A question of balance: achieving appropriate nutrient levels in biofortified staple crops.

PubMed

Sanahuja, Georgina; Farré, Gemma; Berman, Judit; Zorrilla-López, Uxue; Twyman, Richard M; Capell, Teresa; Christou, Paul; Zhu, Changfu

2013-12-01

The biofortification of staple crops with vitamins is an attractive strategy to increase the nutritional quality of human food, particularly in areas where the population subsists on a cereal-based diet. Unlike other approaches, biofortification is sustainable and does not require anything more than a standard food-distribution infrastructure. The health-promoting effects of vitamins depend on overall intake and bioavailability, the latter influenced by food processing, absorption efficiency and the utilisation or retention of the vitamin in the body. The bioavailability of vitamins in nutritionally enriched foods should ideally be adjusted to achieve the dietary reference intake in a reasonable portion. Current vitamin biofortification programmes focus on the fat-soluble vitamins A and E, and the water-soluble vitamins C and B9 (folate), but the control of dosage and bioavailability has been largely overlooked. In the present review, we discuss the vitamin content of nutritionally enhanced foods developed by conventional breeding and genetic engineering, focusing on dosage and bioavailability. Although the biofortification of staple crops could potentially address micronutrient deficiency on a global scale, further research is required to develop effective strategies that match the bioavailability of vitamins to the requirements of the human diet.

Investigation of fusion gene expression in HCT116 cells.

PubMed

Zhang, Yanmei; Ren, Juan; Fang, Mengdie; Wang, Xiaoju

2017-12-01

Colon cancer is the most common type of gastrointestinal cancer. A number of specific and sensitive biomarkers facilitate the diagnosis and monitoring of patients with colon cancer. Fusion genes are typically identified in cancer and a majority of the newly identified fusion genes are oncogenic in nature. Therefore, fusion genes are potential biomarkers and/or therapy targets in cancer. In the present study, the regulation of specific candidate fusion genes were investigated using Brother of the Regulator of Imprinted Sites (BORIS) in the HCT116 colon cancer cell line, which is a paralog of the fusion gene regulator CCCTC-binding factor (CTCF). The copy number of BORIS increased correspondingly to the progression of colorectal carcinoma from the M0 to the M1a stage. It was identified that EIF3E(e1)-RSPO2(e2) , EIF3E(e1)-RSPO2(e3) , PTPRK(e1)-RSPO3(e2) , PTPRK(e7)-RSPO3(e2), TADA2A-MEF2B and MED13L-CD4 are fusion transcripts present in the transcriptome of the HCT116 colon cancer cell line. CDC42SE2-KIAAO146 is a genomic fusion transcript, which originates from DNA arrangement in HCT116 cells. BORIS suppresses the expression of EIF3E , RSPO2 , PTPRK , RSPO3 , TADA2A and CD4 to inhibit the expression of fusion transcripts in HCT116 cells. It was hypothesized that the fusion transcripts investigated in the present study may not be oncogenic in HCT116 cells. As BORIS is not colorectal carcinoma-specific, the fusion genes investigated may be a biomarker assemblage for monitoring the progression of colorectal carcinoma.

Investigation of fusion gene expression in HCT116 cells

PubMed Central

Zhang, Yanmei; Ren, Juan; Fang, Mengdie; Wang, Xiaoju

2017-01-01

Colon cancer is the most common type of gastrointestinal cancer. A number of specific and sensitive biomarkers facilitate the diagnosis and monitoring of patients with colon cancer. Fusion genes are typically identified in cancer and a majority of the newly identified fusion genes are oncogenic in nature. Therefore, fusion genes are potential biomarkers and/or therapy targets in cancer. In the present study, the regulation of specific candidate fusion genes were investigated using Brother of the Regulator of Imprinted Sites (BORIS) in the HCT116 colon cancer cell line, which is a paralog of the fusion gene regulator CCCTC-binding factor (CTCF). The copy number of BORIS increased correspondingly to the progression of colorectal carcinoma from the M0 to the M1a stage. It was identified that EIF3E(e1)-RSPO2(e2), EIF3E(e1)-RSPO2(e3), PTPRK(e1)-RSPO3(e2), PTPRK(e7)-RSPO3(e2), TADA2A-MEF2B and MED13L-CD4 are fusion transcripts present in the transcriptome of the HCT116 colon cancer cell line. CDC42SE2-KIAAO146 is a genomic fusion transcript, which originates from DNA arrangement in HCT116 cells. BORIS suppresses the expression of EIF3E, RSPO2, PTPRK, RSPO3, TADA2A and CD4 to inhibit the expression of fusion transcripts in HCT116 cells. It was hypothesized that the fusion transcripts investigated in the present study may not be oncogenic in HCT116 cells. As BORIS is not colorectal carcinoma-specific, the fusion genes investigated may be a biomarker assemblage for monitoring the progression of colorectal carcinoma. PMID:29181107

BOREAS Elevation Contours over the NSA and SSA in ARC/INFO Generate Format

NASA Technical Reports Server (NTRS)

Knapp, David; Nickeson, Jaime; Hall, Forrest G. (Editor)

2000-01-01

This data set was prepared by BORIS Staff by reformatting the original data into the ARC/INFO Generate format. The original data were received in SIF at a scale of 1:50,000. BORIS staff could not find a format document or commercial software for reading SIF; the BOREAS HYD-08 team pro-vided some C source code that could read some of the SIF files. The data cover the BOREAS NSA and SSA. The original data were compiled from information available in the 1970s and 1980s. The data are available in ARC/INFO Generate format files.

Safety Evaluations of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI.

PubMed

Kim, Min Jeong; Ku, Seockmo; Kim, Sun Young; Lee, Hyun Ha; Jin, Hui; Kang, Sini; Li, Rui; Johnston, Tony V; Park, Myeong Soo; Ji, Geun Eog

2018-05-09

Over the past decade, a variety of lactic acid bacteria have been commercially available to and steadily used by consumers. However, recent studies have shown that some lactic acid bacteria produce toxic substances and display properties of virulence. To establish safety guidelines for lactic acid bacteria, the Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) has suggested that lactic acid bacteria be characterized and proven safe for consumers’ health via multiple experiments (e.g., antibiotic resistance, metabolic activity, toxin production, hemolytic activity, infectivity in immune-compromised animal species, human side effects, and adverse-outcome analyses). Among the lactic acid bacteria, Bifidobacterium and Lactobacillus species are probiotic strains that are most commonly commercially produced and actively studied. Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI have been used in global functional food markets (e.g., China, Germany, Jordan, Korea, Lithuania, New Zealand, Poland, Singapore, Thailand, Turkey, and Vietnam) as nutraceutical ingredients for decades, without any adverse events. However, given that the safety of some newly screened probiotic species has recently been debated, it is crucial that the consumer safety of each commercially utilized strain be confirmed. Accordingly, this paper details a safety assessment of B. bifidum BGN4 and B. longum BORI via the assessment of ammonia production, hemolysis of blood cells, biogenic amine production, antimicrobial susceptibility pattern, antibiotic resistance gene transferability, PCR data on antibiotic resistance genes, mucin degradation, genome stability, and possession of virulence factors. These probiotic strains showed neither hemolytic activity nor mucin degradation activity, and they did not produce ammonia or biogenic amines (i.e., cadaverine, histamine or tyramine). B. bifidum BGN4 and B. longum BORI produced a small amount of putrescine, commonly found in living cells, at levels similar to or lower than that found in other foods (e.g., spinach, ketchup, green pea, sauerkraut, and sausage). B. bifidum BGN4 showed higher resistance to gentamicin than the European Food Safety Authority (EFSA) cut-off. However, this paper shows the gentamicin resistance of B. bifidum BGN4 was not transferred via conjugation with L. acidophilus ATCC 4356, the latter of which is highly susceptible to gentamicin. The entire genomic sequence of B. bifidum BGN4 has been published in GenBank (accession no.: CP001361.1), documenting the lack of retention of plasmids capable of transferring an antibiotic-resistant gene. Moreover, there was little genetic mutation between the first and 25th generations of B. bifidum BGN4. Tetracycline-resistant genes are prevalent among B. longum strains; B. longum BORI has a tet (W) gene on its chromosome DNA and has also shown resistance to tetracycline. However, this research shows that its tetracycline resistance was not transferred via conjugation with L. fermentum AGBG1, the latter of which is highly sensitive to tetracycline. These findings support the continuous use of B. bifidum BGN4 and B. longum BORI as probiotics, both of which have been reported as safe by several clinical studies, and have been used in food supplements for many years.

Barnacles as biomonitors of trace metal availabilities in Hong Kong coastal waters: changes in space and time.

PubMed

Rainbow, P S; Blackmore, G

2001-06-01

The use of selected organisms as biomonitors of trace metal bioavailabilities allows comparisons to be made over space and time. The concentrations of 11 trace metals (arsenic, cadmium, chromium, cobalt, copper, iron, lead, manganese, nickel, silver, zinc) were measured in the bodies of two barnacle species, Balanus amphitrite and Tetraclita squamosa, from up to 18 littoral sites from Hong Kong coastal waters in April 1998. These data provide evidence on the geographical variation in metal bioavailabilities at this time, and are compared selectively against historical data sets for 1986 and 1989. Geographical variation in bioavailabilities is clear for several metals, with hotspots for arsenic, copper, nickel and silver at Chai Wan Kok, and for lead in Junk Bay. Victoria Harbour sites head the rankings for silver and arsenic, and Tolo Harbour sites exhibit relatively elevated cobalt, manganese and zinc. Many bioavailabilities of trace metals to barnacles are lower in Hong Kong coastal waters in 1998 than in 1986. The two barnacle species are widespread and the extensive data set presented is a benchmark which can be compared to the results of similar biomonitoring programmes elsewhere in the Indo-Pacific and beyond.

Generation of Vorticity by Slow Conductive Cooling Flows.

NASA Astrophysics Data System (ADS)

Meerson, Baruch; Glasner, Ami; Livne, Eli

1996-11-01

Rapid energy release in a gas produces a ``hot channel" or ``fireball", depending on the energy release geometry. During its relaxation, the ``hot channel" develops significant vorticity and turbulence(J.M. Picone, J.P. Boris, J.R. Greig, M. Raleigh, and R.F. Fernsler, J. Atmos. Sci. 38), 2056 (1981). that strongly enhance its cooling. Picone and Boris(J.M. Picone and J.P. Boris, Phys. Fluids 26), 365 (1983). attributed the effect to an earlier, plasma-expansion-related stage of the process. We show that vorticity can also be produced on a longer time scale. After a few acoustic times, the plasma pressure becomes very close to the ambient pressure. As the temperature is still high, slow (subacoustic) conductive cooling flow (CCF) develops that cools the cavity and fills it with gas from the periphery(B. Meerson, Phys. Fluids A 1), 887 (1989); D. Kaganovich, B. Meerson, A. Zigler, C. Cohen, and J. Levin, Phys. Plasmas 3, 631 (1996).. Due to asymmetries, this flow develops significant vorticity on the heat-conduction time scale. We present a simplified theory for this effect that employs, as a zero-order solution, a novel two-dimensional (2d) similarity solution for an irrotational isobaric CCF. We also report on gas-dynamic simulations in 2d (with the heat transfer taken into account) which show vorticity generation by the slow CCF.

Bioavailability of voriconazole in hospitalised patients.

PubMed

Veringa, Anette; Geling, Sanne; Span, Lambert F R; Vermeulen, Karin M; Zijlstra, Jan G; van der Werf, Tjip S; Kosterink, Jos G W; Alffenaar, Jan-Willem C

2017-02-01

An important element in antimicrobial stewardship programmes is early switch from intravenous (i.v.) to oral antimicrobial treatment, especially for highly bioavailable drugs. The antifungal agent voriconazole is available both in i.v. and oral formulations and bioavailability is estimated to be >90% in healthy volunteers, making this drug a suitable candidate for such a transition. Recently, two studies have shown that the bioavailability of voriconazole is substantially lower in patients. However, for both studies various factors that could influence the voriconazole serum concentration, such as inflammation, concomitant intake of food with oral voriconazole, and gastrointestinal complications, were not included in the evaluation. Therefore, in this study a retrospective chart review was performed in adult patients treated with both oral and i.v. voriconazole at the same dose and within a limited (≤5 days) time interval in order to evaluate the effect of switching the route of administration on voriconazole serum concentrations. A total of 13 patients were included. The mean voriconazole trough concentration was 2.28 mg/L [95% confidence interval (CI) 1.29-3.26 mg/L] for i.v. voriconazole administration and 2.04 mg/L (95% CI 0.78-3.30 mg/L) for oral administration. No significant difference was found in the mean oral and i.v. trough concentrations of voriconazole (P = 0.390). The mean bioavailability was 83.0% (95% CI 59.0-107.0%). These findings suggest that factors other than bioavailability may cause the observed difference in voriconazole trough concentrations between oral and i.v. administration in the earlier studies and stress the need for an antimicrobial stewardship team to guide voriconazole dosing. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Simulation of an expanding plasma using the Boris algorithm

NASA Astrophysics Data System (ADS)

Neal, Luke; Aguirre, Evan; Steinberger, Thomas; Good, Timothy; Scime, Earl

2017-10-01

We present a Boris algorithm simulation in a cylindrical geometry of charged particle motion in a helicon plasma confined by a diverging magnetic field. Laboratory measurements of ion velocity distribution functions (ivdfs) provide evidence for acceleration of ions into the divergent field region in the center of the discharge. The increase in ion velocity is inconsistent with expectations for simple magnetic moment conservation given the magnetic field mirror ratio and is therefore attributed to the presence of a double layer in the literature. Using measured electric fields and ivdfs (at different radial locations across the entire plasma column) upstream and downstream of the divergent magnetic field region, we compare predictions for the downstream ivdfs to measurements. We also present predictions for the evolution of the electron velocity distribution function downstream of the divergent magnetic field. This work was supported by U.S. National Science Foundation Grant No. PHY-1360278.

BOREAS Level-4c AVHRR-LAC Ten-Day Composite Images: Surface Parameters

NASA Technical Reports Server (NTRS)

Cihlar, Josef; Chen, Jing; Huang, Fengting; Nickeson, Jaime; Newcomer, Jeffrey A.; Hall, Forrest G. (Editor)

2000-01-01

The BOReal Ecosystem-Atmosphere Study (BOREAS) Staff Science Satellite Data Acquisition Program focused on providing the research teams with the remotely sensed satellite data products they needed to compare and spatially extend point results. Manitoba Remote Sensing Center (MRSC) and BOREAS Information System (BORIS) personnel acquired, processed, and archived data from the Advanced Very High Resolution Radiometer (AVHRR) instruments on the NOAA-11 and -14 satellites. The AVHRR data were acquired by CCRS and were provided to BORIS for use by BOREAS researchers. These AVHRR level-4c data are gridded, 10-day composites of surface parameters produced from sets of single-day images. Temporally, the 10-day compositing periods begin 11-Apr-1994 and end 10-Sep-1994. Spatially, the data cover the entire BOREAS region. The data are stored in binary image format files. Note: Some of the data files on the BOREAS CD-ROMs have been compressed using the Gzip program.

BOREAS Level-4b AVHRR-LAC Ten-Day Composite Images: At-sensor Radiance

NASA Technical Reports Server (NTRS)

Cihlar, Josef; Chen, Jing; Nickerson, Jaime; Newcomer, Jeffrey A.; Huang, Feng-Ting; Hall, Forrest G. (Editor)

2000-01-01

The BOReal Ecosystem-Atmosphere Study (BOREAS) Staff Science Satellite Data Acquisition Program focused on providing the research teams with the remotely sensed satellite data products they needed to compare and spatially extend point results. Manitoba Remote Sensing Center (MRSC) and BOREAS Information System (BORIS) personnel acquired, processed, and archived data from the Advanced Very High Resolution Radiometer (AVHRR) instruments on the National Oceanic and Atmospheric Administration (NOAA-11) and -14 satellites. The AVHRR data were acquired by CCRS and were provided to BORIS for use by BOREAS researchers. These AVHRR level-4b data are gridded, 10-day composites of at-sensor radiance values produced from sets of single-day images. Temporally, the 10- day compositing periods begin 11-Apr-1994 and end 10-Sep-1994. Spatially, the data cover the entire BOREAS region. The data are stored in binary image format files.

Comment on “Symplectic integration of magnetic systems”: A proof that the Boris algorithm is not variational

DOE PAGES

Ellison, C. L.; Burby, J. W.; Qin, H.

2015-11-01

One popular technique for the numerical time advance of charged particles interacting with electric and magnetic fields according to the Lorentz force law [1], [2], [3] and [4] is the Boris algorithm. Its popularity stems from simple implementation, rapid iteration, and excellent long-term numerical fidelity [1] and [5]. Excellent long-term behavior strongly suggests the numerical dynamics exhibit conservation laws analogous to those governing the continuous Lorentz force system [6]. Moreover, without conserved quantities to constrain the numerical dynamics, algorithms typically dissipate or accumulate important observables such as energy and momentum over long periods of simulated time [6]. Identification of themore » conservative properties of an algorithm is important for establishing rigorous expectations on the long-term behavior; energy-preserving, symplectic, and volume-preserving methods each have particular implications for the qualitative numerical behavior [6], [7], [8], [9], [10] and [11].« less

ARC-2010-ACD10-0110-076

NASA Image and Video Library

2010-06-09

2010 NASA Honor Awards Awards Group Achievement Award to VMS Space Shuttle Visual Database Development Team. Boris M. Rabin accepting. Presenters are on left Mr. Charles H. Scales, NASA Associate Deputy Administrator, on right Dr. S. Pete Worden, Director, NASA Ames Research Center.

Fluoride availability from natural resources in The Gambia--implications for oral health care.

PubMed

Jordan, Rainer A; Markovic, Ljubisa; Gaengler, Peter

2008-10-01

Changing food patterns in combination with ineffective oral hygiene measures and insufficient bioavailability of fluoride from drinking water and other sources seem to impair the dental health status in developing countries, especially in the younger population. Therefore, preventive programmes in controlling dental caries progression should be based on local conditions. For mapping the drinking water fluoride content throughout The Gambia, samples of water from rural community wells, public water taps, commercial mineral water, and from the Gambia-River were measured. Additionally, fluoride concentrations of locally extracted table salt and green tea were determined. Showed the need for supplementary fluoride intake, because natural dietary fluoride availability is very low. Age-related recommendations for oral health care and for additional fluoride bioavailability are given, taking into account local socio-economic conditions in the Republic of The Gambia and similar developing countries.

75 FR 18837 - Findings of Research Misconduct

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Findings of Research Misconduct... Research Integrity (ORI) and the Assistant Secretary for Health have taken final action in the following... Boris Cheskis, Ph.D., former senior scientist, Discovery Research, Women's Health, Wyeth Pharmaceuticals...

BOREAS RSS-14 Level-1a GOES-8 Visible, IR and Water Vapor Images

NASA Technical Reports Server (NTRS)

Hall, Forrest G. (Editor); Newcomer, Jeffrey A.; Faysash, David; Cooper, Harry J.; Smith, Eric A.

2000-01-01

The BOREAS RSS-14 team collected and processed several GOES-7 and GOES-8 image data sets that covered the BOREAS study region. The level-1a GOES-8 images were created by BORIS personnel from the level-1 images delivered by FSU personnel. The data cover 14-Jul-1995 to 21-Sep-1995 and 12-Feb-1996 to 03-Oct-1996. The data start out as three bands with 8-bit pixel values and end up as five bands with 10-bit pixel values. No major problems with the data have been identified. The differences between the level-1 and level-1a GOES-8 data are the formatting and packaging of the data. The images missing from the temporal series of level-1 GOES-8 images were zero-filled by BORIS staff to create files consistent in size and format. In addition, BORIS staff packaged all the images of a given type from a given day into a single file, removed the header information from the individual level-1 files, and placed it into a single descriptive ASCII header file. The data are contained in binary image format files. Due to the large size of the images, the level-1a GOES-8 data are not contained on the BOREAS CD-ROM set. An inventory listing file is supplied on the CD-ROM to inform users of what data were collected. The level-1a GOES-8 image data are available from the Earth Observing System Data and Information System (EOSDIS) Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC). See sections 15 and 16 for more information. The data files are available on a CD-ROM (see document number 20010000884).

[On a contribution of Boris Balinsky to the comparative and ecological embryology of amphibians].

PubMed

Desnitskiĭ, A G

2014-01-01

The outstanding embryologist Boris Ivanovich Balinsky (1905-1997) worked in the Soviet Union up to 1941 and in South Africa since 1949. His experimental studies fulfilled during the Soviet period of his scientific career mainly on the embryos of the caudate amphibians are widely known. After moving to Africa (Johannesburg), he continued the research of amphibian development, with using those possibilities, which were offered by the diverse fauna of local Anura. Other embryologists started complex studies of tropical frog ontogenies (mainly from South and Central America) 30-40 years later than Balinsky. Unfortunately, his pioneering works on numerous African species are poorly known (with the exceptions of the description of the development of endodermal derivatives in Xenopus laevis and the analysis of limb induction in the toad genus Amietophrynus). In this paper, the works of Balinsky are analyzed (with the emphasis on comparative and ecological aspects) and his priority in using of "nonmodel" tropical and subtropical anurans in embryological studies has been shown.

Renormalization of minimally doubled fermions

NASA Astrophysics Data System (ADS)

Capitani, Stefano; Creutz, Michael; Weber, Johannes; Wittig, Hartmut

2010-09-01

We investigate the renormalization properties of minimally doubled fermions, at one loop in perturbation theory. Our study is based on the two particular realizations of Boriçi-Creutz and Karsten-Wilczek. A common feature of both formulations is the breaking of hyper-cubic symmetry, which requires that the lattice actions are supplemented by suitable counterterms. We show that three counterterms are required in each case and determine their coefficients to one loop in perturbation theory. For both actions we compute the vacuum polarization of the gluon. It is shown that no power divergences appear and that all contributions which arise from the breaking of Lorentz symmetry are cancelled by the counterterms. We also derive the conserved vector and axial-vector currents for Karsten-Wilczek fermions. Like in the case of the previously studied Boriçi-Creutz action, one obtains simple expressions, involving only nearest-neighbour sites. We suggest methods how to fix the coefficients of the counterterms non-perturbatively and discuss the implications of our findings for practical simulations.

Pushing particles in extreme fields

NASA Astrophysics Data System (ADS)

Gordon, Daniel F.; Hafizi, Bahman; Palastro, John

2017-03-01

The update of the particle momentum in an electromagnetic simulation typically employs the Boris scheme, which has the advantage that the magnetic field strictly performs no work on the particle. In an extreme field, however, it is found that onerously small time steps are required to maintain accuracy. One reason for this is that the operator splitting scheme fails. In particular, even if the electric field impulse and magnetic field rotation are computed exactly, a large error remains. The problem can be analyzed for the case of constant, but arbitrarily polarized and independent electric and magnetic fields. The error can be expressed in terms of exponentials of nested commutators of the generators of boosts and rotations. To second order in the field, the Boris scheme causes the error to vanish, but to third order in the field, there is an error that has to be controlled by decreasing the time step. This paper introduces a scheme that avoids this problem entirely, while respecting the property that magnetic fields cannot change the particle energy.

Snapshots from the 1950s

NASA Astrophysics Data System (ADS)

Orlov, Yuri F.

2013-06-01

It happened that our careers in physics - that of Boris Lazarevich Ioffe and mine - started almost simultaneously at the Institute of Theoretical and Experimental Physics (ITEP) in Moscow. Half a century later, my memories of this time are still vivid...

Polymers by Non-Redox Processes: Synthesis, Physical Studies and Application

DTIC Science & Technology

1992-12-31

Schiff Base," in lournal Polymer Science Polymer Chemitry , 29 749 (1991), Y. Wei, R. Hariharan and J.K. Ray. 1991-25 "Fast Atom Bombardment Mass...Graduate Student - Georgia Arbuckle Graduate Student - David Swanson Visiting Graduate Student - Angela Fagot Technician - Boris Vuchic Computer

CMMI on the Web: Remastered

DTIC Science & Technology

2009-09-01

Patrick Kirwin: www.sei.cmu.edu/library/abstracts/webinars/18jul2008.cfm  Also see: www.sei.cmu.edu/prime  ISO 9001/15504/ 12207 /15288 Process...Improvement with CMMI V1.2 and ISO Standards by Boris Mutafelija and Harvey Stromberg (Book)  www.sei.cmu.edu/library/abstracts/presentations/Mutafelija

Developing Professional-Level Language Proficiency.

ERIC Educational Resources Information Center

Leaver, Betty Lou, Ed.; Shekhtman, Boris, Ed.

This collection of papers examines approaches to teaching near-native ability in foreign languages. The 13 papers focus on the following: (1) "Principles and Practices in Teaching Superior-Level Language Skills: Not Just More of the Same" (Betty Lou Leaver and Boris Shekhtman); (2) "Toward Academic Level Foreign Language Abilities:…

East Europe Report.

DTIC Science & Technology

1986-06-19

deputy chairman. 74. Vidin Electoral District. Kiril Dimitrov Zarev, BCP Central Committee secretary. 75. Vidin Electoral District. Georgi Vulkanov...Blagoevgrad. 4. Simitli Electoral District. Boris Dimitrov Karanfilov, BCP Central Committee member, deputy minister of national defense. 5. Strumyan...Electoral District. Emiliya Mircheva Kostova, chairman okrug BZNS management. 6. Sandanski Electoral District. Lalyu Ivanov Dimitrov , BCP Central

Temperature Compensation Techniques and Technologies-An Overview

DTIC Science & Technology

1991-10-01

03801-5423 General Electric Company 1 Physics International Company Tactical Systems Department ATTN: Library, H. Wayne Wampler ATN: J. Mandzy 2700...Keilasanath Office Dr. C. Li ATN: COL D. S. Jackson Dr. J. Boris 5321 Riggs Road Dr. E. Oran Gaithersburg, MD 20882 Washington, DC 20375-5000 AFOSR/NA 1 Amtec

The Soviet Objective of War Termination: Limits and Constraints

DTIC Science & Technology

1988-06-01

results, even the best, must be regarded as a base, as a trampoline , for achieving still higher indicators. What is considered a success today may no...organizations. According to Boris Ponomarev, former head of the Soviet’s International Department, such contacts would establish "broad alliances covering the

Heavy metals in soils from Baia Mare mining impacted area (Romania) and their bioavailability

NASA Astrophysics Data System (ADS)

Roba, Carmen; Baciu, Calin; Rosu, Cristina; Pistea, Ioana; Ozunu, Alexandru

2015-04-01

Keywords: heavy metals, soil contamination, bioavailability, Romania The fate of various metals, including chromium, nickel, copper, manganese, mercury, cadmium, and lead, and metalloids, like arsenic, antimony, and selenium, in the natural environment is of great concern, particularly in the vicinity of former mining sites, dumps, tailings piles, and impoundments, but also in urban areas and industrial centres. Most of the studies focused on the heavy metal pollution in mining areas present only the total amounts of metals in soils. The bioavailable concentration of metals in soil may be a better predictor for environmental impact of historical and current dispersion of metals. Assessment of the metal bioavailability and bioaccessibility is critical in understanding the possible effects on soil biota. The bioavailability of metals in soil and their retention in the solid phase of soil is affected by different parameters like pH, metal amount, cation-exchange capacity, content of organic matter, or soil mineralogy. The main objectives of the present study were to determine the total fraction and the bioavailable fraction of Cu, Cd, Pb and Zn from soil in a well-known mining region in Romania, and to evaluate the influence of soil pH on the metal bioavailability in soil. The heavy metal contents and their bioavailability were monitored in a total of 50 soil samples, collected during June and July 2014 from private gardens of the inhabitants from Baia-Mare area. The main mining activities developed in the area consisted of non-ferrous sulphidic ores extraction and processing, aiming to obtain concentrates of lead, copper, zinc and precious metals. After 2006, the metallurgical industry has considerably reduced its activity by closing or diminishing its production capacity. The analysed soil samples proved to have high levels of Pb (50 - 830 mg/kg), Cu (40 - 600 mg/kg), Zn (100 - 700 mg/kg) and Cd (up to 10 mg/kg). The metal abundance in the total fraction is following the sequence Zn > Pb > Cu > Cd, while the bioavailable fractions were considerably lower and their sequence was as follows: Cd > Cu > Pb > Zn. Higher proportions of mobile fractions of metals were detected in samples taken from soils with acidic pH. Acknowledgments: This paper is a result of a post-doctoral research made possible by the financial support of the Sectorial Operational Programme for Human Resources Development 2007-2013, co-financed by the European Social Fund, under the project POSDRU/159/1.5/S/133391 - "Doctoral and postdoctoral excellence programs for training highly qualified human resources for research in the fields of Life Sciences, Environment and Earth".

Passive sampling devices enable capacity building and characterization of bioavailable pesticide along the Niger, Senegal and Bani Rivers of Africa

PubMed Central

Anderson, Kim A.; Seck, Dogo; Hobbie, Kevin A.; Traore, Anna Ndiaye; McCartney, Melissa A.; Ndaye, Adama; Forsberg, Norman D.; Haigh, Theodore A.; Sower, Gregory J.

2014-01-01

It is difficult to assess pollution in remote areas of less-developed regions owing to the limited availability of energy, equipment, technology, trained personnel and other key resources. Passive sampling devices (PSDs) are technologically simple analytical tools that sequester and concentrate bioavailable organic contaminants from the environment. Scientists from Oregon State University and the Centre Régional de Recherches en Ecotoxicologie et de Sécurité Environnementale (CERES) in Senegal developed a partnership to build capacity at CERES and to develop a pesticide-monitoring project using PSDs. This engagement resulted in the development of a dynamic training process applicable to capacity-building programmes. The project culminated in a field and laboratory study where paired PSD samples were simultaneously analysed in African and US laboratories with quality control evaluation and traceability. The joint study included sampling from 63 sites across six western African countries, generating a 9000 data point pesticide database with virtual access to all study participants. PMID:24535398

Passive sampling devices enable capacity building and characterization of bioavailable pesticide along the Niger, Senegal and Bani Rivers of Africa.

PubMed

Anderson, Kim A; Seck, Dogo; Hobbie, Kevin A; Traore, Anna Ndiaye; McCartney, Melissa A; Ndaye, Adama; Forsberg, Norman D; Haigh, Theodore A; Sower, Gregory J

2014-04-05

It is difficult to assess pollution in remote areas of less-developed regions owing to the limited availability of energy, equipment, technology, trained personnel and other key resources. Passive sampling devices (PSDs) are technologically simple analytical tools that sequester and concentrate bioavailable organic contaminants from the environment. Scientists from Oregon State University and the Centre Régional de Recherches en Ecotoxicologie et de Sécurité Environnementale (CERES) in Senegal developed a partnership to build capacity at CERES and to develop a pesticide-monitoring project using PSDs. This engagement resulted in the development of a dynamic training process applicable to capacity-building programmes. The project culminated in a field and laboratory study where paired PSD samples were simultaneously analysed in African and US laboratories with quality control evaluation and traceability. The joint study included sampling from 63 sites across six western African countries, generating a 9000 data point pesticide database with virtual access to all study participants.

Recursive Optimization of Digital Circuits

DTIC Science & Technology

1990-12-14

Obverse- Specification . . . A-23 A.14 Non-MDS Optimization of SAMPLE .. .. .. .. .. .. ..... A-24 Appendix B . BORIS Recursive Optimization System...Software ...... B -i B .1 DESIGN.S File . .... .. .. .. .. .. .. .. .. .. ... ... B -2 B .2 PARSE.S File. .. .. .. .. .. .. .. .. ... .. ... .... B -1i B .3...TABULAR.S File. .. .. .. .. .. .. ... .. ... .. ... B -22 B .4 MDS.S File. .. .. .. .. .. .. .. ... .. ... .. ...... B -28 B .5 COST.S File

Appendix C: GLEES Macroinvertebrates

Treesearch

B. C. Kondratieff

1994-01-01

This Appendix identifies macroinvertebrate species found in streams and lakes at GLEES during a preliminary qualitative survey conducted in the summer of 1988 by Dr. Boris Kondratieff. The littoral zones of each lake and each stream were sampled by hand-picking and with a triangle net. Insect voucher specimens are maintained in the Gillette Entomological Museum at...

The Efficacy of Bifidobacterium longum BORI and Lactobacillus acidophilus AD031 Probiotic Treatment in Infants with Rotavirus Infection.

PubMed

Park, Myeong Soo; Kwon, Bin; Ku, Seockmo; Ji, Geun Eog

2017-08-16

A total of 57 infants hospitalized with rotavirus disease were included in this study. The children were randomly divided into the study's two treatment groups: three days of the oral administration of (i) a probiotics formula containing both Bifidobacterium longum BORI and Lactobacillus acidophilus AD031 ( N = 28); or (ii) a placebo (probiotic-free skim milk, N = 29) and the standard therapy for diarrhea. There were no differences in age, sex, or blood characteristics between the two groups. When the 57 cases completed the protocol, the duration of the patients' diarrhea was significantly shorter in the probiotics group (4.38 ± 1.29, N = 28) than the placebo group (5.61 ± 1.23, N = 29), with a p -value of 0.001. Symptoms such as duration of fever ( p = 0.119), frequency of diarrhea ( p = 0.119), and frequency of vomiting ( p = 0.331) tended to be ameliorated by the probiotic treatment; however, differences were not statistically significant between the two groups. There were no serious, adverse events and no differences in the frequency of adverse events in both groups.

EDITORIAL: Optical orientation Optical orientation

NASA Astrophysics Data System (ADS)

SAME ADDRESS *, Yuri; Landwehr, Gottfried

2008-11-01

Boris Petrovitch Zakharchenya (1928-2005) This issue is dedicated to the memory of Boris Petrovich Zakharchenya, who died at the age of 77 in April 2005. He was an eminent scientist and a remarkable man. After studying physics at Leningrad University he joined the Physico-Technical Institute (now the A F Ioffe Institute) in 1952 and became the co-worker of Evgeny Feodorovich Gross, shortly after the exciton was discovered in his laboratory. The experiments on cuprous oxide crystals in the visible spectral range showed a hydrogen-like spectrum, which was interpreted as excitonic absorption. The concept of the exciton had been conceived some years earlier by Jacov Frenkel at the Physico-Technical Institute. Immediately after joining Gross, Zakharchenya succeeded in producing spectra of unprecedented quality. Subsequently the heavy and the light hole series were found. Also, Landau splitting was discovered when a magnetic field was applied. The interpretation of the discovery was thrown into doubt by Russian colleagues and it took some time, before the correct interpretation prevailed. Shortly before his death, Boris wrote the history of the discovery of the exciton, which has recently been published in Russian in a book celebrating the 80th anniversary of his birth [1]. The book also contains essays by Boris on various themes, not only on physics, but also on literature. Boris was a man of unusually wide interests, he was not only fascinated by physics, but also loved literature, art and music. This can be seen in the first article of this issue The Play of Light in Crystals which is an abbreviated version of his more complete history of the discovery of the exciton. It also gives a good impression of the personality of Boris. One of us (GL) had the privilege to become closely acquainted with him, while he was a guest professor at the University of Würzburg. During that time we had many discussions, and I recall his continuing rage on the wrong attribution of the priority of the discovery in the literature, which was partly caused by the existence of the Iron Curtain. I had already enjoyed contact with Boris in the 1980s when the two volumes of Landau Level Spectroscopy were being prepared [2]. He was one of the pioneers of magneto-optics in semiconductors. In the 1950s the band structure of germanium and silicon was investigated by magneto-optical methods, mainly in the United States. No excitonic effects were observed and the band structure parameters were determined without taking account of excitons. However, working with cuprous oxide, which is a direct semiconductor with a relative large energy gap, Zakharchenya and his co-worker Seysan showed that in order to obtain correct band structure parameters, it is necessary to take excitons into account [3]. About 1970 Boris started work on optical orientation. Early work by Hanle in Germany in the 1920s on the depolarization of luminescence in mercury vapour by a transverse magnetic field was not appreciated for a long time. Only in the late 1940s did Kastler and co-workers in Paris begin a systematic study of optical pumping, which led to the award of a Nobel prize. The ideas of optical pumping were first applied by Georges Lampel to solid state physics in 1968. He demonstrated optical orientation of free carriers in silicon. The detection method was nuclear magnetic resonance; optically oriented free electrons dynamically polarized the 29Si nuclei of the host lattice. The first optical detection of spin orientation was demonstrated by with the III-V semiconductor GaSb by Parsons. Due to the various interaction mechanisms of spins with their environment, the effects occurring in semiconductors are naturally more complex than those in atoms. Optical detection is now the preferred method to detect spin alignment in semiconductors. The orientation of spins in crystals pumped with circularly polarized light is deduced from the degree of circular polarization of the recombination radiation. The major results of the systematic work on optical orientation, both experimental and theoretical, at the Ioffe Institute and the Ecole Normale Supérieure in Paris are documented in the book Optical Orientation, edited by F Meier and B P Zakharchenya in the series Modern Problems in Condensed Matter Sciences [4], in which the foundations of optical orientation are comprehensively presented by renowned authors. This book is still the unsurpassed standard work in the field. If one asks what has become new since that publication in 1984 it is obviously the arrival of low-dimensional structures, two-dimensional heterostructures and zero-dimensional quantum dots. It has turned out that the quantum confinement can significantly modify the spin lifetime and the spin relaxation. The experimental work on spin alignment was done by a relative small number of researchers. However, the situation has substantially changed during the last decade. Research on spin-related phenomena has become very popular and the word 'spintronics' was coined. Spin research is no longer considered to be somewhat esoteric, since the replacement of silicon microelectronics based on the electron charge by spin-based electronics is being discussed. Whether these proposals can be realized remains to be seen. But one consequence has been a worldwide increase of high level basic research in spin phenomena. Another line of current research which has contributed to the popularity of spin-related research is quantum computing, based on spin-qubits. To be useful, solid state systems require long spin relaxation times and weak interaction with the environment. This is indispensable for low error rates. The difficulties in achieving these goals have been extensively discussed in the literature. Nowadays, because of the volume and diversity of spin-related work worldwide, a book on optical orientation like that edited by Meyer and Zakharchenya does not seem possible, so in this special issue of Semiconductor Science and Technology we try, with examples, to give an impression of that current state of research. The articles will not be discussed individually but their titles reveal that most deal with low-dimensional systems. The study of spin relaxation plays a major role. Interface effects at the ferromagnet/semiconductor boundary are subtle and important for spin injection from a ferromagnet. Each of the contributions is a combination of review and recent results and stands by itself. The affiliations of the authors reveal that the majority come from St Petersburg, clearly indicating that the heritage of Boris Zakharchenya is alive and thriving. We would like to thank all authors for their cooperation, especially for delivering their manuscripts in a reasonable time. Claire Bedrock and Adam Day of the IOP Publishing deserve thanks for their support in the publication process. We are much indebted to Ruslana Zakharchenya for making the manuscript on the discovery of the exciton available and especially to Nina Nikolaevna Vasil'eva for her translation. References [1] Zakharchenya B P 2008 The Happiness of Creativity (St Petersburg, in Russian) [2] Rashba E I and Landwehr G (ed) 1991 Landau Level Spectroscopy (Modern Problems in Condensed Matter Sciences vol 27) (Amsterdam: Elsevier) [3] Seisyan R B and Zakharchenya B P 1991 Landau Level Spectroscopy ed E I Rashba and G Landwehr (Modern Problems in Condensed Matter Sciences vol 27) (Amsterdam: Elsevier) p 345 [4] Meier F and Zakharchenya B P (ed) 1984 Optical Orientation (Modern Problems in Condensed Matter Sciences vol 8) (Amsterdam: Elsevier) An obituary of Boris Petrovich Zakharchenyia, contributed to Uspekhi Fizicheskikh Nauk by his Russian colleagues, is available at http://www.iop.org/EJ/abstract/1063-7869/49/8/M09

Satellite Splat: An Inelastic Collision with a Surface-launched Projectile

DTIC Science & Technology

2015-04-23

v v v2 1 2( ) 1 2( ) . (9)P S P S Pr Sr From these new components we can calculate the postcollision values of ε and h for the combined object using...the application of Newtonian mechanics to manmade objects in space such as rockets and spacecraft.’ Acknowledgments Helpful discussions with Boris

STS-106 TCDT Photo Opportunity

NASA Technical Reports Server (NTRS)

2000-01-01

STS-106 crewmembers Commander Terrence W. Wilcutt, Pilot Scott D. Altman, and Mission Specialists Daniel C. Burbank, Edward T. Lu, Richard A. Mastracchio, Yuri Ivanovich Malenchenko, and Boris V. Morukov are seen during the Terminal Countdown and Demonstration Test (TCDT) activity of meeting the press. Each crewmember introduces himself and then they answer questions from the press about the upcoming mission.

Role of ets Oncogenes in the Progression of Breast Cancer

DTIC Science & Technology

1998-10-01

8217 References 167 Arias J, Alberts AS, Brindle P, Claret FX, Smeal T, Karin M, May WA, Lessnick SL, Braun BS, Klemsz M, Lewis BC, Feramisco J and Montminy M...0 and Shaw PE. (1994). Mol. Cell. Oncogene, 8, 3459-3464. Biol., 14, 4815-4824. Bories J, Willerford DM, Grevin D, Davidson L, Camus A, Lopez M

Composition of the Active Fleet, U.S. Navy, 1961-1985.

DTIC Science & Technology

1980-12-01

Amberjack SS 324 Blenny SS 523 Grampus SS 331 Bugara SS 524 Pickerel SS 337 Carbonero SS 525 Grenadier SS 338 Carp SS 550 Barracuda SS 339 Catfish SS...LKA 57 Bordelon DD 881 Carbonero SS 337 Borie DD 704 Carl Vinson CVN 70 Boston CA 69 Caroline County LST 525 Boston SSN 703 Caron DD 970 Botetourt LPA

Semiannual Report October 1, 1999 through March 31, 2000

DTIC Science & Technology

2000-04-01

Mark Carpenter (NASA Langley). Textbook Multigrid Efficiency for the Navier-Stokes Equations Boris Diskin A typical modern Reynolds-Averaged...defined as textbook multigrid efficiency (TME), meaning the solutions to the governing system of equations are attained in a computational work...basic elements of the barriers to be overcome in extending textbook efficiencies to the compressible RANS equations, namely entering flows, far wake

The Efficacy of Bifidobacterium longum BORI and Lactobacillus acidophilus AD031 Probiotic Treatment in Infants with Rotavirus Infection

PubMed Central

Park, Myeong Soo; Kwon, Bin; Ku, Seockmo; Ji, Geun Eog

2017-01-01

A total of 57 infants hospitalized with rotavirus disease were included in this study. The children were randomly divided into the study’s two treatment groups: three days of the oral administration of (i) a probiotics formula containing both Bifidobacterium longum BORI and Lactobacillus acidophilus AD031 (N = 28); or (ii) a placebo (probiotic-free skim milk, N = 29) and the standard therapy for diarrhea. There were no differences in age, sex, or blood characteristics between the two groups. When the 57 cases completed the protocol, the duration of the patients’ diarrhea was significantly shorter in the probiotics group (4.38 ± 1.29, N = 28) than the placebo group (5.61 ± 1.23, N = 29), with a p-value of 0.001. Symptoms such as duration of fever (p = 0.119), frequency of diarrhea (p = 0.119), and frequency of vomiting (p = 0.331) tended to be ameliorated by the probiotic treatment; however, differences were not statistically significant between the two groups. There were no serious, adverse events and no differences in the frequency of adverse events in both groups. PMID:28813007

Atmospheric transport of trace elements and nutrients to the oceans

PubMed Central

Chance, R.

2016-01-01

This paper reviews atmospheric inputs of trace elements and nutrients to the oceans in the context of the GEOTRACES programme and provides new data from two Atlantic GEOTRACES cruises. We consider the deposition of nitrogen to the oceans, which is now dominated by anthropogenic emissions, the deposition of mineral dust and related trace elements, and the deposition of other trace elements which have a mixture of anthropogenic and dust sources. We then consider the solubility (as a surrogate for bioavailability) of the various elements. We consider briefly the sources, atmospheric transport and transformations of these elements and how this results in strong spatial deposition gradients. Solubility of the trace elements also varies systematically between elements, reflecting their sources and cycling, and for some trace elements there are also systematic gradients in solubility related to dust loading. Together, these effects create strong spatial gradients in the inputs of bioavailable trace elements to the oceans, and we are only just beginning to understand how these affect ocean biogeochemistry. This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’. PMID:29035252

MOVEMENT IN THE CYANOPHYCEAE

PubMed Central

Burkholder, Paul R.

1933-01-01

The effect of pH upon the velocity of translatory movement of Oscillatoria formosa Bory in inorganic culture solutions was determined. Unhindered movement occurred in the range of about pH 6.4 to 9.5. Above and below these limits inhibition was marked. In the unfavorable acid and alkaline ranges inhibition was progressive with exposure time; in the favorable range continuous movement was maintained for 24 hours. PMID:19872745

The Two-Headed Eagle: Faces of Russian Foreign Policy

DTIC Science & Technology

2015-06-01

of laissez - faire capitalism” including an “idealized picture of the United States” placed him on a collision trajectory with Putin’s coercive...landscape.19 As President Boris Yeltsin stepped into the breach to fill the leadership void, a newly independent Russia entered a tumultuous decade...Near Abroad. Russian leadership , custodianship, and protection roles after WWII through the first presidential term of President Vladimir Putin will

Bioavailability and soil-to-plant transfer factors as indicators of potentially toxic element contamination in agricultural soils.

PubMed

Adamo, Paola; Iavazzo, Pietro; Albanese, Stefano; Agrelli, Diana; De Vivo, Benedetto; Lima, Annamaria

2014-12-01

Soil pollution in agricultural lands poses a serious threat to food safety, and suggests the need for consolidated methods providing advisory indications for soil management and crop production. In this work, the three-step extraction procedure developed by the EU Measurement and Testing Programme and two soil-to-plant transfer factors (relative to total and bioavailable concentration of elements in soil) were applied on polluted agricultural soils from southern Italy to obtain information on the retention mechanisms of metals in soils and on their level of translocation to edible vegetables. The study was carried out in the Sarno river plain of Campania, an area affected by severe environmental degradation potentially impacting the health of those consuming locally produced vegetables. Soil samples were collected in 36 locations along the two main rivers flowing into the plain. In 11 sites, lettuce plants were collected at the normal stage of consumption. According to Italian environmental law governing residential soils, and on the basis of soil background reference values for the study area, we found diffuse pollution by Be, Sn and Tl, of geogenic origin, Cr and Cu from anthropogenic sources such as tanneries and intensive agriculture, and more limited pollution by Pb, Zn and V. It was found that metals polluting soils as a result of human activities were mainly associated to residual, oxidizable and reducible phases, relatively immobile and only potentially bioavailable to plants. By contrast, the essential elements Zn and Cu showed a tendency to become more readily mobile and bioavailable as their total content in soil increased and were more easily transported to the edible parts of lettuce than other pollutants. According to our results, current soil pollution in the studied area does not affect the proportion of metals taken up by lettuce plants and there is a limited health risk incurred. Copyright © 2014 Elsevier B.V. All rights reserved.

A Valentine's Day bouquet for Temperature readers: pleasing with prizes, searching for the right words, and keeping things mysterious.

PubMed

Romanovsky, Andrej A

2015-01-01

This editorial tells its readers that the journal Temperature awards its first prizes for best papers to Boris Kingma and Assaf Yacobi. It also discusses the use of several thermoregulation-related terms and expressions, including "cold temperature," "thermoneutral temperature," and "warm-sensitive" and offers, arguably, better alternatives. The editorial also contains a new puzzle: how can color affect temperature perception?

Russian Energy Policy vis-a-vis Europe: Natural Resources as a Means of Foreign Policy

DTIC Science & Technology

2012-06-01

that lag. For instance, after the March 2011 Fukushima disaster , German political leadership decided...memories for the rest of my life. xii THIS PAGE INTENTIONALLY LEFT BLANK 1 I. INTRODUCTION A. BACKGROUND After the resignation of Boris Yeltsin...the first president of the Russian Federation after the dissolution of the USSR, on December 31, 1999, and de facto appointment of his successor

Converting Existing Copper Wire Firing System to a Fiber Optically Controlled Firing System for Electromagnetic Pulsed Power Experiments

DTIC Science & Technology

2017-12-19

Firing System for Electromagnetic Pulsed Power Experiments by Robert Borys Jr and Colby Adams Approved for public release...Belcamp, MD Approved for public release; distribution is unlimited. ii REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188... Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions

III Potsdam-V Kiev International Workshop on Nonlinear Processes in Physics. Held in Potsdam, New York on August 1-11, 1991

DTIC Science & Technology

1991-08-01

Bona, Burke, Grundbaum, Hasagawa, Horton, Krichever, Kruskal, Kuznetsov , Lax, McLaughlin, Mikhailov., Rubenchik, Sabatier, Tabor, Zabusky) for their...British Telecom Lab., GB Fibers Oleg Bogoyavlenskij Breaking Solitons Steklov Mathematical Institute USSR Marco Boiti Real and Virtual Multidimensional...Beyond Rutgers University, USA Boris Kupershmidt Relativistic Analogs of Lax Equations Tennessee Space Institute, USA E.A. Kuznetsov Weak MHD Turbulence

The Multi-Lens Array Architecture

DTIC Science & Technology

2007-02-26

slowly with respect to f, numerical integration using Simpson’s 1/3 Rule is a convenient method to evaluate Eq. 11. It can be shown the result can...quality of the paper. The author also has had stimulating discussions with Mr. David Curtis, Dr. Boris Tomasic and Dr. Peter Franchi . 24...REFERENCES [1] W. Rotman, P. Franchi , “Cylindrical Microwave Lens Antenna for Wideband Scanning Application”, Antennas and Prop. Int. Symposium, vol. 18

Progress towards quantum simulating the classical O(2) Model

DTIC Science & Technology

2014-12-01

approach by building up on simple models sharing some of the basic features of lattice QCD . In the context of condensed matter, a proof of principle that...independently. Explicit Hilbert space repre- sentations of the physical states and of their matrix elements are mostly absent from today’s lattice QCD ...to lattice QCD , seems possible and interesting. ACKNOWLEDGMENTS We thank Masanori Hanada, Peter Orland, Lode Pollet, Boris Svistunov, the participants

JPRS Report, Soviet Union, Political Affairs.

DTIC Science & Technology

1989-09-07

Rehabilitates Cardinal Vaivods [SOVETSKAYA LATVIYA, 15 Jun 89] 35 Church Built By Boris Godunov Conducts Religious Services [I. Serebryakov...from 1920 through 1940; —the history of the LSDRP [Latvian Social-Democratic Workers Party] from 1918 ; —the evaluation of the 23 August 1939...parallels with the 1918 situation in Lithuania in our arguments are incorrect. Let us recall the fact alone that Lithuania at that time used 400 tons of

Personality as a Social Process: where Peter Giordano Meets Boris Parygin.

PubMed

Mironenko, Irina A

2018-06-01

In this paper I comment on the "Individual personality is best understood as process, not structure: A Confucian-inspired perspective" article by Peter Giordano (Culture & Psychology, 23(4), 502-518 (2017)), which addresses the question of how to comprehend a personality which is continuously changing and varying with changes in social contexts and situations. The issue which Giordano turns up I believe to be of great importance and topicality in the quickly changing globalizing contemporary world. Giordano's paper highlights an important problem in the development of contemporary personality psychology, but much remains to be clarified concerning his process-centric model. I introduce the theory of Boris Parygin, which can make a contribution to the discussion of personality as a process. Parygin's theory addresses the same issues that Giordano focuses on: human personality exists and develops in the context of social situation. Parygin's theoretical model of personality involves two personality schemas: a "static" one and a "dynamic" one. The "structure" and the "process" -centered approaches are joint here to complement each other. Personality life-span development, formation of personality structures, is considered as a process of interaction and dialectical confrontation with the social environment, in the course of which the personality, originally engendered by social factors, builds up its autonomy and realizes its unique individual spiritual potential.

Kosovo and U.S. Policy: Background to Independence

DTIC Science & Technology

2008-06-20

Assembly chose a President and a government in March 2002. LDK leader Ibrahim Rugova was elected as President and Bajram Rexhepi of the PDK became Prime... Agim Ceku, who was formerly head of the KLA and head of the Kosovo Protection Corps. The new government pledged to implement standards set by the...July 24, 2006, Kosovo President Fatmir Sejdiu and Prime Minister Agim Ceku met with their Serbian counterparts Boris Tadic and Vojislav Kostunica to

Kosovo and U.S. Policy

DTIC Science & Technology

2006-08-07

Agim Ceku met in Vienna with their Serbian counterparts Boris Tadic and Vojislav Kostunica to discuss the status issue, in the first direct, high-level...President. Kosovo’s Prime Minister is Bajram Rexhepi of the PDK. The government consisted of members of the LDK, PDK and AAK. One cabinet post was...replaced by Agim Ceku, who was formerly head of the KLA and head of the Kosovo Protection Corps. The new government pledged to implement standards set by

Kosovo and U.S. Policy: Background and Current Issues

DTIC Science & Technology

2007-10-24

is Bajram Rexhepi of the PDK. The government consisted of members of the LDK, PDK and AAK. One cabinet post was reserved for a Kosovo Serb...2006, Kosovo Prime Minister Bajram Kosumi stepped down after criticism of his performance, even within his own party. He was replaced by Agim Ceku...Fatmir Sejdiu and Prime Minister Agim Ceku met with their Serbian counterparts Boris Tadic and Vojislav Kostunica to discuss the status issue, in the

JPRS Report, Soviet Union, USA: Economics, Politics, Ideology, No. 9, September 1987

DTIC Science & Technology

1988-03-10

music and "infor- mational imperialism"—but also the Americanization of the political process, distinguished by attempts to stan- dardize political...and business groups geared to the entertainment , leisure, and service industries grew stronger. These groups were particularly dissatisfied with...Shostakovich’s operas was described as "cacophony instead of music " in our country and when Boris Pasternak was later stigmatized for writing "Doc- tor

Bell's theorem and quantum mechanics

NASA Astrophysics Data System (ADS)

Rosen, Nathan

1994-02-01

Bell showed that assuming locality leads to a disagreement with quantum mechanics. Here the nature of the nonlocality that follows from quantum mechanics is investigated. Note by the Editor—Readers will recognize Professor Rosen, author of this paper, as one of the co-authors of the famous EPR paper, Albert Einstein, Boris Podolsky, and Nathan Rosen, ``Can Quantum-Mechanical Description of Physical Reality be considered Complete?'', Phys. Rev. 47, 770-780 (1935). Robert H. Romer, Editor

Meteor Beliefs Project: Meteoric imagery in SF, Part II - H. P. Lovecraft's The Colour Out Of Space

NASA Astrophysics Data System (ADS)

McBeath, Alastair; Gheorghe, Andrei Dorian

2005-12-01

A brief biography of American horror-fiction writer H. P. Lovecraft (1890-1937) precedes details from his story `The Colour Out Of Space', concerning a deadly life-form brought to Earth in a meteorite. This allows a comparison with details from the 1965 film derived from this tale, `Die, Monster, Die!', featuring the great horror actor Boris Karloff in one of his last, best roles.

JPRS Report, Science & Technology, USSR: Science & Technology Policy

DTIC Science & Technology

1990-01-10

development and introduction in practice of new methods for the diag- nosis, prevention and treatment of pseudotuberculosis. 17. Boris Ivanovich...Its Prevention , Diagnosis, and Treatment ," 1962-1988. Submitted by the Tbilisi Institute of the Advanced Training of Physicians of the Georgian SSR...research only with the forces of "one’s own" academy? What prevents a republic, say, from enlisting for this any institute of the USSR Academy of Sciences

Fixed-dose combination drugs for tuberculosis: application in standardised treatment regimens.

PubMed

Blomberg, Bjørn; Fourie, Bernard

2003-01-01

Short-course chemotherapy is highly efficacious in treating tuberculosis (TB). However, the length (>/=6 months) and complexity (three or four different drugs) of the treatment makes adherence difficult. Erratic treatment not only fails to cure patients but also creates chronically contagious cases, who may excrete drug-resistant TB bacteria. The Directly Observed Treatment Short-course (DOTS) strategy recommended by WHO provides a comprehensive organisational and infrastructural framework for the rational use of diagnosis, drug supply, as well as case and programme management services, in TB control. WHO and other organisations recommend fixed-dose combination formulations (FDCs) as a further step to facilitate the optimal drug treatment of TB. Using FDCs in TB control will simplify the doctor's prescription and patient's drug intake, as well as the drug supply management of the programme. By preventing monotherapy and facilitating the ingestion of adequate doses of the constituent anti-TB drugs, FDCs are expected to help prevent the emergence of drug resistance. This article presents the international recommendations for the use of FDCs in TB programmes. The fundamental issue is to obtain drug supplies of good quality. A laboratory network for quality testing, including bioavailability testing of FDCs exists, and the recently established Global TB Drug Facility (GDF) supplies quality TB drugs, including 4-drug FDCs, to countries requesting assistance. This articles deals with the requirements for a successful transition to FDC-based treatment. It emphasises the need for appropriately revised programme documentation (programme manual, training modules, treatment guidelines and forms), training of staff at all levels, carefully calculated drug needs, and a plan for the exhaustion of existing stocks of loose tablets and the phasing-in of FDCs at all levels of the programme at the same time. Loose drugs for individualised treatment of patients with adverse effects should be kept at district or central health institutions.

Kosovo and U.S. Policy: Background and Current Issues

DTIC Science & Technology

2008-05-02

President and Bajram Rexhepi of the PDK became Prime Minister. The government consisted of members of the LDK, PDK and AAK. One cabinet post was reserved...party. He was replaced by Agim Ceku, who was formerly head of the KLA and head of the Kosovo Protection Corps. The new government pledged to implement...Sejdiu and Prime Minister Agim Ceku met with their Serbian counterparts Boris Tadic and Vojislav Kostunica to discuss the status issue, in the first

Area Handbook Series: Egypt: A Country Study

DTIC Science & Technology

1991-01-01

iI~torical Settinlg Sphinx and pyramids at Giza (Al jizah) THE ROOTS OF EGYPTIAN civilization go back more than 6,000 years to the beginning of...built by Snoferu, the first king of the Fourth Dynasty. His son and successor, Kheops, built the Great Pyramid at Giza (AlJizah); this, with its two... Pyramid and Sphinx at Giza , Fourth Dynasty, ca. 2540 B. C. Courtesy Boris Boguslavsky 19 Egypt: A Country Study In June 640, reinforcements for the Arab

The Politics and Policy of U.S. Bases in Poland: A Political-Military Analysis

DTIC Science & Technology

2012-12-01

end, after 15 unsuccessful attempts at resolution, Polish president Lech Walesa persuaded Russian president Boris Yeltsin to accept the “zero option...surrounded by its allies, protected by America.ඣ Also the Polish President, Lech Kaczyński declared that: “I cannot say that I am happy [about...Central and Eastern European intellectuals and policy makers under the leadership of Lech Walesa, former leader of Solidarity movement and President

A Valentine's Day bouquet for Temperature readers: pleasing with prizes, searching for the right words, and keeping things mysterious

PubMed Central

Romanovsky, Andrej A

2015-01-01

This editorial tells its readers that the journal Temperature awards its first prizes for best papers to Boris Kingma and Assaf Yacobi. It also discusses the use of several thermoregulation-related terms and expressions, including “cold temperature,” “thermoneutral temperature,” and “warm-sensitive” and offers, arguably, better alternatives. The editorial also contains a new puzzle: how can color affect temperature perception? PMID:27226997

50 CFR 697.24 - Exempted waters for Maine State American lobster permits.

Code of Federal Regulations, 2012 CFR

2012-10-01

....5 deg.40′33″ W. long. (d) South of Boris Bubert Island in the area located north of the line 44.5... Federal and State regulations: (a) West of Monhegan Island in the area located north of the line 43.5 deg...) East of Monhegan Island in the area located west of the line 43.5 deg.44′00″ N. lat., 69.5 deg.15′05″ W...

PREFACE: Physics and Mathematics of Nonlinear Phenomena 2013 (PMNP2013)

NASA Astrophysics Data System (ADS)

Konopelchenko, B. G.; Landolfi, G.; Martina, L.; Vitolo, R.

2014-03-01

Modern theory of nonlinear integrable equations is nowdays an important and effective tool of study for numerous nonlinear phenomena in various branches of physics from hydrodynamics and optics to quantum filed theory and gravity. It includes the study of nonlinear partial differential and discrete equations, regular and singular behaviour of their solutions, Hamitonian and bi- Hamitonian structures, their symmetries, associated deformations of algebraic and geometrical structures with applications to various models in physics and mathematics. The PMNP 2013 conference focused on recent advances and developments in Continuous and discrete, classical and quantum integrable systems Hamiltonian, critical and geometric structures of nonlinear integrable equations Integrable systems in quantum field theory and matrix models Models of nonlinear phenomena in physics Applications of nonlinear integrable systems in physics The Scientific Committee of the conference was formed by Francesco Calogero (University of Rome `La Sapienza', Italy) Boris A Dubrovin (SISSA, Italy) Yuji Kodama (Ohio State University, USA) Franco Magri (University of Milan `Bicocca', Italy) Vladimir E Zakharov (University of Arizona, USA, and Landau Institute for Theoretical Physics, Russia) The Organizing Committee: Boris G Konopelchenko, Giulio Landolfi, Luigi Martina, Department of Mathematics and Physics `E De Giorgi' and the Istituto Nazionale di Fisica Nucleare, and Raffaele Vitolo, Department of Mathematics and Physics `E De Giorgi'. A list of sponsors, speakers, talks, participants and the conference photograph are given in the PDF. Conference photograph

A synopsis of the Joint Environment and Human Health Programme in the UK.

PubMed

Moore, Michael N; Kempton, Pamela D

2009-12-21

The Joint Environment and Human Health (E&HH) Programme has explored how both man-made and natural changes to the environment can influence human health. Scientists have tackled the complicated mix of environmental, social and economic factors that influence health, particularly focusing on naturally occurring toxins, man-made pollutants, nanoparticles and pathogens to see:* how they spread within the environment* how their properties change as they interact with other substances or organisms* how we become exposed to them, and* their impact on human health.The Programme has not only succeeded in bringing together scientists from a broad range of environmental, social and biomedical backgrounds, but also fostered new relationships with end users and policy makers. This new community is helping to provide the multidisciplinary capacity able to respond in an interdisciplinary way to resolve problems that are intrinsically interfacial in character. Many of these questions relate to complex issues such as the environmental biology and geochemistry of soils and how these influence the transport, accessibility and bioavailability of chemical pollutants and infectivity of pathogens. The dispersion of harmful particles in the atmosphere is another area of major concern where the E&HH Programme has broken new ground by showing how the chemical and physical properties of such particles influence their environmental behaviour and may govern their toxicity and resultant pathological reactions induced following inhalation. Working groups and networks have identified potential health problems concerning the transport and emergence of human pathogens associated with food, soil, air and water. The consequence(s) of global and regional climate change for the environmental behaviours of pollutants and pathogens have been considered by a number of the projects supported by the E&HH programme.The selection of articles in this supplement reflect the broad scope of the E&HH programme. By effectively identifying and interconnecting these interdisciplinary elements, the E&HH programme has fostered the emergence of new ways of solving problems in areas of research that have, until recently, had little connection with one another. This has not only helped build new research groupings, but has also led to exciting new scientific developments as described in this issue of Environmental Health.

sts106-s-005

NASA Image and Video Library

2000-09-08

STS106-S-005 (8 September 2000) --- This distant view of the STS-106 liftoff was photographed across marsh waters around Mosquito Lagoon and Banana Creek, looking toward the Atlantic Ocean. The perfect on-time liftoff of the Space Shuttle Atlantis occurred at 8:45:47 a.m. (EDT), September 8, 2000. Onboard the shuttle were astronauts Terrence W. Wilcutt, Scott D. Altman, Edward T. Lu, Richard A. Mastracchio and Daniel C. Burbank, along with cosmonauts Yuri I. Malenchenko and Boris V. Morukov who represent the Russian Aviation and Space Agency.

Less reality, more security

NASA Astrophysics Data System (ADS)

Ekert, Artur

2009-09-01

On 25 March 1935 John Tate, the then editor of Physical Review, received a paper that Einstein had co-authored with Boris Podolsky and Nathan Rosen, his younger colleagues at Princeton. The logbooks of Physical Review show that the EPR paper, as it has since become known, bypassed the refereeing process and went straight to press. Four printed pages of beautifully constructed argument appeared in the 15 May issue. They were heralded by a brief article in the New York Times titled "Einstein attacks quantum theory". And so he did.

Iran’s Influence on the Former Soviet Muslim Republics and the Implications for U.S. Strategic Policy

DTIC Science & Technology

1992-03-25

Union. =7 This was followed by a most dramatic improvement in Soviet-Iranian relations. Soviet Foreign Minister Eduard Shevardnadze visited Iran in...Iran has been wary of a reemergence of Russian imperialisml the Iranian Foreign Minister , Dr. All Akbar Velayati, in September criticized Boris Yeltsin...with Foreign Minister Velayati’s visit to Moscow. Moscow radio confirmed the opening of the new consulates 11 on 19 December 1991. 4𔃺 ENDNOTES 1

Naval War College Review. Volume 66, Number 3, Summer 2013

DTIC Science & Technology

2013-01-01

of-fered a wake - up call in a speech to the Marine Corps Association in 2010: “It [is] time to redefine the purpose and size of the Marine Corps.” The...bring to private industry. In a recent Harvard Business review article, Boris Groysberg and his colleagues note that former military officers make up ...naval war college review Naval War College Press 686 Cushing road Newport, rI 02841-1207 Summer 2013 Volume 66, Number 3 Report Documentation Page

Cloak and Dagger Boys in Our Midst: Sex and Security

DTIC Science & Technology

1966-04-22

finally married a Russian girl but then he always was the male of the pair. They gave the impression that they had been outraged at the "immoral" practices ...abnormal sex acts (homosexuality, sodomy, group masturbation or Don Juanism/nymphomania) were turned down, they couldn’t fill one tenth of their 1...intercourse practiced for its own sake. Boris Morros has pointed out that both Soviet men and women agents are expected to subordinate their sex drive to

Characterization of an Mg-implanted GaN p-i-n Diode

DTIC Science & Technology

2016-03-31

unintentionally doped GaN layer was grown by metal organic chemical vapor deposition (MOCVD) on a n+ Ga -face c-oriented GaN substrate. The as-grown MOCVD film...their proper lattice sites. In the case of Mg implanted GaN , the Mg must replace Ga to result in p-type material. In many other semiconductor...Characterization of an Mg-implanted GaN p-i-n Diode Travis J. Anderson, Jordan D. Greenlee, Boris N. Feigelson, Karl D. Hobart, and Francis J

MS Morukov prepares Zvezda for habitation during STS-106

NASA Image and Video Library

2000-09-13

S106-E-5173 (13 September 2000) --- Cosmonaut Boris V. Morukov, mission specialist representing the Russian Aviation and Space Agency, is part of the team effort to ready the International Space Station (ISS) for permanent habitation. The STS-106 astronauts and cosmonauts are continuing electrical work and transfer activities as they near the halfway point of docked operations with the International Space Station. In all, the crew will have 189 hours, 40 minutes of planned Atlantis-ISS docked time.

KSC-99pp1489

NASA Image and Video Library

1999-12-09

KENNEDY SPACE CENTER, FLA. -- During a Crew Equipment Interface Test (CEIT) at SPACEHAB, in Cape Canaveral, Fla., members of the STS-101 crew learn about some of the cargo that will be on their mission. At left are Mission Specialists Jeffrey N. Williams and Edward Tsang Lu (Ph.D.); at right are Commander James Donald Halsell Jr., and Mission Specialist Boris W. Morukov, who is with the Russian Space Agency (RSA). Other crew members are Pilot Scott Horowitz, and Mission Specialists Mary Ellen Weber, (Ph.D.) and Boris W. Morukov and Yuri Malenchenko, who are with the Russian Space Agency. The primary objective of the STS-101 mission is to complete the initial outfitting of the International Space Station, making it fully ready for the first long-term crew. The seven-member crew will transfer almost two tons of equipment and supplies from SPACEHAB's Logistics Double Module. Additionally, they will unpack a shipment of supplies delivered earlier by a Russian Progress space tug and begin outfitting the newly arrived Zvezda Service Module. Three astronauts will perform two space walks to transfer and install parts of the Russian Strela cargo boom that are attached to SPACEHAB's Integrated Cargo Container, connect utility cables between Zarya and Zvezda, and install a magnetometer/pole assembly on the Service Module. Additional activities for the STS-101 astronauts include working with the Space Experiment Module (SEM-06) and the Mission to America's Remarkable Schools (MARS), two educational initiatives. STS-101 is scheduled for launch no earlier than March 16, 2000

Accreditation at a crossroads: are we on the right track?

PubMed

Touati, Nassera; Pomey, Marie-Pascale

2009-05-01

By comparing Canada, where accreditation is optional, to France, where it is required, this study evaluates the extent to which the accreditation process acts as a tool for bureaucratic coercion as opposed to a tool for learning. Our study consists of a qualitative meta-analysis of studies of French and Canadian accreditation experiences between 1996 and 2006. Using the conceptual framework of Adler and Borys [Adler P, Borys B. Two types of bureaucracy: enabling and coercitive. Administration Science Quarterly 1996;41:61-89], we assess the characteristics of accreditation in the French and the Canadian environments and distinguish between coercive and enabling modi operandi. Results show that accreditation has positive impacts in the two countries but is more coercion-oriented in France than in Canada. This is because in France: (1) the fact that accreditation is compulsory and certain standards are required by law limits participant's opportunities to influence the process; (2) standards are not adapted to various clinical programs and as a result, participants contest their legitimacy; (3) ambiguity about the use of accreditation visit results has sullied global transparency. Despite differences between the French and Canadian systems, however, both systems are converging towards a mixed model that includes elements of both philosophies, with the Canadian model becoming more coercive and the French model becoming more flexible and learning-oriented. Comparison of the two cases shows that current trends in the evolution of accreditation threaten the very purpose of the accreditation process.

STS-101 crew take part in CEIT at SPACEHAB

NASA Technical Reports Server (NTRS)

1999-01-01

During a Crew Equipment Interface Test (CEIT) at SPACEHAB, in Cape Canaveral, Fla., members of the STS-101 crew learn about some of the cargo that will be on their mission. At left are Mission Specialists Jeffrey N. Williams and Edward Tsang Lu (Ph.D.); at right are Commander James Donald Halsell Jr., and Mission Specialist Boris W. Morukov, who is with the Russian Space Agency (RSA). Other crew members are Pilot Scott Horowitz, and Mission Specialists Mary Ellen Weber, (Ph.D.) and Boris W. Morukov and Yuri Malenchenko, who are with the Russian Space Agency. The primary objective of the STS-101 mission is to complete the initial outfitting of the International Space Station, making it fully ready for the first long-term crew. The seven-member crew will transfer almost two tons of equipment and supplies from SPACEHAB's Logistics Double Module. Additionally, they will unpack a shipment of supplies delivered earlier by a Russian Progress space tug and begin outfitting the newly arrived Zvezda Service Module. Three astronauts will perform two space walks to transfer and install parts of the Russian Strela cargo boom that are attached to SPACEHAB's Integrated Cargo Container, connect utility cables between Zarya and Zvezda, and install a magnetometer/pole assembly on the Service Module. Additional activities for the STS-101 astronauts include working with the Space Experiment Module (SEM-06) and the Mission to America's Remarkable Schools (MARS), two educational initiatives. STS-101 is scheduled for launch no earlier than March 16, 2000.

Desert Research Institute cloud droplet videometer measurements in support of MASTEX

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-02-13

In support of the Monterey Area Ship-Track Experiment (MASTEX) the Desert Research Institute completed modifications to an existing cloud droplet videometer and construction of a second unit for deployment on board the RV Glorita during the month of June 1994. Dr. Randolph Borys accompanied the instrumentation during the period the ship was at sea and assisted in the day-to-day experiments which were conducted on board. Unusually clear conditions and high winds contributed to the lack of opportunities to deploy the new instrument from the ship.

Sea Ice Observations from the Winter Weddell Gyre Study - 󈨝

DTIC Science & Technology

1991-02-01

Winter Weddell Gyre Study-󈨝 Debra A. Meese. John W. Govoni. Vladimir Churijn. Borns Ivanov, Victor Komarovskiy. Vasily Shilnikov and Andre Zachek P...A MEESE, JOHN W GOVMN, VLADIMIR CHJURUN. BORIS IVANOV, VICrOR KONIAROVSKIY. VASILY SHILNIKOV AND ANDRE ZACHEK INTRODUCTION 18 September 1989 (day 261...station 24, ,0 f 1 2 150 300 5 JIE1IOBAfl OBOTAIIOBKA OoeaIorpadliuecxanI CTaIIW~lf Pit Itjara: ~ 18 ’= 67𔃿o, ’fP 67-50𔃿 ) 𔃾:S A = iis 5 ~~v BPe.fn

STS-106 Crew Activities Report/Flight Day 04 Highlights

NASA Technical Reports Server (NTRS)

2000-01-01

On this fourth day of the STS-106 Atlantis mission, the flight crew, Commander Commander Terrence W. Wilcutt, Pilot Scott D. Altman, and Mission Specialists Daniel C. Burbank, Edward T. Lu, Richard A. Mastracchio, Yuri Ivanovich Malenchenko, and Boris V. Morukov are seen preparing for the scheduled space walk. Lu and Malenchenko are seen coming through the hatch of the International Space Station (ISS). Also shown are Lu and Malenchenko attaching a magnetometer and boom to Zvezda. Mastracchio operates the robot arm moving the extravehicular activity (EVA) crew outside of the ISS.

The Russians Debate the Kuril Islands Territorial Dispute: An Aspect of Russo-Japanese Relations in the Post-Cold War World

DTIC Science & Technology

1993-06-01

the existence of a territorial problem up until the time of President Mikhail Gorbachev. When Gorbachev visited Japan in April 1991, he admitted that...Alexei Arbatov and Boris Makeyev , ’The Kuril Barrier," New Times (42.92), p. 26. 34 diplomats and politicians which has taken shape has yet to be overcome...in English GMT 3 Mar 92 (FBIS-SOV-92-042, 3 March 1992, p. 22). 52 IV. ECONOMIC INTERESTS A. OVERVIEW Mikhail Gorbachev officially announced his

Note on online books and articles about the history of dissociation.

PubMed

Alvarado, Carlos S

2008-01-01

Students of the history of dissociation will be interested in the materials on the subject available in the digital document database Google Book Search. This includes a variety of books and journals covering automatic writing, hypnosis, mediumship, multiple personality, trance, somnambulism, and other topics. Among the authors represented in the database are: Eugène Azam, Alfred Binet, James Braid, Jean-Martin Charcot, Pierre Janet, Frederic W.H. Myers, Morton Prince, and Boris Sidis, among others. The database includes examples of case reports, conceptual discussions, and psychiatric and psychological textbook literature.

Sorption, transport and biodegradation - An insight into bioavailability of persistent organic pollutants in soil.

PubMed

Ren, Xiaoya; Zeng, Guangming; Tang, Lin; Wang, Jingjing; Wan, Jia; Liu, Yani; Yu, Jiangfang; Yi, Huan; Ye, Shujing; Deng, Rui

2018-01-01

Contamination of soils with persistent organic pollutants (POPs), such as organochlorine pesticide, polybrominated diphenyl ethers, halohydrocarbon, polycyclic aromatic hydrocarbons (PAHs) is of increasing concern. Microbial degradation is potential mechanism for the removal of POPs, but it is often restricted by low bioavailability of POPs. Thus, it is important to enhance bioavailability of POPs in soil bioremediation. A series of reviews on bioavailability of POPs has been published in the past few years. However, bioavailability of POPs in relation to soil organic matter, minerals and soil microbes has been little studied. To fully understand POPs bioavailability in soil, research on interactions of POPs with soil components and microbial responses in bioavailability limitation conditions are needed. This review focuses on bioavailability mechanisms of POPs in terms of sorption, transport and microbial adaptation, which is particularly novel. In consideration of the significance of bioavailability, further studies should investigate the influence of various bioremediation strategies on POPs bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

Systems Biological Approach of Molecular Descriptors Connectivity: Optimal Descriptors for Oral Bioavailability Prediction

PubMed Central

Ahmed, Shiek S. S. J.; Ramakrishnan, V.

2012-01-01

Background Poor oral bioavailability is an important parameter accounting for the failure of the drug candidates. Approximately, 50% of developing drugs fail because of unfavorable oral bioavailability. In silico prediction of oral bioavailability (%F) based on physiochemical properties are highly needed. Although many computational models have been developed to predict oral bioavailability, their accuracy remains low with a significant number of false positives. In this study, we present an oral bioavailability model based on systems biological approach, using a machine learning algorithm coupled with an optimal discriminative set of physiochemical properties. Results The models were developed based on computationally derived 247 physicochemical descriptors from 2279 molecules, among which 969, 605 and 705 molecules were corresponds to oral bioavailability, intestinal absorption (HIA) and caco-2 permeability data set, respectively. The partial least squares discriminate analysis showed 49 descriptors of HIA and 50 descriptors of caco-2 are the major contributing descriptors in classifying into groups. Of these descriptors, 47 descriptors were commonly associated to HIA and caco-2, which suggests to play a vital role in classifying oral bioavailability. To determine the best machine learning algorithm, 21 classifiers were compared using a bioavailability data set of 969 molecules with 47 descriptors. Each molecule in the data set was represented by a set of 47 physiochemical properties with the functional relevance labeled as (+bioavailability/−bioavailability) to indicate good-bioavailability/poor-bioavailability molecules. The best-performing algorithm was the logistic algorithm. The correlation based feature selection (CFS) algorithm was implemented, which confirms that these 47 descriptors are the fundamental descriptors for oral bioavailability prediction. Conclusion The logistic algorithm with 47 selected descriptors correctly predicted the oral bioavailability, with a predictive accuracy of more than 71%. Overall, the method captures the fundamental molecular descriptors, that can be used as an entity to facilitate prediction of oral bioavailability. PMID:22815781

Systems biological approach of molecular descriptors connectivity: optimal descriptors for oral bioavailability prediction.

PubMed

Ahmed, Shiek S S J; Ramakrishnan, V

2012-01-01

Poor oral bioavailability is an important parameter accounting for the failure of the drug candidates. Approximately, 50% of developing drugs fail because of unfavorable oral bioavailability. In silico prediction of oral bioavailability (%F) based on physiochemical properties are highly needed. Although many computational models have been developed to predict oral bioavailability, their accuracy remains low with a significant number of false positives. In this study, we present an oral bioavailability model based on systems biological approach, using a machine learning algorithm coupled with an optimal discriminative set of physiochemical properties. The models were developed based on computationally derived 247 physicochemical descriptors from 2279 molecules, among which 969, 605 and 705 molecules were corresponds to oral bioavailability, intestinal absorption (HIA) and caco-2 permeability data set, respectively. The partial least squares discriminate analysis showed 49 descriptors of HIA and 50 descriptors of caco-2 are the major contributing descriptors in classifying into groups. Of these descriptors, 47 descriptors were commonly associated to HIA and caco-2, which suggests to play a vital role in classifying oral bioavailability. To determine the best machine learning algorithm, 21 classifiers were compared using a bioavailability data set of 969 molecules with 47 descriptors. Each molecule in the data set was represented by a set of 47 physiochemical properties with the functional relevance labeled as (+bioavailability/-bioavailability) to indicate good-bioavailability/poor-bioavailability molecules. The best-performing algorithm was the logistic algorithm. The correlation based feature selection (CFS) algorithm was implemented, which confirms that these 47 descriptors are the fundamental descriptors for oral bioavailability prediction. The logistic algorithm with 47 selected descriptors correctly predicted the oral bioavailability, with a predictive accuracy of more than 71%. Overall, the method captures the fundamental molecular descriptors, that can be used as an entity to facilitate prediction of oral bioavailability.

Animal versus human oral drug bioavailability: Do they correlate?

PubMed Central

Musther, Helen; Olivares-Morales, Andrés; Hatley, Oliver J.D.; Liu, Bo; Rostami Hodjegan, Amin

2014-01-01

Oral bioavailability is a key consideration in development of drug products, and the use of preclinical species in predicting bioavailability in human has long been debated. In order to clarify whether any correlation between human and animal bioavailability exist, an extensive analysis of the published literature data was conducted. Due to the complex nature of bioavailability calculations inclusion criteria were applied to ensure integrity of the data. A database of 184 compounds was assembled. Linear regression for the reported compounds indicated no strong or predictive correlations to human data for all species, individually and combined. The lack of correlation in this extended dataset highlights that animal bioavailability is not quantitatively predictive of bioavailability in human. Although qualitative (high/low bioavailability) indications might be possible, models taking into account species-specific factors that may affect bioavailability are recommended for developing quantitative prediction. PMID:23988844

Volcanic Plumes Tower over Mount Etna

NASA Image and Video Library

2013-11-06

Twin volcanic plumes—one of ash, one of gas—rose from Sicily’ Mount Etna on the morning of October 26, 2013. L’Istituto Nazionale di Geofisica e Vulcanologia (INGV) Osservatorio Etneo (National Institute of Geophysics and Volcanology Etna Observatory) reported that Etna was experiencing its first paroxysm in six months. Multiple eruption columns are common at Etna, a result of complex plumbing within the volcano. The Northeast Crater, one of several on Etna’s summit, was emitting the ash column, while the New Southeast Crater was simultaneously venting mostly gas. This natural-color image collected by Landsat 8 shows the view from space at 11:38 a.m. local time. The towering, gas-rich plume cast a dark shadow over the lower, ash-rich plume and Etna’s northwestern flank. Relatively fresh lava flows (less than a century or so old) are dark gray; vegetation is green; and the tile-roofed buildings of Bronte and Biancavilla lend the towns an ochre hue. NASA Earth Observatory image by Jesse Allen and Robert Simmon, using Landsat data from the USGS Earth Explorer. Photograph ©2013, Boris Behncke. Caption by Robert Simmon with contributions from Boris Behncke. Instrument: Landsat 8 - OLI More info: 1.usa.gov/1cEcOFi Credit: NASA Earth Observatory NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Volcanic Plumes Tower over Mount Etna [annotated

NASA Image and Video Library

2013-11-06

Twin volcanic plumes—one of ash, one of gas—rose from Sicily’ Mount Etna on the morning of October 26, 2013. L’Istituto Nazionale di Geofisica e Vulcanologia (INGV) Osservatorio Etneo (National Institute of Geophysics and Volcanology Etna Observatory) reported that Etna was experiencing its first paroxysm in six months. Multiple eruption columns are common at Etna, a result of complex plumbing within the volcano. The Northeast Crater, one of several on Etna’s summit, was emitting the ash column, while the New Southeast Crater was simultaneously venting mostly gas. This natural-color image collected by Landsat 8 shows the view from space at 11:38 a.m. local time. The towering, gas-rich plume cast a dark shadow over the lower, ash-rich plume and Etna’s northwestern flank. Relatively fresh lava flows (less than a century or so old) are dark gray; vegetation is green; and the tile-roofed buildings of Bronte and Biancavilla lend the towns an ochre hue. NASA Earth Observatory image by Jesse Allen and Robert Simmon, using Landsat data from the USGS Earth Explorer. Photograph ©2013, Boris Behncke. Caption by Robert Simmon with contributions from Boris Behncke. Instrument: Landsat 8 - OLI More info: 1.usa.gov/1cEcOFi Credit: NASA Earth Observatory NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Research Opportunities at Storm Peak Laboratory

NASA Astrophysics Data System (ADS)

Hallar, A. G.; McCubbin, I. B.

2006-12-01

The Desert Research Institute (DRI) operates a high elevation facility, Storm Peak Laboratory (SPL), located on the west summit of Mt. Werner in the Park Range near Steamboat Springs, Colorado at an elevation of 3210 m MSL (Borys and Wetzel, 1997). SPL provides an ideal location for long-term research on the interactions of atmospheric aerosol and gas- phase chemistry with cloud and natural radiation environments. The ridge-top location produces almost daily transition from free tropospheric to boundary layer air which occurs near midday in both summer and winter seasons. Long-term observations at SPL document the role of orographically induced mixing and convection on vertical pollutant transport and dispersion. During winter, SPL is above cloud base 25% of the time, providing a unique capability for studying aerosol-cloud interactions (Borys and Wetzel, 1997). A comprehensive set of continuous aerosol measurements was initiated at SPL in 2002. SPL includes an office-type laboratory room for computer and instrumentation setup with outside air ports and cable access to the roof deck, a cold room for precipitation and cloud rime ice sample handling and ice crystal microphotography, a 150 m2 roof deck area for outside sampling equipment, a full kitchen and two bunk rooms with sleeping space for nine persons. The laboratory is currently well equipped for aerosol and cloud measurements. Particles are sampled from an insulated, 15 cm diameter manifold within approximately 1 m of its horizontal entry point through an outside wall. The 4 m high vertical section outside the building is capped with an inverted can to exclude large particles.

PREFACE Preface

NASA Astrophysics Data System (ADS)

Bleicher, Markus; Caines, Helen; Calderon de la Barca Sanchez, Manuel; de Falco, Alessandro; Fries, Rainer; Granier de Cassagnac, Raphael; Hippolyte, Boris; Mischke, Andre; Nardi, Marzia; Salgado, Carlos A.

2011-01-01

The 4th Workshop for Young Scientists on the Physics of Ultrarelativistic Nucleus-nucleus Collisions (Hot Quarks 2010) was held in La Londe-Les-Maures, France, from June 21-26, 2010. Following the traditions of the conference, this meeting gathered more than 70 participants in the first years of their scientific careers. The present issue contains the proceedings of this workshop. The articles published in this volume clearly show the presence of a dynamic new generation of physicists interested in the different aspects of high energy nuclear collisions. The newest results from RHIC at Brookhaven and SPS at CERN were presented, as well as the latest results from the proton-proton programme from the LHC at CERN, while waiting for the data of the lead-lead collisions only available some months after the meeting. Along with these experimental findings, the corresponding theoretical research was also extensively discussed as well as the new perspectives for future facilities like FAIR, EIC and LHeC. We wish to thank the sponsors of the Hot Quarks 2010 Conference, who supported the authors of this volume: IN2P3/CNRS (France), EMMI (Germany), Institut Pluridisciplinaire Hubert Curien (France), National Science Foundation (USA), CERN (Switzerland), Helmholtz International Center for FAIR (Germany), Xunta de Galicia (Spain) and the Journal of Physics G. Markus Bleicher (Frankfurt (HIC4FAIR), Germany)Helen Caines (Yale University, USA)Manuel Calderon de la Barca Sanchez (UC Davis, USA)Alessandro de Falco (Cagliari/INFN, Italy)Rainer Fries (Texas A & M University, USA) Raphael Granier de Cassagnac (Ecole Polytechnique, France)Boris Hippolyte (IPHC, Strasbourg, France)Andre Mischke (Utrecht University, The Netherlands)Marzia Nardi (Torino/INFN, Italy)Carlos A Salgado (Universidade de Santiago de Compostela, Galicia, Spain)

The bioavailability of chemicals in soil for earthworms

USGS Publications Warehouse

Lanno, R.; Wells, J.; Conder, Jason M.; Bradham, K.; Basta, N.

2004-01-01

The bioavailability of chemicals to earthworms can be modified dramatically by soil physical/chemical characteristics, yet expressing exposure as total chemical concentrations does not address this problem. In order to understand the effects of modifying factors on bioavailability, one must measure and express chemical bioavailability to earthworms in a consistent, logical manner. This can be accomplished by direct biological measures of bioavailability (e.g., bioaccumulation, critical body residues), indirect biological measures of bioavailability (e.g., biomarkers, reproduction), or indirect chemical measures of bioavailability (e.g., chemical or solid-phase extracts of soil). If indirect chemical measures of bioavailability are to be used, they must be correlated with some biological response. Bioavailability can be incorporated into ecological risk assessment during risk analysis, primarily in the estimation of exposure. However, in order to be used in the site-specific ecological risk assessment of chemicals, effects concentrations must be developed from laboratory toxicity tests based on exposure estimates utilizing techniques that measure the bioavailable fraction of chemicals in soil, not total chemical concentrations. ?? 2003 Elsevier Inc. All rights reserved.

pH-dependent solubility and permeability profiles: A useful tool for prediction of oral bioavailability.

PubMed

Sieger, P; Cui, Y; Scheuerer, S

2017-07-15

pH-dependent solubility - permeability profiles offer a simple way to predict bioavailability after oral application, if bioavailability is only solubility and permeability driven. Combining both pH-dependent solubility and pH-dependent permeability in one diagram provides a pH-window (=ΔpH sol-perm ) from which the conditions for optimal oral bioavailability can be taken. The size of this window is directly proportional to the observed oral bioavailability. A set of 21 compounds, with known absolute human oral bioavailability, was used to establish this correlation. Compounds with ΔpH sol-perm <2 exhibit poor oral bioavailability (<25%). An increase of ΔpH sol-perm by one pH-unit increases oral bioavailability typically by approximately 25%. For compounds where ΔpH sol-perm ≥3 but still showing poor bioavailability, most probably other pharmacokinetic aspects (e.g. high clearance), are limiting exposure. Interestingly, the location of this pH-window seems to have a negligible influence on the observed oral bioavailability. In scenarios, where the bioavailability is impaired by certain factors, like for example proton pump inhibitor co-medication or food intake, the exact position of this pH-window might be beneficial for understanding the root cause. Copyright © 2017 Elsevier B.V. All rights reserved.

The bioavailability of oxalate from Oca (Oxalis tuberosa).

PubMed

Albihn, P B; Savage, G P

2001-08-01

It is believed that soluble oxalate has higher bioavailability than insoluble oxalate. Oca (Oxalis tuberosa) is moderately high in oxalate and contains oxalate in soluble form only. We estimated the bioavailability of oxalate in oca based on the urinary excretion of oxalate after oxalate loading with oca to estimate the bioavailability of oxalate in oca. We also clarified whether bioavailability differs in various oxalate loads from the same food source and studied the effect of an additional calcium source on the bioavailability of oxalate from oca. Four men and 4 women ingested 50, 100 and 150 gm. oca as well as 100 gm. oca with 100 gm. sour cream. Oxalate was measured in a 6-hour urine sample from each volunteer. The mean bioavailability of oxalate from oca plus or minus standard deviation was 1.44% +/- 1.31% during the 6-hour period after intake. There was no significant difference in oxalate bioavailability among oxalate intake levels in this study, although oca consumption with sour cream significantly decreased the uptake of oxalate (p <0.01). The variation in bioavailability among individuals was high in our study. The bioavailability of oxalate in oca appears to be similar to that in spinach. However, bioavailability varies among individuals and depends on other constituents of a combined meal.

The Nutraceutical Bioavailability Classification Scheme: Classifying Nutraceuticals According to Factors Limiting their Oral Bioavailability.

PubMed

McClements, David Julian; Li, Fang; Xiao, Hang

2015-01-01

The oral bioavailability of a health-promoting dietary component (nutraceutical) may be limited by various physicochemical and physiological phenomena: liberation from food matrices, solubility in gastrointestinal fluids, interaction with gastrointestinal components, chemical degradation or metabolism, and epithelium cell permeability. Nutraceutical bioavailability can therefore be improved by designing food matrices that control their bioaccessibility (B*), absorption (A*), and transformation (T*) within the gastrointestinal tract (GIT). This article reviews the major factors influencing the gastrointestinal fate of nutraceuticals, and then uses this information to develop a new scheme to classify the major factors limiting nutraceutical bioavailability: the nutraceutical bioavailability classification scheme (NuBACS). This new scheme is analogous to the biopharmaceutical classification scheme (BCS) used by the pharmaceutical industry to classify drug bioavailability, but it contains additional factors important for understanding nutraceutical bioavailability in foods. The article also highlights potential strategies for increasing the oral bioavailability of nutraceuticals based on their NuBACS designation (B*A*T*).

Relative Bioavailability and Bioaccessability and Speciation of ...

EPA Pesticide Factsheets

Background: Assessment of soil arsenic (As) bioavailability may profoundly affect the extent of remediation required at contaminated sites by improving human exposure estimates. Because small adjustments in soil As bioavailability estimates can significantly alter risk assessments and remediation goals, convenient, rapid, reliable, and inexpensive tools are needed to determine soil As bioavailability. Objectives: We evaluated inexpensive methods for assessing As bioavailability in soil as a means to improve human exposure estimates and potentially reduce remediation costs. Methods: Nine soils from residential sites affected by mining or smelting activity and two National Institute of Standards and Technology standard reference materials were evaluated for As bioavailability, bioaccessibility, and speciation. Arsenic bioavailability was determined using an in vivo mouse model, and As bioaccessibility was determined using the Solubility/Bioavailability Research Consortium in vitro assay. Arsenic speciation in soil and selected soil physicochemical properties were also evaluated to determine whether these parameters could be used as predictors of As bio¬availability and bioaccessibility. Results: In the mouse assay, we compared bioavailabilities of As in soils with that for sodium arsenate. Relative bioavailabilities (RBAs) of soil As ranged from 11% to 53% (mean, 33%). In vitro soil As bioaccessibility values were strongly correlated with soil As RBAs (R

The bioavailability of iron, zinc, protein and vitamin A is highly variable in French individual diets: Impact on nutrient inadequacy assessment and relation with the animal-to-plant ratio of diets.

PubMed

Perignon, Marlène; Barré, Tangui; Gazan, Rozenn; Amiot, Marie-Josèphe; Darmon, Nicole

2018-01-01

Nutritional adequacy depends on nutrient intakes and bioavailability which strongly varies with the plant- or animal-origin of foods. The aim was to estimate iron, zinc, protein and vitamin A bioavailability from individual diets, and investigate its relation with the animal-to-plant ratio (A/P) of diets. Bioavailability was estimated in 1899 French diets using diet-based algorithms or food-group specific conversion factors. Nutrient inadequacy was estimated based on i) bioavailability calculated in each individual diet and ii) average bioavailability assumed for Western-diets. Mean iron absorption, zinc absorption, protein quality and β-carotene conversion factor were 13%, 30%, 92%, and 17:1, respectively. Bioavailability displayed a high variability between individual diets, poorly explained by their A/P. Using individual bioavailability led to different inadequacy prevalence than with average factors assumed for Western-diets. In this population, the A/P does not seem sufficient to predict nutrient bioavailability and the corresponding recommended intakes. Nutritional adequacy should be assessed using bioavailability accounting for individual diets composition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Arsenic bioavailability in soils before and after soil washing: the use of Escherichia coli whole-cell bioreporters.

PubMed

Yoon, Youngdae; Kang, Yerin; Chae, Yooeun; Kim, Sunghoon; Lee, Youngshim; Jeong, Seung-Woo; An, Youn-Joo

2016-02-01

We investigated the quantification of bioavailable arsenic in contaminated soils and evaluation of soil-washing processes in the aspect of bioavailability using a novel bacterial bioreporter developed in present study. The whole-cell bioreporter (WCB) was genetically engineered by fusing the promoter of nik operon from Escherichia coli and green fluorescent protein as a sensing domain and reporter domain. Among eight well-known hazardous heavy metals and metalloid, this system responded specifically to arsenic, thereby inferring association of As(III) with NikR inhibits the repression. Moreover, the response was proportional to the concentration of As(III), thereby it was capable to determine the amount of bioavailable arsenic quantitatively in contaminated soils. The bioavailable portion of arsenic was 5.9 (3.46-10.96) and 0.9 (0.27-1.74) % of total from amended and site soils, respectively, suggesting the bioavailability of arsenic in soils was related to the soil properties and duration of aging. On the other hand, only 1.37 (0.21-2.97) % of total arsenic was extracted into soil solutions and 19.88 (11.86-28.27) % of arsenic in soil solution was bioavailable. This result showed that the soluble arsenic is not all bioavailable and most of bioavailable arsenic in soils is water non-extractable. In addition, the bioavailable arsenic was increased after soil-washing while total amount was decreased, thereby suggesting the soil-washing processes release arsenic associated with soil materials to be bioavailable. Therefore, it would be valuable to have a tool to assess bioavailability and the bioavailability should be taken into consideration for soil remediation plans.

Earth Observations taken by the Expedition 13 crew

NASA Image and Video Library

2006-09-09

ISS013-E-79496 (9 Sept. 2006) --- This picture, photographed from the International Space Station by an Expedition 13 crewmember, includes the Baikonur launch complex and thus has special significance for the Expedition 13 crew and all crews who have launched aboard Soyuz craft to join the orbital outpost. Baikonur, formerly known as Leninsk, is a city within Kazakhstan, but it is rented and administered by Russia. It was constructed to service the Baikonur Cosmodrome and was officially renamed Baikonur by Boris Yeltsin on December 20, 1995. The name Baikonur is Kazakh for "wealthy brown," i.e. "fertile land with many herbs."

STS-106 Mission Specialist Morukov suits up before launch

NASA Technical Reports Server (NTRS)

2000-01-01

STS-106 Mission Specialist Boris V. Morukov gives a thumbs up for launch during suitup in the Operations and Checkout Building before launch. This is Morukov'''s first space flight. Space Shuttle Atlantis is set to lift off 8:45 a.m. EDT on the fourth flight to the International Space Station. During the 11-day mission, the seven-member crew will perform support tasks on orbit, transfer supplies and prepare the living quarters in the newly arrived Zvezda Service Module. The first long-duration crew, dubbed '''Expedition One,''' is due to arrive at the Station in late fall.

Bioavailability of xenobiotics in the soil environment.

PubMed

Katayama, Arata; Bhula, Raj; Burns, G Richard; Carazo, Elizabeth; Felsot, Allan; Hamilton, Denis; Harris, Caroline; Kim, Yong-Hwa; Kleter, Gijs; Koedel, Werner; Linders, Jan; Peijnenburg, J G M Willie; Sabljic, Aleksandar; Stephenson, R Gerald; Racke, D Kenneth; Rubin, Baruch; Tanaka, Keiji; Unsworth, John; Wauchope, R Donald

2010-01-01

It is often presumed that all chemicals in soil are available to microorganisms, plant roots, and soil fauna via dermal exposure. Subsequent bioaccumulation through the food chain may then result in exposure to higher organisms. Using the presumption of total availability, national governments reduce environmental threshold levels of regulated chemicals by increasing guideline safety margins. However, evidence shows that chemical residues in the soil environment are not always bioavailable. Hence, actual chemical exposure levels of biota are much less than concentrations present in soil would suggest. Because "bioavailability" conveys meaning that combines implications of chemical sol persistency, efficacy, and toxicity, insights on the magnitude of a chemicals soil bioavailability is valuable. however, soil bioavailability of chemicals is a complex topic, and is affected by chemical properties, soil properties, species exposed, climate, and interaction processes. In this review, the state-of-art scientific basis for bioavailability is addressed. Key points covered include: definition, factors affecting bioavailability, equations governing key transport and distributive kinetics, and primary methods for estimating bioavailability. Primary transport mechanisms in living organisms, critical to an understanding of bioavailability, also presage the review. Transport of lipophilic chemicals occurs mainly by passive diffusion for all microorganisms, plants, and soil fauna. Therefore, the distribution of a chemical between organisms and soil (bioavailable proportion) follows partition equilibrium theory. However, a chemical's bioavailability does not always follow partition equilibrium theory because of other interactions with soil, such as soil sorption, hysteretic desorption, effects of surfactants in pore water, formation of "bound residue", etc. Bioassays for estimating chemical bioavailability have been introduced with several targeted endpoints: microbial degradation, uptake by higher plants and soil fauna, and toxicity to organisms. However, there bioassays are often time consuming and laborious. Thus, mild extraction methods have been employed to estimate bioavailability of chemicals. Mild methods include sequential extraction using alcohols, hexane/water, supercritical fluids (carbon dioxide), aqueous hydroxypropyl-beta-cyclodextrin extraction, polymeric TENAX beads extraction, and poly(dimethylsiloxane)-coated solid-phase microextraction. It should be noted that mild extraction methods may predict bioavailability at the moment when measurements are carried out, but not the changes in bioavailability that may occur over time. Simulation models are needed to estimate better bioavailability as a function of exposure time. In the past, models have progressed significantly by addressing each group of organisms separately: microbial degradation, plant uptake via evapotranspiration processes, and uptake of soil fauna in their habitat. This approach has been used primarily because of wide differences in the physiology and behaviors of such disparate organisms. However, improvement of models is badly needed, Particularly to describe uptake processes by plant and animals that impinge on bioavailability. Although models are required to describe all important factors that may affect chemical bioavailability to individual organisms over time (e.g., sorption/desorption to soil/sediment, volatilization, dissolution, aging, "bound residue" formation, biodegradation, etc.), these models should be simplified, when possible, to limit the number of parameters to the practical minimum. Although significant scientific progress has been made in understanding the complexities in specific methodologies dedicated to determining bioavailability, no method has yet emerged to characterized bioavailability across a wide range of chemicals, organisms, and soils/sediments. The primary aim in studying bioavailability is to define options for addressing bioremediation or environmental toxicity (risk assessment), and that is unlikely to change. Because of its importance in estimating research is needed to more comprehensively address the key environmental issue of "bioavailability of chemicals in soil/sediment."

From conceptual model to remediation: bioavailability, a key to clean up heavy metal contaminated soils.

NASA Astrophysics Data System (ADS)

Petruzzelli, Gianniantonio; Pedron, Francesca; Pezzarossa, Beatrice

2013-04-01

Processes of metal bioavailability in the soil To know the bioavailability processes at site specific levels is essential to understand in detail the risks associated with pollution, and to support the decision-making process, i.e. description of the conceptual model and choice of clean up technologies. It is particularly important to assess how chemical, physical and biological processes in the soil affect the reactions leading to adsorption, precipitation or release of contaminants. The measurement of bioavailability One of the main difficulties in the practical application of the bioavailability concept in soil remediation is the lack of consensus on the method to be used to measure bioavailability. The best strategy is to apply a series of tests to assess bioavailability, since no applicable method is universally valid under all conditions. As an example, bioavailability tests for phytotechnology application should consider two distinct aspects: a physico-chemical driven solubilization process and a physiologically driven uptake process. Soil and plant characteristics strongly influence bioavailability. Bioavailability as a tool in remediation strategies Bioavailability can be used at all stages in remediation strategies: development of the conceptual model, evaluation of risk assessment, and selection of the best technology, considering different scenarios and including different environmental objectives. Two different strategies can be followed: the reduction and the increase of bioavailability. Procedures that reduce bioavailability aim to prevent the movement of pollutants from the soil to the living organisms, essentially by: i) removal of the labile phase of the contaminant, i.e. the fraction which is intrinsic to the processes of bioavailability (phytostabilization); ii) conversion of the labile fraction into a stable fraction (precipitation or adsorption); iii) increase of the resistance to mass transfer of the contaminants (inertization). Procedures that aim to increase the bioavailability of pollutants are used in technologies which remove or destroy the solubilized contaminants. These procedures can increase mass transfer from the absorbed phase by means of sieving in order to decrease the diffusion processes (soil washing), by increasing the temperature (low temperature thermal desorption), or through the addition of chemical additives, such as chelating agents (Phytoextraction Elektrokinetic remediation). Concluding remarks Bioavailability should be a key component of the exposure evaluation in order to develop the conceptual model and to select the technology, in particular when: • only some chemical forms of contaminants are a source of risk for the site; • default assumptions regarding bioavailability are not suitable because of the site's specific characteristics; • the final destination of the site will not be modified at least in the near future.

Bioavailability of Carbon Nanomaterial-Adsorbed Polycyclic Aromatic Hydrocarbons to Pimphales promelas: Influence of Adsorbate Molecular Size and Configuration.

PubMed

Linard, Erica N; Apul, Onur G; Karanfil, Tanju; van den Hurk, Peter; Klaine, Stephen J

2017-08-15

Despite carbon nanomaterials' (CNMs) potential to alter the bioavailability of adsorbed contaminants, information characterizing the relationship between adsorption behavior and bioavailability of CNM-adsorbed contaminants is still limited. To investigate the influence of CNM morphology and organic contaminant (OC) physicochemical properties on this relationship, adsorption isotherms were generated for a suite of polycyclic aromatic hydrocarbons (PAHs) on multiwalled carbon nanotubes (MWCNTs) and exfoliated graphene (GN) in conjunction with determining the bioavailability of the adsorbed PAHs to Pimphales promelas using bile analysis via fluorescence spectroscopy. Although it appeared that GN adsorbed PAHs indiscriminately compared to MWCNTs, the subsequent bioavailability of GN-adsorbed PAHs was more sensitive to PAH morphology than MWCNTs. GN was effective at reducing bioavailability of linear PAHs by ∼70%, but had little impact on angular PAHs. MWCNTs were sensitive to molecular size, where bioavailability of two-ringed naphthalene was reduced by ∼80%, while bioavailability of the larger PAHs was reduced by less than 50%. Furthermore, the reduction in bioavailability of CNM-adsorbed PAHs was negatively correlated with the amount of CNM surface area covered by the adsorbed-PAHs. This study shows that the variability in bioavailability of CNM-adsorbed PAHs is largely driven by PAH size, configuration and surface area coverage.

Drug Bioavailability Data: (Un)Available.

ERIC Educational Resources Information Center

Capomacchia, Anthony C.; And Others

1979-01-01

The obtainability of drug bioavailability data from both brand-name and generic-drug manufacturers was studied to document the relative change in availability to pharmacy students of drug bioavailability data between 1978 and 1976 for drugs exhibiting bioavailability problems. The results indicate no major change. (JMD)

Kaempferol in red and pinto bean seed (Phaseolus vulgaris L.) coats inhibits iron bioavailability using an in vitro digestion/human Caco-2 cell model.

PubMed

Hu, Ying; Cheng, Zhiqiang; Heller, Larry I; Krasnoff, Stuart B; Glahn, Raymond P; Welch, Ross M

2006-11-29

Four different colored beans (white, red, pinto, and black beans) were investigated for factors affecting iron bioavailability using an in vitro digestion/human Caco-2 cell model. Iron bioavailability from whole beans, dehulled beans, and their hulls was determined. The results show that white beans contained higher levels of bioavailable iron compared to red, pinto, and black beans. These differences in bioavailable iron were not due to bean-iron and bean-phytate concentrations. Flavonoids in the colored bean hulls were found to be contributing to the low bioavailability of iron in the non-white colored beans. White bean hulls contained no detectable flavonoids but did contain an unknown factor that may promote iron bioavailability. The flavonoids, kaempferol and astragalin (kaempferol-3-O-glucoside), were identified in red and pinto bean hulls via HPLC and MS. Some unidentified anthocyanins were also detected in the black bean hulls but not in the other colored bean hulls. Kaempferol, but not astragalin, was shown to inhibit iron bioavailability. Treating in vitro bean digests with 40, 100, 200, 300, 400, 500, and 1000 microM kaempferol significantly inhibited iron bioavailability (e.g., 15.5% at 40 microM and 62.8% at 1000 microM) in a concentration-dependent fashion. Thus, seed coat kaempferol was identified as a potent inhibitory factor affecting iron bioavailability in the red and pinto beans studied. Results comparing the inhibitory effects of kaempferol, quercitrin, and astragalin on iron bioavailability suggest that the 3',4'-dihydroxy group on the B-ring in flavonoids contributes to the lower iron bioavailability.

Bioavailability Challenges Associated with Development of Anti-Cancer Phenolics

PubMed Central

Gao, Song; Hu, Ming

2010-01-01

Phenolics including many polyphenols and flavonoids have the potentials to become chemoprevention and chemotherapy agents. However, poor bioavailability limits their biological effects in vivo. This paper reviews the factors that affect phenolics absorption and their bioavailabilities from the points of view of their physicochemical properties and disposition in the gastrointestinal tract. The up-to-date research data suggested that solubility and metabolism are the primary reasons that limit phenolic aglycones’ bioavailability although stability and poor permeation may also contribute to the poor bioavailabilities of the glycosides. Future investigations should further optimize phenolics’ bioavailabilities and realize their chemopreventive and chemotherapeutic effects in vivo. PMID:20370701

Measurement of soil lead bioavailability and influence of soil types and properties: A review.

PubMed

Yan, Kaihong; Dong, Zhaomin; Wijayawardena, M A Ayanka; Liu, Yanju; Naidu, Ravi; Semple, Kirk

2017-10-01

Lead (Pb) is a widespread heavy metal which is harmful to human health, especially to young children. To provide a human health risk assessment that is more relevant to real conditions, Pb bioavailability in soils is increasingly employed in the assessment procedure. Both in vivo and in vitro measurements for lead bioavailability are available. In vivo models are time- consuming and expensive, while in vitro models are rapid, economic, reproducible, and reliable while involving more uncertainties. Uncertainties in various measurements create difficulties in accurately predicting Pb bioavailability, resulting in the unnecessary remediation of sites. In this critical review, we utilised available data from in vivo and in vitro studies to identify the key parameters influencing the in vitro measurements, and presented uncertainties existing in Pb bioavailability measurements. Soil type, properties and metal content are reported to influence lead bioavailability; however, the differences in methods for assessing bioavailability and the differences in Pb source limit one's ability to conduct statistical analyses on influences of soil factors on Pb bioavailability. The information provided in the review is fundamentally useful for the measurement of bioavailability and risk assessment practices. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bioavailability of Dissolved Organic Carbon and Nitrogen From Tropical Montane Rainforest Streams Across a Geologic age Gradient

NASA Astrophysics Data System (ADS)

Wiegner, T. N.

2005-05-01

Dissolved organic matter (DOM) is metabolically important in streams. Its bioavailability is influenced by organic matter sources to streams and inorganic nutrient availability. As forest canopies and soils develop over time, organic matter inputs to streams should switch from algal to watershed sources. Across this succession gradient, nutrient limitation should also change. This study examines how chemical composition and bioavailability of DOM from tropical montane rainforest streams on Hawaii change across a geologic age gradient from 4 ky to 150 ky. Dissolved organic C (DOC) and N (DON) concentrations, chemical characteristics, and bioavailability varied with site age. With increasing stream age, DOC and DON concentrations, DOM aromaticity, and the C:N of the stream DOM increased. Changes in stream DOM chemistry and inorganic nutrient availability affected DOM bioavailability. Fifty percent of the DOC from the 4 ky site was bioavailable, where little to none was bioavailable from the older streams. Inorganic nutrient availability did not affect DOC bioavailability. In contrast, DON bioavailability was similar (12%) across sites and was affected by inorganic nutrient availability. This study demonstrates that the chemistry and metabolism of streams draining forests change with ecosystem age and development.

Iron Bioavailability and Provitamin A from Sweet Potato- and Cereal-Based Complementary Foods

PubMed Central

Christides, Tatiana; Amagloh, Francis Kweku; Coad, Jane

2015-01-01

Iron and vitamin A deficiencies in childhood are public health problems in the developing world. Introduction of cereal-based complementary foods, that are often poor sources of both vitamin A and bioavailable iron, increases the risk of deficiency in young children. Alternative foods with higher levels of vitamin A and bioavailable iron could help alleviate these micronutrient deficiencies. The objective of this study was to compare iron bioavailability of β-carotene-rich sweet potato-based complementary foods (orange-flesh based sweet potato (OFSP) ComFa and cream-flesh sweet potato based (CFSP) ComFa with a household cereal-based complementary food (Weanimix) and a commercial cereal (Cerelac®), using the in vitro digestion/Caco-2 cell model. Iron bioavailability relative to total iron, concentrations of iron-uptake inhibitors (fibre, phytates, and polyphenols), and enhancers (ascorbic acid, ß-carotene and fructose) was also evaluated. All foods contained similar amounts of iron, but bioavailability varied: Cerelac® had the highest, followed by OFSP ComFa and Weanimix, which had equivalent bioavailable iron; CFSP ComFa had the lowest bioavailability. The high iron bioavailability from Cerelac® was associated with the highest levels of ascorbic acid, and the lowest levels of inhibitors; polyphenols appeared to limit sweet potato-based food iron bioavailability. Taken together, the results do not support that CFSP- and OFSP ComFa are better sources of bioavailable iron compared with non-commercial/household cereal-based weaning foods; however, they may be a good source of provitamin A in the form of β-carotene. PMID:28231217

21 CFR 320.21 - Requirements for submission of bioavailability and bioequivalence data.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Requirements for submission of bioavailability and... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.21 Requirements for...

A review on the relationship between food structure, processing, and bioavailability.

PubMed

Sensoy, Ilkay

2014-01-01

This review highlights the effects of processing and food matrix on bioaccessibility and bioavailability of functional components. Human digestive system is reviewed as an element in bioavailability. Methods for bioaccessibility and bioavailability determination are described. Information about the location of functional compounds in the tissue is presented to portray the matrix information. Research data on the effects of food matrix and processing on bioaccessibility and bioavailability are summarized. Finally, trends in the development of functional component delivery systems are included.

Role of oxate, phytate, tannins and cooking on iron bioavailability from foods commonly consumed in Mexico.

PubMed

Sotelo, Angela; González-Osnaya, Liliana; Sánchez-Chinchillas, Argelia; Trejo, Alberto

2010-02-01

The objectives of this research were to assess the bioavailability of iron in foodstuffs found in the Mexican diet, to provide data on the content of iron absorption inhibitors present in plant origin products and to assess the inhibitory effect of these compounds and of cooking on iron bioavailability; therefore, total content and bioavailable iron, tannins, phytic and oxalic acid were determined in vegetables, cereals, legumes and animal products, before and after cooking. Vegetables, although rich in iron, have poor iron bioavailability and a high content of inhibitory factors; cooking reduced the content of iron and inhibitory factors, whereas in animal products the treatment of cooking did not significantly reduce it. Iron bioavailability, phytate content and the phytate to iron molar ratio predicted poor iron bioavailability and, therefore, a negative impact on the nutritional status of people who rely on them as staple foods could be expected.

21 CFR 320.29 - Analytical methods for an in vivo bioavailability or bioequivalence study.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Analytical methods for an in vivo bioavailability..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.29...

Assessment of microplastic-sorbed contaminant bioavailability through analysis of biomarker gene expression in larval zebrafish.

PubMed

Sleight, Victoria A; Bakir, Adil; Thompson, Richard C; Henry, Theodore B

2017-03-15

Microplastics (MPs) are prevalent in marine ecosystems. Because toxicants (termed here "co-contaminants") can sorb to MPs, there is potential for MPs to alter co-contaminant bioavailability. Our objective was to demonstrate sorption of two co-contaminants with different physicochemistries [phenanthrene (Phe), log 10 K ow =4.57; and 17α-ethinylestradiol (EE2), log 10 K ow =3.67] to MPs; and assess whether co-contaminant bioavailability was increased after MP settlement. Bioavailability was indicated by gene expression in larval zebrafish. Both Phe and EE2 sorbed to MPs, which reduced bioavailability by a maximum of 33% and 48% respectively. Sorption occurred, but was not consistent with predictions based on co-contaminant physicochemistry (Phe having higher log 10 K ow was expected to have higher sorption). Contaminated MPs settled to the bottom of the exposures did not lead to increased bioavailability of Phe or EE2. Phe was 48% more bioavailable than predicted by a linear sorption model, organism-based measurements therefore contribute unique insight into MP co-contaminant bioavailability. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mechanisms for retention of bioavailable nitrogen in volcanic rainforest soils

NASA Astrophysics Data System (ADS)

Huygens, Dries; Boeckx, Pascal; Templer, Pamela; Paulino, Leandro; van Cleemput, Oswald; Oyarzún, Carlos; Müller, Christoph; Godoy, Roberto

2008-08-01

Nitrogen cycling is an important aspect of forest ecosystem functioning. Pristine temperate rainforests have been shown to produce large amounts of bioavailable nitrogen, but despite high nitrogen turnover rates, loss of bioavailable nitrogen is minimal in these ecosystems. This tight nitrogen coupling is achieved through fierce competition for bioavailable nitrogen by abiotic processes, soil microbes and plant roots, all of which transfer bioavailable nitrogen to stable nitrogen sinks, such as soil organic matter and above-ground forest vegetation. Here, we use a combination of in situ 15N isotope dilution and 15N tracer techniques in volcanic soils of a temperate evergreen rainforest in southern Chile to further unravel retention mechanisms for bioavailable nitrogen. We find three processes that contribute significantly to nitrogen bioavailability in rainforest soils: heterotrophic nitrate production, nitrate turnover into ammonium and into a pool of dissolved organic nitrogen that is not prone to leaching loss, and finally, the decoupling of dissolved inorganic nitrogen turnover and leaching losses of dissolved organic nitrogen. Identification of these biogeochemical processes helps explain the retention of bioavailable nitrogen in pristine temperate rainforests.

Prebiotics increase heme iron bioavailability and do not affect non-heme iron bioavailability in humans.

PubMed

Weinborn, Valerie; Valenzuela, Carolina; Olivares, Manuel; Arredondo, Miguel; Weill, Ricardo; Pizarro, Fernando

2017-05-24

The aim of this study was to establish the effect of a prebiotic mix on heme and non-heme iron (Fe) bioavailability in humans. To this purpose, twenty-four healthy women were randomized into one of two study groups. One group ate one yogurt per day for 12 days with a prebiotic mix (prebiotic group) and the other group received the same yogurt but without the prebiotic mix (control group). Before and after the intake period, the subjects participated in Fe absorption studies. These studies used 55 Fe and 59 Fe radioactive isotopes as markers of heme Fe and non-heme Fe, respectively, and Fe absorption was measured by the incorporation of radioactive Fe into erythrocytes. The results showed that there were no significant differences in heme and non-heme Fe bioavailability in the control group. Heme Fe bioavailability of the prebiotic group increased significantly by 56% post-prebiotic intake. There were no significant differences in non-heme Fe bioavailability in this group. We concluded that daily consumption of a prebiotic mix increases heme Fe bioavailability and does not affect non-heme iron bioavailability.

Comparing different methods for assessing contaminant bioavailability during sediment remediation.

PubMed

Jia, Fang; Liao, Chunyang; Xue, Jiaying; Taylor, Allison; Gan, Jay

2016-12-15

Sediment contamination by persistent organic pollutants from historical episodes is widespread and remediation is often needed to clean up severely contaminated sites. Measuring contaminant bioavailability in a before-and-after manner lends to improved assessment of remediation effectiveness. However, a number of bioavailability measurement methods have been developed, posing a challenge in method selection for practitioners. In this study, three different bioavailability measurement methods, i.e., solid phase microextraction (SPME), Tenax desorption, and isotope dilution method (IDM), were compared in evaluating changes in bioavailability of DDT and its degradates in sediment following simulated remediation treatments. When compared to the unamended sediments, all three methods predicted essentially the same degrees of changes in bioavailability after amendment with activated carbon, charcoal or sand. After normalizing over the unamended control, measurements by different methods were linearly correlated with each other, with slopes close to 1. The same observation was further made with a Superfund site marine sediment. This finding suggests that different methods may be used in evaluating remediation efficiency. However, Tenax desorption or IDM consistently offered better sensitivity than SPME in detecting bioavailability changes. Results from this study highlight the value of considering bioavailability when evaluating remediation effectiveness and provide guidance on the selection of bioavailability measurement methods in such assessments. Copyright © 2016 Elsevier B.V. All rights reserved.

Computational modeling of human oral bioavailability: what will be next?

PubMed

Cabrera-Pérez, Miguel Ángel; Pham-The, Hai

2018-06-01

The oral route is the most convenient way of administrating drugs. Therefore, accurate determination of oral bioavailability is paramount during drug discovery and development. Quantitative structure-property relationship (QSPR), rule-of-thumb (RoT) and physiologically based-pharmacokinetic (PBPK) approaches are promising alternatives to the early oral bioavailability prediction. Areas covered: The authors give insight into the factors affecting bioavailability, the fundamental theoretical framework and the practical aspects of computational methods for predicting this property. They also give their perspectives on future computational models for estimating oral bioavailability. Expert opinion: Oral bioavailability is a multi-factorial pharmacokinetic property with its accurate prediction challenging. For RoT and QSPR modeling, the reliability of datasets, the significance of molecular descriptor families and the diversity of chemometric tools used are important factors that define model predictability and interpretability. Likewise, for PBPK modeling the integrity of the pharmacokinetic data, the number of input parameters, the complexity of statistical analysis and the software packages used are relevant factors in bioavailability prediction. Although these approaches have been utilized independently, the tendency to use hybrid QSPR-PBPK approaches together with the exploration of ensemble and deep-learning systems for QSPR modeling of oral bioavailability has opened new avenues for development promising tools for oral bioavailability prediction.

Bioavailability of Micronutrients from Plant Foods: An Update.

PubMed

Platel, Kalpana; Srinivasan, Krishnapura

2016-07-26

Deficiencies of iron, zinc, iodine and vitamin A are widespread in the developing countries, poor bioavailability of these micronutrients from plant-based foods being the major reason for their wide prevalence. Diets predominantly vegetarian are composed of components that enhance as well as inhibit mineral bioavailability, the latter being predominant. However, prudent cooking practices and use of ideal combinations of food components can significantly improve micronutrient bioavailability. Household processing such as heat treatment, sprouting, fermentation and malting have been evidenced to enhance the bioavailability of iron and β-carotene from plant foods. Food acidulants amchur and lime are also shown to enhance the bioavailability of not only iron and zinc, but also of β-carotene. Recently indentified newer enhancers of micronutrient bioaccessibility include sulphur compound-rich Allium spices-onion and garlic, which also possess antioxidant properties, β-carotene-rich vegetables-carrot and amaranth, and pungent spices-pepper (both red and black) as well as ginger. Information on the beneficial effect of these dietary compounds on micronutrient bioaccessibility is novel. These food components evidenced to improve the bioavailability of micronutrients are common ingredients of Indian culinary, and probably of other tropical countries. Fruits such as mango and papaya, when consumed in combination with milk, provide significantly higher amounts of bioavailable β-carotene. Awareness of the beneficial influence of these common dietary ingredients on the bioavailability of micronutrients would help in devising dietary strategies to improve the bioavailability of these vital nutrients.

Bioavailability of bioactive food compounds: a challenging journey to bioefficacy

PubMed Central

Rein, Maarit J.; Renouf, Mathieu; Cruz‐Hernandez, Cristina; Actis‐Goretta, Lucas; Thakkar, Sagar K.; da Silva Pinto, Marcia

2013-01-01

Bioavailability is a key step in ensuring bioefficacy of bioactive food compounds or oral drugs. Bioavailability is a complex process involving several different stages: liberation, absorption, distribution, metabolism and elimination phases (LADME). Bioactive food compounds, whether derived from various plant or animal sources, need to be bioavailable in order to exert any beneficial effects. Through a better understanding of the digestive fate of bioactive food compounds we can impact the promotion of health and improvement of performance. Many varying factors affect bioavailability, such as bioaccessibility, food matrix effect, transporters, molecular structures and metabolizing enzymes. Bioefficacy may be improved through enhanced bioavailability. Therefore, several technologies have been developed to improve the bioavailability of xenobiotics, including structural modifications, nanotechnology and colloidal systems. Due to the complex nature of food bioactive compounds and also to the different mechanisms of absorption of hydrophilic and lipophilic bioactive compounds, unravelling the bioavailability of food constituents is challenging. Among the food sources discussed during this review, coffee, tea, citrus fruit and fish oil were included as sources of food bioactive compounds (e.g. (poly)phenols and polyunsaturated fatty acids (PUFAs)) since they are examples of important ingredients for the food industry. Although there are many studies reporting on bioavailability and bioefficacy of these bioactive food components, understanding their interactions, metabolism and mechanism of action still requires extensive work. This review focuses on some of the major factors affecting the bioavailability of the aforementioned bioactive food compounds. PMID:22897361

Milk fluoridation for the prevention of dental caries.

PubMed

Bánóczy, Jolán; Rugg-Gunn, Andrew; Woodward, Margaret

2013-11-01

The aim of this review is to give an overview of 55 years experience of milk fluoridation and draw conclusions about the applicability of the method. Fluoridated milk was first investigated in the early 1950s, almost simultaneously in Switzerland, the USA and Japan. Stimulated by the favourable results obtained from these early studies, the establishment of The Borrow Dental Milk Foundation (subsequently The Borrow Foundation) in England gave an excellent opportunity for further research, both clinical and non-clinical, and a productive collaboration with the World Health Organization which began in the early 1980s. Numerous peer-reviewed publications in international journals showed clearly the bioavailability of fluoride in various types of milk. Clinical trials were initiated in the 1980s - some of these can be classed as randomised controlled trials, while most of the clinical studies were community preventive programmes. These evaluations showed clearly that the optimal daily intake of fluoride in milk is effective in preventing dental caries. The amount of fluoride added to milk depends on background fluoride exposure and age of the children: commonly in the range 0.5 to 1.0 mg per day. An advantage of the method is that a precise amount of fluoride can be delivered under controlled conditions. The cost of milk fluoridation programmes is low, about € 2 to 3 per child per year. Fluoridation of milk can be recommended as a caries preventive measure where the fluoride concentration in drinking water is suboptimal, caries experience in children is significant, and there is an existing school milk programme. Copyright © 2013 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Determination of cadmium relative bioavailability in contaminated soils and its prediction using in vitro methodologies.

PubMed

Juhasz, Albert L; Weber, John; Naidu, Ravi; Gancarz, Dorota; Rofe, Allan; Todor, Damian; Smith, Euan

2010-07-01

In this study, cadmium (Cd) relative bioavailability in contaminated (n = 5) and spiked (n = 2) soils was assessed using an in vivo mouse model following administration of feed containing soil or Cd acetate (reference material) over a 15 day exposure period. Cadmium relative bioavailability varied depending on whether the accumulation of Cd in the kidneys, liver, or kidney plus liver was used for relative bioavailability calculations. When kidney plus liver Cd concentrations were used, Cd relative bioavailability ranged from 10.1 to 92.1%. Cadmium relative bioavailability was higher (14.4-115.2%) when kidney Cd concentrations were used, whereas lower values (7.2-76.5%) were derived when liver Cd concentrations were employed in calculations. Following in vivo studies, four in vitro methodologies (SBRC, IVG, PBET, and DIN), encompassing both gastric and intestinal phases, were assessed for their ability to predict Cd relative bioavailability. Pearson correlations demonstrated a strong linear relationship between Cd relative bioavailability and Cd bioaccessibility (0.62-0.91), however, stronger in vivo-in vitro relationships were observed when Cd relative bioavailability was calculated using kidney plus liver Cd concentrations. Whereas all in vitro assays could predict Cd relative bioavailability with varying degrees of confidence (r(2) = 0.348-0.835), large y intercepts were calculated for a number of in vitro assays which is undesirable for in vivo-in vitro predictive models. However, determination of Cd bioaccessibility using the intestinal phase of the PBET assay resulted in a small y intercept (5.14; slope =1.091) and the best estimate of in vivo Cd relative bioavailability (r(2) = 0.835).

Comparing soluble ferric pyrophosphate to common iron salts and chelates as sources of bioavailable iron in a Caco-2 cell culture model.

PubMed

Zhu, Le; Glahn, Raymond P; Nelson, Deanna; Miller, Dennis D

2009-06-10

Iron bioavailability from supplements and fortificants varies depending upon the form of the iron and the presence or absence of iron absorption enhancers and inhibitors. Our objectives were to compare the effects of pH and selected enhancers and inhibitors and food matrices on the bioavailability of iron in soluble ferric pyrophosphate (SFP) to other iron fortificants using a Caco-2 cell culture model with or without the combination of in vitro digestion. Ferritin formation was the highest in cells treated with SFP compared to those treated with other iron compounds or chelates. Exposure to pH 2 followed by adjustment to pH 7 markedly decreased FeSO(4) bioavailability but had a smaller effect on bioavailabilities from SFP and sodium iron(III) ethylenediaminetetraacetate (NaFeEDTA), suggesting that chelating agents minimize the effects of pH on iron bioavailability. Adding ascorbic acid (AA) and cysteine to SFP in a 20:1 molar ratio increased ferritin formation by 3- and 2-fold, respectively, whereas adding citrate had no significant effect on the bioavailability of SFP. Adding phytic acid (10:1) and tannic acid (1:1) to iron decreased iron bioavailability from SFP by 91 and 99%, respectively. The addition of zinc had a marked inhibitory effect on iron bioavailability. Calcium and magnesium also inhibited iron bioavailability but to a lesser extent. Incorporating SFP in rice greatly reduced iron bioavailability from SFP, but this effect can be partially reversed with the addition of AA. SFP and FeSO(4) were taken up similarly when added to nonfat dry milk. Our results suggest that dietary factors known to enhance and inhibit iron bioavailability from various iron sources affect iron bioavailability from SFP in similar directions. However, the magnitude of the effects of iron absorption inhibitors on SFP iron appears to be smaller than on iron salts, such as FeSO(4) and FeCl(3). This supports the hypothesis that SFP is a promising iron source for food fortification and dietary supplements.

Notes on the hatching phases and the size of the juveniles in the Snake-eyed skink Ablepharus kitaibelii (Bibron & Bory de Saint-Vincent, 1833)

NASA Astrophysics Data System (ADS)

Vergilov, Vladislav; Natchev, Nikolay

2018-03-01

Most of the studies dealing with the Snake-eyed skink (Ablepharus kitaibelii) treat predominantly aspects of the distribution and taxonomy of the species. In the present study we provide information concerning the mechanism of hatching in the Snake-eyed skink and the dimensions of the hatched specimens. We collected data from wild animals, as well as from indoor incubated juveniles. The present study provides the first data concerning the weight of the newly hatched juveniles of the species and discuss on potential misleading data concerning the size of the juveniles in A. kitaibelii.

STS-106 Crew Activities Report/Flight Day 9 Highlights

NASA Technical Reports Server (NTRS)

2000-01-01

On this ninth day of the STS-106 Atlantis mission, the flight crew, Commander Commander Terrence W. Wilcutt, Pilot Scott D. Altman, and Mission Specialists Daniel C. Burbank, Edward T. Lu, Richard A. Mastracchio, Yuri Ivanovich Malenchenko, and Boris V. Morukov are shown transferring supplies and equipment. Equipment includes an exercise treadmill, for use by the first resident crew. Altman, Lu, Burbank and Morukov are seen installing the treadmill in the Zvezda module. Footage also shows Lu and Altman participating in a telecommunication interview. A beautiful night shot of the International Space Station (ISS) and Atlantis complex above the Earth is also shown.

Enduring Strategic Rivalries

DTIC Science & Technology

2014-08-01

I N S T I T U T E F O R D E F E N S E A N A L Y S E S August 2014 Approved for public release; distribution is unlimited. IDA Paper P-5178 Log: H...license under the clause at DFARS 252.227-7013 (a)(16) [Jun 2013] I N S T I T U T E F O R D E F E N S E A N A L Y S E S IDA Paper P-5178 Enduring...City and its Countryside (London: G. Phillip, 1987), 75-81. 9 See John S. Morrison, John F. Coates, and N . Boris Rankov, The Athenian Trireme: The

Russian Scientists Visitors

NASA Image and Video Library

1959-11-29

Russian Scientists from the Commission of Interplanetary Travel of the Soviet Academy of Science November 21,1959 Left to right: Front row: Yury S. Galkin, Anatoly A. Blagonravov, and Prof. Leonid I. Sedov (Chair of the Commission for Interplanetary Travel)-Soviet Academy of Science, Leninski Gory, Moscow, Russia Dr. H.J. E. Reid and Floyd L. Thompson Langley Research Center. Second row: Boris Kit Translator, Library of Congress, Washington, D.C. Eugene C. Draley and Laurence K. Loftin, Jr. -Langley Research Center Arnold W. Frutkin and Harold R. Lawrence NASA Headquarters. Back row: T.Melvin Butler-Langley Research Center John W. Townsend Goddard Space Flight Center, NASA, Washington D.C., and George M. Low NASA Headquarters.

BOREAS Regional Soils Data in Raster Format and AEAC Projection

NASA Technical Reports Server (NTRS)

Monette, Bryan; Knapp, David; Hall, Forrest G. (Editor); Nickeson, Jaime (Editor)

2000-01-01

This data set was gridded by BOREAS Information System (BORIS) Staff from a vector data set received from the Canadian Soil Information System (CanSIS). The original data came in two parts that covered Saskatchewan and Manitoba. The data were gridded and merged into one data set of 84 files covering the BOREAS region. The data were gridded into the AEAC projection. Because the mapping of the two provinces was done separately in the original vector data, there may be discontinuities in some of the soil layers because of different interpretations of certain soil properties. The data are stored in binary, image format files.

Development of a fortified juice beverage: assessment of iron bioavailability using an established caco-2 cell bioassay

USDA-ARS?s Scientific Manuscript database

Poor iron bioavailability is a contributing factor to the high prevalence of iron deficiency anemia in India, and food fortification with bioavailable iron is one strategy to help address the problem. Validated in vitro methods to measure iron (Fe) bioavailability are useful tools that can be levera...

21 CFR 320.27 - Guidelines on the design of a multiple-dose in vivo bioavailability study.

Code of Federal Regulations, 2011 CFR

2011-04-01

... vivo bioavailability study. 320.27 Section 320.27 Food and Drugs FOOD AND DRUG ADMINISTRATION... Guidelines on the design of a multiple-dose in vivo bioavailability study. (a) Basic principles. (1) In... labeling of the test product. (3) A multiple-dose study may be required to determine the bioavailability of...

Iron bioavailability of maize hemoglobin in a Caco-2 cell culture model

USDA-ARS?s Scientific Manuscript database

Maize is an important staple crop in many parts of the world but has low iron bioavailability, in part due to its high phytate content. Hemoglobin is a form of iron that is highly bioavailable and its bioavailability is not inhibited by phytate. We hypothesize that maize hemoglobin is a highly bioav...

[Bioavailability and factors influencing its rate].

PubMed

Vraníková, Barbora; Gajdziok, Jan

Bioavailability can be defined as the rate and range of active ingredient absorption, when it becomes available in the systemic circulation or at the desired site of drug action, respectively. Drug bioavailability after oral administration is affected by anumber of different factors, including physicochemical properties of the drug, physiological aspects, the type of dosage form, food intake, biorhythms, and intra- and interindividual variability of the human population. This article is the first from the series dealing with the bioavailability and methods leading to its improvement. The aim of the present paper is to provide an overview of aspects influencing the rate of bioavailability after oral administration of the active ingredient. Subsequentarticles will provide detailed descriptions of methods used for dug bioavailability improvement, which are here only summarized.

Micronutrient bioavailability: Dietary Reference Intakes and a future perspective1234

PubMed Central

2010-01-01

This article provides a review of how the challenge of bioavailability was approached in establishing the Dietary Reference Intakes, with a special focus on folic acid, vitamin B-12, β-carotene, iron, selenium, and zinc, the targeted micronutrients for this workshop. In a future perspective, the necessity of having a clear working definition of bioavailability is emphasized. The bioavailability of micronutrients should be considered, with advantage, under subheadings determined by the broad factors that affect bioavailability. Special emphasis is given to giving greater and specific attention to factors involved in the maintenance of homeostasis. These factors, it is argued, are best considered separately from even a broad definition of bioavailability and have the potential to provide new insights into some micronutrient requirements. PMID:20200261

Bioavailability of bioactive food compounds: a challenging journey to bioefficacy.

PubMed

Rein, Maarit J; Renouf, Mathieu; Cruz-Hernandez, Cristina; Actis-Goretta, Lucas; Thakkar, Sagar K; da Silva Pinto, Marcia

2013-03-01

Bioavailability is a key step in ensuring bioefficacy of bioactive food compounds or oral drugs. Bioavailability is a complex process involving several different stages: liberation, absorption, distribution, metabolism and elimination phases (LADME). Bioactive food compounds, whether derived from various plant or animal sources, need to be bioavailable in order to exert any beneficial effects. Through a better understanding of the digestive fate of bioactive food compounds we can impact the promotion of health and improvement of performance. Many varying factors affect bioavailability, such as bioaccessibility, food matrix effect, transporters, molecular structures and metabolizing enzymes. Bioefficacy may be improved through enhanced bioavailability. Therefore, several technologies have been developed to improve the bioavailability of xenobiotics, including structural modifications, nanotechnology and colloidal systems. Due to the complex nature of food bioactive compounds and also to the different mechanisms of absorption of hydrophilic and lipophilic bioactive compounds, unravelling the bioavailability of food constituents is challenging. Among the food sources discussed during this review, coffee, tea, citrus fruit and fish oil were included as sources of food bioactive compounds (e.g. (poly)phenols and polyunsaturated fatty acids (PUFAs)) since they are examples of important ingredients for the food industry. Although there are many studies reporting on bioavailability and bioefficacy of these bioactive food components, understanding their interactions, metabolism and mechanism of action still requires extensive work. This review focuses on some of the major factors affecting the bioavailability of the aforementioned bioactive food compounds. © 2012 Nestec S. A.. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Optimizing Oral Bioavailability in Drug Discovery: An Overview of Design and Testing Strategies and Formulation Options.

PubMed

Aungst, Bruce J

2017-04-01

For discovery teams working toward new, orally administered therapeutic agents, one requirement is to attain adequate systemic exposure after oral dosing, which is best accomplished when oral bioavailability is optimized. This report summarizes the bioavailability challenges currently faced in drug discovery, and the design and testing methods and strategies currently utilized to address the challenges. Profiling of discovery compounds usually includes separate assessments of solubility, permeability, and susceptibility to first-pass metabolism, which are the 3 most likely contributors to incomplete oral bioavailability. An initial assessment of absorption potential may be made computationally, and high throughput in vitro assays are typically performed to prioritize compounds for in vivo studies. The initial pharmacokinetic study is a critical decision point in compound evaluation, and the importance of the effect the dosing vehicle or formulation can have on oral bioavailability, especially for poorly water soluble compounds, is emphasized. Dosing vehicles and bioavailability-enabling formulations that can be used for discovery and preclinical studies are described. Optimizing oral bioavailability within a chemical series or for a lead compound requires identification of the barrier limiting bioavailability, and methods used for this purpose are outlined. Finally, a few key guidelines are offered for consideration when facing the challenges of optimizing oral bioavailability in drug discovery. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Proceedings: ISEA Bioavailability Symposium, Durham, North Carolina Use of InVitro Bioaccessibility/Relative Bioavailability Estimates for Metals in Regulatory Settings: What is Needed?

EPA Science Inventory

Oral ingestion of soil and dust is a key pathway for human exposures to metal and metalloid contaminants. It is widely recognized that the site-specific bioavailability of metals in soil and dust may be reduced relative to the metal bioavailability in media such as water and food...

Research progress on berberine with a special focus on its oral bioavailability.

PubMed

Liu, Chang-Shun; Zheng, Yu-Rong; Zhang, Ying-Feng; Long, Xiao-Ying

2016-03-01

The natural product berberine (BBR) has become a potential drug in the treatment of diabetes, hyperlipidemia, and cancer. However, the oral delivery of BBR is challenged by its poor bioavailability. It is necessary to improve the oral bioavailability of BBR before it can be used in many clinical applications. Understanding the pharmacokinetic characteristics of BBR will enable the development of suitable formulas that have improved oral bioavailability. The key considerations for BBR are how to enhance the drug absorption and to avoid the intestinal first-pass effect. This review summarizes the pharmacological activities of BBR and analyzes the factors that lead to its poor oral bioavailability. In particular, the therapeutic potential of BBR in new indications from the aspect of oral bioavailability is discussed. In conclusion, BBR is a promising drug candidate for metabolic disorders and cancer but faces considerable challenges due to its poor oral bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

In vivo and in vitro testing for selenium and selenium compounds bioavailability assessment in foodstuff.

PubMed

Moreda-Piñeiro, Jorge; Moreda-Piñeiro, Antonio; Bermejo-Barrera, Pilar

2017-03-04

The assessment of selenium and selenium species bioavailability in foodstuff is of special concern on the context of human nutrition. In vivo (human and animal), and in vitro tests are important approaches for estimating the bioavailability of toxic and essential compounds to humans. An overview on in vivo and in vitro bioavailability assays for releasing selenium and selenium species in foodstuffs is summarized. Se and Se species content in a foodstuff critically influence Se bioavailability and bioactivity to humans and animals. Se bioavailability is affected by foodstuff-matrix major composition and minor components. Foodstuffs processing and/or treatments could enhancement or decrease Se bioavailability. Experimental conditions such as the selection of healthy status of examined people (in in vivo humans approaches), the selection of animal model (in vivo animals approaches), or the selection of GI conditions (in in vitro tests) could determines the results. Thus, international standardized protocol for in vivo and in vitro approaches assessment is mandatory.

Evaluation of Iodine Bioavailability in Seaweed Using in Vitro Methods.

PubMed

Domínguez-González, M Raquel; Chiocchetti, Gabriela M; Herbello-Hermelo, Paloma; Vélez, Dinoraz; Devesa, Vicenta; Bermejo-Barrera, Pilar

2017-09-27

Due to the high levels of iodine present in seaweed, the ingestion of a large amount of this type of food can produce excessive intake of iodine. However, the food after ingestion undergoes different chemistry and physical processes that can modify the amount of iodine that reaches the systemic circulation (bioavailability). Studies on the bioavailability of iodine from food are scarce and indicate that the bioavailable amount is generally lower than ingested. Iodine in vitro bioavailability estimation from different commercialized seaweed has been studied using different in vitro approaches (solubility, dialyzability, and transport and uptake by intestinal cells). Results indicate that iodine is available after gastrointestinal digestion for absorption (bioaccessibility: 49-82%), kombu being the seaweed with the highest bioaccessibility. The incorporation of dialysis cell cultures to elucidate bioavailability modifies the estimation of the amount of iodine that may reach the systemic circulation (dialysis, 5-28%; cell culture, ≤3%). The paper discusses advantages and drawbacks of these methodologies for iodine bioavailability in seaweed.

Role of organic acids on the bioavailability of selenium in soil: A review.

PubMed

Dinh, Quang Toan; Li, Zhe; Tran, Thi Anh Thu; Wang, Dan; Liang, Dongli

2017-10-01

Organic Acids (OAs) are important components in the rhizosphere soil and influence Se bioavailability in soil. OAs have a bidirectional contrasting effect on Se bioavailability. Understanding the interaction of OAs with Se is essential to assessing Se bioavailability in soil and clarifying the role of OAs in controlling the behavior and fate of Se in soil. This review examines the mechanisms for the (im)mobilization of Se by OAs and discusses the practical implications of these mechanisms in relation to sequestration and bioavailability of Se in soil. Copyright © 2017 Elsevier Ltd. All rights reserved.

BIOSURFACES AND BIOAVAILABILITY: A NANOSCALE OVERVIEW

EPA Science Inventory

Environmentally, contaminant bioavailability is a key parameter in determining exposure assessment and ultimately risk assessment/risk management. Defining bioavailability requires knowledge of the contaminant spatial/temporal disposition and transportability and the thermodyna...

Bioavailability and ecotoxicity of arsenic species in solution culture and soil system: implications to remediation.

PubMed

Bolan, Nanthi; Mahimairaja, Santiago; Kunhikrishnan, Anitha; Seshadri, Balaji; Thangarajan, Ramya

2015-06-01

In this work, bioavailability and ecotoxicity of arsenite (As(III)) and arsenate (As(V)) species were compared between solution culture and soil system. Firstly, the adsorption of As(III) and As(V) was compared using a number of non-allophanic and allophanic soils. Secondly, the bioavailability and ecotoxicity were examined using germination, phytoavailability, earthworm, and soil microbial activity tests. Both As-spiked soils and As-contaminated sheep dip soils were used to test bioavailability and ecotoxicity. The sheep dip soil which contained predominantly As(V) species was subject to flooding to reduce As(V) to As(III) and then used along with the control treatment soil to compare the bioavailability between As species. Adsorption of As(V) was much higher than that of As(III), and the difference in adsorption between these two species was more pronounced in the allophanic than non-allophanic soils. In the solution culture, there was no significant difference in bioavailability and ecotoxicity, as measured by germination and phytoavailability tests, between these two As species. Whereas in the As-spiked soils, the bioavailability and ecotoxicity were higher for As(III) than As(V), and the difference was more pronounced in the allophanic than non-allophanic soils. Bioavailability of As increased with the flooding of the sheep dip soils which may be attributed to the reduction of As(V) to As(III) species. The results in this study have demonstrated that while in solution, the bioavailability and ecotoxicity do not vary between As(III) and As(V), in soils, the latter species is less bioavailable than the former species because As(V) is more strongly retained than As(III). Since the bioavailability and ecotoxicity of As depend on the nature of As species present in the environment, risk-based remediation approach should aim at controlling the dynamics of As transformation.

The rationale for recommending fixed-dose combination tablets for treatment of tuberculosis.

PubMed Central

Blomberg, B.; Spinaci, S.; Fourie, B.; Laing, R.

2001-01-01

There is considerable exigency to take all necessary steps to cure tuberculosis cases and prevent further emergence of drug-resistant tuberculosis. The most important of these steps is to ensure that the treatment, particularly of sputum smear-positive cases, is adequate and that patients adhere to their treatment by supervised, direct observation of drug-taking according to the standardized regimens. Use of fixed-dose combinations (FDCs) of tablets against tuberculosis is now being recommended by WHO and the International Union Against Tuberculosis and Lung Disease (IUATLD) as an additional step to ensuring proper treatment. FDCs simplify the prescription of drugs and the management of drug supply, and may also limit the risk of drug-resistant tuberculosis arising as a result of inappropriate drug selection and monotherapy. Only FDCs of proven quality and proven rifampicin bioavailability should be purchased and used. In most situations, blood levels of the drugs are inadequate because of poor drug quality rather than poor absorption. This is true irrespective of the human immunodeficiency virus (HIV) infection status of the tuberculosis patients (other than those with overt acquired immunodeficiency syndrome, with CD4 counts < 200 cells/mm3). Currently, WHO, IUATLD and their partners are developing strategies for ensuring that only quality FDCs are used in tuberculosis programmes. A simplified and effective protocol for assessment of rifampicin bioavailability has been developed, and laboratories are being recruited to form a supranational network for quality assurance of FDCs. Standardization of FDC drug formulations has been proposed, which limits rifampicin-containing preparations to nine (including a four-drug FDC and three paediatric FDCs). PMID:11217670

Carotenoids are more bioavailable from papaya than from tomato and carrot in humans: a randomised cross-over study

PubMed Central

Schweiggert, Ralf M.; Kopec, Rachel E.; Villalobos-Gutierrez, Maria G.; Högel, Josef; Quesada, Silvia; Esquivel, Patricia; Schwartz, Steven J.; Carle, Reinhold

2014-01-01

Carrot, tomato and papaya represent important dietary sources of β-carotene and lycopene. The main objective of the present study was to compare the bioavailability of carotenoids from these food sources in healthy human subjects. A total of sixteen participants were recruited for a randomised cross-over study. Test meals containing raw carrots, tomatoes and papayas were adjusted to deliver an equal amount of β-carotene and lycopene. For the evaluation of bioavailability, TAG-rich lipoprotein (TRL) fractions containing newly absorbed carotenoids were analysed over 9.5 h after test meal consumption. The bioavailability of β-carotene from papayas was approximately three times higher than that from carrots and tomatoes, whereas differences in the bioavailability of β-carotene from carrots and tomatoes were insignificant. Retinyl esters appeared in the TRL fractions at a significantly higher concentration after the consumption of the papaya test meal. Similarly, lycopene was approximately 2.6 times more bioavailable from papayas than from tomatoes. Furthermore, the bioavailability of β-cryptoxanthin from papayas was shown to be 2.9 and 2.3 times higher than that of the other papaya carotenoids β-carotene and lycopene, respectively. The morphology of chromoplasts and the physical deposition form of carotenoids were hypothesised to play a major role in the differences observed in the bioavailability of carotenoids from the foods investigated. Particularly, the liquid-crystalline deposition of β-carotene and the storage of lycopene in very small crystalloids in papayas were found to be associated with their high bioavailability. In conclusion, papaya was shown to provide highly bioavailable β-carotene, β-cryptoxanthin and lycopene and may represent a readily available dietary source of provitamin A for reducing the incidence of vitamin A deficiencies in many subtropical and tropical developing countries. PMID:23931131

The effect of dietary factors on strawberry anthocyanins oral bioavailability.

PubMed

Xiao, Di; Sandhu, Amandeep; Huang, Yancui; Park, Eunyoung; Edirisinghe, Indika; Burton-Freeman, Britt M

2017-11-15

Strawberries are a dietary source of anthocyanins, particularly pelargonidin glycosides. Dietary anthocyanins have received increasing attention among researchers and consumers due to their health benefits. The oral bioavailability of anthocyanins is reported to be low and various dietary factors may influence their oral bioavailability further. Milk is suggested to reduce (poly)phenols' oral bioavailability. However, the effect of milk on anthocyanin oral bioavailability remains uncertain. Likewise, mixed nutrient meals may influence the oral bioavailability of anthocyanins. Therefore, the purpose of this study was to assess the effect of milk on the oral bioavailability and other pharmacokinetic (PK) variables of strawberry anthocyanins consumed with and without a meal. Nine healthy participants consumed a strawberry beverage prepared in milk or water with a standard meal on two occasions. On two additional occasions, the beverages were given to a subset (n = 4) of participants to determine the impact of the meal on anthocyanin PK variables, including oral bioavailability. Independent of the meal, beverages prepared in milk significantly reduced the peak plasma concentrations (C max ) of pelargonidin-3-O-glucoside (P-3-G), pelargonidin-glucuronide (PG) and pelargonidin-3-O-rutinoside (P-3-R), as well as the PG and P-3-R area under the curve (AUC) (p < 0.05) compared to beverages prepared in water. Milk did not influence the oral relative bioavailability of pelargonidin anthocyanins under meal conditions; however, the oral relative bioavailability of pelargonidin anthocyanins was reduced by ∼50% by milk under without meal conditions (p < 0.05). Consuming strawberry beverages made with milk and consuming those made with water with and without a meal influenced different aspects of strawberry anthocyanin PKs. The significance of this effect on clinical efficacy requires additional research.

Saccharides enhance iron bioavailability to Southern Ocean phytoplankton

PubMed Central

Hassler, Christel S.; Nichols, Carol Mancuso; Butler, Edward C. V.; Boyd, Philip W.

2011-01-01

Iron limits primary productivity in vast regions of the ocean. Given that marine phytoplankton contribute up to 40% of global biological carbon fixation, it is important to understand what parameters control the availability of iron (iron bioavailability) to these organisms. Most studies on iron bioavailability have focused on the role of siderophores; however, eukaryotic phytoplankton do not produce or release siderophores. Here, we report on the pivotal role of saccharides—which may act like an organic ligand—in enhancing iron bioavailability to a Southern Ocean cultured diatom, a prymnesiophyte, as well as to natural populations of eukaryotic phytoplankton. Addition of a monosaccharide (>2 nM of glucuronic acid, GLU) to natural planktonic assemblages from both the polar front and subantarctic zones resulted in an increase in iron bioavailability for eukaryotic phytoplankton, relative to bacterioplankton. The enhanced iron bioavailability observed for several groups of eukaryotic phytoplankton (i.e., cultured and natural populations) using three saccharides, suggests it is a common phenomenon. Increased iron bioavailability resulted from the combination of saccharides forming highly bioavailable organic associations with iron and increasing iron solubility, mainly as colloidal iron. As saccharides are ubiquitous, present at nanomolar to micromolar concentrations, and produced by biota in surface waters, they also satisfy the prerequisites to be important constituents of the poorly defined “ligand soup,” known to weakly bind iron. Our findings point to an additional type of organic ligand, controlling iron bioavailability to eukaryotic phytoplankton—a key unknown in iron biogeochemistry. PMID:21169217

Physicochemical Modifications and Nano Particulate Strategies for Improved Bioavailability of Poorly Water Soluble Drugs.

PubMed

Siddiqui, Komal; Waris, Abdul; Akber, Habiba; Munir, Kinza; Mir, Maria; Khan, Muhammad Waseem; Aman, Waqar; Fakhar-Ud-Din

2017-01-01

Bioavailability is the segment of dose that is bioavailable for its therapeutic effect on the systemic circulation without any change in its characteristics, after administration by either route. It is one of the fundamental pharmacokinetic properties of drugs. It is important because, it defines the amount of drug to be administered for its intended therapeutic effect. If drug is more bioavailable, less amount of it is required to obtain therapeutic effect. However, it is also worth mentioning that most of the newly discovered therapeutic agents have poor solubility and thus low bioavailability. In this article, various methods including conventional and advanced, have been reviewed that could be potentially used for the enhancement of bioavailability. Moreover, the benefits and drawbacks of all the strategies are deliberated to comprehend the probable use of each method supported by latest references. Various strategies have been developed to enhance the solubility and thus bioavailability of numerous drugs, some of which are discussed here. All these strategies involve different approaches to improve the bioavailability including physical adaptation, chemical modification and controlling particle size of the engineered particle. These strategies, particularly the nano-particulate systems, not only improve the bioavailability of drugs but at the same time diminish the possible toxicities of the incorporated drugs. It can be concluded that this would be a new source of information for the readers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Use of Tunable Whole-Cell Bioreporters to Assess Bioavailable Cadmium and Remediation Performance in Soils

PubMed Central

Yoon, Youngdae; Kim, Sunghoon; Chae, Yooeun; Kang, Yerin; Lee, Youngshim; Jeong, Seung-Woo; An, Youn-Joo

2016-01-01

It is important to have tools to measure the bioavailability to assess the risks of pollutants because the bioavailability is defined as the portions of pollutants showing the biological effects on living organisms. This study described the construction of tunable Escherichia coli whole-cell bioreporter (WCB) using the promoter region of zinc-inducible operon and its application on contaminated soils. It was verified that this WCB system showed specific and sensitive responses to cadmium rather than zinc in the experimental conditions. It was inferred that Cd(II) associates stronger with ZntR, a regulatory protein of zinc-inducible operon, than other metal ions. Moreover, the expression of reporter genes, egfp and mcherry, were proportional to the concentration of cadmium, thereby being a quantitative sensor to monitor bioavailable cadmium. The capability to determine bioavailable cadmium was verified with Cd(II) amended LUFA soils, and then the applicability on environmental systems was investigated with field soils collected from smelter area in Korea before and after soil-washing. The total amount of cadmium was decreased after soil washing, while the bioavailability was increased. Consequently, it would be valuable to have tools to assess bioavailability and the effectiveness of soil remediation should be evaluated in the aspect of bioavailability as well as removal efficiency. PMID:27171374

Use of Tunable Whole-Cell Bioreporters to Assess Bioavailable Cadmium and Remediation Performance in Soils.

PubMed

Yoon, Youngdae; Kim, Sunghoon; Chae, Yooeun; Kang, Yerin; Lee, Youngshim; Jeong, Seung-Woo; An, Youn-Joo

2016-01-01

It is important to have tools to measure the bioavailability to assess the risks of pollutants because the bioavailability is defined as the portions of pollutants showing the biological effects on living organisms. This study described the construction of tunable Escherichia coli whole-cell bioreporter (WCB) using the promoter region of zinc-inducible operon and its application on contaminated soils. It was verified that this WCB system showed specific and sensitive responses to cadmium rather than zinc in the experimental conditions. It was inferred that Cd(II) associates stronger with ZntR, a regulatory protein of zinc-inducible operon, than other metal ions. Moreover, the expression of reporter genes, egfp and mcherry, were proportional to the concentration of cadmium, thereby being a quantitative sensor to monitor bioavailable cadmium. The capability to determine bioavailable cadmium was verified with Cd(II) amended LUFA soils, and then the applicability on environmental systems was investigated with field soils collected from smelter area in Korea before and after soil-washing. The total amount of cadmium was decreased after soil washing, while the bioavailability was increased. Consequently, it would be valuable to have tools to assess bioavailability and the effectiveness of soil remediation should be evaluated in the aspect of bioavailability as well as removal efficiency.

Assessing the bioavailability and risk from metal-contaminated ...

EPA Pesticide Factsheets

Exposure to contaminated soil and dust is an important pathway in human health risk assessment. Physical and chemical characteristics, as well as biological factors, determine the bioaccessibility/bioavailability of soil and dust contaminants. Within a single sample, contamination may arise from multiple sources of toxic elements that may exist as different forms (species) which impact bioavailability. In turn, the bioaccessibility/bioavailability of soil and dust contaminants has a direct impact on human health risk assessment and risk management practices. Novel research efforts focusing on development and application of in vitro and in vivo methods to measure the bioaccessibility/bioavailability of metal contaminated soils have advanced in the past few years. The objective of this workshop was to focus on recent developments in assessing the bioaccessibility/bioavailability of arsenic contaminated soils, metal contamination in urban residences in Canada and potential children’s exposures to toxic elements in house dust, a community-based study known as the West Oakland Residential Lead Assessment , studies of the bioavailability of soil cadmium, chromium, nickel and mercury and human exposures to contaminated Brownfield soils. These presentations covered issues related to human health and bioavailability along with the most recent studies on community participation in assessing metal contamination, studies of exposures to residential contamination, and

Bioavailability of zinc, copper, and manganese from infant diets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bell, J.G.

1987-01-01

A series of trace element absorption experiments were performed using the Sprague-Dawley suckling rat put and infant rhesis monkey (Macaca mulatta) with extrinsic radiolabeling to assess the bioavailability of Zn, Cu, and Mn from infant diets and to examine specific factors that affect absorption of these essential nutrients. Bioavailability of Cu as assessed by 6 h liver uptake (% of /sup 64/Cu dose) was highest from human milk and cow milk based formula and significantly lower from cow milk and soy based formula. Copper bioavailability from infant cereal products as assessed by whole body uptake (% of /sup 64/Cu dose)more » in d 20 rats, 9 h postintubation, was low compared to the bioavailability from cow milk or human milk alone. /sup 65/Zn uptake in d 20 rats, 9 h postintubation, was significantly lower from cereals fed alone or in combination with cow or human milk as compared to the uptake from the milks fed alone. Zn bioavailability varied among cereal diets, (lowest from cereals containing phytate and highest from cereal/fruit products). Mn bioavailability from infant diets was assessed using a modified suckling rat pup model. Bioavailability (24 h whole body retention of /sup 54/Mn) was high from all milks and commercial formulas tested.« less

Aluminum bioavailability from basic sodium aluminum phosphate, an approved food additive emulsifying agent, incorporated in cheese

PubMed Central

Yokel, Robert A.; Hicks, Clair L.; Florence, Rebecca L.

2008-01-01

Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of ~ 1 gm cheese containing 1.5 or 3% basic SALP resulted in oral Al bioavailability (F) of ~ 0.1 and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8 to 9 h. These Al bioavailability results were intermediate to previously reported results from drinking water (F ~ 0.3%) and acidic-SALP incorporated into a biscuit (F ~ 0.1%), using the same methods. Considering the similar oral bioavailability of Al from food vs. water, and their contribution to the typical human’s daily Al intake (~ 95 and 1.5%, respectively), these results suggest food contributes much more Al to systemic circulation, and potential Al body burden, than does drinking water. These results do not support the hypothesis that drinking water provides a disproportionate contribution to total Al absorbed from the gastrointestinal tract. PMID:18436363

Aluminum bioavailability from basic sodium aluminum phosphate, an approved food additive emulsifying agent, incorporated in cheese.

PubMed

Yokel, Robert A; Hicks, Clair L; Florence, Rebecca L

2008-06-01

Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of approximately 1g cheese containing 1.5% or 3% basic SALP resulted in oral Al bioavailability (F) of approximately 0.1% and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8-9h. These Al bioavailability results were intermediate to previously reported results from drinking water (F approximately 0.3%) and acidic-SALP incorporated into a biscuit (F approximately 0.1%), using the same methods. Considering the similar oral bioavailability of Al from food vs. water, and their contribution to the typical human's daily Al intake ( approximately 95% and 1.5%, respectively), these results suggest food contributes much more Al to systemic circulation, and potential Al body burden, than does drinking water. These results do not support the hypothesis that drinking water provides a disproportionate contribution to total Al absorbed from the gastrointestinal tract.

In Vitro Iron Bioavailability of Brazilian Food-Based by-Products.

PubMed

Chiocchetti, Gabriela M; De Nadai Fernandes, Elisabete A; Wawer, Anna A; Fairweather-Tait, Susan; Christides, Tatiana

2018-05-16

Background : Iron deficiency is a public health problem in many low- and middle-income countries. Introduction of agro-industrial food by-products, as additional source of nutrients, could help alleviate this micronutrient deficiency, provide alternative sources of nutrients and calories in developed countries, and be a partial solution for disposal of agro-industry by-products. Methods : The aim of this study was to determine iron bioavailability of 5 by-products from Brazilian agro-industry (peels from cucumber, pumpkin, and jackfruit, cupuaçu seed peel, and rice bran), using the in vitro digestion/ Caco-2 cell model; with Caco-2 cell ferritin formation as a surrogate marker of iron bioavailability. Total and dialyzable Fe, macronutrients, the concentrations of iron-uptake inhibitors (phytic acid, tannins, fiber) and their correlation with iron bioavailability were also evaluated. Results : The iron content of all by-products was high, but the concentration of iron and predicted bioavailability were not related. Rice bran and cupuaçu seed peel had the highest amount of phytic acid and tannins, and lowest iron bioavailability. Cucumber peels alone, and with added extrinsic Fe, and pumpkin peels with extrinsic added iron, had the highest iron bioavailability. Conclusion : The results suggest that cucumber and pumpkin peel could be valuable alternative sources of bioavailable Fe to reduce iron deficiency in at-risk populations.

SOIL METAL BIOAVAILABILITY

EPA Science Inventory

Reducing risks associated with metals in soil has typically been accomplished by soil removal, covering, or dilution by mixing with uncontaminated soil. However, as our understanding of bioavailability and the relationship between metal form and bioavailability increases we are ...

Higher bioavailability of iron from whole wheat bread compared with iron-fortified white breads in caco-2 cell model: an experimental study.

PubMed

Nikooyeh, Bahareh; Neyestani, Tirang R

2017-06-01

Bread, as the staple food of Iranians, with average per capita consumption of 300 g d -1 , could potentially be a good vehicle for many fortificants, including iron. In this study, iron bioavailability from flat breads (three fortified and one whole wheat unfortified) was investigated using in vitro simulation of gastrointestinal digestion and absorption in a caco-2 cell model. Despite having a lower ferritin/protein ratio in comparison with fortified breads, whole wheat bread showed higher iron bioavailability than the other three types of bread. Assuming iron bioavailability from the ferrous sulfate supplement used as standard was about 10%, the estimated bioavailability of iron from the test breads was calculated as 5.0-8.0%. Whole wheat bread (∼8%), as compared with the fortified breads (∼5-6.5%), had higher iron bioavailability. Iron from unfortified whole wheat bread is more bioavailable than from three types of iron-fortified breads. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Arsenic Bioavailability, Bioaccessibility, And Speciation

EPA Science Inventory

The term bioavailability has many different meanings across various disciplines. Often bioavailability is concerned with human health aspects such as the case of urban children interacting with contaminated soil. The still utilized approach to base risk assessment on total meta...

Mouse Assay for Determination of Arsenic Bioavailability in Contaminated Soils

EPA Science Inventory

Background: Accurate assessment of human exposure estimates from arsenic-contaminated soils depends upon estimating arsenic (As) soil bioavailability. Development of bioavailability assays provides data needed for human health risk assessments and supports development and valida...

Excipient-mediated alteration in drug bioavailability in the rat depends on the sex of the animal.

PubMed

Mai, Yang; Afonso-Pereira, Francisco; Murdan, Sudaxshina; Basit, Abdul W

2017-09-30

The pharmaceutical excipient, polyethylene glycol 400 (PEG 400), unexpectedly alters the bioavailability of the BCS class III drug ranitidine in a sex-dependent manner. As ranitidine is a substrate for the efflux transporter P-glycoprotein (P-gp), we hypothesized that the sex-related influence could be due to interactions between PEG 400 and P-gp. In this study, we tested this hypothesis by: i) measuring the influence of PEG 400 on the oral bioavailability of another P-gp substrate (ampicillin) and of a non-P-gp substrate (metformin); and ii) measuring the effect of PEG 400 on drug bioavailability in the presence of a P-gp inhibitor (cyclosporine A) in male and female rats. We found that PEG 400 significantly increased (p<0.05) the bioavailability of ampicillin (the P-gp substrate) in male rats, but not in female ones. In contrast, PEG 400 had no influence on the bioavailability of the non-P-gp substrate, metformin in male or female rats. Inhibition of P-gp by oral pre-treatment with cyclosporine A increased the bioavailability of the P-gp substrates (ampicillin and ranitidine) in males and females (p<0.05), and to a greater extent in males, but had no influence on the bioavailability of metformin in either male or female rats. These results prove the hypothesis that the sex-specific effect of PEG 400 on the bioavailability of certain drugs is due to the interaction of PEG 400 with the efflux transporter P-gp. Copyright © 2017 Elsevier B.V. All rights reserved.

Relative Bioavailability and Bioaccessability and Speciation of Arsenic in Contaminated Soils

EPA Science Inventory

Background: Assessment of soil arsenic (As) bioavailability may profoundly affect the extent of remediation required at contaminated sites by improving human exposure estimates. Because small adjustments in soil As bioavailability estimates can significantly alter risk assessment...

Water relations, thallus structure and photosynthesis in Negev Desert lichens

NASA Technical Reports Server (NTRS)

Palmer, R. J. Jr; Friedmann, E. I.

1990-01-01

The role of lichen thallus structure in water relations and photosynthesis was studied in Ramalina maciformis (Del.) Bory and Teloschistes lacunosus (Rupr.) Sav. Water-vapour adsorption and photosynthesis are dependent upon thallus integrity and are significantly lower in crushed thalli. Cultured phycobiont (Trebouxia sp.) cells are capable of photosynthesis over the same relative humidity range (> 80% RH) as are intact lichens. Thus, water-vapour adsorption by the thallus and physiological adaptation of the phycobiont contribute to the ability of these lichens to photosynthesize in an arid environment. Despite differences in their anatomical structure and water-uptake characteristics, their CO2 incorporation is similar. The two lichens use liquid water differently and they occupy different niches.

On the numerical calculation of hydrodynamic shock waves in atmospheres by an FCT method

NASA Astrophysics Data System (ADS)

Schmitz, F.; Fleck, B.

1993-11-01

The numerical calculation of vertically propagating hydrodynamic shock waves in a plane atmosphere by the ETBFCT-version of the Flux Corrected Transport (FCT) method by Boris and Book is discussed. The results are compared with results obtained by a characteristic method with shock fitting. We show that the use of the internal energy density as a dependent variable instead of the total energy density can give very inaccurate results. Consequent discretization rules for the gravitational source terms are derived. The improvement of the results by an additional iteration step is discussed. It appears that the FCT method is an excellent method for the accurate calculation of shock waves in an atmosphere.

Loading amorphous Asarone in mesoporous silica SBA-15 through supercritical carbon dioxide technology to enhance dissolution and bioavailability.

PubMed

Zhang, Zhengzan; Quan, Guilan; Wu, Qiaoli; Zhou, Chan; Li, Feng; Bai, Xuequn; Li, Ge; Pan, Xin; Wu, Chuanbin

2015-05-01

The aim of this study was to load amorphous hydrophobic drug into ordered mesoporous silica (SBA-15) by supercritical carbon dioxide technology in order to improve the dissolution and bioavailability of the drug. Asarone was selected as a model drug due to its lipophilic character and poor bioavailability. In vitro dissolution and in vivo bioavailability of the obtained Asarone-SBA-15 were significantly improved as compared to the micronized crystalline drug. This study offers an effective, safe, and environmentally benign means of solving the problems relating to the solubility and bioavailability of hydrophobic molecules. Copyright © 2015 Elsevier B.V. All rights reserved.

Microbial reporters of metal bioavailability

PubMed Central

Magrisso, Sagi; Erel, Yigal; Belkin, Shimshon

2008-01-01

Summary When attempting to assess the extent and the implications of environmental pollution, it is often essential to quantify not only the total concentration of the studied contaminant but also its bioavailable fraction: higher bioavailability, often correlated with increased mobility, signifies enhanced risk but may also facilitate bioremediation. Genetically engineered microorganisms, tailored to respond by a quantifiable signal to the presence of the target chemical(s), may serve as powerful tools for bioavailability assessment. This review summarizes the current knowledge on such microbial bioreporters designed to assay metal bioavailability. Numerous bacterial metal‐sensor strains have been developed over the past 15 years, displaying very high detection sensitivities for a broad spectrum of environmentally significant metal targets. These constructs are based on the use of a relatively small number of gene promoters as the sensing elements, and an even smaller selection of molecular reporter systems; they comprise a potentially useful panel of tools for simple and cost‐effective determination of the bioavailability of heavy metals in the environment, and for the quantification of the non‐bioavailable fraction of the pollutant. In spite of their inherent advantages, however, these tools have not yet been put to actual use in the evaluation of metal bioavailability in a real environmental remediation scheme. For this to happen, acceptance by regulatory authorities is essential, as is a standardization of assay conditions. PMID:21261850

Organic carbon content effects on bioavailability of pyrethroid insecticides and validation of solid phase extraction with Poly (2,6-diphenyl-p-phenylene oxide) Polymer by Daphnia magna toxicity tests.

PubMed

Feo, M L; Corcellas, C; Barata, C; Ginebreda, A; Eljarrat, E; Barceló, D

2013-01-01

Solid phase extraction with Poly (2,6-diphenyl-p-phenylene oxide) Polymer (Tenax) was used for determining the bioavailability of eleven pyrethroids in field collected sediments with different organic carbon content (OC). The bioavailable fraction of pyrethroids decreased with increasing OC in sediments; the percentages of desorption ranged from 10 to 20% for sediment with higher OC content (5.8%) and 15-40% for that with lower OC (2%). Generally pyrethroids showed low bioavailability and cyfluthrin resulted to be the most bioavailable among the studied pyrethroids. Acute toxicity tests with Daphnia magna were carried out on sediment spiked with three selected pyrethroids (λ-cyhalothrin, cypermethrin and deltamethrin) and served to validate the efficiency of Tenax as a method for assessing the bioavailability of pyrethroids. Toxicity test demonstrated that Tenax was able to remove the toxic bio-available fraction of pyrethroids in sediment. Extracts from Tenax beads after the desorption experiments and spiked sediment before desorption had an equivalent toxicity (LC50) to D. magna neonates at 48 and 72 h of exposure. These results indicate that Tenax beds can be used to predict bio-available and toxic fractions of pyrethroids sorbed to sediments to aquatic organisms like D. magna. Copyright © 2012 Elsevier B.V. All rights reserved.

Improving the accuracy of effect-directed analysis: the role of bioavailability.

PubMed

You, Jing; Li, Huizhen

2017-12-13

Aquatic ecosystems have been suffering from contamination by multiple stressors. Traditional chemical-based risk assessment usually fails to explain the toxicity contributions from contaminants that are not regularly monitored or that have an unknown identity. Diagnosing the causes of noted adverse outcomes in the environment is of great importance in ecological risk assessment and in this regard effect-directed analysis (EDA) has been designed to fulfill this purpose. The EDA approach is now increasingly used in aquatic risk assessment owing to its specialty in achieving effect-directed nontarget analysis; however, a lack of environmental relevance makes conventional EDA less favorable. In particular, ignoring the bioavailability in EDA may cause a biased and even erroneous identification of causative toxicants in a mixture. Taking bioavailability into consideration is therefore of great importance to improve the accuracy of EDA diagnosis. The present article reviews the current status and applications of EDA practices that incorporate bioavailability. The use of biological samples is the most obvious way to include bioavailability into EDA applications, but its development is limited due to the small sample size and lack of evidence for metabolizable compounds. Bioavailability/bioaccessibility-based extraction (bioaccessibility-directed and partitioning-based extraction) and passive-dosing techniques are recommended to be used to integrate bioavailability into EDA diagnosis in abiotic samples. Lastly, the future perspectives of expanding and standardizing the use of biological samples and bioavailability-based techniques in EDA are discussed.

Assessing arsenic bioavailability through the use of bioassays

NASA Astrophysics Data System (ADS)

Diesel, E.; Nadimpalli, M.; Hull, M.; Schreiber, M. E.; Vikesland, P.

2009-12-01

Various methods have been used to characterize the bioavailability of a contaminant, including chemical extractions from soils, toxicity tests, bioaccumulation measurements, estimation from soil properties, in vitro/in vivo tests, and microbial biossays. Unfortunately, these tests are all unique (i.e. they measure bioavailability through different mechanisms) and it is difficult to compare measurements collected using one method to those collected from another. Additionally, there are fundamental aspects of bioavailability research that require further study. In particular, changes in bioavailability over time are not well understood, as well as what the geochemical controls are on changes in bioavailability. In addition, there are no studies aimed at the integration of bioavailability measurements and potential geochemical controls. This research project seeks to find a standard set of assays and sensors that can be used to assess arsenic bioavailability at any field site, as well as to use these tools and techniques to better understand changes in, and controls on, arsenic bioavailability. The bioassays to be utilized in this research are a bioluminescent E. coli assay and a Corbicula fluminea (Asian clam) assay. Preliminary experiments to determine the suitability of the E. coli and C. fluminea assays have been completed. The E. coli assay can be utilized to analyze As(III) and As(V) with a linear standard curve between 5 and 200 ppb for As(III) and 100 ppb and 5 ppm for As(V); no bioluminescent response above background was elicited in the presence of Roxarsone, an organoarsenical. The C. fluminea assay is capable of bioaccumulating As(III), As(V), Roxarsone, and MSMA, with As(III) being the most readily accumulated, followed by As(V), Roxarsone and MSMA, respectively. Additional research will include assessing bioavailability of various arsenic species adsorbed to natural colloidal materials (i.e. clays, iron oxides, NOM) to the E. coli and C. fluminea assays, as well as with natural samples collected at an arsenic contaminated field site. Once the testing of these assays has been completed, they will be used in conjunction with an electrochemical sensor array to determine arsenic bioavailability controls and changes at a contaminated field site.

Effect of Photochemical Transformation on Dissolved Organic Carbon Concentration and Bioavailability from Watersheds with Varying Landcover

NASA Astrophysics Data System (ADS)

Vermilyea, A.; Sanders, A.; Vazquez, E.

2017-12-01

The transformation of freshwater dissolved organic carbon (DOC) can have important implications for water quality, aquatic ecosystem health, and our climate. DOC is an important nutrient for heterotrophic microorganisms near the base of the aquatic food chain and the extent of conversion of DOC to CO2 is a critical piece of the global carbon cycle. Photochemical pathways have the potential to transform recalcitrant DOC into more labile forms that can then be converted to smaller DOC molecules and eventually be completely mineralized to CO2. This may lead to a DOC pool with different bioavailability depending on the structural composition of the original DOC pool and the mechanistic pathways undergone during transformation. This study aimed to measure the changes in DOC concentration and bioavailability due solely to photochemical processes in three watersheds of northern Vermont, USA that have varied land cover, land use (LCLU) attributes. Our hypothesis was that photochemical transformations will lead to (1) an overall loss of DOC due to mineralization to CO2 and (2) a relative increase in the bioavailable fraction of DOC. Additionally, the influence of LCLU and base flow versus storm flow on both mineralization rates and changes in DOC bioavailability was investigated. Irradiation of filtered samples in quartz vessels under sunlight led to small changes in DOC concentration over time, but significant changes in DOC bioavailability. In general, fluorescence excitation-emission matrices (EEMs) showed a shift from an initially more humic-like DOC pool, to a more protein-like (bioavailable) DOC pool. Specific UV index (SUVA) along with bioavailable DOC (BDOC) incubations were also used to characterize DOC and its bioavailability. There were only small differences in the DOC transformation that took place among sites, possibly due to only small differences in the initial bioavailability and fluorescent properties between water samples. Photochemical transformation appears to play an important role in the transformation of a more recalcitrant (humic) pool of DOC into a more bioavailable DOC pool that can then be utilized by aquatic heterotrophs and ultimately be converted to CO2.

PREFACE: SQM2007 International Conference on Strangeness in Quark Matter

NASA Astrophysics Data System (ADS)

Šafařík, Karel; Šándor, Ladislav; Tomášik, Boris

2008-04-01

The International Conference on `Strangeness in Quark Matter' (SQM) was held from 24-29 June 2007 at the Congress Hall of the city cultural centre in the charming mediaeval town of Levoča in north-eastern Slovakia. The Institute of Experimental Physics of the Slovak Academy of Science and the Faculty of Science of the P J Šafárik University in Košice shared the duties of main organizers of the conference. SQM2007 was attended by more than 100 participants from about 20 countries. The natural beauty and the rich cultural and historical monuments of the surrounding Spiš (Scepusium) region created an inspiring setting for the scientific, social and cultural framework of the conference. Continuing the trend started at the SQM2006 conference, heavy flavour physics in heavy-ion collisions was a topic given equal importance in the SQM2007 programme alongside strange quark physics. The Symposium for Students, from Students, organized by Christian Klein-Boesing and Boris Tomášik on the basis of the contributed abstracts, was again an integral and successful part of the conference. The jury, drawn from the organizers, awarded William A Horowitz (Columbia University) the title of best student contribution. The good news is that many students and younger researchers attended the conference. This could not have happened without generous support from our sponsors whom we would like to thank for valuable financial support: CERN, Journal of Physics G, the Prešov self-governing region authorities and the Slovak Physical Society. The kind assistance of the mayor of the town of Levoča is also warmly acknowledged. We would like to extend our gratitude to our colleagues and students from the organizing institutions for their diligent work prior to and during the conference, which ensured that everything worked smoothly. Our special thanks go to our secretaries, Adri Chomičová and Mery Šemš'aková, as well as to the management of the SATEL Hotel in Levoča for their highly professional work in preparing and running the conference. We thank all the speakers and session chairpersons for their active contribution to the inspiring scientific atmosphere at the conference. We also thank Emanuele Quercigh for an enlightening after-dinner speech. Finally, it is our pleasure to express thanks to all members of the SQM International Advisory Committee for their valuable input to the scientific programme and conference arrangement.

78 FR 35283 - Agency Information Collection Activities; Proposed Collection; Comment Request: Investigational...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-12

... for Bioavailability and Bioequivalence Studies in Humans AGENCY: Food and Drug Administration, HHS... requirements and safety reporting requirements for bioavailability and bioequivalence studies. DATES: Submit... Biological Products and Safety Reporting Requirements for Bioavailability and Bioequivalence Studies in...

Subcutaneous bioavailability of therapeutic antibodies as a function of FcRn binding affinity in mice

PubMed Central

Meng, Y Gloria; Hoyte, Kwame; Lutman, Jeff; Lu, Yanmei; Iyer, Suhasini; DeForge, Laura E; Theil, Frank-Peter; Fielder, Paul J; Prabhu, Saileta

2012-01-01

The neonatal Fc receptor (FcRn) plays an important and well-known role in immunoglobulin G (IgG) catabolism; however, its role in the disposition of IgG after subcutaneous (SC) administration, including bioavailability, is relatively unknown. To examine the potential effect of FcRn on IgG SC bioavailability, we engineered three anti-amyloid β monoclonal antibody (mAb) reverse chimeric mouse IgG2a (mIgG2a) Fc variants (I253A.H435A, N434H and N434Y) with different binding affinities to mouse FcRn (mFcRn) and compared their SC bioavailability to that of the wild-type (WT) mAb in mice. Our results indicated that the SC bioavailability of mIgG2a was affected by mFcRn-binding affinity. Variant I253A.H435A, which did not bind to mFcRn at either pH 6.0 or pH 7.4, had the lowest bioavailability (41.8%). Variant N434Y, which had the greatest increase in binding affinity at both pH 6.0 and pH 7.4, had comparable bioavailability to the WT antibody (86.1% vs. 76.3%), whereas Variant N434H, which had modestly increased binding affinity at pH 6.0 to mFcRn and affinity comparable to the WT antibody at pH 7.4, had the highest bioavailability (94.7%). A semi-mechanism-based pharmacokinetic model, which described well the observed data with the WT antibody and variant I253A.H435A, is consistent with the hypothesis that the decreased bioavailability of variant I253A.H435A was due to loss of the FcRn-mediated protection from catabolism at the absorption site. Together, these data demonstrate that FcRn plays an important role in SC bioavailability of therapeutic IgG antibodies. PMID:22327433

In vivo efficacy and bioavailability of lumefantrine: Evaluating the application of Pheroid technology.

PubMed

du Plessis, Lissinda H; Govender, Katya; Denti, Paolo; Wiesner, Lubbe

2015-11-01

The oral absorption of compounds with low aqueous solubility, such as lumefantrine, is typically limited by the dissolution rate in the gastro-intestinal tract, resulting in erratic absorption and highly variable bioavailability. In previous studies we reported on the ability of Pheroid vesicles to improve the bioavailability of poorly soluble drugs. In the present study a Pro-Pheroid formulation, a modification of the previous formulation, was applied to improve the solubility of lumefantrine after oral administration and compared to lumefantrine in DMSO:water (1:9 v/v) solution (reference solution). A bioavailability study of lumefantrine was conducted in a mouse model in fed and fasted states. When using the reference solution, the bioavailability of the lumefantrine heavily depended on food intake, resulting in a 2.7 times higher bioavailability in the fed state when compared to the fasted state. It also showed large between-subject variability. When formulated using Pro-Pheroid, the bioavailability of lumefantrine was 3.5 times higher as compared to lumefantrine in the reference solution and fasting state. Pro-Pheroid also dramatically reduced the effects of food intake and the between-subject variability for bioavailability observed with the reference. In vivo antimalarial efficacy was also evaluated with lumefantrine formulated using Pro-Pheroid technology compared to the reference solution. The results indicated that lumefantrine in Pro-Pheroid formulation exhibited improved antimalarial activity in vitro by 46.8%, when compared to the reference. The results of the Peters' 4-day suppressive test indicated no significant difference in the efficacy or mean survival time of the mice in the Pro-Pheroid formulation and reference test groups when compared to the positive control, chloroquine. These findings suggest that using the Pro-Pheroid formulation improves the bioavailability of lumefantrine, eliminates the food effect associated with lumefantrine as well as significantly reduces the between subject variability in bioavailability when compared to the reference solution. Copyright © 2015 Elsevier B.V. All rights reserved.

MR measures of renal perfusion, oxygen bioavailability and total renal blood flow in a porcine model: noninvasive regional assessment of renal function.

PubMed

Wentland, Andrew L; Artz, Nathan S; Fain, Sean B; Grist, Thomas M; Djamali, Arjang; Sadowski, Elizabeth A

2012-01-01

Magnetic resonance imaging (MRI) may be a useful adjunct to current methods of evaluating renal function. MRI is a noninvasive imaging modality that has the ability to evaluate the kidneys regionally, which is lacking in current clinical methods. Other investigators have evaluated renal function with MRI-based measurements, such as with techniques to measure cortical and medullary perfusion, oxygen bioavailability and total renal blood flow (TRBF). However, use of all three techniques simultaneously, and therefore the relationships between these MRI-derived functional parameters, have not been reported previously. To evaluate the ability of these MRI techniques to track changes in renal function, we scanned 11 swine during a state of hyperperfusion with acetylcholine and a saline bolus and subsequently scanned during a state of hypoperfusion with the prolonged use of isoflurane anesthesia. For each time point, measurements of perfusion, oxygen bioavailability and TRBF were acquired. Measurements of perfusion and oxygen bioavailability were compared with measurements of TRBF for all swine across all time points. Cortical perfusion, cortical oxygen bioavailability, medullary oxygen bioavailability and TRBF significantly increased with the acetylcholine challenge. Cortical perfusion, medullary perfusion, cortical oxygen bioavailability and TRBF significantly decreased during isoflurane anesthesia. Cortical perfusion (Spearman's correlation coefficient = 0.68; P < 1 × 10(-6)) and oxygen bioavailability (Spearman's correlation coefficient = -0.60; P < 0.0001) correlated significantly with TRBF, whereas medullary perfusion and oxygen bioavailability did not correlate with TRBF. Our results demonstrate expected changes given the pharmacologically induced changes in renal function. Maintenance of the medullary oxygen bioavailability in low blood flow states may reflect the autoregulation particular to this region of the kidney. The ability to non-invasively measure all three parameters of kidney function in a single MRI examination and to evaluate the relationships between these functional parameters is potentially useful for evaluating the state of the human kidneys in situ in future studies.

Elevating bioavailability of curcumin via encapsulation with a novel formulation of artificial oil bodies.

PubMed

Chang, Ming-Tsung; Tsai, Tong-Rong; Lee, Chun-Yann; Wei, Yu-Sheng; Chen, Ying-Jie; Chen, Chun-Ren; Tzen, Jason T C

2013-10-09

Utilization of curcumin has been limited due to its poor oral bioavailability. Oral bioavailability of hydrophobic compounds might be elevated via encapsulation in artificial seed oil bodies. This study aimed to improve oral bioavailability of curcumin via this encapsulation. Unfortunately, curcumin was indissoluble in various seed oils. A mixed dissolvent formula was used to dissolve curcumin, and the admixture was successfully encapsulated in artificial oil bodies stabilized by recombinant sesame caleosin. The artificial oil bodies of relatively small sizes (150 nm) were stably solidified in the forms of powder and tablet. Oral bioavailability of curcumin with or without encapsulation in artificial oil bodies was assessed in Sprague-Dawley male rats. The results showed that encapsulation of curcumin significantly elevated its bioavailability and provided the highest maximum whole blood concentration (Cmax), 37 ± 28 ng/mL, in the experimental animals 45 ± 17 min (t(max)) after oral administration. Relative bioavailability calculated on the basis of the area under the plasma concentration-time curve (AUC) was increased by 47.7 times when curcumin was encapsulated in the artificial oil bodies. This novel formulation of artificial oil bodies seems to possess great potential to encapsulate hydrophobic drugs for oral administration.

Utilization of nanoemulsions to enhance bioactivity of pharmaceuticals, supplements, and nutraceuticals: Nanoemulsion delivery systems and nanoemulsion excipient systems.

PubMed

Aboalnaja, Khaled Omer; Yaghmoor, Soonham; Kumosani, Taha Abdullah; McClements, David Julian

2016-09-01

The efficacy of many hydrophobic bioactives (pharmaceuticals, supplements, and nutraceuticals) is limited due to their relatively low or highly variable bioavailability. Nanoemulsions consisting of small lipid droplets (r < 100 nm) dispersed in water can be designed to improve bioavailability. The major factors limiting the oral bioavailability of hydrophobic bioactive agents are highlighted: bioaccessibility, absorption and transformation. Two nanoemulsion-based approaches to control these processes and improve bioavailability are discussed: nanoemulsion delivery systems (NDS) and nanoemulsion excipient systems (NES). In NDS, hydrophobic bioactives are dissolved within the lipid phase of oil-in-water nanoemulsions. In NES, the bioactives are present within a conventional drug, supplement, or food, which is consumed with an oil-in-water nanoemulsion. Examples of NDS and NES utilization to improve bioactive bioavailability are given. Considerable progress has been made in nanoemulsion design, fabrication, and testing. This knowledge facilitates the design of new formulations to improve the bioavailability of pharmaceuticals, supplements, and nutraceuticals. NDS and NES must be carefully designed based on the major factors limiting the bioavailability of specific bioactives. Research is still required to ensure these systems are commercially viable, and to demonstrate their safety and efficacy using animal and human feeding studies.

Improved Dissolution and Oral Bioavailability of Celecoxib by a Dry Elixir System.

PubMed

Cho, Kwan Hyung; Jee, Jun-Pil; Yang, Da A; Kim, Sung Tae; Kang, Dongjin; Kim, Dae-Young; Sim, Taeyong; Park, Sang Yeob; Kim, Kyeongsoon; Jang, Dong-Jin

2018-02-01

The purpose of this study was to develop and evaluate a dry elixir (DE) system for enhancing the dissolution rate and oral bioavailability of celecoxib. DE system has been used for improving solubility, oral bioavailability of poorly water-soluble drugs. The encapsulated drugs or solubilized drugs in the matrix are rapidly dissolved due to the co-solvent effect, resting in both an enhanced dissolution and bioavailability. DEs containing celecoxib were prepared by spray-drying method and characterized by morphology, drug/ethanol content, drug crystallinity, dissolution rate and oral bioavailability. The ethanol content and drug content in DE system could be easily altered by controlling the spraydrying conditions. The dissolution profile of celecoxib from DE proved to be much higher than that of celecoxib powder due to the nano-structured matrix, amorphous state and encapsulated ethanol. The bioavailability of celecoxib from DEs was compared with celecoxib powder alone and commercial product (Celebrex®) in rats. In particular, blood concentrations of celecoxib form DE formulation were much greater than those of native celecoxib and market product. The data demonstrate that the DE system could provide an useful solid dosage form to enhance the solubility, dissolution rate and oral bioavailability of celecoxib.

Estimating Lead (Pb) Bioavailability In A Mouse Model

EPA Science Inventory

Children are exposed to Pb through ingestion of Pb-contaminated soil. Soil Pb bioavailability is estimated using animal models or with chemically defined in vitro assays that measure bioaccessibility. However, bioavailability estimates in a large animal model (e.g., swine) can be...

COMPETITIVE INFLUENCE OF PHOSPHORUS AND CALCIUM ON PB IN-VITRO BIOAVAILABILITY

EPA Science Inventory

The bioavailability of a metal is heavily related to the speciation of the particular metal. Further, the complexity of examining metal bioavailability is compounded by the presence of competitive ions. Thus, equally contaminated soils with varying concentrations of competitive e...

Bioaccessibility tests accurately estimate bioavailability of lead to quail

USGS Publications Warehouse

Beyer, W. Nelson; Basta, Nicholas T; Chaney, Rufus L.; Henry, Paula F.; Mosby, David; Rattner, Barnett A.; Scheckel, Kirk G.; Sprague, Dan; Weber, John

2016-01-01

Hazards of soil-borne Pb to wild birds may be more accurately quantified if the bioavailability of that Pb is known. To better understand the bioavailability of Pb to birds, we measured blood Pb concentrations in Japanese quail (Coturnix japonica) fed diets containing Pb-contaminated soils. Relative bioavailabilities were expressed by comparison with blood Pb concentrations in quail fed a Pb acetate reference diet. Diets containing soil from five Pb-contaminated Superfund sites had relative bioavailabilities from 33%-63%, with a mean of about 50%. Treatment of two of the soils with phosphorus significantly reduced the bioavailability of Pb. Bioaccessibility of Pb in the test soils was then measured in six in vitro tests and regressed on bioavailability. They were: the “Relative Bioavailability Leaching Procedure” (RBALP) at pH 1.5, the same test conducted at pH 2.5, the “Ohio State University In vitro Gastrointestinal” method (OSU IVG), the “Urban Soil Bioaccessible Lead Test”, the modified “Physiologically Based Extraction Test” and the “Waterfowl Physiologically Based Extraction Test.” All regressions had positive slopes. Based on criteria of slope and coefficient of determination, the RBALP pH 2.5 and OSU IVG tests performed very well. Speciation by X-ray absorption spectroscopy demonstrated that, on average, most of the Pb in the sampled soils was sorbed to minerals (30%), bound to organic matter (24%), or present as Pb sulfate (18%). Additional Pb was associated with P (chloropyromorphite, hydroxypyromorphite and tertiary Pb phosphate), and with Pb carbonates, leadhillite (a lead sulfate carbonate hydroxide), and Pb sulfide. The formation of chloropyromorphite reduced the bioavailability of Pb and the amendment of Pb-contaminated soils with P may be a thermodynamically favored means to sequester Pb.

Candesartan cilexetil loaded nanodelivery systems for improved oral bioavailability.

PubMed

Dudhipala, Narendar; Veerabrahma, Kishan

2017-02-01

Candesartan cilexetil (CC), an antihypertensive drug, has low oral bioavailability due to poor solubility and hepatic first-pass metabolism. These are major limitations in oral delivery of CC. Several approaches are known to reduce the problems of solubility and improve the bioavailability of CC. Among various approaches, nanotechnology-based delivery of CC has potential to overcome the challenges associated with the oral administration. This review focuses on various nano-based delivery systems available and tried for improving the aqueous solubility, dissolution and consequently bioavailability of CC upon oral administration. Of all, solid lipid nanoparticles appear to be promising delivery system, based on current reported results, for delivery of CC, as this system improved the oral bioavailability and possessed prolonged pharmacodynamic effect.

Considerations for Incorporating Bioavailability in Effect-Directed Analysis and Toxicity Identification Evaluation.

EPA Science Inventory

In order to avoid a bias toward highly toxic but poorly bioavailable compounds in the effect-directed analysis (EDA) of soils and sediments, approaches are discussed to consider bioavailability in EDA procedures. In parallel, complimentary approaches for making toxicity identific...

Advances In Assessing Bioavailability Of Metal(Loid)s In Contaminated Soils

EPA Science Inventory

The term bioavailability has many different meanings across various disciplines of toxicology and pharmacology. Often bioavailability is concerned with human health aspects such as in the case of lead (Pb) ingestion by children. However, some of the most contaminated sites are ...

Bioavailability and biodistribution of nanodelivered lutein

USDA-ARS?s Scientific Manuscript database

The aim of the study was to evaluate the ability of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to enhance lutein bioavailability. The bioavailability of free lutein and PLGA-NP lutein in rats was assessed by determining plasma pharmacokinetics and deposition in selected tissues. Lutein ...

FIELD EVALUATION OF THE IN-SITU TREATMENTS TO REDUCE SOIL LEAD BIOAVAILABILITY: CONCLUSIONS

EPA Science Inventory

This presentation summarizes the conclusion of the technical issues associated with the Pb bioavailability experiment which IINERT has been conducting and further to illustrate that although bioavailability is a simple concept, its measurement and the implementation of the measur...

ASSESSING SOIL ARSENIC BIOAVAILABILITY IN THE LABORATORY MOUSE

EPA Science Inventory

Variation among soils in the bioavailability of arsenic can be a critical determinant of the risk posed by exposure to these soils. Although in vitro techniques can provide vital data on aspects of bioavailability of metals and metalloids from soils, these results must be valida...

Biomonitoring of trace metal bioavailabilities to the barnacle Amphibalanus amphitrite along the Iranian coast of the Persian Gulf.

PubMed

Nasrolahi, A; Smith, B D; Ehsanpour, M; Afkhami, M; Rainbow, P S

2014-10-01

The fouling barnacle Amphibalanus amphitrite is a cosmopolitan biomonitor of trace metal bioavailabilities, with an international comparative data set of body metal concentrations. Bioavailabilities of As, Cd, Cr, Cu, Fe, Mn, Pb, V and Zn to A. amphitrite were investigated at 19 sites along the Iranian coast of the understudied Persian Gulf. Commercial and fishing ports showed extremely high Cu bioavailabilities, associated with high Zn bioavailabilities, possibly from antifouling paints and procedures. V availability was raised at one port, perhaps associated with fuel leakage. Cd bioavailabilities were raised at sites near the Strait of Hormuz, perhaps affected by adjacent upwelling off Oman. The As data allow a reinterpretation of the typical range of accumulated As concentrations in A. amphitrite. The Persian Gulf data add a new region to the A. amphitrite database, confirming its importance in assessing the ecotoxicologically significant trace metal contamination of coastal waters across the world. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bioavailability and bioaccumulation of metal-based engineered nanomaterials in aquatic environments: concepts and processes: chapter 5

USGS Publications Warehouse

Luoma, Samuel N.; Khan, Farhan R.; Croteau, Marie-Noële

2014-01-01

Bioavailability of Me-ENMs to aquatic organisms links their release into the environment to ecological implications. Close examination shows some important differences in the conceptual models that define bioavailability for metals and Me-ENMs. Metals are delivered to aquatic animals from Me-ENMs via water, ingestion, and incidental surface exposure. Both metal released from the Me-ENM and uptake of the nanoparticle itself contribute to bioaccumulation. Some mechanisms of toxicity and some of the metrics describing exposure may differ from metals alone. Bioavailability is driven by complex interaction of particle attributes, environmental transformations, and biological traits. Characterization of Me-ENMs is an essential part of understanding bioavailability and requires novel methodologies. The relative importance of the array of processes that could affect Me-ENM bioavailability remains poorly known, but new approaches and models are developing rapidly. Enough is known, however, to conclude that traditional approaches to exposure assessment for metals would not be adequate to assess risks from Me-ENMs.

Development of lycopene micelle and lycopene chylomicron and a comparison of bioavailability

NASA Astrophysics Data System (ADS)

Jyun Chen, Yi; Inbaraj, Baskaran Stephen; Shiau Pu, Yeong; Chen, Bing Huei

2014-04-01

The objectives of this study were to develop lycopene micelles and lycopene chylomicrons from tomato extracts for the enhancement and comparison of bioavailability. Lycopene micelles and chylomicrons were prepared by a microemulsion technique involving tomato extract, soybean oil, water, vitamin E and surfactant Tween 80 or lecithin in different proportions. The encapsulation efficiency of lycopene was 78% in micelles and 80% in chylomicrons, with shape being roughly spherical and mean particle size being 7.5 and 131.5 nm. A bioavailability study was conducted in rats by both gavage and i.v. administration, with oral bioavailability of lycopene, phytoene and phytofluene being 6.8, 4.3 and 3.1% in micelles and 9.5, 9.4 and 7.1% in chylomicrons, respectively. This outcome reveals higher lycopene bioavailability through incorporation into micelle or chylomicron systems. Both size and shape should be considered for oral bioavailability determination. For i.v. injection, lycopene micelles should be more important than lycopene chylomicrons for future clinical applications.

Geochemical partitioning of Cu and Ni in mangrove sediments: relationships with their bioavailability.

PubMed

Chakraborty, Parthasarathi; Ramteke, Darwin; Chakraborty, Sucharita

2015-04-15

Sequential extraction study was performed to determine the concentrations of non-residual metal-complexes in the mangrove sediments from the Divar Island, (west coast of India). Accumulation of metal in the mangrove roots (from the same location) was determined and used as an indicator of bioavailability of metal. An attempt was made to establish a mechanistic linkage between the non-residual metal complexes and their bioavailability in the mangrove system. The non-residual fractions of Cu and Ni were mainly associated with Fe/Mn oxyhydroxide and organic phases in the sediments. A part of these metal fractions were bioavailable in the system. These two phases were the major controlling factors for Ni speciation and their bioavailability in the studied sediments. However, Cu was found to interact more strongly with the organic phases than Ni in the mangrove sediments. Organic phases in the mangrove sediments acted as buffer to control the speciation and bioavailability of Cu in the system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Utilizing food effects to overcome challenges in delivery of lipophilic bioactives: structural design of medical and functional foods.

PubMed

McClements, David Julian

2013-12-01

The oral bioavailability of many lipophilic bioactives, such as pharmaceuticals and nutraceuticals, is relatively low due to their poor solubility, permeability and/or chemical stability within the human gastrointestinal tract (GIT). The oral bioavailability of lipophilic bioactives can be improved by designing food matrices that control their release, solubilization, transport and absorption within the GIT. This article discusses the challenges associated with delivering lipophilic bioactive components, the impact of food composition and structure on oral bioavailability and the design of functional and medical foods for improving the oral bioavailability of lipophilic bioactives. Food-based delivery systems can be used to improve the oral bioavailability of lipophilic bioactives. There are a number of potential advantages to delivering lipophilic bioactives using functional or medical foods: greater compliance than conventional delivery forms; increased bioavailability and efficacy; and reduced variability in biological effects. However, food matrices are structurally complex multicomponent materials and research is still needed to identify optimum structures and compositions for particular bioactives.

Oral heparin delivery: design and in vivo evaluation of a stomach-targeted mucoadhesive delivery system.

PubMed

Schmitz, Thierry; Leitner, Verena M; Bernkop-Schnürch, Andreas

2005-05-01

Low molecular weight heparin (LMWH) is an agent of choice in the anti-coagulant therapy and prophylaxis of thrombosis and coronary syndromes. However, the therapeutic use is partially limited due to a poor oral bioavailability. It was therefore the aim of this study to design and evaluate a highly efficient stomach-targeted oral delivery system for LMWH. In order to appraise the influence of the molecular weight on the oral bioavailability, mini-tablets comprising 3 kDa (279 IU) and 6 kDa (300 IU) LMWH, respectively, were generated and tested in vivo in rats. The potential of the test formulations based on thiolated polycarbophil, was evaluated in comparison to hydroxyethylcellulose (HEC) as control carrier matrix. The plasma levels of LMWH after oral versus subcutaneous administration were determined in order to calculate the relative bioavailability. With the delivery system containing 3 kDa LMWH (279 IU) a relative bioavailability of 19.1% was achieved, offering a significantly (p < 0.05) better bioavailability than the control system displaying a relative bioavailability of 8.1% The 6 kDa LMWH (300 IU) formulation displayed a relative bioavailability of 10.7% in contrast to the control displaying a relative bioavailability of 2.1%. In conclusion, these results suggest that mucoadhesive thiolated polymers are a promising tool for the non-invasive stomach-targeted systemic delivery of LMWH as model for a hydrophilic macromolecular polysaccharide. Copyright 2005 Wiley-Liss, Inc

Alterations of the arginine metabolome in asthma.

PubMed

Lara, Abigail; Khatri, Sumita B; Wang, Zeneng; Comhair, Suzy A A; Xu, Weiling; Dweik, Raed A; Bodine, Melanie; Levison, Bruce S; Hammel, Jeffrey; Bleecker, Eugene; Busse, William; Calhoun, William J; Castro, Mario; Chung, Kian Fan; Curran-Everett, Douglas; Gaston, Benjamin; Israel, Elliot; Jarjour, Nizar; Moore, Wendy; Peters, Stephen P; Teague, W Gerald; Wenzel, Sally; Hazen, Stanley L; Erzurum, Serpil C

2008-10-01

As the sole nitrogen donor in nitric oxide (NO) synthesis and key intermediate in the urea cycle, arginine and its metabolic pathways are integrally linked to cellular respiration, metabolism, and inflammation. We hypothesized that arginine (Arg) bioavailability would be associated with airflow abnormalities and inflammation in subjects with asthma, and would be informative for asthma severity. Arg bioavailability was assessed in subjects with severe and nonsevere asthma and healthy control subjects by determination of plasma Arg relative to its metabolic products, ornithine and citrulline, and relative to methylarginine inhibitors of NO synthases, and by serum arginase activity. Inflammatory parameters, including fraction of exhaled NO (Fe(NO)), IgE, skin test positivity to allergens, bronchoalveolar lavage, and blood eosinophils, were also evaluated. Subjects with asthma had greater Arg bioavailability, but also increased Arg catabolism compared with healthy control subjects, as evidenced by higher levels of Fe(NO) and serum arginase activity. However, Arg bioavailability was positively associated with Fe(NO) only in healthy control subjects; Arg bioavailability was unrelated to Fe(NO) or other inflammatory parameters in severe or nonsevere asthma. Inflammatory parameters were related to airflow obstruction and reactivity in nonsevere asthma, but not in severe asthma. Conversely, Arg bioavailability was related to airflow obstruction in severe asthma, but not in nonsevere asthma. Modeling confirmed that measures of Arg bioavailabilty predict airflow obstruction only in severe asthma. Unlike Fe(NO), Arg bioavailability is not a surrogate measure of inflammation; however, Arg bioavailability is strongly associated with airflow abnormalities in severe asthma.

EFFECT OF SOIL PROPERTIES ON LEAD BIOAVAILABILITY AND TOXCITY TO EARTHWORMS

EPA Science Inventory

Soil properties are important factors modifying metal bioavailability to ecological receptors. Twenty-one soils with a wide range of soil properties were amended with a single concentration of Pb (2000 mg/kg) to determine the effects of soil properties on Pb bioavailability and ...

BIOACCESSIBILITY TESTS ACCURATELY ESTIMATE BIOAVAILABILITY OF LEAD TO QUAIL

EPA Science Inventory

Hazards of soil-borne Pb to wild birds may be more accurately quantified if the bioavailability of that Pb is known. To better understand the bioavailability of Pb to birds, we measured blood Pb concentrations in Japanese quail (Coturnix japonica) fed diets containing Pb-contami...

COMPETITIVE INFLUENCE OF PHOSPHORUS AND CALCIUM ON PB IN-VITRO BIOAVAILABILITY (S11-SCHECKEL101231-POSTER)

EPA Science Inventory

The bioavailability of a metal is heavily related to the speciation of the particular metal. Further, the complexity of examining metal bioavailability is compounded by the presence of competitive ions. Thus, equally contaminated soils with varying concentrations of competitive e...

EARLY INDICATORS OF NITRATE STRESS; EFFECTS TO ECOSYSTEMS OF CHRONIC EXPOSURE TO LOW DOSES OF BIOAVAILABLE NITROGEN

EPA Science Inventory

Throughout the eastern United States, from the Front Range of the Rocky Mountains to the Atlantic Ocean, bioavailable nitrogen has been falling in the rain since the industrial revolution. Bioavailable nitrogen is a limiting nutrient throughout this region. While long-term rese...

21 CFR 320.23 - Basis for measuring in vivo bioavailability or demonstrating bioequivalence.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS... bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which... labeling, is not essential to the attainment of effective body drug concentrations on chronic use, and is...

21 CFR 320.23 - Basis for measuring in vivo bioavailability or demonstrating bioequivalence.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS... bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which... labeling, is not essential to the attainment of effective body drug concentrations on chronic use, and is...

21 CFR 320.23 - Basis for measuring in vivo bioavailability or demonstrating bioequivalence.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS... bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which... labeling, is not essential to the attainment of effective body drug concentrations on chronic use, and is...

21 CFR 320.23 - Basis for measuring in vivo bioavailability or demonstrating bioequivalence.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS... bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which... labeling, is not essential to the attainment of effective body drug concentrations on chronic use, and is...

21 CFR 320.23 - Basis for measuring in vivo bioavailability or demonstrating bioequivalence.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS... bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which... labeling, is not essential to the attainment of effective body drug concentrations on chronic use, and is...

Advances in Assessing Bioavailability of Metal(loid)s in Contaminated Soils

USDA-ARS?s Scientific Manuscript database

The term bioavailability has many different meanings across various disciplines of toxicology and pharmacology. Often bioavailability is concerned with human health aspects such in the case of lead (Pb) ingestion by children. However, some of the most contaminated sites are found in non-public acc...

Bioaccessibility tests accurately estimate bioavailability of lead to quail

USDA-ARS?s Scientific Manuscript database

Hazards of soil-borne Pb to wild birds may be more accurately quantified if the bioavailability of that Pb is known. To better understand the bioavailability of Pb, we incorporated Pb-contaminated soils or Pb acetate into diets for Japanese quail (Coturnix japonica), fed the quail for 15 days, and ...

On definition and use of the term bioavailability.

PubMed

Rescigno, A; Thakur, A K; Marzo, A

1994-10-01

In common usage, the rate of absorption of an active ingredient or its therapeutic moiety is generally not mentioned in the context of bioavailability. In this communication it is shown that exclusion of the rate of absorption may have serious consequence on the interpretation of bioavailability depending on the underlying model for the system under study. In the case of endogenous substances, the term "bioavailability" is ambiguous unless one specifies whether it refers to availability of the exogenous substance only or the sum total of the exogenous and endogenous substances.

Food processing strategies to enhance phenolic compounds bioaccessibility and bioavailability in plant-based foods.

PubMed

Ribas-Agustí, Albert; Martín-Belloso, Olga; Soliva-Fortuny, Robert; Elez-Martínez, Pedro

2017-06-13

Phenolic compounds are important constituents of plant-based foods, as their presence is related to protective effects on health. To exert their biological activity, phenolic compounds must be released from the matrix during digestion in an absorbable form (bioaccessible) and finally absorbed and transferred to the bloodstream (bioavailable). Chemical structure and matrix interactions are some food-related factors that hamper phenolic compounds bioaccessibility and bioavailability, and that can be counteracted by food processing. It has been shown that food processing can induce chemical or physical modifications in food that enhance phenolic compounds bioaccessibility and bioavailability. These changes include: (i) chemical modifications into more bioaccessible and bioavailable forms; (ii) cleavage of covalent or hydrogen bonds or hydrophobic forces that attach phenolic compounds to matrix macromolecules; (iii) damaging microstructural barriers such as cell walls that impede the release from the matrix; and (iv) create microstructures that protect phenolic compounds until they are absorbed. Indeed, food processing can produce degradation of phenolic compounds, however, it is possible to counteract it by modulating the operating conditions in favor of increased bioaccessibility and bioavailability. This review compiles the current knowledge on the effects of processing on phenolic compounds bioaccessibility or bioavailability, while suggesting new guidelines in the search of optimal processing conditions as a step forward towards the design of healthier foods.

Bioavailability enhancement of atovaquone using hot melt extrusion technology.

PubMed

Kate, Laxman; Gokarna, Vinod; Borhade, Vivek; Prabhu, Priyanka; Deshpande, Vinita; Pathak, Sulabha; Sharma, Shobhona; Patravale, Vandana

2016-04-30

Emerging parasite resistance and poor oral bioavailability of anti-malarials are the two cardinal issues which hinder the clinical success of malaria chemotherapy. Atovaquone-Proguanil is a WHO approved fixed dose combination used to tackle the problem of emerging resistance. However, Atovaquone is a highly lipophilic drug having poor aqueous solubility (less than 0.2 μg/ml) thus reducing its oral bioavailability. The aim of the present investigation was to explore hot melt extrusion (HME) as a solvent-free technique to enhance solubility and oral bioavailability of Atovaquone and to develop an oral dosage form for Atovaquone-Proguanil combination. Solid dispersion of Atovaquone was successfully developed using HME. The solid dispersion was characterized for DSC, FTIR, XRD, SEM, and flow properties. It was filled in size 2 hard gelatin capsules. The formulation showed better release as compared to Malarone® tablets, and 3.2-fold and 4.6-fold higher bioavailability as compared to Malarone® tablets and Atovaquone respectively. The enhanced bioavailability also resulted in 100% anti-malarial activity in murine infection model at 1/8(th) therapeutic dose. Thus the developed methodology shows promising potential to solve the problems associated with Atovaquone therapy, namely its high cost and poor oral bioavailability, resulting in increased therapeutic efficacy of Atovaquone. Copyright © 2016 Elsevier B.V. All rights reserved.

Rapid and sensitive Nitrosomonas europaea biosensor assay for quantification of bioavailable ammonium sensu strictu in soil.

PubMed

Nguyen, Minh Dong; Risgaard-Petersen, Nils; Sørensen, Jan; Brandt, Kristian K

2011-02-01

Knowledge on bioavailable ammonium sensu strictu (i.e., immediately available for cellular uptake) in soil is required to understand nutrient uptake processes in microorganisms and thus of vital importance for plant production. We here present a novel ammonium biosensor approach based on the lithoautotrophic ammonia-oxidizing bacterium Nitrosomonas europaea transformed with a luxAB sensor plasmid. Bioluminescence-based ammonium detection was achieved within 10 min with a quantification limit in liquid samples of ∼20 μM and a linear response range up to 400 μM. Biosensor and conventional chemical quantification of ammonium in soil solutions agreed well across a range of sample and assay conditions. The biosensor was subsequently applied for a solid phase-contact assay allowing for direct interaction of biosensor cells with soil particle-associated (i.e., exchangeable plus fixed) ammonium. The assay successfully quantified bioavailable ammonium even in unfertilized soil and demonstrated markedly higher ratios of bioavailable ammonium to water- or 2 M KCl-exchangeable ammonium in anoxic soil than in corresponding oxic soil. Particle-associated ammonium contributed by at least 74% and 93% of the total bioavailable pool in oxic and anoxic soil, respectively. The N. europaea biosensor should have broad relevance for environmental monitoring of bioavailable ammonium and processes depending on ammonium bioavailability.

High bioavailability iron maize (Zea mays L.) developed through molecular breeding provides more absorbable iron in vitro (Caco-2 model) and in vivo (Gallus gallus).

PubMed

Tako, Elad; Hoekenga, Owen A; Kochian, Leon V; Glahn, Raymond P

2013-01-04

Iron (Fe) deficiency is the most common micronutrient deficiency worldwide. Iron biofortification is a preventative strategy that alleviates Fe deficiency by improving the amount of absorbable Fe in crops. In the present study, we used an in vitro digestion/Caco 2 cell culture model as the guiding tool for breeding and development of two maize (Zea mays L.) lines with contrasting Fe bioavailability (ie. Low and High). Our objective was to confirm and validate the in vitro results and approach. Also, to compare the capacities of our two maize hybrid varieties to deliver Fe for hemoglobin (Hb) synthesis and to improve the Fe status of Fe deficient broiler chickens. We compared the Fe-bioavailability between these two maize varieties with the presence or absence of added Fe in the maize based-diets. Diets were made with 75% (w/w) maize of either low or high Fe-bioavailability maize, with or without Fe (ferric citrate). Chicks (Gallus gallus) were fed the diets for 6 wk. Hb, liver ferritin and Fe related transporter/enzyme gene-expression were measured. Hemoglobin maintenance efficiency (HME) and total body Hb Fe values were used to estimate Fe bioavailability from the diets. DMT-1, DcytB and ferroportin expressions were higher (P<0.05) in the "Low Fe" group than in the "High Fe" group (no added Fe), indicating lower Fe status and adaptation to less Fe-bioavailability. At times, Hb concentrations (d 21,28,35), HME (d 21), Hb-Fe (as from d 14) and liver ferritin were higher in the "High Fe" than in the "Low Fe" groups (P<0.05), indicating greater Fe absorption from the diet and improved Fe status. We conclude that the High Fe-bioavailability maize contains more bioavailable Fe than the Low Fe-bioavailability maize, presumably due to a more favorable matrix for absorption. Maize shows promise for Fe biofortification; therefore, human trials should be conducted to determine the efficacy of consuming the high bioavailable Fe maize to reduce Fe deficiency.

Bioaccessibility tests accurately estimate bioavailability of lead to quail.

PubMed

Beyer, W Nelson; Basta, Nicholas T; Chaney, Rufus L; Henry, Paula F P; Mosby, David E; Rattner, Barnett A; Scheckel, Kirk G; Sprague, Daniel T; Weber, John S

2016-09-01

Hazards of soil-borne lead (Pb) to wild birds may be more accurately quantified if the bioavailability of that Pb is known. To better understand the bioavailability of Pb to birds, the authors measured blood Pb concentrations in Japanese quail (Coturnix japonica) fed diets containing Pb-contaminated soils. Relative bioavailabilities were expressed by comparison with blood Pb concentrations in quail fed a Pb acetate reference diet. Diets containing soil from 5 Pb-contaminated Superfund sites had relative bioavailabilities from 33% to 63%, with a mean of approximately 50%. Treatment of 2 of the soils with phosphorus (P) significantly reduced the bioavailability of Pb. Bioaccessibility of Pb in the test soils was then measured in 6 in vitro tests and regressed on bioavailability: the relative bioavailability leaching procedure at pH 1.5, the same test conducted at pH 2.5, the Ohio State University in vitro gastrointestinal method, the urban soil bioaccessible lead test, the modified physiologically based extraction test, and the waterfowl physiologically based extraction test. All regressions had positive slopes. Based on criteria of slope and coefficient of determination, the relative bioavailability leaching procedure at pH 2.5 and Ohio State University in vitro gastrointestinal tests performed very well. Speciation by X-ray absorption spectroscopy demonstrated that, on average, most of the Pb in the sampled soils was sorbed to minerals (30%), bound to organic matter (24%), or present as Pb sulfate (18%). Additional Pb was associated with P (chloropyromorphite, hydroxypyromorphite, and tertiary Pb phosphate) and with Pb carbonates, leadhillite (a lead sulfate carbonate hydroxide), and Pb sulfide. The formation of chloropyromorphite reduced the bioavailability of Pb, and the amendment of Pb-contaminated soils with P may be a thermodynamically favored means to sequester Pb. Environ Toxicol Chem 2016;35:2311-2319. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.

1H NMR Metabolomics: A New Molecular Level Tool for Assessment of Organic Contaminant Bioavailability to Earthworms in Soil

NASA Astrophysics Data System (ADS)

McKelvie, J. R.; Wolfe, D. M.; Celejewski, M. A.; Simpson, A. J.; Simpson, M. J.

2009-05-01

At contaminated field sites, the complete removal of polycyclic aromatic hydrocarbons (PAHs) is rarely achieved since a portion of these compounds remain tightly bound to the soil matrix. The concentration of PAHs in soil typically decreases until a plateau is reached, at which point the remaining contaminant is considered non- bioavailable. Numerous soil extraction techniques, including cyclodextrin extraction, have been developed to estimate contaminant bioavailability. However, these are indirect methods that do not directly measure the response of organisms to chemical exposure in soil. Earthworm metabolomics offers a promising new way to directly evaluate the bioavailability and toxicity of contaminants in soil. Metabolomics involves the measurement of changes in small-molecule metabolites, including sugars and amino acids, in living organisms due to an external stress, such as contaminant exposure. The objective of this study was to compare cyclodextrin extraction of soil (a bioavailability proxy) and 1H NMR metabolomic analysis of aqueous earthworm tissue extracts as indicators of contaminant bioavailability. A 30 day laboratory experiment was conducted using phenanthrene-spiked sphagnum peat soil and the OECD recommended earthworm species for toxicity testing, Eisenia fetida. The initial phenanthrene concentration in the soil was 320 mg/kg. Rapid biodegradation of phenanthrene occurred and concentrations decreased to 16 mg/kg within 15 days. After 15 days, phenanthrene biodegradation slowed and cyclodextrin extraction of the soil suggested that phenanthrene was no longer bioavailable. Multivariate statistical analysis of the 1H NMR spectra for E. fetida tissue extracts indicated that the metabolic profile of phenanthrene exposed earthworms differed from control earthworms throughout the 30 day experiment. This suggests that the residual phenanthrene remaining in the soil after 15 days continued to elicit a metabolic response, even though it was not extractable using cyclodextrin. Hence, while cyclodextrin extraction may serve as a good proxy for microbial bioavailability, our results suggest that it may not serve as a good proxy for earthworm bioavailability. 1H NMR metabolomics therefore offers considerable promise as a novel, molecular-level method to directly monitor earthworm bioavailability of potentially toxic and persistent compounds in the environment.

PAH effects on meio- and microbial benthic communities strongly depend on bioavailability.

PubMed

Lindgren, J Fredrik; Hassellöv, Ida-Maja; Dahllöf, Ingela

2014-01-01

The effects of anthropogenic pollutants in dissimilar habitats can vary depending on differences in bioavailability. The factors determining bioavailability are not yet fully understood. This study was performed to evaluate whether analysis of total PAH concentrations in sediments is a satisfactory measurement to indicate environmental effects or if bioavailability is needed to be taken into account. We have here performed a 60-day experiment, where nominal PAH concentrations of 1,300 μg/kg sediment were added to three different marine sediments. Meiofaunal and microbial communities were analyzed for alterations in community response at 30 and 60 days. Results showed that bioavailability of PAHs varied between the three different sediments. Nonetheless, the petroleum addition gave rise to significant negative effects on all three sediments at both time points. The two direct measurements of toxicity on the microbial community, potential nitrification and denitrification, displayed a lower effect of the PAH addition in the muddy sediment at both time points, compared to the other two sediment types. No effects were seen in the analysis of meiofaunal community structure. Measurements of PAH bioavailability in the three sediment types concurred with the results from the microbial community, revealing a lower bioavailability in the muddy sediment compared to the other two sediment types, 34% compared to sandy and 18% compared to organic at day 0. At day 60 it was 61% lower compared to sandy and 20% lower compared to organic. The negative effects of the PAH addition on the microbial nitrogen cycle were in six out of eight cases best correlated to the amount of alkylated bioavailable PAH in the sediments, and thus microbial nitrogen cycle is a possible good indicator for assessing PAH-induced stress. The results presented here have implications for risk analysis studies of petroleum-contaminated marine sediments; consequently, sediment characteristics and its effects on bioavailability are important to include. In addition, these results add to the understanding that bioavailability measurements of PAHs are a more correct assessment compared to measurements of total PAH concentrations, and need to be included when estimating effects of PAHs in marine benthic communities. Copyright © 2013 Elsevier B.V. All rights reserved.

Iron bioavailability in corn-masa tortillas is improved by the addition of disodium EDTA.

PubMed

Walter, Tomás; Pizarro, Fernando; Olivares, Manuel

2003-10-01

Corn-masa flour flat bread tortillas are the main staple of Mexican and Central American populations. Due to high concentrations of inhibitors of iron absorption, the bioavailability from this matrix is unknown. We wanted to determine the most suitable fortificant that would efficaciously improve iron bioavailability. In tortillas prepared with commercial precooked, lime-treated, corn-masa flour, we examined the in vitro solubility of the following forms of iron: native iron with and without Na2EDTA, elemental reduced iron plus Na2EDTA, ferrous fumarate with and without Na2EDTA, bisglycine iron, ferrous sulfate and NaFeEDTA. We also examined the in vivo bioavailability in humans with double radioiron erythrocyte incorporation of ferrous fumarate with and without Na2EDTA, bisglycine iron, NaFeEDTA and native iron plus Na2EDTA, beans and rice. In vitro, solubility ranged from 1% in iron forms without Na2EDTA to 19.4% for NaFeEDTA. Forms of iron with Na2EDTA had intermediate values. In vivo radioiron studies showed that iron forms without Na2EDTA also had low bioavailability (< or =1%). NaFeEDTA had the highest bioavailability (5.3%). The bioavailability of all iron forms improved significantly when tested with Na2EDTA (<0.05). Adding Na2EDTA to ferrous fumarate increased bioavailability from 0.87% to 2.9% (P < 0.001). We conclude that NaFeEDTA is the form of iron best absorbed, but alternatively, ferrous fumarate plus Na2EDTA comprises a feasible option as a fortificant.

Does ascorbic acid supplementation affect iron bioavailability in rats fed micronized dispersible ferric pyrophosphate fortified fruit juice?

PubMed

Haro-Vicente, Juan Francisco; Pérez-Conesa, Darío; Rincón, Francisco; Ros, Gaspar; Martínez-Graciá, Carmen; Vidal, Maria Luisa

2008-12-01

Food iron (Fe) fortification is an adequate approach for preventing Fe-deficiency anemia. Poorly water-soluble Fe compounds have good sensory attributes but low bioavailability. The reduction of the particle size of Fe fortificants and the addition of ascorbic acid might increase the bioavailability of low-soluble compounds. The present work aims to compare the Fe absorption and bioavailability of micronized dispersible ferric pyrophosphate (MDFP) (poorly soluble) to ferrous sufate (FS) (highly soluble) added to a fruit juice in presence or absence of ascorbic acid (AA) by using the hemoglobin repletion assay in rats. After a hemoglobin depletion period, four fruit juices comprised of (1) FS, (2) MDFP, (3) FS + AA, (4) MDFP + AA were produced and administered to a different group of rats (n = 18) over 21 days. During the repletion period, Fe balance, hemoglobin regeneration efficiency (HRE), relative bioavailability (RBV) and Fe tissue content were determined in the short, medium and long term. Fe absorption and bioavailability showed no significant differences between fortifying the fruit juice with FS or MDFP. The addition of AA to the juice enhanced Fe absorption during the long-term balance study within the same Fe source. HRE and Fe utilization increased after AA addition in both FS and MDFP groups in every period. Fe absorption and bioavailability from MDFP were comparable to FS added to a fruit juice in rats. Further, the addition of AA enhanced Fe absorption in the long term, as well as Fe bioavailability throughout the repletion period regardless of the Fe source employed.

A new perspective of using sequential extraction: To predict the deficiency of trace elements during anaerobic digestion.

PubMed

Cai, Yafan; Wang, Jungang; Zhao, Yubin; Zhao, Xiaoling; Zheng, Zehui; Wen, Boting; Cui, Zongjun; Wang, Xiaofen

2018-09-01

Trace elements were commonly used as additives to facilitate anaerobic digestion. However, their addition is often blind because of the complexity of reaction conditions, which has impeded their widespread application. Therefore, this study was conducted to evaluate deficiencies in trace elements during anaerobic digestion by establishing relationships between changes in trace element bioavailability (the degree to which elements are available for interaction with biological systems) and digestion performance. To accomplish this, two batch experiments were conducted. In the first, sequential extraction was used to detect changes in trace element fractions and then to evaluate trace element bioavailability in the whole digestion cycle. In the second batch experiment, trace elements (Co, Fe, Cu, Zn, Mn, Mo and Se) were added to the reaction system at three concentrations (low, medium and high) and their effects were monitored. The results showed that sequential extraction was a suitable method for assessment of the bioavailability of trace elements (appropriate coefficient of variation and recovery rate). The results revealed that Se had the highest (44.2%-70.9%) bioavailability, while Fe had the lowest (1.7%-3.0%). A lack of trace elements was not directly related to their absolute bioavailability, but was instead associated with changes in their bioavailability throughout the digestion cycle. Trace elements were insufficient when their bioavailability was steady or increased over the digestion cycle. These results indicate that changes in trace element bioavailability during the digestion cycle can be used to predict their deficiency. Copyright © 2018 Elsevier Ltd. All rights reserved.

Development of a novel l-sulpiride-loaded quaternary microcapsule: Effect of TPGS as an absorption enhancer on physicochemical characterization and oral bioavailability.

PubMed

Kim, Dong Shik; Kim, Dong Wuk; Kim, Kyeong Soo; Choi, Jong Seo; Seo, Youn Gee; Youn, Yu Seok; Oh, Kyung Taek; Yong, Chul Soon; Kim, Jong Oh; Jin, Sung Giu; Choi, Han-Gon

2016-11-01

The aim of this study was to assess the effect of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on the physicochemical characterization and oral bioavailability of a novel l-sulpiride-loaded quaternary microcapsule (QMC). The effect of carriers on drug solubility was investigated. Among the carriers tested, polyvinyl pyrrolidone (PVP), sodium lauryl sulphate (SLS) and TPGS were selected as polymer, surfactant and absorption enhancer, respectively, due to their high drug solubility. Using the solvent evaporation method, numerous QMCs with different ratios of l-sulpiride, PVP, SLS and TPGS were prepared, and their physicochemical properties, solubility and release were evaluated. In addition, the influence of TPGS concentration on the oral bioavailability of various drug doses was evaluated. All QMCs converted the crystalline drug to the amorphous form and remarkably improved the solubility, release and oral bioavailability of the drug. Furthermore, the TPGS concentration in the QMCs hardly affected the crystallinity, particle size and release, but considerably increased the solubility and oral bioavailability of the drug. In particular, as the dose of administered drug was increased, TPGS provided a greater improvement in oral drug bioavailability. Thus, TPGS played an important role in improving the oral bioavailability of l-sulpiride. Moreover, the QMC with a drug/PVP/SLS/TPGS weight ratio of 5:12:1 :20 with approximately 3.3-fold improved oral bioavailability would be recommended as a commercial pharmaceutical product for oral administration of l-sulpiride. Copyright © 2016 Elsevier B.V. All rights reserved.

Artificial neural network model for predicting the bioavailability of tacrolimus in patients with renal transplantation

PubMed Central

Thishya, Kalluri; Vattam, Kiran Kumar; Naushad, Shaik Mohammad; Raju, Shree Bhushan

2018-01-01

The objective of the current study was to explore the role of ABCB1 and CYP3A5 genetic polymorphisms in predicting the bioavailability of tacrolimus and the risk for post-transplant diabetes. Artificial neural network (ANN) and logistic regression (LR) models were used to predict the bioavailability of tacrolimus and risk for post-transplant diabetes, respectively. The five-fold cross-validation of ANN model showed good correlation with the experimental data of bioavailability (r2 = 0.93–0.96). Younger age, male gender, optimal body mass index were shown to exhibit lower bioavailability of tacrolimus. ABCB1 1236 C>T and 2677G>T/A showed inverse association while CYP3A5*3 showed a positive association with the bioavailability of tacrolimus. Gender bias was observed in the association with ABCB1 3435 C>T polymorphism. CYP3A5*3 was shown to interact synergistically in increasing the bioavailability in combination with ABCB1 1236 TT or 2677GG genotypes. LR model showed an independent association of ABCB1 2677 G>T/A with post transplant diabetes (OR: 4.83, 95% CI: 1.22–19.03). Multifactor dimensionality reduction analysis (MDR) revealed that synergistic interactions between CYP3A5*3 and ABCB1 2677 G>T/A as the determinants of risk for post-transplant diabetes. To conclude, the ANN and MDR models explore both individual and synergistic effects of variables in modulating the bioavailability of tacrolimus and risk for post-transplant diabetes. PMID:29621269

Bioavailability of heavy metals in soils: definitions and practical implementation--a critical review.

PubMed

Kim, Rog-Young; Yoon, Jeong-Ki; Kim, Tae-Seung; Yang, Jae E; Owens, Gary; Kim, Kwon-Rae

2015-12-01

Worldwide regulatory frameworks for the assessment and remediation of contaminated soils have moved towards a risk-based approach, taking contaminant bioavailability into consideration. However, there is much debate on the precise definition of bioavailability and on the standardization of methods for the measurement of bioavailability so that it can be reliably applied as a tool for risk assessment. Therefore, in this paper, we reviewed the existing definitions of heavy metal bioavailability in relation to plant uptake (phytoavailability), in order to better understand both the conceptual and operational aspects of bioavailability. The related concepts of specific and non-specific adsorption, as well as complex formation and organic ligand affinity were also intensively discussed to explain the variations of heavy metal solubility and mobility in soils. Further, the most frequently used methods to measure bioavailable metal soil fractions based on both chemical extractions and mechanistic geochemical models were reviewed. For relatively highly mobile metals (Cd, Ni, and Zn), a neutral salt solution such as 0.01 M CaCl2 or 1 M NH4NO3 was recommended, whereas a strong acid or chelating solution such as 0.43 M HNO3 or 0.05 M DTPA was recommended for strongly soil-adsorbed and less mobile metals (Cu, Cr, and Pb). While methods which assessed the free metal ion activity in the pore water such as DGT and DMT or WHAM/Model VI, NICA-Donnan model, and TBLM are advantageous for providing a more direct measure of bioavailability, few of these models have to date been properly validated.

21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

Code of Federal Regulations, 2010 CFR

2010-04-01

... pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of in vivo bioavailability data with an acute pharmacological effect or clinical evidence of safety and...

DISTRIBUTION OF PARAMETERS DETERMINING BIOAVAILABILITY OF METALS IN EUROPEAN SOILS

EPA Science Inventory

As part of a program to develop a predictive model of bioavailability and toxicity of copper in soils to terrestrial organisms, 19 soils from 9 countries of the EU were collected and analyzed for use in bioavailability tests. However, it is desired that the model be of use on a ...

In Vitro And In Vivo Approaches For The Measurement Of Oral Bioavailability Of Lead (Pb) In Contaminated Soils: A Review

EPA Science Inventory

We reviewed the published evidence of lead (Pb) contamination of urban soils, soil Pb risk to children through hand-to-mouth activity, reduction of soil Pb bioavailability due to soil amendments, and methods to assess bioaccessibility which correlate with bioavailability of soil ...

FY06 ORD PILOT STUDY: DETERMINE BIOAVAILABILITY AND BIOACCESSIBILITY OF ARSENIC IN SOIL AND DEVELOP ARSENIC SPECIATION METHODS

EPA Science Inventory

The product is a presentation requested by the organizers of the 2005 US EPA Bioavailability Technical Review Workgroup. It presents an overview, approaches (in-vivo & in-vitro), and logistics of the ORD pilot study on bioavailability of arsenic in soil. The overall project was ...

Utilizing Polymer-Coated Vials to Illustrate the Fugacity and Bioavailability of Chlorinated Pesticide Residues in Contaminated Soils

ERIC Educational Resources Information Center

Andrade, Natasha A.; McConnell, Laura L.; Torrents, Alba; Hapeman, Cathleen J.

2013-01-01

Fugacity and bioavailability can be used to facilitate students' understanding of potential environmental risks associated with toxic chemicals and, therefore, should be incorporated in environmental chemistry and science laboratories. Although the concept of concentration is easy to grasp, fugacity and bioavailability can be challenging…

21 CFR 320.25 - Guidelines for the conduct of an in vivo bioavailability study.

Code of Federal Regulations, 2010 CFR

2010-04-01

... conduct of an in vivo bioavailability study. (a) Guiding principles. (1) The basic principle in an in vivo... not been approved for marketing can be used to measure the following pharmacokinetic data: (i) The bioavailability of the formulation proposed for marketing; and (ii) The essential pharmacokinetic characteristics...

Relative bioavailability of iron in Bangledeshi traditional meals prepared with iron-fortified lentil dal

USDA-ARS?s Scientific Manuscript database

Due to low Fe bioavailability and low consumption per meal, lentil must be fortified to contribute significant bioavailable Fe in the Bangladeshi diet. Moreover, since red lentil is dehulled prior to consumption, opportunity exists at this point to fortify lentil with Fe. Thus, in the present study...

Assessment of bioavailability of heavy metal pollutants using soil isolates of Chlorella sp.

PubMed

Krishnamurti, Gummuluru S R; Subashchandrabose, Suresh R; Megharaj, Mallavarapu; Naidu, Ravi

2015-06-01

Biotests conducted with plants are presently used to estimate metal bioavailability in contaminated soils. But when plants are grown in soils, especially the plants with fine roots, root collection is easily biased and tedious. Indeed, at harvest, small amounts of soil can adhere to roots, resulting in overestimation of root metal content, and the finest roots are often discarded from the analysis because of their difficult and almost impossible recovery. This report presents a novel method for assessing the bioavailability of heavy metals in soils using microalgae. Two species of green unicellular microalgae were isolated from two highly contaminated soils and identified by phylogenetic and molecular evolutionary analyses as Chlorella sp. RBM and Chlorella sp. RHM. These two cultures were used to determine the metal uptake from metal-contaminated soils of South Australia as a novel, cost-effective, simple and rapid method for assessing the bioavailability of heavy metals in soils. The suggested method is an attempt to achieve a realistic estimate of bioavailability which overcomes the inherent drawback of root metal contamination in the bioavailability indices so far reported.

Effect of ferrous sulfate fortification in germinated brown rice on seed iron concentration and bioavailability.

PubMed

Wei, Yanyan; Shohag, M J I; Ying, Feng; Yang, Xiaoe; Wu, Chunyong; Wang, Yuyan

2013-06-01

The present study evaluated the effectiveness of germination and iron fortification on iron concentration and bioavailability of brown rice. Iron fortification during germination process with 0.05-2 g/L ferrous sulfate increased the iron concentration in germinated brown rice from 1.1 to 15.6 times than those in raw brown rice. Based on the recommended dietary allowance of iron, maximum germination rate and γ-aminobutyric acid, we recommend the brown rice fortified with 0.25 g/L FeSO(4) as a suitable fortification level to use in germination process. Iron fortification during the germination process has a positive effect on iron concentration and bioavailability. A significant difference was observed among the cultivars in respect to the capacity for iron accumulation and bioavailability. Germination alone could improve in vitro iron solubility, but had no effect on iron bioavailability in Caco-2 cell, the additional fortification process should be combined to get high amount of bioavailable iron from the brown rice. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lipopolysaccharide based oral nanocarriers for the improvement of bioavailability and anticancer efficacy of curcumin.

PubMed

Chaurasia, Sundeep; Patel, Ravi R; Chaubey, Pramila; Kumar, Nagendra; Khan, Gayasuddin; Mishra, Brahmeshwar

2015-10-05

Soluthin MD(®), a unique phosphatidylcholine-maltodextrin based hydrophilic lipopolysaccharide, which exhibits superior biocompatibility and bioavailability enhancer properties for poorly water soluble drug(s). Curcumin (CUR) is a potential natural anticancer drug with low bioavailability due to poor aqueous solubility. The study aims at formulation and optimization of CUR loaded lipopolysaccharide nanocarriers (C-LPNCs) to enhance oral bioavailability and anticancer efficacy in colon-26 tumor-bearing mice in vitro and in vivo. The Optimized C-LPNCs demonstrated favorable mean particle size (108 ± 3.4 nm) and percent entrapment efficiency (65.29 ± 1.0%). Pharmacokinetic parameters revealed ∼130-fold increase in oral bioavailability and cytotoxicity studies demonstrated ∼23-fold reduction in 50% cell growth inhibition when treated with optimized C-LPNCs as compared to pure CUR. In vivo anticancer study performed with optimized C-LPNCs showed significant increase in efficacy compared with pure CUR. Thus, lipopolysaccharide nanocarriers show potential delivery strategy to improve oral bioavailability and anticancer efficacy of CUR in the treatment of colorectal cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Emerging role of nanocarriers to increase the solubility and bioavailability of curcumin.

PubMed

Mohanty, Chandana; Das, Manasi; Sahoo, Sanjeeb K

2012-11-01

Curcumin is a safe, affordable and natural bioactive molecule of turmeric (Curcuma longa). It has gained considerable attention in recent years for its multiple pharmacological activities. However, its optimum pharmaceutical potential has been limited by its lack of aqueous solubility and poor bioavailability. To mitigate the above limitations, recently various nanostructured water-soluble delivery systems were developed to increase the solubility and bioavailability of curcumin. Major reasons contributing to the low bioavailability of curcumin appear to be owing to its poor solubility, low absorption, rapid metabolism and rapid systemic elimination. The present review summarizes the strategies using curcumin in various nanocarrier delivery systems to overcome poor solubility and inconsistent bioavailability of curcumin and describes the current status and challenges for the future. The development of various drug delivery systems to deliver curcumin will certainly provide a step up towards augmenting the therapeutic activity of curcumin thereby increasing the solubility and bioavailability of curcumin. However, the future of such delivery technology will be highly dependent on the development of safe, non-toxic and non-immunogenic nanocarriers.

Bioavailability of Fe and Zn in selected legumes, cereals, meat and milk products consumed in Fiji.

PubMed

Singh, Poonam; Prasad, Surendra; Aalbersberg, William

2016-09-15

The present study reports contents and the bioavailability of Fe and Zn from 25 selected raw and cooked food samples. The results showed highest variation of Fe content in raw food samples ranging from 2.19 ± 0.04 to 0.93 ± 0.03 mg/100g in legumes. The raw black eye bean, cheese and fish showed high Zn content up to 8.85 ± 0.01, 12.93 ± 0.26 and 172.03 ± 5.09 mg/100g, respectively. Pulses and cereals showed high level of ionizable Fe. Zn bioavailability was quite low in cereals as compared to pulses; 4.02% in yellow split to 17.40% in Bengal gram. Zn bioavailability of 17.40% is in cheese. Fe bioavailability is high in cooked rice 160.60%, white bread 428.30% and milk powder 241.67% showing that Fe bioavailability increased after cooking whereas the lowest in fish 0.84%. The multivariate and cluster analysis categorized studied foods into two main groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of compost addition on lead and arsenic bioavailability in reclaimed orchard soil assessed using Porcellio scaber bioaccumulation test

PubMed Central

Udovic, M.; McBride, M.B.

2015-01-01

A long history of lead arsenate application in orchards has led to significant accumulation of Pb and As in the topsoil. Besides the threat that such soils represent for the environment, reclamation of old orchards for agricultural purposes implies the exposure of humans to Pb and As. In this study we assessed the influence of vegetable compost addition (as a sustainable agricultural practice) to contaminated acidic orchard soil on Pb and As bioavailability, assessed with two selective non-exhaustive chemical extractions and with an in vivo bioaccumulation test with an isopod (P. scaber). The treatment with compost caused a significant increase in soil pH and total carbon content, resulting in a consistent decrease of Pb bioavailability. In contrast, the bioavailability of As increased, indicating that a complementary treatment should be used for reducing the bioavailability of As in old orchard soils. This is the first report on the use of As accumulation in P. scaber as a tool for the assessment of As bioavailability in contaminated orchard soil. PMID:22240057

Integrating bioavailability approaches into waste rock evaluations

USGS Publications Warehouse

Ranville, James F.; Blumenstein, E. P.; Adams, Michael J.; Choate, LaDonna M.; Smith, Kathleen S.; Wildeman, Thomas R.

2006-01-01

The presence of toxic metals in soils affected by mining, industry, agriculture and urbanization, presents problems to human health, the establishment and maintenance of plant and animal habitats, and the rehabilitation of affected areas. A key to managing these problems is predicting the fraction of metal in a given soil that will be biologically labile, and potentially harmful ('bioavailable'). The molecular form of metals and metalloids, particularly the uncomplexed (free) form, controls their bioavailability and toxicity in solution. One computational approach for determining bioavailability, the biotic ligand model (BLM), takes into account not only metal complexation by ligands in solution, but also competitive binding of hardness cations (Ca 2+,Mg 2+,) and metal ions to biological receptor sites. The more direct approach to assess bioavailability is to explicitly measure the response of an organism to a contaminant. A number of microbial enzyme tests have been developed to assess the impact of pollution in a rapid and procedurally simple way. These different approaches in making bioavailability predictions may have value in setting landuse priorities, remediation goals, and habitat reclamation strategies.

Preparation, Characterization and Evaluation of Quetiapine Fumarate Solid Lipid Nanoparticles to Improve the Oral Bioavailability

PubMed Central

Narala, Arjun; Veerabrahma, Kishan

2013-01-01

Quetiapine fumarate is an antipsychotic drug with poor oral bioavailability (9%) due to first-pass metabolism. Present work is an attempt to improve oral bioavailability of quetiapine fumarate by incorporating in solid lipid nanoparticles (SLN). Six quetiapine fumarate SLN formulations were developed using three different lipids by hot homogenisation followed by ultrasonication. The drug excipient compatibility was studied by differential scanning calorimetry (DSC). Stable quetiapine fumarate SLNs having a mean particle size of 200–250 nm with entrapment efficiency varying in between 80% and 92% were developed. The physical stability of optimized formulation F3 was checked at room temperature for 2 months. Comparative bioavailability studies were conducted in male Wistar rats after oral administration of quetiapine fumarate suspension and SLN formulation. The relative bioavailability of quetiapine fumarate from optimized SLN preparation was increased by 3.71 times when compared with the reference quetiapine fumarate suspension. The obtained results are indicative of SLNs as potential lipid carriers for improving the bioavailability of quetiapine fumarate by minimizing first-pass metabolism. PMID:26555970

Flavonoid Bioavailability and Attempts for Bioavailability Enhancement

PubMed Central

Thilakarathna, Surangi H.; Rupasinghe, H. P. Vasantha

2013-01-01

Flavonoids are a group of phytochemicals that have shown numerous health effects and have therefore been studied extensively. Of the six common food flavonoid classes, flavonols are distributed ubiquitously among different plant foods whereas appreciable amounts of isoflavones are found in leguminous plant-based foods. Flavonoids have shown promising health promoting effects in human cell culture, experimental animal and human clinical studies. They have shown antioxidant, hypocholesterolemic, anti-inflammatory effects as well as ability to modulate cell signaling and gene expression related disease development. Low bioavailability of flavonoids has been a concern as it can limit or even hinder their health effects. Therefore, attempts to improve their bioavailability in order to improve the efficacy of flavonoids are being studied. Further investigations on bioavailability are warranted as it is a determining factor for flavonoid biological activity. PMID:23989753

Amine functionalized cubic mesoporous silica nanoparticles as an oral delivery system for curcumin bioavailability enhancement

NASA Astrophysics Data System (ADS)

Budi Hartono, Sandy; Hadisoewignyo, Lannie; Yang, Yanan; Meka, Anand Kumar; Antaresti; Yu, Chengzhong

2016-12-01

In the present work, a simple method was used to develop composite curcumin-amine functionalized mesoporous silica nanoparticles (MSN). The nanoparticles were used to improve the bioavailability of curcumin in mice through oral administration. We investigated the effect of particle size on the release profile, solubility and oral bioavailability of curcumin in mice, including amine functionalized mesoporous silica micron-sized-particles (MSM) and MSN (100-200 nm). Curcumin loaded within amine functionalized MSN (MSN-A-Cur) had a better release profile and a higher solubility compared to amine MSM (MSM-A-Cur). The bioavailability of MSN-A-Cur and MSM-A-Cur was considerably higher than that of ‘free curcumin’. These results indicate promising features of amine functionalized MSN as a carrier to deliver low solubility drugs with improved bioavailability via the oral route.

Effects of polymer molecular weight on relative oral bioavailability of curcumin.

PubMed

Tsai, Yin-Meng; Chang-Liao, Wan-Ling; Chien, Chao-Feng; Lin, Lie-Chwen; Tsai, Tung-Hu

2012-01-01

Polylactic-co-glycolic acid (PLGA) nanoparticles have been used to increase the relative oral bioavailability of hydrophobic compounds and polyphenols in recent years, but the effects of the molecular weight of PLGA on bioavailability are still unknown. This study investigated the influence of polymer molecular weight on the relative oral bioavailability of curcumin, and explored the possible mechanism accounting for the outcome. Curcumin encapsulated in low (5000-15,000) and high (40,000-75,000) molecular weight PLGA (LMw-NPC and HMw-NPC, respectively) were prepared using an emulsification-solvent evaporation method. Curcumin alone and in the nanoformulations was administered orally to freely mobile rats, and blood samples were collected to evaluate the bioavailability of curcumin, LMw-NPC, and HMw-NPC. An ex vivo experimental gut absorption model was used to investigate the effects of different molecular weights of PLGA formulation on absorption of curcumin. High-performance liquid chromatography with diode array detection was used for quantification of curcumin in biosamples. There were no significant differences in particle properties between LMw-NPC and HMw-NPC, but the relative bioavailability of HMw-NPC was 1.67-fold and 40-fold higher than that of LMw-NPC and conventional curcumin, respectively. In addition, the mean peak concentration (C(max)) of conventional curcumin, LMw-NPC, and HMw-NPC was 0.028, 0.042, and 0.057 μg/mL, respectively. The gut absorption study further revealed that the HMw-PLGA formulation markedly increased the absorption rate of curcumin in the duodenum and resulted in excellent bioavailability compared with conventional curcumin and LMw-NPC. Our findings demonstrate that different molecular weights of PLGA have varying bioavailability, contributing to changes in the absorption rate at the duodenum. The results of this study provide the rationale for design of a nanomedicine delivery system to enhance the bioavailability of water-insoluble pharmaceutical compounds and functional foods.

Effects of polymer molecular weight on relative oral bioavailability of curcumin

PubMed Central

Tsai, Yin-Meng; Chang-Liao, Wan-Ling; Chien, Chao-Feng; Lin, Lie-Chwen; Tsai, Tung-Hu

2012-01-01

Background Polylactic-co-glycolic acid (PLGA) nanoparticles have been used to increase the relative oral bioavailability of hydrophobic compounds and polyphenols in recent years, but the effects of the molecular weight of PLGA on bioavailability are still unknown. This study investigated the influence of polymer molecular weight on the relative oral bioavailability of curcumin, and explored the possible mechanism accounting for the outcome. Methods Curcumin encapsulated in low (5000–15,000) and high (40,000–75,000) molecular weight PLGA (LMw-NPC and HMw-NPC, respectively) were prepared using an emulsification-solvent evaporation method. Curcumin alone and in the nanoformulations was administered orally to freely mobile rats, and blood samples were collected to evaluate the bioavailability of curcumin, LMw-NPC, and HMw-NPC. An ex vivo experimental gut absorption model was used to investigate the effects of different molecular weights of PLGA formulation on absorption of curcumin. High-performance liquid chromatography with diode array detection was used for quantification of curcumin in biosamples. Results There were no significant differences in particle properties between LMw-NPC and HMw-NPC, but the relative bioavailability of HMw-NPC was 1.67-fold and 40-fold higher than that of LMw-NPC and conventional curcumin, respectively. In addition, the mean peak concentration (Cmax) of conventional curcumin, LMw-NPC, and HMw-NPC was 0.028, 0.042, and 0.057 μg/mL, respectively. The gut absorption study further revealed that the HMw-PLGA formulation markedly increased the absorption rate of curcumin in the duodenum and resulted in excellent bioavailability compared with conventional curcumin and LMw-NPC. Conclusion Our findings demonstrate that different molecular weights of PLGA have varying bioavailability, contributing to changes in the absorption rate at the duodenum. The results of this study provide the rationale for design of a nanomedicine delivery system to enhance the bioavailability of water-insoluble pharmaceutical compounds and functional foods. PMID:22745556

Causal inference between bioavailability of heavy metals and environmental factors in a large-scale region.

PubMed

Liu, Yuqiong; Du, Qingyun; Wang, Qi; Yu, Huanyun; Liu, Jianfeng; Tian, Yu; Chang, Chunying; Lei, Jing

2017-07-01

The causation between bioavailability of heavy metals and environmental factors are generally obtained from field experiments at local scales at present, and lack sufficient evidence from large scales. However, inferring causation between bioavailability of heavy metals and environmental factors across large-scale regions is challenging. Because the conventional correlation-based approaches used for causation assessments across large-scale regions, at the expense of actual causation, can result in spurious insights. In this study, a general approach framework, Intervention calculus when the directed acyclic graph (DAG) is absent (IDA) combined with the backdoor criterion (BC), was introduced to identify causation between the bioavailability of heavy metals and the potential environmental factors across large-scale regions. We take the Pearl River Delta (PRD) in China as a case study. The causal structures and effects were identified based on the concentrations of heavy metals (Zn, As, Cu, Hg, Pb, Cr, Ni and Cd) in soil (0-20 cm depth) and vegetable (lettuce) and 40 environmental factors (soil properties, extractable heavy metals and weathering indices) in 94 samples across the PRD. Results show that the bioavailability of heavy metals (Cd, Zn, Cr, Ni and As) was causally influenced by soil properties and soil weathering factors, whereas no causal factor impacted the bioavailability of Cu, Hg and Pb. No latent factor was found between the bioavailability of heavy metals and environmental factors. The causation between the bioavailability of heavy metals and environmental factors at field experiments is consistent with that on a large scale. The IDA combined with the BC provides a powerful tool to identify causation between the bioavailability of heavy metals and environmental factors across large-scale regions. Causal inference in a large system with the dynamic changes has great implications for system-based risk management. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bioavailability of syrup and tablet formulations of cefetamet pivoxil.

PubMed

Ducharme, M P; Edwards, D J; McNamara, P J; Stoeckel, K

1993-12-01

Two studies examining the bioavailability of cefetamet pivoxil in healthy male subjects were conducted. In the first, the bioavailabilities of the 250-mg (M250) and M500 tablet formulations of cefetamet pivoxil to be marketed were compared with that of a tablet used in clinical trials. All products were given with food at a dose of 500 mg. In the second study, the bioavailability of the syrup formulation was evaluated under both fasting and nonfasting conditions and compared with that of the M500 tablet formulation given with food. The absolute bioavailabilities of the M500 and M250 tablets (55.0% +/- 8.0% and 55.7% +/- 7.0%, respectively) were not significantly different from that of the clinical-trial formulation (49.8% +/- 8.5%). The newer tablet formulations exhibited faster absorption as evidenced by higher peak concentrations (3.8 [M500] and 3.9 [M250] mg/liter compared with 3.2 mg/liter for the clinical-trial formulation), a shorter time to peak concentration, and a shorter mean absorption time. The syrup formulation was found to have significantly lower absolute bioavailability (37.9% +/- 6.0%) compared with that of the M500 tablet (58.4% +/- 9.0%) when both were given with food. Food had no significant effect on the bioavailability of the syrup, which averaged 34.0% +/- 8.6% under fasting conditions, although absorption was delayed by food (mean absorption time increased from 2.2 to 3.9 h). This contrasts with the results of previous studies documenting significant increases in tablet bioavailability with food. Despite the lower bioavailability of the syrup, unbound-cefetamet concentrations are expected to remain above the MICs for 90% of the strains tested for susceptible organisms for approximately 10 h of the usual 12-h dosing interval with both syrup and tablet formulations of cefetamet pivoxil given with food.

Bioavailability of syrup and tablet formulations of cefetamet pivoxil.

PubMed Central

Ducharme, M P; Edwards, D J; McNamara, P J; Stoeckel, K

1993-01-01

Two studies examining the bioavailability of cefetamet pivoxil in healthy male subjects were conducted. In the first, the bioavailabilities of the 250-mg (M250) and M500 tablet formulations of cefetamet pivoxil to be marketed were compared with that of a tablet used in clinical trials. All products were given with food at a dose of 500 mg. In the second study, the bioavailability of the syrup formulation was evaluated under both fasting and nonfasting conditions and compared with that of the M500 tablet formulation given with food. The absolute bioavailabilities of the M500 and M250 tablets (55.0% +/- 8.0% and 55.7% +/- 7.0%, respectively) were not significantly different from that of the clinical-trial formulation (49.8% +/- 8.5%). The newer tablet formulations exhibited faster absorption as evidenced by higher peak concentrations (3.8 [M500] and 3.9 [M250] mg/liter compared with 3.2 mg/liter for the clinical-trial formulation), a shorter time to peak concentration, and a shorter mean absorption time. The syrup formulation was found to have significantly lower absolute bioavailability (37.9% +/- 6.0%) compared with that of the M500 tablet (58.4% +/- 9.0%) when both were given with food. Food had no significant effect on the bioavailability of the syrup, which averaged 34.0% +/- 8.6% under fasting conditions, although absorption was delayed by food (mean absorption time increased from 2.2 to 3.9 h). This contrasts with the results of previous studies documenting significant increases in tablet bioavailability with food. Despite the lower bioavailability of the syrup, unbound-cefetamet concentrations are expected to remain above the MICs for 90% of the strains tested for susceptible organisms for approximately 10 h of the usual 12-h dosing interval with both syrup and tablet formulations of cefetamet pivoxil given with food. PMID:8109939

Bioavailability and soil-to-crop transfer of heavy metals in farmland soils: A case study in the Pearl River Delta, South China.

PubMed

Zhang, Jingru; Li, Huizhen; Zhou, Yongzhang; Dou, Lei; Cai, Limei; Mo, Liping; You, Jing

2018-04-01

Soil-bound heavy metals are of great concern for human health due to the potential exposure via food chain transfer. In the present study, the occurrence, the bioavailability and the soil-to-crop transfer of heavy metals in farmland soils were investigated based on data from two agricultural areas, i.e. Sihui and Shunde in South China. Six heavy metals (As, Cu, Hg, Mn, Ni and Pb) were quantified in the farmland soils. The mean single pollution level indices (PI) were all lower than 1 except for Hg in soils from Shunde (PI = 1.51 ± 0.46), suggesting the farmland soils were within clean and slightly polluted by heavy metals. As, Cu, Ni and Pb were found to be mostly present in the non-bioavailable form. The majority of Hg was considered potentially bioavailable, and Mn was found to be largely bioavailable. Soil pH was an important factor influencing bioavailability of soil-bound heavy metals. The concentrations of heavy metals in vegetables from Sihui and Shunde were within the food hygiene standards, while the rice grain from Sihui was polluted by Pb (PI = 10.3 ± 23.4). Total soil concentrations of heavy metals were not correlated to their corresponding crop concentrations, instead, significant correlations were observed for bioavailable concentrations in soil. The results supported the notion that the bioavailability of the investigated heavy metals in the soil was largely responsible for their crop uptake. The soil-to-crop transfer factors based on bioavailable concentrations suggested that Cu, As and Hg in soils of the study area had greater tendency to be accumulated in the vegetables than other heavy metals, calling for further human health assessment by consuming the contaminated crops. Copyright © 2017 Elsevier Ltd. All rights reserved.

STS106-s-015

NASA Image and Video Library

2000-09-08

STS106-S-015 (8 September 2000) --- The Space Shuttle Atlantis streaks into the sky on mission STS-106 after a perfect on-time launch at 8:45:47 a.m. (EDT), September 8, 2000. Blue mach diamonds are barely visible beneath the main engine nozzles. On the 11-day mission to the International Space Station, the seven-member crew will perform support tasks on orbit; transfer supplies and prepare the living quarters in the newly arrived Zvezda Service Module. The first long-duration crew is due to arrive at the Station in late fall. Onboard the spacecraft were astronauts Terrance W. Wilcutt, Scott D. Altman, Edward T. Lu, Richard A. Mastracchio and Daniel C. Burbank, along with cosmonauts Yuri I. Malenchenko and Boris Morukov, both of whom represent Rosaviakosmos.

Observations of Orionids and eta-Aquariids in 2006 from Bulgaria

NASA Astrophysics Data System (ADS)

Bozhurova, Eva; Zhivkova, Desislava

2010-12-01

We present observations of the eta-Aquariid and Orionid meteor showers collected during observing expeditions. The 2006 May 4-6 expedition with two observers yielded 63 meteors in 4.14 h of total effective observing time. A radiant was derived from 34 eta-Aquariids. The October campaign surprised all observers with the unusually high Orionid activity about twice as high as the average. In our analysis we include observing data of Boris Stoilov (STOBO), Natasha Ivanova (IVANA) and Ivan Gradinarov (GRAIV). Based on 107 recorded meteors from which 47 were Orionids seen in 9.8 total effective time for the night of 21/22 October, we obtained a mean ZHR equal to 41.5 assuming a population index r = 2.0.

Assessment of heavy metals bioavailability and toxicity toward Vibrio fischeri in sediment of the Huelva estuary.

PubMed

Rosado, Daniel; Usero, José; Morillo, José

2016-06-01

Relationship between toxicity and bioavailable metals in sediments from the Huelva estuary and its littoral of influence was analyzed. Toxicity was assessed with Microtox® bioassay using a marine luminescent bacterium: Vibrio fischeri. Bioavailable metals were considered as both, acid extractable fraction of BCR procedure and the sum of exchangeable and bound to carbonates fractions of Tessier sequential extraction. A bioavailable metals index was calculated to integrate results in a single figure. Toxicity and bioavailable metals showed a similar pattern. Higher levels were found in the estuary than in the littoral (140 TU/g). In Huelva estuary, highest levels were found in the Tinto estuary (5725 TU/g), followed by the Odiel estuary (5100 TU/g) and the Padre Santo Canal (2500 TU/g). Results in this area were well over than those in nearby estuaries. Furthermore, they are similar to or even higher than those in other polluted sediments around the world. Bioavailable metal index showed a stronger correlation with acid extractable fraction of BCR (R(2) = 0.704) than that for the sum of exchangeable and bound to carbonates fractions of Tessier (R(2) = 0.661). These results suggest that bioavailable metals are an important source of sediment toxicity in the Huelva estuary and its littoral of influence, an area with one of the highest mortality risks of Spain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preclinical pilot study monitoring topical drug penetration and dermal bioavailability of a peptidase inhibitor from different galenic formulations into pig dermis, using cutaneous microdialysis.

PubMed

Quist, S R; Heimburg, A; Bank, U; Mahnkopf, D; Koch, G; Gollnick, H; Täger, M; Ansorge, S

2017-08-01

Cutaneous microdialysis (CM) is an ex vivo technique that allows study of tissue chemistry, including bioavailability of actual tissue concentration of unbound drug in the interstitial fluid of the body. To test the penetration and dermal bioavailability of galenic formulations of the small-molecule IP10.C8, a dual-protease inhibitor of the dipeptidyl peptidase and aminopeptidase families. Using CM, we tested the penetration and dermal bioavailability of IP10.C8 into the dermis and subcutis of pigs, and determined the tissue concentration of IP10.C8 enzymatically, using an enzyme activity assay (substrate Gly-Pro-pNA) and high performance liquid chromatography. Dermal bioavailability was enhanced by using microemulsion or the addition of the penetration enhancer oleic acid to a hydroxyethylcellulose (HEC) gel formulation. Dermal bioavailability was also enhanced when galenic formulations were prepared with higher pH (7.5 vs. 6.5) or higher drug concentration (5% vs. 1%) in HEC gel. It seems possible, using CM for topical skin penetration testing in anaesthetized domestic pigs, to test the bioavailability of newly designed drugs. However, the experimental time is limited due to the anaesthesia, and is dependent on drug recovery. Validation of this technique for routine use is challenging, and more experiments are needed to validate this preclinical set-up. © 2017 British Association of Dermatologists.

Enhanced ferrihydrite dissolution by a unicellular, planktonic cyanobacterium: a biological contribution to particulate iron bioavailability.

PubMed

Kranzler, Chana; Kessler, Nivi; Keren, Nir; Shaked, Yeala

2016-12-01

Iron (Fe) bioavailability, as determined by its sources, sinks, solubility and speciation, places severe environmental constraints on microorganisms in aquatic environments. Cyanobacteria are a widespread group of aquatic, photosynthetic microorganisms with especially high iron requirements. While iron exists predominantly in particulate form, little is known about its bioavailability to cyanobacteria. Some cyanobacteria secrete iron solubilizing ligands called siderophores, yet many environmentally relevant strains do not have this ability. This work explores the bioavailability of amorphous synthetic Fe-oxides (ferrihydrite) to the non-siderophore producing, unicellular cyanobacterium, Synechocystis sp PCC 6803. Iron uptake assays with 55 ferrihydrite established dissolution as a critical prerequisite for iron transport. Dissolution assays with the iron binding ligand, desferrioxamine B, demonstrated that Synechocystis 6803 enhances ferrihydrite dissolution, exerting siderophore-independent biological influence on ferrihydrite bioavailability. Dissolution mechanisms were studied using a range of experimental conditions; both cell-particle physical proximity and cellular electron flow were shown to be important determinants of bio-dissolution by Synechocystis 6803. Finally, the effects of ferrihydrite stability on bio-dissolution rates and cell physiology were measured, integrating biological and chemical aspects of ferrihydrite bioavailability. Collectively, these findings demonstrate that Synechocystis 6803 actively dissolves ferrihydrite, highlighting a significant biological component to mineral phase iron bioavailability in aquatic environments. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Lipid-based formulations for danazol containing a digestible surfactant, Labrafil M2125CS: in vivo bioavailability and dynamic in vitro lipolysis.

PubMed

Larsen, Anne; Holm, René; Pedersen, Mette Lund; Müllertz, Anette

2008-12-01

To evaluate the use of Labrafil M2125CS as a lipid vehicle for danazol. Further, the possibility of predicting the in vivo behavior with a dynamic in vitro lipolysis model was evaluated. Danazol (28 mg/kg) was administered orally to rats in four formulations: an aqueous suspension, two suspensions in Labrafil M2125CS (1 and 2 ml/kg) and a solution in Labrafil M2125CS (4 ml/kg). The obtained absolute bioavailabilities of danazol were 1.5 +/- 0.8%; 7.1 +/- 0.6%; 13.6 +/- 1.4% and 13.3 +/- 3.4% for the aqueous suspension, 1, 2 and 4 ml Labrafil M2125CS per kg respectively. Thus administration of danazol with Labrafil M2125CS resulted in up to a ninefold increase in the bioavailability, and the bioavailability was dependent on the Labrafil M2125CS dose. In vitro lipolysis of the formulations was able to predict the rank order of the bioavailability from the formulations, but not the absorption profile of the in vivo study. The bioavailability of danazol increased when Labrafil M2125CS was used as a vehicle, both when danazol was suspended and solubilized in the vehicle. The dynamic in vitro lipolysis model could be used to rank the bioavailabilities of the in vivo data.

Accounting for metal bioavailability in assessing water quality: A step change?

PubMed

Merrington, Graham; Peters, Adam; Schlekat, Christian E

2016-02-01

Bioavailability of metals to aquatic organisms can be considered to be a combination of the physicochemical factors governing metal behavior and the specific pathophysiological characteristics of the organism's biological receptor. Effectively this means that a measure of bioavailability will reflect the exposures that organisms in the water column actually "experience". This is important because it has long been established that measures of total metal in waters have limited relevance to potential environmental risk. The concept of accounting for bioavailability in regard to deriving and implementing environmental water quality standards is not new, but the regulatory reality has lagged behind the development of scientific evidence supporting the concept. Practical and technical reasons help to explain this situation. For example, concerns remain from regulators and the regulated that the efforts required to change existing systems of metal environmental protection that have been in place for over 35 yr are so great as not to be commensurate with likely benefits. However, more regulatory jurisdictions are now considering accounting for metal bioavailability in assessments of water quality as a means to support evidence-based decision-making. In the past decade, both the US Environmental Protection Agency and the European Commission have established bioavailability-based standards for metals, including Cu and Ni. These actions have shifted the debate toward identifying harmonized approaches for determining when knowledge is adequate to establish bioavailability-based approaches and how to implement them. © 2016 SETAC.

BIOACCESSIBILITY TESTS ACCURATELY ESTIMATE ...

EPA Pesticide Factsheets

Hazards of soil-borne Pb to wild birds may be more accurately quantified if the bioavailability of that Pb is known. To better understand the bioavailability of Pb to birds, we measured blood Pb concentrations in Japanese quail (Coturnix japonica) fed diets containing Pb-contaminated soils. Relative bioavailabilities were expressed by comparison with blood Pb concentrations in quail fed a Pb acetate reference diet. Diets containing soil from five Pb-contaminated Superfund sites had relative bioavailabilities from 33%-63%, with a mean of about 50%. Treatment of two of the soils with P significantly reduced the bioavailability of Pb. The bioaccessibility of the Pb in the test soils was then measured in six in vitro tests and regressed on bioavailability. They were: the “Relative Bioavailability Leaching Procedure” (RBALP) at pH 1.5, the same test conducted at pH 2.5, the “Ohio State University In vitro Gastrointestinal” method (OSU IVG), the “Urban Soil Bioaccessible Lead Test”, the modified “Physiologically Based Extraction Test” and the “Waterfowl Physiologically Based Extraction Test.” All regressions had positive slopes. Based on criteria of slope and coefficient of determination, the RBALP pH 2.5 and OSU IVG tests performed very well. Speciation by X-ray absorption spectroscopy demonstrated that, on average, most of the Pb in the sampled soils was sorbed to minerals (30%), bound to organic matter 24%, or present as Pb sulfate 18%. Ad

21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Correlation of bioavailability with an acute pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of in...

ß-Carotene from Red Carrot Maintains Vitamin A Status, but Lycopene Bioavailability Is Lower Relative to Tomato Paste in Mongolian Gerbils

USDA-ARS?s Scientific Manuscript database

Red carrots contain lycopene in addition to ß-Carotene. The utility of red carrot as a functional food depends in part on the bioavailability of its constituent carotenoids. Lycopene bioavailability was compared in Mongolian gerbils (Meriones unguiculatus) fed freeze-dried red carrot and tomato pa...

A chick bioassay approach for determining the bioavailable choline concentration in normal and overheated soybean meal, canola meal and peanut meal.

PubMed

Emmert, J L; Baker, D H

1997-05-01

Our objectives were to use a soy protein isolate (SPI) diet containing 2-amino-2-methyl-1-propanol, an inhibitor of choline biosynthesis, to determine the bioavailable choline content of normal and overheated soybean meal (SBM), canola meal (CM) and peanut meal (PM). In the first four experiments, it was determined that weight gain of chicks fed the basal diet would respond linearly (P < 0.05) to graded levels of crystalline choline and would not respond to betaine, and that when fortified with adequate choline, no weight gain or feed intake response would occur upon addition of 100 g/kg SBM, CM or PM to the basal diet. Furthermore, addition of crystalline amino acids simulating the amino acid composition of 100 g/kg SBM did not alter the utilization of crystalline choline. In Experiment 5, feeding graded doses of choline, SBM, CM or PM resulted in linear (P < 0.05) increases in weight gain. Multiple linear regression analysis indicated bioavailable choline concentrations of 1708, 1545 and 1203 mg/kg for SBM, CM and PM, respectively. In Experiment 6, no differences (P > 0.05) in bioavailable choline concentrations occurred between normal and overheated SBM, CM or PM, and the bioavailable choline concentration of normal SBM, CM and PM was 2002, 1464 and 1320 mg/kg, respectively. Average bioavailable choline levels were 83, 24 and 76% of analytically determined choline levels in SBM, CM and PM, respectively. Canola meal, although three times as rich in total choline as SBM, has less bioavailable choline than SBM. A substantial portion of choline in SBM, CM and PM is unavailable, and overheating does not appear to decrease the bioavailability of choline in these products.

Importance of suspended sediment (SPS) composition and grain size in the bioavailability of SPS-associated pyrene to Daphnia magna.

PubMed

Xia, Xinghui; Zhang, Xiaotian; Zhou, Dong; Bao, Yimeng; Li, Husheng; Zhai, Yawei

2016-07-01

Hydrophobic organic compounds (HOCs) tend to associate with suspended sediment (SPS) in aquatic environments; the composition and grain size of SPS will affect the bioavailability of SPS-associated HOCs. However, the bioavailability of HOCs sorbed on SPS with different compositions and grain sizes is not well understood. In this work, passive dosing devices were made to control the freely dissolved concentration of pyrene, a typical HOC, in the exposure systems. The effect of pyrene associated with amorphous organic carbon (AOC), black carbon (BC), and minerals of SPS with grain sizes of 0-50 μm and 50-100 μm on the immobilization and enzymatic activities of Daphnia magna was investigated to quantify the bioavailability of pyrene sorbed on SPS with different grain sizes and compositions. The results showed that the contribution of AOC-, BC-, and mineral-associated pyrene to the total bioavailability of SPS-associated pyrene was approximately 50%-60%, 10%-29%, and 20%-30%, respectively. The bioavailable fraction of pyrene sorbed on the three components of SPS was ordered as AOC (22.4%-67.3%) > minerals (20.1%-46.0%) > BC (9.11%-16.8%), and the bioavailable fraction sorbed on SPS of 50-100 μm grain size was higher than those of 0-50 μm grain size. This is because the SPS grain size will affect the ingestion of SPS and the SPS composition will affect the desorption of SPS-associated pyrene in Daphnia magna. According to the results obtained in this study, a model has been developed to calculate the bioavailability of HOCs to aquatic organisms in natural waters considering both SPS grain size and composition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessing nickel bioavailability in smelter-contaminated soils.

PubMed

Everhart, Jeffrey L; McNear, David; Peltier, Edward; van der Lelie, Daniel; Chaney, Rufus L; Sparks, Donald L

2006-08-31

Metal contaminants in soil environments derived from industrial pollution have clearly established the need for research on bioavailability and potential health risks. Much research has been conducted on metal sorption in soils. However, there is still a need to better understand the availability of metal contaminants to plants and microbes. Such information will enhance both human health and decisions about remediation efforts. In this study, Welland Loam (Typic epiaquoll) and Quarry Muck (Terric haplohemist) Ni contaminated soils from Port Colborne (Canada) which had been treated and untreated with limestone, were employed in greenhouse and bioavailability studies. These soils varied in pH from 5.1 to 7.5, in organic matter content from 6% to 72%, and in total Ni from 63 to 22,000 mg/kg. Oat (Avena sativa), a nonhyperaccumulator, and Alyssum murale, a hyperaccumulating plant species, were grown on these soils in greenhouse studies for 45 and 120 days, respectively, to estimate Ni accumulation. A Ni specific bacterial biosensor was also used to determine Ni bioavailability, and the results were compared to those from the greenhouse studies and more conventional, indirect chemical extraction techniques (employing MgCl2 and a Sr(NO3)2). Results from the greenhouse, chemical extraction, and biosensor studies suggested that as the pH of the soil was increased with liming, Ni bioavailability decreased. However, the phytoextraction capability of A. murale increased as soil pH increased, which was not the case for A. sativa. Furthermore, the Ni specific bacterial biosensor was successful in predicting Ni bioavailability in the soils and suggested that higher Ni bioavailabilities occur in the soils at pH values of 5.1 and 6. The combination of plant growth, chemical extraction, and bacterial biosensor approaches are recommended for assessing bioavailability of toxic metals.

The influence of bioavailable heavy metals and microbial parameters of soil on the metal accumulation in rice grain.

PubMed

Xiao, Ling; Guan, Dongsheng; Peart, M R; Chen, Yujuan; Li, Qiqi; Dai, Jun

2017-10-01

A field-based study was undertaken to analyze the effects of soil bioavailable heavy metals determined by a sequential extraction procedure, and soil microbial parameters on the heavy metal accumulation in rice grain. The results showed that Cd, Cr, Cu, Ni, Pb and Zn concentrations in rice grain decreases by 65.9%, 78.9%, 32.6%, 80.5%, 61.0% and 15.7%, respectively in the sites 3 (far-away), compared with those in sites 1 (close-to). Redundancy analysis (RDA) indicated that soil catalase activity, the MBC/MBN ratio, along with bioavailable Cd, Cr and Ni could explain 68.9% of the total eigenvalue, indicating that these parameters have a great impact on the heavy metal accumulation in rice grain. The soil bioavailable heavy metals have a dominant impact on their accumulation in rice grain, with a variance contribution of 60.1%, while the MBC/MBN has a regulatory effect, with a variance contribution of 4.1%. Stepwise regression analysis showed that the MBC/MBN, urease and catalase activities are the key microbial parameters that affect the heavy metal accumulation in rice by influencing the soil bioavailable heavy metals or the translocation of heavy metals in rice. RDA showed an interactive effect between Cu, Pb and Zn in rice grain and the soil bioavailable Cd, Cr and Ni. The heavy metals in rice grain, with the exception of Pb, could be predicted by their respective soil bioavailable heavy metals. The results suggested that Pb accumulation in rice grain was mainly influenced by the multi-metal interactive effects, and less affected by soil bioavailable Pb. Copyright © 2017 Elsevier Ltd. All rights reserved.

Total sulfane sulfur bioavailability reflects ethnic and gender disparities in cardiovascular disease.

PubMed

Rajpal, Saurabh; Katikaneni, Pavan; Deshotels, Matthew; Pardue, Sibile; Glawe, John; Shen, Xinggui; Akkus, Nuri; Modi, Kalgi; Bhandari, Ruchi; Dominic, Paari; Reddy, Pratap; Kolluru, Gopi K; Kevil, Christopher G

2018-05-01

Hydrogen sulfide (H 2 S) has emerged as an important physiological and pathophysiological signaling molecule in the cardiovascular system influencing vascular tone, cytoprotective responses, redox reactions, vascular adaptation, and mitochondrial respiration. However, bioavailable levels of H 2 S in its various biochemical metabolite forms during clinical cardiovascular disease remain poorly understood. We performed a case-controlled study to quantify and compare the bioavailability of various biochemical forms of H 2 S in patients with and without cardiovascular disease (CVD). In our study, we used the reverse-phase high performance liquid chromatography monobromobimane assay to analytically measure bioavailable pools of H 2 S. Single nucleotide polymorphisms (SNPs) were also identified using DNA Pyrosequencing. We found that plasma acid labile sulfide levels were significantly reduced in Caucasian females with CVD compared with those without the disease. Conversely, plasma bound sulfane sulfur levels were significantly reduced in Caucasian males with CVD compared with those without the disease. Surprisingly, gender differences of H 2 S bioavailability were not observed in African Americans, although H 2 S bioavailability was significantly lower overall in this ethnic group compared to Caucasians. We also performed SNP analysis of H 2 S synthesizing enzymes and found a significant increase in cystathionine gamma-lyase (CTH) 1364 G-T allele frequency in patients with CVD compared to controls. Lastly, plasma H 2 S bioavailability was found to be predictive for cardiovascular disease in Caucasian subjects as determined by receiver operator characteristic analysis. These findings reveal that plasma H 2 S bioavailability could be considered a biomarker for CVD in an ethnic and gender manner. Cystathionine gamma-lyase 1346 G-T SNP might also contribute to the risk of cardiovascular disease development. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Evaluation of different methods for assessing bioavailability of DDT residues during soil remediation.

PubMed

Wang, Jie; Taylor, Allison; Xu, Chenye; Schlenk, Daniel; Gan, Jay

2018-07-01

Compared to the total chemical concentration, bioavailability is a better measurement of risks of hydrophobic organic contaminants (HOCs) to biota in contaminated soil or sediment. Many different bioavailability estimation methods have been introduced to assess the effectiveness of remediation treatments. However, to date the different methods have rarely been evaluated against each other, leading to confusions in method selection. In this study, four different bioavailability estimation methods, including solid phase microextraction (SPME) and polyethylene passive sampling (PE) aiming to detect free chemical concentration (C free ), and Tenax desorption and isotope dilution method (IDM) aiming to measure chemical accessibility, were used in parallel to estimate in bioavailability of DDT residues (DDXs) in a historically contaminated soil after addition of different black carbon sorbents. Bioaccumulation into earthworm (Eisenia fetida) was measured concurrently for verification. Activated carbon or biochar amendment at 0.2-2% decreased earthworm bioaccumulation of DDXs by 83.9-99.4%, while multi-walled carbon nanotubes had a limited effect (4.3-20.7%). While all methods correctly predicted changes in DDX bioavailability after black carbon amendment, passive samplers offered more accurate predictions. Predicted levels of DDXs in earthworm lipid using the estimated bioavailability and empirical BCFs matched closely with the experimentally derived tissue concentrations. However, Tenax and IDM overestimated bioavailability when the available DDX levels were low. Our findings suggested that both passive samplers and bioaccessibility methods can be used in assessing remediation efficiency, presenting flexibility in method selection. While accessibility-oriented methods offer better sensitivity and shorter sampling time, passive samplers may be more advantageous because of their better performance and computability for in situ deployment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Using SPME fibers and Tenax to predict the bioavailability of pyrethroids and chlorpyrifos in field sediments.

PubMed

Harwood, Amanda D; Landrum, Peter F; Weston, Donald P; Lydy, Michael J

2013-02-01

The presence of pyrethroids in both urban and agricultural sediments at levels lethal to invertebrates has been well documented. However, variations in bioavailability among sediments make accurate predictions of toxicity based on whole sediment concentrations difficult. A proposed solution to this problem is the use of bioavailability-based estimates, such as solid phase microextraction (SPME) fibers and Tenax beads. This study compared three methods to assess the bioavailability and ultimately toxicity of pyrethroid pesticides including field-deployed SPME fibers, laboratory-exposed SPME fibers, and a 24-h Tenax extraction. The objective of the current study was to compare the ability of these methods to quantify the bioavailable fraction of pyrethroids in contaminated field sediments that were toxic to benthic invertebrates. In general, Tenax proved a more sensitive method than SPME fibers and a correlation between Tenax extractable concentrations and mortality was observed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Food synergies for improving bioavailability of micronutrients from plant foods.

PubMed

Nair, K Madhavan; Augustine, Little Flower

2018-01-01

Plant foods are endowed with micronutrients but an understanding of bioavailability is essential in countries primarily dependent on plant based foods. Bioavailability depends majorly on food synergies. This review examines the nature of certain food synergies and methods to screen and establish it as a strategy to control micronutrient deficiency in the populations. Strong evidence on the synergistic effect of inclusion of vitamin C rich fruits and non-vegetarian foods in enhancing the bioavailability of iron has been demonstrated. Fat is found to be synergistic for vitamin A absorption. Red wine and protein have been explored for zinc absorption and effect of fat has been studied for vitamin D. Methods for screening of bioavailability, and biomarkers to demonstrate the synergistic effects of foods are required. Translation of food synergy as a strategy requires adaptation to the context and popularization of intelligent food synergies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Flavonoid interactions during digestion, absorption, distribution and metabolism: a sequential structure-activity/property relationship-based approach in the study of bioavailability and bioactivity.

PubMed

Gonzales, Gerard Bryan; Smagghe, Guy; Grootaert, Charlotte; Zotti, Moises; Raes, Katleen; Van Camp, John

2015-05-01

Flavonoids are a group of polyphenols that provide health-promoting benefits upon consumption. However, poor bioavailability has been a major hurdle in their use as drugs or nutraceuticals. Low bioavailability has been associated with flavonoid interactions at various stages of the digestion, absorption and distribution process, which is strongly affected by their molecular structure. In this review, we use structure-activity/property relationship to discuss various flavonoid interactions with food matrices, digestive enzymes, intestinal transporters and blood proteins. This approach reveals specific bioactive properties of flavonoids in the gastrointestinal tract as well as various barriers for their bioavailability. In the last part of this review, we use these insights to determine the effect of different structural characteristics on the overall bioavailability of flavonoids. Such information is crucial when flavonoid or flavonoid derivatives are used as active ingredients in foods or drugs.

Enhanced bioavailability of orally administered flurbiprofen by combined use of hydroxypropyl-cyclodextrin and poly(alkyl-cyanoacrylate) nanoparticles.

PubMed

Zhao, Xiaoyun; Li, Wei; Luo, Qiuhua; Zhang, Xiangrong

2014-03-01

Flurbiprofen was formulated into nanoparticle suspension to improve its oral bioavailability. Hydroxypropyl-β-cyclodextrin inclusion-flurbiprofen complex (HP-β-CD-FP) was prepared, then incorporating this complex into poly(alkyl-cyanoacrylate) (PACA) nanoparticles. HP-β-CD-FP-PACA nanoparticle was prepared by the emulsion solvent polymerization method. The zeta potential was -26.8 mV, the mean volume particle diameter was 134 nm, drug encapsulation efficiency was 53.3 ± 3.6 % and concentration was 1.5 mg/mL. The bioavailability of flurbiprofen from optimized nanoparticles was assessed in male Wistar rats at a dose of 15 mg/kg. As compared to the flurbiprofen suspension, 211.6 % relative bioavailability was observed for flurbiprofen nanoparticles. The reduced particle size and increased surface area may contribute to improve oral bioavailability of flurbiprofen.

Development of novel ibuprofen-loaded solid dispersion with enhanced bioavailability using cycloamylose.

PubMed

Baek, Hyung Hee; Kim, Dae-Hwan; Kwon, So Young; Rho, Shin-Joung; Kim, Dong-Wuk; Choi, Han-Gon; Kim, Yong-Ro; Yong, Chul Soon

2012-03-01

To develop a novel ibuprofen-loaded solid dispersion with enhanced bioavailability using cycloamylose, it was prepared using spray-drying techniques with cycloamylose at a weight ratio of 1:1. The effect of cycloamylose on aqueous solubility of ibuprofen was investigated. The physicochemical properties of solid dispersions were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction. The dissolution and bioavailability in rats were evaluated compared with ibuprofen powder. This ibuprofen-loaded solid dispersion improved about 14-fold drug solubility. Ibuprofen was present in an unchanged crystalline state, and cycloamylose played the simple role of a solubilizing agent in this solid dispersion. Moreover, the dispersion gave 2-fold higher AUC (area under the drug concentration-time curve) value compared with a ibuprofen powder, indicating that it improved the oral bioavailability of ibuprofen in rats. Thus, the solid dispersion may be useful to deliver ibuprofen with enhanced bioavailability without crystalline change.

The combined application of the Caco-2 cell bioassay coupled with in vivo (Gallus gallus) feeding trial represents an effective approach to predicting Fe bioavailability in humans

USDA-ARS?s Scientific Manuscript database

Research methods that predict Fe bioavailability for humans can be extremely useful in evaluating food fortification strategies, developing Fe-biofortified enhanced staple food crops and assessing the Fe bioavailability of meal plans that include such crops. In this review, research from four recent...

Seed coat removal improves Fe bioavailability in cooked lentils: studies using an in vitro digestion/Caco-2 cell culture model

USDA-ARS?s Scientific Manuscript database

This study examined the range of Fe concentration and relative Fe bioavailability of 24 varieties of cooked lentils, as well as the impact of seed coat removal on lentil Fe nutritional quality. Relative Fe bioavailability was assessed by the in vitro/Caco-2 cell culture method. While Fe concentrat...

Assessing the dietary bioavailability of metals associated with natural particles: Extending the use of the reverse labeling approach to zinc

USGS Publications Warehouse

Croteau, Marie-Noele; Cain, Daniel J.; Fuller, Christopher C.

2017-01-01

We extend the use of a novel tracing technique to quantify the bioavailability of zinc (Zn) associated with natural particles using snails enriched with a less common Zn stable isotope. Lymnaea stagnalis is a model species that has relatively fast Zn uptake rates from the dissolved phase, enabling their rapid enrichment in 67Zn during the initial phase of labeling. Isotopically enriched snails were subsequently exposed to algae mixed with increasing amounts of metal-rich particles collected from two acid mine drainage impacted rivers. Zinc bioavailability from the natural particles was inferred from calculations of 66Zn assimilation into the snail’s soft tissues. Zinc assimilation efficiency (AE) varied from 28% for the Animas River particles to 45% for the Snake River particles, indicating that particle-bound, or sorbed Zn, was bioavailable from acid mine drainage wastes. The relative binding strength of Zn sorption to the natural particles was inversely related to Zn bioavailability; a finding that would not have been possible without using the reverse labeling approach. Differences in the chemical composition of the particles suggest that their geochemical properties may influence the extent of Zn bioavailability.

Simulation of Food Folate Digestion and Bioavailability of an Oxidation Product of 5-Methyltetrahydrofolate

PubMed Central

Ringling, Christiane

2017-01-01

Generating bioavailability data from in vivo studies is time-consuming and expensive. In vitro simulation can help to investigate factors influencing bioavailability or facilitate quantifying the impact of such factors. For folates, an efficient deconjugation of polyglutamates to the corresponding monoglutamates is crucial for bioavailability and highly dependent on the food matrix. Therefore, the bioaccessibility of folates of different foodstuffs was examined using a simulated digestion model with respect to folate stability and the efficiency of deconjugation. For realistic simulated deconjugation, porcine brush border membrane was used during the phase of the simulated digestion in the small intestine. For a better understanding of folate behaviour during digestion, single folate monoglutamates were also investigated with this in vitro digestion model. The results for bioaccessibility were compared with data from a human bioavailability study. They support the idea that both stability and deconjugation have an influence on bioaccessibility and thus on bioavailability. Tetrahydrofolate is probably lost completely or at least to a high extent and the stability of 5-methyltetrahydrofolate depends on the food matrix. Additionally, 5-methyltetrahydrofolate can be oxidised to a pyrazino-s-triazine (MeFox), whose absorption in the human intestinal tract was shown tentatively. PMID:28862677

Rectal bioavailability of delta-9-tetrahydrocannabinol from the hemisuccinate ester in monkeys.

PubMed

ElSohly, M A; Stanford, D F; Harland, E C; Hikal, A H; Walker, L A; Little, T L; Rider, J N; Jones, A B

1991-10-01

Oral administration of delta-9-tetrahydrocannabinal (delta 9-THC) was shown to result in low and erratic bioavailability, while the drug showed no bioavailability from various suppository formulations. delta 9-THC-Hemisuccinate was formulated as a prodrug for delta 9-THC in suppositories using Witepsol H15 base. The bioavailability of delta 9-THC from this formulation was evaluated in monkeys. The plasma levels of delta 9-THC and its metabolite 11-nor-delta 9-THC-9-COOH were determined using GC/MS analysis. The calculated bioavailability of delta 9-THC from this formulation was found to be 13.5%. Non-compartmental analysis of the plasma concentration data using statistical moments showed the mean residence time (MRT) for delta 9-THC in the body to be 3 h following iv administration of delta 9-THC or its hemisuccinate ester (3.4 and 2.7 h, respectively), as compared with 5.8 h following rectal administration of the delta 9-THC hemisuccinate. The observed rectal bioavailability of delta 9-THC from suppositories containing the hemisuccinate ester as a prodrug is of significant importance in developing an alternative approach to oral administration of the drug.

Comparison of bioavailable vanadium in alfalfa rhizosphere soil extracted by an improved BCR procedure and EDTA, HCl, and NaNO₃ single extractions in a pot experiment with V-Cd treatments.

PubMed

Yang, Jie; Teng, Yanguo; Zuo, Rui; Song, Liuting

2015-06-01

The BCR sequential extraction procedure was compared with EDTA, HCl, and NaNO3 single extractions for evaluating vanadium bioavailability in alfalfa rhizosphere soil. The amounts of vanadium extracted by these methods were in the following order: BCR (bioavailable V) > EDTA ≈ HCl > NaNO3. Both correlation analysis and stepwise regression were adopted to illustrate the extractable vanadium between different reagents. The correlation coefficients between extracted vanadium and the vanadium contents in alfalfa roots were R NaNO3 = 0.948, R HCl = 0.902, R EDTA = 0.816, and R bioavailable V = 0.819. The stepwise multiple regression equation of the NaNO3 extraction was the most significant at a 95 % confidence interval. The influence of pH, total organic carbon, and cadmium content of soil to vanadium bioavailability were not definite. In summary, both the BCR sequential extraction and the single extraction methods were valid approaches for predicting vanadium bioavailability in alfalfa rhizosphere soil, especially the single extractions.

Bioavailability enhancers of herbal origin: An overview

PubMed Central

Kesarwani, Kritika; Gupta, Rajiv

2013-01-01

Recently, the use of herbal medicines has been increased all over the world due to their therapeutic effects and fewer adverse effects as compared to the modern medicines. However, many herbal drugs and herbal extracts despite of their impressive in-vitro findings demonstrates less or negligible in-vivo activity due to their poor lipid solubility or improper molecular size, resulting in poor absorption and hence poor bioavailability. Nowadays with the advancement in the technology, novel drug delivery systems open the door towards the development of enhancing bioavailability of herbal drug delivery systems. For last one decade many novel carriers such as liposomes, microspheres, nanoparticles, transferosomes, ethosomes, lipid based systems etc. have been reported for successful modified delivery of various herbal drugs. Many herbal compounds including quercetin, genistein, naringin, sinomenine, piperine, glycyrrhizin and nitrile glycoside have demonstrated capability to enhance the bioavailability. The objective of this review is to summarize various available novel drug delivery technologies which have been developed for delivery of drugs (herbal), and to achieve better therapeutic response. An attempt has also been made to compile a profile on bioavailability enhancers of herbal origin with the mechanism of action (wherever reported) and studies on improvement in drug bioavailability, exhibited particularly by natural compounds. PMID:23620848

Oral bioavailability enhancement and hepatoprotective effects of thymoquinone by self-nanoemulsifying drug delivery system.

PubMed

Kalam, Mohd Abul; Raish, Mohammad; Ahmed, Ajaz; Alkharfy, Khalid M; Mohsin, Kazi; Alshamsan, Aws; Al-Jenoobi, Fahad I; Al-Mohizea, Abdullah M; Shakeel, Faiyaz

2017-07-01

Thymoquinone (TQ) is a poorly water soluble bioactive compound which shows poor oral bioavailability upon oral administration. Due to poor aqueous solubility and bioavailability of TQ, various self-nanoemulsifying drug delivery systems (SNEDDS) of TQ were developed and evaluated for enhancement of its hepatoprotective effects and oral bioavailability. Hepatoprotective and pharmacokinetic studies of TQ suspension and TQ-SNEDDS were carried out in rat models. Different SNEDDS formulations of TQ were developed and thermodynamically stable TQ-SNEDDS were characterized for physicochemical parameters and evaluated for drug release studies via dialysis membrane. Optimized SNEDDS formulation of TQ was selected for further evaluation of in vivo evaluation. In vivo hepatoprotective investigations showed significant hepatoprotective effects for optimized TQ-SNEDDS in comparison with TQ suspension. The oral administration of optimized SNEDDS showed significant improvement in in vivo absorption of TQ in comparison with TQ suspension. The relatively bioavailability of TQ was enhanced 3.87-fold by optimized SNEDDS in comparison with TQ suspension. The results of this research work indicated the potential of SNEDDS in enhancing relative bioavailability and therapeutic effects of natural bioactive compounds such as TQ. Copyright © 2017 Elsevier B.V. All rights reserved.

Model of transient drug diffusion across cornea.

PubMed

Zhang, Wensheng; Prausnitz, Mark R; Edwards, Aurélie

2004-09-30

A mathematical model of solute transient diffusion across the cornea to the anterior chamber of the eye was developed for topical drug delivery. Solute bioavailability was predicted given solute molecular radius and octanol-to-water distribution coefficient (Phi), ocular membrane ultrastructural parameters, tear fluid hydrodynamics, as well as solute distribution volume (Vd) and clearance rate (Cla) in the anterior chamber. The results suggest that drug bioavailability is primarily determined by solute lipophilicity. In human eyes, bioavailability is predicted to range between 1% and 5% for lipophilic molecules (Phi>1), and to be less than 0.5% for hydrophilic molecules (Phi<0.01). The simulations indicate that the distribution coefficient that maximizes bioavailability is on the order of 10. It was also found that the maximum solute concentration in the anterior chamber (Cmax) and the time needed to reach Cmax significantly depend on Phi, Vd, and Cla. Consistent with experimental findings, model predictions suggest that drug bioavailability can be increased by lowering the conjunctival-to-corneal permeability ratio and reducing precorneal solute drainage. Because of its mechanistic basis, this model will be useful to predict drug transport kinetics and bioavailability for new compounds and in diseased eyes.

Recent Advances in Delivery Systems and Therapeutics of Cinnarizine: A Poorly Water Soluble Drug with Absorption Window in Stomach

PubMed Central

Pathak, Kamla

2014-01-01

Low solubility causing low dissolution in gastrointestinal tract is the major problem for drugs meant for systemic action after oral administration, like cinnarizine. Pharmaceutical products of cinnarizine are commercialized globally as immediate release preparations presenting low absorption with low and erratic bioavailability. Approaches to enhance bioavailability are widely cited in the literature. An attempt has been made to review the bioavailability complications and clinical therapeutics of poorly water soluble drug: cinnarizine. The interest of writing this paper is to summarize the pharmacokinetic limitations of drug with special focus on strategies to improvise bioavailability along with effectiveness of novel dosage forms to circumvent the obstacle. The paper provides insight to the approaches to overcome low and erratic bioavailability of cinnarizine by cyclodextrin complexes and novel dosage forms: self-nanoemulsifying systems and buoyant microparticulates. Nanoformulations need to systematically explored in future, for their new clinical role in prophylaxis of migraine attacks in children. Clinical reports have affirmed the role of cinnarizine in migraine prophylaxis. Research needs to be dedicated to develop dosage forms for efficacious bioavailability and drug directly to brain. PMID:25478230

Digestive kinetics determines bioavailability of pollutants. Final report, 1 July 1993--30 September 1998

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayer, L.M.

1998-09-30

The bioavailability of sedimentary contaminants to animals in harbor sediments was addressed by studying the mechanisms by which animals solubilize contaminants during feeding and digestion. Digestive physiology work on many different animal species revealed patterns of enzymes, surfactants and dissolved organic matter that correlate with feeding mode, phyletic position, and diet. Incubation of digestive fluids to dissolve contaminants from polluted sediments was developed to provide numerical estimates of bioavailability, and showed that much higher fractions of total contaminant loading are available than predicted by currently established, aqueous equilibrium approaches. The kinetics of reactions are slow enough that variations in feedingmore » rates will influence overall bioavailability. Experimental manipulations showed mechanisms of bioavailability. Dissolved amino acids, in the form of enzyme proteins and hydrolyzed food, are responsible for solubilization of metals such as copper. At high levels, copper can inactivate digestive enzymes. Metals in sedimentary sulfide minerals were largely impervious to digestive fluid attack. Surfactants are responsible for most solubilization of polycyclic aromatic hydrocarbons (PAH), though other agents also appear to play a role. Bioavailability of both metals and PAH can be limited by saturating the digestive agents responsible for their dissolution.« less

Simulation of Food Folate Digestion and Bioavailability of an Oxidation Product of 5-Methyltetrahydrofolate.

PubMed

Ringling, Christiane; Rychlik, Michael

2017-09-01

Generating bioavailability data from in vivo studies is time-consuming and expensive. In vitro simulation can help to investigate factors influencing bioavailability or facilitate quantifying the impact of such factors. For folates, an efficient deconjugation of polyglutamates to the corresponding monoglutamates is crucial for bioavailability and highly dependent on the food matrix. Therefore, the bioaccessibility of folates of different foodstuffs was examined using a simulated digestion model with respect to folate stability and the efficiency of deconjugation. For realistic simulated deconjugation, porcine brush border membrane was used during the phase of the simulated digestion in the small intestine. For a better understanding of folate behaviour during digestion, single folate monoglutamates were also investigated with this in vitro digestion model. The results for bioaccessibility were compared with data from a human bioavailability study. They support the idea that both stability and deconjugation have an influence on bioaccessibility and thus on bioavailability. Tetrahydrofolate is probably lost completely or at least to a high extent and the stability of 5-methyltetrahydrofolate depends on the food matrix. Additionally, 5-methyltetrahydrofolate can be oxidised to a pyrazino-s-triazine (MeFox), whose absorption in the human intestinal tract was shown tentatively.

Assessing the Dietary Bioavailability of Metals Associated with Natural Particles: Extending the Use of the Reverse Labeling Approach to Zinc.

PubMed

Croteau, Marie-Noële; Cain, Daniel J; Fuller, Christopher C

2017-03-07

We extend the use of a novel tracing technique to quantify the bioavailability of zinc (Zn) associated with natural particles using snails enriched with a less common Zn stable isotope. Lymnaea stagnalis is a model species that has relatively fast Zn uptake rates from the dissolved phase, enabling their rapid enrichment in 67 Zn during the initial phase of labeling. Isotopically enriched snails were subsequently exposed to algae mixed with increasing amounts of metal-rich particles collected from two acid mine drainage impacted rivers. Zinc bioavailability from the natural particles was inferred from calculations of 66 Zn assimilation into the snail's soft tissues. Zinc assimilation efficiency (AE) varied from 28% for the Animas River particles to 45% for the Snake River particles, indicating that particle-bound, or sorbed Zn, was bioavailable from acid mine drainage wastes. The relative binding strength of Zn sorption to the natural particles was inversely related to Zn bioavailability; a finding that would not have been possible without using the reverse labeling approach. Differences in the chemical composition of the particles suggest that their geochemical properties may influence the extent of Zn bioavailability.

C60 reduces the bioavailability of mercury in aqueous solutions.

PubMed

Shi, Wen-Juan; Menn, Fu-Min; Xu, Tingting; Zhuang, Zibo T; Beasley, Clara; Ripp, Steven; Zhuang, Jie; Layton, Alice C; Sayler, Gary S

2014-01-01

The effects of C60 on mercury bioavailability and sorption were investigated at different C60 dosages, reaction times, and pH ranges using the merR::luxCDABE bioluminescent bioreporter Escherichia coli ARL1. The results demonstrated that the bioavailability of mercury (Hg(2+)) decreased with increasing C60 dosage. Approximately 30% of aqueous mercury became biologically unavailable 2h after interaction with C60 at a mass ratio of C60 to mercury as low as 0.01. However, this reduction in bioavailability plateaued at a mass ratio of C60 to mercury of 10 with a further increase in C60 concentrations resulting in only a 20% additional decrease in bioavailability. If this reduction in bioluminescence output is attributable to mercury sorption on C60, then each one log-order increase in C60 concentration resulted in a 0.86 log-order decrease in the mercury partitioning coefficient (Kd). This relationship implies the presence of high mercury-affinitive sites on C60. The length of reaction time was found to play a more important role than C60 dosage in reducing Hg(2+) bioavailability, suggesting an overall slow kinetics of the C60-Hg interactions. In addition, lowering the pH from 7.2 to 5.8 decreased mercury bioavailability due likely to the increase in mercury's association with C60. These results suggest that C60 may be useful in capturing soluble mercury and thus reducing mercury biotoxicity. Published by Elsevier Ltd.

Effects of Estrogen and Estrus Cycle on Pharmacokinetics, Absorption and Disposition of Genistein in Female Sprague-Dawley Rats

PubMed Central

Kulkarni, Kaustubh H.; Yang, Zhen; Tao, Niu; Hu, Ming

2014-01-01

Genistein is an active soy isoflavone with anticancer activities but it is unknown why it has a higher oral bioavailability in female than in male rats. Our study determined the effects of estrus cycle on genistein’s oral bioavailability. Female rats with various levels of estrogen were orally administered with genistein or used in a four-site rat intestinal perfusion experiment. Rats in “proestrus” group (with elevated estrogen) had significantly reduced (57% decrease, p<0.05) oral bioavailability of total genistein (aglycone+conjugates) than those in “metoestrus” group (with basal level of estrogen). Female ovariectomized rats, due to lack of estrogen, showed oral bioavailability of total genistein similar to the “metoestrus” group but higher (155% increase, p<0.05) than the “proestrus” group. Based on intestinal perfusion studies, the increased bioavailability was partially attributed to the higher (>100% increase, p<0.05) hepatic disposition via glucuronidation and possibly more efficient enterohepatic recycling of genistein in the “metoestrus” group. Furthermore, chronic exogenous supplementation of estradiol in ovariectomized rats significantly reduced (77%, p<0.05) the oral bioavailability of total genistein, mostly via increased sulfation (>10 folds) in liver, to a level comparable to those in the “proestrus” group. In conclusion, the oral bioavailability of total genistein was inversely proportional to elevated estrogen levels in female rats, which is partially mediated through the regulation of hepatic enzymes responsible disposition of genistein. PMID:22757747

The oral bioavailability and toxicokinetics of methylmercury in common loon (Gavia immer) chicks

USGS Publications Warehouse

Fournier, F.; Karasov, W.H.; Kenow, K.P.; Meyer, M.W.; Hines, R.K.

2002-01-01

We compared the toxicokinetics of methylmercury in captive common loon chicks during two time intervals to assess the impact of feather growth on the kinetics of mercury. We also determined the oral bioavailability of methylmercury during these trials to test for age-related changes. The blood concentration-time curves for individuals dosed during feather development (initiated 35 days post hatch) were best described by a one-compartment toxicokinetic model with an elimination half-life of 3 days. The data for birds dosed following completion of feather growth (84 days post hatch) were best fitted by a two-compartment elimination model that includes an initial rapid distribution phase with a half-life of 0.9 days, followed by a slow elimination phase with a half-life of 116 days. We determined the oral bioavailability of methylmercury during the first dosing interval by comparing the ratios of the area under the blood concentration-time curves (AUC0→∞) for orally and intravenously dosed chicks. The oral bioavailability of methylmercury during the first dosing period was 0.83. We also determined bioavailability during both dosing periods using a second measure because of irregularities with intravenous results in the second period. This second bioavailability measure estimated the percentage of the dose that was deposited in the blood volume (f), and the results show that there was no difference in bioavailability among dosing periods. The results of this study highlight the importance of feather growth on the toxicokinetics of methylmercury.

Zinc and selenium accumulation and their effect on iron bioavailability in common bean seeds.

PubMed

de Figueiredo, Marislaine A; Boldrin, Paulo F; Hart, Jonathan J; de Andrade, Messias J B; Guilherme, Luiz R G; Glahn, Raymond P; Li, Li

2017-02-01

Common beans (Phaseolus vulgaris) are the most important legume crops. They represent a major source of micronutrients and a target for essential trace mineral enhancement (i.e. biofortification). To investigate mineral accumulation during seed maturation and to examine whether it is possible to biofortify seeds with multi-micronutrients without affecting mineral bioavailability, three common bean cultivars were treated independently with zinc (Zn) and selenium (Se), the two critical micronutrients that can be effectively enhanced via fertilization. The seed mineral concentrations during seed maturation and the seed Fe bioavailability were analyzed. Common bean seeds were found to respond positively to Zn and Se treatments in accumulating these micronutrients. While the seed pods showed a decrease in Zn and Se along with Fe content during pod development, the seeds maintained relatively constant mineral concentrations during seed maturation. Selenium treatment had minimal effect on the seed accumulation of phytic acid and polyphenols, the compounds affecting Fe bioavailability. Zinc treatment reduced phytic acid level, but did not dramatically affect the concentrations of total polyphenols. Iron bioavailability was found not to be greatly affected in seeds biofortified with Se and Zn. In contrast, the inhibitory polyphenol compounds in the black bean profoundly reduced Fe bioavailability. These results provide valuable information for Se and Zn enhancement in common bean seeds and suggest the possibility to biofortify with these essential nutrients without greatly affecting mineral bioavailability to increase the food quality of common bean seeds. Published by Elsevier Masson SAS.

Bioavailability of intranasal promethazine dosage forms in dogs

NASA Technical Reports Server (NTRS)

Ramanathan, R.; Geary, R. S.; Bourne, D. W.; Putcha, L.

1998-01-01

Intramuscular promethazine (PMZ) is used aboard the US Space Shuttle to ameliorate symptoms of space motion sickness. Bioavailability after an oral dose of PMZ during space flight is thought to be impaired because of gastrointestinal disturbances associated with weightlessness and space motion sickness. In an attempt to find an alternative dosage form for use in space, we evaluated two intranasal (i.n.) dosage forms of PMZ in dogs for absorption and bioavailability relative to that of an equivalent intramuscular dose. Promethazine (5 mg kg-1) was administered as two intranasal dosage forms and as an intramuscular (i.m.) dose to three dogs in a randomised cross-over design. Serial blood samples were taken and analysed for PMZ concentrations and the absorption and bioavailability of PMZ were calculated for the three dosage forms. PMZ absorption from the carboxymethyl cellulose microsphere i.n. dosage form was more rapid and complete than from the myverol cubic gel formulation or from an i.m. injection. Bioavailability of the microsphere formulation was also greater than that of the gel formulation (AUC 3009 vs 1727 ng h ml-1). The bioavailability of the two i.n. dosage forms (relative to that of the i.m. injection) were 94% (microsphere) and 54% (gel). The i.n. microsphere formulation of PMZ offers great promise as an effective non-invasive alternative for treating space motion sickness due to its rapid absorption and bioavailability equivalent to the i.m. dose.

Inclusion of guava enhances non-heme iron bioavailability but not fractional zinc absorption from a rice-based meal in adolescents

USDA-ARS?s Scientific Manuscript database

Assessing the bioavailability of non-heme iron and zinc is essential for recommending diets that meet the increased growth-related demand for these nutrients. We studied the bioavailability of iron and zinc from a rice-based meal in 16 adolescent boys and girls, 13–15 y of age, from 2 government-run...

The effect of pH on chronic aquatic nickel toxicity is dependent on the pH itself: Extending the chronic nickel bioavailability models.

PubMed

Nys, Charlotte; Janssen, Colin R; Van Sprang, Patrick; De Schamphelaere, Karel A C

2016-05-01

The environmental quality standard for Ni in the European Commission's Water Framework Directive is bioavailability based. Although some of the available chronic Ni bioavailability models are validated only for pH ≤ 8.2, a considerable fraction of European surface waters has a pH > 8.2. Therefore, the authors investigated the effect of a change in pH from 8.2 to 8.7 on chronic Ni toxicity in 3 invertebrate (Daphnia magna, Lymnaea stagnalis, and Brachionus calyciflorus) and 2 plant species (Pseudokirchneriella subcapitata and Lemna minor). Nickel toxicity was almost always significantly higher at pH 8.7 than at pH 8.2. To test whether the existing chronic Ni bioavailability models developed for pH ≤ 8.2 can be used at higher pH levels, Ni toxicity at pH 8.7 was predicted based on Ni toxicity observed at pH 8.2. This resulted in a consistent underestimation of toxicity. The results suggest that the effect of pH on Ni(2+) toxicity is dependent on the pH itself: the slope of the pH effect is steeper above than below pH 8.2 for species for which a species-specific bioavailability model exists. Therefore, the existing chronic Ni bioavailability models were modified to allow predictions of chronic Ni toxicity to invertebrates and plants in the pH range of 8.2 to 8.7 by applying a pH slope (SpH ) dependent on the pH of the target water. These modified Ni bioavailability models resulted in more accurate predictions of Ni toxicity to all 5 species (within 2-fold error), without the bias observed using the bioavailability models developed for pH ≤ 8.2. The results of the present study can decrease the uncertainty in implementing the bioavailability-based environmental quality standard under the Water Framework Directive for high-pH regions in Europe. © 2015 SETAC.

High bioavailablilty iron maize (Zea mays L.) developed through molecular breeding provides more absorbable iron in vitro (Caco-2 model) and in vivo (Gallus gallus)

PubMed Central

2013-01-01

Background Iron (Fe) deficiency is the most common micronutrient deficiency worldwide. Iron biofortification is a preventative strategy that alleviates Fe deficiency by improving the amount of absorbable Fe in crops. In the present study, we used an in vitro digestion/Caco 2 cell culture model as the guiding tool for breeding and development of two maize (Zea mays L.) lines with contrasting Fe bioavailability (ie. Low and High). Our objective was to confirm and validate the in vitro results and approach. Also, to compare the capacities of our two maize hybrid varieties to deliver Fe for hemoglobin (Hb) synthesis and to improve the Fe status of Fe deficient broiler chickens. Methods We compared the Fe-bioavailability between these two maize varieties with the presence or absence of added Fe in the maize based-diets. Diets were made with 75% (w/w) maize of either low or high Fe-bioavailability maize, with or without Fe (ferric citrate). Chicks (Gallus gallus) were fed the diets for 6 wk. Hb, liver ferritin and Fe related transporter/enzyme gene-expression were measured. Hemoglobin maintenance efficiency (HME) and total body Hb Fe values were used to estimate Fe bioavailability from the diets. Results DMT-1, DcytB and ferroportin expressions were higher (P < 0.05) in the "Low Fe" group than in the "High Fe" group (no added Fe), indicating lower Fe status and adaptation to less Fe-bioavailability. At times, Hb concentrations (d 21,28,35), HME (d 21), Hb-Fe (as from d 14) and liver ferritin were higher in the "High Fe" than in the "Low Fe" groups (P < 0.05), indicating greater Fe absorption from the diet and improved Fe status. Conclusions We conclude that the High Fe-bioavailability maize contains more bioavailable Fe than the Low Fe-bioavailability maize, presumably due to a more favorable matrix for absorption. Maize shows promise for Fe biofortification; therefore, human trials should be conducted to determine the efficacy of consuming the high bioavailable Fe maize to reduce Fe deficiency. PMID:23286295

Challenges of curcumin bioavailability: novel aerosol remedies.

PubMed

Subramani, Parasuraman Aiya; Narala, Venkata R

2013-01-01

Nanoparticles are promising aids for drug delivery for previously challenging diseases, and many incurable ones. Curcumin (diferuloylmethane) is a pleiotropic molecule having various target molecules in the body. Despite its effects, curcumin-based drugs are not readily available in the market because of their low bioavailability. Although dietary intake and knowledge about the potential of curcumin are high in countries like India, studies indicate that the bioavailability problem still persists. However, administration of curcumin through inhalation has received little consideration. In this review we discuss the potential of curcumin, approaches made to overcome the bioavailability challenges, and novel approaches that could be applied in order to deliver curcumin in a pressurized metered dose inhaler (pMDI).

In Vitro Bioavailability of Calcium, Magnesium, Iron, Zinc, and Copper from Gluten-Free Breads Supplemented with Natural Additives.

PubMed

Regula, J; Cerba, A; Suliburska, J; Tinkov, A A

2018-03-01

The aim of this study was to measure the content of calcium, magnesium, iron, zinc, and copper and determine the bioavailability of these ingredients in gluten-free breads fortified with milk and selected seeds. Due to the increasing prevalence of celiac disease and mineral deficiencies, it has become necessary to produce food with higher nutritional values which maintains the appropriate product characteristics. This study was designed for gluten-free breads fortified with milk and seeds such as flax, poppy, sunflower seeds, pumpkin seeds or nuts, and flour with amaranth. Subsequently, digestion was performed in vitro and the potential bioavailability of the minerals was measured. In the case of calcium, magnesium, iron, and copper, higher bioavailability was observed in rice bread, and, in the case of copper and zinc, in buckwheat bread. This demonstrated a clear increase in bioavailability of all the minerals when the bread were enriched. However, satisfactory results are obtained only for the individual micronutrients.

Excipient foods: designing food matrices that improve the oral bioavailability of pharmaceuticals and nutraceuticals.

PubMed

McClements, David Julian; Xiao, Hang

2014-07-25

The oral bioavailability of many lipophilic bioactive agents (pharmaceuticals and nutraceuticals) is limited due to various physicochemical and physiological processes: poor release from food or drug matrices; low solubility in gastrointestinal fluids; metabolism or chemical transformation within the gastrointestinal tract; low epithelium cell permeability. The bioavailability of these agents can be improved by specifically designing food matrices that control their release, solubilization, transport, metabolism, and absorption within the gastrointestinal tract. This article discusses the impact of food composition and structure on oral bioavailability, and how this knowledge can be used to design excipient foods for improving the oral bioavailability of lipophilic bioactives. Excipient foods contain ingredients or structures that may have no bioactivity themselves, but that are able to promote the bioactivity of co-ingested bioactives. These bioactives may be lipophilic drugs in pharmaceutical preparations (such as capsules, pills, or syrups) or nutraceuticals present within food matrices (such as natural or processed foods and beverages).

Fabrication of a Soybean Bowman-Birk Inhibitor (BBI) Nanodelivery Carrier To Improve Bioavailability of Curcumin.

PubMed

Liu, Chun; Cheng, Fenfen; Yang, Xiaoquan

2017-03-22

Curcumin is a poorly water-soluble drug, and its oral bioavailability is very low. Here, a novel self-assembly nanoparticle delivery carrier has been successfully developed by using soybean Bowman-Birk inhibitor (BBI) to improve the solubility, bioaccessibility, and oral absorption of curcumin. BBI is a unique protein, which can be resistant to the pH range and proteolytic enzymes in the gastrointestinal tract (GIT), bioavailable, and not allergenic. The encapsulation efficiencies (EE) and the loading capacities (LC) of curcumin in the curcumin-loaded BBI nanoparticles (Cur-BBI-NPs, size = 90.09 nm, PDI = 0.103) were 86.17 and 10.31%, respectively. The in vitro bioaccessibility of Cur-BBI-NPs was superior to that of curcumin-loaded sodium caseinate (SC) nanoparticles (Cur-SC-NPs) (as control). Moreover, Cur-BBI-NPs significantly enhanced the bioavailability of curcumin in rats compared with Cur-SC-NPs, and the clathrin-mediated endocytosis pathway probably contributed to the favorable bioavailability of Cur-BBI-NPs, as revealed by the cellular uptake inhibition study.

Application of an in vivo swine model for the determination of arsenic bioavailability in contaminated vegetables.

PubMed

Juhasz, Albert L; Smith, Euan; Weber, John; Rees, Matthew; Rofe, Allan; Kuchel, Tim; Sansom, Lloyd; Naidu, Ravi

2008-05-01

Considerable information is available in the literature regarding the uptake of arsenic (As) from contaminated soil and irrigation water by vegetables. However, few studies have investigated As speciation in these crops while a dearth of information is available on As bioavailability following their consumption. In this study, the concentration and speciation of As in chard, radish, lettuce and mung beans was determined following hydroponic growth of the vegetables using As-contaminated water. In addition, As bioavailability was assessed using an in vivo swine feeding assay. While As concentrations ranged from 3.0 to 84.2mg As kg(-1) (dry weight), only inorganic As (arsenite and arsenate) was detected in the edible portions of the vegetables. When As bioavailability was assessed through monitoring blood plasma As concentrations following swine consumption of As-contaminated vegetables, between 50% and 100% of the administered As dose was absorbed and entered systemic circulation. Arsenic bioavailability decreased in the order mung beans>radish>lettuce=chard.

Lecithin-Based Nano-emulsification Improves the Bioavailability of Conjugated Linoleic Acid.

PubMed

Heo, Wan; Kim, Jun Ho; Pan, Jeong Hoon; Kim, Young Jun

2016-02-17

In this study, we investigated the effects of lecithin-based nano-emulsification on the heat stability and bioavailability of conjugated linoleic acid (CLA) in different free fatty acid (FFA) and triglyceride (TG) forms. CLA nano-emulsion in TG form exhibited a small droplet size (70-120 nm) compared to CLA nano-emulsion in FFA form (230-260 nm). Nano-emulsification protected CLA isomers in TG form, but not in free form, against thermal decomposition during the heat treatment. The in vitro bioavailability test using monolayers of Caco-2 human intestinal cells showed that nano-emulsification increased the cellular uptake of CLA in both FFA and TG forms. More importantly, a rat feeding study showed that CLA content in small intestinal tissues or plasma was higher when CLA was emulsified, indicating an enhanced oral bioavailability of CLA by nano-emulsification. These results provide important information for development of nano-emulsion-based delivery systems that improve thermal stability and bioavailability of CLA.

Predicting chemical bioavailability using microarray gene expression data and regression modeling: A tale of three explosive compounds.

PubMed

Gong, Ping; Nan, Xiaofei; Barker, Natalie D; Boyd, Robert E; Chen, Yixin; Wilkins, Dawn E; Johnson, David R; Suedel, Burton C; Perkins, Edward J

2016-03-08

Chemical bioavailability is an important dose metric in environmental risk assessment. Although many approaches have been used to evaluate bioavailability, not a single approach is free from limitations. Previously, we developed a new genomics-based approach that integrated microarray technology and regression modeling for predicting bioavailability (tissue residue) of explosives compounds in exposed earthworms. In the present study, we further compared 18 different regression models and performed variable selection simultaneously with parameter estimation. This refined approach was applied to both previously collected and newly acquired earthworm microarray gene expression datasets for three explosive compounds. Our results demonstrate that a prediction accuracy of R(2) = 0.71-0.82 was achievable at a relatively low model complexity with as few as 3-10 predictor genes per model. These results are much more encouraging than our previous ones. This study has demonstrated that our approach is promising for bioavailability measurement, which warrants further studies of mixed contamination scenarios in field settings.

Distribution and bioavailability of cadmium in ornithogenic coral-sand sediments of the Xisha archipelago, South China Sea.

PubMed

Liu, Xiaodong; Lou, Chuangneng; Xu, Liqiang; Sun, Liguang

2012-09-01

Total cadmium (Cd) concentrations in four ornithogenic coral-sand sedimentary profiles displayed a strong positive correlation with guano-derived phosphorus, but had no correlation with plant-originated organic matter in the top sediments. These results indicate that the total Cd distributions were predominantly controlled by guano input. Bioavailable Cd and zinc (Zn) had a greater input rate in the top sediments with respect to total Cd and total Zn, and a positive correlation with total organic carbon (TOC) derived from plant humus. Multi-regression analysis showed that the total Cd and TOC explained over 80% of the variation of bioavailable Cd, suggesting that both guano and plant inputs could significantly influence the distribution of bioavailable Cd, and that plant biocycling processes contribute more to the recent increase of bioavailable Cd. A pollution assessment indicates that the Yongle archipelago is moderately to strongly polluted with guano-derived Cd. Copyright © 2012 Elsevier Ltd. All rights reserved.

Elucidating the impact of micro-scale heterogeneous bacterial distribution on biodegradation

NASA Astrophysics Data System (ADS)

Schmidt, Susanne I.; Kreft, Jan-Ulrich; Mackay, Rae; Picioreanu, Cristian; Thullner, Martin

2018-06-01

Groundwater microorganisms hardly ever cover the solid matrix uniformly-instead they form micro-scale colonies. To which extent such colony formation limits the bioavailability and biodegradation of a substrate is poorly understood. We used a high-resolution numerical model of a single pore channel inhabited by bacterial colonies to simulate the transport and biodegradation of organic substrates. These high-resolution 2D simulation results were compared to 1D simulations that were based on effective rate laws for bioavailability-limited biodegradation. We (i) quantified the observed bioavailability limitations and (ii) evaluated the applicability of previously established effective rate concepts if microorganisms are heterogeneously distributed. Effective bioavailability reductions of up to more than one order of magnitude were observed, showing that the micro-scale aggregation of bacterial cells into colonies can severely restrict the bioavailability of a substrate and reduce in situ degradation rates. Effective rate laws proved applicable for upscaling when using the introduced effective colony sizes.

Improved oral bioavailability of probucol by dry media-milling.

PubMed

Li, Jia; Yang, Yan; Zhao, Meihui; Xu, Hui; Ma, Junyuan; Wang, Shaoning

2017-09-01

The polymer/probucol co-milled mixtures were prepared to improve drug dissolution rate and oral bioavailability. Probucol, a BCS II drug, was co-milled together with Copovidone (Kollidon VA64, VA64), Soluplus, or MCC using the dry media-milling process with planetary ball-milling equipment. The properties of the milled mixtures including morphology, crystal form, vitro drug dissolution and in vivo oral bioavailability in rats were evaluated. Probucol existed as an amorphous in the matrix of the co-milled mixtures containing VA64, which helped to enhance drug dissolution. The ternary mixture composed of VA64, RH40, and probucol showed increased dissolution rates in both sink and non-sink conditions. It also had a higher oral bioavailability compared to the reference formulation. Dry-media milling of binary or ternary mixtures composed of drug, polymer and surfactant possibly have wide applications to improve dissolution rate and oral bioavailability of water-insoluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmacokinetics and Bioavailability of the Isoflavones Formononetin and Ononin and Their in Vitro Absorption in Ussing Chamber and Caco-2 Cell Models.

PubMed

Luo, Li-Yu; Fan, Miao-Xuan; Zhao, Hai-Yu; Li, Ming-Xing; Wu, Xu; Gao, Wen-Yuan

2018-03-21

Formononetin and its glycoside ononin are bioactive isoflavones widely present in legumes. The present study investigated the pharmacokinetics, bioavailability, and in vitro absorption of formononetin and ononin. After an oral administration to rats, formononetin showed a higher systemic exposure over ononin. The oral bioavailability of formononetin and ononin were 21.8% and 7.3%, respectively. Ononin was more bioavailable than perceived, and its bioavailability reached 21.7% when its metabolite formononetin was taken into account. Both formononetin and ononin exhibited better absorption in large intestine segments than that in small intestine segments. Formononetin displayed a better permeability in all intestinal segments over ononin. Transport of formononetin across Caco-2 cell monolayer was mainly through passive diffusion, while ononin was actively pumped out by MRP2 but not P-gp. The results provide evidence for better understanding of the pharmacological actions of formononetin and ononin, which advocates more in vivo evaluations or human trials.

Physicochemical properties and oral bioavailability of ursolic acid nanoparticles using supercritical anti-solvent (SAS) process.

PubMed

Yang, Lei; Sun, Zhen; Zu, Yuangang; Zhao, Chunjian; Sun, Xiaowei; Zhang, Zhonghua; Zhang, Lin

2012-05-01

The objective of the study was to prepare ursolic acid (UA) nanoparticles using the supercritical anti-solvent (SAS) process and evaluate its physicochemical properties and oral bioavailability. The effects of four process variables, pressure, temperature, drug concentration and drug solution flow rate, on drug particle formation during SAS process, were investigated. Particles with mean particle size ranging from 139.2±19.7 to 1039.8±65.2nm were obtained by varying the process parameters. The UA was characterised by scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, thermal gravimetric analysis, specific surface area, dissolution test and bioavailability test. It was concluded that physicochemical properties and bioavailability of crystalline UA could be improved by physical modification, such as particle size reduction and generation of amorphous state using SAS process. Further, SAS process was a powerful methodology for improving the physicochemical properties and bioavailability of UA. Copyright © 2011 Elsevier Ltd. All rights reserved.

In vitro evaluation of dietary compounds to reduce mercury bioavailability.

PubMed

Jadán-Piedra, Carlos; Vélez, Dinoraz; Devesa, Vicenta

2018-05-15

Mercury in foods, in inorganic form [Hg(II)] or as methylmercury (CH 3 Hg), can have adverse effects. Its elimination from foods is not technologically viable. To reduce human exposure, possible alternatives might be based on reducing its intestinal absorption. This study evaluates the ability of 23 dietary components to reduce the amount of mercury that is absorbed and reaches the bloodstream (bioavailability). We determined their effect on uptake of mercury in Caco-2 cells, a model of intestinal epithelium, exposed to Hg(II) and CH 3 Hg standards and to swordfish bioaccessible fractions. Cysteine, homocysteine, glutathione, quercetin, albumin and tannic reduce bioavailability of both mercury species. Fe(II), lipoic acid, pectin, epigallocatechin and thiamine are also effective for Hg(II). Some of these strategies also reduce Hg bioavailability in swordfish (glutathione, cysteine, homocysteine). Moreover, extracts and supplements rich in these compounds are also effective. This knowledge may help to define dietary strategies to reduce in vivo mercury bioavailability. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Effect of Soil Properties on Metal Bioavailability: Field Scale Validation to Support Regulatory Acceptance

DTIC Science & Technology

2013-06-01

Bioavailability, metals, soil, bioaccessibility, ecological risk, arsenic, cadmium , chromium, lead 16. SECURITY CLASSIFICATION OF:U 17. LIMITATION...located in Sacramento, CA. Soils from a former wastewater treatment lagoon are contaminated with high concentrations of lead , chromium, and cadmium ...in soil. Soil and Sediment Contamination, 2003. 12(1): p. 1-21. 23. Pierzynski, G.M. and A.P. Schwab, Bioavailability of Zinc, Cadmium , and Lead

Self-microemulsifying drug delivery system improves curcumin dissolution and bioavailability.

PubMed

Wu, Xuemei; Xu, Jianhua; Huang, Xiuwang; Wen, Caixia

2011-01-01

Curcumin has a wide spectrum of biological and pharmacological activities, but it has not yet been approved as a therapeutic agent because of its low solubility and stability in aqueous solution, and the relatively low bioavailability in vivo. To overcome these limitations, self-microemulsifying drug delivery system (SMEDDS) of curcumin was developed. Various oils, surfactants, and cosurfactants were selected to optimize the formulation. Pseudoternary phase diagrams were constructed and orthogonal design was used to compare the oil-in-water (o/w) microemulsion-forming capacity of different oils/surfactants/cosurfactants. The solubility of curcumin in various oils and cosurfactants was determined to find suitable ingredients with a good solubilizing capacity. Droplet size was measured to obtain the concentration of oil, surfactant, and cosurfactant for forming stable microemulsion. Furthermore, its quality and bioavailability in mice were assessed. Pseudoternary phase diagrams and solubility test showed that the formulation of SMEDDS composed of 20% ethanol, 60% Cremophor RH40®, and 20% isopropyl myristate, in which the concentration of curcumin reached 50 mg/mL. Curcumin was released completely from SMEDDS at 10 minutes. The developed SMEDDS formulation improved the oral bioavailability of curcumin significantly, and the relative oral bioavailability of SMEDDS compared with curcumin suspension was 1213%. The SMEDDS can significantly increase curcumin dissolution in vitro and bioavailability in vivo.

SNEDDS curcumin formulation leads to enhanced protection from pain and functional deficits associated with diabetic neuropathy: an insight into its mechanism for neuroprotection.

PubMed

Joshi, Rayanta P; Negi, Geeta; Kumar, Ashutosh; Pawar, Yogesh B; Munjal, Bhushan; Bansal, Arvind K; Sharma, Shyam S

2013-08-01

Curcumin has shown to be effective against various diabetes related complications. However major limitation with curcumin is its low bioavailability. In this study we formulated and characterized self nano emulsifying drug delivery system (SNEDDS) curcumin formulation to enhance its bioavailability and then evaluated its efficacy in experimental diabetic neuropathy. Bioavailability studies were performed in male Sprague Dawley rats. Further to evaluate the efficacy of formulation in diabetic neuropathy various parameters like nerve function and sensorimotor perception were assessed along with study of inflammatory proteins (NF-κB, IKK-β, COX-2, iNOS, TNF-α and IL-6). Nanotechnology based formulation resulted in prolonged plasma exposure and bioavailability. SNEDDS curcumin provided better results against functional, behavioural and biochemical deficits in experimental diabetic neuropathy, when compared with naive curcumin. Further western blot analysis confirmed the greater neuroprotective action of SNEDDS curcumin. SNEDDS curcumin formulation due to higher bioavailability was found to afford enhanced protection in diabetic neuropathy. In this study the authors formulated and characterized a self-emulsifying drug delivery system for formulation to enhance curcumin bioavailability in experimental diabetic neuropathy. Enhanced efficacy was demonstrated in a rat model. Copyright © 2013 Elsevier Inc. All rights reserved.

Association between serum levels of bioavailable vitamin D and negative symptoms in first-episode psychosis.

PubMed

Yee, Jie Yin; See, Yuen Mei; Abdul Rashid, Nur Amirah; Neelamekam, Sasi; Lee, Jimmy

2016-09-30

Total vitamin D levels had been commonly reported to be lowered in patients with chronic psychotic illnesses in countries from the higher latitudes. However, studies on patients with first episode psychosis (FEP) are limited. In this study we investigated serum concentrations of total and bioavailable vitamin D levels in FEP patients compared to healthy controls and the association between symptom severity and vitamin D components. A total of 31 FEP patients and 31 healthy controls were recruited from Institute of Mental Health, Singapore. FEP patients were identified using Structured Clinical Interview for DSM-IV Axis I disorders (SCID-1) and severity symptoms were assessed using the positive and negative syndrome scale (PANSS). Sera from participants were analyzed for total vitamin D, vitamin D-binding protein (DBP) and bioavailable vitamin D. Linear regressions were performed to examine the associations between serum total and bioavailable vitamin D and the PANSS subscales. Current study noted a significantly lower bioavailable vitamin D was in the FEP group and an association between bioavailable vitamin D and negative symptoms in FEP patients in a population with a consistent supply of sun exposure throughout the year. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Improving the relationship between soil characteristics and metal bioavailability by using reactive fractions of soil parameters in calcareous soils.

PubMed

de Santiago-Martín, Ana; van Oort, Folkert; González, Concepción; Quintana, José R; Lafuente, Antonio L; Lamy, Isabelle

2015-01-01

The contribution of the nature instead of the total content of soil parameters relevant to metal bioavailability in lettuce was tested using a series of low-polluted Mediterranean agricultural calcareous soils offering natural gradients in the content and composition of carbonate, organic, and oxide fractions. Two datasets were compared by canonical ordination based on redundancy analysis: total concentrations (TC dataset) of main soil parameters (constituents, phases, or elements) involved in metal retention and bioavailability; and chemically defined reactive fractions of these parameters (RF dataset). The metal bioavailability patterns were satisfactorily explained only when the RF dataset was used, and the results showed that the proportion of crystalline Fe oxides, dissolved organic C, diethylene-triamine-pentaacetic acid (DTPA)-extractable Cu and Zn, and a labile organic pool accounted for 76% of the variance. In addition, 2 multipollution scenarios by metal spiking were tested that showed better relationships with the RF dataset than with the TC dataset (up to 17% more) and new reactive fractions involved. For Mediterranean calcareous soils, the use of reactive pools of soil parameters rather than their total contents improved the relationships between soil constituents and metal bioavailability. Such pool determinations should be systematically included in studies dealing with bioavailability or risk assessment. © 2014 SETAC.

Higher iron bioavailability of a human-like collagen iron complex.

PubMed

Zhu, Chenhui; Yang, Fan; Fan, Daidi; Wang, Ya; Yu, Yuanyuan

2017-07-01

Iron deficiency remains a public health problem around the world due to low iron intake and/or bioavailability. FeSO 4 , ferrous succinate, and ferrous glycinate chelate are rich in iron but have poor bioavailability. To solve the problem of iron deficiency, following previous research studies, a thiolated human-like collagen-ironcomplex supplement with a high iron content was prepared in an anaerobic workstation. In addition, cell viability tests were evaluated after conducting an MTT assay, and a quantitative analysis of the thiolated human-like collagen-iron digesta samples was performed using the SDS-PAGE method coupled with gel filtration chromatography. The iron bioavailability was assessed using Caco-2 cell monolayers and iron-deficiency anemia mice models. The results showed that (1) one mole of thiolated human-like collagen-iron possessed approximately 35.34 moles of iron; (2) thiolated human-like collagen-iron did not exhibit cytotoxity and (3) thiolated human-like collagen- iron digesta samples had higher bioavailability than other iron supplements, including FeSO 4 , ferrous succinate, ferrous glycine chelate and thiolated human-like collagen-Fe iron. Finally, the iron bioavailability was significantly enhanced by vitamin C. These results indicated that thiolated human-like collagen-iron is a promising iron supplement for use in the future.

Assessment of relative bioavailability of heavy metals in soil using in vivo mouse model and its implication for risk assessment compared with bioaccessibility using in vitro assay.

PubMed

Kang, Yuan; Pan, Weijian; Liang, Siyun; Li, Ning; Zeng, Lixuan; Zhang, Qiuyun; Luo, Jiwen

2016-10-01

There is limited study to simultaneously determine the relative bioavailability of heavy metals such as Cd, Pb, Cu, Cr(VI), and Ni in soil samples. In the present study, the bioaccessibility of heavy metals using in vitro assay was compared with the relative bioavailability of heavy metals using in vivo mouse model. The bioaccessibility of heavy metals ranged from 9.05 ± 0.97 % (Cr) to 42.8 ± 3.52 % (Cd). The uptake profile of heavy metals in soil and solution samples in mouse revealed that the uptake kinetics could be fitted to a two-compartment model. The relative bioavailability of heavy meals ranged from 34.8 ± 7.0 % (Ni) to 131 ± 20.3 % (Cu). Poor correlation between bioaccessibility and relative bioavailability of heavy metals was observed (r (2) = 0.11, p > 0.05). The relative bioavailability of heavy metals was significantly higher than the bioaccessibility of heavy metals (p < 0.05). The present study indicated that the in vitro digestion method should be carefully employed in risk assessment.

Development and evaluation of a novel microemulsion formulation of elacridar to improve its bioavailability

PubMed Central

Sane, Ramola; Mittapalli, Rajendar K.; Elmquist, William F.

2014-01-01

The study objective was to develop a formulation of elacridar to overcome its dissolution-rate limited bioavailability. Elacridar is a P-gp and BCRP inhibitor that has been used to improve the brain distribution of drugs that are substrates of P-gp and BCRP. The chronic use of elacridar is restricted due to poor solubility leading to poor oral bioavailability. A microemulsion formulation using Cremophor EL, Carbitol and Captex 355 (6:3:1) was developed. The elacridar microemulsion was effective in the inhibition of P-gp and Bcrp in MDCKII-transfected cells. FVBn mice were used to determine the bioavailability of elacridar after a 10 mg/kg dose of elacridar in the microemulsion, intraperitoneally and orally; and the absolute bioavailability was determined to be 1.3 and 0.47, respectively. Co-administration of elacridar microemulsion intraperitoneally with oral erlotinib in FVBn mice improved the erlotinib brain penetration three-fold. The current study shows that a microemulsion formulation of elacridar is effective in improving the bioavailability of elacridar and is an effective inhibitor of P-gp and Bcrp; in-vitro and in-vivo. It offers an alternative to the suspension and allows a decrease in the dose required to achieve a significant inhibitory effect at the blood-brain barrier. PMID:23334925

Periphyton: an important regulator in optimizing soil phosphorus bioavailability in paddy fields.

PubMed

Wu, Yonghong; Liu, Junzhuo; Lu, Haiying; Wu, Chenxi; Kerr, Philip

2016-11-01

Periphyton is ubiquitous in paddy field, but its importance in influencing the bioavailability of phosphorus (P) in paddy soil has been rarely recognized. A paddy field was simulated in a greenhouse to investigate how periphyton influences P bioavailability in paddy soil. Results showed that periphyton colonizing on paddy soil greatly reduced P content in paddy floodwater but increased P bioavailability of paddy soil. Specifically, all the contents of water-soluble P (WSP), readily desorbable P (RDP), algal-available P (AAP), and NaHCO 3 -extractable P (Olsen-P) in paddy soil increased to an extent compared to the control (without periphyton) after fertilization. In particular, Olsen-P was the most increased P species, up to 216 mg kg -1 after fertilization, accounting for nearly 60 % of total phosphorus (TP) in soil. The paddy periphyton captured P up to 1.4 mg g -1 with Ca-P as the dominant P fraction and can be a potential crop fertilizer. These findings indicated that the presence of periphyton in paddy field benefited in improving P bioavailability for crops. This study provides valuable insights into the roles of periphyton in P bioavailability and migration in a paddy ecosystem and technical support for P regulation.

Agronomic Approach of Zinc Biofortification Can Increase Zinc Bioavailability in Wheat Flour and thereby Reduce Zinc Deficiency in Humans

PubMed Central

Liu, Dunyi; Liu, Yumin; Zhang, Wei; Chen, Xinping; Zou, Chunqin

2017-01-01

Zinc (Zn) deficiency is a common disorder of humans in developing countries. The effect of Zn biofortification (via application of six rates of Zn fertilizer to soil) on Zn bioavailability in wheat grain and flour and its impacts on human health was evaluated. Zn bioavailability was estimated with a trivariate model that included Zn homeostasis in the human intestine. As the rate of Zn fertilization increased, the Zn concentration increased in all flour fractions, but the percentages of Zn in standard flour (25%) and bran (75%) relative to total grain Zn were constant. Phytic acid (PA) concentrations in grain and flours were unaffected by Zn biofortification. Zn bioavailability and the health impact, as indicated by disability-adjusted life years (DALYs) saved, increased with the Zn application rate and were greater in standard and refined flour than in whole grain and coarse flour. The biofortified standard and refined flour obtained with application of 50 kg/ha ZnSO4·7H2O met the health requirement (3 mg of Zn obtained from 300 g of wheat flour) and reduced DALYs by >20%. Although Zn biofortification increased Zn bioavailability in standard and refined flour, it did not reduce the bioavailability of iron, manganese, or copper in wheat flour. PMID:28481273

Octacosanol educes physico-chemical attributes, release and bioavailability as modified nanocrystals.

PubMed

Sen Gupta, Surashree; Ghosh, Mahua

2017-10-01

Octacosanol is a lesser known nutraceutical with the potential for treatment of several inflammatory diseases, high cholesterol, Parkinson's symptoms and tumour growth along with the capacity to improve athletic performance. But its lipophilicity and large structure inhibits extended solubility in water resulting in poor absorption and a low bioavailability. In the present work, sodium salt of octacosyl sulfate was synthesized. It displayed improved water solubility. Its nanocrystals, synthesized by means of nanoprecipitation technique, enhanced diffusion velocity, antioxidant capacity, shelf-life, penetrability and bioavailability. Particle size of the nanocrystals ranged between 197 and 220nm. Both modified octacosanol and its nanocrystals displayed maximum lipid peroxidation activities at a concentration 1000ppm, but nanocrystals demonstrated higher prevention. From freeze-thaw cycles it was evident that normal octacosanol crystals were far more prone to temperature variations than the nanocrystals. A pronounced increase in release/diffusion rate and bioavailability was observed for the nanocrystals of the modified octacosanol. In vitro release kinetics, bioavailability and bioequivalence were studied. Relative bioavailability for gastric passage and pancreatic passage of nanocrystals was 2.58 times and 1.81 times that of normal crystals respectively. Furthermore the nanocrystals displayed a superior in vitro release rate, while following a non-Fickian mode. Copyright © 2017 Elsevier B.V. All rights reserved.

Bioavailable Citrus sinensis Extract: Polyphenolic Composition and Biological Activity.

PubMed

Pepe, Giacomo; Pagano, Francesco; Adesso, Simona; Sommella, Eduardo; Ostacolo, Carmine; Manfra, Michele; Chieppa, Marcello; Sala, Marina; Russo, Mariateresa; Marzocco, Stefania; Campiglia, Pietro

2017-04-15

Citrus plants contain large amounts of flavonoids with beneficial effects on human health. In the present study, the antioxidant and anti-inflammatory potential of bioavailable polyphenols from Citrus sinensis was evaluated in vitro and ex vivo, using the murine macrophages cell line J774A.1 and primary peritoneal macrophages. Following simulated gastro-intestinal digestion, the in vitro bioavailability of Citrus sinensis polyphenolic extract was assessed using the human cell line Caco-2 grown as monolayers on a transwell membrane. Data demonstrated a relative permeation of its compounds (8.3%). Thus, the antioxidant and anti-inflammatory effect of polyphenolic Citrus sinensis fraction (Cs) was compared to the bioavailable one (CsB). Results revealed that Citrus extract were able to reduce macrophages pro-inflammatory mediators, including nitric oxide, iNOS, COX-2 and different cytokines. Moreover, the effect of Citrus sinensis polyphenols was associated with antioxidant effects, such as a reduction of reactive oxygen species (ROS) and heme-oxygenase-1 (HO-1) increased expression. Our results provide evidence that the bioavailable polyphenolic constituents of the Citrus sinensis extract accumulate prevalently at intestinal level and could reach systemic circulation exerting their effect. The bioavailable fraction showed a higher anti-inflammatory and antioxidant potential compared to the initial extract, thus highlighting its potential nutraceutical value.

Plants may alter competition by modifying nutrient bioavailability in rhizosphere: a modeling approach.

PubMed

Raynaud, Xavier; Jaillard, Benoît; Leadley, Paul W

2008-01-01

Plants modify nutrient availability by releasing chemicals in the rhizosphere. This change in availability induced by roots (bioavailability) is known to improve nutrient uptake by individual plants releasing such compounds. Can this bioavailability alter plant competition for nutrients and under what conditions? To address these questions, we have developed a model of nutrient competition between plant species based on mechanistic descriptions of nutrient diffusion, plant exudation, and plant uptake. The model was parameterized using data of the effects of root citrate exudation on phosphorus availability. We performed a sensitivity analysis for key parameters to test the generality of these effects. Our simulations suggest the following. (1) Nutrient uptake depends on the number of roots when nutrients and exudates diffuse little, because individual roots are nearly independent in terms of nutrient supply. In this case, bioavailability profits only species with exudates. (2) Competition for nutrients depends on the spatial arrangement of roots when nutrients diffuse little but exudates diffuse widely. (3) Competition for nutrients depends on the nutrient uptake capacity of roots when nutrients and exudates diffuse widely. In this case, bioavailability profits all species. Mechanisms controlling competition for bioavailable nutrients appear to be diverse and strongly depend on soil, nutrient, and plant properties.

Improving oral bioavailability of resveratrol by a UDP-glucuronosyltransferase inhibitory excipient-based self-microemulsion.

PubMed

Yang, Fei-Fei; Zhou, Jing; Hu, Xiao; Cong, Zhao-Qing; Liu, Chun-Yu; Pan, Rui-Le; Chang, Qi; Liu, Xin-Min; Liao, Yong-Hong

2018-03-01

Self-microemulsifying (SME) drug delivery system has been developed to increase oral bioavailabilities, and inhibitory excipients are capable of improving oral bioavailability by inhibiting enzyme mediated intestinal metabolism. However, the potential of enzyme inhibitory excipients containing SME in boosting resveratrol bioavailability remains largely uninvestigated. In this study, we set out to prepare SME-1 with UGT inhibitory excipients (excipients without inhibitory activities named SME-2 as control) to increase the bioavailability of RES by inhibiting intestinal metabolism. Results demonstrated that similar physicochemical properties such as size, polydistribution index and in vitro release, cellular uptake and permeability in Caco-2 cells as well as in vivo lymphatic distribution between inhibitory SME-1 and non-inhibitory SME-2 were observed. In vivo study demonstrated that the molar ratios of RES-G/RES were 7.25±0.48 and 5.06±2.42 for free drug and SME-2, respectively, and the molar ratio decreased to 0.36±0.10 in SME-1 group. Pharmacokinetic study confirmed that the inhibitory excipients containing SME demonstrated potential in increasing bioavailability of RES from 6.5% for the free RES and 12.9% for SME-2 to 76.1% in SME-1 through modulating the glucuronidation by UGT inhibitory excipients. Copyright © 2018 Elsevier B.V. All rights reserved.

Biogeochemical controls of uranium bioavailability from the dissolved phase in natural freshwaters

USGS Publications Warehouse

Croteau, Marie-Noele; Fuller, Christopher C.; Cain, Daniel J.; Campbell, Kate M.; Aiken, George R.

2016-01-01

To gain insights into the risks associated with uranium (U) mining and processing, we investigated the biogeochemical controls of U bioavailability in the model freshwater speciesLymnaea stagnalis (Gastropoda). Bioavailability of dissolved U(VI) was characterized in controlled laboratory experiments over a range of water hardness, pH, and in the presence of complexing ligands in the form of dissolved natural organic matter (DOM). Results show that dissolved U is bioavailable under all the geochemical conditions tested. Uranium uptake rates follow first order kinetics over a range encompassing most environmental concentrations. Uranium uptake rates in L. stagnalis ultimately demonstrate saturation uptake kinetics when exposure concentrations exceed 100 nM, suggesting uptake via a finite number of carriers or ion channels. The lack of a relationship between U uptake rate constants and Ca uptake rates suggest that U does not exclusively use Ca membrane transporters. In general, U bioavailability decreases with increasing pH, increasing Ca and Mg concentrations, and when DOM is present. Competing ions did not affect U uptake rates. Speciation modeling that includes formation constants for U ternary complexes reveals that the aqueous concentration of dicarbonato U species (UO2(CO3)2–2) best predicts U bioavailability to L. stagnalis, challenging the free-ion activity model postulate.

Fractionation of (137)Cs and Pu in natural peatland.

PubMed

Mihalík, Ján; Bartusková, Miluše; Hölgye, Zoltán; Ježková, Tereza; Henych, Ondřej

2014-08-01

High Cs-137 concentrations in plants growing on peatland inspired us to investigate the quantity of its bioavailable fraction in natural peat. Our investigation aims to: a) estimate the quantity of bioavailable Cs-137 and Pu present in peat, b) verify the similarity of Cs-137 and K-40 behaviours, and c) perform a quantification of Cs-137 and Pu transfer from peat to plants. We analysed the vertical distribution of Cs-137 and Pu isotopes in the peat and their concentrations in plants growing on these places. Bioavailability of radionuclides was investigated by sequential extraction. Sequential analyses revealed that it was the upper layer which contained the majority of Cs-137 in an available form while deeper layers retained Cs-137 in immobile fractions. We can conclude that 18% of all Cs-137 in the peat is still bioavailable. Despite of the low quantity of bioavailable fraction of Cs-137 its transfer factor reached extremely high values. In the case of Pu, 64% of its total amount was associated with fulvic/humic acids which resulted in the high transfer factor from peat to plants. 27 years after the Chernobyl nuclear accident, the significant part of radionuclides deposited in peatland is still bioavailable. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Helix-Stabilizing Linker Improves Subcutaneous Bioavailability of a Helical Peptide Independent of Linker Lipophilicity.

PubMed

Zhang, Liang; Navaratna, Tejas; Thurber, Greg M

2016-07-20

Stabilized peptides address several limitations to peptide-based imaging agents and therapeutics such as poor stability and low affinity due to conformational flexibility. There is also active research in developing these compounds for intracellular drug targeting, and significant efforts have been invested to determine the effects of helix stabilization on intracellular delivery. However, much less is known about the impact on other pharmacokinetic parameters such as plasma clearance and bioavailability. We investigated the effect of different fluorescent helix-stabilizing linkers with varying lipophilicity on subcutaneous (sc) bioavailability using the glucagon-like peptide-1 (GLP-1) receptor ligand exendin as a model system. The stabilized peptides showed significantly higher protease resistance and increased bioavailability independent of linker hydrophilicity, and all subcutaneously delivered conjugates were able to successfully target the islets of Langerhans with high specificity. The lipophilic peptide variants had slower absorption and plasma clearance than their respective hydrophilic conjugates, and the absolute bioavailability was also lower likely due to the longer residence times in the skin. Their ease and efficiency make double-click helix stabilization chemistries a useful tool for increasing the bioavailability of peptide therapeutics, many of which suffer from rapid in vivo protease degradation. Helix stabilization using linkers of varying lipophilicity can further control sc absorption and clearance rates to customize plasma pharmacokinetics.

Agronomic Approach of Zinc Biofortification Can Increase Zinc Bioavailability in Wheat Flour and thereby Reduce Zinc Deficiency in Humans.

PubMed

Liu, Dunyi; Liu, Yumin; Zhang, Wei; Chen, Xinping; Zou, Chunqin

2017-05-06

Zinc (Zn) deficiency is a common disorder of humans in developing countries. The effect of Zn biofortification (via application of six rates of Zn fertilizer to soil) on Zn bioavailability in wheat grain and flour and its impacts on human health was evaluated. Zn bioavailability was estimated with a trivariate model that included Zn homeostasis in the human intestine. As the rate of Zn fertilization increased, the Zn concentration increased in all flour fractions, but the percentages of Zn in standard flour (25%) and bran (75%) relative to total grain Zn were constant. Phytic acid (PA) concentrations in grain and flours were unaffected by Zn biofortification. Zn bioavailability and the health impact, as indicated by disability-adjusted life years (DALYs) saved, increased with the Zn application rate and were greater in standard and refined flour than in whole grain and coarse flour. The biofortified standard and refined flour obtained with application of 50 kg/ha ZnSO₄·7H₂O met the health requirement (3 mg of Zn obtained from 300 g of wheat flour) and reduced DALYs by >20%. Although Zn biofortification increased Zn bioavailability in standard and refined flour, it did not reduce the bioavailability of iron, manganese, or copper in wheat flour.

Metal forms in sediments from Arctic coastal environments in Kandalaksha Bay, White Sea, under separation processes

NASA Astrophysics Data System (ADS)

Koukina, S. E.; Vetrov, A. A.

2013-09-01

This study focuses on sediments from small restricted exchange environments along the Karelian shore of Kandalaksha Bay (White Sea, Russian Arctic), which are known as separating basins and are characterised by contrasting oxidising conditions within the water column and the occurrence of anoxia. In the basins that were studied, no significant contamination by trace heavy metals (Pb, Cu, Zn and Cr, in particular) was detected. The comparative study of the two most bioavailable metal forms, namely, labile (acid soluble) and organically bound (alkali soluble) forms, indicated that acetic acid and sodium pyrophosphate released 3-11% and 2-12%, respectively, of the total metal content from sediments. The most bioavailable parts of metals are weakly bound to organic matter and, to a greater extent, associated with easily soluble amorphous Fe-oxides. Among the studied elements, most of the bioavailable Zn and Cu was most likely bound to organic substances, whereas bioavailable Cr and Mn were controlled to a greater extent by the formation of Fe-oxyhydroxide. The elements studied could be arranged in the following decreasing order of average potential bioavailability: Cu > Zn > Mn > Fe > Cr > Pb. In the separating basins, the relative proportion of labile bioavailable metals is enhanced in relation to the neighbouring open coastal sea.

Bioavailability of atrazine, pyrene and benzo[a]pyrene in European river waters

USGS Publications Warehouse

Akkanen, J.; Penttinen, S.; Haitzer, M.; Kukkonen, J.V.K.

2001-01-01

Thirteen river waters and one humic lake water were characterized. The effects of dissolved organic matter (DOM) on the bioavailability of atrazine, pyrene and benzo[a]pyrene (B[a]P) was evaluated. Binding of the chemicals by DOM was analyzed with the equilibrium dialysis technique. For each of the water samples, 24 h bioconcentration factors (BCFs) of the chemicals were measured in Daphnia magna. The relationship between DOM and other water characteristics (including conductivity, water hardness and pH), and bioavailability of the chemicals was studied by performing several statistical analyses, including multiple regression analyses, to determine how much of the variation of BCF values could be explained by the quantity and quality of DOM. The bioavailability of atrazine was not affected by DOM or any other water characteristics. Although equilibrium dialysis showed binding of pyrene to DOM, the bioavailability of pyrene was not significantly affected by DOM. The bioavailability of B[a]P was significantly affected by both the quality and quantity of DOM. Multiple regression analyses, using the quality (ABS270 and HbA%) and quantity of DOM as variables, explainedup to 70% of the variation in BCF of B[a]P in the waters studied. ?? 2001 Elsevier Science Ltd. All rights reserved.

Bioaccessibility and bioavailability of phenolic compounds in bread: a review.

PubMed

Angelino, Donato; Cossu, Marta; Marti, Alessandra; Zanoletti, Miriam; Chiavaroli, Laura; Brighenti, Furio; Del Rio, Daniele; Martini, Daniela

2017-07-19

Cereal-based products, like breads, are a vehicle for bioactive compounds, including polyphenols. The health effects of polyphenols like phenolic acids (PAs) are dependent on their bioaccessibility and bioavailability. The present review summarizes the current understanding of potential strategies to improve phenolic bioaccessibility and bioavailability and the main findings of in vitro and in vivo studies investigating these strategies applied to breads, including the use of raw ingredients with greater phenolic content and different pre-processing technologies, such as fermentation and enzymatic treatment of ingredients. There is considerable variability between in vitro studies, mainly resulting from the use of different methodologies, highlighting the need for standardization. Of the few in vivo bioavailability studies identified, acute, single-dose studies demonstrate that modifications to selected raw materials and bioprocessing of bran could increase the bioavailability, but not necessarily the net content, of bread phenolics. The two medium-term identified dietary interventions also demonstrated greater phenolic content, resulting from the modification of the raw materials used. Overall, the findings suggest that several strategies can be used to develop new bread products with greater phenolic bioaccessibility and bioavailability. However, due to the large variability and the few studies available, further investigations are required to determine better the usefulness of these innovative processes.

STS-106 Crew Activity Report/Flight Day 8 Highlights

NASA Technical Reports Server (NTRS)

2000-01-01

On this eighth day of the STS-106 Atlantis mission, the flight crew, Commander Terrence W. Wilcutt, Pilot Scott T. Altman, and Mission Specialists Daniel C. Burbank, Edward T. Lu, Richard A. Mastracchio, Yuri Ivanovich Malenchenko, and Boris V. Morukov move into the second half of preparing the International Space Station (ISS) for its first resident crew. Lu and Malenchenko are seen installing the power converters in the Zvezda module and components of the primary oxygen generation system. Mastracchio and Wilcutt moves supplies and logistics from the payload of Atlantis to the ISS. Wilcutt and Altman participate in several interviews and the crew wishes the Olympiads in Sydney good luck in their endeavors. Scenes also include external views of the ISS and images of Earth, including Sydney, Australia.

Observations of the June Bootid Meteor Shower in 2006 from Bulgaria

NASA Astrophysics Data System (ADS)

Velkov, Valentin; Gospodinova, Galina

2010-12-01

We present visual observations of the June Bootids in 2006. Three observers of the Astronomical Club Canopus - Boris Stoilov (STOBO), Vyara Georgieva (GEOVY) and Valentin Velkov (VELVA) - carried out our traditional June Bootid watch in Bolyarci village (27.47'52'' E, 43.04'10'' N) in the period 26-29 June 2006. In 17.67h of effective observing time 133 meteors were recorded, from which 32 were June Böotids, 64 sporadic meteors and 37 belonging to other active showers (Sagittariids, alpha-Cygnids, lambda-Sagittariids and a few daytime Arietids. A low but stable level of the June Böotid activity we registered, was due to the background component of the stream. A radiant position was obtained for the main branch of the Böotid shower.

BOREAS Level 3-b AVHRR-LAC Imagery: Scaled At-sensor Radiance in LGSOWG Format

NASA Technical Reports Server (NTRS)

Hall, Forrest G. (Editor); Nickeson, Jaime; Newcomer, Jeffrey A.; Cihlar, Josef

2000-01-01

The BOREAS Staff Science Satellite Data Acquisition Program focused on providing the research teams with the remotely sensed satellite data products they needed to compare and spatially extend point results. Data acquired from the AVHRR instrument on the NOAA-9, -11, -12, and -14 satellites were processed and archived for the BOREAS region by the MRSC and BORIS. The data were acquired by CCRS and were provided for use by BOREAS researchers. A few winter acquisitions are available, but the archive contains primarily growing season imagery. These gridded, at-sensor radiance image data cover the period of 30-Jan-1994 to 18-Sep-1996. Geographically, the data cover the entire 1,000-km x 1,000-km BOREAS region. The data are stored in binary image format files.

Released fraction of polychlorinated biphenyls from soil-biosolid system using a leaching procedure and its comparison with bioavailable fraction determined by wheat plant uptake.

PubMed

Jachero, Lourdes; Leiva, Claudio; Ahumada, Inés; Richter, Pablo

2017-11-01

The bioavailability of polychlorinated biphenyls (PCBs) in soils amended with biosolids was estimated using an aqueous leaching process of the compounds combined with rotating disk sorptive extraction (RDSE), and compared with bioavailability determined through of PCB absorption in wheat plants growing in the same soil-biosolid matrix. The matrices consisted of soil amended with biosolids at doses of 30, 90, and 200 Mg/ha, which increase concomitantly the organic matter content of the matrix. Considering that PCBs were natively absent in both the biosolids and soil used, the compounds were spiked in the biosolids and aged for 10 days. For each biosolid dose, the aqueous leaching profile was studied and equilibrium time was calculated to be 33 h. The leaching fractions determined by RDSE, considering total PCBs studied, were 12, 7, and 6% and the bioavailable fractions absorbed by the wheat root were found to be 0.5, 0.3, and 0.2% for 30, 90, and 200 Mg/ha doses, respectively. Both fractions leachable and bioavailable decrease with both increasing hydrophobicity of the compound (Kow) and increasing in the biosolid dose. It was found that both fractions (leaching and bioavailable) correlated according to the bivariate least squares regression, represented by a coefficient of correlation of 0.86. Therefore, the application of the chemical method involving a leaching procedure is an alternative to estimate the bioavailable fraction of PCBs in wheat plants in a simpler and in a shorter time.

Fabrication and Optimization of Self-Microemulsions to Improve the Oral Bioavailability of Total Flavones of Hippophaë rhamnoides L.

PubMed

Guo, Ruixue; Guo, Xinbo; Hu, Xiaodan; Abbasi, Arshad Mehmood; Zhou, Lin; Li, Tong; Fu, Xiong; Liu, Rui Hai

2017-12-01

The purpose of this work was to improve the oral bioavailability of a poorly soluble functional food ingredient, the total flavones of Hippophaë rhamnoides L. (TFH). A self-microemulsion drug delivery system (SMEDDS) was developed to overcome the problems of poor absorption of TFH in vivo. The optimal SMEDDS significantly enhanced the solubility of TFH up to 530 times compared to that in water. The mean droplet size was 61.76 nm with uniform distribution. And the loaded system was stable at 25 °C for 3 mo with transparent appearance. The in vitro release of TFH from SMEDDS was faster and more complete than that from suspension. After oral administration of TFH-SMEDDS in rats, the relative bioavailability of TFH was dramatically improved for 3.09 times compared with the unencapsulated form. The investigation indicated the potential application of SMEDDS as a vehicle to improve the oral bioavailability of TFH. The lipid-based nanotechnology, namely self-microemulsion drug delivery system (SMEDDS) was used to improve the bioavailability and oral delivery of total flavones of Hippophaë rhamnoides L. (TFH). The relevant bioavailability of TFH could be remarkably 3-fold improved by the optimized SMEDDS. The SMEDDS produced via a simple one-step process for poorly soluble TFH to achieve a significant improvement in the bioavailability, may endorse the promising utilization of TFH in functional foods as well as pharmaceutical fields with an enhanced absorption in vivo. © 2017 Institute of Food Technologists®.

Pharmacokinetics and Bioavailability of Inhaled Esketamine in Healthy Volunteers.

PubMed

Jonkman, Kelly; Duma, Andreas; Olofsen, Erik; Henthorn, Thomas; van Velzen, Monique; Mooren, René; Siebers, Liesbeth; van den Beukel, Jojanneke; Aarts, Leon; Niesters, Marieke; Dahan, Albert

2017-10-01

Esketamine is traditionally administered via intravenous or intramuscular routes. In this study we developed a pharmacokinetic model of inhalation of nebulized esketamine with special emphasis on pulmonary absorption and bioavailability. Three increasing doses of inhaled esketamine (dose escalation from 25 to 100 mg) were applied followed by a single intravenous dose (20 mg) in 19 healthy volunteers using a nebulizer system and arterial concentrations of esketamine and esnorketamine were obtained. A multicompartmental pharmacokinetic model was developed using population nonlinear mixed-effects analyses. The pharmacokinetic model consisted of three esketamine, two esnorketamine disposition and three metabolism compartments. The inhalation data were best described by adding two absorption pathways, an immediate and a slower pathway, with rate constant 0.05 ± 0.01 min (median ± SE of the estimate). The amount of esketamine inhaled was reduced due to dose-independent and dose-dependent reduced bioavailability. The former was 70% ± 5%, and the latter was described by a sigmoid EMAX model characterized by the plasma concentration at which absorption was impaired by 50% (406 ± 46 ng/ml). Over the concentration range tested, up to 50% of inhaled esketamine is lost due to the reduced dose-independent and dose-dependent bioavailability. We successfully modeled the inhalation of nebulized esketamine in healthy volunteers. Nebulized esketamine is inhaled with a substantial reduction in bioavailability. Although the reduction in dose-independent bioavailability is best explained by retention of drug and particle exhalation, the reduction in dose-dependent bioavailability is probably due to sedation-related loss of drug into the air.

Pharmacokinetics of isochlorgenic acid C in rats by HPLC-MS: Absolute bioavailability and dose proportionality.

PubMed

Huang, Li Hua; Xiong, Xiao Hong; Zhong, Yun Ming; Cen, Mei Feng; Cheng, Xuan Ge; Wang, Gui Xiang; Zang, Lin Quan; Wang, Su Jun

2016-06-05

Isochlorgenic acid C (IAC), one of the bioactive compounds of Lonicera japonica, exhibited diverse pharmacological effects. However, its pharmacokinetic properties and bioavailability remained unresolved. To determine the absolute bioavailability in rats and the dose proportionality on the pharmacokinetics of single oral dose of IAC. A validated HPLC-MS method was developed for the determination of IAC in rat plasma. Plasma concentration versus time data were generated following oral and intravenous dosing. The pharmacokinetic analysis was performed using DAS 3.0 software analysis. Absolute bioavailability in rats was determined by comparing pharmacokinetic data after administration of single oral (5, 10 and 25mgkg(-1)) and intravenous (5mgkg(-1)) doses of IAC. The dose proportionality of AUC(0-∞) and Cmax were analyzed by linear regression. Experimental data showed that absolute oral bioavailability of IAC in rats across the doses ranged between 14.4% and 16.9%. The regression analysis of AUC(0-∞) and Cmax at the three doses (5, 10 and 25mgkg(-1)) indicated that the equations were y=35.23x+117.20 (r=0.998) and y=121.03x+255.74 (r=0.995), respectively. A new HPLC-MS method was developed to determine the bioavailability and the dose proportionality of IAC. Bioavailability of IAC in rats was poor and both Cmax and AUC(0-∞) of IAC had a positive correlation with dose. Evaluation of the pharmacokinetics of IAC will be useful in assessing concentration-effect relationships for the potential therapeutic applications of IAC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Determining bioavailability of food folates in a controlled intervention study.

PubMed

Hannon-Fletcher, Mary P; Armstrong, Nicola C; Scott, John M; Pentieva, Kristina; Bradbury, Ian; Ward, Mary; Strain, J J; Dunn, Adele A; Molloy, Anne M; Kerr, Maeve A; McNulty, Helene

2004-10-01

The concept of dietary folate equivalents (DFEs) in the United States recognizes the differences in bioavailability between natural food folates and the synthetic vitamin, folic acid. However, many published reports on folate bioavailability are problematic because of several confounding factors. We compared the bioavailability of food folates with that of folic acid under controlled conditions. To broadly represent the extent to which natural folates are conjugated in foods, we used 2 natural sources of folate, spinach (50% polyglutamyl folate) and yeast (100% polyglutamyl folate). Ninety-six men were randomly assigned according to their screening plasma homocysteine (tHcy) concentration to 1 of 4 treatment groups for an intervention period of 30 d. Each subject received (daily under supervision) either a folate-depleted "carrier" meal or a drink plus 1) placebo tablet, 2) 200 microg folic acid in a tablet, 3) 200 microg natural folate provided as spinach, or 4) 200 microg natural folate provided as yeast. Among the subjects who completed the intervention, responses (increase in serum folate, lowering of tHcy) relative to those in the placebo group (n = 18) were significant in the folic acid group (n = 18) but not in the yeast folate (n = 19) or the spinach folate (n = 18) groups. Both natural sources of folate were significantly less bioavailable than was folic acid. Overall estimations of folate bioavailability relative to that of folic acid were found to be between 30% (spinach) and 59% (yeast). Relative bioavailability estimates were consistent with the estimates from the metabolic study that were used as a basis to derive the US DFE value.

[Gender Aspects in Gastrointestinal Tumours and Their Prognosis in Regard to Multimodal Treatment Concepts].

PubMed

Seeland, U; Heger, U; Heise, K; Ott, K

2015-06-01

Systematic analyses of gender effects in gastrointestinal malignancies are currently lacking, partly because sex and gender have not been used as stratification criteria in major studies on the topic. It is, however, indisputable that gastrointestinal tumours differ in risk factors, incidence and prognosis between the genders. This review summarises the most important findings on differences related to biological sex and sociocultural gender and discusses anatomic specifics with immediate significance for surgical interventions. Epidemiological differences in upper gastrointestinal malignancies are most prominent in regard to histological subtypes, directly affecting diagnostics, therapy, and prognosis. Women have a better prognosis in many of these tumour subtypes. For colorectal carcinoma, sex hormones, specifically oestrogens, appear to play a distinct role in tumourigenesis. Histopathological analysis of the expression of oestrogen receptor beta (ERβ) in the tumour tissue has attracted interest since it was shown that women with low ERβ expression have a better prognosis than men with comparable ERβ status. Data on the higher incidence of right-sided colon carcinoma and non-polypoid neoplasms in women could lead to improved screening programmes. Men and women cite differing reasons for avoidance of screening colonoscopies, thus gender specific approaches could improve colon cancer prevention programmes. Data on differing bioavailability of 5-fluorouracil between the genders are useful to minimise adverse effects of chemotherapy and should be accounted for in dosage. Further systematic analysis of gender effects on gastrointestinal tumours is warranted and would be a substantial step towards personalised oncological surgery. Georg Thieme Verlag KG Stuttgart · New York.

Characteristics of bioavailable organic phosphorus in sediment and its contribution to lake eutrophication in China.

PubMed

Ni, Zhaokui; Wang, Shengrui; Wang, Yuemin

2016-12-01

This study aims to establish the relative importance of sediment organic phosphorus (P o ) to the total P and the major classes of organic molecules that contribute to sediment P o , determined by measuring their susceptibility to enzymatic hydrolysis, across a suite of lakes ranging from oligotrophic to eutrophic status. The results showed that P o accounted for 21-60% of total P, and bioavailable P o accounted for 9-34% of P o in the sediments. The bioavailable P o includes mainly labile (H 2 O-P o ) and moderately labile (NaOH-P o ) P forms. For H 2 O-P o (accounting for only1.4% of P o ), 53% (average) was labile monoester P, 28% was diester P and 17% was phytate-like P. For NaOH-P o (accounting for 9-33% of P o ), 32% was labile monoester P, 33% was phytate-like P and 18% was diester P. The composition of bioavailable P o , determined by enzyme assays, was related to the lake nutrient levels, which implies that sediment bioavailable P o could act as an effective indicator for lake eutrophic status. With the increase of lake nutrient levels, bioavailable P o content and alkaline phosphatase activity in the sediment all increased, indicating that P o represents an important and bioavailable source of P that increases with eutrophication, and could contribute to internal loading and resistance of eutrophic lakes to remediation. This implies that eutrophic lakes would maintain long-term eutrophic status and algal bloom phenomena even after the external input of P was controlled and the total P concentration of water has declined. Thus, in order to reduce the release risk of sediment P more efficiently and effectively, sediment P control technique should focus not only on reducing the total P and inorganic P, but should also pay close attention to the removal of bioavailable P o . Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of clay minerals and organic matter in formulated sediments on the bioavailability of sediment-associated uranium to the freshwater midge, Chironomus dilutus.

PubMed

Crawford, Sarah E; Liber, Karsten

2015-11-01

It is well established that bioavailability influences metal toxicity in aquatic ecosystems. However, the factors and mechanisms that influence uranium (U) bioavailability and toxicity in sediment have not been thoroughly evaluated, despite evidence that suggests different sediment components can influence the sorption and interaction of some metals. Given that dissolved U is generally accepted as being the primary bioavailable fraction of U, it is hypothesized that adsorption and interaction of U with different sediment components will influence the bioavailability of U in sediment. We investigated the effects of key sediment physicochemical properties on the bioavailability of U to a model freshwater benthic invertebrate, Chironomus dilutus. Several 10-day spiked sediment bioaccumulation experiments were performed, exposing C. dilutus larvae to a variety of formulated sediments spiked with different concentrations of U (5, 50 and/or 200 mg U/kg d.w.). Mean accumulation of U in C. dilutus larvae decreased significantly from 1195 to 10 mg U/kg d.w. as kaolin clay content increased from 0% to 60% in sediment spiked with 50 mg U/kg d.w. Similarly, higher organic matter content also resulted in a significant reduction of U bioaccumulation in C. dilutus larvae, indicating a reduction in U bioavailability. Concentrations of U in both the overlying water and sediment pore water displayed a strong positive relationship to U bioaccumulation in C. dilutus larvae (r(2) = 0.77, p<0.001 and r(2) = 0.57, p < 0.001, respectively) for all experiments, while total U concentrations in the sediment had a poor relationship to U bioaccumulation (r(2) = 0.10, p = 0.028). Results from this research confirm that sediment clay and organic matter content play a significant role in altering U bioavailability, which is important in informing risk assessments of U contaminated sites and in the development of site-specific sediment quality guidelines for U. Copyright © 2015 Elsevier B.V. All rights reserved.

Metal bioavailability in ecological risk assessment of freshwater ecosystems: From science to environmental management.

PubMed

Väänänen, Kristiina; Leppänen, Matti T; Chen, XuePing; Akkanen, Jarkko

2018-01-01

Metal contamination in freshwater ecosystems is a global issue and metal discharges to aquatic environments are monitored in order to protect aquatic life and human health. Bioavailability is an important factor determining metal toxicity. In aquatic systems, metal bioavailability depends on local water and sediment characteristics, and therefore, the risks are site-specific. Environmental quality standards (EQS) are used to manage the risks of metals in aquatic environments. In the simplest form of EQSs, total concentrations of metals in water or sediment are compared against pre-set acceptable threshold levels. Now, however, the environmental administration bodies have stated the need to incorporate metal bioavailability assessment tools into environmental regulation. Scientific advances have been made in metal bioavailability assessment, including passive samplers and computational models, such as biotic ligand models (BLM). However, the cutting-edge methods tend to be too elaborate or laborious for standard environmental monitoring. We review the commonly used metal bioavailability assessment methods and introduce the latest scientific advances that might be applied to environmental management in the future. We present the current practices in environmental management in North America, Europe and China, highlighting the good practices and the needs for improvement. Environmental management has met these new challenges with varying degrees of success: the USA has implemented site-specific environmental risk assessment for water and sediment phases, and they have already implemented metal mixture toxicity evaluation. The European Union is promoting the use of bioavailability and BLMs in ecological risk assessment (ERA), but metal mixture toxicity and sediment phase are still mostly neglected. China has regulation only for total concentrations of metals in surface water. We conclude that there is a need for (1) Advanced and up-to-date guidelines and legislation, (2) New and simple scientific methods for assessing metal bioavailability and (3) Improvement of knowledge and skills of administrators. Copyright © 2017 Elsevier Inc. All rights reserved.

Niosomal carriers enhance oral bioavailability of carvedilol: effects of bile salt-enriched vesicles and carrier surface charge.

PubMed

Arzani, Gelareh; Haeri, Azadeh; Daeihamed, Marjan; Bakhtiari-Kaboutaraki, Hamid; Dadashzadeh, Simin

2015-01-01

Carvedilol (CRV) is an antihypertensive drug with both alpha and beta receptor blocking activity used to preclude angina and cardiac arrhythmias. To overcome the low, variable oral bioavailability of CRV, niosomal formulations were prepared and characterized: plain niosomes (without bile salts), bile salt-enriched niosomes (bilosomes containing various percentages of sodium cholate or sodium taurocholate), and charged niosomes (negative, containing dicetyl phosphate and positive, containing hexadecyl trimethyl ammonium bromide). All formulations were characterized in terms of encapsulation efficiency, size, zeta potential, release profile, stability, and morphology. Various formulations were administered orally to ten groups of Wistar rats (n=6 per group). The plasma levels of CRV were measured by a validated high-performance liquid chromatography (HPLC) method and pharmacokinetic properties of different formulations were characterized. Contribution of lymphatic transport to the oral bioavailability of niosomes was also investigated using a chylomicron flow-blocking approach. Of the bile salt-enriched vesicles examined, bilosomes containing 20% sodium cholate (F2) and 30% sodium taurocholate (F5) appeared to give the greatest enhancement of intestinal absorption. The relative bioavailability of F2 and F5 formulations to the suspension was estimated to be 1.84 and 1.64, respectively. With regard to charged niosomes, the peak plasma concentrations (Cmax) of CRV for positively (F7) and negatively charged formulations (F10) were approximately 2.3- and 1.7-fold higher than after a suspension. Bioavailability studies also revealed a significant increase in extent of drug absorption from charged vesicles. Tissue histology revealed no signs of inflammation or damage. The study proved that the type and concentration of bile salts as well as carrier surface charge had great influences on oral bioavailability of niosomes. Blocking the lymphatic absorption pathway significantly reduced oral bioavailability of CRV niosomes. Overall twofold enhancement in bioavailability in comparison with drug suspension confers the potential of niosomes as suitable carriers for improved oral delivery of CRV.

Temporal assessment of copper speciation, bioavailability and toxicity in UK freshwaters using chemical equilibrium and biotic ligand models: Implications for compliance with copper environmental quality standards.

PubMed

Lathouri, Maria; Korre, Anna

2015-12-15

Although significant progress has been made in understanding how environmental factors modify the speciation, bioavailability and toxicity of metals such as copper in aquatic environments, the current methods used to establish water quality standards do not necessarily consider the different geological and geochemical characteristics of a given site and the factors that affect copper fate, bioavailability potential and toxicity. In addition, the temporal variation in the concentration and bioavailable metal fraction is also important in freshwater systems. The work presented in this paper illustrates the temporal and seasonal variability of a range of water quality parameters, and Cu speciation, bioavailability and toxicity at four freshwaters sites in the UK. Rivers Coquet, Cree, Lower Clyde and Eden (Kent) were selected to cover a broad range of different geochemical environments and site characteristics. The monitoring data used covered a period of around six years at almost monthly intervals. Chemical equilibrium modelling was used to study temporal variations in Cu speciation and was combined with acute toxicity modelling to assess Cu bioavailability for two aquatic species, Daphnia magna and Daphnia pulex. The estimated copper bioavailability, toxicity levels and the corresponding ecosystem risks were analysed in relation to key water quality parameters (alkalinity, pH and DOC). Although copper concentrations did not vary much during the sampling period or between the seasons at the different sites; copper bioavailability varied markedly. In addition, through the chronic-Cu BLM-based on the voluntary risk assessment approach, the potential environmental risk in terms of the chronic toxicity was assessed. A much higher likelihood of toxicity effects was found during the cold period at all sites. It is suggested that besides the metal (copper) concentration in the surface water environment, the variability and seasonality of other important water quality parameters should be considered in setting appropriately protective environmental quality standards for metals. Copyright © 2015 Elsevier B.V. All rights reserved.

Interactions between active pharmaceutical ingredients and excipients affecting bioavailability: impact on bioequivalence.

PubMed

García-Arieta, Alfredo

2014-12-18

The aim of the present paper is to illustrate the impact that excipients may have on the bioavailability of drugs and to review existing US-FDA, WHO and EMA regulatory guidelines on this topic. The first examples illustrate that small amounts of sorbitol (7, 50 or 60mg) affect the bioavailability of risperidone, a class I drug, oral solution, in contrast to what is stated in the US-FDA guidance. Another example suggests, in contrast to what is stated in the US-FDA BCS biowaivers guideline, that a small amount of sodium lauryl sulphate (SLS) (3.64mg) affects the bioavailability of risperidone tablets, although the reference product also includes SLS in an amount within the normal range for that type of dosage form. These factors are considered sufficient to ensure that excipients do not affect bioavailability according to the WHO guideline. The alternative criterion, defined in the WHO guideline and used in the FIP BCS biowaivers monographs, that asserts that excipients present in generic products of the ICH countries do not affect bioavailability if used in normal amounts, is shown to be incorrect with an example of alendronate (a class III drug) tablets, where 4mg of SLS increases bioavailability more than 5-fold, although a generic product in the USA contains SLS. Finally, another example illustrates that a 2mg difference in SLS may affect bioavailability of a generic product of a class II drug, even if SLS is contained in the comparator product, and in all cases its amount was within the normal range. Therefore, waivers of in vivo bioequivalence studies (e.g., BCS biowaivers, waivers of certain dosage forms in solution at the time of administration and variations in the excipient composition) should be assessed more cautiously. Copyright © 2014 Elsevier B.V. All rights reserved.

Aluminum bioavailability from the approved food additive leavening agent acidic sodium aluminum phosphate, incorporated into a baked good, is lower than from water.

PubMed

Yokel, Robert A; Florence, Rebecca L

2006-10-03

There are estimates of oral aluminum (Al) bioavailability from drinking water, but little information on Al bioavailability from foods. Foods contribute approximately 95% and drinking water 1-2% of the typical human's daily Al intake. The objectives were to estimate oral Al bioavailability from a representative food containing the food additive acidic sodium aluminum phosphate (acidic SALP), a leavening agent in baked goods. Rats were acclimated to a special diet that resulted in no stomach contents 14 h after its withdrawal. They were trained to rapidly consume a biscuit containing 1.5% acidic SALP. Oral Al bioavailability was then determined from a biscuit containing 1% or 2% acidic SALP, synthesized to contain (26)Al. The rats received concurrent (27)Al infusion. Blood was repeatedly withdrawn and serum analyzed for (26)Al by accelerator mass spectrometry. Total Al was determined by atomic absorption spectrometry. Oral (26)Al bioavailability was determined from the area under the (26)Al, compared to (27)Al, serum concentrationxtime curves. Oral Al bioavailability (F) from biscuit containing 1% or 2% acidic (26)Al-SALP averaged approximately 0.11% and 0.13%; significantly less than from water, which was previously shown to be approximately 0.3%. The time to maximum serum (26)Al concentration was 4.2 and 6h after consumption of biscuit containing 1% or 2% (26)Al-acidic SALP, respectively, compared to 1-2h following (26)Al in water. These results of oral Al bioavailability from acidic (26)Al-SALP in a biscuit (F approximately 0.1%) and results from (26)Al in water (F approximately 0.3%) x the contributions of food and drinking water to the typical human's daily Al intake ( approximately 5-10mg from food and 0.1mg from water, respectively) suggest food provides approximately 25-fold more Al to systemic circulation, and potential Al body burden, than does drinking water.

Bioavailability of rifampicin following concomitant administration of ethambutol or isoniazid or pyrazinamide or a combination of the three drugs.

PubMed

Immanuel, Chandra; Gurumurthy, Prema; Ramachandran, Geetha; Venkatesan, P; Chandrasekaran, V; Prabhakar, R

2003-09-01

Poor bioavailability of rifampicin (R) in combination with other anti-tuberculosis drugs such as isoniazid (H), pyrazinamide (Z), and ethambutol (E) is a subject of much concern for the last few decades. This could be due to an interaction between R and other drugs. An investigation was therefore undertaken to examine the bioavailability of R in the presence of H, Z and E or a combination of the three drugs. The study included eight healthy volunteers, each being investigated on four occasions at weekly intervals once with R alone and with three of the four combinations on the three remaining occasions. A partially balanced incomplete block design was employed and the allocation of R or the drug combinations was random. Plasma concentrations of R at intervals up to 12 h were determined by microbiological assay using Staphylococcus aureus as the test organism. The proportion (%) dose of R as R plus desacetyl R (DR) in urine excreted over the periods 0-8 and 8-12 h was also determined. Bioavailability was expressed as an index (BI) of area under time concentration curve (AUC) calculated from the plasma concentrations or proportion of dose of R excreted as R plus DR in urine with the combinations to that with R alone. The bioavailability indices based on AUC were 0.96 with RE, 0.76 with RH, 1.08 with RZ and 0.65 with REHZ. The indices based on urine estimations (0-8 h) were similar, the values being 0.94, 0.84, 0.94 and 0.75, respectively. A second investigation revealed that the decrease of bioavailability of R with H was not due to the excipients present in H tablets. Isoniazid alone or in combination with E and Z reduces the bioavailability of R. Urinary excretion data offer a simple and non invasive method for the assessment of bioavailability of R.

Bioaccessibility and bioavailability of methylmercury from seafood commonly consumed in North America: In vitro and epidemiological studies.

PubMed

Siedlikowski, Maia; Bradley, Mark; Kubow, Stan; Goodrich, Jaclyn M; Franzblau, Alfred; Basu, Niladri

2016-08-01

Methylmercury (MeHg) is a global contaminant of concern and human exposures are largely realized via seafood consumption. While it is assumed that 95-100% of the ingested MeHg from seafood reaches systemic circulation, recent in vitro studies have yielded results to suggest otherwise. Of the published studies to have characterized the bioaccessibility or bioavailability of MeHg from seafood, only a handful of seafood species have been characterized, there exists tremendous variability in data within and across species, few species of relevance to North America have been studied, and none of the in vitro studies have adapted results to an epidemiology study. The objective of the current study was two-fold: (a) to characterize in vitro MeHg bioaccessibility and bioavailability from ten commonly consumed types of seafood in North America; and (b) to apply the bioaccessibility and bioavailability data from the in vitro study to an existing human MeHg exposure assessment study. Raw seafood samples (cod, crab, halibut, salmon, scallop, shrimp, tilapia, and three tuna types: canned light, canned white, fresh) were purchased in Montreal and their MeHg concentrations generally overlapped with values reported elsewhere. The bioaccessibility of MeHg from these samples ranged from 50.1±19.2 (canned white tuna) to 100% (shrimp and scallop) of the amount measured in the raw undigested sample. The bioavailability of MeHg from these samples ranged from 29.3±10.4 (crab) to 67.4±9.7% (salmon) of the value measured in the raw undigested sample. There were significant correlations between the initial MeHg concentration in seafood with the percent of that Hg that was bioaccessible (r=-0.476) and bioavailable (r=-0.294). When the in vitro data were applied to an existing MeHg exposure assessment study, the estimated amount of MeHg absorbed into systemic circulation decreased by 25% and 42% when considering bioaccessibility and bioavailability, respectively. When the in vitro data were integrated into a regression model relating dietary MeHg intake from seafood with hair and blood Hg biomarkers, there were no differences in key model parameters when comparing the default model (that assumes 100% bioavailability) with models adjusted for the in vitro bioaccessibility and bioavailability data. In conclusion this work adds to a growing number of studies that together suggest that MeHg bioavailability from seafood may be less than 100%, but also documents the challenges when integrating such in vitro data into human exposure and risk assessments. Copyright © 2016 Elsevier Inc. All rights reserved.

Bioaccessibility and bioavailability of methylmercury from seafood commonly consumed in North America: In vitro and epidemiological studies

PubMed Central

Siedlikowski, Maia; Bradley, Mark; Kubow, Stan; Goodrich, Jaclyn M.; Franzblau, Alfred; Basu, Niladri

2016-01-01

Methylmercury (MeHg) is a global contaminant of concern and human exposures are largely realized via seafood consumption. While it is assumed that 95 to 100% of the ingested MeHg from seafood reaches systemic circulation, recent in vitro studies have yielded results to suggest otherwise. Of the published studies to have characterized the bioaccessibility or bioavailability of MeHg from seafood, only a handful of seafood species have been characterized, there exists tremendous variability in data within and across species, few species of relevance to North America have been studied, and none of the in vitro studies have adapted results to an epidemiology study. The objective of the current study was two-fold: a) to characterize in vitro MeHg bioaccessibility and bioavailability from ten commonly consumed types of seafood in North America; and b) to apply the bioaccessibility and bioavailability data from the in vitro study to an existing human MeHg exposure assessment study. Raw seafood samples (cod, crab, halibut, salmon, scallop, shrimp, tilapia, and three tuna types: canned light, canned white, fresh) were purchased in Montreal and their MeHg concentrations generally overlapped with values reported elsewhere. The bioaccessibility of MeHg from these samples ranged from 50.1±19.2 (canned white tuna) to 100% (shrimp and scallop) of the amount measured in the raw undigested sample. The bioavailability of MeHg from these samples ranged from 29.3±10.4 (crab) to 67.4±9.7% (salmon) of the value measured in the raw undigested sample. There were significant correlations between the initial MeHg concentration in seafood with the percent of that Hg that was bioaccessible (r= -0.476) and bioavailable (r=-0.294). When the in vitro data were applied to an existing MeHg exposure assessment study, the estimated amount of MeHg absorbed into systemic circulation decreased by 25% and 42% when considering bioaccessibility and bioavailability, respectively. When the in vitro data were integrated into a regression model relating dietary MeHg intake from seafood with hair and blood Hg biomarkers, there were no differences in key model parameters when comparing the default model (that assumes 100% bioavailability) with models adjusted for the in vitro bioaccessibility and bioavailability data. In conclusion this work adds to a growing number of studies that together suggest that MeHg bioavailability from seafood may be less than 100%, but also documents the challenges when integrating such in vitro data into human exposure and risk assessments. PMID:26896323

Phospholipid-based solid drug formulations for oral bioavailability enhancement: A meta-analysis.

PubMed

Fong, Sophia Yui Kau; Brandl, Martin; Bauer-Brandl, Annette

2015-12-01

Low bioavailability nowadays often represents a challenge in oral dosage form development. Solid formulations composed of drug and phospholipid (PL), which, upon contact with water, eventually form multilamellar liposomes (i.e. 'proliposomes'), are an emerging approach to solve such issue. Regarded as an 'improved' version of liposomes concerning storage stability, the potential and versatility of a range of such formulations for oral drug delivery have been extensively discussed. However, a systematic and quantitative analysis of the studies that applied solid PL for oral bioavailability enhancement is currently lacking. Such analysis is necessary for providing an overview of the research progress and addressing the question on how promising this approach can be on bioavailability enhancement. The current review performed a systematic search of references in three evidence-based English databases, Medline, Embase, and SciFinder, from the year of 1985 up till March 2015. A total of 112 research articles and 82 patents that involved solid PL-based formulations were identified. The majority of such formulations was intended for oral drug delivery (55%) and was developed to address low bioavailability issues (49%). A final of 54 studies that applied such formulations for bioavailability enhancement of 43 different drugs with poor water solubility and/or permeability were identified. These proof-of-concept studies with in vitro (n=31) and/or animal (n=23) evidences have been systematically summarized. Meta-analyses were conducted to measure the overall enhancement power (percent increase compared to control group) of solid PL formulations on drugs' solubility, permeability and oral bioavailability, which were found to be 127.4% (95% CI [86.1, 168.7]), 59.6% (95% CI [30.1, 89.0]), and 18.5% (95% CI [10.1, 26.9]) respectively. Correlations between the enhancement factors and in silico physiochemical properties of drugs were also performed to check if such approach can be used to identify the best candidates for oral solid PL formulation. In addition to scientific literature, 13 solid PL formulation-related patents that addressed the issue of low oral bioavailability have been identified and summarized; whereas no clinical study was identified from the current search. By providing systematic information and meta-analysis on studies that applied the principle of 'proliposomes' for oral bioavailability enhancement, the current review should be insightful for formulation scientists who wish to adopt the PL based approach to overcome the solubility, permeability and bioavailability issues of orally delivered drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

[Studies on formulations of Panax notoginsenosides for intranasal administration].

PubMed

Xu, Qing-fang; Fang, Xiao-ling; Chen, Dao-feng; Li, Jun-chan

2003-11-01

To develop high bioavailability preparations without irritation for Panax notoginsenosides. The effects of some additives such as microcrystalline cellulose, beta-cyclodextrin and hydroxypropyl cellulose on drug in the preparations were examined. Saponins of Panax notoginseng (PNS) was absorbed in rabbits more when administered intranasally than through other routines, and the formulations including MCC both gave high bioavailability and low irritation. Bioavailability of Panax notoginsenosides can be increased through changing routine of administration and formulations.

Chemistry, Toxicity, and Bioavailability of Copper and its Relationship to Regulation in the Marine Environment

DTIC Science & Technology

1998-11-01

The majority (70%) of commercial ship hulls still use tributyltin ( TBT ) coatings, which also contain approximately 30% to 40% copper. The Navy spends...TECHNICAL DOCUMENT 3044 November 1998 Chemistry, Toxicity , and Bioavailability of Copper and Its Relationship to Regulation in the Marine Environment...participated in a Workshop on Chemistry, Toxicity , and Bioavailability of Copper and Its Relationship to Regulation in the Marine Environment. The goal

Administration of resveratrol: What formulation solutions to bioavailability limitations?

PubMed

Amri, A; Chaumeil, J C; Sfar, S; Charrueau, C

2012-03-10

Resveratrol (3,5,4'-trihydroxystilbene), a naturally occurring polyphenol, has attracted considerable interest for its beneficial potentials for human health, which include anti-oxidant, anti-inflammatory, cardioprotective and anti-tumor activities. However, the in vivo biological effects of resveratrol appear strongly limited by its low bioavailability, which is a barrier to the development of therapeutic applications. In this context, an increasing number of recent studies have aimed at designing novel resveratrol formulations to overcome its poor solubility, limited stability, high metabolization and weak bioavailability. This review outlines physicochemical and pharmacokinetic limitations to resveratrol bioavailability, describes formulations tested for resveratrol administration, controlled release and targeting, and identifies future opportunities for resveratrol delivery. Copyright © 2011 Elsevier B.V. All rights reserved.

Bioavailability of butachlor and myclobutanil residues in soil to earthworms.

PubMed

Yu, Y L; Wu, X M; Li, S N; Fang, H; Tan, Y J; Yu, J Q

2005-05-01

To establish chemical extraction procedures for predicting bioavailability of butachlor and myclobutanil in soil, several solvent systems, including methanol, methanol-water (9:1), methanol-water (1:1), acetone-water (5:3), petroleum ether and water, were assessed for their feasibility in determining extractability of the target compounds from soil samples. Experimental data showed that the extractability of butachlor and myclobutanil by the solvents was well linearly correlated with their bioavailability to Eisenia foetida and Allolobophora caliginosa, indicating that these extraction procedures may be efficient for predicting bioavailability of the two pesticides. The concentrations of the pesticides accumulated in E. foetida and A. caliginosa varied with species, suggesting that the availability of the soil-sequestered pesticide is a species-dependent process.

Enhanced Oral Bioavailability of Pueraria Flavones by a Novel Solid Self-microemulsifying Drug Delivery System (SMEDDS) Dropping Pills.

PubMed

Guan, Qingxiang; Zhang, Guangyuan; Sun, Shilin; Fan, Hongbo; Sun, Cheng; Zhang, Shaoyuan

2016-05-01

To improve bioavailability of pueraria flavones (PF), a self-microemulsifying drug delivery system (SMEDDS) dropping pills composed of PF, Crodamol GTCC, Maisine 35-1, Cremophor RH 40, 1,2-propylene glycol and polyethylene glycol 6000 (PEG6000) was developed. Particle size, zeta potential, morphology and in vitro drug release were investigated, respectively. Pharmacokinetics, bioavailability of PF-SMEDDS dropping pills and commercial Yufengningxin dropping pills were also evaluated and compared in rats. Puerarin treated as the representative component of PF was analyzed. Dynamic light scattering showed the ability of PF-SMEDDS dropping pills to form a nanoemulsion droplet size in aqueous media. The type of media showed no significant effects on the release rate of PF. PF-SMEDDS dropping pills were able to improve the in vitro release rate of PF, and the in vitro release of these dropping pills was significantly faster than that of Yufengningxin dropping pills. There was a dramatic difference between the mean value of t1/2, peak concentration (Cmax), the area of concentration-time curve from 0 to 6 h (AUC0-6 h) of PF-SMEDDS dropping pills and that of commercial Yufengningxin dropping pills. A pharmacokinetic study showed that the bioavailability of PF was greatly enhanced by PF-SMEDDS dropping pills. The value of Cmax and relative bioavailability of PF-SMEDDS dropping pills were dramatically improved by an average of 1.69- and 2.36-fold compared with that of Yufengningxin dropping pills after gavage administration, respectively. It was concluded that bioavailability of PF was greatly improved and that PF-SMEDDS dropping pills might be an encouraging strategy to enhance the oral bioavailability of PF.

Organic Exudates Enhance Iron Bioavailability to Trichodesmium (IMS101) by Modifying Fe Speciation

NASA Astrophysics Data System (ADS)

Tohidi Farid, H.; Rose, A.; Schulz, K.

2016-02-01

Although ferrous iron (Fe (II)) is believed to be the most readily absorbed form of Fe by cells, under alkaline and oxygenated conditions typical of marine environments, the thermodynamically stable Fe(III) state dominates. In marine environments, this Fe(III) is primarily presents as organic Fe(III)L complexes whose bioavailability is highly variable. However, it has been demonstrated that some eukaryotic marine algae are able to release organic ligands into their surrounding environments that change Fe bioavailability through complexation and/or redox reactions. Nevertheless, it is unclear how Fe(II) oxidation and Fe(III) reduction rates might be modified by these exudates and how this might increase or decrease iron bioavailability to microorganisms. Here, the role of natural organic ligands excreted by the cyanobacterium Trichodesmium erythraeum on the oxidation kinetics of Fe(II) was studied using the luminol chemiluminescence technique. The oxidation kinetics of Fe(II) were examined at nanomolar Fe concentrations in presence of different concentrations of EDTA and dissolved organic carbon exuded by Trichodesmium cells. The results indicated that an increase in the concentration of exuded organic matter, and consequently L:Fe(II) ratio, resulted in decreasing rates of Fe(II) oxidation by oxygen, primarily due to formation of Fe(II) complexes. Moreover, the results demonstrated that the exudates from Trichodesmium may be able to reduce Fe(III) to the more bioavailable Fe(II) state under some circumstances. This study therefore supports the ability of microorganisms to manipulate Fe bioavailability by releasing organic compounds into the extracellular environment that retard Fe(II) oxidation rates or reducing Fe(III) species to Fe(II). It also provides new insight into the potential mechanism(s) by which Trichdesmium may acquire Fe under conditions where Fe bioavailability is otherwise limited.

Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections.

PubMed

Kutob, Leila F; Justo, Julie Ann; Bookstaver, P Brandon; Kohn, Joseph; Albrecht, Helmut; Al-Hasan, Majdi N

2016-11-01

There is paucity of data evaluating intravenous-to-oral antibiotic switch options for Gram-negative bloodstream infections (BSIs). This retrospective cohort study examined the effectiveness of oral antibiotics for definitive treatment of Gram-negative BSI. Patients with Gram-negative BSI hospitalised for <14 days at Palmetto Health Hospitals in Columbia, SC, from 1 January 2010 through 31 December 2013 and discharged on oral antibiotics were included in this study. The cohort was stratified into three groups based on bioavailability of oral antibiotics prescribed (high, ≥95%; moderate, 75-94%; and low, <75%). Kaplan-Meier analysis and multivariate Cox proportional hazards regression were used to examine treatment failure. Among the 362 patients, high, moderate and low bioavailability oral antibiotics were prescribed to 106, 179 and 77 patients, respectively, for definitive therapy of Gram-negative BSI. Mean patient age was 63 years, 217 (59.9%) were women and 254 (70.2%) had a urinary source of infection. Treatment failure rates were 2%, 12% and 14% in patients receiving oral antibiotics with high, moderate and low bioavailability, respectively (P = 0.02). Risk of treatment failure in the multivariate Cox model was higher in patients receiving antibiotics with moderate [adjusted hazard ratio (aHR) = 5.9, 95% CI 1.6-38.5; P = 0.005] and low bioavailability (aHR = 7.7, 95% CI 1.9-51.5; P = 0.003) compared with those receiving oral antimicrobial agents with high bioavailability. These data demonstrate the effectiveness of oral antibiotics with high bioavailability for definitive therapy of Gram-negative BSI. Risk of treatment failure increases as bioavailability of the oral regimen declines. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Calcium bioavailability and kinetics of calcium ascorbate and calcium acetate in rats.

PubMed

Cai, Jianwei; Zhang, Qinmin; Wastney, Meryl E; Weaver, Connie M

2004-01-01

The objective was to investigate the bioavailability and mechanism of calcium absorption of calcium ascorbate (ASC) and calcium acetate (AC). A series of studies was performed in adult Sprague-Dawley male rats. In the first study, each group of rats (n = 10/group) was assigned to one of the five test meals labeled with (45)Ca: (i) 25 mg calcium as heated ASC or (ii) unheated ASC, (iii) 25 mg calcium as unheated AC, (iv) 3.6 mg Ca as unheated ASC, or (v) unheated AC. Femur uptake indicated better calcium bioavailability from ASC than AC at both calcium loads. A 5-min heat treatment partly reduced bioavailability of ASC. Kinetic studies were performed to further investigate the mechanism of superior calcium bioavailability from ASC. Two groups of rats (n = 10/group) received oral doses of 25 mg Ca as ASC or AC. Each dose contained 20 micro Ci (45)Ca. Two additional groups of rats (n = 10/group) received an intravenous injection (iv) of 10 micro Ci (45)Ca after receiving an unlabeled oral dose of 25 mg calcium as ASC or AC. Sequential blood samples were collected over 48 hrs. Urine and fecal samples were collected every 12 hrs for 48 hrs and were analyzed for total calcium and (45)Ca content. Total calcium and (45)Ca from serum, urine, and feces were fitted by a compartment kinetics model with saturable and nonsaturable absorption pathways by WinSAAM (Windows-based Simulation Analysis and Modeling). The difference in calcium bioavailability between the two salts was due to differences in saturable rather than passive intestinal absorption and not to endogenous secretion or calcium deposition rate. The higher bioavailability of calcium ascorbate was due to a longer transit time in the small intestine compared with ASC.

Nanostructured lipid carriers versus microemulsions for delivery of the poorly water-soluble drug luteolin.

PubMed

Liu, Ying; Wang, Lan; Zhao, Yiqing; He, Man; Zhang, Xin; Niu, Mengmeng; Feng, Nianping

2014-12-10

Nanostructured lipid carriers and microemulsions effectively deliver poorly water-soluble drugs. However, few studies have investigated their ability and difference in improving drug bioavailability, especially the factors contributed to the difference. Thus, this study was aimed at investigating their efficiency in bioavailability enhancement based on studying two key processes that occur in NLC and ME during traverse along the intestinal tract: the solubilization process and the intestinal permeability process. The nanostructured lipid carriers and microemulsions had the same composition except that the former were prepared with solid lipids and the latter with liquid lipids; both were evaluated for particle size and zeta potential. Transmission electron microscopy, differential scanning calorimetry, and X-ray diffraction were performed to characterize their properties. Furthermore, in vitro drug release, in situ intestinal absorption, and in vitro lipolysis were studied. The bioavailability of luteolin delivered using nanostructured lipid carriers in rats was compared with that delivered using microemulsions and suspensions. The in vitro analysis revealed different release mechanisms for luteolin in nanostructured lipid carriers and microemulsions, although the in situ intestinal absorption was similar. The in vitro lipolysis data indicated that digestion speed and extent were higher for microemulsions than for nanostructured lipid carriers, and that more of the former partitioned to the aqueous phase. The in vivo bioavailability analysis in rats indicated that the oral absorption and bioavailability of luteolin delivered using nanostructured lipid carriers and microemulsions were higher than those of luteolin suspensions. Nanostructured lipid carriers and microemulsions improved luteolin's oral bioavailability in rats. The rapid lipid digestion and much more drug solubilized available for absorption in microemulsions may contribute to better absorption and higher bioavailability. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparisons of coarse and fine versions of two carbons for reducing the bioavailabilities of sediment-bound hydrophobic organic contaminants

USGS Publications Warehouse

Lebo, J.A.; Huckins, J.N.; Petty, J.D.; Cranor, W.L.; Ho, K.T.

2003-01-01

Coarse (whole) and finely ground Ambersorb 1500 and coarse and fine coconut charcoal were compared as to their efficiencies in scavenging organic contaminants desorbed from sediment. Aqueous slurries of a test sediment spiked (1 ppm) with p,p???-DDE (DDE), 2,2???,5,5???-tetrachlorobiphenyl (TCB), naphthalene (NAP), or phenanthrene (PHEN), and containing 1% levels of the test carbons were treated by shaking at 35 ??C while exposed to clusters of low-density polyethylene membrane (detox spiders). Controls consisted of spiked sediments and detox spiders but no added carbon of any kind and thus represented unimpeded bioavailabilities (to the spiders). After the treatments - agitation periods from 2.5 to 60 h, depending on contaminant hydrophobicity - the exposed detox spiders were analyzed. The fine carbon of either type was more effective than its coarser variant in obstructing contaminant bioavailabilities. The finer variants of both carbons obstructed the bioavailabilities of NAP and PHEN equally well as did the coarser variants of both. Whole Ambersorb 1500 and coarse coconut charcoal were similarly ineffective in intercepting TCB and DDE. Ground Ambersorb 1500 obstructed virtually all bioavailability of all four contaminants and was far more effective than fine coconut charcoal in intercepting DDE and TCB. An additional experiment compared the effectiveness of ground Ambersorb 1500 and fine coconut charcoal in obstructing the bioavailabilities from sediment of a broad array of spiked organochlorine pesticides. The performance of ground Ambersorb 1500 was again found to be superior; the bioavailable levels of each of the 27 pesticides were markedly lower in the presence of ground Ambersorb 1500 than in the presence of fine coconut charcoal.

Statistical modeling, optimization and characterization of solid self-nanoemulsifying drug delivery system of lopinavir using design of experiment.

PubMed

Patel, Grishma; Shelat, Pragna; Lalwani, Anita

2016-10-01

Lopinavir (LPV), an antiretroviral protease inhibitor shows poor bioavailability because of poor aqueous solubility and extensive hepatic first-pass metabolism. The aim of the present work was to investigate the potential of the solid self-nanoemulsifying drug delivery system (S-SNEDDS) in improving dissolution rate and oral bioavailability of LPV. Liquid SNEDDS (L-SNEDDS) of LPV were prepared using Capmul MCM C8, Cremophor RH 40 and propylene glycol and their amounts were optimized by Scheffe's mixture design. L-SNEDDS formulations were evaluated for different physicochemical and in vitro drug release parameters. S-SNEDDS were prepared by adsorbing L-SNEDDS on Neusilin US2 and characterized for solid-state properties. In vivo bioavailability of S-SNEDDS, marketed Lopinavir + Ritonavir (LPV/RTV) formulation and pure LPV was studied in Wistar rats. Stability study of S-SNEDDS was performed as per ICH guidelines. Optimized L-SNEDDS obtained by Scheffe design had drug loading 160 ± 1.15 mg, globule size 32.9 ± 1.45 nm and drug release >95% within 15 min. Solid state studies suggested the transformation of the crystalline drug to amorphous drug. The size and zeta potential of globules obtained on dilution S-SNEDDS remained similar to L-SNEEDS. In vivo bioavailability study revealed that S-SNEDDS has 2.97 and 1.54-folds higher bioavailability than pure LPV and LPV/RTV formulation, respectively. The optimized S-SNEDDS was found to be stable and had a shelf life of 2.85 years. The significant increase in drug dissolution and bioavailability by prepared SNEDDS suggest that the developed S-SNEDDS is a useful solid platform for improving oral bioavailability of poorly soluble LPV.

Pharmacokinetics and relative bioavailability of clofazimine in relation to food, orange juice and antacid.

PubMed

Nix, D E David E; Adam, R D Rodney D; Auclair, Barbara; Krueger, T S Todd S; Godo, P G Paul G; Peloquin, C A Charles A

2004-01-01

Clofazimine is potentially useful for the treatment of disease due to multidrug resistant Mycobacterium tuberculosis, as well as leprosy and certain chronic skin diseases. Its pharmacokinetics have been incompletely characterized. This study was conducted to explore issues relating to bioavailability in the presence of food, orange juice, and antacid. A 5 drug regimen consisting of clofazimine, cycloserine, ethionamide, para-aminosalicyclic acid, and pyridoxime was administered to healthy subjects four times using a four period cross-over design with two weeks washout between treatments. Subjects also received orange juice, a high fat meal, aluminum/magnesium antacid, or only water in random order with the drug regimen. The pharmacokinetics of clofazimine were assessed using individual- and population-based methods and relative bioavailability compared to fasting administration was determined. Clofazimine exhibited a sometimes prolonged and variable lag-time and considerable variability in plasma concentrations. From the population analysis (one-compartment model), the mean oral clearance was 76.7 l/h (CV=74.2%) and mean apparent volume of distribution was 1470 l (CV=36.3%). The first-order absorption rate constant ranged from 0.716 to 1.33 h(-1) (pooled CV=61.7%). Residual (proportional) error was 49.1%. Estimates of bioavailability compared to fasting administration were 145% (90% CI, 107-183%) for administration with high fat food, 82.0% (63.2-101%) for administration with orange juice, and 78.5% (55.1-102%) for administration with antacid. Administration of clofazimine with a high fat meal provides the greatest bioavailability, however, bioavailability is associated with high inter- and intra-subject variability. Both orange juice and aluminum-magnesium antacid produced a reduction in mean bioavailability of clofazimine.

Impact of wastewater derived dissolved organic carbon on reduction, mobility, and bioavailability of As(V) and Cr(VI) in contaminated soils.

PubMed

Kunhikrishnan, Anitha; Choppala, Girish; Seshadri, Balaji; Wijesekara, Hasintha; Bolan, Nanthi S; Mbene, Kenneth; Kim, Won-Il

2017-01-15

In this work, the effects of various wastewater sources (storm water, sewage effluent, piggery effluent, and dairy effluent) on the reduction, and subsequent mobility and bioavailability of arsenate [As(V)] and chromate [Cr(VI)] were compared using both spiked and field contaminated soils. Wastewater addition to soil can increase the supply of carbon, nutrients, and stimulation of microorganisms which are considered to be important factors enhancing the reduction of metal(loid)s including As and Cr. The wastewater-induced mobility and bioavailability of As(V) and Cr(VI) were examined using leaching, earthworm, and soil microbial activity tests. The rate of reduction of As(V) was much less than that of Cr(VI) both in the presence and absence of wastewater addition. Wastewater addition increased the reduction of both As(V) and Cr(VI) compared to the control (Milli-Q water) and the effect was more pronounced in the case of Cr(VI). The leaching experiment indicated that Cr(VI) was more mobile than As(V). Wastewater addition increased the mobility and bioavailability of As(V), but had an opposite effect on Cr(VI). The difference in the mobility and bioavailability of Cr(VI) and As(V) between wastewater sources can be attributed to the difference in their dissolved organic carbon (DOC) content. The DOC provides carbon as an electron donor for the reduction of As(V) and Cr(VI) and also serves as a complexing agent thereby impacting their mobility and bioavailability. The DOC-induced reduction increased both the mobility and bioavailability of As, but it caused an opposite effect in the case of Cr. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Review of Mercury Bioavailability in Humans and Fish.

PubMed

Bradley, Mark A; Barst, Benjamin D; Basu, Niladri

2017-02-10

To estimate human exposure to methylmercury (MeHg), risk assessors often assume 95%-100% bioavailability in their models. However, recent research suggests that assuming all, or most, of the ingested mercury (Hg) is absorbed into systemic circulation may be erroneous. The objective of this paper is to review and discuss the available state of knowledge concerning the assimilation or bioavailability of Hg in fish and humans. In fish, this meant reviewing studies on assimilation efficiency, that is the difference between ingested and excreted Hg over a given period of time. In humans, this meant reviewing studies that mostly investigated bioaccessibility (digestive processes) rather than bioavailability (cumulative digestive + absorptive processes), although studies incorporating absorption for a fuller picture of bioavailability were also included where possible. The outcome of this review shows that in a variety of organisms and experimental models that Hg bioavailability and assimilation is less than 100%. Specifically, 25 studies on fish were reviewed, and assimilation efficiencies ranged from 10% to 100% for MeHg and from 2% to 51% for Hg(II). For humans, 20 studies were reviewed with bioaccessibility estimates ranging from 2% to 100% for MeHg and 0.2% to 94% for Hg(II). The overall absorption estimates ranged from 12% to 79% for MeHg and 49% to 69% for Hg(II), and were consistently less than 100%. For both fish and humans, a number of cases are discussed in which factors (e.g., Hg source, cooking methods, nutrients) are shown to affect Hg bioavailability. The summaries presented here challenge a widely-held assumption in the Hg risk assessment field, and the paper discusses possible ways forward for the field.

Does the scientific underpinning of regulatory tools to estimate bioavailability of nickel in freshwaters matter? The European-wide environmental quality standard for nickel.

PubMed

Peters, Adam; Schlekat, Christian E; Merrington, Graham

2016-10-01

A bioavailability-based environmental quality standard (EQS) was established for nickel in freshwaters under the European Union's Water Framework Directive. Bioavailability correction based on pH, water hardness, and dissolved organic carbon is a demonstrable improvement on existing hardness-based quality standards, which may be underprotective in high-hardness waters. The present study compares several simplified bioavailability tools developed to implement the Ni EQS (biomet, M-BAT, and PNECPro) against the full bioavailability normalization procedure on which the EQS was based. Generally, all tools correctly distinguished sensitive waters from insensitive waters, although with varying degrees of accuracy compared with full normalization. Biomet and M-BAT predictions were consistent with, but less accurate than, full bioavailability normalization results, whereas PNECpro results were generally more conservative. The comparisons revealed important differences in tools in development, which results in differences in the predictions. Importantly, the models used for the development of PNECpro use a different ecotoxicity dataset, and a different bioavailability normalization approach using fewer biotic ligand models (BLMs) than that used for the derivation of the Ni EQS. The failure to include all of the available toxicity data, and all of the appropriate NiBLMs, has led to some significant differences between the predictions provided by PNECpro and those calculated using the process agreed to in Europe under the Water Framework Directive and other chemicals management programs (such as REACH). These considerable differences mean that PNECpro does not reflect the behavior, fate, and ecotoxicity of nickel, and raises concerns about its applicability for checking compliance against the Ni EQS. Environ Toxicol Chem 2016;35:2397-2404. © 2016 SETAC. © 2016 SETAC.

Assessment of nickel bioavailability through chemical extractants and red clover (Trifolium pratense L.) in an amended soil: Related changes in various parameters of red clover.

PubMed

Shahbaz, Ali Khan; Iqbal, Muhammad; Jabbar, Abdul; Hussain, Sabir; Ibrahim, Muhammad

2018-03-01

Application of immobilizing agents may efficiently reduce the bioavailability of nickel (Ni) in the soil. Here we report the effect of biochar (BC), gravel sludge (GS) and zeolite (ZE) as a sole treatment and their combinations on the bioavailability of Ni after their application into a Ni-polluted soil. The bioavailability of Ni after the application of immobilizing agents was assessed through an indicator plant (red clover) and chemical indicators of bioavailability like soil water extract (SWE), DTPA and Ca(NO 3 ) 2 extracts. Additionally, the effects of Ni bioavailability and immobilizing agents on the growth, physiological and biochemical attributes of red clover were also observed. Application of ZE significantly reduced Ni concentrations in all chemical extracts compared to rest of the treatments. Similarly, the combined application of BC and ZE (BC+ ZE) significantly reduced Ni concentrations, reactive oxygen species (ROS) whereas, significant enhancement in the growth, physiological and biochemical attributes along with an improvement in antioxidant defence machinery of red clover plant, compared to rest of the treatments, were observed. Furthermore, BC+ ZE treatment significantly reduced bioconcentration factor (BCF) and bioaccumulation factor (BAF) of Ni in red clover, compared to rest of the treatments. The Ni concentrations in red clover leaves individually reflected a good correlation with Ni concentrations in the extracts (SWE at R 2 =0.79, DTPA extract at R 2 =0.84 and Ca(NO 3 ) 2 extracts at R 2 =0.86). Our results indicate that combined application of ZE and BC can significantly reduce the Ni bioavailability in the soil while in parallel improve the antioxidant defence mechanism in plants. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of a Novel Simplified PBPK Absorption Model to Explain the Higher Relative Bioavailability of the OROS® Formulation of Oxybutynin.

PubMed

Olivares-Morales, Andrés; Ghosh, Avijit; Aarons, Leon; Rostami-Hodjegan, Amin

2016-11-01

A new minimal Segmented Transit and Absorption model (mSAT) model has been recently proposed and combined with intrinsic intestinal effective permeability (P eff,int ) to predict the regional gastrointestinal (GI) absorption (f abs ) of several drugs. Herein, this model was extended and applied for the prediction of oral bioavailability and pharmacokinetics of oxybutynin and its enantiomers to provide a mechanistic explanation of the higher relative bioavailability observed for oxybutynin's modified-release OROS® formulation compared to its immediate-release (IR) counterpart. The expansion of the model involved the incorporation of mechanistic equations for the prediction of release, transit, dissolution, permeation and first-pass metabolism. The predicted pharmacokinetics of oxybutynin enantiomers after oral administration for both the IR and OROS® formulations were in close agreement with the observed data. The predicted absolute bioavailability for the IR formulation was within 5% of the observed value, and the model adequately predicted the higher relative bioavailability observed for the OROS® formulation vs. the IR counterpart. From the model predictions, it can be noticed that the higher bioavailability observed for the OROS® formulation was mainly attributable to differences in the intestinal availability (F G ) rather than due to a higher colonic f abs , thus confirming previous hypotheses. The predicted f abs was almost 70% lower for the OROS® formulation compared to the IR formulation, whereas the F G was almost eightfold higher than in the IR formulation. These results provide further support to the hypothesis of an increased F G as the main factor responsible for the higher bioavailability of oxybutynin's OROS® formulation vs. the IR.

Development of an abiraterone acetate formulation with improved oral bioavailability guided by absorption modeling based on in vitro dissolution and permeability measurements.

PubMed

Solymosi, Tamás; Ötvös, Zsolt; Angi, Réka; Ordasi, Betti; Jordán, Tamás; Semsey, Sándor; Molnár, László; Ránky, Soma; Filipcsei, Genovéva; Heltovics, Gábor; Glavinas, Hristos

2017-10-30

Particle size reduction of drug crystals in the presence of surfactants (often called "top-down" production methods) is a standard approach used in the pharmaceutical industry to improve bioavailability of poorly soluble drugs. Based on the mathematical model used to predict the fraction dose absorbed this formulation approach is successful when dissolution rate is the main rate limiting factor of oral absorption. In case compound solubility is also a major factor this approach might not result in an adequate improvement in bioavailability. Abiraterone acetate is poorly water soluble which is believed to be responsible for its very low bioavailability in the fasted state and its significant positive food effect. In this work, we have successfully used in vitro dissolution, solubility and permeability measurements in biorelevant media to describe the dissolution characteristics of different abiraterone acetate formulations. Mathematical modeling of fraction dose absorbed indicated that reducing the particle size of the drug cannot be expected to result in significant improvement in bioavailability in the fasted state. In the fed state, the same formulation approach can result in a nearly complete absorption of the dose; thereby, further increasing the food effect. Using a "bottom-up" formulation method we improved both the dissolution rate and the apparent solubility of the compound. In beagle dog studies, this resulted in a ≫>10-fold increase in bioavailability in the fasted state when compared to the marketed drug and the elimination of the food effect. Calculated values of fraction dose absorbed were in agreement with the observed relative bioavailability values in beagle dogs. Copyright © 2017 Elsevier B.V. All rights reserved.

A Review of Mercury Bioavailability in Humans and Fish

PubMed Central

Bradley, Mark A.; Barst, Benjamin D.; Basu, Niladri

2017-01-01

To estimate human exposure to methylmercury (MeHg), risk assessors often assume 95%–100% bioavailability in their models. However, recent research suggests that assuming all, or most, of the ingested mercury (Hg) is absorbed into systemic circulation may be erroneous. The objective of this paper is to review and discuss the available state of knowledge concerning the assimilation or bioavailability of Hg in fish and humans. In fish, this meant reviewing studies on assimilation efficiency, that is the difference between ingested and excreted Hg over a given period of time. In humans, this meant reviewing studies that mostly investigated bioaccessibility (digestive processes) rather than bioavailability (cumulative digestive + absorptive processes), although studies incorporating absorption for a fuller picture of bioavailability were also included where possible. The outcome of this review shows that in a variety of organisms and experimental models that Hg bioavailability and assimilation is less than 100%. Specifically, 25 studies on fish were reviewed, and assimilation efficiencies ranged from 10% to 100% for MeHg and from 2% to 51% for Hg(II). For humans, 20 studies were reviewed with bioaccessibility estimates ranging from 2% to 100% for MeHg and 0.2% to 94% for Hg(II). The overall absorption estimates ranged from 12% to 79% for MeHg and 49% to 69% for Hg(II), and were consistently less than 100%. For both fish and humans, a number of cases are discussed in which factors (e.g., Hg source, cooking methods, nutrients) are shown to affect Hg bioavailability. The summaries presented here challenge a widely-held assumption in the Hg risk assessment field, and the paper discusses possible ways forward for the field. PMID:28208586

Bioavailable dissolved and particulate organic carbon flux from coastal temperate rainforest watersheds

NASA Astrophysics Data System (ADS)

Fellman, J.; Hood, E. W.; D'Amore, D. V.; Moll, A.

2017-12-01

Coastal temperate rainforest (CTR) watersheds of southeast Alaska have dense soil carbon stocks ( 300 Mg C ha-1) and high specific discharge (1.5-7 m yr-1) driven by frontal storms from the Gulf of Alaska. As a result, dissolved organic carbon (DOC) fluxes from Alaskan CTR watersheds are estimated to exceed 2 Tg yr-1; however, little is known about the export of particulate organic carbon (POC). The magnitude and bioavailability of this land-to-ocean flux of terrigenous organic matter ultimately determines how much metabolic energy is translocated to downstream and coastal marine ecosystems in this region. We sampled streamwater weekly from May through October from four watersheds of varying landcover (gradient of wetland to glacial coverage) to investigate changes in the concentration and flux of DOC and POC exported to the coastal ocean. We also used headspace analysis of CO2 following 14 day laboratory incubations to determine the flux of bioavailable DOC and POC exported from CTR watersheds. Across all sites, bioavailable DOC concentrations ranged from 0.2 to 1.9 mg L-1 but were on average 0.6 mg L-1. For POC, bioavailable concentrations ranged from below detection to 0.3 mg L-1 but were on average 0.1 mg L-1. The concentration, flux and bioavailability of DOC was higher than for POC highlighting the potential importance of DOC as a metabolic subsidy to downstream and coastal environments. Ratios of DOC to POC decreased during high flow events because the increase in POC concentrations with discharge exceeds that for DOC. Overall, our findings suggest that projected increases in precipitation and storm intensity will drive changes in the speciation, magnitude and bioavailability of the organic carbon flux from CTR watersheds.

Higher bioavailability of isoflavones after a single ingestion of a soya-based supplement than a soya-based food in young healthy males.

PubMed

Vergne, Sébastien; Bennetau-Pelissero, Catherine; Lamothe, Valérie; Chantre, Philippe; Potier, Mylène; Asselineau, Julien; Perez, Paul; Durand, Marlène; Moore, Nicholas; Sauvant, Patrick

2008-02-01

Soya isoflavones, genistein and daidzein, are the focus of numerous studies investigating their potential effects on health and results remain controversial. Bioavailability is clearly a crucial factor influencing their bioefficacy and could explain these discrepancies. This study aimed at assessing: (1) the isoflavone content of sixty-nine European soya-derivative products sold on the French market; (2) the bioavailability of isoflavones comparing supplement with food. Twelve healthy volunteers were recruited in a randomized two-way crossover trial and received 35 mg isoflavones equivalent aglycone either through supplements or through cheese, both containing different patterns of isoflavone conjugates and different daidzein:genistein ratios. A specific ELISA method was used to assess the plasma and urinary concentrations of isoflavones and thus the pharmacokinetic parameters, which were then normalized to mg of each isoflavone ingested. Results showed that the normalized Cmax of daidzein (P = 0.002) and similarly the normalized AUC0 --> infinity and Cmax of genistein (P = 0.002) from soya-based capsules were higher than that from soya-based cheese. In conclusion, this work completes studies on isoflavone bioavailability and presents new data regarding isoflavone concentrations in soya-derivative products. Assuming that isoflavone conjugation patterns do not influence isoflavone bioavailability, this study shows that isoflavones contained in capsules are more bioavailable than those contained in soya-based cheese. Although the supplement is more bioavailable, the relative importance of this is difficult to interpret as there is little evidence that supplements are biologically active in human subjects to date and further studies will be necessary for this specific supplement to prove its efficacy.

Nanostructured lipid carriers used for oral delivery of oridonin: an effect of ligand modification on absorption.

PubMed

Zhou, Xiaotong; Zhang, Xingwang; Ye, Yanghuan; Zhang, Tianpeng; Wang, Huan; Ma, Zhiguo; Wu, Baojian

2015-02-20

Oridonin (Ori) is a natural compound with notable anti-inflammation and anti-cancer activities. However, therapeutic use of this compound is limited by its poor solubility and low bioavailability. Here a novel biotin-modified nanostructured lipid carrier (NLC) was developed to enhance the bioavailability of Ori. The effect of ligand (biotin) modification on oral absorption of Ori encapsulated in NLCs was also explored. Ori-loaded NLCs (Ori-NLCs) were prepared by the melt dispersion-high pressure homogenization method. Biotin modification of Ori-NLCs was achieved by EDC and NHS in aqueous phase. The obtained biotin-decorated Ori-NLCs (Bio-Ori-NLCs) were 144.9nm in size with an entrapment efficiency of 49.54% and a drug load of 4.81%. Oral bioavailability was enhanced by use of Bio-Ori-NLCs with a relative bioavailability of 171.01%, while the value of non-modified Ori-NLCs was improved to 143.48%. Intestinal perfusion showed that Ori solution unexpectedly exhibited a moderate permeability, indicating that permeability was not a limiting factor of Ori absorption. Ori could be rapidly metabolized that was the main cause of low bioavailability. However, there was a difference in the enhancement of bioavailability between Bio-Ori-NLCs and conventional NLCs. Although severe lipolyses happened both on Bio-Ori-NLCs and non-modified NLCs, the performance of Bio-Ori-NLCs in the bioavailability improvement was more significant. Overall, Bio-Ori-NLCs can further promote the oral absorption of Ori by a ligand-mediated active transport. It may be a promising carrier for the oral delivery of Ori. Copyright © 2014 Elsevier B.V. All rights reserved.

Thiol-Based Selective Extraction Assay to Comparatively Assess Bioavailable Mercury in Sediments

PubMed Central

Ticknor, Jonathan L.; Kucharzyk, Katarzyna H.; Porter, Kaitlyn A.; Deshusses, Marc A.; Hsu-Kim, Heileen

2015-01-01

Abstract Bioaccumulation of methylmercury in the aquatic food web is governed in part by the methylation of inorganic divalent mercury (Hg(II)) by anaerobic microorganisms. In sulfidic settings, a small fraction of total Hg(II) is typically bioavailable to methylating microorganisms. Quantification of this fraction is difficult due to uncertainties in the speciation of Hg(II) and the mechanisms of uptake by methylating microbes. However, recent studies have shown that the bioavailable fraction is likely to include a portion of Hg(II) associated with solid phases, that is, nanostructured mercuric sulfides. Moreover, addition of thiols to suspensions of methylating cultures coincides with increased uptake into cells and methylmercury production. Here, we present a thiol-based selective extraction assay to provide information on the bioavailable Hg fraction in sediments. In the procedure, sediment samples were exposed to a nitrogen-purged solution of glutathione (GSH) for 30 min and the amount of GSH-leachable mercury was quantified. In nine sediment samples from a marine location, the relative GSH-leachable mercury concentration was strongly correlated to the relative amount of methylmercury in the sediments (r2=0.91, p<0.0001) across an order of magnitude of methylmercury concentration values. The approach was further applied to anaerobic sediment slurry microcosm experiments in which sediments were cultured under the same microbial growth conditions but were amended with multiple forms of Hg with a known spectrum of bioavailability. GSH-leachable Hg concentrations increased with observed methylmercury concentrations in the microcosms, matching the trend of species bioavailability in our previous work. Results suggest that a thiol-based selective leaching approach is an improvement compared with other proposed methods to assess Hg bioavailability in sediment and that this approach could provide a basis for comparison of sites where Hg methylation is a concern. PMID:26244001

Iron bioavailability and weight gains to iron-deficient rats fed a commonly consumed Tunisian meal 'bean seeds ragout' with or without beef and with green or black tea decoction.

PubMed

Hamdaoui, Mohamed Hédi; Chabchoub, Soufia; Hédhili, Abderrazek

2003-01-01

The Fe bioavailability and the weight gains were evaluated in rats fed a commonly consumed Tunisian meal 'bean seeds ragout' (BSR), with or without beef and with black or green tea decoction. The Fe bioavailability was evaluated in Fe-deficient rats by the hemoglobin repletion method and the Fe stored in the liver. The addition of beef to the BSR significantly increased the Fe bioavailability from this meal by 147% and the reserve of Fe stored in the liver by 77% (P < 0.001). In contrast, both black and green tea decoctions caused a significant decrease of the Fe bioavailability from BSR meal (-19.6 +/- 4.9% and -14.9 +/- 4.1%, respectively). The reserve of Fe stored in the liver was significantly lower in the BSR, the black and the green tea groups than in the positive control group (FeSO4). The weight gains were significantly lower in the black and the green tea groups (3.9 +/- 5.7 g, 13 +/- 1.9 g, respectively) than in the BSR group (24.9 +/- 6 g). The addition of beef to BSR meal counteracted the inhibitory effect of the kidney bean and considerably improved the Fe bioavailability and the Fe stored in the liver of rats. The green tea decoction, which constitutes an important source of antioxidant factors, had the same inhibitory effect as the black tea decoction on the Fe bioavailability from BSR meal. In addition, both black and green teas significantly reduced the weight gains, where the black tea decoction has the most effect.

Bioavailability and mobility of organic contaminants in soil: new three-step ecotoxicological evaluation.

PubMed

Prokop, Zbyněk; Nečasová, Anežka; Klánová, Jana; Čupr, Pavel

2016-03-01

A novel approach was developed for rapid assessment of bioavailability and potential mobility of contaminants in soil. The response of the same test organism to the organic extract, water extract and solid phase of soil was recorded and compared. This approach was designed to give an initial estimate of the total organic toxicity (response to organic extractable fraction), as well as the mobile (response to water extract) and bioavailable fraction (response to solid phase) of soil samples. Eighteen soil samples with different levels of pollution and content of organic carbon were selected to validate the novel three-step ecotoxicological evaluation approach. All samples were chemically analysed for priority contaminants, including aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), hexachlorocyclohexane (HCH) and dichlordiphenyltrichloroethane (DDT). The ecotoxicological evaluation involved determination of toxicity of the organic, mobile and bioavailable fractions of soil to the test organism, bacterium Bacillus cereus. We found a good correlation between the chemical analysis and the toxicity of organic extract. The low toxicity of water extracts indicated low water solubility, and thus, low potential mobility of toxic contaminants present in the soil samples. The toxicity of the bioavailable fraction was significantly greater than the toxicity of water-soluble (mobile) fraction of the contaminants as deduced from comparing untreated samples and water extracts. The bioavailability of the contaminants decreased with increasing concentrations of organic carbon in evaluated soil samples. In conclusion, the three-step ecotoxicological evaluation utilised in this study can give a quick insight into soil contamination in context with bioavailability and mobility of the contaminants present. This information can be useful for hazard identification and risk assessment of soil-associated contaminants. Graphical Abstract New three-step ecotoxicological evaluation by using the same organism.

Viscoelastic Emulsion Improved the Bioaccessibility and Oral Bioavailability of Crystalline Compound: A Mechanistic Study Using in Vitro and in Vivo Models.

PubMed

Ting, Yuwen; Jiang, Yike; Lan, Yaqi; Xia, Chunxin; Lin, Zhenyu; Rogers, Michael A; Huang, Qingrong

2015-07-06

The oral bioavailability of hydrophobic compound is usually limited by the poor aqueous solubility in the gastrointestinal (GI) tract. Various oral formulations were developed to enhance the systemic concentration of such molecules. Moreover, compounds with high melting temperature that appear as insoluble crystals imposed a great challenge to the development of oral vehicle. Polymethoxyflavone, an emerging category of bioactive compounds with potent therapeutic efficacies, were characterized as having a hydrophobic and highly crystalline chemical structure. To enhance the oral dosing efficiency of polymethoxyflavone, a viscoelastic emulsion system with a high static viscosity was developed and optimized using tangeretin, one of the most abundant polymethoxyflavones found in natural sources, as a modeling compound. In the present study, different in vitro and in vivo models were used to mechanistically evaluate the effect of emulsification on oral bioavailability of tangeretin. In vitro lipolysis revealed that emulsified tangeretin was digested and became bioaccessible much faster than unprocessed tangeretin oil suspension. By simulating the entire human GI tract, TNO's gastrointestinal model (TIM-1) is a valuable tool to mechanistically study the effect of emulsification on the digestion events that lead to a better oral bioavailability of tangeretin. TIM-1 result indicated that tangeretin was absorbed in the upper GI tract. Thus, a higher oral bioavailability can be expected if the compound becomes bioaccessible in the intestinal lumen soon after dosing. In vivo pharmacokinetics analysis on mice again confirmed that the oral bioavailability of tangeretin increased 2.3 fold when incorporated in the viscoelastic emulsion than unformulated oil suspension. By using the combination of in vitro and in vivo models introduced in this work, the mechanism that underlie the effect of viscoelastic emulsion on the oral bioavailability of tangeretin was well-elucidated.

Bioavailability and Pharmacodynamics of Promethazine on Long Duration Missions to the International Space Station

NASA Technical Reports Server (NTRS)

Putcha, Lakshmi; Boyd, Jason L.; Cintron, Nitza; Berens, Kurt L.

2004-01-01

Space motion sickness (SMS) is often treated in space with promethazine (PMZ). Common side effects of PMZ administration (50 mg intramuscular) on the ground are drowsiness and impaired cognitive performance. Anecdotal reports indicate that these effects are absent or less pronounced in space. This suggests that the availability of PMZ to the body (bioavailability) and/or the response of the body to PMZ (pharmacodynamics) may change during space flight. Opportunities for clinical research in space are limited. The study described here is our response to a NASA Research Announcement for proposals for flight-based research needed to improve, or answer specific questions about, diagnosis and therapy during space flight, and post-flight rehabilitation. We propose here to evaluate noninvasive methods for determining the bioavailability and pharmacodynamics of PMZ. The specific objectives of the proposed research are to 1) compare pharmacokinetic and pharmacodynamic parameters of PMZ, estimated from saliva and plasma levels after administration of PMZ, 2) estimate the relative bioavailability of the three dosage forms of PMZ that are often administered to control motion sickness symptoms in space, and 3) establish the dose-response relationship of PMZ. We will estimate the bioavailability of an intramuscular injection (IM), oral tablet, and rectal suppository of PMZ in noma1 subjects during ambulatory and antiorthostatic bed rest (ABR) conditions using novel stable isotope techniques. We will compare and contrast the bioavailability of PMZ during normal and microgravity conditions to examine changes in drug absorption and bioavailability during microgravit. Results of this study will validate methods for an approved in-flight investigation with this medication awaiting an opportunity for manifestation..

Fabrication and in vivo evaluation of Nelfinavir loaded PLGA nanoparticles for enhancing oral bioavailability and therapeutic effect

PubMed Central

Venkatesh, D. Nagasamy; Baskaran, Mahendran; Karri, Veera Venkata Satyanarayana Reddy; Mannemala, Sai Sandeep; Radhakrishna, Kollipara; Goti, Sandip

2015-01-01

Nelfinavir mesylate (NFV) is an anti-viral drug, used in the treatment of Acquired Immunodeficiency Syndrome (AIDS). Poor oral bioavailability and shorter half-life (3.5–5 h) remain a major clinical limitation of NFV leading to unpredictable drug bioavailability and frequent dosing. In this context, the objective of the present study was to formulate NFV loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), which can increase the solubility and oral bioavailability along with sustained release of the drug. NFV loaded PLGA-NPs were prepared by nanoprecipitation method using PLGA and Poloxomer 407. The prepared NPs were evaluated for particle size, zeta potential, morphology, drug content, entrapment efficiency (EE) and in vitro dissolution studies. Oral bioavailability studies were carried out in New Zealand rabbits by administering developed NFV PLGA-NPs and pure drug suspension. PLGA-NPs prepared by using 1:4 ratio of drug and PLGA, with a stirring rate of 1500 rpm for 4 h. The prepared NPs were in the size of 185 ± 0.83 nm with a zeta potential of 28.7 ± 0.09 mV. The developed NPs were found to be spherical with uniform size distribution. The drug content and EE of the optimized formulation were found to be 36 ± 0.19% and 72 ± 0.47% respectively. After oral administration of NFV PLGA-NPs, the relative bioavailability was enhanced about 4.94 fold compared to NFV suspension as a control. The results describe an effective strategy for oral delivery of NFV loaded PLGA NPs that helps in enhancing bioavailability and reduce the frequency of dosing. PMID:26702262

Boosting the bioavailability of hydrophobic nutrients, vitamins, and nutraceuticals in natural products using excipient emulsions.

PubMed

McClements, David Julian; Saliva-Trujillo, Laura; Zhang, Ruojie; Zhang, Zipei; Zou, Liqiang; Yao, Mingfei; Xiao, Hang

2016-10-01

Many highly hydrophobic bioactives, such as non-polar nutrients, nutraceuticals, and vitamins, have a relatively low or variable oral bioavailability. The poor bioavailability profile of these bioactives may be due to limited bioaccessibility, poor absorption, and/or chemical transformation within the gastrointestinal tract (GIT). The bioavailability of hydrophobic bioactives can be improved using specially designed oil-in-water emulsions consisting of lipid droplets dispersed within an aqueous phase. The bioactives may be isolated from their natural environment and then incorporated into the lipid phase of emulsion-based delivery systems. Alternatively, the bioactives may be left in their natural environment (e.g., fruits or vegetables), and then ingested with emulsion-based excipient systems. An excipient emulsion may have no inherent health benefits itself, but it boosts the biological activity of bioactive ingredients co-ingested with it by altering their bioaccessibility, absorption, and/or chemical transformation. This review discusses the design and fabrication of excipient emulsions, and gives some examples of recent research that demonstrates their potential efficacy for improving the bioavailability of hydrophobic bioactives. The concept of excipient emulsions could be used to formulate emulsion-based food products (such as excipient sauces, dressings, dips, creams, or yogurts) specifically designed to increase the bioavailability of bioactive agents in natural foods, such as fruits and vegetables. Copyright © 2015 Elsevier Ltd. All rights reserved.

Using soil properties to predict in vivo bioavailability of lead in soils.

PubMed

Wijayawardena, M A Ayanka; Naidu, Ravi; Megharaj, Mallavarapu; Lamb, Dane; Thavamani, Palanisami; Kuchel, Tim

2015-11-01

Soil plays a significant role in controlling the potential bioavailability of contaminants in the environment. In this study, eleven soils were used to investigate the relationship between soil properties and relative bioavailability (RB) of lead (Pb). To minimise the effect of source of Pb on in vivo bioavailability, uncontaminated study soils were spiked with 1500 mg Pb/kg soil and aged for 10-12 months prior to investigating the relationships between soil properties and in vivo RB of Pb using swine model. The biological responses to oral administration of Pb in aqueous phase or as spiked soils were compared by applying a two-compartment pharmacokinetic model to blood Pb concentration. The study revealed that RB of Pb from aged soils ranged from 30±9% to 83±7%. The very different RB of Pb in these soils was attributed to variations in the soils' physico-chemical properties. This was established using sorption studies showing: firstly, Freundlich partition coefficients that ranged from 21 to 234; and secondly, a strongly significant (R(2)=0.94, P<0.001) exponential relationship between RB and Freundlich partition coefficient (Kd). This simple exponential model can be used to predict relative bioavailability of Pb in contaminated soils. To the best of our knowledge, this is the first such model derived using sorption partition coefficient to predict the relative bioavailability of Pb. Copyright © 2015 Elsevier Ltd. All rights reserved.

Assessing bioavailability levels of metals in effluent-affected rivers: effect of Fe(III) and chelating agents on the distribution of metal speciation.

PubMed

Han, Shuping; Naito, Wataru; Masunaga, Shigeki

To assess the effects of Fe(III) and anthropogenic ligands on the bioavailability of Ni, Cu, Zn, and Pb, concentrations of bioavailable metals were measured by the DGT (diffusive gradients in thin films) method in some urban rivers, and were compared with concentrations calculated by a chemical equilibrium model (WHAM 7.0). Assuming that dissolved Fe(III) (<0.45 μm membrane filtered) was in equilibrium with colloidal iron oxide, the WHAM 7.0 model estimated that bioavailable concentrations of Ni, Cu, and Zn were slightly higher than the corresponding values estimated assuming that dissolved Fe(III) was absent. In contrast, lower levels of free Pb were predicted by the WHAM 7.0 model when dissolved Fe(III) was included. Estimates showed that most of the dissolved Pb was present as colloidal iron-Pb complex. Ethylene-diamine-tetra-acetic acid (EDTA) concentrations at sampling sites were predicted from the relationship between EDTA and the calculated bioavailable concentration of Zn. When both colloidal iron and predicted EDTA concentrations were included in the WHAM 7.0 calculations, dissolved metals showed a strong tendency to form EDTA complexes, in the order Ni > Cu > Zn > Pb. With the inclusion of EDTA, bioavailable concentrations of Ni, Cu, and Zn predicted by WHAM 7.0 were different from those predicted considering only humic substances and colloidal iron.

Rivaroxaban crushed tablet suspension characteristics and relative bioavailability in healthy adults when administered orally or via nasogastric tube.

PubMed

Moore, Kenneth T; Krook, Mark A; Vaidyanathan, Seema; Sarich, Troy C; Damaraju, C V; Fields, Larry E

2014-07-01

Because some patients have difficulty swallowing a whole tablet, we investigated the relative bioavailability of a crushed 20 mg rivaroxaban tablet and of 2 alternative crushed tablet dosing strategies. Stability and nasogastric (NG) tube adsorption characteristics of a crushed rivaroxaban tablet were assessed. Then, in 55 healthy adults, relative bioavailability of rivaroxaban administered orally as a whole tablet (Reference [Whole-Oral]), crushed tablet in applesauce suspension (Crushed-Oral), or crushed tablet in water suspension via NG tube (Crushed-NG) were determined. There were no significant changes in mean percent of non-degraded rivaroxaban recovered over 4 hours from crushed tablet suspensions (>98.4% recovery across all suspensions and time points) or after NG tube exposure (recovery: 99.1% for silicone and 98.9% for polyvinyl chloride NG tubes). Relative bioavailability was similar between Crushed-Oral and Reference dosing (Cmax and AUC∞ were within the 80-125% bioequivalence limits). Relative bioavailability was also similar between the Crushed-NG and Reference dosing (AUC∞ was within bioequivalence limits; Cmax [90% CI range: 78.5-85.8%] was only slightly below the 80% lower bioequivalence limit). A crushed rivaroxaban tablet was stable and when administered orally or via NG tube, displayed similar relative bioavailability compared to a whole tablet administered orally. © 2014, The American College of Clinical Pharmacology.

A Helix-Stabilizing Linker Improves Subcutaneous Bioavailability of a Helical Peptide Independent of Linker Lipophilicity

PubMed Central

Zhang, Liang; Navaratna, Tejas; Thurber, Greg M.

2016-01-01

Stabilized peptides address several limitations to peptide-based imaging agents and therapeutics such as poor stability and low affinity due to conformational flexibility. There is also active research in developing these compounds for intracellular drug targeting, and significant efforts have been invested to determine the effects of helix stabilization on intracellular delivery. However, much less is known about the impact on other pharmacokinetic parameters such as plasma clearance and bioavailability. We investigated the effect of different fluorescent helix-stabilizing linkers with varying lipophilicity on subcutaneous (SC) bioavailability using the glucagon-like peptide-1 (GLP-1) receptor ligand exendin as a model system. The stabilized peptides showed significantly higher protease resistance and increased bioavailability independent of linker hydrophilicity, and all subcutaneously delivered conjugates were able to successfully target the islets of Langerhans with high specificity. The lipophilic peptide variants had slower absorption and plasma clearance than their respective hydrophilic conjugates, and the absolute bioavailability was also lower likely due to the longer residence times in the skin. The ease and efficiency of double-click helix stabilization chemistries is a useful tool for increasing the bioavailability of peptide therapeutics, many of which suffer from rapid in vivo protease degradation. Helix stabilization using linkers of varying lipophilicity can further control SC absorption and clearance rates to customize plasma pharmacokinetics. PMID:27327034

In vivo application of chitosan to improve bioavailability of cyanocobalamin, a form of vitamin B12, following intraintestinal administration in rats.

PubMed

Goto, Yuko; Masuda, Ayumi; Aiba, Tetsuya

2015-04-10

The effect of chitosan on the intestinal absorption of cyanocobalamin (VB12), a stable form of vitamin B12, was investigated in vivo in rats, with the aim of improving the oral bioavailability of VB12 for anemia treatment in patients with gastrectomy. The bioavailability was evaluated based on the plasma concentration profile of VB12 following intraintestinal administration of the VB12 solution containing chitosan at various concentrations. The bioavailability of VB12 was 0.6±0.2% when the chitosan-free VB12 solution was administered, while it increased to 10.5±3.3% when chitosan was dissolved in the VB12 solution at a concentration of 1%. The bioavailability of VB12 increases with the chitosan concentration, in which chitosan seems to augment the amount of VB12 absorbed without affecting the absorption rate constant of VB12. It was also shown that the bioavailability of VB12 does not increase further when the degree of chitosan deacetylation is increased from 83 to 100% by substitutively employing the fully deacetylated chitosan. These findings suggest that the oral administration of VB12 with readily available chitosan may be a practical approach for anemia treatment in patients with gastrectomy. Copyright © 2015 Elsevier B.V. All rights reserved.

The pharmacokinetics study of ginkgolide A, B and the effect of food on bioavailability after oral administration of ginkgolide extracts in beagle dogs.

PubMed

Aa, Lixiang; Fei, Fei; Tan, Zhaoyi; Aa, Jiye; Wang, Guangji; Liu, Changxiao

2018-06-01

Ginkgolides are the primarily active components in Ginkgo products that are popular worldwide. However, few studies have evaluated the bioavailability of ginkgolides and the effects of food on it after oral administration of ginkgolides. In this article, pharmacokinetics and absolute bioavailability of the primary components in ginkgolide extracts were evaluated in beagle dogs. For the first time, we showed that the fed dogs had significantly increased area under the concentration-time curve and peak concentration relative to the fasted dogs based on the data from both the prototype form and total lactones of ginkgolide A (GA) and ginkgolide B (GB). In terms of the free form of the prototype ginkgolides, the absolute bioavailabilities of GA and GB were 34.8 and 5.2% in the fasted dogs, respectively, which significantly increased to an average of 78.6 and 17.0%, respectively, in the fed dogs. In terms of acidified total lactones, the absolute bioavailabilities of GA and GB were 7.5 and 14.5% in the fed dogs, and the percentages declined to 4.1 and 3.7% in the fasted dogs, respectively. It was suggested that administration of ginkgolides after meals could promote the in vivo exposure and the bioavailability of GA and GB, and hence potentially enhance therapeutic outcomes. Copyright © 2018 John Wiley & Sons, Ltd.

Prediction of the bioavailability of potentially toxic elements in freshwaters. Comparison between speciation models and passive samplers.

PubMed

Sierra, Jordi; Roig, Neus; Giménez Papiol, Gemma; Pérez-Gallego, Elena; Schuhmacher, Marta

2017-12-15

The aim of this work is to predict the bioavailability of the Potentially Toxic Elements (PTEs) Cd, Pb, Hg, Ni, Cu, Zn, As, Cr and Se in 6 sites within the Ebro River basin. In situ Diffusive gradient in thin-films (DGTs) and classical sampling have been used and compared. The potentially bioavailable fractions of each PTE was estimated by modelling their chemical speciation using three programs (WHAM 7.0, Visual MINTEQ 3.1 and Bio-met), following the suggestions published in recent European regulations. Results of the equilibrium-based models WHAM 7.0 and Visual MINTEQ 3.1 indicate that As, Cd, Ni, Se and Zn, predominate as free metals ions or forming inorganic soluble complexes. Copper, Pb and Hg bioavailability is conditioned by their affinity to dissolved humic substances. According to Visual MINTEQ 3.1, Cr is subjected to redox reactions, being Cr (VI) present (at low concentrations) in the studied rivers. According to Bio-met model, the bioavailability of Cu and Zn is highly influenced by soluble organic matter and water hardness, respectively. For most PTEs, the bioavailability estimated by deploying DGTs in river waters tends to be slightly lower than the estimation obtained with speciation models, since in real conditions more environmental factors take place comparing to the finite number of parameters considered in models. Copyright © 2017 Elsevier B.V. All rights reserved.

Napoli and Volcanism - Vesuvius and Mt. Etna

NASA Technical Reports Server (NTRS)

2002-01-01

For more than 240 million years the region now known as Italy has been the scene of episodic volcanic activity. East-southeast of Napoli (Naples) stands the imposing cone of Vesuvius, which erupted explosively in 79 A.D. to bury Pompeii and Herculaneum. More recently, when the crew of Space Shuttle mission STS-104 captured this view, Mt. Etna (Sicily, not seen in this image, but photographed the day before) was spewing ash and gas thousands of meters into the air, some of which can be seen as a brownish smear over Isola d' Ischia and the Tyrrhenian Sea. The Appenine ranges extend from northern Italy, down the boot of the peninsula and westward into Sicily. This photograph of the Appenino Napoletano is part of an 18-frame stereophoto mapping strip that spans the entire mountain chain. The almost 1200-km-long belt of volcanoes and folded/faulted mountains is a result of the ongoing collision of Africa and Eurasia, accompanied by the progressive closing of the Mediterranean Sea. Using overlapping pairs of stereophotos, and a special viewer, scientists can get a three-dimensional perspective on the ranges that surpasses any image viewed alone. For more information, see another image of Mt. Vesuvius, taken by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER). References: Behncke, Boris, 2000, Vesuvio - The eruption of A.D. 79: Italy's Volcanoes - The Cradle of Volcanology [http://www.geo.mtu.edu/boris/VESUVIO_79.html (accessed 10/18/01)] Doglioni, C., and Flores, G., 1997, Italy, in Moores, E. M., and Fairbridge, R. W., editors, Encyclopedia of European and Asian Regional Geology: London, Chapman and Hall, p. 414-435 Shuttle photograph STS104-710-60 was taken 23 July 2001 from the orbiter Atlantis using a Hasselblad camera with 250-mm lens. The image is provided by the Earth Sciences and Image Analysis Laboratory at Johnson Space Center. The entire mapping series (of frames numbered in sequence from 50 through 68) can also be downloaded from the database and printed for stereo viewing and analysis. Searching and viewing of additional images taken by astronauts and cosmonauts is available at the NASA-JSC Gateway to Astronaut Photography of Earth.

The role of sorption and bacteria in mercury partitioning and bioavailability in artificial sediments.

PubMed

Zhong, Huan; Wang, Wen-Xiong

2009-03-01

This study compared the relative importance of three types of sorption (organic matter-particle, mercury-organic matter and mercury-particle) in controlling the overall mercury partitioning and bioavailability in sediments. We found that all three types of sorption were important for both inorganic mercury (Hg) and methylated mercury (MeHg). Mercury-particle sorption was more important than mercury-fulvic acid (FA) sorption in increasing the mercury concentrations with increasing aging. Bioavailability (quantified by gut juice extraction from sipunculans) was mainly controlled by mercury-particle sorption, while FA-particle and mercury-FA sorption were not as important, especially for MeHg. Bacterial activity also increased the partitioning of Hg or MeHg in the sediments and was further facilitated by the presence of organic matter. The bioavailability of Hg or MeHg from sediments was only slightly influenced by bacterial activity. This study highlights the importance of sorption from various sources (especially mercury-particle sorption) as well as bacteria in controlling the partitioning and bioavailability of Hg or MeHg in sediments.

Bioavailability of curcumin: problems and promises.

PubMed

Anand, Preetha; Kunnumakkara, Ajaikumar B; Newman, Robert A; Aggarwal, Bharat B

2007-01-01

Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.

Enhanced oral bioavailability and anticancer efficacy of fisetin by encapsulating as inclusion complex with HPβCD in polymeric nanoparticles.

PubMed

Kadari, Amrita; Gudem, Sagarika; Kulhari, Hitesh; Bhandi, Murali Mohan; Borkar, Roshan M; Kolapalli, Venkata Ramana Murthy; Sistla, Ramakrishna

2017-11-01

Fisetin (FST), a potent anticancer phytoconstituent, exhibits poor aqueous solubility and hence poor bioavailability. The aim of the present study is to improve the oral bioavailability of FST by encapsulating into PLGA NPs (poly-lactide-co-glycolic acid nanoparticles) as a complex of HPβCD (hydroxyl propyl beta cyclodextrin) and to assess its anti-cancer activity against breast cancer cells. FST-HPβCD inclusion complex (FHIC) was prepared and the supramolecular complex formation was characterized by FTIR, DSC, PXRD and 1 H NMR. FHIC encapsulated PLGA nanoparticles (FHIC-PNP) were prepared and were studied for in vitro anticancer activity, cellular uptake, apoptosis and reactive oxygen species generation in MCF-7 human breast cancer cells. Comparative bioavailability of FST was determined after oral administration in C57BL6 mice as pure FST and FHIC-PNP. The results revealed that FHIC-PNP not only enhanced the anti-cancer activity and apoptosis of FST against MCF-7 cells but also improved its oral bioavailability, as demonstrated by increased peak plasma concentration and total drug absorbed.

Preparation and evaluation of self-microemulsifying drug delivery system containing vinpocetine.

PubMed

Cui, Shu-Xia; Nie, Shu-Fang; Li, Li; Wang, Chang-Guang; Pan, Wei-San; Sun, Jian-Ping

2009-05-01

The main purpose of current investigation is to prepare a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of vinpocetine, a poorly water-soluble drug. Suitable vehicles were screened by determining the solubility of vinpocetine in them. Certain surfactants were selected according to their emulsifying ability with different oils. Ternary phase diagrams were used to identify the efficient self-microemulsifying region and to screen the effect of surfactant/cosurfactant ratio (K(m)). The optimized formulation for in vitro dissolution and bioavailability assessment was oil (ethyl oleate, 15%), surfactant (Solutol HS 15, 50%), and cosurfactant (Transcutol P, 35%). The release rate of vinpocetine from SMEDDS was significantly higher than that of the commercial tablet. Pharmacokinetics and bioavailability of SMEDDS were evaluated. It was found that the oral bioavailability of vinpocetine of SMEDDS was 1.72-fold higher as compared with that of the commercial tablet. These results obtained demonstrated that vinpocetine absorption was enhanced significantly by employing SMEDDS. Therefore, SMEDDS might provide an efficient way of improving oral bioavailability of poorly water-soluble drugs.

Cooking and Fe fortification have different effects on Fe bioavailability of bread and tortillas.

PubMed

Hernández, Miguel; Sousa, Virginia; Villalpando, Salvador; Moreno, Ambar; Montalvo, Irene; López-Alarcón, Mardya

2006-02-01

To identify iron sources for wheat- (WF) and corn-flour (CF) fortification taking into account the effect of cooking. Sixty-six Fe-depleted rats were replete with various Fe sources. Fe bioavailability and utilization in wheat bread (WB) and corn tortillas (CT) fortified with various Fe sources was assessed after the depletion and repletion periods. Baking decreased the phytates content of WF by 97%. Improvements in Hb and FeHb were greater in rats fed unfortified WB than in those fed unfortified WF. Fe fortification had no benefit. In contrast, phytates content was unchanged by tortilla preparation, but fortification improved iron availability. Iron bioavailability indicators were best in rats fed CT fortified with ferrous sulfate and NaFe(III)EDTA than in those fed unfortified CT or CT plus reduced Fe. We concluded that baking WF bread improved the bioavailability of native Fe with no further effect of fortification. Pan-cooking of lime-treated CF did not improve Fe bioavailability, but addition of Ferrous sulfate or NaFe(III)EDTA did it, despite the high phytate and calcium content of tortillas.

Bioavailability of classical and novel flame retardants: Effect of fullerene presence.

PubMed

Santín, Giselle; Eljarrat, Ethel; Barceló, Damià

2016-09-15

To understand the behavior of some emerging flame retardants (FRs) in the environment, a nonexhaustive extraction using Tenax was applied to study their behavior in aquatic ecosystems. Desorption of 8 polybrominated diphenyl ethers (PBDEs), 8 methoxylated PBDEs, 3 emerging brominated FRs and 6 halogenated norbornenes from sediments spiked in the laboratory was studied. Results showed that emerging FRs have a similar bioavailability than that of legacy FRs, already banned. In addition, some parameters such as sediment total organic carbon (TOC), aging or nanomaterial (NMs) presence in the sediment were modified in order to study their effects on the bioavailability of FRs. Bioavailability increases with a diminution of sediment TOC, while diminishes with an increase of aging. The study of effect of NM presence was performed at three different pH (acidic, neutral and basic), and for the three scenarios, FR bioavailability decreased with NM presence. The retention of pollutants in the sediment seems to be favoured by NM presence, minimizing their impact on living organisms. Copyright © 2016 Elsevier B.V. All rights reserved.

Solid dispersion tablets of breviscapine with polyvinylpyrrolidone K30 for improved dissolution and bioavailability to commercial breviscapine tablets in beagle dogs.

PubMed

Cong, Wenjuan; Shen, Lan; Xu, Desheng; Zhao, Lijie; Ruan, Kefeng; Feng, Yi

2014-09-01

Breviscapine, one of cardiovascular drugs extracted from a Chinese herb Erigeron breviscapinus, has been frequently used to treat cardiovascular diseases such as hypertension, angina pectoris, coronary heart disease and stroke. However, its poor water solubility and low bioavailability in vivo severely restrict the clinical application. To overcome these drawbacks, breviscapine solid dispersion tablets consisting of breviscapine, polyvinylpyrrolidone K30 (PVP K30), microcrystalline cellulose and crospovidone were appropriately prepared. In vitro dissolution profiles showed that breviscapine released percentage of solid dispersion tablets reached 90 %, whereas it was only 40 % for commercial breviscapine tablets. Comparative pharmacokinetic study between solid dispersion tablets and commercial products was investigated on the normal beagle dogs after oral administration. Results showed that the bioavailability of breviscapine was greatly increased by 3.45-fold for solid dispersion tablets. The greatly improved dissolution rate and bioavailability might be attributed to intermolecular hydrogen bonding reactions between PVP K30 and scutellarin. These findings suggest that our solid dispersion tablets can greatly improve the bioavailability as well as the dissolution rate of breviscapine.

Food Stabilizing Antioxidants Increase Nutrient Bioavailability in the in Vitro Model.

PubMed

Mika, Magdalena; Wikiera, Agnieszka; Antończyk, Anna; Grabacka, Maja

2017-01-01

We investigated whether antioxidants may enhance bioavailability of lipids and carbohydrates and therefore increase the risk of obesity development. We tested how supplementation with antioxidants (0.01% butylated hydroxytoluene [BHT], α-tocopherol, and green tea catechins) of a diet containing butter and wheat bread affects bioavailability of fats and carbohydrates. The absorption of the in vitro digested diet was estimated in the intestinal epithelia model of the Caco-2 cells cultured in Transwell chambers. In the case of the antioxidant-supplemented diets, we observed increased bioavailability of glucose, cholesterol, and lipids, as well as elevated secretion of the main chylomicron protein apoB-48 to the basal compartment. Importantly, we did not detect any rise in the concentrations of lipid peroxidation products (malondialdehyde, MDA) in the control samples prepared without antioxidants. Addition of antioxidants (in particular BHT) to the diet increases bioavailability of lipids and carbohydrates, which consequently may increase the risk of obesity development. The dose of antioxidants is a factor of fundamental importance, particularly for catechins: low doses increase absorption of lipids, whereas high doses exert the opposite effect.

Dry elixir formulations of dexibuprofen for controlled release and enhanced oral bioavailability.

PubMed

Kim, Seo-Ryung; Kim, Jin-Ki; Park, Jeong-Sook; Kim, Chong-Kook

2011-02-14

The objective of this study was to achieve an optimal formulation of dexibuprofen dry elixir (DDE) for the improvement of dissolution rate and bioavailability. To control the release rate of dexibuprofen, Eudragit(®) RS was employed on the surface of DDE resulting in coated dexibuprofen dry elixir (CDDE). Physicochemical properties of DDE and CDDE such as particle size, SEM, DSC, and contents of dexibuprofen and ethanol were characterized. Pharmacokinetic parameters of dexibuprofen were evaluated in the rats after oral administration. The DDE and CDDE were spherical particles of 12 and 19 μm, respectively. The dexibuprofen and ethanol contents in the DDE were dependent on the amount of dextrin and maintained for 90 days. The dissolution rate and bioavailability of dexibuprofen loaded in dry elixir were increased compared with those of dexibuprofen powder. Moreover, coating DDE with Eudragit(®) RS retarded the dissolution rate of dexibuprofen from DDE without reducing the bioavailability. Our results suggest that CDDE may be potential oral dosage forms to control the release and to improve the bioavailability of poorly water-soluble dexibuprofen. Copyright © 2010 Elsevier B.V. All rights reserved.

Bioavailable iron in the Southern Ocean: the significance of the iceberg conveyor belt.

PubMed

Raiswell, Rob; Benning, Liane G; Tranter, Martyn; Tulaczyk, Slawek

2008-05-30

Productivity in the Southern Oceans is iron-limited, and the supply of iron dissolved from aeolian dust is believed to be the main source from outside the marine reservoir. Glacial sediment sources of iron have rarely been considered, as the iron has been assumed to be inert and non-bioavailable. This study demonstrates the presence of potentially bioavailable Fe as ferrihydrite and goethite in nanoparticulate clusters, in sediments collected from icebergs in the Southern Ocean and glaciers on the Antarctic landmass. Nanoparticles in ice can be transported by icebergs away from coastal regions in the Southern Ocean, enabling melting to release bioavailable Fe to the open ocean. The abundance of nanoparticulate iron has been measured by an ascorbate extraction. This data indicates that the fluxes of bioavailable iron supplied to the Southern Ocean from aeolian dust (0.01-0.13 Tg yr(-1)) and icebergs (0.06-0.12 Tg yr(-1)) are comparable. Increases in iceberg production thus have the capacity to increase productivity and this newly identified negative feedback may help to mitigate fossil fuel emissions.

Phosphorous bioavailability along a soil chronosequence

NASA Astrophysics Data System (ADS)

Roberts, K.; Vokhshoori, N. L.; Rosenthanl, A.; Turner, B. L.; Condron, L.; Paytan, A.

2011-12-01

In humid environments, as soils age nutrient loss through leaching and chemical trasformations affect the succession and composition of the biological communities. In particular phosphorus (P), often a limiting nutrient in terrestrial systems, tends to evolve into less bio-available forms over time, compounding loss through leaching. Thus P availability has the potential to strongly affect community productivity and structure. Low standing stock of P may not necessarily imply P limitation as the bio-available P pool is continuously recycled and re-utilized. Thus extensive recycling can reduce to varying extents the effect of P limitation. The bio-availability and recycling rates of P are difficult to measure; multiple sequential extraction processes have been developed to try to define and quantify the bio-availability of both inorganic and organic forms of P. In this preliminary study, we will present results of P concentrations in different soil fractions and oxygen isotopes in phosphate. These data together increase our understanding of P dynamics as soils age. The work is being done with a well characterized and dated chronosequence from the west coast of the South Island of New Zealand near the Haast River.

Surface modification of solid lipid nanoparticles for oral delivery of curcumin: Improvement of bioavailability through enhanced cellular uptake, and lymphatic uptake.

PubMed

Baek, Jong-Suep; Cho, Cheong-Weon

2017-08-01

Curcumin has been reported to exhibit potent anticancer effects. However, poor solubility, bioavailability and stability of curcumin limit its in vivo efficacy for the cancer treatment. Solid lipid nanoparticles (SLN) are a promising delivery system for the enhancement of bioavailability of hydrophobic drugs. However, burst release of drug from SLN in acidic environment limits its usage as oral delivery system. Hence, we prepared N-carboxymethyl chitosan (NCC) coated curcumin-loaded SLN (NCC-SLN) to inhibit the rapid release of curcumin in acidic environment and enhance the bioavailability. The NCC-SLN exhibited suppressed burst release in simulated gastric fluid while sustained release was observed in simulated intestinal fluid. Furthermore, NCC-SLN exhibited increased cytotoxicity and cellular uptake on MCF-7 cells. The lymphatic uptake and oral bioavailability of NCC-SLN were found to be 6.3-fold and 9.5-fold higher than that of curcumin solution, respectively. These results suggest that NCC-SLN could be an efficient oral delivery system for curcumin. Copyright © 2017 Elsevier B.V. All rights reserved.

Packaging DNA Origami into Viral Protein Cages.

PubMed

Linko, Veikko; Mikkilä, Joona; Kostiainen, Mauri A

2018-01-01

The DNA origami technique is a widely used method to create customized, complex, spatially well-defined two-dimensional (2D) and three-dimensional (3D) DNA nanostructures. These structures have huge potential to serve as smart drug-delivery vehicles and molecular devices in various nanomedical and biotechnological applications. However, so far only little is known about the behavior of these novel structures in living organisms or in cell culture/tissue models. Moreover, enhancing pharmacokinetic bioavailability and transfection properties of such structures still remains a challenge. One intriguing approach to overcome these issues is to coat DNA origami nanostructures with proteins or lipid membranes. Here, we show how cowpea chlorotic mottle virus (CCMV) capsid proteins (CPs) can be used for coating DNA origami nanostructures. We present a method for disassembling native CCMV particles and isolating the pure CP dimers, which can further bind and encapsulate a rectangular DNA origami shape. Owing to the highly programmable nature of DNA origami, packaging of DNA nanostructures into viral protein cages could find imminent uses in enhanced targeting and cellular delivery of various active nano-objects, such as enzymes and drug molecules.

The Role of Chloride Complexation on Anaerobic and Aerobic Mercury Bioavailability

NASA Astrophysics Data System (ADS)

Stenzler, B.; Ruuskanen, M.; Hinz, A.; Poulain, A.

2016-12-01

In the absence of dissolved organic matter, chloride and sulphide are the dominant complexing agents affecting mercury (Hg) speciation in the environment. Bioreporters are good tools in evaluating bioavailable species of Hg. However, signal production for current Hg bioreporters requires oxygen, namely for lux and gfp gene encoded proteins, resulting in a paucity of data in anaerobic bioavailability of Hg species where it is methylated to toxic CH3Hg+. We developed and optimized a whole-cell Hg bioreporter using Escherichia coli 5α capable of functioning in aerobic and anaerobic conditions by transforming a vector containing the gene fusion between the regulatory circuitry of the mer-operon and a flavin mononucleotide-based fluorescent protein. The bioreporter exhibited no physiological limitations with respect to signal production over a chloride gradient ranging from 0 to 0.7 M. The bioreporter had a detection limit of 1 nM Hg(II) however we used 5nM Hg(II) as the optimal working concentration for Hg speciation assays. We report that HgCl42- is highly bioavailable under anoxic conditions in contrast to what was observed under oxic conditions where Hg was not bioavailable. HgCl3- was not bioavailable regardless of the presence of oxygen which we attributed to either coordination polymers consisting of [HgCl3-]x chains on the cell surface or molecular mimicry of HgCl42- onto anaerobically expressed periplasmic binding proteins specific for divalent polyatomic anions shuttling Hg to the inner membrane. In the presence of HgCl42- in saline media and Hg(OH)2 in non-saline media the addition of 2.5 and 5 μM Zn, respectively, completely inhibited uptake of neutral and negatively charged Hg species regardless of the presence of oxygen. The presence of S2- inhibited Hg uptake regardless of the presence or absence of chloride. Our experiments also suggest that ligand exchange occurred faster between S2- and Cl- than between S2- and OH-. The unexpected bioavailability of HgCl42- indicates the possibility of a novel mechanism for Hg uptake in marine environments while the bioavailability of HgS species is dependent on equilibration time and salinity.

Bioavailability assessment of toxic metals using the technique "acid-volatile sulfide (AVS)-simultaneously extracted metals (SEM)" in marine sediments collected in Todos os Santos Bay, Brazil.

PubMed

Silva, Jucelino B; Nascimento, Rodrigo A; de Oliva, Sergio T; de Oliveira, Olívia M C; Ferreira, Sergio L C

2015-10-01

This paper reports the bioavailability of the metals (cadmium, copper, zinc, lead, and nickel) in sediment samples collected in seven stations from the São Paulo Estuary, Todos os Santos Bay, Brazil. The bioavailability was determined by employing the technique "acid-volatile sulfide (AVS) and simultaneously extracted metal (SEM)". The elements cadmium, copper, lead, and zinc were determined using differential pulse anodic stripping voltammetry (DPASV), while nickel was quantified utilizing electrothermal atomic absorption spectrometry (ET AAS). The accuracy of these methods was confirmed using a certified reference material of estuarine sediment (NIST 1646). The sulfide was quantified using potentiometry with selective electrode and the organic matter determination employing an indirect volumetric method using potassium dichromate and iron(II) sulfate solutions. The bioavailability of the metals was estimated by relationship between the concentration of AVS and the sum of the concentrations of the simultaneously extracted metals (ΣSEM), considering a significant toxicity when (ΣSEM)/(AVS) is higher than 1. The bioavailability values in the seven stations studied varied from 0.93 to 1.31 (June, 2014) and from 0.34 to 0.58 (September, 2014). These results demonstrated a critical condition of toxicity (bioavailability >1) in six of the seven sediment samples collected during the rainy season (June, 2014). In the other period (September, 2014), the bioavailability was always lower than 1 for all sediment samples collected in the seven stations. The individual values of the concentrations of the five metals were compared with the parameters PEL (probable effects level) and TEL (threshold effects level), which are commonly employed for characterization of ecological risk in environmental systems. This comparison revealed that all metals have concentrations lower than the PEL and only zinc and lead in some stations have contents higher than the TEL. The bioavailability evaluation and the concentrations achieved for the five elements in the sediments samples analyzed demonstrated that the ecosystem studied does not present an environmental risk.

21 CFR 320.36 - Requirements for maintenance of records of bioequivalence testing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.36 Requirements for...

Risk of Low Dose/Low Dose Rate Ionizing Radiation to Humans Symposium Annual Meeting of the Environmental Mutagen Society: Agenda and Abstracts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veigl, Martina L.; Morgan, William F.; Schwartz, Jeffrey L.

The low dose symposium thoughtfully addressed controversy of risk from low dose radiation exposure, hormesis and radon therapy. The stem cell symposium cogently considered the role of DNA damage and repair in hematopoietic stem cells underlying aging and malignancy and provocatively presented evidence that stem cells may have distinct morphologies and replicative properties, as well as special roles in cancer initiation. In the epigenetics symposium, studies illustrated the long range interaction of epigenetic mechanisms, the roles of CTCF and BORIS in region/specific regulation of epigenetic processes, the impact of DNA damage on epigenetic processes as well as links between epigeneticmore » mechanisms and early nutrition and bystander effects. This report shows the agenda and abstracts for this symposium.« less

STS-106 Crew Activity Report/Flight Day 1 Highlights

NASA Technical Reports Server (NTRS)

2000-01-01

On this first day of the STS-106 Atlantis mission, the flight crew, Commander Terrence W. Wilcutt, Pilot Scott D. Altman, and Mission Specialists Daniel C. Burbank, Edward T. Lu, Richard A. Mastracchio, Yuri Ivanovich Malenchenko, and Boris V. Morukov are seen performing pre-launch activities. They are shown sitting around the breakfast table with the traditional cake, suiting-up, and riding out to the launch pad. The final inspection team is seen as they conduct their final check of the space shuttle on the launch complex. Also, included are various panoramic views of the shuttle on the pad. The crew is readied in the 'white room' for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters.

STS-106 Crew Activities Report/Flight Day 07 Highlights

NASA Technical Reports Server (NTRS)

2000-01-01

On this seventh day of the STS-106 Atlantis mission, the flight crew, Commander Commander Terrence W. Wilcutt, Pilot Scott D. Altman, and Mission Specialists Daniel C. Burbank, Edward T. Lu, Richard A. Mastracchio, Yuri Ivanovich Malenchenko, and Boris V. Morukov are seen participating in several outfitting activities. Burbank and Morukov remove and replace a fourth battery in Zarya. Lu and Malenchenko finish installing the third and final battery and other electrical equipment inside the Zvezda Service Module. While Altman and Wilcutt perform a series of jet firings, Altman is shown as he narrates a tour of the Zvezda Service Module. Scenes also include Lu and Malenchenko unpacking the Russian-made Orlan space suits, Burbank and Wilcutt participating in an interview, and a beautiful night shot of the International Space Station (ISS) and Atlantis complex above the Earth.

Relativistic extension of a charge-conservative finite element solver for time-dependent Maxwell-Vlasov equations

NASA Astrophysics Data System (ADS)

Na, D.-Y.; Moon, H.; Omelchenko, Y. A.; Teixeira, F. L.

2018-01-01

Accurate modeling of relativistic particle motion is essential for physical predictions in many problems involving vacuum electronic devices, particle accelerators, and relativistic plasmas. A local, explicit, and charge-conserving finite-element time-domain (FETD) particle-in-cell (PIC) algorithm for time-dependent (non-relativistic) Maxwell-Vlasov equations on irregular (unstructured) meshes was recently developed by Moon et al. [Comput. Phys. Commun. 194, 43 (2015); IEEE Trans. Plasma Sci. 44, 1353 (2016)]. Here, we extend this FETD-PIC algorithm to the relativistic regime by implementing and comparing three relativistic particle-pushers: (relativistic) Boris, Vay, and Higuera-Cary. We illustrate the application of the proposed relativistic FETD-PIC algorithm for the analysis of particle cyclotron motion at relativistic speeds, harmonic particle oscillation in the Lorentz-boosted frame, and relativistic Bernstein modes in magnetized charge-neutral (pair) plasmas.

STS106-s-013

NASA Image and Video Library

2000-09-08

STS106-S-013 (8 September 2000)--- This view of shock-wave condensation collars backlit by the Sun occurred during the launch of the Space Shuttle Atlantis on September 8, 2000. The scene was captured on 35mm motion picture film. One frame was digitized to make this still image. Although the primary effect is created by the forward fuselage of the Atlantis, secondary effects can be seen on the solid rocket booster (SRB) forward skirt, shuttle vertical stabilizer and wing trailing edge, behind the Space Shuttle Main Engines (SSME). The perfect on-time launch took place at 8:45:47 a.m. (EDT), September 8, 2000. Onboard the shuttle were astronauts Terrence W. Wilcutt, Scott D. Altman, Edward T. Lu, Richard A. Mastracchio and Daniel C. Burbank, along with cosmonauts Yuri I. Malenchenko and Boris V. Morukov who represent the Russian Aviation and Space Agency.

BOREAS Forest Cover Data Layers of the NSA in Raster Format

NASA Technical Reports Server (NTRS)

Hall, Forrest G. (Editor); Knapp, David; Tuinhoff, Manning

2000-01-01

This data set was processed by BORIS staff from the original vector data of species, crown closure, cutting class, and site classification/subtype into raster files. The original polygon data were received from Linnet Graphics, the distributor of data for MNR. In the case of the species layer, the percentages of species composition were removed. This reduced the amount of information contained in the species layer of the gridded product, but it was necessary in order to make the gridded product easier to use. The original maps were produced from 1:15,840-scale aerial photography collected in 1988 over an area of the BOREAS NSA MSA. The data are stored in binary, image format files and they are available from Oak Ridge National Laboratory. The data files are available on a CD-ROM (see document number 20010000884).

21 CFR 320.24 - Types of evidence to measure bioavailability or establish bioequivalence.

Code of Federal Regulations, 2011 CFR

2011-04-01

... effectiveness of the drug product, for purposes of measuring bioavailability, or appropriately designed comparative clinical trials, for purposes of demonstrating bioequivalence. This approach is the least accurate...

21 CFR 320.24 - Types of evidence to measure bioavailability or establish bioequivalence.

Code of Federal Regulations, 2013 CFR

2013-04-01

... effectiveness of the drug product, for purposes of measuring bioavailability, or appropriately designed comparative clinical trials, for purposes of demonstrating bioequivalence. This approach is the least accurate...

21 CFR 320.24 - Types of evidence to measure bioavailability or establish bioequivalence.

Code of Federal Regulations, 2014 CFR

2014-04-01

... effectiveness of the drug product, for purposes of measuring bioavailability, or appropriately designed comparative clinical trials, for purposes of demonstrating bioequivalence. This approach is the least accurate...

21 CFR 320.24 - Types of evidence to measure bioavailability or establish bioequivalence.

Code of Federal Regulations, 2012 CFR

2012-04-01

... effectiveness of the drug product, for purposes of measuring bioavailability, or appropriately designed comparative clinical trials, for purposes of demonstrating bioequivalence. This approach is the least accurate...

21 CFR 320.24 - Types of evidence to measure bioavailability or establish bioequivalence.

Code of Federal Regulations, 2010 CFR

2010-04-01

... effectiveness of the drug product, for purposes of measuring bioavailability, or appropriately designed comparative clinical trials, for purposes of demonstrating bioequivalence. This approach is the least accurate...

21 CFR 320.32 - Procedures for establishing or amending a bioequivalence requirement.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.32 Procedures for...

Curcumin Nanotechnologies and Its Anticancer Activity.

PubMed

Subramani, Parasuraman Aiya; Panati, Kalpana; Narala, Venkata Ramireddy

2017-04-01

Cancer is one of the leading causes of death worldwide. Curcumin is a well-established anticancer agent in vitro but its efficacy is yet to be proven in clinical trials. Poor bioavailability of curcumin is the principal reason behind the lack of efficiency of curcumin in clinical trials. Many studies prove that the bioavailability of curcumin can be improved by administering it through nanoparticle drug carriers. This review focuses on the efforts made in the field of nanotechnology to improve the bioavailability of curcumin. Nanotechnologies of curcumin come in various shapes and sizes. The simplest curcumin nanoparticle that increased the bioavailability of curcumin is the curcumin-metal complex. On the other hand, we have intricate thermoresponsive nanoparticles that can release curcumin upon stimulation (analogous to a remote control). Future research required for developing potent curcumin nanoparticles is also discussed.

Bioavailability of Tetracycline and Doxycycline in Fasted and Nonfasted Subjects

PubMed Central

Welling, Peter G.; Koch, Patricia A.; Lau, Curtis C.; Craig, William A.

1977-01-01

The influence of various test meals and fluid volumes on the relative bioavailability of commercial formulations of doxycycline hyclate and tetracycline hydrochloride was studied in healthy human volunteers. Serum levels of tetracycline were uniformly reduced by approximately 50% by all test meals, whereas serum levels of doxycycline were reduced by 20%. The reduction of tetracycline serum levels will likely be of clinical significance. The bioavailability of each drug was almost identical from an oral solution and from capsules in fasted subjects. The rate of doxycycline absorption was reduced when capsules were administered with a small volume of water, but the overall efficiency of absorption of both drugs was essentially independent of co-administered fluid volume. The use of 8-h serum data provides a reliable estimate of drug bioavailability for tetracycline and, to a lesser extent, for doxycycline. PMID:856000

Utilizing thin-film solid-phase extraction to assess the effect of organic carbon amendments on the bioavailability of DDT and dieldrin to earthworms

USGS Publications Warehouse

Andrade, Natasha A.; Centofanti, Tiziana; McConnell, Laura L.; Hapeman, Cathleen J.; Torrents, Alba; Anh, Nguyen; Beyer, W. Nelson; Chaney, Rufus L.; Novak, Jeffrey M.; Anderson, Marya O.; Cantrell, Keri B.

2014-01-01

Improved approaches are needed to assess bioavailability of hydrophobic organic compounds in contaminated soils. Performance of thin-film solid-phase extraction (TF-SPE) using vials coated with ethylene vinyl acetate was compared to earthworm bioassay (Lumbricus terrestris). A DDT and dieldrin contaminated soil was amended with four organic carbon materials to assess the change in bioavailability. Addition of organic carbon significantly lowered bioavailability for all compounds except for 4,4′-DDT. Equilibrium concentrations of compounds in the polymer were correlated with uptake by earthworms after 48d exposure (R2 = 0.97; p 40yr of aging. Results show that TF-SPE can be useful in examining potential risks associated with contaminated soils and to test effectiveness of remediation efforts.

Significance of excipients to enhance the bioavailability of poorly water-soluble drugs in oral solid dosage forms: A Review

NASA Astrophysics Data System (ADS)

Vadlamudi, Manoj Kumar; Dhanaraj, Sangeetha

2017-11-01

Nowadays most of the drug substances are coming into the innovation pipeline with poor water solubility. Here, the influence of excipients will play a significant role to improve the dissolution of poorly aqueous soluble compounds. The drug substance needs to be dissolved in gastric fluids to get the better absorption and bioavailability of an orally administered drug. Dissolution is the rate-controlling stage for drugs which controls the rate and degree of absorption. Usually, poorly soluble oral administrated drugs show a slower dissolution rate, inconsistent and incomplete absorption which can lead to lower bioavailability. The low aqueous solubility of BCS class II and IV drugs is a major challenge in the drug development and delivery process. Several technologies have been used in an attempt to progress the bioavailability of poorly water-soluble drug compounds which include solid dispersions, lipid-based formulations, micronization, solvent evaporation, co-precipitation, ordered mixing, liquid-solid compacts, solvent deposition inclusion complexation, and steam aided granulation. In fact, most of the technologies require excipient as a carrier which plays a significant role in improving the bioavailability using Hypromellose acetate succinate, Cyclodextrin, Povidone, Copovidone, Hydroxypropyl cellulose, Hydroxypropyl methylcellulose, Crospovidone, Starch, Dimethylacetamide, Polyethylene glycol, Sodium lauryl sulfate, Polysorbate, Poloxamer. Mesoporous silica and so on. This review deliberates about the excipients significance on bioavailability enhancement of drug products in a single platform along with pragmatically proved applications so that user can able to select the right excipients as per the molecule.

Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol-rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo-controlled, crossover trial.

PubMed

Hollands, Wendy J; Hart, David J; Dainty, Jack R; Hasselwander, Oliver; Tiihonen, Kirsti; Wood, Richard; Kroon, Paul A

2013-07-01

Flavanol-rich foods are known to exert beneficial effects on cardiovascular health. The biological effects depend on bioavailability of flavanols which may be influenced by food matrix and dose ingested. We compared the bioavailability and dose-response of epicatechin from whole apple and an epicatechin-rich extract, and the effects on plasma and urinary nitric oxide (NO) metabolites. In a randomized, placebo-controlled, crossover trial, subjects consumed drinks containing 70 and 140 mg epicatechin from an apple extract and an apple puree containing 70 mg epicatechin. Blood and urine samples were collected for 24 h post ingestion. Maximum plasma concentration, AUC(0-24 h) , absorption and urinary excretion were all significantly higher after ingestion of both epicatechin drinks compared with apple puree (p < 0.05). Time to maximum plasma concentration was significantly later for the puree compared with the drinks (p < 0.01). Epicatechin bioavailability was >2-fold higher after ingestion of the 140 mg epicatechin drink compared to the 70 mg epicatechin drink (p < 0.05). Excretion of NO metabolites was higher for all test products compared with placebo, which was significant for the high dose drink (p = 0.016). Oral bioavailability of apple epicatechin increases at higher doses, is reduced by whole apple matrix and has the potential to increase NO bioavailability. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phase behavior and oral bioavailability of amorphous Curcumin.

PubMed

Pawar, Yogesh B; Shete, Ganesh; Popat, Dharmesh; Bansal, Arvind K

2012-08-30

Amorphous form has been used as a means to improve aqueous solubility and oral bioavailability of poorly water soluble drugs. The objective of present study was to characterize thermodynamic and kinetic parameters of amorphous form of Curcumin (CRM-A). CRM-A was found to be a good glass former with glass transition temperature (T(g)) of 342.64K and critical cooling rate below 1K/min. CRM-A had a moderate tendency of crystallization and exhibited Kauzmann temperature (T(KS)) of 294.23 K. CRM-A was found to be fragile in nature as determined by T(m)/T(g) (1.32), C(p)(1 iq):C(p)(glass) (1.22), strength parameter (D<10), fragility index (m>75), T(K)/T(g) (0.85), and T(g)-T(K) (48.41). Theoretically predicted aqueous solubility advantage of 43.15-folds, was reduced to 17-folds under practical conditions. This reduction in solubility was attributed to water induced devitrification, as evident through PXRD and SEM analysis. Further, oral bioavailability study of CRM-A was undertaken to investigate bioavailability benefits, if any. C(max) was improved by 1.97-folds (statistically significant difference over control). However, oral bioavailability (AUC(0-)(∞)) was improved by 1.45-folds (statistically non significant difference over control). These observations pointed towards role of rapid devitrification of CRM-A in GIT milieu, thus limiting its oral bioavailability advantage. Copyright © 2012 Elsevier B.V. All rights reserved.

Diffusive gradients in thin films for predicting methylmercury bioavailability in freshwaters after photodegradation.

PubMed

Fernández-Gómez, C; Bayona, J M; Díez, S

2015-07-01

Determination of the dissolved-bioavailable fraction of methylmercury (MeHg) and its degradation pathways in freshwaters deserve attention, to further our understanding of the potential risk and toxicity of MeHg. Since the photodegradation of MeHg is the most important known abiotic process able to demethylate MeHg, this study investigated the role of sunlight on MeHg bioavailability in freshwater environments. Experiments to calculate photodegradation rate constants of MeHg in different types of freshwater in combination with experiments to distinguish the labile fraction of MeHg after being exposed to sunlight were performed. The ability of diffusive gradients in thin films based on polyacrylamide (P-DGT) to assess DGT-labile MeHg during photodegradation was successfully tested. First order photodegradation rate constants (kpd) of bioavailable MeHg determined in five different types of waters with different amount of dissolved organic matter (DOM), were in the range 0.073-0.254 h(-1), confirming previous findings that once there is DOM in solution, which would favour the photodegradation process, the kpd is mainly affected by light attenuation. Simulated sunlight seems not to alter the lability of MeHg, although photodegradation processes may decrease the concentrations of MeHg, contributing to reduce the amount of bioavailable MeHg (i.e. MeHg uptake by DGT). However, the quality of DOM, rather than the quantity, plays an important role in the bioavailability of MeHg in freshwater. Copyright © 2015 Elsevier Ltd. All rights reserved.

Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system.

PubMed

Chen, Zhi-Qiang; Liu, Ying; Zhao, Ji-Hui; Wang, Lan; Feng, Nian-Ping

2012-01-01

Indirubin, isolated from the leaves of the Chinese herb Isatis tinctoria L, is a protein kinase inhibitor and promising antitumor agent. However, the poor water solubility of indirubin has limited its application. In this study, a supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) was developed to improve the oral bioavailability of indirubin. A prototype S-SMEDDS was designed using solubility studies and phase diagram construction. Precipitation inhibitors were selected from hydrophilic polymers according to their crystallization-inhibiting capacity through in vitro precipitation tests. In vitro release of indirubin from S-SMEDDS was examined to investigate its likely release behavior in vivo. The in vivo bioavailability of indirubin from S-SMEDDS and from SMEDDS was compared in rats. The prototype formulation of S-SMEDDS comprised Maisine™ 35-1:Cremophor(®) EL:Transcutol(®) P (15:40:45, w/w/w). Polyvinylpyrrolidone K17, a hydrophilic polymer, was used as a precipitation inhibitor based on its better crystallization-inhibiting capacity compared with polyethylene glycol 4000 and hydroxypropyl methylcellulose. In vitro release analysis showed more rapid drug release from S-SMEDDS than from SMEDDS. In vivo bioavailability analysis in rats indicated that improved oral absorption was achieved and that the relative bioavailability of S-SMEDDS was 129.5% compared with SMEDDS. The novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of indirubin in rats. The results suggest that S-SMEDDS is a superior means of oral delivery of indirubin.

Enhanced effect and mechanism of water-in-oil microemulsion as an oral delivery system of hydroxysafflor yellow A

PubMed Central

Qi, Jianping; Zhuang, Jie; Wu, Wei; Lu, Yi; Song, Yunmei; Zhang, Zhetao; Jia, Jia; Ping, Qineng

2011-01-01

Background: A microemulsion is an effective formulation for improving the oral bioavailability of poorly soluble drugs. In this paper, a water-in-oil (w/o) microemulsion was investigated as a system for enhancing the oral bioavailability of Biopharmaceutic Classification System (BCS) III drugs. Methods: The microemulsion formulation was optimized using a pseudoternary phase diagram, comprising propylene glycol dicaprylocaprate (PG), Cremophor® RH40, and water (30/46/24 w/w). Results: The microemulsion increased the oral bioavailability of hydroxysafflor yellow A which was highly water-soluble but very poorly permeable. The relative bioavailability of hydroxysafflor yellow A microemulsion was about 1937% compared with a control solution in bile duct-nonligated rats. However, the microemulsion showed lower enhanced absorption ability in bile duct-ligated rats, and the relative bioavailability was only 181%. In vitro experiments were further employed to study the mechanism of the enhanced effect of the microemulsion. In vitro lipolysis showed that the microemulsion was digested very quickly by pancreatic lipase. About 60% of the microemulsion was digested within 1 hour. Furthermore, the particle size of the microemulsion after digestion was very small (53.3 nm) and the digested microemulsion had high physical stability. An everted gut sac model demonstrated that cumulative transport of the digested microemulsion was significantly higher than that of the diluted microemulsion. Conclusion: These results suggested that digestion of the microemulsion by pancreatic lipase plays an important role in enhancing oral bioavailability of water-soluble drugs. PMID:21720510

Creatinine-based non-phospholipid vesicular carrier for improved oral bioavailability of Azithromycin.

PubMed

Ullah, Shafi; Shah, Muhammad Raza; Shoaib, Mohammad; Imran, Muhammad; Shah, Syed Wadood Ali; Ali, Imdad; Ahmed, Farid

2017-06-01

Novel, safe, efficient and cost effective nano-carriers from renewable resources have got greater interest for enhancing solubility and bioavailability of hydrophobic dugs. This study reports the synthesis of a novel biocompatible non-phospholipid human metabolite "Creatinine" based niosomal delivery system for Azithromycin improved oral bioavailability. Synthesized surfactant was characterized through spectroscopic and spectrometric techniques and then the potential for niosomal vesicle formation was evaluated using Azithromycin as model drug. Drug loaded vesicles were characterized for size, polydispersity index (PDI), shape, drug encapsulation efficiency (EE), in vitro release and drug-excipient interaction using zetasizer, atomic force microscope (AFM), LC-MS/MS and FTIR. The biocompatibility of surfactant was investigated through cells cytotoxicity, blood hemolysis and acute toxicity. Azithromycin encapsulated in niosomes was investigated for in vivo bioavailability in rabbits. The vesicles were spherical with 247 ± 4.67 nm diameter hosting 73.29 ± 3.51% of the drug. Surfactant was nontoxic against cell cultures and caused 5.80 ± 0.51% hemolysis at 1000 µg/mL. It was also found safe in mice up to 2.5 g/kg body weight. Synthesized surfactant based niosomal vesicles revealed enhanced oral bioavailability of Azithromycin in rabbits. The results of the present study confirm that the novel surfactant is highly biocompatible and the niosomal vesicles can be efficiently used for improving the oral bioavailability of poor water soluble drugs.

Nanoparticulation improves bioavailability of Erlotinib.

PubMed

Yang, Kyung Mi; Shin, In Chul; Park, Joo Won; Kim, Kab-Sig; Kim, Dae Kyong; Park, Kyungmoon; Kim, Kunhong

2017-09-01

Nanoparticulation using fat and supercritical fluid (NUFS TM ) is a drug delivery platform technology enabling efficient and effective formulation of poorly soluble drugs. We performed experiments to examine whether NUFS™ could improve poor bioavailability and reduce fed-fasted bioavailability variances of erlotinib (Ert). NUFS-Ert was prepared using NUFS™ technology; its physical properties were characterized, and drug release was measured. Furthermore, in vitro and in vivo efficacy tests and pharmacokinetic analysis were performed. NUFS-Ert nanoparticles had an average size of 250 nm and were stable for 2 months at 40 °C, 4 °C, and room temperature. The dissolution rate of NUFS-Ert increased in bio-relevant dissolution media. NUFS-Ert was more potent in inhibiting EGF signaling and in suppressing the proliferation of A549, a human non-small cell lung cancer cell line. Furthermore, A549 xenografts in BALB/c nude mice treated with NUFS-Ert regressed more efficiently than those in the mice treated with vehicle or Tarceva ® . In addition, experimental lung metastasis was more efficiently inhibited by NUFS-Ert than by Tarceva ® . The relative bioavailability of NUFS-Ert compared with that of Tarceva ® was 550% and the ratio of the area under the concentration-time curve (AUC) of fed state to the AUC of fasted state was 1.8 for NUFS-Ert and 5.8 for Tarceva ® . NUFS-Ert could improve poor bioavailability and reduce fed-fasted bioavailability variances of Ert. NUFS-Ert was more efficacious than Tarceva ® .

Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best?

PubMed

Uysal, Nazan; Kizildag, Servet; Yuce, Zeynep; Guvendi, Guven; Kandis, Sevim; Koc, Basar; Karakilic, Aslı; Camsari, Ulas M; Ates, Mehmet

2018-04-21

Magnesium is an element of great importance functioning because of its association with many cellular physiological functions. The magnesium content of foods is gradually decreasing due to food processing, and magnesium supplementation for healthy living has become increasingly popular. However, data is very limited on the bioavailability of various magnesium preparations. The aim of this study is to investigate the bioavailability of five different magnesium compounds (magnesium sulfate, magnesium oxide, magnesium acetyl taurate, magnesium citrate, and magnesium malate) in different tissues. Following a single dose 400 mg/70 kg magnesium administration to Sprague Dawley rats, bioavailability was evaluated by examining time-dependent absorption, tissue penetration, and the effects on the behavior of the animals. Pharmacokinetically, the area under the curve calculation is highest in the magnesium malate. The magnesium acetyl taurate was found to have the second highest area under the curve calculation. Magnesium acetyl taurate was rapidly absorbed, able to pass through to the brain easily, had the highest tissue concentration level in the brain, and was found to be associated with decreased anxiety indicators. Magnesium malate levels remained high for an extended period of time in the serum. The commonly prescribed dietary supplements magnesium oxide and magnesium citrate had the lowest bioavailability when compared to our control group. More research is needed to investigate the bioavailability of magnesium malate and acetyl taurate compounds and their effects in specific tissues and on behavior.

Enrichment and Bioavailability of Trace Elements in Soil in Vicinity of Railways in Japan.

PubMed

Wang, Zhen; Watanabe, Izumi; Ozaki, Hirozaku; Zhang, Jianqiang

2018-01-01

This study focuses on the concentrations, distribution, pollution levels, and bioavailability of 12 trace elements in soils along 6 different railways in Japan. Three diesel powered railways and three electricity powered railways were chosen as target. Surface soils (< 3 cm) were collected in vicinity of railways for analysis. Digestion and extraction were performed before concentration and bioavailability analysis. Enrichment factor was applied to investigate contamination levels of selected elements. The mean concentrations of Cr, Co, Ni, Cu, Zn, Sn, and Pb in soil samples were higher than soil background value in Japan. Concentrations of trace elements in soils along different railway had different characteristics. Horizontal distribution of Cu, Zn, Cd, Sn, and Pb in soil samples showed obviously downtrend with distance along railways with high frequency. Concentrations of V, Mn, Fe, and Co were higher in soils along railways which pass through city center. According to principal component analysis and cluster analysis, concentrations of Cu, Zn, Sn, and Pb could be considered as the indicators of soil contamination level along electricity powered trains, whereas indicators along diesel powered trains were not clear. Enrichment factor analysis proved that operation of freight trains had impact on pollution level of Cr, Ni, and Cd. Bioavailability of Mn, Co, Zn, and Cd in soil along electricity-powered railways were higher, and bioavailability of Pb in railways located in countryside was lower. Thus, enrichment and bioavailability of trace elements can be indicators of railway-originated trace elements pollution in soil.

Dissolved organic matter kinetically controls mercury bioavailability to bacteria.

PubMed

Chiasson-Gould, Sophie A; Blais, Jules M; Poulain, Alexandre J

2014-03-18

Predicting the bioavailability of inorganic mercury (Hg) to bacteria that produce the potent bioaccumulative neurotoxin monomethylmercury remains one of the greatest challenges in predicting the environmental fate and transport of Hg. Dissolved organic matter (DOM) affects mercury methylation due to its influence on cell physiology (as a potential nutrient) and its influence on Hg(II) speciation in solution (as a complexing agent), therefore controlling Hg bioavailability. We assessed the role of DOM on Hg(II) bioavailability to a gram-negative bacterium bioreporter under oxic pseudo- and nonequilibrium conditions, using defined media and field samples spanning a wide range of DOM levels. Our results showed that Hg(II) was considerably more bioavailable under nonequilibrium conditions than when DOM was absent or when Hg(II) and DOM had reached pseudoequilibrium (24 h) prior to cell exposure. Under these enhanced uptake conditions, Hg(II) bioavailability followed a bell shaped curve as DOM concentrations increased, both for defined media and natural water samples, consistent with bioaccumulation results in a companion paper (this issue) observed for amphipods. Experiments also suggest that DOM may not only provide shuttle molecules facilitating Hg uptake, but also alter cell wall properties to facilitate the first steps toward Hg(II) internalization. We propose the existence of a short-lived yet critical time window (<24 h) during which DOM facilitates the entry of newly deposited Hg(II) into aquatic food webs, suggesting that the bulk of mercury incorporation in aquatic food webs would occur within hours following its deposition from the atmosphere.

Origins and bioavailability of dissolved organic matter in groundwater

USGS Publications Warehouse

Shen, Yuan; Chapelle, Francis H.; Strom, Eric W.; Benner, Ronald

2015-01-01

Dissolved organic matter (DOM) in groundwater influences water quality and fuels microbial metabolism, but its origins, bioavailability and chemical composition are poorly understood. The origins and concentrations of dissolved organic carbon (DOC) and bioavailable DOM were monitored during a long-term (2-year) study of groundwater in a fractured-rock aquifer in the Carolina slate belt. Surface precipitation was significantly correlated with groundwater concentrations of DOC, bioavailable DOM and chromophoric DOM, indicating strong hydrological connections between surface and ground waters. The physicochemical and biological processes shaping the concentrations and compositions of DOM during its passage through the soil column to the saturated zone are conceptualized in the regional chromatography model. The model provides a framework for linking hydrology with the processes affecting the transformation, remineralization and microbial production of DOM during passage through the soil column. Lignin-derived phenols were relatively depleted in groundwater DOM indicating substantial removal in the unsaturated zone, and optical properties of chromophoric DOM indicated lower molecular weight DOM in groundwater relative to surface water. The prevalence of glycine, γ-aminobutyric acid, and d-enantiomers of amino acids indicated the DOM was highly diagenetically altered. Bioassay experiments were used to establish DOC-normalized yields of amino acids as molecular indicators of DOM bioavailability in groundwater. A relatively small fraction (8 ± 4 %) of DOC in groundwater was bioavailable. The relatively high yields of specific d-enantiomers of amino acids indicated a substantial fraction (15–34 %) of groundwater DOC was of bacterial origin.

Bioavailability of silver and silver sulfide nanoparticles to lettuce (Lactuca sativa): Effect of agricultural amendments on plant uptake.

PubMed

Doolette, Casey L; McLaughlin, Michael J; Kirby, Jason K; Navarro, Divina A

2015-12-30

Silver nanoparticles (AgNPs) can enter terrestrial systems as sulfidised AgNPs (Ag2S-NPs) through the application of biosolids to soil. However, the bioavailability of Ag2S-NPs in soils is unknown. The two aims of this study were to investigate (1) the bioavailability of Ag to lettuce (Lactuca sativa) using a soil amended with biosolids containing Ag2S-NPs and (2) the effect of commonly used agricultural fertilisers/amendments on the bioavailability of Ag, AgNPs and Ag2S-NPs to lettuce. The study used realistic AgNP exposure pathways and exposure concentrations. The plant uptake of Ag from biosolids-amended soil containing Ag2S-NPs was very low for all Ag treatments (0.02%). Ammonium thiosulfate and potassium chloride fertilisation significantly increased the Ag concentrations of plant roots and shoots. The extent of the effect varied depending on the type of Ag. Ag2S-NPs, the realistic form of AgNPs in soil, had the lowest bioavailability. The potential risk of AgNPs in soils is low; even in the plants that had the highest Ag concentrations (Ag(+)+thiosulfate), only 0.06% of added Ag was found in edible plant parts (shoots). Results from the study suggest that agricultural practises must be considered when carrying out risk assessments of AgNPs in terrestrial systems; such practises can affect AgNP bioavailability. Copyright © 2015 Elsevier B.V. All rights reserved.

Bioavailability and in vivo release behavior of controlled-release multiple-unit theophylline dosage forms in beagle dogs, cynomolgus monkeys, and göttingen minipigs.

PubMed

Ikegami, Kengo; Tagawa, Kozo; Osawa, Takashi

2006-09-01

To determine the usefulness of monkey as an animal model, bioavailability and in vivo release behaviors of theophylline (TP) after oral administration of controlled-release beads in dogs, monkeys, and minipigs were evaluated. Controlled-release beads were prepared using a centrifugal-fluid type granulator, that is, CF-granulator, and Ethylcellulose (EC) was used as controlled-release coating agent. Aqueous solution and EC-coated beads, which contained TP were orally administered to animals after at least 1-week intervals. In dogs and minipigs, their relative bioavailabilities of EC-coated beads were 33.1% and 47.0%, respectively, and in vivo TP release from EC-coated beads in the gastrointestinal tract of dogs and minipigs were not reflected in vitro data. In monkeys, relative bioavailability of EC-coated beads was 80.0% and the highest among the three species, and release amount of TP from EC-coated beads at 24 h after oral administration was 82.8% and 92.4%, which was almost correlated to in vitro data. Therefore, the discrepancy of the relative bioavailability in three species is considered to be due to the difference of in vivo release behavior of TP. The monkey may be useful animal model for bioavailability studies of controlled-release dosage forms of TP from the viewpoint of in vitro-in vivo release correlation. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association.

Correlation Between An In-vitro Method And An In-vivo Method In Assessing Bioavailable Arsenic In Two Pesticide-Amended Soils

NASA Astrophysics Data System (ADS)

Quazi, S.; Sarkar, D.; Sylvia, V.; Datta, R.

2006-05-01

Health risk assessment of Arsenic (As) enriched soil requires the estimation of bioavailable fraction of total metal. Research has been conducted to gain a better understanding of the relationship between metal availability and risk assessment. Some baseline risk assessments developed for contaminated sites have used the conservative assumption that all (i.e. 100%) of the As present in soils and wastes is bioavailable, due to tremendous cost associated with in-vivo bioavailability studies. This potentially overestimates the actual health risk, elevating the expenses associated with site cleanup. Health risk from direct exposure to soil-As via the hand-to-mouth exposure route is restricted only to those fractions of As in the soil that are available to the human gastrointestinal system. A reasonable approach is to develop in-vitro methods that simulate the complex and dynamic human gastrointestinal system and correlate well with the results of in-vivo method. Thus this study aims in addressing the potential of one such in-vitro method developed by our research group in assessing the bioavailability of soil-As. Two soils with drastically different chemical characteristics in regards to As reactivity (Immokalee-low As retention capacity; Millhopper-high As retention capacity) spiked with a pesticide (sodium arsenate) were used. Soils were amended at two rates representing concentrations typically found at Superfund sites: 675 and 1500 mg/kg of As. In-vitro bioavailability experiments were performed in order to obtain an estimate of the amount of As likely to be available in the human gastrointestinal system as well as the fraction potentially absorbed onto the intestinal linings. Following the in-vitro study selective in-vivo bioavailability studies using As-contaminated soils were conducted on male and female mice to validate the in-vitro results via comparison with the in-vivo data. Soils were administered orally to the BALB/c mice immediately after spiking. Treatments comprised of a soil group (As in soil), a positive control group (only As) and a negative control group (no soil, no As). Blood samples were collected at different time periods to determine As concentrations. Correlation between the in-vitro and in-vivo data was determined. Information obtained from this study will serve as the first step towards the future development of a semi-quantitative model for predicting bioavailable As. This in turn will result in designing appropriate, cost-effective remedial strategies for As contaminated sites. Keywords: Bioavailability, In-vitro, In-vivo, Arsenic, Soil, Risk Assessment

Effect of piperine on the bioavailability and pharmacokinetics of emodin in rats.

PubMed

Di, Xin; Wang, Xin; Di, Xin; Liu, Youping

2015-11-10

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) has been widely used as a traditional medicine and was shown to possess a multitude of health-promoting properties in pre-clinical studies, but its bioavailability was low due to the extensive glucuronidation in liver and intestine, hindering the development of emodin as a feasible chemopreventive agent. In this study, piperine, as a bioenhancer, was used to enhance the bioavailability of emodin by inhibiting its glucuronidation. The pharmacokinetic profiles of emodin after oral administration of emodin (20mg/kg) alone and in combination with piperine (20mg/kg) to rats were investigated via a validated LC/MS/MS method. As the in vivo pharmacokinetic studies had indicated, the AUC and Cmax of emodin were increased significantly after piperine treatment, and the glucuronidation of emodin was markedly inhibited. Our study demonstrated that piperine significantly improved the in vivo bioavailability of emodin and the influence of piperine on the pharmacokinetics of emodin may be attributed to the inhibition of glucuronidation of emodin. Further research is needed to investigate the detailed mechanism of improved bioavailability of emodin via its combination with piperine. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of deposition and spray pattern of nasal powders on insulin bioavailability.

PubMed

Pringels, E; Callens, C; Vervaet, C; Dumont, F; Slegers, G; Foreman, P; Remon, J P

2006-03-09

The influence of the deposition pattern and spray characteristics of nasal powder formulations on the insulin bioavailability was investigated in rabbits. The formulations were prepared by freeze drying a dispersion containing a physical mixture of drum dried waxy maize starch (DDWM)/Carbopol 974P (90/10, w/w) or a spray-dried mixture of Amioca starch/Carbopol 974P (25/75, w/w). The deposition in the nasal cavity of rabbits and in a silicone human nose model after actuation of three nasal delivery devices (Monopowder, Pfeiffer and experimental system) was compared and related to the insulin bioavailability. Posterior deposition of the powder formulation in the nasal cavity lowered the insulin bioavailability. To study the spray pattern, the shape and cross-section of the emitted powder cloud were analysed. It was concluded that the powder bulk density of the formulation influenced the spray pattern. Consequently, powders of different bulk density were prepared by changing the solid fraction of the freeze dried dispersion and by changing the freezing rate during freeze drying. After nasal delivery of these powder formulations no influence of the powder bulk density and of the spray pattern on the insulin bioavailability was observed.

Chemical and biological methods to evaluate the availability of heavy metals in soils of the Siena urban area (Italy).

PubMed

Nannoni, Francesco; Protano, Giuseppe

2016-10-15

A biogeochemistry field study was conducted in the Siena urban area (Italy) with the main objective of establishing the relationship between available amounts of heavy metals in soil assessed by a chemical method (soil fractionation) and bioavailability assessed by a biological method (bioaccumulation in earthworm tissues). The total content of traffic-related (Cd, Cu, Pb, Sb, Zn) and geogenic (Co, Cr, Ni, U) heavy metals in uncontaminated and contaminated soils and their concentrations in soil fractions and earthworms were used for this purpose. The bioavailability of heavy metals assessed by earthworms did not always match the availability defined by soil fractionation. Earthworms were a good indicator to assess the bioavailability of Pb and Sb in soil, while due to physiological mechanisms of regulation and excretion, Cd, Cu and Zn tissue levels in these invertebrates gave misleading estimates of their bioavailable pool. No relationship was identified between chemical and biological availability for the geogenic heavy metals, characterized by a narrow range of total contents in soil. The study highlighted that chemical and biological methods should be combined to provide more complete information about heavy element bioavailability in soils. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of taste masking technology on fast dissolving oral film: dissolution rate and bioavailability.

PubMed

Zhu, Ying; You, Xinru; Huang, Keqing; Raza, Faisal; Lu, Xin; Chen, Yuejian; Dhinakar, Arvind; Zhang, Yuan; Kang, Yang; Wu, Jun; Ge, Liang

2018-07-27

Fast dissolving oral film is a stamp-style, drug-loaded polymer film with rapid disintegration and dissolution. This new kind of drug delivery system requires effective taste masking technology. Suspension intermediate and liposome intermediate were prepared, respectively, for the formulation of two kinds of fast dissolving oral films with the aim of studying the effect of taste masking technology on the bioavailability of oral films. Loratadine was selected as the model drug. The surface pH of the films was close to neutral, avoiding oral mucosal irritation or side effects. The thickness of a 2 cm × 2 cm suspension oral film containing 10 mg of loratadine was 100 μm. Electron microscope analysis showed that liposomes were spherical before and after re-dissolution, and drugs with obvious bitterness could be masked by the encapsulation of liposomes. Dissolution of the two films was superior to that of the commercial tablets. Rat pharmacokinetic experiments showed that the oral bioavailability of the suspension film was significantly higher than that of the commercial tablets, and the relative bioavailability of the suspension film was 175%. Liposomal film produced a certain amount of improvement in bioavailability, but lower than that of the suspension film.

Biorelevant Dissolution Models for a Weak Base To Facilitate Formulation Development and Overcome Reduced Bioavailability Caused by Hypochlordyria or Achlorhydria.

PubMed

Kou, Dawen; Dwaraknath, Sudharsan; Fischer, Yannick; Nguyen, Daniel; Kim, Myeonghui; Yiu, Hiuwing; Patel, Preeti; Ng, Tania; Mao, Chen; Durk, Matthew; Chinn, Leslie; Winter, Helen; Wigman, Larry; Yehl, Peter

2017-10-02

In this study, two dissolution models were developed to achieve in vitro-in vivo relationship for immediate release formulations of Compound-A, a poorly soluble weak base with pH-dependent solubility and low bioavailability in hypochlorhydric and achlorhydric patients. The dissolution models were designed to approximate the hypo-/achlorhydric and normal fasted stomach conditions after a glass of water was ingested with the drug. The dissolution data from the two models were predictive of the relative in vivo bioavailability of various formulations under the same gastric condition, hypo-/achlorhydric or normal. Furthermore, the dissolution data were able to estimate the relative performance under hypo-/achlorhydric and normal fasted conditions for the same formulation. Together, these biorelevant dissolution models facilitated formulation development for Compound-A by identifying the right type and amount of key excipient to enhance bioavailability and mitigate the negative effect of hypo-/achlorhydria due to drug-drug interaction with acid-reducing agents. The dissolution models use readily available USP apparatus 2, and their broader utility can be evaluated on other BCS 2B compounds with reduced bioavailability caused by hypo-/achlorhydria.

Effect of taste masking technology on fast dissolving oral film: dissolution rate and bioavailability

NASA Astrophysics Data System (ADS)

Zhu, Ying; You, Xinru; Huang, Keqing; Raza, Faisal; Lu, Xin; Chen, Yuejian; Dhinakar, Arvind; Zhang, Yuan; Kang, Yang; Wu, Jun; Ge, Liang

2018-07-01

Fast dissolving oral film is a stamp-style, drug-loaded polymer film with rapid disintegration and dissolution. This new kind of drug delivery system requires effective taste masking technology. Suspension intermediate and liposome intermediate were prepared, respectively, for the formulation of two kinds of fast dissolving oral films with the aim of studying the effect of taste masking technology on the bioavailability of oral films. Loratadine was selected as the model drug. The surface pH of the films was close to neutral, avoiding oral mucosal irritation or side effects. The thickness of a 2 cm × 2 cm suspension oral film containing 10 mg of loratadine was 100 μm. Electron microscope analysis showed that liposomes were spherical before and after re-dissolution, and drugs with obvious bitterness could be masked by the encapsulation of liposomes. Dissolution of the two films was superior to that of the commercial tablets. Rat pharmacokinetic experiments showed that the oral bioavailability of the suspension film was significantly higher than that of the commercial tablets, and the relative bioavailability of the suspension film was 175%. Liposomal film produced a certain amount of improvement in bioavailability, but lower than that of the suspension film.

In vitro bioavailability and cellular bioactivity studies of flavonoids and flavonoid-rich plant extracts: questions, considerations and future perspectives.

PubMed

Gonzales, Gerard Bryan

2017-08-01

In vitro techniques are essential in elucidating biochemical mechanisms and for screening a wide range of possible bioactive candidates. The number of papers published reporting in vitro bioavailability and bioactivity of flavonoids and flavonoid-rich plant extracts is numerous and still increasing. However, even with the present knowledge on the bioavailability and metabolism of flavonoids after oral ingestion, certain inaccuracies still persist in the literature, such as the use of plant extracts to study bioactivity towards vascular cells. There is therefore a need to revisit, even question, these approaches in terms of their biological relevance. In this review, the bioavailability of flavonoid glycosides, the use of cell models for intestinal absorption and the use of flavonoid aglycones and flavonoid-rich plant extracts in in vitro bioactivity studies will be discussed. Here, we focus on the limitations of current in vitro systems and revisit the validity of some in vitro approaches, and not on the detailed mechanism of flavonoid absorption and bioactivity. Based on the results in the review, there is an apparent need for stricter guidelines on publishing data on in vitro data relating to the bioavailability and bioactivity of flavonoids and flavonoid-rich plant extracts.

Bioavailability assessment of thiacloprid in soil as affected by biochar.

PubMed

Li, Yao; Zhu, Yulong; Liu, Xingang; Wu, Xiaohu; Dong, Fengshou; Xu, Jun; Zheng, Yongquan

2017-03-01

Biochars can significantly sorb pesticides, and reduce their bioavailability in agricultural soils. In this study, the effects of a type of biochar (BC500) on the sorption, degradation, bioaccumulation and bioavailability of thiacloprid, which is a commonly used insecticide, were investigated. The thiacloprid sorption constant (K f values) increased by 14 times after 2% BC500 application, and the degradation of the insecticide decreased with increasing amounts of the biochars in the soil. Coupled with the exhaustive extraction and single-point Tenax method, the bioavailability of thiacloprid was predicted in the presence of the biochar. In soils amended with BC500, the thiacloprid concentrations accumulated in Tenax correlated well with those observed in earthworms (R 2  = 0.887), whereas the concentrations extracted by exhaustive method followed a less significant relationship with those in earthworms (R 2  = 0.624). The results of Tenax extractions and earthworm bioassays indicate that biochar reduces the bioavailability of thiacloprid in soil, but the delayed degradation and increased earthworm accumulation in aged biochar-amended soil imply that the environmental risks of biochar application to earthworms remain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mind the gap—deficits in our knowledge of aspects impacting the bioavailability of phytochemicals and their metabolites—a position paper focusing on carotenoids and polyphenols

PubMed Central

McDougall, Gordon J.; Alegría, Amparo; Alminger, Marie; Arrigoni, Eva; Aura, Anna‐Marja; Brito, Catarina; Cilla, Antonio; El, Sedef N.; Karakaya, Sibel; Martínez‐Cuesta, Marie C.; Santos, Claudia N.

2015-01-01

Various secondary plant metabolites or phytochemicals, including polyphenols and carotenoids, have been associated with a variety of health benefits, such as reduced incidence of type 2 diabetes, cardiovascular diseases, and several types of cancer, most likely due to their involvement in ameliorating inflammation and oxidative stress. However, discrepancies exist between their putative effects when comparing observational and intervention studies, especially when using pure compounds. These discrepancies may in part be explained by differences in intake levels and their bioavailability. Prior to exerting their bioactivity, these compounds must be made bioavailable, and considerable differences may arise due to their matrix release, changes during digestion, uptake, metabolism, and biodistribution, even before considering dose‐ and host‐related factors. Though many insights have been gained on factors affecting secondary plant metabolite bioavailability, many gaps still exist in our knowledge. In this position paper, we highlight several major gaps in our understanding of phytochemical bioavailability, including effects of food processing, changes during digestion, involvement of cellular transporters in influx/efflux through the gastrointestinal epithelium, changes during colonic fermentation, and their phase I and phase II metabolism following absorption. PMID:25988374

On the bioavailability of trace metals in surface sediments: a combined geochemical and biological approach.

PubMed

Roosa, Stéphanie; Prygiel, Emilie; Lesven, Ludovic; Wattiez, Ruddy; Gillan, David; Ferrari, Benoît J D; Criquet, Justine; Billon, Gabriel

2016-06-01

The bioavailability of metals was estimated in three river sediments (Sensée, Scarpe, and Deûle Rivers) impacted by different levels of Cu, Cd, Pb, and Zn (Northern France). For that, a combination of geochemistry and biological responses (bacteria and chironomids) was used. The results obtained illustrate the complexity of the notion of "bioavailability." Indeed, geochemical indexes suggested a low toxicity, even in surface sediments with high concentrations of total metals and a predicted severe effect levels for the organisms. This was also suggested by the abundance of total bacteria as determined by DAPI counts, with high bacterial cell numbers even in contaminated areas. However, a fraction of metals may be bioavailable as it was shown for chironomid larvae which were able to accumulate an important quantity of metals in surface sediments within just a few days.We concluded that (1) the best approach to estimate bioavailability in the selected sediments is a combination of geochemical and biological approaches and that (2) the sediments in the Deûle and Scarpe Rivers are highly contaminated and may impact bacterial populations but also benthic invertebrates.

Comparison of single extraction procedures and the application of an index for the assessment of heavy metal bioavailability in river sediments.

PubMed

Sakan, Sanja; Popović, Aleksandar; Škrivanj, Sandra; Sakan, Nenad; Đorđević, Dragana

2016-11-01

Metals in sediments are present in different chemical forms which affect their ability to transfer. The objective of this body of work was to compare different extraction methods for the bioavailability evaluation of some elements, such as Ba, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Ni, Pb, V and Zn from Serbian river sediments. A bioavailability risk assessment index (BRAI) was used for the quantification of heavy metal bioavailability in the sediments. Actual and potential element availability was assessed by single extractions with mild (CaCl 2 and CH 3 COONH 4 ) and acidic (CH 3 COOH) extractants and complexing agents (EDTA). Aqua regia extraction was used for the determination of the pseudo-total element content in river sediments. In different single extraction tests, higher extraction of Cd, Cu, Zn and Pb was observed than for the other elements. The results of the single extraction tests revealed that there is a considerable chance of metal leaching from the sediments assessed in this study. When the BRAI was applied, the results showed a high risk of heavy metal bioavailability in Serbian river sediments.

Comparison of DGT with traditional extraction methods for assessing arsenic bioavailability to Brassica chinensis in different soils.

PubMed

Dai, Yunchao; Nasir, Mubasher; Zhang, Yulin; Gao, Jiakai; Lv, Yamin; Lv, Jialong

2018-01-01

Several predictive models and methods have been used for heavy metals bioavailability, but there is no universally accepted approach in evaluating the bioavailability of arsenic (As) in soil. The technique of diffusive gradients in thin-films (DGT) is a promising tool, but there is a considerable debate with respect to its suitability. The DGT method was compared with other traditional chemical extractions techniques (soil solution, NaHCO 3 , NH 4 Cl, HCl, and total As method) for estimating As bioavailability in soil based on a greenhouse experiment using Brassica chinensis grown in various soils from 15 provinces in China. In addition, we assessed whether these methods are independent of soil properties. The correlations between plant and soil As concentration measured with traditional extraction techniques were pH and iron oxide (Fe ox ) dependent, indicating that these methods are influenced by soil properties. In contrast, DGT measurements were independent of soil properties and also showed a better correlation coefficient than other traditional techniques. Thus, DGT technique is superior to traditional techniques and should be preferable for evaluating As bioavailability in different type of soils. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Effect of Radix euphorbiae pekinensis extract on bioavailability of paclitaxel after their oral co-administration].

PubMed

Li, Minghua; Peng, Li; Yang, Fuheng; Liu, Sijia; Wang, Shengqi

2015-06-01

To evaluate the effect of Radix euphorbiae pekinensis extract on the permeability and bioavailability of paclitaxel co-administered orally. Based on Ussing Chamber and in vivo experiment, the permeability and bioavailability of paclitaxel were evaluated after oral co-administration with radix euphorbiae pekinensis in rats. The contents of paclitaxel in the permeates and the blood samples were determined using HPLC and LC-MS/MS method, respectively. In Radix euphorbiae pekinensis co-administration group, the Papp of the mucosal-to-serosal (M-S) transport or serosal-to-mucosal transport (S-M) of paclitaxel in the jejunum or ileum segment differed significantly from those in verapamil co-administration group and blank control group (P<0.05), but the Papp of S-M transport in the colon showed no significant difference from that in the blank control group. In the blank group, the average absolute bioavailability (AB%) of orally administered paclitaxel was only 2.81%, compared to that of 7.63% in radix euphorbiae pekinensis group. The average AB% in verapamil group was about 1.5 times that of the blank group. Co-administration of Radix euphorbiae pekinensis extract can increase the bioavailability of orally administered paclitaxel.

Enhanced bioavailability of opiates after intratracheal administration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Findlay, J.W.A.; Jones, E.C.; McNulty, M.J.

1986-03-01

Several opiate analgesics have low oral bioavailabilities in the dog because of presystemic metabolism. Intratracheal administration may circumvent this first-pass effect. Three anesthetized beagles received 5-mg/kg doses of codeine phosphate intratracheally (i.t.), orally (p.o.) and intravenously (i.v.) in a crossover study. The following drugs were also studied in similar experiments: ethylmorphine hydrochloride (5 mg/kg), pholcodine bitartrate (10 mg/kg, hydrocodone bitartrate (4 mg/kg) and morphine sulfate (2.5 mg/kg). Plasma drug concentrations over the 24- to 48-hr periods after drug administrations were determined by radioimmunoassays. I.t. bioavailabilities (codeine (84%), ethylmorphine (100%), and morphine (87%)) of drugs with poor oral availabilities were allmore » markedly higher than the corresponding oral values (14, 26, and 23%, respectively). I.t. bioavailabilities of pholcodine (93%) and hydrocodone (92%), which have good oral availabilities (74 and 79%, respectively), were also enhanced. In all cases, peak plasma concentrations occurred more rapidly after i.t. (0.08-0.17 hr) than after oral (0.5-2 hr) dosing and i.t. disposition often resembled i.v. kinetics. I.t. administration may be a valuable alternative dosing route, providing rapid onset of pharmacological activity for potent drugs with poor oral bioavailability.« less

Estimation of the bioaccessibility and bioavailability of Fe, Mn, Cu, and Zn in Chinese vegetables using the in vitro digestion/Caco-2 cell model: the influence of gut microbiota.

PubMed

Cai, Xiaolin; Chen, Xiaochen; Yin, Naiyi; Du, Huili; Sun, Guoxin; Wang, Lihong; Xu, Yudong; Chen, Yuqing; Cui, Yanshan

2017-12-13

The influence of the human gut microbiota on the bioaccessibility and bioavailability of trace elements in vegetables has barely been studied. An in vitro digestion model combining the physiologically based extraction test (PBET) and the Simulator of Human Intestinal Microbial Ecosystem (SHIME) was applied. Results showed that the gut microbiota increased the bioaccessibility of iron (Fe) in ten test vegetables by 1.3-1.8 times, but reduced the bioaccessibility of manganese (Mn), copper (Cu), and zinc (Zn) in vegetables in the colon phase by 3.7% to 89.6%, 24.8% to 100.0%, and 59.9% to 100.0%, respectively. Using the Caco-2 cell model to simulate the human absorption process, the bioavailable contents and the bioavailability of the trace elements were further determined. Swamp cabbage was the best source of Fe and Cu; spinach and lettuce provided the highest amounts of bioavailable Mn and Zn, respectively. Referring to the daily reference intakes of trace elements, the obtained data provide a scientific basis for both reasonable ingestion of vegetables in diets and diversification of diets.

Seasonal change of non-point source pollution-induced bioavailable phosphorus loss: A case study of Southwestern China

NASA Astrophysics Data System (ADS)

Gao, Yang; Zhu, Bo; Wang, Tao; Wang, Yafeng

2012-02-01

SummaryBioavailable phosphorus (P) losses due to agriculture activity in a purple soil watershed in the Sichuan Basin of Southwestern China were monitored to define the hydrological controls of P transport. Our results indicate that the proportion of P that was transported in particulate form increased in the rainy season, and that the mass of total bioavailable P (BAP) loads exhibited seasonal fluctuations, wherein the majority (over 90%) was observed to have been exported between June and September. The proportion of bioavailable dissolved P (BDP) in the BAP discharge budget in the watershed varied between 11% and 15% during the monitoring period. The bioavailable particulate P (BPP) and BDP concentrations of stream water under rainstorm events increased by over 40% in comparison to their annual mean concentrations, and the annual BAP load was primarily dominated by the loads that occurred during rainstorm events in the study year. BAP concentration in groundwater significantly fluctuated with the seasons, and the ratio of total BAP in groundwater to that in surface water gradually increased during the rainy season. Thus, the impact of agriculture on the water quality of this watershed becomes clearly evident.

Aluminum bioavailability from tea infusion.

PubMed

Yokel, Robert A; Florence, Rebecca L

2008-12-01

The objective was to estimate oral Al bioavailability from tea infusion in the rat, using the tracer (26)Al. (26)Al citrate was injected into tea leaves. An infusion was prepared from the dried leaves and given intra-gastrically to rats which received concurrent intravenous (27)Al infusion. Oral Al bioavailability (F) was calculated from the area under the (26)Al, compared to (27)Al, serum concentration x time curves. Bioavailability from tea averaged 0.37%; not significantly different from water (F=0.3%), or basic sodium aluminum phosphate (SALP) in cheese (F=0.1-0.3%), but greater than acidic SALP in a biscuit (F=0.1%). Time to maximum serum (26)Al concentration was 1.25, 1.5, 8 and 4.8h, respectively. These results of oral Al bioavailability x daily consumption by the human suggest tea can provide a significant amount of the Al that reaches systemic circulation. This can allow distribution to its target organs of toxicity, the central nervous, skeletal and hematopoietic systems. Further testing of the hypothesis that Al contributes to Alzheimer's disease may be more warranted with studies focusing on total average daily food intake, including tea and other foods containing appreciable Al, than drinking water.

Aluminum bioavailability from tea infusion

PubMed Central

Yokel, Robert A.; Florence, Rebecca L.

2008-01-01

The objective was to estimate oral Al bioavailability from tea infusion in the rat, using the tracer 26Al. 26Al citrate was injected into tea leaves. An infusion was prepared from the dried leaves and given intra-gastrically to rats which received concurrent intravenous 27Al infusion. Oral Al bioavailability (F) was calculated from the area under the 26Al, compared to 27Al, serum concentration × time curves. Bioavailability from tea averaged 0.37%; not significantly different from water (F = 0.3%), or basic sodium aluminum phosphate (SALP) in cheese (F = 0.1 to 0.3%), but greater than acidic SALP in a biscuit (F = 0.1%). Time to maximum serum 26Al concentration was 1.25, 1.5, 8 and 4.8 h, respectively. These results of oral Al bioavailability × daily consumption by the human suggest tea can provide a significant amount of the Al that reaches systemic circulation. This can allow distribution to its target organs of toxicity, the central nervous, skeletal and hematopoietic systems. Further testing of the hypothesis that Al contributes to Alzheimer's disease may be more warranted with studies focusing on total average daily food intake, including tea and other foods containing appreciable Al, than drinking water. PMID:18848597

Biocompatible nanoemulsions based on hemp oil and less surfactants for oral delivery of baicalein with enhanced bioavailability

PubMed Central

Yin, Juntao; Xiang, Cuiyu; Wang, Peiqing; Yin, Yuyun; Hou, Yantao

2017-01-01

Baicalein (BCL) possesses high pharmacological activities but low solubility and stability in the intestinal tract. This study aimed to probe the potential of nanoemulsions (NEs) consisting of hemp oil and less surfactants in ameliorating the oral bioavailability of BCL. BCL-loaded NEs (BCL-NEs) were prepared by high-pressure homogenization technique to reduce the amount of surfactants. BCL-NEs were characterized by particle size, entrapment efficiency (EE), in vitro drug release, and morphology. Bioavailability was studied in Sprague-Dawley rats following oral administration of BCL suspensions, BCL conventional emulsions, and BCL-NEs. The obtained NEs were ~90 nm in particle size with an EE of 99.31%. BCL-NEs significantly enhanced the oral bioavailability of BCL, up to 524.7% and 242.1% relative to the suspensions and conventional emulsions, respectively. BCL-NEs exhibited excellent intestinal permeability and transcellular transport ability. The cytotoxicity of BCL-NEs was documented to be low and acceptable for oral purpose. Our findings suggest that such novel NEs and preparative process provide a promising alternative to current formulation technologies and suitable for oral delivery of drugs with bioavailability issues. PMID:28435268

Bioavailability of an extemporaneous suspension of propafenone made from tablets.

PubMed

Olguín, Hugo Juárez; Pérez, Carmen Flores; Pérez, Janett Flores; Mendiola, Blanca Ramírez; Portugal, Miriam Carrasco; Chávez, Jesús Bobadilla

2006-07-01

Propafenone is an effective antiarrhythmic agent used in children, while in Mexico no specific formulation for children is available, which causes errors in adequate dosage. The aim of this study was to determine the bioavailability of a suspension prepared extemporaneously using commercial tablets of propafenone. The bioavailability was determined in two groups of rabbits (n = 8): the first group received a single intravenous dose of 2 mg/kg of propafenone; the second was orally administered an extemporaneous suspension of propafenone prepared from commercial tablets. Blood samples were drawn at several times during the next 24 h and analysed by HPLC to determine drug levels. The extemporaneous suspension was tested previously with satisfactory results regarding physicochemical and microbiologic stability. The area under the curve (AUC) for the i.v. route was 5600.6 ng/ml.h and for oral administration the AUC was 3327.6 ng/ml.h. The bioavailability was calculated at 59.41%. These results are consistent with previous reports for solid dosage forms. The propafenone suspension prepared extemporaneously using commercial tablets is bioavailable using an animal model; nevertheless, it is necessary to carry out human studies either in volunteers or in patients to confirm these results.

Effects of cooking and food matrix on estimated mineral bioavailability in Mloukhiya, a Mediterranean dish based on jute leaves and meat.

PubMed

Njoumi, Sondos; Bellagha, Sihem; Icard-Vernière, Christèle; Picq, Christian; Amiot, Marie Josèphe; Mouquet-Rivier, Claire

2018-03-01

Traditional Mediterranean plant-based dishes could allow tackling malnutrition while preserving the cultural heritage. To determine the effect of the cooking method on mineral bioavailability, the content in minerals and chelators of Mloukhiya, a Mediterranean dish based on jute leaves (Corchorus olitorius) that contains also meat, was monitored during the whole cooking process. Mineral bioaccessibility was assessed by measuring in vitro dialyzability. Model equation was also used to estimate mineral bioavailability. Comparison of Mloukhiya samples collected at different cooking time points showed that the dish total mineral content did not change despite the exchanges between sauce and meat during cooking. However, iron bioavailability decreased, because 58% of heme iron was degraded after 5h of cooking and non-heme iron showed poor bioaccessibility (1.2%), mainly due to its high content of phenolic compounds. The bioaccessibility of other minerals (zinc, calcium, magnesium and potassium) was high, indicating that the food matrix had no or little effect. The mineral bioavailability values predicted by using mathematical models were of the same order of magnitude as the bioaccessibility values. Copyright © 2017 Elsevier Ltd. All rights reserved.

A microemulsion of puerarin-phospholipid complex for improving bioavailability: preparation, in vitro and in vivo evaluations.

PubMed

Wu, Jun-Yong; Li, Yong-Jiang; Han, Meng; Hu, Xiong-Bin; Yang, Le; Wang, Jie-Min; Xiang, Da-Xiong

2018-08-01

Puerarin is a phytochemical with various pharmacological effects, but poor water solubility and low oral bioavailability limited usage of puerarin. The purpose of this study was to develop a new microemulsion (ME) based on phospholipid complex technique to improve the oral bioavailability of puerarin. Puerarin phospholipid complex (PPC) was prepared by a solvent evaporation method and was characterized by X-ray diffraction and infrared spectroscopy. Pseudo-ternary phase diagrams were constructed to investigate the effects of different oil on the emulsifying performance of the blank ME. Intestinal mucosal injury test was conducted to evaluate safety of PPC-ME, and no sign of damage on duodenum, jejunum and ileum of rats was observed using hematoxylin-eosin staining. In pharmacokinetic study of PPC-ME, a significantly greater C max (1.33 µg/mL) was observed when compared to puerarin (C max 0.55 µg/mL) or PPC (C max 0.70 µg/mL); the relative oral bioavailability of PPC-ME was 3.16-fold higher than puerarin. In conclusion, the ME combined with the phospholipid complex technique was a promising strategy to enhance the oral bioavailability of puerarin.

Biocompatible nanoemulsions based on hemp oil and less surfactants for oral delivery of baicalein with enhanced bioavailability.

PubMed

Yin, Juntao; Xiang, Cuiyu; Wang, Peiqing; Yin, Yuyun; Hou, Yantao

2017-01-01

Baicalein (BCL) possesses high pharmacological activities but low solubility and stability in the intestinal tract. This study aimed to probe the potential of nanoemulsions (NEs) consisting of hemp oil and less surfactants in ameliorating the oral bioavailability of BCL. BCL-loaded NEs (BCL-NEs) were prepared by high-pressure homogenization technique to reduce the amount of surfactants. BCL-NEs were characterized by particle size, entrapment efficiency (EE), in vitro drug release, and morphology. Bioavailability was studied in Sprague-Dawley rats following oral administration of BCL suspensions, BCL conventional emulsions, and BCL-NEs. The obtained NEs were ~90 nm in particle size with an EE of 99.31%. BCL-NEs significantly enhanced the oral bioavailability of BCL, up to 524.7% and 242.1% relative to the suspensions and conventional emulsions, respectively. BCL-NEs exhibited excellent intestinal permeability and transcellular transport ability. The cytotoxicity of BCL-NEs was documented to be low and acceptable for oral purpose. Our findings suggest that such novel NEs and preparative process provide a promising alternative to current formulation technologies and suitable for oral delivery of drugs with bioavailability issues.

In Vivo Methods for the Assessment of Topical Drug Bioavailability

PubMed Central

Herkenne, Christophe; Alberti, Ingo; Naik, Aarti; Kalia, Yogeshvar N.; Mathy, François-Xavier; Préat, Véronique

2007-01-01

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described. PMID:17985216

Bioavailability of sediment-bound contaminants to marine organisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, B.; Neff, J.

1993-09-01

The bioavailability of sediment-bound contaminants to marine organisms indicates that there exists a potential for transfer of these contaminants through marine food webs to commercial fisheries products consumed by humans. However, there has been relatively little effort to combine and synthesize data on chemical/biological interactions between benthic animals and seagrasses and the sediments in which they reside on the one hand, and on the chemistry of bioaccumulation on the other. This report provides a conceptual basis for an approach to bioavailability and biomagnification of sediment-bound contaminants that reviews biological and chemical approaches.

Reducing bioavailability and phytotoxicity of 2,4-dinitrotoluene by sorption on K-smectite clay.

PubMed

Roberts, Michael G; Rugh, Clayton L; Li, Hui; Teppen, Brian J; Boyd, Stephen A

2007-02-01

Smectite clays demonstrate high affinities for nitroaromatics that strongly depend on the exchangeable cation. The K-smectites have high affinities for nitroaromatics, but Ca-smectites do not. Here we evaluate the ability of K-smectite to attenuate the bioavailability and hence toxicity of 2,4-dinitrotoluene (2,4-DNT) to the aquatic plant duckweed. In the absence of K-smectite, 2,4-DNT was highly toxic to duckweed. Small amounts of K-smectite reduced toxicity substantially, presumably by reducing 2,4-DNT bioavailability via sorption.

Hollow silicon microneedle array based trans-epidermal antiemetic patch for efficient management of chemotherapy induced nausea and vomiting

NASA Astrophysics Data System (ADS)

Kharbikar, Bhushan N.; Kumar S., Harish; Kr., Sindhu; Srivastava, Rohit

2015-12-01

Chemotherapy Induced Nausea and Vomiting (CINV) is a serious health concern in the treatment of cancer patients. Conventional routes for administering anti-emetics (i.e. oral and parenteral) have several drawbacks such as painful injections, poor patient compliance, dependence on skilled personnel, non-affordability to majority of population (parenteral), lack of programmability and suboptimal bioavailability (oral). Hence, we have developed a trans-epidermal antiemetic drug delivery patch using out-of-plane hollow silicon microneedle array. Microneedles are pointed micron-scale structures that pierce the epidermal layer of skin to reach dermal blood vessels and can directly release the drug in their vicinity. They are painless by virtue of avoiding significant contact with dermal sensory nerve endings. This alternate approach gives same pharmacodynamic effects as par- enteral route at a sparse drug-dose requirement, hence negligible side-effects and improved patient compliance. Microneedle design attributes were derived by systematic study of human skin anatomy, natural micron-size structures like wasp-sting and cactus-spine and multi-physics simulations. We used deep reactive ion etching with Bosch process and optimized recipe of gases to fabricate high-aspect-ratio hollow silicon microneedle array. Finally, microneedle array and polydimethylsiloxane drug reservoir were assembled to make finished anti-emetic patch. We assessed microneedles mechanical stability, physico-chemical properties and performed in-vitro, ex- vivo and in-vivo studies. These studies established functional efficacy of the device in trans-epidermal delivery of anti-emetics, its programmability, ease of use and biosafety. Thus, out-of-plane hollow silicon microneedle array trans-epidermal antiemetic patch is a promising strategy for painless and effective management of CINV at low cost in mainstream healthcare.

Pilot Study on Folate Bioavailability from a Camembert Cheese Reveals Contradictory Findings to Recent Results from a Human Short-term Study.

PubMed

Mönch, Sabine; Netzel, Michael; Netzel, Gabriele; Ott, Undine; Frank, Thomas; Rychlik, Michael

2016-01-01

Different dietary sources of folate have differing bioavailabilities, which may affect their nutritional "value." In order to examine if these differences also occur within the same food products, a short-term human pilot study was undertaken as a follow-up study to a previously published human trial to evaluate the relative native folate bioavailabilities from low-fat Camembert cheese compared to pteroylmonoglutamic acid as the reference dose. Two healthy human subjects received the test foods in a randomized cross-over design separated by a 14-day equilibrium phase. Folate body pools were saturated with a pteroylmonoglutamic acid supplement before the first testing and between the testings. Folates in test foods and blood plasma were analyzed by stable isotope dilution assays. The biokinetic parameters C max, t max, and area under the curve (AUC) were determined in plasma within the interval of 0-12 h. When comparing the ratio estimates of AUC and C max for the different Camembert cheeses, a higher bioavailability was found for the low-fat Camembert assessed in the present study (≥64%) compared to a different brand in our previous investigation (8.8%). It is suggested that these differences may arise from the different folate distribution in the soft dough and firm rind as well as differing individual folate vitamer proportions. The results clearly underline the importance of the food matrix, even within the same type of food product, in terms of folate bioavailability. Moreover, our findings add to the increasing number of studies questioning the general assumption of 50% bioavailability as the rationale behind the definition of folate equivalents. However, more research is needed to better understand the interactions between individual folate vitamers and other food components and the potential impact on folate bioavailability and metabolism.

Pilot Study on Folate Bioavailability from a Camembert Cheese Reveals Contradictory Findings to Recent Results from a Human Short-term Study

PubMed Central

Mönch, Sabine; Netzel, Michael; Netzel, Gabriele; Ott, Undine; Frank, Thomas; Rychlik, Michael

2016-01-01

Different dietary sources of folate have differing bioavailabilities, which may affect their nutritional “value.” In order to examine if these differences also occur within the same food products, a short-term human pilot study was undertaken as a follow-up study to a previously published human trial to evaluate the relative native folate bioavailabilities from low-fat Camembert cheese compared to pteroylmonoglutamic acid as the reference dose. Two healthy human subjects received the test foods in a randomized cross-over design separated by a 14-day equilibrium phase. Folate body pools were saturated with a pteroylmonoglutamic acid supplement before the first testing and between the testings. Folates in test foods and blood plasma were analyzed by stable isotope dilution assays. The biokinetic parameters Cmax, tmax, and area under the curve (AUC) were determined in plasma within the interval of 0–12 h. When comparing the ratio estimates of AUC and Cmax for the different Camembert cheeses, a higher bioavailability was found for the low-fat Camembert assessed in the present study (≥64%) compared to a different brand in our previous investigation (8.8%). It is suggested that these differences may arise from the different folate distribution in the soft dough and firm rind as well as differing individual folate vitamer proportions. The results clearly underline the importance of the food matrix, even within the same type of food product, in terms of folate bioavailability. Moreover, our findings add to the increasing number of studies questioning the general assumption of 50% bioavailability as the rationale behind the definition of folate equivalents. However, more research is needed to better understand the interactions between individual folate vitamers and other food components and the potential impact on folate bioavailability and metabolism. PMID:27092303

Screening of chelating ligands to enhance mercury accumulation from historically mercury-contaminated soils for phytoextraction.

PubMed

Wang, Jianxu; Xia, Jicheng; Feng, Xinbin

2017-01-15

Screening of optimal chelating ligands which not only have high capacities to enhance plant uptake of mercury (Hg) from soil but also can decrease bioavailable Hg concentration in soil is necessary to establish a viable chemically-assisted phytoextraction. Therefore, Brassica juncea was exposed to historically Hg-contaminated soil (total Hg, 90 mg kg -1 ) to investigate the efficiency of seven chelating agents [ammonium thiosulphate, sodium thiosulphate, ammonium sulfate, ammonium chloride, sodium nitrate, ethylenediaminetetraacetic acid (EDTA), and sodium sulfite] at enhancing Hg phytoextraction; the leaching of bioavailable Hg caused by these chelating agents was also investigated. The Hg concentration in control (treated with double-distilled water) plant tissues was below 1 mg kg -1 . The remarkably higher Hg concentration was found in plants receiving ammonium thiosulphate and sodium sulfite treatments. The bioaccumulation factors and translocation factors of ammonium thiosulphate and sodium sulfite treatments were significantly higher than those of the other treatments. The more efficient uptake of Hg by plants upon treatment with ammonium thiosulphate and sodium sulfite compared to the other treatments might be explained by the formation of special Hg-thiosulphate complexes that could be preferentially taken up by the roots and transported in plant tissues. The application of sulfite significantly increased bioavailable Hg concentration in soil compared with that in initial soil and control soil, whereas ammonium thiosulphate significantly decreased bioavailable Hg concentration. The apparent decrease of bioavailable Hg in ammonium thiosulphate-treated soil compared with that in sodium sulfite-treated soil might be attributable to the unstable Hg-thiosulphate complexes formed between thiosulphate and Hg; they could react to produce less bioavailable Hg in the soil. The results of this study indicate that ammonium thiosulphate may be an optimal chelating ligand for phytoextraction due to its great potential to enhance Hg accumulation in plants while decreasing bioavailable Hg concentration in the soil. Copyright © 2016 Elsevier Ltd. All rights reserved.

The influence of particles on bioavailability and toxicity of pesticides in surface water.

PubMed

Knauer, Katja; Homazava, Nadzeya; Junghans, Marion; Werner, Inge

2017-07-01

Environmental risk assessment is an essential part of the approval process for pesticides. Exposure concentrations are compared with ecotoxicological data obtained from standardized laboratory studies and, if available, from field studies to determine the risk of a substance or formulation for aquatic communities. Predicted concentrations in surface waters are derived using, for example, the European FOrum for the Co-ordination of pesticide fate models and their USe (FOCUS) or the German Exposit models, which distinguish between exposure to dissolved and particle-associated pesticide concentrations, because the dissolved concentration is thought to be the best predictor of bioavailability and toxicity. Water and particle-associated concentrations are estimated based on the organic carbon-water partitioning coefficient (K OC ). This review summarizes published information on the influence of natural suspended solids on bioavailability and toxicity of pesticides to aquatic organisms (algae, invertebrates and fish), and the value of log K OC and log K OW (octanol-water coefficient) as sole predictors of the bioavailable fraction is discussed. The information showed that: 1) the quality and origin of suspended solids played an important role in influencing pesticide bioavailability and toxicity; 2) a decrease in toxicity due to the presence of suspended solids was shown only for pyrethroid insecticides with log K OW greater than 5, but the extent of this reduction depended on particle concentration and size, and potentially also on the ecotoxicological endpoint; 3) for pesticides with a log K OW less than 3 (e.g., triazines, carbamates, and organophosphates), the impact of particles on bioavailability and toxicity is small and species dependent; and 4) pesticide bioavailability is greatly influenced by the test species and their physiology (e.g., feeding behavior or digestion). We conclude that exposure of aquatic organisms to pesticides and environmental risk of many pesticides might be underestimated in prospective risk assessment, when predicted environmental concentration is estimated based on the K OC of a compound. Integr Environ Assess Manag 2017;13:585-600. © 2016 SETAC. © 2016 SETAC.

Development of surface stabilized candesartan cilexetil nanocrystals with enhanced dissolution rate, permeation rate across CaCo-2, and oral bioavailability.

PubMed

Jain, Sanyog; Reddy, Venkata Appa; Arora, Sumit; Patel, Kamlesh

2016-10-01

Candesartan cilexetil (CC), an ester prodrug of candesartan, is BCS class II drug with extremely low aqueous solubility limiting its oral bioavailability. The present research aimed to develop a nanocrystalline formulation of CC with improved saturation solubility in gastrointestinal fluids and thereby, exhibiting enhanced oral bioavailability. CC nanocrystals were prepared using a low energy antisolvent precipitation methodology. A combination of hydroxypropyl methylcellulose (HPMC) and Pluronic® F 127 (50:50 w/w) was found to be optimum for the preparation of CC nanocrystals. The particle size, polydispersity index (PDI), and zeta potential of optimized formulation was found to be 159 ± 8.1 nm, 0.177 ± 0.043, and -23.7 ± 1.02 mV, respectively. Optimized formulation was found to possess irregular, plate-like morphology as evaluated by scanning electron microscopy and crystalline as evaluated by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). A significant increase in saturation solubility and dissolution rate of the optimized nanosuspension was observed at all the tested pH conditions. Optimized CC nanocrystals exhibited a storage stability of more than 3 months when stored under cold and room temperature conditions. In vitro Caco-2 permeability further revealed that CC nanocrystals exhibited nearly 4-fold increase in permeation rate compared to the free CC. In vivo oral bioavailability studies of optimized CC nanocrystals in murine model revealed 3.8-fold increase in the oral bioavailability and twice the C max as compared with the free CC when administered orally. In conclusion, this study has established a crystalline nanosuspension formulation of CC with improved oral bioavailability in murine model. Graphical Abstract Antisolvent precipitation methodology for the preparation of Candesartan Cilexetil nanocrystals for enhanced solubility and oral bioavailability.

Preparation, characterization and in vitro/vivo evaluation of tectorigenin solid dispersion with improved dissolution and bioavailability.

PubMed

Shuai, Shuping; Yue, Shanlan; Huang, Qingting; Wang, Wei; Yang, Junyi; Lan, Ke; Ye, Liming

2016-08-01

The purpose of this study was to develop and evaluate a novel amorphous solid dispersion system for tectorigenin (TG). TG is one of isoflavone aglycones extracted from Iris tectorum and flowers of Pueraria thunbergiana, but its poor water solubility and low membrane permeability have severely restricted the clinical application. To increase the aqueous solubility and oral bioavailability of TG, we prepared the solid dispersions of tectorigenin (TG-SD) using a simple solvent evaporation process with TG, polyvinylpyrrolidone (PVP) and PEG4000 at weight ratio of 7:54:9 after tested in several ratios. The prepared solid dispersions of tectorigenin are duly characterized for drug morphological conversion, in vitro dissolution and in vivo bioavailability. The X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) studies have indicated the morphological conversion of tectorigenin to amorphous form. In vitro release profiles revealed that the % release of TG-SD was achieved 4.35-fold higher than that of the pure drug after 150 min. The oral bioavailability of the solid dispersion in rats was also increased based on AUC0-t and C max of TG-SD, which were 4.8- and 13.1-fold higher than that of TG crystal, respectively. It is worth noting that physical mixture containing TG, PEG4000 and PVP produced a similar level of oral exposure as TG-SD, suggesting that PEG4000 and PVP were able to enhance bioavailability of TG in rats. However, with the reduction of particle size, TG-SD provided the fastest oral absorption compared to physical mixture and pure drug. These results demonstrated that the efficacy of solid dispersions for the enhancement of TG oral bioavailability was by increasing its aqueous solubility and the solid dispersion formulation could be a viable option for enhancing the oral bioavailability of TG.

Induced metal redistribution and bioavailability enhancement in contaminated river sediment during in situ biogeochemical remediation.

PubMed

Liu, Tongzhou; Zhang, Zhen; Mao, Yanqing; Yan, Dickson Y S

2016-04-01

In situ sediment remediation using Ca(NO3)2 or CaO2 for odor mitigation and acid volatile sulfide (AVS) and organic pollutant (such as TPH and PAHs) removal was reported in many studies and fieldwork. Yet, the associated effects on metal mobilization and potential distortion in bioavailability were not well documented. In this study, contaminated river sediment was treated by Ca(NO3)2 and CaO2 in bench studies. Through the investigation of AVS removal, organic matter removal, the changes in sediment oxidation-reduction potential (ORP), microbial activity, and other indigenous parameters, the effects on metal bioavailability, bioaccessibility, and fraction redistribution in sediment were evaluated. The major mechanisms for sediment treated by Ca(NO3)2 and CaO2 are biostimulation with indigenous denitrifying bacteria and chemical oxidation, respectively. After applying Ca(NO3)2 and CaO2, the decreases of metal concentrations in the treated sediment were insignificant within a 35-day incubation period. However, the [SEMtot-AVS]/f OC increased near to the effective boundary of toxicity (100 μmol g(-1) organic carbon (OC)), indicating that both bioavailability and bioaccessibility of metals (Cu, Zn, and Ni) to benthic organisms are enhanced after remediation. Metals were found redistributed from relatively stable fractions (oxidizable and residual fractions) to weakly bound fractions (exchangeable and reducible fractions), and the results are in line with the enhanced metal bioavailability. Compared with Ca(NO3)2, CaO2 led to higher enhancement in metal bioavailability and bioaccessibility, and more significant metal redistribution, probably due to its stronger chemical reactive capacity to AVS and sediment organic matter. The reactions in CaO2-treated sediment would probably shift from physicochemical to biochemical heterotrophic oxidation for sediment organic matter degradation. Therefore, further investigation on the long-term metal redistribution and associated mobility as well as bioavailability is recommended.

A critical review of approaches and limitations of inhalation bioavailability and bioaccessibility of metal(loid)s from ambient particulate matter or dust.

PubMed

Kastury, Farzana; Smith, Euan; Juhasz, Albert L

2017-01-01

Inhalation of metal(loid)s in ambient particulate matter (APM) represents a significant exposure pathway to humans. Although exposure assessment associated with this pathway is currently based on total metal(loid) content, a bioavailability (i.e. absorption in the systemic circulation) and/or bioaccessibility (i.e. solubility in simulated lung fluid) based approach may more accurately quantify exposure. Metal(loid) bioavailability-bioaccessibility assessment from APM is inherently complex and lacks consensus. This paper reviews the discrepancies that impede the adoption of a universal protocol for the assessment of inhalation bioaccessibility. Exposure assessment approaches for in-vivo bioavailability, in-vitro cell culture and in-vitro bioaccessibility (composition of simulated lungs fluid, physico-chemical and methodological considerations) are critiqued in the context of inhalation exposure refinement. An important limitation of bioavailability and bioaccessibility studies is the use of considerably higher than environmental metal(loid) concentration, which diminishing their relevance to human exposure scenarios. Similarly, individual metal(loid) studies have been criticised due to complexities of APM metal(loid) mixtures which may impart synergistic or antagonistic effects compared to single metal(loid) exposure. Although a number of different simulated lung fluid (SLF) compositions have been used in metal(loid) bioaccessibility studies, information regarding the comparative leaching efficiency among these different SLF and comparisons to in-vivo bioavailability data is lacking. In addition, the particle size utilised is often not representative of what is deposited in the lungs while assay parameters (extraction time, solid to liquid ratio, temperature and agitation) are often not biologically relevant. Research needs are identified in order to develop robust in-vitro bioaccessibility protocols for the assessment or prediction of metal(loid) bioavailability in APM for the refinement of inhalation exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

Bioavailability of indomethacin-saccharin cocrystals.

PubMed

Jung, Min-Sook; Kim, Jeong-Soo; Kim, Min-Soo; Alhalaweh, Amjad; Cho, Wonkyung; Hwang, Sung-Joo; Velaga, Sitaram P

2010-11-01

Pharmaceutical cocrystals are new solid forms with physicochemical properties that appear promising for drug product development. However, the in-vivo bioavailability of cocrystals has rarely been addressed. The cocrystal of indomethacin (IND), a Biopharmaceutical Classification System class II drug, with saccharin (SAC) has been shown to have higher solubility than IND at all pH. In this study, we aimed to evaluate the in-vitro dissolution and in-vivo bioavailability of IND-SAC cocrystals in comparison with IND in a physical mixture and the marketed product Indomee. Scale-up of the cocrystals was undertaken using cooling batch crystallisation without seeding. The chemical and physical purity of the up-scaled material was verified using high-performance liquid chromatography, differential scanning calorimetry and powder X-ray diffraction. The IND-SAC cocrystals and IND plus SAC were mixed with lactose and the formulations were placed into gelatin capsules. In-vitro dissolution studies were then performed using the rotating basket dissolution method. The intrinsic dissolution rate of IND and IND-SAC cocrystals was also determined. Finally, a bioavailability study for the formulations was conducted in beagle dogs. The plasma samples were analysed using high-performance liquid chromatography and the pharmacokinetic data were analysed using standard methodologies.   The bulk cocrystals (i.e. scaled-up material) were chemically and physically pure. The in-vitro dissolution rate of the cocrystals was higher than that of IND and similar to that of Indomee at pH 7.4 and pH 1.2. The in-vivo bioavailability of the IND-SAC cocrystals in dogs was significantly higher (ANOVA, P<0.05) than that of IND but not significantly different from Indomee (ANOVA, P>0.05). The study indicates that the improved aqueous solubility of the cocrystals leads to improved bioavailability of IND. Thus, the cocrystals are a viable alternative solid form that can improve the dissolution rate and bioavailability of poorly soluble drugs. © 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society of Great Britain.

Influence of hardness on the bioavailability of silver to a freshwater snail after waterborne exposure to silver nitrate and silver nanoparticles.

PubMed

Stoiber, Tasha; Croteau, Marie-Noële; Römer, Isabella; Tejamaya, Mila; Lead, Jamie R; Luoma, Samuel N

2015-01-01

The release of Ag nanoparticles (AgNPs) into the aquatic environment is likely, but the influence of water chemistry on their impacts and fate remains unclear. Here, we characterize the bioavailability of Ag from AgNO(3) and from AgNPs capped with polyvinylpyrrolidone (PVP AgNP) and thiolated polyethylene glycol (PEG AgNP) in the freshwater snail, Lymnaea stagnalis, after short waterborne exposures. Results showed that water hardness, AgNP capping agents, and metal speciation affected the uptake rate of Ag from AgNPs. Comparison of the results from organisms of similar weight showed that water hardness affected the uptake of Ag from AgNPs, but not that from AgNO(3). Transformation (dissolution and aggregation) of the AgNPs was also influenced by water hardness and the capping agent. Bioavailability of Ag from AgNPs was, in turn, correlated to these physical changes. Water hardness increased the aggregation of AgNPs, especially for PEG AgNPs, reducing the bioavailability of Ag from PEG AgNPs to a greater degree than from PVP AgNPs. Higher dissolved Ag concentrations were measured for the PVP AgNPs (15%) compared to PEG AgNPs (3%) in moderately hard water, enhancing Ag bioavailability of the former. Multiple drivers of bioavailability yielded differences in Ag influx between very hard and deionized water where the uptake rate constants (k(uw), l g(-1) d(-1) ± SE) varied from 3.1 ± 0.7 to 0.2 ± 0.01 for PEG AgNPs and from 2.3 ± 0.02 to 1.3 ± 0.01 for PVP AgNPs. Modeling bioavailability of Ag from NPs revealed that Ag influx into L. stagnalis comprised uptake from the NPs themselves and from newly dissolved Ag.

Influence of hardness on the bioavailability of silver to a freshwater snail after waterborne exposure to silver nitrate and silver nanoparticles

USGS Publications Warehouse

Stoiber, Tasha L.; Croteau, Marie-Noele; Romer, Isabella; Tejamaya, Mila; Lead, Jamie R.; Luoma, Samuel N.

2015-01-01

The release of Ag nanoparticles (AgNPs) into the aquatic environment is likely, but the influence of water chemistry on their impacts and fate remains unclear. Here, we characterize the bioavailability of Ag from AgNO3 and from AgNPs capped with polyvinylpyrrolidone (PVP AgNP) and thiolated polyethylene glycol (PEG AgNP) in the freshwater snail, Lymnaea stagnalis, after short waterborne exposures. Results showed that water hardness, AgNP capping agents, and metal speciation affected the uptake rate of Ag from AgNPs. Comparison of the results from organisms of similar weight showed that water hardness affected the uptake of Ag from AgNPs, but not that from AgNO3. Transformation (dissolution and aggregation) of the AgNPs was also influenced by water hardness and the capping agent. Bioavailability of Ag from AgNPs was, in turn, correlated to these physical changes. Water hardness increased the aggregation of AgNPs, especially for PEG AgNPs, reducing the bioavailability of Ag from PEG AgNPs to a greater degree than from PVP AgNPs. Higher dissolved Ag concentrations were measured for the PVP AgNPs (15%) compared to PEG AgNPs (3%) in moderately hard water, enhancing Ag bioavailability of the former. Multiple drivers of bioavailability yielded differences in Ag influx between very hard and deionized water where the uptake rate constants (kuw, l g-1 d-1 ± SE) varied from 3.1 ± 0.7 to 0.2 ± 0.01 for PEG AgNPs and from 2.3 ± 0.02 to 1.3 ± 0.01 for PVP AgNPs. Modeling bioavailability of Ag from NPs revealed that Ag influx into L. stagnalis comprised uptake from the NPs themselves and from newly dissolved Ag.

21 CFR 320.27 - Guidelines on the design of a multiple-dose in vivo bioavailability study.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE... subjects in the fasting or nonfasting state, depending upon the conditions reflected in the proposed...

CORRELATING METAL SPECIATION IN SOILS

EPA Science Inventory

Understanding bioavailability of metals from exposure to contaminated soils is a challenging aspect of environmental research. This presentation will examine three areas of research with respect to metal speciation in soils as it relates to bioavailability: 1) Pb immobilization a...

Enhancing the bioavailability of magnolol in rabbits using melting solid dispersion with polyvinylpyrrolidone.

PubMed

Lin, Shiuan-Pey; Hou, Yu-Chi; Liao, Tzu-Yun; Tsai, Shang-Yuan

2014-03-01

Preparation of magnolol-loaded amorphous solid dispersion was investigated for improving the bioavailability. A solid dispersion of magnolol was prepared with polyvinylpyrrolidone K-30 (PVP) by melting method, and the physical properties were characterized by using differential scanning calorimetry, powder X-ray diffractometry, Fourier transformation-infrared spectroscopy and scanning electron microscope. In addition, dissolution test was also performed. Subsequently, the bioavailability of magnolol pure compound, its physical mixture and solid dispersion were compared in rabbits. The blood samples withdrawn via marginal ear vein at specific time points were assayed by HPLC method. Oral administration of the solid dispersion of magnolol with PVP significantly increased the systemic exposures of magnolol and magnolol sulfates/glucuronides by 80.1% and 142.8%, respectively, compared to those given with magnolol pure compound. Magnolol-loaded amorphous solid dispersion with PVP has demonstrated enhanced bioavailability of magnolol in rabbits.

Preparation and enhancement of oral bioavailability of curcumin using microemulsions vehicle.

PubMed

Hu, Liandong; Jia, Yanhong; Niu, Feng; Jia, Zheng; Yang, Xun; Jiao, Kuiliang

2012-07-25

A new microemulsions system of curcumin (CUR-MEs) was successfully developed to improve the solubility and bioavailability of curcumin. Several formulations of the microemulsions system were prepared and evaluated using different ratios of oils, surfactants, and co-surfactants (S&CoS). The optimal formulation, which consists of Capryol 90 (oil), Cremophor RH40 (surfactant), and Transcutol P aqueous solution (co-surfactant), could enhance the solubility of curcumin up to 32.5 mg/mL. The pharmacokinetic study of microemulsions was performed in rats compared to the corresponding suspension. The stability of microemulsions after dilution was excellence. Microemulsions have significantly increased the C(max) and area under the curve (AUC) in comparison to that in suspension (p < 0.05). The relative bioavailability of curcumin in microemulsions was 22.6-fold higher than that in suspension. The results indicated that the CUR-MEs could be used as an effective formulation for enhancing the oral bioavailability of curcumin.

Risk analysis of pyrolyzed biochar made from paper mill effluent treatment plant sludge for bioavailability and eco-toxicity of heavy metals.

PubMed

Devi, Parmila; Saroha, Anil K

2014-06-01

The risk analysis was performed to study the bioavailability and eco-toxicity of heavy metals in biochar obtained from pyrolysis of sludge of pulp and paper mill effluent treatment plant. The sludge was pyrolyzed at different temperatures (200-700°C) and the resultant biochar were analyzed for fractionation of heavy metals by sequential extraction procedure. It was observed that all the heavy metals get enriched in biochar matrix after pyrolysis, but the bioavailability and eco-toxicity of the heavy metals in biochar were significantly reduced as the mobile and bioavailable heavy metal fractions were transformed into the relatively stable fractions. Moreover, it was observed that the leaching potential of heavy metals decreased after pyrolysis and the best results were obtained for biochar pyrolyzed at 700°C. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biofortification with Iron and Zinc Improves Nutritional and Nutraceutical Properties of Common Wheat Flour and Bread.

PubMed

Ciccolini, Valentina; Pellegrino, Elisa; Coccina, Antonio; Fiaschi, Anna Ida; Cerretani, Daniela; Sgherri, Cristina; Quartacci, Mike Frank; Ercoli, Laura

2017-07-12

The effect of field foliar Fe and Zn biofortification on concentration and potential bioavailability of Fe and Zn and health-promoting compounds was studied in wholemeal flour of two common wheat varieties (old vs modern). Moreover, the effect of milling and bread making was studied. Biofortification increased the concentration of Zn (+78%) and its bioavailability (+48%) in the flour of the old variety, whereas it was ineffective in increasing Fe concentration in both varieties. However, the old variety showed higher concentration (+41%) and bioavailability (+26%) of Fe than the modern one. As regard milling, wholemeal flour had higher Fe, Zn concentration and health-promoting compounds compared to white flour. Bread making slightly change Fe and Zn concentration but greatly increased their bioavailability (77 and 70%, respectively). All these results are of great support for developing a production chain of enriched functional bread having a protective role against chronic cardio-vascular diseases.

Porous aerosil loading probucol using supercritical carbon dioxide: preparation, in vitro and in vivo characteristics.

PubMed

Chu, Chunxia; Liu, Muhua; Wang, Dongmei; Guan, Jibin; Cai, Cuifang; Sun, Yuanpeng; Zhang, Tianhong

2014-06-01

The aim of this study was to enhance the dissolution rate and oral bioavailability of probucol. Probucol was adsorbed onto aerosils via supercritical carbon dioxide (ScCO2) and the physicochemistry properties of probucol-aerosil powder were evaluated by differential scanning calorimetry, X-ray diffraction, infrared spectroscopy and scanning electron microscopy. Tablets of the probucol-aerosil powder were prepared by direct compression method. In the dissolution test, the probucol-aerosil tablets showed a significant enhanced dissolution rate compared with commercial tablets. Bioavailability study was carried out in beagle dogs. Probucol-aerosil tablets exhibited higher AUC and Cmax than commercial tablets. The improved dissolution and bioavailability of probucol-aerosil tablets were attributed to the amorphous state and good dispersion of probucol. It is a feasible method to enhance the oral bioavailability by adsorbing probucol onto aerosils via ScCO2.

Pan-Arctic Distribution of Bioavailable Dissolved Organic Matter and Linkages With Productivity in Ocean Margins

NASA Astrophysics Data System (ADS)

Shen, Yuan; Benner, Ronald; Kaiser, Karl; Fichot, Cédric G.; Whitledge, Terry E.

2018-02-01

Rapid environmental changes in the Arctic Ocean affect plankton productivity and the bioavailability of dissolved organic matter (DOM) that supports microbial food webs. We report concentrations of dissolved organic carbon (DOC) and yields of amino acids (indicators of labile DOM) in surface waters across major Arctic margins. Concentrations of DOC and bioavailability of DOM showed large pan-Arctic variability that corresponded to varying hydrological conditions and ecosystem productivity, respectively. Widespread hot spots of labile DOM were observed over productive inflow shelves (Chukchi and Barents Seas), in contrast to oligotrophic interior margins (Kara, Laptev, East Siberian, and Beaufort Seas). Amino acid yields in outflow gateways (Canadian Archipelago and Baffin Bay) indicated the prevalence of semilabile DOM in sea ice covered regions and sporadic production of labile DOM in ice-free waters. Comparing these observations with surface circulation patterns indicated varying shelf subsidies of bioavailable DOM to Arctic deep basins.

Intestinal "bioavailability" of solutes and water: we know how but not why.

PubMed Central

Charney, A. N.

1996-01-01

Only minimal quantities of ingested and normally secreted solutes and water are excreted in the stool. This near 100% bioavailability means that the diet and kidneys are relatively more important determinants of solute, water and acid-base balance than the intestine. Intestinal bioavailability is based on excess transport capacity under normal conditions and the ability to adapt to altered or abnormal conditions. Indeed, the regulatory system of the intestine is as complex, segmented and multi factorial as in the kidney. Alterations in the rate and intestinal site of absorption reflect this regulation, and the diagnosis and treatment of various clinical abnormalities depend on the integrity of intestinal absorptive processes. However, the basis for this regulation an bioavailability are uncertain. Perhaps they had survival value for mammals, a phylogenic class that faced the twin threats of intestinal pathogens and shortages of solutes and water. PMID:9273987

Copper bioavailability and toxicity to Mytilus galloprovincialis in Shelter Island Yacht Basin, San Diego, CA.

PubMed

Bosse, Casey; Rosen, Gunther; Colvin, Marienne; Earley, Patrick; Santore, Robert; Rivera-Duarte, Ignacio

2014-08-15

The bioavailability and toxicity of copper (Cu) in Shelter Island Yacht Basin (SIYB), San Diego, CA, USA, was assessed with simultaneous toxicological, chemical, and modeling approaches. Toxicological measurements included laboratory toxicity testing with Mytilus galloprovincialis (Mediterranean mussel) embryos added to both site water (ambient) and site water spiked with multiple Cu concentrations. Chemical assessment of ambient samples included total and dissolved Cu concentrations, and Cu complexation capacity measurements. Modeling was based on chemical speciation and predictions of bioavailability and toxicity using a marine Biotic Ligand Model (BLM). Cumulatively, these methods assessed the natural buffering capacity of Cu in SIYB during singular wet and dry season sampling events. Overall, the three approaches suggested negligible bioavailability, and isolated observed or predicted toxicity, despite an observed gradient of increasing Cu concentration, both horizontally and vertically within the water body, exceeding current water quality criteria for saltwater. Published by Elsevier Ltd.

Examining the proportion of dietary phosphorus from plants, animals and food additives excreted in urine

PubMed Central

St-Jules, David E; Jagannathan, Ram; Gutekunst, Lisa; Kalantar-Zadeh, Kamyar; Sevick, Mary Ann

2016-01-01

Phosphorus bioavailability is an emerging topic of interest in the field of renal nutrition that has important research and clinical implications. Estimates of phosphorus bioavailability, based on digestibility, indicate that bioavailability of phosphorus increases from plants to animals to food additives. In this commentary, we examined the proportion of dietary phosphorus from plants, animals and food additives excreted in urine from four controlled feeding studies conducted in healthy adults and patients with chronic kidney disease. As expected, a smaller proportion of phosphorus from plant foods was excreted in urine compared to animal foods. However, contrary to expectations, phosphorus from food additives appeared to be incompletely absorbed. The apparent discrepancy between digestibility of phosphorus additives and the proportion excreted in urine suggests a need for human balance studies to determine the bioavailability of different sources of phosphorus. PMID:27810171

Examining the Proportion of Dietary Phosphorus From Plants, Animals, and Food Additives Excreted in Urine.

PubMed

St-Jules, David E; Jagannathan, Ram; Gutekunst, Lisa; Kalantar-Zadeh, Kamyar; Sevick, Mary Ann

2017-03-01

Phosphorus bioavailability is an emerging topic of interest in the field of renal nutrition that has important research and clinical implications. Estimates of phosphorus bioavailability, based on digestibility, indicate that bioavailability of phosphorus increases from plants to animals to food additives. In this commentary, we examined the proportion of dietary phosphorus from plants, animals, and food additives excreted in urine from four controlled-feeding studies conducted in healthy adults and patients with chronic kidney disease. As expected, a smaller proportion of phosphorus from plant foods was excreted in urine compared to animal foods. However, contrary to expectations, phosphorus from food additives appeared to be incompletely absorbed. The apparent discrepancy between digestibility of phosphorus additives and the proportion excreted in urine suggests a need for human balance studies to determine the bioavailability of different sources of phosphorus. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Encapsulation of anthocyanins from bilberries - Effects on bioavailability and intestinal accessibility in humans.

PubMed

Mueller, Dolores; Jung, Kathrin; Winter, Manuel; Rogoll, Dorothee; Melcher, Ralph; Kulozik, Ulrich; Schwarz, Karin; Richling, Elke

2018-05-15

Anthocyanins are flavonoids that have been suggested to provide beneficial health effects. The biological activity of anthocyanins is influenced by their pharmacokinetic properties, but anthocyanins are associated with limited bioavailability in humans. In the presented study, we investigated how the encapsulation of bilberry extract (BE), a source of anthocyanins, with either whey protein or citrus pectin influences the bioavailability and intestinal accessibility of anthocyanins in humans. We performed an intervention study that analyzed anthocyanins and their degradation products in the urine, plasma, and ileal effluent of healthy volunteers and ileostomists (subjects without an intact colon). We were able to show, that whey protein encapsulation modulated short-term bioavailability and that citrus pectin encapsulation increased intestinal accessibility during passage through the small intestine and modulated the formation of the degradation product phloroglucinol aldehyde (PGAL) in human plasma. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Effect of amphiphilic graft co-polymer-carrier on physical stability of bosentan nanocomposite: Assessment of solubility, dissolution and bioavailability.

PubMed

Kendre, Prakash N; Chaudhari, Pravin D

2018-05-01

Bosentan is a dual endothelin receptor antagonist used in the treatment of pulmonary arterial hypertension (PAH). But the solubility and bioavailability of this drug are poor, which has restricted the design and development of dosage forms for efficient and successful therapy. The present study was carried out to develop nanocomposites using an amphiphilic graft co-polymer (Soluplus®) as a carrier to enhance the solubility and bioavailability of bosentan. The graft co-polymer-based nanocomposite formulation was prepared using the single-emulsion technique. The nanocomposite was characterised in terms of particle size analysis, solubility, percentage entrapment efficiency, drug-loading capacity, surface morphology, drug content, in vitro dissolution, stability and bioavailability. FT-IR study revealed that there was no interaction between the drug and Soluplus®. DSC analysis of the nanocomposite formulation confirmed that the bosentan was completely encapsulated within a Soluplus®. XRD analysis showed that the drug was converted to an amorphous form irreversibly. SEM images showed that the particles were of size 96-129μm and had slightly smooth to rough textured surface. TEM analysis indicated that the diameters of the prepared bosentan nanocomposite after dispersion in distilled water were 13.69-96.78nm. Statistically significant increases in the solubility, dissolution and bioavailability of the drug were observed. It was confirmed that the use of a graft co-polymer carrier-based nanocomposite formulation is a good approach for efficient delivery of bosentan, the solubility and bioavailability being increased manifold. Copyright © 2017 Elsevier B.V. All rights reserved.

Absorption Study of Genistein Using Solid Lipid Microparticles and Nanoparticles: Control of Oral Bioavailability by Particle Sizes.

PubMed

Kim, Jeong Tae; Barua, Sonia; Kim, Hyeongmin; Hong, Seong-Chul; Yoo, Seung-Yup; Jeon, Hyojin; Cho, Yeongjin; Gil, Sangwon; Oh, Kyungsoo; Lee, Jaehwi

2017-07-01

In this study, the effect of particle size of genistein-loaded solid lipid particulate systems on drug dissolution behavior and oral bioavailability was investigated. Genistein-loaded solid lipid microparticles and nanoparticles were prepared with glyceryl palmitostearate. Except for the particle size, other properties of genistein-loaded solid lipid microparticles and nanoparticles such as particle composition and drug loading efficiency and amount were similarly controlled to mainly evaluate the effect of different particle sizes of the solid lipid particulate systems on drug dissolution behavior and oral bioavailability. The results showed that genistein-loaded solid lipid microparticles and nanoparticles exhibited a considerably increased drug dissolution rate compared to that of genistein bulk powder and suspension. The microparticles gradually released genistein as a function of time while the nanoparticles exhibited a biphasic drug release pattern, showing an initial burst drug release, followed by a sustained release. The oral bioavailability of genistein loaded in solid lipid microparticles and nanoparticles in rats was also significantly enhanced compared to that in bulk powders and the suspension. However, the bioavailability from the microparticles increased more than that from the nanoparticles mainly because the rapid drug dissolution rate and rapid absorption of genistein because of the large surface area of the genistein-solid lipid nanoparticles cleared the drug to a greater extent than the genistein-solid lipid microparticles did. Therefore, the findings of this study suggest that controlling the particle size of solid-lipid particulate systems at a micro-scale would be a promising strategy to increase the oral bioavailability of genistein.

Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied nanoemulsion

PubMed Central

Shakeel, Faiyaz; Baboota, Sanjula; Ahuja, Alka; Ali, Javed; Shafiq, Sheikh

2008-01-01

Background Celecoxib, a selective cyclo-oxygenase-2 inhibitor has been recommended orally for the treatment of arthritis and osteoarthritis. Long term oral administration of celecoxib produces serious gastrointestinal side effects. It is a highly lipophilic, poorly soluble drug with oral bioavailability of around 40% (Capsule). Therefore the aim of the present investigation was to assess the skin permeation mechanism and bioavailability of celecoxib by transdermally applied nanoemulsion formulation. Optimized oil-in-water nanoemulsion of celecoxib was prepared by the aqueous phase titration method. Skin permeation mechanism of celecoxib from nanoemulsion was evaluated by FTIR spectral analysis, DSC thermogram, activation energy measurement and histopathological examination. The optimized nanoemulsion was subjected to pharmacokinetic (bioavailability) studies on Wistar male rats. Results FTIR spectra and DSC thermogram of skin treated with nanoemulsion indicated that permeation occurred due to the disruption of lipid bilayers by nanoemulsion. The significant decrease in activation energy (2.373 kcal/mol) for celecoxib permeation across rat skin indicated that the stratum corneum lipid bilayers were significantly disrupted (p < 0.05). Photomicrograph of skin sample showed the disruption of lipid bilayers as distinct voids and empty spaces were visible in the epidermal region. The absorption of celecoxib through transdermally applied nanoemulsion and nanoemulsion gel resulted in 3.30 and 2.97 fold increase in bioavailability as compared to oral capsule formulation. Conclusion Results of skin permeation mechanism and pharmacokinetic studies indicated that the nanoemulsions can be successfully used as potential vehicles for enhancement of skin permeation and bioavailability of poorly soluble drugs. PMID:18613981

Curcumin Monoglucoside Shows Improved Bioavailability and Mitigates Rotenone Induced Neurotoxicity in Cell and Drosophila Models of Parkinson's Disease.

PubMed

Pandareesh, M D; Shrivash, M K; Naveen Kumar, H N; Misra, K; Srinivas Bharath, M M

2016-11-01

Curcumin (CUR), a dietary polyphenol has diverse pharmacologic effects, but is limited by poor bioavailability. This is probably due to decreased solubility, cellular uptake and stability. In order to enhance its solubility and bioavailability, we synthesized the CUR bioconjugate curcumin monoglucoside (CMG) and tested its bioavailability, neuroprotective and anti-apoptotic propensity against rotenone (ROT) induced toxicity in N27 dopaminergic neuronal cells and Drosophila models. Our results elucidate that CMG showed improved bioavailability than CUR in N27 cells. Pre-treatment with CMG protected against ROT neurotoxicity and exerted antioxidant effects by replenishing cellular glutathione levels and significantly decreasing reactive species. CMG pre-treatment also restored mitochondrial complex I and IV activities inhibited by ROT. ROT-induced nuclear damage was also restored by CMG as confirmed by comet assay. CMG induced anti-apoptotic effects was substantiated by decreased phosporylation of JNK3 and c-jun, which in turn decreased the cleavage of pro-caspase 3. Q-PCR analysis of redox genes showed up-regulation of NOS2 and down-regulation of NQO1 upon ROT exposure and this was attenuated by CMG pre-treatment. Studies in the Drosophila ROT model revealed that, CMG administration showed better survival rate and locomotor activity, improved antioxidant activity and dopamine content than ROT treated group and was comparable with the CUR group. Based on these data, we surmise that CMG has improved bioavailability and offered neuroprotection comparable with CUR, against ROT-induced toxicity both in dopaminergic neuronal cell line and Drosophila models, with therapeutic implications for PD.

Inorganic mercury binding with different sulfur species in anoxic sediments and their gut juice extractions.

PubMed

Zhong, Huan; Wang, Wen-Xiong

2009-09-01

To investigate the roles of different sulfur (S) species in controlling the partitioning and bioavailability of inorganic mercury (Hg) in anoxic sediments, we examined the differential binding of Hg with three key S species in anoxic sediment (mackinawite [FeS], pyrite [FeS2], and S(2-)) and then quantified their extraction by the gut juice of deposit-feeding sipunculans Sipunculus nudus. A sequential extraction method was simultaneously used to distinguish Hg sorption with different sediment components. All three S-containing sediment components could lead to a high binding of Hg in sediments, but most Hg was sorbed with FeS or FeS2 instead of formation of Hg sulfide despite the presence of S(2-) or humic acid. The gut juice extraction was relatively low and constant whenever FeS and FeS2 were in the sediment, indicating that both FeS and FeS2 controlled the Hg gut juice extraction and thus bioavailability. Mercury sorbed with FeS2 had higher gut juice extraction than that with FeS, while Hg sulfide was not extracted, strongly suggesting that Hg sorbed with FeS2 was more bioavailable than that with other S species. Mercury sorbed with FeS had very low bioavailability to sipunculans at a low Hg:S ratio in the sediment but was more bioavailable with increasing Hg:S ratio up to a maximum (approximately 1:10, mole based). The present study showed that different S species (FeS, FeS2) and Hg:S ratios significantly affected the binding and bioavailability of Hg in anoxic sediments.

A combination of complexation and self-nanoemulsifying drug delivery system for enhancing oral bioavailability and anticancer efficacy of curcumin.

PubMed

Shukla, Mahendra; Jaiswal, Swati; Sharma, Abhisheak; Srivastava, Pradeep Kumar; Arya, Abhishek; Dwivedi, Anil Kumar; Lal, Jawahar

2017-05-01

Curcumin, the golden spice from Indian saffron, has shown chemoprotective action against many types of cancer including breast cancer. However, poor oral bioavailability is the major hurdle in its clinical application. In the recent years, self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising tool to improve the oral absorption and enhancing the bioavailability of poorly water-soluble drugs. In this context, complexation with lipid carriers like phospholipid has also shown the tremendous potential to improve the solubility and therapeutic efficacy of certain drugs with poor oral bioavailability. In the present investigation, a systematic combination of both the approaches is utilized to prepare the phospholipid complex of curcumin and facilitate its incorporation into SNEDDS. The combined use of both the approaches has been explored for the first time to enhance the oral bioavailability and in turn increase the anticancer activity of curcumin. As evident from the pharmacokinetic studies and in situ single pass intestinal perfusion studies in Sprague-Dawley rats, the optimized SNEDDS of curcumin-phospholipid complex has shown enhanced oral absorption and bioavailability of curcumin. The cytotoxicity study in metastatic breast carcinoma cell line has shown the enhancement of cytotoxic action by 38.7%. The primary tumor growth reduction by 58.9% as compared with the control group in 4T1 tumor-bearing BALB/c mice further supported the theory of enhancement of anticancer activity of curcumin in SNEDDS. The developed formulation can be a potential and safe carrier for the oral delivery of curcumin.

Pharmacokinetics and bioavailability of denaverine hydrochloride in healthy subjects following intravenous, oral and rectal single doses.

PubMed

Staab, Alexander; Schug, Barbara S; Larsimont, Véronique; Elze, Martina; Thümmler, Daniela; Mutschler, Ernst; Blume, Henning

2003-02-01

The neurotropic-musculotropic spasmolytic agent denaverine hydrochloride is used mainly in the treatment of smooth muscle spasms of the gastrointestinal and urogenital tract. Despite its commercial availability as a solution for intravenous or intramuscular administration (ampoule) and as a suppository formulation, no pharmacokinetic data in man was available to date. Therefore, the objectives of this clinical trial were to determine the basic pharmacokinetic parameters of denaverine after intravenous administration, to assess the feasibility of using the oral route of administration and to characterise the bioavailability of the suppository formulation. To achieve this, healthy subjects received 50 mg denaverine hydrochloride intravenously, orally and rectally in aqueous solutions and rectally as suppository in an open, randomised crossover design. Total body clearance, volume of distribution at steady-state and half-life of denaverine are 5.7 ml/min per kg, 7.1 l/kg and 33.8 h, respectively. The absolute bioavailability after oral administration of an aqueous solution is 37%. First-pass metabolism leading to the formation of N-monodemethyl denaverine was found to be one reason for the incomplete bioavailability after oral administration. Rectal administration of an aqueous solution of denaverine hydrochloride resulted in a decreased rate (median of C(max) ratios: 26%, difference in median t(max) values: 1.9 h) and extent (31%) of bioavailability compared to oral administration. Using the suppository formulation led to a further reduction in rate (median of C(max) ratios: 30%, difference in median t(max) values: 3 h) and extent (42%) of bioavailability compared to the rectal solution.

Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system

PubMed Central

Chen, Zhi-Qiang; Liu, Ying; Zhao, Ji-Hui; Wang, Lan; Feng, Nian-Ping

2012-01-01

Background Indirubin, isolated from the leaves of the Chinese herb Isatis tinctoria L, is a protein kinase inhibitor and promising antitumor agent. However, the poor water solubility of indirubin has limited its application. In this study, a supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) was developed to improve the oral bioavailability of indirubin. Methods A prototype S-SMEDDS was designed using solubility studies and phase diagram construction. Precipitation inhibitors were selected from hydrophilic polymers according to their crystallization-inhibiting capacity through in vitro precipitation tests. In vitro release of indirubin from S-SMEDDS was examined to investigate its likely release behavior in vivo. The in vivo bioavailability of indirubin from S-SMEDDS and from SMEDDS was compared in rats. Results The prototype formulation of S-SMEDDS comprised Maisine™ 35-1:Cremophor® EL:Transcutol® P (15:40:45, w/w/w). Polyvinylpyrrolidone K17, a hydrophilic polymer, was used as a precipitation inhibitor based on its better crystallization-inhibiting capacity compared with polyethylene glycol 4000 and hydroxypropyl methylcellulose. In vitro release analysis showed more rapid drug release from S-SMEDDS than from SMEDDS. In vivo bioavailability analysis in rats indicated that improved oral absorption was achieved and that the relative bioavailability of S-SMEDDS was 129.5% compared with SMEDDS. Conclusion The novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of indirubin in rats. The results suggest that S-SMEDDS is a superior means of oral delivery of indirubin. PMID:22403491

Biochemical indicators for the bioavailability of organic carbon in ground water

USGS Publications Warehouse

Chapelle, F.H.; Bradley, P.M.; Goode, D.J.; Tiedeman, C.; Lacombe, P.J.; Kaiser, K.; Benner, R.

2009-01-01

The bioavailability of total organic carbon (TOC) was examined in ground water from two hydrologically distinct aquifers using biochemical indicators widely employed in chemical oceanography. Concentrations of total hydrolyzable neutral sugars (THNS), total hydrolyzable amino acids (THAA), and carbon-normalized percentages of TOC present as THNS and THAA (referred to as "yields") were assessed as indicators of bioavailability. A shallow coastal plain aquifer in Kings Bay, Georgia, was characterized by relatively high concentrations (425 to 1492 ??M; 5.1 to 17.9 mg/L) of TOC but relatively low THNS and THAA yields (???0.2%-1.0%). These low yields are consistent with the highly biodegraded nature of TOC mobilized from relatively ancient (Pleistocene) sediments overlying the aquifer. In contrast, a shallow fractured rock aquifer in West Trenton, New Jersey, exhibited lower TOC concentrations (47 to 325 ??M; 0.6 to 3.9 mg/L) but higher THNS and THAA yields (???1% to 4%). These higher yields were consistent with the younger, and thus more bioavailable, TOC being mobilized from modern soils overlying the aquifer. Consistent with these apparent differences in TOC bioavailability, no significant correlation between TOC and dissolved inorganic carbon (DIC), a product of organic carbon mineralization, was observed at Kings Bay, whereas a strong correlation was observed at West Trenton. In contrast to TOC, THNS and THAA concentrations were observed to correlate with DIC at the Kings Bay site. These observations suggest that biochemical indicators such as THNS and THAA may provide information concerning the bioavailability of organic carbon present in ground water that is not available from TOC measurements alone.

Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses.

PubMed

Linardi, Renata L; Stokes, Ashley M; Keowen, Michael L; Barker, Steven A; Hosgood, Giselle L; Short, Charles R

2012-02-01

To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses. 6 healthy adult horses. Horses received single doses (each 0.15 mg/kg) of an oral formulation of methadone hydrochloride orally or intragastrically or an injectable formulation of the drug orally, intragastrically, or IV (5 experimental treatments/horse; 2-week washout period between each experimental treatment). A blood sample was collected from each horse before and at predetermined time points over a 360-minute period after each administration of the drug to determine serum drug concentration by use of gas chromatography-mass spectrometry analysis and to estimate pharmacokinetic parameters by use of a noncompartmental model. Horses were monitored for adverse effects. In treated horses, serum methadone concentrations were equivalent to or higher than the effective concentration range reported for humans, without induction of adverse effects. Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL/min/kg), and small apparent volume of distribution corrected for bioavailability (0.6 to 0.9 L/kg). The bioavailability of methadone administered orally was approximately 3 times that associated with intragastric administration. Absorption of methadone in the small intestine in horses appeared to be limited owing to the low bioavailability after intragastric administration. Better understanding of drug disposition, including absorption, could lead to a more appropriate choice of administration route that would enhance analgesia and minimize adverse effects in horses.

Relative bioavailability of 13C5-folic acid in pectin-coated folate fortified rice in humans using stable isotope techniques.

PubMed

de Ambrosis, A; Vishnumohan, S; Paterson, J; Haber, P; Arcot, J

2017-01-01

The aim of the study was to measure the relative bioavailability of labeled pteroylglutamic acid (13C5-PteGlu) from a pectin-coated fortified rice in vivo to measure any effect of the edible coating on folic acid bioavailability. Healthy volunteers (N=26) aged 18-39 years received three test meals in three randomized short-term cross-over trials: Trial 1: aqueous 400 μg 13C5-PteGlu, Trial 2: 200 g cooked white rice+400 μg 13C5-PteGlu,Trial 3: 200 g fortified cooked white rice with pectin-coated premix containing 400 μg 13C5-PteGlu. Blood samples were drawn at 0,1,2,5 and 8 h postprandial. The concentration of 13C5-5 methyl-tetrahydrofolate appearing in plasma was quantified using high performance liquid chromatography-mass spectrometry (MS)/MS. For 24 h before baseline estimation and during the area under the curve (AUC) study, the subjects were placed on a low folate diet (∼100 μg/day). The relative bioavailability of the folic acid following Trial 3 was measured by comparing the 13C5-5 methyl-tetrahydrofuran (THF) AUC with Trials 1 and 2. The bioavailability of folic acid in a pectin-coated rice premix was 68.7% (range 47-105) and 86.5% (range 65-115) in uncoated fortified rice relative to aqueous folic acid. This study is the first demonstration of the bioavailability of folate in pectin-coated fortified rice in humans.

Absolute Bioavailability and Pharmacokinetics of Linezolid in Hospitalized Patients Given Enteral Feedings

PubMed Central

Beringer, Paul; Nguyen, Megan; Hoem, Nils; Louie, Stan; Gill, Mark; Gurevitch, Michael; Wong-Beringer, Annie

2005-01-01

Linezolid is a new antimicrobial agent effective against drug-resistant gram-positive pathogens which are common causes of infections in hospitalized patients. Many such patients rely on the intravenous or enteral route for nutrition and drug administration. Therefore, the bioavailability of linezolid administered enterally in the presence of enteral feedings in hospitalized patients was examined. Eighteen subjects were assessed in a randomized single-dose crossover study; 12 received continuous enteral feedings, while 6 did not (controls). Both groups received linezolid 600 mg intravenously and orally (control) or enterally, with the alternate route of administration separated by a 24-h washout period. Pharmacokinetic parameters derived from noncompartmental and compartmental analysis incorporating linear and nonlinear elimination pathways were compared between groups: F, Ka, Vs, K23, K32, Vmax, Km, and K20 (bioavailability, absorption rate constant, volume of central compartment normalized to body weight, intercompartmental rate constants, maximum velocity, Michaelis-Menten constant, and elimination rate constant, respectively). Pharmacokinetic (PK) data were available from 17 patients. The linezolid oral suspension was rapidly and completely absorbed by either the oral or enteral route of administration. Bioavailability was unaltered in the presence of enteral feedings. PK estimates remain similar regardless of the model applied. At the therapeutic dose used, only slight nonlinearity in elimination was observed. A linezolid oral suspension may be administered via the enteral route to hospitalized patients without compromise in its excellent bioavailability and rapid rate of absorption. Compartmental pharmacokinetic analysis offers a more flexible study application, since bioavailability (F) can be estimated directly with intermixed intravenous/oral doses without a need for a washout period. PMID:16127039