Discovery of a 25-cm asteroid clast in the giant Morokweng impact crater, South Africa.

Meteorites provide a sample of Solar System bodies and so constrain the types of objects that have collided with Earth over time. Meteorites analysed to date, however, are unlikely to be representative of the entire population and it is also possible that changes in their nature have occurred with time. Large objects are widely believed to be completely melted or vaporized during high-angle impact with the Earth. Consequently, identification of large impactors relies on indirect chemical tracers, notably the platinum-group elements. Here we report the discovery of a large (25-cm), unaltered, fossil meteorite, and several smaller fragments within the impact melt of the giant (> 70 km diameter), 145-Myr-old Morokweng crater, South Africa. The large fragment (clast) resembles an LL6 chondrite breccia, but contains anomalously iron-rich silicates, Fe-Ni sulphides, and no troilite or metal. It has chondritic chromium isotope ratios and identical platinum-group element ratios to the bulk impact melt. These features allow the unambiguous characterization of an impactor at a large crater. Furthermore, the unusual composition of the meteorite suggests that the Morokweng asteroid incorporated part of the LL chondrite parent body not represented by objects at present reaching the Earth.

Racial differences in response to acute dosing with hydrochlorothiazide.

Blacks demonstrate a higher response rate to diuretic therapy for hypertension than do whites. This study examined the pharmacokinetic (PK), pharmacodynamic, and neurohumoral effects of hydrochlorothiazide (HCTZ) administration in a matched group of 9 black and 9 white hypertensive patients (mean +/- SD for black and white). After a 4-week washout period and 7-day control diet, subjects received a single dose of HCTZ (25 mg at 8 AM) with serial blood and urine collections for 36 hours. After HCTZ sodium excretion increased comparably in both groups (blacks: 122 +/- 42 pre to 265 +/- 49 mEq/24 hours post; whites: 117 +/- 29 pre to 255 beta 39 mEq/24 hrs post). Potassium excretion tended to be higher at baseline and was significantly higher following HCTZ in whites (blacks: 45 beta 20 pre to 66 beta 13 mEq at 24 hours post; blacks: 57 +/- 9 pre to 86 +/- 14 mEq at 24 hours post) with most of the post-dosing difference being observed in the hours 0 to 12 after HCTZ. There were no between group PK differences for urinary HCTZ. Aldosterone excretion followed a normal circadian pattern in the whites but did not show this pattern in the blacks. Aldosterone excretion (0 to 12 hours) was generally lower post-dosing in blacks. In conclusion, whereas the PK and single-dose natriuretic response for HCTZ were not racially distinct, potassium excretion was notably less in blacks. Aldosterone excretion was also lower in blacks and without its normal circadian pattern which may, in part, explain their altered potassium excretion pattern.

Effects of candesartan cilexetil in patients with severe systemic hypertension. Candesartan Cilexetil Study Investigators.

The efficacy, tolerability, and safety of the potent angiotensin II receptor blocker candesartan cilexetil were evaluated in 217 adult patients (68% men, 41% black) with severe systemic hypertension on background therapy with hydrochlorothiazide (HCTZ) in a 4-week, multicenter, randomized, double-blind, placebo-controlled study. Patients with sitting diastolic blood pressure (BP) > or =110 mm Hg during the placebo run-in received HCTZ 12.5 mg once daily for 1 week. Those with sitting diastolic BP >95 mm Hg after the HCTZ run-in were randomized (2:1) to receive candesartan cilexetil 8 mg once daily (n = 141) or placebo (n = 76), plus HCTZ 12.5 mg. After 1 week of double-blind treatment, patients with sitting diastolic BP > or =90 mm Hg were uptitrated to candesartan cilexetil 16 mg once daily or matching placebo, plus HCTZ 12.5 mg; 84% required uptitration. Primary efficacy measurement was a change in trough (24+/-3 hours after treatment) sitting diastolic BP from the end of the HCTZ run-in to double-blind week 4. Mean changes in systolic and diastolic BP were significantly greater with candesartan cilexetil than with placebo, -11.3/-9.1 mm Hg versus -4.1/-3.1 mm Hg, p <0.001/p <0.001, respectively. Patients with higher sitting diastolic BP at the end of the HCTZ run-in tended to have greater decreases in BP (p <0.05). Most patients (53%) receiving candesartan cilexetil were responders (diastolic BP <90 mm Hg or > or =10 mm Hg decrease) and 32% were controlled (diastolic BP <90 mm Hg). Tolerability and safety profiles were similar in the candesartan and placebo groups. In conclusion, candesartan cilexetil 8 to 16 mg once daily was an effective and well-tolerated therapy for lowering BP when added to HCTZ 12.5 mg in a diverse population of patients with severe systemic hypertension in the United States.

Simple method for determination of hydrochlorothiazide in human urine by high performance liquid chromatography utilizing narrowbore chromatography.

A simple high performance liquid chromatographic (HPLC) method utilizing narrowbore chromatography was developed for the determination of hydrochlorothiazide in human urine. A mobile phase of 0.1% aqueous acetic acid--acetonitrile (93:7, v/v) pH 3 was used with a C18 analytical column and ultraviolet detection (UV). The method demonstrated linearity from 2 to 50 micrograms ml-1 using 50 microliters of urine with a detection limit of 1 microgram ml-1. The method was utilized in a study evaluating if racial differences are present in the pharmacokinetic and pharmacodynamic effects of hydrochlorothiazide.

Pharmacokinetics of sematilide in renal failure.

A randomized, two-period, two-treatment study was conducted to investigate the effect of renal impairment on the pharmacokinetics of the Class III antiarrhythmic sematilide HCl. The pharmacokinetic-pharmacologic effect relationship and tolerability of sematilide HCl were also studied. The study included 22 subjects: 6 healthy volunteers and 16 patients with various degrees of renal impairment, including functionally anephric patients on intermittent hemodialysis. Separated by a 14-day washout period, the subjects received a constant rate intravenous infusion of 40 mg sematilide HCl over 30 minutes and a tablet containing 100 mg of the drug. The functionally anephric patients were studied during and off dialysis after intravenous and oral administration of the drug, respectively. Blood and urine samples were collected at defined times up to 48 hours and 72 hours, respectively, after administration. Sematilide concentrations in plasma, urine, and dialysate were measured by a validated high-performance liquid chromatography (HPLC) method with ultraviolet detection. The pharmacokinetic data analysis used a compartment model independent approach. The heart rate-corrected Lead II QT interval was recorded as a pharmacologic endpoint. Subjective symptoms, cardiovascular parameters, routine serum chemistry, and hematology and urinalysis parameters were measured to assess tolerability. Mean renal clearance after intravenous and oral administration was reduced in patients with severe renal impairment. Statistically significant linear correlations existed between total clearance of sematilide and creatinine clearance for all subjects who could be evaluated after both intravenous and oral administration. Steady-state volume of distribution, absolute bioavailability, and nonrenal clearance of sematilide were independent of renal function. The mean dialysis clearance was 98 mL/min, indicating effective removal of the drug by hemodialysis. In accord with the drug's Class III pharmacologic activity, the heart rate corrected Lead II QT intervals were prolonged in all subjects after intravenous and oral administration of the drug. The pharmacologic effect to plasma concentration relationship in renal patients and in healthy subjects was comparable. Based on the experimentally determined linear relationship between total clearance of sematilide and creatinine clearance, modified dose regimens for sematilide HCl in patients with renal impairment and functionally anephric patients off hemodialysis were developed.

Drought as a natural disaster

Droughts are major natural disasters for many parts of the world. Dry areas, where the precipitation pattern is markedly seasonal, or is otherwise highly variable, are the most susceptible. The Canadian Prairies, together with the U.S. Great Plains, are one such area. While immediate loss of life is seldom a feature of most droughts, malnutrition and even starvation do follow severe droughts in some parts of the world. In Canada, economic losses, particularly in the agricultural sector, may reach several hundred millions of dollars in a drought year, with major socio-economic repercussions affecting the entire region. Environmental damages include soil degradation and erosion, vegetation damage, slough and lake deterioration and wildlife loss. Unlike most other natural disasters, drought onset is difficult to identify. Droughts develop slowly, and until human activity begins to be affected by an on-going reduction of precipitation, their existence is unrecognized. Development and applications of specific soil moisture and drought indices based on cumulative precipitation deficits have enhanced drought monitoring programs. These in turn provide guidance on the need for mitigate measures that can be initiated early in the course of a drought.(AU)

Saccharification, fermentation, and protein recovery from low-temperature AFEX-treated coastal bermudagrass.

Coastal bermudagrass was pretreated by a low-temperature ammonia fiber explosion (AFEX) process, which soaked the grass in liquid ammonia and then explosively released the pressure. Saccharifying enzymes were systematically applied to the AFEX-treated grass corresponding to low, medium, and high loadings of cellulase/hemicellulase (from Trichoderma reesei), cellobiase, glucoamylase, and pectinase. Three-day sugar yields linearly correlated with the logarithm of the cellulase loading. Supplemental enzymes (cellobiase, pectinase) caused upward shifts in the lines. The linearity and upward shifts are consistent with the HCH-1 model of cellulose hydrolysis. The hydrolysis sugars were converted to ethanol using yeast (Saccharomyces cerevisiae). The solid residues were treated with proteases to attempt recovery of valuable proteins. The low-temperature AFEX pretreatment was able o nearly double sugar yields. At the highest cellulase loadings (30 IU/g), the best reducing sugar and ethanol yields were 53% and 44% of the maximum potential, respectively. Protein recovery was, at most, 59%.

Hormonal, blood pressure, and peritoneal transport response to short-term ACE inhibition.

OBJECTIVES: To evaluate the hormonal, blood pressure, and peritoneal transport effects of intraperitoneal enalaprilat and oral enalapril. DESIGN: A nonrandomized, nonblinded, prospective clinical trial was performed. SETTING: The study was conducted at the Clinical Research Unit at the Medical College of Virginia, a tertiary care center. PATIENTS: Six continuous ambulatory peritoneal dialysis (CAPD) patients with hypertension were enrolled in the study. All 6 patients received intraperitoneal enalaprilat. Five of the patients also received oral enalapril. INTERVENTIONS: Hormonal, clinical, and transport parameters were investigated in patients given intraperitoneal enalaprilat and oral enalapril. Standardized 2-L exchanges were performed during a control period, following 2.5 mg intraperitoneal enalaprilat and after a week of oral enalapril. Inulin, blood urea nitrogen (BUN) and creatinine clearances, and glucose absorption were determined during these exchanges. RESULTS: After intraperitoneal enalaprilat, both systolic and diastolic blood pressure significantly declined, reaching maximal decreases of -21.7 +/- 14.2% at 95 +/- 92 minutes, and of -23.3 +/- 15.4% at 105 +/- 105 minutes, respectively. Plasma angiotensin converting enzyme (ACE) activity was suppressed below detectable limits at four hours following intraperitoneal enalaprilat, and remained suppressed throughout all sampling time points following oral enalapril treatment. There was no significant change in drain volumes, glucose absorption, or BUN, creatinine, or inulin clearances, whether enalaprilat was administered intraperitoneally or enalapril orally. CONCLUSION: This study demonstrates that intraperitoneal administration of enalaprilat is a rapidly effective route of administration of this ACE inhibitor. There were no changes in peritoneal transport characteristics demonstrated.

The effect of nonsteroidal agents (NSAIDs) on the pharmacokinetics and pharmacodynamics of metolazone.

NSAIDs attenuate the natriuretic response to loop diuretics. Their effect on the action of distal tubular diuretics is poorly explored. Accordingly, the pharmacokinetics and pharmacodynamics of metolazone [M], a distal tubular diuretic, with and without indomethacin [M+I] or sulindac [M+S] were examined in six healthy volunteers. Urine samples were obtained over 36 hours post-metolazone dosing for the determination of sodium, potassium and metolazone concentration. Though cumulative M excretion 750 +/- 247 [mucg/36 h] [M]; 749 +/- 239 [M+I]; 848 +/- 443 [M+S] was comparable between treatment groups, total sodium [Na+] excretion was significantly depressed in the presence of S or I, 685 +/- 114 [mEq/36 h] [M]; 454 +/- 90 [M+I] (p < or = 0.05); 553 +/- 123 [M+S] (p < or = 0.05). Peak Na+ excretion [muEq/min] was significantly decreased by I only and time to peak Na+ excretion did not differ amongst treatment groups. Total potassium [K+] excretion 160 +/- 39 [mEq/36 h] [M]; 111 +/- 53 [M+I] (p < or = 0.05); 135 +/- 31 [M+S] significantly decreased with I. This phenomenon was most evident between 12 and 36 hours. The administration of I or S with M significantly blunted sodium excretion on a purely pharmacodynamic basis while the decline in urinary potassium excretion upon addition of I to M related probably to an attenuation of braking phenomenon induced kaliuresis. These findings likely reflect NSAID-induced sodium reabsorption at loci prior to the site of action of metolazone.