognitive performance with effect sizes comparable with those from pharmaceutical interventions in human trials. In the memory domain, it is currently debated whether glucose facilitation of performance is due to differential targeting of hippocampal memory or whether task effort is a more important determinant. Using a placebo-controlled, double-blind, crossover 2(Drink: glucose/placebo) × 2(Effort: ± secondary task) design, 20 healthy young adults' recognition memory performance was measured using the 'remember-know' procedure. Two high effort conditions (one for each drink) included secondary hand movements during word presentation. A 25 g glucose or 30 mg saccharine (placebo) drink was consumed 10 min prior to the task. The presence of a secondary task resulted in a global impairment of memory function. There were significant Drink × Effort interactions for overall memory accuracy but no differential effects for 'remember' or 'know' responses. These data suggest that, in some circumstances, task effort may be a more important determinant of the glucose facilitation of memory effect than hippocampal mediation. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

Multicomponent analysis of fat- and water-soluble vitamins and auxiliary substances in multivitamin preparations by qNMR.

Science.gov (United States)

Eiff, Julia; Monakhova, Yulia B; Diehl, Bernd W K

2015-04-01

A nuclear magnetic resonance (NMR) spectroscopic method was tested to control 12 vitamins and accompanying substances in multivitamin preparations. The limits of detection (LODs) and limits of quantification (LOQs) varied in the 9.0-77.0 mg/kg and in the 34.5-93.5 mg/kg range, respectively. The coefficients of variation (CVs) ranged between 0.9% and 12%. The (1)H NMR spectra showed linearity for the 140-260 mg sample weight (R(2) > 0.918). The NMR spectra of multivitamin preparations showed the presence of different degradation products of ascorbic acid. The NMR method was applied to 13 different multivitamin preparations including tablets, capsules, and effervescent tablets with average recovery rates between 85% and 132%. A number of accompanying substances (citric acid, mannitol, saccharin, cyclamate, sum of steviol glycosides, and butylhydroxytoluene) were additionally identified and quantified. NMR was found to be suitable for the simultaneous qualitative measurement of water- and fat-soluble vitamins and accompanying substances and shows some promise for quantitative determination of at least 5 vitamins (B1, B3, B5, B6, and E) in multivitamin preparations.

An EPR study on tea: Identification of paramagnetic species, effect of heat and sweeteners

Science.gov (United States)

Bıyık, Recep; Tapramaz, Recep

2009-10-01

Tea ( Camellia Sinensis) is the most widely consumed beverage in the world, and is known to be having therapeutic, antioxidant and nutritional effects. Electron paramagnetic resonance (EPR) spectral studies made on the tea cultivated along the shore of Black Sea, Turkey, show Mn 2+ and Fe 3+ centers in green tea leaves and in black tea extract. Dry black tea flakes and dry extract show additional sharp line attributed to semiquinone radical. The origins of the paramagnetic species in black tea are defined and discussed. Effect of humidity and heat are investigated. It is observed that dry extract of black tea melts at 100 °C and the semiquinone radical lives up to 140 °C while Mn 2+ sextet disappears just above 100 °C in tea extract. Natural and synthetics sweeteners have different effects on the paramagnetic centers. White sugar (sucrose) quenches the Mn 2+ and semiquinone lines in black tea EPR spectrum, and glucose, fructose, lactose and maltose quench Fe 3+ line while synthetic sweeteners acesulfam potassium, aspartame and sodium saccharine do not have any effect on paramagnetic species in tea.

Comparison of performance of three different types of respiratory protection devices.

Science.gov (United States)

Lawrence, Robert B; Duling, Matthew G; Calvert, Catherine A; Coffey, Christopher C

2006-09-01

qualitative (Bitrex and saccharin) and quantitative (N95-Companion) fit testing were performed on the N95 filtering- and elastomeric-facepiece respirators. It was found that passing a fit test generally improves the protection afforded the wearer. Passing the Bitrex fit test resulted in 5th percentile SWPFs of 11.1 and 7.9 for elastomeric and filtering-facepiece respirators, respectively. After passing the saccharin tests, the elastomeric respirators provided a 5th percentile of 11.7, and the filtering-facepiece respirators provided a 5th percentile of 11.0. The 5th percentiles after passing the N95-Companion were 13.0 for the elastomeric respirators and 20.5 for the filtering-facepiece respirators. The data supports fit testing as an essential element of a complete respiratory protection program.

Operation condition for continuous anti-solvent crystallization of CBZ-SAC cocrystal considering deposition risk of undesired crystals

Science.gov (United States)

Nishimaru, Momoko; Nakasa, Miku; Kudo, Shoji; Takiyama, Hiroshi

2017-07-01

Crystallization operation of cocrystal production has deposition risk of undesired crystals. Simultaneously, continuous manufacturing processes are focused on. In this study, conditions for continuous cocrystallization considering risk reduction of undesired crystals deposition were investigated on the view point of thermodynamics and kinetics. The anti-solvent cocrystallization was carried out in four-component system of carbamazepine, saccharin, methanol and water. From the preliminary batch experiment, the relationships among undesired crystal deposition, solution composition decided by mixing ratio of solutions, and residence time for the crystals were considered, and then the conditions of continuous experiment were decided. Under these conditions, the continuous experiment was carried out. The XRD patterns of obtained crystals in the continuous experiment showed that desired cocrystals were obtained without undesired crystals. This experimental result was evaluated by using multi-component phase diagrams from the view point of the operation point's movement. From the evaluation, it was found that there is a certain operation condition which the operation point is fixed with time in the specific domain without the deposition risk of undesired single component crystals. It means the possibility of continuous production of cocrystals without deposition risk of undesired crystals was confirmed by using multi-component phase diagrams.

Is the use of benzalkonium chloride as a preservative for nasal formulations a safety concern? A cautionary note based on compromised mucociliary transport.

Science.gov (United States)

Bernstein, I L

2000-01-01

Topical nasal solution and suspension delivery systems are available for short- and long-acting vasoconstrictors, ipratropium, cromolyn, azelastine, and glucocorticosteroids. The use of intranasal glucocorticosteroids has increased substantially because the efficacy of these agents has been well established for the treatment of perennial and seasonal allergic rhinitis. Adverse local effects of burning, irritation, and dryness are occasionally associated with glucocorticosteroid nasal preparations. Benzalkonium chloride (BKC) is a quaternary ammonium antimicrobial agent included in some nasal solutions (including glucocorticosteroids) to prevent the growth of bacteria. Some reports suggest that BKC in nasal sprays may cause adverse effects, including reduced mucociliary transport, rhinitis medicamentosa, and neutrophil dysfunction. This article summarizes recent literature about possible adverse biologic effects associated with BKC as a nasal spray preservative by examining its effects on the following properties of mucociliary transport: ciliary motion, ciliary form, ciliary beat frequency, electron microscopy, and particle movement/saccharin clearance tests. Both animal and human in vitro data suggest that BKC promotes ciliostasis and reduction in mucociliary transport that may be partially masked by absorption and dilution effects occurring in respiratory mucus. These possible confounding factors may account for several disparate human in vivo results. The use of BKC-free glucocorticosteroid formulations should be considered, particularly in patients who complain of nasal burning, dryness, or irritation.

Dietary saccharides and sweet tastants have differential effects on colonization of Drosophila oocytes by Wolbachia endosymbionts

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Moises Camacho

2017-07-01

Full Text Available Wolbachia bacteria are widespread, maternally transmitted endosymbionts of insects. Maintenance of sufficient Wolbachia titer in maternal germline cells is required for transmission efficacy. The mechanisms that regulate Wolbachia titer are not well understood; however, dietary sucrose was reported to elevate oocyte Wolbachia titer in Drosophila melanogaster whereas dietary yeast decreased oocyte titer. To further investigate how oocyte Wolbachia titer is controlled, this study analyzed the response of wMel Wolbachia to diets enriched in an array of natural sugars and other sweet tastants. Confocal imaging of D. melanogaster oocytes showed that food enriched in dietary galactose, lactose, maltose and trehalose elevated Wolbachia titer. However, oocyte Wolbachia titers were unaffected by exposure to the sweet tastants lactulose, erythritol, xylitol, aspartame and saccharin as compared to the control. Oocyte size was generally non-responsive to the nutrient-altered diets. Ovary size, however, was consistently smaller in response to all sugar- and sweetener-enriched diets. Furthermore, most dietary sugars administered in tandem with dietary yeast conferred complete rescue of oocyte titer suppression by yeast. All diets dually enriched in yeast and sugar also rescued yeast-associated ovary volume changes. This indicates oocyte colonization by Wolbachia to be a nutritionally sensitive process regulated by multiple mechanistic inputs.

Fate of artificial sweeteners through wastewater treatment plants and water treatment processes.

Science.gov (United States)

Li, Shaoli; Ren, Yuhang; Fu, Yingying; Gao, Xingsheng; Jiang, Cong; Wu, Gang; Ren, Hongqiang; Geng, Jinju

2018-01-01

Five full-scale wastewater treatment plants (WWTPs) in China using typical biodegradation processes (SBR, oxidation ditch, A2/O) were selected to assess the removal of four popular artificial sweeteners (ASs). All four ASs (acesulfame (ACE), sucralose (SUC), cyclamate (CYC) and saccharin (SAC)) were detected, ranging from 0.43 to 27.34μg/L in the influent. Higher concentrations of ASs were measured in winter. ACE could be partly removed by 7.11-50.76% through biodegradation and especially through the denitrifying process. The A2/O process was the most efficient at biodegrading ASs. Adsorption (by granular activated carbon (GAC) and magnetic resin) and ultraviolet radiation-based advanced oxidation processes (UV/AOPs) were evaluated to remove ASs in laboratory-scale tests. The amounts of resin adsorbed were 3.33-18.51 times more than those of GAC except for SUC. The adsorption ability of resin decreased in the order of SAC > ACE > CYC > SUC in accordance with the pKa. Degradation of ASs followed pseudo-first-order kinetics in UV/H2O2 and UV/PDS. When applied to the secondary effluent, ASs could be degraded from 30.87 to 99.93% using UV/PDS in 30 minutes and UV/PDS was more efficient and economic.

Sodium butyrate into the insular cortex during conditioned taste-aversion acquisition delays aversive taste memory extinction.

Science.gov (United States)

Núñez-Jaramillo, Luis; Reyes-López, Julian; Miranda, María Isabel

2014-04-16

Histone acetylation is one mechanism that promotes gene expression, and it increases during learning of various tasks. Specifically, novel taste consumption produces an increased acetylation of histone lysine residues in the insular cortex (IC), where protein synthesis is crucial during memory consolidation of conditioned taste aversion (CTA). However, the role of this elevated histone acetylation during CTA learning has not been examined directly. Thus, the present study investigated the effects of sodium butyrate (NaBu), a histone deacetylase inhibitor, injected into the IC during CTA acquisition. Male Wistar rats, IC bilaterally implanted, were injected 60 min before saccharine presentation, with a total volume of 0.5 µl of NaBu solution (100, 500, and 10 µg/0.5 µl) or saline; 30 min later animals were injected intraperitoneally with lithium chloride, a malaise-inducing drug. The next day, CTA retrieval was tested. No effects of NaBu were observed during acquisition or retrieval, but during extinction trials, a significant delay in aversive memory extinction was observed in the group injected with the lowest NaBu dose. This result indicates that NaBu in the IC strengthens CTA and delays aversive memory extinction, and suggests that histone acetylation could increase long-term taste-aversive memory strength.

Improvement of the tool life of a micro-end mill using nano-sized SiC/Ni electroplating method.

Science.gov (United States)

Park, Shinyoung; Kim, Kwang-Su; Roh, Ji Young; Jang, Gyu-Beom; Ahn, Sung-Hoon; Lee, Caroline Sunyong

2012-04-01

High mechanical properties of a tungsten carbide micro-end-mill tool was achieved by extending its tool life by electroplating nano-sized SiC particles (electroplating method on the surface of the micro-end-mill tool was applied using SiC particles and Ni particles. Organic additives (saccharin and ammonium chloride) were added in a Watts bath to improve the nickel matrix density in the electroplating bath and to smooth the surface of the co-electroplating. The morphology of the coated nano-sized SiC particles and the composition were measured using Scanning Electron Microscope and Energy Dispersive Spectrometer. As the Ni/SiC co-electroplating layer was applied, the hardness and friction coefficient improved by 50%. Nano-sized SiC particles with 7 wt% were deposited on the surface of the micro-end mill while the Ni matrix was smoothed by adding organic additives. The tool life of the Ni/SiC co-electroplating coating on the micro-end mill was at least 25% longer than that of the existing micro-end mills without Ni/SiC co-electroplating. Thus, nano-sized SiC/Ni coating by electroplating significantly improves the mechanical properties of tungsten carbide micro-end mills.

Simultaneous determination of artificial sweeteners, preservatives, caffeine, theobromine and theophylline in food and pharmaceutical preparations by ion chromatography.

Science.gov (United States)

Chen, Q C; Wang, J

2001-12-07

A novel ion chromatographic method was proposed for the simultaneous determination of artificial sweeteners (sodium saccharin, aspartame, acesulfame-K), preservatives (benzoic acid, sorbic acid), caffeine, theobromine and theophylline. The separation was performed on an anion-exchange analytical column operated at 40 degrees C within 45 min by an isocratic elution with 5 mM aqueous NaH2PO4 (pH 8.20) solution containing 4% (v/v) acetonitrile as eluent, and the determination by wavelength-switching ultraviolet absorbance detection. The detection limits (signal-to-noise ratio 3:1) for all analytes were below the sub-microg/ml level. Under the experimental conditions, several organic acids, including citric acid, malic acid, tartaric acid and ascorbic acid, did not interfere with the determination. The method has been successfully applied to the analysis of various food and pharmaceutical preparations, and the average recoveries for real samples ranged from 85 to 104%. The levels of all analytes determined by this method were in good agreement with those obtained by the high-performance liquid chromatographic procedure. The results also indicated that ion chromatography would be possibly a beneficial alternative to conventional high-performance liquid chromatography for the separation and determination of these compounds.

Fructose:Glucose Ratios—A Study of Sugar Self-Administration and Associated Neural and Physiological Responses in the Rat

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AnneMarie Levy

2015-05-01

Full Text Available This study explored whether different ratios of fructose (F and glucose (G in sugar can engender significant differences in self-administration and associated neurobiological and physiological responses in male Sprague-Dawley rats. In Experiment 1, animals self-administered pellets containing 55% F + 45% G or 30% F + 70% G, and Fos immunoreactivity was assessed in hypothalamic regions regulating food intake and reward. In Experiment 2, rats self-administered solutions of 55% F + 42% G (high fructose corn syrup (HFCS, 50% F + 50% G (sucrose or saccharin, and mRNA of the dopamine 2 (D2R and mu-opioid (MOR receptor genes were assessed in striatal regions involved in addictive behaviors. Finally, in Experiment 3, rats self-administered HFCS and sucrose in their home cages, and hepatic fatty acids were quantified. It was found that higher fructose ratios engendered lower self-administration, lower Fos expression in the lateral hypothalamus/arcuate nucleus, reduced D2R and increased MOR mRNA in the dorsal striatum and nucleus accumbens core, respectively, as well as elevated omega-6 polyunsaturated fatty acids in the liver. These data indicate that a higher ratio of fructose may enhance the reinforcing effects of sugar and possibly lead to neurobiological and physiological alterations associated with addictive and metabolic disorders.

Fructose:glucose ratios--a study of sugar self-administration and associated neural and physiological responses in the rat.

Science.gov (United States)

Levy, AnneMarie; Marshall, Paul; Zhou, Yan; Kreek, Mary Jeanne; Kent, Katrina; Daniels, Stephen; Shore, Ari; Downs, Tiana; Fernandes, Maria Fernanda; Mutch, David M; Leri, Francesco

2015-05-22

This study explored whether different ratios of fructose (F) and glucose (G) in sugar can engender significant differences in self-administration and associated neurobiological and physiological responses in male Sprague-Dawley rats. In Experiment 1, animals self-administered pellets containing 55% F + 45% G or 30% F + 70% G, and Fos immunoreactivity was assessed in hypothalamic regions regulating food intake and reward. In Experiment 2, rats self-administered solutions of 55% F + 42% G (high fructose corn syrup (HFCS)), 50% F + 50% G (sucrose) or saccharin, and mRNA of the dopamine 2 (D2R) and mu-opioid (MOR) receptor genes were assessed in striatal regions involved in addictive behaviors. Finally, in Experiment 3, rats self-administered HFCS and sucrose in their home cages, and hepatic fatty acids were quantified. It was found that higher fructose ratios engendered lower self-administration, lower Fos expression in the lateral hypothalamus/arcuate nucleus, reduced D2R and increased MOR mRNA in the dorsal striatum and nucleus accumbens core, respectively, as well as elevated omega-6 polyunsaturated fatty acids in the liver. These data indicate that a higher ratio of fructose may enhance the reinforcing effects of sugar and possibly lead to neurobiological and physiological alterations associated with addictive and metabolic disorders.

The role of artificial and natural sweeteners in reducing the consumption of table sugar: A narrative review.

Science.gov (United States)

Mooradian, Arshag D; Smith, Meridith; Tokuda, Masaaki

2017-04-01

The rapid increase in the prevalence of obesity worldwide has been partially attributed to the overconsumption of added sugars. Recent guidelines call for limiting the consumption of simple sugars to less than 10% of daily caloric consumption. High intensity sweeteners are regulated as food additives and include aspartame, acesulfame-k, neotame, saccharin, sucralose, cyclamate and alitame. Steviol glycosides and Luo Han Guo fruit extracts are high intensity sweeteners that are designated as generally recognized as safe (GRAS). Commonly used non-caloric artificial sweeteners may have unfavorable effect on health including glucose intolerance and failure to cause weight reduction. The nutritive sweeteners include sugar alcohols such as sorbitol, xylitol, lactitol, mannitol, erythritol, trehalose and maltitol. Naturally occurring rare sugars have recently emerged as an alternative category of sweeteners. These monosaccharides and their derivatives are found in nature in small quantities and lack significant calories. This category includes d-allulose (d-psicose), d-tagatose, d-sorbose and d-allose. Limiting consumption of any sweetener may well be the best health advice. Identifying natural sweeteners that have favorable effects on body weight and metabolism may help achieving the current recommendations of restricting simple sugar consumption. Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Reshaping the gut microbiota: Impact of low calorie sweeteners and the link to insulin resistance?

Science.gov (United States)

Nettleton, Jodi E; Reimer, Raylene A; Shearer, Jane

2016-10-01

Disruption in the gut microbiota is now recognized as an active contributor towards the development of obesity and insulin resistance. This review considers one class of dietary additives known to influence the gut microbiota that may predispose susceptible individuals to insulin resistance - the regular, long-term consumption of low-dose, low calorie sweeteners. While the data are controversial, mounting evidence suggests that low calorie sweeteners should not be dismissed as inert in the gut environment. Sucralose, aspartame and saccharin, all widely used to reduce energy content in foods and beverages to promote satiety and encourage weight loss, have been shown to disrupt the balance and diversity of gut microbiota. Fecal transplant experiments, wherein microbiota from low calorie sweetener consuming hosts are transferred into germ-free mice, show that this disruption is transferable and results in impaired glucose tolerance, a well-known risk factor towards the development of a number of metabolic disease states. As our understanding of the importance of the gut microbiota in metabolic health continues to grow, it will be increasingly important to consider the impact of all dietary components, including low calorie sweeteners, on gut microbiota and metabolic health. Copyright © 2016 Elsevier Inc. All rights reserved.

Availability and characteristics of betel products in the U.S.

Science.gov (United States)

Blank, Melissa; Deshpande, Laxmikant; Balster, Robert L

2008-09-01

Betel use involves oral placement of shards of areca nut (Areca catechu palm seed containing the cholinergic agonist arecoline) wrapped with slaked lime in a betel leaf (Piper betle plant) or various chopped or powdered products containing areca nut and/or parts of the betel plant. Additives to this mixture include catechu (areca palm extract), spices/ sweeteners (e.g., saccharin, cloves), and/or tobacco. Betel use is most common in Asia and East India; however, little is known about the availability and characteristics of these products outside of this region. Thus, a representative sample of betel products and additives was purchased in the Richmond, Virginia area. Five venues were visited between March and May, 2006. Products successfully purchased were those containing betel alone (seven), betel/tobacco (three), tobacco alone (four), and additives (four). Most betel products listed ingredients on the packaging, though some did not explicitly distinguish between those with versus without tobacco. Importantly, seven of seven betel alone and one of three betel/tobacco products omitted any health-related warnings. All products were inexpensive and relatively obtainable in the groceries visited. More research is warranted in order to accurately estimate product emergence into the U.S. and other world markets, and the consequent impact on public health.

AVAILABILITY AND CHARACTERISTICS OF BETEL PRODUCTS IN THE U.S.†

Science.gov (United States)

Blank, Melissa; Deshpande, Laxmikant; Balster, Robert L.

2009-01-01

Betel use involves oral placement of shards of areca nut (Areca catechu palm seed containing the cholinergic agonist arecoline) wrapped with slaked lime in a betel leaf (Piper betle plant) or various chopped or powdered products containing areca nut and/or parts of the betel plant. Additives to this mixture include catechu (areca palm extract), spices/sweeteners (e.g., saccharin, cloves), and/or tobacco. Betel use is most common in Asia and East India; however, little is known about the availability and characteristics of these products outside of this region. Thus, a representative sample of betel products and additives was purchased in the Richmond, Virginia area. Five venues were visited between March and May, 2006. Products successfully purchased were those containing betel alone (seven), betel/tobacco (three), tobacco alone (four), and additives (four). Most betel products listed ingredients on the packaging, though some did not explicitly distinguish between those with versus without tobacco. Importantly, seven of seven betel alone and one of three betel/tobacco products omitted any health-related warnings. All products were inexpensive and relatively obtainable in the groceries visited. More research is warranted in order to accurately estimate product emergence into the U.S. and other world markets, and the consequent impact on public health. PMID:19004423

[Pathogenetic correction of postoperative inflammation in modern rhinosurgery].

Science.gov (United States)

Kim, I A; Nosulia, E V

2010-01-01

This study included 20 patients presenting with polypous rhinosinusitis examined before and after endoscopic intervention in the nasal cavity and paranasal sinuses. Nitric oxide (NO) content in nasal secretion and polypoid tissue was estimated from the concentration of nitrates that, together with nitrites, are the final products of oxidation of nitric oxide and serve as markers of endogenous NO. Nitrates in the nasal secretion, endonasal mucosa, and polypous tissue were determined by the ionometric technique. Their content was additionally measured in 12 subjects without polypous rhinosinusitis. The nasal secretion and polypous tissue of PRS patients were found to contain nitrates at a higher concentration compared with healthy subjects. Nitrate concentrations in the nasal secretion and polypous tissue of PRS patients were not significantly different. Mean saccharine transport time in the nasal cavity of the patients with an elevated level of nitrates in the nasal secretion was significantly higher than in PRS patients with the lowered nitrate levels. It means that high concentrations of nitric oxide markers in the nasal secretion and polypous tissue of the patients with polypous rhinosinusitis have negative effect on the efficiency of mucociliary transport. In addition, results of the study confirm the possibility of anti-inflammatory therapy with Erespal (fenspirid) for the correction of inflammatory changes during the postoperative period.

Synthesis, Molecular Modelling and Biological Evaluation of Novel Heterodimeric, Multiple Ligands Targeting Cholinesterases and Amyloid Beta

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Michalina Hebda

2016-03-01

Full Text Available Cholinesterases and amyloid beta are one of the major biological targets in the search for a new and efficacious treatment of Alzheimer’s disease. The study describes synthesis and pharmacological evaluation of new compounds designed as dual binding site acetylcholinesterase inhibitors. Among the synthesized compounds, two deserve special attention—compounds 42 and 13. The former is a saccharin derivative and the most potent and selective acetylcholinesterase inhibitor (EeAChE IC50 = 70 nM. Isoindoline-1,3-dione derivative 13 displays balanced inhibitory potency against acetyl- and butyrylcholinesterase (BuChE (EeAChE IC50 = 0.76 μM, EqBuChE IC50 = 0.618 μM, and it inhibits amyloid beta aggregation (35.8% at 10 μM. Kinetic studies show that the developed compounds act as mixed or non-competitive acetylcholinesterase inhibitors. According to molecular modelling studies, they are able to interact with both catalytic and peripheral active sites of the acetylcholinesterase. Their ability to cross the blood-brain barrier (BBB was confirmed in vitro in the parallel artificial membrane permeability BBB assay. These compounds can be used as a solid starting point for further development of novel multifunctional ligands as potential anti-Alzheimer’s agents.

Fate of artificial sweeteners through wastewater treatment plants and water treatment processes

Science.gov (United States)

Li, Shaoli; Ren, Yuhang; Fu, Yingying; Gao, Xingsheng; Jiang, Cong; Wu, Gang; Ren, Hongqiang

2018-01-01

Five full-scale wastewater treatment plants (WWTPs) in China using typical biodegradation processes (SBR, oxidation ditch, A2/O) were selected to assess the removal of four popular artificial sweeteners (ASs). All four ASs (acesulfame (ACE), sucralose (SUC), cyclamate (CYC) and saccharin (SAC)) were detected, ranging from 0.43 to 27.34μg/L in the influent. Higher concentrations of ASs were measured in winter. ACE could be partly removed by 7.11–50.76% through biodegradation and especially through the denitrifying process. The A2/O process was the most efficient at biodegrading ASs. Adsorption (by granular activated carbon (GAC) and magnetic resin) and ultraviolet radiation-based advanced oxidation processes (UV/AOPs) were evaluated to remove ASs in laboratory-scale tests. The amounts of resin adsorbed were 3.33–18.51 times more than those of GAC except for SUC. The adsorption ability of resin decreased in the order of SAC > ACE > CYC > SUC in accordance with the pKa. Degradation of ASs followed pseudo-first-order kinetics in UV/H2O2 and UV/PDS. When applied to the secondary effluent, ASs could be degraded from 30.87 to 99.93% using UV/PDS in 30 minutes and UV/PDS was more efficient and economic. PMID:29293534

Distribution of artificial sweeteners in dust and soil in China and their seasonal variations in the environment of Tianjin.

Science.gov (United States)

Gan, Zhiwei; Sun, Hongwen; Yao, Yiming; Zhao, Yangyang; Li, Yan; Zhang, Yanwei; Hu, Hongwei; Wang, Ruonan

2014-08-01

A nationwide investigation on the occurrence of artificial sweeteners (ASs) was conducted by collecting 98 paired outdoor dust and soil samples from mainland China. The ASs were widely detected in Chinese atmospheric dry deposition and soil samples, at concentrations up to 6450 and 1280 ng/g, respectively. To give a picture on AS distribution and source in the whole environment, the concentrations and seasonal variations of ASs in Tianjin were studied, including atmosphere, soil, and water samples. The AS levels were significantly higher in Haihe river at TJW (a sampling site in central city) in winter, while no obviously seasonal trends were obtained at BYL (close to a AS factory) and the site at a wastewater treatment plant. Saccharin, cyclamate, and acesulfame were the dominant ASs in both gas and particulate phase, with concentrations varying from 0.02 to 1940 pg/m(3). Generally, gas phase concentrations of the ASs were relatively higher in summer, while opposite results were acquired for particulate phase. Wet and dry deposition fluxes were calculated based on the measured AS levels. The results indicated that both wet and dry deposition could efficiently remove ASs in the atmosphere and act as important pollutant sources for the ASs in surface environment. Copyright © 2014 Elsevier B.V. All rights reserved.

Fate of artificial sweeteners through wastewater treatment plants and water treatment processes.

Directory of Open Access Journals (Sweden)

Shaoli Li

Full Text Available Five full-scale wastewater treatment plants (WWTPs in China using typical biodegradation processes (SBR, oxidation ditch, A2/O were selected to assess the removal of four popular artificial sweeteners (ASs. All four ASs (acesulfame (ACE, sucralose (SUC, cyclamate (CYC and saccharin (SAC were detected, ranging from 0.43 to 27.34μg/L in the influent. Higher concentrations of ASs were measured in winter. ACE could be partly removed by 7.11-50.76% through biodegradation and especially through the denitrifying process. The A2/O process was the most efficient at biodegrading ASs. Adsorption (by granular activated carbon (GAC and magnetic resin and ultraviolet radiation-based advanced oxidation processes (UV/AOPs were evaluated to remove ASs in laboratory-scale tests. The amounts of resin adsorbed were 3.33-18.51 times more than those of GAC except for SUC. The adsorption ability of resin decreased in the order of SAC > ACE > CYC > SUC in accordance with the pKa. Degradation of ASs followed pseudo-first-order kinetics in UV/H2O2 and UV/PDS. When applied to the secondary effluent, ASs could be degraded from 30.87 to 99.93% using UV/PDS in 30 minutes and UV/PDS was more efficient and economic.

Radiofrequency Thermal Ablation versus Bipolar Electrocautery for the Treatment of Inferior Turbinate Hypertrophy: Comparison of Efficacy and Postoperative Morbidity

Directory of Open Access Journals (Sweden)

Uluyol, Sinan

2015-04-01

Full Text Available Introduction Numerous surgical methods are used to treat nasal obstruction due to inferior turbinate hypertrophy. The primary goal of the therapy is to maximize the nasal airway for as extended a period of time as possible while minimizing therapeutic complications. Objectives The aim of this study was to assess the effects of radiofrequency thermal ablation (RFTA and bipolar electrocautery (BEC on the removal of nasal obstruction in patients with inferior turbinate hypertrophy and on nasal mucociliary clearance (MCC. Patients in both groups were also evaluated in terms of postoperative morbidity. Methods We compared the outcomes of two groups of patients: those treated with RFTA (n = 23 and those who underwent BEC (n = 20. Nasal obstruction was graded using a visual analog scale (VAS and MCC was measured using a saccharin clearance test. Both measurements were performed before and 2 months after treatment. Results Pre- and postoperative VAS scores showed significant improvement for both groups. However, MCC results did not significantly differ between two groups. Neither edema nor crust formation persisted for more than 1 week in any patients. Conclusion Submucosal cauterization with preservation of the nasal mucosa and periosteum is as effective and safe as RFTA and should be considered when planning inferior turbinate interventions.

Indirect fluorometric detection techniques on thin layer chromatography and effect of ultrasound on gel electrophoresis

Energy Technology Data Exchange (ETDEWEB)

Yinfa, Ma.

1990-12-10

Thin-layer chromatography (TLC) is a broadly applicable separation technique. It offers many advantages over high performance liquid chromatography (HPLC), such as easily adapted for two-dimensional separation, for whole-column'' detection and for handling multiple samples, etc. However, due to its draggy development of detection techniques comparing with HPLC, TLC has not received the attention it deserves. Therefore, exploring new detection techniques is very important to the development of TLC. It is the principal of this dissertation to present a new detection method for TLC -- indirect fluorometric detection method. This detection technique is universal sensitive, nondestructive, and simple. This will be described in detail from Sections 1 through Section 5. Section 1 and 3 describe the indirect fluorometric detection of anions and nonelectrolytes in TLC. In Section 2, a detection method for cations based on fluorescence quenching of ethidium bromide is presented. In Section 4, a simple and interesting TLC experiment is designed, three different fluorescence detection principles are used for the determination of caffeine, saccharin and sodium benzoate in beverages. A laser-based indirect fluorometric detection technique in TLC is developed in Section 5. Section 6 is totally different from Sections 1 through 5. An ultrasonic effect on the separation of DNA fragments in agarose gel electrophoresis is investigated. 262 refs.

Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex.

Science.gov (United States)

Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Lénárd, László; Karádi, Zoltán

2018-02-01

Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX-XXX, 2017.- Special chemosensory cells, the glucose-monitoring (GM) neurons, reportedly involved in the central feeding control, exist in the medial orbitofrontal (ventrolateral prefrontal) cortex (mVLPFC). Electrophysiological, metabolic and behavioral studies reveal complex functional attributes of these cells and raise their homeostatic significance. Single neuron recordings, by means of the multibarreled microelectrophoretic technique, elucidate differential sensitivities of limbic forebrain neurons in the rat and the rhesus monkey to glucose and other chemicals, whereas gustatory stimulations demonstrate their distinct taste responsiveness. Metabolic examinations provide evidence for alteration of blood glucose level in glucose tolerance test and elevation of plasma triglyceride concentration after destruction of the local GM cells by streptozotocin (STZ). In behavioral studies, STZ microinjection into the mVLPFC fails to interfere with the acquisition of saccharin conditioned taste avoidance, does cause, however, taste perception deficit in taste reactivity tests. Multiple functional attributes of GM neurons in the mVLPFC, within the frame of the hierarchically organized central GM neuronal network, appear to play important role in the maintenance of the homeostatic balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

On the issue of higher human sensitivity to carcinogenic substances in early childhood; Zur Frage einer hoeheren Empfindlichkeit von Kindern gegenueber krebserzeugenden Stoffen

Energy Technology Data Exchange (ETDEWEB)

Schneider, K [comp.

1998-09-01

Age-dependent carcinogenesis in humans has been proven with high probability for a number of substances investigated within one or several model systems. Sometimes, very high tumor incidence after short exposure time was observed. Extreme differences were found in some models. (A) Vinyl chloride, Maltoni et al.,1981: 6000 ppm, hepatic angiosarcoma incidence: - Exposure for 4 weeks, from day 1: 40.5 %, - exposure for 4 weeks, from week 13: 0%, - exposure for 52 weeks, from week 13: 22%. Hepatoma incidence: - Exposure for 4 weeks, from day 1: 47.6%, exposure for 4 weeks, from week 13: 0%, exposure for 52 weeks, from week 13: 1.7%. (B) Diethyl nitrosamine, Dyroff et al., 1986: (DEN + phenobarbital), hepatic carcinoma after exposure of rats for 6 weeks: - as from 4 weeks of age: 100% incidence, - as from 8 weeks of age: 0% incidence. (C) Benzopyrene, Vesselinovitch et al., 1975: Hepatic tumor incidence after single, parenteral administration to rats: - at day 1: males: 81%, females: 18%, - at day 42: males: 9%, females: 0%. As is shown by the study on vinyl chloride by Maltoni et al., the same exposure concentration may lead to higher tumor incidence in young animals after short exposure times than it does in long-term experiments with adult animals. Genetic toxicity was detected for all substances, except for saccharin. So it can be assumed that the mechanism of carcinogenesis has an essential influence on the age-dependence. This conclusion agrees well with mechanistic approaches. (orig./CB) [German] Fuer eine Reihe von Schadstoffen ist eine Altersabhaengigkeit der Kanzerogenese mit hoher Wahrscheinlichkeit in einem oder mehreren Modellsystemen gezeigt worden. Dabei wurden zum Teil bereits nach kurzer Expositionszeit sehr hohe Tumorausbeuten erzielt. Extreme Unterschiede wurden in folgenden Modellen beobachtet. (A) Vinylchlorid, Maltoni et al., 1981: 6000 ppm, Inzidenz Leberangiosarkome: - Exposition ueber 4 Wochen ab Tag 1: 40,5%, - Exposition ueber 4 Wochen ab 13

Addition of sucralose enhances the release of satiety hormones in combination with pea protein.

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Geraedts, Maartje C P; Troost, Freddy J; Saris, Wim H M

2012-03-01

Exposing the intestine to proteins or tastants, particularly sweet, affects satiety hormone release. There are indications that each sweetener has different effects on this release, and that combining sweeteners with other nutrients might exert synergistic effects on hormone release. STC-1 cells were incubated with acesulfame-K, aspartame, saccharine, sucralose, sucrose, pea, and pea with each sweetener. After a 2-h incubation period, cholecystokinin(CCK) and glucagon-like peptide 1 (GLP-1) concentrations were measured. Using Ussing chamber technology, the mucosal side of human duodenal biopsies was exposed to sucrose, sucralose, pea, and pea with each sweetener. CCK and GLP-1 levels were measured in basolateral secretions. In STC-1 cells, exposure to aspartame, sucralose, sucrose, pea, and pea with sucralose increased CCK levels, whereas GLP-1 levels increased after addition of all test products. Addition of sucrose and sucralose to human duodenal biopsies did not affect CCK and GLP-1 release; addition of pea stimulated CCK and GLP-1 secretion. Combining pea with sucrose and sucralose induced even higher levels of CCK and GLP-1. Synchronous addition of pea and sucralose to enteroendocrine cells induced higher levels of CCK and GLP-1 than addition of each compound alone. This study shows that combinations of dietary compounds synergize to enhance satiety hormone release. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

T1R3 homomeric sweet taste receptor regulates adipogenesis through Gαs-mediated microtubules disassembly and Rho activation in 3T3-L1 cells.

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Yosuke Masubuchi

Full Text Available We previously reported that 3T3-L1 cells express a functional sweet taste receptor possibly as a T1R3 homomer that is coupled to Gs and negatively regulates adipogenesis by a Gαs-mediated but cAMP-independent mechanism. Here, we show that stimulation of this receptor with sucralose or saccharin induced disassembly of the microtubules in 3T3-L1 preadipocytes, which was attenuated by overexpression of the dominant-negative mutant of Gαs (Gαs-G226A. In contrast, overexpression of the constitutively active mutant of Gαs (Gαs-Q227L as well as treatment with cholera toxin or isoproterenol but not with forskolin caused disassembly of the microtubules. Sweetener-induced microtubule disassembly was accompanied by activation of RhoA and Rho-associated kinase (ROCK. This was attenuated with by knockdown of GEF-H1, a microtubule-localized guanine nucleotide exchange factor for Rho GTPase. Furthermore, overexpression of the dominant-negative mutant of RhoA (RhoA-T19N blocked sweetener-induced dephosphorylation of Akt and repression of PPARγ and C/EBPα in the early phase of adipogenic differentiation. These results suggest that the T1R3 homomeric sweet taste receptor negatively regulates adipogenesis through Gαs-mediated microtubule disassembly and consequent activation of the Rho/ROCK pathway.

Low-/No-Calorie Sweeteners: A Review of Global Intakes

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Danika Martyn

2018-03-01

Full Text Available The current review examined published data on the intake of all major low-/no-calorie sweeteners—aspartame, acesulfame-K, saccharin, sucralose, cyclamate, thaumatin and steviol glycosides—globally over the last decade. The most detailed and complex exposure assessments were conducted in Europe, following a standardized approach. Japan and Korea similarly had up-to-date and regular intake data available. The data for other Asian countries, Latin America, Australia/New Zealand and global estimates, evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA, while available, were shown to be more limited in terms of design. Overall, the studies conducted since 2008 raised no concerns with respect to exceedance of individual sweetener acceptable daily intake (ADIs among the general population globally. The data identified do not suggest a shift in exposure over time, with several studies indicating a reduction in intake. However, some data suggest there may have been an increase in the numbers of consumers of low-/no-calorie-sweetened products. Future research should consider a more standardized approach to allow the monitoring of potential changes in exposure based upon events such as sugar reduction recommendations, to ensure there is no shift in intake, particularly for high-risk individuals, including diabetics and children with specific dietary requirements, and to ensure risk management decisions are based on quality intake analyses.

The facilitative effects of glucose ingestion on memory retrieval in younger and older adults: is task difficulty or task domain critical?

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Riby, Leigh M; McMurtrie, Hazel; Smallwood, Jonathan; Ballantyne, Carrie; Meikle, Andrew; Smith, Emily

2006-02-01

The ingestion of a glucose-containing drink has been shown to improve cognitive performance, particularly memory functioning. However, it remains unclear as to the extent to which task domain and task difficulty moderate the glucose enhancement effect. The aim of this research was to determine whether boosts in performance are restricted to particular classes of memory (episodic v. semantic) or to tasks of considerable cognitive load. A repeated measures (25 g glucose v. saccharin), counterbalanced, double-blind design was used with younger and older adults. Participants performed a battery of episodic (e.g. paired associate learning) and semantic memory (e.g. category verification) tasks under low and high cognitive load. Electrophysiological measures (heart rate and galvanic skin response) of arousal and mental effort were also gathered. The results indicated that whilst glucose appeared to aid episodic remembering, cognitive load did not exaggerate the facilitative effect. For semantic memory, there was little evidence to suggest that glucose can boost semantic memory retrieval even when the load was manipulated. One exception was that glucose facilitated performance during the difficult category fluency task. Regardless, the present findings are consistent with the domain-specific account in which glucose acts primarily on the hippocampal region, which is known to support episodic memory. The possible contribution of the hippocampus in semantic memory processing is also discussed.

Antiglycating potential of acesulfame potassium: an artificial sweetener.

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Ali, Ahmad; More, Tejashree Anil; Hoonjan, Amaritpal Kaur; Sivakami, Subramanian

2017-10-01

Sweeteners have replaced the natural sugars in the food and beverage industry because of many reasons, such as hyperglycemia and cost. Saccharin, sucralose, aspartame and acesulfame-K are the most commonly used sweeteners. In the present study, the abovementioned artificial sweeteners were used to assess their glycating properties by established methods such as browning, fructosamine assay, determination of carbonyl content, protein aggregation, and measurement of fluorescence. Amadori and advanced glycation end products (AGEs) are formed as a result of the interaction between carbonyl groups of reducing sugars and amino groups of proteins and other macromolecules during glycation. The objective of this study was to investigate the influence of artificial sweeteners on the formation of AGEs and protein oxidation in an in vitro model of glucose-mediated protein glycation. The results indicated that the abovementioned artificial sweeteners do not enhance the process of glycation. On the other hand, acesulfame-K was found to have antiglycating potential as it caused decreased formation of Amadori products and AGEs. Further studies are essential in the characterization of Amadori products and AGEs produced as a result of interaction between sweeteners and proteins, which are interfered with by sweeteners. This study is significant in understanding the probable role of artificial sweeteners in the process of glycation and the subsequent effect on macromolecular alteration.

A history of diabetes insipidus: paving the road to internal water balance.

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Eknoyan, Garabed

2010-12-01

Diabetes insipidus is an ancient disease considered under the rubric of diabetes, the Greek descriptive term for polyuria, which was unrecognized even after the sweetness of urine was reported as a characteristic of diabetes mellitus in the 17th century. It would be another century before diabetes insipidus was identified from the insipid rather than saccharine taste of urine in cases of polyuria. After its increased recognition, pathologic observations and experimental studies connected diabetes insipidus to the pituitary gland in the opening decades of the 20th century. Simultaneously, posterior pituitary lobe extracts were shown to be vasoconstrictive (vasopressin) and antidiuretic (antidiuretic hormone). As vasopressin was purified and synthesized and its assay became available, it was shown to be released in response to both osmotic and volume stimuli that are integrated in the hypothalamus, and vasopressin thereby was essential to maintaining internal water balance. The antidiuretic properties of vasopressin to treat the rare cases of diabetes insipidus were of limited clinical utility until its vasoconstrictive effects were resuscitated in the 1970s, with the consequent increasing wider use of vasopressin for the treatment of compromised hemodynamic states. In addition, the discovery of antidiuretic hormone receptor blockers has led to their increasing use in managing hypo-osmolar states. Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Reversal of dopamine system dysfunction in response to high-fat diet.

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Carlin, Jesselea; Hill-Smith, Tiffany E; Lucki, Irwin; Reyes, Teresa M

2013-12-01

To test whether high-fat diet (HFD) decreases dopaminergic tone in reward regions of the brain and evaluate whether these changes reverse after removal of the HFD. Male and female mice were fed a 60% HFD for 12 weeks. An additional group was evaluated 4 weeks after removal of the HFD. These groups were compared with control fed, age-matched controls. Sucrose and saccharin preference was measured along with mRNA expression of dopamine (DA)-related genes by Real Time-quantitative PCR (RT-qPCR). DA and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured using high-performance liquid chromatography. DNA methylation of the dopamine transporter (DAT) promoter was measured by methylated DNA immunoprecipitation and RT-qPCR. After chronic HFD, sucrose preference was reduced, and then normalized after removal of the HFD. Decreased expression of DA genes, decreased DA content and alterations in DAT promoter methylation, was observed. Importantly, response to HFD and the persistence of changes depended on sex and brain region. These data identify diminished DA tone after early-life chronic HFD with a complex pattern of reversal and persistence that varies by both sex and brain region. Central nervous system changes that did not reverse after HFD withdrawal may contribute to the difficulty in maintaining weight-loss after diet intervention. Copyright © 2013 The Obesity Society.

Fructose- and glucose-conditioned preferences in FVB mice: strain differences in post-oral sugar appetition

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Zukerman, Steven; Ackroff, Karen

2014-01-01

Recent studies indicate that, unlike glucose, fructose has little or no post-oral preference conditioning actions in C57BL/6J (B6) mice. The present study determined whether this is also the case for FVB mice, which overconsume fructose relative to B6 mice. In experiment 1, FVB mice strongly preferred a noncaloric 0.1% sucralose + 0.1% saccharin (S+S) solution to 8% fructose in a 2-day choice test but switched their preference to fructose after separate experience with the two sweeteners. Other FVB mice displayed a stronger preference for 8% glucose over S+S. In a second experiment, ad libitum-fed FVB mice trained 24 h/day acquired a significant preference for a flavor (CS+) paired with intragastric (IG) self-infusions of 16% fructose over a different flavor (CS−) paired with IG water infusions. IG fructose infusions also conditioned flavor preferences in food-restricted FVB mice trained 1 h/day. IG infusions of 16% glucose conditioned stronger preferences in FVB mice trained 24- or 1 h/day. Thus, fructose has post-oral flavor conditioning effects in FVB mice, but these effects are less pronounced than those produced by glucose. Further studies of the differential post-oral conditioning effects of fructose and glucose in B6 and FVB mice should enhance our understanding of the physiological processes involved in sugar reward. PMID:25320345

Theophylline cocrystals prepared by spray drying: physicochemical properties and aerosolization performance.

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Alhalaweh, Amjad; Kaialy, Waseem; Buckton, Graham; Gill, Hardyal; Nokhodchi, Ali; Velaga, Sitaram P

2013-03-01

The purpose of this work was to characterize theophylline (THF) cocrystals prepared by spray drying in terms of the physicochemical properties and inhalation performance when aerosolized from a dry powder inhaler. Cocrystals of theophylline with urea (THF-URE), saccharin (THF-SAC) and nicotinamide (THF-NIC) were prepared by spray drying. Milled THF and THF-SAC cocrystals were also used for comparison. The physical purity, particle size, particle morphology and surface energy of the materials were determined. The in vitro aerosol performance of the spray-dried cocrystals, drug-alone and a drug-carrier aerosol, was assessed. The spray-dried particles had different size distributions, morphologies and surface energies. The milled samples had higher surface energy than those prepared by spray drying. Good agreement was observed between multi-stage liquid impinger and next-generation impactor in terms of assessing spray-dried THF particles. The fine particle fractions of both formulations were similar for THF, but drug-alone formulations outperformed drug-carrier formulations for the THF cocrystals. The aerosolization performance of different THF cocrystals was within the following rank order as obtained from both drug-alone and drug-carrier formulations: THF-NIC>THF-URE>THF-SAC. It was proposed that micromeritic properties dominate over particle surface energy in terms of determining the aerosol performance of THF cocrystals. Spray drying could be a potential technique for preparing cocrystals with modified physical properties.

Pontine and Thalamic Influences on Fluid Rewards: III. Anticipatory Contrast for Sucrose and Corn Oil

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Liang, Nu-Chu; Norgren, Ralph; Grigson, Patricia S

2011-01-01

An anticipatory contrast effect (ACE) occurs when, across daily trials, an animal comes to respond less than normally to a first stimulus when it is followed shortly by a second, more preferred solution. Classically, ACE is studied using a low (L) concentration of saccharin or sucrose, followed by access to a higher (H) concentration of sucrose. Subjects in the control condition have two bouts of access to the weaker solution presented on the same schedule. The ACE is measured by the difference in intake of the first bout low solution between subjects in the low-low (L-L) vs. the low-high (L-H) conditions. Here we used this paradigm with sham feeding rats and determined that nutritional feedback was unnecessary for the development of ACE with two concentrations of sucrose or with two concentrations of corn oil. Next we showed that ibotenic acid lesions centered in the orosensory thalamus spared ACEs for both sucrose and corn oil. In contrast, lesions of the pontine parabrachial nuclei (PBN), the second central relay for taste in the rat, disrupted ACEs for both sucrose and corn oil. Although the sensory modalities needed for the oral detection of fats remain controversial, it appears that the PBN is involved in processing the comparison of disparate concentrations of sucrose and oil reward. PMID:21703289

Sex differences in the effects of ethanol pre-exposure during adolescence on ethanol-induced conditioned taste aversion in adult rats.

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Sherrill, Luke K; Berthold, Claire; Koss, Wendy A; Juraska, Janice M; Gulley, Joshua M

2011-11-20

Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol's aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0g/kg ethanol in a binge-like pattern during postnatal days (PD) 35-45. In adulthood (>PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females. Copyright © 2011 Elsevier B.V. All rights reserved.

The ontogeny of ethanol aversion.

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Saalfield, Jessica; Spear, Linda

2016-03-15

Recent work has suggested separate developmental periods within the broader framework of adolescence, with data suggesting distinct alterations and vulnerabilities within these intervals. While previous research has suggested reduced sensitivity to the aversive effects of alcohol in adolescence relative to adults, a more detailed ontogeny of this effect has yet to be conducted. The adolescent brain undergoes significant transitions throughout adolescence, including in regions linked with drug reward and aversion. The current study aimed to determine the ontogeny of ethanol aversion by utilizing a conditioned taste aversion procedure at six different ages to test the hypothesis that the transitions into, through, and out of adolescence are associated with ontogenetic alterations in sensitivity to the aversive properties of ethanol. Non-deprived animals given Boost® as the conditioned stimulus (CS) were used in Experiment 1, whereas Experiment 2 used water-restricted animals provided with a saccharin/sucrose solution as the CS. In both experiments, an attenuated sensitivity to the aversive properties of ethanol was evident in adolescents compared to adults, although more age differences were apparent in water deprived animals than when a highly palatable CS was given to ad libitum animals. Overall, the data suggest an attenuated sensitivity to the aversive properties of ethanol that is most pronounced during pre- and early adolescence, declining thereafter to reach the enhanced aversive sensitivity of adults. Copyright © 2016 Elsevier Inc. All rights reserved.

Targeting the subthalamic nucleus in a preclinical model of alcohol use disorder.

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Pelloux, Yann; Baunez, Christelle

2017-07-01

The subthalamic nucleus (STN) has only recently been considered to have a role in reward processing. In rats, inactivation of the STN by lesion or high-frequency stimulation (HFS) decreases motivation for cocaine but increases motivation for sucrose. For ethanol, the effect of STN lesion depends on the individual's baseline intake; decreasing motivation for ethanol in rats with lower ethanol intake, while increasing motivation for ethanol in rats with higher-but still limited-ethanol intake. However, the involvement of the STN in behaviour more closely resembling some aspects of alcohol use disorder has not been assessed. This study aimed to determine the effect of STN lesions on the escalation of ethanol intake, subsequent increases in the motivation to "work" for ethanol and the choice of ethanol over a non-drug alternative. We found that STN lesion prevented increases in ethanol intake observed during intermittent ethanol access and after a long period of ethanol privation. STN lesion also decreased the motivation to work for ethanol after escalated intake. Surprisingly, STN lesion increased the choice of alcohol over saccharin. This was associated with a blunting of the hedonic responses to the taste of the reinforcement alternatives. These results evidence the involvement of the STN in different ethanol-motivated behaviours and therefore position the STN as an interesting target for the treatment of alcohol use disorders.

Adsorptive Removal of Artificial Sweeteners from Water Using Metal-Organic Frameworks Functionalized with Urea or Melamine.

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Seo, Pill Won; Khan, Nazmul Abedin; Hasan, Zubair; Jhung, Sung Hwa

2016-11-02

A highly porous metal-organic framework (MOF), MIL-101, was modified to introduce urea or melamine via grafting on open metal sites of the MOF. Adsorptive removal of three artificial sweeteners (ASWs) was studied using the MOFs, with or without modifications (including nitration), and activated carbon (AC). The adsorbed quantities (based on the weight of the adsorbent) of saccharin (SAC) under various conditions decreased in the order urea-MIL-101 > melamine-MIL-101 > MIL-101 > AC > O 2 N-MIL-101; however, the quantities based on unit surface area are in the order melamine-MIL-101 > urea-MIL-101 > MIL-101 > O 2 N-MIL-101. Similar ASWs [acesulfame (ACE) and cyclamate (CYC)] showed the same tendency. The mechanism for very favorable adsorption of SAC, ACE, and CYC over urea- and melamine-MIL-101 could be explained by H-bonding on the basis of the contents of -NH 2 groups on the MOFs and the adsorption results under a wide range of pH values. Moreover, the direction of H-bonding could be clearly defined (H acceptor: ASWs; H donor: MOFs). Urea-MIL-101 and melamine-MIL-101 could be suggested as competitive adsorbents for organic contaminants (such as ASWs) with electronegative atoms, considering their high adsorption capacity (for example, urea-MIL-101 had 2.3 times the SAC adsorption of AC) and ready regeneration.

Mechanistic Basis of Cocrystal Dissolution Advantage.

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Cao, Fengjuan; Amidon, Gordon L; Rodríguez-Hornedo, Naír; Amidon, Gregory E

2018-01-01

Current interest in cocrystal development resides in the advantages that the cocrystal may have in solubility and dissolution compared with the parent drug. This work provides a mechanistic analysis and comparison of the dissolution behavior of carbamazepine (CBZ) and its 2 cocrystals, carbamazepine-saccharin (CBZ-SAC) and carbamazepine-salicylic acid (CBZ-SLC) under the influence of pH and micellar solubilization. A simple mathematical equation is derived based on the mass transport analyses to describe the dissolution advantage of cocrystals. The dissolution advantage is the ratio of the cocrystal flux to drug flux and is defined as the solubility advantage (cocrystal to drug solubility ratio) times the diffusivity advantage (cocrystal to drug diffusivity ratio). In this work, the effective diffusivity of CBZ in the presence of surfactant was determined to be different and less than those of the cocrystals. The higher effective diffusivity of drug from the dissolved cocrystals, the diffusivity advantage, can impart a dissolution advantage to cocrystals with lower solubility than the parent drug while still maintaining thermodynamic stability. Dissolution conditions where cocrystals can display both thermodynamic stability and a dissolution advantage can be obtained from the mass transport models, and this information is useful for both cocrystal selection and formulation development. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Botanical and Protein Sweeteners

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D.A. Agboola

2014-10-01

Full Text Available Plant species with unusual taste properties such as bitterness, sourness or sweetness and others with a taste- modifying components; have long been known to man, although their exploitation has been limited. Exponential growth in the number of patients suffering from diseases caused by the consumption of sugar has become a threat to mankind's health. Artificial low calorie sweeteners available in the market may have severe side effects. It takes time to figure out the long term side effects and by the time these are established, they are replaced by a new low calorie sweetener. Saccharine has been used for centuries to sweeten foods and beverages without calories or carbohydrate. It was also used on a large scale during the sugar shortage of the two world wars but was abandoned as soon as it was linked with the development of bladder cancer. Naturally occurring sweet and taste modifying proteins (Thaumatin, Curculin, Miraculin, Brazzein, Pentadin, Monellin, Mabinlin present in  plants such as Thaumatococcus daniellii (Marantaceae, Curculigo latifolia (Hypoxidaceae, Synsepalum dulcificum (Sapotaceae, Pentadiplandra brazzeana (Pentadiplandraceae, Dioscoreophyllum cumminsii (Menispermaceae, Capparis masaikai (Capparaceae are being seen as potential replacements for the currently available artificial low calorie sweeteners. Most protein sweetener plants such as S. dulcificum, P. brazzeana, C. masaikai, are shrubs; C. latifolia, T. danielli, are perennial herbs while D. Cumminsii is an annual liana.

A search for markers of sugarcane evolution

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M. Bacci Jr.

2001-12-01

Full Text Available To determine the phylogenetic relationship between sugarcane cultivars and other members of the Saccharinae subtribe, we identified the fast evolving ITS1-5.8S-ITS2 (ITS = internal transcribed spacer; 5.8S = 5.8S ribosomal DNA region of the sugarcane genome in the Sugarcane Expressed Sequence Tag (SUCEST genome project database. Parsimony analysis utilizing this region and homologs belonging to the 23 closely related Andropogoneae currently deposited in the GenBank database has shown sugarcane as the sister group of Saccharum sinense. However, because there are few parsimony-informative characters and high homoplasy in the ITS1-5.8S-ITS2 region we were not able to determine with confidence the phylogenetic relationship between sugarcane and some of the remaining members of Saccharine subtribe. To find alternatives for the phylogenetic reconstruction of sugarcane evolutionary history, we selected 17 markers (nuclear, chloroplastic or mitochondrial from the SUCEST database of which apha-tubulin, ribosomal protein L16 (rpl16 and DNA-directed RNA polymerase beta chain (rpoC2 were found to have a low incidence of polymorphism and comparable, or even faster, rates of evolution than the ITS1-5.8S-ITS2 region. We suggest that these markers should be considered as preferential choices for phylogenetic studies of Saccharinae subtribe.Com o propósito de determinar a relação filogenética entre a cana-de-açúcar e membros da subtribo Saccharinae, a região gênica nuclear ITS1-5,8S-ITS2 (ITS: espaçador interno transcrito; 5,8S: DNA ribossomal 5.8S, com alta taxa evolutiva, foi identificada no banco de dados do projeto genoma "Sugarcane Expressed Sequence Tag" (SUCEST. Uma análise através do método de parcimônia, utilizando esta região e seqüências homólogas de 23 Andropogoneae retiradas da base de dados GenBank, indicou que a cana-de-açúcar é o grupo-irmão de Saccharum sinense. No entanto, devido à pequena quantidade de caracteres

O uso de adoçantes na gravidez: uma análise dos produtos disponíveis no Brasil The use of sweeteners in pregnancy: an analysis of products available in Brazil

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Maria Regina Torloni

2007-05-01

Full Text Available Os adoçantes são freqüentemente utilizados por mulheres em idade reprodutiva. Esta é uma revisão narrativa da literatura a respeito dos adoçantes atualmente comercializados no mercado brasileiro. Existem poucas informações sobre o uso da sacarina e ciclamato na gestação, e seus efeitos sobre o feto. Devido às limitadas informações disponíveis e ao seu potencial carcinogênico em animais, a sacarina e o ciclamato devem ser evitados durante a gestação (risco C. O aspartame tem sido extensivamente estudado em animais, sendo considerado seguro para uso na gestação (risco B, exceto para mulheres homozigóticas para fenilcetonúria (risco C. A sucralose e o acessulfame-K não são tóxicos, carcinogênico ou mutagênicos em animais, mas não existem estudos controlados em humanos. Porém, como esses dois adoçantes não são metabolizados, parece improvável que seu uso durante a gestação possa ser prejudicial (risco B. A estévia, substância derivada de uma planta nativa brasileira, não produz efeitos adversos sobre a gestação em animais, porém não existem estudos em humanos (risco B. Os agentes de corpo usados na formulação dos adoçantes (manitol, sorbitol, xilitol, eritrol, lactilol, isomalte, maltilol, lactose, frutose, maltodextrina, dextrina e açúcar invertido são substâncias consideradas seguras para o consumo humano. Concluindo, segundo as evidências atualmente disponíveis, o aspartame, a sucralose, o acessulfame e a estévia podem ser utilizados com segurança durante a gestação.Sweeteners are frequently used by women of reproductive age. This is a narrative review about the sweeteners currently sold in the Brazilian commerce. There is a few information on the use of saccharin and cyclamates in pregnancy and their effects on the fetus. Due to the limited information available and their carcinogenic potential in animal species, saccharin and cyclamates should be avoided during pregnancy (risk C. Aspartame

A rentabilidade da beterraba sacarina vs a agro-pecuária nos Açores The profitability of the saccharine beetroot vs dairy farming in the Azores

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Luísa Calado

2008-01-01

Full Text Available Nos Açores a produção de beterraba sacarina com fim industrial é exclusiva da ilha de S. Miguel onde, ao longo do último século, tem ocupado áreas com altitude até 300 metros e declives inferiores a 7%. A área variou entre 3000 hectares na década de sessenta e 200 hectares actualmente. A produtividade é variável situando-se entre as 20 e as 90 toneladas por hectare. Nos Açores a SINAGA é responsável pela transformação e distribuição dos produtos da beterraba. Com base num modelo de programação linear que estima o comportamento dos agricultores dos Açores foi possível concluir que o preço da beterraba influencia a quantidade de beterraba produzida, enquanto o preço do leite tem uma influência reduzida; que o maior efeito no aumento de produção é conseguido com o aumento de área mobilizável para a cultura o que só é possível com a redefinição do apoio técnico ao maneio da cultura.In the Azores the production of sugar beet for industrial uses is exclusive of the island of S. Miguel where along the last century it has occupied areas up to 300 meters and slopes inferior to 7 %. The used area varied between 3000 hectares in the sixties and 200 hectares at present. The productivity is variable being situated between 20 and 90 tons per hectare. In the Azores the SINAGA is responsible for the transformation and distribution of the products of the sugar beet. Using a linear programming model to explain the behaviour of farmers in the Azores it was possible to conclude that the price of sugar beet influences the quantity produced of beetroot while the price of the milk has a reduced influence; and that the biggest effect in the increase of production is got by the increase of cultivable area and with technical support.

Artificial sweeteners and mixture of food additives cause to break oral tolerance and induce food allergy in murine oral tolerance model for food allergy.

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Yamashita, H; Matsuhara, H; Miotani, S; Sako, Y; Matsui, T; Tanaka, H; Inagaki, N

2017-09-01

Processed foods are part of daily life. Almost all processed foods contain food additives such as sweeteners, preservatives and colourants. From childhood, it is difficult to avoid consuming food additives. It is thought that oral tolerance for food antigens is acquired during early life. If tolerance fails, adverse immune responses to food proteins may occur. We hypothesized that food additives prevent acquisition of oral tolerance and aimed to verify the safety of food additives. We induced experimental oral tolerance in mice for ovalbumin (OVA), a food antigen, by previous oral treatment with OVA before sensitization with OVA injections. Food additives were administered at the induction of oral tolerance, and food allergy was induced by repeated administration of OVA. Symptoms of food allergy were defined as a change in body temperature and allergic diarrhoea. Saccharin sodium and a mixture of food additives inhibited acquisition of oral tolerance. Hypothermia and allergic diarrhoea with elevation of OVA-specific IgE were induced in the murine model of oral tolerance. Analyses of antigen-presenting cells in mesenteric lymph nodes showed that food additives affected their manner of migration. Additionally, food additives decreased the proportion of CD25 hi regulatory T cells among CD4 + T cells in the mesenteric lymph nodes. A large amount of food additives may prevent acquisition of oral tolerance. Intake of food additives in early life may increase the risk of food allergies. © 2017 John Wiley & Sons Ltd.

Analysis of nine food additives in red wine by ion-suppression reversed-phase high-performance liquid chromatography using trifluoroacetic acid and ammonium acetate as ion-suppressors.

Science.gov (United States)

Zhao, Yong-Gang; Chen, Xiao-Hong; Yao, Shan-Shan; Pan, Sheng-Dong; Li, Xiao-Ping; Jin, Mi-Cong

2012-01-01

A reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for the simultaneous determination of nine food additives, i.e., acesulfame, saccharin, caffeine, aspartame, benzoic acid, sorbic acid, stevioside, dehydroacetic acid and neotame in red wine. The effects of ion-suppressors, i.e., trifluoroacetic acid (TFA) and ammonium acetate (AmAc) on retention behavior of nine food additives in RP-HPLC separation were discussed in detail. The relationships between retention factors of solutes and volume percent of ion-suppressors in the mobile-phase systems of acetonitrile-TFA aqueous solution and acetonitrile-TFA-AmAc aqueous solution were quantitatively established, respectively. The results showed that the ion suppressors had not only an ion suppression effect, but also an organic modification effect on the acidic analytes. The baseline separation of nine food additives was completed by a gradient elution with acetonitrile-TFA(0.01%, v/v)-AmAc(2.5 mmol L(-1)) aqueous solution as the mobile phase. The recoveries were between 80.2 - 99.5% for all analytes with RSDs in the range of 1.5 - 8.9%. The linearities were in the range of 0.2 - 100.0 mg L(-1) with determination coefficients (r(2)) higher than 0.9991 for all analytes. The limits of quantification (LOQs) were between 0.53 - 0.99 mg L(-1). The applicability of the proposed method to detect and quantify food additives has been demonstrated in the analysis of 30 real samples.

Investigation of mechanical properties and operative deformation mechanism in nano-crystalline Ni–Co/SiC electrodeposits

International Nuclear Information System (INIS)

Lari Baghal, S.M.; Amadeh, A.; Heydarzadeh Sohi, M.

2012-01-01

Highlights: ► The tensile properties of Ni–Co and Ni–Co/SiC deposits were investigated. ► The SiC particles enhanced tensile strength and ductility of nano-structured composites. ► The deformation mechanism at low and high strain rates were studied. - Abstract: Ni–Co/SiC nano-composites were prepared via electrodeposition from a modified Watts bath containing SiC particles with average particle size of 50 nm, SDS as surfactant and saccharin as grain refiner in appropriate amounts. The effect of nano-particle incorporation on microstructure, mechanical properties and deformation mechanism of electrodeposits were investigated. The mechanical properties of electrodeposits were investigated by Vickers microhardness and tensile tests. The results indicated that incorporation of SiC particles into a 15 nm Ni–Co matrix had no considerable effect on its microhardness and yield strength, that is, dispersion hardening did not operate in this range of grain size. However it was observed that co-deposition of uniform distributed SiC particles can significantly improve the ultimate tensile strength and elongation to failure of the deposits. Calculation of apparent activation volume from tensile test results at different strain rates proved that incorporation of SiC nano-particles are responsible for stress-assisted activation of GB atoms mechanism that can significantly increase the plasticity. Nano-crystalline Ni–Co matrix showed a mixed mod behavior of ductile and brittle fracture whereas incorporation of SiC particles and increasing the strain rate promoted ductile fracture mode.

Relationship between vomiting and taste aversion learning in the ferret: studies with ionizing radiation, lithium chloride, and amphetamine.

Science.gov (United States)

Rabin, B M; Hunt, W A

1992-09-01

The relationship between emesis and taste aversion learning was studied in ferrets (Mustela putorius furo) following exposure to ionizing radiation (50-200 cGy) or injection of lithium chloride (1.5-3.0 mEq/kg, ip). When 10% sucrose or 0.1% saccharin was used as the conditioned stimulus, neither unconditioned stimulus produced a taste aversion, even when vomiting was produced by the stimulus (Experiments 1 and 2). When a canned cat food was used as the conditioned stimulus, lithium chloride, but not ionizing radiation, produced a taste aversion (Experiment 3). Lithium chloride was effective in producing a conditioned taste aversion when administration of the toxin was delayed by up to 90 min following the ingestion of the canned cat food, indicating that the ferrets are capable of showing long-delay learning (Experiment 4). Experiment 5 examined the capacity of amphetamine, which is a qualitatively different stimulus than lithium chloride or ionizing radiation, to produce taste aversion learning in rats and cats as well as in ferrets. Injection of amphetamine (3 mg/kg, ip) produced a taste aversion in rats and cats but not in ferrets which required a higher dose (> 5 mg/kg). The results of these experiments are interpreted as indicating that, at least for the ferret, there is no necessary relationship between toxin-induced illness and the acquisition of a CTA and that gastrointestinal distress is not a sufficient condition for CTA learning.

Biodegradation and detoxification of chlorimuron-ethyl by Enterobacter ludwigii sp. CE-1.

Science.gov (United States)

Pan, Xiong; Wang, Saige; Shi, Nan; Fang, Hua; Yu, Yunlong

2018-04-15

The application of the herbicide chlorimuron-ethyl has a lasting toxic effect on some succession crops. Here, a bacterium capable of utilizing chlorimuron-ethyl as the sole source of nitrogen was isolated from the contaminated soil and was identified as Enterobacter ludwigii sp. CE-1, and its detoxification and degradation of the herbicide were then examined. The biodegradation of chlorimuron-ethyl by the isolate CE-1 was significantly accelerated with increasing concentration (1-10mg/l) and temperature (20-40°C). The optimal pH for the degradation of chlorimuron-ethyl by the isolate CE-1 was pH 7.0. A pathway for the biodegradation of chlorimuron-ethyl by the isolate CE-1 was proposed, in which it could be first converted into 2-amino-4-chloro-6-methoxypyrimidine and an intermediate product by the cleavage of the sulfonylurea bridge and then transformed into saccharin via hydrolysis and amidation. The plant height and fresh weight of corn that had been incubated in nutrient solution containing 0.2mg/l of chlorimuron-ethyl significantly recovered to 83.9% and 83.1% compared with those in the uninoculated control, although the root growth inhibition of chlorimuron-ethyl could not be alleviated after inoculation for 14 d. The results indicate that the isolate CE-1 is a promising bacterial resource for the biodegradation and detoxification of chlorimuron-ethyl. Copyright © 2017 Elsevier Inc. All rights reserved.

Safe taste memory consolidation is disrupted by a protein synthesis inhibitor in the nucleus accumbens shell.

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Pedroza-Llinás, R; Ramírez-Lugo, L; Guzmán-Ramos, K; Zavala-Vega, S; Bermúdez-Rattoni, F

2009-07-01

Consolidation is the process by which a new memory is stabilized over time, and is dependent on de novo protein synthesis. A useful model for studying memory formation is gustatory memory, a type of memory in which a novel taste may become either safe by not being followed by negative consequences (attenuation of neophobia, AN), or aversive by being followed by post-digestive malaise (conditioned taste aversion, CTA). Here we evaluated the effects of the administration of a protein synthesis inhibitor in the nucleus accumbens (NAc) shell for either safe or aversive taste memory trace consolidation. To test the effects on CTA and AN of protein synthesis inhibition, anisomycin (100microg/microl) was bilaterally infused into the NAc shell of Wistar rats' brains. We found that post-trial protein synthesis blockade impaired the long-term safe taste memory. However, protein synthesis inhibition failed to disrupt the long-term memory of CTA. In addition, we infused anisomycin in the NAc shell after the pre-exposure to saccharin in a latent inhibition of aversive taste. We found that the protein synthesis inhibition impaired the consolidation of safe taste memory, allowing the aversive taste memory to form and consolidate. Our results suggest that protein synthesis is required in the NAc shell for consolidation of safe but not aversive taste memories, supporting the notion that consolidation of taste memory is processed in several brain regions in parallel, and implying that inhibitory interactions between both taste memory traces do occur.

Hydrophilic interaction liquid chromatography coupled to high-resolution mass spectrometry to determine artificial sweeteners in environmental waters.

Science.gov (United States)

Salas, Daniela; Borrull, Francesc; Fontanals, Núria; Marcé, Rosa Maria

2015-06-01

Artificial sweeteners are food additives employed as sugar substitutes which are now considered to be emerging organic contaminants. In the present study, a method is developed for the determination of a group of artificial sweeteners in environmental waters. Considering the polar and hydrophilic character of these compounds, hydrophilic interaction liquid chromatography is proposed for their separation as an alternative to traditional reversed-phase liquid chromatography. Two stationary phases with different chemistry were compared for this purpose. For the detection of the analytes, high-resolution mass spectrometry (Orbitrap) was employed to take advantage of its benefits in terms of reliable quantification and confirmation for the measurement of accurate masses. Solid-phase extraction was chosen as the sample treatment, in which the extract in a mixture of NH4OH:MeOH:ACN (1:4:15) was directly injected into the chromatographic system, simplifying the analytical procedure. The optimized method was validated on river and waste water samples. For example, in the case of effluent water samples, limits of detection ranged from 0.002 to 0.7 μg/L and limits of quantification ranged from 0.004 to 1.5 μg/L. Apparent (whole method) recoveries ranged from 57 to 74% with intra-day precision (%RSD, n = 5) ranging from 6 to 25%. The method was successfully applied to water samples from different rivers in Catalonia and different waste water treatment plants in Tarragona. Acesulfame, cyclamate, saccharine and sucralose were found in several samples.

Effect of cobalt content on wear and corrosion behaviors of electrodeposited Ni-Co/WC nano-composite coatings.

Science.gov (United States)

Amadeh, A; Ebadpour, R

2013-02-01

Metal-ceramic composite coatings are widely used in automotive and aerospace industries as well as micro-electronic systems. Electrodeposition is an economic method for application of these coatings. In this research, nickel-cobalt coatings reinforced by nano WC particles were applied on carbon steel substrate by pulse electrodeposition from modified Watts bath containing different amounts of cobalt sulphate as an additive. Saccharin and sodium dodecyl sulphate (SDS) were also added to electroplating bath as grain refiner and surfactant, respectively. The effect of cobalt content on wear and corrosion behavior of the coatings was investigated. Wear and corrosion properties were assessed by pin-on-disk and potentiodynamic polarization methods, respectively. Phase analysis was performed by X-ray diffraction (XRD) using CuK(alpha) radiation and the worn surfaces were studied by means of Scanning Electron Microscopy (SEM). The results showed that the addition of cobalt improved the wear resistance of the coatings. In the presence of 18 g/L cobalt in electrodeposition bath, the wear rate of the coating decreased to 0.002 mg/m and the coefficient of friction reduced to 0.695 while they were 0.004 mg/m and 0.77 in the absence of cobalt, respectively. This improvement in wear properties can be attributed to the formation of hcp phase in metallic matrix. Meanwhile, the corrosion resistance of the coatings slightly reduced because cobalt is more active metal with respect to nickel.

Further studies on the genetic damage to bone marrow and other somatic effects following exposure to low level tritium

International Nuclear Information System (INIS)

Carsten, A.L.; Benz, R.D.; Commerford, S.L.; Hughes, W.; Ichimasa, Y.; Ikushima, T.; Tezuka, H.

1984-01-01

This paper emphasizes results obtained over the last 3 years, supplementing information presented at the first 3 H workshop. Sister chromtid exchange (SCE) measurements on mice maintained on 3.0 μCi/ml of tritiated water (HTO) or receiving an equal depth dose 137 Cs gamma exposure for 52 weeks have been completed. Small but significantly higher numbers of SCEs were found in animals receiving gamma exposures or maintained on HTO than in their controls. In animals removed from the HTO regimen after 27 weeks, the number of SCEs decreases with time, but did not return to control levels within the first 30 weeks. Comparative studies with the 137 Cs exposures indicate an RBE not significantly different than 1.0. Mice were also maintained on 7.5, 15.0 and 30.0 μCi/ml HTO for SCE studies. Results similar to those described for 3.0 μCi/ml were found. Maintaining animals on a 0.15% saccharin solution is the most effective of those tested for increasing the animals' water intake and for enhancing excretion of 3 H. The rate of disappearance of 3 H from animals maintained chronically on HTO indicated a two phase 3 H disappearance curve from hemoglobin. Single injections of HTO showed a brief delay in incorporation of 3 H followed by a disappearance paralleling the slower phase of the chronic exposure curve, and indicating a RBC lifetime of approximately 40 days. 21 references, 7 figures, 1 table

Probabilistic modelling of human exposure to intense sweeteners in Italian teenagers: validation and sensitivity analysis of a probabilistic model including indicators of market share and brand loyalty.

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Arcella, D; Soggiu, M E; Leclercq, C

2003-10-01

For the assessment of exposure to food-borne chemicals, the most commonly used methods in the European Union follow a deterministic approach based on conservative assumptions. Over the past few years, to get a more realistic view of exposure to food chemicals, risk managers are getting more interested in the probabilistic approach. Within the EU-funded 'Monte Carlo' project, a stochastic model of exposure to chemical substances from the diet and a computer software program were developed. The aim of this paper was to validate the model with respect to the intake of saccharin from table-top sweeteners and cyclamate from soft drinks by Italian teenagers with the use of the software and to evaluate the impact of the inclusion/exclusion of indicators on market share and brand loyalty through a sensitivity analysis. Data on food consumption and the concentration of sweeteners were collected. A food frequency questionnaire aimed at identifying females who were high consumers of sugar-free soft drinks and/or of table top sweeteners was filled in by 3982 teenagers living in the District of Rome. Moreover, 362 subjects participated in a detailed food survey by recording, at brand level, all foods and beverages ingested over 12 days. Producers were asked to provide the intense sweeteners' concentration of sugar-free products. Results showed that consumer behaviour with respect to brands has an impact on exposure assessments. Only probabilistic models that took into account indicators of market share and brand loyalty met the validation criteria.

Rats' learned preferences for flavors encountered early or late in a meal paired with the postingestive effects of glucose.

Science.gov (United States)

Myers, Kevin P; Whitney, Margaret C

2011-03-28

Rats learn to prefer flavors that are followed by postingestive effects of nutrients. This experiment investigated whether the timing of a flavor (specifically, in the first or second half of the meal) influences learning about that flavor. Stronger learning about earlier or later flavors would indicate when the rewarding postingestive effects of nutrients are sensed. Rats with intragastric (IG) catheters drank saccharin-sweetened, calorically-dilute solutions with distinct flavors added, accompanied by IG infusion of glucose (+sessions) or water (-sessions). In both types of sessions, an "Early" flavor was provided for the first 8 min and a "Late" flavor for the last 8 min. Thus, rats were trained with Early(+) and Late(+) in high-calorie meals, and Early(-) and Late(-) in low-calorie meals. Strength of the learned preference for Early(+) and Late(+) was then assessed in a series of two-bottle choice tests between Early(+) vs. Early(-), Late(+) vs. Late(-), Early(+) vs. Late(+), and Early(-) vs. Late(-). Rats preferred both Early(+) and Late(+) over the respective (-) flavors. But Early(+) was only preferred when rats were tested hungry. Late(+) was preferred when rats were tested hungry or recently satiated. This indicates qualitatively different associations learned about flavors at different points in the meal. While not supporting the idea that postingestive effects become most strongly associated with later-occurring ("dessert") flavors, it does suggest a reason dessert flavors may remain attractive in the absence of hunger. Copyright © 2010 Elsevier Inc. All rights reserved.

Suitability of pharmaceuticals and personal care products (PPCPs) and artificial sweeteners (ASs) as wastewater indicators in the Pearl River Delta, South China.

Science.gov (United States)

Yang, Yuan-Yuan; Liu, Wang-Rong; Liu, You-Sheng; Zhao, Jian-Liang; Zhang, Qian-Qian; Zhang, Min; Zhang, Jin-Na; Jiang, Yu-Xia; Zhang, Li-Juan; Ying, Guang-Guo

2017-07-15

Wastewater indicator is a useful tool for evaluating the wastewater impact on natural water, but there is little information about the suitability of wastewater indicators for different regions. This study aimed to select suitable wastewater indicators in the Pearl River Delta region, south China by screening a range of wastewater related organic compounds. The screening campaign was carried out by investigating the occurrence and removal efficiencies of 93 pharmaceuticals and personal care products (PPCPs) and 5 artificial sweeteners (ASs) in nine wastewater treatment plants (WWTPs) located in the region, and the occurrence of these target compounds in the contaminated and clean surface water of the Pearl River. An ideal wastewater indicator should be hydrophilic, source-specific for domestic wastewater, ubiquitous in contaminated surface water with detection frequency (DF) >80% and absent in background water samples. For liable indicators, high removal rates (>90%) should be observed in WWTPs and they should be detected in all the influent samples at concentrations fifty times higher than their limits of quantification. For conservative indicators, low removal rates (<50%) should be observed in WWTPs and they should be detected in all the effluent samples at concentrations fifty times higher than their limits of quantification. Based on the above criteria, sucralose and fluconazole were selected as conservative indicators in the region, while cyclamate, saccharin, methyl paraben, ethyl paraben, propyl paraben, paracetamol, salicylic acid and caffeine were selected as liable indicators. Copyright © 2017 Elsevier B.V. All rights reserved.

The efficacy of (+)-Naltrexone on alcohol preference and seeking behaviour is dependent on light-cycle.

Science.gov (United States)

Jacobsen, Jonathan Henry W; Buisman-Pijlman, Femke T A; Mustafa, Sanam; Rice, Kenner C; Hutchinson, Mark R

2018-01-01

Circadian rhythm affects drug-induced reward behaviour and the innate immune system. Peaks in reward-associated behaviour and immune responses typically occur during the active (dark) phase of rodents. While the role of the immune system, specifically, Toll-like receptor 4 (TLR4, an innate immune receptor) in drug-induced reward is becoming increasingly appreciated, it is unclear whether its effects vary according to light-cycle. Therefore, the aim of this study was to characterise the effects of the phase of the light-cycle and the state of the innate immune system on alcohol reward behaviour and subsequently determine whether the efficacy of targeting the immune component of drug reward depends upon the light-cycle. This study demonstrates that mice exhibit greater alcohol-induced conditioned place preference and alcohol two-bottle choice preference during the dark cycle. This effect overlapped with elevations in reward-, thirst- and immune-related genes. Administration of (+)-Naltrexone, a TLR4 antagonist, reduced immune-related gene mRNA expression and alcohol preference with its effects most pronounced during the dark cycle. However, (+)-Naltrexone, like other TLR4 antagonists exhibited off-target side effects, with a significant reduction in overall saccharin intake - an effect likely attributable to a reduction in tyrosine hydroxylase (Th) mRNA expression levels. Collectively, the study highlights a link between a time-of-day dependent influence of TLR4 on natural and alcohol reward-like behaviour in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Drugs and taste aversion

International Nuclear Information System (INIS)

Rondeau, D.B.; Jolicoeur, F.B.; Merkel, A.D.; Wayner, M.J.

1981-01-01

The literature on the effects of drugs on the acquisition and the magnitude of taste aversion is reviewed and discussed. Then, the results of a series of experiments on the effects of phenobarbital and related drugs on taste aversion are reported. A standard taste aversion model was used in all experiments; test drugs were injected prior to drinking in a one bottle situation on the first test day following the taste aversion treatment. Phenobarbital in doses ranging from 20 to 80 mg/kg significantly attenuated taste aversion induced by lithium chloride (LiCl) and x-radiation, the maximal effect occurred with the 60 mg/kg dose. The attenuating effect was found to be dependent upon the magnitude of the aversion to the sapid solution. Phenobarbital completely abolished aversion produced by 0.375 mEq LiCl while the attenuation effect decreased linearly with higher doses of LiCl. Results also indicate that phenobarbital's attenuating effect cannot be solely attributed to its dipsogenic characteristic or to its state dependent learning effect. Attenuation of LiCl aversion to a saccharin solution was also observed following single doses of amobarbital, 30 mg/kg, pentobarbital, 15 mg/kg, and chloropromazine, 0.75 mg/kg. Taste aversion was not affected by other doses of those drugs or by hexobarbital, barbital, and chlordiazepoxide. Phenobarbital's attenuating effect on taste aversion is discussed in relation to other known behavioral and neurophysiological effects of the drug

Phenobarbital increases monkey in vivo nicotine disposition and induces liver and brain CYP2B6 protein

Science.gov (United States)

Lee, Anna M; Miksys, Sharon; Tyndale, Rachel F

2006-01-01

CYP2B6 is a drug-metabolizing enzyme expressed in the liver and brain that can metabolize bupropion (Zyban®, a smoking cessation drug), activate tobacco-smoke nitrosamines, and inactivate nicotine. Hepatic CYP2B6 is induced by phenobarbital and induction may affect in vivo nicotine disposition, while brain CYP2B6 induction may affect local levels of centrally acting substrates. We investigated the effect of chronic phenobarbital treatment on induction of in vivo nicotine disposition and CYP2B6 expression in the liver and brain of African Green (Vervet) monkeys. Monkeys were split into two groups (n=6 each) and given oral saccharin daily for 22 days; one group was supplemented with 20 mg kg−1 phenobarbital. Monkeys were given a 0.1 mg kg−1 nicotine dose subcutaneously before and after treatment. Phenobarbital treatment resulted in a significant, 56%, decrease (P=0.04) in the maximum nicotine plasma concentration and a 46% decrease (P=0.003) in the area under the concentration–time curve. Phenobarbital also increased hepatic CYP2B6 protein expression. In monkey brain, significant induction (Pphenobarbital treatment in monkeys resulted in increased in vivo nicotine disposition, and induced hepatic and brain CYP2B6 protein levels and cellular expression. This induction may alter the metabolism of CYP2B6 substrates including peripherally acting drugs such as cyclophosphamide and centrally acting drugs such as bupropion, ecstasy and phencyclidine. PMID:16751792

Purification and inhibition studies with anions and sulfonamides of an α-carbonic anhydrase from the Antarctic seal Leptonychotes weddellii.

Science.gov (United States)

Cincinelli, Alessandra; Martellini, Tania; Innocenti, Alessio; Scozzafava, Andrea; Supuran, Claudiu T

2011-03-15

A high activity α-carbonic anhydrase (CA, EC 4.2.1.1) has been purified from various tissues of the Antarctic seal Leptonychotes weddellii. The new enzyme, denominated lwCA, has a catalytic activity for the physiologic CO(2) hydration to bicarbonate reaction, similar to that of the high activity human isoform hCA II, with a k(cat) of 1.1×10(6) s(-1), and a k(cat)/K(m) of 1.4×10(8) M(-1) s(-1). The enzyme was highly inhibited by cyanate, thiocyanate, cyanide, bicarbonate, carbonate, as well as sulfamide, sulfamate, phenylboronic/phenylarsonic acids (K(I)s in the range of 46-100 μM). Many clinically used sulfonamides, such as acetazolamide, methazolamide, dorzolamide, brinzolamide and benzolamide were low nanomolar inhibitors, with K(I)s in the range of 5.7-67 nM. Dichlorophenamide, zonisamide, saccharin and hydrochlorothiazide were weaker inhibitors, with K(I)s in the range of 513-5390 nM. The inhibition profile with anions and sulfonamides of the seal enzyme was rather different from those of the human isoforms hCA I and II. The high sensitivity to bicarbonate inhibition of lwCA, unlike that of the human enzymes, may reflect an evolutionary adaptation to the deep water, high CO(2) partial pressure and hypoxic conditions in which Weddell seals spend much of their life. Copyright © 2011 Elsevier Ltd. All rights reserved.

A series of silver(I) coordination polymers with saccarinate and flexible aliphatic diamines

Energy Technology Data Exchange (ETDEWEB)

Yeşilel, Okan Zafer, E-mail: yesilel@ogu.edu.tr [Department of Chemistry, Faculty of Arts and Sciences, Eskişehir Osmangazi University, 26480 Eskişehir (Turkey); Karamahmut, Bingül [Department of Chemistry, Faculty of Arts and Sciences, Eskişehir Osmangazi University, 26480 Eskişehir (Turkey); Semerci, Fatih [Department of Energy Systems Engineering, Faculty of Technology, Kırklareli University, 39000 Kırklareli (Turkey); Darcan, Cihan [Department of Molecular Biology and Genetic, Faculty of Arts and Sciences, Bilecik Şeyh Edebali University, Gülümbe-Bilecik (Turkey); Yılmaz, Filiz [Department of Chemistry, Faculty of Sciences, Anadolu University, Eskişehir (Turkey)

2017-05-15

A series of Ag(I) complexes with aliphatic diamines having a different chain length (NH{sub 2}-(CH{sub 2}){sub n}-NH{sub 2}, n=4–9), with the formulas, [Ag(μ-sac)(μ-db){sub 0.5}]{sub n} (1), ([Ag{sub 4}(sac){sub 4}(μ-dp){sub 2}]·4H{sub 2}O){sub n} (2){sub ,} ([Ag{sub 2}(sac){sub 2}(μ-dz)]·2H{sub 2}O){sub n} (3), ([Ag{sub 2}(sac){sub 2}(μ-dh)]·H{sub 2}O){sub n} (4), ([Ag{sub 2}(sac){sub 2}(μ-do)]·H{sub 2}O){sub n} (5a), [Ag{sub 2}(sac){sub 2}(μ-do){sub 2}] (5b) and [Ag{sub 4}(sac){sub 4}(μ-dn){sub 2}]·2H{sub 2}O (6), where sac=saccharinate, db=1,4-diaminobutane, dp=1,5-diaminopentane, dz=1,6-diaminohexane, dh=1,7-diaminoheptane, do=1,8-diaminooctane and dn=1,9-diaminononane, were synthesized and characterized by elemental analysis, infrared spectra and single-crystal X-ray diffraction analysis. In 1, the sac ligand bridges adjacent Ag(I) ions through the nitrogen and carbonyl oxygen atoms to form eight-membered bimetallic rings with the Ag···Ag distance being 3.897 Å, which are linked by db ligands to give a 1D zigzag chain. The complexes 2–5a consist of a one-dimensional (1D) linear cationic chains and discrete mononuclear anions. The discreet complex units are further connected by ligand unsupported argentophilic interactions. In 6, the dn ligands bridge adjacent silver centers to form 24-membered macrometallacyclic rings, which are further connected to the anionic [Ag(sac){sub 2}]{sup -} units by argentophilic Ag1···Ag2 interactions to form a tetranuclear structure. The adjacent dinuclear units are further linked together through ligand-unsupported argentophilic Ag···Ag (3.207(1) Å) interactions, generating a one-dimensional linear chain. The most striking feature of complexes is the presence of the rare intermolecular C-H···Ag interactions. In 5b, the do ligand bridges two Ag(I) ions to form a dinuclear with a 22-membered macrometallacyclic ring. Furthermore, biological activities, luminescence properties and thermal analysis (TG

[Influences of ion-suppressors on retention behaviors of nine food additives in reversed-phase high performance liquid chromatographic separation].

Science.gov (United States)

Zhao, Yonggang; Chen, Xiaohong; Li, Xiaoping; Yao, Shanshan; Jin, Micong

2011-10-01

The influences of ion-suppressors on retention behaviors of nine food additives, i.e., acesulfame, saccharin, caffeine, aspartame, benzoic acid, sorbic acid, stevioside, dehydroacetic acid and neotame in reversed-phase high performance liquid chromatographic (RP-HPLC) separation were investigated. The organic modification effects of acids, i. e. , trifluoroacetic acid (TFA) and buffer salts, i. e. , TFA-ammonium acetate (AmAc) were studied emphatically. The relationships between retention factors of solutes and volume percentages of ion-suppressors in the mobile phase systems of acetonitrile-TFA aqueous solution and acetonitrile-TFA-AmAc aqueous solution were quantitatively established, separately. The separation of nine food additives was completed by a gradient elution with acetonitrile-TFA (0.01%, v/v)-AmAc (2. 5 mmol/L) aqueous solution as the mobile phases. An RP-HPLC method was established for the simultaneous determination of nine food additives in red wine. In the range of 10. 0 - 100. 0 mg/L, nine food additives showed good linearity with the correlation coefficients ( r2 ) larger than 0. 999 1. The limits of detection (LODs) were in the range of 0. 33 - 2. 36 mg/L and the limits of quantification (LOQs) were in the range of 1. 11 - 7. 80 mg/L. The spiked recoveries were between 87. 61% and 108. 4% with the relative standard deviations (RSDs) of 2. 2% -9. 4%. These results are of referential significance for the rapid establishment and accu- rate optimization of RP-HPLC separation for the simultaneous determination of food additives in other foods.

Neuropsychiatric Phenotypes Produced by GABA Reduction in Mouse Cortex and Hippocampus.

Science.gov (United States)

Kolata, Stefan M; Nakao, Kazuhito; Jeevakumar, Vivek; Farmer-Alroth, Emily L; Fujita, Yuko; Bartley, Aundrea F; Jiang, Sunny Zhihong; Rompala, Gregory R; Sorge, Robert E; Jimenez, Dennisse V; Martinowich, Keri; Mateo, Yolanda; Hashimoto, Kenji; Dobrunz, Lynn E; Nakazawa, Kazu

2018-05-01

Whereas cortical GAD67 reduction and subsequent GABA level decrease are consistently observed in schizophrenia and depression, it remains unclear how these GABAergic abnormalities contribute to specific symptoms. We modeled cortical GAD67 reduction in mice, in which the Gad1 gene is genetically ablated from ~50% of cortical and hippocampal interneurons. Mutant mice showed a reduction of tissue GABA in the hippocampus and cortex including mPFC, and exhibited a cluster of effort-based behavior deficits including decreased home-cage wheel running and increased immobility in both tail suspension and forced swim tests. Since saccharine preference, progressive ratio responding to food, and learned helplessness task were normal, such avolition-like behavior could not be explained by anhedonia or behavioral despair. In line with the prevailing view that dopamine in anterior cingulate cortex (ACC) plays a role in evaluating effort cost for engaging in actions, we found that tail-suspension triggered dopamine release in ACC of controls, which was severely attenuated in the mutant mice. Conversely, ACC dopamine release by progressive ratio responding to reward, during which animals were allowed to effortlessly perform the nose-poking, was not affected in mutants. These results suggest that cortical GABA reduction preferentially impairs the effort-based behavior which requires much effort with little benefit, through a deficit of ACC dopamine release triggered by high-effort cost behavior, but not by reward-seeking behavior. Collectively, a subset of negative symptoms with a reduced willingness to expend costly effort, often observed in patients with schizophrenia and depression, may be attributed to cortical GABA level reduction.

Physiological and subjective responses to low relative humidity.

Science.gov (United States)

Sunwoo, Yujin; Chou, Chinmei; Takeshita, Junko; Murakami, Motoko; Tochihara, Yutaka

2006-01-01

In order to investigate the influence of low relative humidity, we measured saccharin clearance time (SCT), frequency of blinking, heart rate (HR), blood pressure, hydration state of skin, transepidermal water loss (TEWL), recovery sebum level and skin temperature as physiological responses. We asked subjects to judge thermal, dryness and comfort sensations as subjective responses using a rating scale. Sixteen non-smoking healthy male students were selected. The pre-room conditions were maintained at an air temperature (Ta) of 25 degrees C and a relative humidity (RH) of 50%. The test room conditions were adjusted to provide a Ta of 25 degrees C and RH levels of 10%, 30% and 50%.RH had no effect on the activity of the sebaceous gland and on cardiovascular reactions like blood pressure and HR. However, it was obvious that low RH affects SCT, the dryness of the ocular mucosa and the stratum corneum of the skin and causes a decrease in mean skin temperature. Under 30% RH, the eyes and skin become dry, and under 10% RH the nasal mucous membrane becomes dry as well as the eyes and skin, and the mean skin temperature decreases. These findings suggested that to avoid dryness of the eyes and skin, it is necessary to maintain an RH greater than 30%, and to avoid dryness of the nasal mucous membrane, it is necessary to maintain an RH greater than 10%. Subjects felt cold immediately after a change in RH while they had only a slight perception of dryness at the change of humidity.

The influence of synthetic food additives and surfactants on the body weight of larvae of Tenebrio molitor (Coleoptera, Tenebrionidae

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V. O. Martynov

2017-08-01

Full Text Available The broad spectrum of negative effects of food additives and surfactants on living organisms and the environment in general indicate a necessity of a detailed study on this issue. The aim of this article is to evaluate the impact of food additives and surfactants in a concentration of 350 mg/kg of fodder on the body weight of third age Tenebrio molitor Linnaeus, 1758 (Coleoptera, Tenebrionidae larvae. A significant change in the body weight of T. molitor larvae was observed when they consumed a diet containing 350 mg/kg of sodium glutamate, sodium cyclamate and sodium benzoate. We observed a tendency towards increase in body weight after addition of the food colouring Allura Red, saccharin, benzoic acid, betaine, emulsifying wax, AOS and SLES, and also we observed a decrease in body weight after addition of Tartrazine and Indigo Carmine in the same concentration. Out of the 18 tested food additives, 3 significantly stimulated an increase in the body weight of third age T. molitor larvae, and 3 manifested the same effect at the level of tendency (stimulated an increase in mass on average by 43–58% over the 14-day experiment, and 2 caused decrease in the body weight of larvae. Also, the 4 studied surfactants manifested a tendency towards increase in the body weight of T. molitor. This study on the impact of food additives and surfactants on organisms of insects is of great significance for protecting rare species of insects.

Vibrational spectroscopic investigation of polymorphs and cocrystals of indomethacin.

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Ali, Hassan Refat H; Alhalaweh, Amjad; Velaga, Sitaram P

2013-05-01

Identification of optimal solid form of an active pharmaceutical ingredient and form control are very important in drug development. Thus, the structural information of these forms and in-depth insight on the modes of molecular interactions are necessary, and vibrational spectroscopic methods are well suited for this purpose. In-depth structural analysis of different solid forms of indomethacin (IND) using Raman and infrared (IR) spectroscopy is the objective. We have investigated the modes of molecular interactions in polymorphs (α and γ), amorphous and discovered cocrystals of IND with nicotinamide (NIC) and trans-cinnamic acid (CIN) coformers. The solid forms of IND have been prepared; their purity has been verified by differential scanning calorimetry and powder X-ray diffractometry and then studied in the solid-state by Raman and IR spectroscopy. The modes of the interactions were closely investigated from the vibrational data. The key vibrational features of IND solid forms have been specified. The IR (C=O) band at 1713 cm(-1) attributed to cyclic acid dimer of γ IND has disappeared in IND-NIC/CIN whilst retained in IND-SAC cocrystal. IND cocrystallizes in different conformations and crystal lattices with different coformers. The cyclic acid dimer of IND has been kept on its cocrystallization with saccharin and it could have been broken with NIC and CIN. The complementary nature of Raman and IR spectroscopy allowed unambiguous investigation of the chemical composition of pharmaceutical materials which is of particular importance in the absence of detailed structural information, as in the case of IND-NIC and IND-CIN.

Selective reward deficit in mice lacking beta-endorphin and enkephalin.

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Hayward, Michael D; Pintar, John E; Low, Malcolm J

2002-09-15

It has been impossible to unequivocally identify which endogenous opioids modulate the incentive value of rewarding stimuli because these peptides are not highly selective for any single opioid receptor subtype. Here, we present evidence based on the measurement of instrumental behavior of beta-endorphin and enkephalin knock-out mice that both opioid peptides play a positive role. A progressive ratio schedule was used to measure how hard an animal would work for food reinforcers. The loss of either opioid reduced responding under this schedule, regardless of the palatability of the three different formulas of reinforcers used. The phenotype of mice lacking both endogenous opioids was nearly identical to the phenotype of mice mutant for either individual opioid. Responses were tested in nondeprived and deprived feeding states but were reduced in beta-endorphin- and enkephalin-deficient mice only when they were maintained under nondeprived conditions. Other operant manipulations ruled out variables that might contribute nonspecifically to this result such as differences in acquisition, early satiation, motor performance deficit, and reduced resistance to extinction. In contrast to the effects on instrumental performance, the loss of either or both endogenous opioids did not influence preference for water flavored with sucrose or saccharin in a two-bottle free-choice drinking paradigm. We conclude that both beta-endorphin and enkephalin positively contribute to the incentive-motivation to acquire food reinforcers. Because the attenuation of operant responding was observed only during a nondeprived motivational state, the hedonics of feeding are likely altered rather than energy homeostasis.

Goal- and signal-directed incentive: conditioned approach, seeking, and consumption established with unsweetened alcohol in rats.

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Krank, Marvin D; O'Neill, Susan; Squarey, Kyna; Jacob, Jackie

2008-02-01

Many theories of addictive behavior propose that cues signaling drug administration influence the likelihood of drug-taking and drug-seeking behavior. We investigated the behavioral impact of cues associated with unsweetened ethanol and their interaction with responding maintained by ethanol self-administration. Our goal was to establish the influence of such cues on ethanol seeking. The experiment used a matching contingency and saccharin-fading procedure to establish equal levels of responding to two spatially distinct levers using unsweetened 10% ethanol solution. After ethanol self-administration was established, a brief cue light located alternately over each lever location was either paired or unpaired (control) with the opportunity to consume the same ethanol solution. Finally, self-administration was re-established, and the effect of the cue was measured in a transfer design. The reaction to lights paired with the opportunity to ingest unsweetened ethanol had three main effects: (1) induction of operant behavior reinforced by ethanol, (2) stimulation of ethanol-seeking behavior (drinker entries), and (3) cue-directed approach and contact behavior (i.e. autoshaping or sign-tracking). Cue-directed behavior to the light interacted with choice behavior in a manner predicted by the location of the cue light, enhancing responding only when the approach response did not interfere with the operant response. These findings replicate and extend the effects of Pavlovian conditioning on ethanol-seeking and support-conditioned incentive theories of addictive behavior. Signals for ethanol influence spatial choice behavior and may be relevant to attentional bias shown to alcohol-associated stimuli in humans.

Viral-mediated knockdown of mGluR7 in the nucleus accumbens mediates excessive alcohol drinking and increased ethanol-elicited conditioned place preference in rats.

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Bahi, Amine

2013-10-01

Whether metabotropic glutamate 7 (mGluR7) -activation enhances or diminishes the reinforcing properties of psychostimulants remains unclear. We have previously shown that systemic mGluR7 activation reduced alcohol consumption and preference as well as locomotor-stimulating and rewarding properties of ethanol. In this study, we further examined the contribution of mGluR7 on the effect of ethanol within the nucleus accumbens (NAcc), a neural target for many drugs of abuse. Using short hairpin RNA (shRNA)-expressing lentiviral vectors (LV) to alter locally the activity of mGluR7 in male rats, we have shown that blocking mGluR7 expression increased ethanol consumption and preference in a two-bottle choice drinking paradigm with no effect either on saccharin or on quinine used for taste discrimination. In addition, mGluR7 knockdown increases preference for environments previously paired with low doses of ethanol in the conditioned place preference (CPP) test, as it shifted the dose-response curve for ethanol CPP to the left, indicating alterations in the rewarding effects of alcohol. More importantly, mGluR7 blockade in the dorsal striatum (DS) neither affected ethanol consumption nor ethanol-elicited CPP. These results show that levels of mGluR7 in the NAcc regulate responsiveness to alcohol. Taken together, these findings clearly demonstrate that mGluR7 signaling within the NAcc is a key modulator of functional responses to ethanol and offer an important target for regulating the addictive effects of alcohol.

Perinatal testosterone contributes to mid-to-post pubertal sex differences in risk for binge eating in male and female rats.

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Culbert, Kristen M; Sinclair, Elaine B; Hildebrandt, Britny A; Klump, Kelly L; Sisk, Cheryl L

2018-02-01

Exposure to testosterone early in life may contribute to sex differences and pubertal changes in risk for eating pathology (i.e., females > males, after pubertal onset). Specifically, perinatal testosterone permanently alters brain structure/function and drives the masculinization of several sex-differentiated behaviors. However, the effects of perinatal testosterone are often not evident until puberty when increases in gonadal hormones activate the expression of sex typical behavior, including eating behaviors (e.g., chow intake; saccharin preference) in rodents. Despite perinatal testosterone's masculinizing effects on general feeding behavior, it remains unknown if perinatal testosterone exposure contributes to sex differences in pathological eating. The current study addressed this gap by examining whether perinatal testosterone exposure decreases risk for binge eating proneness after pubertal onset in male and female rats. Sprague-Dawley rats (n = 40 oil-treated control females; n = 39 testosterone-treated females; n = 40 oil-treated control males) were followed longitudinally across pre-to-early puberty, mid-to-late puberty, and adulthood. The binge eating prone (BEP)/binge eating resistant (BER) rodent model was used to identify individual differences in binge eating proneness across the dimensional spectrum. As expected, testosterone-treated females and control males showed masculinized (i.e., lower) risk for binge eating as compared to control females, but only after midpuberty. These animal data are significant in suggesting that perinatal testosterone exposure may protect against binge eating and underlie sex differences in binge eating prevalence during and after puberty. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation

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Hermsen, Sanne A.B., E-mail: Sanne.Hermsen@rivm.nl [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands); Pronk, Tessa E. [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht (Netherlands); Brandhof, Evert-Jan van den [Centre for Environmental Quality, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Ven, Leo T.M. van der [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Piersma, Aldert H. [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands)

2013-10-01

The zebrafish embryotoxicity test is a promising alternative assay for developmental toxicity. Classically, morphological assessment of the embryos is applied to evaluate the effects of compound exposure. However, by applying differential gene expression analysis the sensitivity and predictability of the test may be increased. For defining gene expression signatures of developmental toxicity, we explored the possibility of using gene expression signatures of compound exposures based on commonly expressed individual genes as well as based on regulated gene pathways. Four developmental toxic compounds were tested in concentration-response design, caffeine, carbamazepine, retinoic acid and valproic acid, and two non-embryotoxic compounds, D-mannitol and saccharin, were included. With transcriptomic analyses we were able to identify commonly expressed genes, which were mostly development related, after exposure to the embryotoxicants. We also identified gene pathways regulated by the embryotoxicants, suggestive of their modes of action. Furthermore, whereas pathways may be regulated by all compounds, individual gene expression within these pathways can differ for each compound. Overall, the present study suggests that the use of individual gene expression signatures as well as pathway regulation may be useful starting points for defining gene biomarkers for predicting embryotoxicity. - Highlights: • The zebrafish embryotoxicity test in combination with transcriptomics was used. • We explored two approaches of defining gene biomarkers for developmental toxicity. • Four compounds in concentration-response design were tested. • We identified commonly expressed individual genes as well as regulated gene pathways. • Both approaches seem suitable starting points for defining gene biomarkers.

Comparison of the responses of the chorda tympani and glossopharyngeal nerves to taste stimuli in C57BL/6J mice

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Hellekant Göran

2003-03-01

Full Text Available Abstract Background Recent progress in discernment of molecular pathways of taste transduction underscores the need for comprehensive phenotypic information for the understanding of the influence of genetic factors in taste. To obtain information that can be used as a base line for assessment of effects of genetic manipulations in mice taste, we have recorded the whole-nerve integrated responses to a wide array of taste stimuli in the chorda tympani (CT and glossopharyngeal (NG nerves, the two major taste nerves from the tongue. Results In C57BL/6J mice the responses in the two nerves were not the same. In general sweeteners gave larger responses in the CT than in the NG, while responses to bitter taste in the NG were larger. Thus the CT responses to cyanosuosan, fructose, NC00174, D-phenylalanline and sucrose at all concentrations were significantly larger than in the NG, whereas for acesulfame-K, L-proline, saccharin and SC45647 the differences were not significant. Among bitter compounds amiloride, atropine, cycloheximide, denatonium benzoate, L-phenylalanine, 6-n-propyl-2-thiouracil (PROP and tetraethyl ammonium chloride (TEA gave larger responses in the NG, while the responses to brucine, chloroquine, quinacrine, quinine hydrochloride (QHCl, sparteine and strychnine, known to be very bitter to humans, were not significantly larger in the NG than in the CT. Conclusion These data provide a comprehensive survey and comparison of the taste sensitivity of the normal C57BL/6J mouse against which the effects of manipulations of its gustatory system can be better assessed.

Evaluation of early changes induced by diuron in the rat urinary bladder using different processing methods for scanning electron microscopy

International Nuclear Information System (INIS)

Fava, Rafaela Marono; Ferragut Cardoso, Ana Paula; Sanches da Rocha, Mitscheli; Nascimento e Pontes, Merielen Garcia; Viana de Camargo, João Lauro; Cotrim Sartor de Oliveira, Maria Luiza

2015-01-01

Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a substituted urea herbicide carcinogenic to the rat urinary bladder at high dietary levels. The suggested non-genotoxic mode of action (MOA) of diuron encompasses cytotoxicity and necrosis followed by regenerative hyperplasia. Prenecrotic swollen cells as observed under scanning electron microscopy (SEM) have been reported as early morphological alterations, putatively related to diuron cytotoxicity. However, these changes were not observed in a previous SEM study conducted in this laboratory. This study evaluated whether these early alterations are actually due to diuron cytotoxicity or artifacts related to different processing methods used for SEM analysis. Male Wistar rats were fed ad libitum with basal diet, 7.1% sodium saccharin (NaS) or 2.500 ppm diuron for seven days or 15 weeks. The urinary bladders were processed for histological and labeling indices examinations and for SEM using two different processing methods. The incidence of simple hyperplasia after 15 weeks of exposure to diuron or to NaS was significantly increased. By SEM, the incidences and severity of lesions were significantly increased in the diuron group independently of exposure time. The different SEM processing methods used allowed for visualization of swollen superficial cells after seven days of diuron exposure. Probably the absence these cells in a previous study was due to the use very few animals. Our results support the hypothesis that the swollen cell is an early key event due to diuron-induced cytotoxicity and is the result of a degenerative process involved in the non-genotoxic carcinogenic mode of action of high doses of diuron

High-speed jet electrodeposition and microstructure of nanocrystalline Ni-Co alloys

International Nuclear Information System (INIS)

Qiao Guiying; Jing Tianfu; Wang Nan; Gao Yuwei; Zhao Xin; Zhou Jifeng; Wang Wei

2005-01-01

The jet electrodeposition from watts baths with a device of electrolyte jet was carried out to prepare nano-crystalline cobalt-nickel alloys. The influence of the concentration of Co 2+ ions in the electrolyte and electrolysis parameters, such as the cathodic current density, the temperature as well as the electrolyte jet speed, on the chemistry and microstructure of Ni-Co-deposit alloys were investigated. Experimental results indicated that increasing the Co 2+ ions concentration in the bath, the electrolyte jet speed and decreasing of the cathodic current density and decrease of the electrolyte temperature all results in an increase of cobalt content in the alloy. Detailed microstructure changes upon the changes of alloy composition and experimental conditions were characterized using X-ray diffraction (XRD) and transmission electron microscopy (TEM). XRD results show the Ni-Co solid solution was formed through the jet electrodeposition. Phase constitution of solid solution changes progressively under different electrolyte concentration. Alloys with low Co concentration exhibit single phase of face-centered cubic (fcc) structure; The Co concentration over 60.39 wt.%, the alloys are composed of face-centered cubic (fcc) phase and hexagonal close-packed (hcp) phase. Furthermore, the formation of the nanostructured Ni-Co alloy deposit is investigated. Increasing the Co 2+ ions concentration in the bath, the cathodic current density, the electrolyte temperature and the electrolyte jet speed all result in the finer grains in the deposits. Additives such as saccharin in the electrolyte also favor the formation of the finer grains in the alloy deposits

A survey on trace organic chemicals in a German water protection area and the proposal of relevant indicators for anthropogenic influences.

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Seitz, Wolfram; Winzenbacher, Rudi

2017-06-01

A comprehensive monitoring programme of trace organic chemicals (TOrC) was conducted for a German water protection area in karstic ground. The aim of this survey was to detect the potential anthropogenic influences of point sources such as wastewater treatment plants and diffuse pollution such as runoff water from roads on the raw water used for drinking water treatment. The programme comprised seven sampling campaigns within 2 years each with up to 20 sampling sites. In total, the programme included 84 anthropogenic compounds from pharmaceuticals, iodinated X-ray contrast media, sweeteners, industrial chemicals (benzotriazoles, melamines and benzothiazoles) and pesticide metabolites. Cyclamate occurred with the highest median concentration of 44 μg l -1 in untreated wastewater and acesulfame occurred with a concentration of 20 μg l -1 in treated wastewater. In runoff water from roads, the most relevant compounds were tolyltriazole with 2.3 μg l -1 and the desphenyl-chloridazon with 1.2 μg l -1 . In the stream waters, the highest median concentrations were found for melamine and acesulfame both at 0.61 μg l -1 . High elimination during conventional wastewater treatment was observed for 5 out of 49 compounds. These are acetyl-sulfamethoxazole, aciclovir, cyclamate, ibuprofen and saccharin. Based on the survey results, we propose a set of nine compounds to be used as indicators for wastewater, untreated wastewater and runoff water from roads for an efficient surveillance. The indicators are intended to detect anthropogenic influences in surface, ground and drinking water.

Mucociliary clearance, airway inflammation and nasal symptoms in urban motorcyclists

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Tereza C.S. Brant

2014-01-01

Full Text Available OBJECTIVES: There is evidence that outdoor workers exposed to high levels of air pollution exhibit airway inflammation and increased airway symptoms. We hypothesized that these workers would experience increased airway symptoms and decreased nasal mucociliary clearance associated with their exposure to air pollution. METHODS: In total, 25 non-smoking commercial motorcyclists, aged 18-44 years, were included in this study. These drivers work 8-12 hours per day, 5 days per week, driving on urban streets. Nasal mucociliary clearance was measured by the saccharine transit test; airway acidification was measured by assessing the pH of exhaled breath condensate; and airway symptoms were measured by the Sino-nasal Outcome Test-20 questionnaire. To assess personal air pollution exposure, the subjects used a passive-diffusion nitrogen dioxide (NO2 concentration-monitoring system during the 14 days before each assessment. The associations between NO2 and the airway outcomes were analyzed using the Mann-Whitney test and the Chi-Square test. Clinicaltrials.gov: NCT01976039. RESULTS: Compared with clearance in healthy adult males, mucociliary clearance was decreased in 32% of the motorcyclists. Additionally, 64% of the motorcyclists had airway acidification and 92% experienced airway symptoms. The median personal NO2 exposure level was 75 mg/m3 for these subjects and a significant association was observed between NO2 and impaired mucociliary clearance (p = 0.036. CONCLUSION: Non-smoking commercial motorcyclists exhibit increased airway symptoms and airway acidification as well as decreased nasal mucociliary clearance, all of which are significantly associated with the amount of exposure to air pollution.

Genomic prediction applied to high-biomass sorghum for bioenergy production.

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de Oliveira, Amanda Avelar; Pastina, Maria Marta; de Souza, Vander Filipe; da Costa Parrella, Rafael Augusto; Noda, Roberto Willians; Simeone, Maria Lúcia Ferreira; Schaffert, Robert Eugene; de Magalhães, Jurandir Vieira; Damasceno, Cynthia Maria Borges; Margarido, Gabriel Rodrigues Alves

2018-01-01

The increasing cost of energy and finite oil and gas reserves have created a need to develop alternative fuels from renewable sources. Due to its abiotic stress tolerance and annual cultivation, high-biomass sorghum ( Sorghum bicolor L. Moench) shows potential as a bioenergy crop. Genomic selection is a useful tool for accelerating genetic gains and could restructure plant breeding programs by enabling early selection and reducing breeding cycle duration. This work aimed at predicting breeding values via genomic selection models for 200 sorghum genotypes comprising landrace accessions and breeding lines from biomass and saccharine groups. These genotypes were divided into two sub-panels, according to breeding purpose. We evaluated the following phenotypic biomass traits: days to flowering, plant height, fresh and dry matter yield, and fiber, cellulose, hemicellulose, and lignin proportions. Genotyping by sequencing yielded more than 258,000 single-nucleotide polymorphism markers, which revealed population structure between subpanels. We then fitted and compared genomic selection models BayesA, BayesB, BayesCπ, BayesLasso, Bayes Ridge Regression and random regression best linear unbiased predictor. The resulting predictive abilities varied little between the different models, but substantially between traits. Different scenarios of prediction showed the potential of using genomic selection results between sub-panels and years, although the genotype by environment interaction negatively affected accuracies. Functional enrichment analyses performed with the marker-predicted effects suggested several interesting associations, with potential for revealing biological processes relevant to the studied quantitative traits. This work shows that genomic selection can be successfully applied in biomass sorghum breeding programs.

The Effect of Nasal Functions on the Integrity of Grafts after Myringoplasty.

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Eser, Başak Çaypınar; Yılmaz, Aslı Şahin; Önder, Serap Şahin; Toros, Sema Zer; Oysu, Çağatay

2017-12-01

We aimed to evaluate the effects of nasal functions for the integrity of grafts after myringoplasty. In our study 78 patients who underwent myringoplasty operation between 2011-2013 were included. Group I was defined as the group with an intact tympanic membrane following surgery. Group II was defined as the group with a tympanic membrane perforation following surgery. Group I consisted of 44 and Group II consisted of 34 patients. Subjective and objective measurements of nasal functions, Eustachian tube function (ETF), and allergic status were performed using nasal obstruction symptom evaluation (NOSE) scale, visual analog scale (VAS), and the score for allergic rhinitis (SFAR) questionnaires and acoustic rhinometry and saccharin test. It was investigated whether there was any difference between these two groups in terms of these parameters. There was statistically no significant difference between groups according to the age, sex and the presence of tubal dysfunction and allergic rhinitis (p>0.05). In the group of intact tympanic membranes, the likelihood of right ear being the operated one was significantly higher compared to the group of myringoplasty failures (p=0.037). The VAS and NOSE scales did not show any significant difference between groups in terms of successful outcome of myringoplasty (p>0.05). The nasal congestion index (NCI) and the mucociliary clearance (MCC) did not show any significant difference between groups in terms of successful outcome of myringoplasty (p>0.05). This study has shown that nasal functions measured by objective and subjective methods had no effects on the success of myringoplasty.

Effects of repeated treatment with MDMA on working memory and behavioural flexibility in mice.

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Viñals, Xavier; Maldonado, Rafael; Robledo, Patricia

2013-03-01

Repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) produces dopaminergic neurotoxicity in mice. However, it is still not clear whether this exposure induces deficits in cognitive processing related to specific subsets of executive functioning. We evaluated the effects of neurotoxic and non-neurotoxic doses of MDMA (0, 3 and 30 mg/kg, twice daily for 4 days) on working memory and attentional set-shifting in mice, and changes in extracellular levels of dopamine (DA) in the striatum. Treatment with MDMA (30 mg/kg) disrupted performance of acquired operant alternation, and this impairment was still apparent 5 days after the last drug administration. Decreased alternation was not related to anhedonia because no differences were observed between groups in the saccharin preference test under similar experimental conditions. Correct responding on delayed alternation was increased 1 day after repeated treatment with MDMA (30 mg/kg), probably because of general behavioural quiescence. Notably, the high dose regimen of MDMA impaired attentional set-shifting related to an increase in total perseveration errors. Finally, basal extracellular levels of DA in the striatum were not modified in mice repeatedly treated with MDMA with respect to controls. However, an acute challenge with MDMA (10 mg/kg) failed to increase DA outflow in mice receiving the highest MDMA dose (30 mg/kg), corroborating a decrease in the functionality of DA transporters. Seven days after this treatment, the effects of MDMA on DA outflow were recovered. These results suggest that repeated neurotoxic doses of MDMA produce lasting impairments in recall of alternation behaviour and reduce cognitive flexibility in mice. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

Autoshaping i.v. cocaine self-administration in rats: effects of nondrug alternative reinforcers on acquisition.

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Carroll, M E; Lac, S T

1993-01-01

The purpose of this experiment was to examine the effects of a nondrug alternative reinforcer and feeding conditions on the acquisition of cocaine self-administration. Rats were autoshaped to press a lever that resulted in a 0.2 mg/kg i.v. cocaine infusion. Responses on the lever were monitored during six consecutive autoshaping sessions that occurred each day. A retractable lever was inserted into the operant chamber on a random time 60 s schedule 10 times per session for six sessions that began each hour. Each day the six autoshaping sessions were followed by a 6-h cocaine self-administration session. During self-administration the lever remained extended, and each response on the lever resulted in a cocaine infusion (0.2 mg/kg). The criterion for acquisition of cocaine-reinforced behavior was met when there were 5 consecutive days during which the mean number of infusions during the 6-h self-administration session was at least 100. This procedure was repeated daily until the criterion was met or 30 days elapsed. The rats were also trained to respond on lick-operated automatic drinking devices that delivered 0.05 ml water or a glucose and saccharin solution (G + S) contingent upon each lick response. Five groups of 12-14 rats were compared. The first four groups constituted a 2 x 2 factorial design whereby either G + S or water was available in the home cage for 3 weeks before autoshaping began and G + S or water was available in the operant chamber during autoshaping. These groups were limited to 20 g food per day and all had free access to water.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of NMDA receptor hypofunction in prefrontal and cortical excitatory neurons to schizophrenia-like phenotypes.

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Gregory R Rompala

Full Text Available Pharmacological and genetic studies support a role for NMDA receptor (NMDAR hypofunction in the etiology of schizophrenia. We have previously demonstrated that NMDAR obligatory subunit 1 (GluN1 deletion in corticolimbic interneurons during early postnatal development is sufficient to confer schizophrenia-like phenotypes in mice. However, the consequence of NMDAR hypofunction in cortical excitatory neurons is not well delineated. Here, we characterize a conditional knockout mouse strain (CtxGluN1 KO mice, in which postnatal GluN1 deletion is largely confined to the excitatory neurons in layer II/III of the medial prefrontal cortex and sensory cortices, as evidenced by the lack of GluN1 mRNA expression in in situ hybridization immunocytochemistry as well as the lack of NMDA currents with in vitro recordings. Mutants were impaired in prepulse inhibition of the auditory startle reflex as well as object-based short-term memory. However, they did not exhibit impairments in additional hallmarks of schizophrenia-like phenotypes (e.g. spatial working memory, social behavior, saccharine preference, novelty and amphetamine-induced hyperlocomotion, and anxiety-related behavior. Furthermore, upon administration of the NMDA receptor antagonist, MK-801, there were no differences in locomotor activity versus controls. The mutant mice also showed negligible levels of reactive oxygen species production following chronic social isolation, and recording of miniature-EPSC/IPSCs from layer II/III excitatory neurons in medial prefrontal cortex suggested no alteration in GABAergic activity. All together, the mutant mice displayed cognitive deficits in the absence of additional behavioral or cellular phenotypes reflecting schizophrenia pathophysiology. Thus, NMDAR hypofunction in prefrontal and cortical excitatory neurons may recapitulate only a cognitive aspect of human schizophrenia symptoms.

Molecularly imprinted sol-gel nanofibers based solid phase microextraction coupled on-line with high performance liquid chromatography for selective determination of acesulfame.

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Moein, Mohammad Mahdi; Javanbakht, Mehran; Karimi, Mohammad; Akbari-Adergani, Behrouz

2015-03-01

Sol-gel based molecularly imprinted polymer (MIP) nanofiber was successfully fabricated by electrospinning technique on the surface of a stainless steel bar. The manufactured tool was applied for on-line selective solid phase microextraction (SPME) and determination of acesulfame (ACF) as an artificial sweetener with high performance liquid chromatography (HPLC). The selective ability of method for the extraction of ACF was investigated in the presence of some selected sweeteners such as saccharine (SCH), aspartame (ASP) and caffeine (CAF). Electrospinning of MIP sol-gel solution on the stainless steel bar provided an unbreakable sorbent with high thermal, mechanical, and chemical stability. Moreover, application of the MIP-SPME tool revealed a unique approach for the selective microextraction of the analyte in beverage samples. In this work, 3-(triethoxysilyl)-propylamine (TMSPA) was chosen as a precursor due to its ability to imprint the analyte by hydrogen bonding, Van der Walls, and dipole-dipole interactions. Nylon 6 was also added as a backbone and support for the precursor in which sol could greatly growth during the sol-gel process and makes the solution electrospinable. Various effective parameters in the extraction efficiency of the MIP-SPME tool such as loading time, flow rate, desorption time, selectivity, and the sample volume were evaluated. The linearity for the ACF in beverage sample was in the range of 0.78-100.5 ng mL(-1). Limit of detection (LOD) and quantification (LOQ) were 0.23 and 0.78 ng mL(-1) respectively. The RSD values (n=5) were all below 3.5%at the 20 ng mL(-1) level. Copyright © 2014 Elsevier B.V. All rights reserved.

Formulation and evaluation of a novel matrix-type orally disintegrating Ibuprofen tablet.

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Tayebi, Hoda; Mortazavi, Seyed Alireza

2011-01-01

Orally disintegrating tablets (ODTs) are capable of turning quickly into a liquid dosage form in contact with the saliva, thus possessing the advantages of both the solid dosage forms particularly stability and liquid dosage forms specially ease of swallowing and pre-gastric absorption of drug. The aim of this study was to prepare a novel matrix-type buccal fast disintegrating ibuprofen tablet formulation using special polymers, water soluble excipients, super-disintegrants and quickly soluble granules. For this purpose different tablet formulations of ibuprofen were prepared. The amount of ibuprofen in each formulation was 100 mg. Eight groups of formulation were prepared (A-H series), accounting for a total number of 45 formulations. Formulations prepared were examined in terms of different physicochemical tests including powder/granule flowability, appearance, thickness, uniformity of weight, hardness, friability and disintegration time. Results of formulation F22a (in series F), was found to be acceptable, making it the chosen formulation for further studies. Then, by adding various flavorants and sweeteners to this formulation, complementary series of formulations, named G and H, were prepared. Following the comparison of their taste with each other through asking 10 volunteers, the most suitable formulation regarding the taste, being formulation F22s, was chosen as the ultimate formulation. This formulation had PVP, ibuprofen and croscarmellose as the intra-granular components and xylitol and saccharin as the extra-granular ingredients. Formulation F22s was found to be acceptable in terms of physicochemical tests conducted, showing quick disintegration within the buccal cavity, appropriate hardness and rather low friability. Hence formulation F22s was selected as the final formulation.

The aryl hydrocarbon receptor is indispensable for dioxin-induced defects in sexually-dimorphic behaviors due to the reduction in fetal steroidogenesis of the pituitary-gonadal axis in rats.

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Hattori, Yukiko; Takeda, Tomoki; Nakamura, Arisa; Nishida, Kyoko; Shioji, Yuko; Fukumitsu, Haruki; Yamada, Hideyuki; Ishii, Yuji

2018-05-16

Many forms of the toxic effects produced by dioxins and related chemicals take place following activation of the aryl hydrocarbon receptor (AHR). Our previous studies have demonstrated that treating pregnant rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic dioxin, attenuates the pituitary expression of gonadotropins to reduce testicular steroidogenesis during the fetal stage, resulting in the impairment of sexually-dimorphic behaviors after the offspring reach maturity. To investigate the contribution of AHR to these disorders, we examined the effects of TCDD on AHR-knockout (AHR-KO) Wistar rats. When pregnant AHR-heterozygous rats were given an oral dose of 1 µg/kg TCDD at gestational day (GD) 15, TCDD reduced the expression of pituitary gonadotropins and testicular steroidogenic proteins in male wild-type fetuses at GD20 without affecting body weight, sex ratio and litter size. However, the same defect did not occur in AHR-KO fetuses. Further, fetal exposure to TCDD impaired the activity of masculine sexual behavior after reaching adulthood only in the wild-type offspring. Also, in female offspring, not only the fetal gonadotropins production but also sexual dimorphism, such as saccharin preference, after growing up were suppressed by TCDD only in the wild-type. Interestingly, in the absence of TCDD, deleting AHR reduced masculine sexual behavior, as well as fetal steroidogenesis of the pituitary-gonadal axis. These results provide novel evidence that 1) AHR is required for TCDD-produced defects in sexually-dimorphic behaviors of the offspring, and 2) AHR signaling plays a role in gonadotropin synthesis during the developmental stage to acquire sexual dimorphism after reaching adulthood. Copyright © 2018 Elsevier Inc. All rights reserved.

CAST/EiJ and C57BL/6J Mice Differ in Their Oral and Postoral Attraction to Glucose and Fructose.

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Sclafani, Anthony; Vural, Austin S; Ackroff, Karen

2017-03-01

A recent study indicated that CAST/EiJ and C57BL/6J mice differ in their taste preferences for maltodextrin but display similar sucrose preferences. The present study revealed strain differences in preferences for the constituent sugars of sucrose. Whereas B6 mice preferred 8% glucose to 8% fructose in 2-day tests, the CAST mice preferred fructose to glucose. These preferences emerged with repeated testing which suggested post-oral influences. In a second experiment, 2-day choice tests were conducted with the sugars versus a sucralose + saccharin (SS) mixture which is highly preferred in brief access tests. B6 mice strongly preferred glucose but not fructose to the non-nutritive SS whereas CAST mice preferred SS to both glucose and fructose even when food restricted. This implied that CAST mice are insensitive to the postoral appetite stimulating actions of the 2 sugars. A third experiment revealed, however, that intragastric glucose and fructose infusions conditioned significant but mild flavor preferences in CAST mice, whereas in B6 mice glucose conditioned a robust preference but fructose was ineffective. Thus, unlike other mouse strains and rats, glucose is not more reinforcing than fructose in CAST mice. Their oral preference for fructose over glucose may be related to a subsensitive maltodextrin receptor or glucose-specific receptor which is stimulated by glucose but not fructose. The failure of CAST mice to prefer glucose to a non-nutritive sweetener distinguishes this strain from other mouse strains and rats. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression

KAUST Repository

Rossetti, Clara

2017-12-06

Obesity and depression are major public health concerns, and there is increasing evidence that they share etiological mechanisms. CREB-regulated transcription coactivator 1 (CRTC1) participates in neurobiological pathways involved in both mood and energy balance regulation. Crtc1 -/- mice rapidly develop a depressive-like and obese phenotype in early adulthood, and are therefore a relevant animal model to explore possible common mechanisms underlying mood disorders and obesity. Here, the obese phenotype of male and female Crtc1 -/- mice was further characterized by investigating CRTC1\\'s role in the homeostatic and hedonic regulation of food intake, as well as its influence on daily locomotor activity. Crtc1 -/- mice showed a strong gender difference in the homeostatic regulation of energy balance. Mutant males were hyperphagic and rapidly developed obesity on normal chow diet, whereas Crtc1 -/- females exhibited mild late-onset obesity without hyperphagia. Overeating of mutant males was accompanied by alterations in the expression of several orexigenic and anorexigenic hypothalamic genes, thus confirming a key role of CRTC1 in the central regulation of food intake. No alteration in preference and conditioned response for saccharine was observed in Crtc1 -/- mice, suggesting that mutant males\\' hyperphagia was not due to an altered hedonic regulation of food intake. Intriguingly, mutant males exhibited a hyperphagic behavior only during the resting (diurnal) phase of the light cycle. This abnormal feeding behavior was associated with a higher diurnal locomotor activity indicating that the lack of CRTC1 may affect circadian rhythmicity. Collectively, these findings highlight the male-specific involvement of CRTC1 in the central control of energy balance and circadian locomotor activity.

Transport of sewage molecular markers through saturated soil column and effect of easily biodegradable primary substrate on their removal.

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Foolad, Mahsa; Ong, Say Leong; Hu, Jiangyong

2015-11-01

Pharmaceutical and personal care products (PPCPs) and artificial sweeteners (ASs) are emerging organic contaminants (EOCs) in the aquatic environment. The presence of PPCPs and ASs in water bodies has an ecologic potential risk and health concern. Therefore, it is needed to detect the pollution sources by understanding the transport behavior of sewage molecular markers in a subsurface area. The aim of this study was to evaluate transport of nine selected molecular markers through saturated soil column experiments. The selected sewage molecular markers in this study were six PPCPs including acetaminophen (ACT), carbamazepine (CBZ), caffeine (CF), crotamiton (CTMT), diethyltoluamide (DEET), salicylic acid (SA) and three ASs including acesulfame (ACF), cyclamate (CYC), and saccharine (SAC). Results confirmed that ACF, CBZ, CTMT, CYC and SAC were suitable to be used as sewage molecular markers since they were almost stable against sorption and biodegradation process during soil column experiments. In contrast, transport of ACT, CF and DEET were limited by both sorption and biodegradation processes and 100% removal efficiency was achieved in the biotic column. Moreover, in this study the effect of different acetate concentration (0-100mg/L) as an easily biodegradable primary substrate on a removal of PPCPs and ASs was also studied. Results showed a negative correlation (r(2)>0.75) between the removal of some selected sewage chemical markers including ACF, CF, ACT, CYC, SAC and acetate concentration. CTMT also decreased with the addition of acetate, but increasing acetate concentration did not affect on its removal. CBZ and DEET removal were not dependent on the presence of acetate. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression

KAUST Repository

Rossetti, Clara; Sciarra, Daniel; Petit, Jean-Marie; Eap, Chin B.; Halfon, Olivier; Magistretti, Pierre J.; Boutrel, Benjamin; Cardinaux, Jean-René

2017-01-01

Obesity and depression are major public health concerns, and there is increasing evidence that they share etiological mechanisms. CREB-regulated transcription coactivator 1 (CRTC1) participates in neurobiological pathways involved in both mood and energy balance regulation. Crtc1 -/- mice rapidly develop a depressive-like and obese phenotype in early adulthood, and are therefore a relevant animal model to explore possible common mechanisms underlying mood disorders and obesity. Here, the obese phenotype of male and female Crtc1 -/- mice was further characterized by investigating CRTC1's role in the homeostatic and hedonic regulation of food intake, as well as its influence on daily locomotor activity. Crtc1 -/- mice showed a strong gender difference in the homeostatic regulation of energy balance. Mutant males were hyperphagic and rapidly developed obesity on normal chow diet, whereas Crtc1 -/- females exhibited mild late-onset obesity without hyperphagia. Overeating of mutant males was accompanied by alterations in the expression of several orexigenic and anorexigenic hypothalamic genes, thus confirming a key role of CRTC1 in the central regulation of food intake. No alteration in preference and conditioned response for saccharine was observed in Crtc1 -/- mice, suggesting that mutant males' hyperphagia was not due to an altered hedonic regulation of food intake. Intriguingly, mutant males exhibited a hyperphagic behavior only during the resting (diurnal) phase of the light cycle. This abnormal feeding behavior was associated with a higher diurnal locomotor activity indicating that the lack of CRTC1 may affect circadian rhythmicity. Collectively, these findings highlight the male-specific involvement of CRTC1 in the central control of energy balance and circadian locomotor activity.

Sexually dimorphic serotonergic dysfunction in a mouse model of Huntington's disease and depression.

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Thibault Renoir

Full Text Available Depression is the most common psychiatric disorder in Huntington's disease (HD patients. In the general population, women are more prone to develop depression and such susceptibility might be related to serotonergic dysregulation. There is yet to be a study of sexual dimorphism in the development and presentation of depression in HD patients. We investigated whether 8-week-old male and female R6/1 transgenic HD mice display depressive-like endophenotypes associated with serotonergic impairments. We also studied the behavioral effects of acute treatment with sertraline. We found that only female HD mice exhibited a decreased preference for saccharin as well as impaired emotionality-related behaviors when assessed on the novelty-suppressed feeding test (NSFT and the forced-swimming test (FST. The exaggerated immobility time displayed by female HD in the FST was reduced by acute administration of sertraline. We also report an increased response to the 5-HT(1A receptor agonist 8-OH-DPAT in inducing hypothermia and a decreased 5-HT(2A receptor function in HD animals. While tissue levels of serotonin were reduced in both male and female HD mice, we found that serotonin concentration and hydroxylase-2 (TPH2 mRNA levels were higher in the hippocampus of males compared to female animals. Finally, the antidepressant-like effects of sertraline in the FST were blunted in male HD animals. This study reveals sex-specific depressive-related behaviors during an early stage of HD prior to any cognitive and motor deficits. Our data suggest a crucial role for disrupted serotonin signaling in mediating the sexually dimorphic depression-like phenotype in HD mice.

Simultaneous Detection of c-Fos Activation from Mesolimbic and Mesocortical Dopamine Reward Sites Following Naive Sugar and Fat Ingestion in Rats.

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Dela Cruz, Julie A D; Coke, Tricia; Bodnar, Richard J

2016-08-24

This study uses cellular c-fos activation to assess effects of novel ingestion of fat and sugar on brain dopamine (DA) pathways in rats. Intakes of sugars and fats are mediated by their innate attractions as well as learned preferences. Brain dopamine, especially meso-limbic and meso-cortical projections from the ventral tegmental area (VTA), has been implicated in both of these unlearned and learned responses. The concept of distributed brain networks, wherein several sites and transmitter/peptide systems interact, has been proposed to mediate palatable food intake, but there is limited evidence empirically demonstrating such actions. Thus, sugar intake elicits DA release and increases c-fos-like immunoreactivity (FLI) from individual VTA DA projection zones including the nucleus accumbens (NAC), amygdala (AMY) and medial prefrontal cortex (mPFC) as well as the dorsal striatum. Further, central administration of selective DA receptor antagonists into these sites differentially reduce acquisition and expression of conditioned flavor preferences elicited by sugars or fats. One approach by which to determine whether these sites interacted as a distributed brain network in response to sugar or fat intake would be to simultaneous evaluate whether the VTA and its major mesotelencephalic DA projection zones (prelimbic and infralimbic mPFC, core and shell of the NAc, basolateral and central-cortico-medial AMY) as well as the dorsal striatum would display coordinated and simultaneous FLI activation after oral, unconditioned intake of corn oil (3.5%), glucose (8%), fructose (8%) and saccharin (0.2%) solutions. This approach is a successful first step in identifying the feasibility of using cellular c-fos activation simultaneously across relevant brain sites to study reward-related learning in ingestion of palatable food in rodents.

Contribution of NMDA receptor hypofunction in prefrontal and cortical excitatory neurons to schizophrenia-like phenotypes.

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Rompala, Gregory R; Zsiros, Veronika; Zhang, Shuqin; Kolata, Stefan M; Nakazawa, Kazu

2013-01-01

Pharmacological and genetic studies support a role for NMDA receptor (NMDAR) hypofunction in the etiology of schizophrenia. We have previously demonstrated that NMDAR obligatory subunit 1 (GluN1) deletion in corticolimbic interneurons during early postnatal development is sufficient to confer schizophrenia-like phenotypes in mice. However, the consequence of NMDAR hypofunction in cortical excitatory neurons is not well delineated. Here, we characterize a conditional knockout mouse strain (CtxGluN1 KO mice), in which postnatal GluN1 deletion is largely confined to the excitatory neurons in layer II/III of the medial prefrontal cortex and sensory cortices, as evidenced by the lack of GluN1 mRNA expression in in situ hybridization immunocytochemistry as well as the lack of NMDA currents with in vitro recordings. Mutants were impaired in prepulse inhibition of the auditory startle reflex as well as object-based short-term memory. However, they did not exhibit impairments in additional hallmarks of schizophrenia-like phenotypes (e.g. spatial working memory, social behavior, saccharine preference, novelty and amphetamine-induced hyperlocomotion, and anxiety-related behavior). Furthermore, upon administration of the NMDA receptor antagonist, MK-801, there were no differences in locomotor activity versus controls. The mutant mice also showed negligible levels of reactive oxygen species production following chronic social isolation, and recording of miniature-EPSC/IPSCs from layer II/III excitatory neurons in medial prefrontal cortex suggested no alteration in GABAergic activity. All together, the mutant mice displayed cognitive deficits in the absence of additional behavioral or cellular phenotypes reflecting schizophrenia pathophysiology. Thus, NMDAR hypofunction in prefrontal and cortical excitatory neurons may recapitulate only a cognitive aspect of human schizophrenia symptoms.

Effects of sex and housing on social, spatial, and motor behavior in adult rats exposed to moderate levels of alcohol during prenatal development.

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Rodriguez, Carlos I; Magcalas, Christy M; Barto, Daniel; Fink, Brandi C; Rice, James P; Bird, Clark W; Davies, Suzy; Pentkowski, Nathan S; Savage, Daniel D; Hamilton, Derek A

2016-10-15

Persistent deficits in social behavior, motor behavior, and behavioral flexibility are among the major negative consequences associated with exposure to ethanol during prenatal development. Prior work from our laboratory has linked moderate prenatal alcohol exposure (PAE) in the rat to deficits in these behavioral domains, which depend upon the ventrolateral frontal cortex (Hamilton et al., 2014) [20]. Manipulations of the social environment cause modifications of dendritic morphology and experience-dependent immediate early gene expression in ventrolateral frontal cortex (Hamilton et al., 2010) [19], and may yield positive behavioral outcomes following PAE. In the present study we evaluated the effects of housing PAE rats with non-exposed control rats on adult behavior. Rats of both sexes were either paired with a partner from the same prenatal treatment condition (ethanol or saccharin) or from the opposite condition (mixed housing condition). At four months of age (∼3 months after the housing manipulation commenced), social behavior, tongue protrusion, and behavioral flexibility in the Morris water task were measured as in (Hamilton et al., 2014) [20]. The behavioral effects of moderate PAE were primarily limited to males and were not ameliorated by housing with a non-ethanol exposed partner. Unexpectedly, social behavior, motor behavior, and spatial flexibility were adversely affected in control rats housed with a PAE rat (i.e., in mixed housing), indicating that housing with a PAE rat has broad behavioral consequences beyond the social domain. These observations provide further evidence that moderate PAE negatively affects social behavior, and underscore the importance of considering potential negative effects of housing with PAE animals on the behavior of critical comparison groups. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation of the electroplated Ni and Co films for applying betavoltaic battery and Moessbauer source

International Nuclear Information System (INIS)

Uhm, Young Rang; Choi, Sang Mu; Kim, Jin Joo; Kim, Jong Bum; Son, Kwang Jae; Hong, Jintae

2016-01-01

The reverse occurs at the anode where metallic nickel is dissolved to form divalent positively charged ions that enter the solution. The nickel ions discharged at the cathode are replenished by those formed at the anode. In this study, a Co-and Ni- plating solution is prepared using two different baths. One is the acid-based buffer (pH 3-4) containing boric acid, sodium chloride, and saccharin. The rest is the base-based buffer (pH 10) containing hydrazine hydrate and ammonium citrate. The optimization of the electroplating parameters for the deposition of Co on plate was considered as indispensable. A betavoltaic battery was fabricated using Ni-63 attached on a P-N junction semiconductor, and the I-V characteristics were measured using a probe station. The thickness-dependent self-shielding effect of the radioisotope layer was investigated. Also, the aim of this work was determination of the optimal parameters for thermal diffusion of the electroplated Co into the Rh structure. To establish preparation of betavoltaic battery, and Moessbauer source, natural Ni and Co were electroplated on the Rh plate. Both the acid-based buffer (pH 3) and the alkarine-based buffer (pH 10) are used for plating bath. The deposition yield of the alkarine electrolyte is relatively higher than those of the acidic bath. optimum conditions for the homogeneous diffusion is determined at annealing temperatures of 1100 .deg. C for 3h under the high vacuum atmosphere (10"-"5 hPa). The proposed condition in this study should be applied to prepare 57Co/Rh Moessbauer source at near future

Preparation of the electroplated Ni and Co films for applying betavoltaic battery and Moessbauer source

Energy Technology Data Exchange (ETDEWEB)

Uhm, Young Rang; Choi, Sang Mu; Kim, Jin Joo; Kim, Jong Bum; Son, Kwang Jae; Hong, Jintae [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2016-10-15

The reverse occurs at the anode where metallic nickel is dissolved to form divalent positively charged ions that enter the solution. The nickel ions discharged at the cathode are replenished by those formed at the anode. In this study, a Co-and Ni- plating solution is prepared using two different baths. One is the acid-based buffer (pH 3-4) containing boric acid, sodium chloride, and saccharin. The rest is the base-based buffer (pH 10) containing hydrazine hydrate and ammonium citrate. The optimization of the electroplating parameters for the deposition of Co on plate was considered as indispensable. A betavoltaic battery was fabricated using Ni-63 attached on a P-N junction semiconductor, and the I-V characteristics were measured using a probe station. The thickness-dependent self-shielding effect of the radioisotope layer was investigated. Also, the aim of this work was determination of the optimal parameters for thermal diffusion of the electroplated Co into the Rh structure. To establish preparation of betavoltaic battery, and Moessbauer source, natural Ni and Co were electroplated on the Rh plate. Both the acid-based buffer (pH 3) and the alkarine-based buffer (pH 10) are used for plating bath. The deposition yield of the alkarine electrolyte is relatively higher than those of the acidic bath. optimum conditions for the homogeneous diffusion is determined at annealing temperatures of 1100 .deg. C for 3h under the high vacuum atmosphere (10{sup -5} hPa). The proposed condition in this study should be applied to prepare 57Co/Rh Moessbauer source at near future.

Cdh13 and AdipoQ gene knockout alter instrumental and Pavlovian drug conditioning.

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King, C P; Militello, L; Hart, A; St Pierre, C L; Leung, E; Versaggi, C L; Roberson, N; Catlin, J; Palmer, A A; Richards, J B; Meyer, P J

2017-09-01

Genome-wide association studies in humans have suggested that variants of the cadherin-13 (CDH13) gene are associated with substance use disorder, subjective response to amphetamine, and attention deficit hyperactivity disorder. To examine the role of the Cdh13 and its peptide ligand adiponectin (AdipoQ) in addiction-related behaviors, we assessed Cdh13 knockout (KO) rats and AdipoQ KO mice using intravenous cocaine self-administration and conditioned place preference (CPP) paradigms. During intravenous cocaine self-administration, male Cdh13 heterozygous (+/-) and KO (-/-) rats showed increased cue-induced reinstatement compared with wild-type (WT) rats when presented with a cocaine-paired stimulus, whereas female Cdh13 rats showed no differences across genotype. Cdh13 -/- rats showed higher responding for a saccharin reinforcer and learned the choice reaction time (RT) task more slowly than WTs. However, we found no differences between Cdh13 -/- and +/+ rats in responding for sensory reinforcement, number of premature responses in the RT task, tendency to approach a Pavlovian food cue, CPP and locomotor activation to cocaine (10 or 20 mg/kg). In AdipoQ -/- mice, there was a significant increase in CPP to methamphetamine (1 mg/kg) but not to a range of d-amphetamine doses (0.5, 1, 2 and 4 mg/kg). Taken together, these data suggest that Cdh13 and AdipoQ regulate sensitivity to psychomotor stimulants and palatable rewards without producing major changes in other behaviors. In humans, these two genes may regulate sensitivity to natural and drug rewards, thus influencing susceptibility to the conditioned drug effects and relapse. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Conditioned taste aversion to ethanol in a social context: impact of age and sex.

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Morales, Melissa; Schatz, Kelcie C; Anderson, Rachel I; Spear, Linda P; Varlinskaya, Elena I

2014-03-15

Given that human adolescents place a high value on social interactions-particularly while consuming alcohol-the current study utilized a novel social drinking paradigm to examine rewarding and aversive properties of ethanol in non-water deprived rats that were housed and tested in groups of five same-sex littermates. On postnatal day P34 (adolescents) or P69 (adults), rats were habituated to the testing apparatus for 30 min. On the next day, animals were placed into the test apparatus and given 30 min access to a supersaccharin solution (3% sucrose; 0.125% saccharin), followed immediately by an intraperitoneal injection of ethanol (0, 0.25, 0.5, 1.0, 1.5 g/kg). Subsequent intake of the supersacharrin solution was assessed on three consecutive test days. Adolescent males were less sensitive to ethanol's aversive effects than adult males, with adolescent males maintaining an aversion on all three test days only at the 1.5 g/kg dose, whereas adults demonstrated aversions across test days to 1 and 1.5 g/kg. Adolescent females maintained aversions to 1 and 1.5 g/kg across days, whereas adult females continued to show an aversion to the 1.5 g/kg dose only. These opposite patterns of sensitivity that emerged among males and females at each age in the propensity to maintain an ethanol-induced taste aversion under social conditions may contribute to age- and sex-related differences in ethanol intake. Testing in social groups may be useful for future work when studying rodent models of adolescent alcohol use given the importance that human adolescents place on drinking in social settings. Copyright © 2014 Elsevier B.V. All rights reserved.

Glucose administration enhances fMRI brain activation and connectivity related to episodic memory encoding for neutral and emotional stimuli.

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Parent, Marise B; Krebs-Kraft, Desiree L; Ryan, John P; Wilson, Jennifer S; Harenski, Carla; Hamann, Stephan

2011-04-01

Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with episodic memory encoding and whether these effects would differ depending on the emotional valence of the material. We used a double-blind, within-participants, crossover design in which either glucose (50g) or a saccharin placebo were administered before scanning, on days approximately 1 week apart. We scanned healthy young male participants with fMRI as they viewed emotionally arousing negative pictures and emotionally neutral pictures, intermixed with baseline fixation. Free recall was tested at 5 min after scanning and again after 1 day. Glucose administration increased activation in brain regions associated with successful episodic memory encoding. Glucose also enhanced activation in regions whose activity was correlated with subsequent successful recall, including the hippocampus, prefrontal cortex, and other regions, and these effects differed for negative vs. neutral stimuli. Finally, glucose substantially increased functional connectivity between the hippocampus and amygdala and a network of regions previously implicated in successful episodic memory encoding. These findings fit with evidence from nonhuman animals indicating glucose modulates memory by selectively enhancing neural activity in brain regions engaged during memory tasks. Our results highlight the modulatory effects of glucose and the importance of examining both regional changes in activity and functional connectivity to fully characterize the effects of glucose on brain function and memory. Copyright © 2011 Elsevier Ltd. All rights reserved.

LC-QTOF MS screening of more than 1,000 licit and illicit drugs and their metabolites in wastewater and surface waters from the area of Bogotá, Colombia.

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Hernández, Félix; Ibáñez, María; Botero-Coy, Ana-María; Bade, Richard; Bustos-López, Martha Cristina; Rincón, Javier; Moncayo, Alejandro; Bijlsma, Lubertus

2015-08-01

A large screening of around 1,000 emerging contaminants, focused on licit and illicit drugs and their metabolites, has been made in urban wastewaters (both influent and effluent) and surface waters from the area of Bogotá, Colombia. After a simple generic solid-phase extraction (SPE) step with Oasis hydrophilic-lipophilic balanced (HLB) cartridges, analyses were made by ultra high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS) under MS(E) mode (sequential acquisition of mass spectra at low energy (LE) and high collision energy (HE)). Accurate mass measurements and the information provided by MS(E) on the presence of the (de)protonated molecule and fragment ions allowed the reliable identification of the compounds detected, even without reference standards being available in some cases (tentative identification). The compounds most frequently found were acetaminophen/paracetamol, carbamazepine and its dihydro-dihydroxylated metabolite, clarithromycin, diclofenac, ibuprofen, gemfibrozil, lincomycin, losartan, valsartan, the two metabolites of metamizole (4-acetamido-antipyrine and 4-formylamino-antipyrine), sucralose, and cocaine and its main metabolite benzoylecgonine. Caffeine, the sweetener saccharin, and two hydroxylated metabolites of losartan were tentatively identified in almost all samples analyzed. Pharmaceutical lidocaine was tentatively identified and subsequently confirmed with reference standard. For the first time, a general overview of the occurrence of drugs and their metabolites in the aquatic environment of Colombia has been reported. In the near future, target methodologies, typically based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), will need to be set up for accurate and sensitive quantification of the contaminants selected on the basis on the information provided in the present paper.

Evaluation of early changes induced by diuron in the rat urinary bladder using different processing methods for scanning electron microscopy.

Science.gov (United States)

Fava, Rafaela Marono; Ferragut Cardoso, Ana Paula; da Rocha, Mitscheli Sanches; Nascimento E Pontes, Merielen Garcia; de Camargo, João Lauro Viana; de Oliveira, Maria Luiza Cotrim Sartor

2015-07-03

Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a substituted urea herbicide carcinogenic to the rat urinary bladder at high dietary levels. The suggested non-genotoxic mode of action (MOA) of diuron encompasses cytotoxicity and necrosis followed by regenerative hyperplasia. Prenecrotic swollen cells as observed under scanning electron microscopy (SEM) have been reported as early morphological alterations, putatively related to diuron cytotoxicity. However, these changes were not observed in a previous SEM study conducted in this laboratory. This study evaluated whether these early alterations are actually due to diuron cytotoxicity or artifacts related to different processing methods used for SEM analysis. Male Wistar rats were fed ad libitum with basal diet, 7.1% sodium saccharin (NaS) or 2.500ppm diuron for seven days or 15 weeks. The urinary bladders were processed for histological and labeling indices examinations and for SEM using two different processing methods. The incidence of simple hyperplasia after 15 weeks of exposure to diuron or to NaS was significantly increased. By SEM, the incidences and severity of lesions were significantly increased in the diuron group independently of exposure time. The different SEM processing methods used allowed for visualization of swollen superficial cells after seven days of diuron exposure. Probably the absence these cells in a previous study was due to the use very few animals. Our results support the hypothesis that the swollen cell is an early key event due to diuron-induced cytotoxicity and is the result of a degenerative process involved in the non-genotoxic carcinogenic mode of action of high doses of diuron. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Environmental enrichment reduces chronic psychosocial stress-induced anxiety and ethanol-related behaviors in mice.

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Bahi, Amine

2017-07-03

Previous research from our laboratory has shown that exposure to chronic psychosocial stress increased voluntary ethanol consumption and preference as well as acquisition of ethanol-induced conditioned place preference (CPP) in mice. This study was done to determine whether an enriched environment could have "curative" effects on chronic psychosocial stress-induced ethanol intake and CPP. For this purpose, experimental mice "intruders" were exposed to the chronic subordinate colony (CSC) housing for 19 consecutive days in the presence of an aggressive "resident" mouse. At the end of that period, mice were tested for their anxiety-like behavior using the elevated plus maze (EPM) test then housed in a standard or enriched environment (SE or EE respectively). Anxiety and ethanol-related behaviors were investigated using the open field (OF) test, a standard two-bottle choice drinking paradigm, and the CPP procedure. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to single housed colony (SHC) controls. In addition, CSC exposure increased voluntary ethanol intake and ethanol-CPP. Interestingly, we found that EE significantly and consistently reduced anxiety and ethanol consumption and preference. However, neither tastants' (saccharin and quinine) intake nor blood ethanol metabolism were affected by EE. Finally, and most importantly, EE reduced the acquisition of CPP induced by 1.5g/kg ethanol. Taken together, these results support the hypothesis that EE can reduce voluntary ethanol intake and ethanol-induced conditioned reward and seems to be one of the strategies to reduce the behavioral deficits and the risk of anxiety-induced alcohol abuse. Copyright © 2017 Elsevier Inc. All rights reserved.

Striatal modulation of BDNF expression using microRNA124a-expressing lentiviral vectors impairs ethanol-induced conditioned-place preference and voluntary alcohol consumption.

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Bahi, Amine; Dreyer, Jean-Luc

2013-07-01

Alcohol abuse is a major health, economic and social concern in modern societies, but the exact molecular mechanisms underlying ethanol addiction remain elusive. Recent findings show that small non-coding microRNA (miRNA) signaling contributes to complex behavioral disorders including drug addiction. However, the role of miRNAs in ethanol-induced conditioned-place preference (CPP) and voluntary alcohol consumption has not yet been directly addressed. Here, we assessed the expression profile of miR124a in the dorsal striatum of rats upon ethanol intake. The results show that miR124a was downregulated in the dorso-lateral striatum (DLS) following alcohol drinking. Then, we identified brain-derived neurotrophic factor (BDNF) as a direct target of miR124a. In fact, BDNF mRNA was upregulated following ethanol drinking. We used lentiviral vector (LV) gene transfer technology to further address the role of miR124a and its direct target BDNF in ethanol-induced CPP and alcohol consumption. Results reveal that stereotaxic injection of LV-miR124a in the DLS enhances ethanol-induced CPP as well as voluntary alcohol consumption in a two-bottle choice drinking paradigm. Moreover, miR124a-silencer (LV-siR124a) as well as LV-BDNF infusion in the DLS attenuates ethanol-induced CPP as well as voluntary alcohol consumption. Importantly, LV-miR124a, LV-siR124a and LV-BDNF have no effect on saccharin and quinine intake. Our findings indicate that striatal miR124a and BDNF signaling have crucial roles in alcohol consumption and ethanol conditioned reward. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Influence of the novel histamine H₃ receptor antagonist ST1283 on voluntary alcohol consumption and ethanol-induced place preference in mice.

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Bahi, Amine; Sadek, Bassem; Schwed, Stephan J; Walter, Miriam; Stark, Holger

2013-07-01

Growing evidence supports a role for the central histaminergic system to have a modulatory influence on drug addiction in general and alcohol-use disorders in particular through histamine H3 receptors (H3R). In the present study, the effects of systemic injection of the newly synthesized H3R antagonist ST1283 on ethanol (EtOH) voluntary intake and EtOH-conditioned reward in mice have been investigated. Oral EtOH, saccharin, and quinine intake was assessed in a two-bottle choice paradigm using escalating concentrations of alcohol or tastant solutions. EtOH-induced place preference (CPP), EtOH-induced locomotor activity, and blood ethanol concentration (BEC) were also measured. Following administration of the H3R antagonist (2.5, 5, and 10 mg/kg, i.p.), there was a significant dose-dependent decrease in alcohol consumption and preference. Importantly, vehicle- and ST1283 (5 mg/kg)-treated mice showed similar consumption and preference to increasing concentration of both sweet and bitter tastes. More interestingly, systemic administration of ST1283 inhibited EtOH-CPP and EtOH-enhanced locomotion. This inhibition was blocked when mice were pretreated with the selective H3R agonist R-(alpha)-methyl-histamine (10 mg/kg). Finally, vehicle- and ST1283-treated mice had similar BECs. Our results show that ST1283 may decrease voluntary EtOH consumption and EtOH-CPP by altering its reinforcing effects, suggesting a novel role for histamine signaling in regulation of alcoholism. Lastly, the results add to the growing literature on H3R modulation in the pharmacotherapy of EtOH addiction.

Norepinephrine is coreleased with serotonin in mouse taste buds.

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Huang, Yijen A; Maruyama, Yutaka; Roper, Stephen D

2008-12-03

ATP and serotonin (5-HT) are neurotransmitters secreted from taste bud receptor (type II) and presynaptic (type III) cells, respectively. Norepinephrine (NE) has also been proposed to be a neurotransmitter or paracrine hormone in taste buds. Yet, to date, the specific stimulus for NE release in taste buds is not well understood, and the identity of the taste cells that secrete NE is not known. Chinese hamster ovary cells were transfected with alpha(1A) adrenoceptors and loaded with fura-2 ("biosensors") to detect NE secreted from isolated mouse taste buds and taste cells. Biosensors responded to low concentrations of NE (>or=10 nm) with a reliable fura-2 signal. NE biosensors did not respond to stimulation with KCl or taste compounds. However, we recorded robust responses from NE biosensors when they were positioned against mouse circumvallate taste buds and the taste buds were stimulated with KCl (50 mm) or a mixture of taste compounds (cycloheximide, 10 microm; saccharin, 2 mm; denatonium, 1 mm; SC45647, 100 microm). NE biosensor responses evoked by stimulating taste buds were reversibly blocked by prazosin, an alpha(1A) receptor antagonist. Together, these findings indicate that taste bud cells secrete NE when they are stimulated. We isolated individual taste bud cells to identify the origin of NE release. NE was secreted only from presynaptic (type III) taste cells and not receptor (type II) cells. Stimulus-evoked NE release depended on Ca(2+) in the bathing medium. Using dual biosensors (sensitive to 5-HT and NE), we found all presynaptic cells secrete 5-HT and 33% corelease NE with 5-HT.

Leaves of Hippophae rhamnoides prevent taste aversion in gamma-irradiated rats.

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Gupta, Vanita; Bala, Madhu; Prasad, Jagdish; Singh, Surinder; Gupta, Manish

2011-12-01

Hippophae rhamnoides (Sea buckthorn), a traditionally known plant for nutritional and therapeutic values, is under active investigation for radioprotective properties. This study investigated effects of aqueous leaf extract from H. rhamnoides on (60)Co-γ-radiation induced changes in behavior, oxidative stress and serotonin levels in jejunum and plasma of rats. Conditioned taste aversion (CTA) was chosen as the assay to record behavioral changes and was assessed in terms of saccharine preference ratio (SPR). Whole body (60)Co-γ-irradiation (2 Gy) induced significant nonrecoverable CTA (25.6 ± 3.6% SPR, t(6) = 3.499, p loss in body weight (b.w.). One time treatment with leaf extract before irradiation, countered radiation induced CTA and loss in body weight. The 12 mg/kg b.w. concentration of leaf extract caused complete extinction of CTA [100.3 ± 6.4% SPR, t(6) = 5.879, p < .01] after day 3 and the effect was significantly higher than positive control, Ondansetrone (70.0 ± 8.9% SPR). Treatment with leaf extract before irradiation significantly countered radiation induced (1) decrease in antioxidant protection, (2) increase in levels of corticosterone (CS) in plasma, (3) increase in levels of serotonin in jejunum and plasma. Present investigation demonstrated that H. rhamnoides leaf extract prevented behavioral changes induced at clinical radiation doses. Hippophae leaves are nontoxic and are being consumed as tea and other beverages. CTA in rats is a considered parallel process to nausea and vomiting in human beings. These findings, put together, suggest that dietary supplements from Hippophae leaves could be developed for preventing behavioral changes in subjects exposed to radiation.

Drug versus sweet reward: greater attraction to and preference for sweet versus drug cues.

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Madsen, Heather B; Ahmed, Serge H

2015-05-01

Despite the unique ability of addictive drugs to directly activate brain reward circuits, recent evidence suggests that drugs induce reinforcing and incentive effects that are comparable to, or even lower than some nondrug rewards. In particular, when rats have a choice between pressing a lever associated with intravenous cocaine or heroin delivery and another lever associated with sweet water delivery, most respond on the latter. This outcome suggests that sweet water is more reinforcing and attractive than either drug. However, this outcome may also be due to the differential ability of sweet versus drug levers to elicit Pavlovian feeding-like conditioned responses that can cause involuntary lever pressing, such as pawing and biting the lever. To test this hypothesis, rats first underwent Pavlovian conditioning to associate one lever with sweet water (0.2% saccharin) and a different lever with intravenous cocaine (0.25 mg) or heroin (0.01 mg). Choice between these two levers was then assessed under two operant choice procedures: one that permitted the expression of Pavlovian-conditioned lever press responses during choice, the other not. During conditioning, Pavlovian-conditioned lever press responses were considerably higher on the sweet lever than on either drug lever, and slightly greater on the heroin lever than on the cocaine lever. Importantly, though these differences in Pavlovian-conditioned behavior predicted subsequent preference for sweet water during choice, they were not required for its expression. Overall, this study confirms that rats prefer the sweet lever because sweet water is more reinforcing and attractive than cocaine or heroin. © 2014 Society for the Study of Addiction.

Effect of combined doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea using rat (Sprague- Dawley) models of conditioned gaping.

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Rock, Erin M; Limebeer, Cheryl L; Parker, Linda A

2015-12-01

Δ(9)-Tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) found in cannabis both reduce the distressing symptom of nausea, but their combined effects are not understood. The potential of combined doses of THC and CBDA to reduce acute nausea and anticipatory nausea in rodent models was assessed. For acute nausea, the potential of cannabinoid pretreatment(s) to reduce LiCl-induced nausea paired with saccharin was evaluated in a subsequent drug free taste reactivity test, followed by a taste avoidance test. For anticipatory nausea, the potential of the cannabinoid pretreatment(s) to reduce the expression of LiCl-induced contextually elicited conditioned gaping was evaluated. Combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) reduced acute nausea. Higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses also reduced acute nausea. THC (10 mg/kg) interfered with conditioned taste avoidance, an effect attenuated by CBDA (10 μg/kg). On the other hand, combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) did not suppress contextually elicited conditioned gaping in a test for anticipatory nausea. However, higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses, also reduced anticipatory nausea. Only at the highest dose (10 mg/kg) did THC impair locomotor activity, but CBDA did not at any dose. Combined subthreshold doses of THC:CBDA are particularly effective as a treatment for acute nausea. At higher doses, CBDA may attenuate THC-induced interference with learning.

Novel 5-HT6 receptor antagonists/D2 receptor partial agonists targeting behavioral and psychological symptoms of dementia.

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Kołaczkowski, Marcin; Marcinkowska, Monika; Bucki, Adam; Śniecikowska, Joanna; Pawłowski, Maciej; Kazek, Grzegorz; Siwek, Agata; Jastrzębska-Więsek, Magdalena; Partyka, Anna; Wasik, Anna; Wesołowska, Anna; Mierzejewski, Paweł; Bienkowski, Przemyslaw

2015-03-06

We describe a novel class of designed multiple ligands (DMLs) combining serotonin 5-HT6 receptor (5-HT6R) antagonism with dopamine D2 receptor (D2R) partial agonism. Prototype hybrid molecules were designed using docking to receptor homology models. Diverse pharmacophore moieties yielded 3 series of hybrids with varying in vitro properties at 5-HT6R and D2R, and at M1 receptor and hERG channel antitargets. 4-(piperazin-1-yl)-1H-indole derivatives showed highest antagonist potency at 5-HT6R, with 7-butoxy-3,4-dihydroquinolin-2(1H)-one and 2-propoxybenzamide derivatives having promising D2R partial agonism. 2-(3-(4-(1-(phenylsulfonyl)-1H-indol-4-yl)piperazin-1-yl)propoxy)benzamide (47) exhibited nanomolar affinity at both 5-HT6R and D2R and was evaluated in rat models. It displayed potent antidepressant-like and anxiolytic-like activity in the Porsolt and Vogel tests, respectively, more pronounced than that of a reference selective 5-HT6R antagonist or D2R partial agonist. In addition, 47 also showed antidepressant-like activity (Porsolt's test) and anxiolytic-like activity (open field test) in aged (>18-month old) rats. In operant conditioning tests, 47 enhanced responding for sweet reward in the saccharin self-administration test, consistent with anti-anhedonic properties. Further, 47 facilitated extinction of non-reinforced responding for sweet reward, suggesting potential procognitive activity. Taken together, these studies suggest that DMLs combining 5-HT6R antagonism and D2R partial agonism may successfully target affective disorders in patients from different age groups without a risk of cognitive deficits. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Ciclamato de sódio e rim fetal Sodium cyclamate and fetal kidney

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José Germano Ferraz de Arruda

2003-06-01

Full Text Available O ciclamato é usado como adoçante artificial não calórico em diversos alimentos e bebidas, sendo 30 vezes mais doce que a sacarose sem o sabor amargo da sacarina. Aparece na composição dos produtos como ciclamato de sódio, ciclamato de cálcio e ácido ciclâmico. O ciclamato e a ciclohexilamina, seu principal metabólito, atravessam a barreira placentária em humanos e desse modo podem ser expostos ao feto. O rim de ratos pode ser afetado por elevadas doses de ciclamato de sódio. Estudos sobre efeitos do ciclamato de sódio na espécie humana são necessários, pois, além de poder substituir a sacarose - prejudicial em casos de diabetes ou quando o controle e a redução do peso corporal são essenciais para a saúde dos pacientes - não propicia desenvolvimento de cárie dentária.Cyclamate is used as an artificial non-caloric sweetener in a variety of foods and beverages, being 30 times as sweet as sugar without the bitter after-taste of saccharin. It is present in the formula of products such as sodium and calcium cyclamates and cyclamic acid. Cyclamate and cyclohexylamine, its principal metabolite, can cross the human placenta exposing the fetus. It has been demonstrated in rats that the kidney may be adversely affected by high doses of cyclamate. Studies on the effects of sodium cyclamate in the human species are necessary, because in addition to replacing saccharose - harmful in individuals with diabetes or patients in whom weight reduction and control are essential for health - it does not cause dental caries.

Evaluation of Brazilian light ketchups II: quantitative descriptive and physicochemical analysis Avaliação de catchups light do mercado brasileiro II: análise descritiva quantitativa e avaliação físico-química

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Gisele Cristina Maziero de Campos Bannwart

2008-03-01

Full Text Available Samples of ketchup available on the Brazilian market, one traditional (sweetened with sucrose and three light versions (sweetened with aspartame, acesulfame-K and a blend of cyclamate, saccharin and stevia were evaluated for their physicochemical characteristics and sensory profile (Quantitative Descriptive Analysis. Four main groups of attributes were generated: appearance, oral texture, aroma and flavor. The samples presented significant differences in all attributes, except for syneresis and overripe tomato flavor. The highest means for sweetener and bitter tastes and aftertastes were observed for the samples sweetened with acesulfame-K and the blend of sweeteners. Although different characteristics were observed among the products evaluated and, despite the differences in the formulations, the light ketchup sweetened with aspartame was the one that presented properties most similar to those of the traditional ketchup.Amostras de catchup disponíveis no mercado brasileiro, uma tradicional (adoçada com sacarose e três light (adoçadas com aspartame, acessulfame-K e uma combinação de ciclamato, sacarina e estévia foram avaliadas quanto às características físico-químicas e ao perfil sensorial (Análise Descritiva Quantitativa. Quatro grandes grupos de atributos foram gerados: aparência, textura bucal, aroma e sabor. As amostras apresentaram diferença significativa em todos os atributos, exceto sinerese e tomate passado. As maiores médias para os atributos relacionados a sabor e sabor residual amargo e de adoçante foram obtidas para as amostras adoçadas com acessulfame-K e com a combinação de edulcorantes. Apesar das diferentes características observadas entre os produtos avaliados e das diferenças entre as formulações, o catchup light adoçado com aspartame foi o que apresentou propriedades mais próximas ao produto tradicional.

Sensitivity to Chronic Methamphetamine Administration and Withdrawal in Mice with Relaxin-3/RXFP3 Deficiency.

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Haidar, Mouna; Lam, Monica; Chua, Berenice E; Smith, Craig M; Gundlach, Andrew L

2016-03-01

Methamphetamine (METH) is a highly addictive psychostimulant, and cessation of use is associated with reduced monoamine signalling, and increased anxiety/depressive states. Neurons expressing the neuropeptide, relaxin-3 (RLN3), and its cognate receptor, RXFP3, constitute a putative 'ascending arousal system', which shares neuroanatomical and functional similarities with serotonin (5-HT)/dorsal raphe and noradrenaline (NA)/locus coeruleus monoamine systems. In light of possible synergistic roles of RLN3 and 5-HT/NA, endogenous RLN3/RXFP3 signalling may compensate for the temporary reduction in monoamine signalling associated with chronic METH withdrawal, which could alter the profile of 'behavioural despair', bodyweight reductions, and increases in anhedonia and anxiety-like behaviours observed following chronic METH administration. In studies to test this theory, Rln3 and Rxfp3 knockout (KO) mice and their wildtype (WT) littermates were injected once daily with saline or escalating doses of METH (2 mg/kg, i.p. on day 1, 4 mg/kg, i.p. on day 2 and 6 mg/kg, i.p. on day 3-10). WT and Rln3 and Rxfp3 KO mice displayed an equivalent sensitivity to behavioural despair (Porsolt swim) during the 2-day METH withdrawal and similar bodyweight reductions on day 3 of METH treatment. Furthermore, during a 3-week period after the cessation of chronic METH exposure, Rln3 KO, Rxfp3 KO and corresponding WT mice displayed similar behavioural responses in paradigms that measured anxiety (light/dark box, elevated plus maze), anhedonia (saccharin preference), and social interaction. These findings indicate that a whole-of-life deficiency in endogenous RLN3/RXFP3 signalling does not markedly alter behavioural sensitivity to chronic METH treatment or withdrawal, but leave open the possibility of a more significant interaction with global or localised manipulations of this peptide system in the adult brain.

Selection and Evaluation of Chemical Indicators for Waste Stream Identification

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DeVita, W. M.; Hall, J.

2015-12-01

Human and animal wastes pose a threat to the quality of groundwater, surface water and drinking water. This is especially of concern for private and public water supplies in agricultural areas of Wisconsin where land spreading of livestock waste occurs on thin soils overlaying fractured bedrock. Current microbial source tracking (MST) methods for source identification requires the use of polymerase chain reaction (PCR) techniques. Due to cost, these tests are often not an option for homeowners, municipalities or state agencies with limited resources. The Water and Environmental Analysis Laboratory sought to develop chemical methods to provide lower cost processes to determine sources of fecal waste using fecal sterols, pharmaceuticals (human and veterinary) and human care/use products in ground and surface waters using solid phase extraction combined with triple quadrupole mass spectrometry. The two separate techniques allow for the detection of fecal sterol and other chemical markers in the sub part per billion-range. Fecal sterol ratios from published sources were used to evaluate drinking water samples and wastewater from onsite waste treatment systems and municipal wastewater treatment plants. Pharmaceuticals and personal care products indicative of human waste included: acetaminophen, caffeine, carbamazepine, cotinine, paraxanthine, sulfamethoxazole, and the artificial sweeteners; acesulfame, saccharin, and sucralose. The bovine antibiotic sulfamethazine was also targeted. Well water samples with suspected fecal contamination were analyzed for fecal sterols and PPCPs. Results were compared to traditional MST results from the Wisconsin State Laboratory of Hygiene. Chemical indicators were found in 6 of 11 drinking water samples, and 5 of 11 were in support of MST results. Lack of detection of chemical indicators in samples contaminated with fecal waste supports the need for confirmatory methods and advancement of chemical indicator detection technologies.

The novel non-imidazole histamine H3 receptor antagonist DL77 reduces voluntary alcohol intake and ethanol-induced conditioned place preference in mice.

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Bahi, Amine; Sadek, Bassem; Nurulain, Syed M; Łażewska, Dorota; Kieć-Kononowicz, Katarzyna

2015-11-01

It has become clear that histamine H3 receptors (H3R) have been implicated in modulating ethanol intake and preference in laboratory animals. The novel non-imidazole H3R antagonist DL77 with excellent selectivity profile shows high in-vivo potency as well as in-vitro antagonist affinity with ED50 of 2.1 ± 0.2 mg/kg and pKi=8.08, respectively. In the present study, and applying an unlimited access two-bottle choice procedure, the anti-alcohol effects of the H3R antagonist, DL77 (0, 3, 10 and 30 mg/kg; i.p.), were investigated in adult mice. In this C57BL/6 line, effects of DL77 on voluntary alcohol intake and preference, as well as on total fluid intake were evaluated. Results have shown that DL77, dose-dependently, reduced both ethanol intake and preference. These effects were very selective as both saccharin and quinine, used to control for taste sensitivity, and intakes were not affected following DL77 pre-application. More importantly, systemic administration of DL77 (10 mg/kg) during acquisition inhibited ethanol-induced conditioned-place preference (EtOH-CPP) as measured using an unbiased protocol. The anti-alcohol activity observed for DL77 was abrogated when mice were pretreated with the selective H3R agonist R-(α)-methyl-histamine (RAMH) (10 mg/kg), or with the CNS penetrant H1R antagonist pyrilamine (PYR) (10mg/kg). These results suggest that DL77 has a predominant role in two in vivo effects of ethanol. Therefore, signaling via H3R is essential for ethanol-related consumption and conditioned reward and may represent a novel therapeutic pharmacological target to tackle ethanol abuse and alcoholism. Copyright © 2015 Elsevier Inc. All rights reserved.

Low Caloric Sweeteners for Diabetes and Obesity Care and Their

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Mohammad Asif

2015-10-01

Full Text Available Diabetes and obesity are two common human disorders that affecting human health and invite various diseases and disorders in normal body functions. These diseases are very common worldwide. Diabetes occurs when high blood sugar levels develop. This happens when body can’t make and use all of the insulin it needs to blood sugar normally to keep blood sugar levels as normal as possible to control diabetes. Diabetic patients will need to follow a diet plan, do exercise and possibly take insulin injections. As part of eating plan, health care provider, and dietitian may ask to limit the amount of carbohydrates eat each day. Low-calorie sweeteners are one easy tool to help for follow eating plan. Obesity is more susceptible and often been associated with frequent ingestion of high energy food in high amount and high intake of sugars such as fermentable sugars such as sucrose, fructose, glucose, and maltose. Both diseases are may be genetically or due to hormonal imbalances. High energy sweeteners may causes caries in the teeth particularly susceptible to the children. Increased calorie intake associated with sugars and carbohydrates, especially when associated with physical inactivity, has been implicated in obesity. Fortunately, low calorie artificial and natural alternatives of sugars have been developed as alternatives to fermentable sugars and have shown promise in these health issues. Although there are only few artificial sweeteners (saccharin, aspartame, acesulfam potassium, sucralose, cyclamate that have been approved as food additives by the Food and Drug Administration and additional other low-caloric sweeteners (sugar alcohols, neotame, stevia, erythritol, xylitol, tagatose that have FDA-generally recognized as safe. Given the health impact of sugars and other carbohydrates, professionals should be aware of the marketed available low caloric sweeteners and both their benefits and potential risks.

Offspring of prenatal IV nicotine exposure exhibit increased sensitivity to the reinforcing effects of methamphetamine

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Steven Brown Harrod

2012-06-01

Full Text Available Maternal smoking during pregnancy is associated with increased substance abuse in offspring. Preclinical research shows that in utero exposure to nicotine, the primary psychoactive compound in tobacco smoke, influences the neurodevelopment of reward systems and alters motivated behavior in offspring. The present study determined if prenatal nicotine (PN exposure altered the sensitivity to the reinforcing and aversive effects of methamphetamine (METH in offspring using a low dose, intravenous (IV exposure method. Pregnant dams were administered nicotine (0.05 mg/kg/injection or prenatal saline (PS 3×/day on gestational days 8-21, and adult offspring were tested using METH self-administration (experiment 1 or METH-induced conditioned taste aversion (CTA; experiment 2 procedures. For METH self-administration, animals were trained to respond for IV METH (0.05 mg/kg/injection; fixed-ratio 3 and they were tested on varying doses the reinforcer (0.0005-1.0 mg/kg/injection. For METH CTA, rats received three saccharin and METH pairings (0, 0.3, or 0.5 mg/kg, sc followed by fourteen daily extinction trials. Experiment 1: PN and PS animals exhibited inverted U-shaped dose-response curves; however, the PN animal’s curve was shifted to the left, suggesting PN animals were more sensitive to the reinforcing effects of METH. Experiment 2: METH CTA was acquired in a dose-dependent manner and the factor of PN exposure was not related to the acquisition or extinction of METH-induced CTA. There were no sex differences in either experiment. These results indicate that adult offspring of IV PN exposure exhibited altered motivation for the reinforcing effects of METH. This suggests that PN exposure, via maternal smoking, will alter the reinforcing effects of METH during later stages of development, and furthermore, will influence substance use vulnerability in adult human offspring.

Expression of Na+/glucose co-transporter 1 (SGLT1) is enhanced by supplementation of the diet of weaning piglets with artificial sweeteners.

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Moran, Andrew W; Al-Rammahi, Miran A; Arora, Daleep K; Batchelor, Daniel J; Coulter, Erin A; Daly, Kristian; Ionescu, Catherine; Bravo, David; Shirazi-Beechey, Soraya P

2010-09-01

In an intensive livestock production, a shorter suckling period allows more piglets to be born. However, this practice leads to a number of disorders including nutrient malabsorption, resulting in diarrhoea, malnutrition and dehydration. A number of strategies have been proposed to overcome weaning problems. Artificial sweeteners, routinely included in piglets' diet, were thought to enhance feed palatability. However, it is shown in rodent models that when included in the diet, they enhance the expression of Na+/glucose co-transporter (SGLT1) and the capacity of the gut to absorb glucose. Here, we show that supplementation of piglets' feed with a combination of artificial sweeteners saccharin and neohesperidin dihydrochalcone enhances the expression of SGLT1 and intestinal glucose transport function. Artificial sweeteners are known to act on the intestinal sweet taste receptor T1R2/T1R3 and its partner G-protein, gustducin, to activate pathways leading to SGLT1 up-regulation. Here, we demonstrate that T1R2, T1R3 and gustducin are expressed together in the enteroendocrine cells of piglet intestine. Furthermore, gut hormones secreted by the endocrine cells in response to dietary carbohydrates, glucagon-like peptides (GLP)-1, GLP-2 and glucose-dependent insulinotrophic peptide (GIP), are co-expressed with type 1 G-protein-coupled receptors (T1R) and gustducin, indicating that L- and K-enteroendocrine cells express these taste elements. In a fewer endocrine cells, T1R are also co-expressed with serotonin. Lactisole, an inhibitor of human T1R3, had no inhibitory effect on sweetener-induced SGLT1 up-regulation in piglet intestine. A better understanding of the mechanism(s) involved in sweetener up-regulation of SGLT1 will allow the identification of nutritional targets with implications for the prevention of weaning-related malabsorption.

A mouse model for binge-like sucrose overconsumption: Contribution of enhanced motivation for sweetener consumption.

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Yasoshima, Yasunobu; Shimura, Tsuyoshi

2015-01-01

Behavioral and neural features of binge-like sugar overconsumption have been studied using rat models. However, few mouse models are available to examine the interaction between neural and genetic underpinnings of bingeing. In the present study, we first aim to establish a simple mouse model of binge-like sucrose overconsumption using daytime limited access training in food-restricted male mice. Trained mice received 4-h limited access to both 0.5M sucrose solution and chow for 10 days. Three control groups received (1) 4-h sucrose and 20-h chow access, (2) 20-h sucrose and 4-h, or (3) 20-h chow access, respectively. Only the trained group showed progressively increased sucrose consumption during brief periods of time and developed binge-like excessive behavior. Next, we examined whether the present mouse model mimicked a human feature of binge eating known as "eating when not physically hungry." Trained mice consumed significantly more sucrose or non-caloric sweetener (saccharin) during post-training days even after they nocturnally consumed substantial chow prior to daytime sweetener access. In other trained groups, both a systemic administration of glucose and substantial chow consumption prior to the daytime limited sucrose access failed to reduce binge-like sucrose overconsumption. Our results suggest that even when caloric consumption is not necessarily required, limited access training shapes and triggers binge-like overconsumption of sweetened solution in trained mice. The binge-like behavior in trained mice may be mainly due to enhanced hedonic motivation for the sweetener's taste. The present study suggests that our mouse model for binge-like sugar overconsumption may mimic some human features of binge eating and can be used to investigate the roles of neural and genetic mechanisms in binge-like overconsumption of sweetened substances in the absence of physical hunger. Copyright © 2014 Elsevier Inc. All rights reserved.

Artificial sweeteners--a recently recognized class of emerging environmental contaminants: a review.

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Lange, Frank T; Scheurer, Marco; Brauch, Heinz-J

2012-07-01

An overview is given of existing trace analytical methods for the determination of seven popular artificial sweeteners [acesulfame (ACE), aspartame, cyclamate (CYC), neotame, neohesperidine dihydrochalcone, saccharin (SAC), and sucralose (SUC)] from aqueous environmental samples. Liquid chromatography-electrospray ionization tandem mass spectrometry and liquid chromatography-electrospray ionization high-resolution mass spectrometry are the methods most widely applied, either directly or after solid-phase extraction. Limits of detection and limits of quantification down to the low nanogram per liter range can be achieved. ACE, CYC, SAC, and SUC were detected in wastewater treatment plants in high microgram per liter concentrations. Per capita loads of individual sweeteners can vary within a wide range depending on their use in different countries. Whereas CYC and SAC are usually degraded by more than 90% during wastewater treatment, ACE and SUC pass through wastewater treatment plants mainly unchanged. This suggests their use as virtually perfect markers for the study of the impact of wastewater on source waters and drinking waters. In finished water of drinking water treatment plants using surface-water-influenced source water, ACE and SUC were detected in concentrations up to 7 and 2.4 μg/L, respectively. ACE was identified as a precursor of oxidation byproducts during ozonation, resulting in an aldehyde intermediate and acetic acid. Although the concentrations of ACE and SUC are among the highest measured for anthropogenic trace pollutants found in surface water, groundwater, and drinking water, the levels are at least three orders of magnitude lower than organoleptic threshold values. However, ecotoxicology studies are scarce and have focused on SUC. Thus, further research is needed both on identification of transformation products and on the ecotoxicological impact of artificial sweeteners and their transformation products.

Preliminary evidence of apathetic-like behavior in aged vesicular monoamine transporter 2 deficient mice

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Aron Baumann

2016-11-01

Full Text Available Apathy is considered to be a core feature of Parkinson’s disease (PD and has been associated with a variety of states and symptoms of the disease, such as increased severity of motor symptoms, impaired cognition, executive dysfunction, and dementia. Apart from the high prevalence of apathy in PD, which is estimated to be about 40%, the underlying pathophysiology remains poorly understood and current treatment approaches are unspecific and proved to be only partially effective. In animal models, apathy has been sub-optimally modeled, mostly by means of pharmacological and stress-induced methods, whereby concomitant depressive-like symptoms could not be ruled out. In the context of PD only a few studies on toxin-based models (i.e. 6-OHDA or MPTP claimed to have determined apathetic symptoms in animals. The assessment of apathetic symptoms in more elaborated and multifaceted genetic animal models of PD could help to understand the pathophysiological development of apathy in PD and eventually advance specific treatments for afflicted patients. Here we report the presence of behavioral signs of apathy in 12 months old mice that express only ~5% of the vesicular monoamine transporter 2 (VMAT2. Apathetic-like behavior in VMAT2 deficient (LO mice was evidenced by impaired burrowing and nest building skills, and a reduced preference for sweet solution in the saccharin preference test, while the performance in the forced swimming test was normal. Our preliminary results suggest that VMAT2 deficient mice show an apathetic-like phenotype that might be independent of depressive-like symptoms. Therefore VMAT2 LO mice could be a useful tool to study of the pathophysiological substrates of apathy and to test novel treatment strategies for apathy in the context of PD.

A double-blind, placebo-controlled clinical trial of the effect of chlorpheniramine on the response of the nasal airway, middle ear and eustachian tube to provocative rhinovirus challenge.

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Doyle, W J; McBride, T P; Skoner, D P; Maddern, B R; Gwaltney, J M; Uhrin, M

1988-03-01

This paper presents the results of a randomized, double-blind, placebo-controlled study of the efficacy of chlorpheniramine in relieving the symptoms and attenuating the pathophysiologic correlates of a rhinovirus "common cold." Forty healthy, adult, nonatopic subjects were randomly assigned to one of two treatment groups: active drug and placebo. On study Day 0, all subjects were challenged intranasally with rhinovirus type 39 (dose = 100 TCID50). Subjects were cloistered from Day 2 to Day 7, at which time they were treated with either chlorpheniramine or placebo. From 3 days before challenge to study Day 19, subjects had nasal patency assessed by rhinomanometry, eustachian tube function assessed by the 9-step test and sonotubometry, middle ear pressure assessed by tympanometry and nasal clearance assessed by the dyed-saccharin technique. Symptom diaries were maintained throughout the period of follow-up. During cloister, symptoms also were scored by interview, nasal secretions were quantified and nasal washings were performed for viral culture. Results showed that 19 (95%) subjects in the active-treatment group and 18 (90%) subjects in the placebo-treatment group shed virus. Symptomatic colds were observed in 63% of the active-treated and 83% of the placebo-treated subjects. Symptoms increased on Day 1 and peaked at Days 4 to 5. Detrimental changes in other measured functions consistent with those previously reported were observed. During the period of treatment, significant differences in the average symptom scores favoring the active-treatment group were observed for sneezing. Also, weight of expelled secretions was greater and mucociliary clearance rate less on some cloister days for the placebo-treated group. No significant differences between treatment groups in the objective measures of nasal congestion or the response of the middle ear and eustachian tube were documented.

MeCP2 regulates ethanol sensitivity and intake.

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Repunte-Canonigo, Vez; Chen, Jihuan; Lefebvre, Celine; Kawamura, Tomoya; Kreifeldt, Max; Basson, Oan; Roberts, Amanda J; Sanna, Pietro Paolo

2014-09-01

We have investigated the expression of chromatin-regulating genes in the prefrontal cortex and in the shell subdivision of the nucleus accumbens during protracted withdrawal in mice with increased ethanol drinking after chronic intermittent ethanol (CIE) vapor exposure and in mice with a history of non-dependent drinking. We observed that the methyl-CpG binding protein 2 (MeCP2) was one of the few chromatin-regulating genes to be differentially regulated by a history of dependence. As MeCP2 has the potential of acting as a broad gene regulator, we investigated sensitivity to ethanol and ethanol drinking in MeCP2(308/) (Y) mice, which harbor a truncated MeCP2 allele but have a milder phenotype than MeCP2 null mice. We observed that MeCP2(308/) (Y) mice were more sensitive to ethanol's stimulatory and sedative effects than wild-type (WT) mice, drank less ethanol in a limited access 2 bottle choice paradigm and did not show increased drinking after induction of dependence with exposure to CIE vapors. Alcohol metabolism did not differ in MeCP2(308/) (Y) and WT mice. Additionally, MeCP2(308/) (Y) mice did not differ from WT mice in ethanol preference in a 24-hour paradigm nor in their intake of graded solutions of saccharin or quinine, suggesting that the MeCP2(308/) (Y) mutation did not alter taste function. Lastly, using the Gene Set Enrichment Analysis algorithm, we found a significant overlap in the genes regulated by alcohol and by MeCP2. Together, these results suggest that MeCP2 contributes to the regulation of ethanol sensitivity and drinking. © 2013 The Authors, Addiction Biology © 2013 Society for the Study of Addiction.

Ongoing ingestive behavior is rapidly suppressed by a preabsorptive, intestinal “bitter taste” cue

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Davidson, Terry L.; Powley, Terry L.

2011-01-01

The discovery that cells in the gastrointestinal (GI) tract express the same molecular receptors and intracellular signaling components known to be involved in taste has generated great interest in potential functions of such post-oral “taste” receptors in the control of food intake. To determine whether taste cues in the GI tract are detected and can directly influence behavior, the present study used a microbehavioral analysis of intake, in which rats drank from lickometers that were programmed to simultaneously deliver a brief yoked infusion of a taste stimulus to the intestines. Specifically, in daily 30-min sessions, thirsty rats with indwelling intraduodenal catheters were trained to drink hypotonic (0.12 M) sodium chloride (NaCl) and simultaneously self-infuse a 0.12 M NaCl solution. Once trained, in a subsequent series of intestinal taste probe trials, rats reduced licking during a 6-min infusion period, when a bitter stimulus denatonium benzoate (DB; 10 mM) was added to the NaCl vehicle for infusion, apparently conditioning a mild taste aversion. Presentation of the DB in isomolar lithium chloride (LiCl) for intestinal infusions accelerated the development of the response across trials and strengthened the temporal resolution of the early licking suppression in response to the arrival of the DB in the intestine. In an experiment to evaluate whether CCK is involved as a paracrine signal in transducing the intestinal taste of DB, the CCK-1R antagonist devazepide partially blocked the response to intestinal DB. In contrast to their ability to detect and avoid the bitter taste in the intestine, rats did not modify their licking to saccharin intraduodenal probe infusions. The intestinal taste aversion paradigm developed here provides a sensitive and effective protocol for evaluating which tastants—and concentrations of tastants—in the lumen of the gut can control ingestion. PMID:21865540

Intragastric preloads of l-tryptophan reduce ingestive behavior via oxytocinergic neural mechanisms in male mice.

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Gartner, Sarah N; Aidney, Fraser; Klockars, Anica; Prosser, Colin; Carpenter, Elizabeth A; Isgrove, Kiriana; Levine, Allen S; Olszewski, Pawel K

2018-06-01

Human and laboratory animal studies suggest that dietary supplementation of a free essential amino acid, l-tryptophan (TRP), reduces food intake. It is unclear whether an acute gastric preload of TRP decreases consumption and whether central mechanisms underlie TRP-driven hypophagia. We examined the effect of TRP administered via intragastric gavage on energy- and palatability-induced feeding in mice. We sought to identify central mechanisms through which TRP suppresses appetite. Effects of TRP on consumption of energy-dense and energy-dilute tastants were established in mice stimulated to eat by energy deprivation or palatability. A conditioned taste aversion (CTA) paradigm was used to assess whether hypophagia is unrelated to sickness. c-Fos immunohistochemistry was employed to detect TRP-induced activation of feeding-related brain sites and of oxytocin (OT) neurons, a crucial component of satiety circuits. Also, expression of OT mRNA was assessed with real-time PCR. The functional importance of OT in mediating TRP-driven hypophagia was substantiated by showing the ability of OT receptor blockade to abolish TRP-induced decrease in feeding. TRP reduced intake of energy-dense standard chow in deprived animals and energy-dense palatable chow in sated mice. Anorexigenic doses of TRP did not cause a CTA. TRP failed to affect intake of palatable yet calorie-dilute or noncaloric solutions (10% sucrose, 4.1% Intralipid or 0.1% saccharin) even for TRP doses that decreased water intake in thirsty mice. Fos analysis revealed that TRP increases activation of several key feeding-related brain areas, especially in the brain stem and hypothalamus. TRP activated hypothalamic OT neurons and increased OT mRNA levels, whereas pretreatment with an OT antagonist abolished TRP-driven hypophagia. We conclude that intragastric TRP decreases food and water intake, and TRP-induced hypophagia is partially mediated via central circuits that encompass OT. Copyright © 2018 Elsevier Ltd. All

Ongoing ingestive behavior is rapidly suppressed by a preabsorptive, intestinal "bitter taste" cue.

Science.gov (United States)

Schier, Lindsey A; Davidson, Terry L; Powley, Terry L

2011-11-01

The discovery that cells in the gastrointestinal (GI) tract express the same molecular receptors and intracellular signaling components known to be involved in taste has generated great interest in potential functions of such post-oral "taste" receptors in the control of food intake. To determine whether taste cues in the GI tract are detected and can directly influence behavior, the present study used a microbehavioral analysis of intake, in which rats drank from lickometers that were programmed to simultaneously deliver a brief yoked infusion of a taste stimulus to the intestines. Specifically, in daily 30-min sessions, thirsty rats with indwelling intraduodenal catheters were trained to drink hypotonic (0.12 M) sodium chloride (NaCl) and simultaneously self-infuse a 0.12 M NaCl solution. Once trained, in a subsequent series of intestinal taste probe trials, rats reduced licking during a 6-min infusion period, when a bitter stimulus denatonium benzoate (DB; 10 mM) was added to the NaCl vehicle for infusion, apparently conditioning a mild taste aversion. Presentation of the DB in isomolar lithium chloride (LiCl) for intestinal infusions accelerated the development of the response across trials and strengthened the temporal resolution of the early licking suppression in response to the arrival of the DB in the intestine. In an experiment to evaluate whether CCK is involved as a paracrine signal in transducing the intestinal taste of DB, the CCK-1R antagonist devazepide partially blocked the response to intestinal DB. In contrast to their ability to detect and avoid the bitter taste in the intestine, rats did not modify their licking to saccharin intraduodenal probe infusions. The intestinal taste aversion paradigm developed here provides a sensitive and effective protocol for evaluating which tastants-and concentrations of tastants-in the lumen of the gut can control ingestion.

Enhanced flavor-nutrient conditioning in obese rats on a high-fat, high-carbohydrate choice diet.

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Wald, Hallie S; Myers, Kevin P

2015-11-01

Through flavor-nutrient conditioning rats learn to prefer and increase their intake of flavors paired with rewarding, postingestive nutritional consequences. Since obesity is linked to altered experience of food reward and to perturbations of nutrient sensing, we investigated flavor-nutrient learning in rats made obese using a high fat/high carbohydrate (HFHC) choice model of diet-induced obesity (ad libitum lard and maltodextrin solution plus standard rodent chow). Forty rats were maintained on HFHC to induce substantial weight gain, and 20 were maintained on chow only (CON). Among HFHC rats, individual differences in propensity to weight gain were studied by comparing those with the highest proportional weight gain (obesity prone, OP) to those with the lowest (obesity resistant, OR). Sensitivity to postingestive food reward was tested in a flavor-nutrient conditioning protocol. To measure initial, within-meal stimulation of flavor acceptance by post-oral nutrient sensing, first, in sessions 1-3, baseline licking was measured while rats consumed grape- or cherry-flavored saccharin accompanied by intragastric (IG) water infusion. Then, in the next three test sessions they received the opposite flavor paired with 5 ml of IG 12% glucose. Finally, after additional sessions alternating between the two flavor-infusion contingencies, preference was measured in a two-bottle choice between the flavors without IG infusions. HFHC-OP rats showed stronger initial enhancement of intake in the first glucose infusion sessions than CON or HFHC-OR rats. OP rats also most strongly preferred the glucose-paired flavor in the two-bottle choice. These differences between OP versus OR and CON rats suggest that obesity is linked to responsiveness to postoral nutrient reward, consistent with the view that flavor-nutrient learning perpetuates overeating in obesity. Copyright © 2015 Elsevier Inc. All rights reserved.

High-performance ion mobility spectrometry with direct electrospray ionization (ESI-HPIMS) for the detection of additives and contaminants in food

International Nuclear Information System (INIS)

Midey, Anthony J.; Camacho, Amanda; Sampathkumaran, Jayanthi; Krueger, Clinton A.; Osgood, Mark A.; Wu, Ching

2013-01-01

Graphical abstract: -- Highlights: •A new ESI source was built for direct ionization from syringe. •Phthalates, food dyes, and sweeteners detected with high-performance IMS. •Phthalates directly detected in cola, soy bubble tea matrices with simple treatment. -- Abstract: High-performance ion mobility spectrometry (HPIMS) with an electrospray ionization (ESI) source detected a series of food contaminants and additive compounds identified as critical to monitoring the safety of food samples. These compounds included twelve phthalate plasticizers, legal and illegal food and cosmetic dyes, and artificial sweeteners that were all denoted as detection priorities. HPIMS separated and detected the range of compounds with a resolving power better than 60 in both positive and negative ion modes, comparable to the commonly used high-performance liquid chromatography (HPLC) methods, but with most acquisition times under a minute. The reduced mobilities, K 0 , have been determined, as have the linear response ranges for ESI-HPIMS, which are 1.5–2 orders of magnitude for concentrations down to sub-ng μL −1 levels. At least one unique mobility peak was seen for two subsets of the phthalates grouped by the country where they were banned. Furthermore, ESI-HPIMS successfully detected low nanogram levels of a phthalate at up to 30 times lower concentration than international detection levels in both a cola matrix and a soy-based bubble tea beverage using only a simplified sample treatment. A newly developed direct ESI source (Directspray) was combined with HPIMS to detect food-grade dyes and industrial dye adulterants, as well as the sweeteners sodium saccharin and sodium cyclamate, with the same good performance as with the phthalates. However, the Directspray method eliminated sources of carryover and decreased the time between sample runs. Limits-of-detection (LOD) for the analyte standards were estimated to be sub-ng μL −1 levels without extensive sample handling

Effect of combined oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models.

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Rock, Erin M; Connolly, Cassidy; Limebeer, Cheryl L; Parker, Linda A

2016-09-01

The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea. The objective of this study was to determine the effect of combining subthreshold oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models of conditioned gaping. The potential of intragastric (i.g.) administration of THC, CBDA, or combined doses, to interfere with acute nausea-induced conditioned gaping (acute nausea) or the expression of contextually elicited conditioned gaping (anticipatory nausea), was evaluated. For acute nausea, i.g. administration of subthreshold doses of THC (0.5 and 1 mg/kg) or CBDA (0.5 and 1 μg/kg) significantly suppressed acute nausea-induced gaping, whereas higher individual doses of both THC and CBDA were maximally effective. Combined i.g. administration of higher doses of THC and CBDA (2.5 mg/kg THC-2.5 μg/kg CBDA; 10 mg/kg THC-10 μg/kg CBDA; 20 mg/kg THC-20 μg/kg CBDA) also enhanced positive hedonic reactions elicited by saccharin solution during conditioning. For anticipatory nausea, combined subthreshold i.g. doses of THC (0.1 mg/kg) and CBDA (0.1 μg/kg) suppressed contextually elicited conditioned gaping. When administered i.g., THC was effective on its own at doses ranging from 1 to 10 mg/kg, but CBDA was only effective at 10 μg/kg. THC alone was equally effective by intraperitoneal (i.p.) and i.g. administration, whereas CBDA alone was more effective by i.p. administration (Rock et al. in Psychopharmacol (Berl) 232:4445-4454, 2015) than by i.g. administration. Oral administration of subthreshold doses of THC and CBDA may be an effective new treatment for acute nausea and anticipatory nausea and appetite enhancement in chemotherapy patients.

Delta-9-tetrahydrocannabinol (THC) history fails to affect THC's ability to induce place preferences in rats.

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Hempel, Briana J; Wakeford, Alison G P; Clasen, Matthew M; Friar, Mary A; Riley, Anthony L

2016-05-01

In pre-clinical models of marijuana abuse, there is relatively limited evidence of delta-9-tetrahydrocannabinol's (THC) rewarding effects, as indexed by its general inability to induce a place preference. One explanation for this failure is that its rewarding effects are masked by its concurrently occurring aversive properties. Consistent with this explanation, THC pre-exposure, which presumably weakens its aversive effects, induces place preferences. Such demonstrations are limited to mice and given reported species differences in THC reactivity, it is unknown to what extent the same shift in affective properties would be evident in rats. The present experiment examined the effect of THC history (3.2mg/kg) on THC (1 or 3.2mg/kg) induced place preference conditioning in rats. An assessment of taste avoidance was also run to independently characterize THC's aversive effects and any changes that occurred with drug pre-exposure. These assessments were made in a combined taste avoidance/place preference procedure in which a novel saccharin solution and environment were paired with THC (0, 1 or 3.2mg/kg). THC did not induce place conditioning, and a history of THC was ineffective in increasing THC's ability to do so, despite the fact that this same history significantly attenuated the aversive effects of THC. The failure of THC to consistently induce place preferences has been argued to be a function of its concurrently occurring aversive effects masking its rewarding properties. The fact that pre-exposure to THC significantly reduced its aversive effects without impacting THC's ability to induce place preferences suggests that THC has weak rewarding effects and/or its residual aversive affects may have still masked its rewarding properties. An important area for future work will be characterizing under what conditions THC is rewarding and whether its overall reinforcing effects are impacted by the relationship between its affective properties. Copyright © 2016

Effects of Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] on the urinary bladder of male Wistar rats

International Nuclear Information System (INIS)

Nascimento, Merielen Garcia; Cotrim Sartor de Oliveira, Maria Luiza; Lima, Adriano Silva; Camargo, Joao Lauro Viana de

2006-01-01

Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide widely used on agricultural crops such as soy, cotton and sugar cane. In a previous long-term study this herbicide exerted carcinogenic activity on the urinary bladder mucosa of male Wistar rats. In general, the genotoxic and mutagenic potentials of Diuron are considered to be negative. The present study aimed to evaluate the mode of action of Diuron on the urinary bladder mucosa of male Wistar rats. Six-week old male Wistar rats were fed pelleted Nuvilab diet mixed with Diuron at 125, 500 and 2500 ppm. As a positive control, 8.3% sodium saccharin (NaS) was fed in the diet. Preceding the sacrifice of the animals at the 20th week, urinary pH was measured and the genotoxic potential of Diuron was evaluated by the comet assay. Histological urothelial lesions in the urinary bladder and in the renal pelvis mucosa, cell proliferation/apoptosis evaluations, and scanning electron microscopy (SEM) of the urinary bladder mucosa were also performed. No DNA changes were found in urothelial or peripheral blood cells, and urinary pH was comparable to controls in all Diuron groups. In the urinary bladder urothelium, the incidence of simple hyperplasia (SH) by light microscopy was significantly increased (7/10; p < 0.005) in the 2500 ppm Diuron group but not at the lower doses. By SEM, three of five animals treated with 2500 ppm Diuron showed urothelial cell necrosis and hyperplasia. In the renal pelvis, the incidence of SH was significantly increased in the Diuron 500 and 2500 ppm and in the NaS 8.3% groups. Cell proliferation was significantly increased in the Diuron 2500 ppm (p < 0.05) and NaS 8.3% (p < 0.05) groups. The results indicate that a high dietary concentration of Diuron is associated with urothelial necrosis and continuous regenerative cell proliferation that leads to urothelial hyperplasia

Ethanol intake under social circumstances or alone in sprague-dawley rats: impact of age, sex, social activity, and social anxiety-like behavior.

Science.gov (United States)

Varlinskaya, Elena I; Truxell, Eric M; Spear, Linda P

2015-01-01

In human adolescents, heavy drinking is often predicted by high sociability in males and high social anxiety in females. This study assessed the impact of baseline levels of social activity and social anxiety-like behavior in group-housed adolescent and adult male and female Sprague-Dawley rats on ethanol (EtOH) intake when drinking alone or in a social group. Social activity and anxiety-like behavior initially were assessed in a modified social interaction test, followed by 6 drinking sessions that occurred every other day in animals given ad libitum food and water. Sessions consisted of 30-minute access to 10% EtOH in a "supersac" (3% sucrose + 0.1% saccharin) solution given alone as well as in groups of 5 same-sex littermates, with order of the alternating session types counterbalanced across animals. Adolescent males and adults of both sexes overall consumed more EtOH under social than alone circumstances, whereas adolescent females ingested more EtOH when alone. Highly socially active adolescent males demonstrated elevated levels of EtOH intake relative to their low and medium socially active counterparts when drinking in groups, but not when tested alone. Adolescent females with high levels of social anxiety-like behavior demonstrated the highest EtOH intake under social, but not alone circumstances. Among adults, baseline levels of social anxiety-like behavior did not contribute to individual differences in EtOH intake in either sex. The results clearly demonstrate that in adolescent rats, but not their adult counterparts, responsiveness to a social peer predicts EtOH intake in a social setting-circumstances under which drinking typically occurs in human adolescents. High levels of social activity in males and high levels of social anxiety-like behavior in females were associated with elevated social drinking, suggesting that males ingest EtOH for its socially enhancing properties, whereas females ingest EtOH for its socially anxiolytic effects. Copyright

Inhibition of urokinase plasminogen activator “uPA” activity alters ethanol consumption and conditioned place preference in mice

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Al Maamari E

2014-09-01

Full Text Available Elyazia Al Maamari,* Mouza Al Ameri, Shamma Al Mansouri, Amine Bahi*Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates*These authors contributed equally to this workAbstract: Urokinase plasminogen activator, uPA, is a serine protease implicated in addiction to drugs of abuse. Using its specific inhibitor, B428, we and others have characterized the role of uPA in the rewarding properties of psychostimulants, including cocaine and amphetamine, but none have examined the role of uPA in ethanol use disorders. Therefore, in the current study, we extended our observations to the role of uPA in ethanol consumption and ethanol-induced conditioned place preference. The general aim of the present series of experiments was to investigate the effects of the administration of the B428 on voluntary alcohol intake and ethanol conditioned reward. A two-bottle choice, unlimited-access paradigm was used to compare ethanol intake between vehicle- and 3, 10, and 30 mg/kg B428-administered mice. For this purpose, the mice were presented with an ethanol solution (2.5%–20% and water, at each concentration for 4 days, and their consumption was measured daily. Consumption of saccharin and quinine solutions was also measured. Systemic administration of B428 dose-dependently decreased ethanol intake and preference. Additionally, B428 mice did not differ from vehicle mice in their intake of graded solutions of tastants, suggesting that the uPA inhibition did not alter taste function. Also, ethanol metabolism was not affected following B428 injection. More importantly, 1.5 g/kg ethanol-induced conditioned place preference acquisition was blocked following B428 administration. Taken together, our results are the first to implicate uPA inhibition in the regulation of ethanol consumption and preference, and suggest that uPA may be considered as a possible therapeutic drug target for alcoholism and

Erosive and cariogenicity potential of pediatric drugs: study of physicochemical parameters.

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Xavier, Alidianne Fábia C; Moura, Eline F F; Azevedo, Waldeneide F; Vieira, Fernando F; Abreu, Mauro H N G; Cavalcanti, Alessandro L

2013-12-10

Pediatric medications may possess a high erosive potential to dental tissues due to the existence of acid components in their formulations. The purpose was to determine the erosive and cariogenic potential of pediatric oral liquid medications through the analysis of their physicochemical properties in vitro. A total of 59 substances were selected from the drug reference list of the National Health Surveillance Agency (ANVISA), which belong to 11 therapeutic classes, as follows: analgesics, non-steroidal anti-inflammatory, corticosteroids, antihistamines, antitussives, bronchodilators, antibacterials, antiparasitics, antiemetics, anticonvulsants and antipsychotics. Measurement of pH was performed by potentiometry, using a digital pH meter. For the Total Titratable Acidity (TTA) chemical assay, a 0.1 N NaOH standard solution was used, which was titrated until drug pH was neutralized. The Total Soluble Solids Contents (TSSC) quantification was carried out by refractometry using Brix scale and the analysis of Total Sugar Content was performed according to Fehling's method. In addition, it was analyzed the information contained in the drug inserts with regard to the presence of sucrose and type of acid and sweetener added to the formulations. All drug classes showed acidic pH, and the lowest mean was found for antipsychotics (2.61 ± 0.08). There was a large variation in the TTA (0.1% - 1.18%) and SST (10.44% - 57.08%) values. High total sugar contents were identified in the antitussives (53.25%) and anticonvulsants (51.75%). As described in the drug inserts, sucrose was added in 47.5% of the formulations, as well as citric acid (39.0%), sodium saccharin (36.4%) and sorbitol (34.8%). The drugs analyzed herein showed physicochemical characteristics indicative of a cariogenic and erosive potential on dental tissues. Competent bodies' strategies should be implemented in order to broaden the knowledge of health professionals, drug manufacturers and general consuming public

High-performance ion mobility spectrometry with direct electrospray ionization (ESI-HPIMS) for the detection of additives and contaminants in food

Energy Technology Data Exchange (ETDEWEB)

Midey, Anthony J., E-mail: anthony.midey@excellims.com; Camacho, Amanda; Sampathkumaran, Jayanthi; Krueger, Clinton A.; Osgood, Mark A.; Wu, Ching

2013-12-04

Graphical abstract: -- Highlights: •A new ESI source was built for direct ionization from syringe. •Phthalates, food dyes, and sweeteners detected with high-performance IMS. •Phthalates directly detected in cola, soy bubble tea matrices with simple treatment. -- Abstract: High-performance ion mobility spectrometry (HPIMS) with an electrospray ionization (ESI) source detected a series of food contaminants and additive compounds identified as critical to monitoring the safety of food samples. These compounds included twelve phthalate plasticizers, legal and illegal food and cosmetic dyes, and artificial sweeteners that were all denoted as detection priorities. HPIMS separated and detected the range of compounds with a resolving power better than 60 in both positive and negative ion modes, comparable to the commonly used high-performance liquid chromatography (HPLC) methods, but with most acquisition times under a minute. The reduced mobilities, K{sub 0}, have been determined, as have the linear response ranges for ESI-HPIMS, which are 1.5–2 orders of magnitude for concentrations down to sub-ng μL{sup −1} levels. At least one unique mobility peak was seen for two subsets of the phthalates grouped by the country where they were banned. Furthermore, ESI-HPIMS successfully detected low nanogram levels of a phthalate at up to 30 times lower concentration than international detection levels in both a cola matrix and a soy-based bubble tea beverage using only a simplified sample treatment. A newly developed direct ESI source (Directspray) was combined with HPIMS to detect food-grade dyes and industrial dye adulterants, as well as the sweeteners sodium saccharin and sodium cyclamate, with the same good performance as with the phthalates. However, the Directspray method eliminated sources of carryover and decreased the time between sample runs. Limits-of-detection (LOD) for the analyte standards were estimated to be sub-ng μL{sup −1} levels without extensive

Preclinical evidence of rapid-onset antidepressant-like effect in Radix Polygalae extract.

Directory of Open Access Journals (Sweden)

Im-Joon Shin

Full Text Available Radix Polygalae (the root of Polygala tenuifolia is a herb widely used in traditional Asian medicine that is thought to exert a variety of neuropsychiatric effects. Radix Polygalae extract can protect against N-methyl D-aspartate (NMDA neurotoxicity and induce brain-derived neurotrophic factor (BDNF expression, suggesting modulatory roles at glutamatergic synapses and possible antidepressant action. In accordance with this hypothesis, Radix Polygalae extract demonstrated antidepressant-like effects in 8-week-old male C57Bl/6 mice by decreasing behavioral despair in the forced swim and tail suspension tasks and increasing hedonic-like behavior in the female urine sniffing test 30 minutes after a single oral administration of 0.1 mg/kg. Reduced latency to acquire a food pellet in the novely suppressed feeding paradigm, without change in anxiety-like behaviors suggested a rapid-onset nature of the antidepressant-like effect. In addition, it decreased the number of failed escapes in the learned helplessness paradigm after two oral administrations 24 hours and 30 minutes before the first test. Finally, it reversed anhedonia as measured by saccharin preference in mice exposed to the chronic stress model after two administrations of 0.1 mg/kg, in contrast to the repeated administration generally needed for similar effect by monoamergic antidepressants. Immobility reduction in tail suspension task was blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptor antagonist NBQX, a pattern previously demonstrated by ketamine and other ketamine-like rapid-onset antidepressants. Also similarly to ketamine, Radix Polygalae appeared to acutely decrease phosphorylation of GluR1 serine-845 in the hippocampus while leaving the phosphorylation of hippocampal mTOR serine 2448 unchanged. These findings serve as preclinical evidence that Radix Polygalae extract exerts rapid-onset antidepressant effects by modulating glutamatergic synapses in

Detection of 10 sweeteners in various foods by liquid chromatography/tandem mass spectrometry

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Chui-Shiang Chang

2014-09-01

Full Text Available The analytical method for sweeteners in various food matrixes is very important for food quality control and regulation enforcement. A simple and rapid method for the simultaneous determination of 10 sweeteners [acesulfame potassium (ACS-K, aspartame (ASP, cyclamate (CYC, dulcin (DUL, glycyrrhizic acid (GA, neotame (NEO, neohesperidin dihydrochalcone (NHDC, saccharin (SAC, sucralose (SCL, and stevioside (STV] in various foods by liquid chromatography/tandem mass chromatography (LC–MS/MS was developed. The chromatographic separation was performed on a Phenomenex Luna Phenyl-Hexyl (5 μm, 4.6 mm × 150 mm column with gradient elution of 10 mM ammonium acetate in water and 10 mM ammonium acetate in methanol. The recoveries of the 10 sweeteners were between 75% and 120%, and the coefficients of variation were less than 20%. The limits of quantification were 0.5 μg/kg for NHDC and SCL. For the other sweeteners, the limits of quantification were 0.1 μg/kg. Compared to the traditional high-performance liquid chromatography method, the LC–MS/MS method could provide better sensitivity, higher throughput, enhanced specificity, and more sweeteners analyzed in a single run. The samples included 27 beverages (16 alcoholic and 11 nonalcoholic beverages and 15 pickled foods (1 pickled pepper, 3 candies, and 11 candied fruits. Two remanufactured wines were found to contain 7.2, 8.5 μg/g SAC and 126.5, 123 μg/g CYC, respectively. ACS-K, ASP, SCL, and NEO were detected in five beverages and drinks. The pickled peppers and candied fruits were found to contain SAC, GA, CYC, ASP, STV, NEO, and ACS-K. The wine with sweeteners detected was remanufactured wine, not naturally fermented wine. Therefore, the ingredient label for the sweeteners of remanufactured wine should be regulated by the proper authority for inspection of sweeteners.

Mass loading of typical artificial sweeteners in a pig farm and their dissipation and uptake by plants in neighboring farmland.

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Ma, Ling; Liu, Yarui; Xu, Jiayao; Sun, Hongwen; Chen, Hao; Yao, Yiming; Zhang, Peng; Shen, Fengju; Alder, Aldredo C

2017-12-15

Pig farm is an important potential source for artificial sweeteners (ASs) in the environment due to their wide use as additives in pig feed. The objective of this study was to evaluate the fate of typical ASs in pig farm and neighboring farmland. For this purpose, the levels of four typical artificial ASs, i.e. saccharin (SAC), cyclamate (CYC), acesulfame (ACE) and sucralose (SUC), in pig feed and manure from a pig farm and water samples from an on-farm wastewater treatment plant (WWTP) in Tianjin, China were measured and the mass loadings and removal efficiencies were assessed. Moreover, the levels of ASs in different layers of soil and vegetables in neighboring farmland that received manure fertilizers and wastewater from the farm were consecutively monitored for 60-80days. The SAC, CYC and ACE were widely determined in all kinds of the samples, while SUC was only found in few soil samples. The mass loadings of the ASs in pig feed were estimated up to 311kg/year for SAC, 59.1kg/year for CYC, and 17.1kg/year for ACE, respectively. The fractions of the total mass of ASs excreted via manure were estimated to be 36.0% for SAC, 59.4% for CYC, and 36.7% for ACE as compared to those in pig feed. High removal efficiencies (>90%) of ASs in the on-farm WWTP was achieved. In greenhouse soils, CYC, SAC, ACE, and SUC were degraded quickly, with half-lives of 4.3-5.9 d, 2.7-4.2 d, 8.4-12.3 d, and 7.3-10.8 d, respectively. Lower levels of ASs were found in deeper soil layer (20-30cm). The ASs were considerably absorbed by plants when the ASs' concentrations were high in soil. This study presents the first comprehensive overview of ASs fate from a pig farm to the neighboring agricultural ecosystem. Copyright © 2017. Published by Elsevier B.V.

Oxytocin signaling in mouse taste buds.

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Sinclair, Michael S; Perea-Martinez, Isabel; Dvoryanchikov, Gennady; Yoshida, Masahide; Nishimori, Katsuhiko; Roper, Stephen D; Chaudhari, Nirupa

2010-08-05

The neuropeptide, oxytocin (OXT), acts on brain circuits to inhibit food intake. Mutant mice lacking OXT (OXT knockout) overconsume salty and sweet (i.e. sucrose, saccharin) solutions. We asked if OXT might also act on taste buds via its receptor, OXTR. Using RT-PCR, we detected the expression of OXTR in taste buds throughout the oral cavity, but not in adjacent non-taste lingual epithelium. By immunostaining tissues from OXTR-YFP knock-in mice, we found that OXTR is expressed in a subset of Glial-like (Type I) taste cells, and also in cells on the periphery of taste buds. Single-cell RT-PCR confirmed this cell-type assignment. Using Ca2+ imaging, we observed that physiologically appropriate concentrations of OXT evoked [Ca2+]i mobilization in a subset of taste cells (EC50 approximately 33 nM). OXT-evoked responses were significantly inhibited by the OXTR antagonist, L-371,257. Isolated OXT-responsive taste cells were neither Receptor (Type II) nor Presynaptic (Type III) cells, consistent with our immunofluorescence observations. We also investigated the source of OXT peptide that may act on taste cells. Both RT-PCR and immunostaining suggest that the OXT peptide is not produced in taste buds or in their associated nerves. Finally, we also examined the morphology of taste buds from mice that lack OXTR. Taste buds and their constituent cell types appeared very similar in mice with two, one or no copies of the OXTR gene. We conclude that OXT elicits Ca2+ signals via OXTR in murine taste buds. OXT-responsive cells are most likely a subset of Glial-like (Type I) taste cells. OXT itself is not produced locally in taste tissue and is likely delivered through the circulation. Loss of OXTR does not grossly alter the morphology of any of the cell types contained in taste buds. Instead, we speculate that OXT-responsive Glial-like (Type I) taste bud cells modulate taste signaling and afferent sensory output. Such modulation would complement central pathways of appetite

Defects in the peripheral taste structure and function in the MRL/lpr mouse model of autoimmune disease.

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Agnes Kim

Full Text Available While our understanding of the molecular and cellular aspects of taste reception and signaling continues to improve, the aberrations in these processes that lead to taste dysfunction remain largely unexplored. Abnormalities in taste can develop in a variety of diseases, including infections and autoimmune disorders. In this study, we used a mouse model of autoimmune disease to investigate the underlying mechanisms of taste disorders. MRL/MpJ-Fas(lpr/J (MRL/lpr mice develop a systemic autoimmunity with phenotypic similarities to human systemic lupus erythematosus and Sjögren's syndrome. Our results show that the taste tissues of MRL/lpr mice exhibit characteristics of inflammation, including infiltration of T lymphocytes and elevated levels of some inflammatory cytokines. Histological studies reveal that the taste buds of MRL/lpr mice are smaller than those of wild-type congenic control (MRL/+/+ mice. 5-Bromo-2'-deoxyuridine (BrdU pulse-chase experiments show that fewer BrdU-labeled cells enter the taste buds of MRL/lpr mice, suggesting an inhibition of taste cell renewal. Real-time RT-PCR analyses show that mRNA levels of several type II taste cell markers are lower in MRL/lpr mice. Immunohistochemical analyses confirm a significant reduction in the number of gustducin-positive taste receptor cells in the taste buds of MRL/lpr mice. Furthermore, MRL/lpr mice exhibit reduced gustatory nerve responses to the bitter compound quinine and the sweet compound saccharin and reduced behavioral responses to bitter, sweet, and umami taste substances compared with controls. In contrast, their responses to salty and sour compounds are comparable to those of control mice in both nerve recording and behavioral experiments. Together, our results suggest that type II taste receptor cells, which are essential for bitter, sweet, and umami taste reception and signaling, are selectively affected in MRL/lpr mice, a model for autoimmune disease with chronic

Oxytocin signaling in mouse taste buds.

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Michael S Sinclair

2010-08-01

Full Text Available The neuropeptide, oxytocin (OXT, acts on brain circuits to inhibit food intake. Mutant mice lacking OXT (OXT knockout overconsume salty and sweet (i.e. sucrose, saccharin solutions. We asked if OXT might also act on taste buds via its receptor, OXTR.Using RT-PCR, we detected the expression of OXTR in taste buds throughout the oral cavity, but not in adjacent non-taste lingual epithelium. By immunostaining tissues from OXTR-YFP knock-in mice, we found that OXTR is expressed in a subset of Glial-like (Type I taste cells, and also in cells on the periphery of taste buds. Single-cell RT-PCR confirmed this cell-type assignment. Using Ca2+ imaging, we observed that physiologically appropriate concentrations of OXT evoked [Ca2+]i mobilization in a subset of taste cells (EC50 approximately 33 nM. OXT-evoked responses were significantly inhibited by the OXTR antagonist, L-371,257. Isolated OXT-responsive taste cells were neither Receptor (Type II nor Presynaptic (Type III cells, consistent with our immunofluorescence observations. We also investigated the source of OXT peptide that may act on taste cells. Both RT-PCR and immunostaining suggest that the OXT peptide is not produced in taste buds or in their associated nerves. Finally, we also examined the morphology of taste buds from mice that lack OXTR. Taste buds and their constituent cell types appeared very similar in mice with two, one or no copies of the OXTR gene.We conclude that OXT elicits Ca2+ signals via OXTR in murine taste buds. OXT-responsive cells are most likely a subset of Glial-like (Type I taste cells. OXT itself is not produced locally in taste tissue and is likely delivered through the circulation. Loss of OXTR does not grossly alter the morphology of any of the cell types contained in taste buds. Instead, we speculate that OXT-responsive Glial-like (Type I taste bud cells modulate taste signaling and afferent sensory output. Such modulation would complement central pathways of

GABAA Receptors Containing ρ1 Subunits Contribute to In Vivo Effects of Ethanol in Mice

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Blednov, Yuri A.; Benavidez, Jillian M.; Black, Mendy; Leiter, Courtney R.; Osterndorff-Kahanek, Elizabeth; Johnson, David; Borghese, Cecilia M.; Hanrahan, Jane R.; Johnston, Graham A. R.; Chebib, Mary; Harris, R. Adron

2014-01-01

GABAA receptors consisting of ρ1, ρ2, or ρ3 subunits in homo- or hetero-pentamers have been studied mainly in retina but are detected in many brain regions. Receptors formed from ρ1 are inhibited by low ethanol concentrations, and family-based association analyses have linked ρ subunit genes with alcohol dependence. We determined if genetic deletion of ρ1 in mice altered in vivo ethanol effects. Null mutant male mice showed reduced ethanol consumption and preference in a two-bottle choice test with no differences in preference for saccharin or quinine. Null mutant mice of both sexes demonstrated longer duration of ethanol-induced loss of righting reflex (LORR), and males were more sensitive to ethanol-induced motor sedation. In contrast, ρ1 null mice showed faster recovery from acute motor incoordination produced by ethanol. Null mutant females were less sensitive to ethanol-induced development of conditioned taste aversion. Measurement of mRNA levels in cerebellum showed that deletion of ρ1 did not change expression of ρ2, α2, or α6 GABAA receptor subunits. (S)-4-amino-cyclopent-1-enyl butylphosphinic acid (“ρ1” antagonist), when administered to wild type mice, mimicked the changes that ethanol induced in ρ1 null mice (LORR and rotarod tests), but the ρ1 antagonist did not produce these effects in ρ1 null mice. In contrast, (R)-4-amino-cyclopent-1-enyl butylphosphinic acid (“ρ2” antagonist) did not change ethanol actions in wild type but produced effects in mice lacking ρ1 that were opposite of the effects of deleting (or inhibiting) ρ1. These results suggest that ρ1 has a predominant role in two in vivo effects of ethanol, and a role for ρ2 may be revealed when ρ1 is deleted. We also found that ethanol produces similar inhibition of function of recombinant ρ1 and ρ2 receptors. These data indicate that ethanol action on GABAA receptors containing ρ1/ρ2 subunits may be important for specific effects of ethanol in vivo. PMID:24454882

Nucleus Accumbens Shell and mPFC but not Insula Orexin-1 Receptors Promote Excessive Alcohol Drinking

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Kelly Lei

2016-08-01

Full Text Available Addiction to alcohol remains a major social and economic problem, in part because of the high motivation for alcohol that humans exhibit and the hazardous binge intake this promotes. Orexin-1-type receptors (OX1Rs promote reward intake under conditions of strong drives for reward, including excessive alcohol intake. While systemic modulation of OX1Rs can alter alcohol drinking, the brain regions that mediate this OX1R enhancement of excessive drinking remain unknown. Given the importance of the nucleus accumbens (NAc and anterior insular cortex (aINS in driving many addictive behaviors, including OX1Rs within these regions, we examined the importance of OX1Rs in these regions on excessive alcohol drinking in C57BL/6 mice during limited-access alcohol drinking in the dark cycle. Inhibition of OX1Rs with the widely used SB-334867 within the medial NAc Shell (mNAsh significantly reduced drinking of alcohol, with no effect on saccharin intake, and no effect on alcohol consumption when infused above the mNAsh. In contrast, intra-mNAsh infusion of the orexin-2 receptor TCS-OX2-29 had no impact on alcohol drinking. In addition, OX1R inhibition within the aINS had no effect on excessive drinking, which was surprising given the importance of aINS-NAc circuits in promoting alcohol consumption and the role for aINS OX1Rs in driving nicotine intake. However, OX1R inhibition within the mPFC did reduce alcohol drinking, indicating cortical OXR involvement in promoting intake. Also, in support of the critical role for mNAsh OX1Rs, SB within the mNAsh also significantly reduced operant alcohol self-administration in rats. Finally, orexin ex vivo enhanced firing in mNAsh neurons from alcohol-drinking mice, with no effect on evoked EPSCs or input resistance; a similar orexin increase in firing without a change in input resistance was observed in alcohol-naïve mice. Taken together, our results strongly suggest that OX1Rs within the mNAsh, but not the aINS, play a

Immune activation in lactating dams alters sucklings' brain cytokines and produces non-overlapping behavioral deficits in adult female and male offspring: A novel neurodevelopmental model of sex-specific psychopathology.

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Arad, Michal; Piontkewitz, Yael; Albelda, Noa; Shaashua, Lee; Weiner, Ina

2017-07-01

Early immune activation (IA) in rodents, prenatal through the mother or early postnatal directly to the neonate, is widely used to produce behavioral endophenotypes relevant to schizophrenia and depression. Given that maternal immune response plays a crucial role in the deleterious effects of prenatal IA, and lactation is a critical vehicle of immunological support to the neonate, we predicted that immune activation of the lactating dam will produce long-term abnormalities in the sucklings. Nursing dams were injected on postnatal day 4 with the viral mimic poly-I:C (4mg/kg) or saline. Cytokine assessment was performed in dams' plasma and milk 2h, and in the sucklings' hippocampus, 6h and 24h following poly-I:C injection. Male and female sucklings were assessed in adulthood for: a) performance on behavioral tasks measuring constructs considered relevant to schizophrenia (selective attention and executive control) and depression (despair and anhedonia); b) response to relevant pharmacological treatments; c) brain structural changes. Maternal poly-I:C injection caused cytokine alterations in the dams' plasma and milk, as well as in the sucklings' hippocampus. Lactational poly-I:C exposure led to sex-dimorphic (non-overlapping) behavioral abnormalities in the adult offspring, with male but not female offspring exhibiting attentional and executive function abnormalities (manifested in persistent latent inhibition and slow reversal) and hypodopaminergia, and female but not male offspring exhibiting despair and anhedonia (manifested in increased immobility in the forced swim test and reduced saccharine preference) and hyperdopaminergia, mimicking the known sex-bias in schizophrenia and depression. The behavioral double-dissociation predicted distinct pharmacological profiles, recapitulating the pharmacology of negative/cognitive symptoms and depression. In-vivo imaging revealed hippocampal and striatal volume reductions in both sexes, as found in both disorders. This is

Association between quality of cheap and unrecorded alcohol products and public health consequences in Poland.

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Lachenmeier, Dirk W; Ganss, Sebastian; Rychlak, Bogumil; Rehm, Jürgen; Sulkowska, Urszula; Skiba, Michał; Zatonski, Witold

2009-10-01

The research aimed to study the quality of cheap alcohol products in Poland. These included unrecorded alcohols (i.e., home-produced or illegally imported), estimated to constitute more than 25% of total consumption and fruit wines. A sample of alcohol products (n = 52) was collected from local markets and chemical analyses were conducted. The parameters studied were alcoholic strength, volatiles (methanol, acetaldehyde, and higher alcohols), ethyl carbamate, inorganic elements, and food additives including preservatives, colors, and sweeteners. The compositions of the beverages were then toxicologically evaluated using international standards. With the exception of 1 fortified wine, the unrecorded alcohols were home-produced fruit-derived spirits (moonshine) and spirits imported from other countries. We did not detect any nonbeverage surrogate alcohol. The unrecorded spirits contained, on average, 45% vol of alcohol. However, some products with considerably higher alcoholic strengths were found (up to 85% vol) with no labeling of the content on the bottles. These products may cause more pronounced detrimental health effects (e.g., liver cirrhosis, injuries, some forms of malignant neoplasms, alcohol use disorders, and cardiovascular disease) than will commercial beverages, especially as the consumer may be unaware of the alcohol content consumed. Fruit wines containing between 9.5 and 12.2% vol alcohol showed problems in terms of their additive content and their labeling (e.g., sulfites, sorbic acid, saccharin, and artificial colors) and should be subjected to stricter control. Regarding the other components investigated, the suspected human carcinogens, acetaldehyde and ethyl carbamate, were found at levels relevant to public health concerns. While acetaldehyde is a typical constituent of fermented beverages, ethyl carbamate was found only in home-produced unrecorded alcohols derived from stone fruits with levels significantly above international guidelines. The

Molecular structure and infrared spectra of the monomeric 3-(methoxy)-1,2-benzisothiazole 1,1-dioxide (methyl pseudosaccharyl ether)

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Kaczor, Agnieszka; Almeida, Rui; Gómez-Zavaglia, Andrea; Cristiano, Maria de Lurdes S.; Fausto, Rui

2008-03-01

The computational description of saccharin (1,2-benzisothiazol-3(2 H)-one-1,1-dioxide) and its derivatives is difficult due to the presence of hypervalent S dbnd O bonds in their structures. Therefore, in this investigation, the HF, DFT/B3LYP and MP2 methods were used to predict the geometry and the infrared spectrum of the saccharyl derivative 3-(methoxy)-1,2-benzisothiazole 1,1-dioxide (MBID). Their relative predictive capabilities were then evaluated by comparing the obtained results with experimentally available data, namely the newly obtained IR spectra of MBID isolated in low-temperature inert matrices. For each method, different basis sets [6-31++G(d,p), 6-31++G(3df,3pd), 6-311++G(d,p), 6-311++G(2df,2pd), 6-311++G(3df,3pd), aug-cc-pVDZ and aug-cc-pVTZ] were considered. The best overall agreement has been achieved at the B3LYP/6-311++G(3df,3pd) and B3LYP/6-31++G(3df,3pd) levels of theory, showing the adequacy of the B3LYP functional to describe the investigated properties in this type of compounds and stressing the relevance of including high-order polarization functions in the basis set. The chosen level of theory [B3LYP/6-311++G(3df,3pd)] was applied to analyze the vibrational spectra and the geometry of the title molecule. In agreement with the experiment, the C sbnd O sbnd C linkage in MBID is predicted by these calculations to exhibit considerably short (1.320 Å) and long (1.442 Å) (N dbnd )C sbnd O and (H 3)C sbnd O bonds, respectively, and a hybridization of the central oxygen atom close to sp 2 (the C sbnd O sbnd C angle is predicted to be ca. 117°). This C sbnd O sbnd C bonding pattern fits the well-known high reactivity of MBID upon thermal rearrangement, which has been shown to result in easy selective [1,3']-isomerization of the compound.

GABAA receptors containing ρ1 subunits contribute to in vivo effects of ethanol in mice.

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Yuri A Blednov

Full Text Available GABAA receptors consisting of ρ1, ρ2, or ρ3 subunits in homo- or hetero-pentamers have been studied mainly in retina but are detected in many brain regions. Receptors formed from ρ1 are inhibited by low ethanol concentrations, and family-based association analyses have linked ρ subunit genes with alcohol dependence. We determined if genetic deletion of ρ1 in mice altered in vivo ethanol effects. Null mutant male mice showed reduced ethanol consumption and preference in a two-bottle choice test with no differences in preference for saccharin or quinine. Null mutant mice of both sexes demonstrated longer duration of ethanol-induced loss of righting reflex (LORR, and males were more sensitive to ethanol-induced motor sedation. In contrast, ρ1 null mice showed faster recovery from acute motor incoordination produced by ethanol. Null mutant females were less sensitive to ethanol-induced development of conditioned taste aversion. Measurement of mRNA levels in cerebellum showed that deletion of ρ1 did not change expression of ρ2, α2, or α6 GABAA receptor subunits. (S-4-amino-cyclopent-1-enyl butylphosphinic acid ("ρ1" antagonist, when administered to wild type mice, mimicked the changes that ethanol induced in ρ1 null mice (LORR and rotarod tests, but the ρ1 antagonist did not produce these effects in ρ1 null mice. In contrast, (R-4-amino-cyclopent-1-enyl butylphosphinic acid ("ρ2" antagonist did not change ethanol actions in wild type but produced effects in mice lacking ρ1 that were opposite of the effects of deleting (or inhibiting ρ1. These results suggest that ρ1 has a predominant role in two in vivo effects of ethanol, and a role for ρ2 may be revealed when ρ1 is deleted. We also found that ethanol produces similar inhibition of function of recombinant ρ1 and ρ2 receptors. These data indicate that ethanol action on GABAA receptors containing ρ1/ρ2 subunits may be important for specific effects of ethanol in vivo.

Chronic moderate alcohol drinking alters insulin release without affecting cognitive and emotion-like behaviors in rats.

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Nelson, Nnamdi G; Suhaidi, Faten A; Law, Wen Xuan; Liang, Nu-Chu

2017-12-16

Because the consumption of alcoholic beverages prevails in society, its effects on diabetes risk is a subject of interest. Extant literature on this issue often disagrees. Here, we probed the effects of chronic moderate ethanol consumption on glucose metabolism in rats. The effect of chronic moderate alcohol drinking on depression- and anxiety-like behaviors and memory was also explored. Adolescent male and female Long-Evans rats consumed saccharin-sweetened 5% (1 week) and 10% ethanol (7 weeks) under a 7.5-h/day (Monday-Friday) access schedule. This exposure was followed by sucrose preference and elevated plus maze (EPM) tests during an intervening week, before a 6-week intermittent-access (Monday, Wednesday, Friday) to 20% unsweetened ethanol in a 2-bottle choice drinking paradigm was implemented (EtOH). A free-feeding control group received water (Water). Our prior work revealed that voluntary ethanol consumption decreases food intake in rats. Hence, a second control group that received water was mildly food-restricted (FR), and their average body weight was matched to that of the EtOH group. During the week following week 6 of intermittent-access to 20% ethanol, rats were submitted to sucrose preference, EPM, and novel object recognition (NOR) tests. Insulin response to a glucose load was subsequently assessed via an oral glucose tolerance test (OGTT). Rats attained and maintained blood ethanol concentrations of ∼55 mg/dL that correlated with the dose of sweetened 10% ethanol ingested. Relative to intake by Water controls, EtOH rats consumed less chow. There was no body weight difference between both groups. Neither sex of EtOH rats showed increased depression- and anxiety-like behaviors, as respectively measured by sucrose preference and EPM, nor did they show deficit in object recognition memory during abstinence. Male EtOH rats, however, showed signs of reduced general activity on the EPM. During OGTT, male EtOH rats showed a time-dependent potentiation

ANOMALOUS ELECTRODEPOSITION OF Fe-Ni ALLOY COATING FROM SIMPLE AND COMPLEX BATHS AND ITS MAGNETIC PROPERTY

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M A Islam

2010-03-01

Full Text Available Electrodeposition of Fe-Ni thin films has been carried on copper substrate under various electrodeposition conditions from two simple and six complex baths. Sulfate baths composing of NiSO4. 7H2O, FeSO4.7H2O, H3BO3 and Na2SO4KEYWORDS: Anomalous Electrodeposition, Fe-Ni Coating, Complexing agent, Current Density, Magnetic Property. 1. INTRODUCTION Alloy electrodeposition technologies can extend tremendously the potential of electrochemical deposition processes to provide coatings that require unique mechanical, chemical and physical properties [1]. There has been a great research interest in the development and characterization of iron-nickel (Fe-Ni thin films due to their operational capacity, economic interest, magnetic and other properties [2]. Due to their unique low coefficient of thermal expansion (CTE and soft magnetic properties, Fe-Ni alloys have been used in industrial applications for over 100 years [3]. Typical examples of applications that are based on the low CTE of Fe-Ni alloys include: thermostatic bimetals, glass sealing, integrated circuit packaging, cathode ray tube, shadow masks, membranes for liquid natural gas tankers; applications based on the soft magnetic properties include: read-write heads for magnetic storage, magnetic actuators, magnetic shielding, high performance transformer cores. comprise the simple baths whereas complex baths were prepared by adding ascorbic acid, saccharin and citric acid in simple baths. The effect of bath composition, pH and applied current density on coating appearance, composition, morphology and magnetic property were studied. Wet chemical analysis technique was used to analyze the coating composition whereas SEM and VSM were used to study the deposit morphology and magnetic property respectively. Addition of complexing agents in plating baths suppressed the anomalous nature of Fe-Ni alloy electrodeposition. Coatings obtained from simple baths were characterized by coarse grained non

Do polymorphisms in chemosensory genes matter for human ingestive behavior?

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Hayes, John E; Feeney, Emma L; Allen, Alissa L

2013-12-01

In the last decade, basic research in chemoreceptor genetics and neurobiology have revolutionized our understanding of individual differences in chemosensation. From an evolutionary perspective, chemosensory variations appear to have arisen in response to different living environments, generally in the avoidance of toxins and to better detect vital food sources. Today, it is often assumed that these differences may drive variable food preferences and choices, with downstream effects on health and wellness. A growing body of evidence indicates chemosensory variation is far more complex than previously believed. However, just because a genetic polymorphism results in altered receptor function in cultured cells or even behavioral phenotypes in the laboratory, this variation may not be sufficient to influence food choice in free living humans. Still, there is ample evidence to indicate allelic variation in TAS2R38 predicts variation in bitterness of synthetic pharmaceuticals (e.g., propylthiouracil) and natural plant compounds (e.g., goitrin), and this variation associates with differential intake of alcohol and vegetables. Further, this is only one of 25 unique bitter taste genes ( TAS2Rs ) in humans, and emerging evidence suggests other TAS2Rs may also contain polymorphisms that a functional with respect to ingestive behavior. For example, TAS2R16 polymorphisms are linked to the bitterness of naturally occurring plant compounds and alcoholic beverage intake, a TAS2R19 polymorphism predicts differences in quinine bitterness and grapefruit bitterness and liking, and TAS2R31 polymorphisms associate with differential bitterness of plant compounds like aristolochic acid and the sulfonyl amide sweeteners saccharin and acesulfame-K. More critically with respect to food choices, these polymorphisms may vary independently from each other within and across individuals, meaning a monolithic one-size-fits-all approach to bitterness needs to be abandoned. Nor are genetic

Evolution of cement based materials in a repository for radioactive waste and their chemical barrier function

International Nuclear Information System (INIS)

Kienzler, Bernhard; Metz, Volker; Schlieker, Martina; Bohnert, Elke

2015-01-01

The use of cementitious materials in nuclear waste management is quite widespread. It covers the solidification of low/intermediate-level liquid as well as solid wastes (e.g. laboratory wastes) and serves as shielding. For both high-level and intermediate-low level activity repositories, cement/concrete likewise plays an important role. It is used as construction material for underground and surface disposals, but more importantly it serves as barrier or sealing material. For the requirements of waste conditioning, special cement mixtures have been developed. These include special mixtures for the solidification of evaporator concentrates, borate binding additives and for spilling solid wastes. In recent years, low-pH cements were strongly discussed especially for repository applications, e.g. (Celine CAU DIT COUMES 2008; Garcia-Sineriz, et al. 2008). Examples for relevant systems are Calcium Silicate Cements (ordinary Portland cement (OPC) based) or Calcium Aluminates Cements (CAC). Low-pH pore solutions are achieved by reduction of the portlandite content by partial substitution of OPC by mineral admixtures with high silica content. The blends follow the pozzolanic reaction consuming Ca(OH) 2 . Potential admixtures are silica fume (SF) and fly ashes (FA). In these mixtures, super plasticizers are required, consisting of polycarboxilate or naphthalene formaldehyde as well as various accelerating admixtures (Garcia-Sineriz, et al. 2008). The pH regime of concrete/cement materials may stabilize radionuclides in solution. Newly formed alteration products retain or release radionuclides. An important degradation product of celluloses in cement is iso-saccharin acid. According to Glaus 2004 (Glaus and van Loon 2004), it reacts with radionuclides forming dissolved complexes. Apart from potentially impacting radionuclide solubility limitations, concrete additives, radionuclides or other strong complexants compete for surface sites for sorbing onto cement phases. In

Physiological and subjective responses to low relative humidity in young and elderly men.

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Sunwoo, Yujin; Chou, Chinmei; Takeshita, Junko; Murakami, Motoko; Tochihara, Yutaka

2006-05-01

In order to compare the physiological and the subjective responses to low relative humidity of elderly and young men, we measured saccharin clearance time (SCT), frequency of blinking, hydration state of the skin, transepidermal water loss (TEWL), sebum level recovery and skin temperatures as physiological responses. We asked subjects to evaluate thermal, dryness and comfort sensations as subjective responses using a rating scale. Eight non-smoking healthy male students (21.7+/-0.8 yr) and eight non-smoking healthy elderly men (71.1+/-4.1 yr) were selected. The pre-room conditions were maintained at an air temperature (Ta) of 25 degrees C and a relative humidity (RH) of 50%. The test-room conditions were adjusted to provide 25 degrees C Ta and RH levels of 10%, 30% and 50%. RH had no effect on the activity of the sebaceous gland or change of mean skin temperature. SCT of the elderly group under 10% RH was significantly longer than that of the young group. In particular, considering the SCT change, the nasal mucous membrane seems to be affected more in the elderly than in the young in low RH. Under 30% RH, the eyes and skin become dry, and under 10% RH the nasal mucous membrane becomes dry as well as the eyes and skin. These findings suggested that to avoid dryness of the eyes and skin, it is necessary to maintain greater than 30% RH, and to avoid dryness of the nasal mucous membrane, it is necessary to maintain greater than 10% RH. On the thermal sensation of the legs, at the lower humidity level, the elderly group felt cooler than the young group. On the dry sensation of the eyes and throat, the young group felt drier than the elderly group at the lower humidity levels. From the above results, the elderly group had difficulty in feeling dryness in the nasal mucous membrane despite being easily affected by low humidity. On the other hand, the young group felt the change of humidity sensitively despite not being severely affected by low humidity. Ocular mucosa and

Rooting of west indian cherry cuttings under indo-butiric acid concentrations / Enraizamento de estacas de acerola sob concentrações de ácido indol-butírico

Directory of Open Access Journals (Sweden)

Thiago Luiz Ragugnetti Furlaneto

2003-05-01

Full Text Available Oncidium varicosum is a native Brazilian orchid popularly known as ‘Golden Shower´ because of its very ramified inflorescence and many yellow flowers. The carboydrate type and concentration are important in promoting plantlet development of in vitro orchids. The present study was carried out to asses the effect of different carbohydrate sources and concentrations on the in vitro growth of O. varicosum plantlets. Murashige e Skoog culture medium was used modified with half concentration of the macronutrients. The plantlets, derived from seeds that were already established in vitro and 0.8 + 0.2 cm in height, were inoculated in the culture media containing the following carbohydrate sources: saccharine, maltose and glucose, at concentrations of 0, 10, 20, 30, 60 and 90 g.L-1. The following variables were analyzed 8 months later: canopy height, number of roots, greatest root length, pseudobulb diameter and fresh weight. A completely randomized block experimental design was used with five replications per treatment. Analysis of variance and the Tukey test (5% were performed to compare the means. It was concluded that 60 g.L-1 saccharose was the best treatment for all the parameters assessed. The sugars 30 g.L-1 glucose and 60 g.L-1 maltose were also suitable, but presented lower pseudobulb diameter and lower fresh weight when compared to 60 g.L-1saccharose.O trabalho teve o objetivo de avaliar a influência do ácido indol-butírico sobre o enraizamento de estacas de acerola (Malpighia emarginata D. C. na Universidade Estadual de Londrina. As plantas matrizes utilizadas pertencem a seleção Camb-6 do IAPAR, tiveram suas estacas colhidas com 10 a 12 cm de comprimento, com três a quatro pares de folhas e foram submetidas a uma imersão rápida (10 segundos em soluções de ácido indol-butírico (AIB com cinco concentrações (0, 500, 1.000, 1.500, 2.000 mg L-1. O delineamento estatístico adotado foi o de blocos ao acaso com cinco repeti

Immediate and short term effects of smoking on nasal mucociliary clearance in smokers

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M. Proença

2011-07-01

Full Text Available Background and objectives: The efficiency of mucociliary transport may vary in different conditions, such as in exposure to harmful particles of the cigarette smoke. The present study evaluated the acute and short term effects of smoking on nasal mucociliary clearance in current smokers by the quantification of the Saccharin Transit Time (STT, and to investigate its correlation with the history of tobacco consumption. Methods: Nineteen current smokers (11 men, 51 ± 16 years; BMI 23 ± 9 kg/m2, 27 ± 11 cigarettes per day, 44 ± 25 pack-years, entering a smoking cessation intervention program, responded to a questionnaire concerning smoking history and were submitted to lung function assessment (spirometry and the STT test. STT was assessed immediately after smoking and 8 hours after smoking. The STT test was also performed in nineteen matched healthy non-smokers’ who served as control group. Results: When compared to STT in non-smokers’ (10 ± 4 min; mean ± standard deviation, smokers presented similar STT immediately after smoking (11 ± 6 min; p = 0.87 and slower STT 8 hours after smoking (16 ± 6 min; p = 0.005 versus non-smokers’ and p = 0.003 versus immediately after smoking. STT 8 hours after smoking correlated positively with age (r = 0.59; p = 0.007, cigarettes per day (r = 0.53; p = 0.02 and pack-years index (r = 0.74; p = 0.0003. Conclusions: In smokers, although the mucociliary clearance immediately after smoking is similar to non-smokers’, eight hours after smoking it is reduced, and this reduction is closely related to the smoking habits. Resumo: Introdução e objectivo: A eficiência do transporte mucociliar pode variar em diferentes condições, como na exposição a partículas nocivas do fumo do cigarro. O presente estudo avaliou os efeitos do cigarro

Efeito imediato e a curto prazo do cigarro sobre o transporte mucociliar nasal de fumadores

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M. Proença

2011-07-01

ísticos. Abstract: Background and objectives: The efficiency of mucociliary transport may vary in different conditions, such as in exposure to harmful particles of the cigarette smoke. The present study evaluated the acute and short term effects of smoking on nasal mucociliary clearance in current smokers by the quantification of the Saccharin Transit Time (STT, and to investigate its correlation with the history of tobacco consumption. Methods: Nineteen current smokers (11 men, 51 ± 16 years; BMI 23 ± 9 kg/m2, 27 ± 11 cigarettes per day, 44 ± 25 pack-years, entering a smoking cessation intervention program, responded to a questionnaire concerning smoking history and were submitted to lung function assessment (spirometry and the STT test. STT was assessed immediately after smoking and 8 hours after smoking. The STT test was also performed in nineteen matched healthy non-smokers’ who served as control group. Results: When compared to STT in non-smokers’ (10 ± 4 min; mean ± standard deviation, smokers presented similar STT immediately after smoking (11 ± 6 min; p = 0.87 and slower STT 8 hours after smoking (16 ± 6 min; p = 0.005 versus non-smokers’ and p = 0.003 versus immediately after smoking. STT 8 hours after smoking correlated positively with age (r = 0.59; p = 0.007, cigarettes per day (r = 0.53; p = 0.02 and pack-years index (r = 0.74; p = 0.0003. Conclusions: In smokers, although the mucociliary clearance immediately after smoking is similar to non-smokers’, eight hours after smoking it is reduced, and this reduction is closely related to the smoking habits. Palavras-chave: Transporte mucociliar nasal, Tabagismo, Teste de trânsito de sacarina, Keywords: Mucociliary clearance, Smoking, Saccharin sodium

Utilização de adoçantes dietéticos entre adultos em Pelotas, Rio Grande do Sul, Brasil: um estudo de base populacional Use of diet sweeteners by adults in Pelotas, Rio Grande do Sul State, Brazil: a population-based study

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Roberta de Vargas Zanini

2011-05-01

Full Text Available Estudo de base populacional avaliou o uso de adoçantes dietéticos na população com idade ≥ 20 anos, residente na zona urbana do Município de Pelotas, Rio Grande do Sul, Brasil. A coleta de dados ocorreu entre janeiro e julho de 2010, e 2.732 indivíduos foram entrevistados. Além das questões específicas quanto ao uso de adoçante dietético, foram coletadas informações sobre características demográficas, socioeconômicas e de saúde. Para as análises estatísticas, foram utilizados testes qui-quadrado de heterogeneidade e de tendência linear. A prevalência de uso de adoçante dietético foi 19% (IC95%: 17,1; 20,9, sendo 3,7 vezes maior entre idosos do que entre aqueles com 20-29 anos de idade. Nível econômico e estado nutricional apresentaram associação direta e significativa com o desfecho. Quase 98% da amostra utilizou adoçantes na forma líquida, sendo os mais consumidos (89,2% aqueles constituídos por sacarina e ciclamato de sódio. A mediana de ingestão diária foi 10 gotas (P25; P75 = 6; 18, entre usuários de adoçante líquido, ou 1,5 sachet (P25; P75 = 1; 4, para adoçante em pó. O uso de adoçante dietético foi maior entre mulheres e idosos.This population-based study evaluated the use of diet sweeteners by adults (> 20 years in Pelotas, Rio Grande do Sul State, Brazil. Data were collected from January to July 2010 (n = 2,732. Besides specific questions on diet sweeteners, demographic, socioeconomic, and health characteristics were recorded. Heterogeneity and linear trend chi-square tests were used for the statistical analysis. Prevalence of sweetener use was 19% (95%CI: 1.1-20.9, and was 3.7 times higher in elderly individuals as compared to 20-29-year-olds. Economic level and nutritional status were significantly associated with sweetener use. Nearly 98% of the sample used liquid sweeteners; the most frequently consumed (89.2% were those containing saccharin or sodium cyclamate. Average intake was 10 drops

Performance, health and physiological responses of newly weaned feedlot cattle supplemented with feed-grade antibiotics or alternative feed ingredients.

Science.gov (United States)

de Souza, K A; Cooke, R F; Schubach, K M; Brandão, A P; Schumaher, T F; Prado, I N; Marques, R S; Bohnert, D W

2018-03-26

With increased regulations regarding the use of feed-grade antimicrobials in livestock systems, alternative strategies to enhance growth and immunity of feedlot cattle are warranted. Hence, this experiment compared performance, health and physiological responses of cattle supplemented with feed-grade antibiotics or alternative feed ingredients during the initial 60 days in the feedlot. Angus×Hereford calves (63 steers+42 heifers) originating from two cow-calf ranches were weaned on day -3, obtained from an auction yard on day -2 and road-transported (800 km; 12 h) to the feedlot. Upon arrival on day -1, shrunk BW was recorded. On day 0, calves were ranked by sex, source and shrunk BW, and allocated to one of 21 pens. Pens were assigned to receive (7 pens/treatment) a free-choice total mixed ration containing: (1) lasalocid (360 mg/calf daily of Bovatec; Zoetis, Florham Park, NJ, USA)+chlortetracycline (350 mg/calf of Aureomycin at cycles of 5-day inclusion and 2-day removal from diet; Zoetis) from days 0 to 32, and monensin only (360 mg/calf daily of Rumensin; Elanco Animal Health, Greenfield, IN, USA) from days 33 to 60 (PC), (2) sodium saccharin-based sweetener (Sucram at 0.04 g/kg of diet dry matter; Pancosma SA; Geneva, Switzerland)+plant extracts containing eugenol, cinnamaldehyde and capsicum (800 mg/calf daily of XTRACT Ruminants 7065; Pancosma SA) from days 0 to 32 and XTRACT only (800 mg/calf daily) from days 33 to 60 (EG) or (3) no supplemental ingredients (CON; days 0 to 60). Calves were assessed for bovine respiratory disease (BRD) signs and dry matter intake was recorded from each pen daily. Calves were vaccinated against BRD pathogens on days 0 and 22. Shrunk BW was recorded on day 61, and blood samples collected on days 0, 6, 11, 22, 33, 43 and 60. Calf ADG was greater (P=0.04) in PC v. EG and tended (P=0.09) to be greater in PC v. CON. Feed efficiency also tended (P=0.09) to be greater in PC v. CON, although main treatment effect for this response

A glucose-centric perspective of hyperglycemia.

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Ramasarma, T; Rafi, M

2016-02-01

targets. Some are effective in slowing formation of glucose in intestines by inhibiting α-glucosidases (e.g., salacia/saptarangi). Knowledge gained from French lilac on active guanidine group helped developing Metformin (1,1-dimethylbiguanide) one of the popular drugs in use. One strategy of keeping sugar content in diets in check is to use artificial sweeteners with no calories, no glucose or fructose and no effect on blood glucose (e.g., steviol, erythrytol). However, the three commonly used non-caloric artificial sweeteners, saccharin, sucralose and aspartame later developed glucose intolerance, the very condition they are expected to evade. Ideal way of keeping blood glucose under 6 mM and HbA1c, the glycation marker of hemoglobin, under 7% in blood is to correct the defects in signals that allow glucose flow into glycogen, still a difficult task with drugs and diets.

Plasma membrane ordering agent pluronic F-68 (PF-68) reduces neurotransmitter uptake and release and produces learning and memory deficits in rats

Science.gov (United States)

Clarke, M. S.; Prendergast, M. A.; Terry, A. V. Jr

1999-01-01

performance, or in tests of general locomotor activity. Furthermore, latencies to select a lever in the DSDT were not affected. These results suggest that PF-68 induced deficits in learning and memory without confounding peripheral motor, sensory, or motivational effects at the tested doses. Furthermore, none of the doses induced a conditioned taste aversion to a novel 0.1% saccharin solution indicating a lack of nausea or gastrointestinal malaise induced by the compound. The data indicate that increases in neuronal plasma membrane order may have significant effects on neurotransmitter function as well as learning and memory processes. Furthermore, compounds such as PF-68 may also offer novel tools for studying the role of neuronal PMO in mnemonic processes and changes in PMO resulting from age-related disorders such as AD.

Equivalência de dulçor e poder edulcorante de edulcorantes em função da temperatura de consumo em bebidas preparadas com chá-mate em pó solúvel Equi-sweetness and sweetening power of different sweetening agents in differents temperatures of consumption of tea drink in soluble power

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Juliana Maria Porto Cardoso

2004-09-01

Full Text Available No presente estudo foi verificado o efeito da temperatura de consumo na equivalência de doçura e no poder edulcorante de diferentes agentes adoçantes em bebida de chá-mate em pó solúvel. Foram avaliados: aspartame, sucralose, mistura ciclamato/sacarina 2:1, Stevia e acessulfame-K, tendo como referência a sacarose. Todos os estudos foram realizados a 6±2ºC e a 45±2ºC. Primeiramente foi determinada a doçura ideal, utillizando-se escala do ideal com 30 provadores consumidores da bebida. Em seguida, foi determinada a doçura equivalente à sacarose (na doçura considerada ideal para cada edulcorante estudado, e seu poder edulcorante nas duas temperaturas de estudo. Para tal foi aplicado o método de estimação de magnitude, utilizando-se uma equipe de 10 provadores selecionados e treinados. A doçura ideal de sacarose foi de 8,3% para a bebida de chá-mate solúvel, sem diferença significativa entre as temperaturas de estudo. Ocorreram diferenças sensoriais importantes em função da temperatura, pois, enquanto para alguns edulcorantes o aumento de temperatura provocou diminuição na potência edulcorante, para outros foi observado aumento do poder edulcorante. Portanto, não se deve generalizar as alterações no poder edulcorante em função da temperatura, pois ela pode variar em função da classe química envolvida e do meio de dispersão em que se encontra.In this work the effect of temperature of consumption in the equi-sweetness and sweetening power of different sweetening agents was verified in tea drink in soluble powder. The panelists had evaluated: aspartame, sucralose, mixture of cyclamate/saccharin (2:1, Stevia [Stevia rebaudiana (Bert. Bertoni] and acesulfame-K as sweeteners, having sucrose as reference. All sensory tests were carried-out at 6±2ºC and 45±2ºC. Firstly the ideal sweetness was determined by just-about-right scale with 30 consumers of tea drink. After the ideal sweetness of sucrose determination, the

Response of the grass-cutting ant Atta capiguara Gonçalves, 1944 (Hymenoptera: Formicidae to sugars and artificial sweeteners Resposta da saúva Atta capiguara Gonçalves, 1944 (Hymenoptera: Formicidae a açúcares e edulcorantes artificiais

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Maria Aparecida Castellani Boaretto

2003-01-01

Full Text Available Using of toxic baits made of dehydrated citric pulp to control grass-cutting ants can lead to unsatisfactory results because of the low attractiveness of the substrate to worker ants. This work aimed to identify attractive substances, with potential for incorporation in a matrix of granulated baits for grass-cutting ants, among several kinds of sugars and substances used in artificial sweeteners. Experiments were carried out in mature nests of Atta capiguara (Hym.: Formicidae set in pasture. Studied substances were sucrose, fructose, soluble starch, raffinose, maltose, lactose, sorbose, cellobiose, arabinose, xylose, glucose, galactose, rhamnose, arabinose, melezitose, saccharine and cyclamate (at 5.0% w/v. Later, on maltose, xylose, sucrose, fructose and glucose solutions were included at 5.0%, 7.5%, 10.0% and 20.0% w/v, respectively. Cellulose rectangles were used as vehicle and number of rectangles carried into the colonies was evaluated. Carrying rates were very low with maximum means of 9.6% for lactose and 6.0% for arabinose and cyclamate, at the 5.0% concentration. No differences (P > 0.05 were observed relatively to the control (distilled water. No effects were detected for solution, concentration and for the interaction of these factors. Sugars and artificial sweeteners studied were not attractive to Atta capiguara workers, turning their inclusion as attractants in toxic ant baits not viable.O uso de iscas tóxicas, formuladas à base de polpa cítrica desidratada, para o controle de formigas cortadeiras de gramíneas pode levar a resultados insatisfatórios devido à baixa atratividade do substrato às operárias. Este trabalho foi realizado com o objetivo de identificar substâncias atrativas e com potencial para incorporação em matrizes de iscas granuladas para formigas cortadeiras de gramíneas, dentre diversos tipos de açúcares e edulcorantes artificiais. Os experimentos foram realizados em ninhos adultos de Atta capiguara Gon

Terapia nutricional no diabetes gestacional Nutritional therapy in gestational diabetes

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Patricia de Carvalho Padilha

2010-02-01

. Nutritional status assessment of the mother should include anthropometric, dietary, biochemical, clinical and functional indicators. In this way, dietary assessment should be thorough, paying attention to the number and kind of meals, and the food groups present. The distribution of macronutrients in relation to the total energy intake per day should be 45-65% carbohydrates, 15-20% proteins and 20-35% lipids. The allowed sweeteners are acesulfame K, aspartame, neotame, saccharin and sucralose. Physical activity should also be included in the strategy to treat diabetes mellitus but the impact of physical activity on neonatal complications still requires minute testing. In addition, some studies have associated nutritional counseling skill with greater adherence to dietary recommendations. Several measures should be taken to ensure successful management of gestational diabetes mellitus, including participation of an inter and multidisciplinary team, early prenatal care with opportune nutritional care, and guaranteed quality care during pregnancy.

Excipientes de medicamentos e as informações da bula Pharmaceutical excipients and the information on drug labels

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Aracy Pereira Silveira Balbani

2006-06-01

preservatives, dyes, sweeteners and flavouring substances in 73 pharmaceutical preparations of 35 medicines for oral administration, according to drug labeling information about the excipients. METHODS: 35 medications were selected, both over-the-counter and prescription durgs, marketed in Brazil. The sample included: analgesic/antipyretic, antimicrobial, mucoregulatory, cough and cold, decongestant, antihistamine, bronchodilator, corticosteroid, antiinflammatory and vitamin medications. We collected data on 73 preparations of these drugs, according to drug labeling information regarding preservatives, dyes, sweeteners and flavourings. RESULTS: Methylparaben and propylparaben were the most common preservatives found (43% and 35.6% respectively. The most common sweeteners were: sucrose (sugar (53.4%, sodium saccharin (38.3% and sorbitol (36.9%. Twenty-one medicines (28,7% contained two sweeteners. Colourless medicines predominated (43.8%, followed by those with sunset yellow dye (FD&C yellow no. 6 (15%. Five products (6.8% contained more than one colour agent. Tartrazine (FD&C yellow no. 5 was present in seven preparations (9.5%. Fruit was the most common flavouring found (83%. Labelings of drugs which contained sugar frequently omitted its exact concentration (77%. Of the four labelings of medicines which contained aspartame, two did not warn patients regarding phenylketonuria. CONCLUSION: Omission and inacuracy of drug labeling information on pharmaceutical excipients may expose susceptible individuals to adverse reactions caused by preservatives and dyes. Complications of inadvertent intake of sugar-containing medicines by diabetics, or aspartame intake by patients with phenylketonuria may also occur.

PENGGUNAAN PENGAWET DAN PEMANIS BUATAN PADA PANGAN JAJANAN ANAK SEKOLAH (PJAS DI WILAYAH KABUPATEN KULON PROGO-DIY (The Use of Preservatives and Artificial Sweeteners in Elementary School-Food in Kulon Progo District of DIY Province

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Chatarina Wariyah

2013-08-01

Full Text Available School-food (SF is processed-foods sold by vendor in the elementary school. Recently, many SF has been found to contain excessive food additives and used hazardous substances those are prohibited i.e. formalin, boric acid and rhodamin. The prebious survey showed that the considerations for buying food of most people in Kulon Progo District of DIY province were price, taste, appearance, and were not of the quality and nutrition. The purpose of this research was to determine the SF profile in Kulon Progo District, especially those used excessive food additive (preservative and artificial sweetener, SF with hazardous substances, and the relation between SF condition and the education level of the vendor. The sampling method used Proportionate Random Sampling consists of two stages, namely: 1 sampling to determine the sub-district samples and 2 sampling to determine the amount of the elementary-school of each sub-district for SF sampling. The data were collected by direct observation, interview and experimental method. Analysis of sodium benzoat and sorbic acid, saccharin, sodium cyclamate, and unrecommended/hazardous substances were conducted in BBPOM Laboratory and BLK of Yoyakarta. The data were statistically analyzed by statistic-descriptive and processed with microsoft excell and SPSS for window version 13 for Spearman correlative test.The research showed that SF at the elementary school in Kulon Progo District indicated to contain excessive food additives and hazardous substances. There were 4% samples containing excessive sodium benzoat, sorbic acid and 8% samples containing excessive artificial sweetener of sodium cyclamate. SF with boric acid was 3% samples (cilok, sosis, kerupuk rambak and with formalin was 1% samples (burjo,cimol. There was a significant correlation between the education level of the SF vendor with knowledge about formalin, boric acid and artificial sweetener. Keywords: School-food, food-additives, unrecommended

Influence of source and concentration of carbohydrate on shoot growth and rooting of Oncidium varicosum Lindl. (Orchidaceae / Influência da fonte e concentração de carboidrato no crescimento vegetativo e enraizamento in vitro de Oncidium varicosum Lindl. (Orchidaceae

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Charlen Saconato

2003-05-01

Full Text Available Oncidium varicosum is a native Brazilian orchid popularly known as ‘Golden Shower´ because of its very ramified inflorescence and many yellow flowers. The carboydrate type and concentration are important in promoting plantlet development of in vitro orchids. The present study was carried out to asses the effect of different carbohydrate sources and concentrations on the in vitro growth of O. varicosum plantlets. Murashige e Skoog culture medium was used modified with half concentration of the macronutrients. The plantlets, derived from seeds that were already established in vitro and 0.8 + 0.2 cm in height, were inoculated in the culture media containing the following carbohydrate sources: saccharine, maltose and glucose, at concentrations of 0, 10, 20, 30, 60 and 90 g.L-1. The following variables were analyzed 8 months later: canopy height, number of roots, greatest root length, pseudobulb diameter and fresh weight. A completely randomized block experimental design was used with five replications per treatment. Analysis of variance and the Tukey test (5% were performed to compare the means. It was concluded that 60 g.L-1 saccharose was the best treatment for all the parameters assessed. The sugars 30 g.L-1 glucose and 60 g.L-1 maltose were also suitable, but presented lower pseudobulb diameter and lower fresh weight when compared to 60 g.L-1saccharose.Oncidium varicosum é uma orquídea nativa do Brasil conhecida popularmente como “chuva de ouro”, devido a sua inflorescência muito ramificada e com inúmeras flores amarelas. O tipo e a concentração dos carboidratos são importantes para promover o desenvolvimento das plântulas das orquídeas in vitro. O presente trabalho teve como objetivo avaliar os efeitos de diferentes fontes e concentrações de carboidratos no crescimento in vitro de plântulas de O. varicosum. Foi utilizado o meio de cultura Murashige e Skoog, modificado pela redução à metade da concentração dos

PHREEQC integrated modelling of plutonium migration from alpha ILL radwaste: organic complexes, concrete degradation and alkaline plume

International Nuclear Information System (INIS)

Cochepin, B.; Munier, I.; Giffaut, E.; Grive, M.

2010-01-01

Document available in extended abstract form only. The effects of organic compounds derived from Long-Lived Intermediate-Level waste (LLILW) degradation need to be precisely described regarding the radionuclide migration in storage cells and argillites. These evaluations play a major role in the final decision for accepting these waste products in the future storage facility. The evaluation process engaged by Andra implies the use of coupled chemical transport tools able to take into account the linking of processes occurring in storage conditions as well as the different cell components (containers, packages, lining...). The relevance of this approach must fundamentally be based on a consistent characterization concerning (i) the waste packages, (ii) their degradation products (nature and kinetics), (iii) the chemical evolution of these products in the storage disposal (for cement material particularly) and in the argillites, and (iv) the correlation with the radionuclide behavior regarding to these sequestering agents (chemistry and transport). Andra is now involved in an internal evaluation of technological organic waste packages contaminated by plutonium coming from the MOX fuel plant called MELOX located at Marcoule (France), considering the consistent work undertaken to characterize these organic agents. This evaluation is based on an integrated representation in terms of chemical processes and transport of the concrete chemical degradation (e.g. waste packages, backfill and lining), the alkaline plume in the near field of argillites and the plutonium-organic complexes. The conceptual model is based on the following assessments: On the chemical aspect: (i) Both concrete and argillites undertake chemical perturbations with dissolution/precipitation, ion exchanges, surface and aqueous complexation. (ii) The degradation products of the MELOX waste organic compounds are limited to five major organic acids: iso-saccharinic (ISA), acetic, phtalic, adipic and

Discinesia ciliar primária: quando o pediatra deve suspeitar e como diagnosticar? Primary ciliary dyskinesia: when the pediatrician must suspect and how to do the diagnosis?

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Mary Anne K. Olm

2007-12-01

from secondary ciliary defects and to describe the clinical features, screening and diagnostic laboratorial tests, and the clinical management of this disorder. DATA SOURCES: A bibliographical search was obtained from Medline, Lilacs and SciELO databases, from 1980 to 2007. DATA SYNTHESIS: PCD is an autossomic recessive disorder with abnormal structure and/or function of the cilia, leading to reduced mucociliary clearance. The clinical manifestations include upper and lower respiratory tracts, with recurrent ear, sinus and lung infections that may progress to bronchiectasis. Situs inversus and male infertility are other clinical features of this disorder. PCD should be suspected by pediatricians in the following clinical situations: full term neonates with respiratory distress without apparent causes, presence of dextrocardia, infants with chronic cough and/or recurrent upper airways infections in the absence of immunodeficiency and cystic fibrosis, children with atypical asthma and bronchiectasis without a definitive cause. The diagnostic screening tests are the saccharine and nasal nitric oxide tests. Functional and ultrastructural evaluations demand an electronic microscopic analysis and the observation of the frequency and the pattern of the ciliary movement. CONCLUSIONS: Although the prevalence of PCD is low, the difficulties in establishing the diagnosis due to the complex investigations demanded and the unfamiliarity of the disease by physicians lead to underdiagnosis. Early diagnosis and treatment of PCD are essential to reduce the morbidity and to avoid complications.

ZZ HATCHES-18, Database for radiochemical modelling

International Nuclear Information System (INIS)

Heath, T.G.

2008-01-01

1 - Description of program or function: HATCHES is a referenced, quality assured, thermodynamic database, developed by Serco Assurance for Nirex. Although originally compiled for use in radiochemical modelling work, HATCHES also includes data suitable for many other applications e.g. toxic waste disposal, effluent treatment and chemical processing. It is used in conjunction with chemical and geochemical computer programs, to simulate a wide variety of reactions in aqueous environments. The database includes thermodynamic data (the log formation constant and the enthalpy of formation for the chemical species) for the actinides, fission products and decay products. The datasets for Ni, Tc, U, Np, Pu and Am are based on the NEA reviews of the chemical thermodynamics of these elements. The data sets for these elements with oxalate, citrate and EDTA are based on the NEA-selected values. For iso-saccharinic acid, additional data (non-selected values) have been included from the NEA review as well as data derived from other sources. HATCHES also includes data for many toxic metals and for elements commonly found in groundwaters or geological materials. HARPHRQ operates by reference to the PHREEQE master species list. Thus the thermodynamic information supplied is: a) the log equilibrium constant for the formation reaction of the requested species from the PHREEQE master species for the corresponding elements; b) the enthalpy of reaction for the formation reaction of the requested species from the PHREEQE master species for the corresponding elements. This version of HATCHES has been updated since the previous release to provide consistency with the selected data from two recent publications in the OECD Nuclear Energy Agency series on chemical thermodynamics: Chemical Thermodynamics Series Volume 7 (2005): Chemical Thermodynamics of Selenium by Aeke Olin (Chairman), Bengt Nolaeng, Lars-Olof Oehman, Evgeniy Osadchii and Erik Rosen and Chemical Thermodynamics Series Volume 8

Mucociliary clearance and its relation with the level of physical activity in daily life in healthy smokers and nonsmokers

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M. Proença

2012-09-01

Full Text Available Objectives: To investigate the relationship between mucociliary transport and physical activity in daily life (PADL in smokers and nonsmokers. Methods: Fifty-two current smokers were submitted to an assessment of mucociliary transport (saccharin transit time, STT, carbon monoxide levels in the exhaled air, lung function and smoking history. In addition, subjects kept a pedometer worn at the waist for six days in order to determine their level of PADL (steps/day. The tests were also performed on 30 matched healthy nonsmokers who served as control group. Results: Light smokers (≤15 cigarettes/day had a STT of 9 (7–11 min (median [confidence interval], which was similar to nonsmokers (8 [8–11] min; p = 0.8. Both moderate (16–25 cigarettes/day and heavy (>25 cigarettes/day smokers had a significantly higher STT (13 [11–17] min and 13 [10–21] min, respectively than nonsmokers and light smokers (p  0.05 for all. In the general group of smokers, STT was not significantly correlated with PADL, pack/years index, years of smoking or age (r  0.09 for all. There was significant negative correlation between STT and PADL only in light smokers (r = −0.55; p = 0.02 and nonsmokers (r = −0.42; p = 0.02, but not in moderate and heavy smokers. Conclusion: In light smokers and non-smokers, better mucociliary function is associated to higher daily physical activity level, as opposed to the decreased mucociliary function observed in smokers, i.e., those with moderate and heavy cigarette consumption. Resumo: Objetivos: Investigar a relação entre o transporte mucociliar e a atividade física na vida diária (AFVD em fumantes e não fumantes. Métodos: Cinquenta e dois fumantes foram submetidos à avaliação do transporte mucociliar (Tempo de Trânsito de Sacarina, TTS, dos níveis de monóxido de carbono no ar expirado, da função pulmonar e do hist

Evolution of near-field physico-chemical characteristics of the SFR repository

Energy Technology Data Exchange (ETDEWEB)

Savage, D [Quintessa Ltd., Nottingham (United Kingdom); Stenhouse, M [Monitor Scientific LLC, Denver, CO (United States); Benbow, S [Quintessa Ltd., Henley-on-Thames (United Kingdom)

2000-08-01

The evaluation of the post-closure performance of the SFR repository needs to consider time dependent evolution of the repository environment. Time-dependent reaction of near-field barriers (cement, steel, bentonite) with saturating groundwater will lead to the development of hyper alkaline repository pore fluids, chemically reducing conditions, and ultimately, the generation of gas through anaerobic corrosion of metals. Cement and concrete will act as chemical conditioning agents to minimise metal corrosion and ultimately, maximise radioelement sorption. The chemical and physical evolution of cement and concrete through reaction with ambient groundwater will thus affect sorption processes through changes in pH, complexing ligands, and solid surface properties. It is desirable that these changes be incorporated into the safety assessment. The sorption behaviour of radionuclides in cementitious systems has been reviewed in detail. The available evidence from experimental work carried out on the influence of organic materials on the sorption behaviour of radionuclides, indicates that most organic degradation products will not affect sorption significantly at the concentrations expected in a cementitious repository. The notable exception to this conclusion involves the degradation products of cellulose and, in particular, polycarboxylic acids represented by iso-saccharinic acid (ISA). Results using ISA indicate a significant reduction in sorption of Pu, by several orders of magnitude, for an ISA concentration of about 10{sup -3} M. More recent data indicate that the negative effect is not as great, though still significant. Therefore, some scoping calculations are advisable to determine how realistic an ISA concentration of about 10{sup -3} M would be for the SFR repository and to estimate concentrations of other relevant organic compounds, in particular EDTA, for comparison. Scoping calculations relevant to the longevity of hyper alkaline pore fluid conditions at SFR

Evolution of near-field physico-chemical characteristics of the SFR repository

International Nuclear Information System (INIS)

Savage, D.; Stenhouse, M.; Benbow, S.

2000-08-01

The evaluation of the post-closure performance of the SFR repository needs to consider time dependent evolution of the repository environment. Time-dependent reaction of near-field barriers (cement, steel, bentonite) with saturating groundwater will lead to the development of hyper alkaline repository pore fluids, chemically reducing conditions, and ultimately, the generation of gas through anaerobic corrosion of metals. Cement and concrete will act as chemical conditioning agents to minimise metal corrosion and ultimately, maximise radioelement sorption. The chemical and physical evolution of cement and concrete through reaction with ambient groundwater will thus affect sorption processes through changes in pH, complexing ligands, and solid surface properties. It is desirable that these changes be incorporated into the safety assessment. The sorption behaviour of radionuclides in cementitious systems has been reviewed in detail. The available evidence from experimental work carried out on the influence of organic materials on the sorption behaviour of radionuclides, indicates that most organic degradation products will not affect sorption significantly at the concentrations expected in a cementitious repository. The notable exception to this conclusion involves the degradation products of cellulose and, in particular, polycarboxylic acids represented by iso-saccharinic acid (ISA). Results using ISA indicate a significant reduction in sorption of Pu, by several orders of magnitude, for an ISA concentration of about 10 -3 M. More recent data indicate that the negative effect is not as great, though still significant. Therefore, some scoping calculations are advisable to determine how realistic an ISA concentration of about 10 -3 M would be for the SFR repository and to estimate concentrations of other relevant organic compounds, in particular EDTA, for comparison. Scoping calculations relevant to the longevity of hyper alkaline pore fluid conditions at SFR have been