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PubMed1994

Effects of aliphatic alcohols and food additives on nicotinic acetylcholine receptors in Xenopus oocytes.

To study the effects of food additives on nicotinic acetylcholine receptors (nAChR), they were expressed in Xenopus oocytes that received an injection of mRNA prepared from electroplax of Electrophorus electricus. The response of nAChR elicited by acetylcholine (ACh) was measured electrophysiologically in the presence and absence of aliphatic alcohols and food additives. All compounds examined inhibited nAChR non-competitively in a concentration-dependent way. The inhibition was stronger when the inhibitors were perfused 1 min before ACh, than when they were perfused simultaneously with ACh. The inhibition of nAChR by aliphatic alcohols (propanol to hexanol) increased as the number of carbon chains increased. The addition of alcohols and food additives did not affect the desensitization of nAChR caused by 2 microM ACh. These results suggest that alcohols and food additives bind to the anesthetic binding site in nAChR and inhibit it noncompetitively. However, these compounds will not hinder signal transmission in neuromuscular junctions under physiological conditions, because their inhibition constants are more than 1 mM and muscles usually have more receptors than the number necessary for signal transmission.

Animals↗
PubMed1991

Priority-based assessment of food additives database of the U.S. Food and Drug Administration Center for Food Safety and Applied Nutrition.

The priority-based assessment of food additives (PAFA) is a database maintained by the U.S. Food and Drug Administration (FDA) Center for Food Safety and Applied Nutrition. PAFA contains extensive administrative, chemical, and toxicological information on 1685 regulated direct food additives. The database also has limited administrative and chemical information on an additional 1236 direct additives. The total 2921 substances represent everything added to food in the United States. PAFA contains up to 150 different kinds of information about each chemical. Administrative and chemical information includes Chemical Abstracts Service Registry numbers, Code of Federal Regulations citations, the annual usage and estimated daily U.S. human consumption, the Joint Committee on Food Additives Allowable Daily Intakes, the FDA Redbook structure categories of the chemicals, and their technical effects. Toxicology information shows the type of studies done for each chemical, the species of animals tested, the toxicological effects observed and the sites where they were seen, the lowest doses that cause a toxicological effect in each study, a source citation, and other types of related information.

Administration, Oral↗
PubMed1982

Physiological changes in hyperactive children following the ingestion of food additives.

This study attempted to determine if the ingestion of artificial food additives would produce detectable changes in autonomic and/or central nervous system activity in hyperactive children. A single-case experimental design was used which entailed the comparison of heart rate and electroencephalographic (EEG) measures for hyperactive and control children. The physiological measures were obtained prior to and following the ingestion of drinks containing food additives or placebos, which were administered in a double-blind, randomized, crossover procedure. The hyperactive children exhibited a greater degree of physiological activity following both the placebo and the drink containing food additives than did the control children. However, the magnitude of physiological changes in the hyperactive children were greater in response to ingestion of the additives than to placebo. These physiological findings are consistent with behavioural data indicating that some hyperactive children are adversely affected by food additives.

Alpha Rhythm↗
PubMed2004

The effects of buffered propionic acid-based additives alone or combined with microbial inoculation on the fermentation of high moisture corn and whole-crop barley.

Buffered propionic acid-based additives (BP) alone or in combination with a microbial inoculant containing lactic acid bacteria (MI) were mixed with ground, high moisture corn or whole-crop barley and ensiled in triplicate laboratory silos to investigate their effects on silage fermentation and aerobic stability. The inoculant and chemicals were applied separately for treatments that included both additives. The addition of MI alone had no effect on DM recovery, fermentation end products, or aerobic stability of high moisture corn. However, treatments with 0.1 and 0.2% BP (alone and the combination) had more than 10- and 100-fold fewer yeasts, respectively, and they also had greater concentrations of propionic acid than did untreated corn. Corn treated with only 0.1 (161 h) and 0.2% (218 h) BP tended to be more stable when exposed to air than untreated corn (122 h). Treatment with MI + 0.2% BP markedly improved the aerobic stability (>400 h) of high moisture corn. With whole-crop barley, the addition of MI alone, BP alone, and combinations of MI and BP prevented the production of butyric acid that was found in untreated silage (0.48%). All barley silages that had MI in their treatments underwent a more efficient fermentation than treatments without MI, as evident by a greater ratio of lactic:acetic acid and more DM recovery than in untreated silage. Increasing levels (0.1 to 0.2%) of BP added together with MI improved the aerobic stability of barley (190 and 429 h) over the addition of MI alone (50 h). These data show that buffered propionic acid-based products are compatible with microbial inoculants and, in some circumstances when used together, they can improve the fermentation and aerobic stability of silages.

Acetic Acid↗
PubMed1989

Oral provocation tests with aspirin and food additives in asthmatic patients.

Aspirin and food additives are known to induce bronchoconstriction, angioedema or urticaria in susceptible patients. To evaluate the incidence of hypersensitivity to aspirin and food additives, 36 subjects with bronchial asthma, 33 of whom were non-allergic asthmatics and 3 were allergic asthmatics who had a history of aspirin sensitivity, were challenged orally with six compounds: acetylsalicylic acid (ASA), sodium bisulfite, tartrazine, sodium benzoate, 4-hydroxy benzoic acid, and monosodium L-glutamate. Significant bronchoconstrictions were found in 15 (41.7%) of the 36 subjects tested. Eight of the 15 subjects showed positive asthmatic responses to the aspirin, two showed asthmatic responses to the food additives, and five responded to both aspirin and the food additives. It is suggested that ASA and food additives could be causes of clinically significant bronchoconstriction in moderately severe non-allergic asthmatic patients.

Adolescent↗
PubMed1983

Efficacy and nontarget effects of Larvadex as a feed additive for controlling house flies in caged-layer poultry manure.

The insect growth regulator N-cyclopropyl-1,3,5-triazine-2,4,6 triamine (Larvadex, CGA 72662, cyromazine) was provided as a feed additive (.3% Premix per ton of feed) to caged laying hens under field conditions in high rise, wide span and narrow poultry houses. The chemical effectively controlled house flies (Musca domestica) and soldier flies (Hermetia illucens). The feed additive had no adverse effect on the populations of manure-inhabiting mites (Macrochelidae and Uropodidae) and histerid beetles (Carcínops pumulio), which prey on fly eggs and larvae. Satisfactory fly control was demonstrated by use of the additive 50% of the time when the interval without the additive in the feed was 4 days but not when the interval was 7 days. Use of a fly monitoring program to time the use of the feed additive is advocated.

Animals↗
PubMed1987

[Food additives from the viewpoint of the food chemist].

Food additives serve the consumer and are a necessity for food retailers and producers. Additives, such as vitamin D and iodine, increase the nutritional physiological value of foodstuffs. Additives, which improve food preservation by preventing microbiological deterioration are especially important. Some additives are added during food production and have no further use in the finished product. They are no longer present (solvents, clarifying agents). With regard to health, many food additives are better tested than most foods.

Food Additives↗
PubMed1979

Nitrite as a food additive.

Nitrite is used for its colouring, antimicrobial and flavouring effects as a food additive for several meat, fish and cheese products. Nitrite combines readily with secondary amines to form carcinogenic nitrosamines. Nitrosamines are found in many food products after nitrite addition and sometimes even without addition. Nitrite is regarded as an effective growth inhibitor for Clostridium botulinum and thereby its production of the lethal toxin. Today this is considered to be the main reason for addition of nitrite to food products. It should be possible to limit the addition of nitrite to a few special food products where Cl botulinum really represents a hazard to human health, i e to canned meat that is not sterilized by heat and some cured and fermented products. In Norway the use of nitrite is limited to products where growth of clostridia is possible, but in a few products nitrite is also allowed as a colour stabilizer. It is reasonable to expect that other countries will decide upon similar regulations. The naturally occurring nitrates in vegetables have to be included in the discussion due to the possibility of microbial reduction to nitrites.

Clostridium↗
PubMedDate not supplied

Animal feed additive regulation in the Common Market: rules, principles and ideas.

The fundamental factors which govern legislation relating to the use of additives are examined. The rules advocated are as follows: 1) All additives unless licensed remain strictly prohibited. 2) There must be a severe but realistic appraisal of additives to be authorised, taking into account the interests of the farmer and the health of the consumer, particularly in respect of cumulative toxicity and relay toxicity. 3) Periodic revision of licenses is necessary in the light of experience acquired and of new scientific knowledge. 4) Strict regulation of veterinary dispensing is necessary and it should not be possible to use prohibited additives through the lack of such a regulation. In other respects the veterinarian should prescribe substances which might leave residues only when there is adequate time for their disappearance before slaughter or in animals where the products are not for human consumption. 5) It should be possible to monitor all regulations. 6) It should be impossible to use compounds or drugs similar to those already authorized without new investigations and experiments on such additives. 7) Guidelines must be produced. Such European guidelines are now being discussed by a committee of experts. We hope that such guidelines will be studied by the FDA and a Joint Committee will be organised with the European Commission for relevant discussions.

Animal Feed↗
PubMed1996

Effects of the addition of hyaluronate segments with different chain lengths on the viscoelasticity of hyaluronic acid solutions.

The effects of the addition of sodium hyaluronate segments (sHA) with different chain lengths on the viscoelasticity of high molecular weight sodium hyaluronate (HA) aqueous solutions were studied. The additive effects of sHA depended on the chain length of sHA. Shorter sHA decreased storage (G') and loss (G") moduli, whereas longer sHA increased both moduli. In physiological saline, the effects of the addition of sHA depended on the chain length of sHA, as in aqueous solutions, except that shorter segments did not decrease both moduli. The effects of the addition of monosaccharides, i.e., N-acetyl glucosamine (GlcNAc) and sodium glucuronate (GlcANa), were also studied. Although GlcNAc increased G' and G", GlcANa decreased both moduli. A shift factor "A," which depended on chain-length effects, a sugar effect, and a salt effect, was developed to explain these additive effects quantitatively.

Carbohydrate Sequence↗
PubMed2004

Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma.

BACKGROUND: Anti-leukotriene (AL) agents are being considered as 'add-on' therapy to inhaled corticosteroids (ICS), in chronic asthma. OBJECTIVES: To examine the safety and efficacy of daily AL plus ICS compared to ICS alone, and determine the corticosteroid-sparing effect of AL when added to ICS in chronic asthma. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CINAHL (until August 2003), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and looked at American Thoracic Society and European Respiratory Society meeting abstracts (1998 to 2003). SELECTION CRITERIA: Randomised placebo-controlled trials of asthmatics aged two years and older with at least one month intervention. DATA COLLECTION AND ANALYSIS: Two reviewers assessed quality and extracted data independently. Trials were grouped by asthma control at baseline (symptomatic or well-controlled) and dose of ICS in the control group (same or double). MAIN RESULTS: Of 587 citations, 27 (25 adult and 2 paediatric) trials met inclusion criteria. Sixteen trials were published in full-text and 16 trials reported data in a way that allowed meta-analysis. In symptomatic patients, addition of licensed doses of anti-leukotrienes to ICS resulted in a non-significant reduction in the risk of exacerbations requiring systemic steroids: Relative Risk (RR) 0.64; 95% Confidence Interval (CI) 0.38 to 1.07). A modest improvement group difference in PEF was seen (Weighted Mean Difference (WMD) 7.7 L/min; 95% CI 3.6 to 11.8 L/min) together with decrease in use of rescue short-acting beta2-agonist use (WMD 1 puff/week; 95%CI 0.5 to 2). With only 3 trials comparing the use of licensed doses of anti-leukotrienes with increasing the dose of inhaled glucocorticoids, no firm conclusion can be drawn about the equivalence of both treatment options. In ICS-sparing studies of patients who were well controlled at baseline, addition of anti-leukotrienes produced no overall difference in dose of inhaled glucocorticoids (WMD -21 mcg/d, 95%CI -65, 23 mcg/d), but it was associated with fewer withdrawals due to poor asthma control (RR 0.63, 95% CI 0.42 to 0.95). REVIEWERS' CONCLUSIONS: The addition of licensed doses of anti-leukotrienes to add-on therapy to inhaled glucocorticoids brings modest improvement in lung function. Although addition of anti-leukotrienes to inhaled glucocorticoids appears comparable to increasing the dose of inhaled steroids, the power of the review is insufficient to confirm the equivalence of both treatment options. Addition of anti-leukotrienes is associated with superior asthma control after glucocorticoid tapering; although the glucocorticoid-sparing effect cannot be quantified at present, it appears modest.

Administration, Inhalation↗
PubMed2002

The hetero-Diels-Alder addition of sulfur dioxide to 1-fluorobuta-1,3-dienes: the sofa conformations preferred by 6-fluorosultines (6-fluoro-3,6-dihydro-1,2-oxathiin-2-oxides) enjoy enthalpic and conformational Anomeric effects.

The reactivity of (E)- and (Z)-1-fluorobuta-1,3-diene ((E)- and (Z)-11), 2-fluorobutadiene (12), (E)- and (Z)-1-(fluoromethylidene)-2-methylidenecyclohexane ((E)- and (Z)-13) toward SO(2) has been explored and compared with that of (Z)- and (E)-1-(fluoromethylidene)-2-methylidene-3,4-dihydronaphthalene ((Z)-8 and (E)-8). In agreement with quantum calculations, 12 is unreactive toward SO(2) (no cycloaddition, only polymerization), whereas (E)-1-fluoro-1,3-dienes react more rapidly than their (Z)-isomers to give the corresponding 6-fluorosultines following the endo (Alder rule) mode of hetero-Diels-Alder addition. No sulfolene has been observed following the cheletropic mode of addition with the fluorodienes, in contrast to other substituted dienes. In agreement with the calculations, cis-2-fluoro-3,4-oxathiabenzobicyclo[4.4.0]dec-1(6),9-diene-4-oxide (cis-9, the sultine obtained by SO(2) addition to (Z)-8 under conditions of kinetic control) adopts a sofa conformation with the oxygen atom of the ring lying in the average plane of the four carbon atoms of its sultine moiety when it is in the crystalline state at -100 degrees C. A similar sofa conformation was found for its trans-isomer, trans-9, obtained by isomerization of cis-9 or by hetero-Diels-Alder addition of SO(2) to (E)-8. Experiments (equilibrium constant for hetero-Diels-Alder additions, bond lengths, and bond angles in crystalline fluorosultines cis-9 and trans-9) and high-level quantum calculations on cis- and trans-6-fluoro-3,6-dihydro-1,2-oxathiin-2-oxide (cis- and trans-20) confirm the existence of a stabilizing, enthalpic, anomeric (gem-disubstitution by sulfinyloxy and fluoro groups) effect, which is interpreted in terms of (lone pair) n(O1)-->sigma*(C-F) hyperconjugative interactions. This effect is strongest in the sofa conformers with a gauche arrangement of the sigma(O1,S2) and sigma(C6,F) bonds. The calculations suggest also that n(O1)-->sigma*(S2,O2'), pi*(S=O), and n(S2)-->sigma*(O1,C6) interactions intervene and affect the relative stability of the conformers (sofa, boat, pseudo-chair) found for 6-fluorosultines cis- and trans-20.

Journal Article↗
PubMed2001

Factors Controlling the Addition of Carbon-Centered Radicals to Alkenes-An Experimental and Theoretical Perspective.

The successful exploitation of syntheses involving the generation of new carbon-carbon bonds by radical reactions rests on some prior knowledge of the rate constants for the addition of carbon-centered radicals to alkenes and other unsaturated molecules, and of the factors controlling them. Two former classical reviews in Angewandte Chemie by Tedder (1982) and by Giese (1983) provided mechanistic insight and led to various qualitative rules on the complex interplay of enthalpic, polar, and steric effects. In the meantime, the field has experienced very rapid progress: many more experimental absolute rate constants have become available, and there have been major advances in the efficiency and reliability of quantum-chemical methods for the accurate calculation of transition structures, reaction barriers, and reaction enthalpies. Herein we review this progress, recommend suitable experimental and theoretical procedures, and display representative data series for radical additions to alkenes. On this basis, and guided by the pictorial tool of the state-correlation diagram for radical additions, we then offer a new and more stringent quantification of the controlling factors. Our analysis leads to a partial revision of the previous qualitative rules, and it more clearly exhibits the interplay of the reaction enthalpy effects, polar charge-transfer contributions, and steric substituent effects on the reaction energy barrier. The various contributions are cast into the form of new, simple, and physically meaningful but non-linear, predictive equations for the preestimation of rate constants. These equations prove successful in several tests but call for additional theoretical and experimental foundation. The kinetics of related reactions such as polymer propagation, copolymerization, and the addition of radicals to alkynes and aromatic compounds is shown to follow the same principles.

Journal Article↗
PubMed2002

Accurately describing weak analyte-additive interactions by capillary electrophoresis.

When modeling analyte-additive interactions in capillary electrophoresis (CE), it is necessary to correct for all changes in the apparent electrophoretic mobility of an analyte that are not due to specific binding. Current models based on dynamic complexation have corrected for bulk viscosity changes in the background electrolyte (BGE) when additives are used, while assuming negligible changes in the dielectric constant and other physicochemical properties of the solution. In this report, a study of weak interactions between deoxyribonucleotides and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) revealed significant nonideality in binding isotherms. Changes in the dielectric properties of the solution due to the addition of high concentrations of HP-beta-CD to the BGE was observed to alter the electrophoretic mobility of analytes. A relative dielectric correction factor was required to normalize analyte mobilities to a reference state of zero additive concentration. The use of both a relative dielectric factor and a viscosity correction factor was found to increase the accuracy of the model, reflected by a higher degree of correlation between predicted and measured analyte mobilities. This type of correction is particularly relevant when studying weak analyte binding interactions or when using high concentrations of additive in the BGE. This work is vital for accurate determination of weak binding constants and mobility values, as well as providing a deeper understanding of the fundamental parameters influencing a separation in CE.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2001

Automatic inducer addition and harvesting of recombinant Escherichia coli cultures based on indirect on-line estimation of biomass concentration and specific growth rate.

This article describes a novel bioreactor configuration for production optimization of recombinant proteins in Escherichia coli. Inducer addition and harvesting are controlled on-line based on indirect estimation of biomass concentration and specific growth rate from addition of NaOH to maintain constant pH. When either a predetermined biomass concentration is reached or the cultures have obtained, a constant specific growth rate inducer is introduced automatically. The induction period is ended by automatic harvesting of the cultures either at a predetermined biomass concentration or when substrate (in this study glucose) is depleted, detected as an increase of pH, or dissolved oxygen tension. During harvesting, metabolic activities are quenched within 3 min by cooling of the cell suspension. The system has been used to optimize expression of glutathione S-transferase (GST) fusion protein of the ligand binding domain of mouse peroxisome proliferator-activated receptor, GST-PPARalpha LBD. Total yield of GST-PPARalpha LBD was independent of the time of inducer addition as long as the length of induction period corresponded to at least 0.25 cell divisions while the yield of soluble GST-PPARalpha LBD, the only active form, increased with the length of induction period. Highest yields were obtained when the inducer was added at low cell concentration as soon as constant specific growth rate was detected, resulting in induction periods corresponding to 3.4 +/- 0.4 cell divisions. The specific growth rate remained almost constant for one cell division after inducer addition, whereafter it decreased. No decrease of specific growth rate was observed when inducer was added in the lag-phase, and no soluble protein was produced. These results suggest that solely soluble GST-PPARalpha LBD acts as a growth inhibitor and that GST-PPARalpha LBD is expressed predominantly as inclusion bodies immediately after inducer addition whereas the proportion expressed as soluble protein is increased after 1 h of induction. Compared to the procedures, which are generally used for protein expression in the laboratory, this system is less labor intensive, it automatically provides recording of biomass concentration and specific growth rate, and it allows direct comparisons between expression of different proteins and performance of different constructs since the induction period is linked to growth.

Animals↗
PubMed2001

Probing the performance limits of the Escherichia coli metabolic network subject to gene additions or deletions.

An optimization-based procedure for studying the response of metabolic networks after gene knockouts or additions is introduced and applied to a linear flux balance analysis (FBA) Escherichia coli model. Both the gene addition problem of optimally selecting which foreign genes to recombine into E. coli, as well as the gene deletion problem of removing a given number of existing ones, are formulated as mixed-integer optimization problems using binary 0-1 variables. The developed modeling and optimization framework is tested by investigating the effect of gene deletions on biomass production and addressing the maximum theoretical production of the 20 amino acids for aerobic growth on glucose and acetate substrates. In the gene deletion study, the smallest gene set necessary to achieve maximum biomass production in E. coli is determined for aerobic growth on glucose. The subsequent gene knockout analysis indicates that biomass production decreases monotonically, rendering the metabolic network incapable of growth after only 18 gene deletions. In the gene addition study, the E. coli flux balance model is augmented with 3,400 non-E. coli reactions from the KEGG database to form a multispecies model. This model is referred to as the Universal model. This study reveals that the maximum theoretical production of six amino acids could be improved by the addition of only one or two genes to the native amino acid production pathway of E. coli, even though the model could choose from 3,400 foreign reaction candidates. Specifically, manipulation of the arginine production pathway showed the most promise with 8.75% and 9.05% predicted increases with the addition of genes for growth on glucose and acetate, respectively. The mechanism of all suggested enhancements is either by: 1) improving the energy efficiency and/or 2) increasing the carbon conversion efficiency of the production route.

Aerobiosis↗
PubMed2005

Site-selective DNA hydrolysis by Ce(IV)-EDTA with the use of one oligonucleotide additive bearing two monophosphates.

Two deoxyuridine derivatives each bearing a monophosphate group at the 5-position with a C3 linker, were incorporated into an oligonucleotide. By using this modified oligonucleotide, a bulge was formed at a predetermined position in a DNA substrate, and two monophosphate groups were placed at both junctions of the bulge. Upon treatment of the mixture with Ce(IV)-EDTA at pH 7.0, the phosphodiester linkages at the bulge site were selectively and efficiently hydrolyzed. The monophosphate groups introduced into the bulge site greatly accelerated site-selective DNA scission. Compared with the previously reported two-additive system, which combines two oligonucleotide additives each with a monophosphate at their termini, the present one-additive system is simpler and more convenient. Furthermore, site-selective DNA hydrolysis by using this one-additive system is successful even at high reaction temperatures (e.g., 55 degrees C). This reflects the thermodynamic stability of the duplexes formed between the substrate and the additive DNA.

Base Sequence↗
PubMed2003

Diastereoselective conjugate addition to chiral alpha,beta-unsaturated carbonyl systems in aqueous media: an enantioselective entry to alpha- and gamma-hydroxy acids and alpha-amino acids.

The stereoselectivity of the ultrasonically induced zinc--copper conjugate addition of iodides to chiral alpha,beta-unsaturated carbonyl systems under aqueous conditions was studied. Alkyl iodides add diastereoselectively to methylenedioxolanone 1 and methyleneoxazolidinone 2 to afford the 1,4-addition products in good yields (38-95 %) and with high diastereomeric excess (44-90 % de). The 1,4-addition to chiral gamma,delta-dioxolanyl-alpha,beta-unsaturated esters 3-5 also proceeds with good yields (51-99 %). The diastereoselectivity is dependent on the geometry of the olefin: the Z isomer 3 gives high diastereoselectivity, while the reactions with the E isomer 4 are nonstereoselective. The reaction proceeds with excellent chemoselectivity and allows the use of iodides bearing ester, hydroxy, and amino groups. Since the 1,4-addition products can be readily hydrolyzed, this methodology constitutes a novel entry for the enantioselective synthesis of alpha- and gamma-hydroxy acids and alpha-amino acids in aqueous media. The results obtained support the radical mechanism proposed by Luche, and represent one of the few examples of a radical stereoselective conjugate addition in aqueous medium.

Amino Acids↗