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Messenger RNA for the Ad2 DNA binding protein: DNA sequences encoding the first leader and heterogenity at the mRNA 5' end.

During the early stage of Ad2 infection of human cells, RNA is transcribed from five separate transcription units. Early region II encodes the mRNA for a 72K single-stranded DNA binding protein (DBP) which functions in DNA replication. This report describes the structure of the first leader of the DBP mRNA and the flanking sequences in the DNA. The leader, labeled in vivo with 32P, was isolated by DNA filter hybridization to the viral restriction fragment Eco RI F, and its RNAase T1 and RNAase A oligonucleotides were analyzed by RNA fingerprinting techniques. Comparison of this RNA sequence information with the DNA sequence of Eco RI F has located a 68 nucleotide region of the Hae III C subfragment at coordinate 75.1 that encodes the leader. This position is near the coordinate to which nascent chain analysis and ultraviolet transcription mapping have mapped an RNA initiation site, or promoter, for the DBP mRNA. The DNA sequence that overlaps the leader on the 3' side contains a donor sequence for splicing this leader to a second downstream leader. The splicing sequence shows a seven base homology with the comparable structure of the Ad2 major late leader, and a mouse globin mRNA splicing sequence. The DNA sequence upstream from the cap, the region oof the potential promoter site does not, however, contain a "TA-TAAA"-type homology of the sort noted by D. Hogness, M. Goldberg and R. Lifton (personal communication) for many cellular transcription units, and by other investigations for the Ad2 major late transcription unit. Also, the leader is found with two distinct capped 5' termini, 7meGpppA and 7meGpppG, which are encoded at adjacent positions in the DNA and thus are from mRNAs which are staggered by one nucleotide in length at the 5' end. The staggering at the 5' terminus and the lack of the upstream homolgy distinguish the DBP mRNA from many viral and cellular messenger. In both these respects, however, the DBP mRNA resembles the late messengers of SV40 and polyoma viruses. In this paper, we discuss the implications of these findings for the mechanism of specifying mRNA 5' ends.

Adenoviruses, Human↗

Raised exercise diastolic blood pressure as indicator of ischaemic left ventricular dysfunction.

91 (16.8%) of 541 consecutive patients investigated for chest pain or after recent uncomplicated myocardial infarction had a rise in diastolic blood pressure (DBP) of more than 15 mm Hg during a symptom-limited treadmill test. 63 also had electrocardiographic evidence of ischaemia, but 28 did not have 1 mm ST segment depression, of whom 24 had angiographic evidence of more than 70% stenosis of two or more major coronary arteries. 55 of these 91 patients underwent coronary artery bypass surgery; repeat angiography in 22 at 12 months showed an improved left ventricular ejection fraction in 18 who had a normal postoperative DBP response, but no change in ejection fraction in the 4 who still had an abnormal rise in DBP on exercise. Exercise-induced ischaemia may cause a reversible fall in cardiac output that sometimes leads to reflex vasoconstriction and a rise in DBP before a fall in systolic blood pressure or ECG evidence of ST segment depression. An abnormal DBP response to exercise may identify some patients at high risk of myocardial infarction who might otherwise have false-negative exercise tests.

Angioplasty, Balloon, Coronary↗

Influence of isolated diastolic hypertension identified by ambulatory blood pressure on target organ damage.

Clinical decisions and controlled studies in regard to hypertension have long emphasized the casual diastolic blood pressure (DBP). The influence of superimposition of high systolic blood pressure (SBP) on the target organ damage has been less studied. To assess the role of isolated diastolic hypertension without interference of superimposition of systolic hypertension, 171 subjects with normal blood pressure, isolated diastolic hypertension (SBP < 140 and DBP > or = 90 mmHg) isolated systolic hypertension (SBP > or = 140 and DBP < 90 mmHg) or combined hypertension (SBP > or = 140 and DBP > or = 90 mmHg) determined by mean 24-h ambulatory blood pressure were compared in relation to target organ damage including ECG abnormality related to hypertension, cardiac enlargement by chest X-ray, proteinuria and retinopathy. The incidence of target organ damage was lower in subjects with normal BP than in the other three groups. The incidence of target organ damage was almost significantly higher in patients with isolated systolic hypertension than in those with isolated diastolic hypertension. No significant difference in the incidence of complications existed between patients with isolated systolic and combined hypertension. These findings demonstrate that the severity of hypertensive complications is more closely related to mean ambulatory SBP than mean ambulatory DBP. The level of systolic BP is important for predicting the severity of target organ damage in patients with high diastolic BP, because there is a significant difference in the incidence of target organ damage between isolated diastolic hypertension and combined hypertension.

Arrhythmias, Cardiac↗

Osteogenesis in composite grafts of allogenic demineralized bone powder and porous hydroxylapatite.

This study evaluated the osteoinductive capabilities of porous hydroxylapatite (PH) and the tissue response following intramuscular implantation of PH alone or in combination with demineralized bone powder (DBP). Six rhesus monkeys each received the implants in three separate soft tissue pockets created in the thoracic region. The implants consisted of 2 cc of either PH alone or DBP alone, or a 1:1 combination of DBP and PH. Two animals were killed at 2 weeks, two at 4 weeks, and two at 12 weeks postimplantation. Histologically, bone formation was seen in the DBP mixed with PH and in the DBP group as early as 4 weeks postimplantation; bone was also occasionally observed within the pores of the PH particles. The PH alone showed no evidence of formation of bone and the material was surrounded by a thick layer of fibrous tissue. It was concluded that PH is not osteoinductive, but can act as a scaffold for growth of bone, and that when mixed with an osteoinductive material, it allows for formation of bone within the implant.

Animals↗

Arm and leg blood pressures--are they really so different in newborns?

Controversy still exists over differences between upper and lower limb blood pressures (BP) in neonates. We measured upper arm and calf systolic (S) and diastolic (D) BP and heart rate (HR) using 2 Dinamap 847 instruments simultaneously every half minute for several measurement periods of 5-10 min. Nine healthy term newborns were studied in active (AS) and quite (QS) sleep on post-natal days 1 and 5. The results were examined using unbalanced analyses of variance. Arm SBP was 62.3 +/- 1.6 mmHg and DBP 35.5 +/- 1.0 mmHg on day 1 in AS and QS. Calf values were not significantly different but were slightly higher (by 2-3 mmHg) in AS. Arm SBP and DBP rose by 8.5 and 5 mmHg, respectively, between days 1 and 5 but calf pressures rose less. Calf SBP and DBP were significantly lower (by 4.6 and 3.4 mmHg, respectively) than the arm values in QS on day 5. Arm SBP and DBP were dependent on post-natal age but not on sleep state while calf SBP and DBP and HR were dependent on both. Mean HR rose with age from 114 to 117.6 bpm in QS and from 118.6 to 122.4 bpm in AS. Our non-invasive BP measurements were similar to available invasive data. We postulate that differences in arm and calf vasoreactivity account for the different dependence on sleep state and for the unequal changes in arm and calf BE from days 1 to 5.

Age Factors↗

Evaluation of drug therapy for treatment of hypertensive urgencies in the emergency department.

Oral nifedipine (N) and clonidine (C) are often used in the treatment of hypertensive urgencies; however, until recently, there were no comparative studies using the same patient population. The authors reviewed the records of hypertensive patients treated in the emergency department between October 1, 1987 and September 30, 1988. Selected patients had a diastolic blood pressure (DBP) of greater than 115 mm Hg without evidence of acute end organ damage. Patients were stratified into three treatment groups: N, C, and group 3 (G3). G3 received a variety of drug therapies but not exclusively N or C. Systolic blood pressure (SBP), DBP, mean arterial pressure (MAP), percent decrease in MAP (%MAP), time to lower blood pressure, admissions, and discharges were evaluated. Efficacy and safety were defined as reaching a DBP less than 110 mm Hg but %MAP of no greater than either 25% or 40%, respectively. Thirty-five N, 32 C, and 27 G3 patients were identified with no statistical difference between groups in race, gender, pretreatment SBP, DBP, or MAP. N, C, and G3 significantly reduced SBP, DBP, and MAP (P less than .01). Comparing N, C, and G3, no differences were observed in %MAP, admissions, discharges, efficacy, or safety. Time required to decrease blood pressure differed between all three groups (44 +/- 32 N v 77 +/- 57 C v 152 +/- 94 min G3) (p less than .05). These results indicate that N, C, and a variety of drug therapies are equally effective and safe in the treatment of hypertensive urgencies.

Adolescent↗

A telecommunications system for monitoring and counseling patients with hypertension. Impact on medication adherence and blood pressure control.

This study was conducted to evaluate the effect of automated telephone patient monitoring and counseling on patient adherence to antihypertensive medications and on blood pressure control. A randomized controlled trial was conducted in 29 greater Boston communities. The study subjects were 267 patients recruited from community sites who were >or= 60 years of age, on antihypertensive medication, with a systolic blood pressure (SBP) of >or= 160 mm Hg and/or a diastolic blood pressure (DBP) of >or= 90 mm Hg. The study compared subjects who received usual medical care with those who used a computer-controlled telephone system in addition to their usual medical care during a period of 6 months. Weekly, subjects in the telephone group reported self-measured blood pressures, knowledge and adherence to antihypertensive medication regimens, and medication side-effects. This information was sent to their physicians regularly. The main study outcome measures were change in antihypertensive medication adherence, SBP and DBP during 6 months, satisfaction of patient users, perceived utility for physicians, and cost-effectiveness. The mean age of the study population was 76.0 years; 77% were women; 11% were black. Mean antihypertensive medication adherence improved 17.7% for telephone system users and 11.7% for controls (P = .03). Mean DBP decreased 5.2 mm Hg in users compared to 0.8 mm Hg in controls (P = .02). Among nonadherent subjects, mean DBP decreased 6.0 mm Hg for telephone users, but increased 2.8 mm Hg for controls (P = .01). For telephone system users, mean DBP decreased more if their medication adherence improved (P = .03). The majority of telephone system users were satisfied with the system. Most physicians integrated it into their practices. The system was cost-effective, especially for nonadherent patient users. Therefore, weekly use of an automated telephone system improved medication adherence and blood pressure control in hypertension patients. This system can be used to monitor patients with hypertension or with other chronic diseases, and is likely to improve health outcomes and reduce health services utilization and costs.

Aged↗

Controlled-release carvedilol in the treatment of essential hypertension.

Carvedilol is a beta1-, beta2-, and alpha1-adrenergic blocker that is approved for the treatment of hypertension. A new once-daily, controlled-release (CR) formulation of carvedilol has been shown to be effective in a double-blind, randomized, multicenter, placebo-controlled, parallel-group study. In this article, we summarize the primary results of, and present additional analyses from, that trial. A total of 338 patients with essential hypertension (sitting diastolic blood pressure [DBP] >/=90 and </=109 mm Hg) were randomized to receive carvedilol CR 20, 40, or 80 mg or placebo for 6 weeks. The primary objective was to compare the effects of the 3 carvedilol CR doses with placebo on 24-hour mean blood pressure using ambulatory blood pressure monitoring (ABPM). Mean DBP and systolic BP (SBP) at the drug trough (20-24 hour) blood levels for carvedilol CR and comparison of DBP and SBP at the drug peak (3-7 hour) blood levels for each dose of carvedilol CR and placebo were investigated. The effects of carvedilol CR on heart rate and pulse pressure were also examined. Once-daily administration of carvedilol CR, alone or in combination with other agents, produced clinically and statistically significant reductions compared with placebo for both DBP and SBP after 6 weeks of treatment for the following parameters: trough blood pressure by office cuff or ABPM measurements, peak blood pressure by ABPM, and 24-hour mean blood pressure by ABPM. Placebo-corrected trough-to-peak ratios for DBP were >0.6 for each carvedilol CR dose. Heart rate and pulse pressure were each significantly reduced compared with placebo for each carvedilol CR dose. We conclude that carvedilol CR is a very effective antihypertensive agent with clear dose-related peak blood pressure reduction and continuous 24-hour control.

Administration, Oral↗

What is the accuracy of clinic blood pressure measurement?

BACKGROUND: In clinical practice, blood pressure (BP) is frequently measured at the end of the visit in patients sitting on one side of the bed and not on a chair according to guidelines. METHODS: In 540 consecutive subjects with essential hypertension (EH) attending a hospital outpatient clinic, BP was measured in the following sequence: 1) patient seated on chair for at least 5 min, 2) patient supine, 3) patient seated on bed, and 4) patient standing for a few minutes. RESULTS: We found that mean (+/-SEM) BP was 143.5/87.2 +/- 0.9/0.5, 153.4/89.7 +/- 1.0/0.5, 148.9/90.9 +/- 1.0/0.5, and 144.8/91.7 +/- 1.0/0.6 mm Hg, respectively (P < .05 v position 1 for all). In 14% of patients, either systolic BP (SBP) or diastolic BP (DBP) was above the conventional upper limits of normality in the seated-on-bed but not in the recommended seated-on-chair position ("false" high clinic BP), whereas SBP and DBP were "false" normal (below limit for bed-seated and above limit for chair-seated position) in only 6% and 2% of patients, respectively. Overall, SBP and DBP increments from the chair- to the bed-seated position were inversely related to the baseline chair-seated values; systolic increments were directly related to age, in particular in the subgroup of untreated EH (n = 70), and to body mass index. A gender-related difference was apparent, as female subjects had more pronounced increments in SBP (+7.4 +/- 0.8 v +3.5 +/- 0.7 mm Hg) and DBP (+4.4 +/- 0.5 v 2.9 +/- 0.4 mm Hg) than did male subjects (P < .05 for both). CONCLUSIONS: Clinic SBP and DBP are overestimated in the bed-seated position at the end of the visit compared with the recommended chair-seated position in treated and untreated patients with EH, in particular in elderly obese women with mild hypertension.

Adult↗

A double-blind, dose-response study of losartan in hypertensive children.

BACKGROUND: The aim of this study was to determine the dose-response relationship for losartan, 2.5 to 100 mg, and to assess the safety and tolerability of losartan in hypertensive children 6 to 16 years of age. METHODS: This was a multicenter, randomized, double-blind, dose-response study. In Period 1, a total of 175 patients were stratified by weight (<50 kg and >/=50 kg) and randomized to one of three dose groups by stratum (low, 2.5/5.0 mg; middle, 25/50 mg; or high, 50/100 mg) for 3 weeks. The ratio of the three dose levels for both weight strata was 1:10:20. In Period 2, patients in each dose group were randomized to continue the same treatment or placebo washout for 2 additional weeks. RESULTS: In Period 1, sitting trough diastolic blood pressure (DBP) decreased in a dose-dependent manner (P < .0001). At week 3, changes in DBP from baseline in the low-, middle-, and high-dose groups were -6.0 mm Hg, -11.7 mm Hg, and -12.2 mm Hg, respectively. In Period 2, DBP increased significantly in patients who switched from middle- and high-dose losartan to placebo (mean increase 6.0 mm Hg, P = .003) relative to DBP in patients who remained on active treatment; however, these levels remained stable in those patients who switched from low-dose losartan to placebo (mean increase 1.1 mm Hg, P = .628). CONCLUSIONS: In hypertensive children 6 to 16 years of age, losartan given once daily reduced blood pressure in a dose-dependent fashion. A once-daily starting dose of losartan, 0.75 mg/kg (maximum 50 mg) effectively lowered DBP within 3 weeks. Losartan up to a dosage of 1.44 mg/kg (maximum 100 mg) once daily is generally well tolerated.

Adolescent↗

Prevalence of uncontrolled hypertension in patients with Fabry disease.

BACKGROUND: Fabry disease is a rare X-linked disease arising from deficiency of alpha-galactosidase A. It results in early death related to renal, cardiac, and cerebrovascular disease, which are also important outcomes in patients with elevated blood pressure (BP). The prevalence of uncontrolled hypertension, as well as the effect of enzyme replacement therapy on BP, in patients with Fabry disease is unknown. METHODS: We examined uncontrolled hypertension (systolic BP [SBP] >or=130 mm Hg or diastolic BP [DBP] >or=80 mm Hg) among 391 patients with Fabry disease who were participating in the Fabry Outcome Survey (FOS). RESULTS: Uncontrolled hypertension was present in 57% of men and 47% of women. In patients with chronic kidney disease (CKD) stage 1 (n100), median SBP was 120 mm Hg and median DBP was 74 mm Hg. In patients with CKD stage 2 (n172), median SBP was 125 mm Hg and median DBP was 75 mm Hg. In patients with CKD stage 3 (n63), median SBP was 130 mm Hg and median DBP was 75 mm Hg. There was a significant decrease in both SBP and DBP during a 2-year course of enzyme replacement therapy. CONCLUSIONS: This study revealed a high prevalence of uncontrolled hypertension among patients with Fabry disease. Thus there is a need to improve BP control and renoprotection in patients with Fabry disease.

Antihypertensive Agents↗

Bromophenols, both present in marine organisms and in industrial flame retardants, disturb cellular Ca2+ signaling in neuroendocrine cells (PC12).

Bromophenols are present in polychaetes as well as in algae in marine environments including the North Sea. They are thought to cause the typical sea-like taste and flavour. The ecological function of brominated phenols is not clear yet, but they may play a role in chemical defence and deterrence [Kicklighter, C.E., Kubaneck, J., Hay, M.E., 2004. Do brominated natural products defend marine worms from consumers? Some do, most don't. Limnol. Oceanogr. 49, 430-441]. Some brominated phenols are commercially used as industrial flame retardants as, e.g., 2,4,6-tribromophenol and are suspected to disrupt the humoral system by showing thyroid hormone-like activity [Legler, I., Brouwer, A., 2003. Are brominated flame retardants endocrine disruptors? Environ. Int. 29, 879-885]. In this study 2-bromophenol (2-BP), 4-bromophenol (4-BP), 2,4-dibromophenol (2,4-DBP), 2,6-dibromophenol (2,6-DBP) and 2,4,6-tribromophenol (2,4,6-TBP), all of which are present in marine organisms, were tested. Especially 2,4-DBP and 2,4,6-TBP showed a significant effect on the Ca2+ homeostasis in endocrine cells (PC 12). The reduction of depolarization induced Ca2+ elevations by 2,4-DBP and 2,4,6-TBP and the increase of intracellular Ca2+ by both substances, partly released from intracellular stores, may suggest a link to the disrupting effect of endocrine systems by brominated phenols. 2,4-DBP was the most potent substance we tested in respect to inhibition of voltage dependent Ca2+ currents as revealed in whole cell patch clamp experiments. Brominated phenols disturb cellular Ca2+ signaling with differential efficacy, depending on the number and position of bromine.

Animals↗

Influences of hyperbaric oxygen on blood pressure, heart rate and blood glucose levels in patients with diabetes mellitus and hypertension.

BACKGROUND: We investigated the influences of hyperbaric oxygen (HBO(2)) on systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and blood glucose level (BGL). METHODS: Forty one patients with hypertension (HTN), diabetes mellitus (DM), HTN and DM and/or no HTN or DM underwent HBO(2) sessions (15-40 sessions for each patient). SBP, DBP, HR and BGL (for diabetics) were recorded before and after each session. RESULTS: HBO(2) caused significant elevation in SBP (11%) and DBP (12%) and a decrease in HR (18%) (p <0.001). Patients with DM and HTN showed higher elevation in SBP and DBP. HBO(2) lowered BGL by 23% (p <0.001). When basal BGL was in the range of 120-170 mg/dl, it dropped to <100 mg/dl in 31/60 treatment sessions (52%). When basal BGL was <120 mg/dl it dropped to <70 mg/dl in 8/34 sessions. There was a possibility of lowered BGL when basal BGL was <170 mg/dl and a marked reduction in BGL occurred when basal BGL was <120 mg/dl. HBO(2) caused a marked elevation in SBP and DBP when basal SBP was >140 mmHg. Critical elevation was obtained when SBP was >160 mmHg. The use of beta blockers caused significant elevation of blood pressure while reducing HR. CONCLUSIONS: HBO(2) causes elevation of blood pressure and lowering of HR and BGL, which were augmented in the presence of HTN, DM, or beta blocker. The use of beta blockers for the management of HTN should be avoided during HBO(2) therapy.

Adrenergic beta-Antagonists↗

About 7-day (circaseptan) and circadian changes in cold pressor test (CPT).

We assess circadian (CD) and circaseptan (CS) changes in the blood pressure (BP) response to a 1-min immersion of the hand into ice water, the cold pressor test (CPT). An about 8 mmHg BP increase in the CPT reported by others for health and an elevation >25 mmHg for patients with "hypertension" have been viewed as predisease, but variables related to the vascular system exhibit prominent CD, CS and circannuals, among other components of their genetically anchored time structure or chronome, and may also have to be considered. Hence, a 16-year-old adolescent (ML) immersed her hand into ice water every 2-4 h for 2 days and once daily in the morning thereafter for 1 week (N = 25), as did, only for <2 days (> or =24 h), four adults 20-66 years of age. BP and heart rate (HR) were monitored automatically around the clock at 15-min intervals and at 1-min intervals before and immediately after the CPT. Data were analyzed by cosinor. The difference between the first post-CPT BP value and the mean of the last seven values prior to the CPT was a measure of CPT response (at 1-min). Overall, ML's systolic (S) BP increased by 8.2 +/- 1.4 mmHg and her diastolic (D) BP by 6.2 +/- 0.9 mmHg (P < 0.001). Increases were found in 96% of the tests for SBP, 92% for DBP and 20% for HR. There was only one tie for HR (4%), resulting in a HR decrease in 76% of CPTs. The BP response to CPT at 1 min was CS-dependent. The CS double amplitudes are 12.5 +/- 4.1 for SBP (P = 0.019) and 7.8 +/- 2.8 mmHg for DBP (P = 0.030), with acrophases occurring on late Sunday, early Monday (at -50 degrees and -67 degrees from 00:00 h from Saturday to Sunday for SBP and DBP, respectively, with 360 degrees identical with 1 week). The response of HR did not allow the detection of a CS rhythm (P = 0.969). The CD response peaked in the early morning hours; with 24 h identical with 360 degrees and 0 degrees = local midnight, the acrophase (phi) for SBP is at -80 degrees and for DBP at -113 degrees, in keeping with earlier results from four adult subjects (SBP: -37 degrees; DBP: -42 degrees ), individual differences notwithstanding. The average timing of the largest overall response of BP to CPT coincides with the timing of the response to other stimuli. The CS acrophases coincide with the times of increased morbidity/mortality from vascular diseases. Chronomes, time structures broader than circadian, notably their about-weekly components, should be considered, not only at the extremes of life when the CS and about-half-weekly rhythms are particularly prominent in BP and HR but also in interpreting BP responses as a gauge of vascular disease status in adolescents.

Adolescent↗

Kinetic assessment of persistent halogenated xenobiotics in cell culture models: comparison of mono- and poly-halogenated compounds.

We evaluated the suitability of single and multiple cell type cultures as model systems to characterise cellular kinetics of highly lipophilic compounds with potential ecotoxicological impact. Confluent mono-layers of human skin fibroblasts, rat astrocytoma C6 cells, non-differentiated and differentiated mouse 3T3 cells were kept in culture medium supplemented with 10% foetal calf serum. For competitive uptake experiments up to four different cell types, grown on glass sectors, were exposed for 3h to (14)C-labelled model compounds, dissolved either in organic solvents or incorporated into unilamellar lecithin liposomes. Bromo-, or chloro-benzenes, decabromodiphenylether (DBP), and dichlorodiphenyl ethylene (DDE) were tested in rather high concentration of 20 microM. Cellular toxicity was low. Compound levels were related to protein, DNA, and triglyceride contents. Cellular uptake was fast and dependent on physico-chemical properties of the compounds (lipophilicity, molecular size), formulation, and cell type. Mono-halogenated benzenes showed low and similar uptake levels (=low accumulation compounds). DBP and DDE showed much higher cellular accumulations (=high accumulation compounds) except for DBP in 3T3 cells. Uptake from liposomal formulations was mostly higher than if compounds were dissolved in organic solvents. The extent of uptake correlated with the cellular content of triglycerides, except for DBP. Uptake competition between different cell types was studied in a sectorial multi-cell culture model. For low accumulation compounds negligible differences were found among C6 cells and fibroblasts. Uptake of DDE was slightly and that of DBP highly increased in fibroblasts. Well-defined cell culture systems, especially the sectorial model, are appropriate to screen for bioaccumulation and cytotoxicity of (unknown) chemical entities in vitro.

Animals↗

Degradation of di-butyl-phthalate by soil bacteria.

Twelve Gram-positive phthalate ester degraders were isolated from soil. Using Biolog GP2 plates, eight of them were identified as belonging to the Corynebacterium-Mycobacterium-Nocardia group, while the remaining four were unidentifiable. When cultured in the presence of di-butyl-phthalate (DBP) in basal salts solution, five of these isolates accomplished more than 90% of DBP degradation within 48 h (fast group), three were placed in the medium group, and the remaining four were placed in the slow group which caused less than 30% of DBP degradation within the same period of time. A 420 bp DNA fragment was amplified from six isolates and none of them fell within the slow group. When compared with the large subunit of phthalate dioxygenase gene (phtA) of Arthrobacter keyseri, 83% and 91% similarities were evident in the nucleotide and amino acid sequences, respectively. However, no correlation between cell surface hydrophobicity and phthalate degradation ability was evident. Six surfactants (Brij 30, Brij 35, Tergitoltype NP-10, Triton N-101, Triton X-100 and SDS) were tested for their abilities to increase degradation rate. When added at the critical micellar concentration (CMC), they all displayed strong growth inhibition against the three bacteria tested, with Brij 30 been the least toxic to isolates G2 and G11, and Brij 35 had the least inhibitory effect for G1. When half the CMC of Brij 30 was incorporated into the basal salts, the inhibitory effect on DBP degradation remained. Soil helped to minimize surfactant toxicity of surfactant and increase the degradation potential of some of the test bacteria. When DBP-amended soil had been aged for three months, decreases in bioavailability were observed but the effect varied tremendously between different organisms. For isolates G1, G2, G5, G7 and G17 the aging effects were almost non-exist. The present study indicates that selection of a suitable degrader may minimize the undesired effect of aging on bioremediation process.

Adsorption↗

Individual and joint association of alpha1A-adrenergic receptor Arg347Cys polymorphism and plasma irbesartan concentration with blood pressure therapeutic response in Chinese hypertensive subjects.

BACKGROUND: Individual variability in the therapeutic response to an antihypertensive drug could have a genetic basis. We investigated whether the alpha1A-adrenergic receptor (alpha1A-AR) Arg347Cys polymorphism is associated with the blood pressure (BP) therapeutic response to irbesartan and whether the association could be altered by the plasma irbesartan level. METHODS: A total of 696 hypertensive subjects were treated with a daily oral dose of 150 mg irbesartan. Baseline BP was measured before the first dose. On the 28th day, after 27 consecutive days of treatment and an overnight fast, BPs and blood samples were obtained before the morning dose (0 hours) and 6 hours after the morning dose was taken. Plasma irbesartan concentrations were measured by use of HPLC-fluorescence. RESULTS: BP therapeutic response was defined as baseline BP minus BP on the 28th day of irbesartan treatment. Relative to noncarriers, alpha1A-AR Cys347 allelic carriers had a significantly greater diastolic blood pressure (DBP) response at 0 hours (mean +/- SD, 7.5 +/- 8.4 mm Hg versus 5.5 +/- 8.4 mm Hg; P = .016) and at 6 hours (16.2 +/- 9.1 mm Hg versus 14.2 +/- 8.9 mm Hg, P = .025). Although the pattern was similar to the DBP response, alpha(1A)-AR Cys347 allelic carriers had only a moderately increased systolic blood pressure (SBP) response at the 2 time points. When subjects were stratified into subgroups with high or low plasma irbesartan concentrations (with the median value used as the cutoff point), Cys347 allelic carriers in the high-concentration group, relative to noncarriers, had a more pronounced DBP response at 0 hours (adjusted beta [+/- SE], 3.0 +/- 1.0 mm Hg; P = .004) and at 6 hours (adjusted beta, 3.0 +/- 1.2 mm Hg; P = .014), and the same was true for the SBP response at 0 hours (adjusted beta, 5.6 +/- 2.1 mm Hg; P = .006) and at 6 hours (adjusted beta, 4.7 +/- 2.0 mm Hg; P = .021). In contrast, in the low-concentration group, there was no significant association between DBP or SBP responses and Arg347Cys genotypes at 0 hours and 6 hours. CONCLUSION: Our data suggest that the alpha1A-AR Arg347Cys polymorphism is associated with BP response (particularly DBP) to short-term irbesartan treatment. Our data also showed evidence of an interaction between the alpha1A-AR Arg347Cys polymorphism and the plasma level of irbesartan in relation to BP therapeutic response. The association of the Arg347Cys polymorphism with the BP therapeutic response was more pronounced in those patients with higher plasma concentrations of irbesartan.

Aged↗

Use of the median for the evaluation of blood pressure self-measurement (BPSM).

BACKGROUND: One of the disadvantages of blood pressure self-measurement (BPSM) is that it requires doctors to carry out cumbersome calculations involving a large number of figures during the medical visit. Here, we compare the use of median blood pressure values to mean blood pressure values as a diagnostic criterion for home BPSM. METHODS: Self-measurements from 253 patients (51.1+/-12.2 years, 48% male and 52% female) were collected. Sixty-two percent of these patients were receiving antihypertensive treatment. Each patient was given an OMROM 705 monitor to carry out the blood pressure measurements at home. A total of 12 measurements were taken, 2 in the morning and 2 in the afternoon for 3 consecutive days. The mean and median values were calculated for each patient. RESULTS: The median SBP (143.04+/-18.53 mmHg) did not differ from the mean SBP (143.1+/-18.85 mmHg). The same was true for DBP (median 82.25+/-9.56; mean 82.26+/-9.39 mmHg). There were no significant differences in the classification of the patients with regard to whether the median or the mean was used. Some 47.3% of the measurements had a mean SBP below 135 and 79.8% had a mean DBP below 85 mmHg. Using the median, SBP was below 135 in 48.4% of the cases and DBP below 85 in 82.01% of the cases. Differences were not significant. The sensitivity of the median for SBP was 97.0% and the specificity was 97.0%. False-positives were 1.60% and false-negatives 1.18%. The sensitivity of the median for DBP was 94.0% and the specificity was 97.0%. False-positives were 1.18% and false-negatives 3.95%. The kappa coefficient was 0.994 for SBP and 0.882 for DBP. CONCLUSIONS: The median seems to be a valid alternative to the mean in the evaluation of BPSN results, offering good sensitivity and specificity and greater ease of use in daily practice.

Journal Article↗