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PubMed2005

Bioavailability of phthalate congeners to earthworms (Eisenia fetida) in artificially contaminated soils.

Bioavailability of phthalate congeners, dimethyl phthalate, diethyl phthalate, di-n-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), and dioctyl phthalate, to earthworms (Eisenia fetida) were studied when earthworms were exposed to two artificially contaminated agricultural and forest soils. Only DBP and DEHP were detected in earthworms. The uptake kinetics of DBP and DEHP in earthworms was fast within the initial 10 days followed by a nearly steady state for the subsequent 20 days. An equilibrium partitioning model could be used to describe the uptake kinetics of DBP and DEHP by earthworm in two types of soils (r = 0.709-0.864). The average biota-to-soil accumulation factors (BSAFs) of DBP and DEHP at 5 mg kg(-1) in soil were 0.27 +/- 0.07 and 0.17 +/- 0.03, respectively, in agricultural soil, while the BSAFs were 0.21 +/- 0.06 and 0.07 +/- 0.02, respectively, in forest soil. The concentrations of phthalates in earthworms increased with increasing concentrations of phthalates in soil. There was a significant correlation between logC(soil) and logC(worm), with r = 0.999-0.993, demonstrating a single linear partitioning of phthalates between soil and earthworms. The bioavailability of DBP and DEHP was assessed by Soxhlet, methanol, and methanol-water (1:1) extraction methods. Our results indicated that the extractable amounts of freshly added DBP and DEHP in soils by these extraction methods were significantly correlated with those in earthworms. It was observed that the extractable DBP and DEHP by the methanol and methanol-water (1:1) extraction methods decreased with their increasing residence time in soil. In contrast, the amount extracted by the Soxhlet extraction method did not show a similar decline. Therefore, Soxhlet extraction was a poor indicator of the bioavailability of DBP and DEHP to earthworms in soil, which could lead to overestimation of the risk of soil-associated DBP and DEHP. The extractable DBP and DEHP by methanol and methanol-water (1:1) significantly decreased over 440 days. Compared with the methanol-water (1:1) extraction method, the methanol extraction method was preferred for its ability to predict the bioavailability of DBP and DEHP in aged soils.

Agriculture↗
PubMed2006

The importance of carcinogen dose in chemoprevention studies: quantitative interrelationships between, dibenzo[a,l]pyrene dose, chlorophyllin dose, target organ DNA adduct biomarkers and final tumor outcome.

Chlorophyllin (CHL) is a potent antimutagen in vitro, an effective anti-carcinogen in several animal models, and significantly reduced urinary biomarkers of aflatoxin B(1) (AFB(1)) exposure in a human population. Here we report an expanded analysis of CHL chemoprevention using the potent environmental hydrocarbon dibenzo[a,l]pyrene (DBP). A dose-dose matrix design employed over 12 000 rainbow trout to evaluate the interrelationships among dietary carcinogen dose, anti-carcinogen dose, carcinogen-DNA adduct levels at exposure and eventual tumor outcome in two target organs. Included was an evaluation of the pharmaceutical CHL preparation (Derifil), used previously in a study of individuals chronically exposed to AFB(1). CHL was pre-, co- and post-fed at doses of 0-6000 p.p.m. and co-fed with DBP at doses of 0-371.5 p.p.m. for 4 weeks. This protocol generated a total of 21 dose-dose treatment groups, each evaluated with three or more replicates of 100 animals. The DBP-only treatment produced dose-responsive increases in liver and stomach DBP-DNA adducts, whereas increasing CHL co-treatment doses produced successive inhibition in liver (49-83%) and stomach (47-75%) adduct levels at each DBP dose examined. The remaining 8711 trout were necropsied, 10 months later. DBP treatment alone produced a logit incidence versus log [DBP] dose-response curve in stomach that was linear; CHL co-treatment provided dose-dependent tumor inhibition which ranged from 30 to 68% and was predictable from the adduct response. The Derifil CHL preparation was also found to effectively reduce DNA adduction and final tumor incidence in stomach (as well as liver), with a potency compatible with its total chlorin content. Liver tumor incidence in the DBP-only groups appeared to plateau near 60%. At DBP doses of <or=80 p.p.m., increasing CHL doses generally reduced tumor incidence and multiplicity consistent with early DNA adducts as biomarkers. At 225 p.p.m. DBP, however, very high CHL doses were required to reduce tumor incidence below the 60% plateau. Apparent tumor multiplicity in liver was neither linear nor monotonic with DBP dose, but peaked at 80 p.p.m. DBP and declined at 225 p.p.m., where it was increased by all but one CHL dose. Consequently, the effects of a given CHL dose and the predictivity of DNA adducts as biomarkers were highly dependent on carcinogen dose. These results underscore the critical importance of establishing carcinogen-end point dose-response relationships in chemoprevention studies, and the potential otherwise for misleading interpretations in chemoprevention studies carried out solely at high-carcinogen dose.

Animals↗
PubMed1990

Adenovirus DNA-binding protein forms a multimeric protein complex with double-stranded DNA and enhances binding of nuclear factor I.

The 72-kilodalton adenovirus DNA-binding protein (DBP) binds to single-stranded DNA as well as to RNA and double-stranded DNA and is essential for the replication of viral DNA. We investigated the binding of DBP to double-stranded DNA by gel retardation analysis. By using a 114-base-pair DNA fragment, five or six different complexes were observed by gel retardation. The mobility of these complexes is dependent on the DBP concentration, suggesting that the complexes arise by sequential binding of DBP molecules to the DNA. In contrast to binding to single-stranded DNA, the binding of DBP to double-stranded DNA appears to be noncooperative. DBP binds to linear DNA as well as to circular DNA, while linear DNA containing the adenovirus terminal protein was also recognized. No specificity for adenovirus origin sequences was observed. To study whether the binding of DBP could influence initiation of DNA replication, we analyzed the effect of DBP on the binding of nuclear factor I (NFI) and NFIII, two sequence-specific origin-recognizing proteins that enhance initiation. At subsaturating levels of NFI, DBP increases the rate of binding of NFI considerably, while no effect was seen on NFIII. This stimulation of NFI binding is specific for DBP and was not observed with another protein (NFIV), which forms a similar DNA-multimeric protein complex. In agreement with enhanced NFI binding, DBP stimulates initiation of adenovirus DNA replication in vitro especially strongly at subsaturating NFI concentrations. We explain our results by assuming that DBP forms a complex with origin DNA that promotes formation of an alternative DNA structure, thereby facilitating the binding of NFI as well as the initiation of DNA replication via NFI.

Adenoviruses, Human↗
PubMed1982

Extraction of vitamin D metabolites by bones of normal adult dogs.

Using the isolated perfused canine tibia we examined the extraction of [(3)H]25(OH)D(3), [(3)H]1,25(OH)(2)D(3) and [(3)H]24,25(OH)(2)D(3) by bone of normal adult dogs. The studies were performed with and without vitamin D binding protein (DBP) in the perfusate to examine the effect of protein binding on the extraction of the vitamin D metabolites. An average of 48+/-2% of [(3)H]25(OH)D(3) was extracted by bone, when no DBP was present. However, addition of only a small amount of DBP ( approximately 720 ng/ml of perfusate) nearly completely abolished the extraction of [(3)H]25(OH)D(3) by bone. No degradation and/or transformation of the labeled 25(OH)D(3) could be demonstrated during passage through the isolated perfused bone. The extraction of [(3)H]24,25(OH)(2)D(3) in a DBP-free medium averaged 33+/-5%. Addition of 720 ng of DBP/ml of perfusate completely inhibited the extraction of this metabolite. The extraction of [(3)H]1,25(OH)(2)D(3) averaged 30+/-3% in a DBP free medium and no inhibition of the extraction was demonstrated after addition of DBP (720 ng/ml of perfusate). However, addition of DBP in a concentration of 14.4 mug/ml of perfusate reduced the extraction of 1,25(OH)(2)D(3) to 8+/-2%, a value still significantly higher than that seen after addition of 20 times less DBP to perfusions with 25(OH)D(3) and 24,25(OH)(2)D(3). It is concluded that the isolated perfused bone of normal dogs can extract significant amounts of 25(OH)D(3), 1,25(OH)(2)D(3), and 24,25(OH)(2)D(3). Small concentrations of DBP (720 ng/ml) in the perfusate significantly inhibited the extraction of 25(OH)D(3) and 24,25(OH)(2)D(3). A carrier role for DBP is suggested and it is proposed that the levels of free vitamin D are important for extraction of the metabolites by bone. Therefore, due to the different affinities of DBP for the various metabolites of vitamin D, only 1,25(OH)(2)D(3) is extracted in vitro in significant amounts by bone of normal adult dogs, in the presence of DBP.

Animals↗
PubMed1992

Response of diastolic blood pressure to long-term sodium restriction is posture related.

Eighty-five subjects, aged 31-55 years, suffering from uncomplicated essential hypertension and receiving no regular medication were randomized to sodium restriction and control groups. Systolic (SBP) and diastolic (DBP) blood pressure were measured during an orthostatic test at baseline and after 6 months sodium restriction. The mean daily sodium excretion of 43 treated subjects decreased from 193 +/- 91 mmol to 95 +/- 70 mmol (p less than 0.001). Treated patients were divided on the basis of their mean overall out-patient clinic (OC) DBP decrease in the sitting position during the 6 months (monthly measurements) into sodium-sensitive (DBP decrease greater than 10 mmHg, n = 17), indeterminate (DBP decrease 5-10 mmHg, n = 18) and sodium-resistant (DBP decrease less than 5 mmHg, n = 8) subgroups. At 6 months the level of DBP in the supine position was lower than at baseline in both sensitive and resistant subgroups, whereas in the standing position a lower DBP than at baseline was seen only in the sodium-sensitive subgroup. The magnitude of the subsequent OC DBP decrease was significantly associated with a high baseline seated OC DBP (p less than 0.001) and a high, for baseline OC DBP adjusted orthostatic DBP increase (p = 0.014). Our data suggest that posture should be included in the concept of sodium sensitivity and that an orthostatic test is useful in the prediction of seated and standing DBP decrease produced by moderate, long-term sodium restriction.

Adult↗
PubMed2002

129X1/SvJ mouse strain has a novel defect in inflammatory cell recruitment.

Vitamin D-binding protein (DBP) has been reported to contribute to innate immunity. To verify prior in vitro and cell-based observations supporting this role, we assessed the ability of a recently developed DBP-null mouse line to recruit neutrophils and macrophages to a site of chemical inflammation. The interrupted DBP allele had been generated by homologous recombination in 129X1/SvJ embryonic stem cells and these cells were subsequently used to generate a line of DBP(-/-) (null) mice. Initial studies revealed a marked defect in the ability of these DBP(-/-) mice to recruit cells to the peritoneum after localized thioglycolate injection. However, progressive outcrossing of the DBP(-/-) mice to the C57BL/6J strain, conducted to provide a uniform genetic background for comparison of DBP-null and control mice, resulted in a progressive increase in cell recruitment by the DBP(-/-) mice and a loss in their apparent recruitment defect when compared with the DPB wild-type controls. These data suggested that the observed recruitment phenotype initially attributed to the absence of DBP was not linked to the DBP locus, but instead reflected the underlying genetic composition of the 129X1/SvJ ES cells used for the initial DBP gene disruption. A profound cell recruitment defect was confirmed in the 129X1/SvJ mice by direct analysis. Each of three commonly used inbred lines was discovered to have a distinct level of cell recruitment to a uniform stimulus (C57BL/6J > BALB/c > CD1 > 129X1/SvJ). Thus, this study failed to support a unique role for DBP in cellular recruitment during a model inflammatory response. Instead, the data revealed a novel and profound defect of cell recruitment in 129X1/SvJ mice, the strain most commonly used for gene deletion studies.

Animals↗
PubMed2006

[Biodegradation of dibutyl phthalate by diatomite adsorptive immobilized microorganism].

OBJECTIVE: To study the biodegradation characteristics of seeding type immobilized microorganism on dibutyl phthalate (DBP). METHODS: The immobilized microorganism was made to adsorb DBP degradation dominant bacteria by using modified diatomite as carrier, then it degraded DBP under different primary concentration, vibration rate, pH, temperature and at the presence of metal compounds. The degradation kinetics was analyzed. RESULTS: When DBP primary concentration was 100-500 mg/L, the adsorptive immobilized microorganism could maintain relatively high activity and the DBP degraded rate was above 80% in 24h. Dissociative and immobilized microorganism could get higher degradation activity in vibration than in stillness. When pH was 6.0 - 9.0, the degradation rate of immobilized microorganism on DBP was above 82% in 24h and its activity is higher than dissociative microorganism. In the range of 20 degrees C to 40 degrees C, the DBP degraded rate by immobilized microorganism could reach 84.5% in 24h. If mental compounds existed in the DBP water sample, the degradation activities of dissociative and immobilized microorganism were inhibited obviously. The form of DBP degradation kinetics could be described as the first-order model. CONCLUSION: The immobilized microorganisms using diatomite as carrier could degrade DBP effectively. The adsorptive immobilized microorganism was more adapted to DBP load, temperature and pH than dissociative microorganism. The mental compounds could inhibited their activities. The degradation reaction of adsorptive immobilized microorganisms on DBP was according with the first-order model.

Adsorption↗
PubMed1998

Antiproliferative effects of N1,N4-dibenzylputrescine in human and rodent tumor cells.

Polyamines (putrescine, spermidine and spermine) increase in proliferating tissues and are essential for cellular growth and cell division processes. We had previously shown that alkyl substituted putrescines can inhibit cell proliferation. We now tested the effects of the (N(alpha),N(omega)-dibenzyl derivatives of the simple diamines putrescine, cadaverine and 1,3-diaminopropane on the growth of three human squamous cell carcinoma (SCC) lines and a rat hepatoma (H-4-II-E) cell line. Survival assays were measured by treating exponentially-growing SCC cultures with N1,N4-dibenzylputrescine (DBP) (270 microM) or a rat hepatoma cell culture with DBP (100 microM) for 48 hrs. Inhibition of cell growth was measured either by the colony forming assay or by cell counting. DBP inhibited proliferation of the rat hepatoma (H-4-II-E) cell line and induced cytotoxicity when used at a concentration of 100 microM for >48 hrs. N1,N5-dibenzylcadaverine (DBC) also induced cytotoxicity at a similar concentration, while N1,N3-dibenzyl-1,3-diaminopropane (DBPr) was a much weaker inhibitor of cell growth. Inhibition of cell growth by DBP resulted in marked modifications of cell morphology, such as vacuole formation, decrease in size, pycnosis, change in staining behavior toward trypan blue and lack of adherence. DBP was also growth inhibitory in the three human SCC cell lines tested. The concentration of DBP required to achieve growth inhibition of SCC cells could be dramatically decreased in the presence of N1,N4-bis(buta-2,3-dienyl)butanediamine, a specific inhibitor of polyamine oxidase (PAOI). Moreover, although the presence of PAOI only prevented the oxidation (debenzylation) of approximately 20% of intracellular DBP over a 5-day period, it produced a 5-fold increase in the inhibition of cell proliferation by DBP. DBP (and DBC) inhibited putrescine uptake by rat hepatoma (H-4-II-E) cells in what appears to be a competitive reaction. A tenfold excess of putrescine over DBP did not inhibit the antiproliferative or cytotoxic effects of the latter. DBP administered for 72 hrs. depleted intracellular levels of putrescine, spermidine and spermine in the SCC lines by 50-100% of control values. It was found that DBP inhibited nucleic acid and protein synthesis at an early stage of cell proliferation, hence its growth inhibitory effect may be related to inhibition of the synthesis of macromolecules.

3T3 Cells↗
PubMed1999

Disruption of androgen-regulated male reproductive development by di(n-butyl) phthalate during late gestation in rats is different from flutamide.

Gestational and lactational exposure to di(n-butyl) phthalate (DBP) at >/=250 mg/kg/day disrupts male rat reproductive development and function. Although this indicates an antiandrogenic mechanism, DBP and its biologically active metabolite do not interact with the androgen receptor (AR) in vitro. In the present study, we compared the effects of DBP and the antiandrogen flutamide using a shorter exposure during the prenatal period of male sexual differentiation in rats. Pregnant CD rats received DBP at 0, 100, 250, or 500 mg/kg/day po (n = 10) or flutamide at 100 mg/kg/day po (n = 5) from Gestation Days 12 to 21. In F1 males, DBP (500 mg/kg/day) and flutamide caused hypospadias; cryptorchidism; agenesis of the prostate, epididymis, and vas deferens; degeneration of the seminiferous epithelium; and interstitial cell hyperplasia of the testis. Flutamide and DBP (250 and 500 mg/kg/day) also produced retained thoracic nipples and decreased anogenital distance. Interstitial cell adenoma occurred at 500 mg DBP/kg/day in two males. The only effect seen at 100 mg DBP/kg/day was delayed preputial separation. In contrast to flutamide, DBP caused a low incidence of prostate agenesis and hypospadias with no vaginal pouch. The low incidence of DBP-induced intraabdominal testes contrasted with the high incidence of inguinal testes seen with flutamide. Thus prenatal male sexual differentiation is a sensitive period for the reproductive toxicity of DBP. A no observed adverse effect level was not established and the lowest observed (adverse) effect level was 100 mg/kg/day. Flutamide and DBP disrupted the androgen signaling necessary for male sexual differentiation but with a different pattern of antiandrogenic effects. DBP is an example of an environmental antiandrogen that disrupts androgen-regulated male sexual differentiation without interacting directly with the AR, as does flutamide.

Abnormalities, Drug-Induced↗
PubMed2006

Upregulation of vitamin D binding protein (Gc-globulin) binding sites during neutrophil activation from a latent reservoir in azurophil granules.

Vitamin D binding protein (DBP) is a multifunctional plasma transport protein that is also found on the surface of many cell types. Cell surface DBP significantly enhances chemotactic activity of complement (C) peptides C5a and C5a des Arg. However, both DBP binding and C5a chemotaxis enhancement can vary among neutrophil donors. To test if activation during cell purification is responsible for this variability, neutrophils were isolated using both standard and lipopolysaccharide (LPS)-free protocols. Cells isolated by the LPS-free method had no DBP-enhanced chemotaxis to C5a or DBP binding to plasma membranes. Moreover, neutrophils treated with LPS bound more avidity to immobilized DBP than sham-treated cells. Subcellular fractionation of neutrophils (standard protocol) revealed a heavy plasma membrane (HM) band that contained components of light plasma membranes and all three granules. The HM band possessed most of the DBP binding activity (58%), and activation of cells with ionomycin greatly increased DBP binding to HM. Azurophil granules contained 33% of the total DBP binding sites and there was a highly significant positive correlation (r=0.988) between release of the granule marker myeloperoxidase and DBP binding. These results indicate that fusion of granules with the plasma membrane forms HM that contains DBP binding sites.

Binding Sites↗
PubMed2002

Measurement of vitamin D-binding protein in pleural fluids and sera by means of a turbidimetric immunoassay measuring system.

BACKGROUND: Vitamin D-binding protein (DBP) has been recognized as a multifunctional plasma protein that can modulate certain immune and inflammatory responses. There may be differences between the DBP concentrations in pleural fluids from various diseases involving a variety of possible responses in the pleural cavity. METHODS: An anti-DBP polyclonal antibody was prepared using commercially available DBP to establish a quantitative measuring system for DBP. With a rabbit antibody, a turbidimetric immunoassay (TIA) was developed for DBP with an automatic analyzer. Using this measuring system, the concentrations of DBP were compared with the protein concentration in pleural fluid and serum specimens from patients with various diseases. RESULTS: The fluid DBP concentrations in transudative (n=11) and exudative (n=41) effusions were 71.9+/-21.2 and 180.7+/-43.7 mg/l, respectively. Among the exudative effusions, the fluid DBP concentrations in the bacterial (n=10), tuberculous (n=13), and malignant (n=18) effusions were 218.8+/-37.3, 186.7+/-26.2, and 155.1+/-41.3 mg/l, respectively. The DBP fluid/serum ratio and the fluid DBP/protein ratio in bacterial effusions were significantly higher than those in tuberculous (p<0.005, p<0.05, respectively) and malignant effusions (p<0.0005, p<0.005, respectively), although no statistically significant differences in the serum DBP/protein ratio between those effusions were found. CONCLUSIONS: Using the TIA assay, the DBP concentrations in bacterial pleural effusions were significantly higher than in tuberculous and malignant effusions.

Aged↗
PubMed1997

Tissue distribution of DNA adducts in rats treated by intramammillary injection with dibenzo[a,l]pyrene, 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene.

Dibenzo[a,l]pyrene (DBP) has recently emerged as a potent environmental carcinogen having greater carcinogenicity in the rat mammary epithelial glands than 7,12-dimethylbenz[a]anthracene (DMBA), previously considered to be the most potent mammary carcinogen and benzo[a]pyrene (BP), a ubiquitous environmental carcinogen. Previous studies on the tumor-initiating potential of DBP, DMBA, and BP demonstrated that DBP was 2.5 times more potent in inducing the tumors in mouse skin and rat mammary glands than DMBA; BP was a weak mammary carcinogen in these animals. The present study was designed to investigate if the significantly increased mammary carcinogenicity of DBP over DMBA and BP was related to increased DNA adduction at the target site. Female Sprague-Dawley rats were treated by intramammillary injection with an equimolar dose of 0.25 micromol/gland of DBP, DMBA, and BP at the 3rd, 4th and 5th mammary glands on both sides. 32P-Postlabeling analysis of mammary epithelial DNA of rats treated with DBP produced two major (nos. 3 and 6) and at least 5 minor adducts. DMBA treatment resulted in one major and 4 minor DNA adducts while BP produced one major and two minor adducts. Quantitation of the adduct radioactivity revealed that DNA adduction was 6- and 9-fold greater in DBP-treated animals than in BP- and DMBA-treated animals, respectively. The adduct levels per 10(9) nucleotides in mammary epithelial cells for DBP, BP and DMBA were in the following descending order: 1828 +/- 378, 300 +/- 45 and 207 +/- 72, respectively. Tissue distribution of DNA adducts in non-target organs following DBP treatment showed similar adduct pattern as found in the mammary epithelial cells except the liver, which resulted in 4 additional adduct spots; vehicle-treated tissue DNA processed in parallel did not show any detectable adducts. DMBA- and BP-DNA adduct patterns in various tissues were similar to that found in mammary epithelial cells, however, significant quantitative differences were found; BP-DNA adducts were undetectable in the pancreas and bladder. Quantitation of adduct radioactivity showed a 15- to 60-fold lower DBP-DNA adduction in these tissues than the levels found in the mammary tissue; similarly 5-20 and 30-100 times lower DNA adduction was found following treatment with DMBA and BP, respectively. The significantly increased binding of DBP to the mammary epithelial DNA over BP and DMBA is in concordance with its known higher mutagenicity and tumorigenicity.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2002

Examination of the bioaccumulation of halogenated dimethyl bipyrroles in an Arctic marine food web using stable nitrogen isotope analysis.

Concentrations of four possibly naturally produced organohalogens--1,1'-dimethyl-3,3',4-tribromo-4,5,5'-trichloro-2,2'-bipyrrole (DBP-Br3Cl3), 1,1'-dimethyl-3,3',4,4'-tetrabromo-5,5'-dichloro-2,2'-bipyrrole (DBP-Br4Cl2), 1,1'-dimethyl-3,3',4,4',5-pentabromo-5'-chloro-2,2'-bipyrrole (DBP-Br5Cl) and 1,1'-dimethyl-3,3',4,4',5,5'-hexabromo-2,2'-bipyrrole (DBP-Br6)--were quantitated and the extent of their magnification through an entire Arctic marine food web [measured as integrated trophic magnification factors (TMFs)] were calculated. The food web consisted of three zooplankton species (Calanus hyperboreus, Mysis oculata, and Sagitta sp.), one fish species [Arctic cod (Boreogadus saida)], four seabird species [dovekie (Alle alle), black guillemot (Cepphus grylle), black-legged kittiwake (Rissa tridactyla), and glaucous gull (Larus hyperboreus)], and one marine mammal species [ringed seal (Phoca hispida)]. Trophic levels in the food web were calculated from ratios of stable isotopes of nitrogen (15N/14N). All halogenated dimethyl bipyrrole (HDBP) congeners were found to significantly (P<0.02) biomagnify, or increase in concentration with trophic level in the invertebrate--fish--seabird food web. DBP-Br4Cl2 (TMF= 14.6) was found to biomagnify to a greater extent than DBP-Br3Cl3 (TMF = 5.2), DBP-Br5Cl (TMF = 6.9), or DBP-Br6 (TMF = 7.0), even though the Kow of DBP-Br4CI2 was predicted to be lower than those of DBP-Br5Cl and DBP-Br6. None of the four HDBP congeners in ringed seals followed the general trend of increasing concentration with trophic level, which was possibly due to an ability of the seals to metabolize HDBPs.

Animals↗
PubMed2001

Should diastolic and systolic blood pressure be considered for cardiovascular risk evaluation: a study in middle-aged men and women.

OBJECTIVES: The goal of this study was to evaluate the role of diastolic blood pressure (DBP) in cardiovascular mortality for different systolic blood pressure (SBP) levels in middle-aged men and women. BACKGROUND: In middle-aged subjects it is unclear whether DBP, in addition to SBP, should be considered for risk evaluation. METHODS: Subjects (77,023 men; 48,480 women) aged 40 to 70 years old, had no major cardiovascular disease, no antihypertensive treatment and were examined at the Centre d'Investigations Preventives et Cliniques between 1972 and 1988. Mortality was assessed for an 8- to 12-year period. RESULTS: In both genders, cardiovascular mortality increased with the SBP level. In men and women with normal SBP levels, DBP did not influence cardiovascular mortality after adjustment for age and SBP. In men with systolic hypertension, a U-shaped curve relationship between cardiovascular mortality and DBP was observed, with the lowest mortality rates in the group with DBP 90 to 99 mm Hg. Compared with this group, age- and SBP-adjusted cardiovascular mortality was higher by 73% (p < 0.02) in the group with DBP <90 mm Hg and by 65% (p < 0.001) in the group with DBP > or =110 mm Hg. In women with systolic hypertension, however, DBP was positively correlated with cardiovascular mortality. CONCLUSIONS: In middle-aged subjects, classification of cardiovascular risk according to DBP levels should take into account gender, especially when SBP levels are elevated. Men with systolic hypertension are at higher risk when their DBP is "normal" than when they present a mild to moderate increase in DBP. In women of the same age, however, systolic-diastolic hypertension represents a higher risk than isolated systolic hypertension.

Adult↗
PubMed1999

Development of blood pressure and the incidence of hypertension in men and women over an 18-year period: results of the Nijmegen Cohort Study.

The objective of this study was to determine the factors that influence diastolic blood pressure (DBP) and the incidence of hypertension. In 1977, DBP and cardiovascular risk factors were measured in 7092 men and women. In 1995, 2335 subjects participated at a second screening. Those patients already under hypertension treatment in 1977 were excluded. The DBP tracking was studied in subjects not under hypertension treatment during the study. Hypertension was defined on two ways in the analysis: under current hypertension treatment or a DBP > 95 mmHg measured at rescreening in 1995. Forty-seven percent of the subjects with a DBP < 75 mmHg in 1977 remained in the same category of DBP in 1995, and 7% had become hypertensive. Of the 75-84 mmHg group in 1977, 40% stayed in the same category in 1995 and 15% became hypertensive. Of the 85-94 mmHg category, 30% stayed in the same category and 30% became hypertensive in 1995. Of the highest category in 1977 (> 95 mmHg), 64% were still in that category in 1995. Baseline DBP in 1977 had the highest predictive value for future DBP. Weight gain over the years increased the risk for future hypertension: in contrast, there was no risk at a low DBP without weight gain. There is no need for regular check-ups for those patients with a low DBP who experience no weight gain. Borderline DBP (85-95 mmHg), together with weight gain, increases the risk of development of hypertension. The risk was especially high for men in the lower socioeconomic class.

Adult↗
PubMed1999

Relationship of blood pressure to cardiovascular death: the effects of pulse pressure in the elderly.

PURPOSE: To investigate the relationship of systolic and diastolic blood pressure to fatal myocardial infarction, fatal stroke and other death related to cardiovascular diseases (CVD). METHODS: The study was based on a prospective longitudinal study conducted by the Veterans Administration at the Boston Outpatient Clinic. Participants are male volunteers from the greater Boston area. Main outcome measures are fatal myocardial infarction, fatal stroke and other deaths related to cardiovascular diseases. The method of pooled logistic regression was used for statistical analysis. RESULTS: For younger men (age 21-59), after adjusting for effects of other risk factors, when systolic and diastolic blood pressure were considered separately, SBP was predictive of cardiovascular death (SBP: RR = 1.23; 95% CI = (1.05, 1.45) per 10 mmHg of increase), and DBP showed a nonsignificant positive trend in relation to cardiovascular death (DBP: RR = 1.27; 95% CI = (0.95, 1.69) per 10 mmHg of increase). For older men (age 60-85), when SBP and DBP were considered separately, SBP (RR = 1.26; 95% CI = (1.02, 1.55) per 15 mmHg of increase) was directly related, but DBP (RR = 1.05; 95% CI = (0.83, 1.32) per 8 mmHg of increase) was not related to cardiovascular death. However, for the elderly group, when SBP and DBP were considered jointly in the regression model, then the regression coefficient of DBP (beta = -0.018, p = 0.30) was of approximately the same absolute magnitude as that of SBP (beta = 0.021, p = 0.02) but opposite in sign. For younger men, when SBP and DBP were considered jointly, SBP (beta = 0.021, p = 0.049) but not DBP (beta = -0.001, p = 0.953) was positively related to cardiovascular death. CONCLUSIONS: We found that, for the elderly, pulse pressure (SBP-DBP) may be a more accurate predictor of cardiovascular death than either SBP or DBP alone. The relative risk per 35 mmHg of increase of pulse pressure, which equals the approximate interval from the 10th to the 90th percentile in the elderly group, is 2.1 with 95% CI = (1.1, 3.8). In younger subjects, SBP, but not DBP, is an independent predictor of fatal CVD.

Adult↗
PubMed2002

Systolic vs diastolic blood pressure: community burden and impact on blood pressure staging.

Systolic blood pressure (SBP) is a more frequent cardiovascular risk factor than diastolic blood pressure (DBP), and has a greater impact on blood pressure staging, though this can vary with age, sex and country. Therefore this paper compares SBP and DBP in terms of community burden and impact on blood pressure staging, among Spain's middle-aged population. Data were drawn from a cross-sectional study on a representative sample of the Spanish population aged 35-64 years. Blood pressure was determined under standardised conditions, and was classified as per WHO-ISH and JNC-VI criteria. Prevalence of SBP > or =140 mm Hg was 34.1%, and that of DBP > or =90 mm Hg, 30.9%. A total of 12% of subjects had isolated systolic hypertension (ISH) and 8.7% had isolated diastolic hypertension (IDH). Of treated hypertensives, 31% had their SBP controlled and 34% their DBP controlled. Of subjects not undergoing antihypertensive drug therapy, 60.8% had congruent SBP and DBP levels, 22.5% were up-staged on the basis of their SBP, and 16.7% were up-staged on the basis of their DBP. SBP alone thus correctly classified JNC-VI staging in 83.3% of subjects vs 77.5% for DBP alone. It was solely among the population >50 years of age, in both sexes, that systolic proved more frequent than diastolic hypertension, ISH greater than IDH prevalence, SBP worse than DBP control, and the percentage of SBP higher than that of DBP up-staged subjects. SBP constitutes a greater community burden than does DBP, and has a greater impact on blood pressure staging in Spain's middle-aged population. However, the differential impact of SBP and DBP upon blood pressure burden and staging is favourable to SBP only among subjects >50 years old. These findings are in accordance with recent guidelines on hypertension management.

Adult↗
PubMed2003

Metabolic disorders associated with uncontrolled hypertension.

AIM: To examine the prevalence and characteristics of uncontrolled hypertension (HT). METHODS: A cross-sectional community-based study (1992-93) was carried out in Skara, Sweden, including 894 patients who consecutively underwent an annual follow-up at the hypertension outpatient clinic in primary care. Controlled HT was defined as diastolic blood pressure (DBP) < or =90 mmHg and systolic blood pressure (SBP) < or =160 mmHg and was used as reference. Uncontrolled DBP was defined as DBP >90 mmHg regardless of SBP level, and isolated uncontrolled SBP was defined as SBP >160 mmHg and DBP < or =90 mmHg. Proportions were age-standardized using the Skara population as reference. RESULTS: The prevalence of uncontrolled HT was 43% (isolated uncontrolled SBP 18% and uncontrolled DBP 25%). Both men and women with isolated uncontrolled SBP were older (73 years, CI: 70-75; and 73 years; CI: 72-75) than patients with controlled HT (64 years, CI: 63-66; and 65 years, CI: 64-66). Men and women with known cardiovascular disease (CVD) less often had isolated uncontrolled SBP (OR: 0.4, CI: 0.2-0.9; and OR: 0.5, CI: 0.3-0.9), whereas men and women with known diabetes more often had uncontrolled DBP (OR: 2.3, CI: 1.3-4.1; and OR: 3.3, CI: 1.9-5.7). Men with known CVD less often had uncontrolled DBP (OR: 0.5, CI: 0.3-1.0, p = 0.04), and men with fasting blood glucose >5.5 mmol/l more often had isolated uncontrolled SBP (OR: 1.9, CI: 1.0-3.5, p = 0.04). In women, the following high risk factor levels were associated with uncontrolled DBP: fasting blood glucose >5.5 mmol/l (OR: 1.4, CI: 1.1-1.8), fasting triglycerides > or =1.7 mmol/l (OR: 1.4, CI: 1.1-1.8), body mass index (BMI) >30 kg/m2 (OR: 1.5, CI: 1.1-1.9), waist/hip ratio (WHR) >0.85 cm/cm (OR: 1.7, CI: 1.3-2.2), insulin resistance (homeostasis model assessment (HOMA) >third quartile) (OR: 1.4, CI: 1.1-1.9) and microalbuminuria (OR: 3.2, CI: 1.7-6.2). CONCLUSION: Uncontrolled DBP is in both sexes related to type 2 diabetes, whereas isolated uncontrolled SBP is related to older age. In women, uncontrolled DBP, furthermore, is related to several other CVD risk factors of the metabolic syndrome. Patients with uncontrolled DBP should be carefully evaluated for metabolic disorders.

Adult↗