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PubMed2006

A multicenter, 14-week study of telmisartan and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure monitoring.

BACKGROUND: Blood pressure (BP) has a circadian pattern with a morning surge that is associated with an increased risk of acute coronary and cerebrovascular events. In a prospective, randomized, open-label, blinded-endpoint, parallel-group, multicenter, forced-titration study of telmisartan and ramipril, the efficacy of both drugs on mean ambulatory diastolic BP (DBP) and systolic BP (SBP) during the last 6 h of a 24-h dosing interval was evaluated. METHODS: After screening and a single-blind run-in phase, 812 adults with mild-to-moderate hypertension (defined as a mean seated DBP > or =95 mm Hg and < or =109 mm Hg and a 24-h ABPM mean DBP 7 > or = 85 mm Hg) were randomized to the open-label, 14-week, forced-titration, active-treatment phase as follows: telmisartan 40 mg/80 mg/80 mg (n = 405) or ramipril 2.5 mg/5 mg/10 mg (n = 407), once daily in the morning. The primary efficacy variable was change from baseline in the last 6-h mean DBP and SBP at 8 and 14 weeks as assessed by ambulatory BP monitoring (ABPM). Secondary efficacy variables were changes from baseline in BP control during each of the 24-h periods and in-clinic trough cuff BP. RESULTS: Telmisartan 80 mg was superior to ramipril 5 mg and 10 mg in change from baseline in the last 6-h ABPM mean DBP and SBP at both 8 and 14 weeks (both P < .0001), respectively. At 14 weeks, the adjusted mean change from baseline in DBP for telmisartan 80 mg was -8.8 mm Hg compared with that for ramipril 10 mg of -5.4 mm Hg (P < .0001). For SBP, the adjusted mean change from baseline for telmisartan 80 mg was -12.7 mm Hg compared with that for ramipril 10 mg of -7.9 mm Hg (P < .0001). At 14 weeks, telmisartan 80 mg also yielded superior reductions from baseline in trough cuff BP compared with ramipril 10 mg (DBP: -11.0 mm Hg v -7.8 mm Hg, respectively; SBP: -14.3 mm Hg v -9.1 mm Hg, respectively; both P < .0001). Measures of 24-h BP control favored telmisartan 80 mg versus ramipril 10 mg (P < .0001), as did other secondary ABPM endpoints during the daytime, night-time, and morning periods. Treatment-related adverse events were uncommon; patients treated with ramipril had a higher incidence of cough than those treated with telmisartan (10.1% v 1.5%, respectively). CONCLUSIONS: Telmisartan 80 mg was consistently more effective than ramipril 10 mg in reducing both DBP and SBP during the last 6 h of the dosing interval, a measure of the early morning period when patients are at greatest risk of life-threatening cardiovascular and cerebrovascular events. Telmisartan 80 mg was also more effective than ramipril 10 mg in reducing BP throughout the entire 24-h dosing interval. Both drugs were well tolerated.

Adult↗

PubMed2006

Effects of endocrine disruptor di-n-butyl phthalate on the growth of Bok choy (Brassica rapa subsp. chinensis).

The effects of the endocrine disrupter, di-n-butyl phthalate (DBP), on the growth of leaf vegetable Bok choy (Brassica rapa subsp. chinensis, white stem Bok choy) were investigated. The results showed that leaves of Bok choy became white in color with the occurrence of chlorosis and necrosis upon treating with 30 mg l(-1) DBP for 42 days. Transmission electron microscopic images revealed that changes in the chloroplast structures accompanied the chlorosis. In addition, a decrease in biomass and chlorophyll, and accumulation of DBP, were found in DBP-treated Bok choy. The growth and morphology of Bok choy showed a significant dose-response relationship upon treatment with DBP in a hydroponic culture medium. The proteome of the leaf tissue was analyzed using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). Six protein spots were identified in 2-DE that showed reproducible differences in expression between the normal control and the DBP-treated sample. Based on proteome level studies two protein spots increased and were identified as superoxide dismutase (SOD) and peroxidase 21 precursor. These proteins are believed to increase in expression in response to free radical exposure as a detoxification mechanism. The other four protein spots that disappeared on treatment with DBP were identified as heat shock cognate protein 80, protein disulfide isomerase precursor, apocytochrome f precursor, and RNA polymerase beta subunit. The first two play an important role in polypeptide folding, the third is associated with electron transport, and the last has a critical function in DNA transcription. This study indicated that DBP affects the proteome formation as well as the physiology and the morphology of Bok choy during growth. The decrease in those four proteins might be related to the growth and development of a plant.

Brassica rapa↗

PubMed2005

Vitamin D-binding protein gene polymorphism association with IA-2 autoantibodies in type 1 diabetes.

BACKGROUND: Vitamin D-binding protein (DBP) is the main systemic transporter of 1.25(OH)2D3 and is essential for its cellular endocytosis. There are two known polymorphisms in exon 11 of the DBP gene resulting in amino acid variants: GAT-->GAG substitution replaces aspartic acid by glutamic acid in codon 416; and ACG-->AAG substitution in codon 420 leads to an exchange of threonine for lysine. These DBP variants lead to differences in the affinity for 1.25(OH)2D3. Correlations between DBP alleles and type 1 diabetes have been described in different populations. Therefore, we investigated the polymorphism in codon 416 of the DBP gene for an association with autoimmune markers of type 1 diabetes. DESIGN AND METHODS: The present analysis was a case control study. 110 patients, 68 controls, and 115 first-degree relatives were genotyped for the DBP polymorphism in codon 416. DNA typing of DBP locus was performed by the PCR-restriction fragment length polymorphism method (RFLP). RESULTS: The frequencies of the Asp/Glu and Glu/Glu were significantly increased in diabetic subjects with detectable IA-2 antibodies (P < 0.01). On the contrary, the DBP Glu-containing genotype was not accompanied by differences in the prevalence of GAD65 antibodies. These finding supports a role of the vitamin D endocrine system in the autoimmune process of type 1 diabetes.

Adult↗

PubMed2005

Manidipine versus enalapril monotherapy in patients with hypertension and type 2 diabetes mellitus: a multicenter, randomized, double-blind, 24-week study.

BACKGROUND: Blood pressure reduction is associated with a reduced risk for cardiovascular events and death, particularly in patients with both hypertension and type 2 diabetes mellitus. OBJECTIVE: The aim of this study was to compare the antihypertensive efficacy, tolerability, and effect on metabolic risk factors of manidipine, a new dihydropyridine calcium channel antagonist, and enalapril, a widely used angiotensin-converting enzyme inhibitor, in patients with mild to moderate essential hypertension and type 2 diabetes. METHODS: This multicenter, double-blind trial compared manidipine and enalapril in patients with type 2 diabetes and hypertension (diastolic blood pressure [DBP] 90-104 mm Hg, systolic blood pressure [SBP] < or =190 mm Hg). Following a 3-week, single-blind placebo run-in period, eligible patients were randomized to receive either manidipine 10 mg or enalapril 10 mg once daily for 24 weeks. The dose was doubled after 3 weeks in patients who had not responded to treatment (DBP > or =90 mm Hg). The primary efficacy end point was change in DBP from baseline to the end of the study. Secondary outcomes were the responder rate (DBP <90 mm Hg and/or a DBP reduction of > or =10 mm Hg) at the end of the study. Other secondary measures were changes from baseline to the end of the study in heart rate and in the following measures obtained by ambulatory blood pressure monitoring (ABPM): 24-hour, daytime, and nighttime mean DBP and SBP, and the trough:peak ratio. Blood glucose, glycosylated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, uric acid, and creatinine were measured at the end of the placebo run-in period and the end of treatment. The study had 80% power to detect a between-treatment difference in mean sitting DBP of >3 mm Hg. RESULTS: One hundred twenty-four patients were enrolled in the study. After the placebo run-in period, 13 patients were excluded from the study: 4 for DBP values outside the specified limits, 7 at their request, and 2 for adverse events. Thus, 111 patients met the eligibility criteria and were randomized to treatment (53 manidipine, 58 enalapril). The population consisted of 61 men and 50 women with a mean (SD) age of 62 (11) years and a body mass index of 28.2 (2.4) kg/m2. Among patients who completed the study, drug doses were doubled in 67.6% (25/37) of patients in the manidipine group and 60.0% (24/40) of patients in the enalapril group (P = NS). Similar reductions in blood pressure were observed in both groups, from a mean (SD) of 164 (12)/97.5 (5) mm Hg at baseline to 141 (12)/84.5 (6) mm Hg at the end of the study in the manidipine group (P < 0.01), and from 159 (12)/98 (4) mm Hg to 139 (12)/86 (8) mm Hg in the enalapril group (P < 0.01). The proportion of responders was 66.7% (32/48) in the manidipine group and 60.0% (30/50) in the enalapril group; the difference between groups was not significant. Twenty-four-hour ABPM revealed significant (P < 0.01) and similar reductions in blood pressure in both groups, with a trough:peak ratio of approximately -50%. Neither drug affected heart rate. Among the statistically significant changes in metabolic parameters, significant reductions in HbA(1c) (from 6.7% [1.4%] to 6.2% [1.1%]) and blood glucose concentrations (from 152 [44] to 143 [44] mg/dL) were observed only in the manidipine group (P < 0.05). The incidence of adverse events was similar between groups. CONCLUSIONS: In the present study, manidipine was as metabolically neutral and as effective as enalapril in reducing blood pressure in hypertensive patients with type 2 diabetes, providing a sustained 24-hour antihypertensive effect.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2005

Blood pressure after cardiac transplantation in childhood.

BACKGROUND: There has been little formal study of blood pressure in children after cardiac transplantation. METHODS: Twenty-four-hour and clinical blood pressure (BP) were measured in 28 children (>6 months after transplantation) and compared with a large amount of normal data. RESULTS: Conventional (clinical) systolic BP (SBP) was elevated in 9 (32.1%) of 28 (95% confidence interval [CI] 15.8 to 52.3), and conventional diastolic BP (DBP) was elevated in 5 (17.8%) of 28 (95% CI 6.0 to 36.8). Mean 24-hour BP was >97.5 percentile in 2 (7.7%) of 26 (95% CI 0.9 to 25.1) for SBP and in 7 (28.0%) of 25 (95% CI 12.1 to 49.4) for DBP. In comparison with the control population, mean nighttime SBP was 8.9 mm Hg higher in the transplanted group (95% CI 4.8 to 13.1), but daytime and mean 24-hour SBP were similar. Mean day, night, and 24-hour DBP was significantly higher in the transplanted patients. The nighttime decrease in BP was significantly less than controls for SBP, but not for DBP. Conventional BP measurement was poorly predictive of 24-hour BP. There was a significant association between mean 24-hour SBP and interventricular septal thickness (r(2)=0.35; p=0.01). DBP was not associated with interventricular septal thickness (r(2)=0.07; p=0.20) but was significantly correlated with the time since transplantation (r=0.42; p=0.03 for conventional DBP and r=0.43; p=0.04 for 24-hour DBP). CONCLUSIONS: The elevation of DBP in children after cardiac transplantation is unexplained. The elevation in nighttime SBP has possible important therapeutic implications and is not predicted by conventional (clinical) BP measurement.

Adolescent↗

PubMed2026

Unveiling phthalate esters biodegradation from microbial community to Pseudarthrobacter scleromae HL-1: Kinetics, genomic insights, pathways, toxicity assessment and environmental remediation.

Phthalate esters (PAEs) are ubiquitous synthetic plasticizer pollutants posing severe ecological and human health risks. This study compared microbial community structures and dibutyl phthalate (DBP) degradation kinetics of two consortia: 7-day enriched MC1 (50 mg/L DBP) and 6-cycle acclimated MC7 (50-1000 mg/L DBP), demonstrating directional DBP stress selection generated a low-diversity, highly specialized degradative community with a 25.4 mg/L/h maximum degradation rate (Vmax), 1.68-fold higher than MC1. Four dominant DBP-degrading strains were isolated from MC7; Pseudarthrobacter scleromae HL-1 showed the highest efficiency with 17.1 mg/L/h Vmax and complete 500 mg/L DBP removal within 72 h, broad substrate spectrum, and strong adaptability after optimization. Whole-genome sequencing and GC-MS/MS elucidated a dual-parallel DBP mineralization pathway, first reported in Pseudarthrobacter, integrating ester hydrolysis and side-chain β-oxidation. ECOSAR and Chlorella vulgaris bioassays confirmed progressive toxicity attenuation, with > 99% relative toxicity reduction after 72 h and no toxic intermediate accumulation. Natural lake water trials with trace background PAEs showed HL-1 successfully colonized aquatic environments, reshaped indigenous communities into synergistic degradative consortia, and achieved 99.2% DBP removal in 84 h. This work provides comprehensive insights into PAE biodegradation mechanisms from community to single strain and highlights HL-1 as a promising candidate for remediating PAE-polluted aquatic ecosystems.

Genomic analysis↗

PubMed2004

Reproductive and developmental toxicity in F1 Sprague-Dawley male rats exposed to di-n-butyl phthalate in utero and during lactation and determination of its NOAEL.

Di-n-butyl phthalate (DBP) is one of the commonly used plasticizers in China. DBP can enter the environment and organisms through various routes and then affect reproductive and developmental processes of the organism and its descendants (mainly affecting male offspring). It is known that animals are sensitive to exposure of DBP in utero and during lactation. In the present study, pregnant rats were treated with different doses of DBP (0, 50, 250, and 500 mg/kg body weight/day) by daily gavage from GD1 to PND21. The developmental condition of F1 rats and the reproductive system of mature F1 male rats were monitored. DBP had no obvious effect on pregnant rats; however, it reduced several parameters including birth weight, number of live pups per litter, body weight gain and male anogenital distance. Severe damage to the reproductive system of mature F1 male rats included testicular atrophy, underdeveloped or absent epididymis, undescended testes, obvious decline of epididymal sperm parameters, total sperm heads per g testis, decrease of organ/body weight ratio of epididymis and prostate, and was observed in the group treated with 250 mg/kg BW/day and higher. These results showed that the male reproductive system was the main target organ of DBP exposure. The NOAEL (no observable adverse effect level) for developmental toxicity of DBP was established based on pup body weight and male reproductive lesions at 50 mg/kg BW/day. Accordingly, the RfD for human exposure to DBP through oral intake was recommended as 500 mg/kg BW/day.

Abnormalities, Drug-Induced↗

PubMed2004

Effects of chlorophyllin on transport of dibenzo(a, l)pyrene, 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine, and aflatoxin B(1) across Caco-2 cell monolayers.

Chlorophyllin (CHL) is a sodium copper derivative of chlorophyll that is capable of forming strong non-covalent complexes with several known carcinogens. Antimutagenic and anticarcinogenic effects, including reduced DNA adduct and tumor formation have been demonstrated for CHL against aflatoxin B(1) (AFB(1)), dibenzo(a,l)pyrene (DBP) and 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP). Alterations in uptake and/or metabolism of planar molecules with at least partial ring structure have been proposed as mechanisms of action for CHL chemoprevention. The Caco-2 cell model of intestinal epithelial transport was used to evaluate the absorption of 1 microM DBP, AFB(1) and PhIP across cell monolayers in the presence of 0, 1, 10, and 100 microM CHL. No significant differences were observed in the permeability (P(e)) of DBP and AFB(1) from the basolateral-to-apical (BL --> AP) compared to apical-to-basolateral (AP --> BL) compartments for DBP and AFB(1), however, the P(e) of PhIP from BL --> AP, 1.26 x 10(5) +/- 2.10 x 10(6) cm/s, was significantly higher than AP --> BL, 5.83 x 10(6) +/- 7.56 x 10(7) cm/s, (P<0.001) suggesting an active efflux pathway. Transport of DBP from AP --> BL compartments was significantly reduced at all CHL concentrations (P<0.05). AP --> BL transport of AFB(1) was significantly reduced by the addition of 100 microM CHL (P<0.05) while 1 microM or 10 microM CHL had no effect. Complexation studies revealed a higher binding affinity (K(b)) for DBP to CHL compared to AFB(1) to CHL in transport buffer. AP --> BL transport of PhIP, which has a lower binding affinity for CHL than AFB(1) or DBP, was not significantly altered by the addition of CHL. These data suggest that the transport of AFB(1) and DBP can be inhibited by CHL, which supports a model of direct binding in the intestinal tract of CHL to these carcinogens with resultant reduction of bioavailability as one mechanism of action as a cancer chemopreventive agent.

Aflatoxin B1↗

PubMed2003

Effect of DBP/DEHP in vegetable planted soil on the quality of capsicum fruit.

Field experiment was conducted to investigate the di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) contamination in Capsicum annum fruit grown in DBP and DEHP contaminated soil, and to evaluate the effect of DBP and DEHP on the quality of capsicum fruit. The top layer soil (0-10 cm) of plots was treated with a mixture of DBP and DEHP (1:1 w/w) and capsicum seedlings were transplanted. After 90 days, capsicum fruit, shoot and root samples were collected. DBP and DEHP concentration in various parts of the samples were determined by gas chromatography. Vitamin C and capsaicin contents in fruit were determined using 2,4-dinitrophenylhydrazine colorimetric analysis and sodium nitrite-sodium molybdate colorimetric analysis, respectively. The results showed that DBP concentration in fruit, shoot and root increased with the increase of soil-applied DBP/DEHP concentration, but DEHP was not detected in all samples. When the soil-applied DBP/DEHP concentration was 5, 10, 20, 40, 80 and 160 mg kg(-1) soil, compared with control, vitamin C and capsaicin content in capsicum fruit decreased by 1.6%, 5.9%, 10.6%/o, 18.2%, 19.2%, 22.6% and 1.6%, 2.5%, 12.9%, 20.1%, 22.2%, respectively. Pearson correlation analysis demonstrated that the decrease of vitamin C and capsaicin content was negatively correlated to the increase of DBP concentration in capsicum fruit, which suggested that DBP uptake by the plant might be mainly responsible for quality degradation of capsicum fruit.

Ascorbic Acid↗

PubMed2001

Blood pressure control in patients with mild to moderate essential hypertension switched from nifedipine gastrointestinal therapeutic system (GITS) 30 mg to nifedipine GITS 20 mg.

BACKGROUND: Nifedipine gastrointestinal therapeutic system (GITS) is a once-daily formulation of nifedipine that provides sustained plasma nifedipine concentrations throughout the 24-hour dosing interval. OBJECTIVE: This study was undertaken to determine if adult patients with mild to moderate essential hypertension whose blood pressure had been controlled for > or = 3 months with nifedipine GITS 30 mg could be successfully switched to a 20-mg daily dose with continued antihypertensive efficacy. METHODS: This was a randomized, double-blind, parallel-group study. Patients entered a 1-week run-in period during which they continued to receive their usual antihypertensive medication, including nifedipine GITS 30 mg. After baseline assessment, patients entered a 6-week treatment period during which they were randomly assigned to receive nifedipine GITS 30 or 20 mg. Men and women were eligible to participate if they were > or = 55 years of age, had received a diagnosis of mild to moderate essential hypertension (sitting diastolic blood pressure [DBP] 95-114 mm Hg), and had exhibited good blood pressure control (sitting DBP < or = 90 mm Hg) while taking nifedipine GITS 30 mg once daily for > or = 3 months. Systolic blood pressure (SBP), DBP, and heart rate were recorded at baseline and after 1, 3, and 6 weeks of treatment. Adverse events were reported by patients. The responder rate was defined as the percentage of patients whose sitting DBP was < 95 mm Hg at the final study assessment. Results were based on the intent-to-treat analyses, which included data for all patients who received > or = 1 dose and had 1 postbaseline blood pressure assessment. Statistical significance was set at P < 0.05. RESULTS: Seventy-five patients entered the 1-week run-in period; 71 patients (94.7%) were randomized to treatment. Twenty-four patients received nifedipine GITS 30 mg for 43.0 +/- 3.3 days, and 47 patients received nifedipine GITS 20 mg for 42.5 +/- 6.7 days. Both groups exhibited a sustained decrease in blood pressure throughout the study; minor variations were not statistically significant. End-point SBP and DBP for the 30- and 20-mg groups were 135.5 +/- 9.8/81.7 +/- 5.4 mm Hg and 138.6 +/- 11.8/82.9 +/- 7.6 mm Hg, respectively. Changes from baseline in end-point SBP and DBP did not differ significantly between groups. At the end of treatment, goal DBP (< 95 mm Hg) was achieved by 24 of 24 patients (100%) receiving the 30-mg dose and 45 of 47 patients (95.7%) receiving the 20-mg dose. Blood pressure control (sitting DBP < 90 mm Hg) was achieved by 21 of 24 (87.5%) patients in the 30-mg group and 35 of 47 (74.5%) patients in the 20-mg group. The most commonly reported adverse event was headache; 2 patients discontinued the study because of adverse events. Overall, 9 of 24 patients (37.5%) in the 30-mg group and 14 of 47 patients (29.8%) in the 20-mg group experienced > or = 1 treatment-related adverse event. CONCLUSIONS: Patients whose mild to moderate essential hypertension is controlled with nifedipine GITS 30 mg once daily may be able to switch to 20 mg once daily with continued antihypertensive efficacy. In addition to safety and economic advantages, such a switch may be a reasonable alternative in patients with lower body weight or as an adjunct to existing antihypertensive therapy.

Aged↗

PubMed1997

Racial differences in the renal response to blood pressure lowering during chronic angiotensin-converting enzyme inhibition: a prospective double-blind randomized comparison of fosinopril and lisinopril in older hypertensive patients with chronic renal insufficiency.

This study was undertaken to compare the effects of chronic angiotensin-converting enzyme (ACE) inhibition on blood pressure (BP) and renal hemodynamics in older black and nonblack hypertensive patients with chronic renal insufficiency. A multicenter, placebo lead-in double-blind, parallel group study was performed to compare the antihypertensive efficacy and renal hemodynamic response to the once-daily ACE inhibitor fosinopril (n = 14) and lisinopril (n = 13) over a 22-week period. The study goal was to lower diastolic blood pressure (DBP) to 90 mm Hg or less. Furosemide was added after 6 weeks if blood pressure goal was not achieved. At outpatient clinics at university medical centers, 27 older hypertensive patients (> or = 45 years; 12 blacks, 15 nonblacks; 19 male, eight female) with DBP of 95 mm Hg or higher and 4-hour creatinine clearance 20 to 70 mL/min/1.73 m2 were studied. Changes (delta) from baseline in BP, glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured. Mean systolic blood pressure (SBP) and DBP decreased significantly and to a similar extent in randomized groups: fosinopril (mean +/- SEM) delta DBP at 6 weeks was -13 +/- 2 (P < 0.0001; 95% CI, -16 to -9) and at 22 weeks was -12 +/- 2 (P < 0.0001; 95% CI, -16 to -9); lisinopril delta DBP at 6 weeks was -14 +/- 6 (P < 0.0001; 95% CI, -10 to -18) and at 22 weeks was -16 +/- 2 (P < 0.0001; 95% CI, -12 to -21). GFR and RPF did not change significantly in either group. BP was significantly reduced and to a similar extent in blacks and nonblacks: for blacks, delta DBP at 6 weeks was -11 +/- 3 (P < 0.05; 95% CI, -0.01 to -9) and at 22 weeks was -16 +/- 2 (P < 0.0001; 95% CI, -11 to -20); for nonblacks, delta DBP at 6 weeks was -14 +/- 1 (P < 0.0001; 95% CI, -12 to -17) and at 22 weeks was -12 +/- 2 (P < 0.0001; 95% CI, -16 to -8). Eight patients (five blacks and three nonblacks) required an addition of furosemide after 6 weeks to reach the DBP goal of < or = 90 mm Hg at 22 weeks. GFR was not significantly altered for either racial group at 6 weeks; however, at 22 weeks; however, at 22 weeks, GFR decreased significantly in blacks (delta GFR, -16 +/- 5; P < 0.006; 95% CI, -26 to -5) and tended to increase in nonblacks (delta GFR, 7 +/- 6; P > 0.25). delta GFR correlated directly with the delta RPF (delta GFR = 0.0611* delta RPF -2.35 +; r = 0.68; P < 0.003). There was no correlation between delta MAP and delta GFR or delta RPF in blacks or nonblacks. We conclude that chronic ACE inhibition with fosinopril and lisinopril alone or in combination with furosemide lowers BP in older blacks and nonblacks with hypertension and chronic renal insufficiency. Racial differences in the renal hemodynamic response to chronic ACE inhibition were noted and appear to be independent of diuretic use and the magnitude of BP lowering.

Aged↗

PubMedDate not supplied

Fetal testosterone insufficiency and abnormal proliferation of Leydig cells and gonocytes in rats exposed to di(n-butyl) phthalate.

Adult male rats previously exposed on gestation days (GD) 12-21 to di(n-butyl) phthalate (DBP) have reproductive tract malformations, particularly agenesis of the epididymis, decreased sperm production, and Leydig cell hyperplasia and adenomas. Although similar effects are produced by the potent androgen receptor (AR) antagonist flutamide and are indicative of disruption of male sexual differentiation via an antiandrogenic mechanism, DBP is not an AR antagonist. The purpose of the study was to determine whether DBP causes pathologic changes and alterations in androgen status in the testis during the prenatal period of male reproductive tract differentiation. Pregnant CD rats were given corn oil, DBP (500 mg/kg/day), or flutamide (100 mg/kg/day) p.o. on GD 12-21. At GD 16-21, DBP caused hyperplasia of Leydig cells, many of which were 3beta-hydroxysteroid dehydrogenase- and/or AR-positive. Focal areas of hyperplasia had increased numbers of Leydig cells positive for proliferating cell nuclear antigen (PCNA). At GD 21, testis atrophy was apparent, seminiferous cords in DBP-exposed fetuses were enlarged and contained multinucleated gonocytes that, unlike controls, were PCNA-positive. DBP, but not flutamide, markedly decreased testicular testosterone levels at GD 18 and 21. Fewer epididymal ducts and reduced AR staining in some ducts were evident with DBP treatment, whereas decreased overall AR staining was seen with flutamide in the presence of mild Leydig cell hyperplasia. Leydig cell proliferation is likely a compensatory mechanism to increase testicular steroidogenesis triggered by testosterone insufficiency. The overall decrease in androgen concentration is not corrected and results in reproductive tract malformations. The multinuclearity and proliferation of gonocytes suggests an underlying Sertoli cell dysfunction.

Abnormalities, Drug-Induced↗

PubMed1996

Phosphorus Chemical Shift Tensors of Phosphole Derivatives Determined by (31)P NMR Spectroscopy of Powder Samples.

The results of a systematic solid-state (31)P NMR study of 5-phenyldibenzophosphole, DBP, its chalcogenides, and some of its transition metal complexes are reported. Phosphorus chemical shift tensors have been obtained from (31)P NMR spectra of stationary samples and of samples spinning about the magic angle. The spans of the phosphorus chemical shift tensors for DBP and its chalcogenides are comparable to those of the corresponding compounds of triphenylphosphine; however, the asymmetry of the tensors for the DBP series reflects the reduced local symmetry at phosphorus. For the complexes (DBP)M(CO)(5) and cis-(DBP)(2)M(CO)(4), where M is a group 6 transition metal (Cr, Mo, W), the most shielded component of the phosphorus shift tensor is found to be relatively independent of the metal or complex, delta(33) = -41 +/- 8 ppm, and is thought to lie along or close to the P-M bond axis direction. In contrast, delta(11) and delta(22) show considerable variation but decrease systematically on descending the group from Cr to W. Group 10 metal complexes, (DBP)(2)MX(2), have also been investigated, including several trans geometric isomers of nickel, cis and trans isomers of palladium, and cis isomers of platinum. The phosphorus shift tensors are nonaxially symmetric with spans in the range 50 -150 ppm. The phosphorus shift tensors of the two nonequivalent DBP ligands of (DBP)(2)PtX(2) (X = Cl, Br) exhibit quite different principal components. The intermediate component of the shift tensor is thought to lie along the Pt-P bond in these complexes. Some of the complexes exhibit interesting MAS-frequency-dependent (31)P NMR spectra.

Journal Article↗

PubMed2000

Antihypertensive treatment and the J-curve.

Unlike the brain, oxygen extraction for the heart is almost maximal at rest, so lowering coronary filling pressure (DBP) below the lower limit of autoregulation with antihypertensive drugs can lead to myocardial ischemia. This situation is exacerbated by the presence of coronary stenosis, which if more than 85% means that coronary flow reserve is virtually zero (particularly in the presence of LVH). Such patients experience a fall in coronary flow and ischemia when DBP is acutely lowered to less than the mid-80s. Ischemic episodes on the 24-hour Holter monitor in treated hypertensives are often immediately preceded by a hypotensive episode. The "J-curve" debate has been going for over 20 years. Those that deny a J-curve relationship between treated DBP and myocardial infarction (MI) quote the continuous DBP/MI relationship seen in the large cohort of MRFIT screenees (with ischemic patients weeded out). However, the actual MRFIT (and similar HDFP) study patients with abnormal ECGs (ischemia or LVH), in contrast to those with normal ECGs, in the special-care group experienced an excess of coronary events associated with a DBP 5 mmHg lower than the referred-care group. Other studies, including the prospective HOT study, have indicated that ischemic hypertensives gain optimal results when DBP is lowered to the mid- to low 80s; below this level, the frequency of MI increases. This treatment-induced J-curve should not be confused with Nature's untreated J-curve, which results from the association of a low DBP (wide pulse-pressure) due to aging, noncompliant arteries, and an increasing frequency of ischemic events. A reasonable conclusion from most treatment studies (including HOT) is that in nonischemic hypertensives there is little point in lowering DBP below the mid- to low 80s in terms of MI prevention--though it is safe to do so. In contrast, ischemic hypertensives should not have their DBP lowered to less than the mid- to low 80s for fear of increasing the risk of MI.

Antihypertensive Agents↗

PubMed1998

A study of losartan, alone or with hydrochlorothiazide vs nifedipine GITS in elderly patients with diastolic hypertension.

We conducted a randomised, double-blind, parallel design study comparing the efficacy and tolerability of the angiotensin II receptor antagonist, losartan, alone or with low-dose hydrochlorothiazide (HCTZ) to the dihydropyridine calcium channel blocker, nifedipine GITS (gastro-intestinal therapeutic system), in elderly patients (> or =65 years old) with a diastolic blood pressure (DBP) between 95 and 115 mm Hg. After a placebo wash out period, 140 patients were randomly assigned to receive either losartan 50 mg or nifedipine GITS 30 mg. Patients were evaluated at 4-week intervals during a 12-week treatment period. Patients receiving losartan had HCTZ 12.5 mg added and increased to 25 mg to reduce DBP <90 mm Hg. Patients receiving nifedipine GITS had their dose increased to 60 mg and 90 mg to reduce DBP <90 mm Hg. Efficacy, tolerability and quality of life were assessed during the 12 weeks on each regimen. Patients treated with the losartan regimen (n = 73) had reductions in trough sitting DBP of -10, -13, and -13 mm Hg after 4, 8, and 12 weeks of therapy, respectively. Patients receiving the nifedipine GITS regimen (n = 67) had DBP reductions of -14, -15, and -15 mm Hg, respectively. There were no significant differences in the DBP response between the treatment groups except at week 4 (P < 0.05). Similar reductions in systolic BP (SBP) between the two treatment groups were observed at all time points. The percentages of patients in the two treatment groups reaching goal DBP (<90 mm Hg or DBP > or =90 mm Hg with a reduction from a baseline of > or =10 mm Hg) were comparable (81% on the losartan regimen and 90% on the nifedipine GITS regimen). There were significantly more adverse events reported in patients receiving nifedipine GITS when compared to the losartan regimen (54% vs 36%, P < 0.05). A patient-reported symptom inventory also showed that swollen ankles was bothersome in significantly more patients treated with the nifedipine GITS regimen when compared to the losartan regimen (24% vs 5%, P = 0.001). Thus, in elderly patients with diastolic hypertension, a regimen of losartan alone or with HCTZ has similar efficacy to a regimen of nifedipine GITS with greater tolerability and less symptom bother due to swollen ankles.

Aged↗

PubMed1999

Relation of ambulatory blood pressure load with left ventricular geometry in untreated patients with mild-to-moderate hypertension.

Whether ambulatory blood pressure (ABP) load is associated with left ventricular (LV) geometry was assessed in 335 patients (range 32-72 years) with stage I-II essential hypertension by performing 24-h ABP monitoring and echocardiographic examination. Of these 335 hypertensive subjects, 116 (34.5%) had normal LV geometry, 136 (40.5%) had concentric LV remodelling, 37 (11%) had eccentric LV hypertrophy and 46 (14%) had concentric LV hypertrophy according to the relative wall thickness and left ventricular mass index. Subjects with concentric LV hypertrophy had significantly increased 24-h systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure as well as increased 24-h SBP and DBP load compared to those with normal LV geometry or concentric LV remodelling while there was no difference in the above parameters in comparison with the subjects with eccentric LV hypertrophy. The incidence of patients with normal LV geometry was significantly decreasing and the incidence of patients with LV-CH was significantly increasing as the degree of ABP loads were increasing. Using multiple regression analysis models with each type of LV geometry as a dependent variable and various degree of ABP loads as independent variables, it was revealed that normal LV geometry was significantly related with normal values of 24-h SBP and DBP load (P < 0.05) while there was not any significant relation between concentric LV remodelling and 24-h SBP or DBP load values. Concentric LV hypertrophy was significantly related with increased values of both 24-h SBP and DBP load (P < 0.05) while eccentric LV hypertrophy was significantly related with increased values of 24-h DBP load only (P < 0.05). In conclusion normal LV geometry is associated with normal values of SBP and DBP load while concentric LV hypertrophy is associated with increased values of both SBP and DBP load.

Adult↗

PubMed1991

Uptake and degradation of filamentous actin and vitamin D-binding protein in the rat.

Tissue uptake and degradation of 125I-tyramine-cellobiose-labelled filamentous actin, vitamin D-binding protein (DBP) and actin-DBP complex were studied in the rat. Actin and actin-DBP complex were cleared from plasma at a faster rate than was DBP. About 40% of injected actin was recovered in the liver between 10 and 30 min after administration. Of the total radioactivity recovered in the liver, about 35% and 40% was detected in parenchymal and endothelial cells respectively when labelled actin or DBP-actin complex was injected intravenously. When labelled DBP alone was injected, approx. 55% of the radioactivity recovered in liver was in the Kupffer cells. These results suggest that actin is targeting the DBP-actin complex to the endothelial and parenchymal liver cells. Filamentous actin was also taken up in large amounts and at a rapid rate in parenchymal as well as non-parenchymal liver cells in vitro. Our data indicate that the rat has a mechanism to clear actin and the DBP-actin complex from plasma and that both parenchymal and non-parenchymal liver cells are involved in this process.

Actins↗

PubMed2000

Effect of socioeconomic status on the blood pressure in children living in a developing country.

BACKGROUND: Lower socioeconomic status has been reported to favor higher blood pressure both during childhood and adulthood, because obesity is more prevalent among this population. The aim of the present study was to evaluate the effect of socioeconomic status on blood pressure and prevalence of obesity among children living in a developing country. METHODS: Prepubertal primary school children (total number 1024, male/female ratio 513/511, mean age 10.32 +/- 0.60 years) living in Izmir, a metropolis of Turkey, were enrolled in the present study. The children were classified into three groups according to the locations of their schools as those from the well-developed (WD; n = 290), moderately developed (MD, n = 356) and underdeveloped (UD, n = 378) areas. Body mass index (BMI), ratio of BMI to the 50th percentile value of BMI for that age (BMI%) and systolic (SBP) and diastolic blood pressures (DBP) were determined in all children. Each socioeconomic group was subdivided into three subgroups with respect to BMI% as those with less than 90% (SG(< 90)), 90-110% (SG(90-110)), and more than 110% (SG(> 110)). Then, mean SBP and DBP in each subgroup of the WD, MD and UD groups were compared with the corresponding blood pressure values of each other to evaluate the effect of socioeconomic status on the blood pressure. In addition, the SBP and DBP of each subgroup were compared with other subgroups within that group to evaluate the effect of BMI on blood pressure. RESULTS: The BMI and BMI% of the UD group were significantly lower than that of the WD and MD groups (P < 0.05). In addition, the number of children with a BMI of more than 95% for their age was significantly lower in the UD group compared with the WD and MD groups (1.7, 1.9 and 0.5% in the WD, MD and UD groups, respectively, P < 0.05). The SBP and DBP were positively correlated with BMI% in each group and in all of the subjects cumulatively (r = 0.26, P < 0.001 for SBP and r = 0.34, P < 0.001 for DBP). The SBP and DBP were significantly higher in SG(> 110) than in SG(90-110) and were also higher in SG(90-110) than in SG(< 90) in each group. Mean DBP values in all subgroups of the MD and UD groups were significantly lower than the respective subgroups of the WD group. The SBP of SG(< 90) and SG(90-110) of the UD group were significantly lower than those of the corresponding subgroups of the WD and MD groups. CONCLUSION: Obesity is not more prevalent among the children of lower socioeconomic classes in Turkey as a developing country. In addition, independent of anthropometric structure, DBP and SBP were shown to be related to the socioeconomic status in childhood age groups and both values were determined to decrease in accordance with a decrease in the socioeconomic level.

Child↗