Heterogeneous mass distribution of the rubble-pile asteroid (101955) Bennu.

The gravity field of a small body provides insight into its internal mass distribution. We used two approaches to measure the gravity field of the rubble-pile asteroid (101955) Bennu: (i) tracking and modeling the spacecraft in orbit about the asteroid and (ii) tracking and modeling pebble-sized particles naturally ejected from Bennu's surface into sustained orbits. These approaches yield statistically consistent results up to degree and order 3, with the particle-based field being statistically significant up to degree and order 9. Comparisons with a constant-density shape model show that Bennu has a heterogeneous mass distribution. These deviations can be modeled with lower densities at Bennu's equatorial bulge and center. The lower-density equator is consistent with recent migration and redistribution of material. The lower-density center is consistent with a past period of rapid rotation, either from a previous Yarkovsky-O'Keefe-Radzievskii-Paddack cycle or arising during Bennu's accretion following the disruption of its parent body.

Gaining insights into reactive fluid-fractured rock systems using the temporal moments of a tracer breakthrough curve.

In this paper, we show that the tracer breakthrough curves (BTCs), when the tracer chemically interacts with the solid matrix of a fractured rock, are considerably different than when it does not. Of particular interest, is the presence of a long pseudo steady state zone in the BTCs, where the tracer concentration is more or less constant over a long period of time. However, such a zone of constant concentration is not visible when either the tracer does not interact with the solid, or does so at an extremely fast rate. We show that these characteristics of the BTCs could be correlated to the parameters of the system. We develop expressions for the mean residence time and its variance for a chemically active and inactive tracer. We show that chemical interaction between the tracer and the solid increases the mean residence time and the increase depends on the distribution coefficient. We also show that the variance of residence time for a chemically active tracer is much larger than that for an inactive tracer, and it depends on both the distribution coefficient and the rate of chemical reaction. We verify these calculations against synthetic tracer BTCs, where the temporal moments are calculated by numerically integrating the tracer evolution curves. Even though we developed the mathematical expressions assuming an idealized fracture-matrix system, we believe that the mathematical expressions developed in this paper can be useful in gaining insights into reactive transport in a real fractured rock system.

Impact of fluid-rock chemical interactions on tracer transport in fractured rocks.

In this paper, we investigate the impact of chemical interactions, in the form of mineral precipitation and dissolution reactions, on tracer transport in fractured rocks. When a tracer is introduced in fractured rocks, it moves through the fracture primarily by advection and it also enters the stagnant water of the surrounding rock matrix through diffusion. Inside the porous rock matrix, the tracer chemically interacts with the solid materials of the rock, where it can precipitate depending on the local equilibrium conditions. Alternatively, it can be dissolved from the solid phase of the rock matrix into the matrix pore water, diffuse into the flowing fluids of the fracture and is advected out of it. We show that such chemical interactions between the fluid and solid phases have significant impact on tracer transport in fractured rocks. We invoke the dual-porosity conceptualization to represent the fractured rocks and develop a semi-analytical solution to describe the transient transport of tracers in interacting fluid-rock systems. To test the accuracy and stability of the semi-analytical solution, we compare it with simulation results obtained with the TOUGHREACT simulator. We observe that, in a chemically interacting system, the tracer breakthrough curve exhibits a pseudo-steady state, where the tracer concentration remains more or less constant over a finite period of time. Such a pseudo-steady condition is not observed in a non-reactive fluid-rock system. We show that the duration of the pseudo-state depends on the physical and chemical parameters of the system, and can be exploited to extract information about the fractured rock system, such as the fracture spacing and fracture-matrix interface area.

Recruitment and baseline characteristics of participants in the Dietary Approaches to Stop Hypertension trial. DASH Collaborative Research Group.

Dietary Approaches to Stop Hypertension (DASH) was a randomized, multicenter feeding study designed to assess the effects of modifying dietary patterns on blood pressure. Among the most challenging aspects of conducting the DASH trial was the recruitment of participants at the 4 clinical centers. As part of the recruitment drive, 347,500 brochures were mailed, 250,500 coupons were distributed in coupon packs, 114 advertisements were published in newspapers or bulletins, 140 radio and 74 television advertisements were broadcast, and 68 screening events and presentations were conducted. These efforts yielded a total of 459 enrolled participants, ahead of schedule. The most common source of participants was mass mailing of individual brochures (n = 194, 42.3%), followed by word-of-mouth (n = 82, 17.8%), and then other types of mass mailing (n = 44, 9.6%). Recruitment of minority participants followed a similar pattern. Among the 3,192 persons attending the first in-person screening visit, the major reason for nonenrollment was low blood pressure (56%) rather than a diet-related factor. The study population was demographically heterogeneous (49% women, 60% African American, 48% married, and 77% employed full-time). On average, the diet of participants before the DASH feeding study was more similar to the trial control diet than to the combination diet, which reduced blood pressure more effectively. In summary, recruitment of a heterogeneous study population that includes a substantial number of minority participants is a feasible undertaking. However, the effort is considerable and requires a major commitment of resources.

Effects of dietary patterns on blood pressure: subgroup analysis of the Dietary Approaches to Stop Hypertension (DASH) randomized clinical trial.

OBJECTIVE: To determine the effects of dietary patterns on blood pressure in subgroups. METHODS: Dietary Approaches to Stop Hypertension (DASH) was a randomized controlled feeding study conducted at 4 academic medical centers. Participants were 459 adults with untreated systolic blood pressure less than 160 mm Hg and diastolic blood pressure 80 to 95 mm Hg. For 3 weeks, participants were fed a "control" diet. They were then randomized to 8 weeks of (1) control diet; (2) a diet rich in fruits and vegetables; or (3) a combination diet rich in fruits, vegetables, and low-fat dairy foods, and reduced in saturated fat, total fat, and cholesterol (the DASH combination diet). Weight and salt intake were held constant. Change in diastolic blood pressure was the primary outcome variable, and systolic blood pressure a secondary outcome. Subgroups analyzed included race, sex, age, body mass index, years of education, income, physical activity, alcohol intake, and hypertension status. RESULTS: The combination diet significantly lowered systolic blood pressure in all subgroups (P<.008), and significantly lowered diastolic blood pressure (P<.01) in all but 2 subgroups. The fruits-and-vegetables diet also reduced blood pressure in the same subgroups, but to a lesser extent. The combination diet lowered systolic blood pressure significantly more in African Americans (6.8 mm Hg) than in whites (3.0 mm Hg), and in hypertensive subjects (11.4 mm Hg) than in nonhypertensive subjects (3.4 mm Hg) (P<.05 for both interactions). CONCLUSIONS: The DASH combination diet, without sodium reduction or weight loss, significantly lowered blood pressure in virtually all subgroups examined, and was particularly effective in African Americans and those with hypertension. The DASH combination diet may be an effective strategy for preventing and treating hypertension in a broad cross section of the population, including segments of the population at highest risk for blood pressure-related cardiovascular disease.

Pharmacokinetics of bambuterol in healthy subjects.

AIMS: To study the pharmacokinetics and bioavailability of the prodrug bambuterol and its bronchodilator moiety terbutaline in healthy subjects. METHODS: Eight healthy subjects (four women) received intravenous doses of bambuterol and terbutaline. On a third occasion, they, plus another four subjects, ingested oral bambuterol as a single dose followed by repeated doses once daily for 7 days. Plasma concentrations and urinary excretion of bambuterol and terbutaline were measured. RESULTS: After intravenous administration, renal clearances of bambuterol and terbutaline were similar (about 140 ml min(-1)), but there was a five-fold difference in total clearance (bambuterol 1.25 l min(-1), terbutaline 0.23 l min(-1)). Volume of distribution (Vss) was 1.6 l kg(-1) b.w. for both substances. A similar renal clearance of bambuterol was found during oral administration but that of terbutaline decreased (to about 120 ml min(-1)). Mean terminal half-life of bambuterol was 2.6 h after intravenous and 12 h after oral administration, implying that uptake was rate-limiting. Mean residence time of terbutaline generated from oral bambuterol was 34 h compared with 8.0 h when terbutaline as such was infused. Generated terbutaline had a bioavailability of 36% (28-46) after intravenous and 10.2% (6.1-13.2) after oral administration of the prodrug. Bambuterol was well tolerated. The mean activity of plasma cholinesterase, an enzyme catalyzing bambuterol metabolism, was inhibited between 30-60% during repeated oral dosing. It virtually regained original activity within 48 h after the last dose. CONCLUSIONS: The plasma concentration ofterbutaline fluctuated little during repeated oral administration (mean peak: trough ratio 1.9), as a result of prolonged absorption of bambuterol and slow formation of terbutaline. Thus, the pharmacokinetic properties of bambuterol make it suitable for oral once-daily dosage.

Relative absorption of the two enantiomers of terbutaline after duodenal administration.

The absorption of the two enantiomers of terbutaline, (+)-terbutaline and (-)-terbutaline, and of the racemate, (+/-)-terbutaline, has been studied in six healthy volunteers using a newly developed intestinal perfusion technique. The area under the plasma concentration curve for the (-)-enantiomer was more than twice that for the (+)-enantiomer. The data demonstrate a clear difference in absorption efficiency between (-)- and (+)-terbutaline, but further studies are required to establish whether (-)-terbutaline influences the absorption of (+)-terbutaline.

Determination of terbutaline enantiomers in biological samples using liquid chromatography with coupled columns.

The purpose of this work was to develop and validate a method for the separation and determination of the enantiomers of terbutaline in plasma and intestinal juice. Terbutaline was extracted from plasma and intestinal juice by liquid-solid extraction on small C18 cartridges. The extract was then analyzed by coupled column liquid chromatography with amperometric detection. For chiral separation a beta-cyclodextrin phase was used. The within-day variation (Cv) on spiked plasma samples was in the range 0.8-6.4% at 3.8-33.8 nmol/liter for the (-)-enantiomer, and 2.6-23.0% at 1.3-11.3 nmol/liter for the (+)-enantiomer. The between-day variation on spiked plasma samples was 5.5% at 10.7 nmol/liter and 13.6% at 4.3 nmol/liter for the (-)-and (+)-enantiomers, respectively. The within-day variation for intestinal juice was in the range 0.7-1.5% at 5.6-30.0 mumol/liter for the (+)-enantiomer.

Pharmacokinetics of terbutaline given in slow-release tablets.

Three pharmacokinetic studies of terbutaline slow-release (SR) tablets, 5 and 7.5 mg, were performed in healthy subjects. Four men and 4 women volunteered for each study. Bricanyl plain tablets were used as reference formulation. Both single- and multiple-dose treatments were performed. For repeated administration, SR tablets were given every 12 h. Plain tablets were given every 8 h in two studies and every 12 h in one. Steady-state bioavailability correlated with the amount dissolved in vitro (paddle method) in 6 h. Single-dose bioavailability was limited by the amount dissolved in 4 h. The difference may have a pharmacological explanation, in that repeated administration of a sympathomimetic drug is known to decrease gastro-intestinal motility. Tablets of both strengths with an intermediate dissolution rate were extensively tested. Plasma concentrations and the rates of urinary excretion of unchanged terbutaline were measured. Mean relative bioavailability compared with plain tablets was 76-77% with 7.5 mg SR tablets and 74-80% with those of 5 mg. Variation in bioavailability between and within subjects was the same or smaller with the SR tablets. They gave smoother plasma concentration profiles with delayed peaks and the same peak/trough concentration ratios as the plain tablets, despite less frequent dosing. However, objectively measured side-effects were not significantly reduced. Measurements after cessation of treatment gave terminal half-lives in plasma of 11.5-23.0 h which is considerably longer than reported in the literature. Renal clearance averaged 140 mL/min, similar to predicted creatinine clearance. From these studies it is concluded that the main advantage with the SR tablets is the twice-daily dosage regimen. This should increase compliance, facilitate combination therapy with prolonged-action formulations of other drugs and better maintain therapeutic levels during the whole night interval.

Multidimensional column liquid chromatography with electrochemical detection for the analysis of terbutaline in human plasma.

Because of low drug concentrations and complex nature of the sample, analytical methods with sensitive and selective detection are necessary for pharmacokinetic studies of terbutaline. Up to now, for non-radiolabelled drugs, usually only methods based on gas chromatography plus mass spectrometry have met these requirements. As an alternative, we have developed an automated method based on liquid chromatography. The necessary sensitivity and selectivity were obtained by using electrochemical detection and a microprocessor-controlled column switching system. The accuracy of the method was compared with a method based on gas chromatography plus mass spectrometry. The overall precision expressed as per cent of the mean was +/- 3.5% and +/- 2.2% at 5 and 50 pmol/mL, respectively. The total absolute recovery for terbutaline and internal standard at these concentration levels were in the range 85-106%.

Relative bioavailability of zinc using weight gain of rats.

Weanling rats were fed semi-purified diets with varying zinc levels in order to derive new measures of relative bioavailability of zinc (RBAZ). The various measures for RBAZ were slope-ratio assays of weight gain, total liver zinc and total femur zinc along with five alternative measures developed from sigmoidal curves for weight gain estimated by a non-linear, least-squares curve fitting computer program. The slopes of weight gains explained a higher proportion of the true measure than similar slopes of femurs or livers as indicated by R2. The 95% confidence intervals of ratios were narrowest for weight gain assays. Four of the five alternative methods had RBAZ similar to the RBAZ of slope-ratio weight gain assays. These new methods provided a diversity of information and allowed more information to be obtained than from slope-ratio assays alone.

Relative bioavailability of zinc from selected cereals and legumes using rat growth.

The relative bioavailability of zinc (RBAZ) in corn, rice, wheat and legumes was determined by the ratio of net weight gains a 6 ppm of added zinc, a measure derived from sigmoidal curves for weight gain estimated by a non-linear, least-squares curve fitting computer program. Each food was prepared as for human consumption, incorporated into a semi-purified diet to provide varying levels of zinc and fed to weanling rats. Among cereals, whole corn and brown rice had low RBAZ (0.58 or less), while whole wheat flour and unleavened whole wheat bread had medium values (0.63-0.74). Refined cereal grains, such as white flour, leavened and unleavened white bread and white rice, had high RBAZ (0.89-1.08) as did leavened whole wheat bread (1.04). Of the legumes, lima beans had a high RBAZ (0.84) while white beans had a medium value (0.74). Phytic acid content of the foods, but not neutral-detergent fiber content, appeared to be inversely related to RBAZ, more so among the cereals than with the legumes.

Composition of miner's lettuce (Montia perfoliata).

Miner's lettuce, a wild, edible plant that grows prolifically in the western U.S., was analyzed for proximate composition, vitamins, minerals, and oxalic and phytic acids. In the raw state, it contained 20 kcal per 100 gm, and 33 per cent of the adult U.S. RDA for ascorbic acid, 22 per cent of the vitamin A allowance, and 10 per cent of the iron. Oxalic acid concentration was low. Nutrient density ratios, compared with 100 kcal of the U.S. RDAs, were greater than one for all constituents analyzed. In terms of nutrient content, miner's lettuce also compared favorably with twenty-one other green, leafy vegetables.

Conjugated catechol derivatives in a transplantable islet cell tumour of the golden hamster.

Two glucuronidated catechol have been identified in a transplantable islet cell tumour of the golden hamster, i.e. dopamine-4-O-glucuronide and 3-methoxytyramine-4-O-glucuronide. L-dopa is rapidly metabolized in the tumour to one or both of these glucuronides. Incubation of tumour homogenates in the presence of beta-glucuronidase shows that dopamine-4-O-glucuronide is present in the tumour in extremely high concentrations.

Formation of cysteinyldopa from glutathionedopa in melanoma.

Glutathionedopa injected intravenously into mice is metabolized and excreted in the urine as a compound with the fluorescence characteristics of cysteinyldopa. Glutathionedopa incubated with a guinea-pig kidney homogenate is metabolized to a compound with the fluorescence characteristics of cysteinyldopa. Boiling of the kidney homogenate prevents the metabolism of glutathionedopa. Incubation of glutathionedopa with a homogenate of a melanoma metastasis led to the formation of a compound with the fluorescence characteristics of cysteinyldopa. Boiling of the melanoma homogenate prevented the metabolism of glutathionedopa. Large amounts of glutathione added to the incubate inhibited the reaction. Lung tissue and blood plasma had no detectable ability to metabolize glutathionedopa. The results show that human melanoma contains one or several enzymes capable of metabolizing glutathionedopa to a smaller dopathioether, probably cysteinyldopa. Such enzymes seem to be normally present in mice and guinea-pigs and have been demonstrated in the guinea-pig kidney.