Embryotoxic effects of di-2-ethylhexyl phthalate (DEHP) and di-n-buty phthalate (DBP) in mice.
Explore the source record for details and available documents.
SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
The presence of disinfection byproducts (DBPs) such as trihalomethanes (THMs) and haloacetic acids (HAAs) in drinking water is of great concern due to their adverse effects on human health. Emerging regulation limiting the concentration of DBPs in drinking water has increased demands for technologies and processes which reduce the formation of DBPs in drinking water. In this study, UV-H2O2 based advance oxidation process (AOP) was used to treat raw surface water. Experiments were conducted using low pressure mercury vapor UV lamps in collimated beam and flow-through annular photoreactors. The effect of UV fluence (0-3500 mJ cm(-2)) and hydrogen peroxide concentration (0-23 mg l(-1)) in reducing the concentration of THMs and HAAs was examined. The UV-H2O2 AOP was then coupled with a downstream biological activated carbon (BAC) treatment to assess the synergetic benefits of combining the two treatments. It was observed that UV-H2O2 AOP was only effective at reducing DBPs at UV fluences of more than 1000 mJ cm(-2) and initial H2O2 concentrations of about or greater than 23 mg l(-1). However, the combined AOP-BAC treatment showed significant reductions of 43%, 52%, and 59% relative to untreated raw water for DBPs, TOC, and UV254, respectively.
A membrane bioreactor and reverse osmosis (MBR-RO) system was developed to assess potential reuse applications of municipal wastewater. The objective of the study was to examine the water quality throughout the system with a focus on waterborne pathogens, disinfection by-products (DBPs) and nitrate. This paper will discuss the presence of these contaminants in MBR effluent and focus on their subsequent removal by RO. This study has shown that high quality reuse water can be produced from municipal wastewater through the use of an MBR-RO system. The water meets California Title 22 reuse regulations for non-potable applications and US EPA drinking water limits for trihalomethanes (THM) (80 microg/L), haloacetic acids (HAA) (60 microg/L), chlorite (1.0 mg/L), total coliform (not detectable), viruses (not detectable), and nitrate/nitrite (10 mg N/L). However, THM formation (182-689 microg/L) attributed to cleaning of the MBR with chlorine and incomplete removal by subsequent RO treatment resulted in reuse water with THM levels (40.2+/-19.9 microg/L) high enough to present a potential concern when considering drinking water applications. Nitrate levels of up to 3.6 mg N/L, which resulted from incomplete removal by the RO membrane, are also a potential concern. A denitrification step in the MBR should be considered in potable water applications.
Chlorination is the most widely used technique for disinfection of drinking water. A consequence of chlorination is the formation of Disinfection By-Products (DBPs). The formation of DBPs in drinking water results from the reaction of chlorine with naturally occurring organic materials, principally humic and fulvic acids. This paper focuses on the effect of humic substances on the formation of twenty-four compounds belonging to different categories of DBPs. This investigation was conducted in two water treatment plants in Greece, Menidi and Galatsi, from July 1999 to April 2000. Humic substances were determined by the diethylaminoethyl (DEAE) method with subsequent UV measurement. The techniques used for the determination of DBPs were liquid-liquid extraction, gas chromatography and mass spectrometry. The concentrations of DBPs were generally low. Total trihalomethanes (TTHMs) ranged from 5.1 to 24.6 microg L(-1), and total haloacetic acids (HAAs) concentration ranged from 8.6 to 28.4 microg L(-1), while haloaketones (HKs) and chloral hydrate (CH) occurred below 1 microg L(-1). The content of humic substances was found to influence the formation of DBPs and especially TTHMs, trichloroacetic acid (TCA), dibromoacetic acid (DBA), CH, 1,1-dichloropropanone (1.1-DCP) and 1,1,1-trichloropropanone (1,1,1-TCP). Seasonal variation of TTHMs and HAAs generally followed that of humic substances content with peaks occurring in autumn and spring. The trends of 1,1-DCP, 1,1,1-TCP and CH formation seemed to be in contrast to TTHMs and HAAs. Trends of formation of individual compounds varied in some cases, probably due to influence of parameters other than humic substances content. Statistical analysis of the results showed that the concentrations of TTHMs, CH, 1,1-DCP, 1,1,1-TCP, TCA and DBA are strongly affected from humic substances content (at 0.01 confidence level). The opposite is true for dichloroacetic acid (DCA) concentration. Humic substances also vary to a statistically significant degree during different months, as well as the concentrations of TTHMs, CH, 1,1-DCP, 1,1,1-TCP, TCA and DCA. The variance of DBA was not statistically significant. Regarding the effect of sampling station, humic substances content showed no statistically significant difference between the two raw water sources studied.
Small water utilities often have difficulty operating complicated treatment processes. The advanced oxidation process investigated here is simple, involving only a pump to add hydrogen peroxide and a power supply for the ultraviolet lamps, and the process does not produce any solid residuals. The results of these studies show that a photon-flux-driven pseudo-first-order model (known as the Prengle-Shimoda rate model) could be used to predict the destruction of total organic carbon, dissolved organic halogen, and dissolved organic halogen precursors.
Tissue-specific carbohydrate structures are thought to result from the selective expression of specific terminal glycosyltransferases responsible for their synthesis. However, little is known about the regulation of the expression of these enzymes. Previous analysis of the distribution of one such enzyme, beta-galactoside alpha 2,6-sialyltransferase, revealed that its expression is tissue restricted, with highest levels being found in the liver. Examination of the gene suggested that its expression is regulated at the level of transcription by multiple promoters, one of which is strongly active in the liver. In this present work, an analysis of the liver-restricted promoter was undertaken to identify the promoter elements necessary for liver-restricted expression. Footprinting studies, 5' deletion analysis, and site-directed mutagenesis identified two cis-elements which were potentially important in the tissue-specific expression of this promoter. One of these elements contains a consensus binding site for the liver-enriched transcription factor hepatocyte nuclear factor-1 alpha, while the other is a consensus binding site for the liver-specific factors D-binding protein and liver-enriched transcriptional activator protein. Expression vectors containing cDNAs of these factors are capable of trans-activating transcription of the alpha 2,6ST promoter, demonstrating their ability to regulate transcription of this promoter. Together, these results suggest that tissue-specific glycosylation can be regulated at the level of transcription by the same factors involved in the expression of a number of other tissue-specific genes.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The HOT study is the largest controlled therapeutic trial conducted to date in hypertension. This international, prospective, randomised trial is designed to determine the optimal blood pressure to be obtained during treatment, in order to achieve optimal reduction of complications and cardiovascular mortality. The HOT study is conducted according to the PROBE methodology (Prospective Randomised Open Blinded Endpoints. It has three objectives: 1) to evaluate the relationship between the development of major cardiovascular events and the DBP target level (DBP < or = 90, DBP < or = 85 or DBP < or = 80 mmHg. 2) to evaluate the relationship between the development of major cardiovascular events and real DBP observed, 3) to determine whether low-dose acetylsalicylic acid (75 mg/day) provides an additional benefit in terms of cardiovascular morbidity and mortality in treated hypertensive subjects. Between April 1992 and October 1994, 18,790 patients, between the ages of 50 and 80 years (26 countries), were randomised to these 3 target DBP groups and several parameters likely to influence the blood pressure fall were identified. The reduction of DBP was all the more pronounced the higher the baseline DBP. For a baseline DBP equal to 100 mmHg, the mean fall was 18 mmHg and for a baseline DBP equal to 110 mmHg, the mean fall was 27 mmHg. Advanced age was also found to be a factor promoting reduction of DBP, which increased after the age of 65 years. Analysed in relation to the type of treatment, this more marked reduction in the elderly showed that monotherapy with a calcium channel blocker was very effective on DBP and especially after the age of 75 years. The data of the study also showed that SBP decreased in parallel to DBP, but to an even greater extent. Thus, a 10 mmHg reduction of DBP induces a reduction of SBP by approximately 20 mmHg. This reduction of SBP related to the level of DBP was even more marked the higher the baseline SBP and the higher the target DBP objective. Thus 80% of patients in the DBP < or = 80 mmHg group had an SBP < or = 150 mmHg during treatment. Among the other factors, weight appeared to clearly influence reduction of DBP, as the reduction of DBP was more marked the lower the patient's weight. In contrast, the body mass index was poorly correlated with the reduction in blood pressure. The blood pressure reduction, regardless of weight, was more marked when a stricter blood pressure objective was adopted (DBP < or = 80 mmHg). Finally, in the particular case of elderly subjects, treatment with a calcium channel blocker appeared to be very effective in reducing the blood pressure.
Because dibenzo[a,l]pyrene (DBP) is the most potent known carcinogenic aromatic hydrocarbon, reference adducts formed by reaction of deoxyribonucleosides with electrophilic intermediates of DBP are essential for identifying the structures of adducts formed in biological systems. Electrochemical oxidation of DBP in the presence of nucleosides leads to adducts from DBP.+. When 6.8 equiv of charge are consumed, three adducts are formed with dG: 7-(DBP-10-yl)Gua (89%), 8-(DBP-10-yl)dG (2%), and 8-(DBP-10-yl)Gua (2%). With 10 equiv of charge, however, only two adducts are formed: 7-(DBP-10-yl)Gua (89%) and 8-(DBP-10-yl)Gua (4%). Anodic oxidation of 8-(DBP-10-yl)dG yields 8-(DBP-10-yl)Gua. Anodic oxidation of DBP in the presence of G produces 7-(DBP-10-yl)Gua (27%) and 8-(DBP-10-yl)G (9%). Anodic oxidation of DBP in the presence of dA affords two adducts, N6-(DBP-10-yl)dA (28%) and 7-(DBP-10-yl)Ade (12%), whereas anodic oxidation in the presence of A produces only N6-(DBP-10-yl)A (24%). The structures of the adducts were elucidated by using UV, NMR, and MS. Formation of these adducts demonstrates that DBP.+ reacts at C-10 with nucleophiles. The most reactive nucleophilic groups for the Gua moiety are the N-7 and C-8, whereas for the Ade moiety they are N-7 and the 6-amino group.
The adenoviral DNA binding protein (DBP) is a multifunctional protein involved in DNA replication and gene expression. In order to investigate the relation between structure and function of DBP, the amino acid sequences of the serotypes 5 and 12 (Ad5 and Ad12) have been compared. The amino acid sequence of Ad5 DBP was previously established by nucleotide sequence analysis of the Ad5 DBP gene (W. Kruijer, F. M. A. Van Schaik, and J. S. Sussenbach, Nucl. Acids Res. 9, 4439-4457, 1981). In this study the analysis of the Ad5 DBP gene and adjacent regions by determination of the sequence of the first leader in late DBP mRNA's and the splice point between the tripartite leader and the main body of the mRNA encoding the 100-kDa protein has been extended. The nucleotide sequence of the Ad12 DBP gene is also described. From the nucleotide sequence and RNA mapping data of Ad12 DBP mRNA's (I. Saito, J. Sato H. Handa, K. Shiraki, and H. Shimojo, Virology 114, 379-398, 1981) the complete Ad12 DBP amino acid sequence could be deduced. Ad12 DBP contains 484 amino acids and has an actual Mr of 54,992. It is 45 amino acids shorter than Ad5 DBP. Comparison of the Ad12 and Ad5 DBP amino acid sequences shows that several longer deletions are present in the N-terminal 125 amino acid residues of Ad12 DBP. In contrast, only a single amino acid deletion and insertion is found in the C-terminal 359 amino acids of Ad12 DBP. The N- and C-terminal domains of Ad12 and Ad5 DBP are 45 and 80% homologous, respectively. This suggests that both domains of DBP are subjected to different evolutionary pressures. Analysis of various Ad5 mutants with an altered DBP gene, has indicated that the C-terminal domain is involved in DNA replication and early gene expression, while the N-terminal domain has a role in late gene expression in monkey cells. These results are discussed in relation to the structure and function of adenovirus DBP.
The metabolic disposition of the plasma binding protein (DBP) for vitamin D and its metabolites was studied in adult rabbits. Apo-DBP was purified from rabbit plasma and enzymatically labeled with radioiodine. The radioiodine-labeled protein retained its ability to bind vitamin D sterols and its physicochemical properties. When 125I-labeled DBP and 131I-labeled rabbit albumin were simultaneously injected intravenously, the 125I was cleared from plasma at a faster rate (t 1/2 = 1.7 d) than 131I (t 1/2 = 5 d) and 125I was present in excess of 131I in kidney, liver, skeletal muscle, heart, lung, intestine, testis, and bone 1 h after injection. In contrast to DBP, 25(OH)D3 was cleared more slowly (t 1/2 = 10.7 d). Compared to albumin, DBP radioactivity appeared earlier and in greater quantity in the urine of catheterized rabbits. Gel filtration analyses of plasma revealed most of the 125I to elute in the position of DBP, with only small amounts in the less than 1,000-dalton region. In contrast, almost all of the urine 125I eluted in this small molecular weight fraction. The molar ratio of DBP to 25(OH)D3 in normal rabbit plasma was 138/1. The extravascular pool of DBP was calculated to be 1.5-2.4 times larger than the intravascular DBP pool, and the molar replacement rate of DBP was 1,350-fold higher than that of 25(OH)D3. The plasma disappearance curves of holo-DBP, prepared either by saturating with 25(OH)D3 or by covalently linking 3 beta-bromoacetoxy-25(OH)D3, were very similar to that of apo-DBP. Neuraminidase treatment of DBP did not alter its plasma survival. These studies indicate that DBP or DBP-25(OH)D3 complex is removed from plasma by a variety of tissues, that the DBP moiety is degraded during this process, and that a significant recirculation of 25(OH)D3 probably occurs. The molar excess of DBP to 25(OH)D3 in plasma, and the relatively rapid turnover of DBP indicate that a high capacity, high affinity, and dynamic transport mechanism for vitamin D sterols exists in rabbit plasma.
A radioimmunoassay for the binding protein for vitamin D and its metabolites (DBP) has been developed. Suitable rabbit anti-DBP antiserum was elicited after primary and one booster injection. Anti-DBP antisera, as well as antigroup-specific component antisera, produced a single, monospecific line of percipitation when reacted against purified DBP and human serum. DBP was iodinated with 125I and 125I-DBP was purified by gel filtration on Sephadex G-200. Binding of 125I-DBP by 20 nl of rabbit anti-DBP antisera was approximately 50% and was sharply competed for by 0.4-4.0 ng of DBP standard. Displacement of 125I-DBP by human serum dilutions or standard DBP gave identical curves, and only weak competition was observed with old and new world primate sera. Apo- and holo-DBP possessed indistinguishable immunoreactivity. The assay detects DBP in 1-10 nl of human serum with reasonable accuracy and with reasonable intra- and interassay precision. The mean serum concentration (+/- SEM) for a group of 40 normal adults was 525 +/- 24 mug/ml and no sex difference was observed. Higher levels were found in sera from pregnant women and women receiving oral contraceptives, and decreased concentrations were observed in premature cord and hypoproteinemic sera. No significant correlation between serum DBP levels and serum 25-hydroxycalciferol levels was found, and the DBP content of sera from vitamin D-deprived and vitamin D-treated subjects was indistinguishable from that of normal adults. DBP accounts for 6- of the alpha globulin in normal human serum. Considering the normal serum content of the parent vitamin and its metabolites to be approximately 0.1-0.2 mum, these immunoassay data confirm previous saturation analyses of human serum antiricketic sterol-binding capacity and suggest that greater than 95% of DBP circulates as the apoprotein under normal conditions.
This study reports the development of a specific and sensitive radioimmunoassay and a simple and accurate radial immunodiffusion (RID) assay for the human serum-binding protein for vitamin D and its metabolites (DBP). These immunoassays employed a monospecific antiserum that was prepared in rabbits against human DBP. The radioimmunoassay effectively measured DBP in amounts of 1-10 ng, whereas the RID assay measured DBP accurately in amounts of 0.2-0.8 mug. The results obtained with the two immunoassays on the same samples of serum agreed well with each other. Using the RID assay, the mean (+/- SD) serum DBP concentration observed in 35 normal persons was 422 +/- 27 micrograms/ml. Generally similar levels were observed in 66 hyperlipidemic subjects. In molar terms, the mean DBP concentration (approximately 8 microgramsM) was of the order of 50 times the usual serum level of 25-hydroxyvitamin D (25-OH-D) plus vitamin D. Thus, most of plasma DBP circulates as apo-DBP, not containing a bound molecule of 25-OH-D or of vitamin D. DBP and 25-OH-D concentrations were measured in a limited number of patients with hypercalcemia, mild hypocalcemia, and markedly elevated serum 25-OH-D levels due to oral vitamin D supplementation. It was found that major changes can occur in the serum levels of 25-OH-D and of calcium with very little or no associated changes occurring in the serum concentration of DBP, The results suggest that neither serum 25-OH-D nor serum calcium plays an important role in the regulation of the metabolism of DBP. Data were obtained that confirmed and extended an earlier report on the identity of the group-specific component (Gc) protein in plasma with the plasma vitamin D-binding protein. On immunodiffusion against whole serum, the line formed with the anti-DBP antiserum showed a complete reaction-of-identity with the line formed with commercial antiserum against Gc protein. Furthermore, serum that had been depleted of DBP by treatment with Sepharose containing covalently coupled antibodies against DBP was found to be depleted also of immunoreactivity against anti-GC protein antiserum. In addition, the properties of the purified DBP preparation agreed closely with those previously reported by others for Gc protein. Finally, a comparative immunology study showed that sera from several different mammalian orders showed some immunoreactivity against the antihuman DBP antiserum. Thus, proteins immunologically similar to human DBP are present in sera from a number of mammalian species and orders.
UNLABELLED: Demineralized bone induces chondrogenic differentiation of human dermal fibroblasts in vitro. Analyses of signaling gene expression showed that DBP and BMP-2 regulate common and distinct pathways. Although BMP-2 was originally isolated as a putative active factor in DBP, rhBMP-2 and DBP do not affect all the same genes or in the same ways. INTRODUCTION: Demineralized bone powder (DBP) induces chondrogenic differentiation of human dermal fibroblasts (hDFs) in 3D culture, but the initiating mechanisms have not been identified. We tested the hypotheses that DBP would affect expression of signaling genes and that DBP's effects would differ from the effects of bone morphogenetic proteins (BMPs). MATERIALS AND METHODS: A chondroinduction model was used in which hDFs were cultured with and without DBP in a porous collagen sponge. BMP-2 was delivered in a square of absorbable collagen felt inserted into a collagen sponge. Total RNA was isolated after 3 days of culture, a time that precedes expression of the chondrocyte phenotype. Gene expression was evaluated with two targeted macroarray screens. Effects of DBP and rhBMP-2 were compared by macroarray, RT-PCR, and Northern hybridization analysis of selected genes in the transforming growth factor (TGF)-beta/BMP signaling pathways. RESULTS: By macroarray analysis of 16 signal transduction pathways, the following pathways were modulated in hDFs by DBP: TGF-beta, insulin/LDL, hedgehog, PI3 kinase/AKT, NF-kappaB, androgen, retinoic acid, and NFAT. There was convergence and divergence in DBP and rhBMP-2 regulation of genes in the TGF-beta/BMP signaling pathway. Smad target genes were the predominant group of DBP- or rhBMP-2-regulated genes. Several genes (IGF-BP3, ID2, and ID3) showed similar responses (increased expression) to DBP and rhBMP-2. In contrast, many of the genes that were greatly upregulated by DBP (TGFBI/betaig-h3, Col3A1, TIMP1, p21/Waf1/Cip1) were barely affected by rhBMP-2. CONCLUSION: These findings indicate that multiple signaling pathways are regulated in fibroblasts by DBP, that one of the major pathways involves Smad target genes, and that DBP and rhBMP-2 elicit different gene expression responses in hDFs. Although BMP-2 was originally isolated as a putative inductive factor in DBP, rhBMP-2 and DBP do not affect all the same genes or in the same ways.