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PubMed2005

Systolic and diastolic blood pressure lowering as determinants of cardiovascular outcome.

Based on individual patient data, we performed a quantitative overview of trials in hypertension to investigate to what extent lowering of systolic blood pressure (SBP) and diastolic blood pressure (DBP) contributed to cardiovascular prevention. We selected trials that tested active antihypertensive drugs against placebo or no treatment. Our analyses included 12,903 young (30 to 49 years of age) patients randomized in 3 trials and 14,324 old (60 to 79 years of age) and 1209 very old (> or =80 years of age) patients enrolled in 8 trials. Antihypertensive treatment reduced SBP/DBP by 8.3/4.6 mm Hg in young patients, by 10.7/4.2 mm Hg in old patients, and by 9.4/3.2 mm Hg in very old patients, respectively, resulting in ratios of DBP to SBP lowering of 0.55, 0.39, and 0.32, respectively (P=0.004 for trend with age). In spite of the differential lowering of SBP and DBP, antihypertensive treatment reduced the risk of all cardiovascular events, stroke and myocardial infarction in the 3 age strata to a similar extent. Absolute benefit increased with age and with lower ratio of DBP to SBP lowering. Furthermore, in patients with a larger-than-median reduction in SBP, active treatment consistently reduced the risk of all outcomes irrespective of the decrease in DBP or the achieved DBP. These findings remained consistent if the achieved DBP averaged <70 mm Hg. In conclusion, our overview suggests that antihypertensive drug treatment improves outcome mainly through lowering of SBP.

Antihypertensive Agents↗
PubMed2005

The significance of various blood pressure indices for long-term stroke, coronary heart disease, and all-cause mortality in men: the Israeli Ischemic Heart Disease study.

BACKGROUND AND PURPOSE: Studies of blood pressure (BP) indices as disease predictors have offered conflicting conclusions. We compare pulse pressure (PP), systolic BP (SBP) and diastolic BP (DBP), and mean arterial pressure (MAP) as risk markers for long-term mortality with emphasis on stroke. METHODS: Male civil servants (40 to 65 years of age; n=9611) were examined in 1963 and followed up until 1986. Multivariate analysis was used to assess the association between BP indices and subsequent mortality. Stroke mortality was analyzed separately for initially normotensive (SBP< or =140 and DBP< or =90 mm Hg), hypertensive (SBP>140 and DBP>90 mm Hg), and men with isolated systolic hypertension (ISH; SBP>140 and DBP< or =90 mm Hg). RESULTS: During follow-up, 3167 men died, including 932 of coronary heart disease and 339 of stroke. All 4 BP indices were predictive of fatal stroke among hypertensive and normotensive men (hazard ratios [HRs] fluctuated between 1.59 and 2.51). In models with 2 BP indices among normotensive men, SBP but not DBP remained a predictor of stroke mortality. MAP and PP were independent predictors of stroke mortality. Among hypertensive men, SBP and DBP were independent predictors of stroke mortality (HRs, 1.68 and 1.51, respectively). MAP but not PP remained a predictor of stroke mortality. In men with ISH, the 4 BP indices predicted fatal stroke, with HRs fluctuating between 1.24 and 2.04. CONCLUSIONS: All 4 BP indices were predictors of stroke mortality among hypertensive and normotensive men, with DBP possibly the weaker predictor among the latter. Models with 2 BP indices yielded complex associations.

Adult↗
PubMed2005

Expression of insulin-like factor 3 protein in the rat testis during fetal and postnatal development and in relation to cryptorchidism induced by in utero exposure to di (n-Butyl) phthalate.

Cryptorchidism is a common reproductive abnormality, possibly resulting from abnormal hormone production/action by the fetal testis. Insulin-like factor 3 (Insl3) is thought to be involved in gubernaculum development and transabdominal testicular descent, but its importance is unclear, due partly to lack of suitable Insl3 antibodies. We generated (by genetic immunization) and validated a novel antirat Insl3 antibody, which we used to characterize immunoexpression of Insl3 in rat Leydig cells (LCs) from fetal life until adulthood and its relationship to cryptorchidism. Immunoexpression was strong on embryonic day (E) 17.5 and E19.5 and from 35 d of age onward but weak from E21.5 until puberty. Because in utero exposure to di (n-butyl) phthalate (DBP) induces cryptorchidism and suppresses Insl3 gene expression, we investigated Insl3 protein expression in fetal and adult rats exposed to 500 mg/kg.d DBP from E13.5 to E21.5. Expression on E17.5 and E19.5 decreased dramatically after DBP exposure, but there was no consistent correlation between this suppression and abnormal testis position. We also compared expression of Insl3 and P450 side-chain cleavage enzyme in fetal testes from rats exposed in utero to DBP or flutamide (50 mg/kg.d). DBP treatment suppressed expression of both P450 side-chain cleavage enzyme and Insl3 at E19.5, but flutamide exposure had no effect on either protein, demonstrating that Insl3 expression in fetal rat LCs is not androgen regulated. In adult rats, Insl3 expression was suppressed in 80% of cryptorchid and 50% of scrotal testes from rats exposed to DBP, suggesting that prenatal DBP exposure also leads to maldevelopment/malfunction of the adult LC population in some animals.

Animals↗
PubMed1986

Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein.

We measured the free fraction of 25-hydroxyvitamin D (25OHD) in human serum and determined that 25OHD bound to a component with an affinity constant of 7 X 10(8) M-1 and a concentration of 4.5 X 10(-6) M. This concentration was equal to that of the vitamin D-binding protein (DBP) in the same serum sample. We removed DBP from the serum using actin affinity columns and found that the affinity for 25OHD of the remaining serum components was equivalent to that of human serum albumin (6 X 10(5) M-1). We then measured the free fractions of 25OHD, DBP, and albumin in normal and cirrhotic subjects. We calculated that 88 +/- 3% (+/- SD) and 83 +/- 8% of the 25OHD were bound to DBP in the serum of normal and cirrhotic subjects, respectively. We compared previously reported data for the free fraction and the free concentration of 1,25-dihydroxyvitamin D in these subjects with the current data for the free fraction and free concentration of 25OHD. The total concentrations and free fractions of both metabolites correlated to each other and to the DBP and albumin concentrations in these subjects, but the free concentrations of these metabolites did not. We conclude that 25OHD, like 1,25-dihydroxyvitamin D, is transported in blood bound primarily to DBP and albumin. Changes in the concentrations of DBP and albumin affected the total and free fractions of 25OHD in serum, but the actual free concentration of 25OHD was independent of such changes.

Adult↗
PubMed1997

Reproductive toxicity of di-n-butylphthalate in a continuous breeding protocol in Sprague-Dawley rats.

The phthalate ester di-n-butylphthalate (DBP) is used extensively in the manufacture of plastics; its reproductive toxicity was tested in rats by the National Toxicology Program's Reproductive Assessment by Continuous Breeding protocol. Levels of 0.1, 0.5, and 1.0% DBP in the diet were selected, and this dosing design yielded average daily DBP intakes of 52, 256, and 509 mg/kg for males and 80, 385, and 794 mg/kg for females, respectively. DBP consumption by F0 rats reduced the total number of live pups per litter in all treated groups by 8-17% and live pup weights in the 0.5% and 1.0% dose groups by < 13%. In tests to determine the affected sex, the number of offspring was unchanged, but the weights of pups from treated females were significantly decreased and offspring from treated males were unchanged. At necropsy, high-dose F0 females had a 14% reduction in body weight, and both sexes had approximately 10-15% increased kidney and liver to body weight ratios compared to controls. Sperm parameters and estrous cyclicity were not affected. In the F1 mating trial, indices of mating, pregnancy, and fertility in the 1.0% dose group were all sharply decreased (one live litter was delivered out of 20 cohabited pairs), concomitant with a 13% decrease in dam body weight. Live F2 pup weights were 6-8% lower in all dose groups. F1 necropsy results revealed that epididymal sperm counts and testicular spermatid head counts were significantly decreased in the 1.0% dose group. Histopathologic investigation showed that 8 of 10 F1 males consuming 1.0% DBP had degenerated seminiferous tubules and 5 of 10 had underdeveloped or otherwise defective epididymides. No ovarian or uterine lesions were observed. In conclusion, this study showed that DBP is a reproductive/developmental toxicant in Sprague-Dawley rats exposed both as adults and during development; it also indicates that the adverse reproductive/developmental effects of DBP on the second generation were greater than on the first generation.

Abnormalities, Drug-Induced↗
PubMed2004

The effects of GH and hormone replacement therapy on serum concentrations of mannan-binding lectin, surfactant protein D and vitamin D binding protein in Turner syndrome.

OBJECTIVE: Studies in animals and humans indicate that growth hormone (GH) and insulin-like growth factor-I (IGF-I) modulate immune function. Recently, it was reported that GH therapy increased the level of mannan-binding lectin (MBL) in normal patients, and that treatment of acromegalics with pegvisomant decreased the levels of MBL. The effect on MBL was thought to be due to a specific action of GH, since IGF-I treatment did not affect MBL. Whether it is advantageous or not to have high or low levels of MBL is not known. Likewise, it is not clear how the modifications induced by GH affect immune function. In the present study we examined whether GH or hormone replacement therapy (HRT) in Turner syndrome (TS) influence the serum concentrations of MBL and two other proteins partaking in the innate immune defence, surfactant protein D (SP-D) and vitamin D binding protein (DBP). DESIGN: Study 1: a double-blind crossover study of 12 healthy TS adolescents examined during treatment with either placebo or GH for 2 months, and compared with a control group. Study 2: triple-blind crossover study of 9 healthy TS adolescents randomized to treatment with placebo, GH or GH+17beta-estradiol. Study 3: 60 adult TS patients (55 received HRT) compared with 59 age-matched controls. Study 4: 27 patients with TS were examined before and during sex hormone replacement with 17beta-estradiol and norethisterone and compared with age-matched controls (n=24). METHODS: Measurement of MBL, SP-D, DBP, and other inflammation markers. RESULTS: Study 1: the levels of MBL (P=0.002) and SP-D (P=0.012) increased during GH treatment, whereas no changes were observed in comparison with controls. DBP was unchanged by GH, but was significantly higher in TS compared with controls (P=0.017). Study 2: treatment with GH increased MBL (P=0.045) and SP-D (P=0.05) concentrations in TS, while treatment with GH+17beta-estradiol did not increase levels further. DBP was unchanged by treatment. Study 3: levels of MBL, SP-D, and DBP were similar in adult TS and control subjects. Study 4: DBP levels decreased in response to HRT, while MBL and SPD levels were unchanged. Levels of all three plasma proteins were similar to controls. CONCLUSION: We show that treatment with GH significantly increases MBL and SP-D concentrations in TS, while HRT marginally decreases DBP. Whether the present findings, suggesting a link between the endocrine and the immune system, have clinical consequences needs to be studied further.

Adolescent↗
PubMed1999

A multidisciplinary approach to the healing of cranial and residual maxillary cleft defects by means of allogenous demineralized osseous implants and polylactic acid casts in dogs.

OBJECTIVE: The aim of this study was to evaluate the healing of artificially induced bony defects in dogs by means of demineralized allogenous bone powder (DBP) implants covered with polyhydroxy lactic acid (PLA) casts compared with DBP implants without the casts. DESIGN: Prospective animal study. SETTING: Research university. SAMPLE: Following a pilot study in which two dogs were used, four mongrel dogs between the ages of 18 and 24 months and weighing approximately 20 kg were used as subjects. INTERVENTIONS: Each experimental animal had bilateral maxillary alveolar clefts created. In a later procedure, each defect was repaired with a DBP implant, half of which were covered with a PLA96 matrix. Each animal also had a circular defect created in each parietal bone that was immediately covered with DBP implants, half of which were similarly covered with a PLA96 disk. MAIN OUTCOME MEASURE: Repeated technetium-99m methylene-diphosphate (99mTC MDP) uptake measurements were performed to evaluate bone metabolism during the healing period, while at relevant intervals, radiographs were taken of the healing alveolar cleft defects to register bone repair. After 1 year, the animals were euthanized for macroscopic and histologic evaluation. RESULTS: Histologically, the grafts covered with PLA96 were at a more advanced stage of healing than those without, and the cranial defects similarly were more advanced in the healing process than the alveolar defects. Uptake of 99mTC MDP into the cranial implants was at its maximal level after 1 week and then gradually decreased until, after 7 weeks, it was not significantly different from zero. Cranial defects covered with a PLA95-enhanced implant showed a mean maximum count rate of 275, while the plain DBP side showed a mean maximal count rate of 150. Alveolar defects with the plain DBP implant showed a maximum count rate in the first week; those with the PLA95 enhanced implant showed maximum uptake during the second week. On both sides, there was a gradual decrease to the base value in the seventh week. The mean maximum count on the PLA96-enhanced side was 285, while on the plain DBP side, the corresponding value was 320. CONCLUSION: Although an advantage of the combination was established for parietal cranial defects, no advantage was seen for alveolar cleft defects in this experimental setup.

Alveoloplasty↗
PubMed1987

Evidence for an interaction of insulin and sex steroids in the regulation of vitamin D metabolism in the rat.

Vitamin D metabolites and vitamin D-binding protein (DBP) were measured in non-diabetic rats and in rats made diabetic with streptozotocin. The animals were studied in the intact state, after gonadectomy and during pregnancy. In male non-diabetic rats the serum concentrations of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and DBP decreased after orchidectomy and were restored by treatment with testosterone. In female non-diabetic rats, these parameters increased after ovariectomy. Increased 1,25-(OH)2D3 and decreased DBP concentrations were found during pregnancy in non-diabetic rats. After the induction of diabetes in intact rats of both sexes, the concentration of DBP decreased, but a significant decrease in the concentration of 1,25-(OH)2D3 was found in male animals only. After ovariectomy, however, 1,25-(OH)2D3 decreased also in female diabetic rats. Both orchidectomy and insulin deficiency depressed serum concentrations of 1,25-(OH)2D3 (-22 and -45% respectively) and DBP (-14 and -29% respectively), but the effects of insulin deficiency were greater than those of androgen withdrawal. Moreover, the testosterone concentration was twofold lower in intact male diabetic rats than in non-diabetic animals. Insulin, but not testosterone treatment, however, restored DBP and 1,25-(OH)2D3 concentrations in diabetic rats, and insulin was effective in intact as well as in gonadectomized animals. This study shows that insulin deficiency decreases the concentrations of DBP and 1,25-(OH)2D3 in the rat, and that these decreases are facilitated by androgens, but counteracted by oestrogens.

Animals↗
PubMedDate not supplied

Dose-related efficacy of irbesartan in patients, with mild-to-moderate essential hypertension.

OBJECTIVE: A prospective open multicentre study was conducted in patients with mild-to-moderate hypertension to compare the efficacy on diastolic blood pressure (DBP) and tolerance of treatment with either irbesartan 150mg od (once daily) or irbesartan 300mg od in patients who were defined as non-normalised responders with irbesartan 150mg od. METHODS AND RESULTS: A total of 14 820 hypertensive patients were included in the study. After 6 weeks with irbesartan 150mg od, in terms of their response to treatment, 8861 (61.9%) were normalised (DBP <90mm Hg), 1963 (13.7%) non-normalised responders (DBP > or = 90mm Hg with a decrease in DBP > or = 10mm Hg) and 3154 (22%) non-normalised non-responders (DBP > or = 90mm Hg with a decrease in DBP <10mm Hg); 842 patients did not respect the protocol and could not be evaluated. The 1963 non-normalised responders were randomly assigned at week 6 to either irbesartan 150mg od (n = 963) or irbesartan 300mg od (n = 1000) for 5 weeks. A greater reduction in mean DBP was found in the group treated with irbesartan 300mg (p < 0.001). There were no significant differences in terms of number or severity of adverse events between the two groups of patients.

Antihypertensive Agents↗
PubMed1997

Exercise blood pressure changes between seasons.

BACKGROUND: Blood pressure (casual and daytime) is higher in winter than it is in summer, and this factor might be partly responsible for the higher cardiovascular mortality in winter. OBJECTIVE: To determine in a prospective study whether there is also a seasonal variation in exercise blood pressure. METHODS: We evaluated the pretest, exercise (five-step treadmill test) and recovery values of systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate of 94 healthy men, aged 20-65 years, during the summer and winter. RESULTS: SBP and DBP values were higher in winter than they were in summer during the resting period immediately before exercise (P = 0.003 and P = 0.07, respectively), and during recovery (both P < 0.0001). Exercise SBP and heart rate values were similar in the two seasons, although exercise DBP was higher in winter than it was in summer (P < 0.0001). The increase in DBP from pretest to stage 3 was 6.5 mmHg in summer and 10.4 mmHg in winter (P = 0.002). After we had controlled for possible confounders, the increase in DBP during exercise was found to be independently associated with season of the year and resting DBP. CONCLUSIONS: Exercise DBP varies according to season whereas exercise SBP does not. Our results suggest that, since measures of the response of blood pressure to exercise testing are frequently used in blood pressure and hypertension research as well as in clinical practice, the seasonal influences should be taken into account.

Journal Article↗
PubMed1999

A new model of risk: implications of increasing pulse pressure and systolic blood pressure on cardiovascular disease.

Diastolic blood pressure (DBP) has historically functioned as the primary indicator of cardiovascular disease (CVD). Many clinical and observational, long-term, large population studies, including the Framingham Heart Study and Multiple Risk Factor Intervention Trial (MRFIT), have repeatedly demonstrated a positive correlation between CVD events and DBP. However, unexplained results, often emerged from the data, in the form of a DBP threshold (where lower rates of DBP were not associated with lower disease rates) and a J-shaped relationship (a decline of DBP that correlated with an increased risk of CVD), have complicated the association of blood pressure to events. In the past decade studies have focused on other indicators to explain these irregularities. From these clinical and observational studies, new evidence has become available which strongly indicates that systolic blood pressure (SBP) and pulse pressure (PP) may be more reliable predictors of CVD events than DBP. Indeed, in several studies, a wide baseline PP has been identified as the only measure of blood pressure that is an independent risk factor for cardiac events. Moreover, pretreatment SBP has linearly predicted future CVD events in treated patients, while DBP has not. These studies of treated patients have also led to the identification of pretreatment risk factors that can be applied to stratify risk among patients who go on to have controlled blood pressure on treatment. This new information can more precisely identify patients at increased risk of CVD events and thus make it possible to more precisely tailor therapy to enhance the potential for CVD prevention.

Blood Pressure↗
PubMedDate not supplied

Blood pressure in pediatric years (8-13 years old) in the Oporto region.

The early detection and treatment of primary and secondary hypertension in children may contribute to the improvement of health later in life. During childhood, the occurrence of arterial hypertension should be understood as a risk situation, even if the clinical signs of the disease are not obvious. Comparatively to other populations, only few epidemiological studies exist in Portugal to be used as clinical references. Thus, the aim of this work was to study the distribution curves of 30, 60 and 90 percentiles of systolic blood pressure (SBP) and diastolic blood pressure (DBP), related to age, height, and weight. To define the "cut off points" of hypertension in our population, we estimated the 95 percentile of SBP and DBP. This is a cross-sectional study. The sample consisted of 474 children (242 boys and 232 girls), aged 8 to 13 years old, randomly selected in 30 different schools of the Oporto region. Weight, height and body mass index were evaluated as anthropometric reference values and blood pressures, SBP and DBP, were measured at rest. The results revealed a gradual increase in blood pressure values with age, height and weight. We found significant correlations (p < or = 0.05; p < or = 0.01) between SBP and DBP to the variables height, weight and blood mass index in both sexes. Multiple regression analysis showed that weight and age explain significantly (p < or = 0.01) the variation of SBP in both sexes. Related to DBP, in males and females, only age accounted significantly for the amount of variance. In conclusion, the present study pointed out the need to associate the SBP and DBP values to the age, weight and height of the subjects, mainly in boys. This work stresses the need for SBP and DBP percentile tables related to age, to weight and to height, for the Portuguese population, particularly for pediatric ages.

Adolescent↗
PubMed2000

Blood pressure, body mass index, heart rate and levels of blood cholesterol and glucose of volunteers during National Heart Weeks, 1995-1997.

The paper presents the results of a health screening programme conducted in 10 major centers in Malaysia--Kuala Lumpur, Penang, Ipoh, Johor Bahru, Alor Star, Kuala Terengganu, Malacca, Kota Bahru, Kuching and Kota Kinabalu during the National Heart Weeks, 1995-1997. There were 6,858 participants of both sexes aged between 6 years to 81 years old. The parameters involved in the screening programme were body mass index, blood pressure, heart rate, cholesterol and glucose. The following are the results of the study:- 1. The mean and standard deviation for the body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), total cholesterol (TC) and non fasting (random) blood glucose (GL) of the volunteers studied were 24.3 +/- 4.0 kg/m2, 128.3 +/- 21.1 mmHg, 79.6 +/- 11.9 mmHg, 77.2 +/- 12.1 bpm, 5.33 +/- 1.37 mmol/l and 5.11 +/- 1.97 mmol/l respectively. 2. There was a rising trend for BMI, SBP, DBP, TC and GL with age. The HR was higher in the younger age group of those below 20 years. Males tended to have higher mean values than females except for HR which was similar in both sexes. 3. The Malays, Chinese and Indians seemed to have closely similar mean values for SBP, DBP and HR but the Indians possessed the highest BMI (25.62 +/- 3.90 kg/m2), TC (5.61 +/- 1.48 mmol/l) and GL (5.41 +/- 2.43 mmol/l) among the three major ethnic groups. While the Ibans had highest TC (6.07 + 1.09 mmol/l), their GL level was the lowest (4.76 +/- 1.15 mmol/l). The Kadazans had the lowest TC level (4.94 +/- 1.39 mmol/l) among all the ethnic groups. 4. Among the participants screened, 31.9% were overweight (BMI > or = 25), 7.6% were obese (BMI > or = 30); 26.8% had raised SBP (> or = 140 mmHg) and 19.3% had raised DBP (> or = 90 mmHg); 13.6% of the participants had increased HR (> or = 90 bpm), 22% had raised TC (> or = 6.20 mmol/l) and 2% had raised GL (> or = 11.00 mmol/l). There was a higher prevalence for abnormal values with increasing age until between the ages of 60 or 70 years, when the values began to fall. 5. Age was positively correlated with SBP (r = 0.41***, df = 4351), DBP (r = 0.27***, df = 4351), TC (r = 0.22***, df = 3303) and GL (r = 0.16***, df = 2442) but negatively correlated with HR (r = -0.13***, df = 4351). The BMI was positively correlated with SBP (r = 0.29***, df = 2769), DBP (r = 0.31***, df = 2769), TC (r = 0.16***, df = 2137) and GL (r = 0.11**, df = 1637) but there was no correlation with HR (r = 0.03NS, df = 2771). The SBP and DBP were highly correlated with each other (r = 0.75***, df = 4351) and they also showed highly significant positive correlation (r = 0.08***-0.13***, df = 2441-3301) with TC and GL. TC was positively correlated with GL (r = 0.05* df = 2319) but only at the 5% probability level.

Adolescent↗
PubMed2001

Effects of di(2-ethylhexyl) phthalate and dibutyl phthalate on the collembolan Folsomia fimetaria.

Lethal and sublethal effects of di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) on adult individuals of the collembolan Folsomia fimetaria were investigated in the laboratory by the use of small microcosms. Effects of DEHP and DBP were also tested on newly hatched collembolans in a multidish system. The endpoints were juvenile mortality, growth, and development. When exposed to DEHP, adults and juveniles were unaffected at all test concentrations, that is, up to 5,000 mg/kg. However, DBP caused increased adult mortality at 250 mg/kg and juvenile mortality at 25 mg/kg. For DBP, adult reproduction was a more sensitive endpoint than was survival, with an EC10 and EC50 of 14 and 68 mg/kg, respectively. Juvenile molting frequency seems to be a sensitive parameter, because number of cuticles produced by young springtails was reduced at 1 mg/kg. Toxicity was reduced when soil spiked with DBP was stored at 20 degrees C for a period of up to 28 d before adding the animals. Reduction in toxicity of DBP may be due a combination of degradation, evaporation, and adsorption of DBP to soil material. This was confirmed by chemical analyses, which showed a rapid initial disappearance followed by a much slower disappearance. Our results lead to the overall conclusion that significant adverse effects of phthalates on collembolans are not likely to occur as a result of normal sewage sludge application.

Animals↗
PubMed2001

In vivo and in vitro percutaneous absorption of [(14)C]di-N-butylphthalate in rat.

This study evaluated the toxicokinetics of [(14)C]di-n-butylphthalate ([(14)C]DBP) after an intravenous administration (1 and 10 mg/kg, in Cremophor) or a topical application (10 microl/cm(2); 10 cm(2), neat) in haired male Sprague-Dawley rats. Additional in vivo and in vitro percutaneous penetration studies of [(14)C]DBP were conducted on male and female haired rats and male hairless rats. After intravenous administration, unchanged DBP disappeared rapidly from the plasma, following a two-exponential function (T1/2beta = 5-7 min). The peak levels of monobutylphthalate (MBP) and its glucuronide conjugate (MBP-Gluc) occurred 1 to 2 and 20 to 30 min after administration, respectively. These metabolites were intensively and rapidly excreted in urine (57% of the dose). However, about 35% of the dose recovered in urine was primarily excreted in bile (mainly as MBP-Gluc) and underwent hepatobiliary recycling. Unchanged DBP was barely detectable in excreta. DBP rapidly penetrated the skin, which constituted a reservoir. The absorption flux determined for 0.5 to 8 and 8 to 48 h of exposure were 43 and 156 microg/cm(2)/h, respectively. The higher flux may be due to radial diffusion of DBP in the stratum and/or epidermis. The in vivo and in vitro experiments revealed that DBP was intensively metabolized into the skin. In vivo percutaneous absorption flux was very similar in male and female haired rats. In contrast, the percutaneous absorption determined in vivo and in vitro was higher in hairless than in haired male rats. Absorption flux was accurately estimated from urinary excretion rate of MBP or MBP-Gluc.

Animals↗
PubMedDate not supplied

Comparative effects of candesartan cilexetil and losartan in patients with systemic hypertension. Candesartan Versus Losartan Efficacy Comparison (CANDLE) Study Group.

The antihypertensive efficacy and tolerability of the novel angiotensin-II (A-II) receptor blocker candesartan cilexetil and the prototype A-II receptor blocker, losartan, were compared in an 8-week, multicenter, double-blind, randomized, parallel-group, titration-to-effect study of 332 adults (42% women, 12% black) with systemic hypertension (sitting diastolic blood pressure [DBP] 95-114 mmHg, inclusive). In patients with a mean trough (24 +/- 3 hours after dose) sitting DBP of 90 mmHg or higher after 4 weeks of once daily administration of candesartan 16 mg or losartan 50 mg, dose was titrated up to candesartan 32 mg or losartan 100 mg once daily. The candesartan regimen was significantly more effective than the losartan regimen in reducing trough sitting DBP at week 8 (11.0 mmHg versus 8.9 mmHg). Candesartan also produced numerically greater reductions in secondary blood pressure parameters, including sitting systolic blood pressure (SBP), trough standing DBP and SBP, and peak (6 +/- 2.5 hours after dose) sitting and standing DBP and SBP. Responder rates (sitting DBP < 90 mmHg or reduction in blood pressure of > or = 10 mmHg) and control rates (sitting DBP <90 mmHg) were higher with candesartan (64% versus 54% and 54% versus 43%, respectively). A total of 1.9% of the patients taking candesartan and 6.5% of those taking losartan discontinued prematurely because of adverse events or lack of efficacy.

Analysis of Variance↗
PubMed2002

Comparison of indapamide and low-dose hydrochlorothiazide monotherapy in black patients with mild to moderate hypertension.

OBJECTIVES: To assess, using ambulatory blood pressure monitoring (ABPM), the antihypertensive efficacy of hydrochlorothiazide 12.5 mg and indapamide 2.5 mg given as a monotherapy over 3 months to black patients with mild to moderate essential hypertension. DESIGN: Single-centre, prospective, randomised open pilot study in three phases: (i) 1-week drug-free washout period; (ii) 2-week placebo run-in phase; and (iii) 3-month prospective open-label active treatment period. RESULTS: Forty-two black patients with mean daytime diastolic BP (DBP) > or = 90 mmHg and < or = 115 mmHg (mean age 57 +/- 11 years, 28 women/14 men) were enrolled into the study. Overall, a profound and sustained BP reduction was achieved with indapamide at 3 months (N = 20). The 24-hour BP decreased from 150 +/- 17/94 +/- 6 mmHg to 130 +/- 19/82 +/- 9 mmHg (P < 0.0001 for systolic BP (SBP) and DBP at 3 months versus baseline); the mean daytime BP decreased from 155 +/- 15/98 +/- 6 mmHg to 134 +/- 18/87 +/- 10 mmHg (P < 0.0001 for SBP and DBP at 3 months versus baseline). The overall control (mean daytime DBP < 90 mmHg) and response (decrease in daytime DBP > or = 10 mmHg) rates achieved with indapamide were 10/20 (50%) and 13/20 (65%), respectively. In contrast, monotherapy with hydrochlorothiazide resulted in more modest BP reduction and control and response rates at 3 months (N = 22). The 24-hour BP decreased from 147 +/- 14/94 +/- 7 mmHg to 139 +/- 19/88 +/- 2 mmHg (P < 0.05 for DBP at 3 months versus baseline, P = NS for SBP); the mean daytime BP decreased from 151 +/- 14/98 +/- 5 mmHg to 144 +/- 16/93 +/- 10 mmHg (P < 0.05 for DBP at 3 months versus baseline, P = NS for SBP). The corresponding control and response rates were 7/22 (32%) and 8/22 (36%). Both hydrocholorothiazide and indapamide caused significant hypokalaemia. CONCLUSIONS: Monotherapy with indapamide is associated with greater BP reduction and control and response rates than monotherapy with low-dose hydrochlorothiazide and may be an appropriate choice of antihypertensive diuretic therapy in black South African patients with mild to moderate hypertension.

Adult↗
PubMed2003

Atheromatous risk factors among Thai labor forces by socioeconomic status.

The purpose of this study was to describe atheromatous risk factors among Thai labor forces by socioeconomic status (SES) such as income, education and occupation. Undesirable levels of artheromatous risk factors were specified as: total serum cholesterol (TC) > 200 mg per cent, body mass index (BMI) > 25 kg/m2, fasting blood sugar (FBS) > 126 mg/dL, systolic blood pressure (SBP) > 140 mmHg and diastolic blood pressure (DBP) > 90 mmHg. Data from the Second National Health Examination survey in Thailand from 1996 to 1997 was used, with a total number of 4,198 participants (1,634 males, 2,561 females) aged 13-60 years old. Results from multivariate analysis demonstrated differences in means TC, BMI, SBP and DBP among different age-groups, both in males and females (p < 0.001). TC, BMI, and SBP increased with age in both sexes, but DBP increased with age in females only. Males who lived in a municipality had a higher risk of having undesirable TC and DBP than those who did not. Risk of undesirable BMI varied according to levels of income in males. Males with an income of 5,001-10,000 and > 25,000 baht/month had OR = 1.57 (95% CI = 1.04-2.39) and OR = 2.59 (95% CI = 1.18-5.66) compared to males with an income of < 5,000 baht/month. TC and DBP varied with levels of income in females. For undesirable TC, females with an income of 5,001-10,000 and > 25,000 baht/month had OR = 1.48 (95% CI = 1.01-2.18) and OR = 2.17 (95% CI = 1.03-4.88) compared to females with an income of < 5,000 baht/month. For undesirable DBP, females with an income > 25,000 baht/month had OR = 3.39 (95% CI = 1.31-8.78) compared to females with income an < 5,000 baht/month. Among different levels of education in males, different risks of undesirable TC, BMI, SBP and DBP were not significant, except a borderline significance in TC among vocational graduates. The same phenomenon was observed among females, except that females only a primary education tended to have a higher risk of undesirable BMI (OR = 2.64, 95% CI = 1.39-5.02) compared to females with graduate studies. The level of occupation seemed not to affect the risk of unfavorable atheromatous risk factors among males. Nonetheless, females in the agricultural section seemed to have a lower risk of undesirable TC (OR = 0.38, 95% CI = 0.18-0.78) compared to the professional group. The results suggested the consideration of critical guidance of epidemiological studies in using SES as the control variable, or for selection of subjects or matching criteria. Specific preventive programs on atheromatous risk factors should be launched for some specific socio-demographic groups in order to prevent coronary heart diseases (CHD) in the future.

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