Usnic acid-loaded biocompatible magnetic PLGA-PVA microsphere thin films fabricated by MAPLE with increased resistance to staphylococcal colonization.

PubMed

Grumezescu, V; Holban, A M; Grumezescu, A M; Socol, G; Ficai, A; Vasile, B S; Truscă, R; Bleotu, C; Lazar, V; Chifiriuc, C M; Mogosanu, G D

2014-09-01

Due to their persistence and resistance to the current therapeutic approaches, Staphylococcus aureus biofilm-associated infections represent a major cause of morbidity and mortality in the hospital environment. Since (+)-usnic acid (UA), a secondary lichen metabolite, possesses antimicrobial activity against Gram-positive cocci, including S. aureus, the aim of this study was to load magnetic polylactic-co-glycolic acid-polyvinyl alcohol (PLGA-PVA) microspheres with UA, then to obtain thin coatings using matrix-assisted pulsed laser evaporation and to quantitatively assess the capacity of the bio-nano-active modified surface to control biofilm formation by S. aureus, using a culture-based assay. The UA-loaded microspheres inhibited both the initial attachment of S. aureus to the coated surfaces, as well as the development of mature biofilms. In vitro bioevalution tests performed on the fabricated thin films revealed great biocompatibility, which may endorse them as competitive candidates for the development of improved non-toxic surfaces resistant to S. aureus colonization and as scaffolds for stem cell cultivation and tissue engineering.

A conceptual framework: redifining forests soil's critical acid loads under a changing climate

Treesearch

Steven G. McNulty; Johnny L. Boggs

2010-01-01

Federal agencies of several nations have or are currently developing guidelines for critical forest soil acid loads. These guidelines are used to establish regulations designed to maintain atmospheric acid inputs below levels shown to damage forests and streams. Traditionally, when the critical soil acid load exceeds the amount of acid that the ecosystem can absorb, it...

Insulin-loaded pH-sensitive hyaluronic acid nanoparticles enhance transcellular delivery.

PubMed

Han, Lina; Zhao, Yuefang; Yin, Lifang; Li, Ruiming; Liang, Yang; Huang, Huan; Pan, Shirong; Wu, Chuanbin; Feng, Min

2012-09-01

In the present study, we developed novel insulin-loaded hyaluronic acid (HA) nanoparticles for insulin delivery. The insulin-loaded HA nanoparticles were prepared by reverse-emulsion-freeze-drying method. This method led to a homogenous population of small HA nanoparticles with average size of 182.2 nm and achieved high insulin entrapment efficiencies (approximately 95%). The pH-sensitive HA nanoparticles as an oral delivery carrier showed advantages in protecting insulin against the strongly acidic environment of the stomach, and not destroying the junction integrity of epithelial cells which promise long-term safety for chronic insulin treatment. The results of transport experiments suggested that insulin-loaded HA nanoparticles were transported across Caco-2 cell monolayers mainly via transcellular pathway and their apparent permeability coefficient from apical to basolateral had more than twofold increase compared with insulin solution. The efflux ratio of P (app) (B to A) to P (app) (A to B) less than 1 demonstrated that HA nanoparticle-mediated transport of insulin across Caco-2 cell monolayers underwent active transport. The results of permeability through the rat small intestine confirmed that HA nanoparticles significantly enhanced insulin transport through the duodenum and ileum. Diabetic rats treated with oral insulin-loaded HA nanoparticles also showed stronger hypoglycemic effects than insulin solution. Therefore, these HA nanoparticles could be a promising candidate for oral insulin delivery.

Reductive dehalogenation of haloacetic acids by hemoglobin-loaded carbon nanotube electrode.

PubMed

Li, Yu-Ping; Cao, Hong-Bin; Zhang, Yi

2007-01-01

Hemoglobin (Hb) was immobilized on carbon nanotube (CNT) electrode to catalyze the dehalogenation of haloacetic acids (HAAs). FTIR and UV measurements were performed to investigate the activity-keep of Hb after immobilization on CNT. The electrocatalytic behaviors of the Hb-loaded electrode for the dehalogenation of HAAs were studied by cyclic voltammmetry and constant-potential electrolysis technique. An Hb-loaded packed-bed flow reactor was also constructed for bioelectrocatalytic dehalogenation of HAAs. The results showed that Hb retained its nature, the essential features of its native secondary structure, and its biocatalytic activity after immobilization on CNT. Chloroacetic acids and bromoacetic acids could be dehalogenated completely with Hb catalysis through a stepwise dehalogenation process at -0.400V (vs. saturated calomel electrode (SCE)) and -0.200V (vs. SCE), respectively. The removal of 10.5mM trichloroacetic acid and dichloroacetic acid is ca. 97% and 63%, respectively, with electrolysis for 300min at -0.400V (vs. SCE) using the Hb-loaded packed-bed flow reactor, and almost 100% of tribromoacetic acid and dibromoacetic acid was removed with electrolysis for 40min at -0.200V (vs. SCE). The average current efficiency of Hb-catalytic dehalogenation almost reaches 100%.

Evaluation of the antitumor effect of dexamethasone palmitate and doxorubicin co-loaded liposomes modified with a sialic acid-octadecylamine conjugate.

PubMed

Sun, Jing; Song, Yanzhi; Lu, Mei; Lin, Xiangyun; Liu, Yang; Zhou, Songlei; Su, Yuqing; Deng, Yihui

2016-10-10

Dexamethasone palmitate has the potential to inhibit the activity of tumor-associated macrophages, which promote cancer proliferation, invasion, and metastasis; however, only very high and frequent doses are capable of inducing antitumor effects. With the aim to reduce the anticancer dose and decrease the nonspecific toxicity, we designed a liposomal system to co-deliver dexamethasone palmitate and doxorubicin. Furthermore, a ligand conjugate sialic acid-octadecylamine, with enhanced affinity towards the membrane receptors over-expressed in tumors, was anchored on the surface of the liposomes to increase drug distribution to the tumor tissue. Co-loaded liposomes were developed using lipid film hydration method to load dexamethasone palmitate and remote loading technology to load doxorubicin. The co-loaded liposomes modified with sialic acid-octadecylamine represented comparable physicochemical properties and blood plasma profiles with conventional co-loaded liposomes, but the biodistribution proved that sialic acid-octadecylamine modified liposomes accumulated more in tumor. The co-loaded liposomes showed higher tumor growth suppression than the single-drug loaded liposomes, while showing no additional drug toxicity in S180-bearing Kunming mice. The co-loaded liposomes modified with sialic acid-octadecylamine achieved a significantly better antitumor effect, and induced "shedding" of cancerous tissue in the mice. These finding suggested that co-loaded liposomes modified with sialic acid-octadecylamine provided a safe therapeutic strategy with outstanding anticancer activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation, characterization and pharmacokinetics of enrofloxacin-loaded solid lipid nanoparticles: influences of fatty acids.

PubMed

Xie, Shuyu; Zhu, Luyan; Dong, Zhao; Wang, Xiaofang; Wang, Yan; Li, Xihe; Zhou, WenZhong

2011-04-01

Enrofloxacin-loaded solid lipid nanoparticles (SLN) were prepared using fatty acids (tetradecanoic acid, palmitic acid, stearic acid) as lipid matrix by hot homogenization and ultrasonication method. The effect of fatty acids on the characteristics and pharmacokinetics of the SLN were investigated. The results showed that the encapsulation efficiency and loading capacity of nanoparticles varied with fatty acids in the order of stearic acid>palmitic acid>tetradecanoic acid. Furthermore, stearic acid-SLN had larger particle size, bigger polydispersity index (PDI) and higher zeta potential compared with the other two fatty acid formulated SLN. The SLN showed sustained releases in vitro and the released enrofloxacin had the same antibacterial activity as that of the native enrofloxacin. Although in vitro release exhibited similar patterns, within 24 h the releasing rates of the three formulations were significantly different (tetradecanoic acid-SLN>palmitic acid-SLN>stearic acid-SLN). Pharmacokinetic study after a single dose of intramuscular administration to mice demonstrated that tetradecanoic acid-SLN, palmitic acid-SLN, and stearic acid-SLN increased the bioavailability by 6.79, 3.56 and 2.39 folds, and extended the mean residence time (MRT) of the drug from 10.60 h to 180.36, 46.26 and 19.09 h, respectively. These results suggest that the enrofloxacin-fatty acid SLN are promising formulations for sustained release while fatty acids had significant influences on the characteristics and performances of the SLN. Copyright © 2010 Elsevier B.V. All rights reserved.

Climate change impacts on forest soil critical acid loads and exceedances at a national scale

Treesearch

Steven G. McNulty; Erika C. Cohen; Jennifer A. Moore Myers

2013-01-01

Federal agencies are currently developing guidelines for forest soil critical acid loads across the United States. A critical acid load is defined as the amount of acid deposition (usually expressed on an annual basis) that an ecosystem can absorb. Traditionally, an ecosystem is considered to be at risk for health impairment when the critical acid load exceeds a level...

Docosahexaenoic acid loaded lipid nanoparticles with bactericidal activity against Helicobacter pylori.

PubMed

Seabra, Catarina Leal; Nunes, Cláudia; Gomez-Lazaro, Maria; Correia, Marta; Machado, José Carlos; Gonçalves, Inês C; Reis, Celso A; Reis, Salette; Martins, M Cristina L

2017-03-15

Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid present in fish oil, has been described as a promising molecule to the treatment of Helicobacter pylori gastric infection. However, due to its highly unsaturated structure, DHA can be easily oxidized loosing part of its bioactivity. This work aims the nanoencapsulation of DHA to improve its bactericidal efficacy against H. pylori. DHA was loaded into nanostructured lipid carriers (NLC) produced by hot homogenization and ultrasonication using a blend of lipids (Precirol ATO5 ® , Miglyol-812 ® ) and a surfactant (Tween 60 ® ). Homogeneous NLC with 302±14nm diameter, -28±3mV surface charge (dynamic and electrophoretic light scattering) and containing 66±7% DHA (UV/VIS spectroscopy) were successfully produced. Bacterial growth curves, performed over 24h in the presence of different DHA concentrations (free or loaded into NLC), demonstrated that nanoencapsulation enhanced DHA bactericidal effect, since DHA-loaded NLC were able to inhibit H. pylori growth in a much lower concentrations (25μM) than free DHA (>100μM). Bioimaging studies, using scanning and transmission electron microscopy and also imaging flow cytometry, demonstrated that DHA-loaded NLC interact with H. pylori membrane, increasing their periplasmic space and disrupting membrane and allowing the leakage of cytoplasmic content. Furthermore, the developed nanoparticles are not cytotoxic to human gastric adenocarcinoma cells at bactericidal concentrations. DHA-loaded NLC should, therefore, be envisaged as an alternative to the current treatments for H. pylori infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Metal loading levels influence on REE distribution on humic acid: Experimental and Modelling approach

NASA Astrophysics Data System (ADS)

Marsac, R.; Davranche, M.; Gruau, G.; Dia, A.

2009-04-01

In natural organic-rich waters, rare earth elements (REE) speciation is mainly controlled by organic colloids such as humic acid (HA). Different series of REE-HA complexation experiments performed at several metal loading (REE/C) displayed two pattern shapes (i) at high metal loading, a middle-REE (MREE) downward concavity, and (ii) at low metal loading, a regular increase from La to Lu (e.g. Sonke and Salters, 2006; Pourret et al., 2007). Both REE patterns might be related to REE binding with different surface sites on HA. To understand REE-HA binding, REE-HA complexation experiments at various metals loading were carried out using ultrafiltration combined with ICP-MS measurements, for the 14 REE simultaneously. The patterns of the apparent coefficients of REE partition between HA and the inorganic solution (log Kd) evolved regularly according to the metal loading. The REE patterns presented a MREE downward concavity at low loading and a regular increase from La to Lu at high loading. The dataset was modelled with Model VI by adjusting two specific parameters, log KMA, the apparent complexation constant of HA low affinity sites and DLK2, the parameter increasing high affinity sites binding strength. Experiments and modelling provided evidence that HA high affinity sites controlled the REE binding with HA at low metal loading. The REE-HA complex could be as multidentate complexes with carboxylic or phenolic sites or potentially with sites constituted of N, P or S as donor atoms. Moreover, these high affinity sites could be different for light and heavy REE, because heavy REE have higher affinity for these sites, in low density, and could saturate them. These new Model VI parameter sets allowed the prediction of the REE-HA pattern shape evolution on a large range of pH and metal loading. According to the metal loading, the evolution of the calculated REE patterns was similar to the various REE pattern observed in natural acidic organic-rich waters (pH<7 and DOC>10

Estimates of critical acid loads and exceedances for forest soils across the conterminous United States.

PubMed

McNulty, Steven G; Cohen, Erika C; Moore Myers, Jennifer A; Sullivan, Timothy J; Li, Harbin

2007-10-01

Concern regarding the impacts of continued nitrogen and sulfur deposition on ecosystem health has prompted the development of critical acid load assessments for forest soils. A critical acid load is a quantitative estimate of exposure to one or more pollutants at or above which harmful acidification-related effects on sensitive elements of the environment occur. A pollutant load in excess of a critical acid load is termed exceedance. This study combined a simple mass balance equation with national-scale databases to estimate critical acid load and exceedance for forest soils at a 1-km(2) spatial resolution across the conterminous US. This study estimated that about 15% of US forest soils are in exceedance of their critical acid load by more than 250eqha(-1)yr(-1), including much of New England and West Virginia. Very few areas of exceedance were predicted in the western US.

High Dietary Protein Intake and Protein-Related Acid Load on Bone Health.

PubMed

Cao, Jay J

2017-12-01

Consumption of high-protein diets is increasingly popular due to the benefits of protein on preserving lean mass and controlling appetite and satiety. The paper is to review recent clinical research assessing dietary protein on calcium metabolism and bone health. Epidemiological studies show that long-term, high-protein intake is positively associated with bone mineral density and reduced risk of bone fracture incidence. Short-term interventional studies demonstrate that a high-protein diet does not negatively affect calcium homeostasis. Existing evidence supports that the negative effects of the acid load of protein on urinary calcium excretion are offset by the beneficial skeletal effects of high-protein intake. Future research should focus on the role and the degree of contribution of other dietary and physiological factors, such as intake of fruits and vegetables, in reducing the acid load and further enhancing the anabolic effects of protein on the musculoskeletal system.

Drainage basin control of acid loadings to two Adirondack lakes

NASA Astrophysics Data System (ADS)

Booty, W. G.; Depinto, J. V.; Scheffe, R. D.

1988-07-01

Two adjacent Adirondack Park (New York) calibrated watersheds (Woods Lake and Cranberry Pond), which receive identical atmospheric inputs, generate significantly different unit area of watershed loading rates of acidity to their respective lakes. A watershed acidification model is used to evaluate the watershed parameters which are responsible for the observed differences in acid loadings to the lakes. The greater overall mean depth of overburden on Woods Lake watershed, which supplies a greater buffer capacity as well as a longer retention time of groundwater, appears to be the major factor responsible for the differences.

Catalytic performance of strong acid catalyst: Methyl modified SBA-15 loaded perfluorinated sulfonic acid obtained by the waste perfluorinated sulfonic acid ion exchange membrane

NASA Astrophysics Data System (ADS)

Jiang, Tingshun; Huang, Qiuyan; Li, Yingying; Fang, Minglan; Zhao, Qian

2018-02-01

Mesoporous molecular sieve (SBA-15) was modified using the trimethylchlorosilane as functional agent and the silylation SBA-15 mesoporous material was prepared in this work. The alcohol solution of perfluorinated sulfonic acid dissolved from the waste perfluorinated sulfonic acid ion exchange membrane (PFSIEM) was loaded onto the resulting mesoporous material by the impregnation method and their physicochemical properties were characterized by FT-IR, N2-physisorption, XRD, TG-DSC and TEM. The catalytic activities of these synthesized solid acid catalysts were evaluated by alkylation of phenol with tert-butyl alcohol. The influence of reaction temperature, weight hour space velocity (WHSV) and reaction time on the phenol conversion and product selectivity were assessed by means of a series of experiments. The results showed that with the increase of the active component of the catalyst, these catalysts still remained good mesoporous structure, but the mesoporous ordering decreased to some extent. These catalysts exhibited good catalytic performance for the alkylation of phenol with tert-butanol. The maximum phenol conversion of 89.3% with 70.9% selectivity to 4-t-butyl phenol (4-TBP) was achieved at 120 °C and the WHSV is 4 h-1. The methyl group was loaded on the surface of the catalyst by trimethylchlorosilane. This is beneficial to retard the deactivation of the catalyst. In this work, the alkylation of phenol with tert-butyl alcohol were carried out using the methyl modified SBA-15 mesoporous materials loaded perfluorinated sulfonic acid as catalysts. The results show that the resulting catalyst exhibited high catalytic activity.

Studies on acid-base status (Stewart's model) of young camels (Camelus dromedarius) after acid-load with NH4Cl.

PubMed

Elkhair, Nawal M; Hartmann, Helmut

2010-01-01

The identification of the reference values of Stewart variables and the changes in the acid-base status of the blood and urine in relation to the age after acid-load were studied in desert species of camels. 14 healthy young camels (age: 3-5 months) and 22 adult camels (age: 5-8 years) were used to provide the reference and percentile ranges of the Stewart variables. In the experiments, 24 healthy young camels (age: < 3-5 months) were infused with 5M NH4Cl solution (dose: 1.0 ml/kg) through a permanent intravenous catheter. Venous blood and urine samples were collected before infusion (0 hours). After the start of infusion, venous blood samples were collected at 2, 4, 6, 8 and 24 hours, and urine samples were collected at 8, 24 and 48 hours. Blood and urine samples were used for the determination of the various acid-base parameters, including the non-respiratory Stewart variables. The reference range of serum-[strong ion difference = SID3] was 39-52 mmol/l for all age groups. The reference values of serum-[acid total = A-] were between 10-17 mmol/l for all age groups. Serum-[Atotprotein] and -[Atot-albumin] showed a reference range of 19-24 mmol/I and 20-28 mmol/l, respectively. By 2-8 hours after the NH4Cl-load, the Stewart variables (serum-[SID3] and serum-[A(tot-protein)]) decreased significantly, and as a consequence, the blood pH decreased. Generally, the loaded young camels showed a transient moderate hyperchloraemic acidosis with a slight hypoproteinaemic alkalosis. These malfunctions were accompanied by increased renal fractional excretion of chloride and sodium and decreased urine pH. The identified reference values of the Stewart variables can be used for the clinical diagnosis of acid-base disturbances in camels. With the assistance of the non-respiratory Stewart variables ([SID3] and [Atot]), we can detect the determining influence of strong electrolytes (Na+, K+ and Cl-) and weak acids (proteins, Pi) on the physiological and pathological acid

A conceptual framework: redefining forest soil's critical acid loads under a changing climate.

PubMed

McNulty, Steven G; Boggs, Johnny L

2010-06-01

Federal agencies of several nations have or are currently developing guidelines for critical forest soil acid loads. These guidelines are used to establish regulations designed to maintain atmospheric acid inputs below levels shown to damage forests and streams. Traditionally, when the critical soil acid load exceeds the amount of acid that the ecosystem can absorb, it is believed to potentially impair forest health. The excess over the critical soil acid load is termed the exceedance, and the larger the exceedance, the greater the risk of ecosystem damage. This definition of critical soil acid load applies to exposure of the soil to a single, long-term pollutant (i.e., acidic deposition). However, ecosystems can be simultaneously under multiple ecosystem stresses and a single critical soil acid load level may not accurately reflect ecosystem health risk when subjected to multiple, episodic environmental stress. For example, the Appalachian Mountains of western North Carolina receive some of the highest rates of acidic deposition in the eastern United States, but these levels are considered to be below the critical acid load (CAL) that would cause forest damage. However, the area experienced a moderate three-year drought from 1999 to 2002, and in 2001 red spruce (Picea rubens Sarg.) trees in the area began to die in large numbers. The initial survey indicated that the affected trees were killed by the southern pine beetle (Dendroctonus frontalis Zimm.). This insect is not normally successful at colonizing these tree species because the trees produce large amounts of oleoresin that exclude the boring beetles. Subsequent investigations revealed that long-term acid deposition may have altered red spruce forest structure and function. There is some evidence that elevated acid deposition (particularly nitrogen) reduced tree water uptake potential, oleoresin production, and caused the trees to become more susceptible to insect colonization during the drought period

Covalent and non-covalent curcumin loading in acid-responsive polymeric micellar nanocarriers

NASA Astrophysics Data System (ADS)

Gao, Min; Chen, Chao; Fan, Aiping; Zhang, Ju; Kong, Deling; Wang, Zheng; Zhao, Yanjun

2015-07-01

Poor aqueous solubility, potential degradation, rapid metabolism and elimination lead to low bioavailability of pleiotropic impotent curcumin. Herein, we report two types of acid-responsive polymeric micelles where curcumin was encapsulated via both covalent and non-covalent modes for enhanced loading capacity and on-demand release. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a hydrazone linker, generating two conjugates differing in architecture (single-tail versus double-tail) and free curcumin was encapsulated therein. The two micelles exhibited similar hydrodynamic size at 95 ± 3 nm (single-tail) and 96 ± 3 nm (double-tail), but their loading capacities differed significantly at 15.0 ± 0.5% (w/w) (single-tail) and 4.8 ± 0.5% (w/w) (double-tail). Under acidic sink conditions (pH 5.0 and 6.0), curcumin displayed a faster release from the single-tail nanocarrier, which was correlated to a low IC50 of 14.7 ± 1.6 (μg mL-1) compared to the value of double-tail micelle (24.9 ± 1.3 μg mL-1) in HeLa cells. The confocal imaging and flow cytometry analysis demonstrated a superior capability of single-tail micelle for intracellular curcumin delivery, which was a consequence of the higher loading capacity and lower degree of mPEG surface coverage. In conclusion, the dual loading mode is an effective means to increase the drug content in the micellar nanocarriers whose delivery efficiency is highly dependent on its polymer-drug conjugate architecture. This strategy offers an alternative nanoplatform for intracellularly delivering impotent hydrophobic agents (i.e. curcumin) in an efficient stimuli-triggered way, which is valuable for the enhancement of curcumin’s efficacy in managing a diverse range of disorders.

Dietary acid load and risk of type 2 diabetes: the E3N-EPIC cohort study.

PubMed

Fagherazzi, Guy; Vilier, Alice; Bonnet, Fabrice; Lajous, Martin; Balkau, Beverley; Boutron-Rualt, Marie-Christine; Clavel-Chapelon, Françoise

2014-02-01

The objective of this study was to evaluate the prospective relationship between dietary acid load, assessed with both the potential renal acid load (PRAL) and the net endogenous acid production (NEAP) scores, and type 2 diabetes risk. A total of 66,485 women from the E3N-EPIC cohort were followed for incident diabetes over 14 years. PRAL and NEAP scores were derived from nutrient intakes. HRs for type 2 diabetes risk across quartiles of the baseline PRAL and NEAP scores were estimated with multivariate Cox regression models. During follow-up, 1,372 cases of incident type 2 diabetes were validated. In the overall population, the highest PRAL quartile, reflecting a greater acid-forming potential, was associated with a significant increase in type 2 diabetes risk, compared with the first quartile (HR 1.56, 95% CI 1.29, 1.90). The association was stronger among women with BMI <25 kg/m2 (HR 1.96, 95% CI 1.43, 2.69) than in overweight women (HR 1.28, 95% CI 1.00, 1.64); statistically significant trends in risk across quartiles were observed in both groups (p trend < 0.0001 and p trend = 0.03, respectively). The NEAP score provided similar findings. We have demonstrated for the first time in a large prospective study that dietary acid load was positively associated with type 2 diabetes risk, independently of other known risk factors for diabetes. Our results need to be validated in other populations, and may lead to promotion of diets with a low acid load for the prevention of diabetes. Further research is required on the underlying mechanisms.

In vitro evaluation of α-lipoic acid-loaded lipid nanocapsules for topical delivery.

PubMed

Xia, Nan; Liu, Tian; Wang, Qiang; Xia, Qiang; Bian, Xiaoli

2017-09-01

This study aimed at in vitro evaluation of α-lipoic acid-loaded lipid nanocapsules for topical delivery, which was prepared by hot high-pressure homogenisation. Stable particles could be formed and particle size was 148.54 ± 2.31 nm with polydispersity index below 0.15. Encapsulation efficiency and drug loading of α-lipoic acid were 95.23 ± 0.45% and 2.81 ± 0.37%. Antioxidant study showed α-lipoic acid could be protected by lipid nanocapsules without loss of antioxidant activity. Sustained release of α-lipoic acid from lipid nanocapsules was obtained and cumulative release was 62.18 ± 1.51%. In vitro percutaneous study showed the amount of α-lipoic acid distributed in skin was 1.7-fold than permeated. Cytotoxicity assay and antioxidant activity on L929 cells indicated this formulation had low cytotoxicity and ability of protecting cells from oxidative damage within specific concentration. These studies suggested α-lipoic acid-loaded lipid nanocapsules could be potential formulation for topical delivery.

Standardization of formulations for the acute amino acid depletion and loading tests.

PubMed

Badawy, Abdulla A-B; Dougherty, Donald M

2015-04-01

The acute tryptophan depletion and loading and the acute tyrosine plus phenylalanine depletion tests are powerful tools for studying the roles of cerebral monoamines in behaviour and symptoms related to various disorders. The tests use either amino acid mixtures or proteins. Current amino acid mixtures lack specificity in humans, but not in rodents, because of the faster disposal of branched-chain amino acids (BCAAs) by the latter. The high content of BCAA (30-60%) is responsible for the poor specificity in humans and we recommend, in a 50g dose, a control formulation with a lowered BCAA content (18%) as a common control for the above tests. With protein-based formulations, α-lactalbumin is specific for acute tryptophan loading, whereas gelatine is only partially effective for acute tryptophan depletion. We recommend the use of the whey protein fraction glycomacropeptide as an alternative protein. Its BCAA content is ideal for specificity and the absence of tryptophan, tyrosine and phenylalanine render it suitable as a template for seven formulations (separate and combined depletion or loading and a truly balanced control). We invite the research community to participate in standardization of the depletion and loading methodologies by using our recommended amino acid formulation and developing those based on glycomacropeptide. © The Author(s) 2015.

Budesonide treatment is associated with increased bile acid absorption in collagenous colitis.

PubMed

Bajor, A; Kilander, A; Gälman, C; Rudling, M; Ung, K-A

2006-12-01

Bile acid malabsorption is frequent in collagenous colitis and harmful bile acids may play a pathophysiological role. Glucocorticoids increase ileal bile acid transport. Budesonide have its main effect in the terminal ileum. To evaluate whether the symptomatic effect of budesonide is linked to increased uptake of bile acids. Patients with collagenous colitis were treated with budesonide 9 mg daily for 12 weeks. Prior to and after 8 weeks of treatment, the (75)SeHCAT test, an indirect test for the active uptake of bile acid-s, measurements of serum 7alpha-hydroxy-4-cholesten-3-one, an indicator of hepatic bile acid synthesis, and registration of symptoms were performed. The median (75)SeHCAT retention increased from 18% to 35% (P < 0.001, n = 25) approaching the values of healthy controls (38%). The 7alpha-hydroxy-4-cholesten-3-one values decreased significantly among those with initially high synthesis (from 36 to 23 ng/mL, P = 0.04, n = 9); however, for the whole group the values were not altered (19 ng/mL vs. 13 ng/mL, P = 0.23, N.S., n = 19). The normalization of the (75)SeHCAT test and the reduction of bile acid synthesis in patients with initially high synthetic rate, suggests that the effect of budesonide in collagenous colitis may be in part due to decreased bile acid load on the colon.

Critical loads of acidity for 90,000 lakes in northern Saskatchewan: A novel approach for mapping regional sensitivity to acidic deposition

NASA Astrophysics Data System (ADS)

Cathcart, H.; Aherne, J.; Jeffries, D. S.; Scott, K. A.

2016-12-01

Atmospheric emissions of sulphur dioxide (SO2) from large point sources are the primary concern for acidic deposition in western Canada, particularly in the Athabasca Oil Sands Region (AOSR) where prevailing winds may potentially carry SO2 over acid-sensitive lakes in northern Saskatchewan. A novel catchment-scale regression kriging approach was used to assess regional sensitivity and critical loads of acidity for the total lake population of northern Saskatchewan (89,947 lakes). Lake catchments were delineated using Thiessen polygons, and surface water chemistry was predicted for sensitivity indicators (calcium, pH, alkalinity, and acid neutralizing capacity). Critical loads were calculated with the steady state water chemistry model using regression-kriged base cations, sulphate, and dissolved organic carbon concentrations modelled from surface water observations (n > 800) and digital landscape-scale characteristics, e.g., climate, soil, vegetation, landcover, and geology maps. A large region (>13,726 km2) of two or more indicators of acid sensitivity (pH < 6 and acid neutralizing capacity, alkalinity, calcium < 50 μeq L-1) and low critical loads < 5 meq m-2 yr-1 were predicted on the Athabasca Basin. Exceedance of critical loads under 2006 modelled total sulphate deposition was predicted for 12% of the lakes (covering an area of 3742 km2), primarily located on the Athabasca Basin, within 100 km of the AOSR. There have been conflicting scientific reports of impacts from atmospheric emissions from the AOSR; the results of this study suggest that catchments in the Athabasca Basin within 100 km of the AOSR have received acidic deposition in excess of their critical loads and many of them may be at risk of ecosystem damage owing to their sensitivity.

Food composition and acid-base balance: alimentary alkali depletion and acid load in herbivores.

PubMed

Kiwull-Schöne, Heidrun; Kiwull, Peter; Manz, Friedrich; Kalhoff, Hermann

2008-02-01

Alkali-enriched diets are recommended for humans to diminish the net acid load of their usual diet. In contrast, herbivores have to deal with a high dietary alkali impact on acid-base balance. Here we explore the role of nutritional alkali in experimentally induced chronic metabolic acidosis. Data were collected from healthy male adult rabbits kept in metabolism cages to obtain 24-h urine and arterial blood samples. Randomized groups consumed rabbit diets ad libitum, providing sufficient energy but variable alkali load. One subgroup (n = 10) received high-alkali food and approximately 15 mEq/kg ammonium chloride (NH4Cl) with its drinking water for 5 d. Another group (n = 14) was fed low-alkali food for 5 d and given approximately 4 mEq/kg NH4Cl daily for the last 2 d. The wide range of alimentary acid-base load was significantly reflected by renal base excretion, but normal acid-base conditions were maintained in the arterial blood. In rabbits fed a high-alkali diet, the excreted alkaline urine (pH(u) > 8.0) typically contained a large amount of precipitated carbonate, whereas in rabbits fed a low-alkali diet, both pH(u) and precipitate decreased considerably. During high-alkali feeding, application of NH4Cl likewise decreased pH(u), but arterial pH was still maintained with no indication of metabolic acidosis. During low-alkali feeding, a comparably small amount of added NH4Cl further lowered pH(u) and was accompanied by a significant systemic metabolic acidosis. We conclude that exhausted renal base-saving function by dietary alkali depletion is a prerequisite for growing susceptibility to NH4Cl-induced chronic metabolic acidosis in the herbivore rabbit.

Doxorubicin-loaded glycyrrhetinic acid modified recombinant human serum albumin nanoparticles for targeting liver tumor chemotherapy.

PubMed

Qi, Wen-Wen; Yu, Hai-Yan; Guo, Hui; Lou, Jun; Wang, Zhi-Ming; Liu, Peng; Sapin-Minet, Anne; Maincent, Philippe; Hong, Xue-Chuan; Hu, Xian-Ming; Xiao, Yu-Ling

2015-03-02

Due to overexpression of glycyrrhetinic acid (GA) receptor in liver cancer cells, glycyrrhetinic acid modified recombinant human serum albumin (rHSA) nanoparticles for targeting liver tumor cells may result in increased therapeutic efficacy and decreased adverse effects of cancer therapy. In this study, doxorubicin (DOX) loaded and glycyrrhetinic acid modified recombinant human serum albumin nanoparticles (DOX/GA-rHSA NPs) were prepared for targeting therapy for liver cancer. GA was covalently coupled to recombinant human serum albumin nanoparticles, which could efficiently deliver DOX into liver cancer cells. The resultant GA-rHSA NPs exhibited uniform spherical shape and high stability in plasma with fixed negative charge (∼-25 mV) and a size about 170 nm. DOX was loaded into GA-rHSA NPs with a maximal encapsulation efficiency of 75.8%. Moreover, the targeted NPs (DOX/GA-rHSA NPs) showed increased cytotoxic activity in liver tumor cells compared to the nontargeted NPs (DOX/rHSA NPs, DOX loaded recombinant human serum albumin nanoparticles without GA conjugating). The targeted NPs exhibited higher cellular uptake in a GA receptor-positive liver cancer cell line than nontargeted NPs as measured by both flow cytometry and confocal laser scanning microscopy. Biodistribution experiments showed that DOX/GA-rHSA NPs exhibited a much higher level of tumor accumulation than nontargeted NPs at 1 h after injection in hepatoma-bearing Balb/c mice. Therefore, the DOX/GA-rHSA NPs could be considered as an efficient nanoplatform for targeting drug delivery system for liver cancer.

The role of low acid load in vegetarian diet on bone health: a narrative review.

PubMed

Burckhardt, Peter

2016-01-01

Vegetarian and vegan diets contain low amounts of protein and calcium. For this reason they are supposed to cause low bone mineral density (BMD) and osteoporosis. But this is not the case, except for vegans with a particularly low calcium intake. The absence of osteoporosis or low BMD can be explained by the low acid load of these diets. Nutritional acid load is negatively correlated with bone mineral density (BMD) and positively with fracture risk. Low acid load is correlated with lower bone resorption and higher BMD. It is linked to high intake of potassium-rich nutrients, such as fruits and vegetables, as found in vegetarian diets. The total nutritional acid load, which not only depends on the potassium content of the nutrition, was recently assessed in several studies on vegetarian and vegan diets and was found to be very low or absent, while the diet of Western-style omnivores produces daily 50 to 70 mEq of acid. This might be an important factor for the protection of vegetarians from osteoporosis.

Improved insulin loading in poly(lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids.

PubMed

García-Díaz, María; Foged, Camilla; Nielsen, Hanne Mørck

2015-03-30

Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique. The nanoparticles were characterized in terms of size, zeta potential, insulin encapsulation efficiency and loading capacity. Upon pre-assembly with lipids, there was an increased distribution of insulin into the organic phase of the emulsion, eventually resulting in significantly enhanced encapsulation efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid-insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer during release studies in buffers, whereas insulin was released in a non-complexed form as a burst of approximately 80% of the loaded insulin. In conclusion, the protein load in PLGA nanoparticles can be significantly increased by employing self-assembled protein-lipid complexes. Copyright © 2014 Elsevier B.V. All rights reserved.

Injectable gentamicin-loaded thermo-responsive hyaluronic acid derivative prevents infection in a rabbit model.

PubMed

Ter Boo, Gert-Jan A; Arens, Daniel; Metsemakers, Willem-Jan; Zeiter, Stephan; Richards, R Geoff; Grijpma, Dirk W; Eglin, David; Moriarty, T Fintan

2016-10-01

Despite the use of systemic antibiotic prophylaxis, the surgical fixation of open fractures with osteosynthesis implants is associated with high infection rates. Antibiotic-loaded biomaterials (ALBs) are increasingly used in implant surgeries across medical specialties to deliver high concentrations of antibiotics to the surgical site and reduce the risk of implant-associated infection. ALBs which are either less or not restricted in terms of spatial distribution and which may be applied throughout complex wounds could offer improved protection against infection in open fracture care. A thermo-responsive hyaluronic acid derivative (hyaluronic acid-poly(N-isopropylacrylamide) (HApN)) was prepared by a direct amidation reaction between the tetrabutyl ammonium (TBA) salt of hyaluronic acid and amine-terminated poly(N-isopropylacrylamide) (pN). The degree of grafting, and gelation properties of this gel were characterized, and the composition was loaded with gentamicin. The rheological- and release properties of this gentamicin-loaded HApN composition were tested in vitro and its efficacy in preventing infection was tested in a rabbit model of osteosynthesis contaminated with Staphylococcus aureus. The gentamicin-loaded HApN composition was able to prevent bacterial colonization of the implant site as shown by quantitative bacteriology. This finding was supported by histopathological evaluation of the humeri samples where no bacteria were found in the stained sections. In conclusion, this gentamicin-loaded HApN hydrogel effectively prevents infection in a complex wound, simulating a contaminated fracture treated with plating osteosynthesis. Fracture fixation after trauma is associated with high infection rates. Antibiotic loaded biomaterials (ALBs) can provide high local concentrations without systemic side effects. However, the currently available ALBs have limited accessibility to contaminated tissues in open fractures because of predetermined shape. Thus, a novel

Enhanced Sucrose Loading Improves Rice Yield by Increasing Grain Size.

PubMed

Wang, Liang; Lu, Qingtao; Wen, Xiaogang; Lu, Congming

2015-12-01

Yield in cereals is a function of grain number and size. Sucrose (Suc), the main carbohydrate product of photosynthesis in higher plants, is transported long distances from source leaves to sink organs such as seeds and roots. Here, we report that transgenic rice plants (Oryza sativa) expressing the Arabidopsis (Arabidopsis thaliana) phloem-specific Suc transporter (AtSUC2), which loads Suc into the phloem under control of the phloem protein2 promoter (pPP2), showed an increase in grain yield of up to 16% relative to wild-type plants in field trials. Compared with wild-type plants, pPP2::AtSUC2 plants had larger spikelet hulls and larger and heavier grains. Grain filling was accelerated in the transgenic plants, and more photoassimilate was transported from the leaves to the grain. In addition, microarray analyses revealed that carbohydrate, amino acid, and lipid metabolism was enhanced in the leaves and grain of pPP2::AtSUC2 plants. Thus, enhancing Suc loading represents a promising strategy to improve rice yield to feed the global population. © 2015 American Society of Plant Biologists. All Rights Reserved.

Increasing the resource of high load compression springs

NASA Astrophysics Data System (ADS)

Zemlyanushnova, N. Y.; Zemlyanushnov, N. A.

2017-10-01

Valve springs of VAZ automobiles’ engines are manufactured by using a new method. The decrease of dispersion of operating load in experimental springs compared to serial ones has been proved. The springs have passed a stress cycling test. With the new method having been used, it has been proved that the resource of high load springs working at high loading speed with coils collision has increased up to 60%.

Effects of a gradually increased load of fish waste silage in co-digestion with cow manure on methane production.

PubMed

Solli, Linn; Bergersen, Ove; Sørheim, Roald; Briseid, Tormod

2014-08-01

This study examined the effects of an increased load of nitrogen-rich organic material on anaerobic digestion and methane production. Co-digestion of fish waste silage (FWS) and cow manure (CM) was studied in two parallel laboratory-scale (8L effective volume) semi-continuous stirred tank reactors (designated R1 and R2). A reactor fed with CM only (R0) was used as control. The reactors were operated in the mesophilic range (37°C) with a hydraulic retention time of 30 days, and the entire experiment lasted for 450 days. The rate of organic loading was raised by increasing the content of FWS in the feed stock. During the experiment, the amount (volume%) of FWS was increased stepwise in the following order: 3% - 6% - 13% - 16%, and 19%. Measurements of methane production, and analysis of volatile fatty acids, ammonium and pH in the effluents were carried out. The highest methane production from co-digestion of FWS and CM was 0.400 L CH4 gVS(-1), obtained during the period with loading of 16% FWS in R2. Compared to anaerobic digestion of CM only, the methane production was increased by 100% at most, when FWS was added to the feed stock. The biogas processes failed in R1 and R2 during the periods, with loadings of 16% and 19% FWS, respectively. In both reactors, the biogas processes failed due to overloading and accumulation of ammonia and volatile fatty acids. Copyright © 2014 Elsevier Ltd. All rights reserved.

Application of PSAT to Load Flow Analysis with STATCOM under Load Increase Scenario and Line Contingencies

NASA Astrophysics Data System (ADS)

Telang, Aparna S.; Bedekar, P. P.

2017-09-01

Load flow analysis is the initial and essential step for any power system computation. It is required for choosing better options for power system expansion to meet with ever increasing load demand. Implementation of Flexible AC Transmission System (FACTS) device like STATCOM, in the load flow, which is having fast and very flexible control, is one of the important tasks for power system researchers. This paper presents a simple and systematic approach for steady state power flow calculations with FACTS controller, static synchronous compensator (STATCOM) using command line usage of MATLAB tool-power system analysis toolbox (PSAT). The complexity of MATLAB language programming increases due to incorporation of STATCOM in an existing Newton-Raphson load flow algorithm. Thus, the main contribution of this paper is to show how command line usage of user friendly MATLAB tool, PSAT, can extensively be used for quicker and wider interpretation of the results of load flow with STATCOM. The novelty of this paper lies in the method of applying the load increase pattern, where the active and reactive loads have been changed simultaneously at all the load buses under consideration for creating stressed conditions for load flow analysis with STATCOM. The performance have been evaluated on many standard IEEE test systems and the results for standard IEEE-30 bus system, IEEE-57 bus system, and IEEE-118 bus system are presented.

Guanidinoacetic acid loading affects plasma γ-aminobutyric acid in healthy men.

PubMed

Ostojic, Sergej M; Stojanovic, Marko

2015-08-01

Guanidinoacetic acid (GAA), a precursor of creatine and an innovative dietary agent, activates γ-amino butyric acid (GABA) receptors yet clinical effects of dietary GAA on GABA metabolism are currently unknown. The main aim of this pilot research was to investigate whether GAA loading affected peripheral GABA homeostasis in healthy humans. Eight healthy male volunteers aged 22-25 years were randomized in a double-blind design to receive either GAA (three grams daily) or placebo by oral administration for 3 weeks. At baseline and after 3 weeks participants provided fasting blood samples for free plasma levels of GABA, GAA, creatine and glutamine. Following 3 weeks of intervention, plasma GABA level dropped significantly in participants receiving 3 g of GAA per day as compared to the placebo (P = 0.03). GAA loading significantly decreased plasma GABA by 88.8 nmol/L (95% confidence interval; 5.4-172.1) after 3 weeks of intervention as compared to the baseline (P = 0.03). GAA intervention positively affected both plasma GAA and creatine (P < 0.05), while no effects of intervention were reported for plasma glutamine. Results indicate that supplemental GAA affects peripheral GABA metabolism, and potentially down-regulates GABA synthesis in peripheral tissues. Possible GABAergic action of dietary GAA adds to the safety profile of this novel dietary supplement.

Physicochemical interactions among α-eleostearic acid-loaded liposomes applied to the development of drug delivery systems

NASA Astrophysics Data System (ADS)

Nogueira, Alessandro Oliveira de Moraes; de Sousa, Robson Simplício; Pereira, Luiza Silveira; Mallmann, Christian; da Silva Ferreira, Ailton; Clementin, Rosilene Maria; de Lima, Vânia Rodrigues

2018-02-01

In this study, α-eleostearic acid-loaded (α-ESA-loaded) dimyristoylphosphatidylcholine (DMPC) liposomes had their physicochemical properties characterized by horizontal attenuated total reflectance Fourier transform infrared (HATR-FTIR) spectroscopy, nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). In vitro thiobarbituric acid reactive substance (TBARS) assays were performed to obtain preliminary information on the oxidative potential of the system. An α-ESA-promoted ordering effect in the lipid phosphate region was observed. It was associated with a rotation restriction due to an increase in the amount of lipid group hydrogen bonds. The fatty acid was responsible for the reduction in the degree of hydration of carbonyl groups located in the interfacial region of lipids. α-ESA disordered the DMPC methylene acyl chains by trans-gauche isomerization and increased its rotation rate. TBARS results showed pro-oxidant behavior on liposomes, induced by α-ESA. The discussion about the responses considered the degree of saturation of phosphatidylcholines and suggested that the α-ESA oxidative effects may be modulated by the liposome lipid composition. The versatility of liposomal carriers may be promising for the development of efficacious α-ESA-based drug delivery systems. Results described in this study contribute to the selection of adequate material to produce them.

Functional and in vitro gastric digestibility of the whey protein hydrogel loaded with nanostructured lipid carriers and gelled via citric acid-mediated crosslinking.

PubMed

Hashemi, Behnaz; Madadlou, Ashkan; Salami, Maryam

2017-12-15

Nanostructured lipid carriers (NLCs) with mean size of 347nm were fabricated and added into a heat-denatured whey protein solution. The subsequent crosslinking of proteins by citric acid or CaCl 2 resulted in the formation of cold-set hydrogels. Fourier transform infrared spectroscopy (FTIR) proposed formation of more hydrogen bonds in gel due to NLC loading or citric acid-mediated gelation. It was also found based on FITR spectroscopy that citric acid crosslinking disordered whey proteins. Scanning electron microscopy (SEM) imaging showed a non-porous and finely meshed microstructure for the crosslinked gels compared to non-crosslinked counterparts. Crosslinking also increased the firmness and water-holding capacity of gels. In pepsin-free fluid, a strong correlation existed between reduction in gel swellability and digestibility over periods up to 60min due to NLC loading and citric acid gelation. However, in peptic fluid, NLC loading and citric acid crosslinking brought about much higher decrease in digestibility than swellability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Estimates of critical acid loads and exceedances for forest soils across the conterminous United States

Treesearch

Steven G. McNulty; Erika C. Cohen; Jennifer A. Moore Myers; Timothy J. Sullivan; Harbin Li

2007-01-01

Concern regarding the impacts of continued nitrogen and sulfur deposition on ecosystem health has prompted the development of critical acid load assessments for forest soils. A critical acid load is a quantitative estimate of exposure to one or more pollutants at or above which harmful acidification-related effects on sensitive elements of the environment occur. A...

Intake of green tea inhibited increase of salivary chromogranin A after mental task stress loads

PubMed Central

2014-01-01

Background Green tea has become renowned for its health benefits. In this study, we investigated the anti-stress effect of two kinds of green tea against a mental stress task load. Methods Warm water, ordinary green tea (Sagara), and shaded white tea, which contains more amino acid components than Sagara, were used as test samples in a randomized cross-over design study. Eighteen students (nine male and nine female) participated in three experimental trials on different days at intervals of seven days. Saliva was collected before beverage intake and after performing the mental stress load tasks. Concentration of chromogranin A (CgA) in the saliva was used as an index of autonomic nervous system activity. Results CgA level increased after the mental tasks, but intake of green tea inhibited this increase; the anti-stress effect was even greater after consumption of shaded white tea. Intake of shaded white tea also lowered Total Mood Disturbance (TMD) score on the Profile of Mood States (POMS); subjects in this condition tended to perform more calculations in the arithmetic task than those in the warm water treatment condition. Conclusions Salivary CgA concentration levels increased after mental stress load tasks, but ingestion of green tea inhibited this increase. This anti-stress effect was larger after the consumption of shaded white tea than after Sagara. Shaded white tea intake also lowered TMD score (POMS) and tended to improve performance on an arithmetic task compared to warm water, suggesting that shaded white tea might also improve mood during and after mental stress load. PMID:25034805

Standardization of formulations for the acute amino acid depletion and loading test

PubMed Central

Badawy, Abdulla A-B; Dougherty, Donald M

2017-01-01

The acute tryptophan (Trp) depletion (ATD) and loading (ATL) and the acute tyrosine (Tyr) plus phenylalanine (Phe) depletion (ATPD) tests are powerful tools for studying the roles of cerebral monoamines in behaviour and symptoms related to various disorders. The tests use either amino acid mixtures or proteins. Current amino acid mixtures lack specificity in humans, but not in rodents, because of the faster disposal of branched-chain amino acids (BCAA) by the latter. The high content of BCAA (30-60%) is responsible for the poor specificity in humans and we recommend, in a 50g dose, the control formulation of Young et al. (1985) with a lowered BCAA content (18%) and minor modifications as a common control for the above tests. With protein-based formulations, α-lactalbumin is specific for ATL, whereas gelatine is only partially effective for ATD. We recommend the use of the whey protein fraction glycomacropeptide (GMP) as an alternative protein. Its BCAA content is ideal for specificity and the absence of Trp, Tyr and Phe render it suitable as a template for 7 formulations (separate and combined depletion or loading and a truly balanced control). We invite the research community to participate in standardization of the depletion and loading methodologies by using our recommended amino acid formulation and developing those based on GMP. PMID:25586395

Preparation and in vitro characterization of gallic acid-loaded human serum albumin nanoparticles

NASA Astrophysics Data System (ADS)

Mohammad-Beigi, Hossein; Shojaosadati, Seyed Abbas; Morshedi, Dina; Arpanaei, Ayyoob; Marvian, Amir Tayaranian

2015-04-01

Gallic acid (GA), as an antioxidant and antiparkinson agent, was loaded onto cationic human serum albumin nanoparticles (HSA NPs). Polyethylenimine (PEI)-coated HSA (PEI-HSA) NPs were prepared using three different methods: (I) coating negatively charged HSA NPs with positively charged PEI through attractive electrostatic interactions, (II) coating HSA NPs with PEI via covalent amide bond formation using N-(3-dimethylaminopropyl)- N-ethylcarbodiimide hydrochloride, and (III) coating HSA NPs with PEI via covalent bonding using glutaraldehyde for linking amine groups of PEI and amine groups of albumin NPs. Method II was selected since it resulted in a higher shift in the zeta potential value (mV) and less zeta potential value deviation, and also less size polydispersity. GA was loaded by adsorption onto the surface of PEI-HSA NPs of two different sizes: 117 ± 2.9 nm (PEI-P1) and 180 ± 3.1 nm (PEI-P2) NPs. Both GA-entrapment and GA-loading efficiencies increased slightly with the increasing size of NPs, and were affected intensely by the mass ratio of GA to PEI-HSA NPs. Free radical scavenging of GA was quantified based on the 2,2-diphenyl-1-picrylhydrazyl method. The obtained results showed that GA remains active during the preparation of GA-loaded PEI-HSA NPs. The cytotoxicities of HSA, PEI-HSA, and GA-loaded PEI-HSA NPs on the PC-12 cells, as the neuroendocrine cell line, were measured. Our results indicate that positively charged PEI-HSA NPs are good candidates for efficient and safe delivery of GA to the brain.

Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality

PubMed Central

2011-01-01

Background Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria. Methods Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined. Results Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological p

Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality.

PubMed

Fenton, Tanis R; Tough, Suzanne C; Lyon, Andrew W; Eliasziw, Misha; Hanley, David A

2011-04-30

Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria. Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined. Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological pH. Finally, randomized studies

l-Tyrosine-loaded nanoparticles increase the antitumoral activity of direct electric current in a metastatic melanoma cell model

PubMed Central

de Campos, Vânia Emerich Bucco; Teixeira, Cesar Augusto Antunes; da Veiga, Venicio Feo; Júnior, Eduardo Ricci; Holandino, Carla

2010-01-01

Inhibition of tumor growth induced by treatment with direct electric current (DC) has been reported in several models. One of the mechanisms responsible for the antitumoral activity of DC is the generation of oxidative species, known as chloramines. With the aim of increasing chloramine production in the electrolytic medium and optimizing the antitumoral effects of DC, poly(ɛ-caprolactone) (PCL) nanoparticles (NPs) loaded with the amino acid tyrosine were obtained. The physical–chemical characterization showed that the NPs presented size in nanometric range and monomodal distribution. A slightly negative electrokinetic potential was also found in both blank NPs and l-tyrosine-loaded PCL NPs. The yield of the loading process was approximately 50%. Within 3 h of dissolution assay, a burst release of about 80% l-tyrosine was obtained. The in vitro cytotoxicity of DC was significantly increased when associated with l-tyrosine-loaded NPs, using a murine multidrug-resistant melanoma cell line model. This study showed that the use of the combination of nanotechnology and DC has a promising antineoplastic potential and opens a new perspective in cancer therapy. PMID:21187948

Aspirin increases mitochondrial fatty acid oxidation

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

Uppala, Radha; Dudiak, Brianne; Beck, Megan E.

The metabolic effects of salicylates are poorly understood. This study investigated the effects of aspirin on fatty acid oxidation. Aspirin increased mitochondrial long-chain fatty acid oxidation, but inhibited peroxisomal fatty acid oxidation, in two different cell lines. Aspirin increased mitochondrial protein acetylation and was found to be a stronger acetylating agent in vitro than acetyl-CoA. However, aspirin-induced acetylation did not alter the activity of fatty acid oxidation proteins, and knocking out the mitochondrial deacetylase SIRT3 did not affect the induction of long-chain fatty acid oxidation by aspirin. Aspirin did not change oxidation of medium-chain fatty acids, which can freely traverse themore » mitochondrial membrane. Together, these data indicate that aspirin does not directly alter mitochondrial matrix fatty acid oxidation enzymes, but most likely exerts its effects at the level of long-chain fatty acid transport into mitochondria. The drive on mitochondrial fatty acid oxidation may be a compensatory response to altered mitochondrial morphology and inhibited electron transport chain function, both of which were observed after 24 h incubation of cells with aspirin. These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders. - Highlights: • Aspirin increases mitochondrial—but inhibits peroxisomal—fatty acid oxidation. • Aspirin acetylates mitochondrial proteins including fatty acid oxidation enzymes. • SIRT3 does not influence the effect of aspirin on fatty acid oxidation. • Increased fatty acid oxidation is likely due to altered mitochondrial morphology and respiration.« less

A novel nanofiber Cur-loaded polylactic acid constructed by electrospinning

NASA Astrophysics Data System (ADS)

Thu Trang Mai, Thi; Thu Thuy Nguyen, Thi; Duong Le, Quang; Ngoan Nguyen, Thi; Cham Ba, Thi; Binh Nguyen, Hai; Bich Hoa Phan, Thi; Tran, Dai Lam; Phuc Nguyen, Xuan; Park, Jun Seo

2012-06-01

Curcumin (Cur), extracted from the Curcuma longa L. plant, is well known for its anti-tumor, anti-oxidant, anti-inflammatory and anti-bacterial properties. Nanofiber mats of polylactic acid (PLA) loading Cur (5 wt%) were fabricated by electrospinning (e-spinning). Morphology and structure of the fibers were characterized by field emission scanning electron microscopy (FE-SEM) and Fourier transform infrared (FTIR) spectroscopy, respectively. The diameters of the obtained fibers varied from 200 to 300 nm. The release capacity of curcumin from curcumin-loaded PLA fibers was investigated in phosphate buffer saline (PBS) containing ethanol. After 24 h, 50% of the curcumin was released from curcumin-loaded PLA fibers. These results of electrospun (e-spun) fibers exhibit the potential for biomedical application.

Cognitive load during route selection increases reliance on spatial heuristics.

PubMed

Brunyé, Tad T; Martis, Shaina B; Taylor, Holly A

2018-05-01

Planning routes from maps involves perceiving the symbolic environment, identifying alternate routes and applying explicit strategies and implicit heuristics to select an option. Two implicit heuristics have received considerable attention, the southern route preference and initial segment strategy. This study tested a prediction from decision-making theory that increasing cognitive load during route planning will increase reliance on these heuristics. In two experiments, participants planned routes while under conditions of minimal (0-back) or high (2-back) working memory load. In Experiment 1, we examined how memory load impacts the southern route heuristic. In Experiment 2, we examined how memory load impacts the initial segment heuristic. Results replicated earlier results demonstrating a southern route preference (Experiment 1) and initial segment strategy (Experiment 2) and further demonstrated that evidence for heuristic reliance is more likely under conditions of concurrent working memory load. Furthermore, the extent to which participants maintained efficient route selection latencies in the 2-back condition predicted the magnitude of this effect. Together, results demonstrate that working memory load increases the application of heuristics during spatial decision making, particularly when participants attempt to maintain quick decisions while managing concurrent task demands.

Enhanced Sucrose Loading Improves Rice Yield by Increasing Grain Size1[OPEN

PubMed Central

Wang, Liang; Lu, Qingtao

2015-01-01

Yield in cereals is a function of grain number and size. Sucrose (Suc), the main carbohydrate product of photosynthesis in higher plants, is transported long distances from source leaves to sink organs such as seeds and roots. Here, we report that transgenic rice plants (Oryza sativa) expressing the Arabidopsis (Arabidopsis thaliana) phloem-specific Suc transporter (AtSUC2), which loads Suc into the phloem under control of the phloem protein2 promoter (pPP2), showed an increase in grain yield of up to 16% relative to wild-type plants in field trials. Compared with wild-type plants, pPP2::AtSUC2 plants had larger spikelet hulls and larger and heavier grains. Grain filling was accelerated in the transgenic plants, and more photoassimilate was transported from the leaves to the grain. In addition, microarray analyses revealed that carbohydrate, amino acid, and lipid metabolism was enhanced in the leaves and grain of pPP2::AtSUC2 plants. Thus, enhancing Suc loading represents a promising strategy to improve rice yield to feed the global population. PMID:26504138

The transfer of movement sequences: effects of decreased and increased load.

PubMed

Muehlbauer, Thomas; Panzer, Stefan; Shea, Charles H

2007-06-01

A number of recent experiments have demonstrated that a movement structure develops during the course of learning a movement sequence that provides the basis for transfer. After learning a movement sequence participants have been shown to be able to effectively produce the sequence when movement demands require that the sequence be rescaled in amplitude or produced with an unpractised set of effectors. The purpose of the present experiment was to determine whether participants, after learning a complex 16-element movement sequence with a 0.567-kg load, could also effectively produce the sequence when the load was decreased (0.0 kg) or increased (1.134 kg). The results indicated that participants were able to effectively compensate for decreased and increased load with virtually no changes in performance characteristics (displacement, velocity, acceleration, and pattern of element durations) while electromyographic (EMG) signals demonstrated that smaller (reduced load) or larger forces (increased load) were spontaneously generated to compensate for the change in load. The muscle activation patterns of the biceps and triceps as well as the level of coactivation appeared to be generally upscaled to generate and dissipate the changes in force requirement needed to compensate for the increased load.

Dietary acid load is associated with serum bicarbonate but not insulin sensitivity in chronic kidney disease

PubMed Central

Ikizler, H. Omer; Zelnick, Leila; Ruzinski, John; Curtin, Laura; Utzschneider, Kristina M.; Kestenbaum, Bryan; Himmelfarb, Jonathan; de Boer, Ian H.

2015-01-01

Objective In chronic kidney disease (CKD), dietary acid may promote metabolic acidosis and insulin resistance, which in turn may contribute to adverse clinical health outcomes. We examined associations between dietary acid load, serum bicarbonate, and insulin sensitivity in CKD. Design In a cross-sectional study, we collected 3-day prospective food diaries to quantify dietary acid load as net endogenous acid production (NEAP, the nonvolatile acid load produced by the diet’s acid balance) and potential renal acid load (PRAL). We measured urine net acid excretion (NAE) in 24-hour urine samples. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp. Subjects 42 patients with CKD stages 3–5 attending nephrology clinics in the Pacific Northwest and 21 control subjects (eGFR ≥60mL/min/1.73m2). Main outcome measures Serum bicarbonate and insulin sensitivity (SIclamp). Results Mean age was 60.8±13.6 years and 54% of participants were men. Mean eGFR and serum bicarbonate concentrations were 34.4±13.1 mL/min/1.73m2 and 24.1±2.9 mEq/L for participants with CKD and 88.6±14.5 mL/min/1.73m2 and 26.3±1.8 mEq/L for control subjects, respectively. Mean NEAP, PRAL, and NAE were 58.2±24.3, 9.7±18.4, and 32.1±19.8 mEq/day, respectively. Considering all participants, dietary acid load was significantly, inversely associated with serum bicarbonate, adjusting for age, sex, race, eGFR, BMI, and diuretic use: −1.2 mEq/L per SD NEAP (95% CI −1.8, −0.6, p<0.0001); −0.9 mEq/L bicarbonate per SD PRAL (95% CI −1.5, −0.4, p=0.0005); −0.7 mEq/L bicarbonate per SD NAE (95% CI −1.2, −0.1, p=0.01). These associations were similar in participants with and without CKD. However, neither NEAP, PRAL, nor NAE was significantly associated with SIclamp. Serum bicarbonate was also not significantly associated with SIclamp. Conclusions In CKD, dietary acid load is associated with serum bicarbonate, suggesting that acidosis may be improved by dietary changes, but

Docetaxel-loaded polylactic acid-co-glycolic acid nanoparticles: formulation, physicochemical characterization and cytotoxicity studies.

PubMed

Pradhan, Roshan; Poudel, Bijay Kumar; Ramasamy, Thiruganesh; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2013-08-01

In the present study, we developed novel docetaxel (DTX)-loaded polylactic acid-co-glycolic acid (PLGA) nanoparticles (NPs) using the combination of sodium lauryl sulfate (SLS) and poloxamer 407, the anionic and non-ionic surfactants respectively for stabilization. The NPs were prepared by emulsification/solvent evaporation method. The combination of these surfactants at weight ratio of 1:0.5 was able to produce uniformly distributed small sized NPs and demonstrated the better stability of NP dispersion with high encapsulation efficiency (85.9 +/- 0.6%). The drug/polymer ratio and phase ratio were 2:10 and 1:10, respectively. The optimized formulation of DTX-loaded PLGA NPs had a particle size and polydispersity index of 104.2 +/- 1.5 nm and 0.152 +/- 0.006, respectively, which was further supported by TEM image. In vitro release study was carried out with dialysis membrane and showed 32% drug release in 192 h. When in vitro release data were fitted to Korsmeyer-Peppas model, the n value was 0.481, which suggested the drug was released by anomalous or non-Fickian diffusion. In addition, DTX-loaded PLGA NPs in 72 h, displayed approximately 75% cell viability reduction at 10 microg/ml DTX concentration, in MCF-7 cell lines, indicating sustained release from NPs. Therefore, our results demonstrated that incorporation of DTX into PLGA NPs could provide a novel effective nanocarrier for the treatment of cancer.

Dietary Acid Load is Associated With Serum Bicarbonate but not Insulin Sensitivity in Chronic Kidney Disease.

PubMed

Ikizler, Halil O; Zelnick, Leila; Ruzinski, John; Curtin, Laura; Utzschneider, Kristina M; Kestenbaum, Bryan; Himmelfarb, Jonathan; de Boer, Ian H

2016-03-01

In chronic kidney disease (CKD), dietary acid may promote metabolic acidosis and insulin resistance, which in turn may contribute to adverse clinical health outcomes. We examined associations between dietary acid load, serum bicarbonate, and insulin sensitivity in CKD. In a cross-sectional study, we collected 3-day prospective food diaries to quantify dietary acid load as net endogenous acid production (NEAP, the nonvolatile acid load produced by the diet's acid balance) and potential renal acid load (PRAL). We measured urine net acid excretion (NAE) in 24-hour urine samples. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp. Forty-two patients with CKD Stages 3 to 5 attending nephrology clinics in the Pacific Northwest and 21 control subjects (estimated glomerular filtration rate [eGFR] ≥ 60 mL/minute/1.73 m(2)). Serum bicarbonate and insulin sensitivity (SIclamp). Mean age was 60.8 ± 13.6 years, and 54% of participants were men. Mean eGFR and serum bicarbonate concentrations were 34.4 ± 13.1 mL/minute/1.73 m(2) and 24.1 ± 2.9 mEq/L for participants with CKD and 88.6 ± 14.5 mL/minute/1.73 m(2) and 26.3 ± 1.8 mEq/L for control subjects, respectively. Mean NEAP, PRAL, and NAE were 58.2 ± 24.3, 9.7 ± 18.4, and 32.1 ± 19.8 mEq/day, respectively. Considering all participants, dietary acid load was significantly, inversely associated with serum bicarbonate, adjusting for age, gender, race, eGFR, body mass index, and diuretic use: -1.2 mEq/L per standard deviation (SD) NEAP (95% confidence interval [CI] -1.8 to -0.6, P < .0001); -0.9 mEq/L bicarbonate per SD PRAL (95% CI -1.5 to -0.4, P = .0005); -0.7 mEq/L bicarbonate per SD NAE (95% CI -1.2 to -0.1, P = .01). These associations were similar in participants with and without CKD. However, neither NEAP and PRAL nor NAE was significantly associated with SIclamp. Serum bicarbonate was also not significantly associated with SIclamp. In CKD, dietary acid load is associated with serum bicarbonate

Practical preparation procedures for docetaxel-loaded nanoparticles using polylactic acid-co-glycolic acid.

PubMed

Keum, Chang-Gu; Noh, Young-Wook; Baek, Jong-Suep; Lim, Ji-Ho; Hwang, Chan-Ju; Na, Young-Guk; Shin, Sang-Chul; Cho, Cheong-Weon

2011-01-01

Nanoparticles fabricated from the biodegradable and biocompatible polymer, polylactic-co-glycolic acid (PLGA), are the most intensively investigated polymers for drug delivery systems. The objective of this study was to explore fully the development of a PLGA nanoparticle drug delivery system for alternative preparation of a commercial formulation. In our nanoparticle fabrication, our purpose was to compare various preparation parameters. Docetaxel-loaded PLGA nanoparticles were prepared by a single emulsion technique and solvent evaporation. The nanoparticles were characterized by various techniques, including scanning electron microscopy for surface morphology, dynamic light scattering for size and zeta potential, x-ray photoelectron spectroscopy for surface chemistry, and high-performance liquid chromatography for in vitro drug release kinetics. To obtain a smaller particle, 0.2% polyvinyl alcohol, 0.03% D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), 2% Poloxamer 188, a five-minute sonication time, 130 W sonication power, evaporation with magnetic stirring, and centrifugation at 8000 rpm were selected. To increase encapsulation efficiency in the nanoparticles, certain factors were varied, ie, 2-5 minutes of sonication time, 70-130 W sonication power, and 5-25 mg drug loading. A five-minute sonication time, 130 W sonication power, and a 10 mg drug loading amount were selected. Under these conditions, the nanoparticles reached over 90% encapsulation efficiency. Release kinetics showed that 20.83%, 40.07%, and 51.5% of the docetaxel was released in 28 days from nanoparticles containing Poloxamer 188, TPGS, or polyvinyl alcohol, respectively. TPGS and Poloxamer 188 had slower release kinetics than polyvinyl alcohol. It was predicted that there was residual drug remaining on the surface from x-ray photoelectron spectroscopy. Our research shows that the choice of surfactant is important for controlled release of docetaxel.

Ibuprofen-loaded poly(lactic-co-glycolic acid) films for controlled drug release.

PubMed

Pang, Jianmei; Luan, Yuxia; Li, Feifei; Cai, Xiaoqing; Du, Jimin; Li, Zhonghao

2011-01-01

Ibuprofen- (IBU) loaded biocompatible poly(lactic-co-glycolic acid) (PLGA) films were prepared by spreading polymer/ibuprofen solution on the nonsolvent surface. By controlling the weight ratio of drug and polymer, different drug loading polymer films can be obtained. The synthesized ibuprofen-loaded PLGA films were characterized with scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. The drug release behavior of the as-prepared IBU-loaded PLGA films was studied to reveal their potential application in drug delivery systems. The results show the feasibility of the as-obtained films for controlling drug release. Furthermore, the drug release rate of the film could be controlled by the drug loading content and the release medium. The development of a biodegradable ibuprofen system, based on films, should be of great interest in drug delivery systems.

A modified approach for estimating the aquatic critical load of acid deposition in northern Saskatchewan, Canada

NASA Astrophysics Data System (ADS)

Whitfield, Colin J.; Mowat, Aidan C.; Scott, Kenneth A.; Watmough, Shaun A.

2016-12-01

Acid-sensitive ecosystems are found in northern Saskatchewan, which lies downwind of major sulphur (S) and nitrogen (N) emissions sources associated with the oil sands extraction industry. In order to protect these ecosystems against acidification, tolerance to acid deposition must be quantified. The suitability of the central empirical relationship used in the Steady-State Water Chemistry (SSWC) model to predict historical sulphate (SO4) concentrations was investigated, and an alternate approach for determining aquatic critical loads of acidity (CL(A)) was employed for the study lakes (n = 260). Critical loads of acidity were often low, with median values of 12-16 mmolc m-2 yr-1, with the lower value reflecting a region-specific limit for acid-neutralizing capacity identified in this study. Uncertain levels of atmospheric deposition in the region, however, are problematic for characterizing acidification risk. Accurate S and chloride (Cl) deposition are needed to identify catchment sources (and sinks) of these elements in the new approach for CL(A) calculation. Likewise, accurate depiction of atmospheric deposition levels can prove useful for evaluation of lake runoff estimates on which estimates of CL(A) are contingent. While CL(A) are low and exceedance may occur according to projected increases in S deposition in the near-term, S retention appears to be an important feature in many catchments and risk of acidification may be overstated should long-term S retention be occurring in peatlands.

Obesity increases oesophageal acid exposure

PubMed Central

El‐Serag, Hashem B; Ergun, Gulchin A; Pandolfino, John; Fitzgerald, Stephanie; Tran, Thomas; Kramer, Jennifer R

2007-01-01

Background Obesity has been associated with gastro‐oesophageal reflux disease (GERD); however, the mechanism by which obesity may cause GERD is unclear. Aim To examine the association between oesophageal acid exposure and total body or abdominal anthropometric measures. Methods A cross‐sectional study of consecutive patients undergoing 24 h pH‐metry was conducted. Standardised measurements of body weight and height as well as waist and hip circumference were obtained. The association between several parameters of oesophageal acid exposures and anthropometric measures were examined in univariate and multivariate analyses. Results 206 patients (63% women) with a mean age of 51.4 years who were not on acid‐suppressing drugs were enrolled. A body mass index (BMI) of >30 kg/m2 (compared with BMI<25 kg/m2) was associated with a significant increase in acid reflux episodes, long reflux episodes (>5 min), time with pH<4, and a calculated summary score. These significant associations have affected total, postprandial, upright and supine pH measurements. Waist circumference was also associated with oesophageal acid exposure, but was not as significant or consistent as BMI. When adjusted for waist circumference by including it in the same model, the association between BMI>30 kg/m2 and measures of oesophageal acid exposure became attenuated for all, and not significant for some, thus indicating that waist circumference may mediate a large part of the effect of obesity on oesophageal acid exposure. Conclusions Obesity increases the risk of GERD, at least partly, by increasing oesophageal acid exposure. Waist circumference partly explains the association between obesity and oesophageal acid exposure. PMID:17127706

Omega-3 Fatty Acid Docosahexaenoic Acid Increases SorLA/LR11, a Sorting Protein with Reduced Expression in Sporadic Alzheimer’s Disease (AD): Relevance to AD Prevention

PubMed Central

Ma, Qiu-Lan; Teter, Bruce; Ubeda, Oliver J.; Morihara, Takashi; Dhoot, Dilsher; Nyby, Michael D.; Tuck, Michael L.; Frautschy, Sally A.; Cole, Greg M.

2008-01-01

Environmental and genetic factors, notably ApoE4, contribute to the etiology of late-onset Alzheimer’s disease (LOAD). Reduced mRNA and protein for an apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate β-amyloid (Aβ). Genetic polymorphisms that reduce LR11 expression are associated with increased AD risk. However these polymorphisms account for only a fraction of cases with LR11 deficits, suggesting involvement of environmental factors. Because lipoprotein receptors are typically lipid-regulated, we postulated that LR11 is regulated by docosahexaenoic acid (DHA), an essential ω-3 fatty acid related to reduced AD risk and reduced Aβ accumulation. In this study, we report that DHA significantly increases LR11 in multiple systems, including primary rat neurons, aged non-Tg mice and an aged DHA-depleted APPsw AD mouse model. DHA also increased LR11 in a human neuronal line. In vivo elevation of LR11 was also observed with dietary fish oil in young rats with insulin resistance, a model for type II diabetes, another AD risk factor. These data argue that DHA induction of LR11 does not require DHA-depleting diets and is not age dependent. Because reduced LR11 is known to increase Aβ production and may be a significant genetic cause of LOAD, our results indicate that DHA increases in SorLA/LR11 levels may play an important role in preventing LOAD. PMID:18160637

Exponential increase in postprandial blood-glucose exposure with increasing carbohydrate loads using a linear carbohydrate-to-insulin ratio.

PubMed

Marran, K J; Davey, B; Lang, A; Segal, D G

2013-04-10

Postprandial glucose excursions contribute significantly to average blood glucose, glycaemic variability and cardiovascular risk. Carbohydrate counting is a method of insulin dosing that balances carbohydrate load to insulin dose using a fixed ratio. Many patients and current insulin pumps calculate insulin delivery for meals based on a linear carbohydrate-to-insulin relationship. It is our hypothesis that a non-linear relationship exists between the amounts of carbohydrate consumed and the insulin required to cover it. To document blood glucose exposure in response to increasing carbohydrate loads on fixed carbohydrate-to-insulin ratios. Five type 1 diabetic subjects receiving insulin pump therapy with good control were recruited. Morning basal rates and carbohydrate- to-insulin ratios were optimised. A Medtronic glucose sensor was used for 5 days to collect data for area-under-the-curve (AUC) analysis, during which standardised meals of increasing carbohydrate loads were consumed. Increasing carbohydrate loads using a fixed carbohydrate-to-insulin ratio resulted in increasing glucose AUC. The relationship was found to be exponential rather than linear. Late postprandial hypoglycaemia followed carbohydrate loads of >60 g and this was often followed by rebound hyperglycaemia that lasted >6 hours. A non-linear relationship exists between carbohydrates consumed and the insulin required to cover them. This has implications for control of postprandial blood sugars, especially when consuming large carbohydrate loads. Further studies are required to look at the optimal ratios, duration and type of insulin boluses required to cover increasing carbohydrate loads.

Influence of Fe loadings on desulfurization performance of activated carbon treated by nitric acid.

PubMed

Guo, Jia-Xiu; Shu, Song; Liu, Xiao-Li; Wang, Xue-Jiao; Yin, Hua-Qiang; Chu, Ying-Hao

2017-02-01

A series of Fe supported on activated carbon treated by nitric acid are prepared by incipient wetness impregnation with ultrasonic assistance and characterized by N 2 adsorption-desorption, X-ray diffraction, Fourier transform infrared spectrum and X-ray photoelectron spectroscopy. It has shown that Fe loadings significantly influence the desulfurization activity. Fe/NAC5 exhibits an excellent removal ability of SO 2 , corresponding to breakthrough sulfur capacity of 323 mg/g. With the increasing Fe loadings, the generated Fe 3 O 4 and Fe 2 SiO 4 increase, but Fe 2 (SO 4 ) 3 is observed after desulfurization. Fe/NAC1 has a Brunauer-Emmett-Teller (BET) surface area of 925 m 2 /g with micropore surface area of 843 m 2 /g and total pore volume of 0.562 cm 3 /g including a micropore volume of 0.300 cm 3 /g. With the increasing Fe loadings, BET surface area and micropore volume decrease, and those of Fe/NAC10 decrease to 706 m 2 /g and 0.249 cm 3 /g. The Fe loadings influence the pore-size distribution, and SO 2 adsorption mainly reacts in micropores at about 0.70 nm. C=O and C-O are observed for all samples before SO 2 removal. After desulfurization, the C-O stretching is still detected, but the C=O stretching vibration of carbonyl groups disappears. The stretching of S-O or S=O in sulfate is observed at 592 cm -1 for the used sample, proving that the existence of [Formula: see text].

Omega 3 Chia seed loading as a means of carbohydrate loading.

PubMed

Illian, Travis G; Casey, Jason C; Bishop, Phillip A

2011-01-01

The purpose of this study was to determine if Omega 3 Chia seed loading is a viable option for enhancing sports performance in events lasting >90 minutes and allow athletes to decrease their dietary intake of sugar while increasing their intake of Omega 3 fatty acids. It has been well documented that a high dietary carbohydrate (CHO) intake for several days before competition is known to increase muscle glycogen stores resulting in performance improvements in events lasting >90 minutes. This study compared performance testing results between 2 different CHO-loading treatments. The traditional CHO-loading treatment served as the control (100% cals from Gatorade). The Omega 3 Chia drink (50% of calories from Greens Plus Omega 3 Chia seeds, 50% Gatorade) served as the Omega 3 Chia loading drink. Both CHO-loading treatments were based on the subject's body weight and were thus isocaloric. Six highly trained male subjects V(O2)max 47.8-84.2 ml · kg(-1); mean (SD) of V(O2)max 70.3 ml · kg(-1) (13.3) performed a 1-hour run at ∼65% of their V(O2)max on a treadmill, followed by a 10k time trial on a track. There were 2 trials in a crossover counterbalanced repeated-measures design with a 2-week washout between testing sessions to allow the participants to recover from the intense exercise and any effects of the treatment. There was no statistical difference (p = 0.83) between Omega 3 Chia loading (mean 10k time = 37 minutes 49 seconds) and CHO loading (mean = 37 minutes 43 seconds). Under our conditions, Omega 3 Chia loading appears a viable option for enhancing performance for endurance events lasting >90 minutes and allows athletes to decrease their dietary intake of sugar while increasing their intake of Omega 3 fatty acids but offered no performance advantages.

Vitamin-loaded electrospun cellulose acetate nanofiber mats as transdermal and dermal therapeutic agents of vitamin A acid and vitamin E.

PubMed

Taepaiboon, Pattama; Rungsardthong, Uracha; Supaphol, Pitt

2007-09-01

The present contribution reports the use of mats of electrospun cellulose acetate (CA; acetyl content=39.8%; Mw=30,000 Da) nanofibers as carriers for delivery of the model vitamins, all-trans retinoic acid or vitamin A acid (Retin-A) and alpha-tocopherol or vitamin E (Vit-E). The amounts of Vit-E and Retin-A loaded in the base CA solution [17% w/v in 2:1 v/v acetone/N,N-dimethylacetamide (DMAc)] were 5 and 0.5 wt% (based on the weight of CA), respectively. Cross-sectionally round and smooth fibers were obtained. The average diameters of these fibers ranged between 247 and 265 nm. The total immersion of the vitamin-loaded as-spun CA fiber mats in the acetate buffer solutions containing either 0.5 vol % Tween 80 or 0.5 vol % Tween 80 and 10 vol % methanol was used to arrive at the cumulative release of the vitamins from the fiber mat samples. The same was also conducted on the vitamin-loaded solution-cast CA films for comparison. In most cases, the vitamin-loaded as-spun fiber mats exhibited a gradual and monotonous increase in the cumulative release of the vitamins over the test periods (i.e., 24 h for Vit-E-loaded samples and 6 h for Retin-A-loaded ones), while the corresponding as-cast films exhibited a burst release of the vitamins.

Development of a Controlled Release of Salicylic Acid Loaded Stearic Acid-Oleic Acid Nanoparticles in Cream for Topical Delivery

PubMed Central

Woo, J. O.; Misran, M.; Lee, P. F.; Tan, L. P.

2014-01-01

Lipid nanoparticles are colloidal carrier systems that have extensively been investigated for controlled drug delivery, cosmetic and pharmaceutical applications. In this work, a cost effective stearic acid-oleic acid nanoparticles (SONs) with high loading of salicylic acid, was prepared by melt emulsification method combined with ultrasonication technique. The physicochemical properties, thermal analysis and encapsulation efficiency of SONs were studied. TEM micrographs revealed that incorporation of oleic acid induces the formation of elongated spherical particles. This observation is in agreement with particle size analysis which also showed that the mean particle size of SONs varied with the amount of OA in the mixture but with no effect on their zeta potential values. Differential scanning calorimetry analysis showed that the SONs prepared in this method have lower crystallinity as compared to pure stearic acid. Different amount of oleic acid incorporated gave different degree of perturbation to the crystalline matrix of SONs and hence resulted in lower degrees of crystallinity, thereby improving their encapsulation efficiencies. The optimized SON was further incorporated in cream and its in vitro release study showed a gradual release for 24 hours, denoting the incorporation of salicylic acid in solid matrix of SON and prolonging the in vitro release. PMID:24578624

Bile Acid-Based Drug Delivery Systems for Enhanced Doxorubicin Encapsulation: Comparing Hydrophobic and Ionic Interactions in Drug Loading and Release.

PubMed

Cunningham, Alexander J; Robinson, Mattieu; Banquy, Xavier; Leblond, Jeanne; Zhu, X X

2018-03-05

Doxorubicin (Dox) is a drug of choice in the design of drug delivery systems directed toward breast cancers, but is often limited by loading and control over its release from polymer micelles. Bile acid-based block copolymers present certain advantages over traditional polymer-based systems for drug delivery purposes, since they can enable a higher drug loading via the formation of a reservoir through their aggregation process. In this study, hydrophobic and electrostatic interactions are compared for their influence on Dox loading inside cholic acid based block copolymers. Poly(allyl glycidyl ether) (PAGE) and poly(ethylene glycol) (PEG) were grafted from the cholic acid (CA) core yielding a star-shaped block copolymer with 4 arms (CA-(PAGE- b-PEG) 4 ) and then loaded with Dox via a nanoprecipitation technique. A high Dox loading of 14 wt % was achieved via electrostatic as opposed to hydrophobic interactions with or without oleic acid as a cosurfactant. The electrostatic interactions confer a pH responsiveness to the system. 50% of the loaded Dox was released at pH 5 in comparison to 12% at pH 7.4. The nanoparticles with Dox loaded via hydrophobic interactions did not show such a pH responsiveness. The systems with Dox loaded via electrostatic interactions showed the lowest IC 50 and highest cellular internalization, indicating the pre-eminence of this interaction in Dox loading. The blank formulations are biocompatible and did not show cytotoxicity up to 0.17 mg/mL. The new functionalized star block copolymers based on cholic acid show great potential as drug delivery carriers.

Effects of a gradually increased load of fish waste silage in co-digestion with cow manure on methane production

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

Solli, Linn, E-mail: linn.solli@bioforsk.no; Bergersen, Ove; Sørheim, Roald

2014-08-15

Highlights: • New results from continuous anaerobic co-digestion of fish waste silage (FWS) and cow manure (CM). • Co-digestion of FWS and CM has a high biogas potential. • Optimal mixing ratio of FWS/CM is 13–16/87–84 volume%. • High input of FWS leads to accumulation of NH4+ and VFAs and process failure. - Abstract: This study examined the effects of an increased load of nitrogen-rich organic material on anaerobic digestion and methane production. Co-digestion of fish waste silage (FWS) and cow manure (CM) was studied in two parallel laboratory-scale (8 L effective volume) semi-continuous stirred tank reactors (designated R1 andmore » R2). A reactor fed with CM only (R0) was used as control. The reactors were operated in the mesophilic range (37 °C) with a hydraulic retention time of 30 days, and the entire experiment lasted for 450 days. The rate of organic loading was raised by increasing the content of FWS in the feed stock. During the experiment, the amount (volume%) of FWS was increased stepwise in the following order: 3% – 6% – 13% – 16%, and 19%. Measurements of methane production, and analysis of volatile fatty acids, ammonium and pH in the effluents were carried out. The highest methane production from co-digestion of FWS and CM was 0.400 L CH4 gVS{sup −1}, obtained during the period with loading of 16% FWS in R2. Compared to anaerobic digestion of CM only, the methane production was increased by 100% at most, when FWS was added to the feed stock. The biogas processes failed in R1 and R2 during the periods, with loadings of 16% and 19% FWS, respectively. In both reactors, the biogas processes failed due to overloading and accumulation of ammonia and volatile fatty acids.« less

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches.

PubMed

Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

2016-01-01

Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications.

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

PubMed Central

Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

2016-01-01

Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications. PMID:27536103

Ascorbic Acid Prevents VEGF-induced Increases in Endothelial Barrier Permeability

PubMed Central

Ulker, Esad; Parker, William H.; Raj, Amita; Qu, Zhi-chao; May, James M.

2015-01-01

Vascular endothelial growth factor (VEGF) increases endothelial barrier permeability, an effect that may contribute to macular edema in diabetic retinopathy. Since vitamin C, or ascorbic acid, can tighten the endothelial permeability barrier, we examined whether it could prevent the increase in permeability due to VEGF in human umbilical vein endothelial cells (HUVECs). As previously observed, VEGF increased HUVEC permeability to radiolabeled inulin within 60 min in a concentration-dependent manner. Loading the cells with increasing concentrations of ascorbate progressively prevented the leakage caused by 100 ng/ml VEGF, with a significant inhibition at 13 μM and complete inhibition at 50 μM. Loading cells with 100 μM ascorbate also decreased basal generation of reactive oxygen species and prevented the increase caused by both 100 ng/ml VEGF. VEGF treatment decreased intracellular ascorbate by 25%, thus linking ascorbate oxidation to its prevention of VEGF-induced barrier leakage. The latter was blocked by treating the cells with 60 μM L-NAME (but not D-NAME) as well as by 30 μM sepiapterin, a precursor of tetrahydrobiopterin that is required for proper function of endothelial nitric oxide synthase (eNOS). These findings suggest that VEGF-induced barrier leakage uncouples eNOS. Ascorbate inhibition of the VEGF effect could thus be due either to scavenging superoxide or to peroxynitrite generated by the uncoupled eNOS, or more likely to its ability to recycle tetrahydrobiopterin, thus avoiding enzyme uncoupling in the first place. Ascorbate prevention of VEGF-induced increases in endothelial permeability opens the possibility that its repletion could benefit diabetic macular edema. PMID:26590088

Aspirin Increases Mitochondrial Fatty Acid Oxidation

PubMed Central

Uppala, Radha; Dudiak, Brianne; Beck, Megan E.; Bharathi, Sivakama S.; Zhang, Yuxun; Stolz, Donna B.; Goetzman, Eric S.

2016-01-01

The metabolic effects of salicylates are poorly understood. This study investigated the effects of aspirin on fatty acid oxidation. Aspirin increased mitochondrial long-chain fatty acid oxidation, but inhibited peroxisomal fatty acid oxidation, in two different cell lines. Aspirin increased mitochondrial protein acetylation and was found to be a stronger acetylating agent in vitro than acetyl-CoA. However, aspirin-induced acetylation did not alter the activity of fatty acid oxidation proteins, and knocking out the mitochondrial deacetylase SIRT3 did not affect the induction of long-chain fatty acid oxidation by aspirin. Aspirin did not change oxidation of medium-chain fatty acids, which can freely traverse the mitochondrial membrane. Together, these data indicate that aspirin does not directly alter mitochondrial matrix fatty acid oxidation enzymes, but most likely exerts its effects at the level of long-chain fatty acid transport into mitochondria. The drive on mitochondrial fatty acid oxidation may be a compensatory response to altered mitochondrial morphology and inhibited electron transport chain function, both of which were observed after 24 hr incubation of cells with aspirin. These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders. PMID:27856258

Plugging the attention deficit: perceptual load counters increased distraction in ADHD.

PubMed

Forster, Sophie; Robertson, David J; Jennings, Alistair; Asherson, Philip; Lavie, Nilli

2014-01-01

Increased vulnerability to extraneous distraction is a key symptom of Attention-Deficit Hyperactivity Disorder (ADHD), which may have particularly disruptive consequences. Here we apply Load Theory of attention to increase understanding of this symptom, and to explore a potential method for ameliorating it. Previous research in nonclinical populations has highlighted increased perceptual load as a means of improving the ability to focus attention and avoid distraction. The present study examines whether adults with ADHD can also benefit from conditions of high perceptual load to improve their focused attention abilities. We tested adults with ADHD and age- and IQ-matched controls on a novel measure of irrelevant distraction under load, designed to parallel the form of distraction that is symptomatic of ADHD. During a letter search task, in which perceptual load was varied through search set size, participants were required to ignore salient yet entirely irrelevant distractors (colorful images of cartoon characters) presented infrequently (10% of trials). The presence of these distractors produced a significantly greater interference effect on the search RTs for the adults with ADHD compared with controls, p = .005, ηp² = .231. Perceptual load, however, significantly reduced distractor interference for the ADHD group and was as effective in reducing the elevated distractor interference in ADHD as it was for controls. These findings clarify the nature of the attention deficit underlying increased distraction in ADHD, and demonstrate a tangible method for overcoming it.

Plugging the Attention Deficit: Perceptual Load Counters Increased Distraction in ADHD

PubMed Central

2013-01-01

Objective: Increased vulnerability to extraneous distraction is a key symptom of Attention-Deficit Hyperactivity Disorder (ADHD), which may have particularly disruptive consequences. Here we apply Load Theory of attention to increase understanding of this symptom, and to explore a potential method for ameliorating it. Previous research in nonclinical populations has highlighted increased perceptual load as a means of improving the ability to focus attention and avoid distraction. The present study examines whether adults with ADHD can also benefit from conditions of high perceptual load to improve their focused attention abilities. Method: We tested adults with ADHD and age- and IQ-matched controls on a novel measure of irrelevant distraction under load, designed to parallel the form of distraction that is symptomatic of ADHD. During a letter search task, in which perceptual load was varied through search set size, participants were required to ignore salient yet entirely irrelevant distractors (colorful images of cartoon characters) presented infrequently (10% of trials). Results: The presence of these distractors produced a significantly greater interference effect on the search RTs for the adults with ADHD compared with controls, p = .005, ηp2 = .231. Perceptual load, however, significantly reduced distractor interference for the ADHD group and was as effective in reducing the elevated distractor interference in ADHD as it was for controls. Conclusions: These findings clarify the nature of the attention deficit underlying increased distraction in ADHD, and demonstrate a tangible method for overcoming it. PMID:24219607

Changes in combat task performance under increasing loads in active duty marines.

PubMed

Jaworski, Rebecca L; Jensen, Andrew; Niederberger, Brenda; Congalton, Robert; Kelly, Karen R

2015-03-01

U.S. Marines perform mission tasks under heavy loads which may compromise performance of combat tasks. However, data supporting this performance decrement are limited. The aim of this study was to determine the effects of load on performance of combat-related tasks. Subjects (N=18) ran a modified Maneuver Under Fire ([MANUF], 300 yards [yd] total: two 25-yd sprints, 25-yd crawl, 75-yd casualty drag, 150-yd ammunition can carry, and grenade toss) portion of the U.S. Marine Corps Combat Fitness Test under 4 trial conditions: neat (no load), 15%, 30%, and 45% of body weight, with a shooting task pre- and post-trial. There was a significant increase in total time to completion as a function of load (p<0.0001) with a relationship between load and time (r=0.592, p<0.0001). Pre- to post-MANUF shot accuracy (p=0.005) and precision (p<0.0001) was reduced. Short aerobic performance is significantly impacted by increasing loads. Marksmanship is compromised as a function of fatigue and load. These data suggest that loads of 45% body weight increase time to cover distance and reduce the ability to precisely hit a target. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Budesonide nanocrystal-loaded hyaluronic acid microparticles for inhalation: In vitro and in vivo evaluation.

PubMed

Liu, Tingting; Han, Meihua; Tian, Fang; Cun, Dongmei; Rantanen, Jukka; Yang, Mingshi

2018-02-01

Most inhaled pharmaceutical formulations on the market are intended to exert immediate pharmacological action, even although inhaled sustained-release formulations can be needed to reduce the frequency of dosing. The purpose of this study was to investigate the pulmonary retention and pharmacokinetics of a poorly water-soluble drug after loading its nanocrystal form into inhalable mucoadhesive microparticles composed of hyaluronic acid. It was intended to prolong the pharmacological effect without compromising the dissolution rate of the poorly water-soluble drug. In this study, budesonide, a corticosteroid anti-inflammatory drug, was used as a model poorly water-soluble drug. Submicron budesonide particles were prepared by wet ball milling, and subsequently loaded into hyaluronic acid microparticles by the spray drying process. The ball-milled budesonide particles and the spray-dried microparticles were characterized using dynamic light scattering (DLS), laser diffraction, Scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). Selected formulations were evaluated in terms of their dissolution/release rate, aerosol performance, muco-adhesion and pharmacokinetics in rats. As shown by XRD and DSC analysis, the nanonized budesonide particles in this study were mainly in crystalline form. The dissolution/release study showed that the in vitro release of budesonide from the microparticles was not significantly sustained compared with the dissolution rate of budesonide nanocrystals (BUD-NC). However, the budesonide in the microparticles exhibited prolonged retention on the surface of porcine tracheal tube owing to the muco-adhesion ability of hyaluronic acid. After intratracheal administration to rats, the BUD-NC exhibited a similar pharmacokinetic profile to that of budesonide solution via i.v. injection. In contrast, budesonide loaded in the mucoadhesive microparticles exhibited a significantly prolonged T max

Increased Soluble Phosphorus Loads to Lake Erie: Unintended Consequences of Conservation Practices?

PubMed

Jarvie, Helen P; Johnson, Laura T; Sharpley, Andrew N; Smith, Douglas R; Baker, David B; Bruulsema, Tom W; Confesor, Remegio

2017-01-01

Cumulative daily load time series show that the early 2000s marked a step-change increase in riverine soluble reactive phosphorus (SRP) loads entering the Western Lake Erie Basin from three major tributaries: the Maumee, Sandusky, and Raisin Rivers. These elevated SRP loads have been sustained over the last 12 yr. Empirical regression models were used to estimate the contributions from (i) increased runoff from changing weather and precipitation patterns and (ii) increased SRP delivery (the combined effects of increased source availability and/or increased transport efficiency of labile phosphorus [P] fractions). Approximately 65% of the SRP load increase after 2002 was attributable to increased SRP delivery, with higher runoff volumes accounting for the remaining 35%. Increased SRP delivery occurred concomitantly with declining watershed P budgets. However, within these watersheds, there have been long-term, largescale changes in land management: reduced tillage to minimize erosion and particulate P loss, and increased tile drainage to improve field operations and profitability. These practices can inadvertently increase labile P fractions at the soil surface and transmission of soluble P via subsurface drainage. Our findings suggest that changes in agricultural practices, including some conservation practices designed to reduce erosion and particulate P transport, may have had unintended, cumulative, and converging impacts contributing to the increased SRP loads, reaching a critical threshold around 2002. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Preparation and properties of BSA-loaded microspheres based on multi-(amino acid) copolymer for protein delivery

PubMed Central

Chen, Xingtao; Lv, Guoyu; Zhang, Jue; Tang, Songchao; Yan, Yonggang; Wu, Zhaoying; Su, Jiacan; Wei, Jie

2014-01-01

A multi-(amino acid) copolymer (MAC) based on ω-aminocaproic acid, γ-aminobutyric acid, L-alanine, L-lysine, L-glutamate, and hydroxyproline was synthetized, and MAC microspheres encapsulating bovine serum albumin (BSA) were prepared by a double-emulsion solvent extraction method. The experimental results show that various preparation parameters including surfactant ratio of Tween 80 to Span 80, surfactant concentration, benzyl alcohol in the external water phase, and polymer concentration had obvious effects on the particle size, morphology, and encapsulation efficiency of the BSA-loaded microspheres. The sizes of BSA-loaded microspheres ranged from 60.2 μm to 79.7 μm, showing different degrees of porous structure. The encapsulation efficiency of BSA-loaded microspheres also ranged from 38.8% to 50.8%. BSA release from microspheres showed the classic biphasic profile, which was governed by diffusion and polymer erosion. The initial burst release of BSA from microspheres at the first week followed by constant slow release for the next 7 weeks were observed. BSA-loaded microspheres could degrade gradually in phosphate buffered saline buffer with pH value maintained at around 7.1 during 8 weeks incubation, suggesting that microsphere degradation did not cause a dramatic pH drop in phosphate buffered saline buffer because no acidic degradation products were released from the microspheres. Therefore, the MAC microspheres might have great potential as carriers for protein delivery. PMID:24855351

High Dietary Acid Load Predicts ESRD among Adults with CKD

PubMed Central

Crews, Deidra C.; Wesson, Donald E.; Tilea, Anca M.; Saran, Rajiv; Ríos-Burrows, Nilka; Williams, Desmond E.; Powe, Neil R.

2015-01-01

Small clinical trials have shown that a reduction in dietary acid load (DAL) improves kidney injury and slows kidney function decline; however, the relationship between DAL and risk of ESRD in a population-based cohort with CKD remains unexamined. We examined the association between DAL, quantified by net acid excretion (NAEes), and progression to ESRD in a nationally representative sample of adults in the United States. Among 1486 adults with CKD age≥20 years enrolled in the National Health and Nutrition Examination Survey III, DAL was determined by 24-h dietary recall questionnaire. The development of ESRD was ascertained over a median 14.2 years of follow-up through linkage with the Medicare ESRD Registry. We used the Fine–Gray competing risks method to estimate the association of high, medium, and low DAL with ESRD after adjusting for demographics, nutritional factors, clinical factors, and kidney function/damage markers and accounting for intervening mortality events. In total, 311 (20.9%) participants developed ESRD. Higher levels of DAL were associated with increased risk of ESRD; relative hazards (95% confidence interval) were 3.04 (1.58 to 5.86) for the highest tertile and 1.81 (0.89 to 3.68) for the middle tertile compared with the lowest tertile in the fully adjusted model. The risk of ESRD associated with DAL tertiles increased as eGFR decreased (P trend=0.001). Among participants with albuminuria, high DAL was strongly associated with ESRD risk (P trend=0.03). In conclusion, high DAL in persons with CKD is independently associated with increased risk of ESRD in a nationally representative population. PMID:25677388

Increasing glucose load while maintaining normoglycemia does not evoke neuronal damage in prolonged critically ill rabbits.

PubMed

Sonneville, Romain; den Hertog, Heleen M; Derde, Sarah; Güiza, Fabian; Derese, Inge; Van den Berghe, Greet; Vanhorebeek, Ilse

2013-12-01

Preventing severe hyperglycemia with insulin reduced the neuropathological alterations in frontal cortex during critical illness. We investigated the impact of increasing glucose load under normoglycemia on neurons and glial cells. Hyperinflammatory critically ill rabbits were randomized to fasting or combined parenteral nutrition containing progressively increasing amounts of glucose (low, intermediate, high) within the physiological range but with a similar amount of amino acids and lipids. In all groups, normoglycemia was maintained with insulin. On day 7, we studied the neuropathological alterations in frontal cortex neurons, astrocytes and microglia, and MnSOD as marker of oxidative stress. The percentage of damaged neurons was comparable among all critically ill and healthy rabbits. Critical illness induced an overall 1.8-fold increase in astrocyte density and activation status, largely irrespective of the nutritional intake. The percentage of microglia activation in critically ill rabbits was comparable with that in healthy rabbits, irrespective of glucose load. Likewise, MnSOD expression was comparable in critically ill and healthy rabbits without any clear impact of the nutritional interventions. During prolonged critical illness, increasing intravenous glucose infusion while strictly maintaining normoglycemia appeared safe for neuronal integrity and did not substantially affect glial cells in frontal cortex. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Comparison among model estimates of critical loads of acidic deposition using different sources and scales of input data

Treesearch

T.C. McDonnell; B.J. Cosby; T.J. Sullivan; S.G. McNulty; E.C. Cohen

2010-01-01

The critical load (CL) of acidic atmospheric deposition represents the load of acidity deposited from the atmosphere to the earth’s surface at which harmful acidification effects on sensitive biological receptors are thought to occur. In this study, the CL for forest soils was estimated for 27 watersheds throughout the United States using a steady-state mass balance...

Vulnerability of boreal zone for increased nitrogen loading due to climate change

NASA Astrophysics Data System (ADS)

Rankinen, Katri; Holmberg, Maria

2016-04-01

The observed rapid warming of the boreal zone that has been observed in Finland (0.14 °C by decade) is expected to continue (http://www.ipcc.ch/report/ar5/wg1/). Also precipitation is assumed to increase in future. These changes may increase nitrogen (N) loading from terrestrial environments to water bodies by accelerating soil organic matter decay and by increasing runoff. Nitrogen is limiting nutrient in the Baltic Sea but also in some lakes, so increased loading may increase eutrophication. Further, high nitrate levels in drinking water may cause methaemoglobin anemia for humans, and nitrate is also connected to increased risk of diabetes and cancer. Thus EU has set upper limits to nitrate concentration in drinking water. MONIMET (LIFE12 ENV/FI/000409) is a project about Climate Change Indicators and Vulnerability of Boreal Zone. We simulated N loading from two boreal catchments to the receiving waters by the dynamic, catchment scale model INCA in different climate change and land use change scenarios. We calculated land use specific N loading values for these two well monitored catchments that belong to the LTER (The Long Term Ecological Research) monitoring network. We upscaled the results to the larger river basin, combining them with the information on drinking water supply to assess the vulnerability. Specific emphasis was paid on nitrate concentrations in soil water and groundwater. In general, land use change has higher influence on N loading than increase in precipitation and temperature alone. Peak runoff will sift from snow melting peak in April to late autumn and winter. Growing season will become longer allowing more efficient vegetation uptake of nutrients. Small groundwater aquifers and private wells in the middle of agricultural fields will be in the risk of increased N concentrations, if agricultural N loading increases due to changes in agricultural patterns and land use change.

Effects of attrition, prior acid-etching, and cyclic loading on the bond strength of a self-etching adhesive system to dentin.

PubMed

Shinkai, Koichi; Ebihara, Takashi; Shirono, Manabu; Seki, Hideaki; Wakaki, Suguru; Suzuki, Masaya; Suzuki, Shiro; Katoh, Yoshiroh

2009-03-01

The purpose of this study was to evaluate the effects of dentin attrition, phosphoric acid etching, and cyclic loading on the microtensile bond strength (microTBS) of a self-etching adhesive system to dentin. Flat dentin surfaces of human molars were assigned to eight experimental groups based on those with or without attrition, prior acid-etching, and cyclic loading. Resin composite paste was placed and polymerized after the bonding procedure according to manufacturer's instructions. The specimens were subjected to microTBS testing at a crosshead speed of 0.5 mm/min. Results showed that the minimum mean value of microTBS was 14.9 MPa in the group without attrition and acid-etching but with loading, while the maximum mean value of microTBS was 40.0 MPa in the group without attrition and loading but with acid etching. Therefore, the value of microTBS to dentin without attrition was significantly decreased by cyclic loading but that to dentin with attrition was not affected.

Dietary acid load and bone turnover during long-duration spaceflight and bed rest.

PubMed

Zwart, Sara R; Rice, Barbara L; Dlouhy, Holly; Shackelford, Linda C; Heer, Martina; Koslovsky, Matthew D; Smith, Scott M

2018-05-01

Bed rest studies document that a lower dietary acid load is associated with lower bone resorption. We tested the effect of dietary acid load on bone metabolism during spaceflight. Controlled 4-d diets with a high or low animal protein-to-potassium (APro:K) ratio (High and Low diets, respectively) were given to 17 astronauts before and during spaceflight. Each astronaut had 1 High and 1 Low diet session before flight and 2 High and 2 Low sessions during flight, in addition to a 4-d session around flight day 30 (FD30), when crew members were to consume their typical in-flight intake. At the end of each session, blood and urine samples were collected. Calcium, total protein, energy, and sodium were maintained in each crew member's preflight and in-flight controlled diets. Relative to preflight values, N-telopeptide (NTX) and urinary calcium were higher during flight, and bone-specific alkaline phosphatase (BSAP) was higher toward the end of flight. The High and Low diets did not affect NTX, BSAP, or urinary calcium. Dietary sulfur and age were significantly associated with changes in NTX. Dietary sodium and flight day were significantly associated with urinary calcium during flight. The net endogenous acid production (NEAP) estimated from the typical dietary intake at FD30 was associated with loss of bone mineral content in the lumbar spine after the mission. The results were compared with data from a 70-d bed rest study, in which control (but not exercising) subjects' APro:K was associated with higher NTX during bed rest. Long-term lowering of NEAP by increasing vegetable and fruit intake may protect against changes in loss of bone mineral content during spaceflight when adequate calcium is consumed, particularly if resistive exercise is not being performed. This trial was registered at clinicaltrials.gov as NCT01713634.

Loading and release mechanisms of a biocide in polystyrene-block-poly(acrylic acid) block copolymer micelles.

PubMed

Vyhnalkova, Renata; Eisenberg, Adi; van de Ven, Theo G M

2008-07-24

The kinetics of loading of polystyrene197-block-poly(acrylic acid)47 (PS197-b-PAA47) micelles, suspended in water, with thiocyanomethylthiobenzothiazole biocide and its subsequent release were investigated. Loading of the micelles was found to be a two-step process. First, the surface of the PS core of the micelles is saturated with biocide, with a rate determined by the transfer of solid biocide to micelles during transient micelle-biocide contacts. Next, the biocide penetrates as a front into the micelles, lowering the Tg in the process (non-Fickian case II diffusion). The slow rate of release is governed by the height of the energy barrier that a biocide molecule must overcome to pass from PS into water, resulting in a uniform biocide concentration within the micelle, until Tg is increased to the point that diffusion inside the micelles becomes very slow. Maximum loading of biocide into micelles is approximately 30% (w/w) and is achieved in 1 h. From partition experiments, it can be concluded that the biocide has a similar preference for polystyrene as for ethylbenzene over water, implying that the maximum loading is governed by thermodynamics.

Higher Estimated Net Endogenous Acid Production May Be Associated with Increased Prevalence of Nonalcoholic Fatty Liver Disease in Chinese Adults in Hong Kong

PubMed Central

Chan, Ruth; Wong, Vincent Wai-Sun; Chu, Winnie Chiu-Wing; Wong, Grace Lai-Hung; Li, Liz Sin; Leung, Jason; Chim, Angel Mei-Ling; Yeung, David Ka-Wai; Sea, Mandy Man-Mei; Woo, Jean; Chan, Francis Ka-Leung; Chan, Henry Lik-Yuen

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) has been associated with reduced growth hormone levels and signaling. Such hormonal changes also occur in metabolic acidosis. Since mild metabolic acidosis can be diet induced, diet-induced acid load may constitute a nutritional factor with possible influence on NAFLD development. This study explored whether a higher diet-induced acid load is associated with an increased likelihood of NAFLD. Apparently healthy Chinese adults (330 male, 463 female) aged 19-72 years were recruited through population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. Estimated net endogenous acid production (NEAP) was calculated using Frassetto’s method and potential renal acid load (PRAL) was calculated using Remer’s method based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at >5% by proton-magnetic resonance spectroscopy. Possible advanced fibrosis was defined as liver stiffness at >7.9 kPa by transient elastography. Multivariate logistic regression models were used to examine the association between each measure of dietary acid load and prevalent NAFLD or possible advanced fibrosis with adjustment for potential anthropometric and lifestyle factors. 220 subjects (27.7%) were diagnosed with NAFLD. Estimated NEAP was positively associated with the likelihood of having NAFLD after adjustment for age, sex, body mass index, current drinker status and the presence of metabolic syndrome [OR (95% CI) = 1.25 (1.02-1.52), p = 0.022]. The association was slightly attenuated but remained significant when the model was further adjusted for other dietary variables. No association between PRAL and NAFLD prevalence was observed. Both estimated NEAP and PRAL were not associated with the presence of possible advance fibrosis. Our findings suggest that there may be a modest association between diet-induced acid load and NAFLD. More studies are needed to

Acid deposition and assessment of its critical load for the environmental health of waterbodies in a subtropical watershed, China

NASA Astrophysics Data System (ADS)

Jia, Junjie; Gao, Yang

2017-12-01

Atmospheric acidic deposition in subtropical watersheds poses an environmental risk of causing acidification of aquatic ecosystems. In this study, we evaluated the frequency of acid deposition in a subtropical forest ecosystem and the associated critical loads of acidity for a sensitive aquatic ecosystem. We found that out of 132 rainfall events, 33(25%) were acidic rainfall occurrences. Estimated wet acid deposition (2282.78 eq·ha-1·yr-1), consistent with SO42- and NH4+ deposition, was high in spring and summer and low in autumn and winter. Waterbodies surrounded by mixed wood and citrus orchard experience severe acidification, mostly from S deposition because acidic deposition exceeds the corresponding critical loads of acidity. Modifications that take acid rain deposition into consideration are needed for land-use and agricultural management strategies to improve the environmental health of waterbodies in subtropical watersheds.

Lose-Shift Responding in Humans Is Promoted by Increased Cognitive Load

PubMed Central

Ivan, Victorita E.; Banks, Parker J.; Goodfellow, Kris; Gruber, Aaron J.

2018-01-01

The propensity of animals to shift choices immediately after unexpectedly poor reinforcement outcomes is a pervasive strategy across species and tasks. We report here on the memory supporting such lose-shift responding in humans, assessed using a binary choice task in which random responding is the optimal strategy. Participants exhibited little lose-shift responding when fully attending to the task, but this increased by 30%–40% in participants that performed with additional cognitive load that is known to tax executive systems. Lose-shift responding in the cognitively loaded adults persisted throughout the testing session, despite being a sub-optimal strategy, but was less likely as the time increased between reinforcement and the subsequent choice. Furthermore, children (5–9 years old) without load performed similarly to the cognitively loaded adults. This effect disappeared in older children aged 11–13 years old. These data provide evidence supporting our hypothesis that lose-shift responding is a default and reflexive strategy in the mammalian brain, likely mediated by a decaying memory trace, and is normally suppressed by executive systems. Reducing the efficacy of executive control by cognitive load (adults) or underdevelopment (children) increases its prevalence. It may therefore be an important component to consider when interpreting choice data, and may serve as an objective behavioral assay of executive function in humans that is easy to measure. PMID:29568264

Enhanced water use efficiency in global terrestrial ecosystems under increasing aerosol loadings

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

Lu, Xiaoliang; Chen, Min; Liu, Yaling

Aerosols play a crucial role in the climate system, affecting incoming radiation and cloud formation. Based on a modelling framework that couples ecosystem processes with the atmospheric transfer of radiation, we analyze the effect of aerosols on surface incoming radiation, gross primary productivity (GPP), water losses from ecosystems through evapotranspiration (ET) and ecosystem water use efficiency (WUE, defined as GPP/ET) for 2003–2010 and validate them at global FLUXNET sites. The total diffuse radiation increases under relatively low or intermediate aerosol loadings, but decreases under more polluted conditions. We find that aerosol-induced changes in GPP depend on leaf area index, aerosolmore » loading and cloudiness. Specifically, low and moderate aerosol loadings cause increases in GPP for all plant types, while heavy aerosol loadings result in enhancement (decrease) in GPP for dense (sparse) vegetation. On the other hand, ET is mainly negatively affected by aerosol loadings due to the reduction in total incoming radiation. Finally, WUE shows a consistent rise in all plant types under increasing aerosol loadings. Overall, the simulated daily WUE compares well with observations at 43 eddy-covariance tower sites (R 2=0.84 and RMSE=0.01gC (kg H 2O) -1) with better performance at forest sites. In addition to the increasing portions of diffuse light, the rise in WUE is also favored by the reduction in radiation- and heat-stress caused by the aerosols, especially for wet and hot climates.« less

Connecting Source with Sink: The Role of Arabidopsis AAP8 in Phloem Loading of Amino Acids1[OPEN

PubMed Central

Santiago, James P.; Tegeder, Mechthild

2016-01-01

Allocation of large amounts of nitrogen to developing organs occurs in the phloem and is essential for plant growth and seed development. In Arabidopsis (Arabidopsis thaliana) and many other plant species, amino acids represent the dominant nitrogen transport forms in the phloem, and they are mainly synthesized in photosynthetically active source leaves. Following their synthesis, a broad spectrum of the amino nitrogen is actively loaded into the phloem of leaf minor veins and transported within the phloem sap to sinks such as developing leaves, fruits, or seeds. Controlled regulation of the source-to-sink transport of amino acids has long been postulated; however, the molecular mechanism of amino acid phloem loading was still unknown. In this study, Arabidopsis AMINO ACID PERMEASE8 (AAP8) was shown to be expressed in the source leaf phloem and localized to the plasma membrane, suggesting its function in phloem loading. This was further supported by transport studies with aap8 mutants fed with radiolabeled amino acids and by leaf exudate analyses. In addition, biochemical and molecular analyses revealed alterations in leaf nitrogen pools and metabolism dependent on the developmental stage of the mutants. Decreased amino acid phloem loading and partitioning to sinks led to decreased silique and seed numbers, but seed protein levels were unchanged, demonstrating the importance of AAP8 function for sink development rather than seed quality. Overall, these results show that AAP8 plays an important role in source-to-sink partitioning of nitrogen and that its function affects source leaf physiology and seed yield. PMID:27016446

Characterization and anticancer potential of ferulic acid-loaded chitosan nanoparticles against ME-180 human cervical cancer cell lines

NASA Astrophysics Data System (ADS)

Panwar, Richa; Sharma, Asvene K.; Kaloti, Mandeep; Dutt, Dharm; Pruthi, Vikas

2016-08-01

Ferulic acid (FA) is a widely distributed hydroxycinnamic acid found in various cereals and fruits exhibiting potent antioxidant and anticancer activities. However, due to low solubility and permeability, its availability to biological systems is limited. Non-toxic chitosan-tripolyphosphate pentasodium (CS-TPP) nanoparticles (NPs) are used to load sparingly soluble molecules and drugs, increasing their bioavailability. In the present work, we have encapsulated FA into the CS-TPP NPs to increase its potential as a therapeutic agent. Different concentrations of FA were tested to obtain optimum sized FA-loaded CS-TPP nanoparticles (FA/CS-TPP NPs) by ionic gelation method. Nanoparticles were characterized by scanning electron microscopy, Fourier transformation infrared spectroscopy (FTIR), thermogravimetric analyses and evaluated for their anticancer activity against ME-180 human cervical cancer cell lines. The FTIR spectra confirmed the encapsulation of FA and thermal analysis depicted its degradation profile. A concentration-dependent relationship between FA encapsulation efficiency and FA/CS-TPP NPs diameter was observed. Smooth and spherical FA-loaded cytocompatible nanoparticles with an average diameter of 125 nm were obtained at 40 µM FA conc. The cytotoxicity of 40 µM FA/CS-TPP NPs against ME-180 cervical cancer cell lines was found to be higher as compared to 40 µM native FA. Apoptotic morphological changes as cytoplasmic remnants and damaged wrinkled cells in ME-180 cells were visualized using scanning electron microscopic and fluorescent microscopic techniques. Data concluded that chitosan enveloped FA nanoparticles could be exploited as an excellent therapeutic drug against cancer cells proliferation.

Bifunctional viscous nanovesicles co-loaded with resveratrol and gallic acid for skin protection against microbial and oxidative injuries.

PubMed

Vitonyte, Justina; Manca, Maria Letizia; Caddeo, Carla; Valenti, Donatella; Peris, Josè Esteban; Usach, Iris; Nacher, Amparo; Matos, Maria; Gutiérrez, Gemma; Orrù, Germano; Fernàndez-Busquets, Xavier; Fadda, Anna Maria; Manconi, Maria

2017-05-01

Resveratrol and gallic acid were co-loaded in phospholipid vesicles aiming at protecting the skin from external injuries, such as oxidative stress and microbial infections. Liposomes were prepared using biocompatible phospholipids dispersed in water. To improve vesicle stability and applicability, the phospholipids and the phenols were dispersed in water/propylene glycol or water/glycerol, thus obtaining PEVs and glycerosomes, respectively. The vesicles were characterized by size, morphology, physical stability, and their therapeutic efficacy was investigated in vitro. The vesicles were spherical, unilamellar and small in size: liposomes and glycerosomes were around 70nm in diameter, while PEVs were larger (∼170nm). The presence of propylene glycol or glycerol increased the viscosity of the vesicle systems, positively affecting their stability. The ability of the vesicles to promote the accumulation of the phenols (especially gallic acid) in the skin was demonstrated, as well as their low toxicity and great ability to protect keratinocytes and fibroblasts from oxidative damage. Additionally, an improvement of the antimicrobial activity of the phenols was shown against different skin pathogens. The co-loading of resveratrol and gallic acid in modified phospholipid vesicles represents an innovative, bifunctional tool for preventing and treating skin affections. Copyright © 2017 Elsevier B.V. All rights reserved.

Metal loading assessment of a small mountainous sub-basin characterized by acid drainage -- Prospect Gulch, upper Animas River watershed, Colorado

USGS Publications Warehouse

Wirt, Laurie; Leib, Kenneth J.; Melick, Roger; Bove, Dana J.

2001-01-01

iron spring yielded 39% of the discharge and 54%, 73%, and 87% of the SO4, Al, and Fe loads; but only 4% of the total Cu and 30% of the total Zn loads in Prospect Gulch. Base flow from the Prospect Gulch sub-basin contributes about 4.8 percent of the total discharge at the mouth of Cement Creek; compared with sampled instream loads of 1.8%, 8.8%, 15.9%, 28%, and 8.6% for SO4, Al, Fe, Cu and Zn, respectively. Water-shed scale remediation efforts targeted at reducing loads of SO4, Al, and Fe at inactive mine sites are likely to fail because the major sources of these constituents in Prospect Gulch are predominantly discharged from natural sources. Remediation goals aimed at reducing acidity and loads of Cu and other base metals, may succeed, however, because changes in pH and loads are disproportionately greater than increases in discharge over the same reach, and a substantial fraction of the metal loading is from mining-impacted reaches. Whether remediation of abandoned mines in Prospect Gulch can be successful depends on how goals are defined?that is, whether the objective is to reduce loads of SO4, Al, and Fe; or whether loads of Cu and other base metals and pH are targeted.

Vestibular control of standing balance is enhanced with increased cognitive load.

PubMed

McGeehan, Michael A; Woollacott, Marjorie H; Dalton, Brian H

2017-04-01

When cognitive load is elevated during a motor task, cortical inhibition and reaction time are increased; yet, standing balance control is often unchanged. This disconnect is likely explained by compensatory mechanisms within the balance system such as increased sensitivity of the vestibulomotor pathway. This study aimed to determine the effects of increased cognitive load on the vestibular control of standing balance. Participants stood blindfolded on a force plate with their head facing left and arms relaxed at their sides for two trials while exposed to continuous electrical vestibular stimulation (EVS). Participants either stood quietly or executed a cognitive task (double-digit arithmetic). Surface electromyography (EMG) and anterior-posterior ground-body forces (APF) were measured in order to evaluate vestibular-evoked balance responses in the frequency (coherence and gain) and time (cumulant density) domains. Total distance traveled for anterior-posterior center of pressure (COP) was assessed as a metric of balance variability. Despite similar distances traveled for COP, EVS-medial gastrocnemius (MG) EMG and EVS-APF coherence and EVS-TA EMG and EVS-MG EMG gain were elevated for multiple frequencies when standing with increased cognitive load. For the time domain, medium-latency peak amplitudes increased by 13-54% for EVS-APF and EVS-EMG relationships with the cognitive task compared to without. Peak short-latency amplitudes were unchanged. These results indicate that reliance on vestibular control of balance is enhanced when cognitive load is elevated. This augmented neural strategy may act to supplement divided cortical processing resources within the balance system and compensate for the acute neuromuscular modifications associated with increased cognitive demand.

Studying the loading effect of acidic type antioxidant on amorphous silica nanoparticle carriers

NASA Astrophysics Data System (ADS)

Ravinayagam, Vijaya; Rabindran Jermy, B.

2017-06-01

The study investigates the suitable nanosilica carriers to transport acidic type cargo molecules for potential targeted drug delivery application. Using phenolic acidic type antioxidant gallic acid (GA) as model compound, the present study investigates the loading effect of GA (0.3-15.9 mmol GA g-1 support) on textural characteristics of amorphous silica nanoparticles such as Q10 silica (1D), structured two-dimensional Si-MCM-41 (2D), and three-dimensional Si-SBA-16 (3D). The variation in the nature of textures after GA loading was analyzed using X-ray diffraction, N2 adsorption, FT-IR, scanning electron microscopy with energy dispersive X-ray spectroscopy, and high-resolution transmission electron microscopy. Among the nanocarriers, high adsorption of GA was found in the following order: Si-SBA-16 (3D)˜Si-KIT-6 (3D) > Si-MCM-41 (2D) > ultralarge pore FDU-12 (ULPFDU-12; 3D) > Q10 (1D)˜mesostructured cellular silica foam (MSU-F). 3D-type silicas Si-SBA-16 and KIT-6 were shown to maintain structural integrity at acidic condition (pH ˜3) and accommodate GA in non-crystalline form. In the case of ULPFDU-12 and MSU-F cellular foam, only crystalline deposition of GA occurs with a significant variation in the surface area and pore volume. [Figure not available: see fulltext.

11β Hydroxysteroid dehydrogenase type 2 and dietary acid load are independently associated with blood pressure in healthy children and adolescents.

PubMed

Krupp, Danika; Shi, Lijie; Maser-Gluth, Christiane; Pietzarka, Marion; Remer, Thomas

2013-03-01

The reduced activity of 11β hydroxysteroid dehydrogenase type 2 (11βHSD2) contributes to elevated blood pressure (BP) in clinical syndromes, but its effect on BP in the physiologic range is unclear. We examined the association of 11βHSD2 activity with BP in healthy children independent of known BP-related dietary and other factors and determined whether the diet-dependent acid load may constitute a dietary factor related to BP. We conducted a cross-sectional analysis in 267 healthy children (age range: 4-14 y) who provided a 24-h urine sample, a parallel 3-d weighed dietary record, and 1-3 BP measurements ±1.5 y around the urine collection. The ratio of urinary free cortisone to cortisol measured by using a radioimmunoassay was used as an index for 11βHSD2. Urinary net acid excretion and the urinary and dietary potential renal acid load (PRAL) were used to predict the diet-dependent acid load. The PRAL was calculated as the sum of major mineral nonbicarbonate anions minus the sum of mineral cations. Sex-, age- and height-independent SD scores (SDSs) of systolic and diastolic BP were used as outcomes in linear regression analyses. 11βHSD2 was inversely associated with systolic BP SDSs in basic models and in analyses adjusted for body size, maternal BP, breastfeeding, and dietary intakes of total energy, salt, and fruit and vegetables (P = 0.03). In models that included indexes of dietary acid load instead of fruit and vegetables, all 3 acid-load biomarkers were significantly (P = 0.006-0.02) directly related to systolic BP. A lower 11βHSD2 activity and higher dietary acid load may independently contribute to higher systolic BP in healthy children.

Gallic acid loaded PEO-core/zein-shell nanofibers for chemopreventive action on gallbladder cancer cells.

PubMed

Acevedo, Francisca; Hermosilla, Jeyson; Sanhueza, Claudia; Mora-Lagos, Barbara; Fuentes, Irma; Rubilar, Mónica; Concheiro, Angel; Alvarez-Lorenzo, Carmen

2018-07-01

Coaxial electrospinning was used to develop gallic acid (GA) loaded poly(ethylene oxide)/zein nanofibers in order to improve its chemopreventive action on human gallbladder cancer cells. Using a Plackett-Burman design, the effects of poly(ethylene oxide) and zein concentration and applied voltage on the diameter and morphology index of nanofibers were investigated. Coaxial nanofibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). GA loading efficiency as high as 77% was obtained under optimal process conditions. The coaxial nanofibers controlled GA release in acid and neutral pH medium. Cytotoxicity and reactive oxygen species (ROS) production on gallbladder cancer cell lines GB-d1 and NOZ in the presence of GA-nanofibers were assessed. GA-nanofibers triggered an increase in the cellular cytotoxicity compared with free GA on GB-d1 and NOZ cells. Statistically significant differences were found in ROS levels of GA-nanofibers compared with free GA on NOZ cells. Differently, ROS production on GB-d1 cell line was similar. Based on these results, the coaxial nanofibers obtained in this study under optimized operational conditions offer an alternative for the development of a GA release system with improved chemopreventive action on gallbladder cancer cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Accelerated fatigue testing of dentin-composite bond with continuously increasing load.

PubMed

Li, Kai; Guo, Jiawen; Li, Yuping; Heo, Young Cheul; Chen, Jihua; Xin, Haitao; Fok, Alex

2017-06-01

The aim of this study was to evaluate an accelerated fatigue test method that used a continuously increasing load for testing the dentin-composite bond strength. Dentin-composite disks (ϕ5mm×2mm) made from bovine incisor roots were subjected to cyclic diametral compression with a continuously increasingly load amplitude. Two different load profiles, linear and nonlinear with respect to the number of cycles, were considered. The data were then analyzed by using a probabilistic failure model based on the Weakest-Link Theory and the classical stress-life function, before being transformed to simulate clinical data of direct restorations. All the experimental data could be well fitted with a 2-parameter Weibull function. However, a calibration was required for the effective stress amplitude to account for the difference between static and cyclic loading. Good agreement was then obtained between theory and experiments for both load profiles. The in vitro model also successfully simulated the clinical data. The method presented will allow tooth-composite interfacial fatigue parameters to be determined more efficiently. With suitable calibration, the in vitro model can also be used to assess composite systems in a more clinically relevant manner. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

[Degradation of Acid Orange 7 with Persulfate Activated by Silver Loaded Granular Activated Carbon].

PubMed

Wang, Zhong-ming; Huang, Tian-yin; Chen, Jia-bin; Li, Wen-wei; Zhang, Li-ming

2015-11-01

Granular activated carbon with silver loaded as activator (Ag/GAC) was prepared using impregnation method. N2 adsorption, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) were adopted to characterize the Ag/GAC, showing that silver was successfully loaded on granular activated carbon. The oxidation degradation of acid orange 7 (AO7) by the Ag/GAC activated by persulfate (PS) was investigated at ambient temperature. The influences of factors such as Ag loading, PS or Ag/GAC dosages and initial pH on the degradation of AO7 were evaluated. The results demonstrated that the degradation rate of AO7 could reach more than 95.0% after 180 min when the Ag loading content, PS/AO7 molar ratio, the Ag/GAC dosage were 12.7 mg x g(-1), 120: 1, 1.0 g x L(-1), respectively. The initial pH had significant effect on the AO7 degradation, with pH 5.0 as the optimal pH for the degradation of AO7. The possible degradation pathway was proposed for the AO7 degradation by using UV-visible spectroscopy and gas chromatography-mass spectrometry (GG/MS). The azo bond and naphthalene ring in the AO7 were destroyed during the degradation, with phthalic acid and acetophenone as the main degradation products.

The Effect of Buffering High Acid Load Meal with Sodium Bicarbonate on Postprandial Glucose Metabolism in Humans-A Randomized Placebo-Controlled Study.

PubMed

Kozan, Pinar; Blythe, Jackson C; Greenfield, Jerry R; Samocha-Bonet, Dorit

2017-08-11

Background: High dietary acid load relates to increased risk of type 2 diabetes in epidemiological studies. We aimed to investigate whether buffering a high acid load meal with an alkalizing treatment changes glucose metabolism post meal. Methods: Non-diabetic participants ( n = 32) were randomized to receive either 1680 mg NaHCO₃ or placebo, followed by a high acid load meal in a double-blind placebo-controlled crossover (1-4 weeks apart) study. Thirty (20 men) participants completed the study. Venous blood pH, serum bicarbonate, blood glucose, serum insulin, C -peptide, non-esterified fatty acid (NEFA), and plasma glucagon-like peptide-1 (GLP-1) concentrations were measured at baseline (fasting) and at 15-30 min intervals for 3 h post meal. Results: The treatment was well tolerated. Venous blood pH declined in the first 15 min post meal with the placebo ( p = 0.001), but not with NaHCO₃ ( p = 0.86) and remained decreased with the placebo for 3 h ( p interaction = 0.04). On average over the 3 h blood pH iAUC was greater with NaHCO₃ compared with placebo ( p = 0.02). However, postprandial glucose, insulin, C -peptide, NEFA and GLP-1 were not different between treatments ( p interaction ≥ 0.07). Conclusions: An alkalizing medication administered pre-meal has no acute effect on glycaemia and insulin response in healthy individuals. Long-term interventions in at-risk populations are necessary to investigate the effect of sustained alkalization on glucose metabolism.

Treadmill walking with load carriage increases aortic pressure wave reflection.

PubMed

Ribeiro, Fernando; Oliveira, Nórton L; Pires, Joana; Alves, Alberto J; Oliveira, José

2014-01-01

The study examined the effects of treadmill walking with load carriage on derived measures of central pressure and augmentation index in young healthy subjects. Fourteen male subjects (age 31.0 ± 1.0 years) volunteered in this study. Subjects walked 10 minutes on a treadmill at a speed of 5 km/h carrying no load during one session and a load of 10% of their body weight on both upper limbs in two water carboys with handle during the other session. Pulse wave analysis was performed at rest and immediately after exercise in the radial artery of the right upper limb by applanation tonometry. The main result indicates that walking with load carriage sharply increased augmentation index at 75 bpm (-5.5 ± 2.2 to -1.4 ± 2.2% vs. -5.2 ± 2.8 to -5.5 ± 2.1%, p<0.05), and also induced twice as high increments in central pulse pressure (7.4 ± 1.5 vs. 3.1 ± 1.4 mmHg, p<0.05) and peripheral (20.5 ± 2.7 vs. 10.3 ± 2.5 mmHg, p<0.05) and central systolic pressure (14.7 ± 2.1 vs. 7.4 ± 2.0 mmHg, p<0.05). Walking with additional load of 10% of their body weight (aerobic exercise accompanied by upper limb isometric contraction) increases derived measures of central pressure and augmentation index, an index of wave reflection and arterial stiffness. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Dietary acid load and chronic kidney disease in elderly adults: Protein and potassium intake.

PubMed

Ko, Byung-Joon; Chang, Yoosoo; Ryu, Seungho; Kim, Eun Mi; Lee, Mi Yeon; Hyun, Young Youl; Lee, Kyu-Beck

2017-01-01

Dietary net endogenous acid production (NEAP), which represents total dietary load of nonvolatile acid, may affect kidney function. Estimated NEAP (eNEAP) is calculated indirectly by the ratio of protein and potassium intake. A few studies are available assessing the association between eNEAP and chronic kidney disease (CKD), and its relation to dietary protein and potassium intake in the elderly. A total 1,369 community-dwelling elderly Koreans in the Kangbuk Samsung Cohort Study (KSCS) were evaluated using a food frequency questionnaire (FFQ) and comprehensive health examination. We evaluated the association between eNEAP and the CKD. We also examined their relation to protein and potassium intake. eNEAP was correlated with potassium intake (r = -0.410, P < 0.001), but was not correlated with protein intake (r = -0.004, P = 0.879). In a full multivariate adjustment for sociodemographic factors, dietary factors, and comorbidities, the participants with higher eNEAP quartiles (Q2, Q3, Q4) had higher odds of CKD compared to the lowest eNEAP quartile (Q1); OR (95% CI) were 1.47 (0.78-2.72), 1.66 (0.85-3.23), and 2.30 (1.16-4.60) respectively (P for trend = 0.019). The odds of CKD decreased for participants with higher potassium intake quartiles (Q2, Q3, Q4) compared to the lowest potassium intake quartile (Q1); OR (95% CI) were 0.52 (0.28-0.95), 0.50 (0.26-0.96), and 0.50 (0.21-0.99) respectively (P for trend = 0.050). Protein intake was not associated with CKD. The association between eNEAP and CKD was similar in subgroup analysis. Dietary acid load was associated with CKD. Among the nutrients related to dietary acid load, potassium intake was negatively associated with CKD, but protein intake was not associated with CKD in elderly adults.

Cyclic loading increases friction and changes cartilage surface integrity in lubricin-mutant mouse knees

PubMed Central

Drewniak, Elizabeth I; Jay, Gregory D; Fleming, Braden C; Zhang, Ling; Warman, Matthew L; Crisco, Joseph J

2012-01-01

Objective To investigate the effects of lubricin gene dosage and cyclic loading on whole joint coefficient of friction and articular cartilage surface integrity in mouse knee joints. Methods Joints from mice with 2 (Prg4+/+), 1 (Prg4+/−), or no (Prg4−/−) functioning lubricin alleles were subjected to 26 hours of cyclic loading using a custom-built pendulum. Coefficient of friction values were measured at multiple time points. Contralateral control joints were left unloaded. Following testing, joints were examined for histologic evidence of damage and cell viability. Results At baseline, the coefficient of friction values in Prg4−/− mice were significantly higher than those in Prg4+/+ and Prg4+/− mice (P < 0.001). Cyclic loading continuously increased the coefficient of friction in Prg4−/− mouse joints. In contrast, Prg4+/− and Prg4+/+ mouse joints had no coefficient of friction increases during the first 4 hours of loading. After 26 hours of loading, joints from all genotypes had increased coefficient of friction values compared to baseline and unloaded controls. Significantly greater increases occurred in Prg4−/− and Prg4+/− mouse joints compared to Prg4+/+ mouse joints. The coefficient of friction values were not significantly associated with histologic evidence of damage or loss of cell viability. Conclusion Our findings indicate that mice lacking lubricin have increased baseline coefficient of friction values and are not protected against further increases caused by loading. Prg4+/− mice are indistinguishable from Prg4+/+ mice at baseline, but have significantly greater coefficient of friction values following 26 hours of loading. Lubricin dosage affects joint properties during loading, and may have clinical implications in patients for whom injury or illness alters lubricin abundance. PMID:21905020

Promotion effect of nickel loaded on CdS for photocatalytic H2 production in lactic acid solution

NASA Astrophysics Data System (ADS)

Chen, Shu; Chen, Xiaoping; Jiang, Qizhong; Yuan, Jian; Lin, Caifang; Shangguan, Wenfeng

2014-10-01

Low-cost Ni modified CdS was prepared via a hydrothermal reduction method. The hydrogen production activity of CdS loaded with 5 wt% Ni under visible light was even higher than that of the one loaded with 0.5 wt% Pt. The highest H2 evolution rate (3004.8 μmol h-1) occurred when the concentration of sacrificial agent (lactic acid) was 50 vol%. The nickel can quickly transfer excited electrons and enhance the photocatalytic H2 production activity. It was also found that the hydrogen evolution in this system was generated steadily from both water and lactic acid.

Systematic review of the association between dietary acid load, alkaline water and cancer.

PubMed

Fenton, Tanis R; Huang, Tian

2016-06-13

To evaluate the evidence for a causal relationship between dietary acid/alkaline and alkaline water for the aetiology and treatment of cancer. A systematic review was conducted on published and grey literature separately for randomised intervention and observational studies with either varying acid-base dietary intakes and/or alkaline water with any cancer outcome or for cancer treatment. Incidence of cancer and outcomes of cancer treatment. 8278 citations were identified, and 252 abstracts were reviewed; 1 study met the inclusion criteria and was included in this systematic review. No randomised trials were located. No studies were located that examined dietary acid or alkaline or alkaline water for cancer treatment. The included study was a cohort study with a low risk of bias. This study revealed no association between the diet acid load with bladder cancer (OR=1.15: 95% CI 0.86 to 1.55, p=0.36). No association was found even among long-term smokers (OR=1.72: 95% CI 0.96 to 3.10, p=0.08). Despite the promotion of the alkaline diet and alkaline water by the media and salespeople, there is almost no actual research to either support or disprove these ideas. This systematic review of the literature revealed a lack of evidence for or against diet acid load and/or alkaline water for the initiation or treatment of cancer. Promotion of alkaline diet and alkaline water to the public for cancer prevention or treatment is not justified. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Cu2+-nitrilotriacetic acid complex improves loading of α-helical double histidine site for precise distance measurements by pulsed ESR

NASA Astrophysics Data System (ADS)

Ghosh, Shreya; Lawless, Matthew J.; Rule, Gordon S.; Saxena, Sunil

2018-01-01

Site-directed spin labeling using two strategically placed natural histidine residues allows for the rigid attachment of paramagnetic Cu2+. This double histidine (dHis) motif enables extremely precise, narrow distance distributions resolved by Cu2+-based pulsed ESR. Furthermore, the distance measurements are easily relatable to the protein backbone-structure. The Cu2+ ion has, till now, been introduced as a complex with the chelating agent iminodiacetic acid (IDA) to prevent unspecific binding. Recently, this method was found to have two limiting concerns that include poor selectivity towards α-helices and incomplete Cu2+-IDA complexation. Herein, we introduce an alternative method of dHis-Cu2+ loading using the nitrilotriacetic acid (NTA)-Cu2+ complex. We find that the Cu2+-NTA complex shows a four-fold increase in selectivity toward α-helical dHis sites. Furthermore, we show that 100% Cu2+-NTA complexation is achievable, enabling precise dHis loading and resulting in no free Cu2+ in solution. We analyze the optimum dHis loading conditions using both continuous wave and pulsed ESR. We implement these findings to show increased sensitivity of the Double Electron-Electron Resonance (DEER) experiment in two different protein systems. The DEER signal is increased within the immunoglobulin binding domain of protein G (called GB1). We measure distances between a dHis site on an α-helix and dHis site either on a mid-strand or a non-hydrogen bonded edge-strand β-sheet. Finally, the DEER signal is increased twofold within two α-helix dHis sites in the enzymatic dimer glutathione S-transferase exemplifying the enhanced α-helical selectivity of Cu2+-NTA.

Manipulation of Foot Strike and Footwear Increases Achilles Tendon Loading During Running.

PubMed

Rice, Hannah; Patel, Mubarak

2017-08-01

The Achilles tendon is the most common site of tendon overuse injury in humans. Running with a forefoot strike pattern and in minimal shoes is a topic of recent interest, yet evidence is currently limited regarding the combined influence of foot strike and footwear on Achilles tendon loading. To investigate the influence of both foot strike and footwear on Achilles tendon loading in habitual rearfoot strike runners. Controlled laboratory study. Synchronized kinematic and force data were collected from 22 habitual rearfoot strikers (11 male), who habitually ran in nonminimal running shoes, during overground running at 3.6 m·s -1 . Participants ran in 3 different footwear conditions (standard running shoe, minimal running shoe, and barefoot) with both a rearfoot strike (RFS) and an imposed forefoot strike (FFS) in each footwear condition. Achilles tendon loading was estimated by use of inverse dynamics, where the Achilles tendon moment arm was determined with a regression equation. A 2-way, repeated-measures analysis of variance was used to compare conditions. Achilles tendon impulse was greater when subjects ran with an FFS rather than an RFS in minimal shoes. Achilles tendon loading rates were higher when subjects ran either in minimal shoes or barefoot than in standard shoes, regardless of foot strike. In runners who habitually rearfoot strike in standard running shoes, running in minimal shoes or barefoot increased the rate of tendon loading, and running with a forefoot strike in minimal shoes increased the magnitude of tendon loading. Transitioning to these running conditions may increase the risk of tendinopathy.

Effect of aeration rate and waste load on evolution of volatile fatty acids and waste stabilization during thermophilic aerobic digestion of a model high strength agricultural waste.

PubMed

Ugwuanyi, J Obeta; Harvey, L M; McNeil, B

2005-04-01

Thermophilic aerobic digestion (TAD) is a relatively new, dynamic and versatile low technology for the economic processing of high strength waste slurries. Waste so treated may be safely disposed of or reused. In this work a model high strength agricultural waste, potato peel, was subjected to TAD to study the effects of oxygen supply at 0.1, 0.25, 0.5 and 1.0 vvm (volume air per volume slurry per minute) under batch conditions at 55 degrees C for 156 h on the process. Process pH was controlled at 7.0 or left unregulated. Effects of waste load, as soluble chemical oxygen demand (COD), on TAD were studied at 4.0, 8.0, 12.0 and 16.0 gl(-1) (soluble COD) at pH 7.0, 0.5 vvm and 55 degrees C. Efficiency of treatment, as degradation of total solids, total suspended solids and soluble solid, as well as soluble COD significantly increased with aeration rate, while acetate production increased as the aeration rate decreased or waste load increased, signifying deterioration in treatment. Negligible acetate, and no other acids were produced at 1.0 vvm. Production of propionate and other acids increased after acetate concentration had started to decrease and, during unregulated reactions coincided with the drop in the pH of the slurry. Acetate production was more closely associated with periods of oxygen limitation than were other acids. Reduction in oxygen availability led to deterioration in treatment efficiency as did increase in waste load. These variables may be manipulated to control treated waste quality.

Association of dietary acid load with cardiovascular disease risk factors in patients with diabetic nephropathy.

PubMed

Haghighatdoost, Fahimeh; Najafabadi, Mojgan Mortazavi; Bellissimo, Nick; Azadbakht, Leila

2015-05-01

An association between dietary acid load and cardiovascular disease risk has been reported in epidemiologic studies; however, there are no reports to our knowledge of this association in patients with diabetic nephropathy (DN). Therefore, the aim of this study was to examine the association between dietary acid load, based on potential renal acid load (PRAL) and protein:potassium ratio (Pro:K) scores, and cardiovascular disease risk factors in individuals with DN. In this cross-sectional study, we randomly enrolled 547 patients with DN. Dietary intake was assessed using a validated food frequency questionnaire. Biochemical and anthropometric measures were assessed using standard methods. Participants had a mean age of 66.8 y and body mass index of 24 kg/m(2). After controlling for potential confounders, participants in the low PRAL group had lower hemoglobin (Hb)A1c (5.7% ± 0.5% versus 7.8% ± 0.5%; P = 0.01), triacylglycerols (246.9 ± 2.3 mg/dL versus 257.4 ± 2.3 mg/dL; P = 0.006), systolic blood pressure (103.6 ± 0.7 mm Hg versus 106.1 ± 0.7 mm Hg; P = 0.03), and lower creatinine and fasting blood sugar compared with the high PRAL group. Pro:K was positively related to HbA1c (5.8% ± 0.5% versus 7.6% ± 0.5%; P = 0.03), but inversely associated with low-density lipoprotein and waist circumference. We found that both PRAL and Pro:K were positively related to HbA1c in the setting of DN, whereas other biochemical and kidney-related markers varied with PRAL and Pro:K status. Future studies are warranted to clarify the clinical outcomes of dietary acid load in older populations as well as in patients with chronic kidney disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Method of increasing conversion of a fatty acid to its corresponding dicarboxylic acid

DOEpatents

Craft, David L.; Wilson, C. Ron; Eirich, Dudley; Zhang, Yeyan

2004-09-14

A nucleic acid sequence including a CYP promoter operably linked to nucleic acid encoding a heterologous protein is provided to increase transcription of the nucleic acid. Expression vectors and host cells containing the nucleic acid sequence are also provided. The methods and compositions described herein are especially useful in the production of polycarboxylic acids by yeast cells.

Increased sternocleidomastoid, but not trapezius, muscle activity in response to increased chewing load.

PubMed

Häggman-Henrikson, Birgitta; Nordh, Erik; Eriksson, Per-Olof

2013-10-01

Previous findings, during chewing, that boluses of larger size and harder texture result in larger amplitudes of both mandibular and head-neck movements suggest a relationship between increased chewing load and incremental recruitment of jaw and neck muscles. The present report evaluated jaw (masseter and digastric) and neck [sternocleidomastoid (SCM) and trapezius] muscle activity during the chewing of test foods of different sizes and textures by 10 healthy subjects. Muscle activity was recorded by surface electromyography and simultaneous mandibular and head movements were recorded using an optoelectronic technique. Each subject performed continuous jaw-opening/jaw-closing movements whilst chewing small and large boluses of chewing gum and rubber silicone (Optosil). For jaw opening/jaw closing without a bolus, SCM activity was recorded for jaw opening concomitantly with digastric activity. During chewing, SCM activity was recorded for jaw closing concomitantly with masseter activity. Trapezius activity was present in some, but not all, cycles. For the masseter and SCM muscles, higher activity was seen with larger test foods, suggesting increased demand and recruitment of these muscles in response to an increased chewing load. This result reinforces the previous notion of a close functional connection between the jaw and the neck motor systems in jaw actions and has scientific and clinical significance for studying jaw function and dysfunction. © 2013 Eur J Oral Sci.

[Synthesis of antibiotic loaded polylactic acid nanoparticles and their antibacterial activity against Escherichia coli O157:H7 and methicillin-resistant Staphylococcus aureus].

PubMed

Herrera, Mónica Tatiana; Artunduaga, Jhon Jhamilton; Ortiz, Claudia Cristina; Torres, Rodrigo Gonzalo

2017-01-24

Polymeric nanoparticles are promising nanotechnology tools to fight pathogenic bacteria resistant to conventional antibiotics. To synthesize polylactic acid nanoparticles loaded with ofloxacin and vancomycin, and to determine their antibacterial activity against Escherichia coli O157:H7 and methicillin-resistant Staphylococcus aureus (MRSA). We synthesized ofloxacin or vancomycin loaded polylactic acid nanoparticles by the emulsification-solvent evaporation method, and characterized them by dynamic light scattering, laser Doppler electrophoresis and scanning electron microscopy. We evaluated in vitro antibacterial activity of ofloxacin- and vancomycin-loaded polylactic acid nanoparticles against E. coli O157:H7 and MRSA using the broth microdilution method. Ofloxacin- and vancomycin-loaded polylactic acid nanoparticles registered a positive surface charge density of 21 mV and an average size lower than 379 nm. In vitro minimum inhibitory concentration (MIC50) of ofloxacin-polylactic acid nanoparticles was 0,001 μg/ml against E. coli O157:H7, i.e., 40 times lower than the free ofloxacin (MIC50: 0.04 μg/ml), indicating enhanced antibacterial activity while the in vitro MIC50 of vancomycin-polylactic acid nanoparticles was 0,005 μg/ml against MRSA, i.e., 100 times lower than that of free vancomycin (MIC50: 0.5 μg/ml). Polylactic acid nanoparticles loaded with ofloxacin and vancomycin showed a higher antibacterial activity. Polymeric nanoparticles are a possible alternative for drug design against pathogenic bacterial strains of public health interest.

Reducing the Dietary Acid Load: How a More Alkaline Diet Benefits Patients With Chronic Kidney Disease.

PubMed

Passey, Caroline

2017-05-01

It has been proposed that a low-protein diet will slow progression of chronic kidney disease although studies have not always supported this belief. The accepted practice is that 60% to 70% of protein comes from high biological value (HBV) protein, but this limits patient choice and patients struggle to follow the diet. When a diet with only 30% HBV protein was trialed, there was a significant increase in serum bicarbonate, and patients preferred the diet. The dietary advice given in predialysis clinics was changed. HBV protein was restricted to approximately 50% of total protein, bread and cereal foods were allowed freely, and fruits and vegetables (F&V) were encouraged. Patients who followed the diet have seen a slowing of progression and occasionally regression of their renal function. Both observations and scientific literature indicate that this is because of a reduction in the acid content of the diet. When foods are metabolized, most proteins produce acid, and most F&V produce alkali. A typical 21 st -century diet produces 50 to 100 mEq H + per day which the kidney is challenged to excrete. Acid is excreted with phosphate and is limited to about 45 mEq H + per day. With chronic kidney disease, this falls progressively to below 20 mEq H + per day. Historically, ammonium excretion was believed to be excretion of acid (NH 3 +  + H + → NH 4 + ), but it is now understood to be a by-product in the neutralization of acid by glutamine. The remaining acid is neutralized or stored within the body. Bone and muscle are lost in order to neutralize the acid. Acid also accumulates within cells, and serum bicarbonate falls. The author postulates that reducing the acid load through a low-protein diet with greater use of vegetable proteins and increased F&V intake will slow progression or occasionally improve renal function while maintaining the nutritional status of the individual. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All

Reduction in bacterial load using hypochlorous acid hygiene solution on ocular skin

PubMed Central

Stroman, David W; Mintun, Keri; Epstein, Arthur B; Brimer, Crystal M; Patel, Chirag R; Branch, James D; Najafi-Tagol, Kathryn

2017-01-01

Purpose To examine the magnitude of bacterial load reduction on the surface of the periocular skin 20 minutes after application of a saline hygiene solution containing 0.01% pure hypochlorous acid (HOCl). Methods Microbiological specimens were collected immediately prior to applying the hygiene solution and again 20 minutes later. Total microbial colonies were counted and each unique colony morphology was processed to identify the bacterial species and to determine the susceptibility profile to 15 selected antibiotics. Results Specimens were analyzed from the skin samples of 71 eyes from 36 patients. Prior to treatment, 194 unique bacterial isolates belonging to 33 different species were recovered. Twenty minutes after treatment, 138 unique bacterial isolates belonging to 26 different species were identified. Staphylococci accounted for 61% of all strains recovered and Staphylococcus epidermidis strains comprised 60% of the staphylococcal strains. No substantial differences in the distribution of Gram-positive, Gram-negative, or anaerobic species were noted before and after treatment. The quantitative data demonstrated a >99% reduction in the staphylococcal load on the surface of the skin 20 minutes following application of the hygiene solution. The total S. epidermidis colony-forming units were reduced by 99.5%. The HOCl hygiene solution removed staphylococcal isolates that were resistant to multiple antibiotics equally well as those isolates that were susceptible to antibiotics. Conclusion The application of a saline hygiene solution preserved with pure HOCl acid reduced the bacterial load significantly without altering the diversity of bacterial species remaining on the skin under the lower eyelid. PMID:28458509

Effects of poly (lactic-co-glycolic acid) as a co-emulsifier on the preparation and hypoglycaemic activity of insulin-loaded solid lipid nanoparticles.

PubMed

Wang, S L; Xie, S Y; Zhu, L Y; Wang, F H; Zhou, W Z

2009-12-01

Poly (lactic-co-glycolic acid) (PLGA) was used as a co-emulsifier in the preparation of insulin-loaded solid lipid nanoparticles (SLN) with hydrogenated castor oil as lipid matrix and lecithin as surfactant by double-emulsion technique. The effects of PLGA on the preparation and hypoglycaemic activity of insulin-loaded SLN were studied. The results showed that with the supplement of PLGA, the encapsulation efficiency and loading capacity were increased significantly from 79.08 +/- 1.62 to 85.57 +/- 3.21% and 1.58 +/- 0.03 to 1.71 +/- 0.06%, whereas the surface charge and particle size were changed insignificantly from -25.87 +/- 2.65 to -22.67 +/- 1.19 mv and 431.0 +/- 16.1 to 397.0 +/- 68.0 nm, respectively. In vivo studies demonstrated that PLGA increased the sustained hypoglycaemic activity from 12 to 36 h and 24 to 120 h in normal and steptozotocin-induced diabetic mice after a single intramuscular injection of the insulin-loaded SLN. These results demonstrated that PLGA could enhance the entrapment of insulin in the nanoparticles, and more importantly, prolong the time of hypoglycaemic activity of the insulin-loaded SLN.

Extremely fast increase in the organic loading rate during the co-digestion of rapeseed oil and sewage sludge in a CSTR--characterization of granules formed due to CaO addition to maintain process stability.

PubMed

Kasina, M; Kleyböcker, A; Michalik, M; Würdemann, H

2015-01-01

In a co-digestion system running with rapeseed oil and sewage sludge, an extremely fast increase in the organic loading rate was studied to develop a procedure to allow for flexible and demand-driven energy production. The over-acidification of the digestate was successfully prevented by calcium oxide dosage, which resulted in granule formation. Mineralogical analyses revealed that the granules were composed of insoluble salts of long chain fatty acids and calcium and had a porous structure. Long chain fatty acids and calcium formed the outer cover of granules and offered interfaces on the inside thereby enhancing the growth of biofilms. With granule size and age, the pore size increased and indicated degradation of granular interfaces. A stable biogas production up to the organic loading rate of 10.4 kg volatile solids m(-3) d(-1) was achieved although the hydrogen concentration was not favorable for propionic acid degradation. However, at higher organic loading rates, unbalanced granule formation and degradation were observed. Obviously, the adaption time for biofilm growth was too short to maintain the balance, thereby resulting in a low methane yield.

Developing Critical Loads of acidity for streams in the Great Smoky Mountains National Park, using PnET-BGC model

NASA Astrophysics Data System (ADS)

Fakhraei, H.

2015-12-01

Acid deposition has impaired acid-sensitive streams and reduced aquatic biotic integrity in Great Smoky Mountains National Park (GRSM) by decreasing pH and acid neutralizing capacity (ANC). Twelve streams in GRSM are listed by the state of Tennessee as impaired due to low stream pH (pH<6.0) under Section 303(d) of the Clean Water Act. A dynamic biogeochemical model, PnET-BGC, was used to evaluate past, current and potential future changes in soil and water chemistry of watersheds of GRSM in response to changes in acid deposition. Calibrating 30 stream-watersheds in GRSM (including 12 listed impaired streams) to the long-term stream chemistry observations, the model was parameterized for the Park. The calibrated model was used to evaluate the level of atmospheric deposition above which harmful effects occur, known as "critical loads", for individual study watersheds. Estimated critical loads and exceedances (levels of deposition above the critical load) of atmospheric sulfur and nitrogen deposition were depicted through geographic information system maps. Accuracy of model simulations in the presence of uncertainties in the estimated model parameters and inputs was assessed using three uncertainty and sensitivity techniques.

Biodistribution of indocyanine green-loaded nanoparticles with surface modifications of PEG and folic acid.

PubMed

Ma, Ying; Sadoqi, Mostafa; Shao, Jun

2012-10-15

To establish the biodistribution profile of the PLGA nanoparticles with dual surface modifications of PEG and folic acid (FA) in mice xenografted with MDA-MB-231 human breast cancer cells with high expression of folate receptor (FR); and to illustrate that the modified nanoparticles can target the loaded indocyanine green (ICG) to the tumor with high FR expression. ICG-loaded nanoparticles were prepared with PLGA (non-modified nanoparticles, NM-NP) or mPEG-PLGA and FA-PLGA (dual modified nanoparticles, DM-NP). Biodistribution of the ICG-loaded nanoparticles (1.25 mg/kg) after i.v. injection was investigated on athymic mice transplanted with MDA-MB-231 tumor. ICG concentration in plasma from the DM-NP group was significantly (p<0.05) higher than the NM-NP group from 90 min to the end of the study (12 h). After 4 h, the drug concentration in the tumor tissue from the DM-NP started to be significantly (p<0.05) higher than the NM-NP until 12 h. Compared to the NM-NP, the DM-NP increased the AUC(0-12 h) in plasma by 245% and the AUC(0-12 h) in tumor by 194%, while decreased the AUC(0-12 h) in liver by 13%. The accumulation of DM-NP into the tumor was significantly higher than NM-NP due to the long circulation and FR-mediated uptake. Copyright © 2012 Elsevier B.V. All rights reserved.

Fumaric Acid Production from Alkali-Pretreated Corncob by Fed-Batch Simultaneous Saccharification and Fermentation Combined with Separated Hydrolysis and Fermentation at High Solids Loading.

PubMed

Li, Xin; Zhou, Jin; Ouyang, Shuiping; Ouyang, Jia; Yong, Qiang

2017-02-01

Production of fumaric acid from alkali-pretreated corncob (APC) at high solids loading was investigated using a combination of separated hydrolysis and fermentation (SHF) and fed-batch simultaneous saccharification and fermentation (SSF) by Rhizopus oryzae. Four different fermentation modes were tested to maximize fumaric acid concentration at high solids loading. The highest concentration of 41.32 g/L fumaric acid was obtained from 20 % (w/v) APC at 38 °C in the combined SHF and fed-batch SSF process, compared with 19.13 g/L fumaric acid in batch SSF alone. The results indicated that a combination of SHF and fed-batch SSF significantly improved production of fumaric acid from lignocellulose by R. oryzae than that achieved with batch SSF at high solids loading.

Is the destabilisation of lake peipsi ecosystem caused by increased phosphorus loading or decreased nitrogen loading?

PubMed

Nõges, T; Laugaste, R; Loigu, E; Nedogarko, I; Skakalski, B; Nõges, P

2005-01-01

Lake Peipsi (3555 km2, mean depth 7.1 m) located on the border of Estonia and Russia is the largest transboundary lake in Europe. L. Peipsi consists of three parts. The shared largest northern part L. Peipsi s.s. (2611 km2, 8.3 m) and the southern L. Pihkva (708 km2, 3.8 m) which belongs mainly to Russia are connected by the river-shaped L. Lämmijärv (236 km2, 2.5 m). The catchment area (44,245 km2 without lake area) is shared between Estonia (33.3%), Russia (58.6%) and Latvia (8%). Intensive eutrophication of L. Peipsi started in the 1970s. The biomass of N2-fixing cyanobacteria was low at heavy nutrient loading in the 1980s. After the collapse of soviet-type agriculture in the early 1990s, the loading of nitrogen sharply decreased. A certain improvement of L. Peipsi s.s. was noticed at the beginning of the 1990s together with the temporary reduction of phosphorus loading from Estonian catchment while in recent years a destabilisation of the ecosystem has been observed. This deterioration has been expressed mainly as intensive blue-green blooms and fish-kills in summer. Reappearance of blooms has been explained by the decrease in N/P loading ratio due to reduced N discharge while in some periods increased phosphorus loading could have supported this trend.

Increased sediment loads cause non-linear decreases in seagrass suitable habitat extent

PubMed Central

Atkinson, Scott; Klein, Carissa Joy; Weber, Tony; Possingham, Hugh P.

2017-01-01

Land-based activities, including deforestation, agriculture, and urbanisation, cause increased erosion, reduced inland and coastal water quality, and subsequent loss or degradation of downstream coastal marine ecosystems. Quantitative approaches to link sediment loads from catchments to metrics of downstream marine ecosystem state are required to calculate the cost effectiveness of taking conservation actions on land to benefits accrued in the ocean. Here we quantify the relationship between sediment loads derived from landscapes to habitat suitability of seagrass meadows in Moreton Bay, Queensland, Australia. We use the following approach: (1) a catchment hydrological model generates sediment loads; (2) a statistical model links sediment loads to water clarity at monthly time-steps; (3) a species distribution model (SDM) factors in water clarity, bathymetry, wave height, and substrate suitability to predict seagrass habitat suitability at monthly time-steps; and (4) a statistical model quantifies the effect of sediment loads on area of seagrass suitable habitat in a given year. The relationship between sediment loads and seagrass suitable habitat is non-linear: large increases in sediment have a disproportionately large negative impact on availability of seagrass suitable habitat. Varying the temporal scale of analysis (monthly vs. yearly), or varying the threshold value used to delineate predicted seagrass presence vs. absence, both affect the magnitude, but not the overall shape, of the relationship between sediment loads and seagrass suitable habitat area. Quantifying the link between sediment produced from catchments and extent of downstream marine ecosystems allows assessment of the relative costs and benefits of taking conservation actions on land or in the ocean, respectively, to marine ecosystems. PMID:29125843

Recruitment of single human low-threshold motor units with increasing loads at different muscle lengths.

PubMed

McNulty, P A; Cresswell, A G

2004-06-01

We investigated the recruitment behaviour of low threshold motor units in flexor digitorum superficialis by altering two biomechanical constraints: the load against which the muscle worked and the initial muscle length. The load was increased using isotonic (low load), loaded dynamic (intermediate load) and isometric (high load) contractions in two studies. The initial muscle position reflected resting muscle length in series A, and a longer length with digit III fully extended in series B. Intramuscular EMG was recorded from 48 single motor units in 10 experiments on five healthy subjects, 21 units in series A and 27 in series B, while subjects performed ramp up, hold and ramp down contractions. Increasing the load on the muscle decreased the force, displacement and firing rate of single motor units at recruitment at shorter muscle lengths (P<0.001, dependent t-test). At longer muscle lengths this recruitment pattern was observed between loaded dynamic and isotonic contractions, but not between isometric and loaded dynamic contractions. Thus, the recruitment properties of single motor units in human flexor digitorum superficialis are sensitive to changes in both imposed external loads and the initial length of the muscle.

Double-Row Capsulolabral Repair Increases Load to Failure and Decreases Excessive Motion.

PubMed

McDonald, Lucas S; Thompson, Matthew; Altchek, David W; McGarry, Michelle H; Lee, Thay Q; Rocchi, Vanna J; Dines, Joshua S

2016-11-01

Using a cadaver shoulder instability model and load-testing device, we compared biomechanical characteristics of double-row and single-row capsulolabral repairs. We hypothesized a greater reduction in glenohumeral motion and translation and a higher load to failure in a mattress double-row capsulolabral repair than in a single-row repair. In 6 matched pairs of cadaveric shoulders, a capsulolabral injury was created. One shoulder was repaired with a single-row technique, and the other with a double-row mattress technique. Rotational range of motion, anterior-inferior translation, and humeral head kinematics were measured. Load-to-failure testing measured stiffness, yield load, deformation at yield load, energy absorbed at yield load, load to failure, deformation at ultimate load, and energy absorbed at ultimate load. Double-row repair significantly decreased external rotation and total range of motion compared with single-row repair. Both repairs decreased anterior-inferior translation compared with the capsulolabral-injured condition, however, no differences existed between repair types. Yield load in the single-row group was 171.3 ± 110.1 N, and in the double-row group it was 216.1 ± 83.1 N (P = .02). Ultimate load to failure in the single-row group was 224.5 ± 121.0 N, and in the double-row group it was 373.9 ± 172.0 N (P = .05). Energy absorbed at ultimate load in the single-row group was 1,745.4 ± 1,462.9 N-mm, and in the double-row group it was 4,649.8 ± 1,930.8 N-mm (P = .02). In cases of capsulolabral disruption, double-row repair techniques may result in decreased shoulder rotational range of motion and improved load-to-failure characteristics. In cases of capsulolabral disruption, repair techniques with double-row mattress repair may provide more secure fixation. Double-row capsulolabral repair decreases shoulder motion and increases load to failure, yield load, and energy absorbed at yield load more than single-row repair. Published by

Dehydration of glycerol over niobia-supported silicotungstic acid catalysts.

PubMed

Lee, Young Yi; Ok, Hye Jeong; Moon, Dong Ju; Kim, Jong Ho; Park, Nam Cook; Kim, Young Chul

2013-01-01

Liquid-phase dehydration of glycerol to acrolein over nanosized niobia-supported silicotungstic acid catalysts was performed to investigate the effect of the silicotungstic acid loading on the catalytic performance of the catalysts. The catalysts were prepared by following an impregnation method with different HSiW loadings in the range of 10-50 wt%. The prepared catalysts were characterized by N2 physisorption, XRD, FT-IR, TPD of ammonia, and TGA. Dehydration of glycerol was conducted in an autoclave reactor under the conditions of controlled reaction temperatures under corresponding pressure. Increasing HSiW loading rapidly increased the acidity of HSiW/Nb205 catalyst and rate of glycerol conversion, but acrolein selectivity decreased due to enhanced deactivation of the catalyst by carbon deposit. Consequently, it was confirmed that catalytic activity for the dehydration of glycerol to acrolein was dependant on the acidity of catalyst and can be controlled by HSiW loading.

Increased Renal Iron Accumulation in Hypertensive Nephropathy of Salt-Loaded Hypertensive Rats

PubMed Central

Naito, Yoshiro; Sawada, Hisashi; Oboshi, Makiko; Fujii, Aya; Hirotani, Shinichi; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Eguchi, Akiyo; Morisawa, Daisuke; Ohyanagi, Mitsumasa; Tsujino, Takeshi; Masuyama, Tohru

2013-01-01

Although iron is reported to be associated with the pathogenesis of chronic kidney disease, it is unknown whether iron participates in the pathophysiology of nephrosclerosis. Here, we investigate whether iron is involved in the development of hypertensive nephropathy and the effects of iron restriction on nephrosclerosis in salt- loaded stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were given either a normal or high-salt diet for 8 weeks. Another subset of SHRSP were fed a high-salt with iron-restricted diet. SHRSP given a high-salt diet developed severe hypertension and nephrosclerosis. As a result, survival rate was decreased after 8 weeks diet. Importantly, massive iron accumulation and increased iron content were observed in the kidneys of salt-loaded SHRSP, along with increased superoxide production, urinary 8-Hydroxy-2′-deoxyguanosine excretion, and urinary iron excretion; however, these changes were markedly attenuated by iron restriction. Of interest, expression of cellular iron transport proteins, transferrin receptor 1 and divalent metal transporter 1, was increased in the tubules of salt-loaded SHRSP. Notably, iron restriction attenuated the development of severe hypertension and nephrosclerosis, thereby improving survival rate in salt-loaded SHRSP. Taken together, these results suggest a novel mechanism by which iron plays a role in the development of hypertensive nephropathy and establish the effects of iron restriction on salt-induced nephrosclerosis. PMID:24116080

Gambogic acid-loaded biomimetic nanoparticles in colorectal cancer treatment

PubMed Central

Zhang, Zhen; Qian, Hanqing; Yang, Mi; Li, Rutian; Hu, Jing; Li, Li; Yu, Lixia; Liu, Baorui; Qian, Xiaoping

2017-01-01

Gambogic acid (GA) is expected to be a potential new antitumor drug, but its poor aqueous solubility and inevitable side effects limit its clinical application. Despite these inhe rent defects, various nanocarriers can be used to promote the solubility and tumor targeting of GA, improving antitumor efficiency. In addition, a cell membrane-coated nanoparticle platform that was reported recently, unites the customizability and flexibility of a synthetic copolymer, as well as the functionality and complexity of natural membrane, and is a new synthetic biomimetic nanocarrier with improved stability and biocompatibility. Here, we combined poly(lactic-co-glycolic acid) (PLGA) with red blood-cell membrane (RBCm), and evaluated whether GA-loaded RBCm nanoparticles can retain and improve the antitumor efficacy of GA with relatively lower toxicity in colorectal cancer treatment compared with free GA. We also confirmed the stability, biocompatibility, passive targeting, and few side effects of RBCm-GA/PLGA nanoparticles. We expect to provide a new drug carrier in the treatment of colorectal cancer, which has strong clinical application prospects. In addition, the potential antitumor drug GA and other similar drugs could achieve broader clinical applications via this biomimetic nanocarrier. PMID:28280328

An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity.

PubMed

Simopoulos, Artemis P

2016-03-02

In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity.

An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity

PubMed Central

Simopoulos, Artemis P.

2016-01-01

In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity. PMID:26950145

Pilot scale dilute acid pretreatment of rice straw and fermentable sugar recovery at high solid loadings.

PubMed

Kapoor, Manali; Soam, Shveta; Agrawal, Ruchi; Gupta, Ravi P; Tuli, Deepak K; Kumar, Ravindra

2017-01-01

The aim of this work was to study the dilute acid pretreatment of rice straw (RS) and fermentable sugar recovery at high solid loadings at pilot scale. A series of pretreatment experiments were performed on RS resulting in >25wt% solids followed by enzymatic hydrolysis without solid-liquid separation at 20 and 25wt% using 10FPU/g of the pretreated residue. The overall sugar recovery including the sugars released in pretreatment and enzymatic hydrolysis was calculated along with a mass balance. Accordingly, the optimized conditions, i.e. 0.35wt% acid, 162°C and 10min were identified. The final glucose and xylose concentrations obtained were 83.3 and 31.9g/L respectively resulting in total concentration of 115.2g/L, with a potential to produce >50g/L of ethanol. This is the first report on pilot scale study on acid pretreatment of RS in a screw feeder horizontal reactor followed by enzymatic hydrolysis at high solid loadings. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biocompatibility of Gd-Loaded Chitosan-Hyaluronic Acid Nanogels as Contrast Agents for Magnetic Resonance Cancer Imaging

PubMed Central

Gheran, Cecilia Virginia; Rigaux, Guillaume; Callewaert, Maité; Berquand, Alexandre; Chuburu, Françoise; Voicu, Sorina Nicoleta; Dinischiotu, Anca

2018-01-01

Although the research on nanogels incorporating Gd chelates for theranostic applications has grown exponentially in recent years, knowledge about their biocompatibility is limited. We compared the biocompatibility of Gd-loaded hyaluronic acid-chitosan-based nanogels (GdCA⊂CS-TPP/HA) with two chitosan concentrations (2.5 and 1.5 mg·mL−1 respectively) using SVEC4-10 murine lymph node endothelial cells. The sulforhodamine B method and released lactate dehydrogenase (LDH) activity were used as cell viability tests. Reactive oxygen species (ROS), reduced glutathione (GSH) and malondialdehyde (MDA) were measured by spectrophotometric and fluorimetric methods. Nrf-2 protein expression was evaluated by Western blot analysis and genotoxicity by alkaline comet assay. After 24 h, the cells viability was not affected by all types and doses of nanogels. The increase of ROS induced a low decrease of GSH concentration and a time-dependent raise of MDA one was produced by citric GdDOTA⊂CS-TPP/HA with a chitosan concentration of 1.5 mg·mL−1, at the highest dose applied. None of the tested nanogels induced changes in Nrf-2 protein expression. A slight but significant genotoxic effect was caused only by citric GdDOTA⊂CS-TPP/HA where CS concentration was 1.5 mg·mL−1. Our results showed a better biocompatibility with lymph node endothelial cells for Gd-loaded hyaluronic acid-chitosan based nanogels with a concentration in chitosan of 2.5 mg·mL−1. PMID:29597306

Dietary potential renal Acid load in venezuelan children.

PubMed

López-Sayers, Mayerling; Bernal, Jennifer; López, Michelle

2015-05-01

Our aim was to determine and analyze the dietary PRAL and food composition pattern in apparently healthy children from 1 to 6 years of age. Parents of 52 children were selected by convenience, in an outpatient clinic of healthy children. Dietary quality and pattern was assessed by 24 hour recall and food frequency questionnaire. We focused on the intake of macronutrients and food groups, such as meats, dairy, fruits and vegetables. Nutrient intake was compared with national and international recommendations. PRAL was determined according to the method described by Remer and Manz. Descriptive statistics and correlations were applied. Dietary intake of proteins, milk and meat was high, while fruits and vegetables intake was low. PRAL was positive in 92% of the children and correlated (p<0.05) with intake of energy, proteins, fat, meat and dairy products. Protein intake was above 2.5 g/kg/day in 46.2% of the children. Food groups with the highest unbalance were meat and dairy products for excessive intake and fruits and vegetables regarding low intake, both of which represent risk factors for endogenous acid production. The diet of the children studied was characterized by an excessive acid load with the risk for the generation of systemic acidosis and its metabolic consequences. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Dietary acid load and renal function have varying effects on blood acid-base status and exercise performance across age and sex.

PubMed

Hietavala, Enni-Maria; Stout, Jeffrey R; Frassetto, Lynda A; Puurtinen, Risto; Pitkänen, Hannu; Selänne, Harri; Suominen, Harri; Mero, Antti A

2017-12-01

Diet composition influences acid-base status of the body. This may become more relevant as renal functional capacity declines with aging. We examined the effects of low (LD) versus high dietary acid load (HD) on blood acid-base status and exercise performance. Participants included 22 adolescents, 33 young adults (YA), and 33 elderly (EL), who followed a 7-day LD and HD in a randomized order. At the end of both diet periods the subjects performed a cycle ergometer test (3 × 10 min at 35%, 55%, 75%, and (except EL) until exhaustion at 100% of maximal oxygen uptake). At the beginning of and after the diet periods, blood samples were collected at rest and after all workloads. Oxygen uptake, respiratory exchange ratio (RER), and heart rate (HR) were monitored during cycling. In YA and EL, bicarbonate (HCO 3 - ) and base excess (BE) decreased over the HD period, and HCO 3 - , BE, and pH were lower at rest after HD compared with LD. In YA and EL women, HCO 3 - and BE were lower at submaximal workloads after HD compared with LD. In YA women, the maximal workload was 19% shorter and maximal oxygen uptake, RER, and HR were lower after HD compared with LD. Our data uniquely suggests that better renal function is associated with higher availability of bases, which may diminish exercise-induced acidosis and improve maximal aerobic performance. Differences in glomerular filtration rate between the subject groups likely explains the larger effects of dietary acid load in the elderly compared with younger subjects and in women compared with men.

Dynamic compressive loading enhances cartilage matrix synthesis and distribution and suppresses hypertrophy in hMSC-laden hyaluronic acid hydrogels.

PubMed

Bian, Liming; Zhai, David Y; Zhang, Emily C; Mauck, Robert L; Burdick, Jason A

2012-04-01

Mesenchymal stem cells (MSCs) are being recognized as a viable cell source for cartilage repair, and there is growing evidence that mechanical signals play a critical role in the regulation of stem cell chondrogenesis and in cartilage development. In this study we investigated the effect of dynamic compressive loading on chondrogenesis, the production and distribution of cartilage specific matrix, and the hypertrophic differentiation of human MSCs encapsulated in hyaluronic acid (HA) hydrogels during long term culture. After 70 days of culture, dynamic compressive loading increased the mechanical properties, as well as the glycosaminoglycan (GAG) and collagen contents of HA hydrogel constructs in a seeding density dependent manner. The impact of loading on HA hydrogel construct properties was delayed when applied to lower density (20 million MSCs/ml) compared to higher seeding density (60 million MSCs/ml) constructs. Furthermore, loading promoted a more uniform spatial distribution of cartilage matrix in HA hydrogels with both seeding densities, leading to significantly improved mechanical properties as compared to free swelling constructs. Using a previously developed in vitro hypertrophy model, dynamic compressive loading was also shown to significantly reduce the expression of hypertrophic markers by human MSCs and to suppress the degree of calcification in MSC-seeded HA hydrogels. Findings from this study highlight the importance of mechanical loading in stem cell based therapy for cartilage repair in improving neocartilage properties and in potentially maintaining the cartilage phenotype.

Loading and concurrent synchronous whole-body vibration interaction increases oxygen consumption during resistance exercise.

PubMed

Serravite, Daniel H; Edwards, David; Edwards, Elizabeth S; Gallo, Sara E; Signorile, Joseph F

2013-01-01

Exercise is commonly used as an intervention to increase caloric output and positively affect body composition. A major challenge is the low compliance often seen when the prescribed exercise is associated with high levels of exertion. Whole-body vibration (WBV) may allow increased caloric output with reduced effort; however, there is limited information concerning the effect of WBV on oxygen consumption (VO2). Therefore, this study assessed the synergistic effects of resistance training and WBV on VO2. We examined VO2 at different loads (0%, 20%, and 40% body weight (BW)) and vibration intensities (No vibration (NV), 35HZ, 2-3mm (35L), 50Hz, 57mm (50H)) in ten men (26.5 ± 5.1 years). Data were collected during different stages (rest, six 30s sets of squatting, and recovery). Repeated measures ANOVA showed a stage x load x vibration interaction. Post hoc analysis revealed no differences during rest; however, a significant vibration x load interaction occurred during exercise. Both 35L and 50H produced greater VO2 than NV at a moderate load of 20%BW. Although 40%BW produced greater VO2 than 20%BW or 0%BW using NV, no significant difference in VO2 was seen among vibratory conditions at 40%BW. Moreover, no significant differences were seen between 50H and 35L at 20%BW and NV at 40%BW. During recovery there was a main effect for load. Post hoc analyses revealed that VO2 at 40%BW was significantly higher than 20%BW or 0%BW, and 20%BW produced higher VO2 than no load. Minute-by-minute analysis revealed a significant impact on VO2 due to load but not to vibratory condition. We conclude that the synergistic effect of WBV and active squatting with a moderate load is as effective at increasing VO2 as doubling the external load during squatting without WBV. Key PointsSynchronous whole body vibration in conjunction with moderate external loading (app 20% BW) can increase oxygen consumption to the same extent as heavier loading (40% BW) during performance of the parallel squat

Recent increase in aerosol loading over the Australian arid zone

NASA Astrophysics Data System (ADS)

Mitchell, R. M.; Campbell, S. K.; Qin, Y.

2009-10-01

Collocated sun photometer and nephelometer measurements at Tinga Tingana in the Australian Outback over the decade 1997-2007 show a significant increase in aerosol loading following the onset of severe drought conditions in 2002. The mean mid-visible scattering coefficient obtained from nephelometer measurements over the period 2003-2007 is approximately double that recorded over the preceding 5 yr, with consistent trends in the column aerosol optical depth derived from the sun photometer. This increase is confined to the season of dust activity, particularly September to March. In contrast, background aerosol levels during May, June and July remained stable. The enhanced aerosol loadings during the latter 5 yr of the study period can be understood as a combination of dune destabilisation through loss of ephemeral vegetation and surface crust, and the changing supply of fluvial sediments to ephemeral lakes and floodplains within the Lake Eyre Basin. Major dust outbreaks are generally highly localised, although significant dust activity was observed at Tinga Tingana on 50% of days when a major event occurred elsewhere in the Lake Eyre Basin, suggesting frequent basin-wide dust mobilisation. Combined analysis of aerosol optical depth and scattering coefficient shows weak correlation between the surface and column aerosol (R2=0.24). The aerosol scale height is broadly distributed with a mode typically between 2-3 km, with clearly defined seasonal variation. Climatological analysis reveals bimodal structure in the annual cycle of aerosol optical depth, with a summer peak related to maximal dust activity, and a spring peak related to lofted fine-mode aerosol. There is evidence for an increase in near-surface aerosol during the period 2003-2007 relative to 1997-2002, consistent with an increase in dust activity. This accords with an independent finding of increasing aerosol loading over the Australian region as a whole, suggesting that rising dust activity over the Lake

A hybrid composite system of biphasic calcium phosphate granules loaded with hyaluronic acid-gelatin hydrogel for bone regeneration.

PubMed

Faruq, Omar; Kim, Boram; Padalhin, Andrew R; Lee, Gun Hee; Lee, Byong-Taek

2017-10-01

An ideal bone substitute should be made of biocompatible materials that mimic the structure, characteristics, and functions of natural bone. Many researchers have worked on the fabrication of different bone scaffold systems including ceramic-polymer hybrid system. In the present study, we incorporated hyaluronic acid-gelatin hydrogel to micro-channeled biphasic calcium phosphate granules as a carrier to improve cell attachment and proliferation through highly interconnected porous structure. This hybrid system is composed of ceramic biphasic calcium phosphate granules measuring 1 mm in diameter with seven holes and hyaluronic acid-gelatin hydrogel. This combination of biphasic calcium phosphate and hyaluronic acid-gelatin retained suitable characteristics for bone regeneration. The resulting scaffold had a porosity of 56% with a suitable pore sizes. The mechanical strength of biphasic calcium phosphate granule increased after loading hyaluronic acid-gelatin from 4.26 ± 0.43 to 6.57 ± 0.25 MPa, which is highly recommended for cancellous bone substitution. Swelling and degradation rates decreased in the hybrid scaffold compared to hydrogel due to the presence of granules in hybrid scaffold. In vitro cytocompatibility studies were observed by preosteoblasts (MC3T3-E1) cell line and the result revealed that biphasic calcium phosphate/hyaluronic acid-gelatin significantly increased cell growth and proliferation compared to biphasic calcium phosphate granules. Analysis of micro-computed tomography data and stained tissue sections from the implanted samples showed that the hybrid scaffold had good osseointegration and better bone formation in the scaffold one and two months postimplantation. Histological section confirmed the formation of dense collagenous tissue and new bone in biphasic calcium phosphate/hyaluronic acid-gelatin scaffolds at two months. Our study demonstrated that such hybrid biphasic calcium phosphate/hyaluronic acid-gelatin scaffold is a

Preparation of Salicylic Acid Loaded Nanostructured Lipid Carriers Using Box-Behnken Design: Optimization, Characterization and Physicochemical Stability.

PubMed

Pantub, Ketrawee; Wongtrakul, Paveena; Janwitayanuchit, Wicharn

2017-01-01

Nanostructured lipid carriers loaded salicylic acid (NLCs-SA) were developed and optimized by using the design of experiment (DOE). Box-Behnken experimental design of 3-factor, 3-level was applied for optimization of nanostructured lipid carriers prepared by emulsification method. The independent variables were total lipid concentration (X 1 ), stearic acid to Lexol ® GT-865 ratio (X 2 ) and Tween ® 80 concentration (X 3 ) while the particle size was a dependent variable (Y). Box-Behnken design could create 15 runs by setting response optimizer as minimum particle size. The optimized formulation consists of 10% of total lipid, a mixture of stearic acid and capric/caprylic triglyceride at a 4:1 ratio, and 25% of Tween ® 80 which the formulation was applied in order to prepare in both loaded and unloaded salicylic acid. After preparation for 24 hours, the particle size of loaded and unloaded salicylic acid was 189.62±1.82 nm and 369.00±3.37 nm, respectively. Response surface analysis revealed that the amount of total lipid is a main factor which could affect the particle size of lipid carriers. In addition, the stability studies showed a significant change in particle size by time. Compared to unloaded nanoparticles, the addition of salicylic acid into the particles resulted in physically stable dispersion. After 30 days, sedimentation of unloaded lipid carriers was clearly observed. Absolute values of zeta potential of both systems were in the range of 3 to 18 mV since non-ionic surfactant, Tween ® 80, providing steric barrier was used. Differential thermograms indicated a shift of endothermic peak from 55°C for α-crystal form in freshly prepared samples to 60°C for β´-crystal form in storage samples. It was found that the presence of capric/caprylic triglyceride oil could enhance encapsulation efficiency up to 80% and facilitate stability of the particles.

Nandrolone decanoate and load increase remodeling and strength in human supraspinatus bioartificial tendons.

PubMed

Triantafillopoulos, Ioannis K; Banes, Albert J; Bowman, Karl F; Maloney, Melissa; Garrett, William E; Karas, Spero G

2004-06-01

To date, no studies document the effect of anabolic steroids on rotator cuff tendons. Controlled laboratory study. Anabolic steroids enhance remodeling and improve the biomechanical properties of bioartificially engineered human supraspinatus tendons. Bioartificial tendons were treated with either nandrolone decanoate (nonload, steroid, n = 18), loading (load, nonsteroid, n = 18), or both (load, steroid, n = 18). A control group received no treatment (nonload, nonsteroid [NLNS], n = 18). Bioartificial tendons' remodeling was assessed by daily scanning, cytoskeletal organization by staining, matrix metalloproteinase-3 levels by ELISA assay, and biomechanical properties by load-to-failure testing. The load, steroid group showed the greatest remodeling and the best organized actin cytoskeleton. Matrix metallo-proteinase-3 levels in the load, steroid group were greater than those of the nonload, nonsteroid group (P <.05). Ultimate stress and ultimate strain in the load, steroid group were greater than those of the nonload, nonsteroid and nonload, steroid groups (P <.05). The strain energy density in the load, steroid group was greater when compared to other groups (P <.05). Nandrolone decanoate and load acted synergistically to increase matrix remodeling and biomechanical properties of bioartificial tendons. Data suggest anabolic steroids may enhance production of bioartificial tendons and rotator cuff tendon healing in vitro. More research is necessary before such clinical use is recommended.

Breeding Vegetables with Increased Content in Bioactive Phenolic Acids.

PubMed

Kaushik, Prashant; Andújar, Isabel; Vilanova, Santiago; Plazas, Mariola; Gramazio, Pietro; Herraiz, Francisco Javier; Brar, Navjot Singh; Prohens, Jaime

2015-10-09

Vegetables represent a major source of phenolic acids, powerful antioxidants characterized by an organic carboxylic acid function and which present multiple properties beneficial for human health. In consequence, developing new varieties with enhanced content in phenolic acids is an increasingly important breeding objective. Major phenolic acids present in vegetables are derivatives of cinnamic acid and to a lesser extent of benzoic acid. A large diversity in phenolic acids content has been found among cultivars and wild relatives of many vegetable crops. Identification of sources of variation for phenolic acids content can be accomplished by screening germplasm collections, but also through morphological characteristics and origin, as well as by evaluating mutations in key genes. Gene action estimates together with relatively high values for heritability indicate that selection for enhanced phenolic acids content will be efficient. Modern genomics and biotechnological strategies, such as QTL detection, candidate genes approaches and genetic transformation, are powerful tools for identification of genomic regions and genes with a key role in accumulation of phenolic acids in vegetables. However, genetically increasing the content in phenolic acids may also affect other traits important for the success of a variety. We anticipate that the combination of conventional and modern strategies will facilitate the development of a new generation of vegetable varieties with enhanced content in phenolic acids.

Soldier-relevant body borne loads increase knee joint contact force during a run-to-stop maneuver.

PubMed

Ramsay, John W; Hancock, Clifford L; O'Donovan, Meghan P; Brown, Tyler N

2016-12-08

The purpose of this study was to understand the effects of load carriage on human performance, specifically during a run-to-stop (RTS) task. Using OpenSim analysis tools, knee joint contact force, grounds reaction force, leg stiffness and lower extremity joint angles and moments were determined for nine male military personnel performing a RTS under three load configurations (light, ~6kg, medium, ~20kg, and heavy, ~40kg). Subject-based means for each biomechanical variable were submitted to repeated measures ANOVA to test the effects of load. During the RTS, body borne load significantly increased peak knee joint contact force by 1.2 BW (p<0.001) and peak vertical (p<0.001) and anterior-posterior (p=0.002) ground reaction forces by 0.6 BW and 0.3 BW, respectively. Body borne load also had a significant effect on hip (p=0.026) posture with the medium load and knee (p=0.046) posture with the heavy load. With the heavy load, participants exhibited a substantial, albeit non-significant increase in leg stiffness (p=0.073 and d=0.615). Increases in joint contact force exhibited during the RTS were primarily due to greater GRFs that impact the soldier with each incremental addition of body borne load. The stiff leg, extended knee and large braking force the soldiers exhibited with the heavy load suggests their injury risk may be greatest with that specific load configuration. Further work is needed to determine if the biomechanical profile exhibited with the heavy load configuration translates to unsafe shear forces at the knee joint and consequently, a higher likelihood of injury. Published by Elsevier Ltd.

Assessment of thermal load on transported goats administered with ascorbic acid during the hot-dry conditions

NASA Astrophysics Data System (ADS)

Minka, N. S.; Ayo, J. O.

2012-03-01

The major factor in the induction of physiological stress during road transportation of livestock is the complex fluctuations of the thermal transport microenvironment, encountered when animals are transported across different ecological zones. Recommended guidelines on optimum "on-board" conditions in which goats should be transported are lacking, and there are no acceptable ranges and limits for the thermal loads to which goats may be subjected during long-distance road transportation in hot-dry conditions. Panting score (PS), rectal temperature (RT), heart rate (HR) and respiratory rate (RR) were employed as reliable stress indices to assess the effects of different thermal loads, measured as temperature humidity index (THI), encountered in the vehicle during 12 h of road transportation of 40 goats, and to suggest the administration of 100 mg/kg body weight of ascorbic acid (AA) as an ameliorating agent. The results obtained showed that the PS, RT, HR and RR rose above normal reference values with increase in the THI and journey duration. The rise in PS value, which is a visual indicator of the severity of thermal load, was the most pronounced. The results suggest that values of THI in the vehicle up to 94.6 constitute no risk, while at of 100 it presents a moderate risk and above 100 may result in severe stress. The relationships between the thermal load and the physiological variables were positive and significant ( P < 0.05). They reflect the degree of stress imposed by each THI value during the transportation, and may be used as recommended ranges and limit thermal load values in transported goats. The results demonstrated that administration of 100 mg/kg body weight of AA before road transportation mitigated the risk of adverse effects of high THI values and other stress factors due to road transportation in goats.

Uncertainty analysis on simple mass balance model to calculate critical loads for soil acidity

Treesearch

Harbin Li; Steven G. McNulty

2007-01-01

Simple mass balance equations (SMBE) of critical acid loads (CAL) in forest soil were developed to assess potential risks of air pollutants to ecosystems. However, to apply SMBE reliably at large scales, SMBE must be tested for adequacy and uncertainty. Our goal was to provide a detailed analysis of uncertainty in SMBE so that sound strategies for scaling up CAL...

Pre-aeration of food waste to augment acidogenic process at higher organic load: Valorizing biohydrogen, volatile fatty acids and biohythane.

PubMed

Sarkar, Omprakash; Venkata Mohan, S

2017-10-01

Application of pre-aeration (AS) to waste prior to feeding was evaluated on acidogenic process in a semi-pilot scale biosystem for the production of biobased products (biohydrogen, volatile fatty acids (VFA) and biohythane) from food waste. Oxygen assisted in pre-hydrolysis of waste along with the suppression of methanogenic activity resulting in enhanced acidogenic product formation. AS operation resulted in 97% improvement in hydrogen conversion efficiency (HCE) and 10% more VFA production than the control. Increasing the organic load (OL) of food waste in association with AS application improved the productivity. The application of AS also influenced concentration and composition of fatty acid. Highest fraction of acetic (5.3g/l), butyric (0.7g/l) and propionic acid (0.84g/l) was achieved at higher OL (100g COD/l) with good degree of acidification (DOA). AS strategy showed positive influence on biofuel (biohydrogen and biohythane) production along with the biosynthesis of short chain fatty acids functioning as a low-cost pretreatment strategy in a single stage bioprocess. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dynamic adjustments in prefrontal, hippocampal, and inferior temporal interactions with increasing visual working memory load.

PubMed

Rissman, Jesse; Gazzaley, Adam; D'Esposito, Mark

2008-07-01

The maintenance of visual stimuli across a delay interval in working memory tasks is thought to involve reverberant neural communication between the prefrontal cortex and posterior visual association areas. Recent studies suggest that the hippocampus might also contribute to this retention process, presumably via reciprocal interactions with visual regions. To characterize the nature of these interactions, we performed functional connectivity analysis on an event-related functional magnetic resonance imaging data set in which participants performed a delayed face recognition task. As the number of faces that participants were required to remember was parametrically increased, the right inferior frontal gyrus (IFG) showed a linearly decreasing degree of functional connectivity with the fusiform face area (FFA) during the delay period. In contrast, the hippocampus linearly increased its delay period connectivity with both the FFA and the IFG as the mnemonic load increased. Moreover, the degree to which participants' FFA showed a load-dependent increase in its connectivity with the hippocampus predicted the degree to which its connectivity with the IFG decreased with load. Thus, these neural circuits may dynamically trade off to accommodate the particular mnemonic demands of the task, with IFG-FFA interactions mediating maintenance at lower loads and hippocampal interactions supporting retention at higher loads.

Cumulative loads increase at the knee joint with slow-speed running compared to faster running: a biomechanical study.

PubMed

Petersen, Jesper; Sørensen, Henrik; Nielsen, Rasmus Østergaard

2015-04-01

Biomechanical cross-sectional study. To investigate the hypothesis that the cumulative load at the knee during running increases as running speed decreases. The knee joint load per stride decreases as running speed decreases. However, by decreasing running speed, the number of strides per given distance is increased. Running a given distance at a slower speed may increase the cumulative load at the knee joint compared with running the same distance at a higher speed, hence increasing the risk of running-related injuries in the knee. Kinematic and ground reaction force data were collected from 16 recreational runners, during steady-state running with a rearfoot strike pattern at 3 different speeds (mean ± SD): 8.02 ± 0.17 km/h, 11.79 ± 0.21 km/h, and 15.78 ± 0.22 km/h. The cumulative load (cumulative impulse) over a 1000-m distance was calculated at the knee joint on the basis of a standard 3-D inverse-dynamics approach. Based on a 1000-m running distance, the cumulative load at the knee was significantly higher at a slow running speed than at a high running speed (relative difference, 80%). The mean load per stride at the knee increased significantly across all biomechanical parameters, except impulse, following an increase in running speed. Slow-speed running decreases knee joint loads per stride and increases the cumulative load at the knee joint for a given running distance compared to faster running. The primary reason for the increase in cumulative load at slower speeds is an increase in number of strides needed to cover the same distance.

Pd-loaded carbon felt as the cathode for selective dechlorination of 2,4-dichlorophenoxyacetic acid in aqueous solution

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

Tsyganok, A.I.; Yamanaka, Ichiro; Otsuka, Kiyoshi

1998-11-01

Electrocatalytic reductive dehalogenation of 2,4-dichlorophenoxyacetic acid (2,4-D) to phenoxyacetic acid in aqueous solution containing MeOH, trifluoroacetic acid, and tetraalkylammonium salt was studied. A Teflon-made two-compartment flow-through cell with a permeable carbon felt cathode and a platinum foil anode was employed. Several noble metals were tested as electrocatalysts. Palladium-loaded carbon felt was found to be the most suitable significantly enhanced its electrocatalytic activity toward 2,4-D dechlorination. The reaction was hypothesized to proceed at carbon-palladium interface areas through 4-chlorine cleavage to form 2-chlorophenoxyacetic acid as the main reaction intermediate.

Paclitaxel-loaded nanoparticles of star-shaped cholic acid-core PLA-TPGS copolymer for breast cancer treatment

NASA Astrophysics Data System (ADS)

Tang, Xiaolong; Cai, Shuyu; Zhang, Rongbo; Liu, Peng; Chen, Hongbo; Zheng, Yi; Sun, Leilei

2013-10-01

A system of novel nanoparticles of star-shaped cholic acid-core polylactide- d-α-tocopheryl polyethylene glycol 1000 succinate (CA-PLA-TPGS) block copolymer was developed for paclitaxel delivery for breast cancer treatment, which demonstrated superior in vitro and in vivo performance in comparison with paclitaxel-loaded poly( d, l-lactide- co-glycolide) (PLGA) nanoparticles and linear PLA-TPGS nanoparticles. The paclitaxel- or couramin 6-loaded nanoparticles were fabricated by a modified nanoprecipitation method and then characterized in terms of size, surface charge, surface morphology, drug encapsulation efficiency, and in vitro drug release. The CA-PLA-TPGS nanoparticles were found to be spherical in shape with an average size of around 120 nm. The nanoparticles were found to be stable, showing no change in the particle size and surface charge during 90-day storage of the aqueous solution. The release profiles of the paclitaxel-loaded nanoparticles exhibited typically biphasic release patterns. The results also showed that the CA-PLA-TPGS nanoparticles have higher antitumor efficacy than the PLA-TPGS nanoparticles and PLGA nanoparticles in vitro and in vivo. In conclusion, such nanoparticles of star-shaped cholic acid-core PLA-TPGS block copolymer could be considered as a potentially promising and effective strategy for breast cancer treatment.

Very Low-Protein Diet (VLPD) Reduces Metabolic Acidosis in Subjects with Chronic Kidney Disease: The "Nutritional Light Signal" of the Renal Acid Load.

PubMed

Di Iorio, Biagio Raffaele; Di Micco, Lucia; Marzocco, Stefania; De Simone, Emanuele; De Blasio, Antonietta; Sirico, Maria Luisa; Nardone, Luca

2017-01-17

Metabolic acidosis is a common complication of chronic kidney disease; current guidelines recommend treatment with alkali if bicarbonate levels are lower than 22 mMol/L. In fact, recent studies have shown that an early administration of alkali reduces progression of CKD. The aim of the study is to evaluate the effect of fruit and vegetables to reduce the acid load in CKD. We conducted a case-control study in 146 patients who received sodium bicarbonate. Of these, 54 patients assumed very low-protein diet (VLPD) and 92 were controls (ratio 1:2). We calculated every three months the potential renal acid load (PRAL) and the net endogenous acid production (NEAP), inversely correlated with serum bicarbonate levels and representing the non-volatile acid load derived from nutrition. Un-paired T -test and Chi-square test were used to assess differences between study groups at baseline and study completion. Two-tailed probability values ≤0.05 were considered statistically significant. At baseline, there were no statistical differences between the two groups regarding systolic blood pressure (SBP), diastolic blood pressure (DBP), protein and phosphate intake, urinary sodium, potassium, phosphate and urea nitrogen, NEAP, and PRAL. VLPD patients showed at 6 and 12 months a significant reduction of SBP ( p < 0.0001), DBP ( p < 0.001), plasma urea ( p < 0.0001) protein intake ( p < 0.0001), calcemia ( p < 0.0001), phosphatemia ( p < 0.0001), phosphate intake ( p < 0.0001), urinary sodium ( p < 0.0001), urinary potassium ( p < 0.002), and urinary phosphate ( p < 0.0001). NEAP and PRAL were significantly reduced in VLPD during follow-up. VLPD reduces intake of acids; nutritional therapy of CKD, that has always taken into consideration a lower protein, salt, and phosphate intake, should be adopted to correct metabolic acidosis, an important target in the treatment of CKD patients. We provide useful indications regarding acid load of food and drinks-the "acid load dietary traffic

Pro-inflammatory cytokines expression increases following low- and high-magnitude cyclic loading of lumbar ligaments

PubMed Central

D’Ambrosia, Peter; King, Karen; Davidson, Bradley; Zhou, Bing He; Lu, Yun

2010-01-01

Repetitive or overuse disorders of the lumbar spine affect the lives of workers and athletes. We hypothesize that repetitive anterior lumbar flexion–extension under low or high load will result in significantly elevated pro-inflammatory cytokines expression several hours post-activity. High loads will exhibit significantly higher expression than low loads. Lumbar spine of in vivo feline was subjected to cyclic loading at 0.25 Hz for six 10-min periods with 10 min of rest in between. One group was subjected to a low peak load of 20 N, whereas the second group to a high peak load of 60 N. Following a 7-h post-loading rest, the supraspinous ligaments of L-3/4, L-4/5 and L-5/6 and the unstimulated T-10/11 were excised for mRNA analysis and IL-1β, IL-6, IL-8, TNFα and TGFβ1 pro-inflammatory cytokines expression. Creep (laxity) developed in the lumbar spine during the loading and the subsequent 7 h of rest was calculated. A two-way mixed model ANOVA was used to assess difference in each cytokines expression between the two groups and control. Tukey HSD post hoc analysis delineated specific significant effects. Significance was set at 0.05. Low and high-load groups exhibited development of creep throughout the cyclic loading period and gradual recovery throughout the 7-h rest period. Residual creep of 24.8 and 30.2% were present in the low and high-load groups, respectively, 7-h post-loading. Significant increases in expression of all cytokines measured relative to control were obtained for supraspinous ligaments from both low and high-load magnitudes. IL-6, IL-8 and TGFβ1 expression in the high-load group were significantly higher relative to the low-load group. Significant increases in cytokines expression indicating tissue inflammation are observed several hours post-repetitive lumbar flexion–extension regardless of the load magnitude applied. Repetitive occupational and athletic activity, regardless of the load applied, may be associated with the

Site-specific critical acid load estimates for forest soils in the Osborn Creek watershed, Michigan

Treesearch

Trevor Hobbs; Jason Lynch; Randy Kolka

2017-01-01

Anthropogenic acid deposition has the potential to accelerate leaching of soil cations, and in turn, deplete nutrients essential to forest vegetation. The critical load concept, employing a simple mass balance (SMB) approach, is often used to model this process. In an evaluation under the U.S. Forest Service Watershed Condition Framework program, soils in all 6th level...

Hypericin-loaded nanoparticles for the photodynamic treatment of ovarian cancer.

PubMed

Zeisser-Labouèbe, Magali; Lange, Norbert; Gurny, Robert; Delie, Florence

2006-12-01

A photodynamic approach has been suggested to improve diagnosis and therapy of ovarian cancer. As Hypericin (Hy), a natural photosensitizer (PS) extracted from Hypericum perforatum, has been shown to be efficient in vitro and in vivo for the detection or treatment of other cancers, Hy could also be a potent tool for the treatment and detection of ovarian cancer. Due to its hydrophobicity, systemic administration of Hy is problematic. Thus, polymeric nanoparticles (NPs) of polylactic acid (PLA) or polylactic-co-glycolic acid (PLGA) were used as a drug delivery system. Hy-loaded NPs were produced with the following characteristics: (i) size in the 200-300 nm range, (ii) negative zeta potential, (iii) low residual PVAL and (iv) drug loading from 0.03 to 0.15% (w/w). Their in vitro photoactivity was investigated on the NuTu-19 ovarian cancer cell model derived from Fischer 344 rats and compared to free drug. Hy-loaded PLA NPs exhibited a higher photoactivity than free drug. Increasing light dose or incubation time with cells induced an enhanced activity of Hy-loaded PLA NPs. Increased NP drug loading had a negative effect on their photoactivity on NuTu-19 cells: at the same Hy concentration, the higher was the drug loading, the lower was the phototoxic effect. The influence of NP drug loading on the Hy release from NPs was also investigated.

Antimicrobial activity of a new synthetic peptide loaded in polylactic acid or poly(lactic-co-glycolic) acid nanoparticles against Pseudomonas aeruginosa, Escherichia coli O157:H7 and methicillin resistant Staphylococcus aureus (MRSA)

NASA Astrophysics Data System (ADS)

Cruz, J.; Flórez, J.; Torres, R.; Urquiza, M.; Gutiérrez, J. A.; Guzmán, F.; Ortiz, C. C.

2017-03-01

Nanocarrier systems are currently being developed for peptide, protein and gene delivery to protect them in the blood circulation and in the gastrointestinal tract. Polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with a new antimicrobial GIBIM-P5S9K peptide were obtained by the double emulsion solvent extraction/evaporation method. PLA- and PLGA-NPs were spherical with sizes between 300 and 400 nm for PLA and 200 and 300 nm for PLGA and <0.3 polydispersity index as determined by dynamic light scattering and scanning electron microscopy), having the zeta potential of >20 mV. The peptide-loading efficiency of PLA-NP and PLGA-NPs was 75% and 55%, respectively. PLA- and PLGA-NPs released around 50% of this peptide over 8 h. In 10% human sera the size of peptide loaded PLA- and PLGA-NPs increased between 25.2% and 39.3%, the PDI changed from 3.2 to 5.1 and the surface charge from -7.15 to 14.6 mV. Both peptide loaded PLA- and PLGA-NPs at 0.5 μM peptide concentration inhibited the growth of Escherichia coli O157:H7 (E. coli O157:H7), methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. aeruginosa (P. aeruginosa). In contrast, free peptide inhibited at 10 μM but did not inhibit at 0.5 and 1 μM. These PLA- and PLGA-NPs presented <10% hemolysis indicating that they are hemocompatible and promising for delivery and protection system of GIBIM-P5S9K peptide.

Cinnamic Acid Increases Lignin Production and Inhibits Soybean Root Growth

PubMed Central

Salvador, Victor Hugo; Lima, Rogério Barbosa; dos Santos, Wanderley Dantas; Soares, Anderson Ricardo; Böhm, Paulo Alfredo Feitoza; Marchiosi, Rogério; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

2013-01-01

Cinnamic acid is a known allelochemical that affects seed germination and plant root growth and therefore influences several metabolic processes. In the present work, we evaluated its effects on growth, indole-3-acetic acid (IAA) oxidase and cinnamate 4-hydroxylase (C4H) activities and lignin monomer composition in soybean (Glycine max) roots. The results revealed that exogenously applied cinnamic acid inhibited root growth and increased IAA oxidase and C4H activities. The allelochemical increased the total lignin content, thus altering the sum and ratios of the p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) lignin monomers. When applied alone or with cinnamic acid, piperonylic acid (PIP, a quasi-irreversible inhibitor of C4H) reduced C4H activity, lignin and the H, G, S monomer content compared to the cinnamic acid treatment. Taken together, these results indicate that exogenously applied cinnamic acid can be channeled into the phenylpropanoid pathway via the C4H reaction, resulting in an increase in H lignin. In conjunction with enhanced IAA oxidase activity, these metabolic responses lead to the stiffening of the cell wall and are followed by a reduction in soybean root growth. PMID:23922685

Cinnamic acid increases lignin production and inhibits soybean root growth.

PubMed

Salvador, Victor Hugo; Lima, Rogério Barbosa; dos Santos, Wanderley Dantas; Soares, Anderson Ricardo; Böhm, Paulo Alfredo Feitoza; Marchiosi, Rogério; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

2013-01-01

Cinnamic acid is a known allelochemical that affects seed germination and plant root growth and therefore influences several metabolic processes. In the present work, we evaluated its effects on growth, indole-3-acetic acid (IAA) oxidase and cinnamate 4-hydroxylase (C4H) activities and lignin monomer composition in soybean (Glycine max) roots. The results revealed that exogenously applied cinnamic acid inhibited root growth and increased IAA oxidase and C4H activities. The allelochemical increased the total lignin content, thus altering the sum and ratios of the p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) lignin monomers. When applied alone or with cinnamic acid, piperonylic acid (PIP, a quasi-irreversible inhibitor of C4H) reduced C4H activity, lignin and the H, G, S monomer content compared to the cinnamic acid treatment. Taken together, these results indicate that exogenously applied cinnamic acid can be channeled into the phenylpropanoid pathway via the C4H reaction, resulting in an increase in H lignin. In conjunction with enhanced IAA oxidase activity, these metabolic responses lead to the stiffening of the cell wall and are followed by a reduction in soybean root growth.

Musculoskeletal stiffness changes linearly in response to increasing load during walking gait.

PubMed

Caron, Robert R; Lewis, Cara L; Saltzman, Elliot; Wagenaar, Robert C; Holt, Kenneth G

2015-04-13

Development of biologically inspired exoskeletons to assist soldiers in carrying load is a rapidly expanding field. Understanding how the body modulates stiffness in response to changing loads may inform the development of these exoskeletons and is the purpose of the present study. Seventeen subjects walked on a treadmill at a constant preferred walking velocity while nine different backpack loading conditions ranging from 12.5% to 40% bodyweight (BW) were introduced in an ascending and then descending order. Kinematic data were collected using Optotrak, a 3D motion analysis system, and used to estimate the position of the center of mass (COM). Two different estimates of stiffness were computed for the stance phase of gait. Both measures of stiffness were positively and linearly related to load magnitudes, with the slopes of the relationships being larger for the descending than the ascending conditions. These results indicate that changes in mechanical stiffness brought about in the musculoskeletal system vary systematically during increases in load to ensure that critical kinematic variables measured in a previous publication remain invariant (Caron et al., 2013). Changes in stiffness and other kinematics measured at the 40% BW condition suggest a boundary in which gait stiffness control limit is reached and a new gait pattern is required. Since soldiers are now carrying up to 96% of body weight, the need for research with even heavier loads is warranted. These findings have implications on the development of exoskeletons to assist in carrying loads. Copyright © 2015 Elsevier Ltd. All rights reserved.

Uric Acid Secretion from Adipose Tissue and Its Increase in Obesity*

PubMed Central

Tsushima, Yu; Nishizawa, Hitoshi; Tochino, Yoshihiro; Nakatsuji, Hideaki; Sekimoto, Ryohei; Nagao, Hirofumi; Shirakura, Takashi; Kato, Kenta; Imaizumi, Keiichiro; Takahashi, Hiroyuki; Tamura, Mizuho; Maeda, Norikazu; Funahashi, Tohru; Shimomura, Iichiro

2013-01-01

Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that had abundant expression and activities of XOR, and adipose tissues in obese mice had higher XOR activities than those in control mice. 3T3-L1 and mouse primary mature adipocytes produced and secreted uric acid into culture medium. The secretion was inhibited by febuxostat in a dose-dependent manner or by gene knockdown of XOR. Surgical ischemia in adipose tissue increased local uric acid production and secretion via XOR, with a subsequent increase in circulating uric acid levels. Uric acid secretion from whole adipose tissue was increased in obese mice, and uric acid secretion from 3T3-L1 adipocytes was increased under hypoxia. Our results suggest that purine catabolism in adipose tissue could be enhanced in obesity. PMID:23913681

An acid/alkaline stress and the addition of amino acids induce a prolonged viability of Lactobacillus plantarum loaded into alginate gel.

PubMed

Bevilacqua, Antonio; Sinigaglia, Milena; Corbo, Maria Rosaria

2010-08-15

This study reports on the investigation on the effects of the conditions used throughout the step of biomass production on the survival of Lactobacillus plantarum loaded into alginate gels. L. plantarum was grown under different conditions (MRS or a laboratory medium-LB(2)-at acidic or alkaline pHs, with NaCl, phenols, vitamins or amino acids) and immobilized in sodium alginate; cell number was evaluated throughout the storage and death (delta(stand)) and first-reduction times (delta) were calculated. The storage of alginate gels at 4 degrees C prolonged cell viability up to 60 days (ca. 20 days for cells produced in MRS and stored at 30 degrees C); however, a similar prolongation was achieved for cells produced in LB(2) adjusted to pH 5.0 and 9.0 or added with amino acids (death time>50-60 days). Copyright 2010 Elsevier B.V. All rights reserved.

Development and evaluation of a novel topical treatment for acne with azelaic acid-loaded nanoparticles.

PubMed

Reis, Catarina Pinto; Gomes, Ana; Rijo, Patrícia; Candeias, Sara; Pinto, Pedro; Baptista, Marina; Martinho, Nuno; Ascensão, Lia

2013-10-01

Azelaic acid (AzA) is used in the treatment of acne. However, side effects and low compliance have been associated with several topical treatments with AzA. Nanotechnology presents a strategy that can overcome these problems. Polymeric nanoparticles can control drug release and targeting and reduce local drug toxicity. The aim of this study was to produce and evaluate an innovative topical treatment for acne with AzA-loaded poly-DL-lactide/glycolide copolymer nanoparticles. A soft white powder of nanoparticles was prepared. The mean size of loaded nanoparticles was < 400 nm and zeta potential was negative. Spherical nanoparticles were observed by scanning electron microscopy. Encapsulation efficiency was around 80% and a strong interaction between the polymer and the drug was confirmed by differential scanning calorimetric analysis. In vitro drug release studies suggested a controlled and pulsatile release profile. System efficacy tests suggested similar results between the loaded nanoparticles and the nonencapsulated drug against the most common bacteria associated with acne. Cytotoxicity of AzA-loaded nanoparticles was concentration dependent, although not pronounced. The occluded patch test seemed to indicate that the formulation excipients were safe and thus AzA-loaded nanoparticles appear to be an efficient and safe treatment for acne.

Mechanical loading increases detection of estrogen receptor-alpha in osteocytes and osteoblasts despite chronic energy restriction.

PubMed

Swift, Sibyl N; Swift, Joshua M; Bloomfield, Susan A

2014-12-01

Estrogen receptor-α (ER-α) is an important mediator of the bone response to mechanical loading. We sought to determine whether restricting dietary energy intake by 40% limits the bone formation rate (BFR) response to mechanical loading (LOAD) by downregulating ER-α-expressing osteocytes, or osteoblasts, or both. Female rats (n = 48, 7 mo old) were randomized to ADLIB-SHAM and ADLIB-LOAD groups fed AIN-93M purified diet ad libitum or to ER40-SHAM and ER40-LOAD groups fed modified AIN-93M with 40% less energy (100% of all other nutrients). After 12 wk, LOAD rats were subjected to a muscle contraction protocol three times every third day. ER40 produced lower proximal tibia bone volume (-22%), trabecular thickness (-14%), and higher trabecular separation (+127%) in SHAM but not LOAD rats. ER40 rats exhibited reductions in mineral apposition rate, but not percent mineralizing surface or BFR. LOAD induced similar relative increases in these kinetic measures of osteoblast activity/recruitment in both diet groups., but absolute values for ER40 LOAD rats were lower vs. ADLIB-LOAD. There were fourfold and eightfold increases in proportion of estrogen receptor-α protein-positive osteoblast and osteocytes, respectively, in LOAD vs. SHAM rats, with no effect of ER40. These data suggest that a brief period of mechanical loading significantly affects estrogen receptor-α in cancellous bone osteoblasts and osteocytes. Chronic energy restriction does result in lower absolute values in indices of osteoblast activity after mechanical loading, but not by a smaller increment relative to unloaded bones; this change is not explained by an associated downregulation of ER-α in osteoblasts or osteocytes.

Increased Production of Fatty Acids and Triglycerides in Aspergillus oryzae by Enhancing Expressions of Fatty Acid Synthesis-Related Genes

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

Tamano, Koichi; Bruno, Kenneth S.; Karagiosis, Sue A.

2013-01-01

Microbial production of fats and oils is being developedas a means of converting biomass to biofuels. Here we investigate enhancing expression of enzymes involved in the production of fatty acids and triglycerides as a means to increase production of these compounds in Aspergillusoryzae. Examination of the A.oryzaegenome demonstrates that it contains twofatty acid synthases and several other genes that are predicted to be part of this biosynthetic pathway. We enhancedthe expressionof fatty acid synthesis-related genes by replacing their promoters with thepromoter fromthe constitutively highly expressedgene tef1. We demonstrate that by simply increasing the expression of the fatty acid synthasegenes wemore » successfullyincreasedtheproduction of fatty acids and triglyceridesby more than two fold. Enhancement of expression of the fatty acid pathway genes ATP-citrate lyase and palmitoyl-ACP thioesteraseincreasedproductivity to a lesser extent.Increasing expression ofacetyl-CoA carboxylase caused no detectable change in fatty acid levels. Increases in message level for each gene were monitored usingquantitative real-time RT-PCR. Our data demonstrates that a simple increase in the abundance of fatty acid synthase genes can increase the detectable amount of fatty acids.« less

Very Low-Protein Diet (VLPD) Reduces Metabolic Acidosis in Subjects with Chronic Kidney Disease: The “Nutritional Light Signal” of the Renal Acid Load

PubMed Central

Di Iorio, Biagio Raffaele; Di Micco, Lucia; Marzocco, Stefania; De Simone, Emanuele; De Blasio, Antonietta; Sirico, Maria Luisa; Nardone, Luca

2017-01-01

Background: Metabolic acidosis is a common complication of chronic kidney disease; current guidelines recommend treatment with alkali if bicarbonate levels are lower than 22 mMol/L. In fact, recent studies have shown that an early administration of alkali reduces progression of CKD. The aim of the study is to evaluate the effect of fruit and vegetables to reduce the acid load in CKD. Methods: We conducted a case-control study in 146 patients who received sodium bicarbonate. Of these, 54 patients assumed very low-protein diet (VLPD) and 92 were controls (ratio 1:2). We calculated every three months the potential renal acid load (PRAL) and the net endogenous acid production (NEAP), inversely correlated with serum bicarbonate levels and representing the non-volatile acid load derived from nutrition. Un-paired T-test and Chi-square test were used to assess differences between study groups at baseline and study completion. Two-tailed probability values ≤0.05 were considered statistically significant. Results: At baseline, there were no statistical differences between the two groups regarding systolic blood pressure (SBP), diastolic blood pressure (DBP), protein and phosphate intake, urinary sodium, potassium, phosphate and urea nitrogen, NEAP, and PRAL. VLPD patients showed at 6 and 12 months a significant reduction of SBP (p < 0.0001), DBP (p < 0.001), plasma urea (p < 0.0001) protein intake (p < 0.0001), calcemia (p < 0.0001), phosphatemia (p < 0.0001), phosphate intake (p < 0.0001), urinary sodium (p < 0.0001), urinary potassium (p < 0.002), and urinary phosphate (p < 0.0001). NEAP and PRAL were significantly reduced in VLPD during follow-up. Conclusion: VLPD reduces intake of acids; nutritional therapy of CKD, that has always taken into consideration a lower protein, salt, and phosphate intake, should be adopted to correct metabolic acidosis, an important target in the treatment of CKD patients. We provide useful indications regarding acid load of food and drinks�

In vitro characterization of pH-sensitive azithromycin-loaded methoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) micelles.

PubMed

Teng, Fangfang; Deng, Peizong; Song, Zhimei; Zhou, Feilong; Feng, Runliang; Liu, Na

2017-06-15

In order to improve azithromycin's antibacterial activity in acidic medium, monomethoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) copolymer was synthesized through allylation, free radical addition, ring-opening polymerization and amidation reactions with methoxy poly (ethylene glycol) as raw material. Drug loading capacity and encapsulation efficiency of azithromycin-loaded micelles prepared via thin film hydration method were 11.58±0.86% and 96.06±1.93%, respectively. The drug-loaded micelles showed pH-dependent property in the respects of particle size, zeta potential at the range of pH 5.5-7.8. It could control drug in vitro release and demonstrate higher release rate at pH 6.0 than that at pH 7.4. In vitro antibacterial experiment indicated that the activity of azithromycin-loaded micelles against S. aureus was superior to free azithromycin in medium at both pH 6.0 and pH 7.4. Using fluorescein as substitute with pH-dependent fluorescence decrease property, laser confocal fluorescence microscopy analysis confirmed that cellular uptake of micelles was improved due to protonation of copolymer's imidazole groups at pH 6.0. The enhanced cellular uptake and release of drug caused its activity enhancement in acidic medium when compared with free drug. The micellar drug delivery system should be potential application in the field of bacterial infection treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Diet-dependent net endogenous acid load of vegan diets in relation to food groups and bone health-related nutrients: results from the German Vegan Study.

PubMed

Ströhle, Alexander; Waldmann, Annika; Koschizke, Jochen; Leitzmann, Claus; Hahn, Andreas

2011-01-01

Dietary composition has been shown to affect acid-base homeostasis and bone health in humans. We investigated the potential renal acid load (PRAL) and the estimated diet-dependent net acid load (net endogenous acid production, NEAP) in adult vegans and evaluated the relationships between NEAP, food groups and intake of bone health-related nutrients. The German Vegan Study (GVS) is a cross-sectional study. Data from healthy men (n = 67) and women (n = 87), aged 21-75 years, who fulfilled the study criteria (vegan diet for ≥1 year prior to study start; age ≥18 years, and no pregnancy/childbirth during the last 12 months) were included in the analysis. NEAP values were calculated from diet composition using two models: one based on the protein/potassium quotient and another taking into account an anthropometry-based loss of urinary organic anions. Mean daily intakes of phosphorus, potassium, sodium, magnesium and vitamin C were above, and vitamin D and calcium below Dietary Reference Intake (DRI). Regardless of the model used, the diet in the GVS was characterized by a nearly neutral NEAP. A strong correlation was observed between the NEAP values of the two models (r(s) = 0.873, p < 0.001). Only the consumption of fruits decreased constantly across the increasing quartiles of NEAP. It can be hypothesized that vegan diets do not affect acid-base homeostasis. With respect to bone health, the significance of this finding needs further investigation. Copyright © 2011 S. Karger AG, Basel.

Increased 13-hydroxyoctadecadienoic acid content in lipopolysaccharide stimulated macrophages.

PubMed

Schade, U F; Burmeister, I; Engel, R

1987-09-15

Endotoxin-stimulated mouse peritoneal macrophages were found to contain 13-hydroxyoctadecadienoic acid, which was released upon alkaline hydrolysis of the cells. Compared to untreated cells, incubation with LPS increased the content of 13-hydroxyoctadecadienoic acid in macrophage hydrolysates to about 8-fold. Analysis of the material on chiralphase HPLC revealed that it consisted prevalently of 13(S)-hydroxyoctadecadienoic acid. This indicates its enzymatic origine.

Using Critical Loads to Look at Improvements in Acidic Surface Water Conditions since the 1990 Amendments to the Clear Air Act: Case Study Adirondack, NY

NASA Astrophysics Data System (ADS)

Lynch, J. A.; Kolian, M. J.; Haeuber, R.

2008-12-01

Acid deposition has affected hundreds of lakes and thousands of miles of headwater streams in the Adirondack region of New York State. The diversity of life in these acidic waters has been greatly reduced. The poor buffering capacity of the thin, acidic soils in the Adirondack Mountains makes the lakes and ponds particularly susceptible to acidification. Since the mid-1990's, lakes in the Adirondack region are finally showing signs of recovery. The good news is that emissions of sulfur dioxide and nitrogen oxides have been reduced and as a result acidic deposition of sulfate and nitrate has decreased in surface waters approximately 26 and 13%, respectively. This has led to improvement in the acid neutralizing capacity (ANC) of these water bodies. Although improvement in water quality is a good sign, it does not tell us if a particular lake or a group of lakes have recovered from decades of acidic deposition. However, the critical loads approach does allow for evaluation of whether a water body has reached recovery for acidic deposition. Critical loads and exceedances for lake surface water and acidity were calculated for 187 lakes in the Adirondack region. The Steady-State Water Chemistry (SSWC) model was used to calculate the critical load, relying on water chemistry data from the TIME/LTM network. An ANC threshold of 50 μeq/L was selected for this case study. Exceedances were calculated from deposition for the period before implementation of the Acid Rain program (ARP) (1989-1991) and for the period of 2004-2006 to judge improvements as a result of the ARP. On average, the critical load for lakes in the Adirondack region is 164 meq/m2/yr, while it is 48 meq/m2/yr for the most sensitive lakes (i.e. ANC less than 100 μeq/L). For the period from 2004 to 2006, 65% of the lakes within the TIME/LTM network continued to receive levels of acid deposition that exceeded the lake's critical load down from 72% of lakes before implementation of the Acid Rain Program

Clofibric acid increases the formation of oleic acid in endoplasmic reticulum of the liver of rats.

PubMed

Hirose, Akihiko; Yamazaki, Tohru; Sakamoto, Takeshi; Sunaga, Katsuyoshi; Tsuda, Tadashi; Mitsumoto, Atsushi; Kudo, Naomi; Kawashima, Yoichi

2011-01-01

The effects of 2-(4-chlorophenoxy)-2-methylpropionic acid (clofibric acid) on the formation of oleic acid (18:1) from stearic acid (18:0) and utilization of the 18:1 formed for phosphatidylcholine (PC) formation in endoplasmic reticulum in the liver of rats were studied in vivo. [¹⁴C]18:0 was intravenously injected into control Wistar male rats and rats that had been fed on a diet containing 0.5% (w/w) clofibric acid for 7 days; and the distribution of radiolabeled fatty acids among subcellular organelles, microsomes, peroxisomes, and mitochondria, was estimated on the basis of correction utilizing the yields from homogenates of marker enzymes for these organelles. The radioactivity was mostly localized in microsomes and the radiolabeled fatty acids present in microsomes were significantly increased by the treatment of rats with clofibric acid. The formation of radiolabeled 18:1 in microsomes markedly increased and incorporations of the formed [¹⁴C]18:1 into PC and phosphatidylethanolamine in microsomes were augmented in response to clofibric acid. The [¹⁴C]18:1 incorporated into PC was mostly located at the C-2 position, but not the C-1 position, of PC, and the radioactivity in 18:1 at the C-2 position of PC was strikingly increased by clofibric acid. These results obtained from the in vivo experiments directly link the findings that clofibric acid treatment induces microsomal stearoyl-CoA desaturase and 1-acylglycerophosphocholine acyltransferase in the liver and the findings that the treatment with the drug elevated absolute mass and mass proportion of 18:1 at the C-2 position, but not the C-1 position, of PC in the liver together.

Catalytic Decarboxylation of Fatty Acids to Aviation Fuels over Nickel Supported on Activated Carbon

PubMed Central

Wu, Jianghua; Shi, Juanjuan; Fu, Jie; Leidl, Jamie A.; Hou, Zhaoyin; Lu, Xiuyang

2016-01-01

Decarboxylation of fatty acids over non-noble metal catalysts without added hydrogen was studied. Ni/C catalysts were prepared and exhibited excellent activity and maintenance for decarboxylation. Thereafter, the effects of nickel loading, catalyst loading, temperature, and carbon number on the decarboxylation of fatty acids were investigated. The results indicate that the products of cracking increased with high nickel loading or catalyst loading. Temperature significantly impacted the conversion of stearic acid but did not influence the selectivity. The fatty acids with large carbon numbers tend to be cracked in this reaction system. Stearic acid can be completely converted at 370 °C for 5 h, and the selectivity to heptadecane was around 80%. PMID:27292280

Target loads of atmospheric sulfur deposition for the protection and recovery of acid-sensitive streams in the Southern Blue Ridge Province

Treesearch

Timothy Sullivan; Bernard Cosby; William Jackson

2011-01-01

An important tool in the evaluation of acidification damage to aquatic and terrestrial ecosystems is the critical load (CL), which represents the steady-state level of acidic deposition below which ecological damage would not be expected to occur, according to current scientific understanding. A deposition load intended to be protective of a specified resource...

Synthesis and Characterization of Quantum Dot-Loaded Poly(lactic-co-glycolic) Acid Nanocomposite Fibers by an Electrospinning Process.

PubMed

Ankireddy, Seshadri Reddy; Kim, Jongsung

2017-04-01

Poly(lactic-co-glycolic) acid (PLGA) is one of the most successfully developed biodegradable polymers. PLGA is a copolymer of polylactic and glycolic acid. In this work, quantum dot (QD)-loaded PLGA nanofibers were fabricated via a simple one-step electrospinning process. The surface morphology of the fibers was characterized by scanning electron microscopy (SEM). It was shown that the PLGA nanofibers had both smooth and rough surfaces with an average fiber diameter of 150 ± 25 nm and 350 ± 60 nm for the PLGA and QD-loaded PLGA nanofibers, respectively. The needle size, applied voltage, and solvent flow rate in the syringe were maintained at 23 G, 20 kV, and 1.5 mL/h, respectively. The SEM analysis showed that nanofibers with a very thin and uniform size were formed and the InP/ZnS QDs were homogeneously loaded into the PLGA nanofiber matrix. The thermal properties of the PLGA-QD nanofibers were explored by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The surface chemical structure and functionalities were characterized by Fourier transform infrared (FTIR) spectroscopy and X-ray powder diffraction (XRPD).

Acid mine drainage and subsidence: effects of increased coal utilization.

PubMed Central

Hill, R D; Bates, E R

1979-01-01

The increases above 1975 levels for acid mine drainage and subsidence for the years 1985 and 2000 based on projections of current mining trends and the National Energy Plan are presented. No increases are projected for acid mine drainage from surface mines or waste since enforcement under present laws should control this problem. The increase in acid mine drainage from underground mines is projected to be 16 percent by 1985 and 10 percent by 2000. The smaller increase in 2000 over 1985 reflects the impact of the PL 95-87 abandoned mine program. Mine subsidence is projected to increase by 34 and 115 percent respectively for 1985 and 2000. This estimate assumes that subsidence will parallel the rate of underground coal production and that no new subsidence control measures are adopted to mitigate subsidence occurrence. PMID:540617

Role of the adrenocortical reaction to physical load in increase in the working capacity of the body

NASA Technical Reports Server (NTRS)

Viru, A. A.

1977-01-01

The maximal duration of swimming by rats with a load of 3% of their body weight increased after 5 weeks of training. This time did not increase in animals receiving dexamethasone in the process of training. The blood corticosterone level of these rats with the maximal load increased less than that of animals trained without administration of dexamethasone.

Prevention of peritendinous adhesions with electrospun ibuprofen-loaded poly(L-lactic acid)-polyethylene glycol fibrous membranes.

PubMed

Liu, Shen; Hu, Changmin; Li, Fengfeng; Li, Xu-jun; Cui, Wenguo; Fan, Cunyi

2013-02-01

Physical barriers are commonly used to reduce peritendinous adhesion after injury. However, the inflammatory response to surgery cannot be prevented. This study was designed to evaluate the ability of ibuprofen-loaded poly(l-lactic acid)-polyethylene glycol (PELA) diblock copolymer fibrous membranes in preventing adhesion formation and reduce inflammation. Electrospun PELA fibrous membranes underwent mechanical testing and were characterized by morphology, surface wettability, drug release, and degradation. Results of an in vitro drug release study showed that a burst release was followed by sustained release from fibrous membranes with high initial ibuprofen content. Fewer L929 mouse fibroblasts adhered to and proliferated on the ibuprofen-loaded PELA fibrous membrane compared with tissue culture plates or PELA fibrous membrane without ibuprofen. In a chicken model of flexor digitorum profundus tendon surgery, the ibuprofen-loaded PELA fibrous membranes prevented tissue adhesion and significantly reduced inflammation. Taken together, these results demonstrate that ibuprofen-loaded PELA fibrous membranes prevent peritendinous adhesion formation better than membranes that do not contain ibuprofen, through anti-adhesion and anti-inflammatory actions.

Working memory load reduces the late positive potential and this effect is attenuated with increasing anxiety.

PubMed

MacNamara, Annmarie; Ferri, Jamie; Hajcak, Greg

2011-09-01

Emotion regulation decreases the processing of arousing stimuli, as indexed by the late positive potential (LPP), an electrocortical component that varies in amplitude with emotional arousal. Emotion regulation increases activity in the prefrontal areas associated with cognitive control, including the dosolateral prefrontal cortex (DLPFC). The present study manipulated working memory load, known to activate the DLPFC, and recorded the LPP elicited by aversive and neutral IAPS pictures presented during the retention interval. The LPP was larger on low-load compared to high-load trials, and on trials with aversive compared to neutral pictures. These LPP data suggest that emotional content and working memory load have opposing effects on attention to distracting stimuli. State anxiety was associated with reduced modulation of the LPP by working memory load. Results are discussed in terms of competition for attention between emotion and cognition and suggest a relationship between DLPFC activation and the allocation of attentional resources to distracting visual stimuli-a relationship that may be disrupted with increasing anxiety.

Development of a total maximum daily load (TMDL) for acid-impaired lakes in the Adirondack region of New York

NASA Astrophysics Data System (ADS)

Fakhraei, Habibollah; Driscoll, Charles T.; Selvendiran, Pranesh; DePinto, Joseph V.; Bloomfield, Jay; Quinn, Scott; Rowell, H. Chandler

2014-10-01

Acidic deposition has impaired acid-sensitive surface waters in the Adirondack region of New York by decreasing pH and acid neutralizing capacity (ANC). In spite of air quality programs over past decades, 128 lakes in the Adirondacks were classified as “impaired” under Section 303(d) of the Clean Water Act in 2010 due to elevated acidity. The biogeochemical model, PnET-BGC, was used to relate decreases in atmospheric sulfur (S) and nitrogen (N) deposition to changes in lake water chemistry. The model was calibrated and confirmed using observed soil and lake water chemistry data and then was applied to calculate the maximum atmospheric deposition that the impaired lakes can receive while still achieving ANC targets. Two targets of ANC were used to characterize the recovery of acid-impaired lakes: 11 and 20 μeq L-1. Of the 128 acid-impaired lakes, 97 currently have ANC values below the target value of 20 μeq L-1 and 83 are below 11 μeq L-1. This study indicates that a moderate control scenario (i.e., 60% decrease from the current atmospheric S load) is projected to recover the ANC of lakes at a mean rate of 0.18 and 0.05 μeq L-1 yr-1 during the periods 2022-2050 and 2050-2200, respectively. The total maximum daily load (TMDL) of acidity corresponding to this moderate control scenario was estimated to be 7.9 meq S m-2 yr-1 which includes a 10% margin of safety.

Airborne soil dust and its importance in buffering of atmospheric acidity and critical load assessment, over the semi arid tract of northern India.

NASA Astrophysics Data System (ADS)

Sharma, Disha; Kulshrestha, Umesh

Airborne soil dust and its importance in buffering of atmospheric acidity and critical load assessment, over the semi arid tract of northern India. The Critical Load approach alongwith integrated assessment models has been used in the European nations for policy formations to reduce acidic emissions. This unique approach was applied to assess the of vulnerability of natural systems to the present day atmospheric pollution scenario. The calculated values of critical loads of sulphur ( 225 - 275 eq/ha/yr) and nitrogen (298 - 303 eq/ha/yr), for the soil system in Delhi, were calculated with respect to Anjan grass, Hibiscus and Black siris. The present loads of sulphur (PL(S) = 26.40 eq/ha/yr) and nitrogen (PL(N) = 36.51 eq/ha/yr) were found to be much lower than their critical loads without posing any danger of atmospheric acidic deposition on the soil systems. The study indicated that the system is still protective due to high pH of soil. The nature of buffering capability of calcium derived from soil dust can be considered as a natural tool to combat acidification in the Indian region. The results showed that the pollution status in Delhi is still within the safe limits. However, at the pace at which the city is growing, it is likely that in coming decades, it may exceed these critical values. In order to set deposition limits and avoid adverse effects of acidic deposition this approach can be applied in India too. Such approach is very useful, not only in abating pollution but also in devising means of cost optimal emission abatement strategies.

Effect of potential renal acid load of foods on urinary citrate excretion in calcium renal stone formers.

PubMed

Trinchieri, Alberto; Lizzano, Renata; Marchesotti, Federica; Zanetti, Giampaolo

2006-02-01

The aim of this study was to investigate the influence of the potential renal acid load (PRAL) of the diet on the urinary risk factors for renal stone formation. The present series comprises 187 consecutive renal calcium stone patients (114 males, 73 females) who were studied in our stone clinic. Each patient was subjected to an investigation including a 24-h dietary record and 24-h urine sample taken over the same period. Nutrients and calories were calculated by means of food composition tables using a computerized procedure. Daily PRAL was calculated considering the mineral and protein composition of foods, the mean intestinal absorption rate for each nutrient and the metabolism of sulfur-containing amino acids. Sodium, potassium, calcium, magnesium, phosphate, oxalate, urate, citrate, and creatinine levels were measured in the urine. The mean daily PRAL was higher in male than in female patients (24.1+/-24.0 vs 16.1+/-20.1 mEq/day, P=0.000). A significantly (P=0.01) negative correlation (R=-0.18) was found between daily PRAL and daily urinary citrate, but no correlation between PRAL and urinary calcium, oxalate, and urate was shown. Daily urinary calcium (R=0.186, P=0.011) and uric acid (R=0.157, P=0.033) were significantly related to the dietary intake of protein. Daily urinary citrate was significantly related to the intakes of copper (R=0.178, P=0.015), riboflavin (R=0.20, P=0.006), piridoxine (R=0.169, P=0.021) and biotin (R=0.196, P=0.007). The regression analysis by stepwise selection confirmed the significant negative correlation between PRAL and urinary citrate (P=0.002) and the significant positive correlation between riboflavin and urinary citrate (P=0.000). Urinary citrate excretion of renal stone formers (RSFs) is highly dependent from dietary acid load. The computation of the renal acid load is advisable to investigate the role of diet in the pathogenesis of calcium stone disease and it is also a useful tool to evaluate the lithogenic potential of

Resin-dentin bonds to EDTA-treated vs. acid-etched dentin using ethanol wet-bonding. Part II: Effects of mechanical cycling load on microtensile bond strengths.

PubMed

Sauro, Salvatore; Toledano, Manuel; Aguilera, Fatima Sánchez; Mannocci, Francesco; Pashley, David H; Tay, Franklin R; Watson, Timothy F; Osorio, Raquel

2011-06-01

To compare microtensile bond strengths (MTBS) subsequent to load cycling of resin bonded acid-etched or EDTA-treated dentin using a modified ethanol wet-bonding technique. Flat dentin surfaces were obtained from extracted human molars and conditioned using 37% H(3)PO(4) (PA) (15s) or 0.1M EDTA (60s). Five experimental adhesives and one commercial bonding agent were applied to the dentin and light-cured. Solvated experimental resins (50% ethanol/50% comonomers) were used as primers and their respective neat resins were used as the adhesives. The resin-bonded teeth were stored in distilled water (24h) or submitted to 5000 loading cycles of 90N. The bonded teeth were then sectioned in beams for MTBS. Modes of failure were examined by scanning electron microscopy. The most hydrophobic resin 1 gave the lowest bond strength values to both acid and EDTA-treated dentin. The hydrophobic resin 2 applied to EDTA-treated dentin showed lower bond strengths after cycling load but this did not occur when it was bonded to PA-etched dentin. Resins 3 and 4, which contained hydrophilic monomers, gave higher bond strengths to both EDTA-treated or acid-etched dentin and showed no significant difference after load cycling. The most hydrophilic resin 5 showed no significant difference in bond strengths after cycling loading when bonded to EDTA or phosphoric acid treated dentin but exhibited low bond strengths. The presence of different functional monomers influences the MTBS of the adhesive systems when submitted to cyclic loads. Adhesives containing hydrophilic comonomers are not affected by cycling load challenge especially when applied on EDTA-treated dentin followed by ethanol wet bonding. Copyright © 2011 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Resveratrol-loaded glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles: Preparation, characterization, and targeting effect on liver tumors.

PubMed

Wu, Mingfang; Lian, Bolin; Deng, Yiping; Feng, Ziqi; Zhong, Chen; Wu, Weiwei; Huang, Yannian; Wang, Lingling; Zu, Chang; Zhao, Xiuhua

2017-08-01

In this study, glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles were prepared to establish a tumor targeting nano-sized drug delivery system. Glycyrrhizic acid was coupled to human serum albumin, and resveratrol was encapsulated in glycyrrhizic acid-conjugated human serum albumin by high-pressure homogenization emulsification. The average particle size of sample nanoparticles prepared under the optimal conditions was 108.1 ± 5.3 nm with a polydispersity index (PDI) of 0.001, and the amount of glycyrrhizic acid coupled with human serum albumin was 112.56 µg/mg. The drug encapsulation efficiency and drug loading efficiency were 83.6 and 11.5%, respectively. The glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles were characterized through laser light scattering, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analyses, and gas chromatography. The characterization results showed that resveratrol in glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles existed in amorphous state and the residual amounts of chloroform and methanol in nanoparticles were separately less than the international conference on harmonization (ICH) limit. The in vitro drug-release study showed that the nanoparticles released the drug slowly and continuously. The inhibitory rate of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide method. The IC50 values of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles and resveratrol were 62.5 and 95.5 µg/ml, respectively. The target ability of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles

Loads and loads and loads: the influence of prospective load, retrospective load, and ongoing task load in prospective memory.

PubMed

Meier, Beat; Zimmermann, Thomas D

2015-01-01

In prospective memory tasks different kinds of load can occur. Adding a prospective memory task can impose a load on ongoing task performance. Adding ongoing task load (OTL) can affect prospective memory performance. The existence of multiple target events increases prospective load (PL) and adding complexity to the to-be-remembered action increases retrospective load (RL). In two experiments, we systematically examined the effects of these different types of load on prospective memory performance. Results showed an effect of PL on costs in the ongoing task for categorical targets (Experiment 2), but not for specific targets (Experiment 1). RL and OTL both affected remembering the retrospective component of the prospective memory task. We suggest that PL can enhance costs in the ongoing task due to additional monitoring requirements. RL and OTL seem to impact the division of resources between the ongoing task and retrieval of the retrospective component, which may affect disengagement from the ongoing task. In general, the results demonstrate that the different types of load affect prospective memory differentially.

Loads and loads and loads: the influence of prospective load, retrospective load, and ongoing task load in prospective memory

PubMed Central

Meier, Beat; Zimmermann, Thomas D.

2015-01-01

In prospective memory tasks different kinds of load can occur. Adding a prospective memory task can impose a load on ongoing task performance. Adding ongoing task load (OTL) can affect prospective memory performance. The existence of multiple target events increases prospective load (PL) and adding complexity to the to-be-remembered action increases retrospective load (RL). In two experiments, we systematically examined the effects of these different types of load on prospective memory performance. Results showed an effect of PL on costs in the ongoing task for categorical targets (Experiment 2), but not for specific targets (Experiment 1). RL and OTL both affected remembering the retrospective component of the prospective memory task. We suggest that PL can enhance costs in the ongoing task due to additional monitoring requirements. RL and OTL seem to impact the division of resources between the ongoing task and retrieval of the retrospective component, which may affect disengagement from the ongoing task. In general, the results demonstrate that the different types of load affect prospective memory differentially. PMID:26082709

Synthesis, characterization, and evaluation of paclitaxel loaded in six-arm star-shaped poly(lactic-co-glycolic acid)

PubMed Central

Chen, Yongxia; Yang, Ziying; Liu, Chao; Wang, Cuiwei; Zhao, Shunxin; Yang, Jing; Sun, Hongfan; Zhang, Zhengpu; Kong, Deling; Song, Cunxian

2013-01-01

Background Star-shaped polymers provide more terminal groups, and are promising for application in drug-delivery systems. Methods A new series of six-arm star-shaped poly(lactic-co-glycolic acid) (6-s-PLGA) was synthesized by ring-opening polymerization. The structure and properties of the 6-s-PLGA were characterized by carbon-13 nuclear magnetic resonance spectroscopy, infrared spectroscopy, gel permeation chromatography, and differential scanning calorimetry. Then, paclitaxel-loaded six-arm star-shaped poly(lactic-co-glycolic acid) nanoparticles (6-s-PLGA-PTX-NPs) were prepared under the conditions optimized by the orthogonal testing. High-performance liquid chromatography was used to analyze the nanoparticles’ encapsulation efficiency and drug-loading capacity, dynamic light scattering was used to determine their size and size distribution, and transmission electron microscopy was used to evaluate their morphology. The release performance of the 6-s-PLGA-PTX-NPs in vitro and the cytostatic effect of 6-s-PLGA-PTX-NPs were investigated in comparison with paclitaxel-loaded linear poly(lactic-co-glycolic acid) nanoparticles (L-PLGA-PTX-NPs). Results The results of carbon-13 nuclear magnetic resonance spectroscopy and infrared spectroscopy suggest that the polymerization was successfully initiated by inositol and confirm the structure of 6-s-PLGA. The molecular weights of a series of 6-s-PLGAs had a ratio corresponding to the molar ratio of raw materials to initiator. Differential scanning calorimetry revealed that the 6-s-PLGA had a low glass transition temperature of 40°C–50°C. The 6-s-PLGA-PTX-NPs were monodispersed with an average diameter of 240.4±6.9 nm in water, which was further confirmed by transmission electron microscopy. The encapsulation efficiency of the 6-s-PLGA-PTX-NPs was higher than that of the L-PLGA-PTX-NPs. In terms of the in vitro release of nanoparticles, paclitaxel (PTX) was released more slowly and more steadily from 6-s-PLGA than from

Low load, high repetition resistance training program increases bone mineral density in untrained adults.

PubMed

Petersen, Bailey A; Hastings, Bryce; Gottschall, Jinger S

2017-01-01

High load, low repetition resistance training increases BMD in untrained adults; however, many older and untrained adults cannot maintain this type of strenuous program. Our goal was to evaluate whether a low load, high repetition resistance training program would increase BMD in untrained adults. Twenty sedentary, but otherwise healthy, adults (6 men and 14 women, age 28-63 yrs) completed a 27-week group exercise program. The participants were randomly assigned to one of two strength groups: one group completed full body, low load, high repetition weight training classes (S-WEIGHT), while the other group completed core focused fusion classes (S-CORE). Both groups also completed indoor cycling classes for cardiovascular conditioning. After a 3-week familiarization period, all participants completed a 12-week block of 5 fitness classes per week (3 cycling + 2 strength) and concluded with another 12-week block of 6 classes per week (3 cycling + 3 strength). We completed iDXA scans at baseline (week 3) and final (week 28). Compared to baseline, BMD significantly increased for S-WEIGHT in the arms (+4%, P<0.001), legs (+8%, P<0.01), pelvis (+6%, P<0.01) and lumbar spine (+4%, P<0.05), whereas BMD did not significantly change for S-CORE at any site. These results suggest that a low load, high repetition resistance training program may be an effective method to improve bone mass in adults.

Dietary salt loading increases nitric oxide synthesis in transgenic mice overexpressing sodium-proton exchanger.

PubMed

Kiraku, J; Nakamura, T; Sugiyama, T; Takahashi, N; Kuro-o, M; Fujii, J; Nagai, R

1999-06-01

We studied the role of nitric oxide (NO) synthesis in amelioration of blood pressure elevation during dietary salt loading in transgenic mice overexpressing sodium proton exchanger. Systolic blood pressure rose after starting salt loading only in the high-salt group of transgenic mice. However, this elevation of blood pressure was not continued. Urinary excretion of inorganic nitrite and nitrate in the high-salt group of transgenic mice was significantly higher than in the high-salt group of control mice. These results suggest that increased NO synthesis in response to salt loading is one of the anti-hypertensive mechanisms in transgenic mice overexpressing sodium proton exchanger.

Chitosan-functionalised poly(2-hydroxyethyl methacrylate) core-shell microgels as drug delivery carriers: salicylic acid loading and release.

PubMed

Mahattanadul, Natshisa; Sunintaboon, Panya; Sirithip, Piyawan; Tuchinda, Patoomratana

2016-09-01

This work presents the evaluation of chitosan-functionalised poly(2-hydroxyethyl methacrylate) (CS/PHEMA) core-shell microgels as drug delivery carriers. CS/PHEMA microgels were prepared by emulsifier-free emulsion polymerisation with N,N '-methylenebisacrylamide (MBA) as a crosslinker. The study on drug loading, using salicylic acid (SA) as a model drug, was performed. The results showed that the encapsulation efficiency (EE) increased as drug-to-microgel ratio was increased. Higher EE can be achieved with the increase in degree of crosslinking, by increasing the amount of MBA from 0.01 g to 0.03 g. In addition, the highest EE (61.1%) was observed at pH 3. The highest release of SA (60%) was noticed at pH 2.4, while the lowest one (49.4%) was obtained at pH 7.4. Moreover, the highest release of SA was enhanced by the presence of 0.2 M NaCl. The pH- and ionic-sensitivity of CS/PHEMA could be useful as a sustained release delivery device, especially for oral delivery.

Persistence of Escherichia coli O157:H7 during pilot-scale processing of iceberg lettuce using flume water containing peroxyacetic acid-based sanitizers and various organic loads.

PubMed

Davidson, Gordon R; Kaminski-Davidson, Chelsea N; Ryser, Elliot T

2017-05-02

In order to minimize cross-contamination during leafy green processing, chemical sanitizers are routinely added to the wash water. This study assessed the efficacy of peroxyacetic acid and mixed peracid against E. coli O157:H7 on iceberg lettuce, in wash water, and on equipment during simulated commercial production in a pilot-scale processing line using flume water containing various organic loads. Iceberg lettuce (5.4kg) inoculated to contain 10 6 CFU/g of a 4-strain cocktail of non-toxigenic, GFP-labeled, ampicillin-resistant E. coli O157:H7, was shredded using a commercial shredder, step-conveyed to a flume tank, washed for 90s using water alone or two different sanitizing treatments (50ppm peroxyacetic acid or mixed peracid) in water containing organic loads of 0, 2.5, 5 or 10% (w/v) blended iceberg lettuce, and then dried using a shaker table and centrifugal dryer. Thereafter, three 5.4-kg batches of uninoculated iceberg lettuce were identically processed. Various product (25g) and water (50ml) samples collected during processing along with equipment surface samples (100cm 2 ) from the flume tank, shaker table and centrifugal dryer were then assessed for numbers of E. coli O157:H7. Organic load rarely impacted (P>0.05) the efficacy of either peroxyacetic acid or mixed peracid, with typical reductions of >5logCFU/ml in wash water throughout processing for all organic loads. Increases in organic load in the wash water corresponded to changes in total solids, chemical oxygen demand, turbidity, maximum filterable volume, and oxidation/reduction potential. After 90s of exposure to flume water, E. coli O157:H7 reductions on inoculated lettuce ranged from 0.97 to 1.74logCFU/g using peroxyacetic acid, with an average reduction of 1.35logCFU/g for mixed peracid. E. coli O157:H7 persisted on all previously uninoculated lettuce following the inoculated batch, emphasizing the need for improved intervention strategies that can better ensure end-product safety. Copyright �

Novel Simvastatin-Loaded Nanoparticles Based on Cholic Acid-Core Star-Shaped PLGA for Breast Cancer Treatment.

PubMed

Wu, Yanping; Wang, Zhongyuan; Liu, Gan; Zeng, Xiaowei; Wang, Xusheng; Gao, Yongfeng; Jiang, Lijuan; Shi, Xiaojun; Tao, Wei; Huang, Laiqiang; Mei, Lin

2015-07-01

A novel nanocarrier system of cholic acid (CA) core, star-shaped polymer consisting of poly(D,L-lactide-co-glycolide) (PLGA) was developed for sustained and controlled delivery of simvastatin for chemotherapy of breast adenocarcinoma. The star-shaped polymer CA-PLGA with three branch arms was synthesized successfully through the core-first approach. The simvastatin-loaded star-shaped CA-PLGA nanoparticles were prepared through a modified nanoprecipitation method. The data showed that the fluorescence star-shaped CA-PLGA nanoparticles could be internalized into MDA-MB-231 and MDA-MB-468 human breast cancer cells. The simvastatin-loaded star-shaped CA-PLGA nanoparticles achieved significantly higher level of cytotoxicity than pristine simvastatin and simvastatin-loaded linear PLGA nanoparticles. Moreover, the expression of the cell cycle protein cyclin D1 was dramatically inhibited by simvastatin in both cells, with simvastatin-loaded star-shaped CA-PLGA nanoparticles having the greatest effect. MDA-MB-231 xenograft tumor model on BALB/c nude mice showed that simvastatin-loaded star-shaped CA-PLGA nanoformulations could effectively inhibit the growth of tumor over a longer period of time than pristine simvastatin and simvastatin-loaded linear PLGA nanoformulations at the same dose. In agreement with these, the nuclear expression of proliferation marker Ki-67 in simvastatin-loaded star-shaped CA-PLGA nanoparticles group was reduced to a most extent among four groups through tumor frozen section immunohistochemistry. In conclusion, the star-shaped CA-PLGA polymers could serve as a novel polymeric nanocarrier for breast cancer chemotherapy.

Paradoxical low-flow aortic stenosis is defined by increased ventricular hydraulic load and reduced longitudinal strain.

PubMed

Holmes, Anthony A; Taub, Cynthia C; Garcia, Mario J; Shan, Jian; Slovut, David P

2017-02-01

Patients with paradoxical low-flow severe aortic stenosis (PLF-AS) reportedly have higher left ventricular hydraulic load and more systolic strain dysfunction than patients with normal-flow aortic stenosis. This study investigates the relationship of systolic loading and strain to PLF-AS to further define its pathophysiology. One hundred and twenty patients (age 79 ± 12 years, 37% men) with an indexed aortic valve area (AVAi) of 0.6 cm/m or less and an ejection fraction of 50% or higher were divided into two groups based on indexed stroke volume (SVi): PLF-AS, SVi ≤ 35 ml/m, N = 46; normal-flow aortic stenosis, SVi > 35 ml/m, N = 74). Valvular and arterial load were assessed using multiple measurements, and strain was assessed using speckle-tracking echocardiography. Patients with PLF-AS were found to have more valvular load (lower AVAi, P = 0.028; lower energy loss coefficient, P = 0.001), more arterial load [decreased arterial compliance and increased systemic vascular resistance (SVR), both P < 0.001] and more total hydraulic load [increased valvuloarterial impedance (Zva), P < 0.001]. Transvalvular gradients and arterial pressures were similar. Longitudinal strain was lower in PLF-AS (P < 0.001), but circumferential and rotation strains were similar. On adjusted regression, AVAi, SVR and longitudinal strain were associated with PLF-AS [odds ratio (OR) = 1.34, P = 0.043; OR = 1.31, P = 0.004; OR = 1.34, P = 0.011, respectively]. When SVR and AVAi were replaced with Zva, longitudinal strain and Zva (OR = 1.38, P = 0.015; OR = 1.33, P < 0.001 for both, respectively) were associated with PLF-AS. Increased hydraulic load, from more severe valvular stenosis and increased vascular resistance, and longitudinal strain impairment are associated with PLF-AS and their interplay is likely fundamental to its pathophysiology.

The effects of biodegradable poly(lactic-co-glycolic acid)-based microspheres loaded with quercetin on stemness, viability and osteogenic differentiation potential of stem cell spheroids.

PubMed

Lee, H; Nguyen, T T; Kim, M; Jeong, J-H; Park, J-B

2018-05-31

Quercetin has been reported to exert many beneficial effects on the protection against various diseases, such as diabetes, cancer, and inflammation. The aim of this study is to evaluate the potential osteogenic differentiation ability of mesenchymal stem cells in the presence of quercetin. Quercetin-loaded poly(lactic-co-glycolic acid) microspheres were prepared using an electrospraying technique. Characterization of the microspheres was evaluated with a scanning electron microscope and release profile. Three-dimensional cell spheroids were fabricated using silicon elastomer-based concave microwells. Qualitative results of cellular viability were seen under a confocal microscope, and quantitative cellular viability was evaluated using the Cell Counting Kit-8 assay. The alkaline phosphatase activity and Alizarin Red S staining were performed. A quantitative real-time polymerase chain reaction and a western blot analysis were performed. Spheroids were well formed irrespective of quercetin concentration. Most of the cells in spheroids emitted green fluorescence, and the morphology was round without significant changes. The application of quercetin-loaded microspheres produced a significant increase in the alkaline phosphatase activity. The real-time polymerase chain reaction results showed a significant increase in Runx2, and western blot results showed higher expression of Runx2 protein expression. Biodegradable microspheres loaded with quercetin produced prolonged release profiles with increased mineralization. Microspheres loaded with quercetin can be used for the enhancement of osteoblastic differentiation in cell therapy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Increased plasma d-lactic acid associated with impaired memory in rats.

PubMed

Hanstock, T L; Mallet, P E; Clayton, E H

2010-12-02

d-Lactic acidosis is associated with memory impairment in humans. Recent research indicates that d-lactic acid may inhibit the supply of energy from astrocytes to neurons involved with memory formation. However, little is known about the effects of increased hind-gut fermentation due to changes in diet on circulating lactic acid concentrations and memory. Thirty-six male Wistar rats were fed three dietary treatments: a commercial rat and mouse chow, a soluble carbohydrate based diet or a fermentable carbohydrate based diet. The parameters estimating memory were examined by employing the object recognition test. Physical parameters of fermentation including hind-gut and plasma lactic acid concentrations were examined after sacrifice, either 3 or 21h after feeding. Increased fermentation in the hind-gut of rats, indicated by lower caecum pH, was associated with increased plasma l-lactic acid (r=-0.41, p=0.020) and d-lactic acid (r=-0.33, p=0.087). Memory, being able to discriminate between a familiar and a novel object during the object recognition test, was reduced with increasing plasma d-lactic acid (r=-0.51, p=0.021). Memory impairment was associated with alterations in plasma d-lactic acid following the fermentation of carbohydrate in the hind-gut. Further work is still required to determine whether these effects are mediated centrally or via direct connections through the enteric nervous system. Copyright © 2010 Elsevier Inc. All rights reserved.

Sex-based differences in lifting technique under increasing load conditions: A principal component analysis.

PubMed

Sheppard, P S; Stevenson, J M; Graham, R B

2016-05-01

The objective of the present study was to determine if there is a sex-based difference in lifting technique across increasing-load conditions. Eleven male and 14 female participants (n = 25) with no previous history of low back disorder participated in the study. Participants completed freestyle, symmetric lifts of a box with handles from the floor to a table positioned at 50% of their height for five trials under three load conditions (10%, 20%, and 30% of their individual maximum isometric back strength). Joint kinematic data for the ankle, knee, hip, and lumbar and thoracic spine were collected using a two-camera Optotrak motion capture system. Joint angles were calculated using a three-dimensional Euler rotation sequence. Principal component analysis (PCA) and single component reconstruction were applied to assess differences in lifting technique across the entire waveforms. Thirty-two PCs were retained from the five joints and three axes in accordance with the 90% trace criterion. Repeated-measures ANOVA with a mixed design revealed no significant effect of sex for any of the PCs. This is contrary to previous research that used discrete points on the lifting curve to analyze sex-based differences, but agrees with more recent research using more complex analysis techniques. There was a significant effect of load on lifting technique for five PCs of the lower limb (PC1 of ankle flexion, knee flexion, and knee adduction, as well as PC2 and PC3 of hip flexion) (p < 0.005). However, there was no significant effect of load on the thoracic and lumbar spine. It was concluded that when load is standardized to individual back strength characteristics, males and females adopted a similar lifting technique. In addition, as load increased male and female participants changed their lifting technique in a similar manner. Copyright © 2016. Published by Elsevier Ltd.

Performance and stability of an expanded granular sludge bed reactor modified with zeolite addition subjected to step increases of organic loading rate (OLR) and to organic shock load (OSL).

PubMed

Pérez-Pérez, T; Pereda-Reyes, I; Pozzi, E; Oliva-Merencio, D; Zaiat, M

2018-01-01

This paper shows the effect of organic shock loads (OSLs) on the anaerobic digestion (AD) of synthetic swine wastewater using an expanded granular sludge bed (EGSB) reactor modified with zeolite. Two reactors (R1 and R2), each with an effective volume of 3.04 L, were operated for 180 days at a controlled temperature of 30 °C and hydraulic retention time of 12 h. In the case of R2, 120 g of zeolite was added. The reactors were operated with an up-flow velocity of 6 m/h. The evolution of pH, total Kjeldahl nitrogen, chemical oxygen demand (COD) and volatile fatty acids (VFAs) was monitored during the AD process with OSL and increases in the organic loading rate (OLR). In addition, the microbial composition and changes in the structure of the bacterial and archaeal communities were assessed. The principal results demonstrate that the presence of zeolite in an EGSB reactor provides a more stable process at higher OLRs and after applying OSL, based on both COD and VFA accumulation, which presented with significant differences compared to the control. Denaturing gradient gel electrophoresis band profiles indicated differences in the populations of Bacteria and Archaea between the R1 and R2 reactors, attributed to the presence of zeolite.

Humic Acid Complexation of Th, Hf and Zr in Ligand Competition Experiments: Metal Loading and Ph Effects

NASA Technical Reports Server (NTRS)

Stern, Jennifer C.; Foustoukos, Dionysis I.; Sonke, Jeroen E.; Salters, Vincent J. M.

2014-01-01

The mobility of metals in soils and subsurface aquifers is strongly affected by sorption and complexation with dissolved organic matter, oxyhydroxides, clay minerals, and inorganic ligands. Humic substances (HS) are organic macromolecules with functional groups that have a strong affinity for binding metals, such as actinides. Thorium, often studied as an analog for tetravalent actinides, has also been shown to strongly associate with dissolved and colloidal HS in natural waters. The effects of HS on the mobilization dynamics of actinides are of particular interest in risk assessment of nuclear waste repositories. Here, we present conditional equilibrium binding constants (Kc, MHA) of thorium, hafnium, and zirconium-humic acid complexes from ligand competition experiments using capillary electrophoresis coupled with ICP-MS (CE- ICP-MS). Equilibrium dialysis ligand exchange (EDLE) experiments using size exclusion via a 1000 Damembrane were also performed to validate the CE-ICP-MS analysis. Experiments were performed at pH 3.5-7 with solutions containing one tetravalent metal (Th, Hf, or Zr), Elliot soil humic acid (EHA) or Pahokee peat humic acid (PHA), and EDTA. CE-ICP-MS and EDLE experiments yielded nearly identical binding constants for the metal- humic acid complexes, indicating that both methods are appropriate for examining metal speciation at conditions lower than neutral pH. We find that tetravalent metals form strong complexes with humic acids, with Kc, MHA several orders of magnitude above REE-humic complexes. Experiments were conducted at a range of dissolved HA concentrations to examine the effect of [HA]/[Th] molar ratio on Kc, MHA. At low metal loading conditions (i.e. elevated [HA]/[Th] ratios) the ThHA binding constant reached values that were not affected by the relative abundance of humic acid and thorium. The importance of [HA]/[Th] molar ratios on constraining the equilibrium of MHA complexation is apparent when our estimated Kc, MHA values

H. pylori in the pathogenesis of duodenal ulcer: interaction between duodenal acid load, bile, and H. pylori.

PubMed

Graham, D Y; Osato, M S

2000-01-01

Helicobacter pylori (H. pylori) growth is inhibited by bile yet it can grow in the duodenal bulb and cause ulcer disease. The aim of this study was to test the effect of bile on H. pylori viability and growth and to determine whether acidification of bile reduces its inhibitory activity. Fresh human bile was collected at laparotomy and tested for inhibitory activity of H. pylori using broth dilution assays. Six clinical isolates of H. pylori obtained from patients with duodenal ulcer were used for each experiment. The bile was diluted from 1:3 to 1:192; its inhibitory effect on H. pylori was tested before and after acidification, treatment with cholestyramine, or chloroform. Bile was acidified to a pH of 2-6, centrifuged at 8000 rpm for 20 min to remove precipitated bile acids, and the supernatant pH readjusted. Controls included BHI broth without bile (positive control) and bile that was acidified to pH 2 and neutralized without centrifugation. Human bile inhibited H. pylori growth in a dose dependent manner. Growth of all strains was supported for all strains only at a dilution of 1:192. In contrast, after acidification to pH < or =5 and centrifugation to remove precipitated bile acids, all strains grew at a bile dilution of 1:12. Neither chloroform extraction of lipids, nor acidification without centrifugation removed the inhibitory action of bile. In contrast, cholestyramine sequestration of bile acids completely removed all inhibitory activity. The duodenal acid load may be the critical factor to explain the ability of H. pylori to colonize the duodenal bulb by precipitating glycine-conjugated bile salts. The combination of a high duodenal acid load and H. pylori infection is likely the critical event in the pathogenesis of H. pylori-related duodenal ulcer disease.

Critical Loads of Acid Deposition for Wilderness Lakes in the Sierra Nevada (California) Estimated by the Steady-State Water Chemistry Model

Treesearch

Glenn D. Shaw; Ricardo Cisneros; Donald Schweizer; James O. Sickman; Mark E. Fenn

2014-01-01

Major ion chemistry (2000-2009) from 208 lakes (342 sample dates and 600 samples) in class I and II wilderness areas of the Sierra Nevada was used in the Steady-State Water Chemistry (SSWC) model to estimate critical loads for acid deposition and investigate the current vulnerability of high elevation lakes to acid deposition. The majority of the lakes were dilute (...

Dietary Protein and Potassium, Diet-Dependent Net Acid Load, and Risk of Incident Kidney Stones.

PubMed

Ferraro, Pietro Manuel; Mandel, Ernest I; Curhan, Gary C; Gambaro, Giovanni; Taylor, Eric N

2016-10-07

Protein and potassium intake and the resulting diet-dependent net acid load may affect kidney stone formation. It is not known whether protein type or net acid load is associated with risk of kidney stones. We prospectively examined intakes of protein (dairy, nondairy animal, and vegetable), potassium, and animal protein-to-potassium ratio (an estimate of net acid load) and risk of incident kidney stones in the Health Professionals Follow-Up Study ( n =42,919), the Nurses' Health Study I ( n =60,128), and the Nurses' Health Study II ( n =90,629). Multivariable models were adjusted for age, body mass index, diet, and other factors. We also analyzed cross-sectional associations with 24-hour urine ( n =6129). During 3,108,264 person-years of follow-up, there were 6308 incident kidney stones. Dairy protein was associated with lower risk in the Nurses' Health Study II (hazard ratio for highest versus lowest quintile, 0.84; 95% confidence interval, 0.73 to 0.96; P value for trend <0.01). The hazard ratios for nondairy animal protein were 1.15 (95% confidence interval, 0.97 to 1.36; P value for trend =0.04) in the Health Professionals Follow-Up Study and 1.20 (95% confidence interval, 0.99 to 1.46; P value for trend =0.06) in the Nurses' Health Study I. Potassium intake was associated with lower risk in all three cohorts (hazard ratios from 0.44 [95% confidence interval, 0.36 to 0.53] to 0.67 [95% confidence interval, 0.57 to 0.78]; P values for trend <0.001). Animal protein-to-potassium ratio was associated with higher risk ( P value for trend =0.004), even after adjustment for animal protein and potassium. Higher dietary potassium was associated with higher urine citrate, pH, and volume ( P values for trend <0.002). Kidney stone risk may vary by protein type. Diets high in potassium or with a relative abundance of potassium compared with animal protein could represent a means of stone prevention. Copyright © 2016 by the American Society of Nephrology.

Dietary Protein and Potassium, Diet–Dependent Net Acid Load, and Risk of Incident Kidney Stones

PubMed Central

Mandel, Ernest I.; Curhan, Gary C.; Gambaro, Giovanni; Taylor, Eric N.

2016-01-01

Background and objectives Protein and potassium intake and the resulting diet–dependent net acid load may affect kidney stone formation. It is not known whether protein type or net acid load is associated with risk of kidney stones. Design, setting, participants, & measurements We prospectively examined intakes of protein (dairy, nondairy animal, and vegetable), potassium, and animal protein-to-potassium ratio (an estimate of net acid load) and risk of incident kidney stones in the Health Professionals Follow-Up Study (n=42,919), the Nurses’ Health Study I (n=60,128), and the Nurses’ Health Study II (n=90,629). Multivariable models were adjusted for age, body mass index, diet, and other factors. We also analyzed cross-sectional associations with 24-hour urine (n=6129). Results During 3,108,264 person-years of follow-up, there were 6308 incident kidney stones. Dairy protein was associated with lower risk in the Nurses’ Health Study II (hazard ratio for highest versus lowest quintile, 0.84; 95% confidence interval, 0.73 to 0.96; P value for trend <0.01). The hazard ratios for nondairy animal protein were 1.15 (95% confidence interval, 0.97 to 1.36; P value for trend =0.04) in the Health Professionals Follow-Up Study and 1.20 (95% confidence interval, 0.99 to 1.46; P value for trend =0.06) in the Nurses’ Health Study I. Potassium intake was associated with lower risk in all three cohorts (hazard ratios from 0.44 [95% confidence interval, 0.36 to 0.53] to 0.67 [95% confidence interval, 0.57 to 0.78]; P values for trend <0.001). Animal protein-to-potassium ratio was associated with higher risk (P value for trend =0.004), even after adjustment for animal protein and potassium. Higher dietary potassium was associated with higher urine citrate, pH, and volume (P values for trend <0.002). Conclusions Kidney stone risk may vary by protein type. Diets high in potassium or with a relative abundance of potassium compared with animal protein could represent a means of

Fatty acids increase neuronal hypertrophy of Pten knockdown neurons

PubMed Central

Fricano, Catherine J.; DeSpenza, Tyrone; Frazel, Paul W.; Li, Meijie; O'Malley, A. James; Westbrook, Gary L.; Luikart, Bryan W.

2014-01-01

Phosphatase and tensin homolog (Pten) catalyzes the reverse reaction of PI3K by dephosphorylating PIP3 to PIP2. This negatively regulates downstream Akt/mTOR/S6 signaling resulting in decreased cellular growth and proliferation. Co-injection of a lentivirus knocking Pten down with a control lentivirus allows us to compare the effects of Pten knockdown between individual neurons within the same animal. We find that knockdown of Pten results in neuronal hypertrophy by 21 days post-injection. This neuronal hypertrophy is correlated with increased p-S6 and p-mTOR in individual neurons. We used this system to test whether an environmental factor that has been implicated in cellular hypertrophy could influence the severity of the Pten knockdown-induced hypertrophy. Implantation of mini-osmotic pumps delivering fatty acids results in increased neuronal hypertrophy and p-S6/p-mTOR staining. These hypertrophic effects were reversed in response to rapamycin treatment. However, we did not observe a similar increase in hypertrophy in response to dietary manipulations of fatty acids. Thus, we conclude that by driving growth signaling with fatty acids and knocking down a critical regulator of growth, Pten, we are able to observe an additive morphological phenotype of increased soma size mediated by the mTOR pathway. PMID:24795563

Increased supraspinatus tendon thickness following fatigue loading in rotator cuff tendinopathy: potential implications for exercise therapy.

PubMed

McCreesh, Karen M; Purtill, Helen; Donnelly, Alan E; Lewis, Jeremy S

2017-01-01

Exercise imparts a load on tendon tissue that leads to changes in tendon properties. Studies suggest that loading immediately reduces tendon thickness, with a loss of this response in symptomatic tendinopathy. No studies investigating the response of tendon dimensions to load for the rotator cuff tendons exist. This study aimed to examine the short-term effect of loading on the thickness of the supraspinatus tendon and acromiohumeral distance those with and without rotator cuff tendinopathy. Participants were 20 painfree controls, and 23 people with painful rotator cuff tendinopathy. Supraspinatus tendon thickness and acromiohumeral distance were measured using ultrasound scans before, and at three time points after loading (1, 6 and 24 hours). Loading involved isokinetic eccentric and concentric external rotation and abduction. There was a significant increase in supraspinatus tendon thickness in the pain group at 1 (7%, ∆=0.38, 95% CI 0.19 to 0.57) and 6 hours (11%, ∆=0.53, 95% CI 0.34 to 0.71), although only the 6 hours difference exceeded minimal detectable difference. In contrast, there was a small non-significant reduction in thickness in controls. The acromiohumeral distance reduced significantly in both groups at 1 hour (controls: ∆=0.64, 95% CI 0.38 to 0.90; pain: ∆=1.1, 95% CI 0.85 to 1.33), with a larger change from baseline in the pain group. Those diagnosed with painful supraspinatus tendinopathy demonstrated increased thickening with delayed return to baseline following loading. Rehabilitation professionals may need to take into account the impact of loading to fatigue when planning rehabilitation programmes.

Increased supraspinatus tendon thickness following fatigue loading in rotator cuff tendinopathy: potential implications for exercise therapy

PubMed Central

McCreesh, Karen M; Purtill, Helen; Donnelly, Alan E; Lewis, Jeremy S

2017-01-01

Background/aim Exercise imparts a load on tendon tissue that leads to changes in tendon properties. Studies suggest that loading immediately reduces tendon thickness, with a loss of this response in symptomatic tendinopathy. No studies investigating the response of tendon dimensions to load for the rotator cuff tendons exist. This study aimed to examine the short-term effect of loading on the thickness of the supraspinatus tendon and acromiohumeral distance those with and without rotator cuff tendinopathy. Methods Participants were 20 painfree controls, and 23 people with painful rotator cuff tendinopathy. Supraspinatus tendon thickness and acromiohumeral distance were measured using ultrasound scans before, and at three time points after loading (1, 6 and 24 hours). Loading involved isokinetic eccentric and concentric external rotation and abduction. Results There was a significant increase in supraspinatus tendon thickness in the pain group at 1 (7%, ∆=0.38, 95% CI 0.19 to 0.57) and 6 hours (11%, ∆=0.53, 95% CI 0.34 to 0.71), although only the 6 hours difference exceeded minimal detectable difference. In contrast, there was a small non-significant reduction in thickness in controls. The acromiohumeral distance reduced significantly in both groups at 1 hour (controls: ∆=0.64, 95% CI 0.38 to 0.90; pain: ∆=1.1, 95% CI 0.85 to 1.33), with a larger change from baseline in the pain group. Conclusion Those diagnosed with painful supraspinatus tendinopathy demonstrated increased thickening with delayed return to baseline following loading. Rehabilitation professionals may need to take into account the impact of loading to fatigue when planning rehabilitation programmes. PMID:29333279

Electrospinning of curcumin loaded chitosan/poly (lactic acid) nanofilm and evaluation of its medicinal characteristics

NASA Astrophysics Data System (ADS)

Dhurai, Bhaarathi; Saraswathy, Nachimuthu; Maheswaran, Ramasamy; Sethupathi, Ponnusamy; Vanitha, Palanisamy; Vigneshwaran, Sukumar; Rameshbabu, Venugopal

2013-12-01

The curcumin loaded chitosan/poly (lactic acid) (PLA) nanofibers were produced using electrospinning. Box—Behnken experimental design was used for the optimization of variables (-1, 0, + 1 coded level) like chitosan/PLA strength (% w/v), curcumin strength (% w/v) and applied voltage (kV) to obtain uniform fiber diameter. The morphology of nanofibers was shown by SEM. Molecular interactions and the presence of each chemical compound of curcumin loaded chitosan/PLA fibers were characterized by FTIR and EDX analysis. Antioxidant, drug release and in vitro cytotoxicity tests were performed to evaluate the suitability of nanofibers that would be used for wound healing. In vivo wound healing studies on excision and incision wounds created on rat model showed significant reduction of wound area when compared to untreated. The better healing efficiency can be attributed to the presence of curcumin and chitosan.

Towards increased waste loading in high level waste glasses: Developing a better understanding of crystallization behavior

DOE PAGES

Marra, James C.; Kim, Dong -Sang

2014-12-18

A number of waste components in US defense high level radioactive wastes (HLW) have proven challenging for current Joule heated ceramic melter (JCHM) operations and have limited the ability to increase waste loadings beyond already realized levels. Many of these ''troublesome'' waste species cause crystallization in the glass melt that can negatively impact product quality or have a deleterious effect on melter processing. Thus, recent efforts at US Department of Energy laboratories have focused on understanding crystallization behavior within HLW glass melts and investigating approaches to mitigate the impacts of crystallization so that increases in waste loading can be realized.more » Advanced glass formulations have been developed to highlight the unique benefits of next-generation melter technologies such as the Cold Crucible Induction Melter (CCIM). Crystal-tolerant HLW glasses have been investigated to allow sparingly soluble components such as chromium to crystallize in the melter but pass out of the melter before accumulating. The Hanford site AZ-101 tank waste composition represents a waste group that is waste loading limited primarily due to high concentrations of Fe 2O 3 (with higher Al 2O 3). Systematic glass formulation development utilizing slightly higher process temperatures and higher tolerance to spinel crystals demonstrated that an increase in waste loading of more than 20% could be achieved for this waste composition, and by extension higher loadings for wastes in the same group.« less

Acute supplementation of amino acids increases net protein accretion in IUGR fetal sheep

PubMed Central

Rozance, Paul J.; Thorn, Stephanie R.; Friedman, Jacob E.; Hay, William W.

2012-01-01

Placental insufficiency decreases fetal amino acid uptake from the placenta, plasma insulin concentrations, and protein accretion, thus compromising normal fetal growth trajectory. We tested whether acute supplementation of amino acids or insulin into the fetus with intrauterine growth restriction (IUGR) would increase net fetal protein accretion rates. Late-gestation IUGR and control (CON) fetal sheep received acute, 3-h infusions of amino acids (with euinsulinemia), insulin (with euglycemia and euaminoacidemia), or saline. Fetal leucine metabolism was measured under steady-state conditions followed by a fetal muscle biopsy to quantify insulin signaling. In CON, increasing amino acid delivery rates to the fetus by 100% increased leucine oxidation rates by 100%. In IUGR, amino acid infusion completely suppressed fetal protein breakdown rates but increased leucine oxidation rate by only 25%, resulting in increased protein accretion rates by 150%. Acute insulin infusion, however, had very little effect on amino acid delivery rates, fetal leucine disposal rates, or fetal protein accretion rates in CON or IUGR fetuses despite robust signaling of the fetal skeletal muscle insulin-signaling cascade. These results indicate that, when amino acids are given directly into the fetal circulation independently of changes in insulin concentrations, IUGR fetal sheep have suppressed protein breakdown rates, thus increasing net fetal protein accretion. PMID:22649066

High Working Memory Load Increases Intracortical Inhibition in Primary Motor Cortex and Diminishes the Motor Affordance Effect.

PubMed

Freeman, Scott M; Itthipuripat, Sirawaj; Aron, Adam R

2016-05-18

Motor affordances occur when the visual properties of an object elicit behaviorally relevant motor representations. Typically, motor affordances only produce subtle effects on response time or on motor activity indexed by neuroimaging/neuroelectrophysiology, but sometimes they can trigger action itself. This is apparent in "utilization behavior," where individuals with frontal cortex damage inappropriately grasp affording objects. This raises the possibility that, in healthy-functioning individuals, frontal cortex helps ensure that irrelevant affordance provocations remain below the threshold for actual movement. In Experiment 1, we tested this "frontal control" hypothesis by "loading" the frontal cortex with an effortful working memory (WM) task (which ostensibly consumes frontal resources) and examined whether this increased EEG measures of motor affordances to irrelevant affording objects. Under low WM load, there were typical motor affordance signatures: an event-related desynchronization in the mu frequency and an increased P300 amplitude for affording (vs nonaffording) objects over centroparietal electrodes. Contrary to our prediction, however, these affordance measures were diminished under high WM load. In Experiment 2, we tested competing mechanisms responsible for the diminished affordance in Experiment 1. We used paired-pulse transcranial magnetic stimulation over primary motor cortex to measure long-interval cortical inhibition. We found greater long-interval cortical inhibition for high versus low load both before and after the affording object, suggesting that a tonic inhibition state in primary motor cortex could prevent the affordance from provoking the motor system. Overall, our results suggest that a high WM load "sets" the motor system into a suppressed state that mitigates motor affordances. Is an irrelevant motor affordance more likely to be triggered when you are under low or high cognitive load? We examined this using physiological measures

Target loads of atmospheric sulfur and nitrogen deposition for protection of acid sensitive aquatic resources in the Adirondack Mountains, New York

USGS Publications Warehouse

Sullivan, T.J.; Cosby, B.J.; Driscoll, C.T.; McDonnell, T.C.; Herlihy, A.T.; Burns, Douglas A.

2012-01-01

The dynamic watershed acid-base chemistry model of acidification of groundwater in catchments (MAGIC) was used to calculate target loads (TLs) of atmospheric sulfur and nitrogen deposition expected to be protective of aquatic health in lakes in the Adirondack ecoregion of New York. The TLs were calculated for two future dates (2050 and 2100) and three levels of protection against lake acidification (acid neutralizing capacity (ANC) of 0, 20, and 50 eq L -1). Regional sulfur and nitrogen deposition estimates were combined with TLs to calculate exceedances. Target load results, and associated exceedances, were extrapolated to the regional population of Adirondack lakes. About 30% of Adirondack lakes had simulated TL of sulfur deposition less than 50 meq m -2 yr to protect lake ANC to 50 eq L -1. About 600 Adirondack lakes receive ambient sulfur deposition that is above this TL, in some cases by more than a factor of 2. Some critical criteria threshold values were simulated to be unobtainable in some lakes even if sulfur deposition was to be decreased to zero and held at zero until the specified endpoint year. We also summarize important lessons for the use of target loads in the management of acid-impacted aquatic ecosystems, such as those in North America, Europe, and Asia. Copyright 2012 by the American Geophysical Union.

Improved Monitoring of Semi-Continuous Anaerobic Digestion of Sugarcane Waste: Effects of Increasing Organic Loading Rate on Methanogenic Community Dynamics

PubMed Central

Leite, Athaydes Francisco; Janke, Leandro; Lv, Zuopeng; Harms, Hauke; Richnow, Hans-Hermann; Nikolausz, Marcell

2015-01-01

The anaerobic digestion of filter cake and its co-digestion with bagasse, and the effect of gradual increase of the organic loading rate (OLR) from start-up to overload were investigated. Understanding the influence of environmental and technical parameters on the development of particular methanogenic pathway in the biogas process was an important aim for the prediction and prevention of process failure. The rapid accumulation of volatile organic acids at high OLR of 3.0 to 4.0 gvs·L−1·day−1 indicated strong process inhibition. Methanogenic community dynamics of the reactors was monitored by stable isotope composition of biogas and molecular biological analysis. A potential shift toward the aceticlastic methanogenesis was observed along with the OLR increase under stable reactor operating conditions. Reactor overloading and process failure were indicated by the tendency to return to a predominance of hydrogenotrophic methanogenesis with rising abundances of the orders Methanobacteriales and Methanomicrobiales and drop of the genus Methanosarcina abundance. PMID:26404240

Enhanced anti-cancer efficacy to cancer cells by doxorubicin loaded water-soluble amino acid-modified β-cyclodextrin platinum complexes.

PubMed

Zhao, Mei-Xia; Zhao, Meng; Zeng, Er-Zao; Li, Yang; Li, Jin-Ming; Cao, Qian; Tan, Cai-Ping; Ji, Liang-Nian; Mao, Zong-Wan

2014-08-01

The effective targeted delivery of insoluble anticancer drugs to increase the intracellular drug concentration has become a focus in cancer therapy. In this system, two water-soluble amino acid-modified β-cyclodextrin (β-CD) platinum complexes were reported. They showed preferable binding ability to DNA and effective inhibition to cancer cells, and they could bind and unwind pBR322 DNA in a manner which was similar to cisplatin. Besides, our platinum complexes could effectively deliver the anticancer drug doxorubicin (Dox) into cells and had higher cell inhibition ratio, but less toxicity on the normal cells, compared with cancer cells. In this combination system, Dox was encapsulated into the hydrophobic cavities of β-CD at the optimum molar ratio of 1:1, which were validated by UV-visible (UV-vis) absorption spectroscopy, fluorescence spectroscopy and MTT experiments. Moreover, the combination system had higher cell inhibition ratio than free Dox and amino acid-modified β-CD platinum complexes, and the results of high content screening (HCS) showed that Dox-loaded amino acid-modified β-CD platinum complexes could permeate the cell membrane and enter cells, suggesting the efficient transport of Dox across the membranes with the aid of the β-CD. We expect that the amino acid-modified β-CD platinum complexes will deliver the antitumor drug Dox to enhance intracellular drug accumulation and such combination system showed great potential as an antitumor drug. Copyright © 2014 Elsevier Inc. All rights reserved.

Characterization of selectively etched halloysite nanotubes by acid treatment

NASA Astrophysics Data System (ADS)

Garcia-Garcia, Daniel; Ferri, Jose M.; Ripoll, Laura; Hidalgo, Montserrat; Lopez-Martinez, Juan; Balart, Rafael

2017-11-01

Halloysite nanotubes (HNTs) are a type of naturally occurring inorganic nanotubes that are characterized by a different composition between their external and internal walls. The internal walls are mainly composed of alumina whilst external walls are composed of silica. This particular structure offers a dual surface chemistry that allows different selective surface treatments which can be focused on increasing the lumen, increasing porosity, etc. In this work, HNTs were chemically treated with different acids (sulphuric, acetic and acrylic acid), for 72 h at a constant temperature of 50 °C. As per the obtained results, the treatment with sulphuric acid is highly aggressive and the particular shape of HNTs is almost lost, with a remarkable increase in porosity. The BET surface area increases from 52.9 (untreated HNTs) up to 132.4 m2 g-1 with sulphuric acid treatment, thus showing an interesting potential in the field of catalysis. On the other hand, the treatment with acetic acid led to milder effects with a noticeable increase in the lumen diameter that changed from 13.8 nm (untreated HNTs) up to 18.4 nm which the subsequent increase in the loading capacity by 77.8%. The aluminium content was measured by X-ray fluorescence (XRF) and laser induced breakdown spectroscopy (LIBS). The final results using two systems, suggest a good correlation between the acid strength and the aluminium reduction. Consequently, is possible to conclude that new applications for HNTs can be derived from selective etching with acids. Sulphuric acid widens the potential of HNTs in the field of catalysis while weak acids such as acetic and acrylic acids give a controlled and homogeneous lumen increase with the corresponding increase in the loading capacity.

Opposite effects of capacity load and resolution load on distractor processing.

PubMed

Zhang, Weiwei; Luck, Steven J

2015-02-01

According to the load theory of attention, an increased perceptual load reduces distractor processing whereas an increased working memory load facilitates distractor processing. Here we raise the possibility that the critical distinction may instead be between an emphasis on resolution and an emphasis on capacity. That is, perceptual load manipulations typically emphasize resolution (fine-grained discriminations), whereas working memory load manipulations typically emphasize capacity (simultaneous processing of multiple relevant stimuli). To test the plausibility of this hypothesis, we used a visual working memory task that emphasized either the number of items to be stored (capacity load, retaining 2 vs. 4 colors) or the precision of the representations (resolution load, detecting small vs. large color changes). We found that an increased capacity load led to increased flanker interference (a measure of distractor processing), whereas an increased resolution load led to reduced flanker interference. These opposite effects of capacity load and resolution load on distractor processing mirror the previously described opposite effects of perceptual load and working memory load.

[Comparison of the effect of continuous and intermittent physical loading in type I diabetics].

PubMed

Rusavý, Z; Lacigová, S; Holecek, T; Srámek, V; Novák, I; Tĕsínský, P

1994-07-01

In order to evaluate the optimal mode of physical loads the authors examined 19 diabetics type I without secondary complications. On the second day of an educational-rehabilitation camp the authors subjected the patients to a continuous load-a 40-minute endurance run at a heart rate equal to 60% of the maximal oxygen requirement. On the fifth day an intermittent load with a maximal intensity--training of 4 x 10 minutes with 5-minute intervals was administered. At the onset, during the 20th and 40th minute of the load the titrable acidity, lactate and blood sugar level were assessed. The intermittent load led already after 20 minutes to marked acidosis (titrable acidity = 12) which did not increase after 40 minutes of the load. The authors recorded a statistically significant rise of the lactate level (4.57 mmol/l) which after 40 minutes of the load rose further to 12.3 mmol/l, as compared with values of titrable acidity during the 20th and 40th minute (0.44 and 1.14) and lactate during the 20th and 40th minute (4.57 and 3.86 mmol/l) during a continuous load. After evaluation by the test of linear correlation it appears with regard to the stability of the blood sugar level during a load that an intermittent load is more favourable. The drop of the blood sugar level in time during a continuous load was at the 1 level of significance, in intermittent loads at the 5% of significance. Both types of loads did not lead to hypoglycaemia or other complications and thus both can be used in diabetics type I.

In vitro antimicrobial activity of solution blow spun poly(lactic acid)/ polyvinylpyrrolidone nanofibers loaded with Copaiba (Copaifera sp.) oil

USDA-ARS?s Scientific Manuscript database

In this study poly(lactic acid)(PLA) and polyvinylpyrrolidone (PVP) micro and nanofibers mats loaded with copaiba (Copaifera sp.) oil were produced by solution blow spinning (SBS). The copaiba (Copaifera sp.) oil was characterized by gas chromatography (GC). Neat PLA and four PLA/ PVP blends contain...

Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools.

PubMed

Taha, Ameer Y; Cheon, Yewon; Faurot, Keturah F; Macintosh, Beth; Majchrzak-Hong, Sharon F; Mann, J Douglas; Hibbeln, Joseph R; Ringel, Amit; Ramsden, Christopher E

2014-05-01

Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, alters unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA plasma concentrations and reduces AA. Published by Elsevier Ltd.

Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools

PubMed Central

Taha, Ameer Y.; Cheon, Yewon; Faurot, Keturah F.; MacIntosh, Beth; Majchrzak-Hong, Sharon F.; Mann, J. Douglas; Hibbeln, Joseph R.; Ringel, Amit; Ramsden, Christopher E.

2014-01-01

Background Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. Objective To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, change unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. Design Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to: (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. Results Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. Conclusion Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFA for 12 weeks further increases n-3 PUFA plasma concentrations, but also reduces AA. PMID:24675168

Formulation and characterization of poly(ethylene glycol)-based, 5-aminolevulinic acid-loaded solid-dosage forms intended for photodynamic and photodiagnostic methodologies in the colorectal region.

PubMed

McCarron, Paul A; Andrews, Gavin P; Morrow, Desmond I J; Woolfson, A David; Donnelly, Ryan F

2007-01-01

Aminolevulinic acid-loaded, poly(ethylene glycol) disks prepared using three molecular weights (1000, 6000, and 10,000) were shown to be of potential for rectal administration as part of photodynamic and photodiagnostic colorectal procedures. The disk-shaped delivery system was mechanically robust, as judged by friability measurements. Calorimetric analysis confirmed that low concentrations of ALA (1% w/w) were dispersed completely throughout the PEG matrix, but higher concentrations (5% w/w and 10% w/w) formed crystalline suspensions. The molecular weight of the PEG determined the melting temperature, with PEG 1000 being suitable for melting around body temperature. The drug release kinetics were shown to be a function of both molecular weight and drug loading. Although the higher molecular weight PEG disks were resistant to surface erosion arising from an aqueous receptor phase, this effect was counterbalanced by more rapid and complete release when the ALA loading was increased. The lowest loading used (1% w/w) produced incomplete release, often not exceeding 30% of the total amount of drug. Results suggest that this simple formulation containing ALA can be administered directly to the colorectal area and is a feasible alternative to peroral dosing of ALA.

Increased Amino Acid Uptake Supports Autophagy-Deficient Cell Survival upon Glutamine Deprivation.

PubMed

Zhang, Nan; Yang, Xin; Yuan, Fengjie; Zhang, Luyao; Wang, Yanan; Wang, Lina; Mao, Zebin; Luo, Jianyuan; Zhang, Hongquan; Zhu, Wei-Guo; Zhao, Ying

2018-06-05

Autophagy is a protein degradation process by which intracellular materials are recycled for energy homeostasis. However, the metabolic status and energy source of autophagy-defective tumor cells are poorly understood. Here, our data show that amino acid uptake from the extracellular environment is increased in autophagy-deficient cells upon glutamine deprivation. This elevated amino acid uptake results from activating transcription factor 4 (ATF4)-dependent upregulation of AAT (amino acid transporter) gene expression. Furthermore, we identify SIRT6, a NAD + -dependent histone deacetylase, as a corepressor of ATF4 transcriptional activity. In autophagy-deficient cells, activated NRF2 enhances ATF4 transcriptional activity by disrupting the interaction between SIRT6 and ATF4. In this way, autophagy-deficient cells exhibit increased AAT expression and show increased amino acid uptake. Notably, inhibition of amino acid uptake reduces the viability of glutamine-deprived autophagy-deficient cells, but not significantly in wild-type cells, suggesting reliance of autophagy-deficient tumor cells on extracellular amino acid uptake. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Reduced knee flexion is a possible cause of increased loading rates in individuals with patellofemoral pain.

PubMed

Silva, Danilo de Oliveira; Briani, Ronaldo Valdir; Pazzinatto, Marcella Ferraz; Ferrari, Deisi; Aragão, Fernando Amâncio; Azevedo, Fábio Mícolis de

2015-11-01

Stair ascent is an activity that exacerbates symptoms of individuals with patellofemoral pain. The discomfort associated with this activity usually results in gait modification such as reduced knee flexion in an attempt to reduce pain. Although such compensatory strategy is a logical approach to decrease pain, it also reduces the normal active shock absorption increasing loading rates and may lead to deleterious and degenerative changes of the knee joint. Thus, the aims of this study were (i) to investigate whether there is reduced knee flexion in adults with PFP compared to healthy controls; and (ii) to analyze loading rates in these subjects, during stair climbing. Twenty-nine individuals with patellofemoral pain and twenty-five control individuals (18-30 years) participated in this study. Each subject underwent three-dimensional kinematic and kinetic analyses during stair climbing on two separate days. Between-groups analyses of variance were performed to identify differences in peak knee flexion and loading rates. Intraclass correlation coefficient was performed to verify the reliability of the variables. On both days, the patellofemoral pain group demonstrated significantly reduced peak knee flexion and increased loading rates. In addition, the two variables obtained high to very high reliability. Reduced knee flexion during stair climbing as a strategy to avoid anterior knee pain does not seem to be healthy for lower limb mechanical distributions. Repeated loading at higher loading rates may be damaging to lower limb joints. Copyright © 2015 Elsevier Ltd. All rights reserved.

Eicosapentaenoic acid and docosahexaenoic acid increase the degradation of amyloid-β by affecting insulin-degrading enzyme.

PubMed

Grimm, Marcus O W; Mett, Janine; Stahlmann, Christoph P; Haupenthal, Viola J; Blümel, Tamara; Stötzel, Hannah; Grimm, Heike S; Hartmann, Tobias

2016-12-01

Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed to be highly beneficial in Alzheimer's disease (AD). AD pathology is closely linked to an overproduction and accumulation of amyloid-β (Aβ) peptides as extracellular senile plaques in the brain. Total Aβ levels are not only dependent on its production by proteolytic processing of the amyloid precursor protein (APP), but also on Aβ-clearance mechanisms, including Aβ-degrading enzymes. Here we show that the omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increase Aβ-degradation by affecting insulin-degrading enzyme (IDE), the major Aβ-degrading enzyme secreted into the extracellular space of neuronal and microglial cells. The identification of the molecular mechanisms revealed that EPA directly increases IDE enzyme activity and elevates gene expression of IDE. DHA also directly stimulates IDE enzyme activity and affects IDE sorting by increasing exosome release of IDE, resulting in enhanced Aβ-degradation in the extracellular milieu. Apart from the known positive effect of DHA in reducing Aβ production, EPA and DHA might ameliorate AD pathology by increasing Aβ turnover.

Pantothenic acid deficiency may increase the urinary excretion of 2-oxo acids and nicotinamide catabolites in rats.

PubMed

Shibata, Katsumi; Inomoto, Kasumi; Nakata, Chifumi; Fukuwatari, Tsutomu

2013-01-01

Pantothenic acid (PaA) is involved in the metabolism of amino acids as well as fatty acid. We investigated the systemic metabolism of amino acids in PaA-deficient rats. For this purpose, urine samples were collected and 2-oxo acids and L-tryptophan (L-Trp) and its metabolites including nicotinamide were measured. Group 1 was freely fed a conventional chemically-defined complete diet and used as an ad lib-fed control, which group was used for showing reference values. Group 2 was freely fed the complete diet without PaA (PaA-free diet) and used as a PaA-deficient group. Group 3 was fed the complete diet, but the daily food amount was equal to the amount of the PaA-deficient group and used as a pair-fed control group. All rats were orally administered 100 mg of L-Trp/kg body weight at 09:00 on day 34 of the experiment and the following 24-h urine samples were collected. The urinary excretion of the sum of pyruvic acid and oxaloacetic acid was higher in rats fed the PaA-free diets than in the rats fed pair-fed the complete diet. PaA deficiency elicited the increased urinary excretion of anthranilic acid and kynurenic acid, while the urinary excretion of xanthurenic acid decreased. The urinary excretion of L-Trp itself, 3-hydroxyanthranilic acid, and quinolinic acid revealed no differences between the rats fed the PaA-free and pair-fed the complete diets. PaA deficiency elicited the increased excretion of N(1)-methylnicotinamide, N(1)-methyl-2-pyridone-5-carboxamide, and N(1)-methyl-4-pyridone-3-carboxamide. These findings suggest that PaA deficiency disturbs the amino acid catabolism.

Urine alkalization facilitates uric acid excretion

PubMed Central

2010-01-01

Background Increase in the incidence of hyperuricemia associated with gout as well as hypertension, renal diseases and cardiovascular diseases has been a public health concern. We examined the possibility of facilitated excretion of uric acid by change in urine pH by managing food materials. Methods Within the framework of the Japanese government's health promotion program, we made recipes which consist of protein-rich and less vegetable-fruit food materials for H+-load (acid diet) and others composed of less protein but vegetable-fruit rich food materials (alkali diet). Healthy female students were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl-,SO42-,PO4-) necessary for the estimation of acid-base balance were measured. Results Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42-] +organic acid-gut alkai) were linearly related with those of the excretion of acid (titratable acidity+ [NH4+] - [HCO3-]), indicating that H+ in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, where uric acid excretion increased from 302 mg/day at pH 5.9 to 413 mg/day at pH 6.5, despite the fact that the alkali diet contained a smaller purine load than the acid diet. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed food is effective for removing uric acid from the body. PMID:20955624

Textured insoles reduce vertical loading rate and increase subjective plantar sensation in overground running.

PubMed

Wilkinson, Michael; Ewen, Alistair; Caplan, Nicholas; O'leary, David; Smith, Neil; Stoneham, Richard; Saxby, Lee

2018-05-01

The effect of textured insoles on kinetics and kinematics of overground running was assessed. 16 male injury-free-recreational runners attended a single visit (age 23 ± 5 yrs; stature 1.78 ± 0.06 m; mass 72.6 ± 9.2 kg). Overground 15-m runs were completed in flat, canvas plimsolls both with and without textured insoles at self-selected velocity on an indoor track in an order that was balanced among participants. Average vertical loading rate and peak vertical force (F peak ) were captured by force platforms. Video footage was digitised for sagittal plane hip, knee and ankle angles at foot strike and mid stance. Velocity, stride rate and length and contact and flight time were determined. Subjectively rated plantar sensation was recorded by visual scale. 95% confidence intervals estimated mean differences. Smallest worthwhile change in loading rate was defined as standardised reduction of 0.54 from a previous comparison of injured versus non-injured runners. Loading rate decreased (-25 to -9.3 BW s -1 ; 60% likely beneficial reduction) and plantar sensation was increased (46-58 mm) with the insole. F peak (-0.1 to 0.14 BW) and velocity (-0.02 to 0.06 m s -1 ) were similar. Stride length, flight and contact time were lower (-0.13 to -0.01 m; -0.02 to-0.01 s; -0.016 to -0.006 s) and stride rate was higher (0.01-0.07 steps s -1 ) with insoles. Textured insoles elicited an acute, meaningful decrease in vertical loading rate in short distance, overground running and were associated with subjectively increased plantar sensation. Reduced vertical loading rate could be explained by altered stride characteristics.

Gender-specific association between dietary acid load and total lean body mass and its dependency on protein intake in seniors.

PubMed

Faure, A M; Fischer, K; Dawson-Hughes, B; Egli, A; Bischoff-Ferrari, H A

2017-12-01

Diet-related mild metabolic acidosis may play a role in the development of sarcopenia. We investigated the relationship between dietary acid load and total lean body mass in male and female seniors age ≥ 60 years. We found that a more alkaline diet was associated with a higher %TLM only among senior women. The aim of this study was to determine if dietary acid load is associated with total lean body mass in male and female seniors age ≥ 60 years. We investigated 243 seniors (mean age 70.3 ± 6.3; 53% women) age ≥ 60 years who participated in the baseline assessment of a clinical trial on vitamin D treatment and rehabilitation after unilateral knee replacement due to severe knee osteoarthritis. The potential renal acid load (PRAL) was assessed based on individual nutrient intakes derived from a food frequency questionnaire. Body composition including percentage of total lean body mass (%TLM) was determined using dual-energy X-ray absorptiometry. Cross-sectional analyses were performed for men and women separately using multivariable regression models controlling for age, physical activity, smoking status, protein intake (g/kg BW per day), energy intake (kcal), and serum 25-hydroxyvitamin D concentration. We included a pre-defined subgroup analysis by protein intake (< 1 g/kg BW day, > 1 g/kg BW day) and by age group (< 70 years, ≥ 70 years). Adjusted %TLM decreased significantly across PRAL quartiles only among women (P trend  = 0.004). Moreover, in subgroup analysis, the negative association between the PRAL and %TLM was most pronounced among women with low protein intake (< 1 g/kg BW per day) and age below 70 years (P = 0.002). Among men, there was no association between the PRAL and %TLM. The association between dietary acid load and %TLM seems to be gender-specific, with a negative impact on total lean mass only among senior women. Therefore, an alkaline diet may be beneficial for preserving total lean mass in senior women

Short branched-chain C6 carboxylic acids result in increased growth, novel 'unnatural' fatty acids and increased membrane fluidity in a Listeria monocytogenes branched-chain fatty acid-deficient mutant.

PubMed

Sen, Suranjana; Sirobhushanam, Sirisha; Hantak, Michael P; Lawrence, Peter; Brenna, J Thomas; Gatto, Craig; Wilkinson, Brian J

2015-10-01

Listeria monocytogenes is a psychrotolerant food borne pathogen, responsible for the high fatality disease listeriosis, and expensive food product recalls. Branched-chain fatty acids (BCFAs) of the membrane play a critical role in providing appropriate membrane fluidity and optimum membrane biophysics. The fatty acid composition of a BCFA-deficient mutant is characterized by high amounts of straight-chain fatty acids and even-numbered iso fatty acids, in contrast to the parent strain where odd-numbered anteiso fatty acids predominate. The presence of 2-methylbutyrate (C5) stimulated growth of the mutant at 37°C and restored growth at 10°C along with the content of odd-numbered anteiso fatty acids. The C6 branched-chain carboxylic acids 2-ethylbutyrate and 2-methylpentanoate also stimulated growth to a similar extent as 2-methylbutyrate. However, 3-methylpentanoate was ineffective in rescuing growth. 2-Ethylbutyrate and 2-methylpentanoate led to novel major fatty acids in the lipid profile of the membrane that were identified as 12-ethyltetradecanoic acid and 12-methylpentadecanoic acid respectively. Membrane anisotropy studies indicated that growth of strain MOR401 in the presence of these precursors increased its membrane fluidity to levels of the wild type. Cells supplemented with 2-methylpentanoate or 2-ethylbutyrate at 10°C shortened the chain length of novel fatty acids, thus showing homeoviscous adaptation. These experiments use the mutant as a tool to modulate the membrane fatty acid compositions through synthetic precursor supplementation, and show how existing enzymes in L. monocytogenes adapt to exhibit non-native activity yielding unique 'unnatural' fatty acid molecules, which nevertheless possess the correct biophysical properties for proper membrane function in the BCFA-deficient mutant. Copyright © 2015 Elsevier B.V. All rights reserved.

Opposite Effects of Capacity Load and Resolution Load on Distractor Processing

PubMed Central

Zhang, Weiwei; Luck, Steven J.

2014-01-01

According to the load theory of attention, an increased perceptual load reduces distractor processing whereas an increased working memory load facilitates distractor processing. Here we raise the possibility that the critical distinction may instead be between an emphasis on resolution and an emphasis on capacity. That is, perceptual load manipulations typically emphasize resolution (fine-grained discriminations), whereas working memory load manipulations typically emphasize capacity (simultaneous processing of multiple relevant stimuli). To test the plausibility of this hypothesis, we used a visual working memory task that emphasized either the number of items to be stored (capacity load, retaining two versus four colors) or the precision of the representations (resolution load, detecting small versus large color changes). We found that an increased capacity load led to increased flanker interference (a measure of distractor processing), whereas an increased resolution load led to reduced flanker interference. These opposite effects of capacity load and resolution load on distractor processing mirror the previously described opposite effects of perceptual load and working memory load. PMID:25365573

Polyacrylic acid@zeolitic imidazolate framework-8 nanoparticles with ultrahigh drug loading capability for pH-sensitive drug release.

PubMed

Ren, Hong; Zhang, Lingyu; An, Jiping; Wang, Tingting; Li, Lu; Si, Xiaoyan; He, Liu; Wu, Xiaotong; Wang, Chungang; Su, Zhongmin

2014-01-28

The polyacrylic acid@zeolitic imidazolate framework-8 (PAA@ZIF-8) nanoparticles (NPs) were first fabricated using a facile and simple route. It is worthwhile noting that the as-fabricated PAA@ZIF-8 NPs possessed ultrahigh doxorubicin (DOX) loading capability (1.9 g DOX g(-1) NPs), which were employed as pH-dependent drug delivery vehicles.

Accumulation of phosphatidic acid increases vancomycin resistance in Escherichia coli.

PubMed

Sutterlin, Holly A; Zhang, Sisi; Silhavy, Thomas J

2014-09-01

In Gram-negative bacteria, lipopolysaccharide (LPS) contributes to the robust permeability barrier of the outer membrane, preventing entry of toxic molecules such as antibiotics. Mutations in lptD, the beta-barrel component of the LPS transport and assembly machinery, compromise LPS assembly and result in increased antibiotic sensitivity. Here, we report rare vancomycin-resistant suppressors that improve barrier function of a subset of lptD mutations. We find that all seven suppressors analyzed mapped to the essential gene cdsA, which is responsible for the conversion of phosphatidic acid to CDP-diacylglycerol in phospholipid biosynthesis. These cdsA mutations cause a partial loss of function and, as expected, accumulate phosphatidic acid. We show that this suppression is not confined to mutations that cause defects in outer membrane biogenesis but rather that these cdsA mutations confer a general increase in vancomycin resistance, even in a wild-type cell. We use genetics and quadrupole time of flight (Q-TOF) liquid chromatography-mass spectrometry (LC-MS) to show that accumulation of phosphatidic acid by means other than cdsA mutations also increases resistance to vancomycin. We suggest that increased levels of phosphatidic acid change the physical properties of the outer membrane to impede entry of vancomycin into the periplasm, hindering access to its target, an intermediate required for the synthesis of the peptidoglycan cell wall. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Preparation of magnetic polylactic acid microspheres and investigation of its releasing property for loading curcumin

NASA Astrophysics Data System (ADS)

Li, Fengxia; Li, Xiaoli; Li, Bin

2011-11-01

In order to obtain a targeting drug carrier system, magnetic polylactic acid (PLA) microspheres loading curcumin were synthesized by the classical oil-in-water emulsion solvent-evaporation method. In the Fourier transform infrared spectra of microspheres, the present functional groups of PLA were all kept invariably. The morphology and size distribution of magnetic microspheres were observed with scanning electron microscopy and dynamic light scattering, respectively. The results showed that the microspheres were regularly spherical and the surface was smooth with a diameter of 0.55-0.75 μm. Magnetic Fe 3O 4 was loaded in PLA microspheres and the content of magnetic particles was 12 wt% through thermogravimetric analysis. The magnetic property of prepared microspheres was measured by vibrating sample magnetometer. The results showed that the magnetic microspheres exhibited typical superparamagnetic behavior and the saturated magnetization was 14.38 emu/g. Through analysis of differential scanning calorimetry, the curcumin was in an amorphous state in the magnetic microspheres. The drug loading, encapsulation efficiency and releasing properties of curcumin in vitro were also investigated by ultraviolet-visible spectrum analysis. The results showed that the drug loading and encapsulation efficiency were 8.0% and 24.2%, respectively. And curcumin was obviously slowly released because the cumulative release percentage of magnetic microspheres in the phosphate buffer (pH=7.4) solution was only 49.01% in 72 h, and the basic release of curcumin finished in 120 h.

Acid mine drainage in the Iberian Pyrite Belt: 1. Hydrochemical characteristics and pollutant load of the Tinto and Odiel rivers.

PubMed

Nieto, Jose M; Sarmiento, Aguasanta M; Canovas, Carlos R; Olias, Manuel; Ayora, Carlos

2013-11-01

Acid mine drainage in the Iberian Pyrite Belt is probably the worst case in the world of surface water pollution associated with mining of sulphide mineral deposits. The Iberian Pyrite Belt is located in SW Iberian Peninsula, and it has been mined during the last 4,500 years. The central and eastern part of the Iberian Pyrite Belt is drained by the Tinto and Odiel rivers, which receive most of the acidic leachates from the mining areas. As a result, the main channels of the Tinto and Odiel rivers are very rich in metals and highly acidic until reaching the Atlantic Ocean. A significant amount of the pollutant load transported by these two rivers is delivered during the rainy season, as is usual in rivers of Mediterranean climate regions. Therefore, in order to have an accurate estimation of the pollutant loads transported by the Tinto and Odiel rivers, a systematic sampling on a weekly basis and a high temporal resolution sampling of floods events were both performed. Results obtained show that metal fluxes are strongly dependent on the study period, highlighting the importance of inter-annual studies involving dry and wet years.

Effects of particle size, helium gas pressure and microparticle dose on the plasma concentration of indomethacin after bombardment of indomethacin-loaded poly-L-lactic acid microspheres using a Helios gun system.

PubMed

Uchida, Masaki; Natsume, Hideshi; Kobayashi, Daisuke; Sugibayashi, Kenji; Morimoto, Yasunori

2002-05-01

We investigated the effects of the particle size of indomethacin-loaded poly-L-lactic acid microspheres (IDM-loaded PLA MS), the helium pressure used to accelerate the particles, and the bombardment dose of PLA MS on the plasma concentration of IDM after bombarding with IDM-loaded PLA MS of different particle size ranges, 20-38, 44-53 and 75-100 microm, the abdomen of hairless rats using the Helios gene gun system (Helios gun system). Using larger particles and a higher helium pressure, produced an increase in the plasma IDM concentration and the area under the plasma concentration-time curve (AUC) and resultant F (relative bioavailability with respect to intracutaneous injection) of IDM increased by an amount depending on the particle size and helium pressure. Although a reduction in the bombardment dose led to a decrease in C(max) and AUC, F increased on decreasing the bombardment dose. In addition, a more efficient F was obtained after bombarding with IDM-loaded PLA MS of 75-100 microm in diameter at each low dose in different sites of the abdomen compared with that after bolus bombardment with a high dose (dose equivalent). These results suggest that the bombardment injection of drug-loaded microspheres by the Helios gun system is a very useful tool for delivering a variety of drugs in powder form into the skin and systemic circulation.

Uncertainty analysis on simple mass balance model to calculate critical loads for soil acidity.

PubMed

Li, Harbin; McNulty, Steven G

2007-10-01

Simple mass balance equations (SMBE) of critical acid loads (CAL) in forest soil were developed to assess potential risks of air pollutants to ecosystems. However, to apply SMBE reliably at large scales, SMBE must be tested for adequacy and uncertainty. Our goal was to provide a detailed analysis of uncertainty in SMBE so that sound strategies for scaling up CAL estimates to the national scale could be developed. Specifically, we wanted to quantify CAL uncertainty under natural variability in 17 model parameters, and determine their relative contributions in predicting CAL. Results indicated that uncertainty in CAL came primarily from components of base cation weathering (BC(w); 49%) and acid neutralizing capacity (46%), whereas the most critical parameters were BC(w) base rate (62%), soil depth (20%), and soil temperature (11%). Thus, improvements in estimates of these factors are crucial to reducing uncertainty and successfully scaling up SMBE for national assessments of CAL.

Barley β-glucan increases fecal bile acid excretion and short chain fatty acid levels in mildly hypercholesterolemic individuals.

PubMed

Thandapilly, Sijo J; Ndou, Saymore P; Wang, Yanan; Nyachoti, Charles M; Ames, Nancy P

2018-06-20

The cholesterol-lowering effect of barley β-glucan has been proposed to be the result of a pleiotropic effect, which involves several biological mechanisms such as gut fermentation, inhibition of intestinal cholesterol absorption and increased bile acid excretion and its synthesis. However, one of the recent studies from our laboratory indicated that increased bile acid excretion and subsequent increase in its synthesis, but not the inhibition of cholesterol absorption or synthesis might be responsible for the cholesterol-lowering effect of barley β-glucan. Accordingly, the primary objective of the present study was to investigate the concentration of bile acids (BA), neutral sterols (NS) and short chain fatty acids (SCFA) excreted through the feces by mildly hypercholesterolemic subjects who consumed diets containing barley β-glucan with varying molecular weights (MW) and concentrations. In a controlled, four phase, crossover trial, 30 mildly hypercholesterolemic but otherwise healthy subjects were randomly assigned to receive breakfast containing 3 g high MW (HMW), 5 g low MW (LMW), 3 g LMW barley β-glucan or a control diet for 5 weeks. The concentrations of BA, NS and SCFA in the feces were measured at the end of each treatment phase. Compared to the other treatment groups, 3 g day-1 HMW barley β-glucan consumption resulted in increased lithocholic acid (LCA) excretion (P < 0.001) but not LMW β-glucan, even at the high dose of 5 g day-1. Increased fermentability of fibre was also evident from a significant increase in fecal total SCFA concentrations in response to the 3 g HMW β-glucan diet compared to the 3 g LMW barley β-glucan and control diet (P = 0.0015). In summary, the current results validate our previous report on the role of fecal bile acid excretion in cholesterol lowering through the consumption of barley β-glucan. In addition, increased SCFA concentrations indicate that an increase in β-glucan molecular weight promotes hindgut fermentation

Effect of training load structure on purine metabolism in middle-distance runners.

PubMed

Zieliński, Jacek; Kusy, Krzysztof; Rychlewski, Tadeusz

2011-09-01

There are no studies analyzing the effect of training loads on purine metabolism during long training periods. The study's purpose was to evaluate the effect of training load changes and subsequent detraining on purine metabolism in middle-distance runners during a 1-yr cycle. In four characteristic points of the training cycle, loads assigned to five intensity zones, pre- and postexercise plasma hypoxanthine (Hx) and uric acid, and erythrocyte Hx-guanine phosphoribosyltransferase (HGPRT) activity were determined in 11 male middle-distance runners at the national level, practicing competitive sport for 8.1 ± 0.3 yr and with a mean age of 22.3 ± 0.7 yr, body mass of 73.0 ± 3.4 kg, and body height of 180 ± 2.2 cm. In the competition phase (CP), training loads in aerobic compensation and threshold zones decreased by 65.4% and by 20.5%, respectively. At the same time, anaerobic training loads increased by 132.5% in the VO(2max) zone and by 74.6% in the lactic acid tolerance zone. Postexercise Hx decreased significantly in CP by 6.2 μmol·L(-1). and increased in the transition phase (TP) by 17.4 μmol·L(-1). Both pre- and postexercise HGPRT activity increased significantly in CP by 9.3 nmol·mg(-1)·h(-1). and by 4.9 nmol·mg(-1)·h(-1). , respectively, and decreased significantly in TP by 10.6 nmol·mg(-1)·h(-1). and by 12.0 nmol·mg(-1)·h(-1). , respectively. A significant uric acid increase of 54 μmol·L(-1). was revealed merely in TP. The effect of anaerobic training on purine metabolism is significant despite of a very short total duration of anaerobic loads. Elevated preexercise HGPRT activity in CP suggests adaptation changes consisting in a "permanent readiness" for purine salvage. The detraining in TP leads to reverse adaptation changes. Probably, plasma Hx concentration and erythrocyte HGPRT activity may be considered as a useful measure of training status.

Preparation and characterization of dutasteride-loaded nanostructured lipid carriers coated with stearic acid-chitosan oligomer for topical delivery.

PubMed

Noor, Norhayati Mohamed; Sheikh, Khalid; Somavarapu, Satyanarayana; Taylor, Kevin M G

2017-08-01

Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair growth. To enhance delivery to the hair follicles and reduce systemic effects, in this study dutasteride has been formulated for topical application, in a nanostructured lipid carrier (NLC) coated with chitosan oligomer-stearic acid (CSO-SA). CSO-SA has been successfully synthesized, as confirmed using 1 H NMR and FTIR. Formulation of dutasteride-loaded nanostructured lipid carriers (DST-NLCs) was optimized using a 2 3 full factorial design. This formulation was coated with different concentrations of stearic acid-chitosan solution. Coating DST-NLCs with 5% SA-CSO increased mean size from 187.6±7.0nm to 220.1±11.9nm, and modified surface charge, with zeta potentials being -18.3±0.9mV and +25.8±1.1mV for uncoated and coated DST-NLCs respectively. Transmission electron microscopy showed all formulations comprised approximately spherical particles. DST-NLCs, coated and uncoated with CSO-SA, exhibited particle size stability over 60days, when stored at 4-8°C. However, NLCs coated with CSO (without conjugation) showed aggregation when stored at 4-8°C after 30days. The measured particle size for all formulations stored at 25°C suggested aggregation, which was greatest for DST-NLCs coated with 10% CSO-SA and 5% CSO. All nanoparticle formulations exhibited rapid release in an in vitro release study, with uncoated NLCs exhibiting the fastest release rate. Using a Franz diffusion cell, no dutasteride permeated through pig ear skin after 48h, such that it was not detected in the receptor chamber for all samples. The amount of dutasteride in the skin was significantly different (p<0.05) for DST-NLCs (6.09±1.09μg/cm 2 ) without coating and those coated with 5% CSO-SA (2.82±0.40μg/cm 2 ), 10% CSO-SA (2.70±0.35μg/cm 2 ) and CSO (2.11±0.64μg/cm 2) . There was a significant difference (p<0.05) in the cytotoxicity (IC 50 ) between dutasteride alone and in the nanoparticles. DST-NLCs coated

The rate of synthesis and decomposition of tissue proteins in hypokinesia and increased muscular activity

NASA Technical Reports Server (NTRS)

Fedorov, I. V.; Chernyy, A. V.; Fedorov, A. I.

1978-01-01

During hypokinesia and physical loading (swimming) of rats, the radioactivity of skeletal muscle, liver, kidney, heart, and blood proteins was determined after administration of radioactive amino acids. Tissue protein synthesis decreased during hypokinesia, and decomposition increased. Both synthesis and decomposition increased during physical loading, but anabolic processes predominated in the total tissue balance. The weights of the animals decreased in hypokinesia and increased during increased muscle activity.

Enhanced itaconic acid production in Aspergillus with increased LaeA expression

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

Dai, Ziyu; Baker, Scott E.

Fungi, such as Aspergillus niger, having a dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase (Alg3) gene genetic inactivation, increased expression of a loss of aflR expression A (LaeA), or both, are described. In some examples, such mutants have several phenotypes, including an increased production of citric acid relative to the parental strain. Methods of using the disclosed fungi to make citric acid are also described, as are compositions and kits including the disclosed fungi. Further described are Aspergillus terreus fungi overexpressing the LaeA gene and the use of such fungi for the production of itaconic acid.

Microwave Energy Increases Fatty Acid Methyl Ester Yield in Human Whole Blood Due to Increased Sphingomyelin Transesterification.

PubMed

Metherel, Adam H; Aristizabal Henao, Juan J; Ciobanu, Flaviu; Taha, Ameer Y; Stark, Ken D

2015-09-01

Dried blood spots (DBS) by fingertip prick collection for fatty acid profiling are becoming increasingly popular due to ease of collection, minimal invasiveness and its amenability to high-throughput analyses. Herein, we assess a microwave-assisted direct transesterification method for the production of fatty acid methyl esters (FAME) from DBS. Technical replicates of human whole blood were collected and 25-μL aliquots were applied to chromatography strips prior to analysis by a standard 3-h transesterification method or microwave-assisted direct transesterification method under various power (variable vs constant), time (1-5 min) and reagent (1-10% H2SO4 in methanol) conditions. In addition, a standard method was compared to a 5-min, 30-W power microwave in 1% H2SO4 method for FAME yield from whole blood sphingomyelin, and sphingomyelin standards alone and spiked in whole blood. Microwave-assisted direct transesterification yielded no significant differences in both quantitative (nmol/100 µL) and qualitative (mol%) fatty acid assessments after as little as 1.5- and 1-min reaction times, respectively, using the variable power method and 5% H2SO4 in methanol. However, 30-W power for 5 min increased total FAME yield of the technical replicates by 14%. This increase appears largely due to higher sphingomyelin-derived FAME yield of up to 109 and 399% compared to the standard method when determined from whole blood or pure standards, respectively. In conclusion, microwave-assisted direct transesterification of DBS achieved in as little as 1-min, and 5-min reaction times increase total fatty acids primarily by significantly improving sphingomyelin-derived fatty acid yield.

Chlorogenic acid increased 5-hydroxymethylfurfural formation when heating fructose alone or with aspartic acid at two pH levels.

PubMed

Zhang, Zhenhua; Zou, Yueyu; Wu, Taigang; Huang, Caihuan; Pei, Kehan; Zhang, Guangwen; Lin, Xiaohua; Bai, Weibin; Ou, Shiyi

2016-01-01

Chlorogenic acid (CGA) is a phenolic acid that ubiquitously exists in fruits. This work aims to investigate whether and how CGA influences HMF formation during heating fructose alone, or with an amino acid. The results showed that that CGA increased 5-hydroxymethylfurfural (HMF) formation. At pH 5.5 and 7.0, the addition of 5.0 μmol/ml CGA increased HMF formation by 49.4% and 25.2%, respectively when heating fructose alone, and by 9.0% and 16.7%, respectively when heating fructose with aspartic acid. CGA significantly increased HMF formation by promoting 3-deoxosone formation, and its conversion to HMF by inhibiting HMF elimination, especially in the Maillard reaction system. A comparison of the catalytic capacity of CGA with its six analogous compounds showed that both its di-hydroxyphenyl and carboxyl groups function in increasing HMF formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Target loads of atmospheric sulfur deposition for the protection and recovery of acid-sensitive streams in the Southern Blue Ridge Province.

PubMed

Sullivan, Timothy J; Cosby, Bernard J; Jackson, William A

2011-11-01

An important tool in the evaluation of acidification damage to aquatic and terrestrial ecosystems is the critical load (CL), which represents the steady-state level of acidic deposition below which ecological damage would not be expected to occur, according to current scientific understanding. A deposition load intended to be protective of a specified resource condition at a particular point in time is generally called a target load (TL). The CL or TL for protection of aquatic biota is generally based on maintaining surface water acid neutralizing capacity (ANC) at an acceptable level. This study included calibration and application of the watershed model MAGIC (Model of Acidification of Groundwater in Catchments) to estimate the target sulfur (S) deposition load for the protection of aquatic resources at several future points in time in 66 generally acid-sensitive watersheds in the southern Blue Ridge province of North Carolina and two adjoining states. Potential future change in nitrogen leaching is not considered. Estimated TLs for S deposition ranged from zero (ecological objective not attainable by the specified point in time) to values many times greater than current S deposition depending on the selected site, ANC endpoint, and evaluation year. For some sites, one or more of the selected target ANC critical levels (0, 20, 50, 100μeq/L) could not be achieved by the year 2100 even if S deposition was reduced to zero and maintained at that level throughout the simulation. Many of these highly sensitive streams were simulated by the model to have had preindustrial ANC below some of these target values. For other sites, the watershed soils contained sufficiently large buffering capacity that even very high sustained levels of atmospheric S deposition would not reduce stream ANC below common damage thresholds. Copyright © 2011 Elsevier Ltd. All rights reserved.

Gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres for gadolinium neutron-capture therapy.

PubMed

Saha, Tapan Kumar; Ichikawa, Hideki; Fukumori, Yoshinobu

2006-12-11

In order to provide a suitable device that would contain water-soluble drugs, highly water-soluble gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres (CMS-Gd-DTPA) were prepared by the emulsion method using glutaraldehyde as a cross-linker and Span 80 as a surfactant for gadolinium neutron-capture therapy of cancer. The gadolinium content and the mass median diameter of CMS-Gd-DTPA were estimated. The size and morphology of the CMS-Gd-DTPA were strongly influenced by the initial applied weight ratio of Gd-DTPA:chitosan. FTIR spectra showed that the electrostatic interaction between chitosan and Gd-DTPA accelerated the formation of gadolinium-enriched chitosan microspheres. Sufficient amounts of glutaraldehyde and Span 80 were necessary for producing discrete CMS-Gd-DTPA. The CMS-Gd-DTPA having a mass median diameter 11.7microm and 11.6% of gadolinium could be used in Gd-NCT following intratumoral injection.

Overexpression of acetyl-CoA synthetase in Saccharomyces cerevisiae increases acetic acid tolerance

PubMed Central

Ding, Jun; Holzwarth, Garrett; Penner, Michael H.; Patton-Vogt, Jana; Bakalinsky, Alan T.

2015-01-01

Acetic acid-mediated inhibition of the fermentation of lignocellulose-derived sugars impedes development of plant biomass as a source of renewable ethanol. In order to overcome this inhibition, the capacity of Saccharomyces cerevisiae to synthesize acetyl-CoA from acetic acid was increased by overexpressing ACS2 encoding acetyl-coenzyme A synthetase. Overexpression of ACS2 resulted in higher resistance to acetic acid as measured by an increased growth rate and shorter lag phase relative to a wild-type control strain, suggesting that Acs2-mediated consumption of acetic acid during fermentation contributes to acetic acid detoxification. PMID:25673654

Production of GMP-grade radioactive holmium loaded poly(L-lactic acid) microspheres for clinical application.

PubMed

Zielhuis, S W; Nijsen, J F W; de Roos, R; Krijger, G C; van Rijk, P P; Hennink, W E; van het Schip, A D

2006-03-27

Radioactive holmium-166 loaded poly(L-lactic acid) microspheres are promising systems for the treatment of liver malignancies. The microspheres are loaded with holmium acetylacetonate (HoAcAc) and prepared by a solvent evaporation method. After preparation, the microspheres (Ho-PLLA-MS) are activated by neutron irradiation in a nuclear reactor. In this paper, the aspects of the production of a (relatively) large-scale GMP batch (4 g, suitable for treatment of 5-10 patients) of Ho-PLLA-MS are described. The critical steps of the Ho-PLLA-MS production process (sieving procedure, temperature control during evaporation and raw materials) were considered and the pharmaceutical quality of the microspheres was evaluated. The pharmaceutical characteristics (residual solvents, possible bacterial contaminations and endotoxins) of the produced Ho-PLLA-MS batches were in compliance with the requirements of the European Pharmacopoeia. Moreover, neutron irradiated Ho-PLLA-MS retained their morphological integrity and the holmium remained stably associated with the microspheres; it was observed that after 270h (10 times the half-life of Ho-166) only 0.3+/-0.1% of the loading was released from the microspheres in an aqueous solution. In conclusion, Ho-PLLA-MS which are produced as described in this paper, can be clinically applied, with respect to their pharmaceutical quality.

Fruit load induces changes in global gene expression and in abscisic acid (ABA) and indole acetic acid (IAA) homeostasis in citrus buds

PubMed Central

Shalom, Liron; Samuels, Sivan; Zur, Naftali; Shlizerman, Lyudmila; Doron-Faigenboim, Adi; Blumwald, Eduardo; Sadka, Avi

2014-01-01

Many fruit trees undergo cycles of heavy fruit load (ON-Crop) in one year, followed by low fruit load (OFF-Crop) the following year, a phenomenon known as alternate bearing (AB). The mechanism by which fruit load affects flowering induction during the following year (return bloom) is still unclear. Although not proven, it is commonly accepted that the fruit or an organ which senses fruit presence generates an inhibitory signal that moves into the bud and inhibits apical meristem transition. Indeed, fruit removal from ON-Crop trees (de-fruiting) induces return bloom. Identification of regulatory or metabolic processes modified in the bud in association with altered fruit load might shed light on the nature of the AB signalling process. The bud transcriptome of de-fruited citrus trees was compared with those of ON- and OFF-Crop trees. Fruit removal resulted in relatively rapid changes in global gene expression, including induction of photosynthetic genes and proteins. Altered regulatory mechanisms included abscisic acid (ABA) metabolism and auxin polar transport. Genes of ABA biosynthesis were induced; however, hormone analyses showed that the ABA level was reduced in OFF-Crop buds and in buds shortly following fruit removal. Additionally, genes associated with Ca2+-dependent auxin polar transport were remarkably induced in buds of OFF-Crop and de-fruited trees. Hormone analyses showed that auxin levels were reduced in these buds as compared with ON-Crop buds. In view of the auxin transport autoinhibition theory, the possibility that auxin distribution plays a role in determining bud fate is discussed. PMID:24706719

Decreasing high postprandial stearic acid in impaired fasting glucose by dietary regulation.

PubMed

Liu, L; Chu, X; Na, L; Yuan, F; Li, Y; Sun, C

2016-07-01

The objective of this study was to determine the postprandial change in free fatty acid (FFA) profiles in subjects with impaired fasting glucose (IFG), and to evaluate the effect of low glycemic index (GI) load on postprandial FFA profiles and inflammation. First, 50 IFG and 50 healthy subjects were recruited; and 2 -h postprandial changes in FFA profiles were determined. Second, the 50 IFG subjects then received three different loads: glucose load (GL), high glycemic index (HGI) load and low glycemic index (LGI) load, respectively. FFA profile, glucose, insulin, glucagon-like peptide 1 (GLP-1) and inflammatory biomarkers were assayed at 0, 30, 60, 90 and 120 min. Postprandial stearic acid (C18:0) increased compared with baseline in all subjects, whereas the change in postprandial C18:0 was more marked in IFG subjects than in healthy subjects. Compared with subjects who received the GL and HGI load, the area under the curve for insulin, GLP-1, C18:0 and tumor necrosis factor-alpha significantly decreased and adiponectin increased in subjects who received the LGI load. The rise in postprandial C18:0 in IFG subjects was inhibited by LGI load.

Increase in the permeability of tonoplast of garlic (Allium sativum) by monocarboxylic acids.

PubMed

Bai, Bing; Li, Lei; Hu, Xiaosong; Wang, Zhengfu; Zhao, Guanghua

2006-10-18

Immersion of intact aged garlic (Allium sativum) cloves in a series of 5% weak organic monocarboxylate solutions (pH 2.0) resulted in green color formation. No color was formed upon treatment with other weak organic acids, such as citric and malic acids, and the inorganic hydrochloric acid under the same conditions. To understand the significance of monocarboxylic acids and their differing function from that of other acids, acetic acid was compared with organic acids citric and malic and the inorganic hydrochloric acid. The effects of these acids on the permeability of plasma and intracellular membrane of garlic cells were measured by conductivity, light microscopy, and transmission electron microscopy. Except for hydrochloric acid, treatment of garlic with all three organic acids greatly increased the relative conductivity of their respective pickling solutions, indicating that all tested organic acids increased the permeability of plasma membrane. Moreover, a pickling solution containing acetic acid exhibited 1.5-fold higher relative conductivity (approximately 90%) as compared to those (approximately 60%) of both citric and malic acids, implying that exposure of garlic cloves to acetic acid not only changed the permeability of the plasma membrane but also increased the permeability of intracellular membrane. Exposure of garlic to acetic acid led to the production of precipitate along the tonoplast, but no precipitate was formed by citric and malic acids. This indicates that the structure of the tonoplast was damaged by this treatment. Further support for this conclusion comes from results showing that the concentration of thiosulfinates [which are produced only by catalytic conversion of S-alk(en)yl-l-cysteine sulfoxides in cytosol by alliinase located in the vacuole] in the acetic acid pickling solution is 1.3 mg/mL, but almost no thiosulfinates were detected in the pickling solution of citric and malic acids. Thus, all present results suggest that damage of

In Vitro and Ex Vivo Evaluation of Novel Curcumin-Loaded Excipient for Buccal Delivery.

PubMed

Laffleur, Flavia; Schmelzle, Franziska; Ganner, Ariane; Vanicek, Stefan

2017-08-01

This study aimed to develop a mucoadhesive polymeric excipient comprising curcumin for buccal delivery. Curcumin encompasses broad range of benefits such as antioxidant, anti-inflammatory, and chemotherapeutic activity. Hyaluronic acid (HA) as polymeric excipient was modified by immobilization of thiol bearing ligands. L-Cysteine (SH) ethyl ester was covalently attached via amide bond formation between cysteine and the carboxylic moiety of hyaluronic acid. Succeeded synthesis was proved by H-NMR and IR spectra. The obtained thiolated polymer hyaluronic acid ethyl ester (HA-SH) was evaluated in terms of stability, safety, mucoadhesiveness, drug release, and permeation-enhancing properties. HA-SH showed 2.75-fold higher swelling capacity over time in comparison to unmodified polymer. Furthermore, mucoadhesion increased 3.4-fold in case of HA-SH and drug release was increased 1.6-fold versus HA control, respectively. Curcumin-loaded HA-SH exhibits a 4.4-fold higher permeation compared with respective HA. Taking these outcomes in consideration, novel curcumin-loaded excipient, namely thiolated hyaluronic acid ethyl ester appears as promising tool for pharyngeal diseases.

Fabrication and in vitro release behavior of a novel antibacterial coating containing halogenated furanone-loaded poly(L-lactic acid) nanoparticles on microarc-oxidized titanium

PubMed Central

Cheng, Yicheng; Wu, Jiang; Gao, Bo; Zhao, Xianghui; Yao, Junyan; Mei, Shenglin; Zhang, Liang; Ren, Huifang

2012-01-01

Background Dental implants have become increasingly common for the management of missing teeth. However, peri-implant infection remains a problem, is usually difficult to treat, and may lead eventually to dental implant failure. The aim of this study was to fabricate a novel antibacterial coating containing a halogenated furanone compound, ie, (Z-)-4-bromo-5-(bromomethylene)-2(5H)-furanone (BBF)-loaded poly(L-lactic acid) (PLLA) nanoparticles on microarc-oxidized titanium and to evaluate its release behavior in vitro. Methods BBF-loaded PLLA nanoparticles were prepared using the emulsion solvent-evaporation method, and the antibacterial coating was fabricated by cross-linking BBF-loaded PLLA nanoparticles with gelatin on microarc-oxidized titanium. Results The BBF-loaded PLLA nanoparticles had a small particle size (408 ± 14 nm), a low polydispersity index (0.140 ± 0.008), a high encapsulation efficiency (72.44% ± 1.27%), and a fine spherical shape with a smooth surface. The morphology of the fabricated antibacterial coating showed that the BBF-loaded PLLA nanoparticles were well distributed in the pores of the microarc oxidation coating, and were cross-linked with each other and the wall pores by gelatin. The release study indicated that the antibacterial coating could achieve sustained release of BBF for 60 days, with a slight initial burst release during the first 4 hours. Conclusion The novel antibacterial coating fabricated in this study is a potentially promising method for prevention of early peri-implant infection. PMID:23152682

Doxorubicin-loaded poly (lactic-co-glycolic acid) nanoparticles coated with chitosan/alginate by layer by layer technology for antitumor applications.

PubMed

Chai, Fujuan; Sun, Linlin; He, Xinyi; Li, Jieli; Liu, Yuanfen; Xiong, Fei; Ge, Liang; Webster, Thomas J; Zheng, Chunli

2017-01-01

Natural polyelectrolyte multilayers of chitosan (CHI) and alginate (ALG) were alternately deposited on doxorubicin (DOX)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) with layer by layer self-assembly to control drug release for antitumor activity. Numerous factors which influenced the multilayer growth on nano-colloidal particles were studied: polyelectrolyte concentration, NaCl concentration and temperature. Then the growth regime of the CHI/ALG multilayers was elucidated. The coated NPs were characterized by transmission electron microscopy, atomic force microscopy, X-ray diffraction and a zeta potential analyzer. In vitro studies demonstrated an undesirable initial burst release of DOX-loaded PLGA NPs (DOX-PLGA NPs), which was relieved from 55.12% to 5.78% through the use of the layer by layer technique. The release of DOX increased more than 40% as the pH of media decreased from 7.4 to 5.0. More importantly, DOX-PLGA (CHI/ALG) 3 NPs had superior in vivo tumor inhibition rates at 83.17% and decreased toxicity, compared with DOX-PLGA NPs and DOX in solution. Thus, the presently formulated PLGA-polyelectrolyte NPs have strong potential applications for numerous controlled anticancer drug release applications.

Mutant E. coli strain with increased succinic acid production

DOEpatents

Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

1998-01-01

A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

Mutant E. coli strain with increased succinic acid production

DOEpatents

Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

2001-09-25

A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

Mutant E. coli strain with increased succinic acid production

DOEpatents

Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

2002-01-01

A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

Arginine, glycine, aspartic acid peptide-modified paclitaxel and curcumin co-loaded liposome for the treatment of lung cancer: in vitro/vivo evaluation.

PubMed

Jiang, Kanqiu; Shen, Mingjing; Xu, Weihua

2018-01-01

In this study, a novel arginine, glycine, aspartic acid peptide (RGD)-modified paclitaxel and curcumin co-loaded liposomes were developed to evaluate their antitumor activity in vitro and in vivo. Co-loaded liposomes were prepared using the solvent evaporation method. The particles had spherical shapes under electron microscopy with sizes <130 nm. By comparison with the free drug, RGD-modified paclitaxel and curcumin co-loaded liposomes and paclitaxel and curcumin co-loaded liposomes have sustained-release properties in vitro. In vivo, there was no significant difference in pharmacokinetic parameters between the RGD-modified paclitaxel and curcumin co-loaded liposomes and paclitaxel and curcumin co-loaded liposomes. A strong green fluorescence was observed in the cytoplasmic region after incubation of RGD-modified paclitaxel and curcumin co-loaded liposomes for 2 h. RGD-modified paclitaxel and curcumin co-loaded liposomes showed a superior antiproliferative effect on A549 cells with a possible mechanism that suppressed the multidrug resistance phenomenon and exhibited a clear synergistic effect. The results indicate that RGD-modified paclitaxel and curcumin co-loaded liposomes had a better antitumor effect in vivo than the non-modified LPs. These results indicate that RGD-modified co-loaded liposomes are a promising candidate for antitumor drug delivery.

Nanostructured lipid carrier-loaded hyaluronic acid microneedles for controlled dermal delivery of a lipophilic molecule

PubMed Central

Lee, Sang Gon; Jeong, Jae Han; Lee, Kyung Min; Jeong, Kyu Ho; Yang, Huisuk; Kim, Miroo; Jung, Hyungil; Lee, Sangkil; Choi, Young Wook

2014-01-01

Nanostructured lipid carriers (NLCs) were employed to formulate a lipophilic drug into hydrophilic polymeric microneedles (MNs). Hyaluronic acid (HA) was selected as a hydrophilic and bioerodible polymer to fabricate MNs, and nile red (NR) was used as a model lipophilic molecule. NR-loaded NLCs were consolidated into the HA-based MNs to prepare NLC-loaded MNs (NLC-MNs). A dispersion of NLCs was prepared by high-pressure homogenization after dissolving NR in Labrafil and mixing with melted Compritol, resulting in 268 nm NLCs with a polydispersity index of 0.273. The NLC dispersion showed a controlled release of NR over 24 hours, following Hixson–Crowell’s cube root law. After mixing the NLC dispersion with the HA solution, the drawing lithography method was used to fabricate NLC-MNs. The length, base diameter, and tip diameter of the NLC-MNs were approximately 350, 380, and 30 μm, respectively. Fluorescence microscopic imaging of the NLC-MNs helped confirm that the NR-loaded NLCs were distributed evenly throughout the MNs. In a skin permeation study performed using a Franz diffusion cell with minipig dorsal skin, approximately 70% of NR was localized in the skin after 24-hour application of NLC-MNs. Confocal laser scanning microscopy (z-series) of the skin at different depths showed strong fluorescence intensity in the epidermal layer, which appeared to spread out radially with the passage of time. This study indicated that incorporation of drug-loaded NLCs into MNs could represent a promising strategy for controlled dermal delivery of lipophilic drugs. PMID:24403833

Synthesis and characterization of 12-aminolauric acid-modified montmorillonite for catalytic application

NASA Astrophysics Data System (ADS)

Pagtalunan, Cris Angelo M.; Sumera, Florentino C.; Conato, Marlon T.

2018-05-01

The simple cation-exchange preparation of 12-aminolauric acid-modified montmorillonite (ALA-Mt), an aluminosilicate clay modified with the alkylammonium surfactant, is reported. Different loadings of 12-aminolauric acid (12-ALA) from 100 to 400 times the cation exchange capacity (CEC) in montmorillonite (Mt) was prepared and studied. Successful intercalation of the organic surfactant was monitored by the increase in basal (d001) spacing of the organoclay compared to the pure Mt. The clay mineral composite have increased surfactant loading resulting to lower degradation temperatures, rougher surface morphology, increased particle size, and increased organophilicity of the organoclay compared to the native Mt. The improved properties of ALA-Mt present it as an attractive catalyst material for polymerization reactions.

Pretreating wheat straw by phosphoric acid plus hydrogen peroxide for enzymatic saccharification and ethanol production at high solid loading.

PubMed

Qiu, Jingwen; Ma, Lunjie; Shen, Fei; Yang, Gang; Zhang, Yanzong; Deng, Shihuai; Zhang, Jing; Zeng, Yongmei; Hu, Yaodong

2017-08-01

Wheat straw was pretreated by phosphoric acid plus hydrogen peroxide (PHP) for enzymatic hydrolysis and ethanol fermentation at high solid loadings. Results indicated solid loading could reach 20% with 77.4% cellulose-glucose conversion and glucose concentration of 164.9g/L in hydrolysate, it even was promoted to 25% with only 3.4% decrease on cellulose-glucose conversion as the pretreated-wheat straw was dewatered by air-drying. 72.9% cellulose-glucose conversion still was achieved as the minimized enzyme input of 20mg protein/g cellulose was employed for hydrolysis at 20% solid loading. In the corresponding conditions, 100g wheat straw can yield 11.2g ethanol with concentration of 71.2g/L by simultaneous saccharification and fermentation. Thus, PHP-pretreatment benefitted the glucose or ethanol yield at high solid loadings with lower enzyme input. Additionally, decreases on the maximal cellulase adsorption and the direct-orange/direct-blue indicated drying the PHP-pretreated substrates negatively affected the hydrolysis due to the shrinkage of cellulase-size-accommodable pores. Copyright © 2017 Elsevier Ltd. All rights reserved.

A biogeochemical comparison of two well-buffered catchments with contrasting histories of acid deposition

USGS Publications Warehouse

Shanley, J.B.; Kram, P.; Hruska, J.; Bullen, T.D.

2004-01-01

Much of the biogeochemical cycling research in catchments in the past 25 years has been driven by acid deposition research funding. This research has focused on vulnerable base-poor systems; catchments on alkaline lithologies have received little attention. In regions of high acid loadings, however, even well-buffered catchments are susceptible to forest decline and episodes of low alkalinity in streamwater. As part of a collaboration between the Czech and U.S. Geological Surveys, we compared biogeochemical patterns in two well-studied, well-buffered catchments: Pluhuv Bor in the western Czech Republic, which has received high loading of atmospheric acidity, and Sleepers River Research Watershed in Vermont, U.S.A., where acid loading has been considerably less. Despite differences in lithology, wetness, forest type, and glacial history, the catchments displayed similar patterns of solute concentrations and flow. At both catchments, base cation and alkalinity diluted with increasing flow, whereas nitrate and dissolved organic carbon increased with increasing flow. Sulfate diluted with increasing flow at Sleepers River, while at Pluhuv Bor the sulfate-flow relation shifted from positive to negative as atmospheric sulfur (S) loadings decreased and soil S pools were depleted during the 1990s. At high flow, alkalinity decreased to near 100 ??eq L-1 at Pluhuv Bor compared to 400 ??eq L-1 at Sleepers River. Despite the large amounts of S flushed from Pluhuv Bor soils, these alkalinity declines were caused solely by dilution, which was greater at Pluhuv Bor relative to Sleepers River due to greater contributions from shallow flow paths at high flow. Although the historical high S loading at Pluhuv Bor has caused soil acidification and possible forest damage, it has had little effect on the acid/base status of streamwater in this well-buffered catchment. ?? 2004 Kluwer Academic Publishers.

Host and tissue variations overshadow the response of boreal moss-associated fungal communities to increased nitrogen load.

PubMed

Davey, Marie L; Skogen, Marte J; Heegaard, Einar; Halvorsen, Rune; Kauserud, Håvard; Ohlson, Mikael

2017-01-01

Human activity has more than doubled the amount of nitrogen entering the global nitrogen cycle, and the boreal forest biome is a nitrogen-limited ecosystem sensitive to nitrogen load perturbation. Although bryophyte-associated microbes contribute significantly to boreal forest ecosystem function, particularly in carbon and nitrogen cycling, little is known about their responses to anthropogenic global change. Amplicon pyrosequencing of the ITS2 region of rDNA was used to investigate how fungal communities associated with three bryophyte species responded to increased nitrogen loads in a long-term fertilization experiment in a boreal Picea abies forest in southern Norway. Overall, OTU richness, community composition and the relative abundance of specific ecological guilds were primarily influenced by host species identity and tissue type. Although not the primary factor affecting fungal communities, nitrogen addition did impact the abundance of specific guilds of fungi and the resulting overall community composition. Increased nitrogen loads decreased ectomycorrhizal abundance, with Amphinema, Cortinarius, Russula and Tylospora OTUs responding negatively to fertilization. Pathogen abundance increased with fertilization, particularly in the moss pathogen Eocronartium. Saprophytic fungi were both positively and negatively impacted by the nitrogen addition, indicating a complex community level response. The overshadowing of the effects of increased nitrogen loads by variation related to host and tissue type highlights the complexity of bryophyte-associated microbial communities and the intricate nature of their responses to anthropogenic global change. © 2016 John Wiley & Sons Ltd.

Prolonged infusion of amino acids increases leucine oxidation in fetal sheep

PubMed Central

Maliszewski, Anne M.; Gadhia, Monika M.; O'Meara, Meghan C.; Thorn, Stephanie R.; Rozance, Paul J.

2012-01-01

Maternal high-protein supplements designed to increase birth weight have not been successful. We recently showed that maternal amino acid infusion into pregnant sheep resulted in competitive inhibition of amino acid transport across the placenta and did not increase fetal protein accretion rates. To bypass placental transport, singleton fetal sheep were intravenously infused with an amino acid mixture (AA, n = 8) or saline [control (Con), n = 10] for ∼12 days during late gestation. Fetal leucine oxidation rate increased in the AA group (3.1 ± 0.5 vs. 1.4 ± 0.6 μmol·min−1·kg−1, P < 0.05). Fetal protein accretion (2.6 ± 0.5 and 2.2 ± 0.6 μmol·min−1·kg−1 in AA and Con, respectively), synthesis (6.2 ± 0.8 and 7.0 ± 0.9 μmol·min−1·kg−1 in AA and Con, respectively), and degradation (3.6 ± 0.6 and 4.5 ± 1.0 μmol·min−1·kg−1 in AA and Con, respectively) rates were similar between groups. Net fetal glucose uptake decreased in the AA group (2.8 ± 0.4 vs. 3.9 ± 0.1 mg·kg−1·min−1, P < 0.05). The glucose-O2 quotient also decreased over time in the AA group (P < 0.05). Fetal insulin and IGF-I concentrations did not change. Fetal glucagon increased in the AA group (119 ± 24 vs. 59 ± 9 pg/ml, P < 0.05), and norepinephrine (NE) also tended to increase in the AA group (785 ± 181 vs. 419 ± 76 pg/ml, P = 0.06). Net fetal glucose uptake rates were inversely proportional to fetal glucagon (r2 = 0.38, P < 0.05), cortisol (r2 = 0.31, P < 0.05), and NE (r2 = 0.59, P < 0.05) concentrations. Expressions of components in the mammalian target of rapamycin signaling pathway in fetal skeletal muscle were similar between groups. In summary, prolonged infusion of amino acids directly into normally growing fetal sheep increased leucine oxidation. Amino acid-stimulated increases in fetal glucagon, cortisol, and NE may contribute to a shift in substrate oxidation by the fetus from glucose to amino acids. PMID:22454287

Mutant E. coli strain with increased succinic acid production

DOEpatents

Donnelly, M.; Millard, C.S.; Stols, L.

1998-06-23

A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria. 2 figs.

Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

PubMed

Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

2015-02-01

Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

The role of non-covalent interactions in anticancer drug loading and kinetic stability of polymeric micelles.

PubMed

Yang, Chuan; Attia, Amalina B Ebrahim; Tan, Jeremy P K; Ke, Xiyu; Gao, Shujun; Hedrick, James L; Yang, Yi-Yan

2012-04-01

A new series of acid- and urea-functionalized polycarbonate block copolymers were synthesized via organocatalytic living ring-opening polymerization using methoxy poly(ethylene glycol) (PEG) as a macroinitiator to form micelles as drug delivery carriers. The micelles were characterized for critical micelle concentration, particle size and size distribution, kinetic stability and loading capacity for a model anticancer drug, doxorubicin (DOX) having an amine group. The acid/urea groups were placed in block forms (i.e. acid as the middle block or the end block) or randomly distributed in the polycarbonate block to investigate molecular structure effect. The micelles formed from the polymers in both random and block forms provided high drug loading capacity due to strong ionic interaction between the acid in the polymer and the amine in DOX. However, the polymers with acid and urea groups placed in the block forms formed micelles with wider size distribution (two size populations), and their DOX-loaded micelles were less stable. The number of acid/urea groups in the random form was further varied from 5 to 8, 13 and 19 to study its effects on self-assembly behaviors and DOX loading. An increased number of acid/urea groups yielded DOX-loaded micelles with smaller size and enhanced kinetic stability because of improved inter-molecular polycarbonate-polycarbonate (urea-urea and urea-acid) hydrogen-bonding and polycarbonate-DOX (acid-amine) ionic interactions. However, when the number of acid/urea groups was 13 or higher, micelles aggregated in a serum-containing medium, and freeze-dried DOX-loaded micelles were unable to re-disperse in an aqueous solution. Among all the polymers synthesized in this study, 1b with 8 acid/urea groups in the random form had the optimum properties. In vitro release studies showed that DOX release from 1b micelles was sustained over 7 h without significant initial burst release. MTT assays demonstrated that the polymer was not toxic towards

Overexpression of acetyl-CoA synthetase in Saccharomyces cerevisiae increases acetic acid tolerance.

PubMed

Ding, Jun; Holzwarth, Garrett; Penner, Michael H; Patton-Vogt, Jana; Bakalinsky, Alan T

2015-01-01

Acetic acid-mediated inhibition of the fermentation of lignocellulose-derived sugars impedes development of plant biomass as a source of renewable ethanol. In order to overcome this inhibition, the capacity of Saccharomyces cerevisiae to synthesize acetyl-CoA from acetic acid was increased by overexpressing ACS2 encoding acetyl-coenzyme A synthetase. Overexpression of ACS2 resulted in higher resistance to acetic acid as measured by an increased growth rate and shorter lag phase relative to a wild-type control strain, suggesting that Acs2-mediated consumption of acetic acid during fermentation contributes to acetic acid detoxification. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Crop load and harvest maturity effects on consumer preferences for apricots.

PubMed

Stanley, Jill; Feng, Jinquan; Olsson, Shane

2015-03-15

Improving apricot fruit quality delivered to consumers is key to ensuring a successful apricot industry. Previous studies have focused on effects of either soluble solids content (SSC) or fruit firmness on consumer preferences, and results have been equivocal. This study evaluated the effects of crop load and harvest maturity how they affected on fruit SSC and firmness, and on subsequent consumer preferences. SSC of apricots was an important factor only when fruit were firmer than 15 N and not immature. When fruit were softer than 15 N, SSC had little influence on consumer liking. In general, consumers preferred fruit that were grown on trees thinned to approximately 10-20% less than typical commercial crop loads and were harvested in a more mature condition. Consumers also preferred fruit that had a higher sugar/acid ratio or BrimA value, which is the °Brix - k × titratable acidity, where k is a constant that varies between species and cultivars depending on the specific acids and sugars present. High apricot flavour and juiciness were associated with greater sweetness. Management practices that increase fruit SSC and sugar/acid ratio, such as reducing crop load, will improve consumer satisfaction as long as fruit are harvested at an adequate maturity stage and are maintained in storage so that they do not soften too quickly. © 2014 Society of Chemical Industry.

X-ray visible and doxorubicin-loaded beads based on inherently radiopaque poly(lactic acid)-polyurethane for chemoembolization therapy.

PubMed

Sang, Lin; Luo, Dongdong; Wei, Zhiyong; Qi, Min

2017-06-01

The aim of current study was to develop drug-loaded polymeric beads with intrinsic X-ray visibility as embolic agents, targeting for noninvasive intraoperative location and postoperative examination during chemoembolization therapy. To endow polymer with inherent radiopacity, 4,4'-isopropylidinedi-(2,6-diiodophenol) (IBPA) was firstly synthesized and employed as a contrast agent, and then a set of radiopaque iodinated poly(lactic acid)-polyurethanes (I-PLAUs) via chain extender method were synthesized and characterized. These I-PLAU copolymers possessed sufficient radiopacity, in vitro non-cytotoxicity with human adipose-derived stem cells, and in vivo biocompatibility and degradability in rabbit model via intramuscular implantation. Doxorubicin (DOX), as a chemotherapeutic agent, was further incorporated into I-PLAU beads via a double emulsification (W/O/W) method. For drug release, two ratios of DOX-loaded I-PLAU beads exhibited calibrated size (200-550μm), porous internal structure, good X-ray visibility, evenly drug loading as well as tunable drug release. A preliminary test on in vitro tumor cell toxicity demonstrated that the DOX-loaded I-PLAU beads performed efficient anti-tumor effect. This study highlights novel X-ray visible drug-loaded I-PLAU beads used as promising embolic agents for non-invasive in situ X-ray tracking and efficient chemotherapy, which could bring opportunities to the next generation of multifunctional embolic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Fruit load induces changes in global gene expression and in abscisic acid (ABA) and indole acetic acid (IAA) homeostasis in citrus buds.

PubMed

Shalom, Liron; Samuels, Sivan; Zur, Naftali; Shlizerman, Lyudmila; Doron-Faigenboim, Adi; Blumwald, Eduardo; Sadka, Avi

2014-07-01

Many fruit trees undergo cycles of heavy fruit load (ON-Crop) in one year, followed by low fruit load (OFF-Crop) the following year, a phenomenon known as alternate bearing (AB). The mechanism by which fruit load affects flowering induction during the following year (return bloom) is still unclear. Although not proven, it is commonly accepted that the fruit or an organ which senses fruit presence generates an inhibitory signal that moves into the bud and inhibits apical meristem transition. Indeed, fruit removal from ON-Crop trees (de-fruiting) induces return bloom. Identification of regulatory or metabolic processes modified in the bud in association with altered fruit load might shed light on the nature of the AB signalling process. The bud transcriptome of de-fruited citrus trees was compared with those of ON- and OFF-Crop trees. Fruit removal resulted in relatively rapid changes in global gene expression, including induction of photosynthetic genes and proteins. Altered regulatory mechanisms included abscisic acid (ABA) metabolism and auxin polar transport. Genes of ABA biosynthesis were induced; however, hormone analyses showed that the ABA level was reduced in OFF-Crop buds and in buds shortly following fruit removal. Additionally, genes associated with Ca(2+)-dependent auxin polar transport were remarkably induced in buds of OFF-Crop and de-fruited trees. Hormone analyses showed that auxin levels were reduced in these buds as compared with ON-Crop buds. In view of the auxin transport autoinhibition theory, the possibility that auxin distribution plays a role in determining bud fate is discussed. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Running speed increases plantar load more than per cent body weight on an AlterG® treadmill.

PubMed

Thomson, Athol; Einarsson, Einar; Witvrouw, Erik; Whiteley, Rod

2017-02-01

AlterG® treadmills allow for running at different speeds as well as at reduced bodyweight (BW), and are used during rehabilitation to reduce the impact load. The aim of this study was to quantify plantar loads borne by the athlete during rehabilitation. Twenty trained male participants ran on the AlterG® treadmill in 36 conditions: all combinations of indicated BW (50-100%) paired with different walking and running speeds (range 6-16 km · hr -1 ) in a random order. In-shoe maximum plantar force (Fmax) was recorded using the Pedar-X system. Fmax was lowest at the 6 km · hr -1 at 50% indicated BW condition at 1.02 ± 0.21BW and peaked at 2.31 ± 0.22BW for the 16 km · hr -1 at 100% BW condition. Greater increases in Fmax were seen when increasing running speed while holding per cent BW constant than the reverse (0.74BW-0.91BW increase compared to 0.19-0.31BW). A table is presented with each of the 36 combinations of BW and running speed to allow a more objective progression of plantar loading during rehabilitation. Increasing running speed rather than increasing indicated per cent BW was shown to have the strongest effect on the magnitude of Fmax across the ranges of speeds and indicated per cent BWs examined.

Preparation, characterization, and antibacterial activity studies of silver-loaded poly(styrene-co-acrylic acid) nanocomposites.

PubMed

Song, Cunfeng; Chang, Ying; Cheng, Ling; Xu, Yiting; Chen, Xiaoling; Zhang, Long; Zhong, Lina; Dai, Lizong

2014-03-01

A simple method for preparing a new type of stable antibacterial agent was presented. Monodisperse poly(styrene-co-acrylic acid) (PSA) nanospheres, serving as matrices, were synthesized via soap-free emulsion polymerization. Field-emission scanning electron microscopy micrographs indicated that PSA nanospheres have interesting surface microstructures and well-controlled particle size distributions. Silver-loaded poly(styrene-co-acrylic acid) (PSA/Ag-NPs) nanocomposites were prepared in situ through interfacial reduction of silver nitrate with sodium borohydride, and further characterized by transmission electron microscopy and X-ray diffraction. Their effects on antibacterial activity including inhibition zone, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and bactericidal kinetics were evaluated. In the tests, PSA/Ag-NPs nanocomposites showed excellent antibacterial activity against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli. These nanocomposites are considered to have potential application in antibacterial coatings on biomedical devices to reduce nosocomial infection rates. Copyright © 2013 Elsevier B.V. All rights reserved.

Exogenous fatty acids affect CDP-choline pathway to increase phosphatidylcholine synthesis in granular pneumocytes

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

Chander, A.; Gullo, J.; Reicherter, J.

1987-05-01

Regulation of phosphatidylcholine (PC) synthesis in rat granular pneumocytes isolated by tryptic digestion of lungs and maintained in primary culture for 24 h was investigated by following effects of exogenous fatty acids on (/sup 3/H-methyl)choline incorporation into PC and disaturated PC (DSPC). At 0.1 mM choline, the rate of choline incorporation into PC and DSPC was 440 +/- and 380 +/- 50 pmol/h/ug Pi (mean +/- SE, n=3-5), respectively, and was linear for up to 3 h. PC synthesis was significantly increased by 0.1 mM each of palmitic, oleic, linoleic, or linolenic acid. However, synthesis of DSPC was increased onlymore » by palmitic acid and this increase was prevented by addition of oleic acid suggesting lack of effect on the remodeling pathway. Pulse-chase experiments with choline in absence or presence of palmitic or oleic acid showed that the label declined in choline phosphate and increased in PC more rapidly in presence of either of the fatty acids, suggesting rapid conversion of choline phosphate to PC. Microsomal choline phosphate cytidyltransferase activity in cells preincubated without or with palmitic acid for 3 h was 0.81 +/- 0.07 and 1.81 +/- 0.09 nmol choline phosphate converted/min/mg protein (n=4). These results suggest that in granular pneumocytes, exogenous fatty acids modulate PC synthesis by increasing choline phosphate cytidyltransferase activity.« less

Competitive effects of humic acid and wastewater on adsorption of Methylene Blue dye by activated carbon and non-imprinted polymers.

PubMed

Murray, Audrey; Örmeci, Banu

2018-04-01

Natural organic matter (NOM), present in natural waters and wastewater, decreases adsorption of micropollutants, increasing treatment costs. This research investigated mechanisms of competition for non-imprinted polymers (NIPs) and activated carbon with humic acid and wastewater. Three different types of activated carbons (Norit PAC 200, Darco KB-M, and Darco S-51) were used for comparison with the NIP. The lower surface area and micropore to mesopore ratio of the NIP led to decreased adsorption capacity in comparison to the activated carbons. In addition, experiments were conducted for single-solute adsorption of Methylene Blue (MB) dye, simultaneous adsorption with humic acid and wastewater, and pre-loading with humic acid and wastewater followed by adsorption of MB dye using NIP and Norit PAC 200. Both the NIP and PAC 200 showed significant decreases of 27% for NIP (p=0.087) and 29% for PAC 200 (p=0.096) during simultaneous exposure to humic acid and MB dye. There was no corresponding decrease for NIP or PAC 200 pre-loaded with humic acid and then exposed to MB. In fact, for PAC 200, the adsorption capacity of the activated carbon increased when it was pre-loaded with humic acid by 39% (p=0.0005). For wastewater, the NIP showed no significant increase or decrease in adsorption capacity during either simultaneous exposure or pre-loading. The adsorption capacity of PAC 200 increased by 40% (p=0.001) for simultaneous exposure to wastewater and MB. Pre-loading with wastewater had no effect on MB adsorption by PAC 200. Copyright © 2017. Published by Elsevier B.V.

Biocompatible 5-Aminolevulinic Acid/Au Nanoparticle-Loaded Ethosomal Vesicles for In Vitro Transdermal Synergistic Photodynamic/Photothermal Therapy of Hypertrophic Scars

NASA Astrophysics Data System (ADS)

Zhang, Zheng; Chen, Yunsheng; Ding, Jiayue; Zhang, Chunlei; Zhang, Amin; He, Dannong; Zhang, Yixin

2017-12-01

Biocompatible 5-aminolevulinic acid/Au nanoparticle-loaded ethosomal vesicle (A/A-ES) is prepared via ultrasonication for synergistic transdermal photodynamic/photothermal therapy (PDT/PTT) of hypertrophic scar (HS). Utilizing ultrasonication, Au nanoparticles (AuNPs) are synthesized and simultaneously loaded in ethosomal vesicles (ES) without any toxic agents, and 5-aminolevulinic acid (ALA) is also loaded in ES with 20% of the entrapment efficiency (EE). The prepared A/A-ES displays strong absorbance in 600-650 nm due to the plasmonic coupling effect between neighboring AuNPs in the same A/A-ES, which can simultaneously stimulate A/A-ES to produce heat and enhance quantum yields of reactive oxygen species (ROS) by using 632 nm laser. In vitro transdermal penetrability study demonstrates that A/A-ES acts as a highly efficient drug carrier to enhance both ALA and AuNPs penetration into HS tissue . Taking human hypertrophic scar fibroblasts (HSF) as therapeutic targets, synergistic PDT/PTT of HS indicates that A/A-ES could enhance quantum yields of ROS by photothermal effect and localized surface plasmon resonance (LSPR) of AuNPs, resulting in a high level of apoptosis or necrosis. In a word, the prepared A/A-ES shows a better synergistic PDT/PTT efficiency for HSF than the individual PDT and PTT, encouraging perspective for treatment of HS.

Silymarin-Loaded Nanoparticles Based on Stearic Acid-Modified Bletilla striata Polysaccharide for Hepatic Targeting.

PubMed

Ma, Yanni; He, Shaolong; Ma, Xueqin; Hong, Tongtong; Li, Zhifang; Park, Kinam; Wang, Wenping

2016-02-29

Silymarin has been widely used as a hepatoprotective drug in the treatment of various liver diseases, yet its effectiveness is affected by its poor water solubility and low bioavailability after oral administration, and there is a need for the development of intravenous products, especially for liver-targeting purposes. In this study, silymarin was encapsulated in self-assembled nanoparticles of Bletilla striata polysaccharide (BSP) conjugates modified with stearic acid and the physicochemical properties of the obtained nanoparticles were characterized. The silymarin-loaded micelles appeared as spherical particles with a mean diameter of 200 nm under TEM. The encapsulation of drug molecules was confirmed by DSC thermograms and XRD diffractograms, respectively. The nanoparticles exhibited a sustained-release profile for nearly 1 week with no obvious initial burst. Compared to drug solutions, the drug-loaded nanoparticles showed a lower viability and higher uptake intensity on HepG2 cell lines. After intravenous administration of nanoparticle formulation for 30 min to mice, the liver became the most significant organ enriched with the fluorescent probe. These results suggest that BSP derivative nanoparticles possess hepatic targeting capability and are promising nanocarriers for delivering silymarin to the liver.

A novel delivery system of doxorubicin with high load and pH-responsive release from the nanoparticles of poly (α,β-aspartic acid) derivative.

PubMed

Wang, Xiaojuan; Wu, Guolin; Lu, Caicai; Zhao, Weipeng; Wang, Yinong; Fan, Yunge; Gao, Hui; Ma, Jianbiao

2012-08-30

A poly (amino acid)-based amphiphilic copolymer was utilized to fabricate a better micellar drug delivery system (DDS) with improved compatibility and sustained release of doxorubicin (DOX). First, poly (ethylene glycol) monomethyl ether (mPEG) and DOX were conjugated onto polyasparihyazide (PAHy), prepared by hydrazinolysis of the poly (succinimide) (PSI), to afford an amphiphilic polymer [PEG-hyd-P (AHy-hyd-DOX)] with acid-liable hydrazone bonds. The DOX, chemically conjugated to the PAHy, was designed to supply hydrophobic segments. PEGs were also grafted to the polymer via hydrazone bonds to supply hydrophiphilic segments and prolong its lifetime in blood circulation. Free DOX molecules could be entrapped into the nanoparticles fabricated by such an amphiphilic polymer (PEG-hyd-P (AHy-hyd-DOX)), via hydrophobic interaction and π-π stacking between the conjugated and free DOX molecules to obtain a pH responsive drug delivery system with high DOX loaded. The drug loading capacity, drug release behavior, and morphology of the micelles were investigated. The biological activity of micelles was evaluated in vitro. The drug loading capacity was intensively augmented by adjusting the feed ratio, and the maximum loading capacity was as high as 38%. Besides, the DOX-loaded system exhibited pH-dependent drug release profiles in vitro. The cumulative release of DOX was much faster at pH 5.0 than that at pH 7.4. The DOX-loaded system kept highly antitumor activity for a long time, compared with free DOX. This easy-prepared DDS, with features of biocompatibility, biodegradability, high drug loading capacity and pH-responsiveness, was a promising controlled release delivery system for DOX. Copyright © 2012 Elsevier B.V. All rights reserved.

Erosion and attrition of human enamel in vitro part II: influence of time and loading.

PubMed

Eisenburger, M; Addy, M

2002-01-01

To determine the influence of load and time on enamel wear by attrition under neutral and acid environments in vitro. Groups of 10 enamel cusp and smooth surface specimens obtained from unerupted third molars were opposed in a wear machine under loads of 200, 400 and 600 g in citric acid at pH 3.2 and in physiological saline at 35 degrees C for 30 min (2280 wear cycles). The experiment was repeated with a load of 600 g for 10 and 20 min accompanied by 10 taped specimens to measure erosion only. Erosion and attrition of smooth surface specimens was determined by profilometry. At a load of 600 g attrition in saline increased with time from 7.9 microm (SD 3.7 microm) at 10 min, 10.2 microm (SD 4.8 microm) at 20-25.5 microm (SD 9.1 microm) after 30 min and combined attrition/erosion in citric acid from 1.5 microm (SD 0.4 microm) to 2.5 microm (SD 0.9 microm) to 6.0 microm (SD 3.7 microm). At a fixed time of 30 min, attrition in saline was 5.2 microm (SD 3.6 microm) at 200 g and 8.1 microm (SD 1.5 microm) at 400 g and combined attrition/erosion in citric acid 2.8 microm (SD 1.2 microm) and 3.6 microm (SD 0.7 microm). Comparison between both environments revealed significant differences at fixed load at all time points (p < 0.01) and at fixed time between 400 and 600 g (p < 0.01). Load and time significantly influence enamel wear both in acid and neutral conditions but the effects were not linear. Copyright 2002 Elsevier Science Ltd.

Load theory behind the wheel; perceptual and cognitive load effects.

PubMed

Murphy, Gillian; Greene, Ciara M

2017-09-01

Perceptual Load Theory has been proposed as a resolution to the longstanding early versus late selection debate in cognitive psychology. There is much evidence in support of Load Theory but very few applied studies, despite the potential for the model to shed light on everyday attention and distraction. Using a driving simulator, the effect of perceptual and cognitive load on drivers' visual search was assessed. The findings were largely in line with Load Theory, with reduced distractor processing under high perceptual load, but increased distractor processing under high cognitive load. The effect of load on driving behaviour was also analysed, with significant differences in driving behaviour under perceptual and cognitive load. In addition, the effect of perceptual load on drivers' levels of awareness was investigated. High perceptual load significantly increased inattentional blindness and deafness, for stimuli that were both relevant and irrelevant to driving. High perceptual load also increased RTs to hazards. The current study helps to advance Load Theory by illustrating its usefulness outside of traditional paradigms. There are also applied implications for driver safety and roadway design, as the current study suggests that perceptual and cognitive load are important factors in driver attention. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Forest ecosystems and the changing patterns of nitrogen input and acid deposition today and in the future based on a scenario.

PubMed

Busch, G; Lammel, G; Beese, F O; Feichter, J; Dentener, F J; Roelofs, G J

2001-01-01

A global assessment of the impact of the anthropogenic perturbation of the nitrogen and sulfur cycles on forest ecosystems is carried out for both the present-day [1980-1990] and for a projection into the future [2040-2050] under a scenario of economic development which represents a medium path of development according to expert guess [IPCC IS92a]. Results show that forest soils will receive considerably increasing loads of nitrogen and acid deposition and that deposition patterns are likely to change. The regions which are most prone to depletion of soils buffering capacity and supercritical nitrogen deposition are identified in the subtropical and tropical regions of South America and Southeast Asia apart from the well known 'hotspots' North-Eastern America and Central Europe. The forest areas likely to meet these two risks are still a minor fraction of the global forest ecosystems, though. But the bias between eutrophication and acidification will become greater and an enhanced growth triggered by the fertilizing effects of increasing nitrogen input cannot be balanced by the forest soils nutrient pools. Results show increasing loads into forest ecosystems which are likely to account for 46% higher acid loads and 36% higher nitrogen loads in relation to the 1980-1990 situation. Global background deposition of up to 5 kg N ha-1 a-1 will be exceeded at more than 25% of global forest ecosystems and at more than 50% of forest ecosystems on acid sensitive soils. More than 33% of forest ecosystems on acid sensitive soils will receive acid loads which exceeds their buffering capacity. About 25% of forest areas with exceeded acid loads will receive critical nitrogen loads.

Olive oil increases the magnitude of postprandial chylomicron remnants compared to milk fat and safflower oil.

PubMed

Higashi, K; Ishikawa, T; Shige, H; Tomiyasu, K; Yoshida, H; Ito, T; Nakajima, K; Yonemura, A; Sawada, S; Nakamura, H

1997-10-01

The acute effects of olive oil, milk fat and safflower oil on postprandial lipemia and remnant lipoprotein metabolism were investigated. Eight Healthy male volunteers randomly underwent three types of oral fat-vitamin A loading tests. The test drink was a mixture of retinyl palmitate (RP)(50,000 IU of aqueous vitamin A/m2 body surface area) and one of the three types of oils (40 g of fat/m2 body surface area): olive oil (70.7% oleic acid of total fatty acids); milk fat (69.3% saturated fatty acid); safflower oil (74.2% linoleic acid). Olive oil significantly increased plasma triacylglycerol and RP concentrations 4 hours after fat loading, as compared to other fats. Increases of remnant like particle concentrations were higher after olive oil than after the other two fats. These results show that olive oil increases the magnitude of postprandial chylomicrons and chylomicron remnants compared to milk fat and safflower oil.

Polyaspartic acid functionalized gold nanoparticles for tumor targeted doxorubicin delivery.

PubMed

Khandekar, Sameera V; Kulkarni, M G; Devarajan, Padma V

2014-01-01

In this paper, we present polyaspartic acid, a biodegradable polymer as a reducing and functionalizing agent for the synthesis of doxorubicin loaded gold nanoparticles by a green process. Gold nanoparticles were stable to electrolytes and pH. Secondary amino groups of polyaspartic acid enabled reduction of gold chloride to form gold nanoparticles of size 55 +/-10 nm, with face centered cubic crystalline structure as confirmed by UV, TEM, SAED and XRD studies. Cationic doxorubicin was readily loaded onto anionic polyaspartic acid gold nanoparticles by ionic complexation. Fluorescence studies confirmed doxorubicin loading while FTIR spectra confirmed ionic complexation. Doxorubicin loading onto polyaspartic acid gold nanoparticles was studied at doxorubicin/polyaspartic acid molar ratios 1:10 to 1:1. As the molar ratio tended to unity, although loading up to 60% was achieved, colloidal instability resulted and is attributed to effective covering of negative charges of polyaspartic acid. Stable doxorubicin loaded polyaspartic acid gold nanoparticles of 105 +/- 15.1 nm with doxorubicin loading of 23.85% w/w and zeta potential value of -28 +/- 0.77 mV were obtained at doxorubicin/polyaspartic acid molar ratio 1:10. Higher doxorubicin release rate from the doxorubicin loaded polyaspartic acid gold nanoparticles in an acid medium (i.e., pH 5.5) as compared to that in pH 7.4 and deionized water is a desirable characteristic for tumor targeted delivery. Enhanced cytotoxicity and 3 fold higher uptake of doxorubicin loaded polyaspartic acid gold nanoparticles as compared to doxorubicin solution were seen in MCF-7 breast cancer cells while polyaspartic acid gold nanoparticles revealed no cytotoxicity confirming safety. Prominent regression in tumor size in-vivo in fibrosarcoma tumor induced mouse model was observed upto 59 days with doxorubicin loaded polyaspartic acid gold nanoparticles while doxorubicin solution treated mice showed regrowth beyond 23rd day. Moreover, a

Dacarbazine-Loaded Hollow Mesoporous Silica Nanoparticles Grafted with Folic Acid for Enhancing Antimetastatic Melanoma Response.

PubMed

Liu, Qianqian; Xu, Nan; Liu, Liping; Li, Jun; Zhang, Yamin; Shen, Chen; Shezad, Khurram; Zhang, Lianbin; Zhu, Jintao; Tao, Juan

2017-07-05

Dacarbazine (DTIC) is one of the most important chemotherapeutic agents for the treatment of melanoma; however, its poor solubility, photosensitivity, instability, and serious toxicity to normal cells limit its clinical applications. In this article, we present a rationally designed nanocarrier based on hollow mesoporous silica nanoparticles (HMSNs) for the encapsulation and targeted release of DTIC for eradicating melanoma. The nanocarrier (DTIC@HMLBFs) is prepared by modifying HMSNs with carboxyl groups to enhance the loading of DTIC, followed by further enveloping of folic acid-grafted liposomes, which act as a melanoma active target for controlled and targeted drug release. In vitro, DTIC@HMLBFs exhibited the strongest cytotoxicity to melanoma cells compared with DTIC@HMSNs and free DTIC. The in vivo investigations demonstrate that the rationally designed nanocarrier loaded with DTIC achieves significant improvement against lung metastasis of melanoma via targeting melanoma cells and tumor-associated macrophages. This study provides a promising platform for the design and fabrication of multifunctional nanomedicines, which are potentially useful for the treatment of melanoma.

Chronic administration of docosahexaenoic acid or eicosapentaenoic acid, but not arachidonic acid, alone or in combination with uridine, increases brain phosphatide and synaptic protein levels in gerbils.

PubMed

Cansev, M; Wurtman, R J

2007-08-24

Synthesis of phosphatidylcholine, the most abundant brain membrane phosphatide, requires three circulating precursors: choline; a pyrimidine (e.g. uridine); and a polyunsaturated fatty acid. Supplementing a choline-containing diet with the uridine source uridine-5'-monophosphate (UMP) or, especially, with UMP plus the omega-3 fatty acid docosahexaenoic acid (given by gavage), produces substantial increases in membrane phosphatide and synaptic protein levels within gerbil brain. We now compare the effects of various polyunsaturated fatty acids, given alone or with UMP, on these synaptic membrane constituents. Gerbils received, daily for 4 weeks, a diet containing choline chloride with or without UMP and/or, by gavage, an omega-3 (docosahexaenoic or eicosapentaenoic acid) or omega-6 (arachidonic acid) fatty acid. Both of the omega-3 fatty acids elevated major brain phosphatide levels (by 18-28%, and 21-27%) and giving UMP along with them enhanced their effects significantly. Arachidonic acid, given alone or with UMP, was without effect. After UMP plus docosahexaenoic acid treatment, total brain phospholipid levels and those of each individual phosphatide increased significantly in all brain regions examined (cortex, striatum, hippocampus, brain stem, and cerebellum). The increases in brain phosphatides in gerbils receiving an omega-3 (but not omega-6) fatty acid, with or without UMP, were accompanied by parallel elevations in levels of pre- and post-synaptic proteins (syntaxin-3, PSD-95 and synapsin-1) but not in those of a ubiquitous structural protein, beta-tubulin. Hence administering omega-3 polyunsaturated fatty acids can enhance synaptic membrane levels in gerbils, and may do so in patients with neurodegenerative diseases, especially when given with a uridine source, while the omega-6 polyunsaturated fatty acid arachidonic acid is ineffective.

Increasing Working Memory Load Reduces Processing of Cross-Modal Task-Irrelevant Stimuli Even after Controlling for Task Difficulty and Executive Capacity

PubMed Central

Simon, Sharon S.; Tusch, Erich S.; Holcomb, Phillip J.; Daffner, Kirk R.

2016-01-01

The classic account of the load theory (LT) of attention suggests that increasing cognitive load leads to greater processing of task-irrelevant stimuli due to competition for limited executive resource that reduces the ability to actively maintain current processing priorities. Studies testing this hypothesis have yielded widely divergent outcomes. The inconsistent results may, in part, be related to variability in executive capacity (EC) and task difficulty across subjects in different studies. Here, we used a cross-modal paradigm to investigate whether augmented working memory (WM) load leads to increased early distracter processing, and controlled for the potential confounders of EC and task difficulty. Twenty-three young subjects were engaged in a primary visual WM task, under high and low load conditions, while instructed to ignore irrelevant auditory stimuli. Demands of the high load condition were individually titrated to make task difficulty comparable across subjects with differing EC. Event-related potentials (ERPs) were used to measure neural activity in response to stimuli presented in both the task relevant modality (visual) and task-irrelevant modality (auditory). Behavioral results indicate that the load manipulation and titration procedure of the primary visual task were successful. ERPs demonstrated that in response to visual target stimuli, there was a load-related increase in the posterior slow wave, an index of sustained attention and effort. Importantly, under high load, there was a decrease of the auditory N1 in response to distracters, a marker of early auditory processing. These results suggest that increased WM load is associated with enhanced attentional engagement and protection from distraction in a cross-modal setting, even after controlling for task difficulty and EC. Our findings challenge the classic LT and offer support for alternative models. PMID:27536226

Increasing Working Memory Load Reduces Processing of Cross-Modal Task-Irrelevant Stimuli Even after Controlling for Task Difficulty and Executive Capacity.

PubMed

Simon, Sharon S; Tusch, Erich S; Holcomb, Phillip J; Daffner, Kirk R

2016-01-01

The classic account of the load theory (LT) of attention suggests that increasing cognitive load leads to greater processing of task-irrelevant stimuli due to competition for limited executive resource that reduces the ability to actively maintain current processing priorities. Studies testing this hypothesis have yielded widely divergent outcomes. The inconsistent results may, in part, be related to variability in executive capacity (EC) and task difficulty across subjects in different studies. Here, we used a cross-modal paradigm to investigate whether augmented working memory (WM) load leads to increased early distracter processing, and controlled for the potential confounders of EC and task difficulty. Twenty-three young subjects were engaged in a primary visual WM task, under high and low load conditions, while instructed to ignore irrelevant auditory stimuli. Demands of the high load condition were individually titrated to make task difficulty comparable across subjects with differing EC. Event-related potentials (ERPs) were used to measure neural activity in response to stimuli presented in both the task relevant modality (visual) and task-irrelevant modality (auditory). Behavioral results indicate that the load manipulation and titration procedure of the primary visual task were successful. ERPs demonstrated that in response to visual target stimuli, there was a load-related increase in the posterior slow wave, an index of sustained attention and effort. Importantly, under high load, there was a decrease of the auditory N1 in response to distracters, a marker of early auditory processing. These results suggest that increased WM load is associated with enhanced attentional engagement and protection from distraction in a cross-modal setting, even after controlling for task difficulty and EC. Our findings challenge the classic LT and offer support for alternative models.

Cardiorespiratory parameters in draught horses before and after short term draught work pulling loads.

PubMed

Pérez, R; Recabarren, S E; Mora, G; Jara, C; Quijada, G; Hetz, E

1992-04-01

In order to establish the relationship between draught force and cardiorespiratory responses to exercise heart rate (HR), respiratory rate (RR), arterial and venous blood gases, pH, hemoglobin concentration and temperature were measured in five draught horses during rest, immediately after exercise and 30 min post-exercise under field conditions. A wagon equipped with an odometer and a hydraulic dynamometer was used for measuring distance and draught force. The wagon was loaded with 946 kg for the low load, 1,979 kg for the medium load and 2,994 kg for the high load, and drawn for a distance of 1,500 m. Draught force and load weight were linearly related. The response of the draught horse to low and medium load exercise was characterized by a moderate increase in HR, RR and temperature with no significant changes in arterial blood gases and pH. An increase in HR, RR and temperature was observed, whereas no changes in arterial PO2 and increases in venous PO2 were noticed after high load exercise. Slight increase in venous lactic acid concentration as a result of high load exercise was observed, suggesting that some anaerobic work was performed. However this was insufficient to produce changes in blood pH. The increase in metabolic requirements during the three levels of draught exercise was associated with increases in arterial hemoglobin concentration and oxygen content of blood.

Elevated carbon dioxide increases salicylic acid in Glycine max.

PubMed

Casteel, Clare L; Segal, Lauren M; Niziolek, Olivia K; Berenbaum, May R; DeLucia, Evan H

2012-12-01

Concentrations of carbon dioxide (CO(2)) are increasing in the atmosphere, affecting soybean (Glycine max L.) phytohormone signaling and herbivore resistance. Whether the impact of elevated CO(2) on phytohormones and induced defenses is a generalized response within this species is an open question. We examined jasmonic acid (JA) and salicylic acid (SA) under ambient and elevated CO(2) concentrations with and without Japanese beetle (Popillia japonica Newman) damage and artificial damage across six soybean cultivars (HS93-4118, Pana, IA 3010, Loda, LN97-15076, and Dwight). Elevated CO(2) reduced constitutive levels of JA and related transcripts in some but not all soybean cultivars. In contrast to the variation in JA, constitutive levels of salicylic were increased universally among soybean cultivars grown under elevated CO(2). Variation in hormonal signaling may underpin observed variation in the response of insect herbivores and pathogens to plants grown under elevated CO(2).

Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes

PubMed Central

Heimann, Emilia; Nyman, Margareta; Degerman, Eva

2014-01-01

Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have “anti-obesity properties” by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic acid and butyric acid inhibit isoproterenol- and adenosine deaminase-stimulated lipolysis as well as isoproterenol-stimulated lipolysis in the presence of a phosphodiesterase (PDE3) inhibitor. In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis. Furthermore, we show that propionic acid and butyric acid increase insulin-stimulated glucose uptake. To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes. Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes. PMID:26167409

Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes.

PubMed

Heimann, Emilia; Nyman, Margareta; Degerman, Eva

2015-01-01

Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have "anti-obesity properties" by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic acid and butyric acid inhibit isoproterenol- and adenosine deaminase-stimulated lipolysis as well as isoproterenol-stimulated lipolysis in the presence of a phosphodiesterase (PDE3) inhibitor. In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis. Furthermore, we show that propionic acid and butyric acid increase insulin-stimulated glucose uptake. To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes. Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes.

Oleic, Linoleic and Linolenic Acids Increase ROS Production by Fibroblasts via NADPH Oxidase Activation

PubMed Central

Hatanaka, Elaine; Dermargos, Alexandre; Hirata, Aparecida Emiko; Vinolo, Marco Aurélio Ramirez; Carpinelli, Angelo Rafael; Newsholme, Philip; Armelin, Hugo Aguirre; Curi, Rui

2013-01-01

The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts. PMID:23579616

Expression of dehydratase domains from a polyunsaturated fatty acid synthase increases the production of fatty acids in Escherichia coli.

PubMed

Oyola-Robles, Delise; Rullán-Lind, Carlos; Carballeira, Néstor M; Baerga-Ortiz, Abel

2014-02-05

Increasing the production of fatty acids by microbial fermentation remains an important step toward the generation of biodiesel and other portable liquid fuels. In this work, we report an Escherichia coli strain engineered to overexpress a fragment consisting of four dehydratase domains from the polyunsaturated fatty acid (PUFA) synthase enzyme complex from the deep-sea bacterium, Photobacterium profundum. The DH1-DH2-UMA enzyme fragment was excised from its natural context within a multi-enzyme PKS and expressed as a stand-alone protein. Fatty acids were extracted from the cell pellet, esterified with methanol and quantified by GC-MS analysis. Results show that the E. coli strain expressing the DH tetradomain fragment was capable of producing up to a 5-fold increase (80.31 mg total FA/L culture) in total fatty acids over the negative control strain lacking the recombinant enzyme. The enhancement in production was observed across the board for all the fatty acids that are typically made by E. coli. The overexpression of the DH tetradomain did not affect E. coli cell growth, thus showing that the observed enhancement in fatty acid production was not a result of effects associated with cell density. The observed enhancement was more pronounced at lower temperatures (3.8-fold at 16 °C, 3.5-fold at 22 °C and 1.5-fold at 30 °C) and supplementation of the media with 0.4% glycerol did not result in an increase in fatty acid production. All these results taken together suggest that either the dehydration of fatty acid intermediates are a limiting step in the E. coli fatty acid biosynthesis machinery, or that the recombinant dehydratase domains used in this study are also capable of catalyzing thioester hydrolysis of the final products. The enzyme in this report is a new tool which could be incorporated into other existing strategies aimed at improving fatty acid production in bacterial fermentations toward accessible biodiesel precursors. Copyright © 2013 Elsevier Inc

Effect of cocoa pod husk filler loading on tensile properties of cocoa pod husk/polylactic acid green biocomposite films

NASA Astrophysics Data System (ADS)

Sanyang, M. L.; Sapuan, S. M.; Haron, M.

2017-10-01

Over the years, cocoa-pod husk (CPH) generation significantly increased due to the growing global demand of chocolate products, since cocoa bean is the main ingredient for chocolate production. Proper utilization of CPH as natural filler for reinforcement of polymer composites provides economic advantages as well as environmental solutions for CPH waste disposal problems. In this study, CPH filled PLA composite films were developed using solution casting method. The effect of CPH loading on the tensile properties of CPH/PLA composite films were investigated. The obtained results manifested that increasing CPH loading from 0% to 10 % significantly increased tensile strength of CPH/PLA composite. However, further addition of CPH loading up to 15 % decreased the tensile strength of film samples. As CPH loading increased from 0% to 15%, tensile modulus of CPH/PLA composite films also increased from 1.5MPa to 10.4MPa, whereas their elongation at break reduced from 190% to 90%. These findings points out CPH as a potential natural filler for reinforcing thermoplastic polymer composites.

Paclitaxel loaded folic acid targeted nanoparticles of mixed lipid-shell and polymer-core: in vitro and in vivo evaluation.

PubMed

Zhao, Peiqi; Wang, Hanjie; Yu, Man; Liao, Zhenyu; Wang, Xianhuo; Zhang, Fei; Ji, Wei; Wu, Bing; Han, Jinghua; Zhang, Haichang; Wang, Huaqing; Chang, Jin; Niu, Ruifang

2012-06-01

A functional drug carrier comprised of folic acid modified lipid-shell and polymer-core nanoparticles (FLPNPs) including poly(D,L-lactide-co-glycolide) (PLGA) core, PEGylated octadecyl-quaternized lysine modified chitosan (PEG-OQLCS) as lipid-shell, folic acid as targeting ligand and cholesterol was prepared and evaluated for targeted delivery of paclitaxel (PTX). Confocal microscopy analysis confirmed the coating of the lipid-shell on the polymer-core. Physicochemical characterizations of FLPNPs, such as particle size, zeta potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. The internalization efficiency and targeting ability of FLPNPs were demonstrated by flow cytometry and confocal microscopy. PTX loaded FLPNPs showed a significantly higher cytotoxicity than the commercial PTX formulation (Taxol®). The intravenous administration of PTX encapsulated FLPNPs led to tumor regression and improvement of animal survival in a murine model, compared with that observed with Taxol® and biodistribution study showed that PTX concentration in tumor for PTX encapsulated FLPNPs was higher than other PTX formulations. Our data indicate that PTX loaded FLPNPs are a promising nano-sized drug formulation for cancer therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

Increased proximal acid reflux is associated with early readmission following lung transplantation.

PubMed

Lo, W-K; Goldberg, H J; Burakoff, R; Feldman, N; Chan, W W

2016-02-01

Gastroesophageal reflux disease has been associated with poor outcomes following lung transplantation. However, the association between pretransplant reflux and post-transplant readmission, an indicator of early clinical outcome, has not been previously assessed. This was a retrospective cohort study of lung transplant recipients undergoing pretransplant multichannel intraluminal impedance and pH (MII-pH) study off acid suppression at a tertiary care center since 2007. Subjects with pretransplant fundoplication were excluded. Time to readmission was defined as duration from post-transplant discharge to next hospital admission for any reason. Subgroup analysis was performed to exclude elective readmissions. Time-to-event analysis was performed using Cox proportional hazards model, with appropriate censoring. Forty-three subjects (60% men, mean age: 57, median follow-up: 1.7 years) met inclusion criteria for the study. Patient demographics and pretransplant cardiopulmonary function were similar between readmission cohorts. Time to all-cause readmission was associated with increased distal acid episodes (HR: 3.15, p = 0.04) and proximal acid episodes (HR: 3.61, p = 0.008) on impedance, increased acid exposure on pH (HR: 2.22, p = 0.04), and elevated Demeester score (HR: 2.26, p = 0.03). When elective readmissions were excluded, early readmission remained significantly associated with increased proximal acid reflux episodes (HR: 2.49, p = 0.04). All findings were confirmed on Kaplan-Meier analysis. Elevated proximal acid reflux on pretransplant MII-pH testing was associated with early readmission following lung transplantation, even after excluding elective readmissions. Exposure to severe acid reflux has measurable effects on early postoperative outcomes such as readmission, and aggressive early antireflux therapy should be considered. © 2015 John Wiley & Sons Ltd.

Root colonization by symbiotic arbuscular mycorrhizal fungi increases sesquiterpenic acid concentrations in Valeriana officinalis L.

PubMed

Nell, Monika; Wawrosch, Christoph; Steinkellner, Siegrid; Vierheilig, Horst; Kopp, Brigitte; Lössl, Andreas; Franz, Chlodwig; Novak, Johannes; Zitterl-Eglseer, Karin

2010-03-01

In some medicinal plants a specific plant-fungus association, known as arbuscular mycorrhizal (AM) symbiosis, increases the levels of secondary plant metabolites and/or plant growth. In this study, the effects of three different AM treatments on biomass and sesquiterpenic acid concentrations in two IN VITRO propagated genotypes of valerian ( VALERIANA OFFICINALIS L., Valerianaceae) were investigated. Valerenic, acetoxyvalerenic and hydroxyvalerenic acid levels were analyzed in the rhizome and in two root fractions. Two of the AM treatments significantly increased the levels of sesquiterpenic acids in the underground parts of valerian. These treatments, however, influenced the biomass of rhizomes and roots negatively. Therefore this observed increase was not accompanied by an increase in yield of sesquiterpenic acids per plant. Furthermore, one of the two genotypes had remarkably high hydroxyvalerenic acid contents and can be regarded as a hydroxyvalerenic acid chemotype. Copyright Georg Thieme Verlag KG Stuttgart New York.

Chronic administration of docosahexaenoic acid or eicosapentaenoic acid, but not arachidonic acid, alone or in combination with uridine, increases brain phosphatide and synaptic protein levels in gerbils

PubMed Central

Cansev, M.; Wurtman, R. J.

2007-01-01

Synthesis of phosphatidylcholine, the most abundant brain membrane phosphatide, requires three circulating precursors: choline; a pyrimidine (e.g., uridine); and a polyunsaturated fatty acid. Supplementing a choline-containing diet with the uridine source uridine-5′-monophosphate (UMP) or, especially, with UMP plus the omega-3 fatty acid docosahexaenoic acid (given by gavage), produces substantial increases in membrane phosphatide and synaptic protein levels within gerbil brain. We now compare the effects of various polyunsaturated fatty acids, given alone or with UMP, on these synaptic membrane constituents. Gerbils received, daily for 4 weeks, a diet containing choline chloride with or without UMP and/or, by gavage, an omega-3 (docosahexaenoic or eicosapentaenoic acid) or omega-6 (arachidonic acid) fatty acid. Both of the omega-3 fatty acids elevated major brain phosphatide levels (by 18-28%, and 21-27%) and giving UMP along with them enhanced their effects significantly. Arachidonic acid, given alone or with UMP, was without effect. After UMP plus docosahexaenoic acid treatment, total brain phospholipids levels and those of each individual phosphatide increased significantly in all brain regions examined (cortex, striatum, hippocampus, brain stem, and cerebellum). The increases in brain phosphatides in gerbils receiving an omega-3 (but not omega-6) fatty acid, with or without UMP, were accompanied by parallel elevations in levels of pre- and post-synaptic proteins (syntaxin-3, PSD-95 and Synapsin-1) but not in those of a ubiquitous structural protein, β-tubulin. Hence administering omega-3 polyunsaturated fatty acids can enhance synaptic membrane levels in gerbils, and may do so in patients with neurodegenerative diseases, especially when given with a uridine source, while the omega-6 polyunsaturated fatty acid arachidonic acid is ineffective. PMID:17683870

Hygienic quality of artificial greywater subjected to aerobic treatment: a comparison of three filter media at increasing organic loading rates.

PubMed

Lalander, Cecilia; Dalahmeh, Sahar; Jönsson, Håkan; Vinnerås, Björn

2013-01-01

With a growing world population, the lack of reliable water sources is becoming an increasing problem. Reusing greywater could alleviate this problem. When reusing greywater for crop irrigation it is paramount to ensure the removal of pathogenic organisms. This study compared the pathogen removal efficiency of pine bark and activated charcoal filters with that of conventional sand filters at three organic loading rates. The removal efficiency of Escherichia coli O157:H7 decreased drastically when the organic loading rate increased fivefold in the charcoal and sand filters, but increased by 2 log10 in the bark filters. The reduction in the virus model organism coliphage phiX174 remained unchanged with increasing organic loading in the charcoal and sand filters, but increased by 2 log10 in the bark filters. Thus, bark was demonstrated to be the most promising material for greywater treatment in terms of pathogen removal.

Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration.

PubMed

Han, Xiaofeng; Wang, Zhe; Wang, Manyuan; Li, Jing; Xu, Yongsong; He, Rui; Guan, Hongyu; Yue, Zhujun; Gong, Muxin

2016-06-01

In order to enhance oral bioavailability and liver targeting delivery of silybin, two amphiphilic hyaluronic acid derivatives, hyaluronic acid-deoxycholic acid (HA-adh-DOCA) and hyaluronic acid-glycyrrhetinic acid (HA-adh-GA) conjugates, were designed and synthesized. Silybin was successfully loaded in HA-adh-DOCA and HA-adh-GA micelles with high drug-loading capacities (20.3% ± 0.5% and 20.6% ± 0.6%, respectively). The silybin-loaded micelles were spherical in shape with the average size around 130 nm. In vitro release study showed that two silybin-loaded micelles displayed similar steady continued-release pattern in simulated gastrointestinal fluids and PBS. Single-pass intestinal perfusion studies indicated that silybin-loaded micelles were absorbed in the whole intestine and transported via a passive diffusion mechanism. Compared with suspension formulation, silybin-loaded HA-adh-DOCA and HA-adh-GA micelles achieved significantly higher AUC and Cmax level. Moreover, liver targeting drug delivery of micelles was confirmed by in vivo imaging analysis. In comparison between the two micellar formulations, HA-adh-GA micelles possessed higher targeting capacity than HA-adh-DOCA micelles, owing to the active hepatic targeting properties of glycyrrhetinic acid. In the treatment of acute liver injury induced by CCl4, silybin-loaded HA-adh-GA micelles displayed better effects over suspension control and silybin-loaded HA-adh-DOCA micelles. Overall, pharmaceutical and pharmacological indicators suggested that the HA-adh-GA conjugates can be successfully utilized for liver targeting of orally administered therapeutics.

C-Myc Induced Compensated Cardiac Hypertrophy Increases Free Fatty Acid Utilization for the Citric Acid Cycle

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

Olson, Aaron; Ledee, Dolena; Iwamoto, Kate

The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc-induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam). Isolated working hearts and 13Carbon (13C )-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing 13C-labeled free fatty acids,more » acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was confirmed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contribution in NTG. Substrate utilization was not significantly altered in 3dMyc versus cont. The free fatty acid FC was significantly greater in 7dMyc vs cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the mechanisms whereby this change

The Molecular Basis for Load-Induced Skeletal Muscle Hypertrophy

PubMed Central

Marcotte, George R.; West, Daniel W.D.; Baar, Keith

2016-01-01

In a mature (weight neutral) animal, an increase in muscle mass only occurs when the muscle is loaded sufficiently to cause an increase in myofibrillar protein balance. A tight relationship between muscle hypertrophy, acute increases in protein balance, and the activity of the mechanistic target of rapamycin complex 1 (mTORC1) was demonstrated 15 years ago. Since then, our understanding of the signals that regulate load-induced hypertrophy has evolved considerably. For example, we now know that mechanical load activates mTORC1 in the same way as growth factors, by moving TSC2 (a primary inhibitor of mTORC1) away from its target (the mTORC activator) Rheb. However, the kinase that phosphorylates and moves TSC2 is different in the two processes. Similarly, we have learned that a distinct pathway exists whereby amino acids activate mTORC1 by moving it to Rheb. While mTORC1 remains at the forefront of load-induced hypertrophy, the importance of other pathways that regulate muscle mass are becoming clearer. Myostatin, is best known for its control of developmental muscle size. However, new mechanisms to explain how loading regulates this process are suggesting that it could play an important role in hypertrophic muscle growth as well. Lastly, new mechanisms are highlighted for how β2 receptor agonists could be involved in load-induced muscle growth and why these agents are being developed as non-exercise-based therapies for muscle atrophy. Overall, the results highlight how studying the mechanism of load-induced skeletal muscle mass is leading the development of pharmaceutical interventions to promote muscle growth in those unwilling or unable to perform resistance exercise. PMID:25359125

Systemic study of solvent-assisted active loading of gambogic acid into liposomes and its formulation optimization for improved delivery.

PubMed

Tang, Wei-Lun; Tang, Wei-Hsin; Szeitz, Andras; Kulkarni, Jayesh; Cullis, Pieter; Li, Shyh-Dar

2018-06-01

The solvent-assisted active loading technology (SALT) was developed for encapsulating a water insoluble weak base into the liposomal core in the presence of 5% DMSO. In this study, we further examined the effect of various water miscible solvents in promoting active loading of other types of drugs into liposomes. To achieve complete drug loading, the amount of solvent required must result in complete drug solubilization and membrane permeability enhancement, but must be below the threshold that induces liposomal aggregation or causes bilayer disruption. We then used the SALT to load gambogic acid (GA, an insoluble model drug that shows promising anticancer effect) into liposomes, and optimized the loading gradient and lipid composition to prepare a stable formulation (Lipo-GA) that displayed >95% drug retention after incubation with serum for 3 days. Lipo-GA contained a high drug-to-lipid ratio of 1/5 (w/w) with a mean particle size of ∼75 nm. It also displayed a prolonged circulation half-life (1.5 h vs. 18.6 h) and enhanced antitumor activity in two syngeneic mice models compared to free GA. Particularly, complete tumor regression was observed in the EMT6 tumor model for 14 d with significant inhibition of multiple oncogenes including HIF-1α, VEGF-A, STAT3, BCL-2, and NF-κB. Copyright © 2018 Elsevier Ltd. All rights reserved.

3-Acetyl-11-keto-beta-boswellic acid loaded-polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity.

PubMed

Goel, Amit; Ahmad, Farhan Jalees; Singh, Raman Mohan; Singh, Gyanendra Nath

2010-02-01

The aim of this study was to develop 3-acetyl-11-keto-beta-boswellic acid (AKBA)-loaded polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity. Polymeric nanomicelles of AKBA were developed by a radical polymerization method using N-isopropylacrylamide, vinylpyrrolidone and acrylic acid. The polymeric nanomicelles obtained were characterized by Fourier transform infrared (FTIR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). In-vitro and in-vivo evaluations of AKBA polymeric nanomicelles gel were carried out for enhanced skin permeability and anti-inflammatory and anti-arthritic activity. TEM and DLS results demonstrated that polymeric nanomicelles were spherical with a mean diameter approximately 45 nm. FTIR data indicated a weak interaction between polymer and AKBA in the encapsulated system. The release of drug in aqueous buffer (pH 7.4) from the polymeric nanomicelles was 23 and 55% after 2 and 8 h, respectively, indicating sustained release. In-vitro skin permeation studies through excised abdominal skin indicated a threefold increase in skin permeability compared with AKBA gel containing the same amount of AKBA as the AKBA polymeric nanomicelles gel. The AKBA polymeric nanomicelle gel showed significantly enhanced anti-inflammatory and anti-arthritic activity compared with the AKBA gel. This study suggested that AKBA polymeric nanomicelle gel significantly enhanced skin permeability, and anti-inflammatory and anti-arthritic activity.

Expiratory muscle loading increases intercostal muscle blood flow during leg exercise in healthy humans

PubMed Central

Athanasopoulos, Dimitris; Louvaris, Zafeiris; Cherouveim, Evgenia; Andrianopoulos, Vasilis; Roussos, Charis; Zakynthinos, Spyros

2010-01-01

We investigated whether expiratory muscle loading induced by the application of expiratory flow limitation (EFL) during exercise in healthy subjects causes a reduction in quadriceps muscle blood flow in favor of the blood flow to the intercostal muscles. We hypothesized that, during exercise with EFL quadriceps muscle blood flow would be reduced, whereas intercostal muscle blood flow would be increased compared with exercise without EFL. We initially performed an incremental exercise test on eight healthy male subjects with a Starling resistor in the expiratory line limiting expiratory flow to ∼ 1 l/s to determine peak EFL exercise workload. On a different day, two constant-load exercise trials were performed in a balanced ordering sequence, during which subjects exercised with or without EFL at peak EFL exercise workload for 6 min. Intercostal (probe over the 7th intercostal space) and vastus lateralis muscle blood flow index (BFI) was calculated by near-infrared spectroscopy using indocyanine green, whereas cardiac output (CO) was measured by an impedance cardiography technique. At exercise termination, CO and stroke volume were not significantly different during exercise, with or without EFL (CO: 16.5 vs. 15.2 l/min, stroke volume: 104 vs. 107 ml/beat). Quadriceps muscle BFI during exercise with EFL (5.4 nM/s) was significantly (P = 0.043) lower compared with exercise without EFL (7.6 nM/s), whereas intercostal muscle BFI during exercise with EFL (3.5 nM/s) was significantly (P = 0.021) greater compared with that recorded during control exercise (0.4 nM/s). In conclusion, increased respiratory muscle loading during exercise in healthy humans causes an increase in blood flow to the intercostal muscles and a concomitant decrease in quadriceps muscle blood flow. PMID:20507965

Enhanced intracellular delivery and antibacterial efficacy of enrofloxacin-loaded docosanoic acid solid lipid nanoparticles against intracellular Salmonella.

PubMed

Xie, Shuyu; Yang, Fei; Tao, Yanfei; Chen, Dongmei; Qu, Wei; Huang, Lingli; Liu, Zhenli; Pan, Yuanhu; Yuan, Zonghui

2017-01-23

Enrofloxacin-loaded docosanoic acid solid lipid nanoparticles (SLNs) with different physicochemical properties were developed to enhance activity against intracellular Salmonella. Their cellular uptake, intracellular elimination and antibacterial activity were studied in RAW 264.7 cells. During the experimental period, SLN-encapsulated enrofloxacin accumulated in the cells approximately 27.06-37.71 times more efficiently than free drugs at the same extracellular concentration. After incubation for 0.5 h, the intracellular enrofloxacin was enhanced from 0.336 to 1.147 μg/mg of protein as the sizes of nanoparticles were increased from 150 to 605 nm, and from 0.960 to 1.147 μg/mg of protein when the charge was improved from -8.1 to -24.9 mv. The cellular uptake was more significantly influenced by the size than it was by the charge, and was not affected by whether the charge was positive or negative. The elimination of optimal SLN-encapsulated enrofloxacin from the cells was significantly slower than that of free enrofloxacin after removing extracellular drug. The inhibition effect against intracellular Salmonella CVCC541 of 0.24 and 0.06 μg/mL encapsulated enrofloxacin was stronger than 0.6 μg/mL free drug after all of the incubation periods and at 48 h, respectively. Docosanoic acid SLNs are thus considered as a promising carrier for intracellular bacterial treatment.

Influence of increased mechanical loading by hypergravity on the microtubule cytoskeleton and prostaglandin E2 release in primary osteoblasts

NASA Technical Reports Server (NTRS)

Searby, Nancy D.; Steele, Charles R.; Globus, Ruth K.

2005-01-01

Cells respond to a wide range of mechanical stimuli such as fluid shear and strain, although the contribution of gravity to cell structure and function is not understood. We hypothesized that bone-forming osteoblasts are sensitive to increased mechanical loading by hypergravity. A centrifuge suitable for cell culture was developed and validated, and then primary cultures of fetal rat calvarial osteoblasts at various stages of differentiation were mechanically loaded using hypergravity. We measured microtubule network morphology as well as release of the paracrine factor prostaglandin E2 (PGE2). In immature osteoblasts, a stimulus of 10x gravity (10 g) for 3 h increased PGE2 2.5-fold and decreased microtubule network height 1.12-fold without affecting cell viability. Hypergravity (3 h) caused dose-dependent (5-50 g) increases in PGE2 (5.3-fold at 50 g) and decreases (1.26-fold at 50 g) in microtubule network height. PGE2 release depended on duration but not orientation of the hypergravity load. As osteoblasts differentiated, sensitivity to hypergravity declined. We conclude that primary osteoblasts demonstrate dose- and duration-dependent sensitivity to gravitational loading, which appears to be blunted in mature osteoblasts.

Changes in Indirect Markers of Muscle Damage and Tendons After Daily Drop Jumping Exercise with Rapid Load Increase

PubMed Central

Paleckis, Vidas; Mickevičius, Mantas; Snieckus, Audrius; Streckis, Vytautas; Pääsuke, Mati; Rutkauskas, Saulius; Steponavičiūtė, Rasa; Skurvydas, Albertas; Kamandulis, Sigitas

2015-01-01

The aim of this study was to assess changes in indirect markers of muscle damage and type I collagen degradation, as well as, patellar and Achilles tendon morphological differences during nine daily drop-jumps sessions with constant load alternated with rapid increases in load to test the hypothesis that frequent drop-jump training results in negative muscular and tendon adaptation. Young men (n = 9) performed daily drop jump workouts with progression every 3 days in terms of number of jumps, platform height and squat amplitude. Voluntary and electrically evoked knee extensor torque, muscle soreness, blood plasma creatine kinase (CK) activity and carboxyterminal cross-linked telopeptide (ICTP), patellar and Achilles tendon thickness and cross-sectional area (CSA) were assessed at different time points during the training period and again on days 1, 3, 10 and 17 after the training. The findings were as follows: (1) steady decline in maximal muscle strength with major recovery within 24 hours after the first six daily training sessions; (2) larger decline in electrically induced muscle torque and prolonged recovery during last three training sessions; (3) increase in patellar and Achilles tendons CSA without change in thickness towards the end of training period; (4) increase in jump height but not in muscle strength after whole training period. Our findings suggest that frequent drop-jump sessions with constant load alternated with rapid increases in load do not induce severe muscle damage or major changes in tendons, nonetheless, this type of loading is not advisable for muscle strength improvement. Key points Frequent drop jump training induces activation mode dependent muscle torque depression late in the training period. No significant changes in the thickness of patellar and Achilles tendons are observed during frequent training, while CSA increases towards the end of training period. Longitudinal effect for jump height but not for muscle strength is evident

Ursodeoxycholic acid increases low-density lipoprotein binding, uptake and degradation in isolated hamster hepatocytes.

PubMed Central

Bouscarel, B; Fromm, H; Ceryak, S; Cassidy, M M

1991-01-01

Ursodeoxycholic acid (UDCA), in contrast to both chenodeoxycholic acid (CDCA), its 7 alpha-epimer, and lithocholic acid, enhanced receptor-dependent low-density lipoprotein (LDL) uptake and degradation in isolated hamster hepatocytes. The increase in cell-associated LDL was time- and concentration-dependent, with a maximum effect observed at approx. 60 min with 1 mM-UDCA. This increase was not associated with a detergent effect of UDCA, as no significant modifications were observed either in the cellular release of lactate dehydrogenase or in Trypan Blue exclusion. The effect of UDCA was not due to a modification of the LDL particle, but rather was receptor-related. UDCA (1 mM) maximally increased the number of 125I-LDL-binding sites (Bmax.) by 35%, from 176 to 240 ng/mg of protein, without a significant modification of the binding affinity. Furthermore, following proteolytic degradation of the LDL receptor with Pronase, specific LDL binding decreased to the level of non-specific binding, and the effect of UDCA was abolished. Conversely, the trihydroxy 7 beta-hydroxy bile acid ursocholic acid and its 7 alpha-epimer, cholic acid, induced a significant decrease in LDL binding by approx. 15%. The C23 analogue of UDCA (nor-UDCA) and CDCA did not affect LDL binding. On the other hand, UDCA conjugated with either glycine (GUDCA) or taurine (TUDCA), increased LDL binding to the same extent as did the free bile acid. The half maximum time (t1/2) to reach the full effect was 1-2 min for UDCA and TUDCA, while GUDCA had a much slower t1/2 of 8.3 min. Ketoconazole (50 microM), an antifungal agent, increased LDL binding, but this effect was not additive when tested in the presence of 0.7 mM-UDCA. The results of the studies indicate that, in isolated hamster hepatocytes, the UDCA-induced increase in receptor-dependent LDL binding and uptake represents a direct effect of this bile acid. The action of the bile acid is closely related to its specific structural conformation, since

Effect of household cooking techniques on the microbiological load and the nutritional quality of mealworms (Tenebrio molitor L. 1758).

PubMed

Caparros Megido, Rudy; Poelaert, Christine; Ernens, Marjorie; Liotta, Marisa; Blecker, Christophe; Danthine, Sabine; Tyteca, Eva; Haubruge, Éric; Alabi, Taofic; Bindelle, Jérôme; Francis, Frédéric

2018-04-01

Mealworms are new food products in Europe, but consumers do not know how to cook them. Although cooking could increase the safety, acceptability, palatability, and digestibility of insects, the heating process could have deleterious effects on protein and lipid quality. Therefore, this study characterized the effects of different household cooking methods (boiling, pan-frying, vacuum cooking, and oven cooking) on the microbial load and nutritive value of mealworms, with a focus on protein digestibility and fatty acid composition. Boiling and cooking under vacuum were the most efficient techniques to reduce microbial load while maintaining the high levels of protein and polyunsaturated fatty acids of mealworms. Cooking method-related changes were very low on macronutrients content except for pan-fried mealworms which exhibited the highest lipid content. Cooking slightly changed fatty acid composition of mealworms by principally decreasing their level of saturated fatty acids but also increased the in vitro crude protein digestibility of mealworms. Copyright © 2018 Elsevier Ltd. All rights reserved.

The influence of increased distal loading on metabolic cost, efficiency, and kinematics of roller ski skating.

PubMed

Bolger, Conor M; Bessone, Veronica; Federolf, Peter; Ettema, Gertjan; Sandbakk, Øyvind

2018-01-01

The purpose of the present study was to examine the influence of increased loading of the roller ski on metabolic cost, gross efficiency, and kinematics of roller ski skating in steep and moderate terrain, while employing two incline-specific techniques. Ten nationally ranked male cross-country skiers were subjected to four 7-minute submaximal intervals, with 0, 0.5, 1.0, and 1.5 kg added beneath the roller-ski in a randomized order. This was done on two separate days, with the G2 skating at 12% incline and 7 km/h speed and G3 skating at 5% incline and 14 km/h speed, respectively. At 12% incline, there was a significant increase in metabolic rate and a decrease in gross efficiency with added weight (P<0.001 and P = 0.002). At 5% incline, no change in metabolic rate or gross efficiency was found (P = 0.89 and P = 0.11). Rating of perceived exertion (RPE) increased gradually with added weight at both inclines (P>0.05). No changes in cycle characteristics were observed between the different ski loadings at either incline, although the lateral and vertical displacements of the foot/skis were slightly altered at 12% incline with added weight. In conclusion, the present study demonstrates that increased loading of the ski increases the metabolic cost and reduces gross efficiency during steep uphill roller skiing in G2 skating, whereas no significant effect was revealed when skating on relatively flat terrain in G3. Cycle characteristics remained unchanged across conditions at both inclines, whereas small adjustments in the displacement of the foot coincided with the efficiency changes in uphill terrain. The increased RPE values with added ski-weight at both inclines indicates that other factors than those measured here could have influenced effort and/or fatigue when lifting a heavier ski.

Patupilone-loaded poly(L-glutamic acid)-graft-methoxy-poly(ethylene glycol) micelle for oncotherapy.

PubMed

Yan, Jing; Zhang, Dawei; Yu, Haiyang; Ma, Lili; Deng, Mingxiao; Tang, Zhaohui; Zhang, Xuefei

2017-03-01

Patupilone, an original natural anti-cancer agent, also known as epothilone B or Epo906, has shown promise for the treatment of a variety of cancers, however, the systematic side effects of patupilone significantly impaired its clinical translation. Herein, patupilone-loaded PLG-g-mPEG micelles were prepared. Patupilone was grafted to a poly(L-glutamic acid)-graft-methoxy-poly(ethylene glycol) (PLG-g-mPEG) by Steglich esterification reaction to give PLG-g-mPEG/Epo906 that could self-assemble to form patupilone-loaded micelles (Epo906-M). The Epo906-M was able to inhibit the proliferation of A549, MCF-7 cancer cells and BEAs-2B cells in vitro. For in vivo treatment of orthotopic xenograft tumor models (MCF-7), the Epo906-M exhibited higher tumor inhibition efficiency with lower side effects as compared with free Epo906. Seventeen percent of the body weight loss appeared in the group treated with free Epo906 of 0.25 mg kg -1 , while the group treated with Epo906-M of 10 mg kg -1 showed less than ten percent of body weight loss and displayed stronger tumor inhibiting effect. Therefore, the polypeptide-patupilone conjugate has improved potential for oncotherapy.

Countermovement Jump Performance with Increased Training Loads in Elite Female Rugby Athletes.

PubMed

Gathercole, R; Sporer, B; Stellingwerff, T

2015-08-01

Countermovement jump (CMJ) performance is typically analyzed through single-point concentric-based variables (e. g., peak power or force and height). However, methodological approaches examining movement strategies may be more sensitive to neuromuscular fatigue. 12 elite female rugby sevens athletes undertook weekly CMJ testing throughout a 6-week training block involving progressively increased training loads. Athletes self-reported training load (TRIMP) and wellness daily. 22 CMJ variables were assessed, incorporating analyses of force, velocity, power and time measured during eccentric and concentric jump phases. Differences over time were examined using the magnitude of change (effect sizes; ES) compared to baseline. Pearson correlations examined relationships between CMJ variables, wellness and TRIMP. TRIMP displayed large increases (mean ES; weeks 2-6: 2.47). Wellness decreased in week 3 (-0.41), with small reductions following (weeks 4-6: -0.34). Flight time (weeks 3-6: -1.84), peak displacement (weeks 2-6: -2.24), time to peak force (weeks 3-6: 2.58), force at zero velocity (F@0V) (weeks 5-6: -1.28) displayed multiple changes indicative of diminished neuromuscular function. Wellness scores and max rate of force development (mean; r=0.32), F@0V (r=0.28) and flight time (r=0.34) displayed positive correlations. Intensified training decreased CMJ output and altered CMJ mechanics. Longitudinal neuromuscular fatigue monitoring of team-sport athletes appears improved through CMJ mechanics analysis. © Georg Thieme Verlag KG Stuttgart · New York.

Idiopathic recurrent calcium urolithiasis (IRCU): an acid meal challenge uncovers inappropriate pH of postprandial, fasting and daily urine: a cross-sectional study of male patients providing insight into post- and pre-load urinary stone substances, crystallization risk, presence of stones, renal transport and systemic metabolic factors.

PubMed

Schwille, Paul O; Wipplinger, J

2008-07-28

In IRCU the possible role of urinary pH (U-pH) as risk factor of calcium (Ca) stones is poorly understood. To evaluate in IRCU the response to an oral acid load, focussing on post- and pre-load U-pH, other urinary, renal and extra-renal factors, and linkage with Ca stones. - 237 male patients, either Ca stone-free (SF) or -bearing (SB), but without overt signs of systemic metabolic acidosis underwent a standardized laboratory programme that included, besides collection of urine and blood, the intake of an oxalate-free acid test meal (proton content 120 mM). Established analytical methods were used. In 79 patients the post-meal load U-pH was < or = 5.30 (in healthy individuals accepted as the upper limit after the same proton load), but >5.30 in 158; in these two subsets the mean fasting pre-load U-pH was 5.84 and 6.37 (p <0.001), the mean U-pH in 24 h urine 5.70 and 6.03 (p <0.001), the mean score of stone formation activity 32 and 42 (p = 0.12), the SF/SB ratio 35/44 and 76/82 (not significant). However, when in pre-load urine undissociated uric acid concentration was low due to the high pH, the SF/SB ratio was 53/66 (p = 0.038), whereas isolated increase of U-pH with SF/SB ratio 54/65 (p = 0.059), urinary supersaturation with Ca phosphate (hydroxyapatite), Ca oxalate, uric acid, and isolated decrease of concentration of total protein, total uric acid and the crystallization inhibitors magnesium and citrate failed to affect significantly the frequency distribution of SF and SB patients. Pre-load U-pH was positively associated with urinary ratio sodium/proton excretion, renal reclaim of sodium and protein, negatively associated with body mass index, fasting insulinemia and uricemia, urinary protein concentration, renal reclaim of phosphate. In IRCU 1) inappropriately high U-pH combined with increase of proteinuria and alteration of renal-tubular transport are frequent; 2) disturbed interactions of renal proton generation with sodium handling, urinary physico

Lipid-drug-conjugate (LDC) solid lipid nanoparticles (SLN) for the delivery of nicotine to the oral cavity - optimization of nicotine loading efficiency.

PubMed

Ding, Yuan; Nielsen, Kent A; Nielsen, Bruno P; Bøje, Niels W; Müller, Rainer H; Pyo, Sung Min

2018-03-12

Nicotine, obtained from tobacco leaves, has been used to promote the cessation of smoking and reduce the risk of COPD and lung cancer. Incorporating the active in lipid nanoparticles is an effective tool to minimize its irritation potential and to use the particles as intermediate to produce final products. However, as a hydrophilic active, it is a challenge to prepare nicotine loaded lipid nanoparticles with high drug loading. In this study, lipid-drug-conjugates (LDC) were formed by nicotine and different fatty acids to enable the production of sufficiently loaded nicotine lipid nanoparticles. The encapsulation efficiency of nicotine in LDC-containing SLN was about 50%, which increased at least fourfold compared to the non-LDC formulations (around 10%) due to the increased lipophilicity of nicotine by strong interactions between positively charged nicotine and negatively charged fatty acids (formation of LDCs). The z-average of all formulations (150 to 350 nm) proved to be in the required submicron size range with a narrow size distribution. In summary, nicotine loaded LDC lipid nanoparticles with high drug loading were successfully developed with Kolliwax® S and stearic acid as counter-ion forming the LDC and hydrogenated sunflower oil (HSO) as lipid particle matrix. Copyright © 2018. Published by Elsevier B.V.

Evaluation of gallic acid loaded zein sub-micron electrospun fibre mats as novel active packaging materials.

PubMed

Neo, Yun Ping; Swift, Simon; Ray, Sudip; Gizdavic-Nikolaidis, Marija; Jin, Jianyong; Perera, Conrad O

2013-12-01

The applicability of gallic acid loaded zein (Ze-GA) electrospun fibre mats towards potential active food packaging material was evaluated. The surface chemistry of the electrospun fibre mats was determined using X-ray photon spectroscopy (XPS). The electrospun fibre mats showed low water activity and whitish colour. Thermogravimetric analysis (TGA) and Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy revealed the stability of the fibre mats over time. The Ze-GA fibre mats displayed similar rapid release profiles, with Ze-GA 20% exhibiting the fastest release rate in water as compared to the others. Gallic acid diffuses from the electrospun fibres in a Fickian diffusion manner and the data obtained exhibited a better fit to Higuchi model. L929 fibroblast cells were cultured on the electrospun fibres to demonstrate the absence of cytotoxicity. Overall, the Ze-GA fibre mats demonstrated antibacterial activity and properties consistent with those considered desirable for active packaging material in the food industry. Copyright © 2013 Elsevier Ltd. All rights reserved.

Fasting rapidly increases fatty acid oxidation in white adipose tissue of young broiler chickens.

PubMed

Torchon, Emmanuelle; Ray, Rodney; Hulver, Matthew W; McMillan, Ryan P; Voy, Brynn H

2017-01-02

Upregulating the fatty acid oxidation capacity of white adipose tissue in mice protects against diet-induced obesity, inflammation and insulin resistance. Part of this capacity results from induction of brown-like adipocytes within classical white depots, making it difficult to determine the oxidative contribution of the more abundant white adipocytes. Avian genomes lack a gene for uncoupling protein 1 and are devoid of brown adipose cells, making them a useful model in which to study white adipocyte metabolism in vivo. We recently reported that a brief (5 hour) period of fasting significantly upregulated many genes involved in mitochondrial and peroxisomal fatty acid oxidation pathways in white adipose tissue of young broiler chickens. The objective of this study was to determine if the effects on gene expression manifested in increased rates of fatty acid oxidation. Abdominal adipose tissue was collected from 21 day-old broiler chicks that were fasted for 3, 5 or 7 hours or fed ad libitum (controls). Fatty acid oxidation was determined by measuring and summing 14 CO 2 production and 14 C-labeled acid-soluble metabolites from the oxidation of [1- 14 C] palmitic acid. Fasting induced a progressive increase in complete fatty acid oxidation and citrate synthase activity relative to controls. These results confirm that fatty acid oxidation in white adipose tissue is dynamically controlled by nutritional status. Identifying the underlying mechanism may provide new therapeutic targets through which to increase fatty acid oxidation in situ and protect against the detrimental effects of excess free fatty acids on adipocyte insulin sensitivity.

Optimization of the Synthesis of Structured Phosphatidylcholine with Medium Chain Fatty Acid.

PubMed

Ochoa-Flores, Angélica A; Hernández-Becerra, Josafat A; Cavazos-Garduño, Adriana; Vernon-Carter, Eduardo J; García, Hugo S

2017-11-01

Structured phosphatidylcholine was successfully produced by acidolysis between phosphatidylcholine and free medium chain fatty acid, using phospholipase A 1 immobilized on Duolite A568. Response surface methodology was applied to optimize the reaction system using three process parameters: molar ratio of substrates (phosphatidylcholine to free medium chain fatty acid), enzyme loading, and reaction temperature. All parameters evaluated showed linear and quadratic significant effects on the production of modified phosphatidylcholine; molar ratio of substrates contributed positively, but temperature influenced negatively. Increased enzyme loading also led to increased production of modified phosphatidylcholine but only during the first 9 hours of the acidolysis reaction. Optimal conditions obtained from the model were a ratio of phosphatidylcholine to free medium chain fatty acid of 1:15, an enzyme loading of 12%, and a temperature of 45°C. Under these conditions a production of modified phosphatidylcholine of 52.98 % were obtained after 24 h of reaction. The prediction was confirmed from the verification experiments; the production of modified phosphatidylcholine was 53.02%, the total yield of phosphatidylcholine 64.28% and the molar incorporation of medium chain fatty acid was 42.31%. The acidolysis reaction was scaled-up in a batch reactor with a similar production of modified phosphatidylcholine, total yield of phosphatidylcholine and molar incorporation of medium chain fatty acid. Purification by column chromatography of the structured phosphatidylcholine yielded 62.53% of phosphatidylcholine enriched with 42.52% of medium chain fatty acid.

Plasma acylcarnitine profiling indicates increased fatty acid oxidation relative to tricarboxylic acid cycle capacity in young, healthy low birth weight men.

PubMed

Ribel-Madsen, Amalie; Ribel-Madsen, Rasmus; Brøns, Charlotte; Newgard, Christopher B; Vaag, Allan A; Hellgren, Lars I

2016-10-01

We hypothesized that an increased, incomplete fatty acid beta-oxidation in mitochondria could be part of the metabolic events leading to insulin resistance and thereby an increased type 2 diabetes risk in low birth weight (LBW) compared with normal birth weight (NBW) individuals. Therefore, we measured fasting plasma levels of 45 acylcarnitine species in 18 LBW and 25 NBW men after an isocaloric control diet and a 5-day high-fat, high-calorie diet. We demonstrated that LBW men had higher C2 and C4-OH levels after the control diet compared with NBW men, indicating an increased fatty acid beta-oxidation relative to the tricarboxylic acid cycle flux. Also, they had higher C6-DC, C10-OH/C8-DC, and total hydroxyl-/dicarboxyl-acylcarnitine levels, which may suggest an increased fatty acid omega-oxidation in the liver. Furthermore, LBW and NBW men decreased several acylcarnitine levels in response to overfeeding, which is likely a result of an upregulation of fatty acid oxidation due to the dietary challenge. Moreover, C10-OH/C8-DC and total hydroxyl-/dicarboxyl-acylcarnitine levels tended to be negatively associated with the serum insulin level, and the total hydroxyl-/dicarboxyl-acylcarnitine level additionally tended to be negatively associated with the hepatic insulin resistance index. This indicates that an increased fatty acid omega-oxidation could be a compensatory mechanism to prevent an accumulation of lipid species that impair insulin signaling. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Assessment of potential aluminum chelators in an octanol/aqueous system and in the aluminum-loaded rabbit.

PubMed

Yokel, R A; Kostenbauder, H B

1987-11-01

Aluminum (Al) solubilization from Al borate and its distribution in an octanol/aqueous system (Do/w) were determined in the absence and presence of 12 potential Al chelators. Citrate, N,N'-bis-(2-hydroxybenzyl)ethylenediamine- N,N'-diacetic acid (HBED), cyclohexane-1,2-diaminotetraacetic acid (CDTA), diethylenetriaminepentaacetic acid (DTPA), nitrilotriacetic acid (NTA), desferrioxamine, and ethylenediamine-N,N'-bis(2-dihydroxyphenylacetic acid) (EDDHA) were 55 to over 100% efficient in solubilizing equimolar amounts of Al. Tetracycline, EDTA, and 2,3-dihydroxybenzoic acid (DHBA) were less than 20% efficient. 1,4-Dioxane and fluoride were ineffective. The Do/w of Al averaged 0.005. The Do/w of the Al.chelator complex was generally less than that of Al, except for HBED and tetracycline (0.04 and 0.96, respectively). The Do/w of DHBA, desferrioxamine, EDDHA, and HBED were not influenced by Al, but tetracycline became more lipophilic. These compounds were tested for their ability to increase urinary Al excretion in Al-loaded rabbits. Chelators were given po weekly beginning 2 weeks after Al loading. Urine was obtained hourly from 3 hr prior to 6 hr after chelator administration and analyzed for Al. Fluoride and tetracycline (450 and 4500 mumol/kg) and citrate, NTA, EDTA, CDTA, DTPA, DHBA, HBED, and 1,4-dioxane (150 and 1500 mumol/kg) were ineffective. Following HBED administration, some of the Al-loaded rabbits died, presumably due to redistribution of Al within the rabbit. Following DTPA administration, some of the Al-loaded rabbits died, presumably due to DTPA. Oral EDDHA (1500 mumol/kg) significantly increased urinary Al excretion. EDDHA and desferrioxamine (150 mumol/kg) were administered by po, sc, and iv routes and were found to have comparable potency. The in vitro results may explain some of the in vivo findings. The in vitro methods may be useful to screen out compounds with no chelation potential. EDDHA-like compounds may have potential as alternatives to

Development of smart delivery system for ascorbic acid using pH-responsive P(MAA-co-EGMA) hydrogel microparticles.

PubMed

Lee, Eunmi; Kim, Kyusik; Choi, Moonjae; Lee, Youngmoo; Park, Jin-Won; Kim, Bumsang

2010-11-01

pH-Responsive P(MAA-co-EGMA) hydrogel microparticles were prepared and their feasibility as intelligent delivery carriers was evaluated. P(MAA-co-EGMA) hydrogel microparticles were synthesized via dispersion photopolymerization. There was a drastic change in the swelling ratio of P(MAA-co-EGMA) microparticles at a pH of ~ 5 and, as the amount of MAA in the hydrogel increased, the swelling ratio increased at a pH above 5. The loading efficiency of the ascorbic acid into the hydrogel was affected more by the degree of swelling of the hydrogel than the electrostatic interaction between the hydrogel and the loaded ascorbic acid. The P(MAA-co-EGMA) hydrogel microparticles showed a pH-sensitive release behavior. Thus, at pH 4 almost none of the ascorbic acid permeated through the skin while at pH 6 relatively high skin permeability was obtained. The ascorbic acid loaded in the hydrogel particles was hardly degraded and its stability was maintained at high temperature.

Enhanced proton conductivity of Nafion composite membrane by incorporating phosphoric acid-loaded covalent organic framework

NASA Astrophysics Data System (ADS)

Yin, Yongheng; Li, Zhen; Yang, Xin; Cao, Li; Wang, Chongbin; Zhang, Bei; Wu, Hong; Jiang, Zhongyi

2016-11-01

Design and fabrication of efficient proton transport channels within solid electrolytes is crucial and challenging to new energy-relevant devices such as proton exchange membrane fuel cells (PEMFCs). In this study, the phosphoric acid (H3PO4) molecules are impregnated into SNW-1-type covalent organic frameworks (COFs) via vacuum assisted method. High loading of H3PO4 in SNW-1 and low guest leaching rate are achieved due to the similar diameter between H3PO4 and micropores in SNW-1. Then the COF-based composite membranes are fabricated for the first time with impregnated COFs (H3PO4@SNW-1) and Nafion matrix. For the composite membranes, the acid-base pairs formed between H3PO4@SNW-1 networks and Nafion optimize the interfacial interactions and hydrophilic domains. The acidic -PO3H2 groups in pores of H3PO4@SNW-1 provide abundant proton transfer sites. As a result, the continuous proton transfer channels with low energy barrier are created. At the filler content of 15 wt%, the composite membrane exhibits a superior proton conductivity of 0.0604 S cm-1 at 51% relative humidity and 80 °C. At the same time, the maximum power density of single fuel cell is 60.3% higher than that of the recast Nafion membrane.

A grape seed extract increases active glucagon-like peptide-1 levels after an oral glucose load in rats.

PubMed

González-Abuín, Noemi; Martínez-Micaelo, Neus; Margalef, Maria; Blay, Mayte; Arola-Arnal, Anna; Muguerza, Begoña; Ardévol, Anna; Pinent, Montserrat

2014-09-01

We have previously reported that procyanidins, a class of flavonoids, improve glycemia and exert an incretin-like effect, which was linked to their proven inhibitory effect on the dipeptidyl-peptidase 4 (DPP4) activity. However, their actual effect on incretin levels has not been reported yet. Therefore, in the present study we have evaluated whether a grape seed extract enriched in procyanidins (GSPE) modulates plasma incretin levels and attempted to determine the mechanisms involved. An acute GSPE treatment in healthy Wistar female rats prior to an oral glucose load induced an increase in plasma active glucagon-like peptide-1 (GLP-1), which was accompanied by an increase in the plasma insulin/glucose ratio and a simultaneous decrease in glucose levels. In agreement with our previous studies, the intestinal DPP4 activity was inhibited by the GSPE treatment. We have also assayed in vitro whether this inhibition occurs in inner intestinal tissues close to GLP-1-producing cells, such as the endothelium of the capillaries. We have found that the main compounds absorbed by intestinal CaCo-2 cells after an acute treatment with GSPE are catechin, epicatechin, B2 dimer and gallic acid, and that they inhibit the DPP4 activity in endothelial HUVEC cells in an additive way. Moreover, an increase in plasma total GLP-1 levels was found, suggesting an increase in GLP-1 secretion. In conclusion, our results show that GSPE improves glycemia through its action on GLP-1 secretion and on the inhibition of the inner intestinal DPP4 activity, leading to an increase in active GLP-1 levels, which, in turn, may affect the insulin release.

N-3 fatty acids reduced trans fatty acids retention and increased docosahexaenoic acid levels in the brain.

PubMed

Lavandera, Jimena Verónica; Saín, Juliana; Fariña, Ana Clara; Bernal, Claudio Adrián; González, Marcela Aída

2017-09-01

The levels of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are critical for the normal structure and function of the brain. Trans fatty acids (TFA) and the source of the dietary fatty acids (FA) interfere with long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis. The aim of this study was to investigate the effect of TFA supplementation in diets containing different proportions of n-9, n-6, and n-3 FA on the brain FA profile, including the retention of TFA, LC-PUFA levels, and n-6/n-3 PUFA ratios. These parameters were also investigated in the liver, considering that LC-PUFA are mainly bioconverted from their dietary precursors in this tissue and transported by serum to the brain. Also, stearoyl-CoA desaturase-1 (SCD1) and sterol regulatory element-binding protein-1c (SREBP-1c) gene expressions were evaluated. Male CF1 mice were fed (16 weeks) diets containing different oils (olive, corn, and rapeseed) with distinct proportions of n-9, n-6, and n-3 FA (55.2/17.2/0.7, 32.0/51.3/0.9, and 61.1/18.4/8.6), respectively, substituted or not with 0.75% of TFA. FA composition of the brain, liver, and serum was assessed by gas chromatography. TFA were incorporated into, and therefore retained in the brain, liver, and serum. However, the magnitude of retention was dependent on the tissue and type of isomer. In the brain, total TFA retention was lower than 1% in all diets. Dietary n-3 PUFA decreased TFA retention and increased DHA accretion in the brain. The results underscore the importance of the type of dietary FA on the retention of TFA in the brain and also on the changes of the FA profile.

Parameters influencing the course of passive drug loading into lipid nanoemulsions.

PubMed

Göke, Katrin; Bunjes, Heike

2018-05-01

Passive drug loading can be used to effectively identify suitable colloidal lipid carrier systems for poorly water-soluble drugs. This method comprises incubation of preformed carrier systems with drug powder and subsequent determination of the resulting drug load of the carrier particles. Until now, the passive loading mechanism is unknown, which complicates reliable routine use. In this work, the influence of drug characteristics on the course of passive loading was investigated systematically varying drug surface area and drug solubility. Fenofibrate and flufenamic acid were used as model drugs; the carrier system was a trimyristin nanodispersion. Loading progress was analyzed by UV spectroscopy or by a novel method based on differential scanning calorimetry. While increasing drug solubility by micelle incorporation did not speed up passive loading, a large drug surface area and high water solubility were key parameters for fast loading. Since both factors are crucial in drug dissolution as described by the Noyes-Whitney equation, these findings point to a dissolution-diffusion-based passive loading mechanism. Accordingly, passive loading also occurred when drug and carrier particles were separated by a dialysis membrane. Knowledge of the loading mechanism allows optimizing the conditions for future passive loading studies and assessing the limitations of the method. Copyright © 2017 Elsevier B.V. All rights reserved.

Lactic acid concentrations that reduce microbial load yet minimally impact colour and sensory characteristics of beef.

PubMed

Rodríguez-Melcón, Cristina; Alonso-Calleja, Carlos; Capita, Rosa

2017-07-01

Lactic acid (LA) has recently been approved in the EU as beef decontaminant. In order to identify the most appropriate concentration, beef samples were spray-treated with LA (2%, 3%, 4% or 5%) or left untreated (control). Microbial load (aerobic plate counts, psychrotrophs and Enterobacteriaceae), pH, instrumental colour and sensory properties were investigated at 0, 24, 72 and 120h of refrigerated storage. The reductions in bacteria after spraying ranged from 0.57 to 0.95 log units. A residual antimicrobial effect was observed so that at 120h LA reduced microbial load by up to 2 log units compared with the control samples. Samples treated with 5% LA showed the lowest redness value (a*) and hedonic scores at all sampling times. Only for samples treated with 4% LA did the sensorial shelf-life limit extend beyond 120h. It is suggested that treatment of beef with 4% LA not only may improve microbiological quality, but also may enhance sensory properties and shelf-life. Copyright © 2017. Published by Elsevier Ltd.

A cellular uptake and cytotoxicity properties study of gallic acid-loaded mesoporous silica nanoparticles on Caco-2 cells

NASA Astrophysics Data System (ADS)

Rashidi, Ladan; Vasheghani-Farahani, Ebrahim; Soleimani, Masoud; Atashi, Amir; Rostami, Khosrow; Gangi, Fariba; Fallahpour, Masoud; Tahouri, Mohammad Taher

2014-03-01

In this study, the effects of intracellular delivery of various concentrations of gallic acid (GA) as a semistable antioxidant, gallic acid-loaded mesoporous silica nanoparticles (MSNs-GA), and cellular uptake of nanoparticles into Caco-2 cells were investigated. MSNs were synthesized and loaded with GA, then characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, N2 adsorption isotherms, X-ray diffraction, and thermal gravimetric analysis. The cytotoxicity of MSNs and MSNs-GA at low and high concentrations were studied by means of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test and flow cytometry. MSNs did not show significant toxicity in various concentrations (0-500 μg/ml) on Caco-2 cells. For MSNs-GA, cell viability was reduced as a function of incubation time and different concentrations of nanoparticles. The in vitro GA release from MSNs-GA exhibited the same antitumor properties as free GA on Caco-2 cells. Flow cytometry results confirmed those obtained using MTT assay. TEM and fluorescent microscopy confirmed the internalization of MSNs by Caco-2 cells through nonspecific cellular uptake. MSNs can easily internalize into Caco-2 cells without deleterious effects on cell viability. The cell viability of Caco-2 cells was affected during MSNs-GA uptake. MSNs could be designed as suitable nanocarriers for antioxidants delivery.

Acid-Base Homeostasis

PubMed Central

Nakhoul, Nazih; Hering-Smith, Kathleen S.

2015-01-01

Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3− and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3− is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys. PMID:26597304

Acidic beverages increase the risk of in vitro tooth erosion.

PubMed

Ehlen, Leslie A; Marshall, Teresa A; Qian, Fang; Wefel, James S; Warren, John J

2008-05-01

Acidic beverages are thought to increase the potential for dental erosion. We report pH and titratable acidities (ie, quantity of base required to bring a solution to neutral pH) of beverages popular in the United States and lesion depths in enamel and root surfaces after beverage exposure, and we describe associations among pH, titratable acidity, and both enamel and root erosive lesion depths. The pH of 100% juices, regular sodas, diet sodas, and sports drinks upon opening and the titratable acidity both upon opening and after 60 minutes of stirring were measured. Enamel and root surfaces of healthy permanent molars and premolars were exposed to individual beverages (4 enamel and 4 root surfaces per beverage) for 25 hours, and erosion was measured. Statistical analyses included 2-sample t tests, analyses of variance with post hoc Tukey studentized range test; and Spearman rank correlation coefficients. All beverages were acidic; the titratable acidity of energy drinks was greater than that of regular and diet sodas that were greater than that of 100% juices and sports drinks (P < .05). Enamel lesion depths after beverage exposures were greatest for Gatorade, followed by those for Red Bull and Coke that were greater than those for Diet Coke and 100% apple juice (P < .05). Root lesion depths were greatest for Gatorade, followed by Red Bull, Coke, 100% apple juice, and Diet Coke (P < .05). Lesion depths were not associated with pH or titratable acidity. Beverages popular in the United States can produce dental erosion.

Acidic beverages increase the risk of in vitro tooth erosion

PubMed Central

Ehlen, Leslie A.; Marshall, Teresa A.; Qian, Fang; Wefel, James S.; Warren, John J.

2008-01-01

Acidic beverages are thought to increase the potential for dental erosion. We report pH and titratable acidities (i.e., quantity of base required to bring a solution to neutral pH) of beverages popular in the United States and lesion depths in enamel and root surfaces following beverage exposure, and we describe associations among pH, titratable acidity and both enamel and root erosive lesion depths. The pH of 100% juices, regular sodas, diet sodas and sports drinks upon opening, and the titratable acidity both upon opening and after 60 minutes of stirring were measured. Enamel and root surfaces of healthy permanent molars and premolars were exposed to individual beverages (4 enamel and 4 root surfaces per beverage) for 25 hours and erosion was measured. Statistical analyses included two-sample t-tests, analyses of variance with post hoc Tukey’s studentized range test; and Spearman rank correlation coefficients. All beverages were acidic; the titratable acidity of energy drinks was greater than regular sodas and diet sodas which were greater than 100% juices and sports drinks (P<0.05). Enamel lesion depths following beverage exposures were greatest for Gatorade® followed by Red Bull® and Coke® which were greater than Diet Coke® and 100% apple juice (P <0.05). Root lesion depths were greatest for Gatorade® followed by Red Bull®, Coke®, 100% apple juice and Diet Coke® (P<0.05). Lesion depths were not associated with pH or titratable acidity. Beverages popular in the United States can produce dental erosion. PMID:19083423

Angiopoietin‐like 4 promotes angiogenesis in the tendon and is increased in cyclically loaded tendon fibroblasts

PubMed Central

Mousavizadeh, Rouhollah; Scott, Alex; Lu, Alex; Ardekani, Gholamreza S; Behzad, Hayedeh; Lundgreen, Kirsten; Ghaffari, Mazyar; McCormack, Robert G

2016-01-01

Key points Angiopoietin‐like 4 (ANGPTL4) modulates tendon neovascularization.Cyclic loading stimulates the activity of transforming growth factor‐β and hypoxia‐inducible factor 1α and thereby increases the expression and release of ANGPTL4 from human tendon cells.Targeting ANGPTL4 and its regulatory pathways is a potential avenue for regulating tendon vascularization to improve tendon healing or adaptation. Abstract The mechanisms that regulate angiogenic activity in injured or mechanically loaded tendons are poorly understood. The present study examined the potential role of angiopoietin‐like 4 (ANGPTL4) in the angiogenic response of tendons subjected to repetitive mechanical loading or injury. Cyclic stretching of human tendon fibroblasts stimulated the expression and release of ANGPTL4 protein via transforming growth factor‐β (TGF‐β) and hypoxia‐inducible factor 1α (HIF‐1α) signalling, and the released ANGPTL4 was pro‐angiogenic. Angiogenic activity was increased following ANGPTL4 injection into mouse patellar tendons, whereas the patellar tendons of ANGPTL4 knockout mice displayed reduced angiogenesis following injury. In human rotator cuff tendons, the expression of ANGPTL4 was correlated with the density of tendon endothelial cells. To our knowledge, this is the first study characterizing a role of ANGPTL4 in the tendon. ANGPTL4 may assist in the regulation of vascularity in the injured or mechanically loaded tendon. TGF‐β and HIF‐1α comprise two signalling pathways that modulate the expression of ANGPTL4 by mechanically stimulated tendon fibroblasts and, in the future, these could be manipulated to influence tendon healing or adaptation. PMID:26670924

Administration of tauroursodeoxycholic acid prevents endothelial dysfunction caused by an oral glucose load

PubMed Central

Walsh, Lauren K.; Restaino, Robert M.; Neuringer, Martha; Manrique, Camila; Padilla, Jaume

2017-01-01

Postprandial hyperglycemia leads to a transient impairment in endothelial function; however, the mechanisms remain largely unknown. Previous work in cell culture models demonstrate that high glucose results in endoplasmic reticulum (ER) stress and, in animal studies, ER stress has been implicated as a cause of endothelial dysfunction. Herein we tested the hypothesis that acute oral administration of tauroursodeoxycholic acid (TUDCA, 1500mg), a chemical chaperone known to alleviate ER stress, would prevent hyperglycemia-induced endothelial dysfunction. In 12 young healthy subjects (seven men, five women), brachial artery flow-mediated dilation (FMD) was assessed at baseline, 1 hour, and 2 hours post an oral glucose challenge. Subjects were tested on two separate visits in a single-blind randomized crossover design: after oral ingestion of TUDCA or placebo capsules. FMD was reduced from baseline during hyperglycemia under the placebo condition (−32% at 1 hr and −28% at 2 hr post oral glucose load; p<0.05 from baseline) but not under the TUDCA condition (−4% at 1 hr and +0.3% at 2 hr post oral glucose load; p>0.05 from baseline). Postprandial plasma glucose and insulin were not altered by TUDCA ingestion. Plasma oxidative stress markers 3-nitrotyrosine and TBARs remained unaltered throughout the oral glucose challenge in both conditions. These results suggest that hyperglycemia-induced endothelial dysfunction can be mitigated by oral administration of TUDCA, thus supporting the hypothesis that ER stress may contribute to endothelial dysfunction during postprandial hyperglycemia. PMID:27503949

Is increased joint loading detrimental to obese patients with knee osteoarthritis? A secondary data analysis from a randomized trial.

PubMed

Henriksen, M; Hunter, D J; Dam, E B; Messier, S P; Andriacchi, T P; Lohmander, L S; Aaboe, J; Boesen, M; Gudbergsen, H; Bliddal, H; Christensen, R

2013-12-01

To investigate whether increased knee joint loading due to improved ambulatory function and walking speed following weight loss achieved over 16 weeks accelerates symptomatic and structural disease progression over a subsequent 1 year weight maintenance period in an obese population with knee osteoarthritis (OA). Data from a prospective study of weight loss in obese patients with knee OA (the CARtilage in obese knee OsteoarThritis (CAROT) study) were used to determine changes in knee joint compressive loadings (model estimated) during walking after a successful 16 week weight loss intervention. The participants were divided into 'Unloaders' (participants that reduced joint loads) and 'Loaders' (participants that increased joint loads). The primary symptomatic outcome was changes in knee symptoms, measured with the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire, during a subsequent 52 weeks weight maintenance period. The primary structural outcome was changes in tibiofemoral cartilage loss assessed semi-quantitatively (Boston Leeds Knee Osteoarthritis Score (BLOKS) from MRI after the 52 weight maintenance period. 157 participants (82% of the CAROT cohort) with medial and/or lateral knee OA were classified as Unloaders (n = 100) or Loaders (n = 57). The groups showed similar significant changes in symptoms (group difference: -2.4 KOOS points [95% CI -6.8:1.9]) and cartilage loss (group difference: -0.06 BLOKS points [95% CI -0.22:0.11) after 1 year, with no statistically significant differences between Loaders and Unloaders. For obese patients undergoing a significant weight loss, increased knee joint loading for 1 year was not associated with accelerated symptomatic and structural disease progression compared to a similar weight loss group that had reduced ambulatory compressive knee joint loads. NCT00655941. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Biodegradable Drug-Loaded Hydroxyapatite Nanotherapeutic Agent for Targeted Drug Release in Tumors.

PubMed

Sun, Wen; Fan, Jiangli; Wang, Suzhen; Kang, Yao; Du, Jianjun; Peng, Xiaojun

2018-03-07

Tumor-targeted drug delivery systems have been increasingly used to improve the therapeutic efficiency of anticancer drugs and reduce their toxic side effects in vivo. Focused on this point, doxorubicin (DOX)-loaded hydroxyapatite (HAP) nanorods consisting of folic acid (FA) modification (DOX@HAP-FA) were developed for efficient antitumor treatment. The DOX-loaded nanorods were synthesized through in situ coprecipitation and hydrothermal method with a DOX template, demonstrating a new procedure for drug loading in HAP materials. DOX could be efficiently released from DOX@HAP-FA within 24 h in weakly acidic buffer solution (pH = 6.0) because of the degradation of HAP nanorods. With endocytosis under the mediation of folate receptors, the nanorods exhibited enhanced cellular uptake and further degraded, and consequently, the proliferation of targeted cells was inhibited. More importantly, in a tumor-bearing mouse model, DOX@HAP-FA treatment demonstrated excellent tumor growth inhibition. In addition, no apparent side effects were observed during the treatment. These results suggested that DOX@HAP-FA may be a promising nanotherapeutic agent for effective cancer treatment in vivo.

Biochemical profile of Achatina fulica (Mollusca: Gastropoda) after infection by different parasitic loads of Angiostrongylus cantonensis (Nematoda, Metastrongylidae).

PubMed

Tunholi-Alves, Vinícius Menezes; Tunholi, Victor Menezes; Amaral, Ludimila Santos; Mota, Esther Maria; Maldonado Júnior, Arnaldo; Pinheiro, Jairo; Garcia, Juberlan

2015-01-01

The effect of experimental infection by different parasitic loads of Angiostrongylus cantonensis (Nematode, Metastrongylidae) on the activities of the aminotransferases and concentration of total proteins, uric acid and urea in the hemolymph of Achatina fulica (Mollusca, Gastropoda) were investigated. There was a significant decrease in the concentration of total proteins in the exposed snails to 5000 or more larvae. This change was accompanied by an increase in the concentrations of urea and uric acid in the hemolymph, suggesting a higher rate of deamination of the amino acids. Besides this, variations in the activities of the aminotransferases were also observed, with the highest values recorded in the groups exposed to greater parasite load. These results suggest an increase in the use of total proteins, since there was increased formation of nitrogenous catabolites, in conformity with an increase in the aminotransferase activities. Infection was verified by the fact that L3 larvae recovered from the snails was proportion to the exposure dose of L1 larvae. Histopathological results also indicated presence of an inflammatory cell infiltrate, favoring an increase of both transaminases. Copyright © 2014 Elsevier Inc. All rights reserved.

Synthesis of polyoxometalate-loaded epoxy composites

DOEpatents

Anderson, Benjamin J

2014-10-07

The synthesis of a polyoxometalate-loaded epoxy uses a one-step cure by applying an external stimulus to release the acid from the polyoxometalate and thereby catalyze the cure reaction of the epoxy resin. Such polyoxometalate-loaded epoxy composites afford the cured epoxy unique properties imparted by the intrinsic properties of the polyoxometalate. For example, polyoxometalate-loaded epoxy composites can be used as corrosion resistant epoxy coatings, for encapsulation of electronics with improved dielectric properties, and for structural applications with improved mechanical properties.

Immediate occlusal loading of double acid-etched surface titanium implants in 41 consecutive full-arch cases in the mandible and maxilla: 6- to 74-month results.

PubMed

Ibañez, Juan C; Tahhan, Marcelo J; Zamar, Juan A; Menendez, Alicia B; Juaneda, Agustina M; Zamar, Nicolas J; Monqaut, Jose L

2005-11-01

The high success rate of dental implants has changed the quality of life for many patients. Immediate loading finds its application in some clinical cases and certainly adds another modality of treatment for the implant patient. Starting with a few implants immediately loaded with a bar overdenture in the mandible, the concept of immediate loading evolved to loading multiple implants in both the maxilla and mandible. In this investigation, 41 consecutive patients who needed full-arch restorations were treated with 343 double acid-etched surface implants between May 1998 and March 2004. The sample included smokers and bruxers. Twenty-three mandibular and 26 maxillary cases were treated, loading the implants within 48 hours, by using resin provisional prostheses, metal-reinforced provisional prostheses, or definitive prostheses (metal-acrylic or metal-ceramic). All implants were followed for 12 to 74 months. Follow-up consisted of clinical as well as radiographic examination. Furthermore, resonance frequency analysis was done in most of the implants during the last 2 years. The success rate obtained was 99.42% (only two mandibular implants that are still surviving were considered failures). The bone level was measured every year. The average radiographic bone level change was 0.56 mm at 12, 0.76 mm at 24, 0.84 mm at 36, 0.82 mm at 48, 0.83 mm at 60, and 0.94 mm at 72 months. A high success rate can be achieved when double acid-etched surface implants are immediately loaded with fixed full-arch restorations in the maxilla and mandible.

[PLA-O-CMC nanoparticles: HGF loading and delivery behaviors in vitro].

PubMed

Li, Zhifeng; Chen, Zhong; Chang, Ren'an

2011-04-01

This paper is aimed to observe the hepatocyte growth factor (HGF) loading and delivery ability of polylactic acid and oxygen carboxymethylated chitosan copolyer nanoparticles (PLA-O-CMC NPs). We prepared PLA-O-CMC NPs loaded with HGF by ultrasound in combination with magnetic stirring method. The NPs were characterized by transmission electron microscopy, embedding ratio; drug loading and drug delivery behaviors were observed by ELISA. The characteristics of PLA-O-CMC NPs loaded with HGF showed that the mean size was 139. 82 nm, polydispersity was 0.108, maximal HGF-embedding ratio was 76. 32%. The cumulative HGF release gradually increased in the first 24 hours in vitro, with sharp increasing in the first 7 hours, and moderate and steady increasing in the following 17 hours. The HGF had a burst release in the first 24 hours, and in this process the released HGF took up 36.7% of the whole release. From the second day,the HGF release decreased obviously, while it kept on releasing steadily (45-55 ng/d) for quite long time up to 30 days. The experiment proved that PLA-O-CMC NPs is a favourable carrier of HGF. PLA-O-CMC NPs loaded with HGF could rapidly release HGF in vitro. The released HGF reached the effective drug concentration and maintained the certain effective drug concentration for a long time.

Age differences in high frequency phasic heart rate variability and performance response to increased executive function load in three executive function tasks

PubMed Central

Byrd, Dana L.; Reuther, Erin T.; McNamara, Joseph P. H.; DeLucca, Teri L.; Berg, William K.

2015-01-01

The current study examines similarity or disparity of a frontally mediated physiological response of mental effort among multiple executive functioning tasks between children and adults. Task performance and phasic heart rate variability (HRV) were recorded in children (6 to 10 years old) and adults in an examination of age differences in executive functioning skills during periods of increased demand. Executive load levels were varied by increasing the difficulty levels of three executive functioning tasks: inhibition (IN), working memory (WM), and planning/problem solving (PL). Behavioral performance decreased in all tasks with increased executive demand in both children and adults. Adults’ phasic high frequency HRV was suppressed during the management of increased IN and WM load. Children’s phasic HRV was suppressed during the management of moderate WM load. HRV was not suppressed during either children’s or adults’ increasing load during the PL task. High frequency phasic HRV may be most sensitive to executive function tasks that have a time-response pressure, and simply requiring performance on a self-paced task requiring frontal lobe activation may not be enough to generate HRV responsitivity to increasing demand. PMID:25798113

Increasing M 2(dobdc) Loading in Selective Mixed-Matrix Membranes: A Rubber Toughening Approach

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

Smith, Zachary P.; Bachman, Jonathan E.; Li, Tao

Mixed-matrix membranes (MMMs) were formed by incorporating M 2(dobdc) (M = Mg, Ni; dobdc 4– = 2,5-dioxido-1,4-benzenedicarboxylate) metal–organic framework (MOF) nanoparticles in a series of poly(ether-imide) copolymers. Addition of the MOF nanoparticles improved the permeability of H 2, N 2, CH 4, and CO 2 relative to the pure copolymer by increasing gas solubility and, in most cases, diffusivity. More limited improvements in diffusivity were observed for the more strongly adsorbing gases. Because of such transport considerations, improvements in permeability and selectivity were most pronounced for H 2/CH 4 and H 2/N 2 separations. Incorporation of a greater ether contentmore » within the copolymers led to the formation of defect-free MMMs by physically sealing polymer–MOF interfacial defects, allowing higher MOF loadings to be achieved. For Mg 2(dobdc), selective, defect-free films could be formed with loadings of up to 51 wt %. However, at these high loadings, films became weak and brittle. The mechanical properties of the composite materials were therefore quantified by tensile tests and compared to those of the neat polymers used commercially for membrane film formation. High contents of flexible ether units and small MOF nanoparticle sizes were found to be necessary to form strong and ductile MMMs, although clear trade-offs exist between transport performance, MOF loading, and mechanical properties. In conclusion, these trade-offs are critically examined to evaluate the current limitations and potential benefits to forming M 2(dobdc) MMMs using this rubber toughening approach.« less

Biomechanical loading on the upper extremity increases from single key tapping to directional tapping.

PubMed

Qin, Jin; Trudeau, Matthieu; Katz, Jeffrey N; Buchholz, Bryan; Dennerlein, Jack T

2011-08-01

Musculoskeletal disorders associated with computer use span the joints of the upper extremity. Computing typically involves tapping in multiple directions. Thus, we sought to describe the loading on the finger, wrist, elbow and shoulder joints in terms of kinematic and kinetic difference across single key switch tapping to directional tapping on multiple keys. An experiment with repeated measures design was conducted. Six subjects tapped with their right index finger on a stand-alone number keypad placed horizontally in three conditions: (1) on single key switch (the number key 5); (2) left and right on number key 4 and 6; (3) top and bottom on number key 8 and 2. A force-torque transducer underneath the keypad measured the fingertip force. An active-marker infrared motion analysis system measured the kinematics of the fingertip, hand, forearm, upper arm and torso. Joint moments for the metacarpophalangeal, wrist, elbow, and shoulder joints were estimated using inverse dynamics. Tapping in the top-bottom orientation introduced the largest biomechanical loading on the upper extremity especially for the proximal joint, followed by tapping in the left-right orientation, and the lowest loading was observed during single key switch tapping. Directional tapping on average increased the fingertip force, joint excursion, and peak-to-peak joint torque by 45%, 190% and 55%, respectively. Identifying the biomechanical loading patterns associated with these fundamental movements of keying improves the understanding of the risks of upper extremity musculoskeletal disorders for computer keyboard users. Copyright © 2010 Elsevier Ltd. All rights reserved.

Use of Adaptive Injection Strategies to Increase the Full Load Limit of RCCI Operation

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

Hanson, Reed; Ickes, Andrew; Wallner, Thomas

2015-01-01

Dual-fuel combustion using port-injection of low reactivity fuel combined with direct injection of a higher reactivity fuel, otherwise known as Reactivity Controlled Compression Ignition (RCCI), has been shown as a method to achieve low-temperature combustion with moderate peak pressure rise rates, low engine-out soot and NOx emissions, and high indicated thermal efficiency. A key requirement for extending to high-load operation is moderating the reactivity of the premixed charge prior to the diesel injection. One way to accomplish this is to use a very low reactivity fuel such as natural gas. In this work, experimental testing was conducted on a 13Lmore » multi-cylinder heavy-duty diesel engine modified to operate using RCCI combustion with port injection of natural gas and direct injection of diesel fuel. Engine testing was conducted at an engine speed of 1200 RPM over a wide variety of loads and injection conditions. The impact on dual-fuel engine performance and emissions with respect to varying the fuel injection parameters is quantified within this study. The injection strategies used in the work were found to affect the combustion process in similar ways to both conventional diesel combustion and RCCI combustion for phasing control and emissions performance. As the load is increased, the port fuel injection quantity was reduced to keep peak cylinder pressure and maximum pressure rise rate under the imposed limits. Overall, the peak load using the new injection strategy was shown to reach 22 bar BMEP with a peak brake thermal efficiency of 47.6%.« less

Increasing M 2(dobdc) Loading in Selective Mixed-Matrix Membranes: A Rubber Toughening Approach

DOE PAGES

Smith, Zachary P.; Bachman, Jonathan E.; Li, Tao; ...

2018-01-30

Mixed-matrix membranes (MMMs) were formed by incorporating M 2(dobdc) (M = Mg, Ni; dobdc 4– = 2,5-dioxido-1,4-benzenedicarboxylate) metal–organic framework (MOF) nanoparticles in a series of poly(ether-imide) copolymers. Addition of the MOF nanoparticles improved the permeability of H 2, N 2, CH 4, and CO 2 relative to the pure copolymer by increasing gas solubility and, in most cases, diffusivity. More limited improvements in diffusivity were observed for the more strongly adsorbing gases. Because of such transport considerations, improvements in permeability and selectivity were most pronounced for H 2/CH 4 and H 2/N 2 separations. Incorporation of a greater ether contentmore » within the copolymers led to the formation of defect-free MMMs by physically sealing polymer–MOF interfacial defects, allowing higher MOF loadings to be achieved. For Mg 2(dobdc), selective, defect-free films could be formed with loadings of up to 51 wt %. However, at these high loadings, films became weak and brittle. The mechanical properties of the composite materials were therefore quantified by tensile tests and compared to those of the neat polymers used commercially for membrane film formation. High contents of flexible ether units and small MOF nanoparticle sizes were found to be necessary to form strong and ductile MMMs, although clear trade-offs exist between transport performance, MOF loading, and mechanical properties. In conclusion, these trade-offs are critically examined to evaluate the current limitations and potential benefits to forming M 2(dobdc) MMMs using this rubber toughening approach.« less

Endogenous flow of amino acids in the avian ileum as influenced by increasing dietary peptide concentrations.

PubMed

Ravindran, Velmurugu; Morel, Patrick C H; Rutherfurd, Shane M; Thomas, Donald V

2009-03-01

The aim of the present study was to establish whether feeding broiler chickens with diets containing increasing dietary peptide concentrations would cause increases in ileal endogenous amino acid flow. The flow of N and most amino acids increased quadratically (P < 0.05 to 0.001) with increasing dietary concentrations of peptides. The exceptions were the flow of threonine, serine, glycine, tyrosine and cystine, which increased linearly (P < 0.001) with dietary peptide levels. Another notable exception to the general trend was the flow of proline, which was significantly higher (P < 0.01) in birds fed the protein-free diet. The amino acid profile of endogenous protein, expressed as proportion of crude protein, indicated that the ratios of threonine, glutamic acid, proline, glycine, leucine, histidine, arginine and cystine were influenced (P < 0.05) with increasing dietary peptide concentrations. In general, compared with the protein-free diet, the ratios of threonine and arginine in endogenous protein were lower (P < 0.05) and those of glutamic acid, glycine and histidine were greater (P < 0.05) in diets with high concentrations of peptides. The ratio of proline was found to decrease (P < 0.05) with increasing dietary peptide concentrations. These changes in the amino acid profile of endogenous protein are probably reflective of changes in the output of one or more of the components of endogenous protein. Overall, the present results demonstrated that increasing dietary peptide concentrations increased the flow of endogenous amino acid flow at the terminal ileum of broiler chickens in a dose-dependent manner and also caused changes in the composition of endogenous protein. The observed changes in endogenous amino flow will influence the maintenance requirements for amino acids and also have implications for the calculation of true digestibility coefficient of feedstuffs.

A Pilot Study to Increase the Efficiency of HIV Outreach Testing Through the Use of Timely and Geolocated HIV Viral Load Surveillance Data

PubMed Central

Jennings, Jacky M.; Schumacher, Christina; Perin, Jamie; Myers, Tanya; Fields, Nathan; Greiner Safi, Amelia; Chaulk, Patrick

2018-01-01

Background Eliminating HIV transmission in a population necessitates identifying population reservoirs of HIV infection and subgroups most likely to transmit. HIV viral load is the single most important predictor of HIV transmission. The objective of this analysis was to evaluate whether a public health practice pilot project based on community viral load resulted in increases in the proportion of time spent testing in high viral load areas (process measure) and 3 outcome measures—the number and percent of overall HIV diagnoses, new diagnoses, and high viral load positives—in one mid-Atlantic US city with a severe HIV epidemic. Methods The evaluation was conducted during three, 3-month periods for 3 years and included the use of community viral load, global positioning system tracking data, and statistical testing to evaluate the effectiveness of the pilot project. Results The proportion of time spent outreach testing in high viral load areas (69%–84%, P < 0.001) and the overall number and percent of HIV positives ((60 (3%) to 127 (6%), P < 0.001) significantly increased for 3 years. The number and percent of new diagnoses (3 (0.1%) to 6 (0.2%)) and high viral load positives (5 (0.2%) to 9 (0.4%)) increased, but the numbers were too small for statistical testing. Discussion These results suggest that using community viral load to increase the efficiency of HIV outreach testing is feasible and may be effective in identifying more HIV positives. The pilot project provides a model for other public health practice demonstration projects. PMID:29420450

Effect of trace element addition and increasing organic loading rates on the anaerobic digestion of cattle slaughterhouse wastewater.

PubMed

Schmidt, Thomas; McCabe, Bernadette K; Harris, Peter W; Lee, Seonmi

2018-05-18

In this study, anaerobic digestion of slaughterhouse wastewater with the addition of trace elements was monitored for biogas quantity, quality and process stability using CSTR digesters operated at mesophilic temperature. The determination of trace element concentrations was shown to be deficient in Fe, Ni, Co, Mn and Mo compared to recommendations given in the literature. Addition of these trace elements resulted in enhanced degradation efficiency, higher biogas production and improved process stability. Higher organic loading rates and lower hydraulic retention times were achieved in comparison to the control digesters. A critical accumulation of volatile fatty acids was observed at an organic loading rate of 1.82 g L -1  d -1 in the control compared to 2.36 g L -1  d -1 in the digesters with trace element addition. The improved process stability was evident in the final weeks of experimentation, in which control reactors produced 84% less biogas per day compared to the reactors containing trace elements. Copyright © 2018 Elsevier Ltd. All rights reserved.

Characterization of the Solution Structure of Human Serum Albumin Loaded with a Metal Porphyrin and Fatty Acids

PubMed Central

Junk, Matthias J.N.; Spiess, Hans W.; Hinderberger, Dariush

2011-01-01

The structure of human serum albumin loaded with a metal porphyrin and fatty acids in solution is characterized by orientation-selective double electron-electron resonance (DEER) spectroscopy. Human serum albumin, spin-labeled fatty acids, and Cu(II) protoporphyrin IX—a hemin analog—form a fully self-assembled system that allows obtaining distances and mutual orientations between the paramagnetic guest molecules. We report a simplified analysis for the orientation-selective DEER data which can be applied when the orientation selection of one spin in the spin pair dominates the orientation selection of the other spin. The dipolar spectra reveal a dominant distance of 3.85 nm and a dominant orientation of the spin-spin vectors between Cu(II) protoporphyrin IX and 16-doxyl stearic acid, the electron paramagnetic resonance reporter group of the latter being located near the entry points to the fatty acid binding sites. This observation is in contrast to crystallographic data that suggest an asymmetric distribution of the entry points in the protein and hence the occurrence of various distances. In conjunction with the findings of a recent DEER study, the obtained data are indicative of a symmetric distribution of the binding site entries on the protein's surface. The overall anisotropic shape of the protein is reflected by one spin-spin vector orientation dominating the DEER data. PMID:21539799

Boric acid-enhanced embedding medium for cryomicrotomy.

PubMed

Lim, Jin Ik; Park, Hun-Kuk

2012-05-01

A polyvinyl alcohol (PVA)/polyethylene glycol (PEG)-based resin is commonly used as a cryoembedding medium for the histological analysis of frozen tissue sections. However, it is not easy to obtain sufficient numbers of satisfactory reproducible sections owing to the differences between the mechanical properties of the medium and embedded tissue and the low cohesive force of the medium. We describe a modified PVA-based cryoembedding medium, composed of PVA (10wt% and 15wt%) with the addition of boric acid (from 0 to 5wt%), that can improve the sectioning properties and efficiency of frozen tissue for histological analysis. The amount of load under the same compressive displacement as well as cohesive force increased with increasing boric acid and PVA contents. 15wt% PVA and 3wt% boric acid was determined as an optimal composition for cryoembedding material based on the sectioning efficiency measured by the numbers of unimpaired sectioned slices and the amount of load under the same compressive displacement test. On the basis of the results of routine hematoxylin and eosin staining of cryosections of tissue embedded in a medium with 3wt% boric acid and PVA, it was concluded that the modified PVA cryoembedding medium can improve the efficiency of cryosectioning for subsequent histological or histochemical analysis of various tissues. Copyright © 2011 Elsevier GmbH. All rights reserved.

Fed levels of amino acids are required for the somatotropin-induced increase in muscle protein synthesis.

PubMed

Wilson, Fiona A; Suryawan, Agus; Orellana, Renán A; Nguyen, Hanh V; Jeyapalan, Asumthia S; Gazzaneo, Maria C; Davis, Teresa A

2008-10-01

Chronic somatotropin (pST) treatment in pigs increases muscle protein synthesis and circulating insulin, a known promoter of protein synthesis. Previously, we showed that the pST-mediated rise in insulin could not account for the pST-induced increase in muscle protein synthesis when amino acids were maintained at fasting levels. This study aimed to determine whether the pST-induced increase in insulin promotes skeletal muscle protein synthesis when amino acids are provided at fed levels and whether the response is associated with enhanced translation initiation factor activation. Growing pigs were treated with pST (0 or 180 microg x kg(-1) x day(-1)) for 7 days, and then pancreatic-glucose-amino acid clamps were performed. Amino acids were raised to fed levels in the presence of either fasted or fed insulin concentrations; glucose was maintained at fasting throughout. Muscle protein synthesis was increased by pST treatment and by amino acids (with or without insulin) (P<0.001). In pST-treated pigs, fed, but not fasting, amino acid concentrations further increased muscle protein synthesis rates irrespective of insulin level (P<0.02). Fed amino acids, with or without raised insulin concentrations, increased the phosphorylation of S6 kinase (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4EBP1), decreased inactive 4EBP1.eIF4E complex association, and increased active eIF4E.eIF4G complex formation (P<0.02). pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of muscle protein synthesis requires fed amino acid levels, but not fed insulin levels. However, under the current conditions, the response to amino acids is not mediated by the activation of translation initiation factors that regulate mRNA binding to the ribosomal complex.

Activation of PPARα by Oral Clofibrate Increases Renal Fatty Acid Oxidation in Developing Pigs.

PubMed

He, Yonghui; Khan, Imad; Bai, Xiumei; Odle, Jack; Xi, Lin

2017-12-08

The objective of this study was to evaluate the effects of peroxisome proliferator-activated receptor α (PPARα) activation by clofibrate on both mitochondrial and peroxisomal fatty acid oxidation in the developing kidney. Ten newborn pigs from 5 litters were randomly assigned to two groups and fed either 5 mL of a control vehicle (2% Tween 80) or a vehicle containing clofibrate (75 mg/kg body weight, treatment). The pigs received oral gavage daily for three days. In vitro fatty acid oxidation was then measured in kidneys with and without mitochondria inhibitors (antimycin A and rotenone) using [1- 14 C]-labeled oleic acid (C18:1) and erucic acid (C22:1) as substrates. Clofibrate significantly stimulated C18:1 and C22:1 oxidation in mitochondria ( p < 0.001) but not in peroxisomes. In addition, the oxidation rate of C18:1 was greater in mitochondria than peroxisomes, while the oxidation of C22:1 was higher in peroxisomes than mitochondria ( p < 0.001). Consistent with the increase in fatty acid oxidation, the mRNA abundance and enzyme activity of carnitine palmitoyltransferase I (CPT I) in mitochondria were increased. Although mRNA of mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (mHMGCS) was increased, the β-hydroxybutyrate concentration measured in kidneys did not increase in pigs treated with clofibrate. These findings indicate that PPARα activation stimulates renal fatty acid oxidation but not ketogenesis.

Acid retention with reduced glomerular filtration rate increases urine biomarkers of kidney and bone injury.

PubMed

Wesson, Donald E; Pruszynski, Jessica; Cai, Wendy; Simoni, Jan

2017-04-01

Diets high in acid of developed societies that do not cause metabolic acidosis in patients with chronic kidney disease nevertheless appear to cause acid retention with associated morbidity, particularly in those with reduced glomerular filtration rate. Here we used a rat 2/3 nephrectomy model of chronic kidney disease to study induction and maintenance of acid retention and its consequences on indicators of kidney and bone injury. Dietary acid was increased in animals eating base-producing soy protein with acid-producing casein and in casein-eating animals with added ammonium chloride. Using microdialysis to measure the kidney cortical acid content, we found that nephrectomized animals had greater acid retention than sham-operated animals when both ate the soy diet. Each increment in dietary acid further increased acid retention more in nephrectomized than in sham rats. Nephrectomized and sham animals achieved similar steady-state daily urine net acid excretion in response to increments in dietary acid but nephrectomized animals took longer to do so, contributing to greater acid retention that was maintained until the increased dietary acid was stopped. Acid retention was associated with increased urine excretion of both N-acetyl-β-D-glucosaminidase and deoxypyridinoline, greater in nephrectomized than control rats, consistent with kidney tubulointerstitial and bone matrix injury, respectively. Greater acid retention in nephrectomized than control animals was induced by a slower increase in urinary net acid excretion rate in response to the increment in dietary acid and also maintained until the dietary acid increment was stopped. Thus, acid retention increased biomarkers of kidney and bone injury in the urine, supporting untoward consequences to these two tissues. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Effects of microbial loading and sporulation temperature on atmospheric plasma inactivation of Bacillus subtilis spores

NASA Astrophysics Data System (ADS)

Deng, X. T.; Shi, J. J.; Shama, G.; Kong, M. G.

2005-10-01

Current inactivation studies of Bacillus subtilis spores using atmospheric-pressure glow discharges (APGD) do not consider two important factors, namely microbial loading at the surface of a substrate and sporulation temperature. Yet these are known to affect significantly microbial resistance to heat and hydrogen peroxide. This letter investigates effects of microbial loading and sporulation temperature on spore resistance to APGD. It is shown that microbial loading can lead to a stacking structure as a protective shield against APGD treatment and that high sporulation temperature increases spore resistance by altering core water content and cross-linked muramic acid content of B. subtilis spores.

Friction and wear of iron in sulfuric acid

NASA Technical Reports Server (NTRS)

Rengstorff, G. W. P.; Miyoshi, K.; Buckley, D. H.

1983-01-01

Elemental iron sliding on aluminum oxide in aerated sulfuric acid concentrations ranging from very dilute (0.000007 N; i.e., 4 ppm) to very concentrated (96 percent acid) was studied. Load and reciprocating sliding speeds were kept constant. With the most dilute acid of 0.7 to 0.0002 N, a complex corrosion product formed that was friable and often increased friction and wear. At concentrations of 0.001 N, metal losses were essentially by wear alone. Because no buildup of corrosion products occurred, this acid concentration became the standard from which to separate metal loss from direct corrosion and mechanical wear losses. When the acid concentration was increased to 5 percent, the high corrosion rate of iron in sulfuric acid strongly dominated the total wear loss. This strong corrosion increased to 30 percent acid, and decreased somewhat at 50 percent in accordance with expectations. However, the low corrosion of iron expected at acid concentrations of 65 to 96 percent was not observed in the wear area. It is apparent that the normal passivating film was being worn away and a galvanic cell established which rapidly attached to the wear area.

Functionalized antibiofilm thin coatings based on PLA-PVA microspheres loaded with usnic acid natural compounds fabricated by MAPLE

NASA Astrophysics Data System (ADS)

Grumezescu, Valentina; Socol, Gabriel; Grumezescu, Alexandru Mihai; Holban, Alina Maria; Ficai, Anton; Truşcǎ, Roxana; Bleotu, Coralia; Balaure, Paul Cǎtǎlin; Cristescu, Rodica; Chifiriuc, Mariana Carmen

2014-05-01

We report the fabrication of thin coatings of PLA-PVA microspheres loaded with usnic acid by matrix assisted pulsed laser evaporation (MAPLE) onto Ti substrate. The obtained coatings have been physico-chemically characterized by scanning electron microscopy (SEM) and infrared microscopy (IRM). In vitro biological assays have been performed in order to evaluate the influence of fabricated microsphere thin coatings on the Staphylococcus aureus biofilm development as well as their biocompatibility. SEM micrographs have revealed a uniform morphology of thin coatings, while IRM investigations have proved both the homogeneity and functional groups integrity of prepared thin coatings. The obtained microsphere-based thin coatings have proved to be efficient vehicles for usnic acid natural compound with antibiofilm activity, as demonstrated by the inhibitory activity on S. aureus mature biofilm development, opening new perspectives for the prevention and therapy associated to biofilm related infections.

Is improved lane keeping during cognitive load caused by increased physical arousal or gaze concentration toward the road center?

PubMed

Li, Penghui; Markkula, Gustav; Li, Yibing; Merat, Natasha

2018-08-01

Driver distraction is one of the main causes of motor-vehicle accidents. However, the impact on traffic safety of tasks that impose cognitive (non-visual) distraction remains debated. One particularly intriguing finding is that cognitive load seems to improve lane keeping performance, most often quantified as reduced standard deviation of lateral position (SDLP). The main competing hypotheses, supported by current empirical evidence, suggest that cognitive load improves lane keeping via either increased physical arousal, or higher gaze concentration toward the road center, but views are mixed regarding if, and how, these possible mediators influence lane keeping performance. Hence, a simulator study was conducted, with participants driving on a straight city road section whilst completing a cognitive task at different levels of difficulty. In line with previous studies, cognitive load led to increased physical arousal, higher gaze concentration toward the road center, and higher levels of micro-steering activity, accompanied by improved lane keeping performance. More importantly, during the high cognitive task, both physical arousal and gaze concentration changed earlier in time than micro-steering activity, which in turn changed earlier than lane keeping performance. In addition, our results did not show a significant correlation between gaze concentration and physical arousal on the level of individual task recordings. Based on these findings, various multilevel models for micro-steering activity and lane keeping performance were conducted and compared, and the results suggest that all of the mechanisms proposed by existing hypotheses could be simultaneously involved. In other words, it is suggested that cognitive load leads to: (i) an increase in arousal, causing increased micro-steering activity, which in turn improves lane keeping performance, and (ii) an increase in gaze concentration, causing lane keeping improvement through both (a) further increased micro

Angiopoietin-like 4 promotes angiogenesis in the tendon and is increased in cyclically loaded tendon fibroblasts.

PubMed

Mousavizadeh, Rouhollah; Scott, Alex; Lu, Alex; Ardekani, Gholamreza S; Behzad, Hayedeh; Lundgreen, Kirsten; Ghaffari, Mazyar; McCormack, Robert G; Duronio, Vincent

2016-06-01

Angiopoietin-like 4 (ANGPTL4) modulates tendon neovascularization. Cyclic loading stimulates the activity of transforming growth factor-β and hypoxia-inducible factor 1α and thereby increases the expression and release of ANGPTL4 from human tendon cells. Targeting ANGPTL4 and its regulatory pathways is a potential avenue for regulating tendon vascularization to improve tendon healing or adaptation. The mechanisms that regulate angiogenic activity in injured or mechanically loaded tendons are poorly understood. The present study examined the potential role of angiopoietin-like 4 (ANGPTL4) in the angiogenic response of tendons subjected to repetitive mechanical loading or injury. Cyclic stretching of human tendon fibroblasts stimulated the expression and release of ANGPTL4 protein via transforming growth factor-β (TGF-β) and hypoxia-inducible factor 1α (HIF-1α) signalling, and the released ANGPTL4 was pro-angiogenic. Angiogenic activity was increased following ANGPTL4 injection into mouse patellar tendons, whereas the patellar tendons of ANGPTL4 knockout mice displayed reduced angiogenesis following injury. In human rotator cuff tendons, the expression of ANGPTL4 was correlated with the density of tendon endothelial cells. To our knowledge, this is the first study characterizing a role of ANGPTL4 in the tendon. ANGPTL4 may assist in the regulation of vascularity in the injured or mechanically loaded tendon. TGF-β and HIF-1α comprise two signalling pathways that modulate the expression of ANGPTL4 by mechanically stimulated tendon fibroblasts and, in the future, these could be manipulated to influence tendon healing or adaptation. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Encapsulation of micronutrients resveratrol, genistein, and curcumin by folic acid-PAMAM nanoparticles.

PubMed

Chanphai, P; Tajmir-Riahi, H A

2018-05-21

It has been shown that encapsulation of dietary polyphenols leads to increased solubility and bioavailability of these micronutrients. The encapsulation of dietary polyphenols resveratrol, genistein, and curcumin by folic acid-PAMAM-G3 and folic acid-PAMAM-G4 nanoparticles was studied in aqueous solution at physiological conditions, using multiple spectroscopic methods, TEM images, and docking studies. The polyphenol bindings are via hydrophilic, hydrophobic, and H-bonding contacts with resveratrol forming more stable conjugates. As folic acid-PAMAM nanoparticle size increased, the loading efficacy and the stability of polyphenol-polymer conjugates were increased. Polyphenol encapsulation induced major alterations of dendrimer morphology. Folic acid-PAMAM nanoconjugates are capable of delivery of polyphenols in vitro.

An oxidized metabolite of linoleic acid increases intracellular calcium in rat adrenal glomerulosa cells.

PubMed

Payet, Marcel D; Goodfriend, Theodore L; Bilodeau, Lyne; Mackendale, Cherilu; Chouinard, Lucie; Gallo-Payet, Nicole

2006-12-01

EKODE, an epoxy-keto derivative of linoleic acid, was previously shown to stimulate aldosterone secretion in rat adrenal glomerulosa cells. In the present study, we investigated the effect of exogenous EKODE on cytosolic [Ca(2+)] increase and aimed to elucidate the mechanism involved in this process. Through the use of the fluorescent Ca(2+)-sensitive dye Fluo-4, EKODE was shown to rapidly increase intracellular [Ca(2+)] ([Ca(2+)](i)) along a bell-shaped dose-response relationship with a maximum peak at 5 microM. Experiments performed in the presence or absence of Ca(2+) revealed that this increase in [Ca(2+)](i) originated exclusively from intracellular pools. EKODE-induced [Ca(2+)](i) increase was blunted by prior application of angiotensin II, Xestospongin C, and cyclopiazonic acid, indicating that inositol trisphosphate (InsP(3))-sensitive Ca(2+) stores can be mobilized by EKODE despite the absence of InsP(3) production. Accordingly, EKODE response was not sensitive to the phospholipase C inhibitor U-73122. EKODE mobilized a Ca(2+) store included in the thapsigargin (TG)-sensitive stores, although the interaction between EKODE and TG appears complex, since EKODE added at the plateau response of TG induced a rapid drop in [Ca(2+)](i). 9-oxo-octadecadienoic acid, another oxidized derivative of linoleic acid, also increases [Ca(2+)](i), with a dose-response curve similar to EKODE. However, arachidonic and linoleic acids at 10 microM failed to increase [Ca(2+)](i) but did reduce the amplitude of the response to EKODE. It is concluded that EKODE mobilizes Ca(2+) from an InsP(3)-sensitive store and that this [Ca(2+)](i) increase is responsible for aldosterone secretion by glomerulosa cells. Similar bell-shaped dose-response curves for aldosterone and [Ca(2+)](i) increases reinforce this hypothesis.

Interactions Between Modality of Working Memory Load and Perceptual Load in Distractor Processing.

PubMed

Koshino, Hideya; Olid, Pilar

2015-01-01

The present study investigated interactions between working memory load and perceptual load. The load theory (Lavie, Hirst, de Fockert, & Viding, 2004 ) claims that perceptual load decreases distractor interference, whereas working memory load increases interference. However, recent studies showed that effects of working memory might depend on the relationship between modalities of working memory and task stimuli. Here, we examined whether the relationship between working memory load and perceptual load would remain the same across modalities. The results of Experiment 1 showed that verbal working memory load did not affect a compatibility effect for low perceptual load, whereas it increased the compatibility effect for high perceptual load. In Experiment 2, the compatibility effect remained the same regardless of visual working memory load. These results suggest that the effects of working memory load and perceptual load depend on the relationship between the modalities of working memory and stimuli.

Lactic Acid Bacteria from Kefir Increase Cytotoxicity of Natural Killer Cells to Tumor Cells.

PubMed

Yamane, Takuya; Sakamoto, Tatsuji; Nakagaki, Takenori; Nakano, Yoshihisa

2018-03-27

The Japanese fermented beverage, homemade kefir, contains six lactic acid bacteria: Lactococcus. lactis subsp. Lactis , Lactococcus . lactis subsp. Cremoris , Lactococcus. Lactis subsp. Lactis biovar diacetylactis , Lactobacillus plantarum , Leuconostoc meseuteroides subsp. Cremoris and Lactobacillus casei . In this study, we found that a mixture of the six lactic acid bacteria from kefir increased the cytotoxicity of human natural killer KHYG-1 cells to human chronic myelogenous leukemia K562 cells and colorectal tumor HCT116 cells. Furthermore, levels of mRNA expression and secretion of IFN-γ (interferon gamma) increased in KHYG-1 cells that had been treated with the six lactic acid bacteria mixture from kefir. The results suggest that the six lactic acid bacteria mixture from kefir has strong effects on natural immunity and tumor cell cytotoxicity.

Increased oxygen load in the prefrontal cortex from mouth breathing: a vector-based near-infrared spectroscopy study.

PubMed