The anisotropy in the optical constants of quartz crystals for soft X-rays.

The refractive index of a y-cut SiO2 crystal surface is reconstructed from orientation-dependent soft X-ray reflectometry measurements in the energy range from 45 to 620 eV. Owing to the anisotropy of the crystal structure in the (100) and (001) directions, a significant deviation of the measured reflectance at the Si L 2,3 and O K absorption edges is observed. The anisotropy in the optical constants reconstructed from these data is also confirmed by ab initio Bethe-Salpeter equation calculations for the O K edge. This new experimental data set expands the existing literature data for quartz crystal optical constants significantly, particularly in the near-edge regions.

Bethe-Salpeter equation calculations of core excitation spectra.

We present a hybrid approach for Bethe-Salpeter equation (BSE) calculations of core excitation spectra, including x-ray absorption (XAS), electron energy loss spectra (EELS), and nonresonant inelastic x-ray scattering (NRIXS). The method is based on ab initio wave functions from the plane-wave pseudopotential code ABINIT; atomic core-level states and projector augmented wave (PAW) transition matrix elements; the NIST core-level BSE solver; and a many-pole self-energy model to account for final-state broadening and self-energy shifts. Multiplet effects are also approximately accounted for. The approach is implemented using an interface dubbed OCEAN (Obtaining Core Excitations using ABINIT and NBSE). To demonstrate the utility of the code we present results for the K edges in LiF as probed by XAS and NRIXS, the K edges of KCl as probed by XAS, the Ti L2,3 edge in SrTiO3 as probed by XAS, and the Mg L2,3 edge in MgO as probed by XAS. These results are compared with experiment and with other theoretical approaches.

Many-Pole Model of Inelastic Losses Applied to Calculations of XANES.

Conventional Kohn-Sham band-structure methods for calculating deep-core x-ray spectra typically neglect photoelectron self-energy effects, which give rise to an energy-dependent shift and broadening of the spectra. Here an a posteriori procedure is introduced to correct for these effects. The method is based on ab initio calculations of the GW self-energy using a many-pole model and a calculation of the dielectric function in the long wavelength limit using either the FEFF8 real-space Green's function code, or the AI2NBSE interface between the National Institute of Standards and Technology (NIST) Bethe-Salpeter equation solver (NBSE) and the ABINIT pseudopotential code. As an example the method is applied to core level x-ray spectra of LiF and MgAl2O4 calculated using (respectively) OCEAN, an extension of the AI2NBSE code for core level excitations, and the PARATEC pseudopotential code with the core-hole treated using a super-cell. The method satisfactorily explains the discrepancy between experiment and calculations.

Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: a Hoosier Oncology Group phase II trial.

BACKGROUND: Gefitinib has demonstrated activity in patients with non-small cell lung cancer (NSCLC). Clinical trials have not demonstrated a relationship between response to gefitinib and over-expression of the epidermal growth factor receptor (EGFR). Although, EGFR is not over-expressed in small cell lung cancer (SCLC), we postulated that gefitinib might affect tumor growth through other mechanisms. Agents that are active in NSCLC usually are also effective in SCLC. METHODS: The primary objective was to assess the clinical control rate: complete response (CR) partial response (PR) and stable disease (SD > 90 days), of gefitinib in patients with chemo-resistant and chemo-sensitive small cell cancers. Eligibility criteria included pathologic proof of a neuroendocrine tumor, especially small cell cancer, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, prior treatment with one or two prior chemotherapy regimens and adequate end-organ function. Patients received gefitinib, 250 mg p.o. daily until disease progression or intolerable side effects. RESULTS: From April 2003 to March 2004, 19 patients were enrolled. Small cell lung cancer accounted for 18 of the 19 patients and one patient had metastatic Merkel cell carcinoma. Twelve patients (63%) had chemo-sensitive disease, defined as progression greater than three months from completion of prior chemotherapy; 7 (37%) had chemo-refractory disease; 13 (68%) had one prior chemotherapy regimen. Other patient characteristics: mean age 64 years (range 52-79 years); ECOG PS 0/1/2 = 7/9/3, M:F = 9:10. Grade 3 toxicities included: fatigue in three patients (15.8%), pulmonary toxicities in three (15.8%) and one patient (5.3%) each with hyperglycemia or pain. Four patients had grade four toxicities: one patient (5.3%) with fatigue and three patients (15.8%) with dyspnea. There were no patients with grade 3 or 4 rash or diarrhea. Two patients had stable disease (<90 days) and 17 had progressive disease as their best response. This study was a two-stage design and because the continuing criterion for stage one was not met, stage 2 was not performed. Median time to progression (TTP) was 50 days (95% CI = 21-58 days). One year overall survival (OS) was 21% (95% CI = 6-45.6%). CONCLUSION: Although gefitinib has activity in select patients with NSCLC, this study failed to demonstrate benefit in patients with small cell lung cancer.

Effect of Aloe vera preparations on the human bioavailability of vitamins C and E.

There are no literature references describing the effect of consumption of Aloe vera liquid preparations on the absorption of water- or fat-soluble vitamins. There is a very large population worldwide which consume vitamins and many people also consume Aloe. Thus we report the effect of Aloe on the human absorption of vitamins C and E, the most popular vitamin supplements. The plasma bioavailability of vitamins C and E were determined in normal fasting subjects, with eight subjects for vitamin C and ten subjects for vitamin E. In a random crossover design, the subjects consumed either 500 mg of ascorbic acid or 420 mg of vitamin E acetate alone (control), or combined with 2 oz of two different Aloe preparations (a whole leaf extract, or an inner fillet gel). Blood was collected periodically up to 24 h after consumption. Plasma was analyzed for ascorbate and tocopherol by-HPLC with UV detection. There was no significant difference in the areas under the plasma ascorbate-time curves among the groups sincerely due to large differences within the groups. For comparative purposes the control area was 100%. The Aloe Gel area was 304%, and Aloe Whole Leaf 80%. Only Aloe Gel caused a significant increase in plasma ascorbate after 8 and 24 h. For vitamin E, the results for the relative areas were control 100%, Gel 369%, and Leaf (198%). Only the Aloes produced a significant increase in plasma tocopherol after 6 and 8 h. Both Aloes were significantly different from the control after 8 h. Aloe Gel was significantly different from the baseline after 24 h. The Aloes slowed down the absorption of both vitamins with maximum concentrations 2-4 h later than the control. There was no difference between the two types of Aloe. The results indicate that the Aloes improve the absorption of both vitamins C and E. The absorption is slower and the vitamins last longer in the plasma with the Aloes. Aloe is the only known supplement to increase the absorption of both of these vitamins and should be considered as a complement to them.

Alcohol: Friend or Foe? Alcoholic Beverage Hormesis for Cataract and Atherosclerosis is Related to Plasma Antioxidant Activity.

OBJECTIVES: To correlate the oxidative state of postabsorptive blood plasma after consumption of one or three drinks of different beverages with known J-shaped epidemiological risk curves. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Red wine, lager beer, stout (alcoholic and alcohol-free), with antioxidant activity, and an aqueous solution of alcohol were compared for the plasma antioxidant or pro-oxidant activity in human volunteers following consumption of one or three typical drinks containing equivalent amounts of alcohol (except for an alcohol-free stout used as a control for stout). RESULTS: One drink of red wine, lager beer, or stout (5% alcohol v/v, and alcohol-free) significantly increased the average antioxidant activity in plasma samples obtained from volunteers averaged over 240 min. Three drinks of red wine, lager beer, or stout (5% alcohol v/v, and alcohol-free) significantly increased the average pro-oxidant activity in plasma samples obtained from volunteers averaged over 360 min. For a solution of alcohol, three drinks resulted in pro-oxidant plasma on average, whereas while one drink did not significantly affect the plasma oxidative status. A preliminary experiment in which two volunteers showed a significantly increased time to metabolize ethanol after ingestion resulted in elevated antioxidant activity in plasma for lager beer and red wine. CONCLUSIONS: One drink of red wine, beer, or stout provided equivalent increases in plasma antioxidant activity. Three drinks of red wine, beer, or stout provided equivalent increases in plasma pro-oxidant activity. This may explain, at least in part, the decreased risk of cataract and atherosclerosis from daily consumption of one drink of different types of alcoholic beverages as well as the increased risk from daily consumption of three drinks of alcoholic beverages. The plasma pro-oxidant activity appears to be due to ethanol metabolism, whereas the antioxidant activity may be due to the absorption of polyphenols in the beverages.

Beneficial effects of a novel IH636 grape seed proanthocyanidin extract and a niacin-bound chromium in a hamster atherosclerosis model.

Atherosclerosis is a disease of the arteries in which fatty plaques develop on the inner arterial wall, which eventually obstructs blood flow. Identified risk factors for atherosclerosis include genetics, diet, lifestyle, smoking, circulating lipid and cholesterol levels, and molecular and circulating signals of chronic vascular inflammation. The link between flavonoids and atherosclerosis is based partly on the evidence that some flavonoids possess antioxidant properties and have been shown to be potent inhibitors of LDL oxidation in vitro. Hypercholesterolemia, a significant cardiovascular risk factor is prevalent in the American population. Grape seed proanthocyanidin extracts are known to exhibit a broad spectrum of chemopreventive and cardioprotective properties against oxidative stress. A recent study has shown that a combination of IH636 grape seed proanthocyanidin extract (GSPE) and a niacin-bound chromium (NBC) can decrease total cholesterol, LDL and oxidized LDL levels in hypercholesterolemic human subjects. In this study, we assessed the efficacy of GSPE supplementation in hamsters, singly and in combination with NBC, since these animals have a similar lipid profile to hypercholesterolemic humans when fed a hypercholesterolemic diet of 0.2% cholesterol and 10% coconut oil (HCD). After 10 weeks of feeding HCD, these animals developed foam cells, which is a biomarker of early stages of atherosclerosis. Atherosclerosis (% of aorta covered with foam cells) was reduced by approximately 50% and 63% following supplementation of these animals with 50 mg/kg and 100 mg/kg of GSPE, respectively, in conjunction with a HCD, while approximately 32% reduction was observed following supplementation of GSPE plus NBC. A range of 7-9 animals was used in each study group. GSPE alone and in combination with NBC exerted a pronounced effect on the cholesterol, and triglyceride levels, as well as oxidative lipid damage as demonstrated by the formation of thiobarbituric acid reactive substances (TBARS). This data demonstrates that GSPE and NBC may provide significant health benefits by dramatically ameliorating the incidence of atherosclerosis as demonstrated by reducing the formation of foam cells.

Measurement of arsenic bioavailability in soil using a primate model.

Several studies have shown limited absorption of arsenic from soils. This has led to increased interest in including measurements of arsenic relative bioavailability from soils in the calculation of risks to human health posed by arsenic-contaminated sites. Most of the information in the literature regarding arsenic bioavailability from soils comes from studies of mining and smelter sites in the western United States. It is unclear whether these observations are relevant to other types of arsenic-contaminated sites. In order to obtain information regarding arsenic bioavailability for other types of sites, relative bioavailability of arsenic from selected soil samples was measured in a primate model. Sodium arsenate was administered to five male Cebus apella monkeys by the intravenous and oral routes, and blood, urine, and feces were collected. Pharmacokinetic behavior of arsenic after intravenous administration and the fractions of dose excreted in urine and feces after both intravenous and oral doses were consistent with previous observations in humans. Soil samples from five waste sites in Florida (one from an electrical substation, one from a wood preservative treatment site, two from pesticide sites, and one from a cattle-dip vat site) were dried and sieved. Soil doses were prepared from these samples and administered orally to the monkeys. Relative bioavailability was assessed based on urinary excretion of arsenic following the soil dose compared with excretion following an oral dose of arsenic in solution. Differences in bioavailability were observed for different sites, with relative bioavailability ranging from 10.7 +/- 4.9% (mean +/- standard deviation) to 24.7 +/- 3.2% for the five soil samples. These observations, coupled with data in the literature, suggest limited oral bioavailability of arsenic in soils from a variety of types of arsenic-contaminated sites.

Phenol antioxidant quantity and quality in foods: fruits.

The free and bound phenols have been measured in 20 fruits commonly consumed in the American diet. Phenols were measured colorimetrically using the Folin-Ciocalteu reagent with catechin as the standard after correction for ascorbic acid contribution. On a fresh weight basis, cranberry had the highest total phenols, and was distantly followed by red grape. Free and total phenol quality in the fruits was analyzed by using the inhibition of lower density lipoprotein oxidation promoted by cupric ion. Ascorbate had only a minor contribution to the antioxidants in fruits with the exception of melon, nectarine, orange, white grape, and strawberry. The fruit extracts' antioxidant quality was better than the vitamin antioxidants and most pure phenols, suggesting synergism among the antioxidants in the mixture. Using our assay, fruits had significantly better quantity and quality of phenol antioxidants than vegetables. Fruits, specifically apples and cranberries, have phenol antioxidants that can enrich lower density lipoproteins and protect them from oxidation. The average per capita consumption of fruit phenols in the U.S. is estimated to be 255 mg/day of catechin equivalents.

Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans.

BACKGROUND: Flavonoids are polyphenolic compounds of plant origin with antioxidant effects. Flavonoids inhibit LDL oxidation and reduce thrombotic tendency in vitro. Little is known about how cocoa powder and dark chocolate, rich sources of polyphenols, affect these cardiovascular disease risk factors. OBJECTIVE: We evaluated the effects of a diet high in cocoa powder and dark chocolate (CP-DC diet) on LDL oxidative susceptibility, serum total antioxidant capacity, and urinary prostaglandin concentrations. DESIGN: We conducted a randomized, 2-period, crossover study in 23 healthy subjects fed 2 diets: an average American diet (AAD) controlled for fiber, caffeine, and theobromine and an AAD supplemented with 22 g cocoa powder and 16 g dark chocolate (CP-DC diet), providing approximately 466 mg procyanidins/d. RESULTS: LDL oxidation lag time was approximately 8% greater (P = 0.01) after the CP-DC diet than after the AAD. Serum total antioxidant capacity measured by oxygen radical absorbance capacity was approximately 4% greater (P = 0.04) after the CP-DC diet than after the AAD and was positively correlated with LDL oxidation lag time (r = 0.32, P = 0.03). HDL cholesterol was 4% greater after the CP-DC diet (P = 0.02) than after the AAD; however, LDL-HDL ratios were not significantly different. Twenty-four-hour urinary excretion of thromboxane B(2) and 6-keto-prostaglandin F(1)(alpha) and the ratio of the 2 compounds were not significantly different between the 2 diets. CONCLUSION: Cocoa powder and dark chocolate may favorably affect cardiovascular disease risk status by modestly reducing LDL oxidation susceptibility, increasing serum total antioxidant capacity and HDL-cholesterol concentrations, and not adversely affecting prostaglandins.

Determination of quantity and quality of polyphenol antioxidants in foods and beverages.

The methods described in this article are quick, simple, and inexpensive to perform. The Folin quantitation method can determine both free and total polyphenol antioxidants in foods and beverages as described, as well as botanical extracts. This assay may also be used to estimate the daily per capita consumption of polyphenols in foods. The dose-response in vitro lower density lipoprotein antioxidant activity measurement (IC50) can be employed to compare antioxidants as pure compounds, or in mixtures after quantitating the polyphenols. The ex vivo lipoprotein-binding antioxidant activity can be measured simply and rapidly to determine possible in vivo binding of pure compounds or extracts from foods. Supplementation and epidemiology studies can utilize the rapid and inexpensive affinity column isolation method of lower density lipoproteins for the determination of lipoprotein oxidative susceptibility.

Red wine, dealcoholized red wine, and especially grape juice, inhibit atherosclerosis in a hamster model.

The French have low coronary heart disease mortality with high fat consumption; this epidemiological anomaly is known as the "French Paradox" and is commonly attributed to the consumption of red wine. However, epidemiology studies have not convincingly shown a superiority of red wine vs. alcohol or other alcoholic beverages. We have used the hamster model of atherosclerosis to determine the active ingredient(s) of red wine responsible for the beneficial effect. Hamsters (nine in each group) were given a cholesterol/saturated fat for 10 weeks to induce foam cell formation. Water or 6.75% ethanol was given to the control groups. Beverages tested included red wine, dealcoholized red wine, and red grape juice, all diluted in half. Ethanol and all beverages caused a significant reduction in atherosclerosis. The combination of ethanol in red wine had the largest effect in decreasing atherosclerosis by both hypolipemic and antioxidant mechanisms. When compared with dealcoholized wine and normalized to polyphenol dose, red wine's beneficial effects can be attributed entirely to the polyphenols. Grape juice had a significant benefit at a much lower dose of polyphenols than the wines. Grape juice was calculated to be much more effective than red wine or dealcoholized red wine at the same polyphenol dose in inhibiting atherosclerosis and improving lipids and antioxidant parameters. This data suggests that polyphenolic beverages from grapes are beneficial in inhibiting atherosclerosis by several mechanisms. Grape juice or non-alcoholic red wine are an excellent alternative to red wine in this model of atherosclerosis.

Nursing's epistemology revisited in relation to professional education competencies.

As nursing continues to debate entry-into-practice issues, it is important to re-examine patterns of knowing as well as their end products for the discipline in relation to the overall competencies of liberal and professional education. The changing landscape of society, along with the needed skills to provide comprehensive care that promotes the health and well-being of the people nursing serves, requires a close examination of what institutions of higher education can provide the discipline of nursing. A discussion of the epistemology of the nursing profession, needed competencies, and the goals of higher education are presented in this article. Patterns of knowing distinguish disciplines from one another. Nursing patterns of knowing and subsequent clinical, conceptual, and empirical knowledge require placement in institutions of higher learning that promotes both professional competencies and attitudes.

Black and green tea and heart disease: a review.

Tea is the second most consumed beverage around the world behind water. Epidemiological evidence points to both green and black tea consumption being protective with respect to heart disease. However, epidemiological evidence does not prove cause and effect and is potentially flawed by confounding variables. The recent evidence with respect to teas' beneficial effects from in vitro and in vivo studies in both animals and humans will be covered in this review. The comparative benefits of green vs. black tea will be considered. Articles published through December, 1999 will be included.

Grape juice, but not orange juice, has in vitro, ex vivo, and in vivo antioxidant properties.

ABSTRACT Polyphenols and particularly flavonoids are well known in vitro antioxidants. Their consumption in foods has been shown to decrease the risk of heart disease in epidemiological studies. We examined two commonly consumed nonalcoholic juices (grape juice and orange juice) for their ability to act as in vitro plasma antioxidants, enrich lower-density lipoproteins after plasma spiking, and protect these lipoproteins from oxidation after supplementation to healthy subjects. We found that grape juice, but not orange juice, possesses all of these antioxidant properties and is an excellent nonalcoholic alternative to red wine. Grape juice is a powerful in vivo antioxidant, and this property, in combination with its platelet aggregation inhibition ability, can potentially reduce the risk of heart disease.

Is ethanol an important antioxidant in alcoholic beverages associated with risk reduction of cataract and atherosclerosis?

It has been reported in the epidemiological literature that cataract, stroke, and atherosclerosis risk is reduced by 50% in people consuming one alcoholic drink per day. Peroxide has been implicated as a causative agent in cataractogenesis, and LDL oxidation appears to play a role in atherosclerosis. The antioxidant activity of alcohol was measured by: (i) use of a luminescent assay developed in our laboratory, confirmed as appropriate; (ii) electron spin resonance (ESR) spin-trapping; and (iii) copper-catalysed oxidation of LDL and VLDL from hamsters fed 6% ethanol in their drinking water. Ethanol reduced the luminescent counts/min from peroxide and superoxide. It significantly reduced the spin-trapped signal of hydroxyl radical, but not the superoxide signal. Other alcohols also showed large reductions in counts from hydrogen peroxide. Plasma from hamsters fed 6% ethanol had lower lipid peroxides and the oxidizability of LDL and VLDL was significantly reduced compared to controls. These data provide a possible explanation for the effect of beverages containing ethanol in the reduction of cataract and atherosclerosis risk observed in human population studies.

1-Benzopyran-4-one antioxidants as aldose reductase inhibitors.

Starting from the inhibitory activity of the flavonoid Quercetin, a series of 4H-1-benzopyran-4-one derivatives was synthesized and tested for inhibition of aldose reductase, an enzyme involved in the appearance of diabetic complications. Some of the compounds obtained display inhibitory activity similar to that of Sorbinil but are more selective than Quercetin and Sorbinil with respect to the closely related enzyme, aldehyde reductase, and also possess antioxidant activity. Remarkably, these compounds possess higher pKa values than carboxylic acids, a characteristic which could make the pharmacokinetics of these compounds very interesting. Molecular modeling investigations on the structures of inhibitors bound at the active site of aldose reductase were performed in order to suggest how these new inhibitors might bind to the enzyme and also to interpret structure-activity relationships.

Desazadesmethyldesferrithiocin analogues as orally effective iron chelators.

Further structure-activity studies of desferrithiocin analogues are carried out. (S)-Desazadesmethyldesferrithiocin, 2-(2-hydroxyphenyl)-Delta2-thiazoline-4(S)-carboxylic acid, serves as the principal framework in the current paper. Desazadesmethyldesferrithiocin can be structurally altered with facility, and data are already available on its iron-clearing properties and toxicity parameters. Four different kinds of structural modifications of this framework are undertaken: introduction of hydroxy, carboxy, or methoxy groups on the aromatic ring; alteration of the thiazoline ring; increasing the distance between the ligand donor atoms; and benz-fusion of the aromatic rings. The structural modifications described are shown to have a tremendous impact on both the iron clearance and toxicity profiles of the desazadesmethyldesferrithiocin molecule. All of the compounds are assessed in a bile-duct-cannulated rodent model to determine iron clearance efficiency. Ligands which demonstrate an efficiency of greater than 2% are carried forward to the iron-overloaded primate for iron-clearing measurements. Ligands with efficiencies greater than 3% in the primate are then evaluated in a formal toxicity study in rodents. On the basis of the results of the present work, 2-(2, 4-dihydroxyphenyl)-Delta2-thiazoline-4(S)-carboxylic acid is a promising candidate for clinical evaluation.