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Influence of Physical States (Crystalized Versus Solubilized) of Bioactive Components And Oil Composition on Bioaccessibility And BioavailabilityXia, Ziyuan 29 August 2014 (has links)
Three systems were compared in the first case study: (1). pre-dissolved β-carotene nanoemulsion (d< 200nm); (2). corn oil emulsion (d< 200nm) with β-carotene crystals being added before digestion; (3). phosphate buffer saline with β-carotene being added before digestion. Oil-in-water nanoemulsions were formed by high-pressure homogenization using Tween 20 as emulsifier and corn oil as carrier oil and then they were subjected to a simulated mouth, stomach and small intestine digestion. The rate and extent of free fatty acid production in small intestine decreased in the order (2)>(1)>(3); whereas the β-carotene bioaccessibility decreased in the order (1)>>(2)>(3). In system (3), even without any fat content, there is still noticeable consumption of NaOH, which is due to the ester bonds existing in the non-ionic surfactant (Tween 20). In the second case study, we developed two comparing groups by differentiating their oil concentration (20%, 4% respectively). The bioaccessibility of the high fat group is only half of the low fat group due to the insufficient digestion of fat in the former group. In the third case study, the bioaccessibility of nobiletin with different physical states (crystalized vs solubilized) and in different delivery system (conventional emulsion vs nanoemulsion) was compared. Not like β-carotene, the bioaccessibility of nobiletin as crystals in slightly lower than it is as solubilized state. Meanwhile, in conventional emulsion, the bioaccessibility is slightly lower than in nanoemulsion. This study provides important information for developing effective delivery systems for lipophilic bioactive components in food and beverage applications.
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Biodostupnost kovových spécií ve vodním ekosystému / Bioavailability of metals species in water ecosystemTandler, Ágnes January 2012 (has links)
Koncentrace volných kovových iontů je často jen malou částí celkové koncentrace kovu v prostředí. Přes tento malý obsah, je ve většině případů koncentrace volných kovových iontů klíčovým faktorem při určování biodostupnosti a toxicity pro organizmus. Membránová technika Donnan se používá k měření koncentrace volných kovových iontů a v této diplomové práci je ověřena pro směsi kovů (Pb + Cu) při absenci a přítomnosti malých organických ligandů. Olovo a měď jsou environmentálně důležité kovy díky své toxicitě a rozdílným vazebným vlastnostem ve vztahu ke studovaným ligandům.
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Investigating the Mechanisms Underlying Enhanced Bioavailability of Artemisinin Delivered Orally as Dried Leaves of Artemisia annuaDesrosiers, Matthew R. 05 May 2020 (has links)
Malaria, a disease caused by parasites of the Plasmodium genus, infects over 220 million people annually, resulting in over 400,000 deaths. Most of these deaths occur in Africa in children < 5 years of age. Artemisia annua L., an ancient Chinese medicinal herb, is known for its foremost phytochemical constituent, artemisinin (AN). Semisynthetic derivatives of AN form the primary component of artemisinin combination therapies (ACTs), the frontline treatment for malaria worldwide. However, ACTs have several drawbacks including cost and availability. Thus, cheaper, more readily available antimalarials are needed. Recent clinical data suggested dried leaves of A. annua (DLA) administered orally as a tea infusion may be as efficacious as ACTs despite a significantly lower AN dose delivered. In mice, AN plasma concentration was improved when administered as DLA compared to pure AN. I therefore hypothesized that phytochemicals within DLA enhanced the oral bioavailability of AN. To investigate this hypothesis, here I examined the effects of DLA on the underlying mechanisms that govern oral bioavailability. Using an in vitro human digestion model, I showed that AN solubility was greater when delivered as DLA, largely due to essential oil in the plant. Furthermore, AN intestinal permeability was enhanced in a Caco-2 cell model of the intestinal epithelium. Extracts, teas, and phytochemicals produced by Artemisia also inhibited the activity of CYP2B6 and CYP3A4, the enzymes responsible for first-pass AN metabolism in the liver. Additionally, AN tissue distribution was improved when delivered as DLA and AN accumulation in tissues was higher in female vs. male rats. Finally, I showed that DLA was a more efficacious anti-inflammatory than pure AN in rats, potentially due to enhanced AN bioavailability. Taken together, these results shed light on the mechanisms behind enhanced oral bioavailability afforded by DLA and demonstrate the potential for DLA to be used as a therapeutic for malaria and other diseases.
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Nanoparticles in Drug Delivery: Mechanism of Action, Formulation and Clinical Application Towards Reduction in Drug-Associated NephrotoxicityCooper, Dustin L., Conder, Christopher M., Harirforoosh, Sam 01 January 2014 (has links)
Introduction: Over the past few decades, nanoparticles (NPs) have gained immeasurable interest in the field of drug delivery. Various NP formulations have been disseminated in drug development in an attempt to increase efficacy, safety and tolerability of incorporated drugs. In this context, NP formulations that increase solubility, control release, and/or affect the in vivo disposition of drugs, were developed to improve the pharmacokinetic and pharmacodynamic properties of encapsulated drugs.Areas covered: In this article, important properties related to NP function such as particle size, surface charge and shape are disseminated. Also, the current understanding of how NP characteristics affect particle uptake and targeted delivery is elucidated. Selected NP systems currently used in delivery of drugs in biological systems and their production methods are discussed as well. Emphasis is placed on current NP formulations that are shown to reduce drug-induced adverse renal complications.Expert opinion: Formulation designs utilizing NP-encapsulated drugs offer alternative pharmacotherapy options with improved safety profiles for current and emerging drugs. NPs have been shown to increase the therapeutic index of several entrapped drugs mostly by decreasing drug localization and side effects on organs. Recent studies on NP-encapsulated chemotherapeutic and antibiotic medications show enhanced therapeutic outcomes by altering drug degradation, increasing systemic circulation and/or enhancing cell specific targeting. They may also reduce the distribution of encapsulated drugs into the kidneys and attenuate drug-associated adverse renal complications. The usefulness of NP formulation in reducing the nephrotoxicity of nonsteroidal anti-inflammatory drugs is an underexplored territory that deserves more attention.
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Potent Human Uric Acid Transporter 1 Inhibitors: In Vitro and in Vivo Metabolism and Pharmacokinetic StudiesWempe, Michael F., Lightner, Janet W., Miller, Bettina, Iwen, Timothy J., Rice, Peter J., Wakui, Shin, Anzai, Naohiko, Jutabha, Promsuk, Endou, Hitoshi 07 November 2012 (has links)
Human uric acid transporter 1 (hURAT1; SLC22A12) is a very important urate anion exchanger. Elevated urate levels are known to play a pivotal role in cardiovascular diseases, chronic renal disease, diabetes, and hypertension. Therefore, the development of potent uric acid transport inhibitors may lead to novel therapeutic agents to combat these human diseases. The current study investigates small molecular weight compounds and their ability to inhibit 14C-urate uptake in oocytes expressing hURAT1. Using the most promising drug candidates generated from our structure-activity relationship fndings, we subsequently conducted in vitro hepatic metabolism and pharmacokinetic (PK) studies in male Sprague-Dawley rats. Compounds were incubated with rat liver microsomes containing cofactors nicotinamide adenine dinucleotide phosphate and uridine 5′-diphosphoglucuronic acid. In vitro metabolism and PK samples were analyzed using liquid chromatography/mass spectrometry-mass spectrometry methods. Independently, six different inhibitors were orally (capsule dosing) or intravenously (orbital sinus) administered to fasting male Sprague-Dawley rats. Blood samples were collected and analyzed; these data were used to compare in vitro and in vivo metabolism and to compute noncompartmental model PK values. Mono-oxidation (Phase I) and glucuronidation (Phase II) pathways were observed in vitro and in vivo. The in vitro data were used to compute hepatic intrinsic clearance, and the in vivo data were used to compute peak blood concentration, time after administration to achieve peak blood concentration, area under the curve, and orally absorbed fraction. The experimental data provide additional insight into the hURAT1 inhibitor structure-activity relationship and in vitro-in vivo correlation. Furthermore, the results illustrate that one may successfully prepare potent inhibitors that exhibit moderate to good oral bioavailability.
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Pharmacokinetics and Bioavailability of Moxifloxacin in Calves Following Different Routes of AdministrationsGoudah, A., Hasabelnaby, S. 01 April 2010 (has links)
Background: Moxifloxacin is a new fourth-generation 8-methoxy fluoroquinolone developed primarily for the treatment of community-acquired pneumonia and upper respiratory tract infections. The aim of the study was to investigate the plasma pharmacokinetics characteristic of moxifloxacin in calves, after intravenous, intramuscular and subcutaneous administration of a single dose. Meanwhile, plasma protein binding and bioavailability of moxifloxacin were also estimated. Methods: Plasma concentrations of moxifloxacin were measured using a modified HPLC method, and the extent of plasma protein binding was determined in vitro using ultrafiltration. Results: Following intravenous administration, the half life of elimination, the volume of distribution at steady state and the area under the curve were 3.29 h, 0.94 l/kg and 24.72 μg·h/ml, respectively. After intramuscular and subcutaneous administration of moxifloxacin at the same dose, the peak plasma concentrations were 2.41 and 2.20 μg/ml and were obtained at 1.54 and 1.59 h, respectively. The systemic bioavailabilities were 87.19 and 75.94%, respectively. The in vitro plasma protein binding of moxifloxacin in plasma of calves was 27%. Conclusion: A high peak plasma concentration, area under the curve, rapid absorption and bioavailability following intramuscular and subcutaneous administration characterize the pharmacokinetics of moxifloxacin in calves.
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Improving Glyburide Solubility and Dissolution by Complexation With Hydroxybutenyl-β-CyclodextrinKlein, Sandra, Wempe, Michael F., Zoeller, Thomas, Buchanan, Norma L., Lambert, Juanelle L., Ramsey, Michael G., Edgar, Kevin J., Buchanan, Charles M. 01 January 2009 (has links)
Objectives Glyburide, an important drug for type 2 diabetes, has extremely poor aqueous solubility and resulting low bioavailability. This study describes the ability of hydroxybutenyl-β-cyclodextrin (HBenBCD) to form complexes with glyburide, with enhanced solubility and dissolution rate in vitro. Method Glyburide and glyburide-HBenBCD were evaluated in various test media known to simulate human gastrointestinal conditions in the fasted and fed states, respectively. Key findings At ~14 wt% drug load, in the presence of HBenBCD, an almost 400-fold increase in glyburide aqueous solubility was observed. In the presence of HBenBCD, glyburide solubility was also significantly improved in all physiologically relevant test media. Subsequent dissolution experiments confirmed the solubility study results; the dissolution rate and total amount of drug released were significantly increased. Conclusions Complexation with HBenBCD may be an effective way to increase the bioavailability of glyburide.
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Biodisponibilidad, aporte y costo por porción de consumo de calcio en Alimentos de la Tabla Peruana de Alimentos / Bioavailability, contribution and cost per share of calcium consumption in foods in the Peruvian food tableBurgos Farfán, Giannina, Zavala Barrientos, María Fernanda 06 May 2020 (has links)
El calcio es un micronutriente que cumple una importante función estructural y participa en diversos procesos de nuestro organismo. Por ello, es muy importante su inclusión en la alimentación. Tras revisar varios artículos, se identificó que en diversos países la población no llega a cubrir sus requerimientos diarios de calcio. Una de las causas es por la promoción del consumo de alimentos vegetales como fuente de este mineral sin considerar su biodisponibilidad.
En la primera etapa del estudio se realizó una revisión de la literatura y se seleccionaron estudios científicos publicados en revistas de cuatro bases de datos distintas. En la segunda etapa se muestran los contenidos de calcio en 71 alimentos seleccionados de la Tabla Peruana de Alimentos y su biodisponibilidad por porción de consumo. Además, se averiguaron los costos por porción en mercados y supermercados de Lima Metropolitana.
Los resultados muestran que el brócoli y los lácteos son los alimentos que tienen mayor biodisponibilidad de calcio con un 61% y 32% respectivamente. Sin embargo, la porción de consumo habitual del brócoli es pequeña comparada a los lácteos, lo que hace que no se obtenga suficiente cantidad de este micronutriente.
Se concluye que, para satisfacer las necesidades de calcio los lácteos son la mejor opción y que, si bien hay algunos alimentos de origen vegetal que pueden aportar gran cantidad de calcio y el costo de la porción de algunos puede ser accesible, su biodisponibilidad por porción de consumo es baja comparada a los lácteos. / Calcium is a micronutrient that plays an important structural function and participates in various processes of our body. Therefore, its inclusion in food is very important. After reviewing several articles, it was identified that in several countries the population does not meet their daily calcium requirements. One of the causes is the promotion of the consumption of plant foods as a source of this mineral without considering its bioavailability.
In the first stage of the study, a review of the literature was carried out and scientific studies published in journals of four different databases were selected. The second stage shows the calcium contents in 71 selected foods from the Peruvian Food Table and its bioavailability by consumption portion. In addition, the costs per portion in markets and supermarkets of Lima Metropolitana were found.
The results show that broccoli and dairy are foods that have the highest bioavailability of calcium with 61% and 32% respectively. However, the usual consumption portion of broccoli is small compared to dairy, which means that not enough of this micronutrient is obtained.
 It is concluded that, to meet calcium needs dairy is the best option and that, while there are some plant-based foods that can provide a lot of calcium and the cost of portioning some may be accessible, their bioavailability by consumption portion is low compared to dairy products. / Tesis
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The Efficacy of Plant Residue Degradation Products on Phosphorus, Iron, Iodine, and Fluorine Bioavailability to PlantsMackowiak, Cheryl L. 01 May 2001 (has links)
Plant and animal wastes degrade in soils to form relatively stable humified compounds, which form ion complexes that affect the bioavailability of elements in the soil solution. Hydroponic studies with wheat and rice were conducted to characterize the effect of humic acid (HA) on phosphorus (P), iron (Fe), fluorine (F), and iodine (I) bioavailability. Ferrihydrite [Fe(OH)3] precipitation was greater on root surfaces without HA or synthetic chelates. Oxides such as ferrihydrite strongly adsorb P and provide exchange sites for metals. HA reduced this precipitate and increased P and Fe uptake. Humic acid had no effect on F toxicity in rice, where solution levels above 0.5 mM F inhibited growth. Data supported the hypothesis that in moderately acidic solutions (pH< 6), F uptake is primarily as HF rather than F. Doubling solution Ca caused a 10-fold increase in root surface CaF2 precipitates, but the additional Ca did not decrease F toxicity. Calcium levels above 1 mM caused HA to flocculate over time, but the addition of F reduced flocculation by competing with HA for Ca. The majority of shoot F was apparently associated with the middle lamella, suggesting that F may bind with phosphates and pectate-Ca. Organic matter promotes aqueous iodine (I2(aq)) reduction to I-, a less toxic species. HA reduced 12( aq) toxicity by 50%. In solutions without HA, 6.5 μM h(aq) was more toxic than 30 μM I-. Humic acid had no effect on I- uptake or toxicity, where I- and IO3- were toxic to rice at 10 and 100 μM, respectively. These data were used to model element cycling through plants in a regenerative human life support system for NASA 's Advanced Life Support program, where HA, P, Fe, F, and I from plant residues and human wastes are recycled to the crop production system.
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The Iron Bioavailability of Mechanically-Deboned MeatsFarmer, Bonnie Rae Anderson 01 May 1977 (has links)
Two separate experiments were used to investigate iron bioavailability of mechanically-deboned meats using hemoglobin regeneration to measure iron utilization. In both studies, male weanling rats were made anemic by bleeding and being fed a low-iron diet. Experimental diets were control fed to the animals and final hemoglobin concentrations were recorded. Animals were sacrificed and liver iron concentrations determined. The first experiment measured the iron bioavailability of mechanically-deboned and hand-deboned beef plate was better utilized by rats than the iron from mechanically- deboned shank and mechanically-deboned plate. The effect of lipid source and level on iron bioavailability of mechanically-deboned turkey meat was investigated in the second experiment. Fat from the meat was extracted before individual diets were prepared. Four lipids (corn oil, pork fat, turkey fat, or beef tallow) at three different levels (12%, 24%, or 36%) served as dietary fat sources, the effect of lipid dietary fat source and level on iron utilization was found to be negligible.
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