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At least 433 records · Page 24Linked to original sources
PubMed2006

Optimization of the conjugation method for a serogroup B/C meningococcal vaccine.

A conjugate meningococcal vaccine against serogroup B/C consisting of capsular PS (polysaccharide) from serogroup C conjugated to OMV (outer membrane vesicle) from serogroup B would be a very useful vaccine in regions where there is a prevalence of both serogroups, for example in Brazil. For this purpose, the conjugation method that uses ADHy (adipic acid dihydrazide) as spacer and a carbodi-imide derivative, EDAC [1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide], as catalyser was optimized looking for synthesis yield and maintenance of the antigenicity of both components. The best synthesis conditions preserving the vaccine immunogenicity resulted in a final yield of approx. 17%. Immunogenicity of the vaccine was highest when 10% of the sialic acid residues of the PS were occupied by the ADHy spacer. Sterilization of the conjugate by filtration through a 0.22-microm-pore-size membrane resulted in a low recovery of protein and PS (approximately 50%), although the vaccine immunogenicity was maintained. Using gamma irradiation on freeze-dried sample, it was possible to maintain the integrity of OMV structure and, consequently, its ability to induce bactericidal antibodies.

Adipates↗
PubMed2000

Identification in Saccharomyces cerevisiae of two isoforms of a novel mitochondrial transporter for 2-oxoadipate and 2-oxoglutarate.

The nuclear genome of Saccharomyces cerevisiae encodes 35 members of a family of membrane proteins. Known members transport substrates and products across the inner membranes of mitochondria. We have localized two hitherto unidentified family members, Odc1p and Odc2p, to the inner membranes of mitochondria. They are isoforms with 61% sequence identity, and we have shown in reconstituted liposomes that they transport the oxodicarboxylates 2-oxoadipate and 2-oxoglutarate by a strict counter exchange mechanism. Intraliposomal adipate and glutarate and to a lesser extent malate and citrate supported [14C]oxoglutarate uptake. The expression of Odc1p, the more abundant isoform, made in the presence of nonfermentable carbon sources, is repressed by glucose. The main physiological roles of Odc1p and Odc2p are probably to supply 2-oxoadipate and 2-oxoglutarate from the mitochondrial matrix to the cytosol where they are used in the biosynthesis of lysine and glutamate, respectively, and in lysine catabolism.

Adipates↗
PubMed2000

Identification of the human mitochondrial oxodicarboxylate carrier. Bacterial expression, reconstitution, functional characterization, tissue distribution, and chromosomal location.

In Saccharomyces cerevisiae, the genes ODC1 and ODC2 encode isoforms of the oxodicarboxylate carrier. They both transport C5-C7 oxodicarboxylates across the inner membranes of mitochondria and are members of the family of mitochondrial carrier proteins. Orthologs are encoded in the genomes of Caenorhabditis elegans and Drosophila melanogaster, and a human expressed sequence tag (EST) encodes part of a closely related protein. Information from the EST has been used to complete the human cDNA sequence. This sequence has been used to map the gene to chromosome 14q11.2 and to show that the gene is expressed in all tissues that were examined. The human protein was produced by overexpression in Escherichia coli, purified, and reconstituted into phospholipid vesicles. It has similar transport characteristics to the yeast oxodicarboxylate carrier proteins (ODCs). Both the human and yeast ODCs catalyzed the transport of the oxodicarboxylates 2-oxoadipate and 2-oxoglutarate by a counter-exchange mechanism. Adipate, glutarate, and to a lesser extent, pimelate, 2-oxopimelate, 2-aminoadipate, oxaloacetate, and citrate were also transported by the human ODC. The main differences between the human and yeast ODCs are that 2-aminoadipate is transported by the former but not by the latter, whereas malate is transported by the yeast ODCs but not by the human ortholog. In mammals, 2-oxoadipate is a common intermediate in the catabolism of lysine, tryptophan, and hydroxylysine. It is transported from the cytoplasm into mitochondria where it is converted into acetyl-CoA. Defects in human ODC are likely to be a cause of 2-oxoadipate acidemia, an inborn error of metabolism of lysine, tryptophan, and hydroxylysine.

Adipates↗
PubMed2000

Plasticizers in total diet samples, baby food and infant formulae.

The plasticizers di-n-butylphthalate (DBP), butylbenzylphthalate (BBP), di-2-(ethylhexyl)phthalate (DEHP) and di-2-(ethylhexyl)adipate (DEHA) were analysed in 29 total diet samples, in 11 samples of baby food and in 11 samples of infant formulae. In all of the total diet samples the presence of one or more of the plasticizers was demonstrated. Maximum and minimum mean concentrations in the total diet samples were: 0.09-0.19 mg DBP/kg, 0.017-0.019 mg BBP/kg, 0.11-0.18 mg DEHP/kg and 0.13-0.14 mg DEHA/kg. One or more of the phthalates was also found in about 50% of the samples of baby food as well as in infant formulae. The calculated mean maximum intakes of the individual compounds from the total diet samples were below 10% of the restrictions proposed by the EU Scientific Committee for Food (SCF), and the spread in individual intakes was considerable. DEHP was the plasticizer determined most frequently and contributed the highest fraction of its tolerable daily intake (TDI). Hence, the maximum calculated intake of DEHP from single samples of the foodstuffs analysed could be up to one-third of the TDI. The calculated mean intake of DEHA was about 1% of the TDI with a maximum value of 13% of the TDI. Violations of the restrictions proposed by the EU Scientific Committee for Food (SCF) in the form of TDI values or specific migration limits were not found in this investigation.

Adipates↗
PubMed2006

Plasticizers in Brazilian food-packaging materials acquired on the retail market.

Packaging materials intended for direct food contact were acquired on the Brazilian retail market and analysed for their plasticizer content. Analyses were carried out by gas chromatography with flame ionization detection. Di-2-ethyl-hexyl adipate (DEHA), di-2-ethyl-hexyl phthalate (DEHP) and di-iso-decyl phthalate (DIDP) plasticizers were identified in films and closure seals in concentrations ranging from 12 to 19% (w/w), 15 to 44% (w/w) and 10 to 11% (w/w), respectively. Brazilian regulations state that for use with foods with a fat content above 5%, the levels of DEHP and DIDP in the plastic material should be no greater than 3%. The results obtained demonstrate a lack of conformity. It would be advisable to include information on the labels of packaging materials about their restrictions of use in order to advise manufacturers and consumers about their proper usage.

Adipates↗
PubMed2005

Dietary exposure to chemical migrants from food contact materials: a probabilistic approach.

A two-dimensional probabilistic model has been developed to estimate the short-term dietary exposure of UK consumers to migrants from food packaging materials. The current EU approach uses a default scenario of assuming that all individuals are 60 kg weight and consume 1 kg of food packaged in the material of interest per day. Using four UK National Dietary and Nutrition Surveys comprising 4-7 day dietary records for different age groups and survey years, a sample representative of the UK population has been obtained consuming around 4200 different food items. Each survey provides records for around 2000 individuals and supplies detailed information on the consumption of food and data on sex, height and socio-economic status which may be used to analyse the exposure of selected groups within the community. As a result we are able to address the variation in consumption of food amongst individuals, and account for actual body weights providing a more accurate representation of the 'true' exposure. The migrants bisphenol A diglycidyl ether (BADGE), di-2-ethylhexyl adipate (DEHA) and styrene were considered as specimen compounds although the methodology employed has the flexibility to adapt to other migrants and packaging types and indeed other food contaminants. Exposure for each individual is estimated by calculating and summing the individual exposure from each item in their diet, and is repeated for all individuals in each survey to produce a distribution of exposures for the population. The packaging type of each food item is assigned by utilizing known packaging types from the database or, by sampling from a distribution based upon market share information. The parameters contributing towards the exposure from a packaged dietary item are migrant concentration and item weight. Distributions are used to represent the inherent variation and uncertainty affecting these parameters. Where data on concentrations for a particular type of food are lacking, expert judgement is used to extrapolate from available data for other food types. The model can also be run using only migration data for food simulants. In this case, concentrations expected for each of the food items are assigned based on the data for the relevant food simulant. The primary outputs of the model are distributions of estimated daily intakes for the selected population. Each distribution gives the variation across the population subject to the uncertain parameters sampled in that iteration of the model. Analysing the ensemble of distributions allows us to obtain the confidence limits around estimates for percentiles due to the uncertainties. The probabilistic approach allows sensitivity analysis to evaluate the relative importance of the input parameters and places confidence bounds on the outputs to show the effect of the uncertainties and the contribution of each food type toward the overall exposure.

Adipates↗
PubMedDate not supplied

Migration from plasticized films into foods. 5. Identification of individual species in a polymeric plasticizer and their migration into foods.

To assess the significance of migration of polymeric plasticizers into foods, chemical characterization and quantification of individual oligomeric species is required. This paper reports the identification of seven individual oligomers isolated from a poly(butylene adipate) plasticizer. Based on mass spectrometry, NMR and chemical degradation, the oligomers were identified as a series of diol-terminated units ranging from a trimer up to an 11-monomer unit, along with a cyclic tetramer, all in the molecular weight range of 300-1100. A study of the migration of polymeric plasticizer from PVC film into olive oil indicated preferential migration of low molecular weight species. These oligomers which comprised 24% of the parent plasticizer contributed more than 90% of the plasticizer migration with the smallest oligomers migrating 90-fold more readily than the bulk of the plasticizer. From a knowledge of total polymeric plasticizer migration from PVC films under actual conditions of food-use, the abundance of individual oligomers in the foods has been estimated.

Adipates↗
PubMedDate not supplied

PVC cling film in contact with cheese: health aspects related to global migration and specific migration of DEHA.

Following exposure to the food simulant olive oil for 10 days at 5, 20 or 40 degrees C a global migration ranging from 20 to 30 mg/dm2 was detected from a common 'low migration' PVC film plasticized with a mixture of di-(ethylhexyl)adipate (DEHA) and a polymeric plasticizer. In a laboratory experiment samples of cheese of the types most commonly consumed in Denmark were wrapped in this 'low migration' PVC film using a procedure simulating the actual pattern of use in retail shops. After a storage time of 2 h at 5 degrees C the level of DEHA was 45 mg/kg of cheese, which after 10 days increased to 150 mg DEHA per kg of cheese, corresponding to an estimated specific migration of 12 mg DEHA/dm2 of cheese surface. Based on statistics on dietary habits it is concluded that the retail packaging of small portions of cheese even in a 'low migration' PVC cling film may lead to consumer intakes of DEHA close to or above the tolerable daily intake of 0.3 mg/kg body weight as defined by the EEC Scientific Committee for Food. Furthermore, it is stressed that measurements of global migration followed by uncritical use of reduction factors may result in erroneous evaluation of the suitability of DEHA-plasticized cling film for the packaging of fatty foods.

Adipates↗
PubMedDate not supplied

Migration from PVC cling films compared with their field of application.

Samples of PVC cling films were taken at importers, wholesalers and retail shops, and their overall migration to the alternative food simulant iso-octane was measured, after establishment of a correlation between overall migration to olive oil at 40 degrees C in 10 days and to iso-octane in 2 h. Results of the migration testing were compared with the recommended and/or actual use of the PVC film and the labelling discussed in relation to the relevant EEC directives on food contact plastics. The correct labelling of plasticized PVC film intended for use in retail packaging is important to avoid the risk of significant consumer intakes of the plasticizer di-(2-ethylhexyl) adipate (DEHA) after the film has been used in contact with fatty foodstuffs. Sixty percent of the films declared for use in contact with fatty foods showed too high overall migration compared with the current interpretation of legislation at the time of sampling. In most instances DEHA made up about 80% of the total amount of plastic constituents migrating to iso-octane. Taking into consideration a specific migration limit of 3 mg DEHA/dm2, 77% of the films used for fatty foodstuff analysed were not acceptable. The migration of DEHA to non-fatty foods defined as the food simulant water was at or below 0.1 mg/dm2 in all PVC-films.

Adipates↗
PubMed2001

The phytotoxicity to tobacco plants of short-chain carboxylic acids at atmospheric concentration levels in urban areas.

In this paper, we describe the influence of monocarboxylic acids (formic acid and acetic acid) and dicarboxylic acids (succinic acid and adipic acid), which are usually contained in aerosol particles and fog water, on the growth of tobacco plant. Their influence was examined by spraying the acid solutions on intact plants and by administering them in a culture medium for suspension-cultured cells. Their growth rates suggest that the influence of short-chain monocarboxylic acids was not significant in both the intact plant experiment and the cell culture experiment. In contrast, dicarboxylic acids exhibited significant influence on the growth of intact plants and no influence on culture cells, indicating that their toxicity is exerted mainly on the tissue of leaf surface. Phytotoxicity of dicarboxylic acids is higher than that of monocarboxylic acids.

Acetic Acid↗
PubMed2003

One step enzyme linked immunosorbent assay for direct estimation of serum testosterone.

One step competitive enzyme linked immunosorbent assay (ELISA) for direct estimation of testosterone in human serum is described. Testosterone-3-O-carboxymethyl-oxime-bovine serum albumin (testosterone-3-O-CMO-BSA), was used as immunogen and testosterone-3-O-carboxymethyl-oxime-adipic-acid dihydrazide-horseradish peroxidase (testosterone-3-O-CMO-ADH-HRP) was used as tracer. To the testosterone antibody coated microtiter wells, standard or serum samples (100 microL), along with testosterone-3-O-CMO-ADH-HRP conjugate (100 microL) were incubated for 1 h at 37 degrees C. Bound enzyme activity was measured by using tetra methyl benzidine/hydrogen peroxide (TMB/H2O2) as a substrate. In this new strategy, charcoal stripped pooled human serum spiked with non-cross reactive C18, C19, C21, and C27 steroids, used for preparing the standards and blocking the sex hormone binding globulin (SHBG)/and other steroid binding globulins (SBG). The sensitivity of the assay was 0.015 ng/mL. The intra-assay and inter-assay coefficients of variation (CVs) were ranged from 7.8 to 11.8 and 4.8 to 10.4, respectively. The serum testosterone values, obtained by this method, were correlated well with those obtained by radioimmunoassay r = .98 (n = 100).

Adipates↗
PubMed2004

Carbodiimide or periodate method to prepare peroxidase hydrazide for its use in immunoassay.

Peroxidase hydrazides were prepared by conjugating horseradish peroxidase (HRP) to adipic acid dihydrazide (ADH) by carbodiimide or periodate oxidation method. The resulting HRP hydrazides (ADH-HRP) were conjugated to cortisol-21-hemisuccinate (cortisol-21-HS) by forming diimide bonds using the N-hydroxysuccinimide (NHS) carbodiimide mediated reaction. The prepared cortisol-21-HS-ADH-HRP enzyme conjugates were utilized for the development of an enzyme linked immunosorbent assay (ELISA) for direct estimation of cortisol. To the cortisol antibody coated microtiter wells, standard or serum sample (50 microL), along with 100 microL of cortisol-21-HS-ADH-HRP enzyme conjugate (ADH-HRP used is prepared by either carbodiimide or periodate oxidation method), was incubated for 1 hr at 37 degrees C. Bound enzyme activity was measured by using tetramethyl benzidine/hydrogen peroxide (TMB/H202) as substrate. The sensitivity, specificity, and recovery of the assays were found to be identical when ELISAs were employed with cortisol enzyme conjugates prepared by conjugating cortisol-21-HS to HRP hydrazide, made either by the carbodiimide method or periodate oxidation method.

Adipates↗
PubMed1985

Comparative chronic toxicities and carcinogenic potentials of 2-ethylhexyl-containing compounds in rats and mice.

Four compounds containing a 2-ethylhexyl moiety [di(2-ethylhexyl)phthalate (DEHP), di(2-ethylhexyl)adipate (DEHA), tris(2-ethylhexyl)phosphate (TEHP), and 2-ethylhexyl sulfate (EHS)] were tested for carcinogenic and other chronic and subchronic toxic effects in 90-day and 2-year studies in male and female Fischer 344 rats and B6C3F1 mice. The low generalized toxic potencies of the test chemicals allowed relatively high doses of all of these compounds to be administered. Despite differences in chemical structure, all four chemicals were related to increased occurrences of hepatocellular neoplasms, principally carcinomas, in female mice. DEHA and DEHP also induced hepatocellular neoplasms in male mice, while DEHP caused hepatocellular neoplasms in both male and female rats. No other neoplasms were considered to be unequivocally related to compound administration in these studies. There was a positive correlation between the magnitude of the hepatocarcinogenic response in female mice and the probability of a hepatocarcinogenic response in male mice and in male and female rats, suggesting quantitative differences in the carcinogenic potentials of these agents. These results suggest that compounds containing a 2-ethylhexyl moiety (and 2-ethylhexanol, by implication) may possess some carcinogenic potential, especially for the rodent liver. No other organ-specific toxic effects common to two or more test chemicals were observed in these studies.

Adipates↗
PubMed1986

In vitro steady-state levels of hydrogen peroxide after exposure of male F344 rats and female B6C3F1 mice to hepatic peroxisome proliferators.

The hypothesis that hepatocarcinogenesis resulting from treatment of rats and mice with peroxisome proliferators is linked to increased cellular levels of hydrogen peroxide from peroxisomal beta-oxidation was investigated. Male F344 rats and female B6C3F1 mice were treated for 14 days with di(2-ethylhexyl)phthalate (DEHP) or di(2-ethylhexyl)adipate (DEHA), industrial plasticizers, or nafenopin, a hypolipidemic drug. Activities of enzymes responsible for the production [peroxisomal palmitoyl CoA oxidase (PCO)] and degradation [catalase (Cat) and glutathione peroxidase (GSHPx)] of H2O2 were assayed in liver homogenates prepared from treated animals. The activities of the peroxisomal enzymes PCO and Cat were enhanced 5- to 25-fold and 1.5- to 3-fold respectively by treatment with the peroxisome proliferators. The activity of GSHPx, a cytoplasmic enzyme, was decreased 40-60% in liver homogenates prepared from treated animals compared to control animals. A kinetic treatment of the rates of formation of hydrogen peroxide by PCO, and of degradation of hydrogen peroxide by catalase was used to estimate steady-state hydrogen peroxide concentrations ([H2O2]) during peroxisomal oxidation of palmitoyl CoA. Increases in peroxisomal steady-state [H2O2] for the F344 rat liver homogenates correlated well with the carcinogenic potential of these chemicals, determined in previous carcinogenicity studies. Increases in the steady-state [H2O2] were also calculated for liver homogenates prepared from mice treated with these compounds. Decreases in liver lipid peroxidation were observed after treatment with each chemical in both species. The results of these studies are consistent with an involvement of increased peroxisomal hydrogen peroxide in the hepatocarcinogenesis of these compounds.

Adipates↗
PubMed1987

Stimulation of DNA synthesis in rat and mouse liver by various tumor promoters.

In order to investigate whether the stimulation of liver DNA synthesis might be used to detect one class of hepatic tumor promoters, the incorporation of orally administered radiolabelled thymidine into liver DNA was determined in rats and mice 24 h after a single oral gavage of test compounds at various dose levels. Three DNA-binding hepatocarcinogens, aflatoxin B1, benzidine and carbon tetrachloride, did not stimulate but rather inhibited DNA synthesis (not for CCl4). Four hepatic tumor promoters, clofibrate, DDT, phenobarbital and thioacetamide, gave rise to a stimulation in a dose-dependent manner. Single oral doses between 0.02 and 0.3 mmol/kg were required to double the level of thymidine incorporation into liver DNA (= doubling dose, DD). Differences between species or sex as observed in long-term carcinogenicity studies were reflected by a different stimulation of liver DNA synthesis. In agreement with the bioassay data, aldrin was positive only in male mice (DD = 0.007 mmol/kg) but not in male rats of female mice. 2,3,7,8-TCDD was positive in male mice (DD = 10(-6) mmol/kg) and in female rats (DD = 2 X 10(-6) mmol/kg) but not in male rats. The assay was also able to distinguish between structural isomers with different carcinogenicities. [alpha]Hexachlorocyclohexane stimulated liver DNA synthesis with a doubling dose of about 0.2 mmol/kg in male rats whereas the [gamma]-isomer was ineffective even at 1 mmol/kg. So far, only one result was inconsistent with carcinogenicity bioassay data. The different carcinogenicity of di(2-ethylhexyl)adipate (negative in rats) and di(2-ethylhexyl)phthalate (positive) was not detectable. Both plasticizers were positive in this short-term system with DD's of 0.7 mmol/kg for DEHA and 0.5 mmol/kg for DEHP. The proposed assay is discussed as an attempt to devise short-term assays for carcinogens not detected by the routine genotoxicity test systems.

Adipates↗
PubMed1985

Simplex optimization of extractive alkylation procedures for organic acids in aqueous samples.

Simplex optimization procedures may be used to optimize the yield from an extractive alkylation procedure. Three variables from the derivatization reaction (pH, methylating agent concentration, and phase transfer agent concentration) were chosen for optimization because they interacted with each other and could not be optimized by conventional means. The yield for methylation of adipic acid was doubled with relatively little effort. This procedure may be easily applied to other systems.

Acids↗
PubMed2004

Homocysteine and the renal epithelial transport and toxicity of inorganic mercury: role of basolateral transporter organic anion transporter 1.

The epithelial cells that line the renal proximal tubule have been shown to be the primary cellular targets where mercuric ions gain entry, accumulate, and induce pathologic effects in vivo. Recent data have implicated at least one of the organic anion transport systems in the basolateral uptake of inorganic mercury (Hg). With the use of a line of type II MDCK cells transfected stably with the human organic anion transporter 1 (hOAT1), the hypothesis that hOAT1 can transport mercuric conjugates of homocysteine (Hcy) was tested. Indeed, MDCK II cells expressing a functional form of hOAT1 gained the ability to transport the mercuric conjugate 2-amino-4-(3-amino-3-carboxy-propylsulfanylmercuricsulfanyl) butyric acid (Hcy-S-Hg-S-Hcy). In addition, p-aminohippurate and the dicarboxylates adipate and glutarate (but not succinate or malonate) inhibited individually the uptake of Hcy-S-Hg-S-Hcy in a concentration-dependent manner. Furthermore, a direct relationship between the uptake of Hcy-S-Hg-S-Hcy and the induction of cellular injury and death was demonstrated in the hOAT1-expressing MDCK II cells only. These data represent the first line of direct evidence implicating one of the organic anion transporters in the uptake of a mercuric conjugate of Hcy in a mammalian cell. Thus, mercuric conjugates of Hcy are potential transportable substrates of OAT1. More important, the findings from the present study implicate the activity of OAT1 in the uptake and toxicity of Hg (when in the form of Hcy-S-Hg-S-Hcy in the extracellular compartment) in proximal tubular epithelial cells in vivo.

Adipates↗
PubMed1981

Participation of the beta-ketoadipate transport system in chemotaxis.

beta-Ketoadipate serves as a chemoattractant for Pseudomonas putida. The chemotactic response is inducible, and a regulatory mutant strain that forms the beta-ketoadipate transport system at high levels exhibits a heightened chemotactic response to beta-ketoadipate. Adipate and succinate, compounds that interact with the transport system, inhibit chemotaxis toward beta-ketoadipate. Some, but not all, mutants that fail to respond chemotactically to beta-ketoadipate lack the beta-ketoadipate transport system. It thus appears that the transport of beta-ketoadipate is associated with its function as a chemoattractant. It is likely that the metabolite attracts fluorescent Pseudomonas species to environments in which complex aromatic polymers undergo microbial dissimilation.

Adipates↗