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PubMed2005

The impact of water consumption, point-of-use filtration and exposure categorization on exposure misclassification of ingested drinking water contaminants.

The use of population-level indices to estimate individual exposures is an important limitation of previous epidemiologic studies of disinfection by-products (DBPs). We examined exposure misclassification resulting from the use of system average DBP concentrations to estimate individual-level exposures. Data were simulated (n=1000 iterations) for 100 subjects across 10 water systems based on the following assumptions: DBP concentrations ranged from 0-99 microg/L with limited intra-system variability; water intake ranged from 0.5-2.5 L/day; 20% of subjects used bottled water exclusively; 20% of subjects used filtered tap water exclusively; DBP concentrations were reduced by 50% or 90% following filtration. DBP exposure percentiles were used to classify subjects into different exposure levels (e.g., low, intermediate, high and very high) for four classification approaches. Compared to estimates of DBP ingestion that considered daily consumption, source type (i.e., unfiltered tap, filtered tap, and bottled water), and filter efficiency (with 90% DBP removal), 48-62% of subjects were misclassified across one category based on system average concentrations. Average misclassification across at least two exposure categories (e.g., from high to low) ranged from 4-14%. The median classification strategy resulted in the least misclassification, and volume of water intake was the most influential modifier of ingestion exposures. These data illustrate the importance of individual water use information in minimizing exposure misclassification in epidemiologic studies of drinking water contaminants.

Chlorine↗
PubMed2006

Diisobutyl phthalate has comparable anti-androgenic effects to di-n-butyl phthalate in fetal rat testis.

UNLABELLED: Phthalates are widely used as plasticizers in various consumer products and building materials. Some of the phthalates are known to interfere with male reproductive development in rats, and di-n-butyl phthalate (DBP), diethylhexyl phthalate (DEHP) and butyl benzyl phthalate (BBP) were recently banned for use in toys in the EU mainly due to their reproductive toxicity. Diisobutyl phthalate (DiBP) has similar structural and application properties as DBP, and is being used as a substitute for DBP. However, knowledge on male reproductive effects of DiBP in experimental animals is lacking. METHODS: In the current study, four groups of pregnant Wistar rats were exposed to either 0mg/kg bw/day or 600 mg/kg bw/day of DiBP from gestation day (GD) 7 to either GD 19 or GD 20/21. Male offspring was examined at GD 19 or GD 20/21 for effects on testicular testosterone production and testicular histopathology. Changes in anogenital distance (AGD) were evaluated as an indication of feminisation of males. RESULTS: Anogenital distance was statistically significantly reduced at GD 20/21 together with reductions in testicular testosterone production and testicular testosterone content. Histopathological effects (Leydig cell hyperplasia, Sertoli cell vacuolisation, central location of gonocytes and presence of multinuclear gonocytes) known for DBP and DEHP were observed in testes of DiBP-exposed animals at GD 20/21. Additionally, immunohistochemical expression of P450scc and StAR proteins in Leydig cells was reduced by DiBP. At GD 19, these effects on anogenital distance, testosterone levels and histopathology were less prominent. CONCLUSION: In this study, GD 20/21 rather than GD 19 appears to be the optimal time for investigating changes in anogenital distance, testosterone levels, and testicular histopathology. DiBP has similar testicular and developmental effects as DBP and DEHP, and although more developmental and especially postnatal studies are needed to clearly identify the reproductive effects of DiBP, this study indicates a reason for concern about the use of DiBP as a substitute for DBP.

Androgen Antagonists↗
PubMedDate not supplied

The factors affecting blood pressure in pediatric renal transplant recipients.

To investigate the parameters affecting systemic blood pressure in pediatric renal transplant recipients, we retrospectively examined the data from 19 adolescent renal transplant recipients including 6 girls overall, mean age of 15,47 +/- 3.56 years. Serum creatinine (Scr), fractional extraction of sodium (FENa), whole blood trough cyclosporine(C0), plasma total cholesterol (TC) and triglyceride levels, and systolic and diastolic blood pressure (SBP and DBP) were monitored during a total of 677 visits. SBP and DBP, classified as <95p (groups 1s and 1d) and >95p (groups 2s and 2d), were correlated with differences between groups 1 and 2. Group 2s Scr and FENa levels were higher than group 1s (P =.002 and P =.048, respectively), whereas C0 and FENa levels were higher in Group 2d than Group 1d (P = 0.028 and P = 0.036, respectively). Among the entire group, SBP and DBP positively correlated with C0; Scr and SBP, with FENa. While there was a positive correlation between SBP and C0 in groups 1s and 2s (r = 0.188, P <.000; and r = 0.145, P =.040), DBP was only associated with C0 in group 1d (P =.03, r = 0.156). In contrast, DBP showed a positive correlation with Scr in group 2d (P =.023, r = 0.132), and SBP with Scr in Group 1s. C0 and Scr levels were correlated in Groups 1s, 1d and 2d. At high BP levels (>95p), SBP is mostly affected by C0; DBP, with Scr. However, in both groups these two parameters positively correlate with each other. Thus, in adolescent renal transplant recipients the cause of high blood pressure does not appear to be solely related to cyclosporine related to induced allograft dysfunction.

Adolescent↗
PubMedDate not supplied

Impact of initial blood pressure on the mortality of diabetics undergoing renal replacement therapy.

The aim of this study was to determine the blood pressure (BP) profiles and their impact on mortality among a cohort of uremic diabetics treated by hemodialysis. The studied population includes all type II diabetics starting hemodialysis for end-stage renal disease between 1990 and 1996. There were 221 patients (144 men, 77 women) aged from 37 to 78 years, were all followed until death or December 2003 without any censored data. Survival analysis to identify predictors of death was performed using the actuarial method, Cox proportional model, including systolic, diastolic, mean, and pulse blood pressures (SBP, DBP, MBP, PP). One hundred seventy-eight patients (80.5%) were hypertensive at the start of dialysis. Hypertension preceded the diagnosis of diabetes in eight cases (4.5%); 154 patients (86.5%) received antihypertensive drugs and only 23 (14.9%) had well-controlled hypertension. Our population was subdivided into four groups according to their BP levels at the time of beginning of dialysis; G1 (19.5%): normal BP (SBP [90 to 140] and DBP [60 to 90]); G2 (30.3%): Hypertension stage 1 (SBP [140 to 160] and/or DBP [90 to 100]); G3 (32.1%): hypertension stage 2 (SBP [160 to 180] and/or DBP [100 to 110]); G4 (18.1%) hypertension stage 3 (SBP [180 to 220] and/or DBP [110 to 120]). Mean age and comorbidities were similar among the four groups. During a cumulative follow-up period of 872 patient-years, 191 patients died, representing a rate of 21.9 per 100 patient-years; 20.42% of these deaths occurred during the first 3 months of dialysis. Normotensive patients showed lower survival rates without any significant difference in comparison with those of other hypertensive groups. None of the initial BP parameters (SBP, DBP, PP, MBP, hypertension stages) seemed to influence early or global mortalities, which were rather related to the urgent onset of renal replacement therapy, to age, to serum albumin, and to the score of associated morbidities. We conclude that mortality of our hemodialyzed diabetics was not influenced by the blood pressure parameters recorded at the onset of dialysis.

Adult↗
PubMed1994

Blood pressure in youth from four ethnic groups: the Pasadena Prevention Project.

To explore the racial differences in blood pressure levels in American youth, and to extend current data to include youth of Asian, black, Hispanic, and non-Hispanic white descent, we recorded blood pressures among ninth graders during the spring of the years 1985 to 1989 in a suburb of Los Angeles. Trained observers, following a standardized protocol, obtained blood pressure measurements from 4577 students (39% black, 30% Hispanic, 21% white, 10% Asian; 50% female) with a mean age of 15 years. With the use of age- and sex-specific 90th percentiles reported in 1987 by the Second Task Force on Blood Pressure Control in Children to define elevated blood pressure, the prevalence of elevated systolic blood pressure (SBP) was 8.1% (diastolic blood pressure (DBP), 9.3%) among female subjects and 16.0% (DBP, 18.5%) among male subjects. Comparisons of the prevalence of elevated blood pressure among ethnic-racial groups within sexes were statistically significant only for Asian girls (SBP, 13.1%; DBP, 14.0%) relative to other female subjects (SBP, 7.6%, p < 0.005; DBP, 8.8%, p < 0.01); these differences persisted after adjustment for body height and body mass index. A similar trend for Asian boys was apparent only for DBP (23.0% vs 18.0%, p = 0.065). Results for group means were comparable: average SBP and DBP were higher for Asian girls than for other ethnic groups. In addition, boys in this sample may have higher blood pressure than boys from other areas of the country. These results suggest that Asians in California may be at greater risk of having early development of hypertension.

Adolescent↗
PubMed1996

Arterial blood pressure changes in children and adolescents with insulin-dependent diabetes mellitus.

Diabetic nephropathy may develop in childhood and is often related to hypertension. The 24-hour ambulatory blood pressures were measured in 63 children with insulin-dependent diabetes mellitus and were compared with those of 54 healthy siblings. The patients were without clinical complications. The 24-hour recording of their blood pressures revealed higher 24-hour systolic blood pressure (SBP) (115.8 +/- 8.2), 24-hour diastolic blood pressure (DBP) (67.5 +/- 4.6), 24-hour mean arterial pressure (MAP) (81.8 +/- 5.2) compared with control subjects: 24-hour SBP (112.7 +/- 6.7), 24-hour DBP (64.7 +/- 4.1), 24-hour MAP (78.9 +/- 4.5) (p = 0.03, p = 0.001, p = 0.002, respectively). Of the daytime blood pressures, SBP, DBP, MAP were also higher (117.7 +/- 8.7, 69.7 +/- 5.2, 83.8 +/- 5.8) compared with those of siblings (114.9 +/- 6.9, 67.3 +/- 4.3, 81.1 +/- 4.9) (p = 0.05, p = 0.009, p = 0.008, respectively). Of the nighttime blood pressures, SBP, DBP, MAP were higher in patients (108.7 +/- 8.9, 59.5 +/- 6.9, 74.6 +/- 6.9) compared with control subjects (104.8 +/- 7.0, 55.1 +/- 5.0, 70.5 +/- 5.1) (p = 0.01, p = 0.0002, p = 0.0006, respectively). Furthermore, the blood pressure burden was evaluated. Blood pressure burden was defined as the percentage of the increased blood pressure readings greater than the 95th percentile divided by the total number of recorded blood pressures during a corresponding period. Patients had a 43% higher 24-hour SBP burden (19.6 +/- 16.5) and a 50% higher 24-hour DBP burden (12.3 +/- 9.6) in relation to that of control subjects (13.7 +/- 12.8, 8.3 +/- 12.3) (p = 0.03, p = 0.009, respectively). The SBP burden (17.9 +/- 14.6) and DBP burden (11.5 +/- 9.2) of the day was approximately 50% higher in the patients in the relation to control subjects (11.9 +/- 11.1, 7.8 +/- 6.7) (p = 0.01, p = 0.01, respectively). Therefore it seems that hemodynamic changes may appear early in children with diabetes.

Adolescent↗
PubMed2002

Correlations between differential absorbance and the formation of individual DBPs.

This study examined correlations between the differential absorbance at 272nm (deltaA272) and the formation of disinfection by-products (DBPs) in chlorinated water from the Tolt River, a water source for Seattle, WA. The DBPs investigated included chloroform (CHCl3), dichlorobromomethane (CHCl2Br), mono-, di- and trichloroacetic acids (MCAA, DCAA, and TCAA, respectively), chloral hydrate (CH), dichloroacetonitrile (DCAN) and 1,1,1-trichloropropanone (TCP). Whereas the kinetics of DBP formation are complex and are non-linear, the same DBP data represented as a function of deltaA272 are quite simple. Absorbance decreases when the water is chlorinated, i.e., deltaA272 is always negative. The DBP vs. -deltaA272 correlations can almost always be quantified by linear equations, at least above some threshold value of -deltaA272, with R2 values > 0.95. The only DBP that did not follow this trend was CH, for which an exponential relationship better described the data. TCP and DCAN were unstable at pH 7 and 8, but at pH 6 linear correlations between their concentrations and -deltaA272 were as strong as those for the more stable DBPs. The threshold -deltaA272 value is approximately the same for many of the DBPs studied, supporting the hypothesis that individual DBPs are released following the formation of a common intermediate, or at least a small group of similar intermediates. The DBP vs. -deltaA272 correlations may have practical value since they provide an alternative approach for monitoring the formation of individual DBP species on-line, but the generality of the relationships needs to be further examined.

Absorption↗
PubMed2002

Probing reactivity of dissolved organic matter for disinfection by-product formation using XAD-8 resin adsorption and ultrafiltration fractionation.

The disinfection by-product (DBP) reactivity (yield and speciation upon reaction with chlorine) of dissolved organic matter (DOM) isolated from two surface waters was investigated. The source waters, each having significantly different specific ultraviolet absorbance (SUVA254), molecular weight (MW) distribution and polarity, were fractionated using XAD-8 resin adsorption and ultrafiltration (UF), with good DOM mass balance closures (based on dissolved organic carbon). It was found that such fractionation preserved both the SUVA and the reactivity of the source waters, as demonstrated by statistically similar DBP formation and speciation from chlorinated source water and source waters reconstituted from XAD-8 or UF fractions. In addition, there was no evidence of synergistic effects among DOM components when reacting with chlorine. Consistent trends between DBP yields and MW were not found. Hydrophobic fractions of DOM (isolated by XAD-8) were the most reactive DOM components; however, hydrophilic components also showed appreciable DBP yields, contributing up to 50% of total DBP formation. In contrast, strong and unique correlations were observed between the SUVA of individual fractions and their trihalomethane (THM) and haloacetic acid (HAA9) yields, confirming that the aromaticity of DOM components is more directly related to reactivity than other physicochemical properties. The finding of a single correlation independent of the fractionation process employed is notable because XAD-8 adsorption and UF fractionate DOM by significantly different mechanisms. These results confirm that SUVA is a distributed parameter that reflects DOM heterogeneity. Therefore, the SUVA distribution within natural water represents an important property that can be used as a reliable predictor of DBP formation. Finally, bromine appears to be more effectively incorporated into low UV-absorbing (i.e., low SUVA), low MW and hydrophilic DOM fractions.

Adsorption↗
PubMed2002

Occurrence and microbial degradation of phthalate esters in Taiwan river sediments.

Concentrations and microbial degradation rates were measured for eight phthalate esters (PAEs) found in 14 surface water and six sediment samples taken from rivers in Taiwan. The tested PAEs were diethyl phthalate (DEP), dipropyl phthalate (DPP), di-n-butyl phthalate (DBP), diphenyl phthalate (DPhP), benzylbutyl phthalate (BBP), dihexyl phthalate (DHP), dicyclohexyl phthalate (DCP), and di-(2-ethylhexyl) phthalate (DEHP). In all samples, concentrations of DEHP and DBP were found to be higher than the other six PAEs. DEHP concentrations in the water and sediment samples ranged from ND to 18.5 microg/l and 0.5 to 23.9 microg/g, respectively; for DBP the concentration ranges were 1.0-13.5 microg/l and 0.3-30.3 microg/g, respectively. Concentrations of DHP, BBP, DCP and DPhP were below detection limits. Under aerobic conditions, average degradation half-lives for DEP, DPP, DBP, DPhP, BBP, DHP, DCP and DEHP were measured as 2.5, 2.8, 2.9, 2.6, 3.1, 9.7, 11.1 and 14.8 days, respectively; under anaerobic conditions, respective average half-lives were measured as 33.6, 25.7, 14.4, 14.6, 19.3, 24.1, 26.4 and 34.7 days. In other words, under aerobic conditions we found that DEP, DPP, DBP, DPhP and BBP were easily degraded, but DEHP was difficult to degrade; under anaerobic conditions, DBP, DPhP and BBP were easily degraded, but DEP and DEHP were difficult to degrade. Aerobic degradation rates were up to 10 times faster than anaerobic degradation rates.

Bacteria, Anaerobic↗
PubMed2004

A systematic review and meta-analysis of the efficacy and safety of a fixed, low-dose perindopril-indapamide combination as first-line treatment of hypertension.

BACKGROUND: A low-dose combination of perindopril and indapamide may effectively reduce blood pressure (BP) in hypertensive patients, but some factors related to study design might have contributed to the between-group differences in the rate of reduction of BP observed in some trials. OBJECTIVE: The aim of this study was to systematically assess the efficacy and safety profiles (through review of randomized, controlled trials) of the fixed, low-dose combination perindopril 2 mg and indapamide 0.625 mg given as 1 tablet daily as first-line antihypertensive therapy in patients with mild to moderate hypertension. METHODS: We searched MEDLINE (1966-April 2003), EMBASE (1980-March 2003), BIOSIS (1999-December 2002), and the Cochrane Library, using the medical subject headings with the search terms perindopril, indapamide, hypertension, randomized controlled trials, randomly, random, randomization, perindopril-indapamide, essential hypertension, and primary hypertension. Additional articles were obtained from the reference lists of relevant reviews and papers. RESULTS: We reviewed 11 trials (5936 individuals). In 5 studies of perindopril-indapamide versus placebo, the between-group weighted mean differences (WMDs) for both systolic and diastolic BP (SBP and DBP, respectively) favored perindopril-indapamide (SBP, -9.03 mm Hg [95% CI, -9.54 to -8.52]; DBP, -5.09 mm Hg [95% Cl, -5.42 to -4.77]; both P < 0.01 for z score for overall effect). In 6 studies of perindopril-indapamide versus routine antihypertensives, the between-group WMDs for SBP and DBP favored perindopril-indapamide (SBP, -3.72 mm Hg [95% CI, -7.11 to 0.33], P = 0.03 for z score for overall effect; DBP, -1.71 mm Hg [95% CI, -2.27 to -1.16], P < 0.01 for z score for overall effect). Five studies compared perindopril-indapamide and placebo; in the remaining 3 studies, which assessed perindopril-indapamide versus routine antihypertensives, the between-group WMDs for SBP and DBP favored perindopril-indapamide (SBP, -4.00 mm Hg [95% CI, -6.54 to -1.47], P < 0.01; DBP, -1.02 mm Hg [95% CI, -1.73 to -0.31], P < 0.01). Adverse events and withdrawals were not significantly different between perindopril-indapamide, placebo, or routine antihypertensive drugs. CONCLUSION: The studies in our analysis consistently demonstrated that a fixed, low-dose perindopril-indapamide combination has a favorable safety profile and may be efficacious as first-line treatment for patients with mild to moderate essential hypertension.

Adult↗
PubMed2002

Effect of dialkyl phthalates on the degranulation and Ca2+ response of RBL-2H3 mast cells.

We examined the effect of three dialkyl phthalates, di-n-butylphthalate (DBP), di-isobutylphthalate (DIBP) and di(2-ethylhexyl)phthalate (DEHP), on antigen-induced degranulation of RBL-2H3 mast cells. Exposure to 50-500 microM DBP, 50-500 microM DIBP, and 500 microM DEHP significantly potentiated antigen-induced beta-hexosaminidase release. Without antigen stimulation, the phthalates did not cause any significant increase in degranulation. Next, we examined the Ca2+ response of RBL-2H3 cells after exposure to these phthalates. The cytosolic calcium ion concentration ([Ca2+]i) of the cells clearly increased when the cells were stimulated with 50-500 microM and 50-500 microM DIBP, and increased slightly when stimulated with 50-500 microM DEHP. Digital imaging fluorescence microscope analysis showed that the addition of DBP evoked Ca2+ oscillation in individual mast cells. Finally, we investigated the relationship between the DBP-sensitive Ca2+ stores and thapsigargin (TG)-sensitive Ca2+ stores. A rise in [Ca2+](i) following challenge with DBP after TG was observed, and thus the DBP-sensitive and TG-sensitive Ca2+ stores in RBL-2H3 cells seem to be different. In conclusion, some dialkyl phthalates increase antigen-induced degranulation in RBL-2H3 cells dependent on the increase of [Ca2+]i.

Animals↗
PubMed2003

In vitro modulation of common carp (Cyprinus carpio L.) phagocytic cells by Di-n-butyl phthalate and Di-2-ethylhexyl phthalate.

The modulation of common carp, Cyprinus carpio L. phagocytic cells by Di-n-butyl phthalate (DBP) and Di-2-ethylhexyl phthalate (DEHP) were analyzed in vitro. Carp head kidney leucocytes were cultured in a RPMI 1640 medium containing DBP or DEHP at concentration of 1-1000 nM and the production of superoxide anion was measured via the in vitro reduction of nitroblue tetrazolium (NBT). Macrophages incubated with 100 up to 1000 nM of DBP showed an increase in their production of superoxide anion in comparison with the control macrophages which, were cultured without DBP. DEHP also increased the production of superoxide anion in phagocytic cells from carp kidneys. Phagocytic cells treated with 10 and 100 ng of DEHP showed increased phagocytic activity. DBP and DEHP also significantly increased the production of nitric oxide in carp macrophages. These results showed that DBP and DEHP modulate the function of phagocytic cells in vitro.

Animals↗
PubMed2005

Depressive mood is independently related to stroke and cardiovascular events in a community.

By means of a multivariate Cox model, we investigated the predictive value of a depressive mood on vascular disease risk in middle-aged community-dwelling people. In 224 people (88 men and 136 women; mean age: 56.8 +/- 11.2 years) of U town, Hokkaido (latitude: 43.45 degrees N, longitude: 141.85 degrees E), a chronoecological health watch was started in April 2001. Consultations were repeated every 3 months. Results at the November 30, 2004 follow-up are presented herein. 7-day/24-h blood pressure (BP) and heart rate (HR) monitoring started on a Thursday, with readings taken at 30-min intervals between 07:00 h and 22:00 h and at 60-min intervals between 22:00 h and 07:00 h. Data stored in the memory of the monitor (TM-2430-15, A and D company, Japan) were retrieved and analyzed on a personal computer with a commercial software for this device. Subjects were asked to answer a self-administered questionnaire inquiring about 15 items of a depression scale, at the start of study and again after 1-2 years. Subjects with a score higher by at least two points at the second versus first screening were classified as having a depressive mood. The other subjects served as the control group. The mean follow-up time was 1064 days, during which four subjects suffered an adverse vascular outcome (myocardial infarction: one man and one woman; stroke: two men). Among the variables used in the Cox proportional hazard models, a depressive mood, assessed by the Geriatric Depression Scale (GDS), as well as the MESOR of diastolic (D) BP (DBP-MESOR) and the circadian amplitude of systolic (S) BP (SBP-Amplitude) showed a statistically significant association with the occurrence of adverse vascular outcomes. The GDS score during the second but not during the first session was statistically significantly associated with the adverse vascular outcome. In univariate analyses, the relative risk (RR) of developing outcomes was predicted by a three-point increase in the GDS scale (RR = 3.088, 95% CI: 1.375-6.935, P = 0.0063). Increases of 5 mmHg in DBP-MESOR and of 3 mmHg in SBP-Amplitude were associated with RRs of 2.143 (95% CI: 1.232-3.727, P = 0.0070) and 0.700 (95% CI: 0.495-0.989, P = 0.0430), respectively. In multivariate analyses, when both the second GDS score and the DBP-MESOR were used as continuous variables in the same model, GDS remained statistically significantly associated with the occurrence of cardiovascular death. After adjustment for DBP-MESOR, a three-point increase in GDS score was associated with a RR of 2.172 (95% CI: 1.123-4.200). Monday endpoints of the 7-day profile showed a statistically significant association with adverse vascular outcomes. A 5 mmHg increase in DBP on Monday was associated with a RR of 1.576 (95% CI: 1.011-2.457, P = 0.0446). The main result of the present study is that in middle-aged community-dwelling people, a depressive mood predicted the occurrence of vascular diseases beyond the prediction provided by age, gender, ABP, lifestyle and environmental conditions, as assessed by means of a multivariate Cox model. A depressive mood, especially enhanced for 1-2 years, was associated with adverse vascular outcomes. Results herein suggest the clinical importance of repetitive assessments of a depressive mood and the need to take sufficient care of depressed subjects. Another result herein is that circadian and circaseptan characteristics of BP variability measured 7-day/24-h predicted the occurrence of vascular disease beyond the prediction provided by age, gender, depressive mood and lifestyle, as assessed by means of a multivariate Cox model. Earlier, we showed that the morning surge in BP on Mondays was statistically significantly higher compared with other weekdays. Although a direct association between the Monday surge in BP and cardiovascular events could not be demonstrated herein, it is possible that the BP surge on Monday mornings may also trigger cardiovascular events. We have shown that depressive people exhibit a more prominent circaseptan variation in SBP, DBP and the double product (DP) compared to non-depressed subjects. In view of the strong relation between depression and adverse cardiac events, studies should be done to ascertain that depression is properly diagnosed and treated. Chronodiagnosis and chronotherapy can reduce an elevated blood pressure and improve the altered variability in BP and HR, thus reducing the incidence of adverse cardiac events. This recommendation stands at the basis of chronomics, focusing on prehabilitation in preference to rehabilitation, as a public service offered in several Japanese towns.

Adult↗
PubMedDate not supplied

Effects of dibutyl phthalate on reproductive function in pregnant and pseudopregnant rats.

In our previous studies, dibutyl phthalate (DBP) was found to be embryolethal and teratogenic in rats. In this study, the effects of DBP on reproductive function were investigated on pregnant and pseudopregnant rats. Rats were given DBP by gastric intubation at 0, 250, 500, 750, 1000, 1250 or 1500 mg/kg on Days 0 to 8 of pregnancy and the pregnancy outcome was determined on Day 20 of pregnancy. The same doses of DBP were given to pseudopregnant rats, with an induced decidual cell response, on Days 0 to 8 of pseudopregnancy, and the uterine weight on Day 9 served as an index of the uterine decidualization. DBP caused significant increases in the incidences of preimplantation loss in females successfully mated at 1250 and 1500 mg/kg and of postimplantation loss in females having implantations at 750 mg/kg and above. The uterine decidualization in pseudopregnant rats was significantly decreased at 750 mg/kg and above. These findings suggest that early embryonic loss due to DBP may be mediated, at least in part, via the suppression of uterine decidualization, an impairment of uterine function.

Animals↗
PubMed1997

Is a series of blood pressure measurements by the general practitioner or the patient a reliable alternative to ambulatory blood pressure measurement? A study in general practice with reference to short-term and long-term between-visit variability.

We studied the reproducibility of a series of blood pressure measurements by general practitioner (GP) and patient in comparison with that of ambulatory blood pressure measurement (ABPM), with reference to short-term and long-term between-visit variability using a prospective, comparative diagnostic study. The study group was 88 potentially hypertensive primary care patients (initial systolic blood pressure [SBP] between 160 and 200 mm Hg or with diastolic blood pressure [DBP] between 95 and 115 mm Hg). ABPMs were measured on 2 separate days (at a 6 month interval). Two series of measurements by the doctor (at 1 to 6 month intervals), and the patient (at a 1 week interval) were measured. Mean differences and standard deviations of mean differences (SDD) between two successive series of measurements, and between two ABPMs were computed. The Wilcoxon signed-ranks test was used to compare these standard deviations. Mean initial office-blood pressures were 161 (SBP) and 102 (DBP) mm Hg. Long-term between-visit variability (measurements by GP) was larger than short-term between-visit variability: SDDs were 16 v 11 mm Hg (SBP), and 10 v 8 mm Hg (DBP). The differences in average SBP and DBP between successive ABPMs and between successive series of office measurements by GP and home measurements by patient were not statistically significant. Mean differences between two series of measurements by GP and patient, and between two ABPMs, were 0 +/- 1 mm Hg. SDDs between successive ABPMs and series of measurements by GP and patient ranged from 8 to 11 mm Hg (SBP), and were 6 mm Hg (DBP). No statistically significant differences were found between the SDDs of the studied measurement procedures (SBP and DBP). In our study the reproducibility of ambulatory blood pressure measurement was not found to be better than that of a series of four duplicate measurements by GP or patient. Long-term (6 months interval) between-visit variability was larger than the short-term (1 week interval) between-visit variability.

Adult↗
PubMed1990

Effect of demineralized bone powder on osteoblast-like cells in culture. A potential rapid quality control assay.

Demineralized bone powder (DBP) has been shown to induce osteogenesis in a variety of bone defects and extra-osseous sites. Previous investigations have been carried out in animal models which are time-consuming and expensive. We studied the effect of DBP on well-established populations of osteoblast and non-osteoblast-like cells in culture to establish an inexpensive, efficient and reliable assay for bone induction. DBP and BP (non-demineralized powder), of particle size 38-53 microns, were prepared from rat long bones. ROS (rat osteosarcoma) 17/2.8 and ROS 24/1 cell lines were subcultured weekly. For both 17/2.8 (well differentiated) and 24/1 (poorly differentiated) cells, proliferation, i.e. cell count, was significantly greater in DBP enriched medium when compared with control or medium with BP. Cell counts for wells with BP were no different from controls. The increased cell count in DBP-enriched medium was significant on days 2-5 (peak effect 2-3 days). Alkaline phosphatase production reached peak levels after day 3 when proliferation was beginning to taper off. In this study a consistent increase in osteoblast proliferation and alkaline phosphatase production under the influence of DBP was demonstrated. The tissue culture assay for proliferation must now be correlated with bone induction in vivo. In future, the method may be useful for investigating the mechanism of bone induction.

Alkaline Phosphatase↗
PubMed1986

Photoaffinity labeling of the rat plasma vitamin D binding protein with [26,27-3H]-25-hydroxyvitamin D3 3 beta-[N-(4-azido-2-nitrophenyl)glycinate].

It is well recognized that the vitamin D binding protein (DBP) is important for the transport of vitamin D, 25-hydroxyvitamin D (25-OH-D), and its metabolites. In an attempt to better understand the molecular-binding properties of this ubiquitous protein, we designed and synthesized a photoaffinity analogue of 25-OH-D3 and its radiolabeled counterpart. This analogue, 25-hydroxyvitamin D3 3 beta-[N-(4-azido-2-nitrophenyl)glycinate] (25-OH-D3-ANG), was recognized by the rat DBP and was about 10 times less active than 25-OH-D3 in terms of binding. Incubation of [3H]25-OH-D3 or [3H]25-OH-D3-ANG with rat DBP revealed that both compounds were specifically bound to a protein with a sedimentation coefficient of 4.1 S. Each was displaced with a 500-fold excess of 25-OH-D3. When [3H]25-OH-D3-ANG was exposed to UV radiation in the presence of rat DBP followed by the addition of a 500-fold excess of 25-OH-D3, there was no displacement of tritium from the 4.1S peak. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiographic analysis of [3H]25-OH-D3-ANG exposed to UV radiation in the presence of rat DBP followed by the addition of a 500-fold excess of 25-OH-D3 revealed one major band with a molecular weight of 52 000. These data provide strong evidence that [3H]25-OH-D3-ANG was covalently linked to the rat DBP. This photoaffinity probe should provide a valuable tool for the analysis of the binding site on this transport protein.

Affinity Labels↗
PubMed1997

Roles of the structure and orientation of ligands and ligand mimics inside the ligand-binding pocket of the vitamin D-binding protein.

1alpha,25-Dihydroxyvitamin D3, the vitamin D hormone, manifests its diverse biological properties by specifically binding to the vitamin D sterol-binding pockets of vitamin D-binding protein (DBP) and vitamin D receptor. In the past, several affinity, photoaffinity, and chemical modification studies have been carried out to probe the vitamin D sterol-binding pocket of DBP and to evaluate the relationship between the structure of this pocket and the functions of the protein. In the present study, we examined the steric requirements inside this pocket by considering conformational structures of various bromoacetate derivatives of 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3 and their abilities to covalently and specifically modify this pocket. We observed that, although 25-hydroxyvitamin D3 3beta-bromoacetate (25-OH-D3-3-BE), 1alpha,25-dihydroxyvitamin D3 3beta-bromoacetate [1alpha,25(OH)2D3-3-BE], 1alpha,25-dihydroxyvitamin D3 1alpha-bromoacetate [1alpha,25(OH)2D3-1-BE], and 1alpha,25-dihydroxyvitamin D3 1alpha,3beta-dibromoacetate [1alpha,25(OH)2D3-1,3-di-BE] bound DBP in a specific manner, only [3H]-25-OH-D3-3-BE and [3H]-1alpha,25(OH)2D3-3-BE affinity labeled the protein. BNPS-skatole cleavages of [3H]-25-OH-D3-3-BE- and 3H-1alpha,25(OH)2D3-3-BE-labeled DBP samples produced the same labeled peptide (N-terminal), demonstrating the specificity of labeling by these analogs. Energy-minimized conformational structures of these bromoacetate derivatives indicated significant changes in the A-ring conformations of these analogs. These structural changes were invoked to explain the inability of [3H]-1alpha,25(OH)2D3-1-BE and [3H]-1alpha,25(OH)2D3-1,3-di-BE to affinity label DBP. Overall, these studies suggested that the vitamin D sterol-binding pocket in DBP is sterically quite restrictive. This information could be potentially important in designing future vitamin D-based drugs for several diseases.

Acetates↗