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PubMed2005

Relative change in diurnal mean ocular perfusion pressure: a risk factor for the diagnosis of primary open-angle glaucoma.

PURPOSE: To investigate diurnal change and pattern of variation in intraocular pressure (IOP) and systolic (SBP) and diastolic (DSP) blood pressures in a group with untreated primary open-angle glaucoma (uPOAG) and compare it with an age-matched, normal group. METHODS: IOP, SBP, and DBP were measured in 14 patients with uPOAG and in 14 normal subjects, every hour between 7 AM and 10 PM and the mean ocular perfusion pressure (MOPP) was calculated. Mixed-effect linear models were used to analyze the repeated-measures data in which both fixed and random effects were included. The relative diurnal change was calculated as the percentage decrease from maximum. RESULTS: The uPOAG group had the higher IOP (P < 0.001) and lower MOPP (P = 0.025). There was a significant diurnal change in IOP, SBP, DBP, and MOPP in both groups (P < 0.001). The pattern of diurnal variation in IOP (P = 0.137), SBP (P = 0.569), and DBP (P = 0.937) was not significantly different between groups but was significantly different for MOPP (P = 0.040). MOPP and IOP were most similar at 7 AM and 1 PM. Postprandial hypotension was significant for SBP, DBP, and MOPP (P < 0.001), but not IOP (P = 0.388) in both groups. The relative change in MOPP was larger in the uPOAG group (38% vs. 26%, P < 0.001), but the change in IOP was similar (42% vs. 41%, P = 0.786). There was a significant effect of DBP on IOP over the course of the day in the uPOAG group (P = 0.011) but not in the normal group (P = 0.733). CONCLUSIONS: The relative diurnal change in IOP was similar in both uPOAG and normal subjects but MOPP showed a significant difference. MOPP significantly decreased after lunch, and was at its lowest in uPOAG at 7 AM, when IOP was at its highest. A significant association was found between diurnal DBP and IOP in uPOAG.

Blood Pressure↗
PubMed1981

Influence of the vitamin D-binding protein on the serum concentration of 1,25-dihydroxyvitamin D3. Significance of the free 1,25-dihydroxyvitamin D3 concentration.

The influence of the serum binding protein (DBP) for vitamin D and its metabolites on the concentration of its main ligands, 25-hydroxyvitamin D(3) (25-OHD(3)) and 1,25-dihydroxyvitamin D(3) (1,25-[OH](2)D(3)) was studied. The concentration of both 1,25-(OH)(2)D(3) and DBP in normal female subjects (45+/-14 ng/liter and 333+/-58 mg/liter, mean+/-SD, respectively; n = 58) increased during the intake of estro-progestogens (69+/-27 ng/liter and 488+/-90 mg/liter, respectively; n = 29), whereas the 25-OHD(3) concentration remained unchanged. A positive correlation was found between the concentrations of 1,25-(OH)(2)D(3) and DBP in these women. At the end of pregnancy, the total concentrations of 1,25-(OH)(2)D(3) (97+/-26 ng/liter, n = 40) and DBP (616+/-84 mg/liter) are both significantly higher than in nonpregnant females and paired cord serum samples (48+/-11 ng/liter and 266+/-41 mg/liter, respectively). A marked seasonal variation of 25-OHD(3) was observed in pregnant females and their infants, whereas in the same samples the concentrations of both DBP and 1,25-(OH)(2)D(3) remained constant throughout the year. The free 1,25-(OH)(2)D(3) index, calculated as the molar ratio of this steroid and DBP, remains normal in women taking estro-progestogens, however, and this might explain their normal intestinal calcium absorption despite a high total 1,25-(OH)(2)D(3) concentration. In pregnancy the free 1,25-(OH)(2)D(3) index remains normal up to 35 wk of gestation, but during the last weeks of gestation, the free 1,25-(OH)(2)D(3) index increases in both circulations. A highly significant correlation exists between the (total and free) 25-OHD(3) and 1,25-(OH)(2)D(3) concentrations in maternal and cord serum both at 35 and 40 wk of gestation.

Adult↗
PubMed1994

A new preparation of nifedipine for sublingual application in hypertensive urgencies.

A new preparation of nifedipine for sublingual application in hypertensive urgencies was investigated in a prospective study. Patients admitted to the Emergency Department with a persistent elevation of systolic blood pressure (SBP) greater than 190 mmHg and/or a diastolic blood pressure (DBP) greater than 100 mmHg received nifedipine 10 mg sublingual with a sprayer. A second dose was administrated fifteen minutes later if an adequate response defined as a stable reduction of SBP below 180 mmHg and DBP below 100 mmHg had not occurred. Of 30 patients, 21 (70%) responded to the first nifedipine application, 7 responded to the second dose, and 2 nonresponders had to be treated with urapidil. Overall mean SBP was 206 +/- 19 mmHg and mean DBP was 113 +/- 15 mmHg before treatment, and a significant antihypertensive effect was noted within fifteen minutes after nifedipine spray (p < 0.05). The maximum antihypertensive effect was for SBP in sixty minutes (146 +/- 19 mmHg) and for DBP after one hundred twenty minutes (78 +/- 18 mmHg). The average reduction in SBP was 29% and in DBP 31%. In first-dose responders (n = 21) a significant antihypertensive effect was noted within fifteen minutes. SBP declined from 205 +/- 21 to a minimum of 142 +/- 15 mmHg (22.3%) after sixty minutes and DBP from 113 +/- 13 to a minimum of 77 +/- 11 mmHg (22.2%) after one hundred twenty minutes. In second-dose responders (n = 7) a significant antihypertensive effect was noted within thirty minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Sublingual↗
PubMed2005

Effect of three months' treatment with irbesartan on blood and pulse pressure of hypertensive type 2 diabetic patients: open, observational study in 31,793 patients.

OBJECTIVES: In hypertensive diabetics the cardiovascular risk is substantially increased. Therefore, an effective reduction of both blood pressure and pulse pressure is of particular importance for these patients. The aim of the prospective observational study in hypertensive type 2 diabetics was to assess the effect of a switch from the previous antihypertensive therapy to the angiotensin-II-receptor antagonist irbesartan (alone or in combination with HCTZ) on the reduction of blood pressure and pulse pressure, the reduction of diabetic nephropathy (microalbuminuria), and tolerability. METHODS: 8714 general practitioners included 31,793 type 2 diabetics aged at least 18 years in an open observational study. After inclusion in to the study the patients received irbesartan 300 mg as monotherapy or in combination with hydrochlorothiazide 12.5 mg (HCTZ). Main outcome measures for efficacy were the reduction of systolic (SBP) and diastolic (DBP) blood pressures, reduction of pulse pressure, and blood pressure responder (reduction in DBP > or = 10 mmHg or diastolic < 90 mmHg), diastolic normalization (DBP < 90 mmHg) and overall normalization rates (SBP < 140 mmHg and DBP < 90 mmHg) after 3 months. Further outcome measures included the reduction of microalbuminuria or proteinuria, and adverse events (AEs) as a measure of tolerability. RESULTS: Thirty-eight per cent of patients received irbesartan 300 mg and 61% irbesartan in combination with HCTZ. Mean systolic blood pressure was reduced by 22.5 mmHg, diastolic blood pressure by 10.7 mmHg (baseline values: 160.2 and 93.2 mmHg). Pulse pressure fell on average by 11.6 mmHg. 83.4% of the patients were responders, with an overall normalization rate of 42.7% (SBP < 140 mmHg and DBP < 90 mmHg), respectively 73.8% (DBP < 90 mmHg). The antihypertensive benefit was achieved irrespective of the previous medication. Mean albuminuria decreased by about 27.7 mg/L. Only 0.3% of patients experienced adverse events. CONCLUSIONS: In type 2 diabetics with hypertension and either uncontrolled or no previous antihypertensive therapy a change to treatment with irbesartan or irbesartan/HCTZ for 3 months resulted in a distinct reduction of systolic and diastolic blood pressures, with concomitant effective reductions of pulse pressure and microalbuminuria.

Adult↗
PubMed2004

Abnormal Leydig Cell aggregation in the fetal testis of rats exposed to di (n-butyl) phthalate and its possible role in testicular dysgenesis.

Fetal exposure of male rats to di (n-butyl) phthalate (DBP) induces testicular changes remarkably similar to testicular dysgenesis syndrome in humans; these include induction of focal areas of dysgenetic tubules in otherwise normal testes. In searching for the fetal origins of the latter, we used image analysis to show that exposure to 500 mg/kg DBP [embryonic day (E)13.5-20.5)] caused abnormal aggregation of Leydig cells centrally in the fetal testis. This aggregation was not due to increase in Leydig cell number, and Leydig cell size was significantly reduced in DBP-exposed animals, as were testosterone levels and immunoexpression of P450 side-chain cleavage enzyme. The Leydig cell aggregates did not exhibit evidence of focal proliferation at E17.5-19.5. Using confocal microscopy and Leydig (3beta-hydroxysteroid dehydrogenase) and Sertoli (anti-Mullerian hormone) cell-specific markers, we show that fetal Leydig cell aggregates in DBP-exposed animals trap isolated Sertoli cells within them at E21.5. These areas of intermingled cells are still apparent on postnatal d 4, after cessation of DBP treatment, when they may form misshapen seminiferous cords that trap (intratubular) Leydig cells within them. These centrally located dysgenetic tubules contain germ cells in early puberty, but by adulthood they are Sertoli cell only, implying that presence of intratubular Leydig cells interferes with spermatogenesis. It is concluded that DBP-induced fetal Leydig cell aggregation may be a key event in formation of focal dysgenetic areas in the testis, and identification of the mechanisms underlying these events may give new insights into the fetal origins of testicular dysgenesis syndrome disorders in the human.

Abnormalities, Drug-Induced↗
PubMed1978

Immunochemical measurement of the vitamin D-binding protein in rat serum.

The vitamin D-binding protein (DBP) was measured in rat serum using a single radial immunodiffusion technique. Normal serum levels at birth (74 +/- 11 mg/liter, mean +/- SD) were lower than during the last day of fetal life (130 +/- 14 mg/liter) and much lower than in adult rats. A marked sex difference in DBP occurred after puberty: male values (656 +/- 52 mg/liter) were significantly higher than female values (472 +/- 46 mg/liter). The sex difference could be abolished by either adult gonadectomy or transpharyngeal hypophysectomy. Implantation of a pituitary gland under the renal capsule in hypophysectomized male rats further decreased the DBP concentration, suggesting that PRL suppresses the DBP level. A similar decrease was also observed at the end of pregnancy and during lactation. Administration of androgens to either normal female or gonadectomized male rats increased their DBP concentration to the normal adult male level. The serum levels of total 25-hydroxyvitamin D did not fluctuate according to the concentration of DBP, indicating that the concentration of "free 25-hydroxyvitamin D" is not regulated at a constant level.

Age Factors↗
PubMed2005

Increased pulse wave velocity in subclinical hypothyroidism.

OBJECTIVE: Subclinical hypothyroidism affects 5-15% of the general population and is associated with increased morbidity from cardiovascular disease. Brachial-ankle pulse wave velocity (baPWV) is a parameter of arterial stiffening and a good independent predictor for the presence of coronary artery disease. This study was performed to assess whether subclinical hypothyroidism might cause enhanced baPWV. PATIENTS AND METHODS: baPWV was examined in subclinical hypothyroid patients (n = 50) and normal control subjects (n = 50). RESULTS: Diastolic blood pressure (DBP), a main risk factor for cardiovascular disease, and baPWV were both significantly higher in subclinical hypothyroid patients than normal subjects. baPWV was significantly positively correlated with age and systolic, diastolic, and pulse pressure and significantly negatively correlated with pulse rate in both subclinical hypothyroid patients and normal subjects. In contrast, there was no significant correlation of baPWV with free T3, free T4, TSH, total, high-density lipoprotein- and low-density lipoprotein-cholesterol, and the preejection time to ejection time ratio. A comparison of individual values of baPWV and DBP and regression slopes in two groups revealed that baPWV values increase to a larger extent than the increase in DBP in subclinical hypothyroid patients. In both groups, stepwise regression analysis showed a significant and independent association of DBP with baPWV. CONCLUSIONS: The present study demonstrated significant increases of baPWV and DBP in subclinical hypothyroid patients. Furthermore, the results suggest that increased DBP might be one of the main factors responsible for increased arterial stiffening in subclinical hypothyroid patients.

Aged↗
PubMed1986

Relationships among vitamin D, 25-hydroxyvitamin D, and vitamin D-binding protein concentrations in the plasma and milk of human subjects.

We measured plasma and milk concentrations of vitamin D2, vitamin D3, 25-hydroxyvitamin D2 (25OHD2), 25-hydroxyvitamin D3 (25OHD3), and vitamin D-binding protein (DBP) in a group of lactating women. All vitamin D compounds were quantitated using competitive protein binding assay, while DBP concentrations were determined by rocket electrophoresis. Vitamin D3 was the most abundant vitamin D compound in human milk, followed by vitamin D2, 25OHD3, and, finally, 25OHD2. The average vitamin D activity in milk was between 33-68 IU/liter, depending on the criterion of biological activity used. DBP concentrations in milk were approximately 3% of those in plasma. Significant relationships were found between plasma and milk levels for all vitamin D compounds. The milk to blood concentration ratio was greatest for vitamin D2, followed by vitamin D3, 25OHD2, and 25OHD3. (Thus, the parent compounds gained access into milk in a much more efficient fashion than their 25-hydroxy metabolites. It is postulated that this differential translocation is controlled by the DBP in the circulation.) There was no significant correlation between plasma and milk DBP concentrations, nor were milk DBP concentrations related to the vitamin D content of milk. This investigation supports the concept that the nutritional status of lactating mothers affects the vitamin D sterol potential of her milk which, in turn, would likely have an effect on the vitamin D status of her nursing infant.

25-Hydroxyvitamin D 2↗
PubMed2000

Variations in vitamin D-binding protein (group-specific component protein) are associated with fasting plasma insulin levels in Japanese with normal glucose tolerance.

The locus of the vitamin D-binding protein (DBP; also known as group-specific component protein or Gc) gene, chromosome 4q12, has been reported to be associated with glucose metabolism in several ethnic groups, including Pima Indians. We have recently reported the association of the DBP genotype with type 2 diabetes mellitus in Japan. The aim of this study was to investigate whether genetic variations of DBP have any influence on glucose metabolism without secondary effects of hyperglycemia or diabetes mellitus using 82 Japanese with normal glucose tolerance. The variations of the DBP gene (Gc 1F, 1S, and 2) were determined by PCR-restriction fragment length polymorphism. Fasting plasma insulin concentration and homeostasis model assessment, an index of insulin resistance, were significantly different based on the DBP genotype (P < 0.01 and P < 0.05, respectively). The people with Gc 1S-2 (5.73 +/- 2.57 microU/mL) and 1S-1S (5.30 +/- 3.46 microU/mL) had significantly higher fasting plasma concentrations than those with 1F-1F (2.84 +/- 1.67 microU/mL) (P < 0.01 and P < 0.03, respectively). There was no significant difference in plasma glucose concentration, body mass index, total cholesterol, triglyceride, and blood pressure. In conclusion, genetic variations of DBP are associated with insulin resistance in Japanese with normal glucose tolerance, which might contribute to the development of type 2 diabetes.

Asian People↗
PubMed2006

Effects of perinatal exposure to phthalate/adipate esters on hypothalamic gene expression and sexual behavior in rats.

Our previous research has identified the granulin (grn) and p130 genes as sex steroid-regulated genes in the neonatal rat hypothalamus that might be involved in sexual differentiation of the brain. Since phthalate/adipate esters such as di-n-butyl phthalate (DBP), diisononyl phthalate (DINP), and di-2-ethylhexyl adipate (DEHA) are suspected to interfere with the endocrine system as environmental endocrine disruptors having estrogenic or antiandrogenic properties, these chemicals may affect sexual differentiation of the brain. The present study assessed the effects of perinatal exposure to DBP, DINP, and DEHA on grn and p130 mRNA expressions in the hypothalamus on postnatal day (PND) 7 and sexual behaviors after maturation in rats. Maternal rats were given a phytoestrogen-free diet containing different doses of DBP (20, 200, 2,000, and 10,000 ppm), DINP (40, 400, 4,000, and 20,000 ppm) and DEHA (480, 2,400, and 12,000 ppm) from gestational day 15 to the day of weaning (PND 21). DBP and DINP exposure during the perinatal period resulted in an increase in hypothalamic grn and p130 mRNA levels in females and males, respectively, but DEHA exposure decreased expression levels of grn in males and p130 in females, although the effects were not dose-dependent. After maturation, male rats that were exposed to several doses of DBP, DINP, and DEHA displayed decreased copulatory behavior. The lordosis quotient was decreased in females perinatally exposed to DBP, DINP, and DEHA at all the doses used. On the other hand, serum levels of LH and FSH in both sexes and the estrous cycles in females were not affected by the treatments. These results suggest that inappropriate expression of grn and/or p130 genes in the brains of male and female neonatal rats by perinatal exposure to these chemicals may exert permanent effects on the hypothalamus, thereby decreasing sexual behavior after maturation.

Adipates↗
PubMed2000

Effects of dibutyl phthalate as an environmental endocrine disruptor on gonadal sex differentiation of genetic males of the frog Rana rugosa.

To examine the effects of dibutyl phthalate (DBP) on gonadal sex differentiation, genetically male tadpoles of Rana rugosa were exposed to dilute solutions of DBP at concentrations of 0.1, 1, or 10 microM during days 19-23 after fertilization, which is the critical period of gonadal sex differentiation in R. rugosa. Tadpoles were necropsied on day 40. The genetically male tadpoles were produced from crossings between males (ZZ) of one local population, in which females are the heterogametic sex, and females (XX) of another local population, in which males are the heterogametic sex. As positive control groups, tadpoles were exposed to dilute solutions of 17beta-estradiol (E(2)) at concentrations of 0. 01, 0.1, or 1 microM during the same period. The internal structure of the gonads was histologically examined in a total of 30 control tadpoles, 86 E(2)-treated tadpoles, and 90 DBP-treated tadpoles. The gonads of the control tadpoles all showed the typical structure of testes. In contrast, 0.01, 0.1, and 1 microM E(2) treatments caused the undifferentiated gonads of 18, 63, and 100% of the tadpoles, respectively, to develop into gonads of complete or partial ovarian structure. After 0.1, 1, and 10 microM DBP treatment, 0, 7, and 17% of tadpoles, respectively, were similarly affected. These findings suggest that DBP was about 1,000-fold less potent than E(2). Nevertheless, DBP is an environmentally dangerous hormone that disrupts the pathways of testicular differentiation in genetically male animals.

Animals↗
PubMed2002

Reverse J-curve relation between diastolic blood pressure and severity of coronary artery lesion in hypertensive patients with angina pectoris.

The existence of the J-curve in hypertension treatment remains controversial. The major question is whether the increase in mortality from coronary disease is induced by the lowering of blood pressure (BP) or by the severity of underlying coronary artery disease. We recruited patients with a history of hypertension (systolic BP (SBP) >160 mmHg and/or diastolic BP (DBP) >90 mmHg) and a diagnosis of angina pectoris with angiographically confirmed coronary artery lesion. The relationship among the treated levels of SBP and DBP, the severity of coronary artery lesion, and the clinical consequences were investigated. Among the 234 enrolled patients, 115 experienced further events, 19 of which were serious. There were no significant differences in the average BP of patients with and those without events, but the coronary severity indices (CSI) were significantly greater in patients with events. As a function of DBP from < or = 74 to 105 < or = mmHg, there was a positive association with the incidence of serious events, and a reversed J-curve in CSI with a nadir at 95-104 mmHg. A similar relationship was observed in SBP, but a potentially unfavorable outcome was suggested in the lowest SBP range of < or = 124 mmHg. In conclusion, there was no J-curve for DBP in hypertensive patients with angina pectoris; rather, the lower the DBP, the better was the prognosis. Interestingly, the severity of coronary lesion is in a reversed J-curve relation with DBP, suggesting that high BP plays a critical role in serious events in hypertensive patients with moderate coronary artery lesions.

Angina Pectoris↗
PubMed2003

Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial of cardiovascular events in high-risk hypertensive patients: rationale, design, and methods.

Hypertension continues to be a major public health issue in the world. To combat this problem, many anti-hypertensive drugs have been developed and proven effective at controlling blood pressure in the last half century. In recent decades, antihypertensive drugs have been shown to have cardiovascular benefits beyond the reduction of blood pressure, and the focus has shifted to clarification of these effects. Angiotensin II receptor antagonists and calcium channel blockers are the most widely used antihypertensive drugs in Japan. However, these two classes of drugs have not yet been compared with respect to their efficacy for treating cardiovascular events. The Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial described herein is a prospective, multicenter, randomized, open-label, active-controlled, 2-arm parallel group comparison with a response-dependent dose titration and blinded assessment of endpoints in high-risk hypertensive patients treated with either an angiotensin II receptor antagonist (candesartan cilexetil) or a third-generation calcium channel blocker (amlodipine besilate). The eligibility criteria in this study were 1) age between 20 and 85 years; 2) systolic blood pressure (SBP) > or = 140 mmHg in those below 70 years of age or > or = 160 mmHg in those above 70 years of age or diastolic blood pressure (DBP) > or = 90 mmHg on two consecutive measurements at clinic; and 3) at least one of the following high risk factors for cardiovascular events: a) SBP > or = 2180 mmHg or DBP > or = 110 mmHg on two consecutive visits, b) type 2 diabetes mellitus (fasting blood glucose > or = 126 mg/dl, casual blood glucose > or = 200 mg/dl, HbA1c > or = 6.5%, 2 h blood glucose on 75 g oral glucose tolerance test (OGTT) > or = 200 mg/dl, or current treatment with hypoglycemic therapy), c) history of cerebral hemorrhage, cerebral infarction, or transient ischemic attack until 6 months prior to the screening, d) left ventricular hypertrophy on either echocardiography or ECG, angina pectoris, or history of myocardial infarction until 6 months prior to screening, e) proteinuria or serum creatinine > or = 1.3 mg/dl, and f) symptoms of arteriosclerotic artery obstruction. The therapeutic goals of blood pressure control were set as follows: SBP < 130 mmHg and DBP < 85 mmHg for patients below 60 years of age, SBP < 140 mmHg and DBP < 90 mmHg for those in their 60s, SBP < 150 mmHg and DBP < 90 mmHg for those in their 70s, and SBP < 160 mmHg and DBP < 90 mmHg for those in their 80s. A total of 3,200 patients, equally allocated to each of the two treatment arms, were required based on a two-sided alpha level 0.05 and 90% power. The CASE-J is also the first study to employ the newly developed Automatic Bar Code Data-Capturing/Allocation, Booking & Trial Coding, Data Management (ABCD) system for data collection and management. Enrollment of patients started in September 2001 and ended in December 2002. Follow-up data will be collected every 6 months until December 2005. The CASE-J trial will provide important evidence on the comparative effectiveness of candesartan cilexetil and amlodipine besilate on cardiovascular morbidity and mortality among Japanese. In addition, the use of the ABCD system is expected to contribute to the development of more efficient data management systems for large-scale clinical trials.

Antihypertensive Agents↗
PubMed2005

Status of home blood pressure measured in morning and evening: evaluation in normotensives and hypertensives in Japanese urban population.

To assess home blood pressure status in a Japanese urban population, we analyzed home blood pressure values in normotensive subjects determined by casual blood pressure (< 140/90 mmHg), hypertensive subjects without medication (> or = 140/90 mmHg) and treated hypertensive patients. The subjects (468 male, 232 female; mean age 41 years old) were recruited from a company located in Tokyo. Home blood pressure was measured with a semi-automatic device (Omron HEM-759P). Subjects were instructed to perform triplicate morning and evening measurements on 7 consecutive days. In the treated hypertensive group (n = 70), there was a significant difference between morning (139 +/- 12/88 +/- 9 mmHg) and evening (130 +/- 12/79 +/- 8 mmHg) home blood pressure. In the normotensive group (n = 558), however, only the diastolic blood pressure (DBP) component of the home blood pressure was significantly different between morning (115 +/- 13/72 +/- 9 mmHg) and evening (114 +/- 12/68 +/- 8 mmHg). In the nontreated hypertensive group (n = 72), casual blood pressure (145 +/- 14/92 +/- 9 mmHg) was higher than morning (138 +/- 16/89 +/- 11 mmHg) and evening (134 +/- 16/83 +/- 11 mmHg) home blood pressure, but no difference was seen between morning and evening systolic blood pressure (SBP). According to the reference value of the Japanese Society of Hypertension 2004 (SBP > or = 135 mmHg and/or DBP > or = 85 mmHg), 7.2% (systolic) and 8.7% (diastolic) of subjects in the normotensive group were classified as hypertensive by home blood pressure. Casual blood pressure in the treated hypertensive group was normal in 64.3% for SBP and 70.0% for DBP. However, their morning SBP (32.9%), morning DBP (40.0%), evening SBP (10.0%), and evening DBP (17.1%) were classified as hypertensive by home blood pressure. Furthermore, patients who were taking antihypertensive drug(s) only in the morning (n = 52) showed higher morning SBP (6 mmHg, p = 0.086) and morning DBP (6 mmHg, p = 0.005) than patients taking drug(s) by other administration schedules (n = 18), but no difference in evening home blood pressure was observed. In conclusion, a proportion of the subjects defined as normotensive by casual blood pressure were classified as hypertensive by home blood pressure in the present urban population. Furthermore, morning home blood pressure control in the treated hypertensive group classified as under control by casual blood pressure was insufficient, especially in patients who were taking medication only in the morning.

Adult↗
PubMed2002

Technical and prognostic outcomes of double-balloon pericardiotomy for large malignancy-related pericardial effusions.

OBJECTIVE: To investigate both the use of immediate or elective double-balloon pericardiotomy (DBP) in patients with a large amount of malignancy-related pericardial effusion, and the prognosis of this subgroup. DESIGN: Observational study after DBP intervention. SETTING: Tertiary referral center. PATIENTS AND INTERVENTIONS: Fifty patients with malignancy, mainly lung and breast cancer, who were admitted to our critical care unit with a large amount of pericardial effusion. All received echocardiographic-guided pericardiocentesis. Group 1 consisted of 12 patients (24%) who received immediate DBP, and group 2 consisted of 38 patients (76%) who received delayed DBP 2.5 +/- 1.7 days later (mean +/- SD) after emergency pericardiocentesis with pigtail catheter drainage. MEASUREMENTS: After the procedure, and at 1 month, 3 months, and 6 months, echocardiography and chest radiography were performed to check for pneumothorax, pericardial effusion reaccumulation, or the appearance of pleural effusion after pigtail catheter removal. MAIN RESULTS: The procedure was successful and without recurrence in 44 patients (88%). Procedural complications were fever in 4 patients (33%) and 10 patients (26%) in group 1 and group 2, respectively (p = 0.72), and mild pneumothorax in 2 patients (17%) and 1 patient (3%) in group 1 and group 2, respectively (p = 0.14). Fifty percent of the patients died within 4 months, while 25% survived to 11 months. High serum calcium, a low albumin/globulin ratio, and positive results on pericardial effusion cytology were poor prognostic factors for long-term survival. CONCLUSION: Both immediate and delayed DBP are a safe and effective method of relieving large pericardial effusions in patients with cancer. Successful DBP without recurrence of pericardial effusion was achieved in 88% of all patients. Survival was related to the extent of the disease.

Adult↗
PubMed2002

Binding of a C-terminal fragment (residues 369 to 435) of vitamin D-binding protein to actin.

The vitamin D-binding protein (DBP) binds to monomeric actin with high affinity. The variation in DBP isoforms is due to genetic polymorphism and varying glycosylation. To obtain a homogeneous preparation, the cDNA for human DBP and truncations thereof were cloned and various systems were applied for heterologous bacterial and yeast expression. The full-length protein and the N- and C-terminal halves of DBP remained insoluble probably because the protein did not fold to its native three-dimensional structure due to formation of accidental intra- and inter-molecular disulfide bonds during expression in bacteria or yeast. This problem was overcome by cloning of a C-terminal fragment comprising residues 369 to 435 that did not contain disulfide bonds and was completely soluble. Binding of the C-terminal fragment to monomeric actin was demonstrated by comigration with actin during native polyacrylamide gel electrophoresis and surface plasmon resonance, however, at considerably lower affinity than full-length DBP. This suggests that in addition to the C-terminal amino acid sequence other parts (amino acid residues or sugar moieties) of DBP participate in actin binding. The C-terminal fragment was found to inhibit denaturation of actin and to decrease the rate of actin polymerisation both at the barbed and at the pointed end in a concentration-dependent manner. According to a quantitative analysis of the polymerisation kinetics, association of actin monomers to nucleate filaments was not prevented by binding of the C-terminal fragment to actin. These data suggest that the sites on the surface of actin that are involved in actin nucleation and elongation are different.

Actins↗
PubMed2002

Diurnal rhythm of plasma 1,25-dihydroxyvitamin D and vitamin D-binding protein in postmenopausal women: relationship to plasma parathyroid hormone and calcium and phosphate metabolism.

OBJECTIVE: Diurnal variations in plasma levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) have previously only been investigated in young individuals, and these studies have failed to demonstrate a diurnal rhythm. We have studied whether plasma levels of 1,25(OH)(2)D and vitamin D-binding protein (DBP) vary in a diurnal rhythm in postmenopausal women. METHODS: Blood and urine were sampled with 2- and 4-h intervals in order to assess diurnal variations in plasma levels of 1,25(OH)(2)D, DBP and parathyroid hormone (PTH), as well as in plasma levels and urinary excretion rates of calcium and phosphate. Additionally, the free 1,25(OH)(2)D index was calculated (the molar ratio of 1,25(OH)(2)D to DBP). RESULTS: Plasma 1,25(OH)(2)D exhibited a diurnal rhythm (P<0.01) with a nadir in the morning (99+/-12 pmol/l), followed by a rapid increase to a plateau during the day (113+/-13 pmol/l, i.e. 14% above nadir level; P=0.005). A similar pattern of variation was found in plasma levels of DBP with peak levels 15% above nadir levels (P<0.01). The free 1,25(OH)(2)D index did not vary in a diurnal rhythm. PTH and plasma levels and urinary excretions of calcium and phosphate exhibited a diurnal pattern of variation. The diurnal rhythm of DBP was correlated with the rhythm of 1,25(OH)(2)D (r=0.47, P<0.01) and plasma albumin (r=0.76, P<0.01). Moreover, the rhythm of plasma calcium and PTH varied inversely (r=-0.36, P=0.02). CONCLUSIONS: With the disclosure of a diurnal rhythm of total plasma 1,25(OH)(2)D, all major hormones and minerals related to calcium homeostasis have now been shown to exhibit diurnal variations. In clinical studies, the diurnal variations of 1,25(OH)(2)D and DBP must be considered, i.e. blood sampling must be standardised according to the time of day.

Aged↗
PubMed1986

Transcortin and vitamin D-binding protein levels in mouse serum.

The influence of age, sex and strain on the serum concentration of transcortin (corticosteroid-binding globulin) and vitamin D-binding protein (DBP) in mice was investigated. The effect of age was studied in two strains, C57BL/6JPfd and BALB/cmHeAPfd. The concentration of transcortin and DBP increased with age. In young animals the concentration of each protein showed a significant strain difference, which disappeared in older mice for DBP, but not for transcortin. In 7-day-old animals, no sex difference was observed for either protein, but in older animals a clear sex difference was found for transcortin. Adult males tended to have somewhat higher levels of DBP than adult females, but this difference was significant only on day 70. The variation in transcortin and DBP levels was further investigated in a large number of mouse strains. The DBP concentration did not markedly vary among strains (5.98-9.65 mumol/l in males and 5.08-8.85 mumol/l in females). Transcortin, however, showed marked strain variations, ranging from 0.72 to 2.06 mumol/l in males and from 1.02 to 4.55 mumol/l in females and there was a significant correlation (r = 0.66, n = 26, P less than 0.001) between the mean transcortin levels in males and females of different strains. Interstrain variation was much higher than intrastrain variation or variation among related strains, suggesting that the transcortin concentration is largely controlled by genetically determined factors. There was a significant correlation (r = 0.82, n = 9, P less than 0.01) between the mean corticosterone and transcortin concentrations (measured at 21.00 h).(ABSTRACT TRUNCATED AT 250 WORDS)

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